Dept of Medicine

DEPT OF MEDICINE

Researcher : Au WY

List of Research Outputs

Au W.Y., Ho J.C.M., Lie A.K.W., Sun J.Z., Zheng L., Liang R.H.S., Lam W.K. and Tsang K.W.T., A prospective study of respiratory ciliary structure and function after stem cell transplantation, Bone Marrow Transplantation. 2006, 38: 243-248.

Au W.Y. and Leung W.C., Challenges and pitfalls in prenatal screening in pregnancies involving allogeneic stem cell transplantation recipients, Bone Marrow Transplantation. 2007, 39(7): 379-382.

Au W.Y., Tsang S.K., Cheung B.K., Siu T.S., Ma E.S.K. and Tam S., Cough mixture abuse as a novel cause of folate deficiency: a prospective, community-based, controlled study, Haematologica. 2007, 92(4): 562-563.

Au W.Y., Lam V.M.S., Pang A.W.K., Lee W.M., Chan L.C., Song Y., Ma E.S.K. and Kwong Y.L., Glucose-6-phosphate dehydrogenase deficiency in female octogenarians, nanogenarians, and centenarians, The Journals of Gerontology Series A: Biological Sciences and Medical Sciences . 2006, 61(10): 1086-1089.

Au W.Y., Fung T.K., Ma E.S.K., Shek T.W.H., Hawkins B.R. and Liang R.H.S., HLA associations, microsatellite instability and epigenetic changes in thyroid lymphoma in Chinese, Leuk Lymphoma. 2007, 48(3): 531-534.

Au W.Y., Fung T.K., Lie A.K.W., Lam K.Y., Lam C.C.K. and Kwong Y.L., Reemergence of JAK2 V617F clone heralds extramedullary leukemia relapse after BMT for transformed essential thrombocytosis, Annals of Hematology. 2006, 86: 145-7.

Au W.Y., Trendell-Smith N.J., Chow C. and Liang R.H.S., Senile EBER positive diffuse large B cell lymphoma relapsing in the nasopharynx, Haematologica. 2006, 91(1): 111.

Au W.Y., Fung A., Liu C.L., Fan S.T., Ma E.S.K., Liang R.H.S. and Kwong Y.L., Serial analysis of JAK2 mutation in a patient who developed essential thrombocythemia after orthotopic liver transplantation (Case Report), American Journal of Hematology. 2006, 81(11): 880-882.

Au W.Y., Au W.Y., Fung T.K., Liu C.L., Fung T.K., Fung T.K., Fan S.T., Ma E.S.K., Liang R.H.S. and Kwong Y.L., Serial analysis of JAK2 mutation in a patient who developed essential thrombocythemia after orthotopic liver transplantation, American Journal of Hematology. 2006, 81(1): 880-882.

Au W.Y., Ma E.S.K., Lee T.L., Ha S.Y., Fung T.K., Lie A.K.W. and Kwong Y.L., Successful treatment of thrombotic microangiopathy after haematopoietic stem cell transplantation with rituximab, British Journal of Haematology. Blackwell Publishing Ltd, 2007, 137: 475-478.

Au W.Y., Fung T.K., Lam K.Y., Lie A.K.W., Liang R.H.S. and Kwong Y.L., Transformed essential thrombocytosi with a JAK2 V617F mutation relapsing as JAK2 Mutation-negative leukaemia after allogeneic stem cell transplantation, Bone Marrow Transplantation. 2006, 38(8): 573-4.

Au W.Y., Fung T.K., Wong K.F., Chan C.H. and Liang R.H.S., Tumor necrosis factor alpha promoter polymorphism and the risk of chronic lymphocytic leukemia and myeloma in the Chinese population, Leukaemia and Lymphoma. 2006, 47(10): 2189-2193.

Chen W.Y.W., Hu X., Liang A.C.T., Au W.Y., So J.C.C., Wong M.L.Y., Shen L., Tao Q., Chu K.M., Kwong Y.L. and Srivastava G., High BCL6 expression predicts better prognosis, independent of BCL6 translocation status, translocation partner, or BCL6 deregulating mutations, in gastric lymphoma, Blood. 2006, 108: 2373-2383.

Chim J.C.S., Lie A.K.W., Liang R.H.S., Au W.Y. and Kwong Y.L., Long-term results of allogeneic bone marrow transplantation for 108 adult patients with acute lymphoblastic leukemia: favorable outcome with BMT at first remission and HLA-matched unrelated donor, Bone Marrow Transplantation. 2007, 40(4): 339-347.

Hon C., Yau K., Shek T.W.H. and Au W.Y., Diffuse large cell B cell lymphoma presenting as a unilateral eye mass, American Journal of Hematology. 2007, 82(4): 325-326.

Hon C., Yau K., Chan E.Y.T., Lee K.K. and Au W.Y., Graves' ophthalmopathy after allogeneic stem cell transplantation, Annals of Hematology. 2006, 85(12): 887-888.

Hon C., Yim S.M., Lam M.F. and Au W.Y., Thrombotic thrombocytopenic purpura after stem cell transplantation presenting as blurred vision and fundal infiltrates, British Journal of Haematology. 2006, 134(1): 1.

Lam M.F., Au W.Y., Tse K.C., Chan D.T.M., Chan G.S., Chan K.W. and Lai K.N., Hyperleptinaemia and chronic inflammation after peritonitis predicts poor nutritional status and mortality in patients on peritoneal dialysis, Nephrology Dialysis Transplantation. 2007, 32: 1445-1450.

Lam M.F., Au W.Y., Tse K.C., Chan D.T.M., Chan G.S.W., Chan K.W. and Lai K.N., Late onset membranous nephropathy complicating donor lymphocyte infusion for Leukaemia relapse after allogeneic stem cell transplantation, American Journal of Hematology. 2007, 82(4): 327-328.

Siu C.W.D., Au W.Y., Yung C.Y., Kumana C.R., Lau C.P., Kwong Y.L. and Tse H.F., Effects of oral arsenic trioxide therapy on QT intervals in patients with acute promyelocytic leukemia: implications on long-term cardiac safety, Blood. 2006, 108(1): 103-106.

So J.C.C., Chan Y.Y., Tsang S.T.Y., Lee C.W., Au W.Y., Ma E.S.K. and Chan L.C., A novel beta-delta globin gene fusion, anti-Lepore Hong Kong, leads to overexpression of delta globin chain and a mild thalassaemia intermedia phenotype when co-inherited with b⁰-thalassaemia, British Journal of Haematology. 2006, 136(1): 158-162.

Researcher : Chan AKK

List of Research Outputs

Tang S.C.W., Leung J.C.K., Chan L.Y., Chan A.K.K., Eddy A.A. and Lai K.N., Impact of angiotensin antagonists and HMG-CoA reductase inhibitors on adriamycin nephropathy, Journal of American Society of Nephrology. 2006, 17: 41A.

Researcher : Chan AOO

List of Research Outputs

Chan A.O.O., Jim M.H., Lam K.F., Siu D.C.W., Tong S.M., Ng F.H., Wong S.Y., Hui W.M., Lam S.K. and Wong B.C.Y., Aspirin does not prevent recurrence of colorrectal adenomas in patients with coronary artery disease. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A194.

Chan A.O.O., Chu K.M., Huang C.Y., Lam K.F., Leung S.Y., Sun Y., Ko S., Xia H.H.X., Cho C.H., Hui W.M., Lam S.K. and Rashid A., Association between Helicobacter pylori infection and interleukin 1beta polymorphism predispose to CpG island methylation in gastric cancer, GUT. 2007, 56: 595-597.

Chan A.O.O., Hui W.M., Leung Y.C., Wong Y.H., Chan P., Hung I.F.H., Hsu A., But D., Lam S.K. and Wong B.C.Y., Better efficacy of tegaserod in constipated patients with slow colonic transit, absent pelvic floor dyssynergy and absent impaired rectal sensation. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A194.

Chan A.O.O., Chow R., Hui W.M., Leung Y.C., Tong S.M., Lam S.K. and Wong B.C.Y., Biofeedback is equally effective in patients with short or long duration of function constipation. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A194.

Chan A.O.O., Liu C.L. and Wong B.C.Y., Choledochal cysts. , In: Baron T, Kozarek R & Carr-Locke D (eds), A Practical Guide to ERCP. Elsevier, 2007.

Chan A.O.O., Hui W.M., Wong Y.H., Leung Y.C., Lam S.K. and Wong B.C.Y., Decreased cortical activation during rectal distention in patients with functional constipation with normal rectal compliance. Digestive Disease Week 2007, Washington DC, USA, May 19-24, Gastroenterology. 2007, 132(4) Suppl 2: A23.

Chan A.O.O., Hui W.M., Leung Y.C., Hu H.C., Lam S.K. and Wong B.C.Y., Efficacy of tegasered for functiona constipation in Chinese subjects: A randomized double blind contolled trial in a single center. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4): A194.

Chan A.O.O., Hui W.M., Leung Y.C., Hu H.C., Lam S.K. and Wong B.C.Y., Efficacy of tegaserod for functional constipation in Chinese subjects: a randomized double-blind controlled trial in a single center, Alimentary Pharmacology and Therapeutics. 2007, 25(4): 463-469.

Chan A.O.O., Hui W.M., Lam K.F., Leung G.K.L., Yuen R.M.F., Lam S.K. and Wong B.C.Y., Familial aggregation in constipated subjects in a tertiary referral center, American Journal of Gastroenterology. Blackwell Publishing, 2007, 102: 149-152.

Chan A.O.O., Huang C.Y., Leung Y.C., Hui W.M., Lam S.K. and Wong B.C.Y., Familial constipationis associated with a2 adrenoceptor polymorphism. Digestive Diseases Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A189.

Chan A.O.O., Lam K.F., Hui W.M., Leung G.K.L., Wong Y.H., Lam S.K. and Wong B.C.Y., Influence of Positive Family History on Clinical Characteristics of Functional Constipation, Clinical Gastroenterology and Hepatology. Elsevier, 2007, 5(2): 197-200.

Chan A.O.O. and Wong B.C.Y., Multi-disciplinary approach to intestinal gastric cancer. Edited by Jankowski J, Kerr D, Sampliner R, Fong YM, In: Gastrointestinal Oncology: A multidisciplinary approach. Blackwell Publishing, 2007.

Chan A.O.O., Jim M.H., Lam K.F., Siu D.C.W., Tong S.M., Ng F.H., Wong S.Y., Hui W.M., Chan C.K., Lai K.C., Cheung T.K., Chan P., Wong G., Yuen R.M.F., Lau Y.K., Lee S.W.L., Seto M.L., Lam S.K. and Wong B.C.Y., Patients with coronary artery disease had high prevalanece of colorectal cancer and adenoma: END-results of metabolic syndrome and smoking. Digestive Disease Week 2007, Washington DEc, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A65.

Chan A.O.O., Hui W.M., Leung G.K.L., Tong T.P.H., Hung I.F.N., Chan P., Hsu A., But D., Wong B.C.Y., Lam S.K. and Lam K.F., Patients with functional constipation do not have increase prevalence of colorectal cancer precursors”, GUT. British Medicial Journal, 2007, 56: 451-452.

Chan A.O.O., Ng F.H., Chang P.C.M., Wong S.Y., Chu W.M., Yuen W.C., Lau Y.K., Cheung T.K. and Wong B.C.Y., Prevalence and prediction of gastrointestinal events in patients receiving a combination of aspirin plus clopidogrel. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A135.

Chan A.O.O., Loo C.K., Leung C.M., Wong S.Y., Ng F.H., Li M.K.W., Lam K.M., Lam S.K. and Wong B.C.Y., Prevalence of colonic lesions after a negative screening colonscopy in a population with rapidly rising colorectal cancer incidence: A prospective multi-center analysis. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A189.

Cheung T.K., Lam B., Ip M.S.M., Wong Y.H., Chan A.O.O., Lam S.K. and Wong B.C.Y., Nocturnal Reflux Symptoms Correlate with Respiratory Events in Patients with Obstructive Sleep Apnea. , AGA Digestive Digestive Disease Week 2007.

Cheung T.K., Lam B., Ip M.S.M., Wong Y.H., Chan A.O.O., Lam S.K. and Wong B.C.Y., Nocturnal reflux symptoms correlate with respiratory events in patients with obstructive sleep apnea. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132 (4) Supp 2: A482.

Lam T.J., Mulder C.J.J., Peña S., Wong B.C.Y., Hui W.M., Lam S.K. and Chan A.O.O., Increased in prevalence of advanced colonic polyps in young patients over the past eight years in Hong Kong. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A195.

Researcher : Chan CF

List of Research Outputs

Chan C.F., Leung A.Y.H., Chan Y.S. and Cheung R.T.F., Intracerebral injection of granulocyte-colony stimulating factor reduces infarct volume following transient middle cerebral artery occlusion in mice, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population. 2007, 57.

Chan C.F., Leung A.Y.H., Chan Y.S. and Cheung R.T.F., Use of granulocyte-colony stimulating factor in a mice stroke model, 11th Research Postgraduate Symposium. 2006, 60.

Researcher : Chan CK

List of Research Outputs

Chan A.O.O., Jim M.H., Lam K.F., Siu D.C.W., Tong S.M., Ng F.H., Wong S.Y., Hui W.M., Chan C.K., Lai K.C., Cheung T.K., Chan P., Wong G., Yuen R.M.F., Lau Y.K., Lee S.W.L., Seto M.L., Lam S.K. and Wong B.C.Y., Patients with coronary artery disease had high prevalanece of colorectal cancer and adenoma: END-results of metabolic syndrome and smoking. Digestive Disease Week 2007, Washington DEc, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A65.

Hu H.C., Lam S.K., Lam C.L.K., Wong R.W.M., Lam K.F., Lai K.C., Wong Y.H., Wong B.C.Y., Chan O.O., Chan C.K., Leung G.M. and Hui W.M., Comparison between Empirical Prokinetics, Helicobacter Test-and-Treat and Empirical Endoscopy in Primary-Care Patients Presenting with Dyspepsia: A One-Year Study, World Journal of Gastroenterology. 2006, 12(31): 5010-5016.

Researcher : Chan DTM

Project Title:	Internalization of anti-DNA antibodies from patients with lupus nephritis by human mesangial cells
Investigator(s):	Chan DTM, Yung SSY
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	11/2003

Abstract:

To characterize HMC membrane and intracellular molecules responsible for binding to anti-DNA antibodies-by trypsin, papain, or pepsin digestion, Western blotting, and protein sequencing; to examine the relationship between the properties of human anti-dsDNA antibodies (isoelectric point, binding to HMC, cellular internalization), their correlation with clinical disease activity, and their effects on cell function, morphology, proliferation, and apoptosis; to elucidate the mechanisms by which anti-dsDNA antibodies bind and penetrate plasma membrane, traverse the cytoplasm, and enter the nucleus of HMC. This will be achieved by kinetic studies using timed flow cytometry, immunohistochemistry, and confocal microscopy. The latter will also be used to investigate the binding between anti-dsDNA antibodies and cytoskeletal structures including myosin. The effects of anti-dsDNA antibodies in the presence or absence of DNA and histones on the synthesis of cytoskeletal molecules will be examined by radiolabelling and immunoprecipitation.

Project Title:	The effect of anti-DNA antibodies on the synthesis of pro-fibrotic cytokines, growth factors and matrix proteins in proximal tubular epithelial cells during lupus nephritis
Investigator(s):	Chan DTM, Yung SSY
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004
Completion Date:	10/2006

Abstract:

To isolate paired polyclonal anti-DNA antibodies from 12 patients with a history of clinically severe lupus nephritis during disease flare and remission; to determine the effect of human polyclonal anti-DNA antibodies on PTEC viability, proliferation and activation; to determine the effect of anti-DNA antibodies on PTEC secretion of cytokines; to investigate how anti-DNA-mediated alterations of cytokines and growth factors modulate changes in matrix synthesis and deposition.

Project Title:	Effects of mycophenolate mofetil and cyclophosphamide on mesangial cell proliferation and function in MRL/1pr mice with lupus nephritis
Investigator(s):	Chan DTM, Yung SSY
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	12/2004

Abstract:

To assess the clinical effects of mycophenolate mofetil (MMF) and cyclophosphamide on disease manifestations in MRL/1pr mice with lupus nephritis; to determine the effects of MMF and cyclophosphamide on serum levels of anti-DNA antibodies, pro-inflammatory mediators, and markers of fibrosis; to examine the effects of MMF and cyclophosphamide on kidney histopathology in MRL/1pr mice with lupus nephritis, focusing on mesangial cell proliferation, synthesis of inflammatory/fibrosis mediators, and production of matrix components. The data will be analyzed in relation to corresponding changes in the parameters indicating disease activity, inflammatory cell infiltration, and immune complex deposition; to isolate mesangial cells from treated and control mice, and to assess in vitro mesangial cell activation and synthesis of inflammatory/fibrosis mediators and matrix components; to investigate whether the actions of MMF or cyclophosphamide on mesangial cells are mediated via the protein kinase C (PKC) pathway.

Project Title:	TGF-beta1 bioactivation in human peritoneal mesothelial cells under elevated glucose concentration - the role of thrombospondin-1
Investigator(s):	Chan DTM, Yung SSY
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	12/2005

Abstract:

Background In Hong Kong, 80% of patients with end stage renal failure are managed with peritoneal dialysis (PD). Normal structure and function of the peritoneum are essential to ensure optimal long-term clinical outcome. Many patients on long-term PD however, develop progressive thickening of the peritoneal membrane with altered transport function. The peritoneum is the most extensive serous membrane in the body, covering the visceral organs and lining the abdominal cavity. It comprises a monolayer of mesothelial cells resting upon a thin basal lamina, underneath which is the interstitium that contains a capillary network and fibroblasts (1). Mesothelial cells are specialized epithelial cells that provide an anatomical barrier and a frictionless interface for the movement of organs and tissues (2). They also play a critical role in the control of peritoneal homeostasis, permselectivity, inflammation and fibrosis. Moreover, mesothelial cells synthesize and secrete multifunctional molecules including matrix proteins and glycosaminoglycans including hyaluronan (HA) (3). During PD a hyperosmolar dialysis solution is allowed to dwell in the peritoneal cavity for several hours. Metabolic waste, electrolytes, and excessive water are removed from the circulation by diffusion or convection across the peritoneal membrane (4, 5). Conventional PD solutions utilize dextrose at high concentrations, usually 15 to 40 times that of physiological levels, to provide the osmotic drive for free water removal. This ‘bio-incompatible’ glucose milieu is a major insult to the structural and functional integrity of the peritoneal membrane (6, 7). The peritoneum in long-term PD exhibits re-duplication of the basal lamina, increased synthesis and deposition of matrix within the submesothelium, and progressive subendothelial hyalinization, with narrowing or obliteration of the vascular lumen (6-8). These structural changes are accompanied by deranged transport properties. In vitro studies have shown that high glucose concentrations alter cellular proliferation and viability, and induce growth factor, cytokine and matrix protein synthesis in human peritoneal mesothelial cells (HPMC) (9-13). Repeated chemical or bacterial injury to the peritoneal mesothelium triggers inflammatory responses and initiates a multitude of reparative processes that aim to heal but which often result in fibrosis. The mechanisms leading to the different outcomes are under intense investigation. In vitro studies have demonstrated that high glucose concentration can modulate cell proliferation and up-regulate matrix synthesis in HPMC. These changes are mediated through protein kinase C, and bioactivation of TGF-beta1. TGF-beta1 is normally synthesized and secreted in its latent form, and must be activated before it can bind to its receptors and elicit functional changes to the cells. Therefore, changes in the expression of latent TGF-beta1 will have no biological effect on HPMC unless mechanisms are present to convert it to its active form. Studies utilizing platelets and endothelial cells have demonstrated that physiocochemical activation of TGF-beta1 can occur by extreme pH or high temperature, limited proteolysis, or binding to various membrane or extracellular matrix components (14, 15). Activation in vivo is more complex and remains to be fully elucidated. Recent studies have demonstrated that the extracellular matrix component thrombospondin-1 (TSP-1) is a key activator of TGF-beta1 in human mesangial cells incubated with elevated concentrated of glucose (16). The mechanism by which TGF-beta1 is activated in HPMC has not been investigated and constitutes the theme of this project. The objectives of this proposal are thus: 1. To assess HPMC proliferation and cell viability under physiological (5mM) and elevated glucose concentrations (30 mM which simulates the concentration of glucose in the peritoneal cavity after equilibration of the PD solution). 2. To determine mRNA and protein synthesis of TGF-beta1, TSP-1 and matrix proteins (fibronectin, and collagen type I and III and IV). TGF-beta1 bioactivation will also be assessed and correlated with TSP-1 expression. 3. To examine the effect of exogenous TSP-1 on TGF-beta1 activity, matrix synthesis, and PKC-signaling pathway. Data will be confirmed in separate studies whereby TSP-1 blocking peptide will be used. References 1. Dobbie JW. In: Gokal R, Nolph KD, Eds. The Textbook of Peritoneal Dialysis. Kluwer Academic Publishers, Netherlands, 1994. 2. Digenis GE. Perit Dial Bull 1984; 4: 63-69. 3. Mutsaers SE. Respirology 2002; 7: 171-191. 4. Moncrief JW, Popovich RP. Kidney Int 1985; 17: S23-S25. 5. Krediet R. In: Gokal R, Khanna R, Krediet R Eds. The Textbook of Peritoneal Dialysis. Kluwer Academic Publishers, Dordrechts, 2000: 135-172. 6. Honda K, Nitta K, Horita S, Yumura W, Nihei H. Nephron 1996; 72: 171-176. 7. Williams JD, Craig KJ, Topley N, et al. J Am Soc Nephrol 2002; 13: 470-479. 8. Gotloib L, Bar-Sella P, Shostak A. Perit Dial Bull 1985; 5: 212-215. 9. Topley N, Mackenzie R, Jorres A, Coles GA, Davies M, Williams JD. Perit Dial Int 1992; 13: S282-285. 10. Ha H, Yu MR, Lee HB. Kidney Int 2001; 59: 463-470. 11. Chan TM, Leung JKH, Tsang RCW, Liu ZH, Li LS, Yung S. Kidney Int 2003; 64: 519-533. 12. Topley N, Liberek T, Davenport A, Li FK, Fear H, Williams JD. Kidney Int Suppl 1996; 56: S17-21. 13. Witowski J, Wisniewska J, Korybalska K, et al. J Am Soc Nephrol 2001; 12: 2434-2441. 14. Brown PD, Wakefield LM, Levinson AD, Sporn MB. Growth Factors. 1990; 3: 35-43. 15. Lyons R, Gentry LE, Purchio AF, Moses HL. J Cell Biol 1990; 110; 1361-1367. 16. Yevdokimova N, Abdel Wahab N, Mason RM. J Am Soc Nephrol 2001; 12: 703-712.

Project Title:	Synthesis of cytokines and growth factors during bacterial peritonitis complicating peritoneal dialysis - in vivo and in vitro studies
Investigator(s):	Chan DTM, Yung SSY
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2006

Abstract:

The peritoneum is the most extensive serous membrane in the body, covering the visceral organs and lining the abdominal cavity (1). It comprises a monolayer of mesothelial cells underneath which lies the interstitium that contains fibroblasts, collagen fibrils, and a capillary network (1). Mesothelial cells are specialized epithelial cells that provide an anatomical barrier and a frictionless interface for the movement of organs and tissues. Moreover, they play a critical role in peritoneal homeostasis, transport functions, inflammation and tissue remodeling through its controlled synthesis of cytokines, chemokines, growth factors and matrix proteins (2-6). Peritoneal dialysis (PD) is recognized as an effective treatment modality for patients with end-stage renal failure. Currently, 80% of patients with end-stage renal failure in Hong Kong are managed with PD. This procedure entails the infusion of a hyperosmolar dialysis solution into the peritoneal cavity for 4-6h, during which time metabolic waste, electrolytes, and excessive water are removed from the circulation by diffusion or convection across the peritoneal membrane (7, 8). Peritonitis is a serious complication of PD and is the single most important cause of technique failure in PD patients. It results in the initiation of acute inflammatory processes that include release of pro-inflammatory cytokines, chemokines, and growth factors, mesothelial cell proliferation, cell transdifferentation and detachment (2, 9). Unabated inflammation results in the increased synthesis and deposition of matrix proteins, reduplication of the peritoneal membrane and thickening of the submesothelium (10). These structural changes are accompanied by deranged transport properties. The mechanisms that alter functional properties of mesothelial cell during peritonitis remain to be fully elucidated and constitute the theme of this project. The objectives of this proposal are thus: 1. To assess the levels of cytokines (IL-1beta, IL-6, TNF-alpha), chemokines (RANTES, MCP-1) and growth factors (TGF-beta1, BMP-7 and VEGF) in sequential samples of spent PD solutions obtained during onset of peritonitis until clinical resolution of peritonitis. Cytokine, chemokine and growth factor levels will be correlated with clinical parameters such as invading microbe, response to antibiotic treatment, catheter removal and repeated peritonitis. 2. To culture primary peritoneal mesothelial cells and to establish an in vitro model to investigate the effects of spent PD solutions on mesothelial cell morphology, proliferation and activation (increased expression of alpha-smooth muscle actin). 3. To assess the effect of spent PD solutions on mesothelial synthesis of cytokines, chemokines and growth factors to determine whether mesothelial cells, in part, contribute to the levels identified in PD fluids. 4. To investigate the signaling pathway induced in mesothelial cells by spent peritonitis-complicating PD solutions. References 1. Dobbie JW. In: Gokal R, Nolph KD, Eds. The Textbook of Peritoneal Dialysis. Kluwer Academic Publishers, Netherlands, 1994. 2. Rampino T, Cancarini G, Gregorini M, et al. Hepatocyte growth factor/scatter factor released during peritonitis is active on mesothelial cells. Am J Pathol 2001; 159: 1275-1285. 3. Chan TM, Leung JKH, Tsang RCW, Liu ZH, Li LS,Yung S. Emodin ameliorates glucose-induced matrix synthesis in human peritoneal mesothelial cells. Kidney Int 2003; 64: 519-533. 4. Bidmon B, Endemann M, Arbeiter K, et al. Over-expression of HSP-72 confers cytoprotection in experimental peritoneal dialysis. Kidney Int 2004; 66: 2300-2307. 5. Aroeira LS, Aguilera A, Selgas R, et al. Mesenchymal conversion of mesothelial cells as a mechanism responsible for high solute transport rate in peritoneal dialysis: role of vascular endothelial growth factor. Am J Kidney Dis 2005; 46: 938-948. 6. Kiribayashi K, Masaki T, Naito T, et al. Angiotensin II induces fibronectin expression in human peritoneal mesothelial cells via ERK1/2 and p38 MAPK. Kidney Int 2005; 67: 1126-1135. 7. Moncrief JW, Popovich RP. Continuous ambulatory peritoneal dialysis best treatment for end-stage renal failure. Kidney Int (Suppl) 1985; 17: S23-25. 8. Krediet R. In: Gokal R, Khanna R, Krediet R Eds. The Textbook of Peritoneal Dialysis. Kluwer Academic Publishers. Dordrechts, 2000: 135-172. 9. Yao V, McCauley R, Cooper D, Platell C, Hall JC. Peritoneal mesothelial cells produce cytokines in a murine model of peritonitis. Surg Infect. 2004; 5: 229-239. 10. Di Paolo N, Sacchi G, De Mia M, et al. Morphology of the peritoneal membrane during continuous ambulatory peritoneal dialysis. Nephron 1986; 44: 204-211.

Project Title:	Effect of rapamycin, alone or in combination with mycophenolate mofetil, in the treatment of murine lupus nephritis
Investigator(s):	Chan DTM, Lui SL, Yung SSY, Chan KW
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2007

Abstract:

To investigate and compare the effects of rapamycin and mycophenolate mofetil (MMF), alone or in combination, on phenotypic, serologic, molecular, and histopathologic manifestations of lupus nephritis in NZBWF1/J mice. Spectifically the expression of inflammatory or fibrosis mediators/markers IL-6, IL-2, IL-1β, TNF-α, IFN-γ, hyaluronan, fibronectin, collagen type I and TGF-&beta1 will be examined, especially in mesangial cell and tubular epithelial cells; to examine the effect of rapamycin and MMF on renal histopathology and immune deposits focusing on renal cell proliferation, inflammatory cell infiltration and renal expression of inflammatory/fibrosis markers; to investigate the correlation between therapeutic effects of these drugs and changes in signaling pathways (PKS-α, PKC-βI, PKC--βII, PKC-γ, p38 MAPK, JNK, and ERK pathways, and NF-κB activation) upstream of cytokine/growth factor induction.

List of Research Outputs

Chan D.T.M., Tsang R.C.W., Chan K.W. and Yung S.S.Y., Anti-DNA antibodies stimulate hyaluronan synthesis in proximal tubular epithelial cells through the induction of IL-6 and IL-1b, Journal of the American Society of Nephrology. 2006, 17: 352A.

Chan D.T.M., Basic studies of novel peritoneal dialysates, 11th Congress of the International Society for Peritoneal Dialysis, 25-28 August, Hong Kong. 2006.

Chan D.T.M., Case studies in the management of lupus nephritis, EDTA-ERA (European Dialysis and Transplantation Association - European Renal Association) Congress, 23-26 June, Barcelona, Spain. 2007.

Chan D.T.M., Co-stimulatory blackade as potential new treatment for lupus nephritis, 8th International SLE Congress, 16-20 May, Shanghai, PR China. 2007.

Chan D.T.M., Consulting Editor (since 1996), Clinical Guidelines in Nephrology, Hospital Authority's publication. 2006.

Chan D.T.M., Current viewpoints - Virtual round table on lupus, www.ciaomed.org published online one 23 April. 2007.

Chan D.T.M., Diabetic nephropathy - risk factors, pathogenesis, presentation, and course, Second National Nephrology Coference, 8-10 December, Brunei Darussalam. 2006.

Chan D.T.M., Differential diagnosis of acute renal failure, Second National Nephrology Conference, 8-10 December, Brunei Darussalam. 2006.

Chan D.T.M., Editor (since 1997), The Nephrology Manual, Department of Medicine, Queen Mary Hospital, Hong Kong, 4th edition. 2007.

Chan D.T.M., Guest Editor (2006-2007), Proceedings of the 2006 International Society for Peritoneal Dialysis Congress, Supplement to Peritoneal Dialysis International (official journal of the International Society for Peritoneal Dialysis). 2006.

Chan D.T.M., Histological deterioration and more flares - the cse against azathioprine plus methylprednisolone in the treatment of proliferative lupus nephritis [Invited Editorial], Arthritis & Rheumatism. 2007, 56: 702-704.

Chan D.T.M., Lupus nehpritis - an update on its treatment, State-of-the-art Nephrolgoy Conference, organized by the Singpore Society of Nephrology and the Duke University USA, 9-13 September, Singpoare. 2006.

Chan D.T.M., Lupus nephritis ad vasculitic diesases of kidney, Second National Nephrology Conference, 8-10 December, Brunei Darussalam. 2006.

Chan D.T.M., Member of Editorial Board (since 2001), Medical Science Monitor [Official Journal of International Medical Association for Experimental and Clinical Reserach]+ . 2007.

Chan D.T.M., Member of Editorial Board (since 1999), Hong Kong Journal of Nephrology. 2007.

Chan D.T.M., Member of Editorial Board (since 2001), Chinese Journal of Practical Internal Medicine. 2007.

Chan D.T.M., Member of Editorial Board (since 2001), Journal of Nephrology, Dialysis, and Kidney Transplantation. 2007.

Chan D.T.M., Member of Editorial Board (since 2003), Chinese Journal of Nephrology, Dialysis & Transplantation. 2007.

Chan D.T.M., Member of Editorial Board (since 2003), Medical Progress. 2007.

Chan D.T.M., Member of Editorial Board (since 2005), Lupus. 2007.

Chan D.T.M., Member of Editorial Board (since 2007), The Open Rheumatology Journal. 2007.

Chan D.T.M., Mycophenolate mofetil in lupus nephritis, I Congresode la Asociacion Andaluza de Enfermedades Autoinmunes and the X Workshop of the European Working Party on Systemic Lupus Erythematosus, 16-18 February, Malaga, Spain. 2007.

Chan D.T.M., Ho S.K.N., Tang C.S.O., Tse K.C., Lam M.F., Lai K.N. and Yung S.S.Y., Pilot study of pegylated interferon-alpha 2a in dialysis patients with chronic hepatitis C virus infection, Nephrology. 2007, 12: 11-17.

Chan D.T.M., Practical approach in the diagnosis and management of proteinuria, Annual Meeting of the Macau Society of Nephrology. 2006.

Chan D.T.M., Severe lupus nephritis - better treatment and better outcomes, Lupus Nephritis Workshop, organized by the Balearic Society of Nephrology, 23 Oct, Palma de Mallorca, Spain. 2006.

Chan D.T.M. and Yung S.S.Y., Studying the effects of new peritoneal dialysis solutions on the peritoneum, Peritoneal Dialysis International . 2007, 27: S87-S93.

Chan D.T.M., Tailoring the PD prescription - use of new dialysates, State-of-the-art Nephrology Conference, organized by the Singapore Society of Nephrology and the Duke Uiversity USA, 9-13 September, Singapore. 2006.

Chan D.T.M., Timely start to renal replacement therapy, State-of-the-art Nephrology Conference, organized by the Singapore Society of Nephroogy and the Duke Univesity USA, 9-13 September, Singapore. 2006.

Chan D.T.M., Treatment of lupus nephritis in 2007, 8th International SLE Congress, 16-20 May, Shanghai, PR China. 2007.

Chan D.T.M., Update on the treatment of lupus nephritis, Asian Pacific League of Arthritis and Rheumatism, 1-3 August, Kuala Lumpur, Malaysia. 2006.

Choy C.B.Y., Chan D.T.M. and Lai K.N., Recurrent glomerulonephritis after kidney transplantation, American Journal of Transplantation. 2006, 6: 2535-2542.

Kong E.K.P., Chong W.P., Wong W.H.S., Chan D.T.M., Ng P.K.M., Song Y., Mak W. and Lau Y.L., p21 Gene Polymorphisms in Systemic Lupus Erythematosus, Rheumatology (Oxford, England). England, Oxford University Press, 2007, 46(2): 220-226.

Lam M.F., Tse K.C., Chan G., Chan K.W., Chan D.T.M. and Lai K.N., De Novo glomerulonephritis after hemopoietic stem cell transplantation, Journal of American Society of Nephrology. 2006, 17: 733A.

Lam M.F., Au W.Y., Tse K.C., Chan D.T.M., Chan G.S., Chan K.W. and Lai K.N., Hyperleptinaemia and chronic inflammation after peritonitis predicts poor nutritional status and mortality in patients on peritoneal dialysis, Nephrology Dialysis Transplantation. 2007, 32: 1445-1450.

Lam M.F., Au W.Y., Tse K.C., Chan D.T.M., Chan G.S.W., Chan K.W. and Lai K.N., Late onset membranous nephropathy complicating donor lymphocyte infusion for Leukaemia relapse after allogeneic stem cell transplantation, American Journal of Hematology. 2007, 82(4): 327-328.

Lui S.L., Chan K.W., Tsang R.C.W., Yung S.S.Y., Lai K.N. and Chan D.T.M., Effect of rapamycin on renal ischemia-reperfusion injury in mice, Transplant International. 2006, 19: 834-839.

Lui S.L., Yung S.S.Y., Tsang R.C.W., Chan K.W., Zhang Q., Tam S., Lai K.N. and Chan D.T.M., Rapamycin attenuates the severity of nephritis in NZB/NZW mice, Journal of the American Society of Nephrology. 2006, 17: 353A.

Lui S.L., Yung S.S.Y., Tsang R.C.W., Chan K.W., Zhang Q., Tam S., Lai K.N. and Chan D.T.M., Rapamycin reduces proteinuria and segmental glomerulosclerosis in murine adriamycin nephropathy, Journal of the American Society of Nephrology. 2006, 17: 743A.

Lui S.L., Yip T., Tse K.C., Chan D.T.M., Lai K.N. and Lo W.K., Tuberculous lymphadenitis in patients undergoing continuous ambulatory peritoneal dialysis, International Urology and Nephrology. 2007.

Mok T.M.Y., Wong S.S.Y., Chan D.T.M., Fong D.Y.T., Wong R.W.S. and Lau W.C.S., Non-tuberculous mycobacterial infection in patients with systemic lupus erythematosus, Rheumatology. Switzerland, Karger, 2007, 46(2): 280-284.

Mok T.M.Y., Wong S.S.Y., Chan D.T.M., Fong D.Y., Wong R.W.S. and Lau W.C.S., Non-tuberculous mycobacterial infection in patients with systemic lupus erythematosus, Rheumatology (Oxford). 2007, 46: 280-284.

Ng Y.C.C., Yung S.S.Y. and Chan D.T.M., Mycophenolic acid reduces anti-DNA antibody binding and cytokine secretion in renal proximal tubular epithelial cells - implications in lupus nephritis, Lupus. 2007, 16 (S1): 46.

Tang S.C.W., Chan K.W., Tang C.S.O., Lam M.F., Leung C.Y., Tse K.C., Li C.S., Ho Y.W., Tong K.L., Lai K.N., Chan D.T.M. and Hong Kong Nephrology Study Group ., Conversion of ciclosporin A to tacrolimus in kidney transplant recipients with chronic allograft nephropathy, Nephrology Dialysis Transplantation. 2006, 21(11): 3243-51.

Tang S.C.W., Ho Y.W., Tang A.W., Yip T., Tse K.C., Wang A.Y.M., Lo W.K., Chan D.T.M., Lai K.N. and Lui S.L., What is the optimal timing of dialysis initiation? , Peritoneal Dialysis International . 2006, Suppl 26: S90.

Tse K.C., Lam M.F., Tang S.C.W., Tang C.S.O., Lai K.N. and Chan D.T.M., A pilot study on tracolimus treatment in membranous or quiescent lupus nephritis with proteinuria resistant to angiotensin inhibition or blockade, Lupus. 2007, 16: 45-51.

Tse K.C., Tang S.C.W., Chan D.T.M. and Lai K.N., Rhodococcus lung abscess complicating kidney transplantation: successful management by combination antibiotic therapy, Transplant Infectious Disease. 2007, 10: 44-47.

Wan C.C., Yung S.S.Y., Tsang R.C.W. and Chan D.T.M., Fibrosis-related growth factors in peritoneal dialysate during peritonitis, Peritoneal Dialysis International. 2006, 26 (Suppl 2): S22.

Yeung C.K., Tse K.C., Lam M.F., Chan D.T.M. and Lai K.N., A renal transplant recipient with mutiple facial nodules, Nephrology Dialysis Transplantation. 2006, 21: 3591-3592.

Yip T., Tse K.C., Lam M.F., Cheng S.W., Lui S.L., Tang S.C.W., Li F.K., Wang A.Y.M., Choy C.B.Y., Ng M.M.T., Chan D.T.M., Lai K.N. and Lo W.K., Risk and outcome of peritonitis after flexible colonoscopy in CAPD patient, Peritoneal Dialysis International . 2006, Suppl 26: S68.

Yung S.S.Y. and Chan D.T.M., Glycosaminoglycans and proteoglycans: overlooked entities?, Peritoneal Dialysis International. 2007, 27: S104-S109.

Yung S.S.Y. and Chan D.T.M., Hyaluronan - regulator and initiator of peritoneal inflammation and remodeling, International Journal of Artifical Organs. 2007, 30: 477-483.

Yung S.S.Y., Wan C.C., Tsang R.C.W., Mak J.C.W., Tsang K.W.T. and Chan D.T.M., Induction of IL-6 and matrix protein synthesis in human peritoneal mesothelial cells by Pseudomonas aeruginosa exotoxin pyocyanin, Journal of the American Society of Nephrology. 2006, 17: 305A.

Yung S.S.Y., Zhang Q., Tsang R.C.W., Mak J.C.W., Tsang K.W.T. and Chan D.T.M., Induction of interleukin-6 secretion and matrix protein synthesis in human peritoneal mesothelial cells (HPMCs) by Pseudomonas aeruginosa exotoxin pyocyanin, Peritoneal Dialysis International. 2006, 26 (Suppl 2): S22.

Yung S.S.Y. and Chan D.T.M., Mesothelial cells, Peritoneal Dialysis International. 2007, 27: S110-S115.

Researcher : Chan HHL

Project Title:	The role of epidermal cooling in improving the outcome of laser therapy in the treatment of Nevus of Ota
Investigator(s):	Chan HHL, Lam LK
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	12/2000

Abstract:

To assess whether epidermal cooling would reduce pain, swelling, complications but improve clinical response and reduce the number of session required for laser treatment for Nevus of Ota.

Project Title:	The use of vascular lasers in the treatment of port wine stain in chinese
Investigator(s):	Chan HHL, Wei WI
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	11/2001

Abstract:

To establish the importance of epidermal cooling when 585nm pulse dye laser is used for the treatment of port wine stain in Chinese; to compare the clinical efficacy, patients' tolerability and complications of two commerical available vascular lasers that are equipped with different cooling devices in the treatment of port wine stain in Chinese.

List of Research Outputs

Chan H.H.L., Yang C., Leung J.C.K., Wei W.I. and Lai K.N., An Animal Study of the Effects on p16 and PCNA Expression of Repeated Treatment with High-Energy Laser and Intense Pulsed Light Exposure, Lasers in Surgery and Medicine. 2007, 39: 8-13.

Chan H.H.L., Introduction to clinical section of the special dermatology plastic surgery issue, Lasers in Surgery and Medicine. 2007, 39(2): 156.

Chan H.H.L., The Cosmetic Applications of Lasers and Similar Radiation Sources in Dermatology. Laser in People of Color., In: Lim H.W., Honigsmann H., Hawk J., Photodermatology. New York, USA, Informa Healthcare, 2007, 1st Edition: 417-432.

Chan H.H.L., The Use of Laser, Intense Pulsed Light Source and Radio Frequency for the Skin Rejuvenation, In: Park J.I., Toriumi D.M. , Asian Facial Cosmetic Surgery. USA, Saunders Elsevier, 2006, 1st Edition: p.401-411.

Chan H.H.L., Manstein D., Yu C.S., Shek S., Kono T. and Wei W.I., The prevalence and risk factors of post-inflammatory hyperpigmentation after fractional resurfacing in Asians, Lasers in Surgery and Medicine. 2007, 39: 381-385.

Ho W.S., Ying S.Y., Chan P.C. and Chan H.H.L., Use of onion extract, heparin, allantoin gel in prevention of scarring in chinese patients having laser removal of tattoos: a prospective randomized controlled trial, Dermatologic Surgery. 2006, 32(7): 891-6.

Kono T., Chan H.H.L., Groff W.F., Manstein D. and Nozaki M., Direct comparison study of fractional resurfacing using different fluences and densities for skin rejuvenation in Asians., Lasers in Surgery and Medicine. 2007, S19: 50.

Kono T., Chan H.H.L., Groff W.F., Manstein D., Sakurai H., Takeuchi M., Yamaki T., Soejima K., Nozaki M. and Nozaki M., Prospective direct comparison study of fractional resurfacing using different fluences and densities for skin rejuvenation in Asians. , Lasers in Surgery and Medicine. 2007, 39(4): 311-4.

Laubach H., Chan H.H.L., Rius F., Anderson R.R. and Manstein D., Effects of skin temperature on lesion size in fractional photothermolysis, Lasers in Surgery and Medicine. 2007, 39(1): 14-8.

Laubach H., Chan H.H.L., Manstein D. and Anderson R.R., Effects of skin temperature on lesion size in fractional resurfacing., Lasers in Surgery and Medicine. 2007, S19: 47.

Lin J.Y. and Chan H.H.L., Pigmentary disorders in Asian skin: treatment with laser and intense pulsed light sources, Skin Therapy Letter. 2006, 11(8): 8-11.

Manstein D., Watanabe K., Chan H.H.L. and Anderson R.R., Threshold, extend and anisotropy of thermally induced skin shrinkage., Lasers in Surgery and Medicine. 2007, S19: 59.

Shek S.Y.N., Yu C.S., Yeung C.K., Kono T. and Chan H.H.L., Non-invasive body contouring with focused ultrasound technology., Lasers in Surgery and Medicine. 2007, S19: 60.

Shek S.Y.N., Yu C.S., Yeung C.K., Kono T. and Chan H.H.L., Non-thermal blue and near-infrared light system with glycolic acid peels and topical vitamin C for photorejuvenation., Lasers in Surgery and Medicine. 2007, S19: 252.

Shek S.Y.N., Yu C.S., Yeung C.K., Kono T. and Chan H.H.L., Treatment of pigmented lesions by Starlux-V handpiece., Lasers in Surgery and Medicine. 2007, S19: 253.

Yeung C.K., Shek S.Y.N., Pjerring P., Yu C.S., Kono T. and Chan H.H.L., A comparative study of intense pulsed light alone and its combination with photodynamic therapy for the treatment of facial acne in Asian skin, Lasers in Surgery and Medicine. 2007, 39(1): 1-6.

Yeung C.K., Shek S.Y.N., Yu C.S. and Chan H.H.L., Treatment of facial acne with 1450nm diode laser in Asians., Lasers in Surgery and Medicine. 2007, S19: 69.

Yu C.S., Shek S.Y.N., Yeung C.K., Kono T. and Chan H.H.L., Combined infrared light and bipolar radiofrequency for skin tightening in Asians., Lasers in Surgery and Medicine. 2007, S19: 65.

Yu C.S., Chan H.H.L. and Tse R.K., Radiosurgery versus carbon dioxide laser for dermatochalasis correction in Asians, Lasers in Surgery and Medicine. 2007, 39(2): 176-9.

Researcher : Chan JCK

Project Title:	Application of the APACHE II and III prognostic scoring methods in the 14-bed Intensive Care Unit at Queen Mary Hospital
Investigator(s):	Chan JCK, Lam WK
Department:	Medicine
Source(s) of Funding:	Health Services Research Fund - Full Grants
Start Date:	07/1995

Abstract:

To evaluate the usefulness of the APACHE II and III prognostic scoring methods in the 14-bed ICU at Queen Mary Hospital; to compare our ICU performance in terms of actual mortality with the predicted mortality based on the APACHE II predictive equation; to correlate the APACHE II and III severity scores. As the mortality prediction equation for APACHE III is only commercially available, a close correlation between APACHE II and III scores would support using the APACHE II scoring and prediction method as the standard method rather than financially investing in the APACHE III system.

Researcher : Chan K

List of Research Outputs

Carnley B.P., Prior J.F., Gilbert A., Lim E., Devenish R., Sing H., Sarin E., Guhadasan R., Sullivan S.G., Wise C.A., Bittles A.H., Chan K., Wong M.S., Chan V.N.Y. and Erber W.N., The prevalence and molecular basis of hemoglobinopathies in Cambodia., Hemoglobin. Taylor and Francis, 2006, 4: 463-470.

Researcher : Chan KH

List of Research Outputs

Chan K.H., Mak W. and Ho S.L., Cryptococcal meningitis with raised intracranial pressure masquerading as malignant hypertension, International Journal Infectious Diseases. International Journal Infectious Diseases, 2007, 11(4): 366-7.

Chan K.H., Lachance D.H. and Lennon V.A., Frequency Of Seronegativity In Adult-Acquired Generalized Myasthenia Gravis, Second International Symposium on Healthy Aging. 2007.

Chan K.H., Tsang K.L., Fong C.Y., Ho S.L., Cheung R.T.F. and Mak W., Idiopathic inflammatory demyelinatng disorders after acute transverse myelitis., European Journal of Neurology. 2006, 13(8): 862-8.

Chan K.H., Mak W., Cheung R.T.F. and Ho S.L., Non-thymoma early-onset- and late-onset-generalized myasthenia gravis-A retrospective hospital-based study, Clinical Neurology Neurosurgery. 2007, 109(8): 686-91.

Chan K.H., Leung S.Y., Cheung R.T.F., Ho S.L. and Mak W., Paraneoplastic motor neuropathy and inflammatory myopathy associated with nasopharyngeal carcinoma, J Neurooncol. 2007, 81(1): 93-6.

Chan K.H., Mak W., Cheung R.T.F. and Ho S.L., Patients With Chronic Inflammatory Demyelinating Polyneuropathy And Diabetes Mellitus In Hong Kong Chinese - A Hospital Based Study, Second International Symposium On Healthy Aging. 2007.

Fong C.Y., Kwok H.H., Song Y., Cheng T.S., Ho W.L., Chu A.C.Y., Kung M.H.W., Chan K.H., Mak W., Cheung R.T.F., Ramsden D.B. and Ho S.L., Clinical phenotypes of a large Chinese multigenerational kindred with autosomal dominant familial ALS due to Ile149Thr SOD1 gene mutation., Amyotrophic Lateral Sclerosis. 2006, 7(3): 142-149.

Lee R., Lui W.M., Cheung R.T.F., Leung G.K.K. and Chan K.H., Mechanical thrombectomy in acute proximal middle cerebral artery thrombosis with the Alligator Retrieval Device, Cerebrovascular Diseases. 2007, 23: 69-71.

Researcher : Chan KH

List of Research Outputs

Chan K.H., Lachance D.H. and Lennon V.A., Frequency Of Seronegativity In Adult-Acquired Generalized Myasthenia Gravis, Second International Symposium on Healthy Aging. 2007.

Chan K.H., Leung S.Y., Cheung R.T.F., Ho S.L. and Mak W., Paraneoplastic motor neuropathy and inflammatory myopathy associated with nasopharyngeal carcinoma, J Neurooncol. 2007, 81(1): 93-6.

Researcher : Chan KH

List of Research Outputs

Chan K.H., Lachance D.H. and Lennon V.A., Frequency Of Seronegativity In Adult-Acquired Generalized Myasthenia Gravis, Second International Symposium on Healthy Aging. 2007.

Chan K.H., Leung S.Y., Cheung R.T.F., Ho S.L. and Mak W., Paraneoplastic motor neuropathy and inflammatory myopathy associated with nasopharyngeal carcinoma, J Neurooncol. 2007, 81(1): 93-6.

Researcher : Chan LCB

List of Research Outputs

Lai K.N., Tang S.C.W., Chan L.C.B. and Leung J.C.K., The modulation of chemokines release in proximal tubular epithelial cell by monocytes/T cells in proteinuric state is mediated by IL-1 and TNF-a, Journal of American Society of Nephrology. 2006, 17: 384A.

Researcher : Chan MMW

Project Title:	A surveillance program of tuberculosis in old age homes in Hong Kong
Investigator(s):	Chan MMW, Chu LW, Lam WK
Department:	Medicine
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	11/2001

Abstract:

To conduct a cross-sectional screening examination for tuberculosis in old age homes in several districts in Hong Kong, SAR; to ensure that directly observed therapy (DOT) is given to those with active disease diagnosed through the screening program in collaboration with the Hong Kong Government Tuberculosis and Chest Service (Chest Service); to provide a screening examination for tuberculosis for new residents on entry to the old age homes participating in the program; to participate, in collaboration with the Chest Service, in contact examination on residents in the same home from which an active case of tuberculosis is being diagnosed; to provide education to the staff of old age homes on early recognition of tuberculosis, its treatment and possible side effects to evaluate the effectiveness of the program.

Project Title:	A surveillance program of tuberculosis in old age homes in Hong Kong
Investigator(s):	Chan MMW, Chu LW, Lam WK
Department:	Medicine
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	01/2004

Abstract:

To conduct a cross-sectional screening examination for tuberculosis in old age homes in several districts in Hong Kong, SAR; to ensure that directly observed therapy (DOT) is given to those with active disease diagnosed through the screening program in collaboration with the Hong Kong Tuberculosis and Chest Service, Department of Health (Chest Service); to provide a screening examination for tuberculosis for new residents on entry to the old age homes participating in the program; to participate, in collaboration with the Chest Service, in contact examination on residents in the same home from which an active case of tuberculosis is being diagnosed; to provide education to the staff of old age homes on early recognition of tuberculosis, its treatment and possible side effects; to evaluate the effectiveness of the program.

List of Research Outputs

Al-Hazmi M., Wooldrage K., Antonisen N.R., Becklake M.R., Bowie D., Chan M.M.W., Dimich-Ward H., Ernst P., Manfreda J., Sears M.R. and Siersted H.C., Airflow obstruction in young adults, Can J Respir. 2007, 14: 221-7.

Begin P., Tremblay K., Daley D., Lemire M., Claveau S., Salesse C., Kacel S., Montpetit A., Becker A. and Chan M.M.W., Association of urokinase-type plasminogen activator with asthma and atopi. , American Journal of Respiratory and Critical Care Medicine. 2007, 175: 1109-16.

Bernstein I.L., Chan M.M.W., Malo J.L. and Berstein D.I., In: Bernstein IL, Chan-Yeung M, Malo JL, Berstein DI. Francis and Taylor, "Asthma in the Workplace" 3rd edition. New York, Francis and Taylor, 2006.

Beyers N., Chan M.M.W. and Pierard C., Access to knowledge for all: the IJTLD in the top 100. , International Journal of Tuberculosis and Lung Disease. 2006, 11: 1.

Beyers N., Enarson D.A., Pierard C. and Chan M.M.W., Response to a case of plagiarism in the International Journal of Tuberculosis and Lung Disease, International Journal of Tuberculosis and Lung Disease. 2007, 11(5): 473.

Beyers N., Pierard C., Enarson D.A. and Chan M.M.W., What new knowledge did we gain through the Internationsl Journal of Tuerbculosis and Lung Disease in 2006? , International Journal of Tuberculosis and Lung Disease. 2007, 11: 237-43.

Chan M.M.W., Ho A.S.S., Cheung A.H.K., Liu R., Yee W.K.S., Sin K.M., Wong M.L., Lam C.W., Chan K.S. and Lam W.K., Determinants of chronic obstructive pulmonary disease (COPD) in Chinese patients in Hong Kong. , International Journal of Tuberculosis and Lung Disease. 2007, 11: 502-7.

Chan M.M.W., Mak J.C.W., Ho S.P., Cheung A.H.K., Wong P.C., Chan K.K. and Ip M.S.M., Glutathione S-transferase (GST) polymorphisms and GST activity in Hong Kong Chinese COPD patients., International Journal of Tuberculosis and Lung Disease. 2007, 11: 508-14.

Chan M.M.W. and Becklake M., Occupational Lung Disease- unrecognised, underestimated and poorly managed- even today., International Journal of Tuberculosis and Lung Disease. 2007, 11: 119.

Chan M.M.W., Kam K.M., Leung C.C., Wang J., Yew W.W., Lam C.W. and Tam C.M., Population-based prospective molecular and conventional epidemiological study of tuberculosis in Hong Kong. , Respirology. 2006, 11(4): 442-8.

Chan M.M.W., Cheung A.H.K., Dai D.L., Chan F.H., Kam K.M., Tam C.M. and Leung C.C., Prevalence and determinants of positive tuberculin reactions of residents in old age homes in Hong Kong. , International Journal of Tuberculosis and Lung Disease. 2006, 10(8): 892-8.

Chan M.M.W., Chan F.H., Cheung A.H.K., Dai D.L. and Chu L.W., Prevalence of tuberculous infection and active tuberculosis in old age homes in Hong Kong. , J Am Geriatr Soc. 2006, 54(9): 1334-40.

Ho J.C.M., Chan M.M.W., Ho S.P., Mak J.C.W., Ip M.S.M., Ooi C.G.C., Wong M.P., Tsang K.W.T. and Lam W.K., Disturbance of systemic antioxidant profile in non-small cell lung carcinoma, Eur Respir J . 2007, 29: 273-278.

Ho J.C.M., Mak J.C.W., Ho S.P., Ip M.S.M., Lam W.K. and Chan M.M.W., Genetic variations of systemic superoxide dismutase and catalase activities in non-small cell lung cancer. Presented at the 11th Congress of the Asian Pacific Society of Respiratory, 19-22 Nov, Respirology. 2006, 11 Suppl 5: A129.

Ho J.C.M., Mak J.C.W., Ho S.P., Ip M.S.M., Tsang K.W.T., Lam W.K. and Chan M.M.W., Manganese superoxide dismutase and catalase genetic polymorphisms, activity levels and lung cancer risk in Chinese in Hong Kong, J. Thorac. Oncol. 2006, 1: 648-653.

Ho P.L., Becker M. and Chan M.M.W., Emerging occupational lung infections., International Journal of Tuberculosis and Lung Disease. 2007, 11(7): 710-21.

Ip M.S.M., Lam W.K., Lai A.Y.K., Ko F.W., Lau A.C., Ling S.O., Chan J.W. and Chan M.M.W., Reference values of diffusing capacity of nonsmoking Chinese in Hong Kong., Respirology. 2007, 12: 599-606.

Lee K.K., Hegele R.G., Manfreda J., Wooldrage K., Becker A.B., Ferguson A.C., Dimich-Ward H., Watson W.T.A. and Chan M.M.W., The Canadian asthma primary prevention study- Exposure to respiratory viruses and onset of asthma and atopy in high risk children: outcome at 2 –years of age., Pediatric Pulmonol . 2007, 42: 290-7.

Mak J.C.W., Ho S.P., Ho J.C.M. and Chan M.M.W., Best Poster - Increased oxidative stress in acute asthma exacerbation in Hong Kong Chinese asthmatics, 12th Medical Research Conference . 2007.

Mak J.C.W., Hui W.S., Ho S.P., So H.L., Chan M.M.W., Lam W.K., Cho C.H. and Ip M.S.M., Best Poster - Systemic oxidative stress and inflammation in cigarette smoke-exposed rat model, 12th Medical Research Conference. 2007.

Mak J.C.W., Ho S.P., Yu W.C., Choo K.L., Chu C.M., Yew W.W., Lam W.K., Chan M.M.W. and Chan M.M.W., Polymorphisms in MnSOD and catalase genes - functional activity study in smokers with or without COPD., Eur Respir J. 2007, e-pub.

Mak J.C.W., Ho S.P., Leung C.M., Cheung A.H.K., Law K.W., Ip M.S.M. and Chan M.M.W., Relationship between glutathione S-transferase gene polymorphisms and enzyme activity in Hong Kong Chinese asthmatics, American Thoracic Society International Conference, San Francisco, USA. American Journal of Respiratory and Critical Care Medicine. 2007, 175: A461.

Researcher : Chan OO

List of Research Outputs

Chan O.O., Lam K.F., Tong T.P.H., Siu D.C.W., Jim M.H., Hui W.M., Lai K.C., Yuen R.M.F., Lam S.K. and Wong B.C.Y., Coexistence between colorectal cancer/adenoma and coronary artery disease: results from 1382 patients. , Alimentary Pharmacology and Therapeutics. 2006, 24(3): 535-9.

Chan O.O., Huang C.Y., Hui W.M., Cho C.H., Yuen R.M.F., Lam S.K., Rashid A. and Wong B.C.Y., Stability of E-cadherin methylation status in gastric mucosa associated with histology changes. , Alimentary Pharmacology and Therapeutics. 2006, 24(5): 831-6.

Hu H.C., Lam S.K., Lam C.L.K., Wong R.W.M., Lam K.F., Lai K.C., Wong Y.H., Wong B.C.Y., Chan O.O., Chan C.K., Leung G.M. and Hui W.M., Comparison between Empirical Prokinetics, Helicobacter Test-and-Treat and Empirical Endoscopy in Primary-Care Patients Presenting with Dyspepsia: A One-Year Study, World Journal of Gastroenterology. 2006, 12(31): 5010-5016.

Lai K.C., Chu K.M., Hui W.M., Wong B.C.Y., Hung W.K., Loo C.K., Hu H.C., Chan O.O., Kwok K.F., Fung T.T., Wong J. and Lam S.K., Esomeprazole with aspirin versus clopidogrel for prevention of recurrent gastrointestinal ulcer complications, Clinical Gastroenterology and Hepatology. 2006, 4: 860-865.

Tang L.P., Cho C.H., Hui W.M., Huang C., Chu K.M., Xia H.H.X., Lam S.K., Rashid A., Wong B.C.Y. and Chan O.O., An inverse correlation between IL-6 and select gene promoter methylation in patients with gastric cancer, Digestion. 2006, 74: 85-90.

Researcher : Chan PS

List of Research Outputs

Cheung R.T.F., Tipoe G.L., Tam S., Ma E.S.K., Zou L. and Chan P.S., Preclinical evaluation of pharmacokinetics and safety of melatonin in propylene glycol for intravenous administration, Journal of Pineal Research. 2006, 41: 337-343.

Researcher : Chan RHW

List of Research Outputs

Ho H.H., Siu C.W.D., Jim M.H., Miu K.M., Chan R.H.W., Lee S.W.L., Lau C.P. and Tse H.F., Leukocytosis and clinical outcomes in acute inferior myocardial infarction, Int J Cardiol. 2006, 118(2): 278-9.

Siu C.W.D., Tse H.F., Lee K.L.F., Chan R.H.W., Chen W.H., Yung C., Lee S.W.L. and Lau C.P., Cardiac resynchronization therapy optimization by ultrasonic cardiac output monitoring (USCOM) device, Pacing Clin Electrophysiology. 2007, 30: 50-55.

Researcher : Chan TK

List of Research Outputs

Chan V.N.Y., Ng E.H.Y., Yam I.Y.L., Yeung W.S.B., Ho P.C. and Chan T.K., Experience in preimplantation genetic diagnosis for exclusion of homozygous a^o thalassaemia, Prenatal Diagnosis. 2006, 26: 1029-1036.

Researcher : Chan TWM

List of Research Outputs

Chan T.W.M., Chan S., Poon Y., Fok J., Epstein J.A., Mak J. and Epstein R., The influence of income and education on drug purchasing decisions in Hong Kong Chinese cancer patients, Proc Am Soc Clin Oncol. 2007, 43: 713.

Researcher : Chan VNY

Project Title:	Localisation of the disease or disease-susceptibility gene for adolescent idiopathic scoliosis
Investigator(s):	Chan VNY, Chan K, Luk KDK, Cheng CK
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	11/2003

Abstract:

To identify genes along the mouse chromosome 17 (which is in synteny to human chromosome 19p), that are expressed in tissues associated with AIS phenotype, such as muscle, bone, cartilage, tendon, etc; to identify by differential gene expression analysis those genes along human chromosome 19p13, expressed (differently- decreased or increased) in AIS patients compared to human control subjects; to sequence those genes of interest in genomic DNA of the indexed patients in the relevant AIS families, in order to identify the causative mutations.

Project Title:	Epigenetic and genetic regulation of the AMIGO3 gene in carcinoma of the breast
Investigator(s):	Chan VNY, Chow LWC
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2006

Abstract:

We have identified in breast tumours several aberrantly methylated DNA fragments, one of which corresponds to the 5' flanking region of the amphoterin-induced gene and ORF3 (AMIGO3). It is a member of a novel family of transmembrane proteins containing six leucine rich repeats and one immunoglobulin-like domain [1]. We observed that AMIGO3 5' flanking region is frequently methylated in primary breast cancers (40.4%) and in 4 breast cancer cell lines. Furthermore, AMIGO3 5' flanking region methylation is associated with over-expression of mRNA and correlated positively with lymph node metastasis (p=0.037). The mechanism for this unexpected epigenetic or genetic effects required further elucidation. Recently another member of this family, AMIGO2 has been found to be associated with human gastric adenocarcinoma, with effects on ploidy, chromosomal stability, cell adhesion/migration and tumorigenicity [2]. A homophilic and heterophilic binding mechanism exists between the members of the AMIGO family. AMIGO expression can be induced by ligation of the Ig superfamily protein RAGE by amphoterin[1]. Since RAGE is known to play a role in tissue injury and in regulation of cell motility [3,4], it is possible that AMIGO3 plays a significant role in cancer cell metastasis. We hope to study the epigenetic and genetic regulation of AMIGO3 and explore its usefulness as a possible molecular marker in breast cancer. References:- [1] Kuja-Panula J, Kiiltomaki M, Yamashiro T, Rouhiainen A, Rauvala H. AMIGO, a transmembrane protein implicated in axon tract development, defines a novel protein family with leucine-rich repeats. J Cell Biol 2003; 160:963-973. [2] Rabenau KE, O'Toole JM, Bassi R, Kotanides H, Witte L, Ludwig DL, Pereira DS. DEGA/AMIGO-2, a leucine-rich repeat family member, differentially expressed in human gastric adenocarcinoma: effects on ploidy, chromosomal stability, cell adhesion/migration and tumorigenicity. Oncogene 2004; 23:5056-5067. [3] Rauvala H, Huttunen HJ, Fages C, Kaksonen M, Kinnunen T, Imai S, Raulo E, Kilpelainen I. Heparin-binding proteins HB-GAM (pleiotrophin) and amphoterin in the regulation of cell motility. Matrix Biol 2000; 19:377-387. [4] Schmidt AM, Yan SD, Yan SF, Stern DM. The biology of the receptor for advanced glycation end products and its ligands. Biochim Biophys Acta 2000;1498:99-111.

Project Title:	Hepatitis B virus array for genotyping and mutation detection
Investigator(s):	Chan VNY, Lai CL, Chan K, Yuen RMF
Department:	Medicine
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	11/2006

Abstract:

To design a comprehensive hepatitis B virus array for the simultaneous analysis of 8 HBV genotypes, 5 precore, 4 core promoter, 23 S gene and 44 polymerase gene mutations. A total of 88 variants will be assessed; to assess the sensitivity of the system; to monitor 50 patients on anti-viral therapy over a period of 18 months to detect any development of drug resistance by detection of viral mutants in their serum sample

Project Title:	A simplified, non-fluorescent based microarray system for Thalassaemia screening and mutation detection
Investigator(s):	Chan VNY, Chan K
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	12/2006

Abstract:

The proposal is to devise another means of signal detection, without using fluorescein label in the AS-APEX reaction on the thalassaemia array, obviating the need for a laser scanner. Hence, this will allow the thalassaemia array screening and mutation detection procedure to be implemented in many more laboratories.This will be a very affordable and rapid method for thal screening and mutation detection that is much needed in many countries in Southeast Asia.

List of Research Outputs

Carnley B.P., Prior J.F., Gilbert A., Lim E., Devenish R., Sing H., Sarin E., Guhadasan R., Sullivan S.G., Wise C.A., Bittles A.H., Chan K., Wong M.S., Chan V.N.Y. and Erber W.N., The prevalence and molecular basis of hemoglobinopathies in Cambodia., Hemoglobin. Taylor and Francis, 2006, 4: 463-470.

Chan V.N.Y., Deputy Chairman, Tenders Board, The University of Hong Kong. 2006.

Chan V.N.Y., Ng E.H.Y., Yam I.Y.L., Yeung W.S.B., Ho P.C. and Chan T.K., Experience in preimplantation genetic diagnosis for exclusion of homozygous a^o thalassaemia, Prenatal Diagnosis. 2006, 26: 1029-1036.

Chan V.N.Y., Genomic Variations in Disease by Allele-Specific Arrayed Primer Extension (AS-APEX) Microarray Detection System, Invited Speaker at the 8^th International Meeting on Human Genome Variation and Complex Genome Analysis (HGV2006), September . 2006.

Chan V.N.Y., Invited Faculty Member, Thalassaemia Workshop, Phnom Penh, Cambodia. 2006.

Chan V.N.Y., Member, Central Committee on Clinical Genetics, Hospital Authority, Hong Kong. 2007.

Chan V.N.Y., Preimplantation Genetic Diagnosis Of Thalassemias, Invited Speaker at the 20^th Anniversary Symposium Reproductive Medicine: Where We are Heading. Hong Kong, November. 2006.

Chan V.N.Y., Preimplantation Genetic Diagnosis of Thalassaemias, Invited Speaker at the Annual Scientific Meeting of the Hong Kong Society of Haematology, April . 2007.

Chan V.N.Y., Reviewer, Genetic Testing. 2007.

Cheung C.L., Huang Q., Ng M.Y.M., Chan V.N.Y., Sham P.C. and Kung A.W.C., Confirmation of linkage to chromosome 1q for spine bone mineral density in Southern Chinese, 11th Research Postgraduate Symposium, HKU, 7 Dec 2006.

Cheung C.L., Huang Q., Ng M.Y.M., Chan V.N.Y., Sham P.C. and Kung A.W.C., Confirmation of linkage to chromosome 1q for spine bone mineral density in southern Chinese, Human Genetics. 2006, 120: 354-359.

Cheung C.L., Huang Q., Ng M.Y.M., Chan V.N.Y., Sham P.C. and Kung A.W.C., Confirmation of linkage to chromosome 1q for spine bone mineral density in southern Chinese, Journal of Bone and Mineral Research. 2006, 21(Suppl 1): S146.

Cheung C.L., Sham P.C., Chan V.N.Y. and Kung A.W.C., Peak-wide association study on chromosome 3p21 identifies the CACNA2D2 gene as a novel susceptibility gene for osteoporosis, 8th International Meeting on Human Genome Variation and Complex Genome Analysis, 14-16 Sep 2006, Hong Kong. 2006.

Huang Q., Cheung C.L., Chan V.N.Y., Sham P.C. and Kung A.W.C., Identification of Two Sex-specific Quantitative Trait Loci in Chromosome 11q for Hip Bone Mineral Density in Chinese , 56th Annual Meeting of The American Society of Human Genetics . 2006.

Huang Q., Ng M.Y.M., Cheung C.L., Chan V.N.Y., Sham P.C. and Kung A.W.C., Identification of two sex-specific quantitative trait loci in chromosome 11q for bone mineral density in southern Chinese, Human Heredity. 2006, 61: 237-243.

Huang Q., Cheung C.L., Chan V.N.Y., Sham P.C. and Kung A.W.C., Peak-wide association study on chromosome 3p21 identifies the CACNA2D2 gene as a novel susceptibility gene for osteoporosis , 8th International Meeting on Human Genome Variation and Complex Genome Analysis (HGV2006). 2006.

Lau H.L., Ng M.Y.M., Cheung W.M.W., Paterson A.D., Luk K.D.K., Chan V.N.Y. and Kung A.W.C., Assessment of linkage and association of 13 genetic loci with bone mineral density, J Bone Miner Metab. 2006, 24: 226-34.

Leung K.Y., Liao C., Li Q.M., Tang M.H.Y., Lee C.P., Lam Y.H. and Chan V.N.Y., A Non-invasive Approach To Prenatal Diagnosis Of Homozygous a^o Thalassemia, XVIII FIGO World Congress of Gnecology and Obstetrics in Kuala Lupmur, Malaysia, 5-10th November 2006.

Leung K.Y., Liao C., Li Q.M., Ma S.Y., Tang M.H.Y., Lee C.P., Chan V.N.Y. and Lam Y.H., A new strategy for prenatal diagnosis of homozygous a⁰-thalassemia, Ultrasound Obstetrics and Gynecology. 2006, 28: 173-177.

Ng M.Y.M., Sham P.C., Paterson A.D., Chan V.N.Y. and Kung A.W.C., Effect of environmental factors and gender on the heritability of bone mineral density and bone size, Ann Hum Genet. 2006, 70: 428-38.

Researcher : Chan WK

List of Research Outputs

Jin O., Kavikondala S., Chan W.K., Rong F., Yeung J.S.L., Mok T.M.Y. and Lau W.C.S., Abnormal Plasmacytoid Dendritic Cell Activity in Systemic Lupus Erythematosus, The American College of Rheumatology Annual Scientific Meeting 10-15 Nov 2006, Washington, DC USA 2006. 54(9) Supplement: Abstract No.1095.

Jin O., Kavikondala S., Chan W.K., Rong F., Yeung J.S.L., Mok T.M.Y. and Lau W.C.S., Functional Abnormalities of Myeloid Dendritic Cells in Systemic Lupus Erythematosus, The American College of Rheumatology Annual Scientific Meeting 10-15 Nov 2006, Washington, DC USA. 2006, 54(9) Supplement: Abstract No.1096.

Kavikondala S., Jin O., Chan W.K., Yeung J.S.L., Rong F., Mok T.M.Y. and Lau W.C.S., Dendritic Cells (DCs): Culprits of B-cell Hyper-responsiveness in Lupus, The American College of Rheumatology Annual Scientific Meeting 10-15 Nov 2006, Washington, DC USA. 2006, 54(9) Supplement: Abstract No. 1075.

Rong F., Jin O., Kavikondala S., Chan W.K., Yeung J.S.L., Mok T.M.Y. and Lau W.C.S., Plasmacytoid-Dendritic Cell Induced T Cell Proliferation and Activation: A Potential Role in the Pathogenesis of Rheumatoid Arthritis, The American College of Rheumatology Annual Scientific Meeting 10-15 Nov 2006, Washington, DC USA. 2006, 54(9) Supplement: Abstract No.424.

Researcher : Chan WL

List of Research Outputs

Cheung W.M.W., Chan W.L., Dai Z. and Kung A.W.C., Rosiglitazone Enhances Osteoblastic Differentiation of Murine Preosteoblast Cells, The 28th Annual Meeting American Society for Bone and Mineral Research, Philadelphia, PA, U.S.A. Poster # SA484. 2006.

Researcher : Chan WM

List of Research Outputs

Ip M.S.M., Lam W.K., Lai A.Y.K., Ko F., Lau A., Ling S.O., Chan J. and Chan W.M., Reference values of diffusing capacity of non-smoking Chinese in Hong Kong, Respirology. 2007, 12: 599-606.

Mak J.C.W., Ko F.W., Chu C.M., Leung C.M., Chan H.W., Cheung A.H.K., Ip M.S.M. and Chan W.M., Polymorphisms in the IL-4, IL-4 receptor alpha chain, TNF-alpha, and lymphotoxin-alpha genes and risk of asthma in Hong Kong Chinese adults, Int Arch Allergy Immunol. 2007, 144: 114-122.

Mak J.C.W., Ho S.P., Leung C.M., Cheung A.H.K., Law K.W., So L.K.Y., Chan W.M., Chau C.H., Lam W.K., Ip M.S.M. and Chan W.M., Relationship between glutathione S-transferase gene polymorphisms and enzyme activity in Hong Kong Chinese asthmatics, Clinical and experimental allergy. 2007, 37: 1150-1157.

Researcher : Chan WM

List of Research Outputs

Ip M.S.M., Lam W.K., Lai A.Y.K., Ko F., Lau A., Ling S.O., Chan J. and Chan W.M., Reference values of diffusing capacity of non-smoking Chinese in Hong Kong, Respirology. 2007, 12: 599-606.

Researcher : Chan YH

List of Research Outputs

Lau G.K.K., Chan Y.H., Yiu K.H., Li S.W., Tam S., Lau C.P., Kwong Y.L. and Tse H.F., Burden of carotid atherosclerosis in patients with stroke: relationships with circulating endothelial progenitor cells and hypertension, Journal of human hypertension. 2007, 21(6): 445-451.

Researcher : Chan YY

List of Research Outputs

Cheung M.S., Shek W.K., Shek W.K., Leung J.C.K., Chan Y.Y., Huang H., Kwong Y.L., Liang R.H.S. and Leung A.Y.H., Aldehyde dehydrogenase activity in leukemic blasts defines a subgroup of acute myeloid leukemia with adverse prognosis and superior NOD/SCID engrafting potential, Leukaemia. 2007, 21: 1423-1430.

Ma C.H., Lin R.H., Chan P.K., Leung J.C.K., Chan Y.Y., Meng A., Verfaillie C.M. and Liang R.H.S., The role of survivin in angiogenesis during zebrafish embryonic development., BMC Developmental Biology. 2007, 7: 50.

Researcher : Chang PCM

List of Research Outputs

Chan A.O.O., Ng F.H., Chang P.C.M., Wong S.Y., Chu W.M., Yuen W.C., Lau Y.K., Cheung T.K. and Wong B.C.Y., Prevalence and prediction of gastrointestinal events in patients receiving a combination of aspirin plus clopidogrel. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A135.

Researcher : Chao DVK

List of Research Outputs

Hong T.C., Lam T.P. and Chao D.V.K., Family Physicians’ Role in Cancer Care, 13th Hong Kong International Cancer Congress . 2006.

Researcher : Chau CM

List of Research Outputs

Chau C.M., Conference grant, CRCG. 2006.

Chau C.M., Cheung R.T.F. and Li L.S.W., Importance of both positive and negative BOLD signal changes in acute stroke patients upon motor recovery, 11th Research Postgraduate Symposium. 2006, 125.

Chau C.M., Importance of both positive and negative BOLD signal changes in acute stroke patients upon motor recovery, 11th Research postgraduate symposium, Faculty of Medicine, University of Hong Kong. 2006.

Chau C.M., Relevance of negative BOLD signal changes in stroke patients upon motor recovery, Neuroscience 2006.

Chau C.M., Cheung R.T.F. and Li L.S.W., Relevance of negative BOLD signal changes in stroke patients upon motor recovery, Society for Neuroscience Annual Meeting. 2006.

Researcher : Chen B

List of Research Outputs

Hoo R.L.C., Lam C.W., Xu A., Chen B. and Lam K.S.L., ENDOPLASMIC RETICULUM STRESS DOWN-REGULATES THE ADIPOCYTE PRODUCTION OF THE ANTI-DIABETIC AND ANTI-ATHEROGENIC HORMONE ADIPONECTIN, XIV International Symposium on Atherosclerosis,Italy 2006. 2007.

Researcher : Chen H

List of Research Outputs

Zhang X., Chen H., Tsang V.Y.C., Tang M.O., Lau C.P. and Tse H.F., Prevalence And Clinical Predictors For New-onset Heart Failure After Permanent Right Ventricular Apical Pacing In Patients With Aquired High-grade Atrioventricular Block, World Congress of Cardiology 2006, Barcelona. 2006.

Researcher : Chen TM

List of Research Outputs

Ho S., Yang W., Lau W.C.S., Chen T.M., Wong W.S. and Lau Y.L., Polymorphisms of Tumour Suppressor P53 Gene with Systemic Lupus Erythematosus in Hong Kong Chinese Patients, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006. 79.

Researcher : Chen WH

Project Title:	Enoxaparin combined with epitfibatide or abciximab versus unfractionated heparin combined with epitfibatide or abciximab in percutaneous coronary intervention: obersvations on efficacy, safety, anticoagulation profile, and level of platelet inhibition
Investigator(s):	Chen WH, Lau CP
Department:	Medicine
Source(s) of Funding:	Other Funding Scheme
Start Date:	06/2001

Abstract:

To compare the safety, efficacy, anticoagulation profile and level of platelet inhibition in patients undergoing percutaneous coronary intervention using enoxaparin/eptifibatide, unfractionated heparin/epitfibatide, enoxaparin/abciximab, and unfractionated heparin/abciximab.

Project Title:	A prospective study to investigate the determinants of the quantity of embolized debris during native vessel percutaneous coronary intervention
Investigator(s):	Chen WH, Lau CP
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2002

Abstract:

To identity the clinical and lesion characteristics that determine the quantity of embolized debris captured by a distal protection device during native vessel PCI.

Project Title:	A prospective study to evaluate the relation between aspirin resistance and the incidence and magnitude of myonecrosis after percutaneous coronary intervention
Investigator(s):	Chen WH, Lau CP
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003

Abstract:

To compare the incidence and magnitude of myoecrosis between aspirin-sensitive and -resistant patients undergoing PCI.

List of Research Outputs

Siu C.W.D., Tse H.F., Lee K.L.F., Chan R.H.W., Chen W.H., Yung C., Lee S.W.L. and Lau C.P., Cardiac resynchronization therapy optimization by ultrasonic cardiac output monitoring (USCOM) device, Pacing Clin Electrophysiology. 2007, 30: 50-55.

Tse H.F., Thambar S., Kwong Y.L., Rowlings P., Bellamy G., McCrohon J., Bastian B., Chen W.H., Chan J.K.F., Lo G., Ho C.L. and Lau C.P., Safety of Catheter-Based Intramyocardial Autologous Bone Marrow Cells Implantation fro Therapeutic Angiogenesis, AM J CARDIOL. 2006, 98(1): 60-62.

Researcher : Chen X

List of Research Outputs

Zhang H., Jin Y., Chen X., Jin C., Law S.Y.K., Tsao G.S.W. and Kwong Y.L., Papillomavirus type 16 E6/E7 and human telomerase reverse transcriptase in esophageal cell immortalization and early transformation, Cancer Letters. 2007, 245(1-2): 184-194.

Researcher : Cheng C

Project Title:	Cultural differences in adaptation to the changing environment: A cultural-moderational model of coping flexibility
Investigator(s):	Cheng C
Department:	Psychology
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2005

Abstract:

To expand the scope of the current conceptualization of coping flexibility from an intra-personal to an interpersonal perspective; to formulate a new conceptual model to explicate cultural differences in coping flexibility and why such cultural differences exist; to develop and validate the various constructs of the proposed model; to adopt a multimethod approach for testing the assumptions and hypotheses of the new model with sophisticated methods.

Project Title:	The Role of Dialectical Thinking in Flexible Coping
Investigator(s):	Cheng C
Department:	Psychology
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	10/2006

Abstract:

Purpose of Proposed Project The proposed project will seek to explore the cognitive underpinning underlying flexible coping processes. Dialectical thinking style is proposed to be a cognitive mechanism underlying coping flexibility. Dialectical thinking is a cognitive style characterized by a set of principles related to dialectic perspectives on change, contradiction, and meaning of events (see e.g., Basseches, 1984; Peng, Spencer-Rodgers, & Nian, 2006). Two studies will be conducted to address this unexplored issue. The major aim of Study 1 will examine the hypothesized link between dialectical thinking and coping flexibility in a cross-sectional design. Study 2 will seek to clarify the direction of this link in an experimental setting. Key Issues and Problems Being Addressed Most previous studies examined the personality characteristics and psychological consequences related to coping flexibility, but not much effort has been made in exploring the cognitive underpinnings of coping flexibility. The mechanisms underlying flexible coping processes thus remained unknown. Exploring the thinking style that influences coping flexibility may help to distinguish flexible copers from inflexible ones, thus enhancing the explanatory and predictive power of findings. In addition, most existing studies have adopted only questionnaires in a cross-sectional design, thus leaving the direction of relationships among the variables unknown. The experimental approach can fill this gap by manipulating the cognitive variables and examining possible changes in behaviors in response to these manipulations. The cognitive variables that constitute such behavioral changes can be clarified in a laboratory setting. References Basseches, M. (1984). Dialectical thinking and adult development. Norwood, NJ: Ablex. Peng, K., Spencer-Rodgers, J., & Nian, Z. (2006). Naive dialecticism and the Tao of Chinese thought. In U. Kim, K. S. Yang & K. K. Hwang (Eds.), Indigenous and cultural psychology: Understanding people in context (pp. 247-262). New York: Springer Science & Business Media.

Researcher : Cheng CH

List of Research Outputs

Cheung B.M.Y., Wat N.M.S., Man Y.B., Tam S., Thomas G.N., Leung G.M., Cheng C.H., Woo J., Janus E.D., Lau C.P., Lam T.H. and Lam K.S.L., Development of diabetes in Chinese with the metabolic syndrome, Diabetes care. 2007, 30: 1430-1436.

Cheung B.M.Y., Wat N.M.S., Man Y.B., Tam S., Cheng C.H., Leung G.M., Woo J., Janus E.D., Lau C.P., Lam T.H. and Lam K.S.L., Predictors of the development of hypertension in the Hong Kong cardiovascular risk factor prevalence study-2 (CRISPS2), The 21st Scientific Meeting of the International Society of Hypertension. 2006.

Cheung B.M.Y., Wat N.M.S., Man Y.U. .B.U.N., Tam S., Cheng C.H., Leung G.M., Woo J.E.A.N., Janus E.D.W.A.R.D. .D., Lau C.P., Lam T.H. and Lam K.S.L., Waist Circumference as a Predictor of Cardiovascular Risk in the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS2), The 21st Scientific Meeting of the International Society of Hypertension. 2006.

Researcher : Cheng CTK

List of Research Outputs

Fung J.Y.Y., Lai C.L., Wong D.K.H., Cheng C.T.K., But D.Y. and Yuen R.M.F., Large Population Study in Liver Stiffness Measurement: Prevalence of Significant Fibrosis and Correlation with Liver Biochemistry in Chronic Hepatitis B, Annual Meeting for European Association for the Study of the Liver (EASL 2007). 2007.

Researcher : Cheng KY

List of Research Outputs

Cheng K.Y., Lam K.S.L., Wang Y. and Xu A., Adiponectin as a key player of inflammation, In: Fantuzzi G, Biomedical Reviews. 2006, 17: 11-22.

Cheng K.Y., Lam K.S.L., Wang Y., Yu H., Carling D., Wu D., Wong C.W. and Xu A., Adiponectin-induced eNOS activation and Nitric Oxide Production are Mediated by APPL1 in Endothelial Cells, Diabetes. 2007, 56: 1387-94.

Rong R., Tao Y., Cheung B.M.Y., Xu A., Cheng K.Y. and Lam K.S.L., Identification and functional characterization of three novel human melanocortin-4 receptor gene variants in an obese Chinese population. , Clinical Endocrinology. 2006, 65: 198-205.

Tso A.W.K., Sham P.C., Wat N.M.S., Xu A., Cheung B.M.Y., Rong R., Fong H.Y., Xu J., Cheng K.Y., Janus E.D. and Lam K.S.L., Polymorphisms of the gene encoding adiponectin and glycaemic outcome of Chinese subjects with impaired glucose tolerance: a 5-year follow-up study, Diabetologia. 2006, 49: 1806-15.

Xu J., Sham P.C., Xu A., Tso A.W.K., Wat N.M.S., Cheng K.Y., Fong H.Y., Janus E.D. and Lam K.S.L., Resistin gene polymorphisms and progression of glycaemia in southern Chinese: a 5-year prospective study, Clin Endocrinol (Oxf). 2007, 66: 211-7.

Researcher : Cheng KY

List of Research Outputs

Cheng K.Y., Lam K.S.L., Wang Y. and Xu A., Adiponectin as a key player of inflammation, In: Fantuzzi G, Biomedical Reviews. 2006, 17: 11-22.

Researcher : Cheng SW

List of Research Outputs

Yip T., Tse K.C., Lam M.F., Cheng S.W., Lui S.L., Tang S.C.W., Li F.K., Wang A.Y.M., Choy C.B.Y., Ng M.M.T., Chan D.T.M., Lai K.N. and Lo W.K., Risk and outcome of peritonitis after flexible colonoscopy in CAPD patient, Peritoneal Dialysis International . 2006, Suppl 26: S68.

Researcher : Cheung AHK

List of Research Outputs

Chan M.M.W., Ho A.S.S., Cheung A.H.K., Liu R., Yee W.K.S., Sin K.M., Wong M.L., Lam C.W., Chan K.S. and Lam W.K., Determinants of chronic obstructive pulmonary disease (COPD) in Chinese patients in Hong Kong. , International Journal of Tuberculosis and Lung Disease. 2007, 11: 502-7.

Chan M.M.W., Mak J.C.W., Ho S.P., Cheung A.H.K., Wong P.C., Chan K.K. and Ip M.S.M., Glutathione S-transferase (GST) polymorphisms and GST activity in Hong Kong Chinese COPD patients., International Journal of Tuberculosis and Lung Disease. 2007, 11: 508-14.

Chan M.M.W., Cheung A.H.K., Dai D.L., Chan F.H., Kam K.M., Tam C.M. and Leung C.C., Prevalence and determinants of positive tuberculin reactions of residents in old age homes in Hong Kong. , International Journal of Tuberculosis and Lung Disease. 2006, 10(8): 892-8.

Chan M.M.W., Chan F.H., Cheung A.H.K., Dai D.L. and Chu L.W., Prevalence of tuberculous infection and active tuberculosis in old age homes in Hong Kong. , J Am Geriatr Soc. 2006, 54(9): 1334-40.

Mak J.C.W., Ko F.W., Chu C.M., Leung C.M., Chan H.W., Cheung A.H.K., Ip M.S.M. and Chan W.M., Polymorphisms in the IL-4, IL-4 receptor alpha chain, TNF-alpha, and lymphotoxin-alpha genes and risk of asthma in Hong Kong Chinese adults, Int Arch Allergy Immunol. 2007, 144: 114-122.

Mak J.C.W., Ho S.P., Leung C.M., Cheung A.H.K., Law K.W., Ip M.S.M. and Chan M.M.W., Relationship between glutathione S-transferase gene polymorphisms and enzyme activity in Hong Kong Chinese asthmatics, American Thoracic Society International Conference, San Francisco, USA. American Journal of Respiratory and Critical Care Medicine. 2007, 175: A461.

Mak J.C.W., Ho S.P., Leung C.M., Cheung A.H.K., Law K.W., So L.K.Y., Chan W.M., Chau C.H., Lam W.K., Ip M.S.M. and Chan W.M., Relationship between glutathione S-transferase gene polymorphisms and enzyme activity in Hong Kong Chinese asthmatics, Clinical and experimental allergy. 2007, 37: 1150-1157.

Researcher : Cheung BMY

Project Title:	Detection of human body temperature with infrared thermographic imaging: accuracy and feasibility in detection of fever in human subjects
Investigator(s):	Cheung BMY, Chan LS, Kumana CR
Department:	Medicine
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	09/2005

Abstract:

The study will provide crucially needed information for the refinement and optimization of the application of the infrared thermography (IRT) technique as a fever screening mechanism.

Project Title:	Identifying a new gene for hypertension on chromosome 17
Investigator(s):	Cheung BMY, Wong LYF
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	10/2006

Abstract:

ObjectivesTo identify a new gene for hypertension in the 17p12 region on chromosome 17BackgroundPrimary or essential hypertension results from the interaction between genetic predisposition and environmental factors. The leading environmental factor is obesity [1]. We have found this both in cross-sectional studies and in the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort [2]. In the last decade, many promising candidate genes for hypertension have been examined. We believe that a gene that causes hypertension is likely to be associated with obesity and other components of the metabolic syndrome.A genome scan of blood pressure-regulating genes done in Chinese sib pairs undertaken in Anhui in collaboration with Harvard University showed that the microsatellite marker D17S1303, which consists of GATA repeats, had a high LOD score [3]. This marker lies close to a quantitative trait locus for abdominal obesity-metabolic syndrome (AOMS2) at 17p12 on chromosome 17 [4]. We confirmed that D17S1303 was associated with hypertension in Hong Kong Chinese [5]. The number of GATA repeats correlated inversely with diastolic blood pressure and BMI. Nine GATA repeats were associated with hypertension whilst 14 GATA repeats were associated with normotension. Next, we studied SNPs around D17S1303 and their association with hypertension (CRCG small project grant 2004 (completed); Title: A gene locus for hypertension and obesity on chromosome 17) [6]. Candidate SNPs within 3kb of D17S1303 were selected from an SNP database (Fig. 1). High-throughput genotyping of the SNPs was performed using the Sequenom MassARRAY system (Sequenom, San Diego CA). There were significant differences in genotype frequencies between hypertensive and normotensive subjects for rs1525402 (p=0.048), rs2692343 (p=0.022), rs2692344 (p=0.017) and rs2321313 (p=0.028). In contrast, the genotype frequencies of rs852320, rs852321 and rs852322, all located telomeric to rs1525402 and D17S1303, did not differ between hypertensive and normotensive subjects. A 4-locus haplotype comprising G at rs1525402, C at rs2692343, C at rs2692344 and G at rs2321313 was associated with lower systolic blood pressure (p=0.023) and normotension (p=0.048). Interestingly, none of the SNPs or haplotypes were related to indices of obesity after controlling for blood pressure. Our results further confirm that there is a gene, as yet unidentified, influencing blood pressure in the vicinity of D17S1303 in a quantitative trait locus for abdominal obesity-metabolic syndrome at 17p12. The consistent findings in different populations using diverse genetic approaches collectively suggest a high probability of a disease susceptibility gene in the locus. Fine mapping of this part of chromosome 17 is therefore needed in order to identify the gene linked to hypertension. Once the gene has been identified, we will proceed to the study of the function and dysfunction of the gene. Although chromosome 17 has been studied in genome scans [7], the region around D17S1303 has not been intensively studied. We are therefore in a unique position to identify a new susceptibility gene for hypertension in Chinese. References1. Cheung et al. Hypertension and diet. In: Caballero B, Trugo LC, Finglas PM, ed. Encyclopaedia of Food Sciences and Nutrition, pp 3194-3199. London: Academic Press, 2003. 2. Cheung et al. The Hong Kong Cardiovascular Risk Factor Prevalence Survey cohort - results at 7 years. J Hypertens 2004; 22 (suppl 2): S268-269. 3. Xu et al. An extreme-sib-pair genome scan for genes regulating blood pressure. Am J Hum Genet 1999; 64: 1694-1701.4. Kissebah et al. Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. Proc Nat Acad Sci 2000; 97: 14478-14483.5. Cheung et al. Association of essential hypertension with a microsatellite marker on chromosome 17. J Human Hypertens 2005; 19(5): 407-11.6. Cheung et al. Association of hypertension with single nucleotide polymorphisms in the quantitative trait locus for abdominal obesity-metabolic syndrome on chromosome 17. J Hum Hypertens 2006; 20: 419-425. 7. Knight et al. Human chromosome 17 in essential hypertension. Ann Hum Genet 2003; 67(Pt 2): 193-206.

List of Research Outputs

Cheung B.M.Y., Leung Y.H., Man Y.U. .B.U.N., Ong K.L., Wong L.Y.F., Lau C.P. and Lam K.S.L., Association of Blood Pressure with Polymorphisms in the Quantitative Trait Locus for Abdominal Obesity-Metabolic Syndrome on Chromosome 17, The 21st Scientific Meeting of the International Society of Hypertension 2006.

Cheung B.M.Y., Comprehensive Lipid Management: Lessons We Learnt from Recent Statin Clinical Trials, Second International Symposium on Healthy Aging. 2007.

Cheung B.M.Y., Wat N.M.S., Man Y.B., Tam S., Thomas G.N., Leung G.M., Cheng C.H., Woo J., Janus E.D., Lau C.P., Lam T.H. and Lam K.S.L., Development of diabetes in Chinese with the metabolic syndrome, Diabetes care. 2007, 30: 1430-1436.

Cheung B.M.Y. and Ong K.L., Junctional adhesion molecule-1 may have a wider role in cardiovascular disease. , Hypertension. 2007, 50: e22.

Cheung B.M.Y., Wat N.M.S., Man Y.B., Tam S., Cheng C.H., Leung G.M., Woo J., Janus E.D., Lau C.P., Lam T.H. and Lam K.S.L., Predictors of the development of hypertension in the Hong Kong cardiovascular risk factor prevalence study-2 (CRISPS2), The 21st Scientific Meeting of the International Society of Hypertension. 2006.

Cheung B.M.Y., Ong K.L., Man Y.B., Lau C.P., Lam K.S.L. and Wong Y.L., Prevalence of the metabolic syndrome in the United States National Health and Nutrition Examination Survey 1999-2002 according to different defining criteria., J Clin Hypertens (Greenwich). 2006, 8(8): 562-70.

Cheung B.M.Y., Ong K.L., Man Y.U. .B.U.N., Wong L.Y.F., Lau C.P. and Lam K.S.L., Prevalence, Awareness, Treatment and Control of Hypertension in the United States 1999-2004, The 21st Scientific Meeting of the International Society of Hypertension. 2006.

Cheung B.M.Y., Prevalence, Awareness, Treatment, and Control of Hypertension in the United States 1999-2004, American Heart Association Scientific Sessions 2006.

Cheung B.M.Y. and Thomas G.N., The metabolic syndrome and vascular disease in Asia, Cardiovascular & Hematological Disorders Drug Targets. 2007, 7(2): 79-85.

Cheung B.M.Y., Wat N.M.S., Man Y.U. .B.U.N., Tam S., Cheng C.H., Leung G.M., Woo J.E.A.N., Janus E.D.W.A.R.D. .D., Lau C.P., Lam T.H. and Lam K.S.L., Waist Circumference as a Predictor of Cardiovascular Risk in the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS2), The 21st Scientific Meeting of the International Society of Hypertension. 2006.

Cheung B.M.Y., Why is the Metabolic Syndrome Important and Relevant to People in Hong Kong, Chengdu - Hong Kong Medical Forum 2007.

Chow W.S., Cheung B.M.Y., Xu A., Wat N.M.S., Fong H.Y., Ong L.H.Y., Tam S., Tan K.C.B., Janus E.D., Lam T.H. and Lam K.S.L., Hypoadiponectinemia as a predictor for the development of hypertension: a 5-year prospective study. , Hypertension. 2007, 49: 1455-61.

Deng H., Thomas G.N., Macfarlane D.J., Chou K.L., Cheung B.M.Y., McGhee S.M. and Lam T.H., Association between cigarette smoking and plasma urate level in elderly Chinese (abstract and poster presentation), 5th Annual Conference of the International Society for the Prevention of Tobacco Induced Disease, 24-26 November 2006, Hong Kong. Hong Kong, Int'l Society for the Prevention of Tobacco Induced Disease, 2006, 48.

Deng H., Thomas G.N., Macfarlane D.J., Chou K.L., Cheung B.M.Y., Chi I., McGhee S.M. and Lam T.H., Validity of the international physical activity questionnaire short form (abstract), Journal of the Hong Kong College of Cardiology. 2006, 14: 78.

Lam C.L. and Cheung B.M.Y., Update on levofloxacin (cravit): focus on respiratory infectious, Medical Progress. 2007, 1: 31-36.

Li Y., Chu L.W., Cheung B.M.Y., Leung Y.H., Yik P.Y., Jin D. and Song Y., Association of ABCA1 Gene with Sporadic Alzheimer's Disease in Chinese Group and Potential Functional Importance for Novel Intronic Polymorphism., 11th Research Postgraduate Symposium, 7 Dec. 2006. The University of Hong Kong, Li Ka Shing Faculty of Medicine. 2006.

Li Y., Chu L.W., Chen Y., Cheung B.M.Y., Leung R.Y., Yik P.Y., Ng K.M.T., Mak W., Jin D., St. George-Hyslop P. and Song Y., Intron 2 (T/C) CYP46 polymorphism is associated with Alzheimer's disease in Chinese patients., Dement Geriatr Cogn Disord 2006. 2006, 22(5-6): 399-404.

Mak A., Cheung B.M.Y., Mok C.C., Leung R. and Lau W.C.S., Adrenomedullin - A Potential Disease Activity Marker and Suppressor of Nephritis Activity in Systemic Lupus Erythematosus, Rheumatology (Oxford, England). England, Oxford University Press, 2006, 45(10): 1266-1272.

Ong K.L., Cheung B.M.Y., Man Y.B., Wong L.Y.F., Lau C.P. and Lam K.S.L., Prevalence, awareness, treatment and control of hypertension among United States adults 1999-2004. , Hypertension. 2007, 49: 69-75.

Ong K.L. and Cheung B.M.Y., Response to non-pharmacologic treatment of hypertension: Impact on prevalence estimates., Hypertension. 2007, 50: e2.

Ong K.L., Cheung B.M.Y., Man Y.B., Wong Y.F., Wat N.M.S., Tan K.C.B. and Lam K.S.L., Treatment and control of diabetes mellitus in the United States National Healthy and Nutrition Examination Survey 1999-2002, Journal of Cardiometabolic Syndrome. 2006, 1: 301-7.

Rong R., Tao Y., Cheung B.M.Y., Xu A., Cheng K.Y. and Lam K.S.L., Identification and functional characterization of three novel human melanocortin-4 receptor gene variants in an obese Chinese population. , Clinical Endocrinology. 2006, 65: 198-205.

Thomas G.N., Schooling C.M., McGhee S.M., Ho D.S.Y., Cheung B.M.Y., Wat N.M.S., Janus E.D. and Lam T.H., Identification of factors differentially associated with isolated impaired fasting glucose and isolated post-load impaired glucose tolerance: The Hong Kong cardiovascular risk factor study, European Journal of Endocrinology. 2006, 155: 623-32.

Thomas G.N., Schooling C.M., McGhee S.M., Ho D.S.Y., Cheung B.M.Y., Wat N.M.S., Janus E.D., Lam K.S.L. and Lam T.H., Metabolic syndrome increases all-cause and vascular mortality: The Hong Kong cardiovascular risk factor study, Clinical Endocrinology. 2007, 66: 666-71.

Thomas G.N., Cheung B.M.Y., Ho D.S.Y., Macfarlane D.J., Deng H., McGhee S.M., Woo J., Lam T.H. and Tomlinson B., Overview of dietary influences on atherosclerotic vascular disease: Epidemiology and prevention, Cardiovascular & Hematological Disorders Drug Targets. 2007, 7: 87-97.

Tso A.W.K., Sham P.C., Wat N.M.S., Xu A., Cheung B.M.Y., Rong R., Fong H.Y., Xu J., Cheng K.Y., Janus E.D. and Lam K.S.L., Polymorphisms of the gene encoding adiponectin and glycaemic outcome of Chinese subjects with impaired glucose tolerance: a 5-year follow-up study, Diabetologia. 2006, 49: 1806-15.

Xu A., Tso A.W., Cheung B.M.Y., Wang Y., Wat N.M.S., Fong H.Y., Yeung C.Y., Janus E.D., Sham P.C. and Lam K.S.L., Circulating adipocyte-fatty acid binding protein levels predict the development of the metabolic syndrome: a 5-year prospective study, Circulation. 2007, 115: 1537-43.

Xu A., Tso A.W.K., Cheung B.M.Y., Wang Y., Wat N.M.S., Fong H.Y., Yeung C.Y., Janus E.D., Sham P.C. and Lam K.S.L., Circulating levels of adipocyte-fatty acid binding protein correlate with its adipose tissue expression and predict the development of the metabolic syndrome. , The Endocrine Society's 89th Annual Meeting, 2-5 June 2007, Toronto. 2007.

Researcher : Cheung CL

List of Research Outputs

Cheung C.L., Huang Q., Ng M.Y.M., Chan V.N.Y., Sham P.C. and Kung A.W.C., Confirmation of linkage to chromosome 1q for spine bone mineral density in Southern Chinese, 11th Research Postgraduate Symposium, HKU, 7 Dec 2006.

Cheung C.L., Huang Q., Ng M.Y.M., Chan V.N.Y., Sham P.C. and Kung A.W.C., Confirmation of linkage to chromosome 1q for spine bone mineral density in southern Chinese, Human Genetics. 2006, 120: 354-359.

Cheung C.L., Huang Q., Ng M.Y.M., Chan V.N.Y., Sham P.C. and Kung A.W.C., Confirmation of linkage to chromosome 1q for spine bone mineral density in southern Chinese, Journal of Bone and Mineral Research. 2006, 21(Suppl 1): S146.

Cheung C.L., Sham P.C., Chan V.N.Y. and Kung A.W.C., Peak-wide association study on chromosome 3p21 identifies the CACNA2D2 gene as a novel susceptibility gene for osteoporosis, 8th International Meeting on Human Genome Variation and Complex Genome Analysis, 14-16 Sep 2006, Hong Kong. 2006.

Huang Q., Cheung C.L., Chan V.N.Y., Sham P.C. and Kung A.W.C., Identification of Two Sex-specific Quantitative Trait Loci in Chromosome 11q for Hip Bone Mineral Density in Chinese , 56th Annual Meeting of The American Society of Human Genetics . 2006.

Huang Q., Ng M.Y.M., Cheung C.L., Chan V.N.Y., Sham P.C. and Kung A.W.C., Identification of two sex-specific quantitative trait loci in chromosome 11q for bone mineral density in southern Chinese, Human Heredity. 2006, 61: 237-243.

Huang Q., Ng M.Y.M., Cheung C.L., Chan V., Sham P.C. and Kung A.W.C., Identification of two sex-specific quantitative trait loci in chromosome 11q for hip bone mineral density in Chinese, Human Heredity. 2006, 61(4): 237-243.

Huang Q., Cheung C.L., Chan V.N.Y., Sham P.C. and Kung A.W.C., Peak-wide association study on chromosome 3p21 identifies the CACNA2D2 gene as a novel susceptibility gene for osteoporosis , 8th International Meeting on Human Genome Variation and Complex Genome Analysis (HGV2006). 2006.

Ip P.P.C., Lam K.W., Cheung C.L., Yeung C.W., Pun T.C., Chan K.Y.Q. and Cheung A.N.Y., 440 tranexamic acid associated infarction of uterine leiomyomas: a clinicopathologic study of 490 cases, XXVI International Congress of the International Academy of Pathology, Montreal, 16-21 September. 2006.

Researcher : Cheung CL

List of Research Outputs

Researcher : Cheung KF

List of Research Outputs

Luk J.M.C., Zhang Q.S., Lee P.Y., Wo Y.H., Leung P.L., Liu L.X., Hu M.Y., Cheung K.F., Hui C.K., Lau G. and Fan S.T., Hepatic stellate cell-targeted delivery of M6P-HSA-glycyrrhetinic acid attenuates hepatic fibrogenesis in a bile duct ligation rat model, Liver International. 2007, 27(4): 548-557.

Researcher : Cheung MS

List of Research Outputs

Cheung M.S., Shek W.K., Shek W.K., Leung J.C.K., Chan Y.Y., Huang H., Kwong Y.L., Liang R.H.S. and Leung A.Y.H., Aldehyde dehydrogenase activity in leukemic blasts defines a subgroup of acute myeloid leukemia with adverse prognosis and superior NOD/SCID engrafting potential, Leukaemia. 2007, 21: 1423-1430.

Cheung M.S., Tam K.H., Chow C.H., Verfaillie C.M. and Liang R.H.S., All-trans retinoic acid induces proliferation of an irradiated stem cell supporting stromal cell line AFT024., Experimental Hematology. 2007, 35: 56-63.

Cheung M.S., Kwong Y.L., Liang R.H.S. and Leung A.Y.H., Stem cell model of hematopoiesis, C7urrent Stem Cell Research and Therapy. 2006, 1: 305-315.

Researcher : Cheung RTF

Project Title:	Use of functional magnetic resonance imaging to predict benefits of acupuncture for stroke patients with persistent motor or language deficits
Investigator(s):	Cheung RTF, Li LSW, Yang ES, Leung KP, Li G
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	10/2004

Abstract:

To use functional magnetic resonance imaging (MRI) to identify stroke patients with or without activations of brain sites relevant to their persistent arm paralysis or language impairment during stimulation of the deficit-implicated acupoints and then apply randomized, double-blinded, acupoint-controlled clinical trials to confirm the benefits of acupuncture in post-stroke rehabilitation of the deficit. The results will confirm the value of functional MRI in identifying responders to acupuncture in post-stroke motor or language rehabilitation and reveal the benefit of acupuncture treatment over certain disease-implicated acupoints.

Project Title:	Role of ischemia in Alzheimer's disease - an experimental study in transgenic mice
Investigator(s):	Cheung RTF
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004

Abstract:

To study (1) the influence of genotype on the cerebral blood flow and infarct volume of transgenic mice overexpressing amyloid precursor protein (APP) alone or with human mutant presenilin-1 (PS-1) gene following photothrombotic stroke, and to study (2) the effects of photothrombotic stroke on the sensorimotor functions and visuospatial memory in the APP transgenic mice and APP/PS-1 double transgenic mice.

Project Title:	Development of Chinese-language versions of internationally-accepted stroke training materials for healthcare professionals treating Chinese stroke patients
Investigator(s):	Cheung RTF
Department:	Medicine
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	04/2005

Abstract:

To develop Chinese-language versions of internationally-accepted stroke training materials, and to make them available to healthcare professionals treating Chinese stroke patients.

Project Title:	Effects of neuropeptide Y-Y1 and Y2 receptor activation or inhibition on free radical generation and intracellular calcium concentration
Investigator(s):	Cheung RTF
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	12/2005

Abstract:

Purpose (1) To study the effects of neuropeptide Y (NPY) and its Y1 or Y2 agonists and antagonists on generation of nitric oxide (NO) and superoxide anion as well as intracellular calcium ion concentration in in vivo and in vitro stroke models (2) To study the interactions of NPY and its Y1 or Y2 agonists and antagonists with inhibitors of NO synthase or NO donor in in vivo and in vitro stroke models Key Issues There is evidence that NPY mediates ischemic damage via its Y1 receptors during focal cerebral ischemia and that inhibition of the Y1 receptors may confer neuroprotection against ischemic injury. The underlying mechanisms are unknown, and preliminary information suggests that the opposite actions of NPY on neuronal and endothelial NO synthase may be relevant. According to the literature, generation of free radicals, such as NO and superoxide anion, mediates ischemic injury. Elevation of intracellular calicum concentration also lead to ischemic damage via activation of intracellular enzymes, including neuronal NOS. On the other hand, activation of endothelial NOS maintains microcirculation and lessens the ischemic injury. Problems being addressed (1) Ability of NPY Y1 or Y2 agonist/antagonist to attenuate/augment ischemia-stimulated increase in brain levels of NO and superoxide anion (2) Ability of NPY Y1 or Y2 agonist/antagonist to attenuate/augment ischemia-stimulated rise in intracellular calcium ion concentration (3) Interactions between NPY Y1 or Y2 agonist/antagonist and NO donor or NO synthase inhibitor in stroke models

Project Title:	Study of bone marrow-derived stem cell transplantation in rodent stroke models
Investigator(s):	Cheung RTF
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2006

Abstract:

Objectives: (1) To evaluate the functional and histological benefits of peripheral blood progenitor cells (PBPC; bone marrow-derived stem cells) mobilized by granulocyte-colony stimulating factor (G-CSF) in an in vivo mice stroke model. (2) To compare among different route of administration of G-CSF-mobilized PBPC in an in vivo mice stroke model. Key issues: (1) Stem cell transplantation can theoretically restore some of the lost brain functions and reconstruct the damaged neuronal circuitry after stroke. (2) The desirable site of transplantation and source of stem cells await clarification. (3) There is preliminary evidence of neuroprotective potentials of G-CSF. (4) G-CSF can mobilize PBPC, a form of pluripotent stem cells derived from the bone marrow. Problems addressed: (1) Potential benefits of autologous bone marrow-derived stem cells in post-stroke functional and histological recovery. (2) Comparing different route of administration of bone marrow-derived stem cells.

List of Research Outputs

Chan C.F., Leung A.Y.H., Chan Y.S. and Cheung R.T.F., Intracerebral injection of granulocyte-colony stimulating factor reduces infarct volume following transient middle cerebral artery occlusion in mice, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population. 2007, 57.

Chan C.F., Leung A.Y.H., Chan Y.S. and Cheung R.T.F., Use of granulocyte-colony stimulating factor in a mice stroke model, 11th Research Postgraduate Symposium. 2006, 60.

Chan K. .H., Leung S.Y., Cheung R.T.F., Ho S.L. and Mak W., Paraneoplastic motor neuropathy and inflammatory myopathy associated with nasopharyngeal carcinoma., Journal of Neurooncology. 2007, 81: 93-96.

Chan K.H., Tsang K.L., Fong C.Y., Ho S.L., Cheung R.T.F. and Mak W., Idiopathic inflammatory demyelinatng disorders after acute transverse myelitis., European Journal of Neurology. 2006, 13(8): 862-8.

Chan K.H., Mak W., Cheung R.T.F. and Ho S.L., Non-thymoma early-onset- and late-onset-generalized myasthenia gravis-A retrospective hospital-based study, Clinical Neurology Neurosurgery. 2007, 109(8): 686-91.

Chan K.H., Leung S.Y., Cheung R.T.F., Ho S.L. and Mak W., Paraneoplastic motor neuropathy and inflammatory myopathy associated with nasopharyngeal carcinoma, J Neurooncol. 2007, 81(1): 93-6.

Chan K.H., Mak W., Cheung R.T.F. and Ho S.L., Patients With Chronic Inflammatory Demyelinating Polyneuropathy And Diabetes Mellitus In Hong Kong Chinese - A Hospital Based Study, Second International Symposium On Healthy Aging. 2007.

Chan K.H., Mak W., Cheung R.T.F. and Ho S.L., Patients with chronic inflammatory demyelinating polyneuropathy and diabetes mellitus in Hong Kong – A hospital based study, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population. 2007, 53.

Chau C.M., Cheung R.T.F. and Li L.S.W., Importance of both positive and negative BOLD signal changes in acute stroke patients upon motor recovery, 11th Research Postgraduate Symposium. 2006, 125.

Chau C.M., Cheung R.T.F. and Li L.S.W., Relevance of negative BOLD signal changes in stroke patients upon motor recovery, Society for Neuroscience Annual Meeting. 2006.

Cheung R.S.K., Cheung R.T.F., Ho S.L. and Mak W., Mah-jong–induced seizures: case reports and review of twenty-three patients. , Hong Kong Medical Journal. . 2007, 13(4): 314-8.

Cheung R.T.F., Adjudicator, The 11th Research Postgraduate Symposium, Faculty of Medicine. 2006.

Cheung R.T.F., An Old Lady with Dizziness Plus Difficulties in Walking and Balance, Weekly Journal Club Meeting, Department of Medicine. 2006.

Cheung R.T.F., Chairman, 12th Medical Research Conference, University Department of Medicine. 2007.

Cheung R.T.F., Chairman, 2007 World Congress on Ageing and Dementia in Chinese Communities, Hong Kong Alzheimer’s Disease Association / Jockey Club MRI Centre of HKU / Clinical Neuroscience Group of CUHK / School of Nursing of HKPU / Hospital Authority. 2007.

Cheung R.T.F., Chairman, First Quarterly Scientific Meeting, Hong Kong Stroke Society. 2007.

Cheung R.T.F., Chairman, International Symposium on Applied Neuroscience: Recovering from Brain Trauma, Faculty of Social Sciences & MacLehose Medical Rehabilitation Centre. 2007.

Cheung R.T.F., Chairman, Scientific Symposium 2007: Transcatheter PFO Closure – Indications & Techniques, Hong Kong College of Cardiology & Hong Kong Stroke Society. 2007.

Cheung R.T.F., Chairman, Symposium on Complementary & Alternative Medicine, 4th World Congress of the International Society of Physical and Rehabilitation Medicine (ISPRM) 2007, COEX, Soeul, Korea. 2007.

Cheung R.T.F., Comparison of Cerebral Atherosclerosis Between Western and Eastern, Second International Stroke Summit, Nanjing, China. 2006.

Cheung R.T.F., Development of Chinese-language versions of internationally-accepted stroke training materials for healthcare professionals treating Chinese stroke patients, Conference for Clinical Advance in Internal Medicine. 2007, 5-6.

Cheung R.T.F., Diagnosis and Management of Stroke, Public Lecture Series on Stroke and Stroke Prevention, BrainCare Link. 2007.

Cheung R.T.F., Editorial Board, Journal of Pineal Research. Blackwell Publishing, 2007.

Cheung R.T.F., Editorial Board, MIMS Neurology & Psychiatry Guide. Medimedia Asia, 2006.

Cheung R.T.F., Editorial Board, Medical Grapevine. Ezyhealth Publishers, 2007.

Cheung R.T.F., Editorial Board, Open Neuroimaging Letters. Bentham Science Publishers, 2007.

Cheung R.T.F., Editorial Board, Open Neuroimaging Reviews. Bentham Science Publishers, 2007.

Cheung R.T.F., Editorial Board, Open Physiology Letters. Bentham Science Publishers, 2007.

Cheung R.T.F., Editorial Board, Open Physiology Reviews. Bentham Science Publishers, 2007.

Cheung R.T.F., Editorial Board, Reviews on Recent Clinical Trials. Bentham Science Publishers, 2007.

Cheung R.T.F., Editorial Board, Stroke. Lippincott Williams & Wilkins, 2006.

Cheung R.T.F., Editorial Board, Stroke. Lippincott Williams & Wilkins, 2007.

Cheung R.T.F., Editorial Board, The Open Medical Imaging Journal. Bentham Science Publishers, 2007.

Cheung R.T.F., Editorial Board, The Open Neuroimaging Journal. Bentham Science Publishers, 2007.

Cheung R.T.F., Editorial Board, The Open Physiology Journal. Bentham Science Publishers, 2007.

Cheung R.T.F., Facilitator & Moderator, Problem Based Workshop in Pain Management 2007, The Hong Kong Pain Society . 2007.

Cheung R.T.F., Faculty Member, Commissioned Training in Neurosurgery: Cerebral Revascularization, Hospital Authority / Hong Kong Neurosurgical Society / Department of Surgery & Department of Anatomy of HKU. 2007.

Cheung R.T.F., Faculty Member, Second International Stroke Summit, Nanjing, China. 2006.

Cheung R.T.F., International Faculty, The Fourth Asia Pacific Conference Against Stroke 2007, New Delhi, India. 2007.

Cheung R.T.F., Member of Organizing Committee, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population, Research Centre of Heart, Brain, Hormone & Healthy Aging. 2007.

Cheung R.T.F., Moderator, SNU International Stroke Symposium, Seoul National University, Korea. 2006.

Cheung R.T.F., Organization Committee Chairman, Scientific Sub-Committee Chairman, Moderator of Sanofi Lunch Symposium, Moderator of Oral Session, The 9th International Symposium on Thrombolysis and Acute Stroke Therapy and The 2006 Annual Scientific Meeting, The Hong Kong Neurological Society . 2006.

Cheung R.T.F., Organizing Committee Member, Moderator of Stroke Symposium, 4th Congress of the Federation of Asian-Oceanian Neuroscience Societies (FAONS). 2006.

Cheung R.T.F., Pathophysiology of Cerebral Ischaemia, Commissioned Training in Neurosurgery on Cerebral Revascularization, COC Neurosurgery, HAHO. 2007.

Cheung R.T.F., Tipoe G.L., Tam S., Ma E.S.K., Zou L. and Chan P.S., Preclinical evaluation of pharmacokinetics and safety of melatonin in propylene glycol for intravenous administration, Journal of Pineal Research. 2006, 41: 337-343.

Cheung R.T.F., Preventing stroke via less intake of salt and fat, Oriental Daily. 2006, A6.

Cheung R.T.F., Program Committee, Second International Conference on Intracranial Atherosclerosis, San Francisco, USA. 2006.

Cheung R.T.F., Risk Factors and Stroke Prevention, The Hong Kong Stroke Society, Public Lecture for World Stroke Day. 2006.

Cheung R.T.F., Scientific Evaluation of Acupuncture and Herbs in Post-Stroke Rehabilitation, Weekly Neurology Meeting, Department of Neurology, Asan Medical Center, Seoul, Korea. 2007.

Cheung R.T.F., Session Chairman, Workshop Chairman, Second Asian Headache Foundation & Third Northern Neuroscience Center Meeting. 2006.

Cheung R.T.F., Spontaneous intracranial hypotension, 2nd Asian Headache Foundation & 3rd Northern Neuroscience Center Meeting, Chiang Mai, Thailand. 2006.

Cheung R.T.F., Stoke, Migraine and PFO, Scientific Symposium 2007 on Transcatheter PFO Closure: Indications and Techniques, Hong Kong College of Cardiology & Hong Kong Stroke Society. 2007.

Cheung R.T.F., Stroke incidence, risk factors and stroke subtypes including trends changes in HK, SNU International Stroke Symposium, Seoul, South Korea. 2006.

Cheung R.T.F., Stroke, Plenary Lecture, Dinner Symposium, Lions Club of Hong Kong Island. 2007.

Cheung R.T.F., Sudden Death: Cardiac, Cerebral and Interactive Mechanisms, Cerebrovascular Disorders: Opportunities for Transdisciplinary Progress, International Stroke Conference 2007, American Stroke Association. 2007.

Cheung R.T.F., Update on Prevention of Stroke in Patients with Ischaemic Stroke or Transient Ischaemic Attack, Symposium on Hypertension and Vascular Diseases, Department of Internal Medicine, Macau Government Hospital. 2006.

Cheung R.T.F., Update on Stroke Management, Dedicated CME programme for non-fellows, Hong Kong Academy of Medicine. 2006.

Cheung R.T.F., Use of Scientific Methods to Evaluate Acupuncture and Herbs in Post-Stroke Rehabilitation, Keynote session on Complementary and Alternative Medicine, 4th World Congress of the International Society of Physical and Rehabilitation Medicine, June 10 to 14, 2007, Seoul, Korea. 2007.

Cheung R.T.F., Use of scientific methods to evaluate acupuncture and herbs in post-stroke rehabilitation, 4th World Congress of the International Society of Physical and Rehabilitation Medicine (ISPRM). 2007, 140.

Fong C.Y., Kwok H.H., Song Y., Cheng T.S., Ho W.L., Chu A.C.Y., Kung M.H.W., Chan K.H., Mak W., Cheung R.T.F., Ramsden D.B. and Ho S.L., Clinical phenotypes of a large Chinese multigenerational kindred with autosomal dominant familial ALS due to Ile149Thr SOD1 gene mutation., Amyotrophic Lateral Sclerosis. 2006, 7(3): 142-149.

Gao J., Cheung R.T.F., Lee T.M.C. and Chan Y.S., Cognitive assessment in normal aging and in the early Alzheimer’s disease, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population. 2007, 57.

Lee A.C.K., Tang S.W., Yu G.K.K. and Cheung R.T.F., Depression After Stroke: Incidence and Predictors , In: LI KA SHING FACULTY OF MEDICINE , THE UNIVERSITY OF HONG KONG LI KA SHING FACULTY OF MEDICINE 11th Research Postgraduate Symposium . 2006.

Lee A.C.K., Tang S.W., Yu G.K.K. and Cheung R.T.F., Smiley diagrams: a simple tool to detect depression after stroke, Evidence-Based Practice in Nursing: Paradigms & Dialogue . Hong Kong, 2007.

Lee A.C.K., Tang S.W., Yu G.K.K. and Cheung R.T.F., The Smiley as a Simple Screening Tool for Depression After Stroke: a preliminary study., International Journal of Nursing Studies. 2007, 45: 1081-1089.

Lee R., Lui W.M., Cheung R.T.F., Leung G.K.K. and Chan K.H., Mechanical thrombectomy in acute proximal middle cerebral artery thrombosis with the Alligator Retrieval Device, Cerebrovascular Diseases. 2007, 23: 69-71.

Li. Lai Fung , Cheung R.T.F. and Leung G.K.K., Relations between intracerebral space-occupying lesions and autonomic activities in terms of heart rate variability (HRV) by 24hr Holter machine, Annual Scientific Meeting of the Hong Kong Neurosurgical Society, Hong Kong, 8 - 9 December 2006.

Ng K.Y., Xu A., Lam K.S.L. and Cheung R.T.F., Aggravated cerebral infarction in diabetic mice following photothrombotic ischemia, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population. 2007, 57.

Ng K.Y., Xu A., Lam K.S.L. and Cheung R.T.F., Increased susceptibility of diabetic transgenic mice to photothrombotic stroke, 11th Research Postgraduate Symposium. 2006, 66.

Ng M.C., Ho J.T., Ho S.L., Lee R., Li G., Cheng T.S., Song Y.Q., Kwok H.H., Ho W.L., Chu C.Y.A., Fong C.Y., Chan K.H., Cheung R.T.F., Li L.S.W., Yang E.S., Luk K.D.K., Hu Y., Ramsden D.B. and Leong Fung L.L.Y., MR-DTI study: abnormal water diffusion pattern in asymptomatic familial amyotrophic lateral sclerosis with SOD1 mutation, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population. 2007, 54.

Zou L., Cheung R.T.F., Liu S.R., Li G. and Huang L., Melatonin reduces infarction volume in a photothrombotic stroke model in the wild-type but not cyclooxygenase-1-gene knockout mice, Journal of Pineal Research. 2006, 41: 150-156.

Researcher : Cheung TK

List of Research Outputs

Chan A.O.O., Jim M.H., Lam K.F., Siu D.C.W., Tong S.M., Ng F.H., Wong S.Y., Hui W.M., Chan C.K., Lai K.C., Cheung T.K., Chan P., Wong G., Yuen R.M.F., Lau Y.K., Lee S.W.L., Seto M.L., Lam S.K. and Wong B.C.Y., Patients with coronary artery disease had high prevalanece of colorectal cancer and adenoma: END-results of metabolic syndrome and smoking. Digestive Disease Week 2007, Washington DEc, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A65.

Chan A.O.O., Ng F.H., Chang P.C.M., Wong S.Y., Chu W.M., Yuen W.C., Lau Y.K., Cheung T.K. and Wong B.C.Y., Prevalence and prediction of gastrointestinal events in patients receiving a combination of aspirin plus clopidogrel. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A135.

Cheung T.K., AstraZeneca Emering Leaders Programme 2007, 2007.

Cheung T.K., Lai C.L., Wong B.C.Y., Fung J.Y.Y. and Yuen R.M.F., Clinical Features, Biochemical Parameters, and Virological Profiles of Patients with Hepatocellular Carcinoma in Hong Kong, Aliment Pharmacol Ther . 2006, 24(4): 573-583.

Cheung T.K., Lai C.L., Wong B.C.Y., Fung J.Y.Y. and Yuen R.M.F., Clinical features, biochemical parameters, and virological profiles of patients with hepatocellular carcinoma in Hong Kong. , Alimentary Pharmacology and Therapeutics. 2006, 24(4): 573-83.

Cheung T.K., Gastroesophageal reflux disease: the challenges in Asia, Gastroenterological Society of Taiwan Autumn Convention 2006. 2006.

Cheung T.K., Xia H.H.X. and Wong B.C.Y., Helicobacter pylori Eradication for Gastric Cancer Prevention., Journal of Gastroenterology. 2007, 42 (Suppl 17): 10-15.

Cheung T.K., Laryngeal reflux and Gastro-esophageal reflux disease, Oriental Daily, 28 February. 2007, A8.

Cheung T.K., Lam B., Ip M.S.M., Wong Y.H., Chan A.O.O., Lam S.K. and Wong B.C.Y., Nocturnal Reflux Symptoms Correlate with Respiratory Events in Patients with Obstructive Sleep Apnea. , AGA Digestive Digestive Disease Week 2007.

Cheung T.K., Lam B., Ip M.S.M., Wong Y.H., Chan A.O.O., Lam S.K. and Wong B.C.Y., Nocturnal reflux symptoms correlate with respiratory events in patients with obstructive sleep apnea. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132 (4) Supp 2: A482.

Cheung T.K., Lim P.W. and Wong B.C.Y., Noncardiac chest pain- An Asia-Pacific survey on the views of primary care physicians, Digestive Diseases and Sciences. 2007, epub.

Cheung T.K. and Wong B.C.Y., PPI Failure/Resistance: Proposed Mechanisms and Therapeutic Algorithm. , Journal of Gastroenterology and Hepatology. 2006, 21 (suppl 5): 119-124.

Cheung T.K., Hu H.C., Lam C.L.K., Hui W.M., Lam S.K. and Wong B.C.Y., Positive association between gastro-oesophageal reflux disease and irritable bowel syndrome in a Chinese population. , Aliment Pharmacol Ther . 2007, 25.

Cheung T.K., Lam K.F., Hu H.C., Wong W.M., Hui W.M., Lam C.L.K., Lai K.C., Lam S.K. and Wong B.C.Y., Positive association between gastro-oesophageal reflux disease and irritable bowel syndrome in a Chinese population, Alimentary Pharmacology & Therapeutics. Blackwell Publishing, 2007, 25: 1099-1104.

Cheung T.K. and Wong B.C.Y., Proton pump inhibitor failure/resistance: Proposed mechanisms and therapeutic algorithm, Journal of Gastroenterology and Hepatology. 2006, 21(S5): S119-S124.

Dai Y., Qiao L., Gu Q., Xia H.H.X., Cheung T.K., Ma J., Zou B. and Wong B.C.Y., Activation of Pparc and inhibition of Xiap in human cancer cells: Synergistic effects on cell proliferation, apoptosis, and tumorigensis. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A425.

Ho K.Y., Cheung T.K. and Wong B.C.Y., Gastroesophageal reflux disease in Asian countries: Disorder of nature or nurture? , Journal of Gastroenterology and Hepatology. 2006, 21 (9): 1362-1365.

Researcher : Cheung WMW

List of Research Outputs

Cheung W.M.W., Jin L., Smith D.K., Cheung P.T., Kwan E.Y.W., Low L.C.K. and Kung A.W.C., A family with osteoporosis pseudoglioma syndrome due to compound heterozygosity of two novel mutations in the LRP5 gene, Bone. 2006, 39: 470-6.

Cheung W.M.W., Chan W.L., Dai Z. and Kung A.W.C., Rosiglitazone Enhances Osteoblastic Differentiation of Murine Preosteoblast Cells, The 28th Annual Meeting American Society for Bone and Mineral Research, Philadelphia, PA, U.S.A. Poster # SA484. 2006.

Dai Z., Cheung W.M.W., Chung S.K. and Kung A.W.C., Identify the potential roles of SMIT-1 in bone formation, 11th Research Postgraduate Symposium, HKU, 7 Dec 2006.

Lau H.L., Ng M.Y.M., Cheung W.M.W., Paterson A.D., Luk K.D.K., Chan V.N.Y. and Kung A.W.C., Assessment of linkage and association of 13 genetic loci with bone mineral density, J Bone Miner Metab. 2006, 24: 226-34.

Researcher : Chim JCS

List of Research Outputs

Chim J.C.S., Liang R.H.S., Leung M.H. and Kwong Y.L., Aberrant gene methylation implicated in the progression of monoclonal gammopathy of undetermined significance to multipl myeloma, Journal of clinical pathology. 2007, 60: 104-106.

Chim J.C.S., Liang R.H.S., Fung T.K., Choi C.L. and Kwong Y.L., Epigenetic dysregulation of the death-associated protein kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in multiple myeloma, Journal of clinical pathology. 2007, 60: 664-669.

Chim J.C.S., Fung T.K., Wong K.F., Lau J.S. and Liang R.H.S., Frequent DAP kinase but not p14 or Apaf-1 hypermethylation in B-cell chronic lymphocytic leukemia, Journal of Human Genetics. 2006, 9: 832-8.

Chim J.C.S., Fung T.K., Wong K.F., Lau J.S. and Liang R.H.S., Infrequent Wnt inhibitory factor-1 (Wif-1) methylation in chronic lymphocytic leukemia, Leukemia Research . 2006, 30(9): 1135-9.

Chim J.C.S., Liang R.H.S., Fung T.K. and Kwong Y.L., Infrequent epigenetic dysregulation of CIP/KIP family of cyclin-dependent kinase inhibitors in multiple myeloma, Leukemia. 2006, 19(12): 2352-5.

Chim J.C.S., Lie A.K.W., Liang R.H.S., Au W.Y. and Kwong Y.L., Long-term results of allogeneic bone marrow transplantation for 108 adult patients with acute lymphoblastic leukemia: favorable outcome with BMT at first remission and HLA-matched unrelated donor, Bone Marrow Transplantation. 2007, 40(4): 339-347.

Zou B., Chim J.C.S., Zeng H., Leung S.Y., Yang Y., Tu S., Lin M.C., Wang J., He H., Jiang S.H., Sun Y., Yu L., Yuen S.T., Kung H.F. and Wong B.C.Y., Correlation Between the Single-site CpG Methylation and Expression Silencing of the XAF1 Gene in Human Gastric and Colon Cancers, Gastroenterology. 2006, 131(6): 1835-1843.

Researcher : Choi CL

List of Research Outputs

Chim J.C.S., Liang R.H.S., Fung T.K., Choi C.L. and Kwong Y.L., Epigenetic dysregulation of the death-associated protein kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in multiple myeloma, Journal of clinical pathology. 2007, 60: 664-669.

Researcher : Chow C

List of Research Outputs

Au W.Y., Trendell-Smith N.J., Chow C. and Liang R.H.S., Senile EBER positive diffuse large B cell lymphoma relapsing in the nasopharynx, Haematologica. 2006, 91(1): 111.

Researcher : Chow CH

List of Research Outputs

Cheung M.S., Tam K.H., Chow C.H., Verfaillie C.M. and Liang R.H.S., All-trans retinoic acid induces proliferation of an irradiated stem cell supporting stromal cell line AFT024., Experimental Hematology. 2007, 35: 56-63.

Leung A.Y.H., Chow C.H., Kwok J.S.Y., Lui C.K., Cheng V.C.C., Yuen K.Y., Lie A.K.W. and Liang R.H.S., Safety of vacinating sibling donors with live-attenuated varicella zoster vaccine before hematopoietic stem cell transplantation, Bone Marrow Transplantation. 2007, 39(11): 661-5.

Researcher : Chow WS

List of Research Outputs

Chow W.S., Cheung B.M.Y., Xu A., Wat N.M.S., Fong H.Y., Ong L.H.Y., Tam S., Tan K.C.B., Janus E.D., Lam T.H. and Lam K.S.L., Hypoadiponectinemia as a predictor for the development of hypertension: a 5-year prospective study. , Hypertension. 2007, 49: 1455-61.

Hoo R.L.C., Chow W.S., Yau M.H., Xu A., Tse H.F., Tso A.W.K., Fong H.Y., Tam S., Chan L. and Lam K.S.L., PPAR-γ agonist induced-suppression of plasminogen activator inhibitor-1 production is mediated through adiponectin. , 2nd International Symposium on Healthy Aging, 3-4 March 2007, Hong Kong. 2007.

Hoo R.L.C., Chow W.S., Tse H.F., Fong H.Y., Tam S., Chan L.C.B. and Lam K.S.L., Ppar-γ Agonist Induced-suppression Of Plasminogen Activator Inhibitor-1 Production Is Mediated Through Adiponectin. , HBHA conference. 2007.

Lam K.S.L., Tso A.W.K., Chow W.S., Hoo R.L.C., Zhang J., Lam C.W. and Xu A., Adipocyte fatty acid binding protein as a potential circulating metabolic hormone: clinical and functional studies. , The Endocrine Society’s 88th Annual Meeting, June 24-27, 2006, Boston, USA. 2007.

Ong L.H.Y., Chow W.S., Tso A.W.K., Wat N.M.S., Xu A., Fong H.Y., Janus E.D. and Lam K.S.L., Hypoadiponectinaemia predicts the development of hypertension in Chinese. , The 19th World Diabetes Congress, 3-7 December 2006, Cape Town, South Africa. 2006.

Tan K.C.B., Shiu S.W.M., Chow W.S., Wong Y., Bucala R. and Betteridge D.J., Arterial stiffness and advanced glycation end products in type 2 diabetes mellitus, The International Diabetes Federation 19th World Diabetes Congress, Cape Town, Dec 2006.

Tan K.C.B., Shiu S.W.M., Chow W.S., Leng L., Bucala R. and Betteridge D.J., Association between serum levels of soluble receptor for advanced glycation end products and circulating advanced glycation end products in type 2 diabetes, Diabetologia. 2006, 49: 2756-62.

Wang Y., Lam K.S.L., Kraegen E.W., Sweeney G., Zhang J., Tso A.W.K., Chow W.S., Wat N.M.S., Xu J., Hoo R.L.C. and Xu A., Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans, Clin Chem. 2007, 53: 34-41.

Wat N.M.S., Tan K.C.B., Chow W.S., Tse P.M., Wong K., Leung E., Hung V., Leung S.K., Yee A., Leung C.Y. and Lam K.S.L., Innovative risk stratification model for high-risk diabetic patients in a tertiary referral centre – triage of the triaged, Health Authority Convention, May 2007.

Zhang X., Yeung C.Y., Wong L.C., Chow W.S., Xu A. and Lam K.S.L., Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans, Second Symposium on Healthy Aging: "Meeting the Challenges of an Aging Population" . 2007.

Researcher : Choy CBY

List of Research Outputs

Choy C.B.Y., Chan D.T.M. and Lai K.N., Recurrent glomerulonephritis after kidney transplantation, American Journal of Transplantation. 2006, 6: 2535-2542.

Yip T., Tse K.C., Lam M.F., Cheng S.W., Lui S.L., Tang S.C.W., Li F.K., Wang A.Y.M., Choy C.B.Y., Ng M.M.T., Chan D.T.M., Lai K.N. and Lo W.K., Risk and outcome of peritonitis after flexible colonoscopy in CAPD patient, Peritoneal Dialysis International . 2006, Suppl 26: S68.

Researcher : Chu ACY

List of Research Outputs

Chu A.C.Y., Ho W.L., Kwok H.H., Wang Y., Ramsden D.B. and Ho S.L., Human uncoupling protein-4 protects neuronal cell death from MPP+ induced toxicity by regulating mitochondrial membrane potential, reducing ROS and maintaining ATP levels., 11th International Congress of Parkinson's disease and Movement Disorders, Istanbul, Turkey. {Abs]. Istanbul, Turkey., Mov Disord, 2007, 22 (Suppl 16):: 67.

Chu A.C.Y., Ho W.L., Kwok H.H., Kung M.H.W., Ramsden D.B. and Ho S.L., Leptin enhances MPP+-induced mitochondrial dysfunction: a potential for neuroprotection in parkinsonism, 10th International Congress of Parkinson's disease and Movement Disorders, Kyoto, Japan. [Abs]. Kyoto, Japan, Mov Disorders, 2006, 21(Suppl 15): 62.

Fong C.Y., Kwok H.H., Song Y., Cheng T.S., Ho W.L., Chu A.C.Y., Kung M.H.W., Chan K.H., Mak W., Cheung R.T.F., Ramsden D.B. and Ho S.L., Clinical phenotypes of a large Chinese multigenerational kindred with autosomal dominant familial ALS due to Ile149Thr SOD1 gene mutation., Amyotrophic Lateral Sclerosis. 2006, 7(3): 142-149.

Ho W.L., Chu A.C.Y., Kwok H.H., Kung M.H.W. and Ho S.L., Leptin enhances MPP+-induced mitochondrial dysfunctions in SH-SY5Y cells: a potential of neuroprotection in Parkinsonism, University of Hong Kong. 2006.

Ho W.L., Chu A.C.Y., Kwok H.H., Kung M.H.W., Ramsden D.B. and Ho S.L., Stable overexperession of human uncoupling protein-4 reduced ATP production in SH-SY5Y cells: a potential candidate to regulate mitochondrial function and efficiency. Late breaking abstract LB-18. , 10th International Congress of Parkinson's disease and Movement Disorders, Kyoto, Japan. [Abs]. Kyoto, Japan, Mov Disorders, 2006, 21(Suppl 15).

Kwok H.H., Chu A.C.Y., Ho W.L., Ramsden D.B., Kung M.H.W. and Ho S.L., Localization and distribution of uncoupling protein 5 (UCP5) in rat brain., 10th International Congress of Parkinson's disease and Movement Disorders, Kyoto, Japan. [Abs]. . Kyoto, Japan, Mov Disorders, 2006, 21(Suppl 15): 55.

Researcher : Chu CYA

List of Research Outputs

Ng M.C., Ho J.T., Ho S.L., Lee R., Li G., Cheng T.S., Song Y.Q., Kwok H.H., Ho W.L., Chu C.Y.A., Fong C.Y., Chan K.H., Cheung R.T.F., Li L.S.W., Yang E.S., Luk K.D.K., Hu Y., Ramsden D.B. and Leong Fung L.L.Y., MR-DTI study: abnormal water diffusion pattern in asymptomatic familial amyotrophic lateral sclerosis with SOD1 mutation, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population. 2007, 54.

Researcher : Chu LW

Project Title:	A dementia outreach programme in Central, Western and Southern districts of Hong Kong
Investigator(s):	Chu LW, Lam KSL, Lee PWH
Department:	Medicine
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	09/2003

Abstract:

To achieve early detection of dementia, through an outreach dementia-screening programme.

List of Research Outputs

Chan M.M.W., Chan F.H., Cheung A.H.K., Dai D.L. and Chu L.W., Prevalence of tuberculous infection and active tuberculosis in old age homes in Hong Kong. , J Am Geriatr Soc. 2006, 54(9): 1334-40.

Cheng Y.H., Wu L.H., Chu L.W. and Law W.J., An exploratory study of the job satisfaction and educational needs of health care workers working in private homes for the elderly in Hong Kong, Hong Kong Medical Journal. 2006, 12(4) Supp 2: 5-6.

Chu L.W., Yik P.Y., Mok W. and Chung C.P., A two-year open-label study of galantamine therapy in Chinese Alzheimer’s disease patients in Hong Kong, Int J Clin Pract. 2007, 61: 403-10.

Li Y., Chu L.W., Cheung B.M.Y., Leung Y.H., Yik P.Y., Jin D. and Song Y., Association of ABCA1 Gene with Sporadic Alzheimer's Disease in Chinese Group and Potential Functional Importance for Novel Intronic Polymorphism., 11th Research Postgraduate Symposium, 7 Dec. 2006. The University of Hong Kong, Li Ka Shing Faculty of Medicine. 2006.

Li Y., Chu L.W., Chen Y., Cheung B.M.Y., Leung R.Y., Yik P.Y., Ng K.M.T., Mak W., Jin D., St. George-Hyslop P. and Song Y., Intron 2 (T/C) CYP46 polymorphism is associated with Alzheimer's disease in Chinese patients., Dement Geriatr Cogn Disord 2006. 2006, 22(5-6): 399-404.

Luk J.K.H., Sin W.S., Ho S.L. and Chu L.W., Striopallidodentate calcifications in a Chinese elderly woman with parkinsonism and dementia, Asian J Gerontol Geriatr. 2006, 1: 113-5.

Researcher : Chung ACK

Project Title:	Involvement of PPAR interacting protein (PRIP) in the kidney complication during diabletic nephropathy
Investigator(s):	Chung ACK, Lan HY
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	05/2007

Abstract:

Diabetes nephropathy (DN) is the leading cause of end stage renal failure (ESRF) and a major complication of diabetes (1). It results in significant morbidity as well as social and economic costs to the community. Peroxisome proliferator-activated receptor (PPAR) agonists have recently been used to cure DN (2) although the means by which this is achieved remains unclear. In addition, major drawbacks of PPAR agonists include hepatotoxicity and fluid retention. Further studies should be performed to search for an alternative therapeutic agent that demonstrates similar benefit to renal function without severe adverse effects. PPARs are members of the nuclear receptor superfamily of ligand-binding transcription factors (3,4). The principal function of three subtypes of this receptor that are differentially expressed in kidneys, PPAR-α, -β, -γ, is to control metabolic mechanisms (3,5). In diabetic kidneys, PPAR-α expression is elevated in the glomeruli, cortical tubules, and renal arterial vessels but mice lacking PPAR-α develop accelerated DN (6,7). The detailed function of PPARs in the kidney is still unclear. After binding to a ligand, PPARs form heterodimers with retinoid X receptor alpha (RXRα) (Fig. 1) (4). These PPAR:RXRα heterodimers bind to a specific DNA motif, PPRE, in the promoter region of target genes to activate gene transcription. Evidence indicates that transcriptional activation of nuclear receptors after ligand binding involves the participation of coactivators (8). These coactivators are recruited to PPAR:RXRα heterodimers to modulate the transcriptional activity of PPAR by remodeling chromatin and establishing physical contact with basal transcriptional initiation machinery (8). Thus the expression of PPAR, availability of PPAR ligands, and presence of coactivators will contribute to the biologic effects of PPAR activity. After PPAR-interacting protein (PRIP) was initially cloned using PPARγ as bait in the yeast two-hybrid system (9), PRIP (otherwise referred to as ASC-2, AIB3, RAP250, NRC, TRBP, or NcoA6) was characterized as a strong transcriptional coactivator for PPAR-α, PPAR-γ, RXRα, ER, and TRβ1 (9,11). PRIP can also bind to basal transcriptional factors TBP and TFIIA (11) and may thus function through bridging the nuclear receptors to the basal transcriptional factors. Noticeably, PRIP is required for proper function of PPAR-γ: mice that lack either PPAR-γ or PRIP die at a similar age (embryonic day 9.5 to 11.5) and possess similar placental phenotypes (12,14). PRIP binds to PPAR-γ through one of its nuclear receptor binding motifs, LXXLL and can potentiate the transcriptional activities of PPAR-γ in mammalian cells (9). In mouse embryonic fibroblast (MEF) cells, inactivation of the PRIP gene significantly attenuates PPAR-γ transcriptional activity (12,14,15). Therefore the presence of PRIP is essential for PPAR-γ transcriptional activation. In the kidney, PRIP is strongly expressed in proximal and distal convoluted tubules in the cortex (16): expression is significantly reduced in the diabetic kidney of the KK/Ta mouse model of type 2 diabetes (17). This suggests that, although not yet proven, the presence of PRIP may play a role in DN. In our preliminary study by the realtime RT-PCR analyses (Fig. 2), PRIP expression in WT MEF cells was significantly decreased after the MEF cells was treated with advanced glycation end (AGE) for 12 hours to develop a DN condition, suggesting that PRIP may play a role in DN. The expression levels of fibrosis-related genes, such as collagan-I, MCP-1, and TNF-α, were also upregulated (Fig. 2), suggesting TGF-β related fibrosis may occur. Loss of PRIP function in MEF cells is able to upregulate more smad3, collagan-I, IL-8, MCP-1, and TNF-α expression (Fig. 2), suggesting fibrosis becomes more severe. These results support the speculation that loss of PRIP function should resemble the mice deficiency of PPAR-α gene in which DN is accelerated. Based on these preliminary observations, our hypothesis is as follows (Fig. 3): In the normal kidney, PRIP coactivates PPAR to control the TGF-β function in the repair of acute injury. In the presence of diabetes, AGE products or high glucose (HG) will induce TGF-β function on fibrosis. AGE or HG may reduce PRIP expression by the kidney and this reduction may impede PPAR function on TGF-β induced fibrosis with resultant DN. During treatment, PPAR agonists can activate PPAR function to suppress DN. Studies on the role of PRIP in DN should clarify and clearly establish the therapeutic role of PRIP in diabetic disease states, and benefit the understanding of DN. The objective of this study is to determine the specific role of PRIP in DN under HG and AGE products by in vitro cell culture approach. This will be achieved by the execution of the two following specific aims: 1. To characterize the specific role of PRIP in MEF cells under DN condition 2. To characterize the specific role of PRIP in kidney cells under DN condition. Ultimately, this study will enable us to explore the new role and novel mechanisms of PRIP in DN, and may provide new information that will aid in the design of a novel therapy for DN.

List of Research Outputs

Chung A.C.K. and Lan H.Y., Loss of PPAR Interacting Protein (PRIP) Function Accelerates the Diabetic Injury Under High Glucose and AGE Conditions, 12th Medical Research Conference of Department of Medicine (3/2/2007). 2007.

Wong L.W., Zhu S.L., Zhang S.Y., Lan X.R., Chung A.C.K., Zhang R., Lam S.K., Wong B.C.Y., Xia H.H.X. and Lan H.Y., Macrophage Migration Inhibitory Factor (MIF) Knockout Mice Are Protected Against Helicobacter Pylori Induced Gastritis., 12th Medical Research Conference (Hong Kong, 3/2/2007). 2007.

Researcher : Chung SSM

Project Title:	Osmoregulation in lens
Investigator(s):	Chung SSM
Department:	Institute of Molecular Biology
Source(s) of Funding:	Outstanding RGC Projects
Start Date:	09/1998

Abstract:

It is imperative to have a better understanding of the mechanisms leading to various cataracts such that preventive measures can be developed. Since maintaining the ionic strength and ionic composition in the lens is essential for the transparency of the lens, we plan to study the mechanism of osmoregulation in this organ. Transgenic mice that over-express aldose reductase and sodium dependent myoinositol transporter in their lenses will be used to increase the lens' level of sorbitol and myoinositol, respectively. We will determine if high level of these osmolytes causes cataract development, and see when the level of one osmolyte is high, will the lens compensate by reducing the level of other osmolytes. We will also determine whether high intracellular osmotic pressure affects the regulation of expression of genes that control the level of osmolytes such as aldose reductase, sodium dependent myoinositol transporter, and taurine transporter.

Project Title:	Effects of early postnatal feeding on fatty acid metabolism
Investigator(s):	Chung SSM, Sheng HP
Department:	Institute of Molecular Biology
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	11/2002

Abstract:

Both epidemiological studies and animal studies have shown that prenatal and early postnatal nutrition not only affects infant growth and development, it also predetermines future metabolism, performance adn morbidity. This study addresses the problems of nutritional environment during the sucking period on lipid metabolism and later-life obesity.

Project Title:	Polyol pathway in diabetic dyslipidemia
Investigator(s):	Chung SSM
Department:	Institute of Molecular Biology
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	01/2003

Abstract:

To determine if AR null mutation reduces plasma TG levels in diabetic mice; to determine if ARI reduces plasma TG in diabetic mice; to determine if AR null mutation or ARI nor ARI normalizes LDL and HDL leviabetic mice.

Project Title:	Mechanism of Nogo-A inhibition of axonal regeneration
Investigator(s):	Chung SSM, Chung SK
Department:	Institute of Molecular Biology
Source(s) of Funding:	NSFC/RGC Joint Research Scheme
Start Date:	01/2003

Abstract:

To develop Nogo gene knockout mice to determine the role of this gene in the inhibition of axonal regeneration and its physiological functions; to develop transgenic mice that overexpress Nogo-A in their Schwann cells to determine if that would make their PNS non-permissive for axonal regeneraton; to develop transgenic mice that overexpress mutant Nogo-A with the Nogo-66 or aa623-640 region deleted to determine which domain is responsible for the inhibitory effect of Nogo-A.

Project Title:	The polyol pathway as a thrifty pathway promoting energy storage
Investigator(s):	Chung SSM
Department:	Physiology
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	09/2003

Abstract:

To determine the in vivo conversion of glucose to fatty acids and triglycerides in normal mice and mice deficient in AR; to determine if AR deficiency affects the activities of lipogenic/adipogenic transcriptional factors including ADD1/SREBP-1 and CHOP-C/EBP-[alpha], anti-obesity transcriptional factor FOXC2, and enzymes fatty acid synthase (FAS) and stearoyl CoA desaturase (SCD); to assess whether administration of inhibitors of aldose reductase (ARI) will affect obesity and improve glucose tolerance in the agouti yellow mice; to determine whether the effects of aldose reductase deficiency on agouti-induced lipogenesis and obesity can be duplicated in diet-induced obesity models.

Project Title:	Aldose reductase in diabetic cataract
Investigator(s):	Chung SSM
Department:	Institute of Molecular Biology
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	10/2004

Abstract:

To determine if the antioxidant can prevent AR-induced slow-developing cataract; to determine the osmolyte content and oxidative status of the slow-developing cataract; to compare the morphological changes in the acute diabetic cataract and the slow developing cataract; to determine if there is apoptosis in the epithelial cells of the precataractous lenses.

Researcher : Dai Y

List of Research Outputs

Dai Y., Qiao L., Gu Q., Xia H.H.X., Cheung T.K., Ma J., Zou B. and Wong B.C.Y., Activation of Pparc and inhibition of Xiap in human cancer cells: Synergistic effects on cell proliferation, apoptosis, and tumorigensis. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A425.

Ma J., Chen M.H., Dai Y. and Qiao L., Enhancing The Efficacy Of Photodynamic Therapy By A Chinese Herbal Medicine For Hepatocellular Carcinoma, In: Editor-in-chief, Wafik S. El-Deiry, M.D., Ph.D.University of Pennsylvania Philadelphia, PA , Cancer Biology & Therapy. USA, Cancer Biol. Ther., 2006, 5: 1117-1119.

Qiao L., Gu Q., Dai Y., Shen Z., Liu X., Ma J. and Wong B.C.Y., XAF1 inhibits angiogenesis of mouse endothelia cells. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A638.

Researcher : Dai Z

List of Research Outputs

Cheung W.M.W., Chan W.L., Dai Z. and Kung A.W.C., Rosiglitazone Enhances Osteoblastic Differentiation of Murine Preosteoblast Cells, The 28th Annual Meeting American Society for Bone and Mineral Research, Philadelphia, PA, U.S.A. Poster # SA484. 2006.

Dai Z., Cheung W.M.W., Chung S.K. and Kung A.W.C., Identify the potential roles of SMIT-1 in bone formation, 11th Research Postgraduate Symposium, HKU, 7 Dec 2006.

Researcher : Deng X

List of Research Outputs

Deng X., Lau C.P. and Li G.R., Cell cycle-dependent expression of potassium channels and cell proliferation in rat mesenchymal stem cells from bone marrow, Biophysical Journal/51th Annual Meeting of Biophysical Society, Baltimore, MD . 2007, 126.

Deng X., Sun H., Lau C.P. and Li G.R., Properties of ion channels in rabbit mesenchymal stem cells from bone marrow , Biochem Biophys Res Commun. 2006, 348(1): 301-309.

Researcher : Eddy AA

List of Research Outputs

Tang S.C.W., Leung J.C.K., Chan L.Y., Chan A.K.K., Eddy A.A. and Lai K.N., Impact of angiotensin antagonists and HMG-CoA reductase inhibitors on adriamycin nephropathy, Journal of American Society of Nephrology. 2006, 17: 41A.

Researcher : Epstein R

Project Title:	Evolutionarily conserved patterns of synonymous codon bias in wild-type orthologous and paralogous gene sequences, and comparison with patterns of bias in human tumour genomes
Investigator(s):	Epstein R
Department:	Medicine
Source(s) of Funding:	Seed Funding for New Staff
Start Date:	09/2003

Abstract:

To clarify whether these evident associations of synonymous codon bias with function and/or with methylation are interdependent or independent.

Project Title:	Environmental and therapeutic modulation of tumour suppressor gene methylation
Investigator(s):	Epstein R, Smith DK
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	09/2005

Abstract:

Lifestyle changes in Hong Kong have been associated with a rapid rise in incidence of certain cancer types, particularly breast, colorectal and prostate cancer. The implicated lifestyle variables (diet and exercise) are not known to cause genetic mutations; it is therefore reasonable to hypothesise: 1. That environmentally induced changes in DNA methylation may contribute to this epidemiologic shift, and if so, that such inducible changes (e.g. caused by high glucose or insulin) in methylation may be detectable by appropriate in vitro model systems. A related observation is that adjuvant (preventive) anticancer treatments are uniquely effective in reducing recurrences of these same lifestyle cancers, raising the possibility that such treatments could act in part via reversing TSG methylation. In this respect it is salient to note that fluoropyrimidine drugs such as 5-fluorouracil are part of the cytotoxic regimens (CMF, FAC, 5FU/FA) for such lifestyle cancers, and that these antimetabolites are chemically related to the potent in vitro hypomethylating agent 5-azacytidine. Hence, a further hypothesis to be tested here is: 2. That TSG promoter methylation in cancer cell lines may be affected by exposures to fluoropyrimidine drugs, and if so, that this finding is relevant to the future development of more effective adjuvant cancer treatments. By providing preliminary data in support of one or other of these hypotheses, this small project grant aims to provide a basis for RGC grant applications in 2006.

List of Research Outputs

Chan P., Yau T., Epstein R., Lam K., Liang R.H.S. and Lo C., Treatment outcomes in anaplastic thyroid carcinoma 1966-2006: failure of overall survival enhancement despite four decades of progress in surgery, radiotherapy and chemoradiation. , Proc Am Soc Clin Oncol. 2007, 43: 672.

Chan T.W.M., Chan S., Poon Y., Fok J., Epstein J.A., Mak J. and Epstein R., The influence of income and education on drug purchasing decisions in Hong Kong Chinese cancer patients, Proc Am Soc Clin Oncol. 2007, 43: 713.

Chan W.F., Cheung P.S.Y., Mak J. and Epstein R., Multidisciplinary approach to the management of breast cancer in Hong Kong, World Journal of Surgery. 2006, 30: 2095-2100.

Epstein R., Adjuvant breast cancer chemotherapy during late-trimester pregnancy – not quite a standard of care, BMC Cancer. 2007, 7: 92-7.

Epstein R. and Leung T.W.T., Reversing hepatocellular carcinoma progression using networked biological therapies, Clin Cancer Res. 2007, 13(1): 11-7.

Hsu C., Tang T., Toh H., Epstein R., Hsiao L. and Cheng A., Modified-dose capecitabine plus bevacizumab for the treatment of advanced metastatic hepatocellular carcinoma: a phase II single-arm study, Proc Am Soc Clin Oncol . 2007, 43: 649.

Leung A.W., Mak J., Cheung P.S.Y. and Epstein R., Clinicopathologic correlates in a cohort of Hong Kong breast cancer patients presenting with screen-detected or symptomatic disease, Hong Kong Medical Journal. 2007, 13: 194-198.

Tang S.M., Zhao Y., Smith D.K. and Epstein R., Intron length and accelerated 3' gene evolution., Genomics. 2006, 88: 682-89.

Tsang J., Yau T., Chan A.T.C., Liang R.H.S., Yeo W. and Epstein R., Costs and benefits of dose-dense chemotherapy scheduling in Hong Kong Chinese patients with primary breast cancer, Proc Am Soc Clin Oncol . 2007, 43: 598.

Yau T., Leong C.H., Chan W.K., Chan J.K., Liang R.H.S. and Epstein R., A case of mixed adult Wilms' tumour and angiosarcoma responsive to carboplatin, etoposide and vincristine (CEO), Cancer Chemother Pharmacol. 2007.

Yau T., Chan P., Tsang J., Liang R.H.S. and Epstein R., Xelox causes less disabling neuropathy than FOLFOX4 for Chinese colorectal cancer patients., Proc Am Soc Clin Oncol . 2007, 43: 632.

Researcher : Fong CY

List of Research Outputs

Chan K.H., Tsang K.L., Fong C.Y., Ho S.L., Cheung R.T.F. and Mak W., Idiopathic inflammatory demyelinatng disorders after acute transverse myelitis., European Journal of Neurology. 2006, 13(8): 862-8.

Fong C.Y., Kwok H.H., Song Y., Cheng T.S., Ho W.L., Chu A.C.Y., Kung M.H.W., Chan K.H., Mak W., Cheung R.T.F., Ramsden D.B. and Ho S.L., Clinical phenotypes of a large Chinese multigenerational kindred with autosomal dominant familial ALS due to Ile149Thr SOD1 gene mutation., Amyotrophic Lateral Sclerosis. 2006, 7(3): 142-149.

Ng M.C., Ho J.T., Ho S.L., Lee R., Li G., Cheng T.S., Song Y.Q., Kwok H.H., Ho W.L., Chu C.Y.A., Fong C.Y., Chan K.H., Cheung R.T.F., Li L.S.W., Yang E.S., Luk K.D.K., Hu Y., Ramsden D.B. and Leong Fung L.L.Y., MR-DTI study: abnormal water diffusion pattern in asymptomatic familial amyotrophic lateral sclerosis with SOD1 mutation, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population. 2007, 54.

Researcher : Fong HY

List of Research Outputs

Chow W.S., Cheung B.M.Y., Xu A., Wat N.M.S., Fong H.Y., Ong L.H.Y., Tam S., Tan K.C.B., Janus E.D., Lam T.H. and Lam K.S.L., Hypoadiponectinemia as a predictor for the development of hypertension: a 5-year prospective study. , Hypertension. 2007, 49: 1455-61.

Hoo R.L.C., Chow W.S., Yau M.H., Xu A., Tse H.F., Tso A.W.K., Fong H.Y., Tam S., Chan L. and Lam K.S.L., PPAR-γ agonist induced-suppression of plasminogen activator inhibitor-1 production is mediated through adiponectin. , 2nd International Symposium on Healthy Aging, 3-4 March 2007, Hong Kong. 2007.

Hoo R.L.C., Chow W.S., Tse H.F., Fong H.Y., Tam S., Chan L.C.B. and Lam K.S.L., Ppar-γ Agonist Induced-suppression Of Plasminogen Activator Inhibitor-1 Production Is Mediated Through Adiponectin. , HBHA conference. 2007.

Ong L.H.Y., Chow W.S., Tso A.W.K., Wat N.M.S., Xu A., Fong H.Y., Janus E.D. and Lam K.S.L., Hypoadiponectinaemia predicts the development of hypertension in Chinese. , The 19th World Diabetes Congress, 3-7 December 2006, Cape Town, South Africa. 2006.

Tso A.W.K., Wat N.M.S., Xu A., Tam S., Fong H.Y., Janus E.D., Tan K.C.B. and Lam K.S.L., Adiponectin/C-reactive protein ratio is an independent surrogate marker predictive of the development of metabolic risks and the metabolic syndrome over 5 years in Chinese, The 6th International Diabetes Federation Western Pacific Region Congress, Bangkok. 2006.

Tso A.W.K., Sham P.C., Wat N.M.S., Xu A., Cheung B.M.Y., Rong R., Fong H.Y., Xu J., Cheng K.Y., Janus E.D. and Lam K.S.L., Polymorphisms of the gene encoding adiponectin and glycaemic outcome of Chinese subjects with impaired glucose tolerance: a 5-year follow-up study, Diabetologia. 2006, 49: 1806-15.

Tso A.W.K., Xu A., Wat N.M.S., Fong H.Y., Janus E.D. and Lam K.S.L., Serum adipocyte fatty acid-binding protein is a predictor of the development of type 2 diabetes mellitus over 5 years. , The Endocrine Society's 89th Annual Meeting, 2-5 June2007, Toronto. 2007.

Xu A., Tso A.W., Cheung B.M.Y., Wang Y., Wat N.M.S., Fong H.Y., Yeung C.Y., Janus E.D., Sham P.C. and Lam K.S.L., Circulating adipocyte-fatty acid binding protein levels predict the development of the metabolic syndrome: a 5-year prospective study, Circulation. 2007, 115: 1537-43.

Xu A., Tso A.W.K., Cheung B.M.Y., Wang Y., Wat N.M.S., Fong H.Y., Yeung C.Y., Janus E.D., Sham P.C. and Lam K.S.L., Circulating levels of adipocyte-fatty acid binding protein correlate with its adipose tissue expression and predict the development of the metabolic syndrome. , The Endocrine Society's 89th Annual Meeting, 2-5 June 2007, Toronto. 2007.

Xu J., Sham P.C., Xu A., Tso A.W.K., Wat N.M.S., Cheng K.Y., Fong H.Y., Janus E.D. and Lam K.S.L., Resistin gene polymorphisms and progression of glycaemia in southern Chinese: a 5-year prospective study, Clin Endocrinol (Oxf). 2007, 66: 211-7.

Yeung C.Y., Xu A., Cheung C.W., Wat N.M.S., Yau M.H., Fong H.Y. and Lam K.S.L., Circulating serum adipocyte-fatty acid-binding protein (A-FABP) levels correlate with carotid intima-media thickness (IMT) in Southern Chinese women. , 89th Annual Meeting of Endocrine Society, 2-5 June 2007, Toronto, Canada. 2007.

Researcher : Fung JYY

List of Research Outputs

Cheung T.K., Lai C.L., Wong B.C.Y., Fung J.Y.Y. and Yuen R.M.F., Clinical Features, Biochemical Parameters, and Virological Profiles of Patients with Hepatocellular Carcinoma in Hong Kong, Aliment Pharmacol Ther . 2006, 24(4): 573-583.

Cheung T.K., Lai C.L., Wong B.C.Y., Fung J.Y.Y. and Yuen R.M.F., Clinical features, biochemical parameters, and virological profiles of patients with hepatocellular carcinoma in Hong Kong. , Alimentary Pharmacology and Therapeutics. 2006, 24(4): 573-83.

Fung J.Y.Y., Lai C.L., Yuen J.C.H., Wong D.K.H., Tanaka Y., Mizokami M. and Yuen R.M.F., Adefovir dipivoxil monotherapy and combination therapy with lamivudine for the treatment of chronic hepatitis B in an Asian population, Antivir Ther. 2007, 12: 41-46.

Fung J.Y.Y., From Hepatitis to Hepatocellular Carcinoma, Hong Kong Society of Interventional Radiology Scientific Meeting, Hong Kong. 2006.

Fung J.Y.Y., Lai C.L., Wong D.K.H., Cheng C.T.K., But D.Y. and Yuen R.M.F., Large Population Study in Liver Stiffness Measurement: Prevalence of Significant Fibrosis and Correlation with Liver Biochemistry in Chronic Hepatitis B, Annual Meeting for European Association for the Study of the Liver (EASL 2007). 2007.

Fung J.Y.Y., Lai C.L., Wong D.K.H. and Yuen R.M.F., Large population study on the natural history of spontaneous hepatitis B e antigen seroconversion: risk of hepatocellular carcinoma. Annual meeting, European Association for the Study of Liver (EASL). Journal of Hepatology. 2007, 46 S1: S181.

Fung J.Y.Y., Lai C.L. and Yuen R.M.F., Overcoming the problem of chronic hepatitis B. Drug Discovery Today, Therapeutic Strategies. 2007, 3: 197-202.

Fung J.Y.Y., Lai C.L. and Yuen R.M.F., Telbivudine : A new treatment option in the management of chronic hepatitis B, Hepatitis B Annual. 2006, 3(1): 14-34.

Wong D.K.H., Yuen R.M.F., Ngai W.S., Fung J.Y.Y. and Lai C.L., One-year entecavir or lamivudine therapy results in reduction of HBV intrahepatic covalently closed circular DNA levels, Antivir Ther . 2006, 11: 909-916.

Wong D.K.H., Yuen R.M.F., Ngai W.S., Fung J.Y.Y. and Lai C.L., One-year entecavir or lamivudine therapy results in reduction of hepatitis B virus intrahepatic covalently closed circular DNA levels., Antiviral Therapy. 2006, 11: 909-916.

Wong D.K.H., Yuen R.M.F., Poon R.T.P., Yuen J.C.H., Fung J.Y.Y. and Lai C.L., Quantification of hepatitis B virus covalently closed circular DNA in patients with hepatocellular carcinoma, Journal of hepatology : the journal of the European Association for the Study of the Liver. 2006, 45: 553-559.

Wong D.K.H., Yuen R.M.F., Poon R.T.P., Yuen J.C.H., Fung J.Y.Y. and Lai C.L., Quantitation of hepatitis B virus covalently closed circular DNA in patients with hepatocellular carcinoma, Journal of Hepatology. 2006, 45: 553-559.

Yuen R.M.F., Tanaka Y., Shinkai N., Poon R.T.P., But D.Y.K., Fong D.Y.T., Fung J.Y.Y., Wong D.K.H., Yuen J.C.H., Mizokami M. and Lai C.L., Risk for hepatocellular carcinoma with respect to hepatitis B virus genotypes B/ C, specific mutations of enhancer II/ core promoter/ precore regions and HBV DNA levels, Gut. 2007, 57: 98-102.

Yuen R.M.F., Tanaka Y., Shinkai N., Poon R.T.P., Fung J.Y.Y., Wong D.K.H., Yuen J.C.H., Mizokami M. and Lai C.L., Role of HBV genotypes, core promoter/precore mutations and HBV DNA levels on hepatocarcinogenesis, Annual meeting, European Association for the Study of Liver (EASL), Barcelona, Spain, 11 - 15 April 2007.

Yuen R.M.F., Sablon E., Libbrecht E., de Velde H.V., Wong D.K.H., Fung J.Y.Y., Wong B.C.Y. and Lai C.L., Significance of HBV viral load, core promoter/ precore mutations and specific sequences of polymerase gene in HBV-infected patients on 3-year lamivudine treatment, Antivir Ther. 2006, 11(6): 779-786.

Yuen R.M.F., Tam S., Fung J.Y.Y., Wong D.K.H., Wong B.C.Y. and Lai C.L., Traditional Chinese medicine causing hepatotoxicity in patients with chronic hepatitis B infection: A one-year prospective study, Alimentary Pharmacology and Therapeutics. 2006, 24(8): 1179-1186.

Researcher : Fung PCW

Project Title:	Development of a novel natural antioxidant with strong anti-aging and protective properties for skin
Investigator(s):	Fung PCW, Shen J
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Applied Research
Start Date:	07/2002

Abstract:

To develop a novel antioxidants from herbal products which can scavenge superoxide, hydroxyl and lipid peroxide free radicals in skin.

Project Title:	Roles of plasma membrane cholesterol homeostasis in regulating neuronal oxidative damage of ischemic stroke
Investigator(s):	Fung PCW, Shen J
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003

Abstract:

To understand the roles of plasma membrane cholesterol homeostasis in protecting neuronal cells from oxidative damage during ischemic stroke.

Project Title:	High level brain activity studies and applications
Investigator(s):	Fung PCW
Department:	Medicine
Source(s) of Funding:	NSFC/RGC Joint Research Scheme
Start Date:	01/2004

Abstract:

To better understand and utilize the functioning of the brain.

List of Research Outputs

Chang C., Xu W., Hung Y.S. and Fung P.C.W., Nonlinear dynamic characterization of intra-atrial ECG signals, Biomedizinische Technik. 2006, 51: A7.

Gao Z., Sun H., Lau C.P., Fung P.C.W. and Li G.R., Evidence for cystic fibrosis transmembrane conductance regulator chloride current in swine ventricular myocytes, J Mol Cell Cardiol. 2007, 42(1): 98-105.

LU G., Shen J., Fung P.C.W. and Chu K.W., 直結腸癌細胞線粒體超微結構與細胞凋亡的關系., 中國誤診學雜誌, China, 2006, 6(17): 3277-3279.

Leung Y.Y., Chang C., Hung Y.S. and Fung P.C.W., Gene selection for brain cancer classification, IEEE International Conference of the Engineering in Medicine and Biology Society (EMBC 2006). New York, USA, 2006, 5846-5849.

Lu G., Shen J., You W.L., Fung P.C.W. and Chu K.W., Relationship between Apoptosis and Ultrastructure of Mitochondria of Colorectal Cancer, Chinese Journal of Misdiagnosis. 2006, 6(17): 3277-3279.

Lu G., You W.L., Zhang D.H., Shen J., Fung P.C.W. and Chu K.W., Sampling details when researching the ultrastructure of mitochondria of colorectal cancer, Modern Medicine & Pharmacy. 2006, 16(4): 1-2.

Ren J., Fung P.C.W., Chang C., Shen G.G., Chan F.H.Y., Liu K.J. and Shen J.G., a Comparison Study On Blood And Tissue Nitric Oxide Concentration During Renal Ischemia-reperfusion Injury With Electron Paramagnetic Resonance Spectroscopy, Applied Magnetic Resonance. 2007.

Ting K.H., Fung P.C.W., Chang C. and Chan F.H.Y., Automatic correction of artifact from single-trial event related potentials by blind source separation using second order statistics only, Medical Engineering & Physics. 2006, 28: 780-794.

Xu R.U.I.A.N., Zhou B., Fung P.C.W. and Li X., Recent advances in the treatment of colon cancer, Histology and Histopathology. 2006, 21: 867-872.

Researcher : Fung TK

List of Research Outputs

Au W.Y., Fung T.K., Ma E.S.K., Shek T.W.H., Hawkins B.R. and Liang R.H.S., HLA associations, microsatellite instability and epigenetic changes in thyroid lymphoma in Chinese, Leuk Lymphoma. 2007, 48(3): 531-534.

Au W.Y., Fung T.K., Lie A.K.W., Lam K.Y., Lam C.C.K. and Kwong Y.L., Reemergence of JAK2 V617F clone heralds extramedullary leukemia relapse after BMT for transformed essential thrombocytosis, Annals of Hematology. 2006, 86: 145-7.

Au W.Y., Au W.Y., Fung T.K., Liu C.L., Fung T.K., Fung T.K., Fan S.T., Ma E.S.K., Liang R.H.S. and Kwong Y.L., Serial analysis of JAK2 mutation in a patient who developed essential thrombocythemia after orthotopic liver transplantation, American Journal of Hematology. 2006, 81(1): 880-882.

Au W.Y., Ma E.S.K., Lee T.L., Ha S.Y., Fung T.K., Lie A.K.W. and Kwong Y.L., Successful treatment of thrombotic microangiopathy after haematopoietic stem cell transplantation with rituximab, British Journal of Haematology. Blackwell Publishing Ltd, 2007, 137: 475-478.

Au W.Y., Fung T.K., Lam K.Y., Lie A.K.W., Liang R.H.S. and Kwong Y.L., Transformed essential thrombocytosi with a JAK2 V617F mutation relapsing as JAK2 Mutation-negative leukaemia after allogeneic stem cell transplantation, Bone Marrow Transplantation. 2006, 38(8): 573-4.

Au W.Y., Fung T.K., Wong K.F., Chan C.H. and Liang R.H.S., Tumor necrosis factor alpha promoter polymorphism and the risk of chronic lymphocytic leukemia and myeloma in the Chinese population, Leukaemia and Lymphoma. 2006, 47(10): 2189-2193.

Chim J.C.S., Liang R.H.S., Fung T.K., Choi C.L. and Kwong Y.L., Epigenetic dysregulation of the death-associated protein kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in multiple myeloma, Journal of clinical pathology. 2007, 60: 664-669.

Chim J.C.S., Fung T.K., Wong K.F., Lau J.S. and Liang R.H.S., Frequent DAP kinase but not p14 or Apaf-1 hypermethylation in B-cell chronic lymphocytic leukemia, Journal of Human Genetics. 2006, 9: 832-8.

Chim J.C.S., Fung T.K., Wong K.F., Lau J.S. and Liang R.H.S., Infrequent Wnt inhibitory factor-1 (Wif-1) methylation in chronic lymphocytic leukemia, Leukemia Research . 2006, 30(9): 1135-9.

Chim J.C.S., Liang R.H.S., Fung T.K. and Kwong Y.L., Infrequent epigenetic dysregulation of CIP/KIP family of cyclin-dependent kinase inhibitors in multiple myeloma, Leukemia. 2006, 19(12): 2352-5.

Researcher : Gao J

List of Research Outputs

Gao J., Cheung R.T.F., Lee T.M.C. and Chan Y.S., Cognitive assessment in normal aging and in the early Alzheimer’s disease, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population. 2007, 57.

Researcher : Gao Z

List of Research Outputs

Gao Z., Sun H., Lau C.P., Fung P.C.W. and Li G.R., Evidence for cystic fibrosis transmembrane conductance regulator chloride current in swine ventricular myocytes, J Mol Cell Cardiol. 2007, 42(1): 98-105.

Researcher : Gu Q

List of Research Outputs

Dai Y., Qiao L., Gu Q., Xia H.H.X., Cheung T.K., Ma J., Zou B. and Wong B.C.Y., Activation of Pparc and inhibition of Xiap in human cancer cells: Synergistic effects on cell proliferation, apoptosis, and tumorigensis. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A425.

Ge R., Sun X., Gu Q., Watt R.M., Tanner J.A., Wong B.C.Y., Xia H.H.X., Huang J.D., He Q.Y. and Sun H., A proteomic approach for the identification of bismuth-binding proteins in Helicobacter pylori, Journal Biol Inorg Chem. 2007, 12: 831.

Qiao L., Gu Q., Dai Y., Shen Z., Liu X., Ma J. and Wong B.C.Y., XAF1 inhibits angiogenesis of mouse endothelia cells. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A638.

Wang J., Yang Y., Xia H.H.X., Gu Q., Lin M.C., Jiang B., Peng Y., Li G., An X., Zhang Y., Zhuang Z., Zhang Z., Kung H.F. and Wong B.C.Y., Suppression of FHL2 Expression Induces Cell Differentiation and Inhibits Gastric and Colon Carcinogenesis , Gastroenterology. 2007, 132: 1066-1076.

Yu L., Wang J., Zou B., Lin M.C., Wu Y.L., Xia H.H.X., Sun Y., Gu Q., He H., Lam S.K., Kung H.F. and Wong B.C.Y., XAF1 Mediates Apoptosis Through an Extracellular Signal-Regulated Kinase Pathway in Colon Cancer , Cancer. 2007, 109(10): 1996-2003.

Researcher : Guo H

List of Research Outputs

Guo H., Leung J.C.K., Lam M.F., Lan H.Y. and Lai K.N., Smad7 transgene attenuates TGF-b induced peritoneal fibrosis in uremic rats on peritoneal dialysis, Journal of American Society of Nephrology. 2006, 17: 29A.

Lai K.N., Leung J.C.K., Chan L.Y., Guo H. and Tang S.C.W., Interaction between proximal tubular epithelial cells and infiltrating monocytes/T cells in the proteinuric state, Kidney International. 2007, 71: 526-538.

Researcher : He H

List of Research Outputs

Yu L., Wang J., Zou B., Lin M.C., Wu Y.L., Xia H.H.X., Sun Y., Gu Q., He H., Lam S.K., Kung H.F. and Wong B.C.Y., XAF1 Mediates Apoptosis Through an Extracellular Signal-Regulated Kinase Pathway in Colon Cancer , Cancer. 2007, 109(10): 1996-2003.

Zou B., Chim J.C.S., Zeng H., Leung S.Y., Yang Y., Tu S., Lin M.C., Wang J., He H., Jiang S.H., Sun Y., Yu L., Yuen S.T., Kung H.F. and Wong B.C.Y., Correlation Between the Single-site CpG Methylation and Expression Silencing of the XAF1 Gene in Human Gastric and Colon Cancers, Gastroenterology. 2006, 131(6): 1835-1843.

Researcher : Ho CME

List of Research Outputs

Ho C.M.E., Lam K.S.L., Chen A.Y.S., Yip C.W., Arvindakshan M., Yamagishi S., Oates P.J., Ellery C.A., Chung S.S.M. and Chung S.K., Aldose reductase-deficient mice are protected from delayed motor nerve conduction velocity, increased c-Jun NH2-terminal kinase activation, depletion of reduced glutathione, increased superoxide accumulation, and DNA damage, Diabetes. 2006, 55(7): 1946-53.

Researcher : Ho JCM

List of Research Outputs

Au W.Y., Ho J.C.M., Lie A.K.W., Sun J.Z., Zheng L., Liang R.H.S., Lam W.K. and Tsang K.W.T., A prospective study of respiratory ciliary structure and function after stem cell transplantation, Bone Marrow Transplantation. 2006, 38: 243-248.

Ho J.C.M., Chan M.M.W., Ho S.P., Mak J.C.W., Ip M.S.M., Ooi C.G.C., Wong M.P., Tsang K.W.T. and Lam W.K., Disturbance of systemic antioxidant profile in non-small cell lung carcinoma, Eur Respir J . 2007, 29: 273-278.

Ho J.C.M., Drugs acting on respiratory system, Advanced Certificate in Pharmacology and Pharmaceutical Management, HKUSPACE, 24 November. 2006.

Ho J.C.M., Mak J.C.W., Ho S.P., Ip M.S.M., Lam W.K. and Chan M.M.W., Genetic variations of systemic superoxide dismutase and catalase activities in non-small cell lung cancer. Presented at the 11th Congress of the Asian Pacific Society of Respiratory, 19-22 Nov, Respirology. 2006, 11 Suppl 5: A129.

Ho J.C.M., Wong M.P. and Lam W.K., Invited review: Lymphoepithelioma-like carcinoma of the lung, Respirology. 2006, 11(5): 539-545.

Ho J.C.M. and Tsang K.W.T., Lessons from SARS: preparing for the next epidemic. , Pulmonary and Critical Care Updates, American College of Chest Physicians. 2007, 21: Lesson 14.

Ho J.C.M., Lung Cancer, MIMS Respiratory Guide 2006/2007. Hong Kong, CMPMedica Pacific Ltd, 2006, 3rd edition: A112-124.

Ho J.C.M., Mak J.C.W., Ho S.P., Ip M.S.M., Tsang K.W.T., Lam W.K. and Chan M.M.W., Manganese superoxide dismutase and catalase genetic polymorphisms, activity levels and lung cancer risk in Chinese in Hong Kong, J. Thorac. Oncol. 2006, 1: 648-653.

Ho J.C.M., Non-small cell lung cancer: from bench to bedside, M.D. thesis, The University of Hong Kong. 2007.

Ho J.C.M. and Lam W.K., Recent advances in pharmacological treatment of non-small cell lung cancer, Internal Medicine Journal of Thailand. 2006, 22: 82-89.

Ho J.C.M. and Lam W.K., Recent advances in the management of non-small cell lung cancer, The Hong Kong Medical Diary . 2007, 12: 13-17.

Ho J.C.M., The development of respiratory medicine in Hong Kong, 20th Anniversary Annual Scientific Meeting, Hong Kong College of Physicians, 15 October. 2006.

Ho J.C.M., Updates on lung cancer, Dipolma in Oncology and Palliative Care for Health Care Professionals, HKUSPACE, 8 January. 2007.

Ho J.C.M., Young Investigator Award 2006, 11th Congress of the Asian Pacific Society of Respirology. Japanese Respiratory Society/Asian Pacific Society of Respirology. 19-22 Nov 2006. Kyoto, Japan. 2006.

Mak J.C.W., Ho S.P., Ho J.C.M. and Chan M.M.W., Best Poster - Increased oxidative stress in acute asthma exacerbation in Hong Kong Chinese asthmatics, 12th Medical Research Conference . 2007.

Wong M.K., Leung W.C., Wang J.K., Lao T.T.H., Ip M.S.M., Lam W.K. and Ho J.C.M., Recurrent pneumothorax in pregnancy: what should we do after placing an intercostals drain, Hong Kong Medical Journal. Hong Kong, 2006, 12: 375-380.

Researcher : Ho SL

List of Research Outputs

Chan K. .H., Leung S.Y., Cheung R.T.F., Ho S.L. and Mak W., Paraneoplastic motor neuropathy and inflammatory myopathy associated with nasopharyngeal carcinoma., Journal of Neurooncology. 2007, 81: 93-96.

Chan K.H., Mak W. and Ho S.L., Cryptococcal meningitis with raised intracranial pressure masquerading as malignant hypertension, International Journal Infectious Diseases. International Journal Infectious Diseases, 2007, 11(4): 366-7.

Chan K.H., Tsang K.L., Fong C.Y., Ho S.L., Cheung R.T.F. and Mak W., Idiopathic inflammatory demyelinatng disorders after acute transverse myelitis., European Journal of Neurology. 2006, 13(8): 862-8.

Chan K.H., Mak W., Cheung R.T.F. and Ho S.L., Non-thymoma early-onset- and late-onset-generalized myasthenia gravis-A retrospective hospital-based study, Clinical Neurology Neurosurgery. 2007, 109(8): 686-91.

Chan K.H., Leung S.Y., Cheung R.T.F., Ho S.L. and Mak W., Paraneoplastic motor neuropathy and inflammatory myopathy associated with nasopharyngeal carcinoma, J Neurooncol. 2007, 81(1): 93-6.

Chan K.H., Mak W., Cheung R.T.F. and Ho S.L., Patients With Chronic Inflammatory Demyelinating Polyneuropathy And Diabetes Mellitus In Hong Kong Chinese - A Hospital Based Study, Second International Symposium On Healthy Aging. 2007.

Chan K.H., Mak W., Cheung R.T.F. and Ho S.L., Patients with chronic inflammatory demyelinating polyneuropathy and diabetes mellitus in Hong Kong – A hospital based study, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population. 2007, 53.

Cheung R.S.K., Cheung R.T.F., Ho S.L. and Mak W., Mah-jong–induced seizures: case reports and review of twenty-three patients. , Hong Kong Medical Journal. . 2007, 13(4): 314-8.

Chu A.C.Y., Ho W.L., Kwok H.H., Wang Y., Ramsden D.B. and Ho S.L., Human uncoupling protein-4 protects neuronal cell death from MPP+ induced toxicity by regulating mitochondrial membrane potential, reducing ROS and maintaining ATP levels., 11th International Congress of Parkinson's disease and Movement Disorders, Istanbul, Turkey. {Abs]. Istanbul, Turkey., Mov Disord, 2007, 22 (Suppl 16):: 67.

Chu A.C.Y., Ho W.L., Kwok H.H., Kung M.H.W., Ramsden D.B. and Ho S.L., Leptin enhances MPP+-induced mitochondrial dysfunction: a potential for neuroprotection in parkinsonism, 10th International Congress of Parkinson's disease and Movement Disorders, Kyoto, Japan. [Abs]. Kyoto, Japan, Mov Disorders, 2006, 21(Suppl 15): 62.

Fong C.Y., Kwok H.H., Song Y., Cheng T.S., Ho W.L., Chu A.C.Y., Kung M.H.W., Chan K.H., Mak W., Cheung R.T.F., Ramsden D.B. and Ho S.L., Clinical phenotypes of a large Chinese multigenerational kindred with autosomal dominant familial ALS due to Ile149Thr SOD1 gene mutation., Amyotrophic Lateral Sclerosis. 2006, 7(3): 142-149.

Ho S.L., Editorial Board Member, In: Editor-in-chief: Professor Peter Lewitt, Clinical Neuropharmacology. USA, Lippincott Williams & Wilkins, 2006.

Ho S.L., Invited Co-Chairperson and Speaker, Review of top ranking clinical posters, Invited Co-Chairperson and Speaker, 10th International Congress of Parkinson’s disease and Movement Disorders, Kyoto, Japan. 2006.

Ho S.L., Medical treatment of motor fluctuations in Parkinson’s disease., Asian Educational Symposium. Tokyo, Japan. [Abs]. Tokyo, Japan, 2007.

Ho S.L., Medical treatment of motor fluctuations in advanced Parkinson’s disease, Invited Speaker , Asian Education Symposium, Tokyo, Japan. 2007.

Ho W.L., Chu A.C.Y., Kwok H.H., Kung M.H.W. and Ho S.L., Leptin enhances MPP+-induced mitochondrial dysfunctions in SH-SY5Y cells: a potential of neuroprotection in Parkinsonism, University of Hong Kong. 2006.

Ho W.L., Chu A.C.Y., Kwok H.H., Kung M.H.W., Ramsden D.B. and Ho S.L., Stable overexperession of human uncoupling protein-4 reduced ATP production in SH-SY5Y cells: a potential candidate to regulate mitochondrial function and efficiency. Late breaking abstract LB-18. , 10th International Congress of Parkinson's disease and Movement Disorders, Kyoto, Japan. [Abs]. Kyoto, Japan, Mov Disorders, 2006, 21(Suppl 15).

Kwok H.H., Chu A.C.Y., Ho W.L., Ramsden D.B., Kung M.H.W. and Ho S.L., Localization and distribution of uncoupling protein 5 (UCP5) in rat brain., 10th International Congress of Parkinson's disease and Movement Disorders, Kyoto, Japan. [Abs]. . Kyoto, Japan, Mov Disorders, 2006, 21(Suppl 15): 55.

Li M., Jiang L., Song Y., Ho S.L. and Sham P.C., Over-Representation Pattern of SNPs in the Genome of Restless Legs Syndrome Samples., ABS# apbc073 . 2007, Jan14-17,2007.

Luk J.K.H., Sin W.S., Ho S.L. and Chu L.W., Striopallidodentate calcifications in a Chinese elderly woman with parkinsonism and dementia, Asian J Gerontol Geriatr. 2006, 1: 113-5.

Ng M.C., Ho S.L., Ho J.T., Luk D.K. and Yang E.S., Comparison study of normalization methods by visual fMRI. , International Society for Magnetic Resonance in Medicine (ISMRM 2007). [Abs] . Berlin, Germany., 2007.

Ng M.C., Ho J.T., Ho S.L., Lee R., Li G., Cheng T.S., Song Y.Q., Kwok H.H., Ho W.L., Chu C.Y.A., Fong C.Y., Chan K.H., Cheung R.T.F., Li L.S.W., Yang E.S., Luk K.D.K., Hu Y., Ramsden D.B. and Leong Fung L.L.Y., MR-DTI study: abnormal water diffusion pattern in asymptomatic familial amyotrophic lateral sclerosis with SOD1 mutation, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population. 2007, 54.

Researcher : Ho SP

List of Research Outputs

Chan M.M.W., Mak J.C.W., Ho S.P., Cheung A.H.K., Wong P.C., Chan K.K. and Ip M.S.M., Glutathione S-transferase (GST) polymorphisms and GST activity in Hong Kong Chinese COPD patients., International Journal of Tuberculosis and Lung Disease. 2007, 11: 508-14.

Ho J.C.M., Chan M.M.W., Ho S.P., Mak J.C.W., Ip M.S.M., Ooi C.G.C., Wong M.P., Tsang K.W.T. and Lam W.K., Disturbance of systemic antioxidant profile in non-small cell lung carcinoma, Eur Respir J . 2007, 29: 273-278.

Ho J.C.M., Mak J.C.W., Ho S.P., Ip M.S.M., Lam W.K. and Chan M.M.W., Genetic variations of systemic superoxide dismutase and catalase activities in non-small cell lung cancer. Presented at the 11th Congress of the Asian Pacific Society of Respiratory, 19-22 Nov, Respirology. 2006, 11 Suppl 5: A129.

Ho J.C.M., Mak J.C.W., Ho S.P., Ip M.S.M., Tsang K.W.T., Lam W.K. and Chan M.M.W., Manganese superoxide dismutase and catalase genetic polymorphisms, activity levels and lung cancer risk in Chinese in Hong Kong, J. Thorac. Oncol. 2006, 1: 648-653.

Mak J.C.W., Ho S.P., Ho J.C.M. and Chan M.M.W., Best Poster - Increased oxidative stress in acute asthma exacerbation in Hong Kong Chinese asthmatics, 12th Medical Research Conference . 2007.

Mak J.C.W., Hui W.S., Ho S.P., So H.L., Chan M.M.W., Lam W.K., Cho C.H. and Ip M.S.M., Best Poster - Systemic oxidative stress and inflammation in cigarette smoke-exposed rat model, 12th Medical Research Conference. 2007.

Mak J.C.W., Ho S.P., Yu W.C., Choo K.L., Chu C.M., Yew W.W., Lam W.K., Chan M.M.W. and Chan M.M.W., Polymorphisms in MnSOD and catalase genes - functional activity study in smokers with or without COPD., Eur Respir J. 2007, e-pub.

Mak J.C.W., Ho S.P., Leung C.M., Cheung A.H.K., Law K.W., Ip M.S.M. and Chan M.M.W., Relationship between glutathione S-transferase gene polymorphisms and enzyme activity in Hong Kong Chinese asthmatics, American Thoracic Society International Conference, San Francisco, USA. American Journal of Respiratory and Critical Care Medicine. 2007, 175: A461.

Mak J.C.W., Ho S.P., Leung C.M., Cheung A.H.K., Law K.W., So L.K.Y., Chan W.M., Chau C.H., Lam W.K., Ip M.S.M. and Chan W.M., Relationship between glutathione S-transferase gene polymorphisms and enzyme activity in Hong Kong Chinese asthmatics, Clinical and experimental allergy. 2007, 37: 1150-1157.

Researcher : Ho WL

List of Research Outputs

Chu A.C.Y., Ho W.L., Kwok H.H., Wang Y., Ramsden D.B. and Ho S.L., Human uncoupling protein-4 protects neuronal cell death from MPP+ induced toxicity by regulating mitochondrial membrane potential, reducing ROS and maintaining ATP levels., 11th International Congress of Parkinson's disease and Movement Disorders, Istanbul, Turkey. {Abs]. Istanbul, Turkey., Mov Disord, 2007, 22 (Suppl 16):: 67.

Chu A.C.Y., Ho W.L., Kwok H.H., Kung M.H.W., Ramsden D.B. and Ho S.L., Leptin enhances MPP+-induced mitochondrial dysfunction: a potential for neuroprotection in parkinsonism, 10th International Congress of Parkinson's disease and Movement Disorders, Kyoto, Japan. [Abs]. Kyoto, Japan, Mov Disorders, 2006, 21(Suppl 15): 62.

Fong C.Y., Kwok H.H., Song Y., Cheng T.S., Ho W.L., Chu A.C.Y., Kung M.H.W., Chan K.H., Mak W., Cheung R.T.F., Ramsden D.B. and Ho S.L., Clinical phenotypes of a large Chinese multigenerational kindred with autosomal dominant familial ALS due to Ile149Thr SOD1 gene mutation., Amyotrophic Lateral Sclerosis. 2006, 7(3): 142-149.

Ho W.L., Leptin enhances MPP+-induced mitochondrial dysfunction: a potential for neuroprotection in Parkinsonism, Medical Research Conference, HKU - Best Presentation Award. 2007.

Ho W.L., Leptin enhances MPP+-induced mitochondrial dysfunction: a potential for neuroprotection in Parkinsonism, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population, The Research Centre of Heart, Brain, Hormone and Healthy Aging, HKU - Outstanding Abstract Prize (Oral). 2007.

Ho W.L., Chu A.C.Y., Kwok H.H., Kung M.H.W. and Ho S.L., Leptin enhances MPP+-induced mitochondrial dysfunctions in SH-SY5Y cells: a potential of neuroprotection in Parkinsonism, University of Hong Kong. 2006.

Ho W.L., Chu A.C.Y., Kwok H.H., Kung M.H.W., Ramsden D.B. and Ho S.L., Stable overexperession of human uncoupling protein-4 reduced ATP production in SH-SY5Y cells: a potential candidate to regulate mitochondrial function and efficiency. Late breaking abstract LB-18. , 10th International Congress of Parkinson's disease and Movement Disorders, Kyoto, Japan. [Abs]. Kyoto, Japan, Mov Disorders, 2006, 21(Suppl 15).

Kwok H.H., Chu A.C.Y., Ho W.L., Ramsden D.B., Kung M.H.W. and Ho S.L., Localization and distribution of uncoupling protein 5 (UCP5) in rat brain., 10th International Congress of Parkinson's disease and Movement Disorders, Kyoto, Japan. [Abs]. . Kyoto, Japan, Mov Disorders, 2006, 21(Suppl 15): 55.

Ng M.C., Ho J.T., Ho S.L., Lee R., Li G., Cheng T.S., Song Y.Q., Kwok H.H., Ho W.L., Chu C.Y.A., Fong C.Y., Chan K.H., Cheung R.T.F., Li L.S.W., Yang E.S., Luk K.D.K., Hu Y., Ramsden D.B. and Leong Fung L.L.Y., MR-DTI study: abnormal water diffusion pattern in asymptomatic familial amyotrophic lateral sclerosis with SOD1 mutation, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population. 2007, 54.

Researcher : Ho WL

List of Research Outputs

Ho W.L., Leptin enhances MPP+-induced mitochondrial dysfunction: a potential for neuroprotection in Parkinsonism, Medical Research Conference, HKU - Best Presentation Award. 2007.

Researcher : Hoo RLC

Project Title:	Role of adiponectin in mediating the therapeutic actions of the anti-diabetic drug thiazolidinediones
Investigator(s):	Hoo RLC, Xu A, Lam KSL
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2005

Abstract:

Thiazolidinediones (TZDs), such as rosiglitazone and pioglitazone, are peroxisome-proliferator-activated receptor gamma (PPAR-gamma) agonists widely used in the treatment of type 2 diabetes. The cellular mechanism of action of TZDs involves binding to the PPAR-gamma, thus altering the expression of PPAR-gamma responsive gene in fat cells, as well as other cell types such as endothelial cells, macrophage, monocytes, vascular smooth cells (1,2). We and others have shown that they can reduce insulin resistance, hyperglycaemia, and endothelial dysfunction, an early change in atherosclerosis (3-6). However, the mechanism underlying the ability of PPAR-gamma agonists to improve in vivo hyperglycemia and insulin resistance is not well understood. Adipose tissue is now recognized as an important endocrine organ as it can secrete a variety of biologically active peptides such as adiponectin, plasminogen activated inhibitor I (PAI-1), resistin, leptin, TNF-alpha and IL-6. These adipokines are suggested to be critically involved in regulating systemic energy metabolism, insulin sensitivity, cardiovascular tone and immune response (6,7). Our group has been actively studying the regulation and function of adiponectin in recent years. We have shown that treatment with adiponectin can result in direct beneficial effects on insulin resistance, hyperglycaemia, dyslipidaemia and atherogenesis. Many pharmacological studies showed that TZDs, including rosiglitazone, can elevate the mRNA expression and plasma levels of adiponectin in animals and in patients with type 2 diabetes (10,11). However, whether adiponectin mediates the TZD's metabolic effects in T2DM and its related metabolic syndrome remains uncertain. Therefore, in the present study, we seek to investigate the mechanism of metabolic action of a potent TZD, rosiglitazone, in the presence or absence of adiponectin, by using a genetically modified mouse model that lacks both the adiponectin gene and leptin receptor. Major Objectives: The major aim of this study is to elucidate the involvement of adiponectin in the therapeutic function of the potent TZD, rosigltiazone, in the treatment of T2DM. The specific objectives are: 1. To knockout the adiponectin gene from the db/db diabetic mouse model. 2. To use the double knockout mice generated in Objective 1 to investigate whether adiponectin is required for the anti-diabetic action of rosiglitazone.

List of Research Outputs

Hoo R.L.C., Lam C.W., Xu A., Chen B. and Lam K.S.L., ENDOPLASMIC RETICULUM STRESS DOWN-REGULATES THE ADIPOCYTE PRODUCTION OF THE ANTI-DIABETIC AND ANTI-ATHEROGENIC HORMONE ADIPONECTIN, XIV International Symposium on Atherosclerosis,Italy 2006. 2007.

Hoo R.L.C., Chan K.Y., Leung K.Y., Lee T.O., Leung P.C. and Chow B.K.C., Involvement of NF-kappaB subunit p65 and retinoic acid receptors, RARalpha and RXRalpha, in transcriptional regulation of the human GnRH II gene. , FEBS J. 2007 Jun;274(11):2695-2706 . FEBS Journal, 2007, 274: 2695-2706.

Hoo R.L.C., Chow W.S., Yau M.H., Xu A., Tse H.F., Tso A.W.K., Fong H.Y., Tam S., Chan L. and Lam K.S.L., PPAR-γ agonist induced-suppression of plasminogen activator inhibitor-1 production is mediated through adiponectin. , 2nd International Symposium on Healthy Aging, 3-4 March 2007, Hong Kong. 2007.

Hoo R.L.C., Chow W.S., Tse H.F., Fong H.Y., Tam S., Chan L.C.B. and Lam K.S.L., Ppar-γ Agonist Induced-suppression Of Plasminogen Activator Inhibitor-1 Production Is Mediated Through Adiponectin. , HBHA conference. 2007.

Lam K.S.L., Tso A.W.K., Chow W.S., Hoo R.L.C., Zhang J., Lam C.W. and Xu A., Adipocyte fatty acid binding protein as a potential circulating metabolic hormone: clinical and functional studies. , The Endocrine Society’s 88th Annual Meeting, June 24-27, 2006, Boston, USA. 2007.

Wang Y., Lam J.B.B., Lam K.S.L., Liu J., Lam C.W., Hoo R.L.C., Wu D., Cooper G.J. and Xu A., Adiponectin modulates the glycogen synthase kinase-3beta/beta-catenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice, Cancer Res. 2006, 66: 11462-70.

Wang Y., Lam K.S.L., Kraegen E.W., Sweeney G., Zhang J., Tso A.W.K., Chow W.S., Wat N.M.S., Xu J., Hoo R.L.C. and Xu A., Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans, Clin Chem. 2007, 53: 34-41.

Researcher : Hu H

List of Research Outputs

Hu H., Lau C.P. and Li G.R., Characterization of Ionic currents in human preadipocytes, Second International Symposium on Healthy Aging: “Meeting the Challenges of an Aging Population”, The University of Hong Kong, Hong Kong . 2007.

Hu H., Lau C.P. and Li G.R., Demonstration of Ion channels in human preadipocytes, Journal of Hong Kong College Cardiology/The 10th Institute of Cardiovascular Science and Medicine . 2006, 14: 87.

Researcher : Hu HC

Project Title:	A study to validate a symptom severity questionnaire for patents with functional dyspepsia
Investigator(s):	Hu HC, Lam CLK
Department:	Medicine
Source(s) of Funding:	Health Services Research Fund - Full Grants
Start Date:	10/1998

Abstract:

To develop and validate an instrument to measure the severity of symptoms in patients with functional dyspepsia.

List of Research Outputs

Chan A.O.O., Hui W.M., Leung Y.C., Hu H.C., Lam S.K. and Wong B.C.Y., Efficacy of tegasered for functiona constipation in Chinese subjects: A randomized double blind contolled trial in a single center. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4): A194.

Chan A.O.O., Hui W.M., Leung Y.C., Hu H.C., Lam S.K. and Wong B.C.Y., Efficacy of tegaserod for functional constipation in Chinese subjects: a randomized double-blind controlled trial in a single center, Alimentary Pharmacology and Therapeutics. 2007, 25(4): 463-469.

Cheung T.K., Hu H.C., Lam C.L.K., Hui W.M., Lam S.K. and Wong B.C.Y., Positive association between gastro-oesophageal reflux disease and irritable bowel syndrome in a Chinese population. , Aliment Pharmacol Ther . 2007, 25.

Cheung T.K., Lam K.F., Hu H.C., Wong W.M., Hui W.M., Lam C.L.K., Lai K.C., Lam S.K. and Wong B.C.Y., Positive association between gastro-oesophageal reflux disease and irritable bowel syndrome in a Chinese population, Alimentary Pharmacology & Therapeutics. Blackwell Publishing, 2007, 25: 1099-1104.

Hu H.C., Lam S.K., Lam C.L.K., Wong R.W.M., Lam K.F., Lai K.C., Wong Y.H., Wong B.C.Y., Chan O.O., Chan C.K., Leung G.M. and Hui W.M., Comparison between Empirical Prokinetics, Helicobacter Test-and-Treat and Empirical Endoscopy in Primary-Care Patients Presenting with Dyspepsia: A One-Year Study, World Journal of Gastroenterology. 2006, 12(31): 5010-5016.

Lai K.C., Chu K.M., Hui W.M., Wong B.C.Y., Hung W.K., Loo C.K., Hu H.C., Chan O.O., Kwok K.F., Fung T.T., Wong J. and Lam S.K., Esomeprazole with aspirin versus clopidogrel for prevention of recurrent gastrointestinal ulcer complications, Clinical Gastroenterology and Hepatology. 2006, 4: 860-865.

Researcher : Huang CY

List of Research Outputs

Chan A.O.O., Chu K.M., Huang C.Y., Lam K.F., Leung S.Y., Sun Y., Ko S., Xia H.H.X., Cho C.H., Hui W.M., Lam S.K. and Rashid A., Association between Helicobacter pylori infection and interleukin 1beta polymorphism predispose to CpG island methylation in gastric cancer, GUT. 2007, 56: 595-597.

Chan A.O.O., Huang C.Y., Leung Y.C., Hui W.M., Lam S.K. and Wong B.C.Y., Familial constipationis associated with a2 adrenoceptor polymorphism. Digestive Diseases Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A189.

Chan O.O., Huang C.Y., Hui W.M., Cho C.H., Yuen R.M.F., Lam S.K., Rashid A. and Wong B.C.Y., Stability of E-cadherin methylation status in gastric mucosa associated with histology changes. , Alimentary Pharmacology and Therapeutics. 2006, 24(5): 831-6.

Researcher : Huang H

List of Research Outputs

Cheung M.S., Shek W.K., Shek W.K., Leung J.C.K., Chan Y.Y., Huang H., Kwong Y.L., Liang R.H.S. and Leung A.Y.H., Aldehyde dehydrogenase activity in leukemic blasts defines a subgroup of acute myeloid leukemia with adverse prognosis and superior NOD/SCID engrafting potential, Leukaemia. 2007, 21: 1423-1430.

Researcher : Huang J

Project Title:	Hepatitis B or Hepatitis C viral infection and genotypes - which subgroup is more prone to the development of hepatocellular carcinoma? A systematic review
Investigator(s):	Huang J, Wong BCY, Lai CL, Yuen RMF
Department:	Clinical Trials Ctr
Source(s) of Funding:	Health and Health Services Research Fund - Full Grants
Start Date:	01/2004

Abstract:

To identify which subgroups of population infected with HBV/HCV are at higher risk for developing hepatocellular carcinoma (HCC).

List of Research Outputs

Wang W.H., Huang J., Zheng G., Xia H.H.X., Wong R.W.M., Liu X.G., Karlberg J.P.E. and Wong B.C.Y., Effects of proton-pump inhibitors on function dyspepsia: A meta-analysis of randomized placebo-controlled trails, Clinical Gastroenterology & Hepatology. 2007, 5(2): 178-185.

Researcher : Huang Q

Project Title:	Powerful and robust association studies of six positional and functional candidate genes with bone mass in Southern Chinese
Investigator(s):	Huang Q, Kung AWC
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	01/2006

Abstract:

Background Osteoporosis is a skeletal disease characterized by low bone mineral density (BMD) and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. The most common clinical outcomes of osteoporosis are fracture of the spine, hip and wrist. Of these, hip fractures are the most severe, leading to a 12-20% reduction of expected survival. The direct cost for hip fractures was around $13.8 billion in the US in 1995 (Ray et al. 1995), and £942 million in the UK in 1998 (Torgerson and Cooper, 1998). At present, osteoporosis affects 200,000 females and 100,000 males in Hong Kong. It is projected that by 2050, more than 50% of the world’s hip fractures will occur in Asia, mainly in China. It is well established that BMD and osteoporosis are under strong genetic control. However, identification of the genetic variants that cause osteoporosis still remains a daunting task for geneticists due to its genetic complexity [1]. Chromosomal regions 1p36, 12q23-24, and 20p12 are linked to osteoporosis in multiple genome-wide linkage studies [2-10]. CNR2, TNFR2, MTHFR, PLOD, IGF1, and BMP2 genes, which have demonstrated biological functional importance in bone metabolism, are located in these regions. Therefore, they are excellent positional and functional candidate genes for osteoporosis. However, whether or not they are associated with bone mass variation in Southern Chinese has not been established. Extensive regular association studies using a limited few markers have generated controversies for prominent candidate genes studied. The International Hapmap project has already been completed [11]. Screening multiple markers ulilizing this new resources is necessary for testing the significance of candidate genes systematically. In this project, we will conduct powerful and robust association studies of six positional and functional candidate genes and bone mass in Sourthern Chinese by using tag SNPs from the International Hapmap project. Objectives 1) To investigate whether genetic variability in six positional and functional candidate genes is associated with bone mass variation. 2) To determine the pattern of linkage disequilibrium, and estimate haplotype distribution at these genes in large Sourthern Chinese populations.

Project Title:	Systematic evaluation and screen of the regions previously linked to osteoporosis in Southern Chinese
Investigator(s):	Huang Q, Kung AWC, Sham PC
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	10/2006

Abstract:

To determine whether the genomic regions previously identified in genome scans contribute to osteoporosis/BMD in Southern Chinese by performing genetic linkage analyses; to investigate whether genetic variability in candidate genes in the region of linkage is associated with BMD variation.

Project Title:	To evaluate the contribution of six monogenic bone disease genes to common osteoporosis in Chinese
Investigator(s):	Huang Q, Kung AWC
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	01/2007

Abstract:

Complex diseases such as osteoporosis result from the combined effects of variation in a number of genes as well as environmental factors (1-2). Identification of susceptibility gene(s) underlying complex diseases remains a difficult challenge in the genome era. Previous efforts to identify osteoporosis genes have focused on three approaches: genome-wide scans, candidate gene study, and animal models (2). Although genome-wide linkage scans in human have identified a few significant or suggestive linkage regions for bone mineral density (BMD), the responsible genes in these linkage regions have not been identified. Previous association studies of functional candidate genes based on one or a few markers have generated inconsistent results. Alox15, the first gene that regulates BMD and is identified by positional cloning in mice has not been consistently confirmed in humans (1). Limited success in identifying osteoporosis susceptibility gene(s) might necessitate the development of new gene identification strategies. Accumulating evidence shows that genes that cause monogenic diseases also contribute to similar complex disease in the general population, and identification and characterization of monogenic disease genes can provides new clues for understanding complex diseases (3-4). A well-known example in the study of bone is the identification of LPR5 gene mutations. Inactivating mutations of the LRP5 gene are the cause of osteoporosis pseudoglioma syndrome (5), whereas activating mutations in the same gene causes autosomal dominant inheritance of high bone mass (6-7). Follow-up studies have shown that LRP5 polymorphisms may also contribute to normal variation in BMD in the general population (1). LPR5 is a co-receptor for Wnt. Of the pathways activated by Wnts, it is signaling through the canonical (i.e., Wnt/beta-catenin) pathway that increases bone mass through a number of mechanisms including renewal of stem cells, stimulation of preosteoblast replication, induction of osteoblastogenesis, and inhibition of osteoblast and osteocyte apoptosis (8). Identification of the LPR5 gene has provided insight into the regulation of bone mass by Wnt signaling, paving the way towards understanding of the molecular mechanism behind common osteoporosis. The discovery of the LRP5 gene as a genetic element in BMD regulation in monogenic bone disease as well as BMD variation in the normal population indicates that 'Mendelian' strategy may be a powerful approach for searching for susceptibility genes that affect complex diseases such as osteoporosis. Osteoporosis is a disease characterized by low BMD, deterioration in bone microarchitecture and increased fracture risk. Osteoporosis and fragility fractures are features of several rare monogenic bone diseases. Spectacular progress has been made in the past few years in identifying genes for rare monogenic bone diseases (1): osteogenesis imperfecta, COLIA1; osteoporosis-pseudoglioma syndrome, LRP5; osteopetrosis, TCIRGI; Camurati-Engelmann disease, TGFß-1; sclerosteosis/van Buchem disease, SOST; severe infantile osteopetrosis, CLCN7; osteopetrosis with renal tubular acidosis, CA2; pyknodysostosis, CTSK; McCune-Albright syndrome, GNAS1; diastrophic dysplasia, DTDST; multiple epiphyseal dysplasia, COMP; and cleidocranial dysplasia, CBFA1. If severe mutations lead to rare monogenic disease, more subtle mutations might play a role in determining susceptibility to common complex diseases. Preliminary studies in Caucasians indicate that some genes that are mutated in rare bone diseases also contribute to the regulation of BMD in the normal population (1). Therefore, mutant genes that give rise to monogenic bone diseases provide a unique opportunity to understand the allelic variability for susceptibility to osteoporosis. The purpose of this project is to determine whether the allelic variation in six monogenic bone disease genes (CLCN7, TCIRGI, SOST, CA2, CSTK, and DTDST) contributes to osteoporosis / BMD variation in the normal Chinese population by performing gene-wide and tag SNP-based association analyses. Preliminary data from this study will provide strong support in using 'Mendelian' strategy to identify the genes/variants involved in susceptibility to osteoporosis in Chinese in future RGC application. References 1. Huang QY, Kung AWC. Genetics of osteoporosis. Mol Genet Metab, 2006, 88: 295-306 2. Huang QY, Recker RR, Deng HW. Searching for the osteoporosis gene(s) in the post-genome era: progress and challenge. Osteoporos Int, 2003, 14(9):701-715 3. Peltonen L, Perola M, Naukkarinen J, Palotie A. Lessons from studying monogenic disease for common disease. Hum Mol Genet, 2006,15: R67-74 4. Antonarakis SE, Beckmann JS. Mendelian disorders deserve more attention. Nat Rev Genet, 2006, 7(4):277-82 5. Gong Y, Slee RB, Fukai N, et al. Osteoporosis-Pseudoglioma Syndrome Collaborative Group. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell, 2001, 107: 513-523 6. Little RD, Carulli JP, Del Mastro RG, et al. A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am J Hum Genet, 2002, 70: 11-19 7. Boyden LM, Mao J, Belsky J, et al. High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med, 2002, 346: 1513-21 8. Krishnan V, Bryant HU, Macdougald OA. Regulation of bone mass by Wnt signaling. J Clin Invest, 2006, 116(5):1202-9

List of Research Outputs

Cheung C.L., Huang Q., Ng M.Y.M., Chan V.N.Y., Sham P.C. and Kung A.W.C., Confirmation of linkage to chromosome 1q for spine bone mineral density in Southern Chinese, 11th Research Postgraduate Symposium, HKU, 7 Dec 2006.

Cheung C.L., Huang Q., Ng M.Y.M., Chan V.N.Y., Sham P.C. and Kung A.W.C., Confirmation of linkage to chromosome 1q for spine bone mineral density in southern Chinese, Human Genetics. 2006, 120: 354-359.

Cheung C.L., Huang Q., Ng M.Y.M., Chan V.N.Y., Sham P.C. and Kung A.W.C., Confirmation of linkage to chromosome 1q for spine bone mineral density in southern Chinese, Journal of Bone and Mineral Research. 2006, 21(Suppl 1): S146.

Huang Q. and Kung A.W.C., Genetics of osteoporosis, Mol Genet Metab. 2006, 88: 295-306.

Huang Q., Genetics of osteoporosis, The International Huaxia Congress of Endocrinology 2006, Hong Kong, 2006-12-18 . 2006.

Huang Q., Cheung C.L., Chan V.N.Y., Sham P.C. and Kung A.W.C., Identification of Two Sex-specific Quantitative Trait Loci in Chromosome 11q for Hip Bone Mineral Density in Chinese , 56th Annual Meeting of The American Society of Human Genetics . 2006.

Huang Q., Ng M.Y.M., Cheung C.L., Chan V.N.Y., Sham P.C. and Kung A.W.C., Identification of two sex-specific quantitative trait loci in chromosome 11q for bone mineral density in southern Chinese, Human Heredity. 2006, 61: 237-243.

Huang Q., Ng M.Y.M., Cheung C.L., Chan V., Sham P.C. and Kung A.W.C., Identification of two sex-specific quantitative trait loci in chromosome 11q for hip bone mineral density in Chinese, Human Heredity. 2006, 61(4): 237-243.

Huang Q., Cheung C.L., Chan V.N.Y., Sham P.C. and Kung A.W.C., Peak-wide association study on chromosome 3p21 identifies the CACNA2D2 gene as a novel susceptibility gene for osteoporosis , 8th International Meeting on Human Genome Variation and Complex Genome Analysis (HGV2006). 2006.

Huang Q., Towards the identification of susceptibility genes for osteoporosis in Chinese, Chengdu - Hong Kong Medical Forum 2007,Chengdu,2007-5-7 . 2007.

Kung A.W.C. and Huang Q., Genetic and environmental determinants of osteoporosis (Invited Review), Journal of Musculoskeletal and Neuronal Interactions. 2007, 7: 26-32.

Kung A.W.C. and Huang Q., Genetic and environmental determinants of osteoporosis, J Musculoskelet Neuronal Interact. 2007, 7: 26-32.

Researcher : Hui CK

List of Research Outputs

Hui C.K., Bowden S., Zhang H.Y., Wong A., Lewin S., Rousseau F., Mommeja-Marin H., Lee N.P., Luk J.M., Locarnini S., Leung N., Naoumov N.V. and Lau G., Comparison of real-time PCR assays for monitoring serum heptatis B virus DNA levels during antiviral therpay., J Clin Microbiol. 2006, 44(8): 2983-7.

Hui C.K., Zhang H., Shek T., Yao H., Yueng Y.H., Leung K.W., Lai S.T., Lai J.Y., Leung N. and Lau G., Disease progression in Chinese chronic hepatitis C patients with persistently normal alanin aminotransaminase levels, Alimentary Pharmacology Therapy. 2007, 25(11): 1283-92.

Hui C.K., Cheung W.W.W., Chan S.C., Lo C.M. and Lau G., Hepatitis B vaccination and preemptive treatment of hepatitis B virus in liver transplantation, Current Opinion in Organ Transplantation. 2006, 11(6): 594-598.

Hui C.K., Lau E., Monto A., Kim M., Luk J.M.C., Poon R.T.P., Leung N., Lo C.M., Fan S.T., Lau G. and Wright T.L., Natural history of patients with recurrent chronic hepatitis C virus and occult hepatitis B co-infection after liver transplantation, American Journal of Transplantation. 2006, 6(7): 1600-1608.

Hui C.K., Liang R.H.S. and Lau G., Reply to "Kinetics of hepatitis B virus reactivation after chemotherapy: more questions than answers , Gastroenterology. 2006, 131(5): 1656-1657.

Hui C.K., Cheung W.W., Zhang H.Y., Au W.Y., Leung N., Luk J.M., Lie A.K.W., Kwong Y.L., Liang R.H.S. and Lau G., Rituximab increases the risk of de novo hepatitis B infection in hepatitis B surface antigen negative patients undergoing cytotoxic chemotherpay, Gastroenterology. 2006, 131(1): 59-68.

Hui C.K., Zhang H., Lee P.Y., Marin H., Yueng Y.H., Leung K.W., Lu L., Leung N., Luk J.M.C., Naoumov N., Huang F. and Lau G., Role of regulatory T cells in natural immunity and sustained pharmacological control hepatitis B infection, The Liver Meeting of The American Association for the Study of Liver, Hepatology. 2006, 44: 543A.

Hui C.K., Zhang H.Y., Lee P.Y., Mommeja-Marin H., Yueng Y.H., Leung K.W., Lu L., Leung N., Luk J.M.C., Naoumov N.N., Huang F.P. and Lau G., Role of regulatory T cells in natural immunity and sustained pharmacological control of chronic hepatitis B infection, Hepatology. 2006, 44(4): 543A-543A.

Lai L., Hui C.K., Poon R.T.P., Shek T.W.H., Lai S.T., Lai J.Y., Lo C.M., Fan S.T., Leung N. and Lau G., The use of transient elastography as a preoperative assessment of hepatic resection (Abstract), The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007. Hepatology International. 2007, 1(1): 51.

Lu L., Sun R.W.Y., Hui C.K., Chen R., Luk J.M.C., Che C.M. and Lau K.K., In Vitro Anti-hepatitis B Virus Activities and Mechanism of Metal-based Nanoparticles , Hepatology . 2006, 44 (Suppl.1): 553A.

Lu L., Sun R.W.Y., Hui C.K., Chen R., Luk J.M.C., Che C.M. and Lau G., In Vitro Anti-hepatitis B Virus Activities and Mechanism of Silver Nanoparticles,The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007, Hepatology International. 2007, 242: 14.

Lu L., Sun R.W.Y., Hui C.K., Chen R., Luk J.M.C., Che C.M. and Lau G., Size-dependent anti-hepatic B virus activities and mechanism of silver nanoparticles, The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007.

Lu L., Sun R.W.Y., Hui C.K., Chen R., Luk J.M.C., Che C.M. and Lau G., Size-dependent anti-hepatitis B virus activities and mechanism of silver nanoparticles (Abstract), Hepatology International. 2007, 1(1): 14.

Luk J.M.C., Zhang Q.S., Lee P.Y., Wo Y.H., Leung P.L., Liu L.X., Hu M.Y., Cheung K.F., Hui C.K., Lau G. and Fan S.T., Hepatic stellate cell-targeted delivery of M6P-HSA-glycyrrhetinic acid attenuates hepatic fibrogenesis in a bile duct ligation rat model, Liver International. 2007, 27(4): 548-557.

Naoumov N.V., Hui C.K., Chen J.J., Cooksley H. and Lau G., Longitudinal analysis of Cytokine and chemokine profiles in patients with HBeAg-positive CHB udner difference therapy regimens, The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007, Hepatology International. 2007, 242: 130.

Wang X., Luk J.M.C., Garcia-Barcelo M.M., Miao X., Leung P.L., Ho D.W.Y., Cheung S.T., Lam B.Y.H., Cheung C.K.Y., Wong S.Y., Lau S.S.M., So M.T., Yu W.C., Cai Q., Liu K.S.Y., Hui C.K., Lau G., Poon R.T.P., Wong J. and Fan S.T., Liver intestine-cadherin (CDH17) haplotype is associated with increased risk of hepatocellular carcinoma, Clinical Cancer Research. 2006, 12(17): 5248-5252 (corresponding author).

Zhang H., Hui C.K., Lee P.Y., Chan W., Yueng Y.H., Leung K.W., Lu L., Leung N., Lo C.M., Fan S.T., Luk J.M.C., Xu A., Lam K.S.L., Kwong Y.L. and Lau G., Serum adiponectin is increased in advancing liver fibrosis and decline with reduction in fibrosis in chronic hepatitis B, The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007, Hepatology International. 2007, 242: 7.

Researcher : Hui CK

Project Title:	Significance of occult hepatitis B infection in patients undergoing autologous HSCT
Investigator(s):	Hui CK, Liang RHS, Lau G, Lie AKW
Department:	Medicine
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	10/2006

Abstract:

(1) The occurrence of de novo HBV or occult HBV infection with or without clinical hepatitis after HSCT in HBsAg negative patients pre-HSCT; (2) the risk of transmitting de novo or occult HBV from occult HBV infected blood products to HBsAg negative immunocompromised patients.

List of Research Outputs

Hui C.K., Liang R.H.S. and Lau G., Reply to "Kinetics of hepatitis B virus reactivation after chemotherapy: more questions than answers , Gastroenterology. 2006, 131(5): 1656-1657.

Researcher : Hui CK

List of Research Outputs

Hui C.K., Liang R.H.S. and Lau G., Reply to "Kinetics of hepatitis B virus reactivation after chemotherapy: more questions than answers , Gastroenterology. 2006, 131(5): 1656-1657.

Researcher : Hui WM

List of Research Outputs

Chan A.O.O., Jim M.H., Lam K.F., Siu D.C.W., Tong S.M., Ng F.H., Wong S.Y., Hui W.M., Lam S.K. and Wong B.C.Y., Aspirin does not prevent recurrence of colorrectal adenomas in patients with coronary artery disease. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A194.

Chan A.O.O., Chu K.M., Huang C.Y., Lam K.F., Leung S.Y., Sun Y., Ko S., Xia H.H.X., Cho C.H., Hui W.M., Lam S.K. and Rashid A., Association between Helicobacter pylori infection and interleukin 1beta polymorphism predispose to CpG island methylation in gastric cancer, GUT. 2007, 56: 595-597.

Chan A.O.O., Hui W.M., Leung Y.C., Wong Y.H., Chan P., Hung I.F.H., Hsu A., But D., Lam S.K. and Wong B.C.Y., Better efficacy of tegaserod in constipated patients with slow colonic transit, absent pelvic floor dyssynergy and absent impaired rectal sensation. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A194.

Chan A.O.O., Chow R., Hui W.M., Leung Y.C., Tong S.M., Lam S.K. and Wong B.C.Y., Biofeedback is equally effective in patients with short or long duration of function constipation. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A194.

Chan A.O.O., Hui W.M., Wong Y.H., Leung Y.C., Lam S.K. and Wong B.C.Y., Decreased cortical activation during rectal distention in patients with functional constipation with normal rectal compliance. Digestive Disease Week 2007, Washington DC, USA, May 19-24, Gastroenterology. 2007, 132(4) Suppl 2: A23.

Chan A.O.O., Hui W.M., Leung Y.C., Hu H.C., Lam S.K. and Wong B.C.Y., Efficacy of tegasered for functiona constipation in Chinese subjects: A randomized double blind contolled trial in a single center. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4): A194.

Chan A.O.O., Hui W.M., Leung Y.C., Hu H.C., Lam S.K. and Wong B.C.Y., Efficacy of tegaserod for functional constipation in Chinese subjects: a randomized double-blind controlled trial in a single center, Alimentary Pharmacology and Therapeutics. 2007, 25(4): 463-469.

Chan A.O.O., Hui W.M., Lam K.F., Leung G.K.L., Yuen R.M.F., Lam S.K. and Wong B.C.Y., Familial aggregation in constipated subjects in a tertiary referral center, American Journal of Gastroenterology. Blackwell Publishing, 2007, 102: 149-152.

Chan A.O.O., Huang C.Y., Leung Y.C., Hui W.M., Lam S.K. and Wong B.C.Y., Familial constipationis associated with a2 adrenoceptor polymorphism. Digestive Diseases Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A189.

Chan A.O.O., Lam K.F., Hui W.M., Leung G.K.L., Wong Y.H., Lam S.K. and Wong B.C.Y., Influence of Positive Family History on Clinical Characteristics of Functional Constipation, Clinical Gastroenterology and Hepatology. Elsevier, 2007, 5(2): 197-200.

Chan A.O.O., Jim M.H., Lam K.F., Siu D.C.W., Tong S.M., Ng F.H., Wong S.Y., Hui W.M., Chan C.K., Lai K.C., Cheung T.K., Chan P., Wong G., Yuen R.M.F., Lau Y.K., Lee S.W.L., Seto M.L., Lam S.K. and Wong B.C.Y., Patients with coronary artery disease had high prevalanece of colorectal cancer and adenoma: END-results of metabolic syndrome and smoking. Digestive Disease Week 2007, Washington DEc, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A65.

Chan A.O.O., Hui W.M., Leung G.K.L., Tong T.P.H., Hung I.F.N., Chan P., Hsu A., But D., Wong B.C.Y., Lam S.K. and Lam K.F., Patients with functional constipation do not have increase prevalence of colorectal cancer precursors”, GUT. British Medicial Journal, 2007, 56: 451-452.

Chan O.O., Lam K.F., Tong T.P.H., Siu D.C.W., Jim M.H., Hui W.M., Lai K.C., Yuen R.M.F., Lam S.K. and Wong B.C.Y., Coexistence between colorectal cancer/adenoma and coronary artery disease: results from 1382 patients. , Alimentary Pharmacology and Therapeutics. 2006, 24(3): 535-9.

Chan O.O., Huang C.Y., Hui W.M., Cho C.H., Yuen R.M.F., Lam S.K., Rashid A. and Wong B.C.Y., Stability of E-cadherin methylation status in gastric mucosa associated with histology changes. , Alimentary Pharmacology and Therapeutics. 2006, 24(5): 831-6.

Cheung T.K., Hu H.C., Lam C.L.K., Hui W.M., Lam S.K. and Wong B.C.Y., Positive association between gastro-oesophageal reflux disease and irritable bowel syndrome in a Chinese population. , Aliment Pharmacol Ther . 2007, 25.

Cheung T.K., Lam K.F., Hu H.C., Wong W.M., Hui W.M., Lam C.L.K., Lai K.C., Lam S.K. and Wong B.C.Y., Positive association between gastro-oesophageal reflux disease and irritable bowel syndrome in a Chinese population, Alimentary Pharmacology & Therapeutics. Blackwell Publishing, 2007, 25: 1099-1104.

Hu H.C., Lam S.K., Lam C.L.K., Wong R.W.M., Lam K.F., Lai K.C., Wong Y.H., Wong B.C.Y., Chan O.O., Chan C.K., Leung G.M. and Hui W.M., Comparison between Empirical Prokinetics, Helicobacter Test-and-Treat and Empirical Endoscopy in Primary-Care Patients Presenting with Dyspepsia: A One-Year Study, World Journal of Gastroenterology. 2006, 12(31): 5010-5016.

Lai K.C., Chu K.M., Hui W.M., Wong B.C.Y., Hung W.K., Loo C.K., Hu H.C., Chan O.O., Kwok K.F., Fung T.T., Wong J. and Lam S.K., Esomeprazole with aspirin versus clopidogrel for prevention of recurrent gastrointestinal ulcer complications, Clinical Gastroenterology and Hepatology. 2006, 4: 860-865.

Lam T.J., Mulder C.J.J., Peña S., Wong B.C.Y., Hui W.M., Lam S.K. and Chan A.O.O., Increased in prevalence of advanced colonic polyps in young patients over the past eight years in Hong Kong. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A195.

Tang L.P., Cho C.H., Hui W.M., Huang C., Chu K.M., Xia H.H.X., Lam S.K., Rashid A., Wong B.C.Y. and Chan O.O., An inverse correlation between IL-6 and select gene promoter methylation in patients with gastric cancer, Digestion. 2006, 74: 85-90.

Researcher : Hui WS

List of Research Outputs

Mak J.C.W., Hui W.S., Ho S.P., So H.L., Chan M.M.W., Lam W.K., Cho C.H. and Ip M.S.M., Best Poster - Systemic oxidative stress and inflammation in cigarette smoke-exposed rat model, 12th Medical Research Conference. 2007.

Pan N.Y., Hui W.S., Tipoe G.L., Taylor G.W., Leung Y.H., Lam W.K., Tsang K.W.T. and Mak J.C.W., Inhibition of pyocyanin-potentiated IL-8 release by steroids in bronchial epithelial cells, Respiratory medicine. 2006, 100(9): 1614-1622.

Researcher : Hung IFN

List of Research Outputs

Chan A.O.O., Hui W.M., Leung G.K.L., Tong T.P.H., Hung I.F.N., Chan P., Hsu A., But D., Wong B.C.Y., Lam S.K. and Lam K.F., Patients with functional constipation do not have increase prevalence of colorectal cancer precursors”, GUT. British Medicial Journal, 2007, 56: 451-452.

Researcher : Ip MSM

Project Title:	The efficacy of the modified oral appliance in the treatment of mild and moderate obstructive Sleep Apnoea
Investigator(s):	Ip MSM
Department:	Medicine
Source(s) of Funding:	Other Funding Scheme
Start Date:	02/1997

Abstract:

To assess the efficacy, side effects and patient acceptance of an oral appliance in the treatment of obstructive sleep apnoea; to define the clinical, anthropometric, polysomnographic and cephalometric characteristics that determine treatment response.

Project Title:	The effect of oral appliance (OA) in treatment of obstructive sleep apnoea
Investigator(s):	Ip MSM, Peh WCG, Cooke MS
Department:	Medicine
Source(s) of Funding:	Other Funding Scheme
Start Date:	06/1997

Abstract:

To study the efficacy of OA in teatment of mild/moderate OSA; to study the safety profile of OA.

Project Title:	Role of adiponectin in obstructive sleep apnoea
Investigator(s):	Ip MSM, Lam KSL
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2002

Abstract:

To investigate serum adiponectin levels in OSA patients with a spectrum of body mass index (BMI) and sleep disordered breathing (no OSA to severe OSA) and define correlative parameters; to investigate for any difference in adiponectin levels in patients with OSA and BMI-matched subjects with no OSA (3) the impact of nasal Continuous Positive Airway pressure (nCPAP) treatment on adiponectin secretion in subjects with OSA.

Project Title:	Candidate genes of obstructive sleep apnoea syndrome in Hong Kong Chinese
Investigator(s):	Ip MSM, Lam KSL, Song Y, Sham PC, Lam CL
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	01/2005

Abstract:

The main objectives of this project are: 1) To study the presence and role of genetic polymorphism of selected candidate genes relating to the obesity phenotypes in the OSA patients in Hong Kong 2) As an initiating project, to provide pilot data on the role of genetic changes in selected candidate genes in Chinese OSA patients, and to prepare for future in-depth studies in family cohorts

Project Title:	Endothelial damage and atherosclerosis in obstructive sleep apnea: the role of advanced glycation end products
Investigator(s):	Ip MSM, Tse HF, Tan KCB, Ooi CGC
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	09/2006

Abstract:

To explore the relationship between insulin resistance and the formation of advanced glycation end products (AGE) in obstructive sleep apnea (OSA); to evaluate the role of AGE in vascular endothelial damage in OSA; to investigate the relationship between AGE and atherosclerosis in OSA.

List of Research Outputs

Chan C.H., Ip M.S.M. and Shum D.K.Y., Targeting heparan sulfate/syndecan-1 in attempts to restore the balance between neutrophil elastase and anti-elastase in bronchiectasis., Gordon Research Conference on Proteoglycans, July 9-14, Andover, New Hampshire, USA . 2006.

Chan M.M.W., Mak J.C.W., Ho S.P., Cheung A.H.K., Wong P.C., Chan K.K. and Ip M.S.M., Glutathione S-transferase (GST) polymorphisms and GST activity in Hong Kong Chinese COPD patients., International Journal of Tuberculosis and Lung Disease. 2007, 11: 508-14.

Cheung T.K., Lam B., Ip M.S.M., Wong Y.H., Chan A.O.O., Lam S.K. and Wong B.C.Y., Nocturnal Reflux Symptoms Correlate with Respiratory Events in Patients with Obstructive Sleep Apnea. , AGA Digestive Digestive Disease Week 2007.

Cheung T.K., Lam B., Ip M.S.M., Wong Y.H., Chan A.O.O., Lam S.K. and Wong B.C.Y., Nocturnal reflux symptoms correlate with respiratory events in patients with obstructive sleep apnea. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132 (4) Supp 2: A482.

Ho J.C.M., Chan M.M.W., Ho S.P., Mak J.C.W., Ip M.S.M., Ooi C.G.C., Wong M.P., Tsang K.W.T. and Lam W.K., Disturbance of systemic antioxidant profile in non-small cell lung carcinoma, Eur Respir J . 2007, 29: 273-278.

Ho J.C.M., Mak J.C.W., Ho S.P., Ip M.S.M., Lam W.K. and Chan M.M.W., Genetic variations of systemic superoxide dismutase and catalase activities in non-small cell lung cancer. Presented at the 11th Congress of the Asian Pacific Society of Respiratory, 19-22 Nov, Respirology. 2006, 11 Suppl 5: A129.

Ho J.C.M., Mak J.C.W., Ho S.P., Ip M.S.M., Tsang K.W.T., Lam W.K. and Chan M.M.W., Manganese superoxide dismutase and catalase genetic polymorphisms, activity levels and lung cancer risk in Chinese in Hong Kong, J. Thorac. Oncol. 2006, 1: 648-653.

Hou H.M., Hagg E.U.O., Sam K., Rabie A.B.M., Wong R.W.K., Lam B. and Ip M.S.M., Dentofacial Characteristics of Chinese Obstructive Sleep Apnea Patients in Relation to Obesity and Severity, The Angle Orthodontist. 2006, 76 No.6: 962-969.

Ip M.S.M., (1) Sleep disordered breathing in Asia - an emerging challenge and (2) OSA and lipids, 2nd World Congress of World Association of Sleep Medicine, Bangkok, Thailand, February 2007. 2007.

Ip M.S.M., Chairperson, (1) Vascular homeostasis in obstructive sleep apnea and (2) Metabolic and cardiovascular function in obstructive sleep apnea, American Thoracic Society International Conference, May 2007. 2007.

Ip M.S.M., Chairperson, Recent advance in the management of obstructive lung diseases, Hong Kong Thoracic Society & American College of Chest Physicians (HK & Macau Chapter) Annual Scientific Meeting, March 2007. 2007.

Ip M.S.M., Chairperson, Sleep and the heart, Annual Scientific Meeting, Hong Kong Society of Sleep Medicine, October 2006. 2006.

Ip M.S.M., Co-Chairperson, Multidisciplinary Symposium - Lung Cancer, Cancer Imaging 2007 - Joint Meeting of the International Cancer Imaging Society (ICIS) & Hong Kong College of Radiologists (HKCR). 2007.

Ip M.S.M., Interactions between insulin resistance, dyslipidemia and obstructive sleep apnea in promoting atherosclerosis, American Thoracic Society International Conference, San Francisco, USA, May 2007. 2007.

Ip M.S.M., Obstructive sleep apnea : what is the evidence for vascular pathogenesis?, Education Seminar of the Asian Pacific Society of Respirology (APSR), Tokyo, Japan, September 2006. 2006.

Ip M.S.M., Obstructive sleep apnea and metabolic dysfunction (Meet the Expert) , 11th Congress of the Asian Pacific Society of Respirology (APSR), Kyoto, Japan, 19-22 September 2006. 2006.

Ip M.S.M., Obstructive sleep apnoea : What is the evidence for vasulcar pathogenesis?, Respirology. 2006, 12 (suppl 2): S12-S14.

Ip M.S.M., Pathophysiology of obstructive sleep apnea and cardiovascular disease, Task Force on Epidemiology and Prevention, International Diabetes Federation, Consensus meeting on OSA and type 2 diabetes, Sydney, Australia, February 2007. 2007.

Ip M.S.M., Yam L.Y.C., Lam C.L.K. and Sam K., Randomized controlled study of treatment for mild and moderate sleep apnoea, Hong Kong Medical Journal. 2007, 13 (suppl 3): S4-7.

Ip M.S.M., Lam W.K., Lai A.Y.K., Ko F., Lau A., Ling S.O., Chan J. and Chan W.M., Reference values of diffusing capacity of non-smoking Chinese in Hong Kong, Respirology. 2007, 12: 599-606.

Ip M.S.M., Lam W.K., Lai A.Y.K., Ko F.W., Lau A.C., Ling S.O., Chan J.W. and Chan M.M.W., Reference values of diffusing capacity of nonsmoking Chinese in Hong Kong., Respirology. 2007, 12: 599-606.

Ip M.S.M. and Mokhlesi B., Sleep and glucose intolerance/diabetes mellitus, In: Collop NA, Medical Disorders and Sleep. Sleep Medicine Clinics. Elsevier Saunders, 2007, 2: 19-29.

Ip M.S.M., Sleep apnea, metabolic changes and atherosclerosis - where are we?, 8th World Congress on Sleep Apnea, Montreal, Canada, September 2006. 2006.

Lam B., Lam C.L. and Ip M.S.M., Obstructive sleep apnoea in Asia, International Journal of Tuberculosis and Lung Disease. 2007, 11: 2-11.

Lam B., Sam K., Mok W.Y.W., Cheung M.T., Fong D.Y.T., Lam J.C.M., Lam C.L., Yam L.Y.C. and Ip M.S.M., Randomized study of three non-surgical treatments in mild to moderate obstructive sleep apnea, Thorax. 2007, 62: 354-359.

Lam B., Wong M.P., Fung S.L., Lam C.L., Wong P.C., Wong T.Y.W., Lam F.M., Ip M.S.M., Ooi C.G.C. and Lam W.K., The clinical value of autofluorescence bronchoscopy for the diagnosis of lung cancer , European Respiratory Journal. 2006, 28(5): 915-919.

Lam B., Sam K., Lam J.C., Lam C.L., Ku P.P. and Ip M.S.M., The efficacy of oral appliance in the treatment of severe obstructive sleep apnea, American Thoracic Society International Conference, San Francisco, USA. American Jouranl of Respiratory and Critical Care Medicine. 2007, 175: A708.

Lam J.C., Tam S., Ooi C.G.C., Ku P.P., Lai A.Y.K., Lam B., Lam K.S.L. and Ip M.S.M., Relationship between sympathetic activity, obesity, and obstructive sleep apnea, 8th World Congress on Sleep Apnea. Montreal, Canada. Sleep Medicine. 2006, 7 (suppl 2): S51 (P321).

Lam J.C., Lam C.L., Xu A., Yan S.W., Lam B., Lam K.S.L. and Ip M.S.M., Serum adipocyte-fatty acid binding protein (AFABP) level correlates with the duration of oxygen desaturation in obstructive sleep apnea (OSA) patients, American Thoracic Society International Conference, San Francisco, USA 2007. American Journal of Respiratory and Critical Care Medicine. 2007, 175: A55.

Lam J.C.M., Tam S., Ooi C.G.C., Ku P.P., Lai A.Y.K., Lam B., Lam K.S.L. and Ip M.S.M., Relationship between sympathetic activity, obesity, and obstructive sleep apnea, 8th World Congress on Sleep Apnea. Montreal, Canada, September 2006. Sleep Medicine. 2006, 7 (suppl 2): S51 (P321).

Lam T.P., Wan X. and Ip M.S.M., Current perspectives of medical education in China. , Medical Education. 2006, 40: 940-949.

Mak J.C.W., Hui W.S., Ho S.P., So H.L., Chan M.M.W., Lam W.K., Cho C.H. and Ip M.S.M., Best Poster - Systemic oxidative stress and inflammation in cigarette smoke-exposed rat model, 12th Medical Research Conference. 2007.

Mak J.C.W., Ko F.W., Chu C.M., Leung C.M., Chan H.W., Cheung A.H.K., Ip M.S.M. and Chan W.M., Polymorphisms in the IL-4, IL-4 receptor alpha chain, TNF-alpha, and lymphotoxin-alpha genes and risk of asthma in Hong Kong Chinese adults, Int Arch Allergy Immunol. 2007, 144: 114-122.

Mak J.C.W., Ho S.P., Leung C.M., Cheung A.H.K., Law K.W., Ip M.S.M. and Chan M.M.W., Relationship between glutathione S-transferase gene polymorphisms and enzyme activity in Hong Kong Chinese asthmatics, American Thoracic Society International Conference, San Francisco, USA. American Journal of Respiratory and Critical Care Medicine. 2007, 175: A461.

Mak J.C.W., Ho S.P., Leung C.M., Cheung A.H.K., Law K.W., So L.K.Y., Chan W.M., Chau C.H., Lam W.K., Ip M.S.M. and Chan W.M., Relationship between glutathione S-transferase gene polymorphisms and enzyme activity in Hong Kong Chinese asthmatics, Clinical and experimental allergy. 2007, 37: 1150-1157.

Mohan A., Bollineni S., Lam B., Lam C.L. and Ip M.S.M., Obstructive sleep apnoea in India: what the mind does not think, the eyes do not see, International Journal of Tuberculosis and Lung Disease. 2007, 11: 932-933.

Tang S.C.W., Lam B., Ku P.P., Leung W.S., Chu C.M., Ho Y.W., Ip M.S.M. and Lai K.N., Alleviation of sleep apnea in patients with chronic renal failure by nocturnal cycler-assisted peritoneal dialysis compared with conventional continuous ambulatory peritoneal dialysis, Journal of American Society of Nephrology. 2006, 17: 2607-2616.

Wong M.K., Leung W.C., Wang J.K., Lao T.T.H., Ip M.S.M., Lam W.K. and Ho J.C.M., Recurrent pneumothorax in pregnancy: what should we do after placing an intercostals drain, Hong Kong Medical Journal. Hong Kong, 2006, 12: 375-380.

Researcher : Jim MH

List of Research Outputs

Ho H.H., Siu C.W.D., Jim M.H., Miu K.M., Chan R.H.W., Lee S.W.L., Lau C.P. and Tse H.F., Leukocytosis and clinical outcomes in acute inferior myocardial infarction, Int J Cardiol. 2006, 118(2): 278-9.

Siu C.W.D., Jim M.H., Ho H.H., Miu R., Lee S.W., Lau C.P. and Tse H.F., Transient Atrial Fibrillation Complicating Acute Inferior Myocardial Infarction: Implications for Future Risk of Ischemic Stroke. , Chest. 2007, 132(1): 44-9.

Researcher : Jin C

List of Research Outputs

Jin C., Jin Y., Gisselsson D., Wennerberg J., Wah T.S., Stomback B., Kwong Y.L. and Mertens F., Molecular cytogenetic characterization of the 11q13 amplicon in head and neck squamous cell carcinoma, Cytogenetic and genome research. 2006, 115(2): 99-106.

Researcher : Jin L

List of Research Outputs

Cheung W.M.W., Jin L., Smith D.K., Cheung P.T., Kwan E.Y.W., Low L.C.K. and Kung A.W.C., A family with osteoporosis pseudoglioma syndrome due to compound heterozygosity of two novel mutations in the LRP5 gene, Bone. 2006, 39: 470-6.

Researcher : Jin O

List of Research Outputs

Jin O., Kavikondala S., Chan W.K., Rong F., Yeung J.S.L., Mok T.M.Y. and Lau W.C.S., Abnormal Plasmacytoid Dendritic Cell Activity in Systemic Lupus Erythematosus, The American College of Rheumatology Annual Scientific Meeting 10-15 Nov 2006, Washington, DC USA 2006. 54(9) Supplement: Abstract No.1095.

Jin O., Kavikondala S., Chan W.K., Rong F., Yeung J.S.L., Mok T.M.Y. and Lau W.C.S., Functional Abnormalities of Myeloid Dendritic Cells in Systemic Lupus Erythematosus, The American College of Rheumatology Annual Scientific Meeting 10-15 Nov 2006, Washington, DC USA. 2006, 54(9) Supplement: Abstract No.1096.

Kavikondala S., Jin O., Chan W.K., Yeung J.S.L., Rong F., Mok T.M.Y. and Lau W.C.S., Dendritic Cells (DCs): Culprits of B-cell Hyper-responsiveness in Lupus, The American College of Rheumatology Annual Scientific Meeting 10-15 Nov 2006, Washington, DC USA. 2006, 54(9) Supplement: Abstract No. 1075.

Rong F., Jin O., Kavikondala S., Chan W.K., Yeung J.S.L., Mok T.M.Y. and Lau W.C.S., Plasmacytoid-Dendritic Cell Induced T Cell Proliferation and Activation: A Potential Role in the Pathogenesis of Rheumatoid Arthritis, The American College of Rheumatology Annual Scientific Meeting 10-15 Nov 2006, Washington, DC USA. 2006, 54(9) Supplement: Abstract No.424.

Sun L.Y., Zhou K.X., Feng X.B., Zhang H.Y., Ding X.Q., Jin O., Lu L., Lau W.C.S., Hou Y.Y. and Fan L.M., Abnormal surface markers expression on bone marrow CD34⁺cells and correlation with disease activity in patients with systemic lupus erythematosus, Clin Rheumatol. 2007, [Epub ahead of print].

Researcher : Jin O

List of Research Outputs

Researcher : Jin Y

Project Title:	Cytogenetic and molecular genetic characterization of esophageal carcinomas
Investigator(s):	Jin Y, Kwong YL, Tsao GSW
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	10/2002

Abstract:

To identify, by cytogenetic, fluorescence in situ hybridization (FISH), and molecular genetic approaches, the genetic changes that are important in the malignant transformation of esophageal epithelium; to investigate genetic differences and similarity between immortalized, preneoplastic esophageal epithelial cells and aquamous cell carcinoma (SCC) of the esophagus.

List of Research Outputs

Jin C., Jin Y., Gisselsson D., Wennerberg J., Wah T.S., Stomback B., Kwong Y.L. and Mertens F., Molecular cytogenetic characterization of the 11q13 amplicon in head and neck squamous cell carcinoma, Cytogenetic and genome research. 2006, 115(2): 99-106.

Researcher : Kavikondala S

List of Research Outputs

Jin O., Kavikondala S., Chan W.K., Rong F., Yeung J.S.L., Mok T.M.Y. and Lau W.C.S., Abnormal Plasmacytoid Dendritic Cell Activity in Systemic Lupus Erythematosus, The American College of Rheumatology Annual Scientific Meeting 10-15 Nov 2006, Washington, DC USA 2006. 54(9) Supplement: Abstract No.1095.

Jin O., Kavikondala S., Chan W.K., Rong F., Yeung J.S.L., Mok T.M.Y. and Lau W.C.S., Functional Abnormalities of Myeloid Dendritic Cells in Systemic Lupus Erythematosus, The American College of Rheumatology Annual Scientific Meeting 10-15 Nov 2006, Washington, DC USA. 2006, 54(9) Supplement: Abstract No.1096.

Kavikondala S., Jin O., Chan W.K., Yeung J.S.L., Rong F., Mok T.M.Y. and Lau W.C.S., Dendritic Cells (DCs): Culprits of B-cell Hyper-responsiveness in Lupus, The American College of Rheumatology Annual Scientific Meeting 10-15 Nov 2006, Washington, DC USA. 2006, 54(9) Supplement: Abstract No. 1075.

Kavikondala S., Nie Y. and Lau W.C.S., Report on the Second Asia Autoimmunity Forum 3-5 March 2006, Hong Kong, Autoimmunity Reviews. Amsterdam, New York: Elsevier, c2002, 2006, 6(2): 115-118.

Rong F., Jin O., Kavikondala S., Chan W.K., Yeung J.S.L., Mok T.M.Y. and Lau W.C.S., Plasmacytoid-Dendritic Cell Induced T Cell Proliferation and Activation: A Potential Role in the Pathogenesis of Rheumatoid Arthritis, The American College of Rheumatology Annual Scientific Meeting 10-15 Nov 2006, Washington, DC USA. 2006, 54(9) Supplement: Abstract No.424.

Researcher : Ku PP

List of Research Outputs

Lam B., Sam K., Lam J.C., Lam C.L., Ku P.P. and Ip M.S.M., The efficacy of oral appliance in the treatment of severe obstructive sleep apnea, American Thoracic Society International Conference, San Francisco, USA. American Jouranl of Respiratory and Critical Care Medicine. 2007, 175: A708.

Lam J.C., Tam S., Ooi C.G.C., Ku P.P., Lai A.Y.K., Lam B., Lam K.S.L. and Ip M.S.M., Relationship between sympathetic activity, obesity, and obstructive sleep apnea, 8th World Congress on Sleep Apnea. Montreal, Canada. Sleep Medicine. 2006, 7 (suppl 2): S51 (P321).

Lam J.C.M., Tam S., Ooi C.G.C., Ku P.P., Lai A.Y.K., Lam B., Lam K.S.L. and Ip M.S.M., Relationship between sympathetic activity, obesity, and obstructive sleep apnea, 8th World Congress on Sleep Apnea. Montreal, Canada, September 2006. Sleep Medicine. 2006, 7 (suppl 2): S51 (P321).

Tang S.C.W., Lam B., Ku P.P., Leung W.S., Chu C.M., Ho Y.W., Ip M.S.M. and Lai K.N., Alleviation of sleep apnea in patients with chronic renal failure by nocturnal cycler-assisted peritoneal dialysis compared with conventional continuous ambulatory peritoneal dialysis, Journal of American Society of Nephrology. 2006, 17: 2607-2616.

Researcher : Kumana CR

List of Research Outputs

Kumana C.R., Prescriptions for sustainable healthcare, Hong Kong Medical Journal. 2007, 13(1): 88.

Siu C.W.D., Au W.Y., Yung C.Y., Kumana C.R., Lau C.P., Kwong Y.L. and Tse H.F., Effects of oral arsenic trioxide therapy on QT intervals in patients with acute promyelocytic leukemia: implications on long-term cardiac safety, Blood. 2006, 108(1): 103-106.

Researcher : Kung AWC

Project Title:	Evaluation of maternal and fetal modulators in the development of postpartum autoimmune thyroiditis in a murine model of experimental autoimmune thyroiditis induced by thyroid peroxidase
Investigator(s):	Kung AWC
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003

Abstract:

To determine the incidence of pregnancy outcome in a murine model of AITD induced by immunizing C57B/6(H2[b]) mice with homologous mouse TPO, and to determine the pathogenicity of anti-TPO Ab against placental and fetal antigen; to determine the severity of postpartum thyroiditis in allogeneic C57B/6(H2[b]) x CBA/J(H2[d]) versus synergeneic C57B/6(H2[b]) x C57B/6(H2[b]) and CBA/J(H2[d]) x CBA/J(H2[d]) animals; to determine the cytokine profile in the above animals during pregnancy and postpartum period

Project Title:	An association screen for osteoporosis susceptibility loci in chromosome 3p
Investigator(s):	Kung AWC, Sham PC, Chan VNY
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004
Completion Date:	10/2006

Abstract:

To identify novel susceptible loci for osteoporosis using BMD as a quantitative trait by conducting a high-density SNP screen in the gene-rich zone of chromosome 3p.

Project Title:	To discover new genes in chromosome 14q11-32 for the determination of osteoporosis and boen mineral density
Investigator(s):	Kung AWC, Luk KDK, Chan VNY, Sham PC
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	08/2005

Abstract:

Phase I: to determine the linkage and association of markers in the chromosomal region 14q11-32 with bone mineral density (BMD) at the spine and hip using two approaches: (1) linkage analysis by multipoint allele-sharing methods in 250 extended southern Chinese families. (2) case-control association study using haploytpe-tagging SNPs in southern Chinese subjects. Phase II: to identify the candidate gene(s) by differential gene expression method.

Project Title:	To evaluate the role of Estrogen Receptor Alpha CA repeat Polymorphism as a Predictor of Osteoporosis and Facture Risk and To determine the Functional Mechanism of this Polymorphism in Human Bone Cells
Investigator(s):	Kung AWC, Luk KDK
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	12/2005
Completion Date:	02/2007

Abstract:

Estrogen deficiency is the major cause of post-menopausal osteoporosis [1]. Current evidence strongly supports that estrogen receptor alpha (ERα) is the main mediator of estrogenic action in bone [2-4]. Both in vitro [5-7] and animal studies [8, 9] have shown that ERα deficiency, as similar to estrogen deficiency, gives rise to low bone mineral density (BMD), rapid bone loss and increased fracture risk [10, 11]. Indeed, the association of low bone mass and delayed skeletal maturation in a young man with mutation of ERα resulting in estrogen resistance confirms the importance of this receptor in bone metabolism in both sexes [12]. ERα is mediated by the ESR1 gene which is located at chromosome 6q25.1 [13]. Previous studies have shown that ESR1 is a susceptibility gene for low bone mass and osteoporotic fractures. A number of intronic polymorphisms such as the XbaI, PvuII, TA repeats of ESR1 are reported to be associated with fracture risk [11, 14] and bone loss [15, 16]. However, the functionality of these intronic polymorphisms is unclear and the mechanism for the association with osteoporosis is ill defined [10]. We hypothesized that other functional polymorphisms of the ESR1 gene is likely to explain the association of ESR1 gene and osteoporosis clinical endpoints. D6S440 is a dinucleotide CA repeat polymorphism recently identified in intron 5 of ESR1. This locus is located 200 kb from the transcription start site of the gene but the importance of this polymorphism has not been studied. In the past, intronic dinucleotide repeat polymorphisms of such distance from the promoter were not considered to have any functional significance. However, recent reports on the intronic CA repeat polymorphism of the endothelial nitric oxide synthase (eNOS) gene has shown that CA repeats near 5' splicing sites may act as splicing enhancers affecting mRNA splicing efficiency [17]. As D6S440 is located 235 base-pairs downstream of the 5' splicing site of exon 5 in the ESR1 gene, we suspected that D6S440 may also be a potential polymorphic site for mRNA splicing modulation. The objective of this study was first, to investigate the role of this locus as a genetic marker for predicting BMD, fracture risk and rate of bone loss and second, to study the relation between CA repeat allele size and ESR1 mRNA transcript levels. Reference: 1. Albright F, et al. Post-menopausal osteoporosis. Trans Assoc Am Physicians. 1940;55:298-305. 2. Penolazzi, L., et al., Methylation analysis of the promoter F of estrogen receptor alpha gene: effects on the level of transcription on human osteoblastic cells. J Steroid Biochem Mol Biol, 2004. 91(1-2): p. 1-9. 3. Lee, K., et al., Endocrinology: bone adaptation requires oestrogen receptor-alpha. Nature, 2003. 424(6947): p. 389. 4. Waters, K.M., et al., Estrogen regulation of human osteoblast function is determined by the stage of differentiation and the estrogen receptor isoform. J Cell Biochem, 2001. 83(3): p. 448-62. 5. Cheng, M.Z., et al., Human osteoblasts' proliferative responses to strain and 17beta-estradiol are mediated by the estrogen receptor and the receptor for insulin-like growth factor I. J Bone Miner Res, 2002. 17(4): p. 593-602. 6. Jessop, H.L., et al., Osteoblast-like cells from estrogen receptor alpha knockout mice have deficient responses to mechanical strain. J Bone Miner Res, 2004. 19(6): p. 938-46. 7. Di Gregorio, G.B., et al., Attenuation of the self-renewal of transit-amplifying osteoblast progenitors in the murine bone marrow by 17 beta-estradiol. J Clin Invest, 2001. 107(7): p. 803-12. 8. Syed, F. and S. Khosla, Mechanisms of sex steroid effects on bone. Biochem Biophys Res Commun, 2005. 328(3): p. 688-96. 9. Gallagher, A., T.J. Chambers, and J.H. Tobias, The estrogen antagonist ICI 182,780 reduces cancellous bone volume in female rats. Endocrinology, 1993. 133(6): p. 2787-91. 10. Gennari, L., et al., Estrogen receptor gene polymorphisms and the genetics of osteoporosis: a HuGE review. Am J Epidemiol, 2005. 161(4): p. 307-20. 11. Ioannidis, J.P., et al., Differential genetic effects of ESR1 gene polymorphisms on osteoporosis outcomes. JAMA, 2004. 292(17): p. 2105-14. 12. Smith, E.P., et al., Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med, 1994. 331(16): p. 1056-61. 13. Menasce, L.P., et al., Localization of the estrogen receptor locus (ESR) to chromosome 6q25.1 by FISH and a simple post-FISH banding technique. Genomics, 1993. 17(1): p. 263-5. 14. Langdahl, B.L., et al., A TA repeat polymorphism in the estrogen receptor gene is associated with osteoporotic fractures but polymorphisms in the first exon and intron are not. J Bone Miner Res, 2000. 15(11): p. 2222-30. 15. Kobayashi, N., et al., Estrogen receptor alpha polymorphism as a genetic marker for bone loss, vertebral fractures and susceptibility to estrogen. Maturitas, 2002. 41(3): p. 193-201. 16. Sowers, M., et al., Estrogen receptor genotypes and their association with the 10-year changes in bone mineral density and osteocalcin concentrations. J Clin Endocrinol Metab, 2004. 89(2): p. 733-9. 17. Hui, J., et al., HnRNP L stimulates splicing of the eNOS gene by binding to variable-length CA repeats. Nat Struct Biol, 2003. 10(1): p. 33-7.

Project Title:	Analysis of Na+/myo-inositol cotransporter (SMIT1) as a regulator of bone growth and bone mass
Investigator(s):	Kung AWC, Chung SK
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	05/2007

Abstract:

OBJECTIVESa. To characterize the bone abnormality of SMIT1-/-knockout mice.b. To identify the embryonic stage that is critical for myo-Inositol (Ins) and SMIT1 involvement in bone development. c. To determine the cellular pathway of SMIT1 in bone cells.Myo-Inositol and its polyphosphoinositide derivatives are important in membrane signaling [1,2]. Synthesis of phosphatidylinositol (PtdIns), the most abundant Ins-containing membrane phospholipids produced by phosphatidylinositol synthase, depends on adequate concentrations of the substrates Ins and CDP-diacylglycerol. Its derivative, phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2), is a key molecule in the ubiquitous cell signaling system that utilizes phospholipase C hydrolysis to yield second messengers inositol-1,4,5,-triphosphate (Ins-1,4,5,-P3) and diacylglycerol. PtdIns. In addition the products of PI-3kinase activities and their inositol phosphate derivatives are important in the structure and function of membrane and cytoskeleton, and certain enzyme activities [3,4]. Furthermore, free Ins is important for the regulation of osmotic pressure. Extracellular inositol is accumulated in cells via the sodium/myo-inositol cotransporter (SMIT1 or SLC5A3) [5,6].In an attempt to evaluate the role of SMIT1 and osmotic stress in brain metabolism and ischaemic brain injury, co-investigator(CI) SK Chung has generated SMIT1-/- knock-out mice by disrupting the open reading frame of SMIT1 [7]. Two mouse lines, 4038 and 4050, derived from 2 independent ES cell lines showed absence of SMIT1 mRNA expression. Interestingly and unexpectedly, these homozygous knockout animals showed unexpected abnormal bone phenotypes with curved and kyphotic spine, thin and bent fore- and hind-limbs, and thin ribs. Homozygous deletion of SMIT1 also resulted in perinatal lethality but the heterozygous SMIT+/- mice have normal body growth. These observations are slightly different from a previous report [8]. These abnormal phenotypes and perinatal death can be prevented by supplementing the animals at the embryonic stage with myoinositol. The homozygous SMIT mice rescued by in-utero supplementation of myoinositol had normal body weight, height, shape.They lived a normal life span but they had shorter and curved forelimbs.The high affinity SMIT1 transporter is responsible for the Ins concentration gradient in the murine fetal-placental unit and fetal brain. In adults, SMIT1 maintains millimolar intracellular concentrations of MI and promotes transepithelial MI transport in the kidney, intestinal, retina and choroid plexus [6,10-13]. The role of myoinositol and SMIT1 in bone metabolism has not been previously described in the literature. The observation of abnormal bone phenotypes in fetal Na+/myo-Inositol Cotransporter knockout (SMIT1-/-) mice suggests that depletion of cellular Ins adversely affects bone growth and differentiation.Bone cells are derived from pluripotent mesenchymal stem cells (MSCs).14 During intramembranous ossification, MSCs condense and differentiate directly into osteoblasts and produce bone matrix. In endochondral ossification that contributes to the limb bones, MSCs differentiate into chondrocytes and form the anlagen before replacement by bone and marrow. Mutations that affect differentiation of cartilage and bone cells may cause severe skeletal disorders [15,16]. Studies of such disorders provide insight into the cellular pathways for differentiation of chondrocytes and osteoblasts.

List of Research Outputs

Cheung C.L., Huang Q., Ng M.Y.M., Chan V.N.Y., Sham P.C. and Kung A.W.C., Confirmation of linkage to chromosome 1q for spine bone mineral density in Southern Chinese, 11th Research Postgraduate Symposium, HKU, 7 Dec 2006.

Cheung C.L., Huang Q., Ng M.Y.M., Chan V.N.Y., Sham P.C. and Kung A.W.C., Confirmation of linkage to chromosome 1q for spine bone mineral density in southern Chinese, Human Genetics. 2006, 120: 354-359.

Cheung C.L., Huang Q., Ng M.Y.M., Chan V.N.Y., Sham P.C. and Kung A.W.C., Confirmation of linkage to chromosome 1q for spine bone mineral density in southern Chinese, Journal of Bone and Mineral Research. 2006, 21(Suppl 1): S146.

Cheung C.L., Sham P.C., Chan V.N.Y. and Kung A.W.C., Peak-wide association study on chromosome 3p21 identifies the CACNA2D2 gene as a novel susceptibility gene for osteoporosis, 8th International Meeting on Human Genome Variation and Complex Genome Analysis, 14-16 Sep 2006, Hong Kong. 2006.

Cheung W.M.W., Jin L., Smith D.K., Cheung P.T., Kwan E.Y.W., Low L.C.K. and Kung A.W.C., A family with osteoporosis pseudoglioma syndrome due to compound heterozygosity of two novel mutations in the LRP5 gene, Bone. 2006, 39: 470-6.

Cheung W.M.W., Chan W.L., Dai Z. and Kung A.W.C., Rosiglitazone Enhances Osteoblastic Differentiation of Murine Preosteoblast Cells, The 28th Annual Meeting American Society for Bone and Mineral Research, Philadelphia, PA, U.S.A. Poster # SA484. 2006.

Dai Z., Cheung W.M.W., Chung S.K. and Kung A.W.C., Identify the potential roles of SMIT-1 in bone formation, 11th Research Postgraduate Symposium, HKU, 7 Dec 2006.

Ho A.Y.Y. and Kung A.W.C., Efficacy and tolerability of alendronate once weekly in Asian postmenopausal osteoporotic women, Ann Pharmacother. 2006, 39: 1428-33.

Huang Q. and Kung A.W.C., Genetics of osteoporosis, Mol Genet Metab. 2006, 88: 295-306.

Huang Q., Cheung C.L., Chan V.N.Y., Sham P.C. and Kung A.W.C., Identification of Two Sex-specific Quantitative Trait Loci in Chromosome 11q for Hip Bone Mineral Density in Chinese , 56th Annual Meeting of The American Society of Human Genetics . 2006.

Huang Q., Ng M.Y.M., Cheung C.L., Chan V.N.Y., Sham P.C. and Kung A.W.C., Identification of two sex-specific quantitative trait loci in chromosome 11q for bone mineral density in southern Chinese, Human Heredity. 2006, 61: 237-243.

Huang Q., Ng M.Y.M., Cheung C.L., Chan V., Sham P.C. and Kung A.W.C., Identification of two sex-specific quantitative trait loci in chromosome 11q for hip bone mineral density in Chinese, Human Heredity. 2006, 61(4): 237-243.

Huang Q., Cheung C.L., Chan V.N.Y., Sham P.C. and Kung A.W.C., Peak-wide association study on chromosome 3p21 identifies the CACNA2D2 gene as a novel susceptibility gene for osteoporosis , 8th International Meeting on Human Genome Variation and Complex Genome Analysis (HGV2006). 2006.

Ioannidis J.P.A., Ng M.Y.M., Sham P.C., Zintzaras E., Lewis C.M., Deng H.W., Econs M.J., Karasik D., Devoto M., Kammerer C.M., Spector T., Andrew T., Cupples L.A., Duncan E.L., Foroud T., Kiel D.P., Koller D., Langdahl B., Mitchell B.D., Peacock M., Recker R., Shen H., Sol-Church K., Spotila L.D., Uitterlinden A.G., Wilson S.G., Kung A.W.C. and Ralston S.H., Meta-analysis of genome-wide scans provides evidence for sex- and site-specific regulation of bone mass, Journal of Bone and Mineral Research. 2007, 22: 173-83.

Kung A.W.C., Clinical review: Thyrotoxic periodic paralysis: a diagnostic challenge, J Clin Endocrinol Metab. 2006, 91: 2490-5.

Kung A.W.C., Epidemiology Session IV (Chairman), 29th Meeting of the American Society of Bone & Mineral Research September 15-19 2006, Philidelphia, USA. 2006.

Kung A.W.C., Epidemiology of Osteoporosis, APLAR Congress in Rheumatology, August 4, 2006, Kuala Lumpa, Malaysia. 2006.

Kung A.W.C., Epidemiology of vitamin D inadequacy among postmenopausal women in Asia (Chairman), Asean Federation of Endocrine Societies Congress, 7-10, Dec 2005, Manila, Philippines. 2006.

Kung A.W.C. and Huang Q., Genetic and environmental determinants of osteoporosis (Invited Review), Journal of Musculoskeletal and Neuronal Interactions. 2007, 7: 26-32.

Kung A.W.C. and Huang Q., Genetic and environmental determinants of osteoporosis, J Musculoskelet Neuronal Interact. 2007, 7: 26-32.

Kung A.W.C., Genetics and environmental determinants of bone mass (Plenary Session), 2nd International Conference on Osteoporosis and Bone Research, 19-23 October 2005, Chengdu, China. 2006.

Kung A.W.C., Genotype and phenotype correlation of calcium-sensing receptor variants. (Invited commentary), Kidney International. 2007, 71: 1085-6.

Kung A.W.C. and Lee K.K., Knowledge of vitamin D and perceptions and attitudes toward sunlight among Chinese middle-aged and elderly women: a population survey in Hong Kong, BMC Public Health . 2006, 6: 226.

Kung A.W.C., Member of Editoral Board, Chinese Medical Journal. 2006.

Kung A.W.C., Member of Editorial Board, China Osteoporosis Journal. 2006.

Kung A.W.C., Member of Editorial Board, Journal of Clinical Endocrinology & Metabolism. 2006.

Kung A.W.C., Member of Editorial Board, MIMS Endocrinology Guide, Singapore. 2006.

Kung A.W.C., Member of Editorial Board, Osteoporosis International. 2006.

Kung A.W.C., Neuromuscular complications of thyrotoxicosis (Invited Review), Clinical Endocrinology. 2007, Epub ahead of print.

Kung A.W.C., Novel Treatment in Osteoporosis, Advanced Osteoporosis Course, October 7, 2006, Puket, Thailand. 2006.

Kung A.W.C., Osteoporosis: Review and Update, Didactic Lecture of The Hong Kong College of Orthopaedic Surgeons, 18 April 2007. 2007.

Kung A.W.C., Osteoporosis: The Scope of the Problem in Hong Kong, Scientific Meeting of Osteoporosis Society of Hong Kong, 8 July 2006. 2006.

Kung A.W.C., Rare haplotypes of Alox 15 gene are associated with spine and hip BMD in postmenopausal Southern Chinese women, 8th American Society for Bone & Mineral Research Meeting, 15-19 Sep 2006, USA. 2006.

Kung A.W.C., Reviewer of abstracts, 28th American Society of Bone and Mineral Research Meeting , 2006, USA . 2006.

Kung A.W.C., Rosiglitazone enhances osteoblastic differentiation of murine preosteoblast cells, 8th American Society for Bone & Mineral Research Meeting, 15-19 Sep 2006, USA. 2006.

Kung A.W.C., Secondary osteoporosis, Hong Kong Allergy Convention, 7 August 2005. 2006.

Kung A.W.C., Strontium Renelate: A New Paradigm in Postmenopausal Osteoporosis, Storntium Ranelate Launch Symposium, 27-28 Jan 2007, Malaysia. 2007.

Kung A.W.C., The role of bone forming agents in the treatment of osteoporosis, 2nd International Symposium on Healthy Aging, 3-4 March 2007, Hong Kong. 2007.

Kung A.W.C., Thyrotoxic Periodic Paralysis, 8th Congress of the Asia-Oceania Thyroid Association, 5-6 Feb 2007, Manila, Philippines. 2007.

Kung A.W.C., Thyrotoxic Periodic Paralysis, Asia Oceania Thyroid Congress, January 17, 2007, Manila, Philippines. 2007.

Kung A.W.C., Vitamin D Insufficiency in Osteoporosis, Asia MagaForum in Osteoporosis, October 25, 2006, Hong Kong . 2006.

Kung A.W.C., 聴聴骨頭說的話 - 預防及治療骨質疏鬆, 聴聴骨頭說的話 - 預防及治療骨質疏鬆症手冊, In: 龔慧慈編著, 經濟日報出版社. 經濟日報出版社, 2006.

Kung A.W.C., 高鈣血症和骨的疾病, 高鈣血症和骨的疾病, In: Liu ZH (Ed), 骨礦與臨床. 骨礦與臨床, 2006.

Lau H.L., Ng M.Y.M., Cheung W.M.W., Paterson A.D., Luk K.D.K., Chan V.N.Y. and Kung A.W.C., Assessment of linkage and association of 13 genetic loci with bone mineral density, J Bone Miner Metab. 2006, 24: 226-34.

Lo C.Y., Lang H.H.B., Chan W.F., Kung A.W.C. and Lam K.S.L., A prospective evaluation of preoperative localization by technetium-99m sestamibi scintigraphy and ultrasonography in primary hyperparathyroidism, American Journal of Surgery. 2007, 193: 155-159.

Ng M.Y.M., Sham P.C., Paterson A.D., Chan V.N.Y. and Kung A.W.C., Effect of environmental factors and gender on the heritability of bone mineral density and bone size, Ann Hum Genet. 2006, 70: 428-38.

Pasion E.G., Sivananthan S.K., Kung A.W.C., Chen S.H., Chen Y.J., Mirasol R., Tay B.K., Shah G.A., Khan M.A., Tam F., Hall B.J. and Thiebaud D., Comparison of raloxifene and bisphosphonates based on adherence and treatment satisfaction in postmenopausal Asian women, Journal of Bone and Mineral Research. 2007, 25: 105-13.

Siu C.W., Zhang X., Yung C., Kung A.W.C., Lau C.P. and Tse H.F., Hemodynamic Changes in Hyperthyroidism Related Pulmonary Hypertension: A Prospective Echocardiographic study, The American College of Cardiology 56th annual Scientific Sessions, New Orleans. 2007.

Siu C.W.D., Zhang X., Yung C., Kung A.W.C., Lau C.P. and Tse H.F., Hemodynamic Changes in Hyperthyroidism Related Pulmonary Hypertension: A Prospective Echocardiographic study, J Clin Endocrinol Metab. 2007, 92(5): 1736-42.

Siu C.W.D., Yeung C.Y., Lau C.P., Kung A.W.C. and Tse H.F., Incidence, clinical characteristics and outcome of congestive heart failure as the initial presentation in patients with primary hyperthyroidism, Heart. 2007, 93 (4): 483-7.

Siu D.C.W., Zhang X., Yung C., Kung A.W.C., Lau C.P. and Tse H.F., Hemodynamic changes in hyperthyroidism-related pulmonary hypertension: a prospective echocardiographic study, Journal of Clinical Endocrinology & Metabolism. 2007, 92: 1736-42.

Wat W.Z.M., Leung J.Y.Y., Tam S. and Kung A.W.C., The prevalence and impact of vitamin D insufficiency in ambulatory southern Chinese adults, Annals of Nutrition and Metabolism. 2007, 51: 59-64.

Researcher : Kung MHW

List of Research Outputs

Chu A.C.Y., Ho W.L., Kwok H.H., Kung M.H.W., Ramsden D.B. and Ho S.L., Leptin enhances MPP+-induced mitochondrial dysfunction: a potential for neuroprotection in parkinsonism, 10th International Congress of Parkinson's disease and Movement Disorders, Kyoto, Japan. [Abs]. Kyoto, Japan, Mov Disorders, 2006, 21(Suppl 15): 62.

Fong C.Y., Kwok H.H., Song Y., Cheng T.S., Ho W.L., Chu A.C.Y., Kung M.H.W., Chan K.H., Mak W., Cheung R.T.F., Ramsden D.B. and Ho S.L., Clinical phenotypes of a large Chinese multigenerational kindred with autosomal dominant familial ALS due to Ile149Thr SOD1 gene mutation., Amyotrophic Lateral Sclerosis. 2006, 7(3): 142-149.

Ho W.L., Chu A.C.Y., Kwok H.H., Kung M.H.W. and Ho S.L., Leptin enhances MPP+-induced mitochondrial dysfunctions in SH-SY5Y cells: a potential of neuroprotection in Parkinsonism, University of Hong Kong. 2006.

Ho W.L., Chu A.C.Y., Kwok H.H., Kung M.H.W., Ramsden D.B. and Ho S.L., Stable overexperession of human uncoupling protein-4 reduced ATP production in SH-SY5Y cells: a potential candidate to regulate mitochondrial function and efficiency. Late breaking abstract LB-18. , 10th International Congress of Parkinson's disease and Movement Disorders, Kyoto, Japan. [Abs]. Kyoto, Japan, Mov Disorders, 2006, 21(Suppl 15).

Kwok H.H., Chu A.C.Y., Ho W.L., Ramsden D.B., Kung M.H.W. and Ho S.L., Localization and distribution of uncoupling protein 5 (UCP5) in rat brain., 10th International Congress of Parkinson's disease and Movement Disorders, Kyoto, Japan. [Abs]. . Kyoto, Japan, Mov Disorders, 2006, 21(Suppl 15): 55.

Researcher : Kwok HH

List of Research Outputs

Chu A.C.Y., Ho W.L., Kwok H.H., Wang Y., Ramsden D.B. and Ho S.L., Human uncoupling protein-4 protects neuronal cell death from MPP+ induced toxicity by regulating mitochondrial membrane potential, reducing ROS and maintaining ATP levels., 11th International Congress of Parkinson's disease and Movement Disorders, Istanbul, Turkey. {Abs]. Istanbul, Turkey., Mov Disord, 2007, 22 (Suppl 16):: 67.

Chu A.C.Y., Ho W.L., Kwok H.H., Kung M.H.W., Ramsden D.B. and Ho S.L., Leptin enhances MPP+-induced mitochondrial dysfunction: a potential for neuroprotection in parkinsonism, 10th International Congress of Parkinson's disease and Movement Disorders, Kyoto, Japan. [Abs]. Kyoto, Japan, Mov Disorders, 2006, 21(Suppl 15): 62.

Fong C.Y., Kwok H.H., Song Y., Cheng T.S., Ho W.L., Chu A.C.Y., Kung M.H.W., Chan K.H., Mak W., Cheung R.T.F., Ramsden D.B. and Ho S.L., Clinical phenotypes of a large Chinese multigenerational kindred with autosomal dominant familial ALS due to Ile149Thr SOD1 gene mutation., Amyotrophic Lateral Sclerosis. 2006, 7(3): 142-149.

Ho W.L., Chu A.C.Y., Kwok H.H., Kung M.H.W. and Ho S.L., Leptin enhances MPP+-induced mitochondrial dysfunctions in SH-SY5Y cells: a potential of neuroprotection in Parkinsonism, University of Hong Kong. 2006.

Ho W.L., Chu A.C.Y., Kwok H.H., Kung M.H.W., Ramsden D.B. and Ho S.L., Stable overexperession of human uncoupling protein-4 reduced ATP production in SH-SY5Y cells: a potential candidate to regulate mitochondrial function and efficiency. Late breaking abstract LB-18. , 10th International Congress of Parkinson's disease and Movement Disorders, Kyoto, Japan. [Abs]. Kyoto, Japan, Mov Disorders, 2006, 21(Suppl 15).

Kwok H.H., Chu A.C.Y., Ho W.L., Ramsden D.B., Kung M.H.W. and Ho S.L., Localization and distribution of uncoupling protein 5 (UCP5) in rat brain., 10th International Congress of Parkinson's disease and Movement Disorders, Kyoto, Japan. [Abs]. . Kyoto, Japan, Mov Disorders, 2006, 21(Suppl 15): 55.

Ng M.C., Ho J.T., Ho S.L., Lee R., Li G., Cheng T.S., Song Y.Q., Kwok H.H., Ho W.L., Chu C.Y.A., Fong C.Y., Chan K.H., Cheung R.T.F., Li L.S.W., Yang E.S., Luk K.D.K., Hu Y., Ramsden D.B. and Leong Fung L.L.Y., MR-DTI study: abnormal water diffusion pattern in asymptomatic familial amyotrophic lateral sclerosis with SOD1 mutation, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population. 2007, 54.

Researcher : Kwok HH

List of Research Outputs

Researcher : Kwong YL

Project Title:	Provision of purine analogues for the treatment of patients with chronic lymphoid malignancies
Investigator(s):	Kwong YL, Liang RHS
Department:	Medicine
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	07/1997

Abstract:

To provide purine analogues for the treatment of patients with chronic lymphoid malignancies who cannot otherwise afford the drugs.

Project Title:	Molecular mechanisms and consequences of downregulation of p73 in natural killer cell lymphoma
Investigator(s):	Kwong YL
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2002

Abstract:

To define if p73 acts as a tumor suppressor gene in natural killer (NK) cell lymphomas; to define the biologic significance of re-expression of p73 in NK lumphoma cells that have p73 inactivated due to aberrant promoter methylation; to define the potential significance of p21 inactivation in NK lymphoma cells.

Project Title:	Molecular basis of arsenic resistance in tumours
Investigator(s):	Kwong YL, Tse EWC
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003

Abstract:

To define the molecular basis of arsenic resistance in tumour cells.

Project Title:	Activation of the JAK/STAT pathways in the molecular pathogenesis of natural killer cell lymphomas
Investigator(s):	Kwong YL
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004
Completion Date:	10/2006

Abstract:

To define the involvement of JAK/STAT, MEK/ERK and PI3-K/Akt signaling pathways in the pathogenesis of natural killer (NK) cell lymphomas.

Project Title:	Provision of free cytogenetic and molecular testing for monitoring of disease relapse after bone marrow transplantation
Investigator(s):	Kwong YL, Liang RHS, Lie AKW, Au WY
Department:	Medicine
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	11/2004

Abstract:

To establish provisions of (a) free molecular / cytogenetic tests for monitoring of BMT patients, (b) free molecular / cytogenetic tests for BMT patients who have relapsed, so that their treatment can be guided and optimized, (c) free molecular / cytogenetic tests for referral patients from other hospitals.

List of Research Outputs

Au W.Y., Lam V.M.S., Pang A.W.K., Lee W.M., Chan L.C., Song Y., Ma E.S.K. and Kwong Y.L., Glucose-6-phosphate dehydrogenase deficiency in female octogenarians, nanogenarians, and centenarians, The Journals of Gerontology Series A: Biological Sciences and Medical Sciences . 2006, 61(10): 1086-1089.

Au W.Y., Fung T.K., Lie A.K.W., Lam K.Y., Lam C.C.K. and Kwong Y.L., Reemergence of JAK2 V617F clone heralds extramedullary leukemia relapse after BMT for transformed essential thrombocytosis, Annals of Hematology. 2006, 86: 145-7.

Au W.Y., Fung A., Liu C.L., Fan S.T., Ma E.S.K., Liang R.H.S. and Kwong Y.L., Serial analysis of JAK2 mutation in a patient who developed essential thrombocythemia after orthotopic liver transplantation (Case Report), American Journal of Hematology. 2006, 81(11): 880-882.

Au W.Y., Au W.Y., Fung T.K., Liu C.L., Fung T.K., Fung T.K., Fan S.T., Ma E.S.K., Liang R.H.S. and Kwong Y.L., Serial analysis of JAK2 mutation in a patient who developed essential thrombocythemia after orthotopic liver transplantation, American Journal of Hematology. 2006, 81(1): 880-882.

Au W.Y., Ma E.S.K., Lee T.L., Ha S.Y., Fung T.K., Lie A.K.W. and Kwong Y.L., Successful treatment of thrombotic microangiopathy after haematopoietic stem cell transplantation with rituximab, British Journal of Haematology. Blackwell Publishing Ltd, 2007, 137: 475-478.

Au W.Y., Fung T.K., Lam K.Y., Lie A.K.W., Liang R.H.S. and Kwong Y.L., Transformed essential thrombocytosi with a JAK2 V617F mutation relapsing as JAK2 Mutation-negative leukaemia after allogeneic stem cell transplantation, Bone Marrow Transplantation. 2006, 38(8): 573-4.

Chan G.C.F., Chan S., Kan A., Au W.Y., Lee T.L., Lie A.K.W., Kwong Y.L., Ha S.Y. and Liang R.H.S., Mesenchymal stromal cells remained to be of recipient in origin after conventional bone marrow transplantation. , Cytotherapy 2007; 9(1)Supp: 144. 2007.

Chen W.Y.W., Hu X., Liang A.C.T., Au W.Y., So J.C.C., Wong M.L.Y., Shen L., Tao Q., Chu K.M., Kwong Y.L. and Srivastava G., High BCL6 expression predicts better prognosis, independent of BCL6 translocation status, translocation partner, or BCL6 deregulating mutations, in gastric lymphoma, Blood. 2006, 108: 2373-2383.

Cheung M.S., Shek W.K., Shek W.K., Leung J.C.K., Chan Y.Y., Huang H., Kwong Y.L., Liang R.H.S. and Leung A.Y.H., Aldehyde dehydrogenase activity in leukemic blasts defines a subgroup of acute myeloid leukemia with adverse prognosis and superior NOD/SCID engrafting potential, Leukaemia. 2007, 21: 1423-1430.

Cheung M.S., Kwong Y.L., Liang R.H.S. and Leung A.Y.H., Stem cell model of hematopoiesis, C7urrent Stem Cell Research and Therapy. 2006, 1: 305-315.

Cheung W.W., Tse E.W.C., Leung A.Y.H., Yuen K.Y. and Kwong Y.L., Regular virologic surveillance showed very frequent cytomegalovirus reactivation in patients treated with alemtuzumab, Blood. 2007, 82(2): 108-11.

Chim J.C.S., Liang R.H.S., Leung M.H. and Kwong Y.L., Aberrant gene methylation implicated in the progression of monoclonal gammopathy of undetermined significance to multipl myeloma, Journal of clinical pathology. 2007, 60: 104-106.

Chim J.C.S., Liang R.H.S., Fung T.K., Choi C.L. and Kwong Y.L., Epigenetic dysregulation of the death-associated protein kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in multiple myeloma, Journal of clinical pathology. 2007, 60: 664-669.

Chim J.C.S., Liang R.H.S., Fung T.K. and Kwong Y.L., Infrequent epigenetic dysregulation of CIP/KIP family of cyclin-dependent kinase inhibitors in multiple myeloma, Leukemia. 2006, 19(12): 2352-5.

Chim J.C.S., Lie A.K.W., Liang R.H.S., Au W.Y. and Kwong Y.L., Long-term results of allogeneic bone marrow transplantation for 108 adult patients with acute lymphoblastic leukemia: favorable outcome with BMT at first remission and HLA-matched unrelated donor, Bone Marrow Transplantation. 2007, 40(4): 339-347.

Hui C.K., Cheung W.W., Zhang H.Y., Au W.Y., Leung N., Luk J.M., Lie A.K.W., Kwong Y.L., Liang R.H.S. and Lau G., Rituximab increases the risk of de novo hepatitis B infection in hepatitis B surface antigen negative patients undergoing cytotoxic chemotherpay, Gastroenterology. 2006, 131(1): 59-68.

Jin C., Jin Y., Gisselsson D., Wennerberg J., Wah T.S., Stomback B., Kwong Y.L. and Mertens F., Molecular cytogenetic characterization of the 11q13 amplicon in head and neck squamous cell carcinoma, Cytogenetic and genome research. 2006, 115(2): 99-106.

Jin Y., Tsao G.S.W. and Kwong Y.L., Re: Wilting et al. Increased gene copy numbers at chromosome 20q are frequent in both squamous cell carcinomas and adenocarcinomas of the cervix, The Journal of Pathology. 2006, 209: 220-230.

Kwong Y.L., Predicting the outcome in non-Hodgkin lymphoma with molecular markers, British Journal of Haematology. 2007, 137(4): 273-287.

Lau G.K.K., Chan Y.H., Yiu K.H., Li S.W., Tam S., Lau C.P., Kwong Y.L. and Tse H.F., Burden of carotid atherosclerosis in patients with stroke: relationships with circulating endothelial progenitor cells and hypertension, Journal of human hypertension. 2007, 21(6): 445-451.

Leung C.K.J., Pang A.W.K., Yuen W.H., Kwong Y.L. and Tse E.W.C., Relationship of Expression of Aquaglyceroporin 9 with Arsenic Uptake and Sensitivity in Leukemia Cells , Blood . 2007, 109: 740-746.

Man C.W.Y., Rosa J., Lee T.O., Lee V.H.Y., Chow B.K.C., Lo K.W., Doxsey S., Wu Z.G., Kwong Y.L., Jin D., Cheung A. and Tsao G.S.W., Latent membrane protein 1 suppresses RASSF1A expression, disrupts microtubule structures and induces chromosomal aberrations in human epithelial cells , Oncogene. Nature Publishing Group, 2007, 26: 3069-3080.

Pang R.W.C., Lee K.W., Man K., Poon R.T.P., Fan S.T., Kwong Y.L. and Tse E.W.C., PIN1 expression contributes to hepatic carcinogenesis, Journal of Pathology. 2006, 210(1): 19-25.

Pang R.W.C., Lee K.W., Poon R.T.P., Fan S.T., Wong K.B., Kwong Y.L. and Tse E.W.C., Pin1 interacts with a specific serine-proline motif in hepatitis B virus X-protein to enhance hepatocarcinogenesis, Gastroenterology. 2007, 132(3): 1088-1103.

Pang R.W.C., Poon R.T.P., Fan S.T., Kwong Y.L. and Tse E.W.C., Pin1: a novel regulator of tumor angiogenesis and invasiveness in hepatocellular carcinoma (Abstract), The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007. Hepatology International. 2007, 1(1): 143.

Pang R.W.C., Poon R.T.P., Fan S.T., Kwong Y.L. and Tse E.W.C., Pin1: a novel regulator of tumor angiogenesis and invasiveness in hepatocellular carcinoma (Abstract), The American Association for Cancer Research Annual Meeting 2007, Los Angeles, U.S.A., 14 - 18 April 2007.

Siu C.W.D., Au W.Y., Yung C.Y., Kumana C.R., Lau C.P., Kwong Y.L. and Tse H.F., Effects of oral arsenic trioxide therapy on QT intervals in patients with acute promyelocytic leukemia: implications on long-term cardiac safety, Blood. 2006, 108(1): 103-106.

Tse H.F., Thambar S., Kwong Y.L., Rowlings P., Bellamy G., McCrohon J., Bastian B., Chen W.H., Chan J.K.F., Lo G., Ho C.L. and Lau C.P., Safety of Catheter-Based Intramyocardial Autologous Bone Marrow Cells Implantation fro Therapeutic Angiogenesis, AM J CARDIOL. 2006, 98(1): 60-62.

Wong A.S.Y., Chan K.H., Cheng V.C.C., Yuen K.Y., Kwong Y.L. and Leung A.Y.H., Relationship of pretransplantation polyoma BK virus serologic findings and BK viral reactivation after hematopoietic stem cell transplantation, Clinical Infectious Disease. 2007, 44(6): 830-837.

Zhang H., Jin Y., Chen X., Jin C., Law S.Y.K., Tsao G.S.W. and Kwong Y.L., Papillomavirus type 16 E6/E7 and human telomerase reverse transcriptase in esophageal cell immortalization and early transformation, Cancer Letters. 2007, 245(1-2): 184-194.

Zhang H., Hui C.K., Lee P.Y., Chan W., Yueng Y.H., Leung K.W., Lu L., Leung N., Lo C.M., Fan S.T., Luk J.M.C., Xu A., Lam K.S.L., Kwong Y.L. and Lau G., Serum adiponectin is increased in advancing liver fibrosis and decline with reduction in fibrosis in chronic hepatitis B, The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007, Hepatology International. 2007, 242: 7.

Researcher : Lai AYK

List of Research Outputs

Ip M.S.M., Lam W.K., Lai A.Y.K., Ko F., Lau A., Ling S.O., Chan J. and Chan W.M., Reference values of diffusing capacity of non-smoking Chinese in Hong Kong, Respirology. 2007, 12: 599-606.

Ip M.S.M., Lam W.K., Lai A.Y.K., Ko F.W., Lau A.C., Ling S.O., Chan J.W. and Chan M.M.W., Reference values of diffusing capacity of nonsmoking Chinese in Hong Kong., Respirology. 2007, 12: 599-606.

Lam J.C., Tam S., Ooi C.G.C., Ku P.P., Lai A.Y.K., Lam B., Lam K.S.L. and Ip M.S.M., Relationship between sympathetic activity, obesity, and obstructive sleep apnea, 8th World Congress on Sleep Apnea. Montreal, Canada. Sleep Medicine. 2006, 7 (suppl 2): S51 (P321).

Lam J.C.M., Tam S., Ooi C.G.C., Ku P.P., Lai A.Y.K., Lam B., Lam K.S.L. and Ip M.S.M., Relationship between sympathetic activity, obesity, and obstructive sleep apnea, 8th World Congress on Sleep Apnea. Montreal, Canada, September 2006. Sleep Medicine. 2006, 7 (suppl 2): S51 (P321).

Researcher : Lai CL

List of Research Outputs

Bourne E.J., Dienstag J.L., Lopez V.A., Sander T.J., Longlet J.M., Hall J.G., Kwiakowski R.W., Wright T., Lai C.L. and Condreay L.D., Quantitative analysis of HBV cccDNA from clinical specimens: correlation with clinical and virological response during antiviral therapy , Journal of Viral Hepatitis. 2007, 14: 55-63.

Bzowej N., Chan H.L.Y., Lai C.L., Cho M., Moon Y.M., Chao Y.C., Heathcote E.J., Myers R., Minuk G., Marcellin P., Jeffers L., Sievert W., Kaiser R., Harb G., Chao G.C. and Brown N.A., A Randomized Trial of Telbivudine (LdT) vs Adefovir for HBeAg-positive Chronic Hepatitis B: Final Week 52 results, Hepatology. 2006, 44(Suppl 1): 1005.

Chang T.T. and Lai C.L., Hepatitis B virus with primary resistance to adefovir, New England Journal of Medicine. 2006, 355: 322-323.

Cheung T.K., Lai C.L., Wong B.C.Y., Fung J.Y.Y. and Yuen R.M.F., Clinical Features, Biochemical Parameters, and Virological Profiles of Patients with Hepatocellular Carcinoma in Hong Kong, Aliment Pharmacol Ther . 2006, 24(4): 573-583.

Cheung T.K., Lai C.L., Wong B.C.Y., Fung J.Y.Y. and Yuen R.M.F., Clinical features, biochemical parameters, and virological profiles of patients with hepatocellular carcinoma in Hong Kong. , Alimentary Pharmacology and Therapeutics. 2006, 24(4): 573-83.

DiBisceglie A A., Lai C.L., Gane E., Chen Y.C., Thongsawat S., Wang Y.M., Chen Y.G., Heathcote E.J., Zeuzem S., Rasenack J., Bzowej N., Han S.H., Naoumov N., Hwang S.G., Lim S.G., Chao G.C., Fielman B.A., Brown N.A. and Study Group The GLOBE , Telbivudine Globe Trial: Maximal Early HBV Suppression is Predictive of Optimal Two-year Efficacy in Nucleoside-treated Hepatitis B Patients, Hepatology. 2006, 44(Suppl 1): 231A.

Fung J.Y.Y., Lai C.L., Yuen J.C.H., Wong D.K.H., Tanaka Y., Mizokami M. and Yuen R.M.F., Adefovir dipivoxil monotherapy and combination therapy with lamivudine for the treatment of chronic hepatitis B in an Asian population, Antivir Ther. 2007, 12: 41-46.

Fung J.Y.Y., Lai C.L., Wong D.K.H., Cheng C.T.K., But D.Y. and Yuen R.M.F., Large Population Study in Liver Stiffness Measurement: Prevalence of Significant Fibrosis and Correlation with Liver Biochemistry in Chronic Hepatitis B, Annual Meeting for European Association for the Study of the Liver (EASL 2007). 2007.

Fung J.Y.Y., Lai C.L., Wong D.K.H. and Yuen R.M.F., Large population study on the natural history of spontaneous hepatitis B e antigen seroconversion: risk of hepatocellular carcinoma. Annual meeting, European Association for the Study of Liver (EASL). Journal of Hepatology. 2007, 46 S1: S181.

Fung J.Y.Y., Lai C.L. and Yuen R.M.F., Overcoming the problem of chronic hepatitis B. Drug Discovery Today, Therapeutic Strategies. 2007, 3: 197-202.

Fung J.Y.Y., Lai C.L. and Yuen R.M.F., Telbivudine : A new treatment option in the management of chronic hepatitis B, Hepatitis B Annual. 2006, 3(1): 14-34.

Gish R., Chang T.T., Lai C.L., de Man R., Gadano A., Poordad F., Zhu J., Yang J. and Brett-Smith H., Hepatitis B Surface Antigen Loss in Antiviral-treated Patients with HBeAg(+) Chronic Hepatits B (CHB) Infection: Observations from Antiviral-naive Patients Treated with Entecavir (ETV) or lamivudine (LVD), Hepatology. 2006, 44(Suppl 1): 992.

Lai C.L., Award Recipient, Outstanding Research Student Supervisor Award. 2006.

Lai C.L., Clinical applicability of the latest AASLD / APASL guidelines in the Asian population, First St. Luke's International Liver Conference held in Manila, Philippines between January 15-16. 2007.

Lai C.L., Clinical applicability of the latest AASLD / APASL guidelines in the Asian population, Telbivudine Indonesian Launch Meeting held in Jarkarta, Indonesia on February 3. 2007.

Lai C.L., Entecavir & Nucs, HBV Day of the 17^th Asian Pacific Association for the Study of the Liver (APASL) Conference "Viral Hepatitis and Hepatocellular Carcinoma in Asia" in Kyoto, Japan between March 27-30. 2007.

Lai C.L., Faculty Presenter and Expert Panelist, DDW CME Satellite Symposium entitled "Challenge the HBV Experts" which was held on May 20, 2007 during the Digestive Disease Week (DDW) in Washington, DC, USA between May 19-22. 2007.

Lai C.L., Grader, 57^th AASLD Annual Meeting abstracts. 2006.

Lai C.L., HBV treatment update, Post Graduate Course of the 17^th Asian Pacific Association for the Study of the Liver (APASL) Conference "Viral Hepatitis and Hepatocellular Carcinoma in Asia" in Kyoto, Japan between March 27-30. 2007.

Lai C.L., Hepatitis B virus treatment update, Novartis Standalone Meeting organized by Novartis India Limited in Hyderbad, India on May 6. 2007.

Lai C.L., Hepatology, 50^th Anniversary Scientific Meeting of The Society of Physicians of Hong Kong on March 18. 2007.

Lai C.L., Lamivudine/Adefovir/Entecavir, HBV Day of the 17^th Asian Pacific Association for the Study of the Liver (APASL) Conference "Viral Hepatitis and Hepatocellular Carcinoma in Asia" in Kyoto, Japan between March 27-30. 2007.

Lai C.L., Member of the Editorial Board, Hepatology International. 2007.

Lai C.L., Member of the Editorial Board, Journal of Viral Hepatitis. 2007.

Lai C.L., Member, Sub-Committee for the Outstanding Researcher Award 2006/07, The University of Hong Kong, Hong Kong. 2007.

Lai C.L., Patient case, BMS Entecavir European Launch Meeting "On the Road to Optimizing HBV Treatment with Baraclude" held in Paris, France between September 22-23. 2006.

Lai C.L., Presentation on New aspect on anti-virals, Round-table Discussion on: New Aspects on Anti-viral Agents for Chronic Hepatitis B organized by Novartis Korea Limited in Seoul, Korea on April 23-24. 2007.

Lai C.L., Rising to the challenge in the management of chronic hepatitis B, BMS Satellite Symposium DDW-Japan 2006 held in Sapporo, Japan on October 12. 2006.

Lai C.L., Rising to the challenge in the management of chronic hepatitis B, HKASLD Scientific Symposium Programme – Raising a New Standard in Chronic Hepatitis B Management, held in Hong Kong on September 28. 2006.

Lai C.L., Role of HBV genotypes in managing CHB among Asians, First St. Luke's International Liver Conference held in Manila, Philippines between January 15-16. 2007.

Lai C.L., Gane E., Hsu C.W., Chen Y.C., Thongsawat S., Wang Y., Chen Y., Naoumov N., Han S.H., Hwang S.G., Lim S.G. and Brown N.A., Telbivudine vs Lamivudine in HBeAg-Positive Patients with CHB: Two-Year Efficacy and Predictors of Response, Oral Presetnation at the Parallel Oral Session of the HBV Day of the 17th Asian Pacific Association for the Study of the Liver (APASL) Conference on March 28. 2007.

Lai C.L., The Natural History and Treatment of Chronic Hepatitis B: Consensus and Controversies, 'FOCUS on Hepatitis B' meeting in Shenzhen on August 26. 2006.

Lai C.L., The Natural History of Chronic Hepatitis B, Journal of Clinical Virology. 2006, 36 (Suppl 2): S45-S46.

Lai C.L., The Natural History of Chronic Hepatitis B, Plenary Session entitled 'HBV and HDV: Virology, Immunology, Natural History, Treatment' in the 12th International Symposium on Viral Hepatitis and Liver Disease, Paris, July 4. 2006.

Lai C.L., The importance of monitoring the disease, Hepatitis B Awareness Campaign HK 2007 organized by The Hong Kong Liver Foundation in Hong Kong on March 18. 2007.

Lai C.L., Treatment guidelines: are we missing patients at risk?, BMS Chronic Hepatitis B Updates "Evidence for Action – Hope for Hepatitis B" held in Trengganu, Malaysia on September 2. 2006.

Lai C.L., Gane E., Hsu C.W., Thongsawat S., Wang Y.M., Chen Y.G., Heathcote E.J., Rasenack J., Bzowej N., Naoumov N., Zeuzem S., Di Bisceglie A., Chao G.C., Barbara A., Constance F., Brown N.A. and Study Group The GLOBE. , Two-year Results from the Globe Trial in Patients with Hepatitis B: Greater Clinical and Antiviral Efficacy for Telbivudine (LdT) vs Lamivudine, Hepatology. 2006, 44 (Suppl 1): 222A.

Lai C.L., Two-year results from the GLOBE Trial in patients with hepatitis B: greater clinical and antiviral efficacy for telbivudine (LdT) vs lamivudine, 57^th AASLD Annual Meeting held in Boston, USA between October 27 – 31. 2006.

Lai C.L., Two-year results from the GLOBE trial: telbivudine (LdT) vs lamivudine, Telbivudine Indonesian Launch Meeting held in Jarkarta, Indonesia on February 3. 2007.

Lai C.L., Understanding HBV disease: viral load and disease progression, 57^th AASLD Annual Meeting: CME-Certified Satellite Symposum "Focus on the Virus: A new paradigm for the management and treatment of HBV" organized by Clinical Care Options, LLC in Boston, USA on October 30. 2006.

Lai C.L., Understanding viral resistance: impact and importance on treatment, BMS Chronic Hepatitis B Updates "Evidence for Action – Hope for Hepatitis B" held in Trengganu, Malaysia on September 2. 2006.

Lai C.L., Update on chronic hepatitis B treatment and guideline, Round Table Discussion organized by Britsol-Myers Squibb (Hong Kong) Ltd. in Hong Kong on April 26. 2007.

Lai C.L., Update on chronic hepatitis B treatment, BMS sponsored CME Symposium entitled "The Importance of Viral Load and Hepatitis B Treatment Update" organized by The Hong Kong Medical Association in Hong Kong on May 10. 2007.

Lai C.L., Viral load and disease progression, BMS Chronic Hepatitis B Updates”Evidence for Action – Hope for Hepatitis B”held in Trengganu, Malaysia on September 2. 2006.

Lai C.L., Viral resistance to nucleos(t)ide analogues and the effect of HBV DNA suppression, International Symposium on Hepatology 2006 organized by The Hong Kong Association for the Study of Liver Diseases held in Hong Kong between November 3-4. 2006.

Lai C.L., Viral resistance to nucleos(t)ide analogues effect of HBV DNA suppression, KASL Autumn Symposium held in Korea on November 22. 2006.

Lai C.L., Who to treat? - A critical ceview of two new treatment guidelines from the States. Comparison of current treatment options, BMS Satellite Symposium at the National Hepatology Congress in Instanbul, Turkey between June 7-10. 2007.

Lee W.Y., Lee P.P.W., Wong W.H.S., Yuen R.M.F., Poon R.T.P., Lai C.L., Fan S.T. and Lau Y.L., Association of Transforming Growth Factor-Beta 1 (TGF-b1) Polymorphisms with Hepatitis B Virus (HBV) Related Fibrosis and Cirrhosis in the Hong Kong Chinese, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006.

Lim S.G., Lai C.L., Thongsawat S., Wang Y., Chen Y., Rasenack J., Naoumov N., Chao G. and Brown N., Maximal Early Hbv Suppression In Nucleoside-treated Hepatitis B Patients Is Associated With Optimal Virologic And Clinical Efficacy At One Year, Journal of Clinical Virology. 2006, 36: S245.

Orito E., Fujiwara K., Tanaka Y., Yuen R.M.F., Lai C.L., Kato T., Sugauchi F., Kusakabe A., Sata M., Okanoue T., Niitsuma H., Sakugawa H., Hasegawa I. and Mizokami M., A case-control study of response to lamivudine therapy for 2 years in Japanese and Chinese patients chronically infected with hepatitis B virus of genotypes Bj, Ba and C, Hepatol Res. 2006, 35(2): 127-34.

Schiff E., Lai C.L., Hadziyannis S., Neuhaus P., Terrault N., Colombo M., Tillmann H., Samuel D., Zeuzem S., Villeneuve J.P., Arterburn S., Borroto-Esoda K., Brosgart C., Chuck S. and Adefovir Dipivoxil Study 45 I.I.G., Adefovir dipivoxil for wait-listed and post-liver transplantation patients with lamivudine-resistant hepatitis B: final long-term results. , Liver Transplantation. 2007, 13: 349-360.

Tanaka Y., Mukaide M., Orito E., Yuen R.M.F., Ito K., Kurbanov F., Sugauchi F., Asahina Y., Izumi N., Kato M., Lai C.L. and Ueda R., Specific mutations in enhancer II/core promoter of hepatitis B virus subgenotypes C1/C2 increase the risk of hepatocellular carcinoma [Epub ahead of print], Journal of hepatology : the journal of the European Association for the Study of the Liver. 2006, 10.

Tanaka Y., Mukaide M., Orito E., Yuen R.M.F., Ito K., Kurbanov F., Sugauchi F., Asahina Y., Izumi N., Kato M., Lai C.L., Ueda R. and Mizokami M., Specific mutations in enhancer II/core promoter of hepatitis B virus subgenotypes C1/C2 increase the risk of hepatocellular carcinoma, Journal of hepatology : the journal of the European Association for the Study of the Liver. 2006, 45: 646-653.

Tanaka Y., Mukaide M., Orito E., Yuen R.M.F., Ito K., Kurbanov F., Sugauchi F., Asahina Y., Izumi N., Kato M., Lai C.L., Ueda R. and Mizokami M., Ueda R, Mizokami M. Specific mutations in enhancer II/ core promoter of hepatitis B virus subgenotypes C1/C2 increase the risk of hepatocellular carcinoma, Journal of hepatology : the journal of the European Association for the Study of the Liver. 2006, 45(5): 646-653.

Wong D.K.H., Yuen R.M.F., Ngai W.S., Fung J.Y.Y. and Lai C.L., One-year entecavir or lamivudine therapy results in reduction of HBV intrahepatic covalently closed circular DNA levels, Antivir Ther . 2006, 11: 909-916.

Wong D.K.H., Yuen R.M.F., Ngai W.S., Fung J.Y.Y. and Lai C.L., One-year entecavir or lamivudine therapy results in reduction of hepatitis B virus intrahepatic covalently closed circular DNA levels., Antiviral Therapy. 2006, 11: 909-916.

Wong D.K.H., Yuen R.M.F., Poon R.T.P., Yuen J.C.H., Fung J.Y.Y. and Lai C.L., Quantification of hepatitis B virus covalently closed circular DNA in patients with hepatocellular carcinoma, Journal of hepatology : the journal of the European Association for the Study of the Liver. 2006, 45: 553-559.

Wong D.K.H., Yuen R.M.F., Poon R.T.P., Yuen J.C.H., Fung J.Y.Y. and Lai C.L., Quantitation of hepatitis B virus covalently closed circular DNA in patients with hepatocellular carcinoma, Journal of Hepatology. 2006, 45: 553-559.

Wong R.W.M., Lai K.C., Yiu M.W.C., Wong B.C.Y., Chan F.L. and Lai C.L., Intestinal tuberculosis mimicking fistulizing Crohn's disease, Journal of Gastroenterology and Hepatology. 2007, 22: 137-139.

Yuan H.J., Wong D.K.H., Doutreloigne J., Sablon E., Lai C.L. and Yuen R.M.F., Precore and core promoter mutations at the time of HBeAg seroclearance in Chinese patients with chronic hepatitis B., Journal of Infection. 2007, 54: 497-503.

Yuen R.M.F., Kim J., Kim C.R., Ngai W.S., Yuen J.C.H., Min C., Kang H.M., Shin B.S., Yoo S.D. and Lai C.L., A Randomized Placebo-controlled, Dose-finding Study of Oral LB80380 in HBeAg-positive Patients with Chronic Hepatitis B, Antivir Ther. 2006, 11(8): 977-983.

Yuen R.M.F. and Lai C.L., A new drug for chronic hepatitis B: entecavir, Medical Progress. 2006, 33(7): 343-346.

Yuen R.M.F. and Lai C.L., Combination therapy for chronic hepatitis B: Simultaneous or sequential, American Journal of Gastroenterology. 2007, 102: 105-106.

Yuen R.M.F., Wong D.K.H., Zheng B., Chan C.C.S., Yuen J.C.H., Wong B.C.Y. and Lai C.L., Difference in T Helper Responses During Hepatitis Flares in HBeAg-positive Patients with Genotypes B and C: Implication for Early HBeAg Seroconversion, Journal of Viral Hepatitis. 2007, 14: 269-275.

Yuen R.M.F. and Lai C.L., HBsAg seroclearance in the natural history of chronic hepatitis B infection, Current Hepatitis Reports. 2006, 5(1): 23-26.

Yuen R.M.F. and Lai C.L., Recommendations and Potential Future Options in the Treatment of Hepatitis B, Expert Opin Pharmacother. 2006, 7(16): 2225-2231.

Yuen R.M.F., Tanaka Y., Shinkai N., Poon R.T.P., But D.Y.K., Fong D.Y.T., Fung J.Y.Y., Wong D.K.H., Yuen J.C.H., Mizokami M. and Lai C.L., Risk for hepatocellular carcinoma with respect to hepatitis B virus genotypes B/ C, specific mutations of enhancer II/ core promoter/ precore regions and HBV DNA levels, Gut. 2007, 57: 98-102.

Yuen R.M.F., Tanaka Y., Shinkai N., Poon R.T.P., Fung J.Y.Y., Wong D.K.H., Yuen J.C.H., Mizokami M. and Lai C.L., Role of HBV genotypes, core promoter/precore mutations and HBV DNA levels on hepatocarcinogenesis, Annual meeting, European Association for the Study of Liver (EASL), Barcelona, Spain, 11 - 15 April 2007.

Yuen R.M.F., Sablon E., Libbrecht E., de Velde H.V., Wong D.K.H., Fung J.Y.Y., Wong B.C.Y. and Lai C.L., Significance of HBV viral load, core promoter/ precore mutations and specific sequences of polymerase gene in HBV-infected patients on 3-year lamivudine treatment, Antivir Ther. 2006, 11(6): 779-786.

Yuen R.M.F., Tam S., Fung J.Y.Y., Wong D.K.H., Wong B.C.Y. and Lai C.L., Traditional Chinese medicine causing hepatotoxicity in patients with chronic hepatitis B infection: A one-year prospective study, Alimentary Pharmacology and Therapeutics. 2006, 24(8): 1179-1186.

Researcher : Lai KC

List of Research Outputs

Chan A.O.O., Jim M.H., Lam K.F., Siu D.C.W., Tong S.M., Ng F.H., Wong S.Y., Hui W.M., Chan C.K., Lai K.C., Cheung T.K., Chan P., Wong G., Yuen R.M.F., Lau Y.K., Lee S.W.L., Seto M.L., Lam S.K. and Wong B.C.Y., Patients with coronary artery disease had high prevalanece of colorectal cancer and adenoma: END-results of metabolic syndrome and smoking. Digestive Disease Week 2007, Washington DEc, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A65.

Chan O.O., Lam K.F., Tong T.P.H., Siu D.C.W., Jim M.H., Hui W.M., Lai K.C., Yuen R.M.F., Lam S.K. and Wong B.C.Y., Coexistence between colorectal cancer/adenoma and coronary artery disease: results from 1382 patients. , Alimentary Pharmacology and Therapeutics. 2006, 24(3): 535-9.

Cheung T.K., Lam K.F., Hu H.C., Wong W.M., Hui W.M., Lam C.L.K., Lai K.C., Lam S.K. and Wong B.C.Y., Positive association between gastro-oesophageal reflux disease and irritable bowel syndrome in a Chinese population, Alimentary Pharmacology & Therapeutics. Blackwell Publishing, 2007, 25: 1099-1104.

Hu H.C., Lam S.K., Lam C.L.K., Wong R.W.M., Lam K.F., Lai K.C., Wong Y.H., Wong B.C.Y., Chan O.O., Chan C.K., Leung G.M. and Hui W.M., Comparison between Empirical Prokinetics, Helicobacter Test-and-Treat and Empirical Endoscopy in Primary-Care Patients Presenting with Dyspepsia: A One-Year Study, World Journal of Gastroenterology. 2006, 12(31): 5010-5016.

Lai K.C., Chu K.M., Hui W.M., Wong B.C.Y., Hung W.K., Loo C.K., Hu H.C., Chan O.O., Kwok K.F., Fung T.T., Wong J. and Lam S.K., Esomeprazole with aspirin versus clopidogrel for prevention of recurrent gastrointestinal ulcer complications, Clinical Gastroenterology and Hepatology. 2006, 4: 860-865.

Wong R.W.M., Lai K.C., Yiu M.W.C., Wong B.C.Y., Chan F.L. and Lai C.L., Intestinal tuberculosis mimicking fistulizing Crohn's disease, Journal of Gastroenterology and Hepatology. 2007, 22: 137-139.

Researcher : Lai KN

Project Title:	Chemokine production and T cell interaction in chronic glomerulo-nephritides and interstitial nephritis: exploration of tubulo-glomerular communication
Investigator(s):	Lai KN, Leung JCK
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	10/2003
Completion Date:	09/2006

Abstract:

To study tubulo-glomerular crosstalk in the presence of proteinuria. Activated PTEC induce proliferation and matrix formation in mesangial cells via soluble factors (alone or with participation of infiltrating T cells/monocytes); to determine whether PTEC may undergo epithelial-mesenchymal transidfferentiation under the influence of glomerulopathic proteins (alone or with participation of infiltrating T cells/monocytes); to examine whether activated mesangial cells (HMC) induce tubular expression of proinflammatory mediators (complement, chemokine, and growth factor) and the subsequent development of tubular epithelial-mesenchymal transdifferentiation via soluble factors (alone or with participation of infiltrating T cells/monocytes).

Project Title:	The role of the renin-angiotensin system in the tubulointerstitial injury of IgA nephropathy (IgAN)
Investigator(s):	Lai KN, Leung JCK
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2004

Abstract:

To define the role of RAS in inducing PTEC/MC damage and; to elucidate the cross-talk between resident cells and infiltrating cells (T-cells/monocytes).

Project Title:	The role of the renin-angiotensin system in the tubulointerstitial injury of IgA nephropathy (IgAN)
Investigator(s):	Lai KN, Leung JCK
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2005

Abstract:

To determine whether there are known IgA receptors in the renal tubules; to determine the presence of any specific binding of pIgA from patients with IgAN to renal tubular epithelial cells; if there is no specific binding of IgA from IgAN to renal tubular epithelial cells, to find out where there are humoral or soluble factors from activated mesangial cells that induce tubular expression of proinflammatory mediators and the subsequent development of tubular epithelial-mesenchymal transdifferentiation; to explore which receptors for these proinflammatory mediators are present in renal tubules; to find out whether tubular damage is mediated via soluble factors alone or infiltrating T-cells/monocytes are also required.

Project Title:	Development of monoclonal antibodies against SARS-associated coronavirus: specific targeting for early diagnosis and future treatment
Investigator(s):	Lai KN, Kwong YL, Chung SSM
Department:	Medicine
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	01/2005
Completion Date:	09/2006

Abstract:

In this project, we propose to express the coronaviral proteins in vitro. B lymphocytes from patients with immunity to the coronavirus will be used to produce specific antibodies against coronaviral anitgens. These monoclonal antibodies will be of tremendous value in providing a safe and rapid serum and tissue diagnosis of SARS-related coronavirus infection. Therapeutic potentials are also possible for these antibodies as an adjuvant immuno-modulatory therapy.

Project Title:	Crosstalk between Podocytes and Mesangial Cells in IgAN
Investigator(s):	Lai KN
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2006

Abstract:

IgA nephropathy (IgAN) is the major leading cause of kidney failure worldwide. The disease is characterized by the deposition of "pathogenetic" polymeric immunoglobulin A (pIgA) in the glomerular mesangium followed by proliferation of the mesangial cell (HMC) and infiltration of immunocompetent cells including T-cells and monocytes. [1] IgAN runs a highly variable clinical course that is often associated with progressive tubulointerstitial damage and subsequent renal failure. The severity of tubulo- interstitial damage is a better prognostic indicator of renal function than glomerular sclerosis, yet IgA deposits are seldom detected in the tubulointerstitium. Although high-grade proteinuria can lead to tubulointerstitial damage and progressive kidney failure in glomerular disease, heavy proteinuria, notably, is not a common feature of IgAN. Hence, the puzzling question is how do IgA deposits in glomerular mesangial cells lead to subsequent tubulointerstitial damage and result in terminal renal failure. Although the causes of kidney failure are diverse, the glomerular filtration barrier is often the target of injury. This barrier separates the blood from urinary spaces, and selectivity permits the removal of excess water and solute while preventing the loss of critical blood proteins such as albumin, immunoglobulins and clotting factors. The filtration barrier consists of glomerular visceral epithelial cells (podocytes) that are in intimate association with fenestrated glomerular capillary endothelial cells, and are separated from each other by a thin glomerular basement membrane (GBM) that measures only 0.3 micron. Glomerular podocytes are highly differentiated cells that play a key role in maintaining the integrity of the glomerular filtration barrier. Their interdigitating foot processes cover the exterior surface of the glomerular basement membrane and, in turn, stabilize the glomerular architecture. In glomerular diseases, podocyte damage is associated with proteinuria and progressive loss of kidney function. [2] Recent genetic studies have highlighted the importance of the podocyte in disease processes that affect the glomerulus. A number of podocyte proteins have been identified and genetic mutations of these podocyte proteins are associated with congenital forms of nephrotic syndrome.[3,4] These genetic breakthroughs have stimulated renewed interest in glomerular epithelial cell biology, both in normal, congenital and acquired disease states. As a consequence of the high degree of differentiation of podocytes in analogy to neurons, these cells are unable to proliferate. An inability to repopulate a damaged glomerulus with functional podocytes corresponds with the progressive ultrastructural lesions seen in podocyte during filtration barrier failure. Investigators from Hong Kong first reported necrosis and detachment of the podocytes from the GBM in IgAN in 1984.[5] Subepithelial accumulation of proteinaceous material from the mesangium leads to degeneration and exfoliation of podocytes. [6] Those IgAN patients with the most severe glomerular dysfunction have a reduced number of podocytes per glomerulus. [7] The degree of podocytopenia is related to the extent of glomerular sclerosis and of impairment of permeability and glomerular filtration rate. Urinary excretion of podocytes is increased in IgAN [8] and this observation complements the histologic finding of podocytopenia. The urinary excretion of podocytes reflects disease activity and the excretion decreases following treatment with either angiotensin-converting enzyme (ACE) inhibitors or statins. [9,10] Despite IgAN being the most common glomerulonephritis worldwide and the abundance of literature on the structural and immunoregulatory abnormalities in IgAN, information on podocyte biology in IgAN is scarce. Our research proposal will examine the following issues:(i) Is there a specific binding of pIgA from patients with IgAN to podocytes?(ii) How does mesangial deposition of IgA lead to glomerular filtration barrier failure in IgAN? Hypothesis and Specific Aims: Our working hypothesis is that the natural progression of tubulointerstitial injury in IgAN is mediated through a "glomerulo-tubular" cross-talk. We postulate that soluble factors are released from glomerular mesangial cells following initial deposition of "pathogenetic" pIgA. A cross-talk network initiated by these soluble factors will orchestrate interactions between infiltrating immunocompetent cells and the resident renal cells, forming a major driving force of tubulointerstitial injury. These humoral factors from mesangial cells (HMC) may reach the tubulointerstitium either by glomerular filtration or by transportation via the post-glomerular capillaries. Podocytes in the Bowen's capsule must play a pivotal controlling role of the traffic of these humoral factors between the glomerular mesangial cells and tubular epithelial cells. We hypothesize that functional and structural changes occur to podocytes in IgAN and thus lead to dysfunction of the filtration barrier. Our present proposal will examine functional and structural abnormalities of podocytes following mesangial IgA deposition. The research also aims to dissect the interaction between podocytes and other renal resident cells in IgAN. References1. Lai KN, Chan LY, Leung JC: Kidney Int Suppl 2005:S110-115.2. Kriz W: Pediatr Nephrol 2003; 18: 617-6223. Kestila M, Lenkkeri U, Mannikko M, et al: Mol Cell 1998; 1: 575-582.4. Boute N, Gribouval O, Roselli S: Nat Genet 2000; 24: 349-354.5. Ng WL, Chan KW, Yeung CK, Kwan S: Pathology 1984; 16: 324-330.6. Shigematsu H, Kobayashi Y, Hiki Y: Ultrastruct Pathol 1990; 14: 129-139.7. Lemley KV, Lafayette RA, Safai M, et al: Kidney Int 2002; 61: 1475-1485.8. Hara M, Yanagihara T, Takada T, et al: Am J Nephrol 1998; 18: 35-41.9. Nakamura T, Ushiyama C, Suzuki C, et al: Am J Nephrol 2000; 20: 373-373339.10. Nakamura T, Ushiyama C, Hirokawa K, et al: Nephrol Dial Transplant 2002; 17: 798-802.

Project Title:	The tubular peroxisome proliferator - activated receptors (PPAR) -γ system in IgA nephropathy: a potential therapeutic target
Investigator(s):	Lai KN
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2007

Abstract:

To test whether the PPAR system in renal tubules is suppressed due to the glomerulo-tubular "cross-talk" that operates in IgAN; to test whether PPAR-γ agonist suppresses the expression of ATR1 in proximal tubular epithelial cells and hence improves the therapeutic efficacy of ATR1 blockade; to test the new therapeutic regimen derived from an in vitro model be applied to an animal model of IgAN

List of Research Outputs

Chan D.T.M., Ho S.K.N., Tang C.S.O., Tse K.C., Lam M.F., Lai K.N. and Yung S.S.Y., Pilot study of pegylated interferon-alpha 2a in dialysis patients with chronic hepatitis C virus infection, Nephrology. 2007, 12: 11-17.

Chan H.H.L., Yang C., Leung J.C.K., Wei W.I. and Lai K.N., An Animal Study of the Effects on p16 and PCNA Expression of Repeated Treatment with High-Energy Laser and Intense Pulsed Light Exposure, Lasers in Surgery and Medicine. 2007, 39: 8-13.

Choy C.B.Y., Chan D.T.M. and Lai K.N., Recurrent glomerulonephritis after kidney transplantation, American Journal of Transplantation. 2006, 6: 2535-2542.

Feldt-Rasmussen B., Lange M., Sulowicz W., Gafter U., Lai K.N., Wiedemann J., Christiansen J.S., El Nahas M. and and the Adult Patients in Chronic Dialysis (APCD) S.G., Growth hormone treatment during hemodialysis in a randomized trial improves mutrition, quality of life, and cardiovascular risk, Journal of American Society of Nephrology. 2007, 18: 2161-2171.

Feldt-Rasmussen B., Lange M., Sulowicz W., Grafter U. and Lai K.N., Improvement of lean body mass, other predictors of mortality and quality of life during growth hormone treatment in patients on chronic hemodialysis: Results from a randomized, double-blind, placebo-controlled trial, Journal of American Society of Nephrology. 2006, 17: 228A.

Guo H., Leung J.C.K., Lam M.F., Lan H.Y. and Lai K.N., Smad7 transgene attenuates TGF-b induced peritoneal fibrosis in uremic rats on peritoneal dialysis, Journal of American Society of Nephrology. 2006, 17: 29A.

Lai K.N., Leung J.C.K., Chan L.Y., Guo H. and Tang S.C.W., Interaction between proximal tubular epithelial cells and infiltrating monocytes/T cells in the proteinuric state, Kidney International. 2007, 71: 526-538.

Lai K.N., Invited Speaker, Treatment of idiopathic membranous nephropathy: Novartis-Cyclosporin Forum, Guangzhou, China, June 15. 2007.

Lai K.N., Managing Editor, Nephrology. 2006.

Lai K.N., Tang S.C.W. and Leung J.C.K., Mediators of inflammation and fibrosis, Peritoneal Dialysis International . 2007, 27: S65-71.

Lai K.N., Membranous nephropathy: when and how to treat, Kidney International. 2007, 71: 841-843.

Lai K.N., Chan L.Y., Saleem P., Mathieson P. and Leung J.C.K., Regulation of Bcl-2 expression in podocytes by mesangial cells derived TNF-a in IgA nephropathy, Journal of American Society of Nephrology. 2006, 17: 254A.

Lai K.N., Tang S.C.W., Chan L.C.B. and Leung J.C.K., The modulation of chemokines release in proximal tubular epithelial cell by monocytes/T cells in proteinuric state is mediated by IL-1 and TNF-a, Journal of American Society of Nephrology. 2006, 17: 384A.

Lai K.N. and Lan H.Y., Ultrasound Microbubble Mediated Genes Delivery System, In: Cooper&Dunham LLP, USA Patent (11/928,109). USA, 2006.

Lam M.F., Tang C.S.O., Wong A.K., Tong K.L., Yu A.W., Li C.S., Cheung K.O. and Lai K.N., ASPD: A prospective study of adequacy in Asian patients on long term, small volume, continuous ambulatory peritoneal dialysis, Peritoneal Dialysis International. 2006, 26: 466-474.

Lam M.F., Tse K.C., Chan G., Chan K.W., Chan D.T.M. and Lai K.N., De Novo glomerulonephritis after hemopoietic stem cell transplantation, Journal of American Society of Nephrology. 2006, 17: 733A.

Lam M.F., Au W.Y., Tse K.C., Chan D.T.M., Chan G.S., Chan K.W. and Lai K.N., Hyperleptinaemia and chronic inflammation after peritonitis predicts poor nutritional status and mortality in patients on peritoneal dialysis, Nephrology Dialysis Transplantation. 2007, 32: 1445-1450.

Lam M.F., Au W.Y., Tse K.C., Chan D.T.M., Chan G.S.W., Chan K.W. and Lai K.N., Late onset membranous nephropathy complicating donor lymphocyte infusion for Leukaemia relapse after allogeneic stem cell transplantation, American Journal of Hematology. 2007, 82(4): 327-328.

Leung J.C.K., Tang S.C.W., Chan L.Y., Yuen Y.M. and Lai K.N., Specific induction of neutrophil gelatinase-associated lipocalin in peritoneal mesothelial cells by interleukin-1, Journal of American Society of Nephrology. 2006, 17: 751A.

Lui S.L., Chan K.W., Tsang R.C.W., Yung S.S.Y., Lai K.N. and Chan D.T.M., Effect of rapamycin on renal ischemia-reperfusion injury in mice, Transplant International. 2006, 19: 834-839.

Lui S.L., Yung S.S.Y., Tsang R.C.W., Chan K.W., Zhang Q., Tam S., Lai K.N. and Chan D.T.M., Rapamycin attenuates the severity of nephritis in NZB/NZW mice, Journal of the American Society of Nephrology. 2006, 17: 353A.

Lui S.L., Yung S.S.Y., Tsang R.C.W., Chan K.W., Zhang Q., Tam S., Lai K.N. and Chan D.T.M., Rapamycin reduces proteinuria and segmental glomerulosclerosis in murine adriamycin nephropathy, Journal of the American Society of Nephrology. 2006, 17: 743A.

Lui S.L., Yip T., Tse K.C., Chan D.T.M., Lai K.N. and Lo W.K., Tuberculous lymphadenitis in patients undergoing continuous ambulatory peritoneal dialysis, International Urology and Nephrology. 2007.

Tang S.C.W., Lam B., Ku P.P., Leung W.S., Chu C.M., Ho Y.W., Ip M.S.M. and Lai K.N., Alleviation of sleep apnea in patients with chronic renal failure by nocturnal cycler-assisted peritoneal dialysis compared with conventional continuous ambulatory peritoneal dialysis, Journal of American Society of Nephrology. 2006, 17: 2607-2616.

Tang S.C.W., Chan K.W., Tang C.S.O., Lam M.F., Leung C.Y., Tse K.C., Li C.S., Ho Y.W., Tong K.L., Lai K.N., Chan D.T.M. and Hong Kong Nephrology Study Group ., Conversion of ciclosporin A to tacrolimus in kidney transplant recipients with chronic allograft nephropathy, Nephrology Dialysis Transplantation. 2006, 21(11): 3243-51.

Tang S.C.W., Yang M.K., Ho Y.W. and Lai K.N., Diagnosis of patent processus vaginalis by CT peritoneography in CAPD, Hong Kong Journal of Nephrology. 2006, 8: 78-79.

Tang S.C.W., Leung J.C.K., Chan L.Y., Tsang W.L. and Lai K.N., Differntial regulation of chemokines expression by angiotensin antagonists and HMG-CoA reductase inhibitors in protein-overloaded human proximal tubular epithelial cells, Journal of American Society of Nephrology. 2006, 17: 844A.

Tang S.C.W., Chu F.S.K., Au W.M. and Lai K.N., Emphysematous cystitis, American Journal of Kidney Diseases. 2006, 48: e11-12.

Tang S.C.W. and Lai K.N., Hepatitis B-related membranous nephropathy should be treated with a specific anti-viral agent, Kidney International. 2006, 70: 818.

Tang S.C.W., Leung J.C.K., Chan L.Y., Chan A.K.K., Eddy A.A. and Lai K.N., Impact of angiotensin antagonists and HMG-CoA reductase inhibitors on adriamycin nephropathy, Journal of American Society of Nephrology. 2006, 17: 41A.

Tang S.C.W., Lee R., Tse K.C., Lai A.S.H. and Lai K.N., Inability to start hemodialysis after a smooth temporary hemodialysis catheter insertion procedure, Hemodialysis International. 2007, 11: 32-34.

Tang S.C.W., Ho Y.W., Tang A.W., Yip T., Tse K.C., Wang A.Y.M., Lo W.K., Chan D.T.M., Lai K.N. and Lui S.L., What is the optimal timing of dialysis initiation? , Peritoneal Dialysis International . 2006, Suppl 26: S90.

Tse K.C., Lam M.F., Tang S.C.W., Tang C.S.O., Lai K.N. and Chan D.T.M., A pilot study on tracolimus treatment in membranous or quiescent lupus nephritis with proteinuria resistant to angiotensin inhibition or blockade, Lupus. 2007, 16: 45-51.

Tse K.C., Tang S.C.W., Chan D.T.M. and Lai K.N., Rhodococcus lung abscess complicating kidney transplantation: successful management by combination antibiotic therapy, Transplant Infectious Disease. 2007, 10: 44-47.

Yeung C.K., Tse K.C., Lam M.F., Chan D.T.M. and Lai K.N., A renal transplant recipient with mutiple facial nodules, Nephrology Dialysis Transplantation. 2006, 21: 3591-3592.

Yip T., Tse K.C., Lam M.F., Cheng S.W., Lui S.L., Tang S.C.W., Li F.K., Wang A.Y.M., Choy C.B.Y., Ng M.M.T., Chan D.T.M., Lai K.N. and Lo W.K., Risk and outcome of peritonitis after flexible colonoscopy in CAPD patient, Peritoneal Dialysis International . 2006, Suppl 26: S68.

Researcher : Lai KWH

List of Research Outputs

Tse H.F., Siu C.W.D., Zhu S., Liao S., Zhang Q.Y., Lai K.W.H., Nicholls J.M. and Tse H.F., Paracrine effects of direct intramyocardial implantation of bone marrow derived cells for enhancement of neovascularization in chronic ischemic myocardium, European Journal Heart Fail. 2007, 9(8): 747-53.

Researcher : Lam B

List of Research Outputs

Cheung T.K., Lam B., Ip M.S.M., Wong Y.H., Chan A.O.O., Lam S.K. and Wong B.C.Y., Nocturnal Reflux Symptoms Correlate with Respiratory Events in Patients with Obstructive Sleep Apnea. , AGA Digestive Digestive Disease Week 2007.

Cheung T.K., Lam B., Ip M.S.M., Wong Y.H., Chan A.O.O., Lam S.K. and Wong B.C.Y., Nocturnal reflux symptoms correlate with respiratory events in patients with obstructive sleep apnea. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132 (4) Supp 2: A482.

Hou H.M., Hagg E.U.O., Sam K., Rabie A.B.M., Wong R.W.K., Lam B. and Ip M.S.M., Dentofacial Characteristics of Chinese Obstructive Sleep Apnea Patients in Relation to Obesity and Severity, The Angle Orthodontist. 2006, 76 No.6: 962-969.

Lam B., Lam C.L. and Ip M.S.M., Obstructive sleep apnoea in Asia, International Journal of Tuberculosis and Lung Disease. 2007, 11: 2-11.

Lam B., Sam K., Mok W.Y.W., Cheung M.T., Fong D.Y.T., Lam J.C.M., Lam C.L., Yam L.Y.C. and Ip M.S.M., Randomized study of three non-surgical treatments in mild to moderate obstructive sleep apnea, Thorax. 2007, 62: 354-359.

Lam B., Recent advance in the diagnosis and treatment of invasive fungal infection, Forum on Invasive Fungal Infection, Guangzhou, China. 2007.

Lam B., Wong M.P., Fung S.L., Lam C.L., Wong P.C., Wong T.Y.W., Lam F.M., Ip M.S.M., Ooi C.G.C. and Lam W.K., The clinical value of autofluorescence bronchoscopy for the diagnosis of lung cancer , European Respiratory Journal. 2006, 28(5): 915-919.

Lam B., Sam K., Lam J.C., Lam C.L., Ku P.P. and Ip M.S.M., The efficacy of oral appliance in the treatment of severe obstructive sleep apnea, American Thoracic Society International Conference, San Francisco, USA. American Jouranl of Respiratory and Critical Care Medicine. 2007, 175: A708.

Lam B., The leading role of doctors and successful factors in smoking cessation, Inauguration of HKPCF Smoking Cessation Alliance. 2007.

Lam B., The leading role of family doctors in smoking cessation, Annual Scientific Meeting of Sun Yat Sen University of Medical Sciences Hong Kong Alumni Association. 2007.

Lam J.C., Tam S., Ooi C.G.C., Ku P.P., Lai A.Y.K., Lam B., Lam K.S.L. and Ip M.S.M., Relationship between sympathetic activity, obesity, and obstructive sleep apnea, 8th World Congress on Sleep Apnea. Montreal, Canada. Sleep Medicine. 2006, 7 (suppl 2): S51 (P321).

Lam J.C., Lam C.L., Xu A., Yan S.W., Lam B., Lam K.S.L. and Ip M.S.M., Serum adipocyte-fatty acid binding protein (AFABP) level correlates with the duration of oxygen desaturation in obstructive sleep apnea (OSA) patients, American Thoracic Society International Conference, San Francisco, USA 2007. American Journal of Respiratory and Critical Care Medicine. 2007, 175: A55.

Lam J.C.M., Tam S., Ooi C.G.C., Ku P.P., Lai A.Y.K., Lam B., Lam K.S.L. and Ip M.S.M., Relationship between sympathetic activity, obesity, and obstructive sleep apnea, 8th World Congress on Sleep Apnea. Montreal, Canada, September 2006. Sleep Medicine. 2006, 7 (suppl 2): S51 (P321).

Mohan A., Bollineni S., Lam B., Lam C.L. and Ip M.S.M., Obstructive sleep apnoea in India: what the mind does not think, the eyes do not see, International Journal of Tuberculosis and Lung Disease. 2007, 11: 932-933.

Tang S.C.W., Lam B., Ku P.P., Leung W.S., Chu C.M., Ho Y.W., Ip M.S.M. and Lai K.N., Alleviation of sleep apnea in patients with chronic renal failure by nocturnal cycler-assisted peritoneal dialysis compared with conventional continuous ambulatory peritoneal dialysis, Journal of American Society of Nephrology. 2006, 17: 2607-2616.

Researcher : Lam CLK

Project Title:	Effectiveness of Traditional Chinese Medicine in Primary Care
Investigator(s):	Lam CLK, Leung KF
Department:	Med - Family Medicine Unit
Source(s) of Funding:	Small Project Funding
Start Date:	12/2005

Abstract:

Primary health care has important contributions to the health of the population by managing over 90%of the illnesses of the population. Although Western medicine is the established system of health care in Hong Kong, 50 to 60% of people in Hong Kong have consulted Traditional Chinese medicine (TCM) practitioners and 13.5% of the people consult TCM frequently or occasionally (1). There are 7707 registered TCM practitioners serving a population of 6.8 million in Hong Kong, most of them provide primary care. Despite the popularity of TCM in primary care in Hong Kong, there are not many research data on its effectiveness. Evidence on the effectiveness of TCM is important to inform the public in their choice of primary care . The evaluation of the effectiveness of TCM needs to use appropriate outcome measures. The outcome measures of TCM should be coherent with its underlying philosophy and theory. Health related quality of life (HRQOL) is probably the most suitable outcome measure of TCM because it matches the latter's emphasis on the enhancement of physical, social and psychological well being. HRQOL has been shown to be a reliable and valid outcome measure of health, illness and treatment in Western medicine. It has also been used as an outcome measure in several TCM clinical trials on cancer, geriatrics, and rehabilitation (2-5). Most of the studies were able to show with HRQOL measures that TCM had an effect on patient's psychological well-being. However, many authors have raised the concern that HRQOL measures developed for Western medicine may not evaluate the effectiveness of TCM adequately because they do not capture all the health concept of TCM. A HRQOL measure specific to the concepts of TCM may be more sensitive and responsive to its treatment effects (5-7). The Chinese Quality of Life Instrument (ChQOL) was developed recently in China for assessing HRQOL based on the philosophy and theory of TCM. It is intended for the monitoring the patient's subjective perception during illness and treatment. The ChQOL has been validated and pilot tested on Chinese populations in Guangzhou and Hong Kong (8). Many Chinese medicine interventions have claimed to improve quality of life but few have been substantiated by research studies measuring HRQOL as the primary outcome and with standard validated measures. The aim of the present study is to evaluate the effectiveness of TCM in enhancing patients' quality of life in primary care by the use of a widely used generic and a TCM-specific HRQOL measures. The study would also determine the psychometric properties of these measures for the evaluation of the effectiveness of TCM in the primary care. Research objectives1) To investigate whether TCM can improve HRQOL of patients in primary care. 2) To investigate the correlation between HRQOL evaluations and the clinical assessment by TCM practitioners. 3) To investigate whether a TCM specific HQOL measure is more sensitive and responsive than a generic HRQOL measure to evaluate the effectiveness of TCM.

Project Title:	A randomized, double blind, placebo-controlled clinical trial of Chinese herbal medicine in the treatment of acute upper respiratory infections
Investigator(s):	Lam CLK, Wong W, Fong DYT
Department:	Med - Family Medicine Unit
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	01/2006

Abstract:

The aim of this study is to test if Chinese herbal medicine (CHM) guided by Traditional Chinese medicine (TCM) diagnosis will significantly increase recovery rate, and reduce the duration and/or severity of symptoms, and improve the quality of life of patients with URTIs in primary care.

Project Title:	Translation and Validation of the Chronic Liver Disease Questionnaire (CLDQ) for Chinese patients with Chronic Hepatitis B Infection in Hong Kong
Investigator(s):	Lam CLK, Lai CL, Yuen RMF
Department:	Med - Family Medicine Unit
Source(s) of Funding:	Small Project Funding
Start Date:	10/2006

Abstract:

Introduction More than 2 billion people have been infected with hepatitis B in the world[1], with an estimated 350 million being chronic carriers and approximately 250-300 million of whom are Chinese. Without treatment, infected individuals may progress through the different stages of liver disease from uncomplicated HB carriers, to chronic hepatitis, to cirrhosis, liver failure and/ or hepatocellular carcinoma (HCC). Chronic hepatitis infection can adversely affect mental and physical health leading to impairment of quality of life (QOL)[2-4]. Younossi et al found an association between scores in HRQOL and the severity of the liver disease[4]. HRQOL has become an important outcome indicator in clinical services and health policies in the last two decades. HRQOL measures can be categorized broadly into two types: generic and disease-specific. Generic measures are applicable to people of all health status and allow comparison between different types of diseases. However, they may not be able to detect small but clinically important differences in HRQOL that are specific to certain diseases, such as fatigue in chronic liver disease. Therefore, a disease-specific measure may be needed to supplement a generic measure to assess the HRQOL of patients with a particular disease. Several HRQOL measures have been developed specific for chronic liver disease patients, such as the Chronic Liver Disease Questionnaire (CLDQ)[5], the Hepatitis Quality of Life (HQLQ)[6], and the Liver Disease Quality of Life (LDQOL)[7]. The Chronic Live Disease Quality of Life (CLDQ) is the first available disease specific HRQOL measure for chronic liver disease (CLD) developed by Younossi et al. It is applicable to patients with different types of chronic liver diseases. It has been shown to have good reliability, validity and sensitivity, and has been validated in different cultures including Italian, German, Chinese (Simplified format) and Thai [8-12]. Therefore, the CLDQ has been shown to be suitable for cross-cultural adaptation. It captures important areas and problems relating to HBV infection, such as, fatigue. The CLDQ has only 29 items and can be completed in less than 15 minutes. The other two liver disease specific HRQOL measures are less widely used because they are much longer, have less validation data and have been tested only on patients with specific types of chronic liver diseases. In Hong Kong, no disease-specific HRQOL measure is available for hepatitis B patients because all existing disease-specific instruments were developed in Western countries and none have been validated for the local Chinese population. The CLDQ has been translated and tested in mainland China, this Chinese version may not be applicable to people in Hong Kong because there are significant differences in the usage of words and terms between Hong Kong and Mainland China. Therefore, it is necessary to develop a Chinese translation that is linguistically appropriate and psychometrically valid for people in Hong Kong. The aim of this study is to translate and validate the CLDQ for the Chinese population in Hong Kong so that we can have a disease specific HRQOL measure applicable to our patients with different stages of chronic HB infection. This will enable the evaluation of the impact of CHB infection on our Chinese population, and assess the effect of treatment on quality of life of these patients.Study objectives1. To develop a Chinese (Hong Kong) version of the CLDQ that is semantically equivalent to the original.2. To test the scaling assumptions of the Chinese (HK) CLDQ.3. To test the internal and test-retest reliability of the Chinese (HK) CLDQ.4. To test the construct validity of the Chinese (Hong Kong) CLDQ by comparing its scores to those of the Chinese (Hong Kong) Short-Form 36 (SF-36).5. To test the construct validity and sensitivity of the Chinese (HK) CLDQ by comparing the scores of patients with different stages of chronic HB infections.6. To test the responsiveness of the Chinese (Hong Kong) CLDQ in detecting the changes in HRQOL of CHB patients over time.

List of Research Outputs

Cheung T.K., Hu H.C., Lam C.L.K., Hui W.M., Lam S.K. and Wong B.C.Y., Positive association between gastro-oesophageal reflux disease and irritable bowel syndrome in a Chinese population. , Aliment Pharmacol Ther . 2007, 25.

Cheung T.K., Lam K.F., Hu H.C., Wong W.M., Hui W.M., Lam C.L.K., Lai K.C., Lam S.K. and Wong B.C.Y., Positive association between gastro-oesophageal reflux disease and irritable bowel syndrome in a Chinese population, Alimentary Pharmacology & Therapeutics. Blackwell Publishing, 2007, 25: 1099-1104.

Ho D.C.W., Lai L.W.C., Chau K.W., Wong S.K., Cheung A.K.C., Yau Y., Ng H.F. and Lam C.L.K., A survey of Sick Building Syndrome (SBS) in private apartment buildings in Hong Kong: preliminary results, The 6th China Urban Housing Conference. Beijing, 2007.

Ho D.C.W., Lai L.W.C., Chau K.W., Wong S.K., Cheung A.K.C., Yau Y., Ng H.F. and Lam C.L.K., A survey of sick building syndrome(SBS) in private apartment buildings in Hong Kong: preliminary results, Proceedings of the Sixth China Urban Housing Conference, Beijing. 2007.

Ho D.C.W., Lai L.W.C., Chau K.W., Wong S.K., Cheung A.K.C., Yau Y., Ng H.F. and Lam C.L.K., Best Paper Award - for a paper titled "A survey of Sick Building Syndrome (SBS) in private apartment buildings in Hong Kong: preliminary results", Ministry of Construction, PRC. 2007.

Hu H.C., Lam S.K., Lam C.L.K., Wong R.W.M., Lam K.F., Lai K.C., Wong Y.H., Wong B.C.Y., Chan O.O., Chan C.K., Leung G.M. and Hui W.M., Comparison between Empirical Prokinetics, Helicobacter Test-and-Treat and Empirical Endoscopy in Primary-Care Patients Presenting with Dyspepsia: A One-Year Study, World Journal of Gastroenterology. 2006, 12(31): 5010-5016.

Ip M.S.M., Yam L.Y.C., Lam C.L.K. and Sam K., Randomized controlled study of treatment for mild and moderate sleep apnoea, Hong Kong Medical Journal. 2007, 13 (suppl 3): S4-7.

Lam C.L.K., Assessment – We don’t like it but we cannot do without it. , HK Pract . 2007, 29: 177-179.

Lam C.L.K., Faculty Teaching Medal, Li Ka Shing Faculty of Medicine, the University of Hong Kong . 2006.

Lam C.L.K., Keynote Lecture on “ Measuring the “Q” of QLAYs”. , Annual General Meeting, Hong Kong Society for Quality of Life. . Hong Kong., 2007.

Lam C.L.K., Keynote on “ Measuring the “Q” of QLAYs”. , Annual General Meeting, Hong Kong Society for Quality of Life. . Hong Kong, 2007.

Lam C.L.K., Seminar paper “ Contributions of Family Medicine to Undergraduate Medical Education”. , Beijing/Hong Kong Medical Exchange Eigth Meeting. . Hong Kong., 2006.

Lam C.L.K., Symposium paper “ The Contribution of Academic Family Medicine to Populaiton Health”. , Primary Care Symposium- the Way Forward. School of Public Health, Chinese University of Hong Kong. . Hong Kong, 2006.

Luo Y., McMillan A.S., Wong M.C.M., Zheng J. and Lam C.L.K., Orofacial pain conditions and impact on quality of life in community-dwelling elderly people in Hong Kong, Journal of Orofacial Pain. 2007, 21: 63-71.

McMillan A.S., Wong M.C.M., Zheng J. and Lam C.L.K., Prevalence of Orofacial Pain and Treatment Seeking in Hong Kong Chinese, Journal of Orofacial Pain. 2006, 20: 218-225.

Wong O.L., Kuntz K., Cowling B.J., Lam C.L.K. and Leung G.M., A cost-effectiveness analysis of mammography screening in Hong Kong (abstract), 28th Annual Meeting of the Society for Medical Decision Making, 15-18 October 2006, Boston, USA . Boston, Society for Medical Decision Making, 2006.

Wong W., Lam C.L.K., Sham J.S.T., Leung K.F., Leung K.F. and Zhao L., Effectiveness of Traditional Chinese Medicine in Primary Care, 13th Annual Conference of the International Society for Quality of Life Research. October 10 - 14, 2006.

Researcher : Lam CW

List of Research Outputs

Hoo R.L.C., Lam C.W., Xu A., Chen B. and Lam K.S.L., ENDOPLASMIC RETICULUM STRESS DOWN-REGULATES THE ADIPOCYTE PRODUCTION OF THE ANTI-DIABETIC AND ANTI-ATHEROGENIC HORMONE ADIPONECTIN, XIV International Symposium on Atherosclerosis,Italy 2006. 2007.

Lam K.S.L., Tso A.W.K., Chow W.S., Hoo R.L.C., Zhang J., Lam C.W. and Xu A., Adipocyte fatty acid binding protein as a potential circulating metabolic hormone: clinical and functional studies. , The Endocrine Society’s 88th Annual Meeting, June 24-27, 2006, Boston, USA. 2007.

Wang Y., Lam J.B.B., Lam K.S.L., Liu J., Lam C.W., Hoo R.L.C., Wu D., Cooper G.J. and Xu A., Adiponectin modulates the glycogen synthase kinase-3beta/beta-catenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice, Cancer Res. 2006, 66: 11462-70.

Wang Y., Lam K.S.L., Lam J.B.B., Lam C.W., Leung P.T.Y., Zhou M.Y. and Xu A., Overexpression of Angiopoietin-like Protein 4 Alters Mitochondria Activities and modulates methionine metabolic cycle in the liver tissues of db/db diabetic mice, Mol Endocrinol. 2007, 21: 972-86.

Researcher : Lam JBB

List of Research Outputs

Wang Y., Lam J.B.B., Lam K.S.L., Liu J., Lam C.W., Hoo R.L.C., Wu D., Cooper G.J. and Xu A., Adiponectin modulates the glycogen synthase kinase-3beta/beta-catenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice, Cancer Res. 2006, 66: 11462-70.

Wang Y., Lam K.S.L., Lam J.B.B., Lam C.W., Leung P.T.Y., Zhou M.Y. and Xu A., Overexpression of Angiopoietin-like Protein 4 Alters Mitochondria Activities and modulates methionine metabolic cycle in the liver tissues of db/db diabetic mice, Mol Endocrinol. 2007, 21: 972-86.

Researcher : Lam KM

List of Research Outputs

Chan A.O.O., Loo C.K., Leung C.M., Wong S.Y., Ng F.H., Li M.K.W., Lam K.M., Lam S.K. and Wong B.C.Y., Prevalence of colonic lesions after a negative screening colonscopy in a population with rapidly rising colorectal cancer incidence: A prospective multi-center analysis. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A189.

Researcher : Lam KSL

Project Title:	Genetic and hormonal influences on phenotypic expression of apolipoprotein (a)
Investigator(s):	Lam KSL
Department:	Medicine
Source(s) of Funding:	Outstanding RGC Projects
Start Date:	11/1998

Abstract:

To enhance research level.

Project Title:	Linking the metabolic syndrome with progressive atherosclerosis: role of fat-derived hormones
Investigator(s):	Lam KSL, Chau MT, Wat NMS, Xu A
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	09/2004

Abstract:

To determine whether serum levels of adiponectin are predictive of progressive atherosclerosis in man in a 5-year prospective study; to establish a sensitive ELISA method for accurate quantification of human PGAR and investigate the relationship of serum PGAR levels with obesity, insulin resistance, glucose tolerance, blood pressure, lipid levels and progression in carotid atherosclerosis; to investigate the effects of adenovirus-mediated chronic administration of adiponectin or PGAR on glucose and lipid metabolism, and development of atherosclerosis in db/db mice, an animal model of the metabolic syndrome.

Project Title:	Application for seed fund for the strategic theme on healthy ageing
Investigator(s):	Lam KSL, Che CM, Lee TMC, Lee WWM, McMillan AS, Chen SF
Department:	Medicine
Source(s) of Funding:	Seed Funding for Strategic Research Theme
Start Date:	05/2005

Abstract:

To integrate the existing strengths in aging related research within HKU through the identification of important themes of common interest; to provide core platforms for interdisciplinary research on aging diseases; to develop novel therapeutic approaches for the promotion of healthy aging.

Project Title:	Macrophage-adipocyte cross-talk in the initiation of obesity-related insulin resistance and type 2 diabetes: role of adiponectin
Investigator(s):	Lam KSL, Xu A, Lao TTH
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	09/2005

Abstract:

To determine the time course and magnitude of macrophage infiltration in fat tissue, changes in the blood and fat tissue levels of adiponectin, pro-inflammatory cytokines and other adipocyte-derived hormones, in relation to changes in glucose tolerance and insulin sensitivity, in db/db mice; to investigate, in db/db mice, an animal model of genetically predisposed obesity and type 2 diabetes, whether the therapeutic use of adiponectin can prevent or reduce the above pro-inflammatory changes, insulin resistance and/or type 2 diabetes; to confirm whether the inflammatory and hormonal changes in the blood and fat tissue of obese mice, and their correlation with glucose tolerance and insulin sensitivity, are also observed in overweight or obese Chinese subjects; to determine, in type 2 diabetic patients, the contribution of changes in circulating adiponectin to the anti-inflammatory and insulin-sensitizing actions of rosiglitazone, a PPAR-γ agonist which can increase adiponectin expression

Project Title:	Human ANGPTL4 Gene: Molecular Scanning and Evaluation of Association with Insulin Resistance and Type 2 diabetes in Chinese
Investigator(s):	Lam KSL, Xu J, Xu A
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	10/2005

Abstract:

The angiopoietin like protein-4 (ANGPTL4) is a hormone, predominantly derived from fat cells, which has been recently shown by our group to decrease blood glucose and hepatic insulin resistance in rodents. The purpose of this project is to determine whether the ANGPTL4 gene plays a significant role in the genetic susceptibility to diabetes and other insulin resistance related traits in humans, using blood and DNA samples collected from on-going cross-sectional and prospective studies.Objectives1. To systematically search for polymorphisms in the human ANGPTL4 gene in southern Chinese2. To perform case control association studies of ANGPTL4 polymorphisms and haplotypes with the risk of T2DM, obesity, insulin resistance, and hyperlipidemia 3. To investigate the role of ANGPTL4 polymorphisms and haplotypes in predicting the development of diabetes in a 10- year prospective follow-up study of 600 non-diabetic subjects4. To determine the role of genetic polymorphisms in regulating circulating ANGPTL4 levels

Project Title:	Adipocyte fatty acid binding proteins: new mediators of the metabolic syndrome and coronary atherosclerosis
Investigator(s):	Lam KSL, Xu A, Sham PC, Lao TTH
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	08/2006

Abstract:

(1) To investigate the genetic regulation of circulating FABP4 and FABP5 levels in man by examining the effects of genetic variants detected from a systematic analysis of the two genes (2) To investigate (a) the associations of genetic variants/serum levels of FABP4 and FABP5 with the metabolic syndrome or its components (Obesity, insulin resistance, dyslipidaemia, glucose intolerance/diabetes, hypertension, chronic inflammation), and coronary atherosclerosis, in cross-sectional and prospective studies, and (b) whether FABP4 and FABP5 interact at genetic or circulating protein levels in such associations (3) To examine the relationship of circulating FABP4 and FABP5 levels with their gene and protein expressions in visceral and subcutaneous adipose tissues, and insulin sensitivity indices (4) To investigate why circulating FABP4 levels are higher in women.

List of Research Outputs

Cheng K.Y., Lam K.S.L., Wang Y. and Xu A., Adiponectin as a key player of inflammation, In: Fantuzzi G, Biomedical Reviews. 2006, 17: 11-22.

Cheng K.Y., Lam K.S.L., Wang Y., Yu H., Carling D., Wu D., Wong C.W. and Xu A., Adiponectin-induced eNOS activation and Nitric Oxide Production are Mediated by APPL1 in Endothelial Cells, Diabetes. 2007, 56: 1387-94.

Cheung B.M.Y., Leung Y.H., Man Y.U. .B.U.N., Ong K.L., Wong L.Y.F., Lau C.P. and Lam K.S.L., Association of Blood Pressure with Polymorphisms in the Quantitative Trait Locus for Abdominal Obesity-Metabolic Syndrome on Chromosome 17, The 21st Scientific Meeting of the International Society of Hypertension 2006.

Cheung B.M.Y., Wat N.M.S., Man Y.B., Tam S., Thomas G.N., Leung G.M., Cheng C.H., Woo J., Janus E.D., Lau C.P., Lam T.H. and Lam K.S.L., Development of diabetes in Chinese with the metabolic syndrome, Diabetes care. 2007, 30: 1430-1436.

Cheung B.M.Y., Wat N.M.S., Man Y.B., Tam S., Cheng C.H., Leung G.M., Woo J., Janus E.D., Lau C.P., Lam T.H. and Lam K.S.L., Predictors of the development of hypertension in the Hong Kong cardiovascular risk factor prevalence study-2 (CRISPS2), The 21st Scientific Meeting of the International Society of Hypertension. 2006.

Cheung B.M.Y., Ong K.L., Man Y.B., Lau C.P., Lam K.S.L. and Wong Y.L., Prevalence of the metabolic syndrome in the United States National Health and Nutrition Examination Survey 1999-2002 according to different defining criteria., J Clin Hypertens (Greenwich). 2006, 8(8): 562-70.

Cheung B.M.Y., Ong K.L., Man Y.U. .B.U.N., Wong L.Y.F., Lau C.P. and Lam K.S.L., Prevalence, Awareness, Treatment and Control of Hypertension in the United States 1999-2004, The 21st Scientific Meeting of the International Society of Hypertension. 2006.

Cheung B.M.Y., Wat N.M.S., Man Y.U. .B.U.N., Tam S., Cheng C.H., Leung G.M., Woo J.E.A.N., Janus E.D.W.A.R.D. .D., Lau C.P., Lam T.H. and Lam K.S.L., Waist Circumference as a Predictor of Cardiovascular Risk in the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS2), The 21st Scientific Meeting of the International Society of Hypertension. 2006.

Chow W.S., Cheung B.M.Y., Xu A., Wat N.M.S., Fong H.Y., Ong L.H.Y., Tam S., Tan K.C.B., Janus E.D., Lam T.H. and Lam K.S.L., Hypoadiponectinemia as a predictor for the development of hypertension: a 5-year prospective study. , Hypertension. 2007, 49: 1455-61.

Fong D.Y.T., Rai S.N. and Lam K.S.L., Use Of Multiple Imputation On Linear Mixed Model And Generalized Estimating Equations For Longitudinal Data Analysis: A Simulation Study, Interdisciplinary Mathematical & Statistical Techniques: Thirteenth International Conference of Forum for Interdisciplinary Mathematics. 2006.

Ho C.M.E., Lam K.S.L., Chen A.Y.S., Yip C.W., Arvindakshan M., Yamagishi S., Oates P.J., Ellery C.A., Chung S.S.M. and Chung S.K., Aldose reductase-deficient mice are protected from delayed motor nerve conduction velocity, increased c-Jun NH2-terminal kinase activation, depletion of reduced glutathione, increased superoxide accumulation, and DNA damage, Diabetes. 2006, 55(7): 1946-53.

Hoo R.L.C., Lam C.W., Xu A., Chen B. and Lam K.S.L., ENDOPLASMIC RETICULUM STRESS DOWN-REGULATES THE ADIPOCYTE PRODUCTION OF THE ANTI-DIABETIC AND ANTI-ATHEROGENIC HORMONE ADIPONECTIN, XIV International Symposium on Atherosclerosis,Italy 2006. 2007.

Hoo R.L.C., Chow W.S., Yau M.H., Xu A., Tse H.F., Tso A.W.K., Fong H.Y., Tam S., Chan L. and Lam K.S.L., PPAR-γ agonist induced-suppression of plasminogen activator inhibitor-1 production is mediated through adiponectin. , 2nd International Symposium on Healthy Aging, 3-4 March 2007, Hong Kong. 2007.

Hoo R.L.C., Chow W.S., Tse H.F., Fong H.Y., Tam S., Chan L.C.B. and Lam K.S.L., Ppar-γ Agonist Induced-suppression Of Plasminogen Activator Inhibitor-1 Production Is Mediated Through Adiponectin. , HBHA conference. 2007.

Lam J.C., Tam S., Ooi C.G.C., Ku P.P., Lai A.Y.K., Lam B., Lam K.S.L. and Ip M.S.M., Relationship between sympathetic activity, obesity, and obstructive sleep apnea, 8th World Congress on Sleep Apnea. Montreal, Canada. Sleep Medicine. 2006, 7 (suppl 2): S51 (P321).

Lam J.C., Lam C.L., Xu A., Yan S.W., Lam B., Lam K.S.L. and Ip M.S.M., Serum adipocyte-fatty acid binding protein (AFABP) level correlates with the duration of oxygen desaturation in obstructive sleep apnea (OSA) patients, American Thoracic Society International Conference, San Francisco, USA 2007. American Journal of Respiratory and Critical Care Medicine. 2007, 175: A55.

Lam J.C.M., Tam S., Ooi C.G.C., Ku P.P., Lai A.Y.K., Lam B., Lam K.S.L. and Ip M.S.M., Relationship between sympathetic activity, obesity, and obstructive sleep apnea, 8th World Congress on Sleep Apnea. Montreal, Canada, September 2006. Sleep Medicine. 2006, 7 (suppl 2): S51 (P321).

Lam K.S.L., Adipocyte fatty acid binding protein as a novel player in the metabolic syndrome: clinical and functional studies. , 2nd Scientific Meeting of the Asia-Pacific Diabetes and Obesity Study Group, Kobe, Japan. 2006.

Lam K.S.L., Tso A.W.K., Chow W.S., Hoo R.L.C., Zhang J., Lam C.W. and Xu A., Adipocyte fatty acid binding protein as a potential circulating metabolic hormone: clinical and functional studies. , The Endocrine Society’s 88th Annual Meeting, June 24-27, 2006, Boston, USA. 2007.

Lam K.S.L., Diabetes in Chinese: Changing epidemiology and novel biomarkers. , MGH-HKU-Nature China Forum, Hong Kong. 2007.

Lam K.S.L., Integrating the Professional and Non-professional Organisations: the Optimal Model, 19th World Diabetes Congress, Cape Town, South Africa. 2006.

Lam K.S.L., Targeting the endocannabinoid system to manage cardiometabolic risk. , Targeting the endocannabinoid system to manage cardiometabolic risk. Rimonabant: A novel approach to cardiometabolic risk management, Singapore. 2007.

Lam K.S.L., The Endocannabinoid system and its role in the pathogenesis of cardiometabolic disease. , Korean Society for the Study of Obesity, 2006 Scientific Meeting, Seoul, Korea. 2006.

Lam K.S.L., The emerging concept of cardio-metabolic risk. , Vascular Event ’07, Sydney, Australia. 2007.

Lam K.S.L., The role of incretins in maintianing physilogic glucose control: effects of insulin and glucagons. , 4th International Huaxia Congress, Hong Kong. 2006.

Lo C.Y., Lang H.H.B., Chan W.F., Kung A.W.C. and Lam K.S.L., A prospective evaluation of preoperative localization by technetium-99m sestamibi scintigraphy and ultrasonography in primary hyperparathyroidism, American Journal of Surgery. 2007, 193: 155-159.

Ng K.Y., Xu A., Lam K.S.L. and Cheung R.T.F., Aggravated cerebral infarction in diabetic mice following photothrombotic ischemia, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population. 2007, 57.

Ng K.Y., Xu A., Lam K.S.L. and Cheung R.T.F., Increased susceptibility of diabetic transgenic mice to photothrombotic stroke, 11th Research Postgraduate Symposium. 2006, 66.

Ong K.L., Cheung B.M.Y., Man Y.B., Wong L.Y.F., Lau C.P. and Lam K.S.L., Prevalence, awareness, treatment and control of hypertension among United States adults 1999-2004. , Hypertension. 2007, 49: 69-75.

Ong K.L., Cheung B.M.Y., Man Y.B., Wong Y.F., Wat N.M.S., Tan K.C.B. and Lam K.S.L., Treatment and control of diabetes mellitus in the United States National Healthy and Nutrition Examination Survey 1999-2002, Journal of Cardiometabolic Syndrome. 2006, 1: 301-7.

Ong L.H.Y., Chow W.S., Tso A.W.K., Wat N.M.S., Xu A., Fong H.Y., Janus E.D. and Lam K.S.L., Hypoadiponectinaemia predicts the development of hypertension in Chinese. , The 19th World Diabetes Congress, 3-7 December 2006, Cape Town, South Africa. 2006.

Rong R., Tao Y., Cheung B.M.Y., Xu A., Cheng K.Y. and Lam K.S.L., Identification and functional characterization of three novel human melanocortin-4 receptor gene variants in an obese Chinese population. , Clinical Endocrinology. 2006, 65: 198-205.

Thomas G.N., Schooling C.M., McGhee S.M., Ho D.S.Y., Cheung B.M.Y., Wat N.M.S., Janus E.D., Lam K.S.L. and Lam T.H., Metabolic syndrome increases all-cause and vascular mortality: The Hong Kong cardiovascular risk factor study, Clinical Endocrinology. 2007, 66: 666-71.

Tso A.W.K., Wat N.M.S., Xu A., Tam S., Fong H.Y., Janus E.D., Tan K.C.B. and Lam K.S.L., Adiponectin/C-reactive protein ratio is an independent surrogate marker predictive of the development of metabolic risks and the metabolic syndrome over 5 years in Chinese, The 6th International Diabetes Federation Western Pacific Region Congress, Bangkok. 2006.

Tso A.W.K., Tan K.C.B., Wat N.M.S., Janus E.D., Lam T.H. and Lam K.S.L., Endothelial nitric oxide synthase G894T (Glu298Asp) polymorphism was predictive of glycemic status in a 5-year prospective study of Chinese subjects with impaired glucose tolerance, Metabolism. 2006, 55: 1155-8.

Tso A.W.K., Sham P.C., Wat N.M.S., Xu A., Cheung B.M.Y., Rong R., Fong H.Y., Xu J., Cheng K.Y., Janus E.D. and Lam K.S.L., Polymorphisms of the gene encoding adiponectin and glycaemic outcome of Chinese subjects with impaired glucose tolerance: a 5-year follow-up study, Diabetologia. 2006, 49: 1806-15.

Tso A.W.K., Xu A., Wat N.M.S., Fong H.Y., Janus E.D. and Lam K.S.L., Serum adipocyte fatty acid-binding protein is a predictor of the development of type 2 diabetes mellitus over 5 years. , The Endocrine Society's 89th Annual Meeting, 2-5 June2007, Toronto. 2007.

Wang Y., Lam J.B.B., Liu J., Lam K.S.L., Cooper G.J.S. and Xu A., Adiponectin Plays Inhibitory Roles in the Proliferation and Tumor Development of Human MDA-MB-231 Breast Cancer Cells, 2nd Modern Drug Discovery & Development Summit. 2006.

Wang Y., Lam K.S.L. and Xu A., Adiponectin as a negative regulator in obesity-related mammary carcinogenesis. , Cell Research. 2007, 17: 280-2.

Wang Y., Lam K.S.L. and Xu A., Adiponectin as a therapeutic target for obesity-related metabolic and cardiovascular diseases., Drugs Development Research. 2006, 67: 677-686.

Wang Y., Lam J.B.B., Lam K.S.L., Liu J., Lam C.W., Hoo R.L.C., Wu D., Cooper G.J. and Xu A., Adiponectin modulates the glycogen synthase kinase-3beta/beta-catenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice, Cancer Res. 2006, 66: 11462-70.

Wang Y., Lam K.S.L., Kraegen E.W., Sweeney G., Zhang J., Tso A.W.K., Chow W.S., Wat N.M.S., Xu J., Hoo R.L.C. and Xu A., Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans, Clin Chem. 2007, 53: 34-41.

Wang Y., Lam K.S.L. and Xu A., Lipocalin-2, a small lipid binding protein as an important mediator at the crossroad of obesity, inflammation and metabolic syndrome, Second International Symposium on Healthy Aging. 2007.

Wang Y., Lam K.S.L., Lam J.B.B., Lam C.W., Leung P.T.Y., Zhou M.Y. and Xu A., Overexpression of Angiopoietin-like Protein 4 Alters Mitochondria Activities and modulates methionine metabolic cycle in the liver tissues of db/db diabetic mice, Mol Endocrinol. 2007, 21: 972-86.

Wang Y., Lam K.S.L., Cooper G.J. and Xu A., Proteomic characterization of human serum proteins associated with the fat-derived hormone adiponectin. , Proteomics. 2006, 6: 3862-70.

Wang Y., Xu L., Lam K.S.L., Lu G., Cooper G.J. and Xu A., Proteomic characterization of human serum proteins associated with the fat-derived hormone adiponectin. , Proteomics. 2006, 6: 3862-70.

Wat N.M.S., Tan K.C.B., Chow W.S., Tse P.M., Wong K., Leung E., Hung V., Leung S.K., Yee A., Leung C.Y. and Lam K.S.L., Innovative risk stratification model for high-risk diabetic patients in a tertiary referral centre – triage of the triaged, Health Authority Convention, May 2007.

Xu A., Wang Y. and Lam K.S.L., Adiponectin, In: Fantuzzi G & mazzone T, Adipose tissue and adipokines in health and disease. Totowa, New Jersey, Human press, 2007, 47-59.

Xu A., Tso A.W., Cheung B.M.Y., Wang Y., Wat N.M.S., Fong H.Y., Yeung C.Y., Janus E.D., Sham P.C. and Lam K.S.L., Circulating adipocyte-fatty acid binding protein levels predict the development of the metabolic syndrome: a 5-year prospective study, Circulation. 2007, 115: 1537-43.

Xu A., Tso A.W.K., Cheung B.M.Y., Wang Y., Wat N.M.S., Fong H.Y., Yeung C.Y., Janus E.D., Sham P.C. and Lam K.S.L., Circulating levels of adipocyte-fatty acid binding protein correlate with its adipose tissue expression and predict the development of the metabolic syndrome. , The Endocrine Society's 89th Annual Meeting, 2-5 June 2007, Toronto. 2007.

Xu J., Sham P.C., Xu A., Tso A.W.K., Wat N.M.S., Cheng K.Y., Fong H.Y., Janus E.D. and Lam K.S.L., Resistin gene polymorphisms and progression of glycaemia in southern Chinese: a 5-year prospective study, Clin Endocrinol (Oxf). 2007, 66: 211-7.

Yee A., Wat N.M.S., Tan K.C.B., Wong K., Leung E., Leung S.C., Hung V., Tse P.M., Leung C.Y. and Lam K.S.L., Innovative intervention mechanism for patients with diabetic nephropathy to achieve blood pressure treatment target, Health Authority Convention, May 2007.

Yeung C.Y., Xu A., Cheung C.W., Wat N.M.S., Yau M.H., Fong H.Y. and Lam K.S.L., Circulating serum adipocyte-fatty acid-binding protein (A-FABP) levels correlate with carotid intima-media thickness (IMT) in Southern Chinese women. , 89th Annual Meeting of Endocrine Society, 2-5 June 2007, Toronto, Canada. 2007.

Zhang H., Hui C.K., Lee P.Y., Chan W., Yueng Y.H., Leung K.W., Lu L., Leung N., Lo C.M., Fan S.T., Luk J.M.C., Xu A., Lam K.S.L., Kwong Y.L. and Lau G., Serum adiponectin is increased in advancing liver fibrosis and decline with reduction in fibrosis in chronic hepatitis B, The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007, Hepatology International. 2007, 242: 7.

Zhang X., Yeung C.Y., Wong L.C., Chow W.S., Xu A. and Lam K.S.L., Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans, Second Symposium on Healthy Aging: "Meeting the Challenges of an Aging Population" . 2007.

Researcher : Lam KY

List of Research Outputs

Au W.Y., Fung T.K., Lie A.K.W., Lam K.Y., Lam C.C.K. and Kwong Y.L., Reemergence of JAK2 V617F clone heralds extramedullary leukemia relapse after BMT for transformed essential thrombocytosis, Annals of Hematology. 2006, 86: 145-7.

Au W.Y., Fung T.K., Lam K.Y., Lie A.K.W., Liang R.H.S. and Kwong Y.L., Transformed essential thrombocytosi with a JAK2 V617F mutation relapsing as JAK2 Mutation-negative leukaemia after allogeneic stem cell transplantation, Bone Marrow Transplantation. 2006, 38(8): 573-4.

Researcher : Lam SK

Project Title:	Chemoprevention of gastric cancer by intervention with Helicobacter pylori and cyclooxygenase pathway
Investigator(s):	Lam SK, Wong BCY
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	12/2001

Abstract:

To assess if the combination of treatment of Helicobacter pylori infection and use of specific cyclooxygenase-2 inhibitors in asymptomatic individuals can reduce the incidence of gastric cancer in a high risk area over a five to ten year period; to assess if the combination of treatment of Helicobacter pylori infection and use of specific cyclooxygenase-2 inhibitors will lead to progression or regression of various precancerous gastric conditions including gastric atrophy, intestinal metaplasia and dysplasia over a three year period; to assess the long term sequelae of Helicobacter pylori eradication and use of specific cyclooxygenase-2 inhibitors histologically, including changes in cell proliferation, apoptosis and oncogene expressions.

Project Title:	Biotech Company in the Faculty of Medicine, The University of Hong Kong
Investigator(s):	Lam SK
Department:	Medicine
Source(s) of Funding:	The University of Hong Kong Foundation Seed Grant
Start Date:	07/2003

Abstract:

To enable the Faculty of Medicine of The University of Hong Kong to establish itself as the regional centre of excellence in the provision of complete solutions to industry from laboratory research services to clinical trials, setting standards and quality benchmarks comparable to the best international practices for other similar centres in the region to follow.

Project Title:	Treatment of gastrointestinal cancer by targeting survivin using adeno-associated virus gene delivery system
Investigator(s):	Lam SK, Wong BCY, Lin MC
Department:	Medical Faculty
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	09/2004

Abstract:

To elucidate the molecular mechanisms of survivin in tumor angiogenesis, to will investigater the effect of overexpression of survivin on the migration and capillary tuber-like networks of endothelial cells, expression of angiogenic factors in gastrointestinal cancer cells and angiogenesis in Chorioallantoic membrane angiogenesis (CAM) model and nude mice xenograft; to establish a novel gene therapy for gastrointestinal cancer by targeting survivin gene with adeno-associated virus vector. We will further study the therapeutic effect of rAAV-mediated survivin mutant on gastrointestinal cancer in vivo and evaluate long-term effect and safety of the rAAV virus.

Project Title:	The prevalence of Obstructive Sleep Apnea Syndrome (OSAS) in patients with gastro-oesophageal reflux disease (GERD) and the effects of proton pump inhibitor therapy on OSAS and quality of sleep in Hong Kong Chinese
Investigator(s):	Lam SK, Wong RWM, Ip MSM
Department:	Medical Faculty
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004

Abstract:

To study the prevalence of Obstructive Sleep Apnea Syndrome (OSAS) in Chinese patients with gastro-oesophageal reflux disease (GERD) and the effects of proton pump inhibitor therapy on OSAS and quality of sleep in patients with GERD.

List of Research Outputs

Chan A.O.O., Jim M.H., Lam K.F., Siu D.C.W., Tong S.M., Ng F.H., Wong S.Y., Hui W.M., Lam S.K. and Wong B.C.Y., Aspirin does not prevent recurrence of colorrectal adenomas in patients with coronary artery disease. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A194.

Chan A.O.O., Chu K.M., Huang C.Y., Lam K.F., Leung S.Y., Sun Y., Ko S., Xia H.H.X., Cho C.H., Hui W.M., Lam S.K. and Rashid A., Association between Helicobacter pylori infection and interleukin 1beta polymorphism predispose to CpG island methylation in gastric cancer, GUT. 2007, 56: 595-597.

Chan A.O.O., Hui W.M., Leung Y.C., Wong Y.H., Chan P., Hung I.F.H., Hsu A., But D., Lam S.K. and Wong B.C.Y., Better efficacy of tegaserod in constipated patients with slow colonic transit, absent pelvic floor dyssynergy and absent impaired rectal sensation. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A194.

Chan A.O.O., Chow R., Hui W.M., Leung Y.C., Tong S.M., Lam S.K. and Wong B.C.Y., Biofeedback is equally effective in patients with short or long duration of function constipation. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A194.

Chan A.O.O., Hui W.M., Wong Y.H., Leung Y.C., Lam S.K. and Wong B.C.Y., Decreased cortical activation during rectal distention in patients with functional constipation with normal rectal compliance. Digestive Disease Week 2007, Washington DC, USA, May 19-24, Gastroenterology. 2007, 132(4) Suppl 2: A23.

Chan A.O.O., Hui W.M., Leung Y.C., Hu H.C., Lam S.K. and Wong B.C.Y., Efficacy of tegasered for functiona constipation in Chinese subjects: A randomized double blind contolled trial in a single center. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4): A194.

Chan A.O.O., Hui W.M., Leung Y.C., Hu H.C., Lam S.K. and Wong B.C.Y., Efficacy of tegaserod for functional constipation in Chinese subjects: a randomized double-blind controlled trial in a single center, Alimentary Pharmacology and Therapeutics. 2007, 25(4): 463-469.

Chan A.O.O., Hui W.M., Lam K.F., Leung G.K.L., Yuen R.M.F., Lam S.K. and Wong B.C.Y., Familial aggregation in constipated subjects in a tertiary referral center, American Journal of Gastroenterology. Blackwell Publishing, 2007, 102: 149-152.

Chan A.O.O., Huang C.Y., Leung Y.C., Hui W.M., Lam S.K. and Wong B.C.Y., Familial constipationis associated with a2 adrenoceptor polymorphism. Digestive Diseases Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A189.

Chan A.O.O., Lam K.F., Hui W.M., Leung G.K.L., Wong Y.H., Lam S.K. and Wong B.C.Y., Influence of Positive Family History on Clinical Characteristics of Functional Constipation, Clinical Gastroenterology and Hepatology. Elsevier, 2007, 5(2): 197-200.

Chan A.O.O., Jim M.H., Lam K.F., Siu D.C.W., Tong S.M., Ng F.H., Wong S.Y., Hui W.M., Chan C.K., Lai K.C., Cheung T.K., Chan P., Wong G., Yuen R.M.F., Lau Y.K., Lee S.W.L., Seto M.L., Lam S.K. and Wong B.C.Y., Patients with coronary artery disease had high prevalanece of colorectal cancer and adenoma: END-results of metabolic syndrome and smoking. Digestive Disease Week 2007, Washington DEc, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A65.

Chan A.O.O., Hui W.M., Leung G.K.L., Tong T.P.H., Hung I.F.N., Chan P., Hsu A., But D., Wong B.C.Y., Lam S.K. and Lam K.F., Patients with functional constipation do not have increase prevalence of colorectal cancer precursors”, GUT. British Medicial Journal, 2007, 56: 451-452.

Chan A.O.O., Loo C.K., Leung C.M., Wong S.Y., Ng F.H., Li M.K.W., Lam K.M., Lam S.K. and Wong B.C.Y., Prevalence of colonic lesions after a negative screening colonscopy in a population with rapidly rising colorectal cancer incidence: A prospective multi-center analysis. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A189.

Chan O.O., Lam K.F., Tong T.P.H., Siu D.C.W., Jim M.H., Hui W.M., Lai K.C., Yuen R.M.F., Lam S.K. and Wong B.C.Y., Coexistence between colorectal cancer/adenoma and coronary artery disease: results from 1382 patients. , Alimentary Pharmacology and Therapeutics. 2006, 24(3): 535-9.

Chan O.O., Huang C.Y., Hui W.M., Cho C.H., Yuen R.M.F., Lam S.K., Rashid A. and Wong B.C.Y., Stability of E-cadherin methylation status in gastric mucosa associated with histology changes. , Alimentary Pharmacology and Therapeutics. 2006, 24(5): 831-6.

Cheung T.K., Lam B., Ip M.S.M., Wong Y.H., Chan A.O.O., Lam S.K. and Wong B.C.Y., Nocturnal Reflux Symptoms Correlate with Respiratory Events in Patients with Obstructive Sleep Apnea. , AGA Digestive Digestive Disease Week 2007.

Cheung T.K., Lam B., Ip M.S.M., Wong Y.H., Chan A.O.O., Lam S.K. and Wong B.C.Y., Nocturnal reflux symptoms correlate with respiratory events in patients with obstructive sleep apnea. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132 (4) Supp 2: A482.

Cheung T.K., Hu H.C., Lam C.L.K., Hui W.M., Lam S.K. and Wong B.C.Y., Positive association between gastro-oesophageal reflux disease and irritable bowel syndrome in a Chinese population. , Aliment Pharmacol Ther . 2007, 25.

Cheung T.K., Lam K.F., Hu H.C., Wong W.M., Hui W.M., Lam C.L.K., Lai K.C., Lam S.K. and Wong B.C.Y., Positive association between gastro-oesophageal reflux disease and irritable bowel syndrome in a Chinese population, Alimentary Pharmacology & Therapeutics. Blackwell Publishing, 2007, 25: 1099-1104.

Hu H.C., Lam S.K., Lam C.L.K., Wong R.W.M., Lam K.F., Lai K.C., Wong Y.H., Wong B.C.Y., Chan O.O., Chan C.K., Leung G.M. and Hui W.M., Comparison between Empirical Prokinetics, Helicobacter Test-and-Treat and Empirical Endoscopy in Primary-Care Patients Presenting with Dyspepsia: A One-Year Study, World Journal of Gastroenterology. 2006, 12(31): 5010-5016.

Lai K.C., Chu K.M., Hui W.M., Wong B.C.Y., Hung W.K., Loo C.K., Hu H.C., Chan O.O., Kwok K.F., Fung T.T., Wong J. and Lam S.K., Esomeprazole with aspirin versus clopidogrel for prevention of recurrent gastrointestinal ulcer complications, Clinical Gastroenterology and Hepatology. 2006, 4: 860-865.

Lam S.K., Gastroesophageal Reflux Disease in Asian Pacific, a New Disease, 5th World Congress of Pharmacology, Beijing (July 2-7, 2006). 2006.

Lam S.K., Helicobacter pylori-Clinical, The 12th International Conference on Ulcer Research and GI Satellite of IUPHAR 2006, Osaka (July 7-9, 2006). 2006.

Lam S.K., Recent Advance in Pathogenesis and Treatment of Gastroduodenal Diseases Associated with Helicobacter pylori Infection, The 12th International Conference on Ulcer Research and GI Satellite of IUPHAR 2006, Osaka (July 7-9, 2006). 2006.

Lam T.J., Mulder C.J.J., Peña S., Wong B.C.Y., Hui W.M., Lam S.K. and Chan A.O.O., Increased in prevalence of advanced colonic polyps in young patients over the past eight years in Hong Kong. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A195.

Ouyang Q., Tandon R., Goh K.L., Pan G.Z., Fock K.M., Fiocchi C., Lam S.K. and Xiao S.D., Management Consensus of Inflammatory Bowel Disease for the Asia-Pacific Region, Journal of Gastroenterology and Hepatology. 2006, 21(12): 1772-1782.

Tang L.P., Cho C.H., Hui W.M., Huang C., Chu K.M., Xia H.H.X., Lam S.K., Rashid A., Wong B.C.Y. and Chan O.O., An inverse correlation between IL-6 and select gene promoter methylation in patients with gastric cancer, Digestion. 2006, 74: 85-90.

Wong L.W., Zhu S.L., Zhang S.Y., Lan X.R., Chung A.C.K., Zhang R., Lam S.K., Wong B.C.Y., Xia H.H.X. and Lan H.Y., Macrophage Migration Inhibitory Factor (MIF) Knockout Mice Are Protected Against Helicobacter Pylori Induced Gastritis., 12th Medical Research Conference (Hong Kong, 3/2/2007). 2007.

Yu L., Wang J., Zou B., Lin M.C., Wu Y.L., Xia H.H.X., Sun Y., Gu Q., He H., Lam S.K., Kung H.F. and Wong B.C.Y., XAF1 Mediates Apoptosis Through an Extracellular Signal-Regulated Kinase Pathway in Colon Cancer , Cancer. 2007, 109(10): 1996-2003.

Researcher : Lam TP

Project Title:	Use of antibiotics by primary care doctors in Hong Kong
Investigator(s):	Lam TP, Ho PL, Lam KF
Department:	Med - Family Medicine Unit
Source(s) of Funding:	Small Project Funding
Start Date:	11/2005
Completion Date:	11/2006

Abstract:

Overuse of antibiotics is a worldwide phenomenon (1, 2) and it contributes to the emergence of antimicrobial resistance (3, 4, 5). Unnecessary use of antibiotics also leads to an increased risk of side effects (6), high costs (7) and medicalising effects (8). In the Fifty-eighth World Health Assembly held in May 2005, it was resolved and agreed by more than 60 countries (including Hong Kong and China) that the containment of antimicrobial resistance is one of the internationally agreed health-related goals but the strategy for it has not been widely implemented. It urges Member States (a) to enhance rational use of antimicrobial agents, including through development and enforcement of national standard practice guidelines for common infections, in public and private health sectors, (b) to monitor regularly the use of antimicrobial agents and the level of antimicrobial resistance in all relevant sectors, and (c) to share actively knowledge andexperience on best practices in promoting the rational use of antimicrobial agents. Primary care doctors prescribe most of all antibiotics and many of these are for infections of the respiratory tract (9) despite research studies demonstrating little or no clinical benefits (10-17). Surveys done by Lam & Lam revealed that antibiotics are frequently used in patients with respiratory tract infections in Hong Kong (18) and many doctors also acknowledged that they might be prescribing antibiotics too often for upper respiratory tract infections (URTI) (19). There are many possible reasons why primary care doctors in Hong Kong are prescribing antibiotics for URTI, for example, their misconceptions about the significance of fever, discoloured sputum or nasal discharge, exudates and lymphadenopathy (18), as well as patients' expectations (19). These findings were based on the primary care doctors' report of their clinical behaviours. They may therefore under estimate or even over estimate their use of antibiotics in these previous studies. There is otherwise no current information available on the actual usage of antibiotics by primary care doctors in Hong Kong. The proposed study represents a step forward in the understanding of the use of antibiotics by primary care doctors in Hong Kong. It aims to examine the primary care doctors' clinical behaviour in the use of antibiotics by detailing the type of antibiotics they use, including the dosage and duration, and the illnesses that they use the antibiotics. Similar study provided useful information to help reduce antibiotics use in Scadinavia (20). Objectives of the proposed study: 1. To document the level of use of antibiotics by primary care doctors in Hong Kong, including the types of antibiotics, dosage and duration. 2. To examine the primary care doctors' use of antibitocs and its relation to common infections in the community. 3. To examine the relationship between patients' expectation of antibiotics and the prescription of antibiotics by primary care doctors. 4. To identify the characteristics of primary care doctors e.g. age, gender, vocational training in general practice/family medicine and the use of antibiotics in the community. Hypotheses It is hypothesized that: 1. Antibiotics are too frequently used for common infections in primary care setting in Hong Kong. 2. Patients' expectation of antibiotics are associated with higher level of use of antibiotics by primary care doctors. 3. There is a close association between the level of use of antibiotics and certain characteristics of primary care doctors e.g. age, gender and vocational training experience. 1. Arroll B, Goodyear-Smith F. General practitioner management of upper respiratory tract infections: when are antibiotics prescribed? New Zealand Medical Journal 2000;113(1122):493-496. 2. Wang EE, Einarson TR, Kellner JD, Conly JM. Antibiotics prescribing for Canadian preschool children: evidence of overprescribing for viral respiratory infections. Clinical Infectious Disease 1999;29(1):155-160. 3. Schwartz B, Bell DM, Hughes JM, et al. Preventing the emergence of antimicrobial resistance. JAMA 1997;278:944-945. 4. Belongia EA, Schwartz B. Strategies for promoting judicious use of antibiotics by doctors and patients. BMJ 1998;317:668-671. 5. Seppala H, Klaukka T, Vuopio-Varkula J, Muotiala A, Helenius H, Lager K, et al. The effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland. N Eng J Med 1997;337:441-6. 6. Arroll B, Kenealy T. Antibiotics for the common cold. Cochrane Database Syst Rev 2000;(2):CD000247. 7. Mainous III G, Hueston WJ. The cost of antibiotics in treating upper respiratory tract infections in a Medicaid population. Arch Fam Med 1999;7:45-9. 8. Little P, Gould C, Williamsen I, Warner G, Gantly M, Kinmonth AL. Reattendance and complications in a randomised trial of prescribing strategies for sore throat: the medicalising effect of prescribing antibiotics. BMJ 1997;315:350-2. 9. De Melker RA, Kuyvenhoven MM. Management of upper respiratory tract infections in Dutch family practice. J Fam Pract. 1994;38:353-7. 10. Little P, Williamson I, Warner G, et al. Open randomised trial of prescribing strategies in managing sore thoat. BMJ 1997;314:722-727. 11. Orr PH, Scherer K, MacDonald A, et al. Randomized placebo-controlled trials of antibiotics for acute bronchitis: a critical review of the Literature. J Fam Pract. 1993;36:507-512. 12. Gonzales R, Sande M. What will it take to stop physicians from prescribing antibiotics in acute bronchitis? Lancet 1995;345:665-666. 13. Verjeij TJM, Hermans J, Mulder JD. Effects of doxycycline in patients with acute cough and purulent sputum: a double-blind, placebo-controlled trial. Br J Gen Pract 1994;44:400-404. 14. Dunlay J, Reinhardt R, Roy LD. A placebo-controlled, double-blind trial of erythromycin in adults with acute bronchitis. J Fam Pract 1987;25:137-141. 15. King DE, Williams WC, Bishop L, et al. Effectiveness of erythromycin in the treatment of acute bronchitis. J Fam Pract 1996;42:601-605. 16. Heikkinen T, Ruuskanen O, Ziegler T, et al. Short-term use of amoxicillin-clavulanate during upper respiratory tract infection for prevention of acute otitis media. J Paediatr 1995;126:313-316. 17. Kaiser L, Lew D, Hirschel B, et al. Effects of antibiotic treatment in the subset of common-cold patients who have bacteria in nasopharyngeal secretions. Lancet 1996;347:1507-1510. 18. Lam TP, Lam KF. Why do family doctors prescribe antibiotics for upper respiratory tract infection? International Journal of Clinical Practice 2003:57(3):167-169 19. Lam TP, Lam KF. What are the non-biomedical reasons which make family doctors over-prescribe antibiotics for upper respiratory tract infection in a mixed private/public Asian setting? Journal of Clinical Pharmacy and Therapeutics. 2003;28:197-201. 20. Mikstra Programme - antimicrobial treatment strategies (Accessed in June 2005 http://www.stakes.fi/mikstra/e/)

Project Title:	What are the stigmatizing opinions about people with mental health problems among Hong Kong residents
Investigator(s):	Lam TP
Department:	Med - Family Medicine Unit
Source(s) of Funding:	Small Project Funding
Start Date:	01/2007

Abstract:

Objectives of the proposed study:1. To investigate the stigmatizing opinions towards patients of different common mental illnesses e.g. anxiety related conditions, depression, schizophrenia, drug and alcohol abuse, and dementia.2. To investigate if health care attendance by family physicians with special training in mental health instead of specialist psychiatrists for minor mental illnesses e.g. anxiety, depression, would affect the readiness of some Hong Kong patients to seek treatment and to continue follow up for their illnesses.According to the US Surgeon General, stigma is the number one barrier to mental health care and this has been supported by recent studies (1). There is also evidence that stigmatizing opinions about people with psychiatric disorders are widely held in the UK. (2) These stigmatizing opinions vary in nature and frequency for different mental disorders. Li et al investigated the barriers to meeting the mental health needs of the Chinese community in UK. (3) They found that stigma associated with mental illness and limited knowledge in the community were the main causes for the widespread discrimination experienced by their participants. It is likely that such stigmatizing opinions exist in Hong Kong, however, little is known about its level of intensity and the specific mental health conditions that they are associated with. This knowledge is of vital importance if we are to aim to reduce such stigmatizing opinions since studies have shown that people's attitudes towards psychiatric patients are susceptible to change. (4) Interventions have been shown to have positive impact on participants' attitudes towards people with mental health problems. (5)Crisp (6) has said that it is general practitioners and their teams who are confronted endlessly by the challenge of mental disorder and related mental health problems in their patients. The primary care team often has the potentially precious advantage, diagnostically speaking, of knowing the ongoing psychological and social dynamics of the family background. Li et al also found that general practitioners were pivotal in the management of their patients' mental health conditions. In Hong Kong, many patients with minor mental health problems e.g. anxiety related illness, depression, are attending specialist psychiatrists, either private or public. Phongsavan et al reported that 64% of Australian general practitioners had found patient feeling uncomfortable being referred to psychiatrists. (7) It is uncertain if attending psychiatrists carries sufficient stigma that would affect the readiness of some Hong Kong patients to seek care and to continue follow up for their mental health conditions. It is therefore of importance to investigate if care by family physicians with special training in mental health would help to reduce such stigma, hence, affect the readiness of some Hong Kong patients to seek care and to continue follow up for their mental illnesses.The Family Medicine Unit of the Department of Medicine, the University of Hong Kong launched a one-year part-time Postgraduate Diploma in Community Psychological Medicine for primary care physicians in September 2002. (8) The objectives of the Course are to improve the knowledge, skills and confidence of primary care physicians in the care of the patients with psychological problems. It also emphasises the aspects of care that are different for these patients. Graduates of the Course have also been recognized by the Hospital Authority as suitable receiving doctors for accepting discharged patients with certain minor mental illnesses from the Specialist Psychiatry Clinics in various public hospitals. References:1. Lewis L. Mood disorders: diagnosis, treatment, and support from a patient perspective. Psychopharmacol Bull 2001 Autumn; 35(4):186-196.2. Crisp AH, Gelder MG, Rix S, Meltzer HI, Rowlands OJ. Sigmatisation of people with mental illnesses. The British Journal of Psychiatry 2000; 177:4-7.3. Li P, Logan S, Yee L, Ng S. Barriers to meeting the mental health needs of the Chinese community. Journal of Public Health Medicine 1999; 21 (1):74-80.4. Schulze B, Richter-Werling M, Matschinger H, Angermeyer MC. Crazy? So what! Effects of a school project on students' attitudes towards people with schizophrenia. Acta Psychiatr Scand 2003 Feb; 107(2):142-150.5. Pinfold V, Toulmin H, Thornicroft G, Huxley P, Farmer P, Graham T. Reducing psychiatric stigma and discrimination: evaluation of educational interventions in UK secondary schools. The British Journal of Psychiatry 2003; 182:342-346.6. Crisp AH. The stigmatization of sufferers with mental disorders. British Journal of General Practice 1999; 49:3-4.7. Phongsavan P, Ward JE, Oldenburg BF, Gordon JJ. Medical Journal of Australia 1995; 162(3):139-142.8. Lam TP, Tse EYY. The setting up of a diploma course in community psychological medicine for primary care doctors. Wonca Asia Pacific Regional Conference in Beijing. 2003 October.

Project Title:	Is there a need to promote family medicine concept in Hong Kong? – Meeting the need for recognition and treatment of depression as a model
Investigator(s):	Lam TP, Li DKT, Lam KF
Department:	Med - Family Medicine Unit
Source(s) of Funding:	Public Policy Research
Start Date:	04/2007

Abstract:

1) To collect in-depth views of some members of the public towards family medicine through focus group interviews. 2) To describe the general public views towards family medicine through a territory wide cross-sectional study, with specific reference to treatment of depression. 3) To describe the relationship between the demographic factors of the public and their views towards family medicine. 4) To describe the doctors' views towards family medicine concept. 5) To describe the relationship between the demographic factors of the doctors and their views towards family medicine.

List of Research Outputs

Hong T.C., Lam T.P. and Chao D.V.K., Family Physicians’ Role in Cancer Care, 13th Hong Kong International Cancer Congress . 2006.

Lam T.P., Wan X. and Ip M.S.M., Current perspectives of medical education in China. , Medical Education. 2006, 40: 940-949.

Lam T.P., Depression in primary care, Asia Pacific Family Medicine. 2006, 5.2.

Lam T.P., How to start a research porject in Family Medicine, Our Lady of Maryknoll Hospital. Hong Kong, 2006.

Lam T.P., Clearihan L. and Leopando Z., Medical writing and publishing your papers workshop, 2006 Wonca Asia Pacific Regional Conference, Nov 2006, Bangkok, Thailand. 2006.

Lam T.P., Postgraduate Education in Family Medicine, Invited Symposium, the 8th Beijing/Hong Kong Medical Exchange, November 2006. 2006.

Lam T.P., Research in Family Medicine, Plenary Lecture, Annual Scientific Meeting, Hong Kong College of Family Physicians, May 2007, Hong Kong. 2007.

Lam T.P., Stigma and mental illness in the community, Hong Kong Practitioner. 2007, 29: 81-82.

Lam T.P., The Australian general practice model and its application in Hong Kong, Invited Symposium, 2006 Wonca Asia Pacific Regional Conference, Nov 2006, Bangkok, Thailand. 2006.

Lam T.P., In: Co-Editor of Asia Pacific Family Medicine - the Official Journal of Wonca Asia Pacific, 2007.

Tan S.M., Evans A.J., Lam T.P. and Cheung K.L., Breast cancer screening in Asia Pacific Region., Breast. 2007, 16: 113-119.

Researcher : Lam WK

List of Research Outputs

Au W.Y., Ho J.C.M., Lie A.K.W., Sun J.Z., Zheng L., Liang R.H.S., Lam W.K. and Tsang K.W.T., A prospective study of respiratory ciliary structure and function after stem cell transplantation, Bone Marrow Transplantation. 2006, 38: 243-248.

Chan M.M.W., Ho A.S.S., Cheung A.H.K., Liu R., Yee W.K.S., Sin K.M., Wong M.L., Lam C.W., Chan K.S. and Lam W.K., Determinants of chronic obstructive pulmonary disease (COPD) in Chinese patients in Hong Kong. , International Journal of Tuberculosis and Lung Disease. 2007, 11: 502-7.

Ho J.C.M., Chan M.M.W., Ho S.P., Mak J.C.W., Ip M.S.M., Ooi C.G.C., Wong M.P., Tsang K.W.T. and Lam W.K., Disturbance of systemic antioxidant profile in non-small cell lung carcinoma, Eur Respir J . 2007, 29: 273-278.

Ho J.C.M., Mak J.C.W., Ho S.P., Ip M.S.M., Lam W.K. and Chan M.M.W., Genetic variations of systemic superoxide dismutase and catalase activities in non-small cell lung cancer. Presented at the 11th Congress of the Asian Pacific Society of Respiratory, 19-22 Nov, Respirology. 2006, 11 Suppl 5: A129.

Ho J.C.M., Wong M.P. and Lam W.K., Invited review: Lymphoepithelioma-like carcinoma of the lung, Respirology. 2006, 11(5): 539-545.

Ho J.C.M., Mak J.C.W., Ho S.P., Ip M.S.M., Tsang K.W.T., Lam W.K. and Chan M.M.W., Manganese superoxide dismutase and catalase genetic polymorphisms, activity levels and lung cancer risk in Chinese in Hong Kong, J. Thorac. Oncol. 2006, 1: 648-653.

Ho J.C.M. and Lam W.K., Recent advances in pharmacological treatment of non-small cell lung cancer, Internal Medicine Journal of Thailand. 2006, 22: 82-89.

Ho J.C.M. and Lam W.K., Recent advances in the management of non-small cell lung cancer, The Hong Kong Medical Diary . 2007, 12: 13-17.

Ip M.S.M., Lam W.K., Lai A.Y.K., Ko F., Lau A., Ling S.O., Chan J. and Chan W.M., Reference values of diffusing capacity of non-smoking Chinese in Hong Kong, Respirology. 2007, 12: 599-606.

Ip M.S.M., Lam W.K., Lai A.Y.K., Ko F.W., Lau A.C., Ling S.O., Chan J.W. and Chan M.M.W., Reference values of diffusing capacity of nonsmoking Chinese in Hong Kong., Respirology. 2007, 12: 599-606.

Lam B., Wong M.P., Fung S.L., Lam C.L., Wong P.C., Wong T.Y.W., Lam F.M., Ip M.S.M., Ooi C.G.C. and Lam W.K., The clinical value of autofluorescence bronchoscopy for the diagnosis of lung cancer , European Respiratory Journal. 2006, 28(5): 915-919.

Lam C.L., Girard L., Suen W.S., Chung L.P., Tin P.C., Lam W.K., Minna J.D. and Wong M.P., Establishment and expression profiling of new lung cancer cell lines from Chinese smokers and life-time never-smokers, Journal of Thoracic Oncology. 2006, 1: 932-942.

Lam C.L., Girard L., Ramirez R., Chau W.S., Suen W.S., Sheridan S., Tin V.P., Chung L.P., Wong M.P., Shay J.W., Gazdar A.F., Lam W.K. and Minna J.D., Expression of nicotinic acetylcholine receptor subunit genes in non small cell lung cancer reveals differences between smokers and nonsmokers, Cancer Research. 2007, 67(10): 4638-4647.

Lam C.L., Girard L., Ramirez R., Chau W.S., Suen W.S., Sheridan S., Tin V.P.C., Chung L.P., Wong M.P., Shay J.W., Gazdar A.F., Lam W.K. and Minna J.D., Nicotinic acetylcholine receptor subunit genes showed difference in expression pattern in smokers and nonsmokers , Annual Meeting of the American Association of Cancer Research. 2007, AACR abstracts: 2430.

Mak J.C.W., Hui W.S., Ho S.P., So H.L., Chan M.M.W., Lam W.K., Cho C.H. and Ip M.S.M., Best Poster - Systemic oxidative stress and inflammation in cigarette smoke-exposed rat model, 12th Medical Research Conference. 2007.

Mak J.C.W., Ho S.P., Yu W.C., Choo K.L., Chu C.M., Yew W.W., Lam W.K., Chan M.M.W. and Chan M.M.W., Polymorphisms in MnSOD and catalase genes - functional activity study in smokers with or without COPD., Eur Respir J. 2007, e-pub.

Mak J.C.W., Ho S.P., Leung C.M., Cheung A.H.K., Law K.W., So L.K.Y., Chan W.M., Chau C.H., Lam W.K., Ip M.S.M. and Chan W.M., Relationship between glutathione S-transferase gene polymorphisms and enzyme activity in Hong Kong Chinese asthmatics, Clinical and experimental allergy. 2007, 37: 1150-1157.

Pan N.Y., Hui W.S., Tipoe G.L., Taylor G.W., Leung Y.H., Lam W.K., Tsang K.W.T. and Mak J.C.W., Inhibition of pyocyanin-potentiated IL-8 release by steroids in bronchial epithelial cells, Respiratory medicine. 2006, 100(9): 1614-1622.

Tsang K.W.T., Shim Y.S., Wong K.S., Laim C.K., Eng P., Lam W.K. and Seto W.H., Possible case scenarios an logistic issues in H5N1 pandemic, Respirology. 2006, 11(5): 520-522.

Wong M.K., Yasufuku K., Nakajima T., Herth F.J., Sekine Y., Shibuya K., Iizasa T., Hiroshima K., Lam W.K. and Fujisawa T., Endobronchial ultrasound : new insight for the diagnosis of sarcoidosis, European Respiratory Journal. 2007, 29: 1182-1186.

Wong M.K., Leung W.C., Wang J.K., Lao T.T.H., Ip M.S.M., Lam W.K. and Ho J.C.M., Recurrent pneumothorax in pregnancy: what should we do after placing an intercostals drain, Hong Kong Medical Journal. Hong Kong, 2006, 12: 375-380.

Researcher : Lam YM

List of Research Outputs

Mok T.M.Y., Tsang P.L., Lo Y., Wong R.W.S., Lau W.C.S. and Lam Y.M., Bosentan Use in Systemic Lupus Erythematosus Patients with Pulmonary Arterial Hypertension, Lupus. England, SAGE, 2007, 16(4): 279-285.

Researcher : Lan HY

Project Title:	Role of smad signaling in regulation of CTGF expression under diabetic conditions
Investigator(s):	Lan HY
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	05/2006

Abstract:

The main objectives of this project are to: (1) examine the regulating role of Smad signaling in CTGF expression under diabetic; (2) dissect the specific role of Smad2 and Smad3 in regulating CTGF expression under diabetic conditions.

Project Title:	Regulation of immune response in glomerulonephritis by TGF-β/smad signaling
Investigator(s):	Lan HY
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	09/2006

Abstract:

(1) To demonstrate that Smad3 plays a pivotal role in the pathogenesis of anti-GBM GN. (2) To determine the mechanisms by which Smad3 regulates T cell immune responses in vivo and in vitro.

Project Title:	C-Reactive Protein in hypertensive cardiovascular disease
Investigator(s):	Lan HY
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	05/2007

Abstract:

Cardiovascular disease (CVD) is the most severe complication in hypertension. Recent studies have suggested that a native protein within the body called c-reactive protein (CRP) is markedly increased in patients with coronary heart disease and atherosclerosis and is a marker of CVD. Thus, the serum levels of CRP have been used clinically as diagnostic and predictor marker of CVD. However, it remains uncertain that CRP is causally related to CVD and the functional role of this molecule in CVD is largely unknown. We hypothesize that CRP may function as either pro-inflammatory or anti-inflammatory molecule in causing or counter-regulating the development of CVD. We plan to test this hypothesis in a mouse model of angiotensin II-induced hypertensive CVD in mice that do or do not over expressed CRP. The potential role of CRP in hypertensive CVD will be studied by examining cardiac function, inflammatory response, and fibrosis. We expect CVD to be promoted in mice that are overexpressing CRP, demonstrating a pathogenic role of CRP in CVD. However, it is also possible that CVD is protected in CRP Tg mice. If this occurs, it will indicate that CRP may act as an antagonist of inflammatory mediator and plays a protective role in angiotensin II-induced hypertensive CVD. In both cases, what mechanisms by which CRP exerts its pathogenic or protective role in CVD will be further investigated. Furthermore, it is also possible that CRP Tg mice cause no difference in terms of cardiovascular injury. This will suggest that CRP may service as a reactive protein and has no role in CVD. Nevertheless, whatever the results are, they are novel and meaningful.

List of Research Outputs

Chakraborty A., Brooks H., Zhang P., Smith W., McReynolds M.R., Hoying J.B., Bick R., Truong L., Poindexter B., Lan H.Y., Elbjeirami W. and Sheikh-Hamad D., Stanniocalcin-1 regulates endothelial gene expression and modulates trans-endothelial migration of leukocytes., AJP: Renal Physiology. 2007, 292: F895-904.

Chung A.C.K. and Lan H.Y., Loss of PPAR Interacting Protein (PRIP) Function Accelerates the Diabetic Injury Under High Glucose and AGE Conditions, 12th Medical Research Conference of Department of Medicine (3/2/2007). 2007.

Cummings K., Lan X.R., Zhang P., Truong L., Lan H.Y., DiMattia G. and Sheikh-Hamad D., Transgenic overexpression of stanniocalcin-1 attenuates anti-GBM glomerulonephritis , ASN's 39th Annual Renal Week Meeting, San Diego (14-19/11/2006) . 2006.

Duan W., Lan X.R., Yu X., Wang W. and Lan H.Y., The Distinctive Role of Smad2 and Smad3 in Mesothelial-to-Myofibroblast Transition and Peritoneal Fibrosis , ASN's 39th Annual Renal Week Meeting, San Diego (14-19/11/2006). 2006.

Duan W.J., Lan X.R., Yu X.Q. and Lan H.Y., Smad3 is a key mediator of TGF-b signaling in peritoneal fibrosis in vitro. , 11th Congress of the International Society for Peritoneal Dialysis(Hong Kong, 25-28/8/2006) . 2006.

Fu P., Liu F., Su S., Wang W., Lan X.R., Entman M.L., Schwartz R.J., Wei L. and Lan H.Y., Signaling Mechanism Of Renal Fibrosis In Unilateral Ureteral Obstructive Kidney Disease In Rock1 Knockout Mice., J Am Soc Nephrol. 2006, 17: 3105-14.

Guo H., Leung J.C.K., Lam M.F., Lan H.Y. and Lai K.N., Smad7 transgene attenuates TGF-b induced peritoneal fibrosis in uremic rats on peritoneal dialysis, Journal of American Society of Nephrology. 2006, 17: 29A.

Ka S.M., Lan X.R., Lan H.Y., Tsai P.Y., Shui H.A. and Chen A., Smad7 Gene Therapy Ameliorates an Autoimmune Crescentic Glomerulonephritis in Mice. , J Am Soc Nephrol. 2007, 18: 1777-1788.

Koka V., Wang W., Lan X.R., Truong L. and Lan H.Y., Angiotensin II induces a positive feedback autoregulatory loop in Hypertensive Nephropathy. , ASN's 39th Annual Renal Week Meeting, San Diego (14-19/11/2006) . 2006.

Lai K.N. and Lan H.Y., Ultrasound Microbubble Mediated Genes Delivery System, In: Cooper&Dunham LLP, USA Patent (11/928,109). USA, 2006.

Lan H.Y., ACE2, A Good Guy in Hypertensive Diseases, 2007 Huaxi-HKU Medical Forum, Chengdu, China. 2007.

Lan H.Y., Advances In Molecular Pathology And Therapy For Diabetic Nephropathy , The 1st Spring Seminar of Taiwan Society of Nephrology (Kaohsiung, 4/3/2007). 2007.

Lan H.Y., Advances In Molecular Signaling And Potential Therapy For Angiotensin ii-mediated Cardiovascular Fibrosis, Department of Physiology, The University of Hong Kong. 2007.

Lan H.Y., Advances in Molecular Pathology and Therapy for Diabetic Nephropathy, Southern Taiwan Society Of Nephrology, Kaohsiung. 2007.

Lan H.Y., Associate Editor, Nephron Experimental Nephrology. 2007.

Lan H.Y., Dual Angiotensin II blockade in diabetic nephropathy , Sun Yat Sen University, Guangzhou, China. 2006.

Lan H.Y., Gene therapy and targeting using ultrasound-microbubble-mediated system, Faculty of Dentistry, The University of Hong Kong, Hong Kong. 2007.

Lan H.Y., Is Combined ACEI and ARB Treatment Necessary for Hypertension?, The 9th South China International Congress Of Cardiology (guangzhou, 6-8/4/2007). . 2007.

Lan H.Y., Is Combined Acei And Arb Treatment Necessary For Hypertensive Cardiovascular Disease., International Cardiology Forum. Guangzhou, China. 2007.

Lan H.Y., Is Dual Angiotensin Blockade Necessary For Treatment Of Hypertension, West China School Of Medicine, Sichuan University, Chengdu, China. 2006.

Lan H.Y., Macrophage Migration Inhibitory Factor (mif) Is A Pro-inflammatory Cytokine Responsible For Immune-mediated Renal Injury And Atherosclerosis , Kaohsiung Medical University Hospital, Kaohsiung. Taiwan. 2007.

Lan H.Y., Macrophage migration inhibitory factor (mif) is a pro-inflammatory cytokine responsible for immune-mediated renal injury and atherosclerosis., The 1st Spring Seminar of Taiwan Society of Nephrology (Kaoshiung, 4/3/2007). 2007.

Lan H.Y., Molecular Targets For Treating Diabetic Renal Disease., Annual Meeting Of Southern Health, Melbourne, Australia . 2006.

Lan H.Y., Visiting Professor and Honorary Director (Renal Lab), West China School of Medicine, Sichuan University, Chengdu, China . 2006.

Lan X.R., Zhang R. and Lan H.Y., Deletion of Smad3 Switches The TH1 to TH2 Immune Response in anti-GBM Glomerulonephritis., 12th Medical Research Conference of Department of Medicine (3/2/2007). 2007.

Nie J., Hao W., Dou X., Wang X., Luo N., Lan H.Y. and Yu X.Q., Effects Of Smad7 Overexpression On Peritoneal Inflammation A Rat Model Of Chronic Peritoneal Infusion, Peritoneal Dialysis International. 2007, 27: 580-8.

Nie J., Dou X., Hao W., Wang X., Peng W., Jia Z., Chen W., Li X., Lan H.Y. and Yu X.Q., Smad7 gene transfer inhibits peritoneal fibrosis, Kidney International. 2007, 72: 1336-44.

Soltero L., Wang W., Lan X.R., Koka V., Dolson G.M., Lan H.Y. and Adrogue H.J., Effect Of Potassium And Sodium Citrate On Fibrosis In 5/6 Nephrectomy Rats., ASN's 39th Annual Renal Week Meeting, San Diego (14-19/11/2006) , 2006 . 2006.

Su S.H., Fu P., Liu F., Wang W., Lan X.R., Wei L. and Lan H.Y., Signaling Mechanisms of Renal Fibrosis in p160 Rock-1 Knockout Mice in a 5-day Unilateral Ureteral Obstruction Model, ASN's 39th Annual Renal Week Meeting (San Diego, USA). 2006.

Tesch G.H., Lan H.Y. and Nikolic-Paterson D.J., Treatment Of Tissue Sections For In Situ Hybridization., Methods Mol Biol. 2006, 326: 1-7.

Wang W., Soltero L., Lan X.R., Koka V., Dolson G.M., Lan H.Y. and Adrogue H.J., The Effect Of Potassium Supplementation On The Renal Inflammatory Response In A Chronic Kidney Disease Model , ASN's 39th Annual Renal Week Meeting, San Diego (14-19/11/2006) , 2006 . 2006.

Wong L.W., Zhu S.L., Zhang S.Y., Lan X.R., Chung A.C.K., Zhang R., Lam S.K., Wong B.C.Y., Xia H.H.X. and Lan H.Y., Macrophage Migration Inhibitory Factor (MIF) Knockout Mice Are Protected Against Helicobacter Pylori Induced Gastritis., 12th Medical Research Conference (Hong Kong, 3/2/2007). 2007.

Yu X., Lin S.G., Lan X.R., Bacher M., Leng L., Bucala R. and Lan H.Y., Macrophage Migration Inhibitory Factor Induces Mmp-9 Expression In Macrophages Via The Mek-erk Map Kinase Pathway. , J Interferon Cytokine Res. 2007, 27: 103-9.

Yu X.Q., Peng W.S., Dou X.R., Hao W.K., Li X.Y., Peng W.X., Nie J. and Lan H.Y., Effects of overexpression Smad7 on the expression of AQP-1,3 in a rat peritoneal fibrosis model , 11th Congress of the International Society for Peritoneal Dialysis(Hong Kong, 25-28/8/2006) . 2006.

Zhang P., Wang W., Sheikh-Hamad D., Lan H.Y. and Truong L., Preconditioning-mediated attenuation of ischemic injury in cultured renal tubular cells is mediated by increased survivin expression and PI3 kinase pathway activation. , ASN's 39th Annual Renal Week Meeting, San Diego (14-19/11/2006) . 2006.

Zhang S.Y., Lan X.R., Lau C.P. and Lan H.Y., Angiotensin II-induced Hypertensive Cardiac Fibrosis and Inflammation Are Enhanced in C-Reactive Protein Transgenic Mice., 12th Medical Research Conference of Department of Medicine (3/2/2007). 2007.

Zhou L., Fu P., Lan X.R. and Lan H.Y., Aristolochic Acid Induces Renal Tubular Epithelial Cell Apoptosis Via the P53 Pathway, Fifth Meeting of Consortium for Globalization of Chinese Medicine (Zhuhai, 20-23/9/2006). 2006.

Researcher : Lan XR

Project Title:	Regulation of ACE2 expression in hypertension
Investigator(s):	Lan XR
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	01/2007

Abstract:

The recent discovery of the Ang II breakdown enzyme ACE2 and alternative Ang II generating pathways such as chymase in addition to ACE has increased the complexity of our understanding of Ang II generation and degradation in hypertension (1, 2). ACE2 is a breakdown enzyme responsible for the degradation of AngII to Angiotensin 1-7 peptide The later has vasodilatory properties and has its own unique receptor the Mas Receptor. (2). Emerging evidence shows that ACE2 plays an important role in negatively regulating hypertension (3). In rat models of hypertension, renal ACE2 mRNA and protein are decreased, although this could not be confirmed in human hypertensive nephropathy in a prior study (4, 5). Further, in rats treated with ACE inhibitors and angiotensin receptor blockers, an increase in local renal ACE2 activity was noted (6). We have earlier shown that ACE is upregulated in human diabetic nephropathy accompanied with hypertension, a condition associated with high AngII levels (7). In preliminary studies, we also found that upregulation of ACE was associated with downregulation of ACE2 in human hypertensive nephropathy. markely Taken together, we hypothesize that there may be an alteration in the ACE/ACE2 balance in hypertension in a manner that favors increased AngII generation (i.e upregulation of ACE) and decreased AngII degradation (i.e downregulation of ACE2) during hypertension. We plan to test this hypothesis by pursuing two Specific Aims 1. To examine ACE versus ACE2 expression in hypertensive nephropathy (HTN) and cardiopathy (HTC) in patients with hypertension. 2. To define the pathogenic mechanisms of downregulation of ACE2 in vivo and in vitro.

List of Research Outputs

Cummings K., Lan X.R., Zhang P., Truong L., Lan H.Y., DiMattia G. and Sheikh-Hamad D., Transgenic overexpression of stanniocalcin-1 attenuates anti-GBM glomerulonephritis , ASN's 39th Annual Renal Week Meeting, San Diego (14-19/11/2006) . 2006.

Duan W., Lan X.R., Yu X., Wang W. and Lan H.Y., The Distinctive Role of Smad2 and Smad3 in Mesothelial-to-Myofibroblast Transition and Peritoneal Fibrosis , ASN's 39th Annual Renal Week Meeting, San Diego (14-19/11/2006). 2006.

Duan W.J., Lan X.R., Yu X.Q. and Lan H.Y., Smad3 is a key mediator of TGF-b signaling in peritoneal fibrosis in vitro. , 11th Congress of the International Society for Peritoneal Dialysis(Hong Kong, 25-28/8/2006) . 2006.

Fu P., Liu F., Su S., Wang W., Lan X.R., Entman M.L., Schwartz R.J., Wei L. and Lan H.Y., Signaling Mechanism Of Renal Fibrosis In Unilateral Ureteral Obstructive Kidney Disease In Rock1 Knockout Mice., J Am Soc Nephrol. 2006, 17: 3105-14.

Ka S.M., Lan X.R., Lan H.Y., Tsai P.Y., Shui H.A. and Chen A., Smad7 Gene Therapy Ameliorates an Autoimmune Crescentic Glomerulonephritis in Mice. , J Am Soc Nephrol. 2007, 18: 1777-1788.

Koka V., Wang W., Lan X.R., Truong L. and Lan H.Y., Angiotensin II induces a positive feedback autoregulatory loop in Hypertensive Nephropathy. , ASN's 39th Annual Renal Week Meeting, San Diego (14-19/11/2006) . 2006.

Lan X.R., Zhang R. and Lan H.Y., Deletion of Smad3 Switches The TH1 to TH2 Immune Response in anti-GBM Glomerulonephritis., 12th Medical Research Conference of Department of Medicine (3/2/2007). 2007.

Soltero L., Wang W., Lan X.R., Koka V., Dolson G.M., Lan H.Y. and Adrogue H.J., Effect Of Potassium And Sodium Citrate On Fibrosis In 5/6 Nephrectomy Rats., ASN's 39th Annual Renal Week Meeting, San Diego (14-19/11/2006) , 2006 . 2006.

Su S.H., Fu P., Liu F., Wang W., Lan X.R., Wei L. and Lan H.Y., Signaling Mechanisms of Renal Fibrosis in p160 Rock-1 Knockout Mice in a 5-day Unilateral Ureteral Obstruction Model, ASN's 39th Annual Renal Week Meeting (San Diego, USA). 2006.

Wang W., Soltero L., Lan X.R., Koka V., Dolson G.M., Lan H.Y. and Adrogue H.J., The Effect Of Potassium Supplementation On The Renal Inflammatory Response In A Chronic Kidney Disease Model , ASN's 39th Annual Renal Week Meeting, San Diego (14-19/11/2006) , 2006 . 2006.

Wong L.W., Zhu S.L., Zhang S.Y., Lan X.R., Chung A.C.K., Zhang R., Lam S.K., Wong B.C.Y., Xia H.H.X. and Lan H.Y., Macrophage Migration Inhibitory Factor (MIF) Knockout Mice Are Protected Against Helicobacter Pylori Induced Gastritis., 12th Medical Research Conference (Hong Kong, 3/2/2007). 2007.

Yu X., Lin S.G., Lan X.R., Bacher M., Leng L., Bucala R. and Lan H.Y., Macrophage Migration Inhibitory Factor Induces Mmp-9 Expression In Macrophages Via The Mek-erk Map Kinase Pathway. , J Interferon Cytokine Res. 2007, 27: 103-9.

Zhang S.Y., Lan X.R., Lau C.P. and Lan H.Y., Angiotensin II-induced Hypertensive Cardiac Fibrosis and Inflammation Are Enhanced in C-Reactive Protein Transgenic Mice., 12th Medical Research Conference of Department of Medicine (3/2/2007). 2007.

Zhou L., Fu P., Lan X.R. and Lan H.Y., Aristolochic Acid Induces Renal Tubular Epithelial Cell Apoptosis Via the P53 Pathway, Fifth Meeting of Consortium for Globalization of Chinese Medicine (Zhuhai, 20-23/9/2006). 2006.

Researcher : Lau CP

Project Title:	Evaluation of the antianginal efficacy and safety of oral chronic administration of ivabradine (5mg b.i.d. then 7.5mg b.i.d or 10mg b.i.d) compared to atenolol (50mg o.d then 100mg o.d), in patients with stable effort angina pectorals
Investigator(s):	Lau CP, Lee KLF
Department:	Medicine
Source(s) of Funding:	Other Funding Scheme
Start Date:	05/2000

Abstract:

To demonstrate the non-inferiority of invabradine 7.5mg b.i.d then 10mg b.i.d in improving exercise capacity in comparison to atenolol given by oral route for 4 and a half months to out-patients with chronic stable angina; to determine pharmacokinetic parameters.

Project Title:	Roles of macrophage migration inhibitory factor (MIF) in acute myocardial infarction
Investigator(s):	Lau CP, Yu CM, Lan HY
Department:	Medicine
Source(s) of Funding:	Low Budget High Impact Programme
Start Date:	11/2000

Abstract:

To investigate the pathogenic role and mechanism of macrophage migration inhibitory factor (MIF) after myocardial infarction (AMI).

List of Research Outputs

Chan S.S.C., Chong S.Y., Chan S.C.C., Lau C.P. and Lam T.H., Characteristic of a group of smoking cardiac patients with different stage of readiness to quit: Implications for stage-matched intervention for smoking cessation, 13th World Conference on Tobacco OR Health: Building capacity of a tobacco-free world, Washington DC, USA, 12-15 July 2006.

Chan S.S.C., Chan S.C.C., Lau C.P. and Lam T.H., The effectiveness of a stage-matched smoking cessation intervention for cardiac patients: a randomized controlled trial, 13th World Conference on Tobacco OR Health: Building capacity of a tobacco-free world, Washington DC, USA, 12-15 July 2006.

Chan S.S.C., Leung Y.P., Lau C.P., Wong V. and Lam T.H., Validation of the Smoking Self-Efficacy Questionnaire (SEQ-12) with a smaple of Chinese cardiac patients in Hong Kong, 5th Annual Conference of the International Society for the Prevention of Tobacco Induced Disease. Book of Abstracts. Hong Kong, 2006, 46.

Cheung B.M.Y., Leung Y.H., Man Y.U. .B.U.N., Ong K.L., Wong L.Y.F., Lau C.P. and Lam K.S.L., Association of Blood Pressure with Polymorphisms in the Quantitative Trait Locus for Abdominal Obesity-Metabolic Syndrome on Chromosome 17, The 21st Scientific Meeting of the International Society of Hypertension 2006.

Cheung B.M.Y., Wat N.M.S., Man Y.B., Tam S., Thomas G.N., Leung G.M., Cheng C.H., Woo J., Janus E.D., Lau C.P., Lam T.H. and Lam K.S.L., Development of diabetes in Chinese with the metabolic syndrome, Diabetes care. 2007, 30: 1430-1436.

Cheung B.M.Y., Wat N.M.S., Man Y.B., Tam S., Cheng C.H., Leung G.M., Woo J., Janus E.D., Lau C.P., Lam T.H. and Lam K.S.L., Predictors of the development of hypertension in the Hong Kong cardiovascular risk factor prevalence study-2 (CRISPS2), The 21st Scientific Meeting of the International Society of Hypertension. 2006.

Cheung B.M.Y., Ong K.L., Man Y.B., Lau C.P., Lam K.S.L. and Wong Y.L., Prevalence of the metabolic syndrome in the United States National Health and Nutrition Examination Survey 1999-2002 according to different defining criteria., J Clin Hypertens (Greenwich). 2006, 8(8): 562-70.

Cheung B.M.Y., Ong K.L., Man Y.U. .B.U.N., Wong L.Y.F., Lau C.P. and Lam K.S.L., Prevalence, Awareness, Treatment and Control of Hypertension in the United States 1999-2004, The 21st Scientific Meeting of the International Society of Hypertension. 2006.

Cheung B.M.Y., Wat N.M.S., Man Y.U. .B.U.N., Tam S., Cheng C.H., Leung G.M., Woo J.E.A.N., Janus E.D.W.A.R.D. .D., Lau C.P., Lam T.H. and Lam K.S.L., Waist Circumference as a Predictor of Cardiovascular Risk in the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS2), The 21st Scientific Meeting of the International Society of Hypertension. 2006.

Deng X., Lau C.P. and Li G.R., Cell cycle-dependent expression of potassium channels and cell proliferation in rat mesenchymal stem cells from bone marrow, Biophysical Journal/51th Annual Meeting of Biophysical Society, Baltimore, MD . 2007, 126.

Deng X., Sun H., Lau C.P. and Li G.R., Properties of ion channels in rabbit mesenchymal stem cells from bone marrow , Biochem Biophys Res Commun. 2006, 348(1): 301-309.

Gao Z., Sun H., Lau C.P., Fung P.C.W. and Li G.R., Evidence for cystic fibrosis transmembrane conductance regulator chloride current in swine ventricular myocytes, J Mol Cell Cardiol. 2007, 42(1): 98-105.

Ho H.H., Siu C.W.D., Jim M.H., Miu K.M., Chan R.H.W., Lee S.W.L., Lau C.P. and Tse H.F., Leukocytosis and clinical outcomes in acute inferior myocardial infarction, Int J Cardiol. 2006, 118(2): 278-9.

Hu H., Lau C.P. and Li G.R., Characterization of Ionic currents in human preadipocytes, Second International Symposium on Healthy Aging: “Meeting the Challenges of an Aging Population”, The University of Hong Kong, Hong Kong . 2007.

Hu H., Lau C.P. and Li G.R., Demonstration of Ion channels in human preadipocytes, Journal of Hong Kong College Cardiology/The 10th Institute of Cardiovascular Science and Medicine . 2006, 14: 87.

Hu R., Lau C.P. and Li G.R., Characterization of intracellular Ca2+ signal pathway in human preadipocytes, Second International Symposium on Healthy Aging: “Meeting the Challenges of an Aging Population", The University of Hong Kong, Hong Kong. 2007.

Hu R., Siu C.W.D., Wang W.Q., Lau C.P. and Tse H.F., Impaired nitrate-mediated dilatation could reflect nitrate tolerance in patients with coronary artery disease, Int J Cardiol. 2006, 120(3): 351-6.

Jim M.H., Siu C.W., Lee S.W.L., Chan A.O. and Lau C.P., Prognostic implications of PR-segment depression in inferior leads in acute inferior myocardial infarction. , Clin Cardiol. 2006, 8: 363-8.

Lau C.P., 9th South China International Congress Cardiology . 2007.

Lau C.P., Asia-Pacific HRS Kick-off Meeting, The 23rd Annual Meeting of the Japanese Society of Electrocardiology and the 21st Annual Meeting of the Japanese Society of Cardiac Pacing and Electrophysiology. 2006.

Lau C.P., BEAUTIFUL Steering Committee Meeting. 2007.

Lau C.P., Cardiac Resynchronisation Therapy in Heart Failure: Is the RV lead necessary?, The 23rd Annual Meeting of the Japanese Society of Electrocardiology and the 21st Annual Meeting of the Japanese Society of Cardiac Pacing and Electrophysiology. 2006.

Lau C.P., Cardiac Resynchronization Therapy: the Importance of the Right Ventricular Lead, International Heart Forum Beijing 2006 . 2006.

Lau C.P., Clinical Relevance of Electromechanical Remodeling of Atrial Fibrillation , 8th Asian Pacific Symposium on Cardiac Pacing and Electrophysiology (8th APSPE). 2006.

Lau C.P., Debate Session: CRT Indications are limited to LBBB Patients , 8th Asian Pacific Symposium on Cardiac Pacing and Electrophysiology (8th APSPE). 2006.

Lau C.P., East Meets West Cardiology 2007. 2007.

Lau C.P., Impact of special pacing site and pacing modality on suppression of AF, The 2nd Asia- pacific Atrial Fibrillation Symposium (APAFS). 2006.

Lau C.P., Is ICD Necessary for Patients with Heart Failure?, China Interventional Therapeutics (CIT) 2007 . 2007.

Lau C.P., Plenary Session 4: Sudden Cardiac Death ' CRT-D vs CRT-P', Cardiorhythm 2007. 2007.

Lau C.P., Poon R.T.P., Cheung S.T., Yu W.C. and Fan S.T., SPARC and Hevin expression correlate with tumour angiogenesis in hepatocellular carcinoma, Journal of Pathology. 2006, 210(4): 459-468.

Lau C.P., Tse H.F. and Kay N.E.A.L., Sensor Driven Pacing: Device Specifics, In: In Ellenbogen KA, Wilkoff BL, Kay GN, Lau CP (eds), Clinical Cardiac Pacing: Defibrillation, and Resynchronization therapy. USA, Saunders Elsevier, 2007, 3rd Edition: 499-530.

Lau C.P., Symposium 6: Basic and Clinical Concepts of Cardiac Resynchronization Therapy (CRT) , 8th Asian Pacific Symposium on Cardiac Pacing and Electrophysiology (8th APSPE). 2006.

Lau C.P., Symposium VI: Treatment of AF in heart failure, The 2nd Asia- pacific Atrial Fibrillation Symposium (APAFS) 2006. 2006.

Lau C.P., Tse H.F. and Mond H.G., The impact of reimbursement on the usage of pacemakers, implantable cardioverter defibrillators and radiofrequency ablation., J Interv Card Electrophysiol. 2007, 17(3): 177-81.

Lau C.P., Workshop 2: Reading Unknown Tracing with Experts (Panelist), Cardiorhythm 2007. 2007.

Lau C.P., 心力衰竭器械治疗 — 同步化监测及除颤器, The 7th Biannual Scientific Sessions Chinese Society of Pacing and Electrophysiology (CSPE) 中华医学会心电生理和起搏分会第七次学术双年会议. 2006.

Lau G.K.K., Chan Y.H., Yiu K.H., Li S.W., Tam S., Lau C.P., Kwong Y.L. and Tse H.F., Burden of carotid atherosclerosis in patients with stroke: relationships with circulating endothelial progenitor cells and hypertension, Journal of human hypertension. 2007, 21(6): 445-451.

Lee K.L.F., Burns J., Mullen T., Hettrick D., Tse H.F. and Lau C.P., Avoidance of right ventricular pacing in cardiac resynchronization therapy improves right ventricular hemodynamics in heart failure patients, J Cardiovas Electrophysiol. 2007, 18(5): 497-504.

Li G.R., Sun H., Chiu S.W. and Lau C.P., The n-3 polyunsaturated fatty acids from fish oil inhibit transient outward and ultra-rapid delayed rectifier potassium currents and voltage-gated sodium current in human atrial myocytes, CardioRhythm-2007/Europace, Hong Kong. 2007, 9(supple 1): 25.

Liu H., Jin M.W., Xiang J.Z., Huang Y., Sun H., Chiu S.W., Lau C.P. and Li G.R., Raloxifene inhibits transient outward and ultra-rapid delayed rectifier potassium currents in human atrial myocytes, Eur J Pharmacol. 2007, 563(1-3): 61-8.

Liu H., Sun H., Lau C.P. and Li G.R., Regulation of voltage-gated cardiac sodium current by epidermal growth factor receptor kinase in guinea pig ventricular myocytes. , J Mol Cell Cardiol. 2007, 42(4): 760-8.

Liu H., Sun H., Lau C.P. and Li G.R., Regulation of voltage-gated cardiac sodium current by epidermal growth factor receptor kinase in guinea pig ventricular myocytes, J Mol Cell Cardiol . 2006, 2007, 42(4): 760-768.

Ong K.L., Cheung B.M.Y., Man Y.B., Wong L.Y.F., Lau C.P. and Lam K.S.L., Prevalence, awareness, treatment and control of hypertension among United States adults 1999-2004. , Hypertension. 2007, 49: 69-75.

Ripley K.L., Gage A.A., Olsen D.B., Van Vleet J.F., Lau C.P. and Tse H.F., Time course of esophageal lesions after catheter ablation with cryothermal and radiofrequency ablation: implication for atrio-esophageal fistula formation after catheter ablation for atrial fibrillation. , J Cardiovasc Electrophysiol. 2007, 18(6): 642-6.

Siu C.W., Zhang X., Yung C., Kung A.W.C., Lau C.P. and Tse H.F., Hemodynamic Changes in Hyperthyroidism Related Pulmonary Hypertension: A Prospective Echocardiographic study, The American College of Cardiology 56th annual Scientific Sessions, New Orleans. 2007.

Siu C.W., Lau C.P., Tse H.F. and Li R.A., Probing the external S5-Pore region of HCN-encoded pacemaker channel by cysteine scanning mutagensis. , HBHA conference 2007 Young Investigator Award (Poster category) . 2007.

Siu C.W., Lau C.P., Tse H.F. and Li R.A., Probing the external S5-Pore region of HCN-encoded pacemaker channel by cysteine scanning mutagensis, MGH-HKU-Nature Forum 2007.

Siu C.W.D., Cheng L.C., Woo P.C., Lau C.P. and Tse H.F., A patient with relapsing pacemaker infection due to "Gram-positive bacilli"., Int J Cardiol. 2007, 114(2): E40-1.

Siu C.W.D., Tse H.F. and Lau C.P., Avoidance of electromagnetic interference to implantable cardiovertor-defibrillator during atrioventricular node ablation for atrial fibrillation using transvenous cryoablation, Pacing Clin Electrophysiology. 2006, 29(8): 914-6.

Siu C.W.D., Tse H.F., Lee K.L.F., Chan R.H.W., Chen W.H., Yung C., Lee S.W.L. and Lau C.P., Cardiac resynchronization therapy optimization by ultrasonic cardiac output monitoring (USCOM) device, Pacing Clin Electrophysiology. 2007, 30: 50-55.

Siu C.W.D., Au W.Y., Yung C.Y., Kumana C.R., Lau C.P., Kwong Y.L. and Tse H.F., Effects of oral arsenic trioxide therapy on QT intervals in patients with acute promyelocytic leukemia: implications on long-term cardiac safety, Blood. 2006, 108(1): 103-106.

Siu C.W.D., Zhang X., Yung C., Kung A.W.C., Lau C.P. and Tse H.F., Hemodynamic Changes in Hyperthyroidism Related Pulmonary Hypertension: A Prospective Echocardiographic study, J Clin Endocrinol Metab. 2007, 92(5): 1736-42.

Siu C.W.D., Yeung C.Y., Lau C.P., Kung A.W.C. and Tse H.F., Incidence, clinical characteristics and outcome of congestive heart failure as the initial presentation in patients with primary hyperthyroidism, Heart. 2007, 93 (4): 483-7.

Siu C.W.D., Jim M.H., Ho H.H., Miu R., Lee S.W., Lau C.P. and Tse H.F., Transient Atrial Fibrillation Complicating Acute Inferior Myocardial Infarction: Implications for Future Risk of Ischemic Stroke. , Chest. 2007, 132(1): 44-9.

Siu D.C.W., Zhang X., Yung C., Kung A.W.C., Lau C.P. and Tse H.F., Hemodynamic changes in hyperthyroidism-related pulmonary hypertension: a prospective echocardiographic study, Journal of Clinical Endocrinology & Metabolism. 2007, 92: 1736-42.

Tao R., Lau C.P. and Li G.R., Inosital 1,4,5-trisphosphate receptors mediating spontaneous Ca2+ oscillation favors proliferation in human mesenchymal stems from bone marrows, 11th Research Postgraduate Symposium, Faculty of Medicine, HKU, 2006 . 2006, 34.

Tao R., Lau C.P. and Li G.R., Inositol 1,4,5-trisphosphate receptors mediating spontaneous Ca2+ oscillation favors proliferation in human mesenchymal stem cells from bone marrow., Blood/48th Annual Meeting of the American-Society-of-Hematology, Orlando, FL. 2006, 108(11): 727A.

Tse H.F. and Lau C.P., Atrial Fibrillation. In Ngygen T, Hu D, Kim MH, grines (eds) Management of Complex Cardiovascular Problems: The Evidence-based Medicine Approach, 3rd Edition, Blackwell Futura Publishing Co Inc, Armonk, NY USA. 2007, 281-318.

Tse H.F., Yiu K.H. and Lau C.P., Bone marrow stem cell therapy for myocardial angiogenesis, Curr Vasc Pharmacol. 2007, 5(2): 103-12.

Tse H.F. and Lau C.P., Clinical trials for cardiac pacing in bradycardia: the end or the beginning?, Circulation. 2006, 114(1): 3-5.

Tse H.F., Kaufman C.L., Bank A.J., Zhang X., Siu C.W., Kaiser D.R. and Lau C.P., Right Ventricular Septal Pacing Upgrade Improves Left Ventricular Performance And Functional Capacity In Patients With Previous Permanent Right Ventricular Apical Pacing Independent Of Ventricular Dyssynchrony , 28th Annual Scientific Sessions of Heart Rhythm Socity, Denver. 2007.

Tse H.F., Thambar S., Kwong Y.L., Rowlings P., Bellamy G., McCrohon J., Bastian B., Chen W.H., Chan J.K.F., Lo G., Ho C.L. and Lau C.P., Safety of Catheter-Based Intramyocardial Autologous Bone Marrow Cells Implantation fro Therapeutic Angiogenesis, AM J CARDIOL. 2006, 98(1): 60-62.

Tse H.F. and Lau C.P., Sensors for Implantable Devices: Ideal Characteristics, Sensor Combination, and Automaticity:, In: In Ellenbogen KA, Wilkoff BL, Kay GN, Lau CP (eds), Clinical Cardiac Pacing, Defibrillation, and Resynchronization Therapy. USA, Saunders Elsevier, 2007, 3rd Edition: 201-233.

Tse H.F. and Lau C.P., Therapeutic angiogenesis with bone marrow derived stem cells, J Cardiovasc Pharmacol Ther. 2007, 12(2): 89-97.

Tse H.F., Lau C.P., Park E., Bornzin G.A., Yu C., Benser M.E., Bloomfield D.M. and Padeletti L., Transient overdrive pacing upon standing prevents orthostatic hypotension in elderly pacemaker patients with chronotropic incompetence. , Pacing Clin Electrophysiol. . 2007, 30(2): 188-92.

Tse H.F., Lau C.P., Park E., Bornzin G.A., Yu C., Benser M., Bloomfield D.M. and Padeletti L., Transient overdrive pacing upon standing prevents orthostatic hypotension in elderly pacemaker patients with chronotropic incompetence., Pacing Clinc Electrophysiology. 2007, 30: 188-192.

Wang M.M., Lau C.P., Zhang X., Siu C.W., Tang M.O. and Tse H.F., Early Improvement Of Diastolic Dyschrony And Myocardial Relaxation Time After Upgrade Of Longstanding Right Ventricular Apical To Right Ventricular Septal Pacing (Oral presentation) , 28th Annual Scientific Sessions of Heart Rhythm Society, Denver, Colorado, May 9-12 2007.

Xue T., Siu C.W.D., Lieu D.K., Lau C.P., Tse H.F. and Li R.A., Mechanistic role of I(f) revealed by induction of ventricular automaticity by somatic gene transfer of gating-engineered pacemaker (HCN) channels., Circulation. 2007, 115(14): 1839-1850.

Yiu K.H., Siu C.W.D., Lee K.L.F., Lau C.P., Lee S.W.L., Fong D.Y.T. and Tse H.F., Emerging trends of community acquired infective endocarditis. , Int Cardiol J . 2006, 121(1): 119-22.

Yiu K.H., Siu C.W., Lau C.P., Lee K.L.F. and Tse H.F., Transvenous catheter-based microwave ablation for atrial flutter., Heart Rhythm. 2007 . 2007, 4(2): 221-3.

Zhang D., Lau C.P. and Li G.R., Regulation of hERG channels by EGFR and Src-related tyrosine kinase, Journal of Hong Kong College Cardiology/The 10th Institute of Cardiovascular Science and Medicine . 2006, 14: 94.

Zhang S.Y., Lan X.R., Lau C.P. and Lan H.Y., Angiotensin II-induced Hypertensive Cardiac Fibrosis and Inflammation Are Enhanced in C-Reactive Protein Transgenic Mice., 12th Medical Research Conference of Department of Medicine (3/2/2007). 2007.

Zhang X., Chen H., Tsang V.Y.C., Tang M.O., Lau C.P. and Tse H.F., Prevalence And Clinical Predictors For New-onset Heart Failure After Permanent Right Ventricular Apical Pacing In Patients With Aquired High-grade Atrioventricular Block, World Congress of Cardiology 2006, Barcelona. 2006.

Researcher : Lau G

Project Title:	Role of intrahepatic close-circular covalent (ccc) DNA in HBV reactivation in hepatitis B surface antigen positive subjects who received chemotherapy
Investigator(s):	Lau G, Liang RHS, He ML
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Applied Research
Start Date:	11/2002

Abstract:

To study the T cell determinants of liver damages during the immune-clearance phase of chronic HBV infection.

Project Title:	Characterization of the HBV-specific cytotoxic T lymphocyte (CTL) activities associated with a sustained remission after anti-HBV therapy in Chinese with chronic HBV infection
Investigator(s):	Lau G, Lin CL, Zhang H
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2004

Abstract:

To compare the frequency and phenotype of the end-of-therapy virus-specific CD8+ T cells in chronic HBV patients who had sustained response to anti-HBV therapy with those who relapse; to compare the characteristics of end-of-therapy HBV-specific CD8+ T cells in those who were treated with nucleoside analogues, such as lamivudine, and those treated with immune therapy, such as pegylated interferon.

Project Title:	Prevalence and Natural History of Non-Alcoholic Fatty Liver Diseases in Hong Kong Chinese
Investigator(s):	Lau G
Department:	Medicine
Source(s) of Funding:	Hong Kong Liver Foundation - General Award
Start Date:	02/2005

Abstract:

To define teh prevalence of non-alcoholic fatty liver diseases (NAFLD) in Hong Kong Chinese; to charaterize the natural history of NAFLD in patients with and without chronic HBV infection.

Project Title:	Role of upregulation of toll-like receptor 7 and functional polymorphisms within the toll-like receptor 7 gene in inducing sustained disease remission in chronic hepatitis B infection
Investigator(s):	Lau G, Hui CK, Luk JMC, Sham PC
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	10/2006

Abstract:

To determine if upregulation of toll-like receptor 7 (TLR7) by interferon-based therapy will lead to activation of HBV specific T cell response via cytokine mediated pathway; to study the genetic variations in the TLR7 gene in Chinese chronic hepatitis B patients which are indicative of the serological clearance of hepatitis B surface antigen (HBsAg) after treatment with pegylated interferon-α.

List of Research Outputs

Bonino F., Marcellin P., Lau G., hadziyannis S., Jin R., Piratvisuth T., Germanidis G., Yurdaydin C., Diago M., Gurel S., Lai M.Y., Brunetto M.R., Farci P., Popescu M. and McCloud P., predicting response to peginterferon alpha-2a, lamivudine adn teh two combined for HBeAg-negative chronic hepatitis B, Gut. 2007, 56(5): 699-705.

Brunetto M., Bonino F., Moriconi F., Marcellin P., Lau G., Farci P., Yurdaydin C., Piratvisuth T., Luo K., Wang Y., Hadziyannis S. and Wolf E., Predictors of HBsAg decline in HBeAg-negative CHB: Peginterferon alfa-2a (40KD) ±Lamivudine, The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007, Hepatology International. 2007, 242: 17.

Chitturi S., Farrell G.C., Hashimoto E., Saibara T., Lau G. and Sollano J.D., Non-alcoholic fatty liver disease in the Asia-Pacific region: Definitions and overview of proposed guidelines, Journal of Gastroenterology and Hepatology. 2007, 22: 778-87.

Farrell G.C., Chitturi S., Lau G. and Sollano J.D., Guidelines fro the assessment and management of non-alcoholic fatty liver disease in the Asia-Pacific region: Executive Summary, Journal of Gastroenterology and Hepatology. 2007, 22: 775-777.

Hui C.K., Bowden S., Zhang H.Y., Wong A., Lewin S., Rousseau F., Mommeja-Marin H., Lee N.P., Luk J.M.C., Locarnini S., Leung N., Naoumov N.V. and Lau G., Comparison of real-time PCR assays for monitoring serum hepatitis B virus DNA levels during antiviral therapy, Journal of Clinical Microbiology. 2006, 44(8): 2983-2987.

Hui C.K., Bowden S., Zhang H.Y., Wong A., Lewin S., Rousseau F., Mommeja-Marin H., Lee N.P., Luk J.M., Locarnini S., Leung N., Naoumov N.V. and Lau G., Comparison of real-time PCR assays for monitoring serum heptatis B virus DNA levels during antiviral therpay., J Clin Microbiol. 2006, 44(8): 2983-7.

Hui C.K., Zhang H., Shek T., Yao H., Yueng Y.H., Leung K.W., Lai S.T., Lai J.Y., Leung N. and Lau G., Disease progression in Chinese chronic hepatitis C patients with persistently normal alanin aminotransaminase levels, Alimentary Pharmacology Therapy. 2007, 25(11): 1283-92.

Hui C.K., Cheung W.W.W., Chan S.C., Lo C.M. and Lau G., Hepatitis B vaccination and preemptive treatment of hepatitis B virus in liver transplantation, Current Opinion in Organ Transplantation. 2006, 11(6): 594-598.

Hui C.K., Lau E., Monto A., Kim M., Luk J.M.C., Poon R.T.P., Leung N., Lo C.M., Fan S.T., Lau G. and Wright T.L., Natural history of patients with recurrent chronic hepatitis C virus and occult hepatitis B co-infection after liver transplantation, American Journal of Transplantation. 2006, 6(7): 1600-1608.

Hui C.K., Liang R.H.S. and Lau G., Reply to "Kinetics of hepatitis B virus reactivation after chemotherapy: more questions than answers , Gastroenterology. 2006, 131(5): 1656-1657.

Hui C.K., Cheung W.W., Zhang H.Y., Au W.Y., Leung N., Luk J.M., Lie A.K.W., Kwong Y.L., Liang R.H.S. and Lau G., Rituximab increases the risk of de novo hepatitis B infection in hepatitis B surface antigen negative patients undergoing cytotoxic chemotherpay, Gastroenterology. 2006, 131(1): 59-68.

Hui C.K., Zhang H., Lee P.Y., Marin H., Yueng Y.H., Leung K.W., Lu L., Leung N., Luk J.M.C., Naoumov N., Huang F. and Lau G., Role of regulatory T cells in natural immunity and sustained pharmacological control hepatitis B infection, The Liver Meeting of The American Association for the Study of Liver, Hepatology. 2006, 44: 543A.

Hui C.K., Zhang H.Y., Lee P.Y., Mommeja-Marin H., Yueng Y.H., Leung K.W., Lu L., Leung N., Luk J.M.C., Naoumov N.N., Huang F.P. and Lau G., Role of regulatory T cells in natural immunity and sustained pharmacological control of chronic hepatitis B infection, Hepatology. 2006, 44(4): 543A-543A.

Lai L., Hui C.K., Poon R.T.P., Shek T.W.H., Lai S.T., Lai J.Y., Lo C.M., Fan S.T., Leung N. and Lau G., The use of transient elastography as a preoperative assessment of hepatic resection (Abstract), The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007. Hepatology International. 2007, 1(1): 51.

Lau G., Lu L., Hui C.K., Zhang H.Y., Yeung Y.H., Cheung K.F. and Luk J.M., "Combination Antiviral Effects Of 2’ 3’- Dideoxy – 3’ Fluoroguanosine with Nucleos(t)ide Analogs Against Hepatitis B Virus In Vitro” , , Hepatology 2007,. 2007, 46(4): 952.

Lau G., "Contraversies in Management of Hepatitis" Part 2: Whom and How long to Treat? Llimited length, 17th Asian Pacific Association for the Study of Liver (27th -30th March, 2007, Kyoto, Japan). 2007.

Lau G., Lu L., Hui C.K., Zhang H.Y., Yeung Y.H., Cheung K.F. and Luk J.M., "Intracellular Levels Of Hepatitis B Virus DNA and Pregenomic RNA In Peripheral Blood mononuclear Cells Of Chronically Infected Patients” , In: Lu L, Hui CK, Zhang HY, Yeung YH, Cheung KF, Luk JM, Lau G K, Hepatology 2007. 46(4): 935.

Lau G., Hui C.K., Leung N., Lai S.T., Lai J.Y., Shek T., Yao H. and Li W.K., "Non-Alcoholic Fatty Liver Disease In Chinese Does Lead To Progressive Disease”, , In: Hui CK, Leung N, Lai ST, Lai JY, Shek T, Yao H, Li WK, Lau GK, , Hepatology 2007, . 2007, 46(4): 1143.

Lau G., "TCM in Liver Fibrosis", International Conference and Exhibition of the Modernization of Chinese Medicine and Health Products (ICMCM). 2006.

Lau G., Associate Editor, Hepatology International. 2007.

Lau G., Combination therapy in the treatment of hepatitis B, New Horizons. 2006, 13: 1-4.

Lau G., Does treatment with interferon-based therapy improve the natural history of chronic hepatitis B infection?, Journal of Hepatology. 2007, 46: 6-8.

Lau G., Early prevention in patients at risk by an anti-viral agent is superior to intervention during hepatitis B reactivation, European Association of the Study of Liver 42nd Annual Meeting (11th-15th April, 2007, Barcelona, Spain). 2007.

Lau G., Editoral Board, Expert Review of Gastroenterology and Hepatology, Journal of Gastroenterology and Hepatology. 2007.

Lau G., Faculty Outstanding Research Output Award, Li Ka Shing Faculty of Medicine, The University of Hong Kong. 2006.

Lau G., HBV in immunosuppression, chemotherapy and transplant recipients. , In: Lau GK., APASL single topic meeting on HBV 2007 (in press). 2007.

Lau G., Zhu R., Lei T., Ng M.Y., Luk J.M.C., Sham P., Chiu J.F. and He Q.Y., Identification of biomarkers for the prediction of HBV related HCC by integrated proteomics (Abstract), The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007.

Lau G., Zhu R., Lei T., Ng M.Y., Luk J.M.C., Sham P., Chiu J.F. and He Q.Y., Identification of biomarkers for the prediction of HBV related HCC by integrated proteomics, Hepatology International. 2007, 1(1): 75.

Lau G., Importance of immune system in HBV infection: from bench to clinic. From basic to translational immunology,, In: Lau GK., 9th Federation of Immunological Societies of Asia-Oceania 2007. 84-5.

Lau G., Importance of immune system in HBV infection: from bench to clinic, Symposium & Workshop on innate & Adaptive immunity in HBV & HCV Infection (5th-6th February, 2007, South Korea). 2007.

Lau G., Lu L., Sun R.W.Y., Hui C.K., Chen R., Luk J.M. and Che C.M., In Vitro Anti-hepatitis B Virus Activities and Mechanism of Silver Nanoparticles., Hep Intl 2007. 242: 14.

Lau G., Zhang H.Y., Li J., Hui C.K., Cheung K.F., Yeung K. and Lu L., Inhibition of Viral Replication With Pegylated Interferon ALFA – 2A Increases IL-17 In Chronic Hepatitis B, Hepatology 2007. 46(4): 934.

Lau G., Longitudinal analysis of Cytokine and chemokine profiles in patients with HBeAg-positive CHB under different therapy regimens. , In: Naoumov NV, Hui CK, Chen JJ, Cooksley H, Lau GKK*. , Hep Intl 2007. 242: 13.

Lau G., Medical Progress, Editorial Board, 2007.

Lau G., New Hepatitis B Vaccination, Inaugural Ceremony of SciGen Vaccine Manufacturing Facility (7th -10th January, 2007, Israel). 2007.

Lau G., Plenary lecture: Chronic Hepatitis Treatment, 2006 Hepato Gastroenterology Congress National Viral Hepatitis Congress (2-6 Sep 2006 Antalya, Turkey). 2006.

Lau G., Plenary lecture: Management of non responder patients with chronic HCV, XIX Congress of the Latinamerican Association for the Liver Study (ALEH) and XIV COngress of Argentine association for the Study of Liver Diseases. 2006.

Lau G., Plenary lecture: Natural history of HBV Infection, International Meeting on Viral Hepatitis (7th -8th Sept, 2006 Barcelona, Spain). 2006.

Lau G., PreS/S hepatitis B Vaccination with Sci B Vac adn means to By[ass Non-response to Conventional Immunization Against Hepatitis B, 17th Asian Pacific Association for the Study of Liver (27th -30th March, 2007, Kyoto, Japan). 2007.

Lau G., Zhang H.Y., Hui C.K., Lee N.P., Chan W., Yeung Y.H., Leung K.W., Lu L., Leung N., Lo C.M. and Fan S.T., Serum adiponectin is increased in advancing liver fibrosis and decline with reduction in fibrosis in chronic hepatitis B. , Hep Intl . 2007, 242: 7.

Lau G., Hui C.K., Leung N., Shek T.W., Yao H., Lee W.K., Lam P., Lai J.Y., Wong W.M., Lai L.S.W. and Poon R.T.P., Sustained disease remission after spontaneous HBeAg seroconversion is associated with reduction in fibrosis progression in Chronic Hepatitis B Chinese patients., Hep Intl 2007. 242: 5.

Lau G., The Importance of Immune Conttrol in CHB: Delivering Durable Response Without Resistance, 17th Asian Pacific Association for the Study of Liver (27th -30th March, 2007, Kyoto, Japan). 2007.

Lau G., The use of transient elastography as a preoperative assessment of hepatic resection., In: Lai L, Hui CK, Poon RTP, Shek T, Lai ST, Lai JY, Lo CM, Fan ST, Leung N, Lau GKK*., Hep Intl 2007. 242: 51.

Lau G., There is still a role of interferon in treatment of HBeAg-negative diseases. , In: Lau GK., APASL single topic meeting on HBV 2007 (in press). 2007.

Lau G., Cheung K.F., Yang Z.F., Hui C.K., Lu L., Zhang H.Y., Poon R.T.P., Tong Y. and Liu P., Traditional Chinese Medicine 319 Recipe Attenuates Liver Fibrosis. , Hep Intl 2007; . 2007, 242:209.

Lau G., Treatment of Hepatitis B e Antigen Positive Disease, 12th International Symposium on viral hepatitis and liver disease (1th - 5th July Paris, France). 2006.

Lau G. and Hui C.K., Treatment of chronic hepatitis b with Pegylated interferon alfa-2a, nucleos(t)ide analogs or both. , Falk Symposium. 2007, 157.

Lau G. and Hui C.K., Why treat patients with HBeAg-positive chronic hepatitis B with Pegylated Interferon? pegylated interferon?, Management of patients with viral hepatitis. 2007, 221-233.

Lee P.Y., Cheung N., Lam B.Y.H., Sham P., Lau G., Fan S.T., Luk J.M.C. and Luk J.M.C., Proteomics of mouse liver from embryo to adult: a lesion for HCC (Abstract), The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007. Hepatology International. 2007, 1(1): 21.

Lo C.M., Lau G., Chan S.C., Fan S.T. and Wong J., Efficacy of a pre-S containing vaccine in patients receiving lamivudine prophylaxis after liver transplantation for chronic hepatitis B, American Journal of Transplantation. 2007, 7(2): 434-439.

Lu L., Sun R.W.Y., Hui C.K., Chen R., Luk J.M.C., Che C.M. and Lau G., In Vitro Anti-hepatitis B Virus Activities and Mechanism of Silver Nanoparticles,The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007, Hepatology International. 2007, 242: 14.

Lu L., Sun R.W.Y., Hui C.K., Chen R., Luk J.M.C., Che C.M. and Lau G., Size-dependent anti-hepatic B virus activities and mechanism of silver nanoparticles, The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007.

Lu L., Sun R.W.Y., Hui C.K., Chen R., Luk J.M.C., Che C.M. and Lau G., Size-dependent anti-hepatitis B virus activities and mechanism of silver nanoparticles (Abstract), Hepatology International. 2007, 1(1): 14.

Luk J.M.C., Zhang Q.S., Lee P.Y., Wo Y.H., Leung P.L., Liu L.X., Hu M.Y., Cheung K.F., Hui C.K., Lau G. and Fan S.T., Hepatic stellate cell-targeted delivery of M6P-HSA-glycyrrhetinic acid attenuates hepatic fibrogenesis in a bile duct ligation rat model, Liver International. 2007, 27(4): 548-557.

Luk J.M.C., Yi X., Lee P.Y., Guan X.Y., Lau G. and Fan S.T., Mortalin-2 is an accurate prognostic biomarker for early recurrence of liver carcinoma (Abstract), The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007. Hepatology International. 2007, 1(1): 68.

Luo Y., Lo C.M., Cheung C.K.Y., Lau G., Fan S.T. and Wong J., Identification of hepatitis B virus-specific lymphocytes in human liver grafts from HBV-immune donors, Liver Transplantation. 2007, 13(1): 71-79.

Marcellin P., Bonino F., Lau G., Farci P., Yurdaydin C., Piratvisuth T., Luo K., Gurel S., Hadzyiannis S., Wang Y. and Popescu M., Suppression of HBV DNA in patients with HBeAg negative CHB treated with peginterferon alfa-2A (40KD) ±lamivudine: 2 year follow-up results, The Liver Meeting of The American Association for the Study of Liver, Hepatology. 2006, 44: 550A.

Naoumov N.V., Hui C.K., Chen J.J., Cooksley H. and Lau G., Longitudinal analysis of Cytokine and chemokine profiles in patients with HBeAg-positive CHB udner difference therapy regimens, The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007, Hepatology International. 2007, 242: 130.

Piratvisuth T., Lau G., Farci P., Yurdaydin C., Luo K., Hadzyannis S., Wang Y., Wu J., Popescu M. and Marcellin P., Durability of virological response at 3 years: Peginterferon Alfa-2a (40KD) for HBeAg-negative CHB, The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007, Hepatology International. 2007, 242: 18.

Wang X., Luk J.M.C., Garcia-Barcelo M.M., Miao X., Leung P.L., Ho D.W.Y., Cheung S.T., Lam B.Y.H., Cheung C.K.Y., Wong S.Y., Lau S.S.M., So M.T., Yu W.C., Cai Q., Liu K.S.Y., Hui C.K., Lau G., Poon R.T.P., Wong J. and Fan S.T., Liver intestine-cadherin (CDH17) haplotype is associated with increased risk of hepatocellular carcinoma, Clinical Cancer Research. 2006, 12(17): 5248-5252 (corresponding author).

Zhang H., Hui C.K., Lee P.Y., Chan W., Yueng Y.H., Leung K.W., Lu L., Leung N., Lo C.M., Fan S.T., Luk J.M.C., Xu A., Lam K.S.L., Kwong Y.L. and Lau G., Serum adiponectin is increased in advancing liver fibrosis and decline with reduction in fibrosis in chronic hepatitis B, The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007, Hepatology International. 2007, 242: 7.

Zhu R., Lei T., Ng M., Luk J.M.C., Sham P., Chiu J.F. and Lau G., Identification of biomakers for the prediction of hepatitis B related hepatocellular carcinoma by integrated proteomics, The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007, Hepatology International. 2007, 242: 75.

Researcher : Lau GKK

Project Title:	Role of intrahepatic close-circular covalent (ccc) DNA in HBV reactivation in hepatitis B surface antigen positive subjects who received chemotherapy
Investigator(s):	Lau G, Liang RHS, He ML
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Applied Research
Start Date:	11/2002

Abstract:

To study the T cell determinants of liver damages during the immune-clearance phase of chronic HBV infection.

Project Title:	Characterization of the HBV-specific cytotoxic T lymphocyte (CTL) activities associated with a sustained remission after anti-HBV therapy in Chinese with chronic HBV infection
Investigator(s):	Lau G, Lin CL, Zhang H
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2004

Abstract:

Project Title:	Prevalence and Natural History of Non-Alcoholic Fatty Liver Diseases in Hong Kong Chinese
Investigator(s):	Lau G
Department:	Medicine
Source(s) of Funding:	Hong Kong Liver Foundation - General Award
Start Date:	02/2005

Abstract:

To define teh prevalence of non-alcoholic fatty liver diseases (NAFLD) in Hong Kong Chinese; to charaterize the natural history of NAFLD in patients with and without chronic HBV infection.

Project Title:	Role of upregulation of toll-like receptor 7 and functional polymorphisms within the toll-like receptor 7 gene in inducing sustained disease remission in chronic hepatitis B infection
Investigator(s):	Lau G, Hui CK, Luk JMC, Sham PC
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	10/2006

Abstract:

List of Research Outputs

Lau G.K.K., Chan Y.H., Yiu K.H., Li S.W., Tam S., Lau C.P., Kwong Y.L. and Tse H.F., Burden of carotid atherosclerosis in patients with stroke: relationships with circulating endothelial progenitor cells and hypertension, Journal of human hypertension. 2007, 21(6): 445-451.

Researcher : Lau GKK

List of Research Outputs

Researcher : Lau HL

List of Research Outputs

Lau H.L., Ng M.Y.M., Cheung W.M.W., Paterson A.D., Luk K.D.K., Chan V.N.Y. and Kung A.W.C., Assessment of linkage and association of 13 genetic loci with bone mineral density, J Bone Miner Metab. 2006, 24: 226-34.

Researcher : Lau KK

List of Research Outputs

Lu L., Sun R.W.Y., Hui C.K., Chen R., Luk J.M.C., Che C.M. and Lau K.K., In Vitro Anti-hepatitis B Virus Activities and Mechanism of Metal-based Nanoparticles , Hepatology . 2006, 44 (Suppl.1): 553A.

Researcher : Lau WCS

Project Title:	Prospective study of the clinical pattern of systemic lupus erythematosus in Hong Kong
Investigator(s):	Lau WCS
Department:	Medicine
Source(s) of Funding:	Other Funding Scheme
Start Date:	01/1993

Abstract:

To study the clinical pattern of systemic lupus erythematosus in Hong Kong.

Project Title:	Effects of sex hormones on lymphocyte function in systemic lupus erythematosus
Investigator(s):	Lau WCS, Mok TMY
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2002

Abstract:

To examine the effects of estrogen, testrogen, testosterone and prolactin on SLE peripheral T- and B-lymphocyte apoptosis and function. Menstruating and postmenopausal female patients and male patients will be studied.

Project Title:	A study to evaluate the immunopathology of Severe Acute Respiratory Syndrome
Investigator(s):	Lau WCS, Chan EYT, Cheung BMY
Department:	Medicine
Source(s) of Funding:	VCO SARS Research Fund
Start Date:	07/2003

Abstract:

To investigate the time course of changes in cytokines in patients with SARS; to investigate the relationship between clinical deterioration and changes in the serum/plasma levels of cytokines; to evaluate the cytokine expression in post-mortem lung tissues of patients with SARS will be studied.

Project Title:	Evaluation of the effects of sex hormones on neutrophils and macrophage apoptosis and macrophage phagocytic clearance of apoptotic neutrophils in systemic lupus erythematosus
Investigator(s):	Lau WCS
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003

Abstract:

To study the effects of oestrogen and progesterone on the rate of apoptosis and secondary necrosis of PMN and M[phi] in SLE patients and controls; to study the effects of oestrogen and progesterone on the ability of phagocytic M[phi] to clear apoptotic bodies in patients with SLE and controls.

Project Title:	Complement deficiency and dendritic cell function in the pathogenesis of systemic lupus erythematosus
Investigator(s):	Lau WCS
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	10/2004

Abstract:

To determine their phenotypic expression i.e. stage of maturity; to study their functional activity through intracellular cytokine detection; to study their capability to phagocytose apoptotic cells and their subsequent functional changes; to evaluate the effects of various complement factors including C1q, C2, C3, C4 and mannose binding lectin on their uptake of apoptotic cells; to determine their interactions with T-cells following ingestion of apoptotic cells and to delineate the subsequent changes in T-cell activity through intracellular cytokine detection.

Project Title:	Dendritic cell function and their effects on B cell activation in systemic lupus erythematosus
Investigator(s):	Lau WCS
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	12/2005

Abstract:

Disturbances in the process of apoptosis and the clearance of apoptotic cells, a major source of auto-antigens, have been suggested as the fundamental pathoaetiological mechanism of systemic lupus erythematosus (SLE) which is characterised by T and B cell activation. Excess apoptotic cells may be captured by dendritic cells (DCs) which may then undergo functional changes and influence the activity of other immune cells, particularly T cells. Previous studies on DCs in SLE have yielded conflicting results with some demonstrating a deficiency in DC function, particularly CD11c+ cells, while others showing SLE serum was capable of inducing DC differentiation and presentation of dying cells to CD4+ T cells. These discrepancies are probably related to the fact that (1) peripheral blood DCs exist in different subtypes with different roles in immune regulation; and (2) previous studies have generally generated DCs from peripheral blood mononuclear cells (PBMCs) cultured with granulocyte-macrophage colony-stimulating factor and interleukin-4, and stimulation with lipopolysaccharide. DCs generated and isolated by this method are not representative of circulating DCs. We now know that there are two main subtypes of peripheral blood DCs - plasmacytoid DCs (pDCs) and myeloid DCs (mDCs). pDCs are characterised by cell surface expression of CD4+, Lin-, CD11C-, CD123bright, CD45RA+, CD2- and BDCA-2+1, while mDCs have cell surface expression of CD4+, CD11cbright, CD123dim, CD45RO+ and CD2+. It is now possible to isolate pDCs and mDCs by positive selection. In one of our recent studies, we showed that mDCs were responsible for the maintenance of immune homoestasis by inducing Th-1 cytokine response, and pDCs in the induction of tolerance in healthy subjects. The number and functional activities of these 2 types of DCs appeared to be altered in SLE. SLE blood had a lower % of mDCs and higher % of pDCs of PBMCs, and SLE mDCs had lower surface CD83 expression when compared with controls. Unlike in healthy subjects, mDCs from SLE patients were less able to present non-self antigens to autologous T cells. On the other hand, SLE pDCs were capable of stimulating T cells in SLE. These results suggest that SLE pDCs have increased activity and this may contribute to the development of autoimmunity in this condition.Recent investigations have also shown DCs may directly interact with B cells in healthy subjects. However, this has not been studied in SLE. The primary objective of this investigation is to evaluate if DCs are capable of interacting directly with B-cells in the absence of T-cells in patients with SLE.

List of Research Outputs

Fan R., Mok T.M.Y. and Lau W.C.S., Cost of Mild Systemic Lupus Erythematosus in Hong Kong, The American College of Rhematology Annual Scientific Meeting 10-15 Nov 2006, Washington, DC USA. 2006, 54(9) Supplement: Abstract No.1198.

Ho S., Yang W., Lau W.C.S., Chen T.M., Wong W.S. and Lau Y.L., Polymorphisms of Tumour Suppressor P53 Gene with Systemic Lupus Erythematosus in Hong Kong Chinese Patients, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006. 79.

Ho Y.W., Yeung J.S., Chiu P.K., Tang W.M., Lin Z.B. and Lau W.C.S., Ganoderma lucidum polysaccharide peptide reduced the production of proinflammatory cytokines in activated rheumatoid synovial fibroblast, Journal of Molecular and Cellular Biochemistry. 2007, 301(1-2): 173-179.

Jin O., Kavikondala S., Chan W.K., Rong F., Yeung J.S.L., Mok T.M.Y. and Lau W.C.S., Abnormal Plasmacytoid Dendritic Cell Activity in Systemic Lupus Erythematosus, The American College of Rheumatology Annual Scientific Meeting 10-15 Nov 2006, Washington, DC USA 2006. 54(9) Supplement: Abstract No.1095.

Jin O., Kavikondala S., Chan W.K., Rong F., Yeung J.S.L., Mok T.M.Y. and Lau W.C.S., Functional Abnormalities of Myeloid Dendritic Cells in Systemic Lupus Erythematosus, The American College of Rheumatology Annual Scientific Meeting 10-15 Nov 2006, Washington, DC USA. 2006, 54(9) Supplement: Abstract No.1096.

Kavikondala S., Jin O., Chan W.K., Yeung J.S.L., Rong F., Mok T.M.Y. and Lau W.C.S., Dendritic Cells (DCs): Culprits of B-cell Hyper-responsiveness in Lupus, The American College of Rheumatology Annual Scientific Meeting 10-15 Nov 2006, Washington, DC USA. 2006, 54(9) Supplement: Abstract No. 1075.

Kavikondala S., Nie Y. and Lau W.C.S., Report on the Second Asia Autoimmunity Forum 3-5 March 2006, Hong Kong, Autoimmunity Reviews. Amsterdam, New York: Elsevier, c2002, 2006, 6(2): 115-118.

Kong K.P., Chong W.P., Wong W.H.S., Lau W.C.S., Chan T.M., Ng P.K.M., Song Y., Mak W.W. and Lau Y.L., p21 gene polymorphisms in systemic lupus erythematosus, Rheumatology. Oxford University Press, 2006, doi:10.1093/rheumatology/kel210: 1-7.

Lau W.C.S., Collateral Benefits of Fish Oil Therapy for Rheumatoid Arthritis, J. Rheumatology. 2006, 33(10): 1931-1933.

Lau W.C.S., Yin G. and Mok T.M.Y., Ethnic and Geographical Differences in Systemic Lupus Erythematosus: An Overview, Lupus. England, SAGE Publications, 2006, 15(11): 715-719.

Lau W.C.S., Kim H.Y. and Nishioka K., Rheumatology in the Asia Pacific Region - Opportunities and Challenges, Nature Clinical Practice. Rheumatology. New York, New York, NY: Nature Pub. Group, c2005, 2007, 3(3): 119.

Lau W.C.S. and Feng P.H., Rheumatology without Borders (Editorial), Nature Clinical Practice. Rhematology. New York, New York, NY: Nature Pub. Group, c2005-, 2007, 3(6): 305.

Mak A., Cheung B.M.Y., Mok C.C., Leung R. and Lau W.C.S., Adrenomedullin - A Potential Disease Activity Marker and Suppressor of Nephritis Activity in Systemic Lupus Erythematosus, Rheumatology (Oxford, England). England, Oxford University Press, 2006, 45(10): 1266-1272.

Mok T.M.Y., Tsang P.L., Lo Y., Wong R.W.S., Lau W.C.S. and Lam Y.M., Bosentan Use in Systemic Lupus Erythematosus Patients with Pulmonary Arterial Hypertension, Lupus. England, SAGE, 2007, 16(4): 279-285.

Mok T.M.Y., Chan E.Y.T., Wong R.W.S. and Lau W.C.S., Intrathecal Immunoglobulin Production in Patients with Systemic Lupus Erythematosus with Neuropsychiatric Manifestations, Annals of Rheumatic Diseases. 2007, 66: 846-847.

Mok T.M.Y., Ip E.W.K., Lau W.C.S., Lo Y., Wong W.H.S. and Lau Y.L., Mannose-binding lectin and susceptibility to Infection in Chinese patients with systemic lupus erythematosus, Journal of Rheumatology. 2007, 34: 1270-6.

Mok T.M.Y., Wong S.S.Y., Chan D.T.M., Fong D.Y.T., Wong R.W.S. and Lau W.C.S., Non-tuberculous mycobacterial infection in patients with systemic lupus erythematosus, Rheumatology. Switzerland, Karger, 2007, 46(2): 280-284.

Mok T.M.Y., Wong S.S.Y., Chan D.T.M., Fong D.Y., Wong R.W.S. and Lau W.C.S., Non-tuberculous mycobacterial infection in patients with systemic lupus erythematosus, Rheumatology (Oxford). 2007, 46: 280-284.

Rong F., Jin O., Kavikondala S., Chan W.K., Yeung J.S.L., Mok T.M.Y. and Lau W.C.S., Plasmacytoid-Dendritic Cell Induced T Cell Proliferation and Activation: A Potential Role in the Pathogenesis of Rheumatoid Arthritis, The American College of Rheumatology Annual Scientific Meeting 10-15 Nov 2006, Washington, DC USA. 2006, 54(9) Supplement: Abstract No.424.

Sun L.Y., Zhou K.X., Feng X.B., Zhang H.Y., Ding X.Q., Jin O., Lu L., Lau W.C.S., Hou Y.Y. and Fan L.M., Abnormal surface markers expression on bone marrow CD34⁺cells and correlation with disease activity in patients with systemic lupus erythematosus, Clin Rheumatol. 2007, [Epub ahead of print].

Zhang J.X., Woo J., Lau W.C.S., Lee P.W.H., Chiu P.K.Y. and Lam D., Effects of use of alternative therapies on quality of life and healthcare spending, The American Journal of Chinese Medicine. 2007, 35: 183-193.

Researcher : Lau YK

List of Research Outputs

Chan A.O.O., Jim M.H., Lam K.F., Siu D.C.W., Tong S.M., Ng F.H., Wong S.Y., Hui W.M., Chan C.K., Lai K.C., Cheung T.K., Chan P., Wong G., Yuen R.M.F., Lau Y.K., Lee S.W.L., Seto M.L., Lam S.K. and Wong B.C.Y., Patients with coronary artery disease had high prevalanece of colorectal cancer and adenoma: END-results of metabolic syndrome and smoking. Digestive Disease Week 2007, Washington DEc, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A65.

Chan A.O.O., Ng F.H., Chang P.C.M., Wong S.Y., Chu W.M., Yuen W.C., Lau Y.K., Cheung T.K. and Wong B.C.Y., Prevalence and prediction of gastrointestinal events in patients receiving a combination of aspirin plus clopidogrel. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A135.

Researcher : Law KW

List of Research Outputs

Mak J.C.W., Ho S.P., Leung C.M., Cheung A.H.K., Law K.W., Ip M.S.M. and Chan M.M.W., Relationship between glutathione S-transferase gene polymorphisms and enzyme activity in Hong Kong Chinese asthmatics, American Thoracic Society International Conference, San Francisco, USA. American Journal of Respiratory and Critical Care Medicine. 2007, 175: A461.

Mak J.C.W., Ho S.P., Leung C.M., Cheung A.H.K., Law K.W., So L.K.Y., Chan W.M., Chau C.H., Lam W.K., Ip M.S.M. and Chan W.M., Relationship between glutathione S-transferase gene polymorphisms and enzyme activity in Hong Kong Chinese asthmatics, Clinical and experimental allergy. 2007, 37: 1150-1157.

Researcher : Lee CP

List of Research Outputs

Leung K.Y., Liao C., Li Q.M., Tang M.H.Y., Lee C.P., Lam Y.H. and Chan V.N.Y., A Non-invasive Approach To Prenatal Diagnosis Of Homozygous a^o Thalassemia, XVIII FIGO World Congress of Gnecology and Obstetrics in Kuala Lupmur, Malaysia, 5-10th November 2006.

Researcher : Lee KLF

List of Research Outputs

Lee K.L.F., Burns J., Mullen T., Hettrick D., Tse H.F. and Lau C.P., Avoidance of right ventricular pacing in cardiac resynchronization therapy improves right ventricular hemodynamics in heart failure patients, J Cardiovas Electrophysiol. 2007, 18(5): 497-504.

Siu C.W.D., Tse H.F., Lee K.L.F., Chan R.H.W., Chen W.H., Yung C., Lee S.W.L. and Lau C.P., Cardiac resynchronization therapy optimization by ultrasonic cardiac output monitoring (USCOM) device, Pacing Clin Electrophysiology. 2007, 30: 50-55.

Yiu K.H., Siu C.W.D., Lee K.L.F., Lau C.P., Lee S.W.L., Fong D.Y.T. and Tse H.F., Emerging trends of community acquired infective endocarditis. , Int Cardiol J . 2006, 121(1): 119-22.

Yiu K.H., Siu C.W., Lau C.P., Lee K.L.F. and Tse H.F., Transvenous catheter-based microwave ablation for atrial flutter., Heart Rhythm. 2007 . 2007, 4(2): 221-3.

Researcher : Lee SWL

List of Research Outputs

Chan A.O.O., Jim M.H., Lam K.F., Siu D.C.W., Tong S.M., Ng F.H., Wong S.Y., Hui W.M., Chan C.K., Lai K.C., Cheung T.K., Chan P., Wong G., Yuen R.M.F., Lau Y.K., Lee S.W.L., Seto M.L., Lam S.K. and Wong B.C.Y., Patients with coronary artery disease had high prevalanece of colorectal cancer and adenoma: END-results of metabolic syndrome and smoking. Digestive Disease Week 2007, Washington DEc, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A65.

Ho H.H., Siu C.W.D., Jim M.H., Miu K.M., Chan R.H.W., Lee S.W.L., Lau C.P. and Tse H.F., Leukocytosis and clinical outcomes in acute inferior myocardial infarction, Int J Cardiol. 2006, 118(2): 278-9.

Jim M.H., Siu C.W., Lee S.W.L., Chan A.O. and Lau C.P., Prognostic implications of PR-segment depression in inferior leads in acute inferior myocardial infarction. , Clin Cardiol. 2006, 8: 363-8.

Siu C.W.D., Tse H.F., Lee K.L.F., Chan R.H.W., Chen W.H., Yung C., Lee S.W.L. and Lau C.P., Cardiac resynchronization therapy optimization by ultrasonic cardiac output monitoring (USCOM) device, Pacing Clin Electrophysiology. 2007, 30: 50-55.

Yiu K.H., Siu C.W.D., Lee K.L.F., Lau C.P., Lee S.W.L., Fong D.Y.T. and Tse H.F., Emerging trends of community acquired infective endocarditis. , Int Cardiol J . 2006, 121(1): 119-22.

Researcher : Leung AYH

Project Title:	Ex-vivo expansion of haematopoietic stem cells derived from human umbilical blood with special reference to the effects of all-trans retinoic acid (ATRA)
Investigator(s):	Leung AYH, Liang RHS
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003
Completion Date:	02/2007

Abstract:

To investigate if ATRA can stimulate expansion of primitive HSC in-vitro, characterized by an increase in scid repopulation; to see if the effects of ATRA are dependent on the presence of stromal feeders; to study the molecular mechnaisms underlying the effects of ATRA on haematopoietic stem/progenitor cells.

Project Title:	A study of normal and deregulated haematopoiesis in zebrafish, with special reference to the role of BMP signaling in haematopoietic stem cell proliferation
Investigator(s):	Leung AYH, Liang RHS, Kung H
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	07/2004

Abstract:

To characterize the cellular features of expanded haematopoietic cells, i.e. do they contain HSC or lineage-committed progenitors or do they contain both? to understand the key signal(s) that drive(s) haematopoietic cell proliferation in the developing embryos in relation to a heightened BMP signaling due to reduced antagonism by chordin.

Project Title:	Function of survivin during embryonichemoatopoiesis and vascular formation in a zebrafish model
Investigator(s):	Leung AYH
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004
Completion Date:	10/2006

Abstract:

To characterize the spatial and temporal expression of survivin in normal zebrafish embryos: is survivin expressed exclusively in hematopoietic or vascular tissues or is it expressed in both tissues? To investigate the effects of survivin knock-down in wild-type zebrafish embryos using anti-sense morpholino and dominant negative survivin mRNA injection: what would be the effect(s) on primitive hematopoiesis, vasculogenesis and angiogenesis?

Project Title:	The roles of survivin in hematopoiesis, angiogenesis and tumorigenesis in a zebrafish knock-down and transgenic model
Investigator(s):	Leung AYH, Wong BCY
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	07/2006

Abstract:

(1) To study the role of survivin in primitive hematopoiesis and angiogenesis (i) Effects of survivin knock-down on hematopoiesis and angiogenesis (ii) Mechanism of action with reference to anti-apoptotic function (iii) To prove the specificity of survivin knock-down phenotype (iv) To distinguish cell autonomous (or non cell autonomous) function of survivin (2) To over-express survivin in hematopoietic cells to investigate the anti-apoptotic and leukemic potential of survivin over-expression (i) Transient expression of survivin in zebrafish embryos (ii) Generation of stable transgenic fish-line over-expressing survivin

Project Title:	Establish a blood cancer model of polycythemia vera in zebrafish to facilitate drug screening targeting at Jak2 activation
Investigator(s):	Leung AYH, Liang RHS
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Applied Research
Start Date:	11/2006

Abstract:

Human polycythemia vera and Janus Kinase 2 (Jak2) In human polycythemia vera (PV), a clonal disorder arising from hematopoietic stem cells in the bone marrow, there is abnormal increase in red cell production, resulting in thrombosis and bleeding which are common causes of morbidity and mortality in this group of patients. Recent studies showed that more than 90% patients with PV carry a gain-of-function mutation at the JH2 pseudokinase domain of the Janus kinase 2 gene (Jak2) in which valine is substituted with phenylalanine (V216F). Jak2 is a member of cytosolic tyrosine kinase that mediates the signal transduction of various cytokines and Jak2V617F can induces cytokine hypersensitivity in cell lines and erythrocytosis in mice. The V617F mutation is also identified from myelofibrosis, essential thrombocythemia as well as leukemia of myeloid lineage suggesting that constitutively active Jak2 kinase may also play a role in the pathogenesis of these disorders. The role of Jak2 during normal hematopoiesis is presently unclear but mice carrying null mutation of Jak2 are embryonic lethal due to defective embryonic hematopoiesis. Zebrafish as a model of blood development and cancer research Zebrafish has recently emerged as a model organism of embryonic blood development and cancer research. The embryos are optically transparent and embryonic blood formation can be visualized under microscopy in the first 48 hours post-fertilization (hpf). The genetic mechanisms regulating these processes as well as the blood lineage development are conserved between zebrafish and the mammalian system. The organisms have also become a model of cancer research and they can be induced to develop different cancers that are histologically similar to those of human. A comparison of human and zebrafish genome sequences have also demonstrated the conservation of genes encoding for cell-cycle, tumor suppressors and oncogenes. More importantly, the organisms are amendable to genetic manipulation. Recently, over-expression of c-myc, an oncogene implicated in human lymphoma, has been shown to induce lymphoid leukemia in zebrafish, highlighting the feasibility of inducing cancers in this organism in a tissue-specific fashion. The small size of zebrafish, its fecundity as well as the ease of maintenance have also made it a unique model for whole-organism chemical screening. Jak2a function in zebrafish We have previously shown that zebrafish Jak2a gene (a homologue of human Jak2) is significantly up-regulated in the chordin mutant in which the intermediate cell mass (ICM, site of hematopoiesis in zebrafish embryos) is expanded. We have knocked-down Jak2a gene in zebrafish embryos using morpholino targeting at the 5’-UTR (untranslated region) of the gene and showed that it reduced primitive hematopoiesis. The effect was specific and angiogenesis was not perturbed. Moreover, the expansion of ICM in the chordin mutant was also reduced. The results have been confirmed using a splice-site morpholino and a soluble inhibitor of the Jak2. These data suggested that zebrafish Jak2a gene, like its mammalian counterparts, is important for the regulation of hematopoiesis under basal as well as stimulated conditions. Key issues The genotype-phenotype correlation of Jak2V617F in human blood cancers as well as the effects of Jak2a knock-down on zebrafish blood formation have provided us with ground for creating a blood cancer model based on Jak2V617F over-expression in zebrafish blood cells. Similar approach has been used successfully to induce blood cancers in zebrafish related to c-Myc and bcl-2. On the other hand, murine bone marrow transduced with human Jak2V617F using retrovirus has also been shown to induce erythrocytosis. Based on these background data, the model of Jak2V617F over-expression in zebrafish embryos should be feasible and will have significant impact to our understanding of Jak2 related cancers as well as the design of better therapeutic agent for these diseases. Objectives of research proposal Specifically, we will focus on the following objectives: 1.To establish a transient expression model in which human Jak2V617F will be over-expressed in zebrafish embryos. 2.To develop a transgenic zebrafish line in which human Jak2V617F is over-expressed under gata1 promoter influence. These models will enable us to address the following issues: 1.The signaling pathways in the pathogenesis of Jak2V617F related blood cancers in human; 2.Provide a high throughput model for the screening of chemical agents which will be useful clinically for the treatment of Jak2V617F related blood cancers.

Project Title:	The roles of Jak2a in primitive hematopoiesis during embryonic development using zebrafish as a model
Investigator(s):	Leung AYH
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2007

Abstract:

1. Background: a. The Janus kinase 2 (Jak2) The Janus kinase/signal transducers and activation of transcription (JAK/STAT) cascade is a ubiquitous signal transduction in responses to extracellular ligands. The Jak family consists of four members in mammals (Jak1-3, Tyk2). In particular, Jak2 has been shown to transduce signals of various hematopoietic cytokines, including erythropoietin, thrombopoietin, granulocyte/macrophage colony-stimulating-factor and interleukin-3. b. Embryonic hematopoiesis occurs in distinct waves – primitive and definitive During embryonic development, hematopoiesis occurs in two successive waves known as primitive and definitive hematopoiesis. The former is primarily erythroid in lineage and is transitory whereas the latter is multi-lineages and persists throughout life. In mammals, primitive hematopoiesis occurs in the extra-embryonic yolk-sac. Definitive hematopoiesis is initiated in the aorto-gonado-mesonephros followed by fetal liver and spleen and eventually the bone marrow (BM). In zebrafish, primitive hematopoiesis occurs in an intra-embryonic structure known as the intermediate cell mass (ICM) whereas definitive hematopoiesis arises from the ventral wall of dorsal aorta and thence the kidney in which it continues throughout life. c. The role of Jak2 in primitive hematopoiesis is presently unclear The role of Jak2 in primitive hematopoiesis is presently unclear. In mice, the intra-utero development of embryos has hampered serial monitoring and detailed mechanistic studies of this process. Although homozygous Jak2null mice showed defective definitive hematopoiesis in the fetal liver, its effects on yolk-sac primitive hematopoiesis, which are under distinctive spatial and temporal regulations, have not been elucidated. d. Gene duplication of Jak2 in zebrafish facilitates study of specific gene function In zebrafish, Jak2 undergoes duplication: Jak2a is expressed predominantly in the ICM whereas Jak2b was expressed primarily in the developing eyes and nephric ducts. Such partitioning of gene functions into Jak2a and Jak2b may allow access to more restricted phenotypes that may not be apparent in the mouse model. In fact, Jak2a expression was disrupted in both zebrafish cloche and spadetail mutants (in which specification of hemangioblasts and early hematopoietic progenitors were defective) but functional studies of Jak2a during primitive hematopoiesis are lacking. Our previous study based on microarray showed that Jak2a expression was significantly up-regulated in a zebrafish chordin mutant (characterized by expansion of primitive hematopoiesis in ICM), suggesting that it may play a role in the regulation of primitive hematopoiesis. 2. Preparatory works towards this project: We have analyzed the gene sequence of zebrafish Jak2a and have designed anti-sense morpholinos (MO) targeting at the exon-intron junction of the Jak2a gene. Defective splicing of Jak2a mRNA in the injected embryos has been confirmed by RT-PCR. This MO is non-toxic at 2 ng dose and at 24 hpf, the injected embryos developed normally but blood circulation was significantly reduced, supporting the hypothesis that Jak2a is specifically involved in the regulation of primitive hematopoiesis. 3. Key questions to be addressed: In this proposal, we will investigate the role of Jak2a by a morpholino-based gene knockdown approach and the result should enable us to answer the following questions: 1. Does Jak2a regulate primitive hematopoiesis in zebrafish under basal and stimulated conditions? 2. If so, what are the molecular and cellular mechanisms? 4. Summary Previous studies using murine knock-out models have not delineated the roles of Jak2 during primitive hematopoiesis in yolk-sac as these models were often limited by the intra-utero development and early embryonic lethality which hamper serial and detailed mechanistic studies. The zebrafish embryos provide a unique model in this regard as they are optically transparent and externally fertilized and their early development does not depend critically on a functional circulatory system, permitting detailed study of this hitherto indispensable gene. Furthermore, the duplication of Jak2 into Jak2a and Jak2b in zebrafish with potential “subfunctionalization” may also allow access to more restricted phenotype which may not be noticeable in the murine models. Therefore, this proposal would very likely provide us with important information about the role of Jak2a in the regulation of primitive hematopoiesis during embryonic development.

List of Research Outputs

Chan C.F., Leung A.Y.H., Chan Y.S. and Cheung R.T.F., Intracerebral injection of granulocyte-colony stimulating factor reduces infarct volume following transient middle cerebral artery occlusion in mice, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population. 2007, 57.

Chan C.F., Leung A.Y.H., Chan Y.S. and Cheung R.T.F., Use of granulocyte-colony stimulating factor in a mice stroke model, 11th Research Postgraduate Symposium. 2006, 60.

Cheung M.S., Shek W.K., Shek W.K., Leung J.C.K., Chan Y.Y., Huang H., Kwong Y.L., Liang R.H.S. and Leung A.Y.H., Aldehyde dehydrogenase activity in leukemic blasts defines a subgroup of acute myeloid leukemia with adverse prognosis and superior NOD/SCID engrafting potential, Leukaemia. 2007, 21: 1423-1430.

Cheung M.S., Kwong Y.L., Liang R.H.S. and Leung A.Y.H., Stem cell model of hematopoiesis, C7urrent Stem Cell Research and Therapy. 2006, 1: 305-315.

Cheung W.W., Tse E.W.C., Leung A.Y.H., Yuen K.Y. and Kwong Y.L., Regular virologic surveillance showed very frequent cytomegalovirus reactivation in patients treated with alemtuzumab, Blood. 2007, 82(2): 108-11.

Leung A.Y.H., Chow C.H., Kwok J.S.Y., Lui C.K., Cheng V.C.C., Yuen K.Y., Lie A.K.W. and Liang R.H.S., Safety of vacinating sibling donors with live-attenuated varicella zoster vaccine before hematopoietic stem cell transplantation, Bone Marrow Transplantation. 2007, 39(11): 661-5.

Ma C.H., Liang R.H.S. and Leung A.Y.H., The role of phospholipase C gamma 1(PLC-g1) in primitive hematopoiesis during zebrafish development, Experimental Hematology. 2007, 35: 368-373.

Wong A.S.Y., Chan K.H., Cheng V.C.C., Yuen K.Y., Kwong Y.L. and Leung A.Y.H., Relationship of pretransplantation polyoma BK virus serologic findings and BK viral reactivation after hematopoietic stem cell transplantation, Clinical Infectious Disease. 2007, 44(6): 830-837.

Researcher : Leung CKJ

List of Research Outputs

Leung C.K.J., Pang A.W.K., Yuen W.H., Kwong Y.L. and Tse E.W.C., Relationship of Expression of Aquaglyceroporin 9 with Arsenic Uptake and Sensitivity in Leukemia Cells , Blood . 2007, 109: 740-746.

Researcher : Leung CM

List of Research Outputs

Chan A.O.O., Loo C.K., Leung C.M., Wong S.Y., Ng F.H., Li M.K.W., Lam K.M., Lam S.K. and Wong B.C.Y., Prevalence of colonic lesions after a negative screening colonscopy in a population with rapidly rising colorectal cancer incidence: A prospective multi-center analysis. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A189.

Mak J.C.W., Ko F.W., Chu C.M., Leung C.M., Chan H.W., Cheung A.H.K., Ip M.S.M. and Chan W.M., Polymorphisms in the IL-4, IL-4 receptor alpha chain, TNF-alpha, and lymphotoxin-alpha genes and risk of asthma in Hong Kong Chinese adults, Int Arch Allergy Immunol. 2007, 144: 114-122.

Mak J.C.W., Ho S.P., Leung C.M., Cheung A.H.K., Law K.W., Ip M.S.M. and Chan M.M.W., Relationship between glutathione S-transferase gene polymorphisms and enzyme activity in Hong Kong Chinese asthmatics, American Thoracic Society International Conference, San Francisco, USA. American Journal of Respiratory and Critical Care Medicine. 2007, 175: A461.

Mak J.C.W., Ho S.P., Leung C.M., Cheung A.H.K., Law K.W., So L.K.Y., Chan W.M., Chau C.H., Lam W.K., Ip M.S.M. and Chan W.M., Relationship between glutathione S-transferase gene polymorphisms and enzyme activity in Hong Kong Chinese asthmatics, Clinical and experimental allergy. 2007, 37: 1150-1157.

Researcher : Leung GKL

List of Research Outputs

Chan A.O.O., Hui W.M., Lam K.F., Leung G.K.L., Yuen R.M.F., Lam S.K. and Wong B.C.Y., Familial aggregation in constipated subjects in a tertiary referral center, American Journal of Gastroenterology. Blackwell Publishing, 2007, 102: 149-152.

Chan A.O.O., Lam K.F., Hui W.M., Leung G.K.L., Wong Y.H., Lam S.K. and Wong B.C.Y., Influence of Positive Family History on Clinical Characteristics of Functional Constipation, Clinical Gastroenterology and Hepatology. Elsevier, 2007, 5(2): 197-200.

Chan A.O.O., Hui W.M., Leung G.K.L., Tong T.P.H., Hung I.F.N., Chan P., Hsu A., But D., Wong B.C.Y., Lam S.K. and Lam K.F., Patients with functional constipation do not have increase prevalence of colorectal cancer precursors”, GUT. British Medicial Journal, 2007, 56: 451-452.

Researcher : Leung JCK

Project Title:	Peritoneal membrane dysfunction in continuous ambulatory peritoneal dialysis (CAPD): the role of connective tissue growth factor (CTGF)
Investigator(s):	Leung JCK, Li FK, Lai KN
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2005

Abstract:

To examine the pathophysiological effects of PDFs and their components on peritoneal cells; to understand the mechanism of CTGF expression and its regulation in peritoneal cells; to explore the feasibility of treating peritoneal membrane dysfunction by blocking CTGF.

Project Title:	Is there a reno-protective role of bone morphogenetic protein-7 in IgA nephropathy?
Investigator(s):	Leung JCK, Lai KN
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2006

Abstract:

To examine the renal expression and regulation of BMP-7 and its receptors in human IgAN; to explore the mechanism of BMP-7 in protecting and reversing pIgA-induced renal injury in IgAN.

Project Title:	The role of leptin on peritoneal mesothelial cell under high glucose
Investigator(s):	Leung JCK, Lai KN
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2006

Abstract:

Continuous ambulatory peritoneal dialysis (CAPD) is an important treatment modality of the renal replacement therapy. Unfortunately, the peritoneal membrane frequently exhibits structural and functional changes following long-term dialysis [1]. During CAPD, peritoneal cells are repeatedly exposed to a non-physiological hypertonic environment that may lead to peritoneal fibrosis and, ultimately, ultrafiltration failure [2].Peritoneal adipocytes, previously regarded as of less importance in peritoneal physiology during CAPD, are ubiquitously found in peritoneal tissues. Contrary to the prevailing view that adipose tissues merely function as energy storage depot, there is now compelling evidence suggesting adipocytes can mediate various physiologic processes through secretion of an array of adipokines including leptin, adiponectin, resistin, tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, transforming growth factor-beta (TGF-beta), tissue factors and other growth factors [3, 4]. Adipocytes also express receptors for leptin, insulin growth factor-1 (IGF-1), TNF-alpha, IL-6, TGF-beta that orchestrate a network of autocrine, paracrine and endocrine signals [4]. In parietal peritoneum, adipocytes lie deep underneath the mesothelium and connective tissue. During the fluid dwell in CAPD, solutes in peritoneal dialysis fluid (PDF) are transported by passive diffusion through the peritoneal barrier and come into contact with the adipocytes. In the omentum, adipocytes are in close contact with mesothelial cells. Ultrastructural study reveals that a portion of adipocytes are protruded from the mesothelial surface suggesting that omental adipocytes may be directly exposed to dialysate [5]. In addition, dialysate can also reach the parietal adipose tissue when there is junctional damage or denudation of the mesothelial monolayer. It is therefore logical to postulate that under repeated exposure to PDF and the continuous changes of the physiologic milieu of the peritoneal cavity during CAPD, peritoneal adipocytes will inevitably be "activated". Yet, study on any impact of CAPD on peritoneal adipocytes is scarce.Leptin, an adipocytes-derived 16-kDa hormone, exerts many biological effects through leptin receptor including regulation of food intake, modification of insulin action, induction of angiogenesis and modulation of the immune system [4, 6]. Leptin receptors belong to the class I cytokine family with six spliced isoforms (Ob-Ra to Ob-Rf) [4]. Only the full-length isoform, Ob-Rb, contains the intracellular motifs essential for the Janus kinase-signal transducers and activation (JAK-STAT) signal transduction pathway [4, 7]. Accumulating evidence for systemic effects of leptin on specific tissues and metabolic pathways indicates that leptin operates both directly and indirectly to orchestrate complex pathophysiological processes [6, 8]. Leptin is cleared principally by the kidney and the serum leptin concentration is increased in patients with chronic renal failure or undergoing dialysis [9]. Marked increase in leptin concentration in serum as well as spent peritoneal dialysate has been reported following CAPD treatment [10]. It is now clear that leptin in peritoneal dialysate is derived not only from plasma but also locally from peritoneal adipose tissue. In vitro experiments using murine adipocyte cell line 3T3-L1 showed glucose-based PDFs induce a higher leptin secretion [11]. The present proposal was designed to determine whether functional leptin receptor is expressed by human peritoneal mesothelial cells (HPMC) and if so, the possible implication in CAPD. We set out to determine whether functional leptin receptors are expressed by HPMC and if so, whether these mesothelial leptin receptors could be triggered by leptin to modulate local TGF-beta production.We hypothesize that:a) Exposure of the peritoneum to PDF and its components will increase leptin synthesis by peritoneal adipocytes.b) Leptin, once released from adipocytes, will act on specific leptin receptors on mesothelial cells or adipocytes and trigger TGF-beta production by means of a specific signal transduction pathway.Specific aims:(i) To examine the pathophysiological effects of glucose on leptin synthesis by peritoneal adipocytes.(ii) To understand the mechanism of leptin regulation and its signaling pathways in peritoneal adipocytes under high glucose.References1. Di Paolo N, Sacchi G, De Mia M, Gaggiotti E, Capotondo L, Rossi P, Bernini M, Pucci AM, Ibba L, Sabatelli P, et al.: Morphology of the peritoneal membrane during continuous ambulatory peritoneal dialysis. Nephron 44:204-211, 19862. Rubin J, Herrera GA, Collins D: An autopsy study of the peritoneal cavity from patients on continuous ambulatory peritoneal dialysis. Am J Kidney Dis 18:97-102, 19913. Friedman JM: Obesity in the new millennium. Nature 404:632-634, 20004. Myers MG, Jr.: Leptin receptor signaling and the regulation of mammalian physiology. Recent Prog Horm Res 59:287-304, 20045. Di Paolo N, Sacchi G: Atlas of peritoneal histology. Perit Dial Int 20 Suppl 3:S5-96, 20006. Pond CM: Adipose tissue and the immune system. Prostaglandins Leukot Essent Fatty Acids 73:17-30, 20057. Ahima RS, Osei SY: Leptin signaling. Physiol Behav 81:223-241, 20048. Fruhbeck G, Gomez-Ambrosi J, Muruzabal FJ, Burrell MA: The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. Am J Physiol Endocrinol Metab 280:E827-847, 20019. Wolf G, Chen S, Han DC, Ziyadeh FN: Leptin and renal disease. Am J Kidney Dis 39:1-11, 200210. Tsujimoto Y, Shoji T, Tabata T, Morita A, Emoto M, Nishizawa Y, Morii H: Leptin in peritoneal dialysate from continuous ambulatory peritoneal dialysis patients. Am J Kidney Dis 34:832-838, 199911. Teta D, Tedjani A, Burnier M, Bevington A, Brown J, Harris K: Glucose-containing peritoneal dialysis fluids regulate leptin secretion from 3T3-L1 adipocytes. Nephrol Dial Transplant 20:1329-1335, 2005

List of Research Outputs

Chan H.H.L., Yang C., Leung J.C.K., Wei W.I. and Lai K.N., An Animal Study of the Effects on p16 and PCNA Expression of Repeated Treatment with High-Energy Laser and Intense Pulsed Light Exposure, Lasers in Surgery and Medicine. 2007, 39: 8-13.

Cheung M.S., Shek W.K., Shek W.K., Leung J.C.K., Chan Y.Y., Huang H., Kwong Y.L., Liang R.H.S. and Leung A.Y.H., Aldehyde dehydrogenase activity in leukemic blasts defines a subgroup of acute myeloid leukemia with adverse prognosis and superior NOD/SCID engrafting potential, Leukaemia. 2007, 21: 1423-1430.

Guo H., Leung J.C.K., Lam M.F., Lan H.Y. and Lai K.N., Smad7 transgene attenuates TGF-b induced peritoneal fibrosis in uremic rats on peritoneal dialysis, Journal of American Society of Nephrology. 2006, 17: 29A.

Lai K.N., Leung J.C.K., Chan L.Y., Guo H. and Tang S.C.W., Interaction between proximal tubular epithelial cells and infiltrating monocytes/T cells in the proteinuric state, Kidney International. 2007, 71: 526-538.

Lai K.N., Tang S.C.W. and Leung J.C.K., Mediators of inflammation and fibrosis, Peritoneal Dialysis International . 2007, 27: S65-71.

Lai K.N., Chan L.Y., Saleem P., Mathieson P. and Leung J.C.K., Regulation of Bcl-2 expression in podocytes by mesangial cells derived TNF-a in IgA nephropathy, Journal of American Society of Nephrology. 2006, 17: 254A.

Lai K.N., Tang S.C.W., Chan L.C.B. and Leung J.C.K., The modulation of chemokines release in proximal tubular epithelial cell by monocytes/T cells in proteinuric state is mediated by IL-1 and TNF-a, Journal of American Society of Nephrology. 2006, 17: 384A.

Leung J.C.K., Tang S.C.W., Chan L.Y., Yuen Y.M. and Lai K.N., Specific induction of neutrophil gelatinase-associated lipocalin in peritoneal mesothelial cells by interleukin-1, Journal of American Society of Nephrology. 2006, 17: 751A.

Leung J.C.K., Winner of Renal Discoveries Extramural Grant Program (EGP), Baxter Healthcare Corporation. The EGP is endorsed by the International Society of Nephrology (ISN). 2006.

Ma C.H., Lin R.H., Chan P.K., Leung J.C.K., Chan Y.Y., Meng A., Verfaillie C.M. and Liang R.H.S., The role of survivin in angiogenesis during zebrafish embryonic development., BMC Developmental Biology. 2007, 7: 50.

Tang S.C.W., Leung J.C.K., Chan L.Y., Tsang W.L. and Lai K.N., Differntial regulation of chemokines expression by angiotensin antagonists and HMG-CoA reductase inhibitors in protein-overloaded human proximal tubular epithelial cells, Journal of American Society of Nephrology. 2006, 17: 844A.

Tang S.C.W., Leung J.C.K., Chan L.Y., Chan A.K.K., Eddy A.A. and Lai K.N., Impact of angiotensin antagonists and HMG-CoA reductase inhibitors on adriamycin nephropathy, Journal of American Society of Nephrology. 2006, 17: 41A.

Researcher : Leung KW

List of Research Outputs

Hui C.K., Zhang H., Shek T., Yao H., Yueng Y.H., Leung K.W., Lai S.T., Lai J.Y., Leung N. and Lau G., Disease progression in Chinese chronic hepatitis C patients with persistently normal alanin aminotransaminase levels, Alimentary Pharmacology Therapy. 2007, 25(11): 1283-92.

Hui C.K., Zhang H., Lee P.Y., Marin H., Yueng Y.H., Leung K.W., Lu L., Leung N., Luk J.M.C., Naoumov N., Huang F. and Lau G., Role of regulatory T cells in natural immunity and sustained pharmacological control hepatitis B infection, The Liver Meeting of The American Association for the Study of Liver, Hepatology. 2006, 44: 543A.

Hui C.K., Zhang H.Y., Lee P.Y., Mommeja-Marin H., Yueng Y.H., Leung K.W., Lu L., Leung N., Luk J.M.C., Naoumov N.N., Huang F.P. and Lau G., Role of regulatory T cells in natural immunity and sustained pharmacological control of chronic hepatitis B infection, Hepatology. 2006, 44(4): 543A-543A.

Zhang H., Hui C.K., Lee P.Y., Chan W., Yueng Y.H., Leung K.W., Lu L., Leung N., Lo C.M., Fan S.T., Luk J.M.C., Xu A., Lam K.S.L., Kwong Y.L. and Lau G., Serum adiponectin is increased in advancing liver fibrosis and decline with reduction in fibrosis in chronic hepatitis B, The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007, Hepatology International. 2007, 242: 7.

Researcher : Leung MH

List of Research Outputs

Chim J.C.S., Liang R.H.S., Leung M.H. and Kwong Y.L., Aberrant gene methylation implicated in the progression of monoclonal gammopathy of undetermined significance to multipl myeloma, Journal of clinical pathology. 2007, 60: 104-106.

Researcher : Leung TWT

List of Research Outputs

Epstein R. and Leung T.W.T., Reversing hepatocellular carcinoma progression using networked biological therapies, Clin Cancer Res. 2007, 13(1): 11-7.

Researcher : Leung YC

List of Research Outputs

Chan A.O.O., Hui W.M., Leung Y.C., Wong Y.H., Chan P., Hung I.F.H., Hsu A., But D., Lam S.K. and Wong B.C.Y., Better efficacy of tegaserod in constipated patients with slow colonic transit, absent pelvic floor dyssynergy and absent impaired rectal sensation. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A194.

Chan A.O.O., Chow R., Hui W.M., Leung Y.C., Tong S.M., Lam S.K. and Wong B.C.Y., Biofeedback is equally effective in patients with short or long duration of function constipation. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A194.

Chan A.O.O., Hui W.M., Wong Y.H., Leung Y.C., Lam S.K. and Wong B.C.Y., Decreased cortical activation during rectal distention in patients with functional constipation with normal rectal compliance. Digestive Disease Week 2007, Washington DC, USA, May 19-24, Gastroenterology. 2007, 132(4) Suppl 2: A23.

Chan A.O.O., Hui W.M., Leung Y.C., Hu H.C., Lam S.K. and Wong B.C.Y., Efficacy of tegasered for functiona constipation in Chinese subjects: A randomized double blind contolled trial in a single center. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4): A194.

Chan A.O.O., Hui W.M., Leung Y.C., Hu H.C., Lam S.K. and Wong B.C.Y., Efficacy of tegaserod for functional constipation in Chinese subjects: a randomized double-blind controlled trial in a single center, Alimentary Pharmacology and Therapeutics. 2007, 25(4): 463-469.

Chan A.O.O., Huang C.Y., Leung Y.C., Hui W.M., Lam S.K. and Wong B.C.Y., Familial constipationis associated with a2 adrenoceptor polymorphism. Digestive Diseases Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A189.

Researcher : Leung YH

List of Research Outputs

Cheung B.M.Y., Leung Y.H., Man Y.U. .B.U.N., Ong K.L., Wong L.Y.F., Lau C.P. and Lam K.S.L., Association of Blood Pressure with Polymorphisms in the Quantitative Trait Locus for Abdominal Obesity-Metabolic Syndrome on Chromosome 17, The 21st Scientific Meeting of the International Society of Hypertension 2006.

Li Y., Chu L.W., Cheung B.M.Y., Leung Y.H., Yik P.Y., Jin D. and Song Y., Association of ABCA1 Gene with Sporadic Alzheimer's Disease in Chinese Group and Potential Functional Importance for Novel Intronic Polymorphism., 11th Research Postgraduate Symposium, 7 Dec. 2006. The University of Hong Kong, Li Ka Shing Faculty of Medicine. 2006.

Pan N.Y., Hui W.S., Tipoe G.L., Taylor G.W., Leung Y.H., Lam W.K., Tsang K.W.T. and Mak J.C.W., Inhibition of pyocyanin-potentiated IL-8 release by steroids in bronchial epithelial cells, Respiratory medicine. 2006, 100(9): 1614-1622.

Researcher : Li CS

List of Research Outputs

Tang S.C.W., Chan K.W., Tang C.S.O., Lam M.F., Leung C.Y., Tse K.C., Li C.S., Ho Y.W., Tong K.L., Lai K.N., Chan D.T.M. and Hong Kong Nephrology Study Group ., Conversion of ciclosporin A to tacrolimus in kidney transplant recipients with chronic allograft nephropathy, Nephrology Dialysis Transplantation. 2006, 21(11): 3243-51.

Researcher : Li FK

List of Research Outputs

Yip T., Tse K.C., Lam M.F., Cheng S.W., Lui S.L., Tang S.C.W., Li F.K., Wang A.Y.M., Choy C.B.Y., Ng M.M.T., Chan D.T.M., Lai K.N. and Lo W.K., Risk and outcome of peritonitis after flexible colonoscopy in CAPD patient, Peritoneal Dialysis International . 2006, Suppl 26: S68.

Researcher : Li G

Project Title:	The Neuroprotective Effect of Coenzyme Q10 in AD mice model
Investigator(s):	Li G, Yang ES, Jack Jr CR
Department:	Medical Faculty
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2006

Abstract:

Alzheimer's disease (AD) and ischemic cerebrovascular disease are two main causes of dementia in elderly people. Recent basic and clinical investigations demonstrate that AD and vascular dementia (VaD), traditionally considered two independent neurological disorders, may interact in an additive manner. In clinical studies, the presence of ischemic lesions enhances the cognitive deficits in patients with AD pathology. Mutations in the genes of beta-amyloid precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2) cause familial AD. In transgenic mice with overexpressed APP, susceptibility to ischemic brain damage caused by middle cerebral artery occlusion (MCAO) is increased. In AD patients, the extent of AD pathology is increased if ischemic stroke coexists. Elderly subjects are more likely to have been demented in life if both AD pathology and ischemic cerebrovascular disease are present at autopsy than if either is pathology is found in isolation. Several studies suggest a possible role of increased oxidative stress and impairment of mitochondrial energy metabolism in the pathogenesis of both AD and stroke. A number of investigators have identified a deficiency in the complex VI, cytochrome c oxidase (COX) of the mitochondrial electron transport chain in AD patients and a reduced activity of complexes I and III in ischemic conditions. Coenzyme Q10 (CoQ10) is an essential biological cofactor produced endogenously in the body and provided in the food chain. As the electron acceptor for mitochondrial complexes I and II, it has an essential role in cellular energy production as an electron and proton carrier. Complex I or II dysfunction are found in neurological disorders such as Parkinson’s disease and Huntington disease. Shults et al. reported a correlation between mitochondrial CoQ10 level and the biological activity of complexes I - IV Parkinson’s disease patients who were administered the highest dose of CoQ10 showed the greatest clinical benefit. Oral CoQ10 supplementation increases brain mitochondrial concentrations and exerts neuroprotective effects. A neuroprotective effect of CoQ10 has been found in various animal models of stroke and this has been attributed to its role as a potent antioxidant and an oxygen derived free radical scavenger. This finding has not been universally replicated, however, as Li and his colleagues found that immediate treatment with CoQ10 via intraperitoneal injection did not prevent neuronal injuries following global and focal ischemia. Mitochondrial abnormalities have been found in human AD patients, and there are a few reports about the therapeutic effect of CoQ10 in AD patients. Results have been mixed however, for example, de Bustos et al. investigated serum levels of CoQ10 in patients with AD and found no relationship with the risk of AD and vascular dementia. CoQ10 has been shown to have a neuroprotective effect in other neurodegenerative diseases, such as Parkinson’s and Huntington’s diseases. In this study, we address the effects of CoQ10 on AD and cerebral ischemia using volume magnetic resonance imaging (MRI) in transgenic animal models. APP/PS1, APP and PS1 transgenic mice with ischemic stroke will be treated with high-dose CoQ10 for 28 days, and then their brain specimens will be examined by MRI to investigate the neuroprotective effects of CoQ10, compared to the non-treated counterparts. Transgenic rather than wild type mice will be employed in order to amplify the destructive effects of stroke in the experimental animals.

Project Title:	Effect of imbalance of kinases and protein phosphatases on deposit of B amyloid and Tau Pathology in double transgenic APP/PS1 Mice
Investigator(s):	Li G, Yang X, Yang ES
Department:	Medical Faculty
Source(s) of Funding:	Germany/Hong Kong Joint Research Scheme
Start Date:	01/2007

Abstract:

1. To investigate the effect of the overactivation of GSK-3 on deposit of amyloid and tau pathology in APP/PS1 double transgenic mice 2. To investigate the effect of the suppression of the two major proteins - phosphatase 2A and phosphatase 1 on deposit of amyloid and tau pathology in APP/PS1 double transgenic mice This is the first of systematical study on effects of GSK-3/PP2A and PP1 on the main two defining pathological feature-SPs and tau pathology in transgenic mice

List of Research Outputs

Chan H.D., Luke K.K., Li G., Li P., Weekes B., Yip V. and Tan L.H., Neural correlates of nouns and verbs in early bilinguals, Annals of the New York Academy of Sciences. New York Academy of Sciences, 2007, 1115: 45-56.

Wang J., Yang Y., Xia H.H.X., Gu Q., Lin M.C., Jiang B., Peng Y., Li G., An X., Zhang Y., Zhuang Z., Zhang Z., Kung H.F. and Wong B.C.Y., Suppression of FHL2 Expression Induces Cell Differentiation and Inhibits Gastric and Colon Carcinogenesis , Gastroenterology. 2007, 132: 1066-1076.

Researcher : Li G

List of Research Outputs

Researcher : Li GR

Project Title:	Volume-sensitive chloride current and cell volume regulation in human atrial myocytes
Investigator(s):	Li GR, Lau CP, Chiu SW, Tse HF
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	12/2001

Abstract:

To determine the intracellular signaling pathways that regulate I_Cl.vol and cell volume in human atrium; to determine whether I_Cl.vol is persistently activated in atrial myocytes from patients with dilated atrial cardiomyopathy.

Project Title:	Ionic channels of mesenchymal stem cells from bone marrow and cell proliferation
Investigator(s):	Li GR, Lau CP, Chung SSM, Tse HF
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	12/2003
Completion Date:	07/2006

Abstract:

To analyze the molecular identities of IK_DR, I_KCa, and I_Na in MSCs from rat bone marrow with semi-quantitative reverse transcript-polymeterase chain reaction (RT-PCR) and patch clamp techniques; to test the hypothesis that the three types of channels (IK_DR, I_KCa and I_Na) are involved in the proliferation of rat MSCs by determining cell proliferation in the absence and presence of channel blockers and modulators.

Project Title:	Studies on Ion Channels in Human Pre-adipocytes
Investigator(s):	Li GR, Lau CP
Department:	Medical Faculty
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	05/2006

Abstract:

Ion channels play an important role in the physiological activities of many types of cells. In excitable cells, activation of ion channels generates action potentials and participates in excitation-contraction (muscles), excitation-secretion (glands), and impulse conduction (nerve and muscles), as well as repolarizing cell membrane potential. In proliferative cells, ion channels are found to be required for cell proliferation. Recent studies have demonstrated that several K channels, eg. inward rectifier K channels (IKir), delayed rectifier K channels (IKDR), ATP-sensitive K channel (IKATP), are involved in the cell cycling of lymphocytes, neuronal glial cells (e.g. astrocytes), epithelial cells, and cancer cells. Blockade of IKDR is believed to inhibit cell proliferation, whereas inhibition of IKIR promotes proliferation in rat spinal cord astrocytes. In addition, volume-sensitive chloride current (ICl.vol) is involved in the proliferation of several types of cells including vascular smooth muscle and endothelial cells, cancer cells etc. These studies indicate an important relationship between ion channels and cell proliferation. There has been a dramatic increase in the incidence of obesity resulting from an excess of white adipose tissue. Obesity is a prevalent health hazard in industrial countries, and is closely associated with the occurrence of type 2 diabetes and cardiovascular disease. Preadipocytes are the origin of fat cells of white adipose tissue. For the past two decades, in vitro systems have been extensively used to study adipocyte differentiation with preadipocytes. Although significant progress has been made in the dissection of the molecular and cellular events taking place during the transition from undifferentiated preadipocytes into mature round fat cells, control of adipocyte differentiation is not completely understood, especially ion channels and thire physiological roles in proliferation/differentiation have not been studied. The present proposal was to study ion channel expression and thire molecular identidies in human pre-adipocytes commercially obtained from CellSicence using whole-cell patch clamp and RT-PCR techniques, and to provide the experimental data for obtaining external RGC grant to further study whether/how ion channels are involved in proliferation/differentiation in human pre-adipocytes.

Project Title:	Studies on ion channels and cell proliferation in human cardiac fibroblasts
Investigator(s):	Li GR, Lau CP
Department:	Medical Faculty
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2007

Abstract:

To analyze the molecular identities of I_KCa, IK_DR, I_CI.vol, and I_Na, in human cardiac fibroblasts with RT-PCR, Western blot analysis, and patch clamp technique; to test the hypothesis that these four types of channels (I_KCa, IK_DR, I_CI.vol, and I_Na are involved in the proliferation of human cardiac fibroblasts. Cell proliferation assays will be conducted in the absence and presence of channel blockers, short interfering RNA (siRNA) oligos targeted to IK_DR, I_KCa, I_CI.vol, and I_Na and channels, and/or signal modulators.

List of Research Outputs

Deng X., Lau C.P. and Li G.R., Cell cycle-dependent expression of potassium channels and cell proliferation in rat mesenchymal stem cells from bone marrow, Biophysical Journal/51th Annual Meeting of Biophysical Society, Baltimore, MD . 2007, 126.

Deng X., Sun H., Lau C.P. and Li G.R., Properties of ion channels in rabbit mesenchymal stem cells from bone marrow , Biochem Biophys Res Commun. 2006, 348(1): 301-309.

Hu H., Lau C.P. and Li G.R., Characterization of Ionic currents in human preadipocytes, Second International Symposium on Healthy Aging: “Meeting the Challenges of an Aging Population”, The University of Hong Kong, Hong Kong . 2007.

Hu R., Lau C.P. and Li G.R., Characterization of intracellular Ca2+ signal pathway in human preadipocytes, Second International Symposium on Healthy Aging: “Meeting the Challenges of an Aging Population", The University of Hong Kong, Hong Kong. 2007.

Li G.R., Ion channels and cardiac arrhythmias, CardioRhythm 2007, Hong Kong. 2007.

Li G.R., Sun H., Chiu S.W. and Lau C.P., The n-3 polyunsaturated fatty acids from fish oil inhibit transient outward and ultra-rapid delayed rectifier potassium currents and voltage-gated sodium current in human atrial myocytes, CardioRhythm-2007/Europace, Hong Kong. 2007, 9(supple 1): 25.

Liu H., Jin M.W., Xiang J.Z., Huang Y., Sun H., Chiu S.W., Lau C.P. and Li G.R., Raloxifene inhibits transient outward and ultra-rapid delayed rectifier potassium currents in human atrial myocytes, Eur J Pharmacol. 2007, 563(1-3): 61-8.

Liu H., Sun H., Lau C.P. and Li G.R., Regulation of voltage-gated cardiac sodium current by epidermal growth factor receptor kinase in guinea pig ventricular myocytes. , J Mol Cell Cardiol. 2007, 42(4): 760-8.

Tao R., Lau C.P. and Li G.R., Inositol 1,4,5-trisphosphate receptors mediating spontaneous Ca2+ oscillation favors proliferation in human mesenchymal stem cells from bone marrow., Blood/48th Annual Meeting of the American-Society-of-Hematology, Orlando, FL. 2006, 108(11): 727A.

Researcher : Li LSW

List of Research Outputs

Chau C.M., Cheung R.T.F. and Li L.S.W., Importance of both positive and negative BOLD signal changes in acute stroke patients upon motor recovery, 11th Research Postgraduate Symposium. 2006, 125.

Chau C.M., Cheung R.T.F. and Li L.S.W., Relevance of negative BOLD signal changes in stroke patients upon motor recovery, Society for Neuroscience Annual Meeting. 2006.

Ng M.C., Ho J.T., Ho S.L., Lee R., Li G., Cheng T.S., Song Y.Q., Kwok H.H., Ho W.L., Chu C.Y.A., Fong C.Y., Chan K.H., Cheung R.T.F., Li L.S.W., Yang E.S., Luk K.D.K., Hu Y., Ramsden D.B. and Leong Fung L.L.Y., MR-DTI study: abnormal water diffusion pattern in asymptomatic familial amyotrophic lateral sclerosis with SOD1 mutation, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population. 2007, 54.

Yuen K.S.L., Lee T.M.C., Wai Y.Y., Liu H.L., Mok E.N.H., Li L.S.W. and Chan C.C.H., Cortical reorganization for response regulation with unilateral thalmamic stroke detected by function MRI, Neurorehabilitation and Neural Repair. 2007, 21(5): 467-471.

Researcher : Li RA

List of Research Outputs

Siu C.W., Lau C.P., Tse H.F. and Li R.A., Probing the external S5-Pore region of HCN-encoded pacemaker channel by cysteine scanning mutagensis. , HBHA conference 2007 Young Investigator Award (Poster category) . 2007.

Siu C.W., Lau C.P., Tse H.F. and Li R.A., Probing the external S5-Pore region of HCN-encoded pacemaker channel by cysteine scanning mutagensis, MGH-HKU-Nature Forum 2007.

Tam K.W., Li R.A., Chan Y.S. and Shum D.K.Y., Chondroitinases ABC I and II from Proteus Vulgaris for Therapuetic Use: Cloning and Characterization., 11th Research Postgraduate Symposium, 7 Dec. 2006. The University of Hong Kong, Li Ka Shing Faculty of Medicine. 2006.

Tse H.F. and Li R.A., Press Release, Investigation on Bioartifical Sinus Node Provides important clinical insights into cardiac impulse generation Sep 8, 2006. 2006.

Xue T., Siu C.W.D., Lieu D.K., Lau C.P., Tse H.F. and Li R.A., Mechanistic role of I(f) revealed by induction of ventricular automaticity by somatic gene transfer of gating-engineered pacemaker (HCN) channels., Circulation. 2007, 115(14): 1839-1850.

Researcher : Li Z

List of Research Outputs

Li Z., Cai S., Rong K., Song G., Li Y. and Guo R., The first compound heterozygosity for HKalpha alpha allele and Southeast Asian deletion allele, Clin Biochem. 2007, 40: 407-410.

Researcher : Liang RHS

Project Title:	Quantification of circulating Epstein Barr viral DNA in patients with malignant lymphoma: diagnostic and prognostic significance
Investigator(s):	Liang RHS, Kwong YL, Au WY
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2002

Abstract:

To define if circulating Epstein-Barr viral (EBV) DNA can be correlated with tumor load in patients with malignant lymphoma; to define the biologic significance and propgnostic value of circulating EBV DNA in malignant lymphoma.

Project Title:	Molecular determinants of arsenic resistance in APL and prognostic factors of APL in the post arsenic era
Investigator(s):	Liang RHS, Kwong YL, Au WY
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003

Abstract:

To define the relative significance of FLT-3 mutation and aberrant p15 methylation in prognostication of acute promyelocytic leukaemia (APL) in the era of arsenic salvage; to define the molecular role of molecular transport proteins, protein kinase and tumor suppressor genes in arsenic resistant APL.

Project Title:	Adoptive transfer of herpes zoster cellular immunity to BMT patients by vaccination of seropositive donors with live-attenuated varicella zoster vaccine
Investigator(s):	Liang RHS, Leung AYH
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	12/2003

Abstract:

To study whether the use of live-attenuated VZV vaccine in VZV-seropositive donors prior to BMT achieves three objectives: boosts the cellular and humoral immunity of the donors, transfers immunity to patients post BMT, and protects BMT patients from the development of HZ after transplantation.

Project Title:	*Effects of all-trans* retinoic acid (ATRA) on stromal cells and haematopoietic stem cell engraftment**
Investigator(s):	Liang RHS, Leung AYH
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2006

Abstract:

To focus on AFT024 stromal cells but not primary bone marrow stromal cells; to perform one set of microarray and conform the gene expression profile using RT-PCR for those that show differential expression; to focus on the effects of ATRA on human bone marrow cell engraftment in the NOD/SCID mouse model.

Project Title:	Roles of survivin in the pathogenesis of multiple myeloma and the therapeutic implication of dominant negative survivin in a murine model of human multiple myeloma
Investigator(s):	Liang RHS
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	01/2006

Abstract:

Background: Multiple myeloma (MM) is a common blood cancer to which there is no effective cure at present. It is characterized by the presence of abnormal plasma cells which are resistant to apoptotic signals. Angiogenesis in the tumor is also increased. The pathogenesis of MM involves multiple ligand (from microenvironment) and receptors\ (on MM cell surface) interactions, resulting in activation of major signaling pathways, notably the STAT-3, PI3K/Akt and NFkB pathways. These pathways overlap to a considerable extend and targeting any one of them may not impact significantly to the eradication of disease. These have led us to investigate whether a downstream component common to these pathways may provide us with an alternative therapeutic target. In particular, survivin, a member of the inhibitor of apoptotic gene family, is one of the downstream mediators of these pathways and may endow MM cells both with their resistance to apoptosis and increased angiogenesis. Preliminary studies showed that survivin is robustly expressed in both primary MM tissues as well as in a MM cell-line U266. The proposed studies have the following objectives: 1. Investigate the effects of transducing myeloma cells with a dominant negative form of survivin (SurDN) with particular reference to apoptosis and cell-cycle status. Recombinant adeno-associated virus (rAAV) will be used for viral transduction. 2. Establish an in-vivo xenogeneic transplantation model in which eGFP+ MM cells are transplanted into NOD/SCID mice via an intra-femoral route. 3. Investigate the effects of injecting rAAV carrying SurDN on the tumorigenesis of MM cells in this model. Information derived from this project will enable us to address the following issues: 1. Is survivin involved in the pathogenesis of MM, if so, how? 2. Is anti-survivin strategy feasible and efficacious in the treatment of this condition? Results of this project will have important impacts on the following aspects: 1. Explore the therapeutic potential of anti-survivin strategy in the treatment of MM 2. Establish a xenogeneic MM transplantation model that is also important for various therapeutic trials for the treatment of this condition.

Project Title:	The roles of aldehyde dehydrogenase 1A1 (ALDH) in defining and regulating leukemia initiating cell activity in acute myeloblastic leukemia
Investigator(s):	Liang RHS, Leung AYH
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2007

Abstract:

Objectives of the research proposal: 1. BACKGROUND a. Concept of Leukemia Initiating Cell (LIC) in Acute Myeloblastic Leukemia (AML) AML is defined morphologically by an abnormal increase in myeloblasts in the bone marrow (BM). They are heterogeneous in morphologic and cytogenetic features as well as prognoses. Recent advances in stem cell biology have led to an analogous hierarchical model in which a rare population known as the leukemia initiating cells (LIC) gives rise to clonogenic leukemic progenitors and leukemia. LIC are derived from transformation of normal hematopoietic stem cells (HSC) as a result of cumulated mutations, but share stem cell features of replicative quiescence and self-renewal potential. The proposition of LIC may explain the late relapses commonly seen in AML after intensive chemotherapy (which targets at leukemic blasts but not LIC) and has made it an ideal target for anti-leukemia therapy. b. Isolation and purification of LIC LIC are characterized by their ability to recapitulate the leukemic phenotypes in xenogeneic NOD/SCID mouse transplantation assay. However, the identification of LIC has remained elusive and was mostly based on strategies adopted for HSC. i. Surface phenotype may not reliably define LIC. Previous studies have shown that like HSC, LIC are enriched in the CD34+CD38- fraction of the AML cells. Further studies have refined the LIC phenotype as CD34+CD38-CD90-CD117-, in contrast to HSC which are mostly CD34+CD38-CD90+CD117+. However, leukemic cells bearing these phenotypes are dissimilar functionally only a small fraction of which contains LIC. Discordant results have been reported in which LIC may be CD34+CD90+ or even CD34-. Therefore, surface phenotype alone may not reliably define LIC. ii. Aldehyde dehydrogenase (ALDH) – a conserved functional and potentially targetable marker of stem cells. This is a family of enzymes involved in the metabolism of aldehydes to their corresponding carboxylic acids. In liver, cytosolic ALDH1A1 (referred herein ALDH) contributes primarily to the biosynthesis of retinoic acid from retinol (vitamin A). It is also highly expressed in human and murine hematopoietic stem and progenitor cells and has been correlated clinically with hematopoietic reconstitution in patients undergoing HSCT (Appendix Ia). Recently, diethylaminobenzaldehyde (DEAB), a specific inhibitor of ALDH, has been shown to deregulate human HSC self-renewal by interfering with endogenous retinoic acid biosynthesis. These data suggested that ALDH may regulate HSC function and is potentially targetable by therapeutic means. More recently, ALDH activity has also been detected in BM samples from AML. Nonetheless, its role in the pathogenesis of AML and its link to LIC are presently unknown. c. Characterization of LIC using xenogeneic NOD/SCID mice transplantation Early studies showed that when AML cells are injected intravenously into the tail vein of 6-8 week old NOD/SCID mice, the engrafting leukemic cells in the recipient bone marrow recapitulate the disease profiles in the patients. Since then, the xenogeneic transplantation model has become the gold-standard for the enumeration of LIC. Subsequent studies showed that in many cases, LIC was contained in the CD34+CD38- fraction (see above), irrespective of the morphologic subtypes and phenotypic features of the leukemic blasts. Limiting dilution analysis showed that LIC occurs in the range of 1 in 105to 106 of leukemic cells. 2. PRELIMINARY WORKS TOWARDS THIS PROJECT a. Hematopoietic stem cell study Our laboratory focuses on the study of HSC under normal and deregulated conditions and is equipped with facilities for HSC processing, FACS and NOD/SCID xenogeneic transplantation. We have demonstrated that exogenous retinoic acid enhances human HSC maintenance in-vitro as shown by long-term culture initiating cells and NOD/SCID transplantation. As ALDH is involved in the biosynthesis of endogenous retinoic acid and is highly expressed in HSC, we examine if this enzyme may regulate LIC activity (leukemic counterparts of HSC) in AML. b. A robust SSCloALDHbr population detectable in some cases of AML We first examined ALDH in BM samples from AML patients and normal donors, using a fluorescent ALDH substrate, BODIDY aminoacetaldehyde (the aldefluorTM, StemCo Biomedical Inc., Durham, NC) that has been validated for the purification of HSC from human umbilical cord blood and peripheral blood stem cells as well as murine bone marrow (Appendix Ia). In normal BM samples, a small SSCloALDHbr cell population could be readily identified. In 43 AML samples, we observed two patterns: ALDH+AML (20/43 cases) characterized by a robust SSCloALDHbr population and ALDH-AML (23/43 cases) with undetectable ALDH activity (Appendix Ib). In normal BM and ALDH+AML, the SSCloALDHbr cells co-express CD34, suggesting that they represent a primitive population during both normal and leukemic hematopoiesis. ALDH+AML are associated with multi-lineage dysplasia and history of preceding myelodysplastic syndrome (with inferior remission rate when treated with intensive chemotherapy) whereas ALDH-AML are associated with translocation t(15;17) and t(8;21) (associated with favorable prognosis) (Appendix Ic). Immunohistochemistry confirmed that SSCloALDHbr cells co-express CD34+ and are scattered throughout the inter-trabecular region (Appendix Id). The presence of SSCloALDHbr cells is unique to AML, as none of the eight cases of acute lymphoblastic leukemia (ALL) was positive for ALDH. c. CD34+SSCloALDHbr cells are enriched with leukemia initiating cells To investigate the leukemia-initiating potential of CD34+SSCloALDHbr cells, we have transplanted 105-106 CD34+ cells from ALDH+AML into NOD/SCID mice via an intra-femoral route to circumvent the problems associated with homing. At 6 week post-transplantation, the recipients showed robust human cell engraftment characterized by the presence of human CD45+ mouse CD45.1- in the recipients’ marrow. Fluorescent in-situ hybridization (FISH) and RT-PCR in two patients showed that the engraftment cells are derived from the leukemic clone (Appendix Ie). The data were consistent with the notion that the CD34+SSCloALDHbr population contains LIC in AML. 3. KEY QUESTIONS TO BE ADDRESSED In this proposal, we test the hypothesis if ALDH may define and regulate LIC activity. Information from this proposal will enable us to address the following questions: A. Can ALDH be used as a functional marker to define LIC in AML? B. Can inhibition of ALDH perturb LIC activity? If so, how? These information will shed light to the mechanisms whereby LIC activity is regulated and may revise the current paradigm of AML treatment by providing a novel pharmacological target specific against LIC.

List of Research Outputs

Au W.Y., Fung T.K., Ma E.S.K., Shek T.W.H., Hawkins B.R. and Liang R.H.S., HLA associations, microsatellite instability and epigenetic changes in thyroid lymphoma in Chinese, Leuk Lymphoma. 2007, 48(3): 531-534.

Au W.Y., Trendell-Smith N.J., Chow C. and Liang R.H.S., Senile EBER positive diffuse large B cell lymphoma relapsing in the nasopharynx, Haematologica. 2006, 91(1): 111.

Au W.Y., Au W.Y., Fung T.K., Liu C.L., Fung T.K., Fung T.K., Fan S.T., Ma E.S.K., Liang R.H.S. and Kwong Y.L., Serial analysis of JAK2 mutation in a patient who developed essential thrombocythemia after orthotopic liver transplantation, American Journal of Hematology. 2006, 81(1): 880-882.

Au W.Y., Fung T.K., Lam K.Y., Lie A.K.W., Liang R.H.S. and Kwong Y.L., Transformed essential thrombocytosi with a JAK2 V617F mutation relapsing as JAK2 Mutation-negative leukaemia after allogeneic stem cell transplantation, Bone Marrow Transplantation. 2006, 38(8): 573-4.

Au W.Y., Fung T.K., Wong K.F., Chan C.H. and Liang R.H.S., Tumor necrosis factor alpha promoter polymorphism and the risk of chronic lymphocytic leukemia and myeloma in the Chinese population, Leukaemia and Lymphoma. 2006, 47(10): 2189-2193.

Chan G.C.F., Chan S., Kan A., Au W.Y., Lee T.L., Lie A.K.W., Kwong Y.L., Ha S.Y. and Liang R.H.S., Mesenchymal stromal cells remained to be of recipient in origin after conventional bone marrow transplantation. , Cytotherapy 2007; 9(1)Supp: 144. 2007.

Chan P., Yau T., Epstein R., Lam K., Liang R.H.S. and Lo C., Treatment outcomes in anaplastic thyroid carcinoma 1966-2006: failure of overall survival enhancement despite four decades of progress in surgery, radiotherapy and chemoradiation. , Proc Am Soc Clin Oncol. 2007, 43: 672.

Cheng K.K.F., Leung S.F., Thompson D.R., Tai J.W.M., Liang R.H.S., Kan A.S.T., Ying F.W.O. and Yeung R.M.W., New measure of health-related quality of life for patients with oropharyngeal mucositis: development and preliminary psychometric evaluation, Cancer. 2007, 109: 2590-2599.

Cheung M.S., Shek W.K., Shek W.K., Leung J.C.K., Chan Y.Y., Huang H., Kwong Y.L., Liang R.H.S. and Leung A.Y.H., Aldehyde dehydrogenase activity in leukemic blasts defines a subgroup of acute myeloid leukemia with adverse prognosis and superior NOD/SCID engrafting potential, Leukaemia. 2007, 21: 1423-1430.

Cheung M.S., Tam K.H., Chow C.H., Verfaillie C.M. and Liang R.H.S., All-trans retinoic acid induces proliferation of an irradiated stem cell supporting stromal cell line AFT024., Experimental Hematology. 2007, 35: 56-63.

Cheung M.S., Kwong Y.L., Liang R.H.S. and Leung A.Y.H., Stem cell model of hematopoiesis, C7urrent Stem Cell Research and Therapy. 2006, 1: 305-315.

Chim J.C.S., Liang R.H.S., Leung M.H. and Kwong Y.L., Aberrant gene methylation implicated in the progression of monoclonal gammopathy of undetermined significance to multipl myeloma, Journal of clinical pathology. 2007, 60: 104-106.

Chim J.C.S., Liang R.H.S., Fung T.K., Choi C.L. and Kwong Y.L., Epigenetic dysregulation of the death-associated protein kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in multiple myeloma, Journal of clinical pathology. 2007, 60: 664-669.

Chim J.C.S., Fung T.K., Wong K.F., Lau J.S. and Liang R.H.S., Frequent DAP kinase but not p14 or Apaf-1 hypermethylation in B-cell chronic lymphocytic leukemia, Journal of Human Genetics. 2006, 9: 832-8.

Chim J.C.S., Fung T.K., Wong K.F., Lau J.S. and Liang R.H.S., Infrequent Wnt inhibitory factor-1 (Wif-1) methylation in chronic lymphocytic leukemia, Leukemia Research . 2006, 30(9): 1135-9.

Chim J.C.S., Liang R.H.S., Fung T.K. and Kwong Y.L., Infrequent epigenetic dysregulation of CIP/KIP family of cyclin-dependent kinase inhibitors in multiple myeloma, Leukemia. 2006, 19(12): 2352-5.

Chim J.C.S., Lie A.K.W., Liang R.H.S., Au W.Y. and Kwong Y.L., Long-term results of allogeneic bone marrow transplantation for 108 adult patients with acute lymphoblastic leukemia: favorable outcome with BMT at first remission and HLA-matched unrelated donor, Bone Marrow Transplantation. 2007, 40(4): 339-347.

Hui C.K., Liang R.H.S. and Lau G., Reply to "Kinetics of hepatitis B virus reactivation after chemotherapy: more questions than answers , Gastroenterology. 2006, 131(5): 1656-1657.

Hui C.K., Cheung W.W., Zhang H.Y., Au W.Y., Leung N., Luk J.M., Lie A.K.W., Kwong Y.L., Liang R.H.S. and Lau G., Rituximab increases the risk of de novo hepatitis B infection in hepatitis B surface antigen negative patients undergoing cytotoxic chemotherpay, Gastroenterology. 2006, 131(1): 59-68.

Leung A.Y.H., Chow C.H., Kwok J.S.Y., Lui C.K., Cheng V.C.C., Yuen K.Y., Lie A.K.W. and Liang R.H.S., Safety of vacinating sibling donors with live-attenuated varicella zoster vaccine before hematopoietic stem cell transplantation, Bone Marrow Transplantation. 2007, 39(11): 661-5.

Ma C.H., Liang R.H.S. and Leung A.Y.H., The role of phospholipase C gamma 1(PLC-g1) in primitive hematopoiesis during zebrafish development, Experimental Hematology. 2007, 35: 368-373.

Ma C.H., Lin R.H., Chan P.K., Leung J.C.K., Chan Y.Y., Meng A., Verfaillie C.M. and Liang R.H.S., The role of survivin in angiogenesis during zebrafish embryonic development., BMC Developmental Biology. 2007, 7: 50.

Tsang J., Yau T., Chan A.T.C., Liang R.H.S., Yeo W. and Epstein R., Costs and benefits of dose-dense chemotherapy scheduling in Hong Kong Chinese patients with primary breast cancer, Proc Am Soc Clin Oncol . 2007, 43: 598.

Yau T., Leong C.H., Chan W.K., Chan J.K., Liang R.H.S. and Epstein R., A case of mixed adult Wilms' tumour and angiosarcoma responsive to carboplatin, etoposide and vincristine (CEO), Cancer Chemother Pharmacol. 2007.

Yau T., Chan P., Tsang J., Liang R.H.S. and Epstein R., Xelox causes less disabling neuropathy than FOLFOX4 for Chinese colorectal cancer patients., Proc Am Soc Clin Oncol . 2007, 43: 632.

Researcher : Liao S

List of Research Outputs

Tse H.F., Siu C.W.D., Zhu S., Liao S., Zhang Q.Y., Lai K.W.H., Nicholls J.M. and Tse H.F., Paracrine effects of direct intramyocardial implantation of bone marrow derived cells for enhancement of neovascularization in chronic ischemic myocardium, European Journal Heart Fail. 2007, 9(8): 747-53.

Researcher : Lie AKW

List of Research Outputs

Au W.Y., Ho J.C.M., Lie A.K.W., Sun J.Z., Zheng L., Liang R.H.S., Lam W.K. and Tsang K.W.T., A prospective study of respiratory ciliary structure and function after stem cell transplantation, Bone Marrow Transplantation. 2006, 38: 243-248.

Au W.Y., Fung T.K., Lie A.K.W., Lam K.Y., Lam C.C.K. and Kwong Y.L., Reemergence of JAK2 V617F clone heralds extramedullary leukemia relapse after BMT for transformed essential thrombocytosis, Annals of Hematology. 2006, 86: 145-7.

Au W.Y., Ma E.S.K., Lee T.L., Ha S.Y., Fung T.K., Lie A.K.W. and Kwong Y.L., Successful treatment of thrombotic microangiopathy after haematopoietic stem cell transplantation with rituximab, British Journal of Haematology. Blackwell Publishing Ltd, 2007, 137: 475-478.

Au W.Y., Fung T.K., Lam K.Y., Lie A.K.W., Liang R.H.S. and Kwong Y.L., Transformed essential thrombocytosi with a JAK2 V617F mutation relapsing as JAK2 Mutation-negative leukaemia after allogeneic stem cell transplantation, Bone Marrow Transplantation. 2006, 38(8): 573-4.

Chan G.C.F., Chan S., Kan A., Au W.Y., Lee T.L., Lie A.K.W., Kwong Y.L., Ha S.Y. and Liang R.H.S., Mesenchymal stromal cells remained to be of recipient in origin after conventional bone marrow transplantation. , Cytotherapy 2007; 9(1)Supp: 144. 2007.

Chim J.C.S., Lie A.K.W., Liang R.H.S., Au W.Y. and Kwong Y.L., Long-term results of allogeneic bone marrow transplantation for 108 adult patients with acute lymphoblastic leukemia: favorable outcome with BMT at first remission and HLA-matched unrelated donor, Bone Marrow Transplantation. 2007, 40(4): 339-347.

Chu F.S.K., Tso W.K. and Lie A.K.W., Percutaneous retrieval of a chronic foreign body with both intravascular and extravascular components, Australasian Radiology. 2007, 51(2): 179-81.

Hui C.K., Cheung W.W., Zhang H.Y., Au W.Y., Leung N., Luk J.M., Lie A.K.W., Kwong Y.L., Liang R.H.S. and Lau G., Rituximab increases the risk of de novo hepatitis B infection in hepatitis B surface antigen negative patients undergoing cytotoxic chemotherpay, Gastroenterology. 2006, 131(1): 59-68.

Leung A.Y.H., Chow C.H., Kwok J.S.Y., Lui C.K., Cheng V.C.C., Yuen K.Y., Lie A.K.W. and Liang R.H.S., Safety of vacinating sibling donors with live-attenuated varicella zoster vaccine before hematopoietic stem cell transplantation, Bone Marrow Transplantation. 2007, 39(11): 661-5.

Researcher : Lin JY

List of Research Outputs

Lin J.Y. and Chan H.H.L., Pigmentary disorders in Asian skin: treatment with laser and intense pulsed light sources, Skin Therapy Letter. 2006, 11(8): 8-11.

Researcher : Lin MC

Project Title:	Basic research on systemic damage in early stage and wound-healing after severe trauma
Investigator(s):	Lin MC
Department:	Institute of Molecular Biology
Source(s) of Funding:	Matching Fund for National Key Basic Research Development Scheme (973 Projects)
Start Date:	04/2001

Abstract:

To study basic research on systemic damage in early stage and wound-healing after severe trauma.

Project Title:	Basic research on the mechanism of aging and the prevention of geriatric disease
Investigator(s):	Lin MC
Department:	Institute of Molecular Biology
Source(s) of Funding:	Matching Fund for National Key Basic Research Development Scheme (973 Projects)
Start Date:	12/2001

Abstract:

To study the mechanism of aging and the prevention of geriatric disease.

Project Title:	Characterization of a novel cell cycle related kinase in glioblastoma
Investigator(s):	Lin MC, Leung SY, Ching YP
Department:	Institute of Molecular Biology
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	12/2002

Abstract:

The project aims at characterizing the role of cell cycle related kinase (CCRK) in cell cycle control, apoptosis, cell division and cell proliferation. Potential tumorigenic function of CCRK in human glioblastoma, fibroblast cell lines, and nude mice xenograft will also be investigated.

Project Title:	Cancer gene therapy using a novel anti-cancer polypeptide hTERTC27 delivered by a novel AAV and Adenovirus Cocktail vector system
Investigator(s):	Lin MC, Wong BCY, Kung H, Peng Y
Department:	Institute of Molecular Biology
Source(s) of Funding:	Innovation and Technology Support Programme
Start Date:	06/2003
Completion Date:	08/2006

Abstract:

To optimize our innovative, novel and patented hTERTC27 cancer gene therapy and the AAV/Adv cocktail vector technologies developed in our laboratory; to establish patented stable cell line and platforms for the large scale production of AAV-hTERTC27 and Adv-hTERTC27; to carry out, using the above, in pre-clinical study for treating solid tumors.

Project Title:	Molecular basis of alcohol-induced birth defects, the critical role of Pax 6
Investigator(s):	Lin MC, Wong BCY, Yang JY, Peng Y
Department:	Institute of Molecular Biology
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	09/2003

Abstract:

To elucidate the signaling pathways leading to alcohol-mediated inhibition of Pax6 expression and to identify the targets downstream of Pax6 responsible for microcephaly. We are particularly interested in the involvements of the PI3 kinase pathways and the reactive oxygen species and reactive nitrogen species; to investigate the molecular mechanisms for alcohol-induced growth retardation, in particular its relationship with gut development; to study alcohol induced eye deformation; to screen for agents that protect against alcohol induced birth defects.

Project Title:	Characterization of HNF-1 Cis-element as a novel insulin negative responsive element and identification of a new anti-diabetic drug targeting this element
Investigator(s):	Lin MC, Lu L, Tam S
Department:	Institute of Molecular Biology
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2006

Abstract:

To determine if the consensus HNF-1 element also displays negative insulin responsiveness; to determine the role of HNF1α versus HNF1β and mutant HNF-1α in this transcription regulation; to evaluate the therapeutic effects / molecular mechanisms of a new anti-diabetic drug targeting this INRE.

Project Title:	System biology study of a novel anti-angiogenesis polypeptide kringle 1 domain of hepatocyte growth factor
Investigator(s):	Lin MC, Yiu SM
Department:	Chemistry
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2006

Abstract:

Kringle domain, a protein module consists of 80 amino acids, function as recognition units for binding of other proteins in solution and on cells. Several of the kringle domain peptide including Angiostatin has been shown to exhibit anti-angiogenesis effect. Recently, my laboratory studied the cancer therapeutic effect of a novel anti-angiogenesis polypeptide, kringle 1 domain of human hepatocyte growth factor (HGFK1). We demonstrated that using a recombinant adeno-associated virus (AAV) carrying the HGFK1 gene (rAAV-HGFK1), we can significantly inhibited the proliferation, migration, and vessel tube formation of mice microvascular endothelial cells in vitro. More importantly, in an in vivo preclinical study conducted in rat orthotropic model of hepatocellular carcinoma (HCC), we showed that rAAV-HGFK1 is more potent than rAAV-Endostatin, the leading anti-angiogenesis gene, in prolonging the survival rate of the tumor bearing rats. Furthermore, rAAV-HGFK1 effectively inhibits tumor growth and metastasis. The objectives of the research proposal is to elucidate the molecular mechanisms underlie the anti-angiogenesis effect of HGFK1 polypeptide using System Biology approach, which will use bioinformatics to integrate data obtained from cDNA microarray experiments, Yeast two hybrid and Proteomic study. Multiple anti-angiogenesis molecules with different efficacies have been identified, however their underlying molecular mechansims remain elusive. These molecules potentially exert their effects through different signal pathways, with different interacting proteins and downstream targets. Information gained from this study will allow us to compare the molecular mechanisms of HGFK1 to that of the current leading anti-angiogenesis polypeptide Endostatin which has recently been reported using similar approaches (Abdollahi, A et al. Molecular Cell 13: 649-663, 2004).

Project Title:	Integrative Cancer Biology: Study the Novel Function of Makorin-2 in Colon Cancer Carcinogenesis
Investigator(s):	Lin MC
Department:	Chemistry
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2007

Abstract:

Many of the developmental genes also play important roles in carcinogenesis. Makorin-2 (HSPC070), originally isolated from hematopoietic stem/progenitor cells, belongs to the makorin family of genes that encode putative ribonucleoproteins. The function of makorin-2 is not known. We have recently shown that Xenopus Makorin-2 (Xmakorin-2) is expressed throughout embryonic development. Embryos over-expressing Xmakorin-2 mRNA exhibited enhanced ventralization and knockdown of Xmakorin-2 caused embryonic death. We further showed that expression of Xmakorin-2 induced hematopoietic markers α-globin and GATA-1. As such, knockdown of Xmakorin-2 suppressed the expressions of α-globin and GATA-2. Furthermore, knockdown of Xmakorin-2 completely blocked BMP-4 induced α-globin expression. These results suggest for the first time that Xmakorin-2 plays an important role in BMP-4 signaling during Xenopus embryonic development (manuscript in preparation). Makorin-2 is characterized by a variety of zinc-finger motifs. To date, nine makorin family loci have been identified and located throughout the human genome [1]. Makorin-2, located on chromosome 3p25, contains 8 exons and its nucleotide sequence shares a sequence of 105bp in 3' UTR with the oncogene c-RAF gene in reversed transcription orientation [2], suggesting that these two proteins may regulate each other. Northern blot analysis showed that makorin-2 was expressed in a variety of tissues, as well as in many of the cancer cell lines examined [2]. These raised the possibility that makorin-2 may have important roles in carcinogenesis. The objective is to use integrative cancer biology approaches to explore the potential role of makorin-2 in carcinogenesis. To achieve this aim, we conducted bioinformatics analysis. From the Gene Expression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo/), a public repository for microarray gene expression data, we found that makorin-2 was significantly upregulated by > 4-fold in metastatic colon cancer cell line SW620, as compared to primary tumor colon cancer cell line SW480 (Fig. 1). This finding suggests that makorin-2 may involve in colon cancer progression (GEO accession number GDS756). References: 1. Gray TA, Hernandez L, Carey AH, Schaldach MA, Smithwick MJ, Rus K, Marshall Graves, JA, Stewart CL, Nicholls RD. The ancient source of a distinct gene family encoding proteins featuring RING and C(3)H zinc-finger motifs with abundant expression in developing brain and nervous system. Genomics 2000;66:76-86. 2. Gray TA, Azama K, Whitmore K, Min A, Abe S, Nicholls RD. Phylogenetic conservation of the makorin-2 gene, encoding a multiple zinc-finger protein, antisense to the RAF1 proto-oncogene. Genomics 2001;77:119-26.

Researcher : Lin RH

List of Research Outputs

Ma C.H., Lin R.H., Chan P.K., Leung J.C.K., Chan Y.Y., Meng A., Verfaillie C.M. and Liang R.H.S., The role of survivin in angiogenesis during zebrafish embryonic development., BMC Developmental Biology. 2007, 7: 50.

Researcher : Liu H

List of Research Outputs

Liu H., Jin M.W., Xiang J.Z., Huang Y., Sun H., Chiu S.W., Lau C.P. and Li G.R., Raloxifene inhibits transient outward and ultra-rapid delayed rectifier potassium currents in human atrial myocytes, Eur J Pharmacol. 2007, 563(1-3): 61-8.

Liu H., Sun H., Lau C.P. and Li G.R., Regulation of voltage-gated cardiac sodium current by epidermal growth factor receptor kinase in guinea pig ventricular myocytes. , J Mol Cell Cardiol. 2007, 42(4): 760-8.

Liu H., Sun H., Lau C.P. and Li G.R., Regulation of voltage-gated cardiac sodium current by epidermal growth factor receptor kinase in guinea pig ventricular myocytes, J Mol Cell Cardiol . 2006, 2007, 42(4): 760-768.

Researcher : Liu H

List of Research Outputs

Researcher : Lo WK

List of Research Outputs

Lo W.K., Bargman J., Burkart J., Krediet R.T., Pollock C., Kawanishi H. and Blake P., The International Society for Peritoneal Dialysis (ISPD) guideline on targets for solute and fluid removal in adult patients on chronic peritoneal dialysis, Peritoneal Dialysis International. 2006, 26: 520-522.

Lui S.L., Yip T., Tse K.C., Chan D.T.M., Lai K.N. and Lo W.K., Tuberculous lymphadenitis in patients undergoing continuous ambulatory peritoneal dialysis, International Urology and Nephrology. 2007.

Tang S.C.W., Ho Y.W., Tang A.W., Yip T., Tse K.C., Wang A.Y.M., Lo W.K., Chan D.T.M., Lai K.N. and Lui S.L., What is the optimal timing of dialysis initiation? , Peritoneal Dialysis International . 2006, Suppl 26: S90.

Yip T., Tse K.C., Lam M.F., Cheng S.W., Lui S.L., Tang S.C.W., Li F.K., Wang A.Y.M., Choy C.B.Y., Ng M.M.T., Chan D.T.M., Lai K.N. and Lo W.K., Risk and outcome of peritonitis after flexible colonoscopy in CAPD patient, Peritoneal Dialysis International . 2006, Suppl 26: S68.

Researcher : Lo Y

List of Research Outputs

Mok T.M.Y., Tsang P.L., Lo Y., Wong R.W.S., Lau W.C.S. and Lam Y.M., Bosentan Use in Systemic Lupus Erythematosus Patients with Pulmonary Arterial Hypertension, Lupus. England, SAGE, 2007, 16(4): 279-285.

Mok T.M.Y., Ip E.W.K., Lau W.C.S., Lo Y., Wong W.H.S. and Lau Y.L., Mannose-binding lectin and susceptibility to Infection in Chinese patients with systemic lupus erythematosus, Journal of Rheumatology. 2007, 34: 1270-6.

Researcher : Lu L

List of Research Outputs

Hui C.K., Zhang H., Lee P.Y., Marin H., Yueng Y.H., Leung K.W., Lu L., Leung N., Luk J.M.C., Naoumov N., Huang F. and Lau G., Role of regulatory T cells in natural immunity and sustained pharmacological control hepatitis B infection, The Liver Meeting of The American Association for the Study of Liver, Hepatology. 2006, 44: 543A.

Hui C.K., Zhang H.Y., Lee P.Y., Mommeja-Marin H., Yueng Y.H., Leung K.W., Lu L., Leung N., Luk J.M.C., Naoumov N.N., Huang F.P. and Lau G., Role of regulatory T cells in natural immunity and sustained pharmacological control of chronic hepatitis B infection, Hepatology. 2006, 44(4): 543A-543A.

Lu L., Sun R.W.Y., Hui C.K., Chen R., Luk J.M.C., Che C.M. and Lau K.K., In Vitro Anti-hepatitis B Virus Activities and Mechanism of Metal-based Nanoparticles , Hepatology . 2006, 44 (Suppl.1): 553A.

Lu L., Sun R.W.Y., Hui C.K., Chen R., Luk J.M.C., Che C.M. and Lau G., In Vitro Anti-hepatitis B Virus Activities and Mechanism of Silver Nanoparticles,The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007, Hepatology International. 2007, 242: 14.

Lu L., Sun R.W.Y., Hui C.K., Chen R., Luk J.M.C., Che C.M. and Lau G., Size-dependent anti-hepatic B virus activities and mechanism of silver nanoparticles, The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007.

Lu L., Sun R.W.Y., Hui C.K., Chen R., Luk J.M.C., Che C.M. and Lau G., Size-dependent anti-hepatitis B virus activities and mechanism of silver nanoparticles (Abstract), Hepatology International. 2007, 1(1): 14.

Zhang H., Hui C.K., Lee P.Y., Chan W., Yueng Y.H., Leung K.W., Lu L., Leung N., Lo C.M., Fan S.T., Luk J.M.C., Xu A., Lam K.S.L., Kwong Y.L. and Lau G., Serum adiponectin is increased in advancing liver fibrosis and decline with reduction in fibrosis in chronic hepatitis B, The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007, Hepatology International. 2007, 242: 7.

Researcher : Lu L

List of Research Outputs

Researcher : Lui SL

List of Research Outputs

Lui S.L., Chan K.W., Tsang R.C.W., Yung S.S.Y., Lai K.N. and Chan D.T.M., Effect of rapamycin on renal ischemia-reperfusion injury in mice, Transplant International. 2006, 19: 834-839.

Lui S.L., Yung S.S.Y., Tsang R.C.W., Chan K.W., Zhang Q., Tam S., Lai K.N. and Chan D.T.M., Rapamycin attenuates the severity of nephritis in NZB/NZW mice, Journal of the American Society of Nephrology. 2006, 17: 353A.

Lui S.L., Yung S.S.Y., Tsang R.C.W., Chan K.W., Zhang Q., Tam S., Lai K.N. and Chan D.T.M., Rapamycin reduces proteinuria and segmental glomerulosclerosis in murine adriamycin nephropathy, Journal of the American Society of Nephrology. 2006, 17: 743A.

Lui S.L., Yip T., Tse K.C., Chan D.T.M., Lai K.N. and Lo W.K., Tuberculous lymphadenitis in patients undergoing continuous ambulatory peritoneal dialysis, International Urology and Nephrology. 2007.

Tang S.C.W., Ho Y.W., Tang A.W., Yip T., Tse K.C., Wang A.Y.M., Lo W.K., Chan D.T.M., Lai K.N. and Lui S.L., What is the optimal timing of dialysis initiation? , Peritoneal Dialysis International . 2006, Suppl 26: S90.

Yip T., Tse K.C., Lam M.F., Cheng S.W., Lui S.L., Tang S.C.W., Li F.K., Wang A.Y.M., Choy C.B.Y., Ng M.M.T., Chan D.T.M., Lai K.N. and Lo W.K., Risk and outcome of peritonitis after flexible colonoscopy in CAPD patient, Peritoneal Dialysis International . 2006, Suppl 26: S68.

Researcher : Luk JKH

List of Research Outputs

Luk J.K.H., Sin W.S., Ho S.L. and Chu L.W., Striopallidodentate calcifications in a Chinese elderly woman with parkinsonism and dementia, Asian J Gerontol Geriatr. 2006, 1: 113-5.

Researcher : Ma CH

List of Research Outputs

Ma C.H., Liang R.H.S. and Leung A.Y.H., The role of phospholipase C gamma 1(PLC-g1) in primitive hematopoiesis during zebrafish development, Experimental Hematology. 2007, 35: 368-373.

Ma C.H., Lin R.H., Chan P.K., Leung J.C.K., Chan Y.Y., Meng A., Verfaillie C.M. and Liang R.H.S., The role of survivin in angiogenesis during zebrafish embryonic development., BMC Developmental Biology. 2007, 7: 50.

Researcher : Ma J

List of Research Outputs

Dai Y., Qiao L., Gu Q., Xia H.H.X., Cheung T.K., Ma J., Zou B. and Wong B.C.Y., Activation of Pparc and inhibition of Xiap in human cancer cells: Synergistic effects on cell proliferation, apoptosis, and tumorigensis. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A425.

Ma J., Chen M.H., Dai Y. and Qiao L., Enhancing The Efficacy Of Photodynamic Therapy By A Chinese Herbal Medicine For Hepatocellular Carcinoma, In: Editor-in-chief, Wafik S. El-Deiry, M.D., Ph.D.University of Pennsylvania Philadelphia, PA , Cancer Biology & Therapy. USA, Cancer Biol. Ther., 2006, 5: 1117-1119.

Ma J., Yuan G. and Chen M.H., Non-steroidal anti-inflammatory drug induced gastropathy and preventive effects of teprenone on the gastropathy in rats, In: Editor-in-chief, Ba Denian,42 Dongsi Xidajie,Beijing, 100710,P.R.China, Zhonghua Yi Xue Za Zhi. China, Zhonghua Yi Xue Za Zhi, 2006, 86: 2868-2873.

Qiao L., Gu Q., Dai Y., Shen Z., Liu X., Ma J. and Wong B.C.Y., XAF1 inhibits angiogenesis of mouse endothelia cells. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A638.

Researcher : Mak JCW

Project Title:	Effects of pseudomonas aeruginosa pyocyanin and 1-hydroxyphenazine on the regulation of glucocorticoid receptor activation and function in airway epithelial cells in vitro
Investigator(s):	Mak JCW, Tsang KWT
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	11/2003

Abstract:

To evaluate the effects of Pseudomonas aeruginosa (PA) exotoxins, pyocyanin (PYO) and 1-hydroxyphenazine (1-HP), on the functional and immunological aspects of human airway epithelial cells in vitro, and examine the signaling pathways involved in PYO- or 1-HP-induced responses; to assess the efficacy of various potential novel therapeutic and chemical agents on the effects of these toxins.

Project Title:	Role of transforming growth factor-beta1 variants in susceptibility to tuberculosis in Hong Kong Chinese population
Investigator(s):	Mak JCW, Chan MMW
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2005

Abstract:

i) To study the role of two common single nucleotide polymorphisms (SNPs) at the promoter (C-509T) and coding regions (T869C) of the TGF-beta1 gene in conferring susceptibility to the development of tuberculosis (TB) in Hong Kong Chinese population. ii) To perform functional analysis in correlating the associated polymorphisms with the plasma level of TGF-beta1 in TB patients and healthy controls. iii) To conduct a study in determining the proportion of patients with chronic obstructive pulmonary disease (COPD) with a past history of tuberculosis since COPD is a major cause of respiratory disability in Hong Kong.

Project Title:	Role of senescence marker protein-30 in susceptibility to chronic obstructive pulmonary disease in Hong Kong Chinese population
Investigator(s):	Mak JCW, Chan MMW
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	04/2007

Abstract:

Chronic obstructive pulmonary disease (COPD) is a major public health concern worldwide, and is projected to be the third leading cause of mortality worldwide within 10 years [1]. COPD is a disease characterized by slowly progressive development of airflow limitation that is not fully reversible. The airflow limitation is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, mainly from cigarette smoke [2]. Smoking accounts for 90% of cases of COPD, but only 15% of smokers develop clinically symptomatic COPD [3]. There are no therapies that can reduce the inevitable progression of this disease at present. COPD is an age-related lung disease that occurs after a prolonged period of cigarette smoking. Oxidative stress is an important feature of COPD. Cigarette smoke is a rich source of oxidants containing over 1015 free radicals/puff in both the gaseous and tar phase [4]. In patients with COPD, biomarkers of oxidative stress, such as protein carbonyls and lipid peroxidation products, are reported to be elevated in the lungs and respiratory muscles [5,6]. Senescence marker protein-30 (SMP30) Senescence marker protein-30 (SMP30), a 34-kD protein that decreases with age, is a multifunctional protein providing protection to cellular functions from age-associated deterioration [7]. It has been proposed as an important aging marker and is functionally identified as a Ca2+ binding protein. In mice, SMP30 transcripts are detected in various organs including lung [8]. In humans, the SMP30 gene is located in the p11.3-q11.2 segment of the X chromosome [9]. The SMP30 knockout (SMP30Y/-) mouse has been developed with gene targeting from C57BL6 mice [10]. Recent findings showed that SMP30 protects mice lungs from oxidative stress, aging and smoking [11]. However, the precise function of SMP30 in terms of oxidant and antioxidant balance remains undetermined. In humans, many studies have concerned with the relationship between aging and oxidative stress. Moderate oxidative stress may gradually develop with age because plasma levels of lipoperoxidation products and antioxidant enzyme activities in red blood cells increase with aging, whereas plasma levels of nutritional antioxidants decrease [12]. The lungs are persistently exposed to oxidants generated endogenously from phagocytes and other cell types or exogenously from air pollutions or cigarette smoke [13]. Previous work done by the applicants There is considerable evidence for increased oxidative stress in COPD. Diminished plasma antioxidant capacity has been found in chronic healthy smokers and patients with COPD [14], but findings on antioxidant enzyme activities in COPD patients have been contradictory [15-17]. Our studies have shown that there is an imbalance of antioxidant enzyme activity with an increase in erythrocyte catalase activity but no change in erythrocyte SOD activity in Chinese COPD patients compared to healthy smokers. Rationale for the proposed study It is unclear whether oxidative stress regulating SMP30 production predisposes to COPD in man. We hypothesize that the lack of SMP30 production may be susceptible to oxidative stress with aging in general population. In addition, aging may lower the injury threshold or amplify mechanisms involved in lung destruction by cigarette smoke. The proposed study is designed to address these important issues. A better understanding of these mechanisms may aid us in defining risk groups and providing potential platforms for novel therapies. Objectives · To study the role of senescence marker protein-30 (SMP30) in susceptibility to the development of chronic obstructive pulmonary disease (COPD) in Hong Kong Chinese population. · To correlate changes between plasma level of SMP30 and the oxidative status in COPD patients and healthy controls. References 1. Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet 1997;349:1498-1504. 2. National Institutes of Health, National Heart, Lung and Blood Institute. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease, NHLBI/WHO Workshop report. NIH Publication No 2701A, March 2001. Update 2005. Available on line at www.goldcopd.com 3. Sethi JM, Rochester CL. Smoking and chronic obstructive pulmonary disease. Clin Chest Med 2000;21:67-86. 4. Pryor WA, Stone K. Oxidants in cigarette smoke. Radicals, hydrogen peroxide, peroxynitrate, and peroxynitrite. Ann NY Acad Sci 1993;686:12-27. 5. Rahman I, van Schadewijk AA, Crowther AJ et al. 4-Hydroxy-2-nonenal, a specific lipid peroxidation product, is elevated in lungs of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:490-495. 6. Barreiro E, de la Puente B, Minguella J et al. Oxidative stress and respiratory muscle dysfunction in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005;171:1116-1124. 7. Fujita T, Shirasawa T, Uchida K, Maruyama N. Gene regulation of senescence marker protein-30 (SMP-30): coordinated up-regulation with tissue maturation and gradual down-regulation with aging. Mech Ageing Dev 1996;87:219-229. 8. Mori T, Ishigami A, Seyama K et al. Senescence marker protein-30 knockout mouse as a novel murine model of senile lung. Pathol Int 2004;54:167-173. 9. Fujita T, Mandel JL, Shirasawa T et al. Isolation of cDNA clone encoding human homolgue of senescence marker protein-30 (SMP30) and its location on the X chromosome. Biochim Biophys Acta 1995;1263:249-252. 10. Ishigami A, Fujita T, Handa S et al. Senescence marker protein-30 knockout mouse liver is highly susceptible to tumor necrosis factor-alpha- and Fas-mediated apoptosis. Am J Pathol 2002;161:1273-1281. 11. Sato T, Seyama K, Sato Y et al. Senescence marker protein-30 protects mice lungs from oxidative stress, aging and smoking. Am J Respir Crit Care Med 2006;174:530-537. 12. Junqueira VB, Barros SB, Chan SS et al. Aging and oxidative stress. Mol Aspects Med 2004;25:5-16. 13. MacNee W. Pulmonary and systemic oxidant/antioxidant imbalance in chronic obstructive pulmonary disease. Proc Am Thorac Soc 2005;2:50-60. 14. Rahman I, Swarska E, Henry M, Stolk J, MacNee W. Is there any relationship between plasma antioxidant capacity and lung function in smokers and in patients with chronic obstructive pulmonary disease? Thorax 2000;55:189-193. 15. Kurys E, Kurys P, Kuzniar A. Analysis of antioxidant enzyme activity and magnesium level in chronic obstructive pulmonary disease (COPD). Ann Univ Mariae Curie Sklodowska 2001;56:261-266. 16. Daga M, Chhabra R, Sharma B, Mishra TK. Effects of exogenous vitamin E supplementation on the levels of oxidants and antioxidants in chronic obstructive pulmonary disease. J Biosci 2003;28:7-11. 17. Hanta I, Kocabas A, Canacankatan N, Kuleci S, Seydaoglu G. Oxidant-antioxidant balance in patients with COPD. Lung 2006;184:51-55.

List of Research Outputs

Chan M.M.W., Mak J.C.W., Ho S.P., Cheung A.H.K., Wong P.C., Chan K.K. and Ip M.S.M., Glutathione S-transferase (GST) polymorphisms and GST activity in Hong Kong Chinese COPD patients., International Journal of Tuberculosis and Lung Disease. 2007, 11: 508-14.

Ho J.C.M., Chan M.M.W., Ho S.P., Mak J.C.W., Ip M.S.M., Ooi C.G.C., Wong M.P., Tsang K.W.T. and Lam W.K., Disturbance of systemic antioxidant profile in non-small cell lung carcinoma, Eur Respir J . 2007, 29: 273-278.

Ho J.C.M., Mak J.C.W., Ho S.P., Ip M.S.M., Lam W.K. and Chan M.M.W., Genetic variations of systemic superoxide dismutase and catalase activities in non-small cell lung cancer. Presented at the 11th Congress of the Asian Pacific Society of Respiratory, 19-22 Nov, Respirology. 2006, 11 Suppl 5: A129.

Ho J.C.M., Mak J.C.W., Ho S.P., Ip M.S.M., Tsang K.W.T., Lam W.K. and Chan M.M.W., Manganese superoxide dismutase and catalase genetic polymorphisms, activity levels and lung cancer risk in Chinese in Hong Kong, J. Thorac. Oncol. 2006, 1: 648-653.

Mak J.C.W., Ho S.P., Ho J.C.M. and Chan M.M.W., Best Poster - Increased oxidative stress in acute asthma exacerbation in Hong Kong Chinese asthmatics, 12th Medical Research Conference . 2007.

Mak J.C.W., Hui W.S., Ho S.P., So H.L., Chan M.M.W., Lam W.K., Cho C.H. and Ip M.S.M., Best Poster - Systemic oxidative stress and inflammation in cigarette smoke-exposed rat model, 12th Medical Research Conference. 2007.

Mak J.C.W., Oxidative stress in airway diseases, The Research Centre of Heart, Brain, Hormone and Healthy Aging (HBHA). 2007.

Mak J.C.W., Ho S.P., Yu W.C., Choo K.L., Chu C.M., Yew W.W., Lam W.K., Chan M.M.W. and Chan M.M.W., Polymorphisms in MnSOD and catalase genes - functional activity study in smokers with or without COPD., Eur Respir J. 2007, e-pub.

Mak J.C.W., Ko F.W., Chu C.M., Leung C.M., Chan H.W., Cheung A.H.K., Ip M.S.M. and Chan W.M., Polymorphisms in the IL-4, IL-4 receptor alpha chain, TNF-alpha, and lymphotoxin-alpha genes and risk of asthma in Hong Kong Chinese adults, Int Arch Allergy Immunol. 2007, 144: 114-122.

Mak J.C.W., Rat model for studying cigarette smoke-induced lung injury, 2006.

Mak J.C.W., Ho S.P., Leung C.M., Cheung A.H.K., Law K.W., Ip M.S.M. and Chan M.M.W., Relationship between glutathione S-transferase gene polymorphisms and enzyme activity in Hong Kong Chinese asthmatics, American Thoracic Society International Conference, San Francisco, USA. American Journal of Respiratory and Critical Care Medicine. 2007, 175: A461.

Mak J.C.W., Ho S.P., Leung C.M., Cheung A.H.K., Law K.W., So L.K.Y., Chan W.M., Chau C.H., Lam W.K., Ip M.S.M. and Chan W.M., Relationship between glutathione S-transferase gene polymorphisms and enzyme activity in Hong Kong Chinese asthmatics, Clinical and experimental allergy. 2007, 37: 1150-1157.

Pan N.Y., Hui W.S., Tipoe G.L., Taylor G.W., Leung Y.H., Lam W.K., Tsang K.W.T. and Mak J.C.W., Inhibition of pyocyanin-potentiated IL-8 release by steroids in bronchial epithelial cells, Respiratory medicine. 2006, 100(9): 1614-1622.

Yung S.S.Y., Wan C.C., Tsang R.C.W., Mak J.C.W., Tsang K.W.T. and Chan D.T.M., Induction of IL-6 and matrix protein synthesis in human peritoneal mesothelial cells by Pseudomonas aeruginosa exotoxin pyocyanin, Journal of the American Society of Nephrology. 2006, 17: 305A.

Yung S.S.Y., Zhang Q., Tsang R.C.W., Mak J.C.W., Tsang K.W.T. and Chan D.T.M., Induction of interleukin-6 secretion and matrix protein synthesis in human peritoneal mesothelial cells (HPMCs) by Pseudomonas aeruginosa exotoxin pyocyanin, Peritoneal Dialysis International. 2006, 26 (Suppl 2): S22.

Researcher : Mak W

List of Research Outputs

Chan K. .H., Leung S.Y., Cheung R.T.F., Ho S.L. and Mak W., Paraneoplastic motor neuropathy and inflammatory myopathy associated with nasopharyngeal carcinoma., Journal of Neurooncology. 2007, 81: 93-96.

Chan K.H., Mak W. and Ho S.L., Cryptococcal meningitis with raised intracranial pressure masquerading as malignant hypertension, International Journal Infectious Diseases. International Journal Infectious Diseases, 2007, 11(4): 366-7.

Chan K.H., Tsang K.L., Fong C.Y., Ho S.L., Cheung R.T.F. and Mak W., Idiopathic inflammatory demyelinatng disorders after acute transverse myelitis., European Journal of Neurology. 2006, 13(8): 862-8.

Chan K.H., Mak W., Cheung R.T.F. and Ho S.L., Non-thymoma early-onset- and late-onset-generalized myasthenia gravis-A retrospective hospital-based study, Clinical Neurology Neurosurgery. 2007, 109(8): 686-91.

Chan K.H., Leung S.Y., Cheung R.T.F., Ho S.L. and Mak W., Paraneoplastic motor neuropathy and inflammatory myopathy associated with nasopharyngeal carcinoma, J Neurooncol. 2007, 81(1): 93-6.

Chan K.H., Mak W., Cheung R.T.F. and Ho S.L., Patients With Chronic Inflammatory Demyelinating Polyneuropathy And Diabetes Mellitus In Hong Kong Chinese - A Hospital Based Study, Second International Symposium On Healthy Aging. 2007.

Chan K.H., Mak W., Cheung R.T.F. and Ho S.L., Patients with chronic inflammatory demyelinating polyneuropathy and diabetes mellitus in Hong Kong – A hospital based study, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population. 2007, 53.

Cheung R.S.K., Cheung R.T.F., Ho S.L. and Mak W., Mah-jong–induced seizures: case reports and review of twenty-three patients. , Hong Kong Medical Journal. . 2007, 13(4): 314-8.

Fong C.Y., Kwok H.H., Song Y., Cheng T.S., Ho W.L., Chu A.C.Y., Kung M.H.W., Chan K.H., Mak W., Cheung R.T.F., Ramsden D.B. and Ho S.L., Clinical phenotypes of a large Chinese multigenerational kindred with autosomal dominant familial ALS due to Ile149Thr SOD1 gene mutation., Amyotrophic Lateral Sclerosis. 2006, 7(3): 142-149.

Li Y., Chu L.W., Chen Y., Cheung B.M.Y., Leung R.Y., Yik P.Y., Ng K.M.T., Mak W., Jin D., St. George-Hyslop P. and Song Y., Intron 2 (T/C) CYP46 polymorphism is associated with Alzheimer's disease in Chinese patients., Dement Geriatr Cogn Disord 2006. 2006, 22(5-6): 399-404.

Researcher : Man YB

List of Research Outputs

Cheung B.M.Y., Ong K.L., Man Y.B., Lau C.P., Lam K.S.L. and Wong Y.L., Prevalence of the metabolic syndrome in the United States National Health and Nutrition Examination Survey 1999-2002 according to different defining criteria., J Clin Hypertens (Greenwich). 2006, 8(8): 562-70.

Ong K.L., Cheung B.M.Y., Man Y.B., Wong Y.F., Wat N.M.S., Tan K.C.B. and Lam K.S.L., Treatment and control of diabetes mellitus in the United States National Healthy and Nutrition Examination Survey 1999-2002, Journal of Cardiometabolic Syndrome. 2006, 1: 301-7.

Researcher : Mok TMY

List of Research Outputs

Chung H.Y. and Mok T.M.Y., Early Diagnosis of Spondyloarthropathies, The Hong Kong Medical Diary. Hong Kong, 2006, 11(11): 3-5.

Fan R., Mok T.M.Y. and Lau W.C.S., Cost of Mild Systemic Lupus Erythematosus in Hong Kong, The American College of Rhematology Annual Scientific Meeting 10-15 Nov 2006, Washington, DC USA. 2006, 54(9) Supplement: Abstract No.1198.

Jin O., Kavikondala S., Chan W.K., Rong F., Yeung J.S.L., Mok T.M.Y. and Lau W.C.S., Abnormal Plasmacytoid Dendritic Cell Activity in Systemic Lupus Erythematosus, The American College of Rheumatology Annual Scientific Meeting 10-15 Nov 2006, Washington, DC USA 2006. 54(9) Supplement: Abstract No.1095.

Jin O., Kavikondala S., Chan W.K., Rong F., Yeung J.S.L., Mok T.M.Y. and Lau W.C.S., Functional Abnormalities of Myeloid Dendritic Cells in Systemic Lupus Erythematosus, The American College of Rheumatology Annual Scientific Meeting 10-15 Nov 2006, Washington, DC USA. 2006, 54(9) Supplement: Abstract No.1096.

Kavikondala S., Jin O., Chan W.K., Yeung J.S.L., Rong F., Mok T.M.Y. and Lau W.C.S., Dendritic Cells (DCs): Culprits of B-cell Hyper-responsiveness in Lupus, The American College of Rheumatology Annual Scientific Meeting 10-15 Nov 2006, Washington, DC USA. 2006, 54(9) Supplement: Abstract No. 1075.

Lau W.C.S., Yin G. and Mok T.M.Y., Ethnic and Geographical Differences in Systemic Lupus Erythematosus: An Overview, Lupus. England, SAGE Publications, 2006, 15(11): 715-719.

Mok T.M.Y., Advances in the Treatment of Ankylosing Spondylitis, The Hong Kong Medical Diary. Hong Kong, 2006, 11(11): 2.

Mok T.M.Y., Autoantibodies: the key to diagnosis of rheumatic diseases , 12th Annual Scientific Meeting of the Hong Kong Society of Rheumatology . 2006.

Mok T.M.Y., Tsang P.L., Lo Y., Wong R.W.S., Lau W.C.S. and Lam Y.M., Bosentan Use in Systemic Lupus Erythematosus Patients with Pulmonary Arterial Hypertension, Lupus. England, SAGE, 2007, 16(4): 279-285.

Mok T.M.Y., Chan E.Y.T., Wong R.W.S. and Lau W.C.S., Intrathecal Immunoglobulin Production in Patients with Systemic Lupus Erythematosus with Neuropsychiatric Manifestations, Annals of Rheumatic Diseases. 2007, 66: 846-847.

Mok T.M.Y., Intrathecal immunoglobulin production by IgG index and oligoclonal bands in various neuropsychiatric manifestations in systemic lupus erythematosus , Pathology Update 2007. 2007.

Mok T.M.Y., Management of rheumatoid arthritis , Pharmacy Central Education Committee. 2006.

Mok T.M.Y., Ip E.W.K., Lau W.C.S., Lo Y., Wong W.H.S. and Lau Y.L., Mannose-binding lectin and susceptibility to Infection in Chinese patients with systemic lupus erythematosus, Journal of Rheumatology. 2007, 34: 1270-6.

Mok T.M.Y., Wong S.S.Y., Chan D.T.M., Fong D.Y.T., Wong R.W.S. and Lau W.C.S., Non-tuberculous mycobacterial infection in patients with systemic lupus erythematosus, Rheumatology. Switzerland, Karger, 2007, 46(2): 280-284.

Mok T.M.Y., Wong S.S.Y., Chan D.T.M., Fong D.Y., Wong R.W.S. and Lau W.C.S., Non-tuberculous mycobacterial infection in patients with systemic lupus erythematosus, Rheumatology (Oxford). 2007, 46: 280-284.

Mok T.M.Y., Profile of lupus autoantibodies found in Asia, APLAR Journal of Rheumatology. 2006, 9(4): 331-335.

Mok T.M.Y., Rheumatoid problems – the often encountered for general practitioners, Refresher Course for Health Care Providers 2005/6 . 2006.

Mok T.M.Y., Update on pain management in patients with arthritis, University of Hong Kong Health Clinic . 2007.

Rong F., Jin O., Kavikondala S., Chan W.K., Yeung J.S.L., Mok T.M.Y. and Lau W.C.S., Plasmacytoid-Dendritic Cell Induced T Cell Proliferation and Activation: A Potential Role in the Pathogenesis of Rheumatoid Arthritis, The American College of Rheumatology Annual Scientific Meeting 10-15 Nov 2006, Washington, DC USA. 2006, 54(9) Supplement: Abstract No.424.

Researcher : Ng FH

List of Research Outputs

Chan A.O.O., Jim M.H., Lam K.F., Siu D.C.W., Tong S.M., Ng F.H., Wong S.Y., Hui W.M., Lam S.K. and Wong B.C.Y., Aspirin does not prevent recurrence of colorrectal adenomas in patients with coronary artery disease. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A194.

Chan A.O.O., Jim M.H., Lam K.F., Siu D.C.W., Tong S.M., Ng F.H., Wong S.Y., Hui W.M., Chan C.K., Lai K.C., Cheung T.K., Chan P., Wong G., Yuen R.M.F., Lau Y.K., Lee S.W.L., Seto M.L., Lam S.K. and Wong B.C.Y., Patients with coronary artery disease had high prevalanece of colorectal cancer and adenoma: END-results of metabolic syndrome and smoking. Digestive Disease Week 2007, Washington DEc, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A65.

Chan A.O.O., Ng F.H., Chang P.C.M., Wong S.Y., Chu W.M., Yuen W.C., Lau Y.K., Cheung T.K. and Wong B.C.Y., Prevalence and prediction of gastrointestinal events in patients receiving a combination of aspirin plus clopidogrel. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A135.

Chan A.O.O., Loo C.K., Leung C.M., Wong S.Y., Ng F.H., Li M.K.W., Lam K.M., Lam S.K. and Wong B.C.Y., Prevalence of colonic lesions after a negative screening colonscopy in a population with rapidly rising colorectal cancer incidence: A prospective multi-center analysis. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A189.

Researcher : Ng KMT

List of Research Outputs

Li Y., Chu L.W., Chen Y., Cheung B.M.Y., Leung R.Y., Yik P.Y., Ng K.M.T., Mak W., Jin D., St. George-Hyslop P. and Song Y., Intron 2 (T/C) CYP46 polymorphism is associated with Alzheimer's disease in Chinese patients., Dement Geriatr Cogn Disord 2006. 2006, 22(5-6): 399-404.

Researcher : Ng KY

List of Research Outputs

Ng K.Y., Xu A., Lam K.S.L. and Cheung R.T.F., Aggravated cerebral infarction in diabetic mice following photothrombotic ischemia, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population. 2007, 57.

Ng K.Y., Xu A., Lam K.S.L. and Cheung R.T.F., Increased susceptibility of diabetic transgenic mice to photothrombotic stroke, 11th Research Postgraduate Symposium. 2006, 66.

Researcher : Ng MMT

List of Research Outputs

Yip T., Tse K.C., Lam M.F., Cheng S.W., Lui S.L., Tang S.C.W., Li F.K., Wang A.Y.M., Choy C.B.Y., Ng M.M.T., Chan D.T.M., Lai K.N. and Lo W.K., Risk and outcome of peritonitis after flexible colonoscopy in CAPD patient, Peritoneal Dialysis International . 2006, Suppl 26: S68.

Researcher : Ng MY

List of Research Outputs

Lau G., Zhu R., Lei T., Ng M.Y., Luk J.M.C., Sham P., Chiu J.F. and He Q.Y., Identification of biomarkers for the prediction of HBV related HCC by integrated proteomics (Abstract), The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007.

Lau G., Zhu R., Lei T., Ng M.Y., Luk J.M.C., Sham P., Chiu J.F. and He Q.Y., Identification of biomarkers for the prediction of HBV related HCC by integrated proteomics, Hepatology International. 2007, 1(1): 75.

Researcher : Ng MYM

List of Research Outputs

Cheung C.L., Huang Q., Ng M.Y.M., Chan V.N.Y., Sham P.C. and Kung A.W.C., Confirmation of linkage to chromosome 1q for spine bone mineral density in Southern Chinese, 11th Research Postgraduate Symposium, HKU, 7 Dec 2006.

Cheung C.L., Huang Q., Ng M.Y.M., Chan V.N.Y., Sham P.C. and Kung A.W.C., Confirmation of linkage to chromosome 1q for spine bone mineral density in southern Chinese, Human Genetics. 2006, 120: 354-359.

Cheung C.L., Huang Q., Ng M.Y.M., Chan V.N.Y., Sham P.C. and Kung A.W.C., Confirmation of linkage to chromosome 1q for spine bone mineral density in southern Chinese, Journal of Bone and Mineral Research. 2006, 21(Suppl 1): S146.

Huang Q., Ng M.Y.M., Cheung C.L., Chan V.N.Y., Sham P.C. and Kung A.W.C., Identification of two sex-specific quantitative trait loci in chromosome 11q for bone mineral density in southern Chinese, Human Heredity. 2006, 61: 237-243.

Huang Q., Ng M.Y.M., Cheung C.L., Chan V., Sham P.C. and Kung A.W.C., Identification of two sex-specific quantitative trait loci in chromosome 11q for hip bone mineral density in Chinese, Human Heredity. 2006, 61(4): 237-243.

Ioannidis J.P.A., Ng M.Y.M., Sham P.C., Zintzaras E., Lewis C.M., Deng H.W., Econs M.J., Karasik D., Devoto M., Kammerer C.M., Spector T., Andrew T., Cupples L.A., Duncan E.L., Foroud T., Kiel D.P., Koller D., Langdahl B., Mitchell B.D., Peacock M., Recker R., Shen H., Sol-Church K., Spotila L.D., Uitterlinden A.G., Wilson S.G., Kung A.W.C. and Ralston S.H., Meta-analysis of genome-wide scans provides evidence for sex- and site-specific regulation of bone mass, Journal of Bone and Mineral Research. 2007, 22: 173-83.

Lau H.L., Ng M.Y.M., Cheung W.M.W., Paterson A.D., Luk K.D.K., Chan V.N.Y. and Kung A.W.C., Assessment of linkage and association of 13 genetic loci with bone mineral density, J Bone Miner Metab. 2006, 24: 226-34.

Ng M.Y.M., Sham P.C., Paterson A.D., Chan V.N.Y. and Kung A.W.C., Effect of environmental factors and gender on the heritability of bone mineral density and bone size, Ann Hum Genet. 2006, 70: 428-38.

Researcher : Ng YCC

List of Research Outputs

Ng Y.C.C., Yung S.S.Y. and Chan D.T.M., Mycophenolic acid reduces anti-DNA antibody binding and cytokine secretion in renal proximal tubular epithelial cells - implications in lupus nephritis, Lupus. 2007, 16 (S1): 46.

Researcher : Ngai WS

List of Research Outputs

Wong D.K.H., Yuen R.M.F., Ngai W.S., Fung J.Y.Y. and Lai C.L., One-year entecavir or lamivudine therapy results in reduction of HBV intrahepatic covalently closed circular DNA levels, Antivir Ther . 2006, 11: 909-916.

Wong D.K.H., Yuen R.M.F., Ngai W.S., Fung J.Y.Y. and Lai C.L., One-year entecavir or lamivudine therapy results in reduction of hepatitis B virus intrahepatic covalently closed circular DNA levels., Antiviral Therapy. 2006, 11: 909-916.

Yuen R.M.F., Kim J., Kim C.R., Ngai W.S., Yuen J.C.H., Min C., Kang H.M., Shin B.S., Yoo S.D. and Lai C.L., A Randomized Placebo-controlled, Dose-finding Study of Oral LB80380 in HBeAg-positive Patients with Chronic Hepatitis B, Antivir Ther. 2006, 11(8): 977-983.

Researcher : Nie Y

List of Research Outputs

Kavikondala S., Nie Y. and Lau W.C.S., Report on the Second Asia Autoimmunity Forum 3-5 March 2006, Hong Kong, Autoimmunity Reviews. Amsterdam, New York: Elsevier, c2002, 2006, 6(2): 115-118.

Researcher : Ong KL

List of Research Outputs

Cheung B.M.Y., Leung Y.H., Man Y.U. .B.U.N., Ong K.L., Wong L.Y.F., Lau C.P. and Lam K.S.L., Association of Blood Pressure with Polymorphisms in the Quantitative Trait Locus for Abdominal Obesity-Metabolic Syndrome on Chromosome 17, The 21st Scientific Meeting of the International Society of Hypertension 2006.

Cheung B.M.Y. and Ong K.L., Junctional adhesion molecule-1 may have a wider role in cardiovascular disease. , Hypertension. 2007, 50: e22.

Cheung B.M.Y., Ong K.L., Man Y.B., Lau C.P., Lam K.S.L. and Wong Y.L., Prevalence of the metabolic syndrome in the United States National Health and Nutrition Examination Survey 1999-2002 according to different defining criteria., J Clin Hypertens (Greenwich). 2006, 8(8): 562-70.

Cheung B.M.Y., Ong K.L., Man Y.U. .B.U.N., Wong L.Y.F., Lau C.P. and Lam K.S.L., Prevalence, Awareness, Treatment and Control of Hypertension in the United States 1999-2004, The 21st Scientific Meeting of the International Society of Hypertension. 2006.

Ong K.L., Cheung B.M.Y., Man Y.B., Wong L.Y.F., Lau C.P. and Lam K.S.L., Prevalence, awareness, treatment and control of hypertension among United States adults 1999-2004. , Hypertension. 2007, 49: 69-75.

Ong K.L. and Cheung B.M.Y., Response to non-pharmacologic treatment of hypertension: Impact on prevalence estimates., Hypertension. 2007, 50: e2.

Ong K.L., Cheung B.M.Y., Man Y.B., Wong Y.F., Wat N.M.S., Tan K.C.B. and Lam K.S.L., Treatment and control of diabetes mellitus in the United States National Healthy and Nutrition Examination Survey 1999-2002, Journal of Cardiometabolic Syndrome. 2006, 1: 301-7.

Researcher : Ong KL

List of Research Outputs

Cheung B.M.Y. and Ong K.L., Junctional adhesion molecule-1 may have a wider role in cardiovascular disease. , Hypertension. 2007, 50: e22.

Ong K.L. and Cheung B.M.Y., Response to non-pharmacologic treatment of hypertension: Impact on prevalence estimates., Hypertension. 2007, 50: e2.

Researcher : Ong LHY

List of Research Outputs

Chow W.S., Cheung B.M.Y., Xu A., Wat N.M.S., Fong H.Y., Ong L.H.Y., Tam S., Tan K.C.B., Janus E.D., Lam T.H. and Lam K.S.L., Hypoadiponectinemia as a predictor for the development of hypertension: a 5-year prospective study. , Hypertension. 2007, 49: 1455-61.

Researcher : Pan NY

List of Research Outputs

Pan N.Y., Hui W.S., Tipoe G.L., Taylor G.W., Leung Y.H., Lam W.K., Tsang K.W.T. and Mak J.C.W., Inhibition of pyocyanin-potentiated IL-8 release by steroids in bronchial epithelial cells, Respiratory medicine. 2006, 100(9): 1614-1622.

Researcher : Pang AWK

List of Research Outputs

Au W.Y., Lam V.M.S., Pang A.W.K., Lee W.M., Chan L.C., Song Y., Ma E.S.K. and Kwong Y.L., Glucose-6-phosphate dehydrogenase deficiency in female octogenarians, nanogenarians, and centenarians, The Journals of Gerontology Series A: Biological Sciences and Medical Sciences . 2006, 61(10): 1086-1089.

Leung C.K.J., Pang A.W.K., Yuen W.H., Kwong Y.L. and Tse E.W.C., Relationship of Expression of Aquaglyceroporin 9 with Arsenic Uptake and Sensitivity in Leukemia Cells , Blood . 2007, 109: 740-746.

Researcher : Pang RWC

List of Research Outputs

Ho J.W.Y., Pang R.W.C., Lau C.P.Y., Sun K.W., Yu W.C., Fan S.T. and Poon R.T.P., Significance of circulating endothelial progenitor cells in hepatocellular carcinoma, Hepatology. 2006, 44(4): 836-843.

Pang R.W.C. and Poon R.T.P., Angiogenesis and antiangiogenic therapy in hepatocellular carcinoma, Cancer Letters. 2006, 242(2): 151-167.

Pang R.W.C. and Poon R.T.P., Clinical implications of angiogenesis in cancers, Vascular Health and Risk Management. 2006, 2(2): 97-108.

Pang R.W.C., Tse E.W.C. and Poon R.T.P., Molecular pathways in hepatocellular carcinoma, Cancer Letters . 2006, 240(2): 157-169.

Pang R.W.C., Lee K.W., Man K., Poon R.T.P., Fan S.T., Kwong Y.L. and Tse E.W.C., PIN1 expression contributes to hepatic carcinogenesis, Journal of Pathology. 2006, 210(1): 19-25.

Pang R.W.C., Lee K.W., Poon R.T.P., Fan S.T., Wong K.B., Kwong Y.L. and Tse E.W.C., Pin1 interacts with a specific serine-proline motif in hepatitis B virus X-protein to enhance hepatocarcinogenesis, Gastroenterology. 2007, 132(3): 1088-1103.

Pang R.W.C., Poon R.T.P., Fan S.T., Kwong Y.L. and Tse E.W.C., Pin1: a novel regulator of tumor angiogenesis and invasiveness in hepatocellular carcinoma (Abstract), The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007. Hepatology International. 2007, 1(1): 143.

Pang R.W.C., Poon R.T.P., Fan S.T., Kwong Y.L. and Tse E.W.C., Pin1: a novel regulator of tumor angiogenesis and invasiveness in hepatocellular carcinoma (Abstract), The American Association for Cancer Research Annual Meeting 2007, Los Angeles, U.S.A., 14 - 18 April 2007.

Poon R.T.P., Ng K.K.C., Tso W.K., Woo R., Pang R.W.C., Tai K.S. and Fan S.T., A phase I/II trial of transarterial chemoembolization for hepatocellular carcinoma using a novel intrarterial drug eluting beads (Abstract), The 5th International Hepatocellular Carcinoma Meeting: Eastern and Western Experiences, Houston, USA, 11 - 13 January 2007.

Poon R.T.P., Lau C.P.Y., Pang R.W.C., Ng K.K.C., Yuen J.H.F. and Fan S.T., High serum vascular endothelial growth factor levels predict poor prognosis after radiofrequency ablation of hepatocellular carcinoma: importance of tumor biomarker in ablative therapies, Annals of Surgical Oncology. 2007, 14(6): 1835-1845.

Researcher : Qiao L

Project Title:	Simultaneous activation of PPARgamma and inhibition of XIAP in human colorectal cancer cells: effects on apoptosis and angiogenesis
Investigator(s):	Qiao L, Wong BCY
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	05/2006

Abstract:

Colorectal cancer (CRC) is the fourth most common malignancies world wide. The estimated annual incidence of CRC is 1 million cases. Although the highest incidences of CRC are in developed countries such North America, Australia/New Zealand, Western Europe, and Japan, its incidence is rapidly increasing in countries where overall risk was formerly low. In China, the incidence of CRC has increased from sixth in 1970s to third in 1990s, with the current estimated annual cancer-related death rate being 10.25/100,000, ranking it the fifth leading cause of cancer mortality in China. In Hong Kong, CRC now represents the second most common malignancies and the third most common causes of cancer-related death in this region. Among the all CRC cases, more than 70% are sporadic, making the screening and prevention difficult. The efficacy of current chemopreventive measures and treatment options for CRC are rather disappointing. In order to develop new chemopreventive and therapeutic approaches for CRC, it is critical to better understand the molecular mechanisms involved in some of the key processes of cancer development and progression including cell proliferation, angiogenesis, and apoptosis. As apoptosis is the major mode of cell death in cancer therapy, targeting apoptosis is a promising strategy for cancer therapy. Apoptosis is a complex process and is tightly regulated by many pro- and anti-apoptotic genes. XIAP and PPARgamma are two molecules that are potentially useful in modulating apoptosis in cancer cells. XIAP (X-linked inhibitor of apoptosis protein) is one of the most potent endogenous inhibitors of apoptosis. It is over-expressed in many cancers. Inhibition of XIAP sensitizes certain cancer cells to apoptosis and leads to reduced tumorigenicity. Therefore, XIAP is regarded as a principal inhibitor of apoptosis in many cancers, and has become a potential target in cancer gene therapy. PPAR (Peroxisome proliferator-activated receptor) is a family of nuclear receptors that act as transcription factors. PPARgamma has been implicated as a strong activator for apoptosis in many cancers including CRC. Abundant PPARgamma is expressed in normal tissues whereas in certain cancers such as HCC and gastric cancers, its expression is significantly lower than in their normal counterparts. PPARgamma activation has been shown as a promising chemopreventive measure in many cancers including colon, skin, lung, brain, liver, and gastric cancers. In vitro studies have shown that ligand-induced activation of PPARgamma inhibits cell growth, induces apoptosis and promotes differentiation in several solid cancers including CRC and HCC cells. PPARgamma agonists are also able to reduce the colonic inflammation and chemically-induced precursor lesions of CRC. However, totally contradictory results have been published in terms of the role of PPARgamma in cancer cells. In CRC, activation of PPARgamma was found to promote cancer cell growth. Down-regulation of PPARgamma by PPARgamma-siRNA or its chemical inhibitor T0070907 could potently cause apoptosis in HCC cells. Activation of PPARgamma stimulates the production of hepatocyte growth factor, a mitogen for HCC. Further, recent phase II clinical trials with thiazolidenediones (Rosiglitazone in liposarcoma patients and Troglitazone in metastatic CRC) did not show any significant efficacy. Therefore, the exact role of PPARgamma in the pathogenesis of CRC remains controversial, and the potential use of PPARgamma agonists as a chemopreventive and a therapeutic agent for CRC still requires further clarification. THE PURPOSE OF THE PROPOSED PROJECT In this proposal, we sought to explore the feasibility of simultaneously targeting XIAP and PPARgamma in CRC cells, and investigate whether such a manipulation can sensitize CRC cells to therapeutic agents-induced cell killing, and if so, what are the underlying molecular mechanisms? The ultimate purpose of this study is to find out whether simultaneous activation of PPARgamma and inhibition of XIAP would be an appropriate approach in the control of CRC growth. KEY ISSUES AND PROBLEMS BEING ADDRESSED In this proposal, we will try to address the following key issues: 1. What are the expression profiles of XIAP and PPARgamma in CRC cells? 2. Does simultaneous inhibition of XIAP and activation of PPARgamma exert anti-apoptotic and anti-angiogeneic effects on CRC? If so, what are the underlying molecular mechanisms? 3. What are the natural interactions between these two proteins?

List of Research Outputs

Dai Y., Qiao L., Gu Q., Xia H.H.X., Cheung T.K., Ma J., Zou B. and Wong B.C.Y., Activation of Pparc and inhibition of Xiap in human cancer cells: Synergistic effects on cell proliferation, apoptosis, and tumorigensis. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A425.

Li Y.M., Praseedom R.K., Butler, A. and Zhou L.G., Qiao L., Cyclooxygenase-2 inhibitor and gastric cancer, COX-2 Inhibitor Research . Nova Science, 2006, 1.

Liu Q., Song Y., Zhou Y. and Qiao L., Bicyclol: a useful agent for chemoprevention of hepatocellular carcinoma? , Cancer Biol Ther . 2006, 5: 1674-6.

Ma J., Chen M.H., Dai Y. and Qiao L., Enhancing The Efficacy Of Photodynamic Therapy By A Chinese Herbal Medicine For Hepatocellular Carcinoma, In: Editor-in-chief, Wafik S. El-Deiry, M.D., Ph.D.University of Pennsylvania Philadelphia, PA , Cancer Biology & Therapy. USA, Cancer Biol. Ther., 2006, 5: 1117-1119.

Nan Y.M., Yu J. and Qiao L., Role of FasL and Fas in the induction of apoptosis in Non-alcoholic Steatohepatitis., In: 12, Chinese J Digestive Diseases . 2006, 12: 432.

Qi R., Gu J., Zhang Z., Yang K., Li B., Fan J., Wang C., He Z., Qiao L., Lin Z. and Liu X.Y., Potent antitumor efficacy of XAF1 delivered by conditionally replicative adenovirus vector via caspase-independent apoptosis, Cancer Gene Ther. 2007, 14: 82-90.

Qiao L., HBV and HCC: Epidemiology and chemoprevention, In: Invited speaker, The Hepatology Workshop, Hainan Medical College, Hai Kou, China. 2006.

Qiao L., HBV-induced Hepatocellular Carcinoma, HBV-induced Hepatocellular Carcinoma. The First Hebei International Workshop on Hepatology, September 27-29, Shihiazhuang, China. 2006.

Qiao L., Gu Q., Dai Y., Shen Z., Liu X., Ma J. and Wong B.C.Y., XAF1 inhibits angiogenesis of mouse endothelia cells. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A638.

Yacoub A., Miller A., Caron R.W., Qiao L., Curiel D.A., Fisher P.B., Hagan M.P., Grant S. and Dent P., Radiotherapy-induced signal transduction. Endocrine-Related Cancer, Endocrine-Related Cancer . 2006, 13: S99-S114.

Zhou Y., Ran J., Tang C., Wu J., Honghua L., Xingwen L., Ning C. and Qiao L., Effect of Celecoxib on E-cadherin, VEGF, microvessel density, and apoptosis in gastric cancer, Cancer Biology & Therapy. 2007, 26: 269-75.

Researcher : Ren Y

Project Title:	Proteomics computational analysis of Severe Acute Respiratory Syndrome
Investigator(s):	Ren Y, Tam PKH, Peiris JSM, He Q
Department:	Surgery
Source(s) of Funding:	VCO SARS Research Fund
Start Date:	07/2003

Abstract:

To investigate by using proteomics approach, combining Western blotting and ELISA: (a) identification of specific pattern in serum for the diagnosis and prognosis, (b) detection of immune-relevant proteins in SARS, (c) detection of proteins in different stages of SARS patients, (d) proteome analysis of SCV (proteome maps), (e) detection of expression patterns in virus infected cells.

Researcher : Rong R

List of Research Outputs

Rong R., Tao Y., Cheung B.M.Y., Xu A., Cheng K.Y. and Lam K.S.L., Identification and functional characterization of three novel human melanocortin-4 receptor gene variants in an obese Chinese population. , Clinical Endocrinology. 2006, 65: 198-205.

Tso A.W.K., Sham P.C., Wat N.M.S., Xu A., Cheung B.M.Y., Rong R., Fong H.Y., Xu J., Cheng K.Y., Janus E.D. and Lam K.S.L., Polymorphisms of the gene encoding adiponectin and glycaemic outcome of Chinese subjects with impaired glucose tolerance: a 5-year follow-up study, Diabetologia. 2006, 49: 1806-15.

Researcher : Rong R

List of Research Outputs

Researcher : Shek SYN

List of Research Outputs

Shek S.Y.N., Yu C.S., Yeung C.K., Kono T. and Chan H.H.L., Non-invasive body contouring with focused ultrasound technology., Lasers in Surgery and Medicine. 2007, S19: 60.

Shek S.Y.N., Yu C.S., Yeung C.K., Kono T. and Chan H.H.L., Non-thermal blue and near-infrared light system with glycolic acid peels and topical vitamin C for photorejuvenation., Lasers in Surgery and Medicine. 2007, S19: 252.

Shek S.Y.N., Yu C.S., Yeung C.K., Kono T. and Chan H.H.L., Treatment of pigmented lesions by Starlux-V handpiece., Lasers in Surgery and Medicine. 2007, S19: 253.

Yeung C.K., Shek S.Y.N., Pjerring P., Yu C.S., Kono T. and Chan H.H.L., A comparative study of intense pulsed light alone and its combination with photodynamic therapy for the treatment of facial acne in Asian skin, Lasers in Surgery and Medicine. 2007, 39(1): 1-6.

Yeung C.K., Shek S.Y.N., Yu C.S. and Chan H.H.L., Treatment of facial acne with 1450nm diode laser in Asians., Lasers in Surgery and Medicine. 2007, S19: 69.

Yu C.S., Shek S.Y.N., Yeung C.K., Kono T. and Chan H.H.L., Combined infrared light and bipolar radiofrequency for skin tightening in Asians., Lasers in Surgery and Medicine. 2007, S19: 65.

Researcher : Shen J

Project Title:	Effects of Buyang Huanwu Decoction on neuronal regeneration after ischemic brain injury
Investigator(s):	Shen J, Fung PCW
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2004

Abstract:

To evaluate the effects of Buyang Huanwu Decoction, a classical formula of Traditional Chinese Medicine (TCM), and its major component Astragalus membranaceus on the regeneration of neurons after ischemic brain injury.

Project Title:	Plasma membrane cholesterol homeostasis and oxidative stress: implication for neuronal oxidative damage in ischemia stroke
Investigator(s):	Shen J, Cheung RTF, Fung PCW
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2005
Completion Date:	12/2006

Abstract:

To investigate the reole of plasma membrane cholesterol in regulating cellular oxygen supply and ROS production in MCAO ischemia-reperfused model; to investigate which cholesterol pools, free cholesterol, choelsterol ester or oxysterols, would aggravate neuronal oxidative damage in ischemia-reperfused neuronal cells; to test the hypothesis that caveolin-1 may be a important target protein linking with neuronal oxidative damage and abnormal choletserol metabolism.

List of Research Outputs

Lu G., Shen J., You W.L., Fung P.C.W. and Chu K.W., Relationship between Apoptosis and Ultrastructure of Mitochondria of Colorectal Cancer, Chinese Journal of Misdiagnosis. 2006, 6(17): 3277-3279.

Lu G., You W.L., Zhang D.H., Shen J., Fung P.C.W. and Chu K.W., Sampling details when researching the ultrastructure of mitochondria of colorectal cancer, Modern Medicine & Pharmacy. 2006, 16(4): 1-2.

Researcher : Shiu SWM

List of Research Outputs

Shiu S.W.M. and Tan K.C.B., Effects of advanced glycation end products on caveolin-1 and endothelial nitric oxide synthase in endothelial cells, Fourth International Huaxia congress of Endocrinology, Hong Kong, Dec 2006.

Tan K.C.B., Shiu S.W.M., Chow W.S., Wong Y., Bucala R. and Betteridge D.J., Arterial stiffness and advanced glycation end products in type 2 diabetes mellitus, The International Diabetes Federation 19th World Diabetes Congress, Cape Town, Dec 2006.

Tan K.C.B., Shiu S.W.M., Chow W.S., Leng L., Bucala R. and Betteridge D.J., Association between serum levels of soluble receptor for advanced glycation end products and circulating advanced glycation end products in type 2 diabetes, Diabetologia. 2006, 49: 2756-62.

Zhou H., Shiu S.W.M., Wong Y. and Tan K.C.B., Impaired serum cholesterol efflux potential is associated with endothelial dysfunction in type 2 diabetes patients, Fourth International Huaxia congress of Endocrinology, Hong Kong, Dec 2006.

Researcher : Shiu WMS

List of Research Outputs

Shiu W.M.S., Huang Y., Wong Y. and Tan K.C.B., Type 2 diabetes and endothelial lipase, Second International Symposium on Healthy Aging, Mar 2007, Hong Kong. 2007.

Tan K.C.B., Shiu W.M.S., Wong Y., Tam S. and Bucala R., Increased serum soluble lectin-like oxidized LDL receptor-1 level in type 2 diabetes is associated with circulating advanced glycation end products, The Endocrine Society’s 89th Annual Meeting, June 2007, Toronto. 2007.

Researcher : Siu CWD

List of Research Outputs

Ho H.H., Siu C.W.D., Jim M.H., Miu K.M., Chan R.H.W., Lee S.W.L., Lau C.P. and Tse H.F., Leukocytosis and clinical outcomes in acute inferior myocardial infarction, Int J Cardiol. 2006, 118(2): 278-9.

Hu R., Siu C.W.D., Wang W.Q., Lau C.P. and Tse H.F., Impaired nitrate-mediated dilatation could reflect nitrate tolerance in patients with coronary artery disease, Int J Cardiol. 2006, 120(3): 351-6.

Siu C.W.D., Cheng L.C., Woo P.C., Lau C.P. and Tse H.F., A patient with relapsing pacemaker infection due to "Gram-positive bacilli"., Int J Cardiol. 2007, 114(2): E40-1.

Siu C.W.D., Tse H.F. and Lau C.P., Avoidance of electromagnetic interference to implantable cardiovertor-defibrillator during atrioventricular node ablation for atrial fibrillation using transvenous cryoablation, Pacing Clin Electrophysiology. 2006, 29(8): 914-6.

Siu C.W.D., Tse H.F., Lee K.L.F., Chan R.H.W., Chen W.H., Yung C., Lee S.W.L. and Lau C.P., Cardiac resynchronization therapy optimization by ultrasonic cardiac output monitoring (USCOM) device, Pacing Clin Electrophysiology. 2007, 30: 50-55.

Siu C.W.D., Au W.Y., Yung C.Y., Kumana C.R., Lau C.P., Kwong Y.L. and Tse H.F., Effects of oral arsenic trioxide therapy on QT intervals in patients with acute promyelocytic leukemia: implications on long-term cardiac safety, Blood. 2006, 108(1): 103-106.

Siu C.W.D., Zhang X., Yung C., Kung A.W.C., Lau C.P. and Tse H.F., Hemodynamic Changes in Hyperthyroidism Related Pulmonary Hypertension: A Prospective Echocardiographic study, J Clin Endocrinol Metab. 2007, 92(5): 1736-42.

Siu C.W.D., Yeung C.Y., Lau C.P., Kung A.W.C. and Tse H.F., Incidence, clinical characteristics and outcome of congestive heart failure as the initial presentation in patients with primary hyperthyroidism, Heart. 2007, 93 (4): 483-7.

Siu C.W.D., Jim M.H., Ho H.H., Miu R., Lee S.W., Lau C.P. and Tse H.F., Transient Atrial Fibrillation Complicating Acute Inferior Myocardial Infarction: Implications for Future Risk of Ischemic Stroke. , Chest. 2007, 132(1): 44-9.

Tse H.F., Siu C.W.D., Zhu S., Liao S., Zhang Q.Y., Lai K.W.H., Nicholls J.M. and Tse H.F., Paracrine effects of direct intramyocardial implantation of bone marrow derived cells for enhancement of neovascularization in chronic ischemic myocardium, European Journal Heart Fail. 2007, 9(8): 747-53.

Xue T., Siu C.W.D., Lieu D.K., Lau C.P., Tse H.F. and Li R.A., Mechanistic role of I(f) revealed by induction of ventricular automaticity by somatic gene transfer of gating-engineered pacemaker (HCN) channels., Circulation. 2007, 115(14): 1839-1850.

Yiu K.H., Siu C.W.D., Lee K.L.F., Lau C.P., Lee S.W.L., Fong D.Y.T. and Tse H.F., Emerging trends of community acquired infective endocarditis. , Int Cardiol J . 2006, 121(1): 119-22.

Researcher : Siu DCW

List of Research Outputs

Siu D.C.W., Zhang X., Yung C., Kung A.W.C., Lau C.P. and Tse H.F., Hemodynamic changes in hyperthyroidism-related pulmonary hypertension: a prospective echocardiographic study, Journal of Clinical Endocrinology & Metabolism. 2007, 92: 1736-42.

Researcher : Sun H

List of Research Outputs

Deng X., Sun H., Lau C.P. and Li G.R., Properties of ion channels in rabbit mesenchymal stem cells from bone marrow , Biochem Biophys Res Commun. 2006, 348(1): 301-309.

Gao Z., Sun H., Lau C.P., Fung P.C.W. and Li G.R., Evidence for cystic fibrosis transmembrane conductance regulator chloride current in swine ventricular myocytes, J Mol Cell Cardiol. 2007, 42(1): 98-105.

Li G.R., Sun H., Chiu S.W. and Lau C.P., The n-3 polyunsaturated fatty acids from fish oil inhibit transient outward and ultra-rapid delayed rectifier potassium currents and voltage-gated sodium current in human atrial myocytes, CardioRhythm-2007/Europace, Hong Kong. 2007, 9(supple 1): 25.

Liu H., Jin M.W., Xiang J.Z., Huang Y., Sun H., Chiu S.W., Lau C.P. and Li G.R., Raloxifene inhibits transient outward and ultra-rapid delayed rectifier potassium currents in human atrial myocytes, Eur J Pharmacol. 2007, 563(1-3): 61-8.

Liu H., Sun H., Lau C.P. and Li G.R., Regulation of voltage-gated cardiac sodium current by epidermal growth factor receptor kinase in guinea pig ventricular myocytes. , J Mol Cell Cardiol. 2007, 42(4): 760-8.

Liu H., Sun H., Lau C.P. and Li G.R., Regulation of voltage-gated cardiac sodium current by epidermal growth factor receptor kinase in guinea pig ventricular myocytes, J Mol Cell Cardiol . 2006, 2007, 42(4): 760-768.

Researcher : Sun JZ

List of Research Outputs

Au W.Y., Ho J.C.M., Lie A.K.W., Sun J.Z., Zheng L., Liang R.H.S., Lam W.K. and Tsang K.W.T., A prospective study of respiratory ciliary structure and function after stem cell transplantation, Bone Marrow Transplantation. 2006, 38: 243-248.

Researcher : Sun Y

List of Research Outputs

Chan A.O.O., Chu K.M., Huang C.Y., Lam K.F., Leung S.Y., Sun Y., Ko S., Xia H.H.X., Cho C.H., Hui W.M., Lam S.K. and Rashid A., Association between Helicobacter pylori infection and interleukin 1beta polymorphism predispose to CpG island methylation in gastric cancer, GUT. 2007, 56: 595-597.

Yu L., Wang J., Zou B., Lin M.C., Wu Y.L., Xia H.H.X., Sun Y., Gu Q., He H., Lam S.K., Kung H.F. and Wong B.C.Y., XAF1 Mediates Apoptosis Through an Extracellular Signal-Regulated Kinase Pathway in Colon Cancer , Cancer. 2007, 109(10): 1996-2003.

Zou B., Chim J.C.S., Zeng H., Leung S.Y., Yang Y., Tu S., Lin M.C., Wang J., He H., Jiang S.H., Sun Y., Yu L., Yuen S.T., Kung H.F. and Wong B.C.Y., Correlation Between the Single-site CpG Methylation and Expression Silencing of the XAF1 Gene in Human Gastric and Colon Cancers, Gastroenterology. 2006, 131(6): 1835-1843.

Researcher : Tam KH

List of Research Outputs

Cheung M.S., Tam K.H., Chow C.H., Verfaillie C.M. and Liang R.H.S., All-trans retinoic acid induces proliferation of an irradiated stem cell supporting stromal cell line AFT024., Experimental Hematology. 2007, 35: 56-63.

Researcher : Tam S

List of Research Outputs

Cheung B.M.Y., Wat N.M.S., Man Y.B., Tam S., Cheng C.H., Leung G.M., Woo J., Janus E.D., Lau C.P., Lam T.H. and Lam K.S.L., Predictors of the development of hypertension in the Hong Kong cardiovascular risk factor prevalence study-2 (CRISPS2), The 21st Scientific Meeting of the International Society of Hypertension. 2006.

Cheung B.M.Y., Wat N.M.S., Man Y.U. .B.U.N., Tam S., Cheng C.H., Leung G.M., Woo J.E.A.N., Janus E.D.W.A.R.D. .D., Lau C.P., Lam T.H. and Lam K.S.L., Waist Circumference as a Predictor of Cardiovascular Risk in the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS2), The 21st Scientific Meeting of the International Society of Hypertension. 2006.

Chow W.S., Cheung B.M.Y., Xu A., Wat N.M.S., Fong H.Y., Ong L.H.Y., Tam S., Tan K.C.B., Janus E.D., Lam T.H. and Lam K.S.L., Hypoadiponectinemia as a predictor for the development of hypertension: a 5-year prospective study. , Hypertension. 2007, 49: 1455-61.

Hoo R.L.C., Chow W.S., Yau M.H., Xu A., Tse H.F., Tso A.W.K., Fong H.Y., Tam S., Chan L. and Lam K.S.L., PPAR-γ agonist induced-suppression of plasminogen activator inhibitor-1 production is mediated through adiponectin. , 2nd International Symposium on Healthy Aging, 3-4 March 2007, Hong Kong. 2007.

Hoo R.L.C., Chow W.S., Tse H.F., Fong H.Y., Tam S., Chan L.C.B. and Lam K.S.L., Ppar-γ Agonist Induced-suppression Of Plasminogen Activator Inhibitor-1 Production Is Mediated Through Adiponectin. , HBHA conference. 2007.

Tan K.C.B., Shiu W.M.S., Wong Y., Tam S. and Bucala R., Increased serum soluble lectin-like oxidized LDL receptor-1 level in type 2 diabetes is associated with circulating advanced glycation end products, The Endocrine Society’s 89th Annual Meeting, June 2007, Toronto. 2007.

Tso A.W.K., Wat N.M.S., Xu A., Tam S., Fong H.Y., Janus E.D., Tan K.C.B. and Lam K.S.L., Adiponectin/C-reactive protein ratio is an independent surrogate marker predictive of the development of metabolic risks and the metabolic syndrome over 5 years in Chinese, The 6th International Diabetes Federation Western Pacific Region Congress, Bangkok. 2006.

Wat W.Z.M., Leung J.Y.Y., Tam S. and Kung A.W.C., The prevalence and impact of vitamin D insufficiency in ambulatory southern Chinese adults, Annals of Nutrition and Metabolism. 2007, 51: 59-64.

Researcher : Tan KCB

Project Title:	Advanced glycation end products and diabetic complications
Investigator(s):	Tan KCB
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	12/2002

Abstract:

Hyperglycaemia leading to the increased formation and accumulation of advanced glycation end products (AGEs) has been implicated in causing many of the complications of diabetes. In this project, the research team plan to explore the underlying mechanisms whereby AGEs may cause defective endothelium-dependent vasodilation.

Project Title:	Endothelial lipase activity in diabetes
Investigator(s):	Tan KCB
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004
Completion Date:	10/2006

Abstract:

To determine whether the expression of EL is increased in diabetes; to investigate the regulation of EL in vitro.

Project Title:	HDL dysfunction and diabetes mellitus
Investigator(s):	Tan KCB
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	12/2005

Abstract:

Background Epidemiological studies have shown that plasma HDL cholesterol levels are strongly inversely associated with cardiovascular disease and HDL is thought to play a protective role against atherosclerosis. The antiatherogenic properties of HDL include promotion of cellular cholesterol efflux and reverse cholesterol transport, as well as antioxidant, anti-inflammatory and anticoagulant properties (1). In addition to promoting efflux of excess cholesterol from cells in the arterial wall and returning cholesterol to the liver for excretion into the bile, HDL inhibits lipid oxidation, reduces the inflammatory response of endothelial cells, promotes the availability of nitric oxide, and inhibits the coagulation pathway. The magnitude of these protective effects of HDL are determined not only by its circulating levels, but also in part by the qualitative function of the HDL species (1,2), and compositional changes in HDL can result in a loss of many of its antiatherogenic properties (3). Functional assays have recently been developed to determine the antiatherogenic profile of an individual’s HDL by measuring the ability of HDL to inactivate and/or to prevent the formation of oxidized lipids (4). HDL dysfunction has been reported in subjects with coronary heart disease (5) and we have recently demonstrated HDL dysfunction in subjects with obstructive sleep apnoea (6). Problems to be addressed and objectives: Patients with type 2 diabetes mellitus frequently have low HDL cholesterol levels and studies involving small number of diabetic subjects have suggested that HDL is dysfunctional in diabetes mellitus. Gowri et al showed that HDL2 exhibited decreased protection against THP1 macrophage-mediated LDL oxidation in 10 poorly controlled type 2 diabetic patients (7), whereas Nobecourt et al reported that it was the antioxidative activity of small dense HDL3 (and not HDL2) that was deficient in 20 well-controlled type 2 diabetic patients (8). What accounts for the observed differences between these studies is not clear and whether HDL dysfunction is related to glycaemic control and/or to the presence of diabetic complications has not been investigated. Functional abnormalities in HDL have also been described in non-diabetic patients with chronic kidney disease (9). Hence, the objectives of this study are (i) to determine whether HDL dysfunction is related to the presence of diabetic nephropathy (both incipient and overt) and its association with the degree of albuminuria. If HDL dysfunction is found to relate to the severity of diabetic nephropathy, does HDL dysfunction improve when diabetic nephropathy is being treated with agents that block the renin-angiotensin system? (ii) Is HDL dysfunction more severe in poorly controlled type 2 diabetic patients? Can it be reversed by improving glycaemic control and is HDL dysfunction due to abnormalities in the intrinsic physicochemical properties of HDL and/or to changes in HDL associated enzymes such as paraoxonase and platelet-activating factor acetylhydrolase which are involved in catalyzing the breakdown of oxidized phospholipids? References: 1) Wang M, Briggs MR. HDL: The metabolism, function, and the therapeutic importance. Chem Rev 2004;104:119-37 2) Rohrer L, Hersberger M, von Eckardstein A. High density lipoproteins in the intersection of diabetes mellitus, inflammation and cardiovascular disease. Curr Opin Lipidol. 2004;15:269-78. 3) Van Lenten BJ, Hama SY, de Beer FC et al. Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response. Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures. J Clin Invest. 1995;96:2758-67. 4) Navab M, Hama SY, Hough GP et al. A cell-free assay for detecting HDL that is dysfunctional in preventing the formation of or inactivating oxidized phospholipids. J Lipid Res. 2001;42:1308-17. 5) Ansell BJ, Navab M, Hama S et al. Inflammatory/antiinflammatory properties of high-density lipoprotein distinguish patients from control subjects better than high-density lipoprotein cholesterol levels and are favorably affected by simvastatin treatment. Circulation. 2003;108:2751-6. 6) Tan KCB, Chow WS, Lam JCM et al. HDL dysfunction in obstructive sleep apnea. Atherosclerosis, in press. 7) Gowri MS, Van der Westhuyzen DR, Bridges SR, Anderson JW. Decreased protection by HDL from porly controlled type 2 diabetic subjects against LDL oxidation may be due to the abnormal composition of HDL. Arterioscler Thromb Vasc Biol. 1999;19:2226-2233. 8) Nobecourt E, Jacqueminet S, Hansel B et al. Defective antioxidative activity of small dense HDL3 particles in type 2 diabetes: relationship to elevated oxidative stress and hyperglycaemia. Diabetologia. 2005;48:529-538. 9) Kaysen GA, Eiserich JP. The role of oxidative stress-altered lipoprotein structure and function and microinflammation on cardiovascular risk in patients with minor renal dysfunction, J Am Soc Nephrol 2004;15:538-548.

Project Title:	Glycosidized LDL and atherosclerosis
Investigator(s):	Tan KCB, Tam S
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	12/2005

Abstract:

To investigate the effects of glycosidized LDL on foam cell formation and reverse cholesterol transport; to evaluate glycosidized LDL as an inflammatory stimulus; to test clinical strategies to lower glycosidized LDL.

Project Title:	Adenosine triphosphate-binding cassette transporters and cholesterol efflux in diabetes
Investigator(s):	Tan KCB
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	10/2006

Abstract:

A low high density lipoprotein (HDL) level is an important risk factor for coronary heart disease and HDL plays a protective role against atherosclerosis by promoting cellular cholesterol efflux and reverse cholesterol transport (RCT). Reverse cholesterol transport is a pathway which transports cholesterol from extrahepatic cells and tissues to the liver for excretion, and consists of multiple steps involving a number of HDL subclasses, lipolytic enzymes, lipid transfer proteins, cellular receptors and transporters [1]. Efflux of cholesterol from macrophages is particularly important with regard to atherosclerosis and is mediated by lipid transporters/receptors including adenosine triphosphate-binding cassette transporters (ATP-binding cassette transporters) and scavenger receptor class B, type 1 (SR-B1) [2]. The recent discovery that mutations in the human ATP-binding cassette transporter ABCA1 gene are the underlying molecular defect in HDL deficiency syndromes such as Tangier disease has improved our understanding of the role of lipid transporters in RCT [3,4]. Targeted disruption of ABCA1 results in a virtual absence of HDL cholesterol while ABCA1 overexpression increases HDL levels [2-4]. ABCA1 mainly mediates the efflux of cholesterol from cells to apolipoprotein (apo) A1 and a newly discovered ATP-binding cassette transporters ABCG1 has been shown to mediate net mass efflux of cellular cholesterol to mature HDL but not to lipid-poor apo A1 [4,5]. ABCG1 knockout mice have marked macrophage cholesterol accumulation whereas ABCG1 overexpression protects tissues from cholesterol accumulation [6]There are recent data suggesting that ABCA1-mediated cholesterol efflux may be impaired in diabetes mellitus. Due to hyperglycaemia and enhanced oxidative stress, there is increased formation of advanced glycation end products in diabetes and Passarelli et al have shown that the advanced glycation end product precursors impair ABCA1-dependent cholesterol removal from cells in vitro [7]. Albrecht et al have reported that leucocyte ABCA1 gene expression was inversely associated with indices of glycemia in non-diabetic normoglycemic men in vivo [8]. Taken together, these data suggest that ABCA1-mediated cholesterol efflux may potentially be abnormal in diabetes mellitus. Whether ABCG1-mediated cholesterol efflux is similarly affected is not known. The rate of cellular cholesterol efflux is dependent not only on the lipid transporters but also on the availability of acceptors of cholesterol in the circulation. Plasma HDL has in the past been viewed as a universal plasma acceptor lipoprotein for cholesterol removed from cells. However, it is increasingly being recognized that plasma level of HDL cholesterol or apolipoprotein (apo) AI per se does not reflect the capacity or efficiency of cholesterol efflux [9]. For instance, in patients with type IIb and type IV hypertriglyceridaemia associated with low HDL, it has been shown that the capacity of sera from these subjects to induce efflux of cholesterol from SR-B1 rich Fu5AH cells was not reduced and type IV patients' sera in fact induced a markedly higher increase in ABCA1-mediated efflux compared to that of control [10]. The regulation of cholesterol efflux in vivo remains poorly understood. Despite the high cardiovascular risk in patients with diabetes, current knowledge about abnormalities in cholesterol efflux in diabetes is limited. De Vries et al reported that in type 1 diabetic patients with moderate hypercholesterolaemia, the capacity of plasma to induce cholesterol efflux out of Fu5AH cells via SR-B1 and out of fibroblasts expressing ABCA1 was enhanced. The relatively higher stimulatory effect of diabetic plasma on cholesterol efflux out of Fu5AH cells compared to fibroblasts suggested that plasma from type 1 diabetic patients predominantly enhanced SR-B1-mediated efflux [11]. On the other hand, in type 2 diabetes, Syvanne et al demonstrated that cholesterol efflux from Fu5AH cells induced by plasma was impaired in diabetic patients with coronary heart disease [12]. There are no data on whether ABCA1 or ABCG1-mediated cholesterol efflux is abnormal in type 2 diabetes or whether it is in fact enhanced to compensate for the reduction in the SR-B1 pathway. The objectives of this study are: 1) to investigate whether monoctye/macrophage ABCA1 and ABCG1 expression is reduced in patients with type 2 diabetes and its relationship to hyperglycaemia; 2) to determine whether there are changes in the capacity of plasma to induce cholesterol efflux via ABCA1 and ABCG1 in type 2 diabetic patients with normoalbuminuria; and 3) to investigate the relationship between cellular cholesterol efflux to plasma and the severity of diabetic nephropathy and proteinuria. A recent study has shown that in non-diabetic subjects with proteinuria, cellular cholesterol efflux via ABCA1 was increased and might potentially attenuate the cardiovascular risk associated with proteinuria [13]. We have preliminary data showing that plasma cholesterol efflux from Fu5AH cells mediated by SR-B1 is impaired in type 2 diabetic patients with microalbuminuria and it is therefore important to determine whether there are changes in ABCA1 and ABCG1-mediated efflux in diabetic nephropathy.References1) Lewis GF, Rader DJ. New insights into the regulation of HDL metabolism and reverse cholesterol transport. Circ Res. 2005;96:1221-32 2) Van Eck M, Pennings M, Hoekstra M, Out R, et al. Scavenger receptor BI and ATP-binding cassette transporter A1 in reverse cholesterol transport and atherosclerosis. Curr Opin Lipidol. 2005;16:307-15.3) van Eck M, Bos IS, Kaminski WE et al. Leukocyte ABCA1 controls susceptibility to atherosclerosis and macrophage recruitment into tissues. Proc Natl Acad Sci U S A. 2002;99:6298-3034) Wang N & Tall AR. Regulation and mechanisms of ATP-binding cassette transporter A1-mediated cellular cholesterol efflux. Arterioscler Thromb Vasc Biol. 2003;23:1178-84. 5) Wang N, Lan D, Chen W et al. ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins. Proc Natl Acad Sci U S A. 2004;101:9774-9.6) Kennedy MA, Barrera GC, Nakamura K et al. ABCG1 has a critical role in mediating cholesterol efflux to HDL and preventing cellular lipid accumulation. Cell Metab. 2005;1:121-31. 7) Passarelli M, Tang C, McDonald TO et al. Advanced glycation end products precursors impair ABCA1-dependent cholesterol removal from cells. Diabetes 2005;54:2198-205 8) Albrecht C, Simon-Vermot I, Elliott JI, Higgins CF, Johnston DG, Valabhji J. Leukocyte ABCA1 gene expression is associated with fasting glucose concentration in normoglycemic men. Metabolsim 2004;53:17-21.9) Wang M, Briggs MR. HDL: The metabolism, function, and the therapeutic importance. Chem Rev 2004;104:11910) Fournier N, Francone O, Rothblat G et al. Enhanced efflux of cholesterol from ABCA1-expressing macrophages to serum from type IV hypertriglyceridemic subjects. Atherosclerosis 2003;171:287-9311) De Vries R, Kerstens MN, Sluiter WJ et al. Cellular cholesterol efflux to plasma from moderately hypercholesterolaemic type 1 diabetic patients is enhanced, and is unaffected by simvastatin treatment. Diabetologia 2005;48:1105-13.12) Syvanne M, Castro G, Dengremont, et al. Cholesterol efflux from Fu5AH hepatoma cells induced by plasma of subjects with of without coronary disease and non-insulin-dependent diabetes: importnace of LpA-I:A-II particles and phospholipids transfer protein. Atherosclerosis 1996;127:245-5313) Vogt L, Laverman GD, van Tol A, Groen AK, Navis G, Dullaart RP. Cellular cholesterol efflux to plasma from proteinuric patients is elevated and remains unaffected by antiproteinuric treatment. Nephrol Dial Transplant. 2006;21:101-6.14) Vaughan AM, Oram JF. ABCG1 redistributes cell cholesterol to domains removable by high density lipoprotein but not by lipid-depleted apolipoproteins. J Biol Chem 2005;280:30150-7

List of Research Outputs

Chow W.S., Cheung B.M.Y., Xu A., Wat N.M.S., Fong H.Y., Ong L.H.Y., Tam S., Tan K.C.B., Janus E.D., Lam T.H. and Lam K.S.L., Hypoadiponectinemia as a predictor for the development of hypertension: a 5-year prospective study. , Hypertension. 2007, 49: 1455-61.

Ong K.L., Cheung B.M.Y., Man Y.B., Wong Y.F., Wat N.M.S., Tan K.C.B. and Lam K.S.L., Treatment and control of diabetes mellitus in the United States National Healthy and Nutrition Examination Survey 1999-2002, Journal of Cardiometabolic Syndrome. 2006, 1: 301-7.

Shiu S.W.M. and Tan K.C.B., Effects of advanced glycation end products on caveolin-1 and endothelial nitric oxide synthase in endothelial cells, Fourth International Huaxia congress of Endocrinology, Hong Kong, Dec 2006.

Shiu W.M.S., Huang Y., Wong Y. and Tan K.C.B., Type 2 diabetes and endothelial lipase, Second International Symposium on Healthy Aging, Mar 2007, Hong Kong. 2007.

Tan K.C.B., 2. Chairman of the Organising Committee of the 3rd International Symposium on Healthy Aging to be held in Mar 2008, Hong Kong. 2007.

Tan K.C.B., An update on the pathogenesis of type 2 diabetes and the risk for atherothrombotic events, Managing Cerebrovascular risk in patients with diabetes, Hong Kong Stroke Society, Hong Kong. 2006.

Tan K.C.B., Shiu S.W.M., Chow W.S., Wong Y., Bucala R. and Betteridge D.J., Arterial stiffness and advanced glycation end products in type 2 diabetes mellitus, The International Diabetes Federation 19th World Diabetes Congress, Cape Town, Dec 2006.

Tan K.C.B., Shiu S.W.M., Chow W.S., Leng L., Bucala R. and Betteridge D.J., Association between serum levels of soluble receptor for advanced glycation end products and circulating advanced glycation end products in type 2 diabetes, Diabetologia. 2006, 49: 2756-62.

Tan K.C.B., Chairman of symposium "The clinical realities of long term complications: what should we tell our patients?", 19th World Diabetes Congress, Cape Town, South Africa. 2006.

Tan K.C.B., Chairman of symposium "Update Insulin Treatment in Diabetes Management", Hong Kong., 2006.

Tan K.C.B., Chairman of the Diabetes Division of Hong Kong Society of Endocrinology, Metabolism and Reproduction. 2006.

Tan K.C.B., Chairman of the Organising Committee of the 3rd International Symposium on Healthy Aging. 2007.

Tan K.C.B., Co-Chairman of the Scientific Committee of the Fourth International Huaxia Congress of Endocrinology. 2006.

Tan K.C.B., Convenor of the Hong Kong Diabetes Advisory Board. 2007.

Tan K.C.B., Diabetes and angiotensin receptor blockers, Selected Topics of Current Clinical Practice, Association of Private Medical Specialist ofHong Kong. 2007.

Tan K.C.B., Editorial Advisory Board Member, MIMS Endocrinology Guide. CMP Medica, 2006.

Tan K.C.B., Endocannabinoid system - beyond weight loss, Second International Symposium on Healthy Aging, Hong Kong. 2007.

Tan K.C.B., Shiu W.M.S., Wong Y., Tam S. and Bucala R., Increased serum soluble lectin-like oxidized LDL receptor-1 level in type 2 diabetes is associated with circulating advanced glycation end products, The Endocrine Society’s 89th Annual Meeting, June 2007, Toronto. 2007.

Tan K.C.B., LDL-C treatment goal of The Asia Lipid Management Expert Forum, Singapore. 2007.

Tan K.C.B., Management of diabetic dyslipidaemia, Meet the Expert, the 4th International Huaxia Congress of Endocrinology, Hong Kong. 2006.

Tan K.C.B., Management of dyslipidemia in the metabolic syndrome, Cardiovasc Hematol Disord Drug Targets. 2007, 7: 99-108. Review.

Tan K.C.B., Member of Diabetes Hongkong. 2006.

Tan K.C.B., Member of the American Heart Association Council on Basic Cardiovascular Sciences. 2006.

Tan K.C.B., Member of the Asian Pacific Society of Atherosclerosis and Vascular Disease. 2006.

Tan K.C.B., Member of the British Diabetic Association. 2006.

Tan K.C.B., Member of the British Endocrine Society. 2006.

Tan K.C.B., Member of the British Hyperlipidaemia Association. 2006.

Tan K.C.B., Member of the Organising Committee of the Fourth International Huaxia Congress of Endocrinology. 2006.

Tan K.C.B., Member of the Osteoporosis Society of Hong Kong. 2006.

Tan K.C.B., Member of the Scientific Committee of the Hong Kong College of Physicians. 2007.

Tan K.C.B., Pharmacological Intervention for Diabetes, Diabetes Care and Education Coursefor Nurses, Hong Kong. 2006.

Tan K.C.B., Reviewer, Arteriosclerosis, Thrombosis and Vascular Biology. 2006.

Tan K.C.B., Reviewer, Atherosclerosis. 2006.

Tan K.C.B., Reviewer, Biomarker Insights. 2006.

Tan K.C.B., Reviewer, Diabetes. 2006.

Tan K.C.B., Reviewer, Diabetes Research and Clinical Practice. 2006.

Tan K.C.B., Reviewer, Diabetes, Obesity and Metabolism. 2006.

Tan K.C.B., Reviewer, Diabetologia. 2006.

Tan K.C.B., Reviewer, Journal of Clinical Endocrinology and Metabolism. 2006.

Tan K.C.B., The Emerging New Standard for More Effective Lipid Management in Diabetic Patients, CME Meetingfor Physicians. St Teresa's Hospital. 2006.

Tan K.C.B., The endocannabinoid system - a new target to manage multiple cardiometabolic risk factors, CME Meeting for Physicians, Hong Kong. 2007.

Tan K.C.B., Vascular dysfunction in diabetes , Plenary lecture, the 4th International Huaxia Congress of Endocrinology, to be held in Dec 2006, Hong Kong. 2006.

Tan K.C.B., Vice President of the Hong Kong Society of Endocrinology, Metabolism and Reproduction . 2006.

Tso A.W.K., Wat N.M.S., Xu A., Tam S., Fong H.Y., Janus E.D., Tan K.C.B. and Lam K.S.L., Adiponectin/C-reactive protein ratio is an independent surrogate marker predictive of the development of metabolic risks and the metabolic syndrome over 5 years in Chinese, The 6th International Diabetes Federation Western Pacific Region Congress, Bangkok. 2006.

Tso A.W.K., Tan K.C.B., Wat N.M.S., Janus E.D., Lam T.H. and Lam K.S.L., Endothelial nitric oxide synthase G894T (Glu298Asp) polymorphism was predictive of glycemic status in a 5-year prospective study of Chinese subjects with impaired glucose tolerance, Metabolism. 2006, 55: 1155-8.

Wat N.M.S., Tan K.C.B., Chow W.S., Tse P.M., Wong K., Leung E., Hung V., Leung S.K., Yee A., Leung C.Y. and Lam K.S.L., Innovative risk stratification model for high-risk diabetic patients in a tertiary referral centre – triage of the triaged, Health Authority Convention, May 2007.

Yee A., Wat N.M.S., Tan K.C.B., Wong K., Leung E., Leung S.C., Hung V., Tse P.M., Leung C.Y. and Lam K.S.L., Innovative intervention mechanism for patients with diabetic nephropathy to achieve blood pressure treatment target, Health Authority Convention, May 2007.

Zhou H., Shiu S.W.M., Wong Y. and Tan K.C.B., Impaired serum cholesterol efflux potential is associated with endothelial dysfunction in type 2 diabetes patients, Fourth International Huaxia congress of Endocrinology, Hong Kong, Dec 2006.

Researcher : Tang CSO

List of Research Outputs

Chan D.T.M., Ho S.K.N., Tang C.S.O., Tse K.C., Lam M.F., Lai K.N. and Yung S.S.Y., Pilot study of pegylated interferon-alpha 2a in dialysis patients with chronic hepatitis C virus infection, Nephrology. 2007, 12: 11-17.

Lam M.F., Tang C.S.O., Wong A.K., Tong K.L., Yu A.W., Li C.S., Cheung K.O. and Lai K.N., ASPD: A prospective study of adequacy in Asian patients on long term, small volume, continuous ambulatory peritoneal dialysis, Peritoneal Dialysis International. 2006, 26: 466-474.

Tang S.C.W., Chan K.W., Tang C.S.O., Lam M.F., Leung C.Y., Tse K.C., Li C.S., Ho Y.W., Tong K.L., Lai K.N., Chan D.T.M. and Hong Kong Nephrology Study Group ., Conversion of ciclosporin A to tacrolimus in kidney transplant recipients with chronic allograft nephropathy, Nephrology Dialysis Transplantation. 2006, 21(11): 3243-51.

Tse K.C., Lam M.F., Tang S.C.W., Tang C.S.O., Lai K.N. and Chan D.T.M., A pilot study on tracolimus treatment in membranous or quiescent lupus nephritis with proteinuria resistant to angiotensin inhibition or blockade, Lupus. 2007, 16: 45-51.

Researcher : Tang CW

Project Title:	Regulation of albumin-induced chemokine expression in human proximal tubular epithelial cells by angiotensin antagonists and HMG-CoA reductase inhibitors
Investigator(s):	Tang SCW
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2005

Abstract:

To explore in vitro the effect of ACEI, ARB, and statins, either singly or in combination, on albumin-induced expression of IL-8, MCP-1 RANTES, and MIF incultured human PTEC; to dissect the intracellular signal transduction pathway governing the anti-inflammatory effects of these pharmacological agents; to investigate the I>in vitro impact of applying combined a ngiotensin II b blockade and statin treatment on enphrotic mice.

Project Title:	Measurement of upper airway water content in continuous ambulatory or nocturnal peritoneal dialysis and after renal transplantation: implications on sleep apnea
Investigator(s):	Tang SCW, Lam B, Khong PL, Pang CBY, Ku PP, Ip MSM, Lai KN
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	04/2007

Abstract:

In developed countries, sleep apnea has emerged as an important health hazard with serious socioeconomic implications. Sleep apnea is an important risk factor for stroke and sudden cardiac death (1), and is strongly associated with the risk of road traffic accidents (2). The issue may be even more relevant in nephrology because some of the factors involved in the pathogenesis of renal disease are the same that cause, or are associated with, sleep apnea. Indeed, sleep disorders such as daytime sleepiness, insomnia, restless legs syndrome, and obstructive sleep apnea syndrome are common in patients with end-stage renal disease (ESRD) (3-5). In patients on continuous ambulatory peritoneal dialysis (CAPD), the prevalence of sleep apnea ranges from 61 to 67% (6,7). In patients on stable maintenance conventional hemodialysis, conversion to nocturnal hemodialysis has been shown to correct sleep apnea associated with chronic renal failure (8). However, this may not be practical in places where nocturnal hemodialysis facilities are not readily available, or where peritoneal dialysis (PD) is the predominant mode of renal replacement therapy, such as Hong Kong (9). Data on the effect of nocturnal peritoneal dialysis (NPD) versus conventional CAPD on sleep apnea in patients with ESRD, however, are lacking. In a recent comparative study using matched controls, we have provided data to suggest that NPD may have a therapeutic edge for sleep apnea in CAPD subjects (10). However, the mechanisms involved are not entirely clear and may be related to reduced total body water as reflected by bioelectrical impedance measurements (10). Furthermore, there is no solid data on whether renal transplantation, another mode of renal replacement therapy, may correct sleep apnea. Successful renal transplantation not only corrects fluid balance, but also restores homeostasis of solutes and excretion of uremic toxins. Whether the latter effect may further contribute to alleviation of sleep apnea is at present unknown. The aim of the present study is to investigate whether upper airway water content, which plays a pivotal role in the pathogenesis sleep apnea, may be reduced by switching from CAPD to NPD or after kidney transplantation. REFERENCES 1. Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. N Engl J Med 2005; 353:2034-2041 2. Terán-Santos J, Jimenez-Gomez A, Cordero-Guevara J. The Association between Sleep Apnea and the Risk of Traffic Accidents. N Engl J Med 1999; 340:847-851 3. Fletcher EC. Obstructive sleep apnea and the kidney. J Am Soc Nephrol 1993;4:1111-1121 4. Kraus MA. Sleep apnea in renal failure. Adv Perit Dial 1997;13:88-92 5. Lui SL, Ng F, Lo WK. Factors associated with sleep disorders in Chinese patients on continuous ambulatory peritoneal dialysis. Perit Dial Int. 2002;22:677-682 6. Stepanski E, Faber M, Zorick F, Basner R, Roth T. Sleep disorders in patients on continuous ambulatory peritoneal dialysis. J Am Soc Nephrol 1995;6:192-197 7. Rodriguez A, Stewart D, Hotchkiss M, Farrell P, Kliger A, Finkelstein F. Sleep apnea in CAPD. Adv Perit Dial 1995;11:123-126 8. Hanly PJ, Pierratos A. Improvement of sleep apnea in patients with chronic renal failure who undergo nocturnal hemodialysis. N Engl J Med 2001;344:102-107 9. Lai KN, Lo WK: Optimal peritoneal dialysis for patients from Hong Kong. Perit Dial Int 19 Suppl 3:S26-S31, 1999 10. Tang SC, Lam B, Ku PP, Leung WS, Chu CM, Ho YW, Ip MS, Lai KN. Alleviation of sleep apnea in patients with chronic renal failure by nocturnal cycler-assisted peritoneal dialysis compared with conventional continuous ambulatory peritoneal dialysis. J Am Soc Nephrol 2006; 17:2607-2616

Researcher : Tang MO

List of Research Outputs

Wang M.M., Lau C.P., Zhang X., Siu C.W., Tang M.O. and Tse H.F., Early Improvement Of Diastolic Dyschrony And Myocardial Relaxation Time After Upgrade Of Longstanding Right Ventricular Apical To Right Ventricular Septal Pacing (Oral presentation) , 28th Annual Scientific Sessions of Heart Rhythm Society, Denver, Colorado, May 9-12 2007.

Zhang X., Chen H., Tsang V.Y.C., Tang M.O., Lau C.P. and Tse H.F., Prevalence And Clinical Predictors For New-onset Heart Failure After Permanent Right Ventricular Apical Pacing In Patients With Aquired High-grade Atrioventricular Block, World Congress of Cardiology 2006, Barcelona. 2006.

Researcher : Tang SCW

Project Title:	Regulation of albumin-induced chemokine expression in human proximal tubular epithelial cells by angiotensin antagonists and HMG-CoA reductase inhibitors
Investigator(s):	Tang SCW
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2005

Abstract:

Project Title:	Measurement of upper airway water content in continuous ambulatory or nocturnal peritoneal dialysis and after renal transplantation: implications on sleep apnea
Investigator(s):	Tang SCW, Lam B, Khong PL, Pang CBY, Ku PP, Ip MSM, Lai KN
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	04/2007

Abstract:

List of Research Outputs

Ho E.T., Tang S.C.W., Chui W.H., Tang A.W., Wong S.S., Wong Y., Lam W.O., Cheng Y.Y., Chau W.S. and Ho Y.W., Video-assisted thoracoscopic TALE pleurodesis for pleuroperitoneal communication in peritoneal dialysis, Peritoneal Dialysis International . 2006, Suppl 26: S118.

Lai K.N., Leung J.C.K., Chan L.Y., Guo H. and Tang S.C.W., Interaction between proximal tubular epithelial cells and infiltrating monocytes/T cells in the proteinuric state, Kidney International. 2007, 71: 526-538.

Lai K.N., Tang S.C.W. and Leung J.C.K., Mediators of inflammation and fibrosis, Peritoneal Dialysis International . 2007, 27: S65-71.

Lai K.N., Tang S.C.W., Chan L.C.B. and Leung J.C.K., The modulation of chemokines release in proximal tubular epithelial cell by monocytes/T cells in proteinuric state is mediated by IL-1 and TNF-a, Journal of American Society of Nephrology. 2006, 17: 384A.

Leung J.C.K., Tang S.C.W., Chan L.Y., Yuen Y.M. and Lai K.N., Specific induction of neutrophil gelatinase-associated lipocalin in peritoneal mesothelial cells by interleukin-1, Journal of American Society of Nephrology. 2006, 17: 751A.

Tang A.W., Wong S.S., Tang S.C.W., Wong Y., Kwok M.W., Lam W.O., Cheng Y.Y. and Ho Y.W., Simultaneous removal and reinsertion of Tenckhoff catheters for the treatment of malfunctioning catheters, Peritoneal Dialysis International . 2006, Suppl 26: S64.

Tang S.C.W., Lam B., Ku P.P., Leung W.S., Chu C.M., Ho Y.W., Ip M.S.M. and Lai K.N., Alleviation of sleep apnea in patients with chronic renal failure by nocturnal cycler-assisted peritoneal dialysis compared with conventional continuous ambulatory peritoneal dialysis, Journal of American Society of Nephrology. 2006, 17: 2607-2616.

Tang S.C.W., Angiotensin II Receptor Blocker: From Hypertension to Organ Protection, Pharmacy Continuing Education Seminar, Hong Kong Pharmacy Central Continuing Education Committee,YMCA International House, Hong Kong. 2007.

Tang S.C.W., Best Presenter Medal, Annual Scientific Meeting, Hong Kong College of Physicians. 2006.

Tang S.C.W., Chronic Kidney Disease: An Epidemiologic Perspective, Hong Kong Society of Clinical Chemistry Annual Scientific Meeting, Hong Kong Society of Clinical Chemistry, Royal Pacific Hotel. 2007.

Tang S.C.W., Chan K.W., Tang C.S.O., Lam M.F., Leung C.Y., Tse K.C., Li C.S., Ho Y.W., Tong K.L., Lai K.N., Chan D.T.M. and Hong Kong Nephrology Study Group ., Conversion of ciclosporin A to tacrolimus in kidney transplant recipients with chronic allograft nephropathy, Nephrology Dialysis Transplantation. 2006, 21(11): 3243-51.

Tang S.C.W., Yang M.K., Ho Y.W. and Lai K.N., Diagnosis of patent processus vaginalis by CT peritoneography in CAPD, Hong Kong Journal of Nephrology. 2006, 8: 78-79.

Tang S.C.W., Leung J.C.K., Chan L.Y., Tsang W.L. and Lai K.N., Differntial regulation of chemokines expression by angiotensin antagonists and HMG-CoA reductase inhibitors in protein-overloaded human proximal tubular epithelial cells, Journal of American Society of Nephrology. 2006, 17: 844A.

Tang S.C.W., Distinguished Research Paper Award for Young Clinicians. Cash Prize: HK$ 5,000, Hong Kong College of Physicians. 2006.

Tang S.C.W., Chu F.S.K., Au W.M. and Lai K.N., Emphysematous cystitis, American Journal of Kidney Diseases. 2006, 48: e11-12.

Tang S.C.W., Estimation Equations for GFR, 12th Hong Kong Medical Forum and Chengdu Medical Forum, Department of Medicine, Faculty of Medicine, The University of Hong Kong, on 5 May 2007: Hong Kong Convention and Exhibition Centre; on 8 May 2007: West China Hospital, West China School of Clinical Medicine, Sichuan University, Chengdu, Sichuan, China. 2007.

Tang S.C.W., Estimation of GFR: where are we?, HA Commissioned Training Program: New Horizons in Laboratory Medicine: Novel Approach to Diagnosis and Management of Diseases, Hong Kong Hospital Authority, Hong Kong Hospital Authority Headquarter. 2007.

Tang S.C.W., Fluid balance, sleep apnea and nocturnal PD, XLIV ERA-EDTA Congress, European Renal Association and European Dialysis and Transplant Association, Barcelona, Spain. 2007.

Tang S.C.W. and Lai K.N., Hepatitis B-related membranous nephropathy should be treated with a specific anti-viral agent, Kidney International. 2006, 70: 818.

Tang S.C.W., Leung J.C.K., Chan L.Y., Chan A.K.K., Eddy A.A. and Lai K.N., Impact of angiotensin antagonists and HMG-CoA reductase inhibitors on adriamycin nephropathy, Journal of American Society of Nephrology. 2006, 17: 41A.

Tang S.C.W., Lee R., Tse K.C., Lai A.S.H. and Lai K.N., Inability to start hemodialysis after a smooth temporary hemodialysis catheter insertion procedure, Hemodialysis International. 2007, 11: 32-34.

Tang S.C.W., Management of HBsAg and Anti-HCV positive allograft recipients, The Transplantation Society New Key Opinion Leader Meeting 2007, The International Transplantation Society, Gold Coast Hotel. 2007.

Tang S.C.W., Renal Medicine: areas we have put Hong Kong on the map of the world, 20th Anniversary Meeting: “Twenty Years of Excellence in Medicine”, Hong Kong College of Physicians, Hong Kong College of Physicians Lecture Theatre. 2006.

Tang S.C.W., Ho Y.W., Tang A.W., Yip T., Tse K.C., Wang A.Y.M., Lo W.K., Chan D.T.M., Lai K.N. and Lui S.L., What is the optimal timing of dialysis initiation? , Peritoneal Dialysis International . 2006, Suppl 26: S90.

Tse K.C., Lam M.F., Tang S.C.W., Tang C.S.O., Lai K.N. and Chan D.T.M., A pilot study on tracolimus treatment in membranous or quiescent lupus nephritis with proteinuria resistant to angiotensin inhibition or blockade, Lupus. 2007, 16: 45-51.

Tse K.C., Tang S.C.W., Chan D.T.M. and Lai K.N., Rhodococcus lung abscess complicating kidney transplantation: successful management by combination antibiotic therapy, Transplant Infectious Disease. 2007, 10: 44-47.

Yip T., Tse K.C., Lam M.F., Cheng S.W., Lui S.L., Tang S.C.W., Li F.K., Wang A.Y.M., Choy C.B.Y., Ng M.M.T., Chan D.T.M., Lai K.N. and Lo W.K., Risk and outcome of peritonitis after flexible colonoscopy in CAPD patient, Peritoneal Dialysis International . 2006, Suppl 26: S68.

Researcher : Tang SM

List of Research Outputs

Tang S.M., Zhao Y., Smith D.K. and Epstein R., Intron length and accelerated 3' gene evolution., Genomics. 2006, 88: 682-89.

Researcher : Tao R

List of Research Outputs

Tao R., Lau C.P. and Li G.R., Inosital 1,4,5-trisphosphate receptors mediating spontaneous Ca2+ oscillation favors proliferation in human mesenchymal stems from bone marrows, 11th Research Postgraduate Symposium, Faculty of Medicine, HKU, 2006 . 2006, 34.

Tao R., Lau C.P. and Li G.R., Inositol 1,4,5-trisphosphate receptors mediating spontaneous Ca2+ oscillation favors proliferation in human mesenchymal stem cells from bone marrow., Blood/48th Annual Meeting of the American-Society-of-Hematology, Orlando, FL. 2006, 108(11): 727A.

Researcher : Tao R

List of Research Outputs

Researcher : Tong KL

List of Research Outputs

Tang S.C.W., Chan K.W., Tang C.S.O., Lam M.F., Leung C.Y., Tse K.C., Li C.S., Ho Y.W., Tong K.L., Lai K.N., Chan D.T.M. and Hong Kong Nephrology Study Group ., Conversion of ciclosporin A to tacrolimus in kidney transplant recipients with chronic allograft nephropathy, Nephrology Dialysis Transplantation. 2006, 21(11): 3243-51.

Researcher : Tong SM

List of Research Outputs

Chan A.O.O., Jim M.H., Lam K.F., Siu D.C.W., Tong S.M., Ng F.H., Wong S.Y., Hui W.M., Lam S.K. and Wong B.C.Y., Aspirin does not prevent recurrence of colorrectal adenomas in patients with coronary artery disease. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A194.

Chan A.O.O., Chow R., Hui W.M., Leung Y.C., Tong S.M., Lam S.K. and Wong B.C.Y., Biofeedback is equally effective in patients with short or long duration of function constipation. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A194.

Chan A.O.O., Jim M.H., Lam K.F., Siu D.C.W., Tong S.M., Ng F.H., Wong S.Y., Hui W.M., Chan C.K., Lai K.C., Cheung T.K., Chan P., Wong G., Yuen R.M.F., Lau Y.K., Lee S.W.L., Seto M.L., Lam S.K. and Wong B.C.Y., Patients with coronary artery disease had high prevalanece of colorectal cancer and adenoma: END-results of metabolic syndrome and smoking. Digestive Disease Week 2007, Washington DEc, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A65.

Researcher : Tong TPH

List of Research Outputs

Chan A.O.O., Hui W.M., Leung G.K.L., Tong T.P.H., Hung I.F.N., Chan P., Hsu A., But D., Wong B.C.Y., Lam S.K. and Lam K.F., Patients with functional constipation do not have increase prevalence of colorectal cancer precursors”, GUT. British Medicial Journal, 2007, 56: 451-452.

Chan O.O., Lam K.F., Tong T.P.H., Siu D.C.W., Jim M.H., Hui W.M., Lai K.C., Yuen R.M.F., Lam S.K. and Wong B.C.Y., Coexistence between colorectal cancer/adenoma and coronary artery disease: results from 1382 patients. , Alimentary Pharmacology and Therapeutics. 2006, 24(3): 535-9.

Researcher : Tsang KWT

Project Title:	Could gastro-oesphageal reflux be a cause of continued airway damage in bronchiectasis?
Investigator(s):	Tsang KWT
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	11/2002

Abstract:

The study is to determine the prevalence and severity of gastro-oesophageal reflux (GOR) in patients with bronchiectasis, the relationship of GOR with airway inflammation parameters, and identify clinical an dother parameters which predict the presence of GOR in patients with bronchiectasis with and without upper abdominal symptoms.

List of Research Outputs

Au W.Y., Ho J.C.M., Lie A.K.W., Sun J.Z., Zheng L., Liang R.H.S., Lam W.K. and Tsang K.W.T., A prospective study of respiratory ciliary structure and function after stem cell transplantation, Bone Marrow Transplantation. 2006, 38: 243-248.

Cheng C., Wong W. and Tsang K.W.T., Perception Of Benefits And Costs During SARS Outbreak: An 18-month Prospective Study, Journal of Consulting and Clinical Psychology. 2006, 74: 870-879.

Ho J.C.M., Chan M.M.W., Ho S.P., Mak J.C.W., Ip M.S.M., Ooi C.G.C., Wong M.P., Tsang K.W.T. and Lam W.K., Disturbance of systemic antioxidant profile in non-small cell lung carcinoma, Eur Respir J . 2007, 29: 273-278.

Ho J.C.M. and Tsang K.W.T., Lessons from SARS: preparing for the next epidemic. , Pulmonary and Critical Care Updates, American College of Chest Physicians. 2007, 21: Lesson 14.

Ho J.C.M., Mak J.C.W., Ho S.P., Ip M.S.M., Tsang K.W.T., Lam W.K. and Chan M.M.W., Manganese superoxide dismutase and catalase genetic polymorphisms, activity levels and lung cancer risk in Chinese in Hong Kong, J. Thorac. Oncol. 2006, 1: 648-653.

Lee A.M., Wong J.G.W.S., McAlonan G.M., Cheung V., Cheung C., Sham P.C., Chu C.M., Wong P.C., Tsang K.W.T. and Chua S.E., Stress and psychological distress among SARS survivors 1 year after the outbreak, Canadian Journal of Psychiatry-Revue Canadienne De Psychiatrie. 2007, 52(4): 233-240.

Pan N.Y., Hui W.S., Tipoe G.L., Taylor G.W., Leung Y.H., Lam W.K., Tsang K.W.T. and Mak J.C.W., Inhibition of pyocyanin-potentiated IL-8 release by steroids in bronchial epithelial cells, Respiratory medicine. 2006, 100(9): 1614-1622.

Tsang K.W.T., Shim Y.S., Wong K.S., Laim C.K., Eng P., Lam W.K. and Seto W.H., Possible case scenarios an logistic issues in H5N1 pandemic, Respirology. 2006, 11(5): 520-522.

Yung S.S.Y., Wan C.C., Tsang R.C.W., Mak J.C.W., Tsang K.W.T. and Chan D.T.M., Induction of IL-6 and matrix protein synthesis in human peritoneal mesothelial cells by Pseudomonas aeruginosa exotoxin pyocyanin, Journal of the American Society of Nephrology. 2006, 17: 305A.

Yung S.S.Y., Zhang Q., Tsang R.C.W., Mak J.C.W., Tsang K.W.T. and Chan D.T.M., Induction of interleukin-6 secretion and matrix protein synthesis in human peritoneal mesothelial cells (HPMCs) by Pseudomonas aeruginosa exotoxin pyocyanin, Peritoneal Dialysis International. 2006, 26 (Suppl 2): S22.

Researcher : Tsang RCW

List of Research Outputs

Chan D.T.M., Tsang R.C.W., Chan K.W. and Yung S.S.Y., Anti-DNA antibodies stimulate hyaluronan synthesis in proximal tubular epithelial cells through the induction of IL-6 and IL-1b, Journal of the American Society of Nephrology. 2006, 17: 352A.

Lui S.L., Chan K.W., Tsang R.C.W., Yung S.S.Y., Lai K.N. and Chan D.T.M., Effect of rapamycin on renal ischemia-reperfusion injury in mice, Transplant International. 2006, 19: 834-839.

Lui S.L., Yung S.S.Y., Tsang R.C.W., Chan K.W., Zhang Q., Tam S., Lai K.N. and Chan D.T.M., Rapamycin attenuates the severity of nephritis in NZB/NZW mice, Journal of the American Society of Nephrology. 2006, 17: 353A.

Lui S.L., Yung S.S.Y., Tsang R.C.W., Chan K.W., Zhang Q., Tam S., Lai K.N. and Chan D.T.M., Rapamycin reduces proteinuria and segmental glomerulosclerosis in murine adriamycin nephropathy, Journal of the American Society of Nephrology. 2006, 17: 743A.

Wan C.C., Yung S.S.Y., Tsang R.C.W. and Chan D.T.M., Fibrosis-related growth factors in peritoneal dialysate during peritonitis, Peritoneal Dialysis International. 2006, 26 (Suppl 2): S22.

Yung S.S.Y., Wan C.C., Tsang R.C.W., Mak J.C.W., Tsang K.W.T. and Chan D.T.M., Induction of IL-6 and matrix protein synthesis in human peritoneal mesothelial cells by Pseudomonas aeruginosa exotoxin pyocyanin, Journal of the American Society of Nephrology. 2006, 17: 305A.

Yung S.S.Y., Zhang Q., Tsang R.C.W., Mak J.C.W., Tsang K.W.T. and Chan D.T.M., Induction of interleukin-6 secretion and matrix protein synthesis in human peritoneal mesothelial cells (HPMCs) by Pseudomonas aeruginosa exotoxin pyocyanin, Peritoneal Dialysis International. 2006, 26 (Suppl 2): S22.

Researcher : Tsang VYC

List of Research Outputs

Zhang X., Chen H., Tsang V.Y.C., Tang M.O., Lau C.P. and Tse H.F., Prevalence And Clinical Predictors For New-onset Heart Failure After Permanent Right Ventricular Apical Pacing In Patients With Aquired High-grade Atrioventricular Block, World Congress of Cardiology 2006, Barcelona. 2006.

Researcher : Tsang WL

List of Research Outputs

Tang S.C.W., Leung J.C.K., Chan L.Y., Tsang W.L. and Lai K.N., Differntial regulation of chemokines expression by angiotensin antagonists and HMG-CoA reductase inhibitors in protein-overloaded human proximal tubular epithelial cells, Journal of American Society of Nephrology. 2006, 17: 844A.

Researcher : Tse EWC

Project Title:	The role of LIM-only protein, LM04, in the pathogenesis of sporadic ovarian cancer in Chinese
Investigator(s):	Tse EWC, Kwong YL
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003

Abstract:

To assess the level of expression of LMO4 in sporadic ovarian cancer; to determine correlation between LMO4 expression and BRCA1 mutations in sporadic ovarian cancer; to determine correlation between LMO4 expression and clinical behaviour of sporadic ovarian cancer.

Project Title:	The study of PIN1 over-expression in multiple myeloma
Investigator(s):	Tse EWC, Kwong YL
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004
Completion Date:	10/2006

Abstract:

To investigate if PIN1 is over-expressed in myeloma cells; to study the effect of PIN1 down-regulation on the proliferation of myeloma cells.

Project Title:	Characterization of the interaction between Pin1 and HBx in human hepatocellular carcinoma
Investigator(s):	Tse EWC, Wong KB
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2006

Abstract:

To characterize the interaction between Pin1 and HBx; to investigate the role of this interaction in the pathogenesis of HCC; to understand the structural basis of this interaction.

List of Research Outputs

Cheung W.W., Tse E.W.C., Leung A.Y.H., Yuen K.Y. and Kwong Y.L., Regular virologic surveillance showed very frequent cytomegalovirus reactivation in patients treated with alemtuzumab, Blood. 2007, 82(2): 108-11.

Leung C.K.J., Pang A.W.K., Yuen W.H., Kwong Y.L. and Tse E.W.C., Relationship of Expression of Aquaglyceroporin 9 with Arsenic Uptake and Sensitivity in Leukemia Cells , Blood . 2007, 109: 740-746.

Pang R.W.C., Tse E.W.C. and Poon R.T.P., Molecular pathways in hepatocellular carcinoma, Cancer Letters . 2006, 240(2): 157-169.

Pang R.W.C., Lee K.W., Man K., Poon R.T.P., Fan S.T., Kwong Y.L. and Tse E.W.C., PIN1 expression contributes to hepatic carcinogenesis, Journal of Pathology. 2006, 210(1): 19-25.

Pang R.W.C., Lee K.W., Poon R.T.P., Fan S.T., Wong K.B., Kwong Y.L. and Tse E.W.C., Pin1 interacts with a specific serine-proline motif in hepatitis B virus X-protein to enhance hepatocarcinogenesis, Gastroenterology. 2007, 132(3): 1088-1103.

Pang R.W.C., Poon R.T.P., Fan S.T., Kwong Y.L. and Tse E.W.C., Pin1: a novel regulator of tumor angiogenesis and invasiveness in hepatocellular carcinoma (Abstract), The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007. Hepatology International. 2007, 1(1): 143.

Pang R.W.C., Poon R.T.P., Fan S.T., Kwong Y.L. and Tse E.W.C., Pin1: a novel regulator of tumor angiogenesis and invasiveness in hepatocellular carcinoma (Abstract), The American Association for Cancer Research Annual Meeting 2007, Los Angeles, U.S.A., 14 - 18 April 2007.

Researcher : Tse HF

Project Title:	Direct intramyocardial implantation of autologous bone marrow cells for enhancement of neovascularization in patients with "End-Staged" coronary artery disease
Investigator(s):	Tse HF, Lau CP, Kwong YL
Department:	Medicine
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	01/2004

Abstract:

To determine the safety and efficacy of direct intramyocardial delivery of bone marrow cells using electromechanical guided injection; to investigate the angiogenic ability of implanting autologous bone marrow cells in patients with end-stage coronary artery disease.

Project Title:	Functional role of pacemaker current, I(f) in sinoatrial node probed by somatic gene transfer of bioengineered HCN channels in swine
Investigator(s):	Tse HF, Lau CP, Li GR
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	09/2004
Completion Date:	09/2006

Abstract:

To demonstrate the efficacy of gene transfer technique to SA node of pigs in vivo by delivering of adenoviral vectors encoding the green fluorescent protein (GFP); to modulate the pacing activity of native endogenous pacemaker cells (SA nodal cells) via dominant-negative suppression by HCNI-AAA or overexpression of HCN constructs with distinct activation profiles using adenoviral vectors.

Project Title:	Relationship between endothelial progenitor cells and markers of thrombogenesis and platelet activation in atrial fibrillation
Investigator(s):	Tse HF, Lip GYH, Lau CP, Kwong YL
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004

Abstract:

We hypothesise a relationship between the numbers of circulating EPCs and the markers of coagulation, platelet activiation and inflammation in patients with AF; we hypothesis that the numbers of circulating EPCs and vascular endothelial function predicts the outcome of cardioversion for AF.

Project Title:	Hypoxia-mediated differentiation of murine and human embryonic stem cells into cardiomyocytes: mechanistic roles of calcium and ion channels
Investigator(s):	Tse HF, Li RA, Fung ML, Wong TM, Lau CP
Department:	Medicine
Source(s) of Funding:	NSFC/RGC Joint Research Scheme
Start Date:	01/2006

Abstract:

The main objectives of this project are: 1/ To determine whether hypoxia is a critical physiological stimulus for the differentiation of CMCs 2/ To determine the role of calcium and its key regulatory protein RyR2 in hypoxia-mediated differentiation of ESCs 3/ To investigate the effect of hypoxia on the development changes of ionic channels during cardiac differentiation of ESCs

Project Title:	Embryonic stem cell transplantation as a novel therapy for post-infarct left ventricular remodeling
Investigator(s):	Tse HF, Li GR, Lau CP
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2006

Abstract:

To determine whether the differentiation status of embryonic stem cells is important in salvaging heart function in chronic heart failure; to determine whether the timing of embryonic stem cell transplantation is important in salvaging heart function in chronic heart failure.

Project Title:	Relationship between Endothelial Progenitor Cells and Initiation, Progression and Clinical Manifestation of Atherosclerosis
Investigator(s):	Tse HF, Lau CP, Kwong YL
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	01/2006

Abstract:

Background: - Cardiovascular risk factors, such as hypertension and smoking, induce endothelial injury and inflammatory response, leading to formation of atherosclerotic lesions. The erosion and rupture of atherosclerotic plaque cause myocardial infarction, sudden cardoiac death and stroke. - Endothelial dysfunction and cell loss are prominent features in atherosclerosis (1). Therefore, maintenance of endothelial integrity is critical for the prevention of athersclerotic diseases. - Endothelial progenitor cells (EPCs) originating from the bone marrow derived cells, which express a variety of endothelial cell markers (2), play a significant role in repair (re-endothelialization) of injured blood vessels (3-5) and neovascularization of ischemic tissues (6-8). - Recent clinical studies demonstrated that cardiovacular risk factors are associated with reduced levels of circulating EPC (9), and the functional integrity of the endothelium correlated with the activities of EPCs (10). - Furthermore, continuous endothelial depletion or exhaustion of a presumed finite supply of EPC in patients with chronic diseases may reduce the number of circulating EPC. Indeed, in patients with chronic diseases, such as heart failure or diabetes, the number of EPC decreased and their function were impaired (9). - Circulating EPC provide an endogenous repair mechanism to counteract ongoing endothelial injury induced by atherosclerotic risk factor and to replace dysfunctional endothelium to prevent the progression of atherosclerosis. - On the other hand, the level of circulating mature endothelial cells may reflect the degree of ongoing endothelium loss from the damage vasculture. - Therefore, detection and quantification of circulating EPCs and mature endothelial cells may provide a novel marker for vascular function in patients with cardiovascular diseases. Whether this novel index of EPCs count reflects the atherosclerotic burden remains not clear. Objective: The aim of this study are - to investigate whether the ratio of the levels of circulating EPCs versus the level of circulating endothlial cells correlate with the amount of atherosclerotic burdens. - to evulate the interaction between atherosclerotic burden and systemic platelet and coagulation activation and inflammation in patients with cardiovascular diseases. References: 1. Drexler H, et al. J Mol Cell Cardiol. 1999;31:51-60. 2. Peichev M, et al. Blood 2000;95:952-8. 3. Kong D, et al. Circulation 2004;110:2039-46. 4. Fuujiyama S, et al. Circ Res. 2003;93:980-9. 5. Werner N, et al. Circ Res. 2003;93:e17-24. 6. Raffi S, et al. Nat Med 2003;9:702-12. 7. Takahashi T, et al. Nat Med. 1999;5:434-8. 8. Dzau VJ, et al. Hypertension 2005/46:7-18. 9. Vasa M, et al. Circ Res 2001;89:e1-7. 10. Hill JM, et al. N Engl J Med 2003;348:593-600.

Project Title:	Genetic enrichment of cardiac derivatives from human embryonic stem cells and their bioengineering for cell-based heart therapies
Investigator(s):	Tse HF, Lau CP
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	09/2006

Abstract:

To generate genetically-engineered nESC lines whose heart derivatives are selectively labeled with a fluorescent protein (e.g. GEP) using lentivirus-mediated gene transfer techniques, followed by FACS-sorted purification; to genetically engineer the electrical phenotypes of nESC-derived CMs by delivering specific normal or engineered ion channel genes in a cardiac-specific manner via lentivirus-mediated gene transfer (for subsequent transplantation); to characterize the gene expression profiles of the FACS-purified nESC-derived CMs at both the transcriptional and translational levels using oligonucleotide array analysis, then compare and contrast to those of mESCs to reveal any species similarities and differences so as to better understand the poorly-studied process of human cardiogenesis.

List of Research Outputs

Chan W.S., Wei W.I. and Tse H.F., "Malignant" baroreflex failure after surgical resection of carotid body tumor., Int J Cardiol. . 2007, 118(3): e81-2.

Cheung S.C., Chow M.K.A., Hui S.K., Yang J., Tse H.F. and Wu E.X., Cell number quantification of USPIO-labeled stem cells by MRI: an in vitro study., 29th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBS). 2006, 476.

Ho H.H., Siu C.W.D., Jim M.H., Miu K.M., Chan R.H.W., Lee S.W.L., Lau C.P. and Tse H.F., Leukocytosis and clinical outcomes in acute inferior myocardial infarction, Int J Cardiol. 2006, 118(2): 278-9.

Hoo R.L.C., Chow W.S., Yau M.H., Xu A., Tse H.F., Tso A.W.K., Fong H.Y., Tam S., Chan L. and Lam K.S.L., PPAR-γ agonist induced-suppression of plasminogen activator inhibitor-1 production is mediated through adiponectin. , 2nd International Symposium on Healthy Aging, 3-4 March 2007, Hong Kong. 2007.

Hoo R.L.C., Chow W.S., Tse H.F., Fong H.Y., Tam S., Chan L.C.B. and Lam K.S.L., Ppar-γ Agonist Induced-suppression Of Plasminogen Activator Inhibitor-1 Production Is Mediated Through Adiponectin. , HBHA conference. 2007.

Hu R., Siu C.W.D., Wang W.Q., Lau C.P. and Tse H.F., Impaired nitrate-mediated dilatation could reflect nitrate tolerance in patients with coronary artery disease, Int J Cardiol. 2006, 120(3): 351-6.

Lau C.P., Tse H.F. and Kay N.E.A.L., Sensor Driven Pacing: Device Specifics, In: In Ellenbogen KA, Wilkoff BL, Kay GN, Lau CP (eds), Clinical Cardiac Pacing: Defibrillation, and Resynchronization therapy. USA, Saunders Elsevier, 2007, 3rd Edition: 499-530.

Lau C.P., Tse H.F. and Mond H.G., The impact of reimbursement on the usage of pacemakers, implantable cardioverter defibrillators and radiofrequency ablation., J Interv Card Electrophysiol. 2007, 17(3): 177-81.

Lau G.K.K., Chan Y.H., Yiu K.H., Li S.W., Tam S., Lau C.P., Kwong Y.L. and Tse H.F., Burden of carotid atherosclerosis in patients with stroke: relationships with circulating endothelial progenitor cells and hypertension, Journal of human hypertension. 2007, 21(6): 445-451.

Lee K.L.F., Burns J., Mullen T., Hettrick D., Tse H.F. and Lau C.P., Avoidance of right ventricular pacing in cardiac resynchronization therapy improves right ventricular hemodynamics in heart failure patients, J Cardiovas Electrophysiol. 2007, 18(5): 497-504.

Lip G.Y. and Tse H.F., Management of atrial fibrillation, Lancet. 2007-08-18, 2007, 370(9587): 604-18.

Ripley K.L., Gage A.A., Olsen D.B., Van Vleet J.F., Lau C.P. and Tse H.F., Time course of esophageal lesions after catheter ablation with cryothermal and radiofrequency ablation: implication for atrio-esophageal fistula formation after catheter ablation for atrial fibrillation. , J Cardiovasc Electrophysiol. 2007, 18(6): 642-6.

Siu C.W., Zhang X., Yung C., Kung A.W.C., Lau C.P. and Tse H.F., Hemodynamic Changes in Hyperthyroidism Related Pulmonary Hypertension: A Prospective Echocardiographic study, The American College of Cardiology 56th annual Scientific Sessions, New Orleans. 2007.

Siu C.W., Lau C.P., Tse H.F. and Li R.A., Probing the external S5-Pore region of HCN-encoded pacemaker channel by cysteine scanning mutagensis. , HBHA conference 2007 Young Investigator Award (Poster category) . 2007.

Siu C.W., Lau C.P., Tse H.F. and Li R.A., Probing the external S5-Pore region of HCN-encoded pacemaker channel by cysteine scanning mutagensis, MGH-HKU-Nature Forum 2007.

Siu C.W.D., Cheng L.C., Woo P.C., Lau C.P. and Tse H.F., A patient with relapsing pacemaker infection due to "Gram-positive bacilli"., Int J Cardiol. 2007, 114(2): E40-1.

Siu C.W.D., Tse H.F. and Lau C.P., Avoidance of electromagnetic interference to implantable cardiovertor-defibrillator during atrioventricular node ablation for atrial fibrillation using transvenous cryoablation, Pacing Clin Electrophysiology. 2006, 29(8): 914-6.

Siu C.W.D., Tse H.F., Lee K.L.F., Chan R.H.W., Chen W.H., Yung C., Lee S.W.L. and Lau C.P., Cardiac resynchronization therapy optimization by ultrasonic cardiac output monitoring (USCOM) device, Pacing Clin Electrophysiology. 2007, 30: 50-55.

Siu C.W.D., Au W.Y., Yung C.Y., Kumana C.R., Lau C.P., Kwong Y.L. and Tse H.F., Effects of oral arsenic trioxide therapy on QT intervals in patients with acute promyelocytic leukemia: implications on long-term cardiac safety, Blood. 2006, 108(1): 103-106.

Siu C.W.D., Zhang X., Yung C., Kung A.W.C., Lau C.P. and Tse H.F., Hemodynamic Changes in Hyperthyroidism Related Pulmonary Hypertension: A Prospective Echocardiographic study, J Clin Endocrinol Metab. 2007, 92(5): 1736-42.

Siu C.W.D., Yeung C.Y., Lau C.P., Kung A.W.C. and Tse H.F., Incidence, clinical characteristics and outcome of congestive heart failure as the initial presentation in patients with primary hyperthyroidism, Heart. 2007, 93 (4): 483-7.

Siu C.W.D., Jim M.H., Ho H.H., Miu R., Lee S.W., Lau C.P. and Tse H.F., Transient Atrial Fibrillation Complicating Acute Inferior Myocardial Infarction: Implications for Future Risk of Ischemic Stroke. , Chest. 2007, 132(1): 44-9.

Siu D.C.W., Zhang X., Yung C., Kung A.W.C., Lau C.P. and Tse H.F., Hemodynamic changes in hyperthyroidism-related pulmonary hypertension: a prospective echocardiographic study, Journal of Clinical Endocrinology & Metabolism. 2007, 92: 1736-42.

Tse H.F., "Atherosclerosis", Second International Symposium on Healthy Aging . 2007.

Tse H.F., 2007- Present Member of the Editorial Board, Europace , 2007.

Tse H.F., 2007- Present Member of the Editorial Board, Southern China Journal of Cardiology , 2007.

Tse H.F. and Lau C.P., Atrial Fibrillation. In Ngygen T, Hu D, Kim MH, grines (eds) Management of Complex Cardiovascular Problems: The Evidence-based Medicine Approach, 3rd Edition, Blackwell Futura Publishing Co Inc, Armonk, NY USA. 2007, 281-318.

Tse H.F., Board Member, The Open Nanoscience Journal, 2007.

Tse H.F., Yiu K.H. and Lau C.P., Bone marrow stem cell therapy for myocardial angiogenesis, Curr Vasc Pharmacol. 2007, 5(2): 103-12.

Tse H.F., Chairman, Organizing Committee, CardioRhythm 2007. 2007.

Tse H.F. and Lau C.P., Clinical trials for cardiac pacing in bradycardia: the end or the beginning?, Circulation. 2006, 114(1): 3-5.

Tse H.F. and Zhou Z., Faculty Outstanding Research Output Award 2006: “Genomic instability in laminopathy-based premature aging. Nature Medicine 2006” , 2006.

Tse H.F., HKU Press Release: Investigation on Bioartificial Sinus Node Provides Important Clinical Insights into Cardiac Impulse Generation, 2006.

Tse H.F., HKU Press conference: Research Find that Combined Therapy for Hypertension and High Cholesterol Reduces 10-Year Risk of Cardiovascular Diseases by more than Half, 2007.

Tse H.F., Holistic Cardiovascular Risk Management, Kuala Lumpur, Malaysia., 10th Pfizer Asian Cardiology Symposium,. 2007.

Tse H.F., Hong Kong Focus " Combo Drug halves CVD Risk, 2007.

Tse H.F., How Cardiac Resynchronization Therapy Works, Indonesia, 2006.

Tse H.F., Hypertension in Patients with Concomitant Cardiac Disorders: Heart Failure, Atrial Fibrillation and Coronary Heart Disease. , In Lip GYH, Hall JE (eds): Comprehensive Hypertension. Elsevier, Inc, New York, USA, . 2007, 753-760.

Tse H.F., Imaging-ECG: In Lau CP(eds), In: Lau CP, Problem-Based Medical Case Management. Hong Kong, Hong Kong University Press, 2006, 299-322.

Tse H.F., International Faculty Member, The 2nd Asia-Pacific Atrial Fibrillation Symposium, Tokyo, Japan. 2006.

Tse H.F., International Press Releases: The 21st Scienfitic Meteing of the International society of Hypertension, Oct 15 – 19, 2006, Fukuoka, Japan.” Gemini AALA presentation”, 2006.

Tse H.F., Invited Faculty, The 1st hong Kong Korea EP Case Conference, Korea. 2006.

Tse H.F., Invited Speaker " How Cardiac Resnchronziation Therapy Works" Moderator "Electropysiology Study Moderator "Current Advances in Tilt Table Test" Moderator " Free paper 6 Ventricular Arrhythmias", 8th APSPE, Jakarta, Indonesia, Aug 3-4,2006. 2006.

Tse H.F., Invited Speaker "Advising Patients on Risk Factors Management of CV Disease", Astra Zeneca Hong Kong Limited. 2006.

Tse H.F., Invited Speaker "Common Heart Diseases, Tung Wah Hospital. 2006.

Tse H.F., Invited Speaker - Biological Pacemaker: Facta nd Fiction,, 3rd stem Cell Therapy in End-Stage Cardiovascular Diseases (SCIENCE III), Shanghai, China. 2006.

Tse H.F., Invited Speaker, " How to Manage Sleep Disorders in Heart Failure", Taiwan Society of Critical Care Medicine, Taiwan. 2006.

Tse H.F., Invited Speaker, "CME Meeting for Physicians", St Teresa's Hospital. 2006.

Tse H.F., Invited Speaker, "CRT Who will Benefit?", American Heart Assocation Scientific Sessions, Chicago, Illinois, USA. 2006.

Tse H.F., Invited Speaker, "Future Prospective for Cardiac Regeneration & Update on Cardiac Resynchronization Therapy, Unviersity of Birmingham , UK. 2007.

Tse H.F., Invited Speaker, "How to Improve HDL Cholesterol, 9th South China International Congress of Cardiology International Symposium on Cardiac Arrhythmia and Heart Failure, China. 2007.

Tse H.F., Invited Speaker, Diabetes as a Cardiovascular Disease - Current Treatment Strategies", K.K. Leung Diabetes Centre, Update on Diabetes Management. 2006.

Tse H.F., Invited Speaker, Durg Therapy for cardiac arrhythmia -what's new and what's to come,"Ventricular arrhythmias- is the management and outlook any better in 2006?, 8th Biannual International Symposium Arrhythmia Lithuania 2006. 2006.

Tse H.F., Invited Speaker, Future Perspective on cardiac regeneration, King's College London, University of London, UK. 2007.

Tse H.F., Invited Speaker, HKU Space, Anti Arrhythmic treatment - Pacing and medication. 2007.

Tse H.F., Invited Speaker, Integration of the Blockade of RAAS in the Heart Failure Treatment, 10th Scientific Meeting. The Institute of Cardiovascular Science and Medicine. 2006.

Tse H.F., Invited speaker Health Talk on: "Common Heart Diseases", Tung Wah Hospital Patient Resource Centre. 2006.

Tse H.F., Member of the Editorial Board, Southern China Journal of Cardiology, 2007.

Tse H.F., Siu C.W.D., Zhu S., Liao S., Zhang Q.Y., Lai K.W.H., Nicholls J.M. and Tse H.F., Paracrine effects of direct intramyocardial implantation of bone marrow derived cells for enhancement of neovascularization in chronic ischemic myocardium, European Journal Heart Fail. 2007, 9(8): 747-53.

Tse H.F. and Li R.A., Press Release, Investigation on Bioartifical Sinus Node Provides important clinical insights into cardiac impulse generation Sep 8, 2006. 2006.

Tse H.F., Public talk- Care for the Heart: “Patients with implantable device”, 2007.

Tse H.F., Kaufman C.L., Bank A.J., Zhang X., Siu C.W., Kaiser D.R. and Lau C.P., Right Ventricular Septal Pacing Upgrade Improves Left Ventricular Performance And Functional Capacity In Patients With Previous Permanent Right Ventricular Apical Pacing Independent Of Ventricular Dyssynchrony , 28th Annual Scientific Sessions of Heart Rhythm Socity, Denver. 2007.

Tse H.F., Thambar S., Kwong Y.L., Rowlings P., Bellamy G., McCrohon J., Bastian B., Chen W.H., Chan J.K.F., Lo G., Ho C.L. and Lau C.P., Safety of Catheter-Based Intramyocardial Autologous Bone Marrow Cells Implantation fro Therapeutic Angiogenesis, AM J CARDIOL. 2006, 98(1): 60-62.

Tse H.F. and Lau C.P., Sensors for Implantable Devices: Ideal Characteristics, Sensor Combination, and Automaticity:, In: In Ellenbogen KA, Wilkoff BL, Kay GN, Lau CP (eds), Clinical Cardiac Pacing, Defibrillation, and Resynchronization Therapy. USA, Saunders Elsevier, 2007, 3rd Edition: 201-233.

Tse H.F. and Lau C.P., Therapeutic angiogenesis with bone marrow derived stem cells, J Cardiovasc Pharmacol Ther. 2007, 12(2): 89-97.

Tse H.F., Lau C.P., Park E., Bornzin G.A., Yu C., Benser M.E., Bloomfield D.M. and Padeletti L., Transient overdrive pacing upon standing prevents orthostatic hypotension in elderly pacemaker patients with chronotropic incompetence. , Pacing Clin Electrophysiol. . 2007, 30(2): 188-92.

Tse H.F., Lau C.P., Park E., Bornzin G.A., Yu C., Benser M., Bloomfield D.M. and Padeletti L., Transient overdrive pacing upon standing prevents orthostatic hypotension in elderly pacemaker patients with chronotropic incompetence., Pacing Clinc Electrophysiology. 2007, 30: 188-192.

Wang M.M., Lau C.P., Zhang X., Siu C.W., Tang M.O. and Tse H.F., Early Improvement Of Diastolic Dyschrony And Myocardial Relaxation Time After Upgrade Of Longstanding Right Ventricular Apical To Right Ventricular Septal Pacing (Oral presentation) , 28th Annual Scientific Sessions of Heart Rhythm Society, Denver, Colorado, May 9-12 2007.

White H.D., Gruber M., Kaatz S., Cunha L., Tse H.F., Husted S., Jerabek O., Rasmussen L.H. and Alberts G.W., Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V. , Arch Intern Med. 2007, 167(3): 239-45.

White H.D., Gruber M., Feyzi J., Tse H.F., Husted S. and Albers G., Comparison of outcomes in patients randomized to warfairn according to anticoagulant control: results from Sportif III , J Am Coll Cardiol. 2007, 41: 408A.

Wu Y., Tang H., Ng M.C., Yang J., Tse H.F., Lau C.P., Yang E.S. and Wu E.X., Study of myocardial fiber length distribution with diffusion tensor MRI, 2006 Proceedings of International Society of Magnetic Resonance in Medicine. 2006, 1222.

Xue T., Siu C.W.D., Lieu D.K., Lau C.P., Tse H.F. and Li R.A., Mechanistic role of I(f) revealed by induction of ventricular automaticity by somatic gene transfer of gating-engineered pacemaker (HCN) channels., Circulation. 2007, 115(14): 1839-1850.

Yiu K.H., Siu C.W.D., Lee K.L.F., Lau C.P., Lee S.W.L., Fong D.Y.T. and Tse H.F., Emerging trends of community acquired infective endocarditis. , Int Cardiol J . 2006, 121(1): 119-22.

Yiu K.H., Siu C.W., Lau C.P., Lee K.L.F. and Tse H.F., Transvenous catheter-based microwave ablation for atrial flutter., Heart Rhythm. 2007 . 2007, 4(2): 221-3.

Zhang X., Chen H., Tsang V.Y.C., Tang M.O., Lau C.P. and Tse H.F., Prevalence And Clinical Predictors For New-onset Heart Failure After Permanent Right Ventricular Apical Pacing In Patients With Aquired High-grade Atrioventricular Block, World Congress of Cardiology 2006, Barcelona. 2006.

Researcher : Tu S

List of Research Outputs

Zou B., Chim J.C.S., Zeng H., Leung S.Y., Yang Y., Tu S., Lin M.C., Wang J., He H., Jiang S.H., Sun Y., Yu L., Yuen S.T., Kung H.F. and Wong B.C.Y., Correlation Between the Single-site CpG Methylation and Expression Silencing of the XAF1 Gene in Human Gastric and Colon Cancers, Gastroenterology. 2006, 131(6): 1835-1843.

Researcher : Wan CC

List of Research Outputs

Wan C.C., Yung S.S.Y., Tsang R.C.W. and Chan D.T.M., Fibrosis-related growth factors in peritoneal dialysate during peritonitis, Peritoneal Dialysis International. 2006, 26 (Suppl 2): S22.

Yung S.S.Y., Wan C.C., Tsang R.C.W., Mak J.C.W., Tsang K.W.T. and Chan D.T.M., Induction of IL-6 and matrix protein synthesis in human peritoneal mesothelial cells by Pseudomonas aeruginosa exotoxin pyocyanin, Journal of the American Society of Nephrology. 2006, 17: 305A.

Researcher : Wang AYM

Project Title:	Endothelial progenitor cells in renal failure patients and its modulation by treatment with the peroxisome proliferator-activated receptor-gamma agonist in relation to clinical atherosclerosis
Investigator(s):	Wang AYM, Lai KN
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2007

Abstract:

To test the hypothesis that endothelial progenitor cells (EPCs) are reduced and show impaired angiogenic function and that contribute to endothelial dysfunction and atherosclerosis in chronic renal failure (CRF) patients; to test the hypothesis that the number and functional activity of EPCs increase with amelioration of uremia by dialysis and that correspond to an improvement in flow-mediated dilatation in CRF patients; to study the short-term and longer-term effects of treatment with the peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist on the proliferation and functional activity of EPCs in relation to endothelial dysfunction and progression of atherosclerosis in chronic renal failure patients.

List of Research Outputs

Tang S.C.W., Ho Y.W., Tang A.W., Yip T., Tse K.C., Wang A.Y.M., Lo W.K., Chan D.T.M., Lai K.N. and Lui S.L., What is the optimal timing of dialysis initiation? , Peritoneal Dialysis International . 2006, Suppl 26: S90.

Yip T., Tse K.C., Lam M.F., Cheng S.W., Lui S.L., Tang S.C.W., Li F.K., Wang A.Y.M., Choy C.B.Y., Ng M.M.T., Chan D.T.M., Lai K.N. and Lo W.K., Risk and outcome of peritonitis after flexible colonoscopy in CAPD patient, Peritoneal Dialysis International . 2006, Suppl 26: S68.

Researcher : Wang J

List of Research Outputs

Wang J., Yang Y., Xia H.H.X., Gu Q., Lin M.C., Jiang B., Peng Y., Li G., An X., Zhang Y., Zhuang Z., Zhang Z., Kung H.F. and Wong B.C.Y., Suppression of FHL2 Expression Induces Cell Differentiation and Inhibits Gastric and Colon Carcinogenesis , Gastroenterology. 2007, 132: 1066-1076.

Yu L., Wang J., Zou B., Lin M.C., Wu Y.L., Xia H.H.X., Sun Y., Gu Q., He H., Lam S.K., Kung H.F. and Wong B.C.Y., XAF1 Mediates Apoptosis Through an Extracellular Signal-Regulated Kinase Pathway in Colon Cancer , Cancer. 2007, 109(10): 1996-2003.

Zou B., Chim J.C.S., Zeng H., Leung S.Y., Yang Y., Tu S., Lin M.C., Wang J., He H., Jiang S.H., Sun Y., Yu L., Yuen S.T., Kung H.F. and Wong B.C.Y., Correlation Between the Single-site CpG Methylation and Expression Silencing of the XAF1 Gene in Human Gastric and Colon Cancers, Gastroenterology. 2006, 131(6): 1835-1843.

Researcher : Wang MM

List of Research Outputs

Wang M.M., Clinical application of tissue Doppler imaging. , Clinical application of tissue Doppler imaging. (Lecture) The 12th Congress of the International Cardiac Doppler Society, Jinan, China. August 4-5. 2006.

Wang M.M., Lau C.P., Zhang X., Siu C.W., Tang M.O. and Tse H.F., Early Improvement Of Diastolic Dyschrony And Myocardial Relaxation Time After Upgrade Of Longstanding Right Ventricular Apical To Right Ventricular Septal Pacing (Oral presentation) , 28th Annual Scientific Sessions of Heart Rhythm Society, Denver, Colorado, May 9-12 2007.

Wang M.M., Echo Measurements Of Dyssynchrony In Heart Failure Patients Implication For Cardiac Resynchronization Therapy, The Hong Kong Society for Ultrasound in Medicine on 28 July . 2007.

Researcher : Wang Y

List of Research Outputs

Chu A.C.Y., Ho W.L., Kwok H.H., Wang Y., Ramsden D.B. and Ho S.L., Human uncoupling protein-4 protects neuronal cell death from MPP+ induced toxicity by regulating mitochondrial membrane potential, reducing ROS and maintaining ATP levels., 11th International Congress of Parkinson's disease and Movement Disorders, Istanbul, Turkey. {Abs]. Istanbul, Turkey., Mov Disord, 2007, 22 (Suppl 16):: 67.

Researcher : Wat NMS

List of Research Outputs

Cheung B.M.Y., Wat N.M.S., Man Y.B., Tam S., Thomas G.N., Leung G.M., Cheng C.H., Woo J., Janus E.D., Lau C.P., Lam T.H. and Lam K.S.L., Development of diabetes in Chinese with the metabolic syndrome, Diabetes care. 2007, 30: 1430-1436.

Cheung B.M.Y., Wat N.M.S., Man Y.B., Tam S., Cheng C.H., Leung G.M., Woo J., Janus E.D., Lau C.P., Lam T.H. and Lam K.S.L., Predictors of the development of hypertension in the Hong Kong cardiovascular risk factor prevalence study-2 (CRISPS2), The 21st Scientific Meeting of the International Society of Hypertension. 2006.

Cheung B.M.Y., Wat N.M.S., Man Y.U. .B.U.N., Tam S., Cheng C.H., Leung G.M., Woo J.E.A.N., Janus E.D.W.A.R.D. .D., Lau C.P., Lam T.H. and Lam K.S.L., Waist Circumference as a Predictor of Cardiovascular Risk in the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS2), The 21st Scientific Meeting of the International Society of Hypertension. 2006.

Chow W.S., Cheung B.M.Y., Xu A., Wat N.M.S., Fong H.Y., Ong L.H.Y., Tam S., Tan K.C.B., Janus E.D., Lam T.H. and Lam K.S.L., Hypoadiponectinemia as a predictor for the development of hypertension: a 5-year prospective study. , Hypertension. 2007, 49: 1455-61.

Ong K.L., Cheung B.M.Y., Man Y.B., Wong Y.F., Wat N.M.S., Tan K.C.B. and Lam K.S.L., Treatment and control of diabetes mellitus in the United States National Healthy and Nutrition Examination Survey 1999-2002, Journal of Cardiometabolic Syndrome. 2006, 1: 301-7.

Ong L.H.Y., Chow W.S., Tso A.W.K., Wat N.M.S., Xu A., Fong H.Y., Janus E.D. and Lam K.S.L., Hypoadiponectinaemia predicts the development of hypertension in Chinese. , The 19th World Diabetes Congress, 3-7 December 2006, Cape Town, South Africa. 2006.

Thomas G.N., Schooling C.M., McGhee S.M., Ho D.S.Y., Cheung B.M.Y., Wat N.M.S., Janus E.D. and Lam T.H., Identification of factors differentially associated with isolated impaired fasting glucose and isolated post-load impaired glucose tolerance: The Hong Kong cardiovascular risk factor study, European Journal of Endocrinology. 2006, 155: 623-32.

Thomas G.N., Schooling C.M., McGhee S.M., Ho D.S.Y., Cheung B.M.Y., Wat N.M.S., Janus E.D., Lam K.S.L. and Lam T.H., Metabolic syndrome increases all-cause and vascular mortality: The Hong Kong cardiovascular risk factor study, Clinical Endocrinology. 2007, 66: 666-71.

Tso A.W.K., Wat N.M.S., Xu A., Tam S., Fong H.Y., Janus E.D., Tan K.C.B. and Lam K.S.L., Adiponectin/C-reactive protein ratio is an independent surrogate marker predictive of the development of metabolic risks and the metabolic syndrome over 5 years in Chinese, The 6th International Diabetes Federation Western Pacific Region Congress, Bangkok. 2006.

Tso A.W.K., Tan K.C.B., Wat N.M.S., Janus E.D., Lam T.H. and Lam K.S.L., Endothelial nitric oxide synthase G894T (Glu298Asp) polymorphism was predictive of glycemic status in a 5-year prospective study of Chinese subjects with impaired glucose tolerance, Metabolism. 2006, 55: 1155-8.

Tso A.W.K., Sham P.C., Wat N.M.S., Xu A., Cheung B.M.Y., Rong R., Fong H.Y., Xu J., Cheng K.Y., Janus E.D. and Lam K.S.L., Polymorphisms of the gene encoding adiponectin and glycaemic outcome of Chinese subjects with impaired glucose tolerance: a 5-year follow-up study, Diabetologia. 2006, 49: 1806-15.

Tso A.W.K., Xu A., Wat N.M.S., Fong H.Y., Janus E.D. and Lam K.S.L., Serum adipocyte fatty acid-binding protein is a predictor of the development of type 2 diabetes mellitus over 5 years. , The Endocrine Society's 89th Annual Meeting, 2-5 June2007, Toronto. 2007.

Wang Y., Lam K.S.L., Kraegen E.W., Sweeney G., Zhang J., Tso A.W.K., Chow W.S., Wat N.M.S., Xu J., Hoo R.L.C. and Xu A., Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans, Clin Chem. 2007, 53: 34-41.

Wat N.M.S., Tan K.C.B., Chow W.S., Tse P.M., Wong K., Leung E., Hung V., Leung S.K., Yee A., Leung C.Y. and Lam K.S.L., Innovative risk stratification model for high-risk diabetic patients in a tertiary referral centre – triage of the triaged, Health Authority Convention, May 2007.

Xu A., Tso A.W., Cheung B.M.Y., Wang Y., Wat N.M.S., Fong H.Y., Yeung C.Y., Janus E.D., Sham P.C. and Lam K.S.L., Circulating adipocyte-fatty acid binding protein levels predict the development of the metabolic syndrome: a 5-year prospective study, Circulation. 2007, 115: 1537-43.

Xu A., Tso A.W.K., Cheung B.M.Y., Wang Y., Wat N.M.S., Fong H.Y., Yeung C.Y., Janus E.D., Sham P.C. and Lam K.S.L., Circulating levels of adipocyte-fatty acid binding protein correlate with its adipose tissue expression and predict the development of the metabolic syndrome. , The Endocrine Society's 89th Annual Meeting, 2-5 June 2007, Toronto. 2007.

Xu J., Sham P.C., Xu A., Tso A.W.K., Wat N.M.S., Cheng K.Y., Fong H.Y., Janus E.D. and Lam K.S.L., Resistin gene polymorphisms and progression of glycaemia in southern Chinese: a 5-year prospective study, Clin Endocrinol (Oxf). 2007, 66: 211-7.

Yee A., Wat N.M.S., Tan K.C.B., Wong K., Leung E., Leung S.C., Hung V., Tse P.M., Leung C.Y. and Lam K.S.L., Innovative intervention mechanism for patients with diabetic nephropathy to achieve blood pressure treatment target, Health Authority Convention, May 2007.

Yeung C.Y., Xu A., Cheung C.W., Wat N.M.S., Yau M.H., Fong H.Y. and Lam K.S.L., Circulating serum adipocyte-fatty acid-binding protein (A-FABP) levels correlate with carotid intima-media thickness (IMT) in Southern Chinese women. , 89th Annual Meeting of Endocrine Society, 2-5 June 2007, Toronto, Canada. 2007.

Researcher : Wong ASY

List of Research Outputs

Wong A.S.Y., Chan K.H., Cheng V.C.C., Yuen K.Y., Kwong Y.L. and Leung A.Y.H., Relationship of pretransplantation polyoma BK virus serologic findings and BK viral reactivation after hematopoietic stem cell transplantation, Clinical Infectious Disease. 2007, 44(6): 830-837.

Researcher : Wong BCY

Project Title:	Effect of XAF1 gene on tumor growth in gastric and colon cancer
Investigator(s):	Wong BCY, Tu S
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	01/2003

Abstract:

To study the effect of XAF1 on tumor growth.

Project Title:	Regulation of hTERT in relation to non-steroidal anti-inflammatory drugs in gastronintestinal carcinogenesis
Investigator(s):	Wong BCY, Lin MC
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	10/2003
Completion Date:	09/2006

Abstract:

Identify the cis-element responsible for NSAIDs-mediated inhibition of hTERT transcription; charaterize the transcription factor(s) and binding sites that is responsible for NSAIDs-mediated inhibition of hTERT transcription.

Project Title:	Role of Bcl-2 family proteins in non-steroidal anti-inflammatory drug-induced apoptosis of gastric cancer
Investigator(s):	Wong BCY, Xia HHX
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2004

Abstract:

To clarify the role of Bcl-2 family proteins in NSAID-induced apoptosis in vitro in this proposal using gastric cancer cell lines.

Project Title:	Helicobacter pylori infection and CpG island methylation in gastric carcinogenesis
Investigator(s):	Wong BCY, Epstein R, Chan AOO
Department:	Medicine
Source(s) of Funding:	Michael Kadoorie Cancer Genetics Research Fund
Start Date:	10/2004

Abstract:

To investigate if CpG island methylation at E-cadherin, as well as other tumor suppressor genes, in normal human gastric mucosa can be reversed by eradicating H. pylori; to establish an animal model to study the regulatory mechnaism of CpG island methylation at E-cadherin in gastirc cancer cell lines by Helicobacter pylori and interleukin 1.

Project Title:	Role of cyclooxygenase in helicobacter pylori-induced gastric carcinogenesis
Investigator(s):	Wong BCY, Xia HHX
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2005

Abstract:

To determine the differences in gastric epithelial proliferation and apoptosis as well as in the incidence of gastric precancerous and cancerous lesions between COX deficient mice and wild-type mice after long-term infection with H. pylori; to determine the effects of NSAIDs and specific COX2 inhibitors on gastric proliferation and apoptosis, and their potential role in the prevention of gastric precancerous and cancerous lesions in H. pylori infected Mongolian gerbils.

List of Research Outputs

Chan A.O.O., Jim M.H., Lam K.F., Siu D.C.W., Tong S.M., Ng F.H., Wong S.Y., Hui W.M., Lam S.K. and Wong B.C.Y., Aspirin does not prevent recurrence of colorrectal adenomas in patients with coronary artery disease. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A194.

Chan A.O.O., Hui W.M., Leung Y.C., Wong Y.H., Chan P., Hung I.F.H., Hsu A., But D., Lam S.K. and Wong B.C.Y., Better efficacy of tegaserod in constipated patients with slow colonic transit, absent pelvic floor dyssynergy and absent impaired rectal sensation. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A194.

Chan A.O.O., Chow R., Hui W.M., Leung Y.C., Tong S.M., Lam S.K. and Wong B.C.Y., Biofeedback is equally effective in patients with short or long duration of function constipation. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A194.

Chan A.O.O., Liu C.L. and Wong B.C.Y., Choledochal cysts. , In: Baron T, Kozarek R & Carr-Locke D (eds), A Practical Guide to ERCP. Elsevier, 2007.

Chan A.O.O., Hui W.M., Wong Y.H., Leung Y.C., Lam S.K. and Wong B.C.Y., Decreased cortical activation during rectal distention in patients with functional constipation with normal rectal compliance. Digestive Disease Week 2007, Washington DC, USA, May 19-24, Gastroenterology. 2007, 132(4) Suppl 2: A23.

Chan A.O.O., Hui W.M., Leung Y.C., Hu H.C., Lam S.K. and Wong B.C.Y., Efficacy of tegasered for functiona constipation in Chinese subjects: A randomized double blind contolled trial in a single center. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4): A194.

Chan A.O.O., Hui W.M., Leung Y.C., Hu H.C., Lam S.K. and Wong B.C.Y., Efficacy of tegaserod for functional constipation in Chinese subjects: a randomized double-blind controlled trial in a single center, Alimentary Pharmacology and Therapeutics. 2007, 25(4): 463-469.

Chan A.O.O., Hui W.M., Lam K.F., Leung G.K.L., Yuen R.M.F., Lam S.K. and Wong B.C.Y., Familial aggregation in constipated subjects in a tertiary referral center, American Journal of Gastroenterology. Blackwell Publishing, 2007, 102: 149-152.

Chan A.O.O., Huang C.Y., Leung Y.C., Hui W.M., Lam S.K. and Wong B.C.Y., Familial constipationis associated with a2 adrenoceptor polymorphism. Digestive Diseases Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A189.

Chan A.O.O., Lam K.F., Hui W.M., Leung G.K.L., Wong Y.H., Lam S.K. and Wong B.C.Y., Influence of Positive Family History on Clinical Characteristics of Functional Constipation, Clinical Gastroenterology and Hepatology. Elsevier, 2007, 5(2): 197-200.

Chan A.O.O. and Wong B.C.Y., Multi-disciplinary approach to intestinal gastric cancer. Edited by Jankowski J, Kerr D, Sampliner R, Fong YM, In: Gastrointestinal Oncology: A multidisciplinary approach. Blackwell Publishing, 2007.

Chan A.O.O., Jim M.H., Lam K.F., Siu D.C.W., Tong S.M., Ng F.H., Wong S.Y., Hui W.M., Chan C.K., Lai K.C., Cheung T.K., Chan P., Wong G., Yuen R.M.F., Lau Y.K., Lee S.W.L., Seto M.L., Lam S.K. and Wong B.C.Y., Patients with coronary artery disease had high prevalanece of colorectal cancer and adenoma: END-results of metabolic syndrome and smoking. Digestive Disease Week 2007, Washington DEc, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A65.

Chan A.O.O., Hui W.M., Leung G.K.L., Tong T.P.H., Hung I.F.N., Chan P., Hsu A., But D., Wong B.C.Y., Lam S.K. and Lam K.F., Patients with functional constipation do not have increase prevalence of colorectal cancer precursors”, GUT. British Medicial Journal, 2007, 56: 451-452.

Chan A.O.O., Ng F.H., Chang P.C.M., Wong S.Y., Chu W.M., Yuen W.C., Lau Y.K., Cheung T.K. and Wong B.C.Y., Prevalence and prediction of gastrointestinal events in patients receiving a combination of aspirin plus clopidogrel. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A135.

Chan A.O.O., Loo C.K., Leung C.M., Wong S.Y., Ng F.H., Li M.K.W., Lam K.M., Lam S.K. and Wong B.C.Y., Prevalence of colonic lesions after a negative screening colonscopy in a population with rapidly rising colorectal cancer incidence: A prospective multi-center analysis. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A189.

Chan O.O., Lam K.F., Tong T.P.H., Siu D.C.W., Jim M.H., Hui W.M., Lai K.C., Yuen R.M.F., Lam S.K. and Wong B.C.Y., Coexistence between colorectal cancer/adenoma and coronary artery disease: results from 1382 patients. , Alimentary Pharmacology and Therapeutics. 2006, 24(3): 535-9.

Chan O.O., Huang C.Y., Hui W.M., Cho C.H., Yuen R.M.F., Lam S.K., Rashid A. and Wong B.C.Y., Stability of E-cadherin methylation status in gastric mucosa associated with histology changes. , Alimentary Pharmacology and Therapeutics. 2006, 24(5): 831-6.

Cheung T.K., Lai C.L., Wong B.C.Y., Fung J.Y.Y. and Yuen R.M.F., Clinical Features, Biochemical Parameters, and Virological Profiles of Patients with Hepatocellular Carcinoma in Hong Kong, Aliment Pharmacol Ther . 2006, 24(4): 573-583.

Cheung T.K., Lai C.L., Wong B.C.Y., Fung J.Y.Y. and Yuen R.M.F., Clinical features, biochemical parameters, and virological profiles of patients with hepatocellular carcinoma in Hong Kong. , Alimentary Pharmacology and Therapeutics. 2006, 24(4): 573-83.

Cheung T.K., Xia H.H.X. and Wong B.C.Y., Helicobacter pylori Eradication for Gastric Cancer Prevention., Journal of Gastroenterology. 2007, 42 (Suppl 17): 10-15.

Cheung T.K., Lam B., Ip M.S.M., Wong Y.H., Chan A.O.O., Lam S.K. and Wong B.C.Y., Nocturnal Reflux Symptoms Correlate with Respiratory Events in Patients with Obstructive Sleep Apnea. , AGA Digestive Digestive Disease Week 2007.

Cheung T.K., Lam B., Ip M.S.M., Wong Y.H., Chan A.O.O., Lam S.K. and Wong B.C.Y., Nocturnal reflux symptoms correlate with respiratory events in patients with obstructive sleep apnea. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132 (4) Supp 2: A482.

Cheung T.K., Lim P.W. and Wong B.C.Y., Noncardiac chest pain- An Asia-Pacific survey on the views of primary care physicians, Digestive Diseases and Sciences. 2007, epub.

Cheung T.K. and Wong B.C.Y., PPI Failure/Resistance: Proposed Mechanisms and Therapeutic Algorithm. , Journal of Gastroenterology and Hepatology. 2006, 21 (suppl 5): 119-124.

Cheung T.K., Hu H.C., Lam C.L.K., Hui W.M., Lam S.K. and Wong B.C.Y., Positive association between gastro-oesophageal reflux disease and irritable bowel syndrome in a Chinese population. , Aliment Pharmacol Ther . 2007, 25.

Cheung T.K., Lam K.F., Hu H.C., Wong W.M., Hui W.M., Lam C.L.K., Lai K.C., Lam S.K. and Wong B.C.Y., Positive association between gastro-oesophageal reflux disease and irritable bowel syndrome in a Chinese population, Alimentary Pharmacology & Therapeutics. Blackwell Publishing, 2007, 25: 1099-1104.

Cheung T.K. and Wong B.C.Y., Proton pump inhibitor failure/resistance: Proposed mechanisms and therapeutic algorithm, Journal of Gastroenterology and Hepatology. 2006, 21(S5): S119-S124.

Chey W.D. and Wong B.C.Y., American College of Gastroenterology Guideline on the management of Helicobacter pylori infection. Practice Parameters Committee of the American College of Gastroenterology, American Journal of Gastroenterology. 2007, epub.

Dai Y., Qiao L., Gu Q., Xia H.H.X., Cheung T.K., Ma J., Zou B. and Wong B.C.Y., Activation of Pparc and inhibition of Xiap in human cancer cells: Synergistic effects on cell proliferation, apoptosis, and tumorigensis. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A425.

Ge R., Sun X., Gu Q., Watt R.M., Tanner J.A., Wong B.C.Y., Xia H.H.X., Huang J.D., He Q.Y. and Sun H., A proteomic approach for the identification of bismuth-binding proteins in Helicobacter pylori, Journal Biol Inorg Chem. 2007, 12: 831.

Ho K.Y., Cheung T.K. and Wong B.C.Y., Gastroesophageal reflux disease in Asian countries: Disorder of nature or nurture? , Journal of Gastroenterology and Hepatology. 2006, 21 (9): 1362-1365.

Hu H.C., Lam S.K., Lam C.L.K., Wong R.W.M., Lam K.F., Lai K.C., Wong Y.H., Wong B.C.Y., Chan O.O., Chan C.K., Leung G.M. and Hui W.M., Comparison between Empirical Prokinetics, Helicobacter Test-and-Treat and Empirical Endoscopy in Primary-Care Patients Presenting with Dyspepsia: A One-Year Study, World Journal of Gastroenterology. 2006, 12(31): 5010-5016.

Lai K.C., Chu K.M., Hui W.M., Wong B.C.Y., Hung W.K., Loo C.K., Hu H.C., Chan O.O., Kwok K.F., Fung T.T., Wong J. and Lam S.K., Esomeprazole with aspirin versus clopidogrel for prevention of recurrent gastrointestinal ulcer complications, Clinical Gastroenterology and Hepatology. 2006, 4: 860-865.

Lam T.J., Mulder C.J.J., Peña S., Wong B.C.Y., Hui W.M., Lam S.K. and Chan A.O.O., Increased in prevalence of advanced colonic polyps in young patients over the past eight years in Hong Kong. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A195.

Ng S.M., Cheung Y.T., An X.M., Chen Y.C., Li M., Li H.Y., Cheung K.C., Sze J., Lai L., Peng Y., Xia H.H.X., Wong B.C.Y., Leung S.Y., Xie D., He M.L., Kung H.F. and Lin M.C., Cell Cycle-related Kinase: A Novel Candidate Oncogene in Human Glioblastoma, Journal of the National Cancer Institute. 2007, 99(12): 936-948.

Qiao L., Gu Q., Dai Y., Shen Z., Liu X., Ma J. and Wong B.C.Y., XAF1 inhibits angiogenesis of mouse endothelia cells. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A638.

Tang L.P., Cho C.H., Hui W.M., Huang C., Chu K.M., Xia H.H.X., Lam S.K., Rashid A., Wong B.C.Y. and Chan O.O., An inverse correlation between IL-6 and select gene promoter methylation in patients with gastric cancer, Digestion. 2006, 74: 85-90.

Tse M.K., Wong B.C.Y. and Sze K.H., Structural and Functional Study of XIAP-Associated Factor 1 (XAF1) Identification and Characterization of a 13 kDa Structural Domain , The 4th Joint Conference of the Hong Kong Biophysical Society and teh Guangdong Biophysical Society, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, January 27, 2007.

Wang J., Yang Y., Xia H.H.X., Gu Q., Lin M.C., Jiang B., Peng Y., Li G., An X., Zhang Y., Zhuang Z., Zhang Z., Kung H.F. and Wong B.C.Y., Suppression of FHL2 Expression Induces Cell Differentiation and Inhibits Gastric and Colon Carcinogenesis , Gastroenterology. 2007, 132: 1066-1076.

Wang W.H., Huang J., Zheng G., Xia H.H.X., Wong R.W.M., Liu X.G., Karlberg J.P.E. and Wong B.C.Y., Effects of proton-pump inhibitors on function dyspepsia: A meta-analysis of randomized placebo-controlled trails, Clinical Gastroenterology & Hepatology. 2007, 5(2): 178-185.

Wong B.C.Y., GERD, Sun Daily, 23 August. 2006, S1.

Wong B.C.Y., Alcohol intoxication, Oriental Daily, 9 October. 2006, A26.

Wong B.C.Y., Asian GERD survey, Press conference covered by major newsapaper, 19 December. 2006.

Wong B.C.Y., Associate Editor, since 2004, Digestive Disease Watch. 2006.

Wong B.C.Y., Associate Editor-in-chief, since 2002, Chinese Journal of Gastroenterology. 2006.

Wong B.C.Y., Associate Editor-in-chief, since 2007, Forum of Gastroenterology and Hepatology. 2007.

Wong B.C.Y., Association between GERD adn IBS, Hong Kong Economics Times, 22 May. 2007, C11.

Wong B.C.Y., Biliary disease and renal impairment, Next Magazine, 5 October. 2006, 38-42.

Wong B.C.Y., Biliary diseases, Next Magazine, 28 September. 2006, 47.

Wong B.C.Y., Charcoal and intestine, Apple Daily, 23 August . 2006, A12.

Wong B.C.Y., Chemoprevention of gastirc cancer with aspirin: bench to bedside, Proceedings, Frontiers in Biomedical Rersearch HKU 2006, Hong Kong, 8 December. 2006, 40-41.

Wong B.C.Y., Chemoprevention of gastric cancer by aspirin; bench to bedside, 4th International Society of Gastroenterological Carcinogenesis Conference, Hawaii, 24-26 August . 2006.

Wong B.C.Y., Chemoprevention of gastric cancer by aspirn: bench to bedside, Kenote Lecture: Frontiers in Biomedical Research HKU 2006, LKS Facutly of Medicine, The University of Hong Kong, 8 December. 2006.

Wong B.C.Y., Chemoprevention of gastric cancer with asprin: bench to bedside, Proceedings, 4th International Society of Gastroenterological Carcinogenesis Conference, Hawaii, USA, 24-26 August. 2006.

Wong B.C.Y., Colon cancer screening, Sudden Weekly Magazine, 6 October. 2006, 128-129.

Wong B.C.Y., Common gastrointestional diseases, Dinner Talk, Hong Kong Commerce and Industry Association, Hong Kong, 14 June . 2007.

Wong B.C.Y., Common liver diseases, Dinner Talk, Kowloon Liaison Office, Chinese General Chamber of Commerce, Hong Kong, 12 April. 2007.

Wong B.C.Y., Constipation, Sing Tao Daily, 7 January. 2007, A8.

Wong B.C.Y., Crohn's disease, Sing Tao Daily Newspaper, 11 April . 2007, A12.

Wong B.C.Y., Diagnosis of GERD, is clinical profile enough? , Asia Pacific Digestive Week 2006, Philippines, 26-29 November. 2006.

Wong B.C.Y., Diagnosis of GERD: Is clinical profile enough?, Proceedings, Asian Pacific Digestive Week 2006, Cebu City, Philippines, 26-29 November. 2006.

Wong B.C.Y., Digestive and liver diseases, Dinner Meeting, Worldwide Chinese Investors Association International Limited, Hong Kong, 20 November. 2006.

Wong B.C.Y., Does helicobacter pyloi eradication prevent gastric cancer, 7th National Digestive Disease Week, Jinan, Shandong, PR China, 7 May. 2007.

Wong B.C.Y., Does helicobacter pylori eradication prevent gastric cancer, Sun Yat Sen Medical University, Guangzhou, PR China, 25 December. 2006.

Wong B.C.Y., Drug trafficking in GI tract, News of Cable TV News Channel, 20 November. 2006.

Wong B.C.Y., Dyspepsia and indigestion, Sing Pao, 21 December. 2006, A14.

Wong B.C.Y., Dyspepsia, Ming Pao Weekly Magazine, 4 November. 2006, S4.

Wong B.C.Y., Dyspepsia, Sun Daily, 27 December. 2006, S6.

Wong B.C.Y., Editor, since 2003, Journal of Gastroenterology and Hepatology. 2006.

Wong B.C.Y., Editorial Baord, since 2004, Gastrointestinal Endoscopy. 2006.

Wong B.C.Y., Editorial Baord, since 2004, World Journal of Gastroenterology. 2006.

Wong B.C.Y., Editorial Board, since 1999, Chinese Journal of Gastroenterology. 2006.

Wong B.C.Y., Editorial Board, since 1999, Journal of Clinical Oncology, Chinese edition. 2006.

Wong B.C.Y., Editorial Board, since 2000, Journal of Gastroenterology and Hepatology. 2006.

Wong B.C.Y., Editorial Board, since 2001, Digestive Endoscopy. 2006.

Wong B.C.Y., Editorial Board, since 2002, Journal of Digestive Disease. 2006.

Wong B.C.Y., Editorial Board, since 2002, MIMS Gastriebterology Guide. 2006.

Wong B.C.Y., Editorial Board, since 2003, Modern Digestion and Intervention. 2006.

Wong B.C.Y., Editorial Board, since 2004, Alimentary Pharmacology and Therapeutics. 2006.

Wong B.C.Y., Editorial Board, since 2004, European Review for Medical and Pharmacologist Sciences. 2006.

Wong B.C.Y., Editorial Board, since 2005, Carcinogenesis. 2006.

Wong B.C.Y., Editorial Board, since 2007, Cancer Epidemiology, Biomarkers & Prevention. 2007.

Wong B.C.Y., Editorial Board, since 2007, Frontiers of Medicine in China. 2007.

Wong B.C.Y., Editorial Board, since 2007, Medical Progress. 2007.

Wong B.C.Y., Endoscopic removal of foreign body, AM730, 14 March. 2007, 1.

Wong B.C.Y., Eradication of H pylori: is it necessary for gastric cancer prevention? - The evidence for / against its effectiveness and strategies in its practice -, Abstract Book, 13th Annual Meeting, The Japanese Society of Helicobacter Research, Osaka, Japan, 21-22 June . 2007, 38.

Wong B.C.Y., Foreign body ingestion, Oriental Daily, 15 March. 2007, A4.

Wong B.C.Y., GERD, 4th Beijing International Digestive Disease Forum, Beijing, PR China, 15 June. 2007.

Wong B.C.Y., GERD, AstraZenca Symposium, Hanoi, Vietnam, 29 June. 2007.

Wong B.C.Y., GERD, AstraZeneca Symposium, Ho Chi Minh City, Vietnam, 30 June. 2007.

Wong B.C.Y., GERD, Health Action Magazine, May. 2007, 12-13.

Wong B.C.Y., GERD, Next Magazine, 1 March. 2007, 106-109.

Wong B.C.Y., GERD, Sing Pao Daily News, 9 January. 2007, R1.

Wong B.C.Y., GERD, Sing Tao Daily, 4 January. 2007, E4.

Wong B.C.Y., GERD, Symposium, Hong Kong College of Family Physicians, Hong Kong, 15 October. 2006.

Wong B.C.Y., GERD, TVB Pleasure and Leisure, 1:15 pm - 2:00 pm, 18 June. 2007.

Wong B.C.Y., GERD, Xiamen University Zhong Shan Hospital, Xiamen, PR China, 12 May. 2007.

Wong B.C.Y., Gastric cancer in blood group A subjects, Apple Daily, 4 July. 2006, A16.

Wong B.C.Y., Gastroenteritis, Sun Daily, 31 January. 2007, S1.

Wong B.C.Y., H pylori treatment and related chemoprevention of gastric cancer in elderly, Symposium of Cancer Prevention in the Elderly, Digestive Disease Week, Washington DC, USA, 23 May. 2007.

Wong B.C.Y., Helicobacter pylori and gastric cancer, Sino Japan Internatonal Conference on Early Gastrointestinal Cancer, Shanghai, PR China, 9-11 November. 2006.

Wong B.C.Y., Helicobacter pylori treatment and related chemoprevention of gastric cancer inthe elderly, Scientific Sessions Handouts, AGA Institute Clinical Symposium, Digestive Disease Week, Washington DC, USA, 19-24 May. 2007, 397-398.

Wong B.C.Y., Inflammatory bowel diseases, Oriental Daily, 3 January. 2007, A20.

Wong B.C.Y., Inflammatory bowel diseases, Sun Daily, 3 January . 2007, A1.

Wong B.C.Y., Ingestion of sharp objects, Sing Tao Daily Newspaper, 4 May. 2007, A8.

Wong B.C.Y., Ingestoin of foreign body, Apple Daily, 29 January. 2007, A8.

Wong B.C.Y., Ingsetion of foreign body, Hong Kong Economic Times, 14 March. 2007, A30.

Wong B.C.Y., Irritable bowel syndrome, Sun Daily, 11 October. 2006, S1.

Wong B.C.Y., Laryngeal reflux and GERD, Oriental Daily, 28 February. 2007, A8.

Wong B.C.Y., Latest development in GERD, Health Plus Magazine, February . 2007, 11.

Wong B.C.Y., Management of Barrett's esophagus and high grade dyplasia, GIHep Singapore 2007, Singapore, 3 March. 2007.

Wong B.C.Y., Management of high grad dysplasia inBarrett's esophagus, Proceedings, 2nd Annual Scientific Meeting, GIHep Singapore, 2 March. 2007, 26.

Wong B.C.Y., Montreal definition of GERD, AstraZeneca Lunch Symposium, Ritze Cartlon Hotel, Hong Kong, 14 September. 2006.

Wong B.C.Y., Montreal definition of GERD, AstraZenece Lunch Symposium, Langham Hotel, Hong Kong, 21 September . 2006.

Wong B.C.Y., Narcotics in GI tract, Appl Daily, 21 November. 2006, A18.

Wong B.C.Y., Narcotics in GI tract, New Daily, 21 November. 2006, A2.

Wong B.C.Y., Non cardiac chest pain, Apple Daily, 18 June. 2007, A14.

Wong B.C.Y., Non-erosive reflux disease , Special Lecture, 2006 Autumn Convention of Gastroenterological Society of Taiwan, 30 September. 2006.

Wong B.C.Y., PPI refractory GERD, Breakfast with Champions Section, Asia Pacific Digestive Week 2006, Philippines, 26-29 November. 2006.

Wong B.C.Y., Peptic ulcer, Men's Uno, January. 2007, 242.

Wong B.C.Y., Peptic ulcers, Sun Daily, 8 November. 2006, S4.

Wong B.C.Y., Prevention of colon cancer, Hong Kong Federation of Women Health Talk Series, HA Headquarter, Hong Kong, 28 April. 2007.

Wong B.C.Y., Targeting apoptosis in GI cancer: Aspirin and beyond, National Cancer Institute, USA, 22 May. 2007.

Wong B.C.Y., Treatment of gastrointestinal bleeding, Oriental Daily, 11 October. 2006, A11.

Wong B.C.Y., Update on treatment of peptic ulcers, AstraZeneca Lunch Symposium, Asia Pacific Digestive Week 2006, Philippines, 26-29 November. 2006.

Wong B.C.Y., Use of COX inhibitiors in prevention of gastric cancer, Proceedings, 3rd Annual Conference, Organisation for Oncology and Translational Reserach, Hong Kong, 22-23 September. 2006, 33.

Wong B.C.Y., Use of COX inhibitors in prevention of gastric cancer, 3rd Annual Conference, Orgainisatoin for Oncology and Translational Research, Hong Kong, 22-23 September. 2006.

Wong B.C.Y., What is the prevalence of GERD in far East countries? , Plenary Session 5: Pathophysiology and Controversies in GERD, in the 8th World Congress, World Organization for Specialized Studies on Diseases of the Esophagus, Avignon, France, 3-6 September, 2006. 2006.

Wong B.C.Y., Which FOBT?, 3rd International Asia Confernce on Cancer Screening, Singapore, 17 November. 2006.

Wong B.C.Y., Why is the incidence of adenocarcinoma of the esophagus and gastric cardia increasing? , Plenary Session 6: 8th World Congress, World Organization for Specialized Studies on Diseases of the Esophagus, Avignon, France, 3-6 September. 2006.

Wong L.W., Zhu S.L., Zhang S.Y., Lan X.R., Chung A.C.K., Zhang R., Lam S.K., Wong B.C.Y., Xia H.H.X. and Lan H.Y., Macrophage Migration Inhibitory Factor (MIF) Knockout Mice Are Protected Against Helicobacter Pylori Induced Gastritis., 12th Medical Research Conference (Hong Kong, 3/2/2007). 2007.

Wong R.W.M., Lai K.C., Yiu M.W.C., Wong B.C.Y., Chan F.L. and Lai C.L., Intestinal tuberculosis mimicking fistulizing Crohn's disease, Journal of Gastroenterology and Hepatology. 2007, 22: 137-139.

Yu L., Wang J., Zou B., Lin M.C., Wu Y.L., Xia H.H.X., Sun Y., Gu Q., He H., Lam S.K., Kung H.F. and Wong B.C.Y., XAF1 Mediates Apoptosis Through an Extracellular Signal-Regulated Kinase Pathway in Colon Cancer , Cancer. 2007, 109(10): 1996-2003.

Yuen R.M.F., Wong D.K.H., Zheng B., Chan C.C.S., Yuen J.C.H., Wong B.C.Y. and Lai C.L., Difference in T Helper Responses During Hepatitis Flares in HBeAg-positive Patients with Genotypes B and C: Implication for Early HBeAg Seroconversion, Journal of Viral Hepatitis. 2007, 14: 269-275.

Yuen R.M.F., Sablon E., Libbrecht E., de Velde H.V., Wong D.K.H., Fung J.Y.Y., Wong B.C.Y. and Lai C.L., Significance of HBV viral load, core promoter/ precore mutations and specific sequences of polymerase gene in HBV-infected patients on 3-year lamivudine treatment, Antivir Ther. 2006, 11(6): 779-786.

Yuen R.M.F., Tam S., Fung J.Y.Y., Wong D.K.H., Wong B.C.Y. and Lai C.L., Traditional Chinese medicine causing hepatotoxicity in patients with chronic hepatitis B infection: A one-year prospective study, Alimentary Pharmacology and Therapeutics. 2006, 24(8): 1179-1186.

Zou B., Chim J.C.S., Zeng H., Leung S.Y., Yang Y., Tu S., Lin M.C., Wang J., He H., Jiang S.H., Sun Y., Yu L., Yuen S.T., Kung H.F. and Wong B.C.Y., Correlation Between the Single-site CpG Methylation and Expression Silencing of the XAF1 Gene in Human Gastric and Colon Cancers, Gastroenterology. 2006, 131(6): 1835-1843.

Researcher : Wong DKH

List of Research Outputs

Fung J.Y.Y., Lai C.L., Yuen J.C.H., Wong D.K.H., Tanaka Y., Mizokami M. and Yuen R.M.F., Adefovir dipivoxil monotherapy and combination therapy with lamivudine for the treatment of chronic hepatitis B in an Asian population, Antivir Ther. 2007, 12: 41-46.

Fung J.Y.Y., Lai C.L., Wong D.K.H., Cheng C.T.K., But D.Y. and Yuen R.M.F., Large Population Study in Liver Stiffness Measurement: Prevalence of Significant Fibrosis and Correlation with Liver Biochemistry in Chronic Hepatitis B, Annual Meeting for European Association for the Study of the Liver (EASL 2007). 2007.

Fung J.Y.Y., Lai C.L., Wong D.K.H. and Yuen R.M.F., Large population study on the natural history of spontaneous hepatitis B e antigen seroconversion: risk of hepatocellular carcinoma. Annual meeting, European Association for the Study of Liver (EASL). Journal of Hepatology. 2007, 46 S1: S181.

Wong D.K.H., Yuen R.M.F., Ngai W.S., Fung J.Y.Y. and Lai C.L., One-year entecavir or lamivudine therapy results in reduction of HBV intrahepatic covalently closed circular DNA levels, Antivir Ther . 2006, 11: 909-916.

Wong D.K.H., Yuen R.M.F., Ngai W.S., Fung J.Y.Y. and Lai C.L., One-year entecavir or lamivudine therapy results in reduction of hepatitis B virus intrahepatic covalently closed circular DNA levels., Antiviral Therapy. 2006, 11: 909-916.

Wong D.K.H., Yuen R.M.F., Poon R.T.P., Yuen J.C.H., Fung J.Y.Y. and Lai C.L., Quantification of hepatitis B virus covalently closed circular DNA in patients with hepatocellular carcinoma, Journal of hepatology : the journal of the European Association for the Study of the Liver. 2006, 45: 553-559.

Wong D.K.H., Yuen R.M.F., Poon R.T.P., Yuen J.C.H., Fung J.Y.Y. and Lai C.L., Quantitation of hepatitis B virus covalently closed circular DNA in patients with hepatocellular carcinoma, Journal of Hepatology. 2006, 45: 553-559.

Yuan H.J., Wong D.K.H., Doutreloigne J., Sablon E., Lai C.L. and Yuen R.M.F., Precore and core promoter mutations at the time of HBeAg seroclearance in Chinese patients with chronic hepatitis B., Journal of Infection. 2007, 54: 497-503.

Yuen R.M.F., Wong D.K.H., Zheng B., Chan C.C.S., Yuen J.C.H., Wong B.C.Y. and Lai C.L., Difference in T Helper Responses During Hepatitis Flares in HBeAg-positive Patients with Genotypes B and C: Implication for Early HBeAg Seroconversion, Journal of Viral Hepatitis. 2007, 14: 269-275.

Yuen R.M.F., Tanaka Y., Shinkai N., Poon R.T.P., But D.Y.K., Fong D.Y.T., Fung J.Y.Y., Wong D.K.H., Yuen J.C.H., Mizokami M. and Lai C.L., Risk for hepatocellular carcinoma with respect to hepatitis B virus genotypes B/ C, specific mutations of enhancer II/ core promoter/ precore regions and HBV DNA levels, Gut. 2007, 57: 98-102.

Yuen R.M.F., Tanaka Y., Shinkai N., Poon R.T.P., Fung J.Y.Y., Wong D.K.H., Yuen J.C.H., Mizokami M. and Lai C.L., Role of HBV genotypes, core promoter/precore mutations and HBV DNA levels on hepatocarcinogenesis, Annual meeting, European Association for the Study of Liver (EASL), Barcelona, Spain, 11 - 15 April 2007.

Yuen R.M.F., Sablon E., Libbrecht E., de Velde H.V., Wong D.K.H., Fung J.Y.Y., Wong B.C.Y. and Lai C.L., Significance of HBV viral load, core promoter/ precore mutations and specific sequences of polymerase gene in HBV-infected patients on 3-year lamivudine treatment, Antivir Ther. 2006, 11(6): 779-786.

Yuen R.M.F., Tam S., Fung J.Y.Y., Wong D.K.H., Wong B.C.Y. and Lai C.L., Traditional Chinese medicine causing hepatotoxicity in patients with chronic hepatitis B infection: A one-year prospective study, Alimentary Pharmacology and Therapeutics. 2006, 24(8): 1179-1186.

Researcher : Wong LC

List of Research Outputs

Zhang X., Yeung C.Y., Wong L.C., Chow W.S., Xu A. and Lam K.S.L., Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans, Second Symposium on Healthy Aging: "Meeting the Challenges of an Aging Population" . 2007.

Researcher : Wong LW

List of Research Outputs

Wong L.W., Zhu S.L., Zhang S.Y., Lan X.R., Chung A.C.K., Zhang R., Lam S.K., Wong B.C.Y., Xia H.H.X. and Lan H.Y., Macrophage Migration Inhibitory Factor (MIF) Knockout Mice Are Protected Against Helicobacter Pylori Induced Gastritis., 12th Medical Research Conference (Hong Kong, 3/2/2007). 2007.

Researcher : Wong LYF

Project Title:	Involvement of NF-κB and cAMP-dependent protein kinase pathways in adrenomedullin-induced cytokine responses in macrophages
Investigator(s):	Wong LYF, Cheung BMY
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004

Abstract:

To assess the involvement of NF-[kappa]B pathway as the link between AM and inflammation; to confirm that AM exerts its effect on cytokine production in macrophages through cyclic-AMP; to identify the cAMP-dependent protein kinase pathway involved in the AM-induced cytokine response in LPS-stimulated macrophages.

List of Research Outputs

Cheung B.M.Y., Leung Y.H., Man Y.U. .B.U.N., Ong K.L., Wong L.Y.F., Lau C.P. and Lam K.S.L., Association of Blood Pressure with Polymorphisms in the Quantitative Trait Locus for Abdominal Obesity-Metabolic Syndrome on Chromosome 17, The 21st Scientific Meeting of the International Society of Hypertension 2006.

Cheung B.M.Y., Ong K.L., Man Y.U. .B.U.N., Wong L.Y.F., Lau C.P. and Lam K.S.L., Prevalence, Awareness, Treatment and Control of Hypertension in the United States 1999-2004, The 21st Scientific Meeting of the International Society of Hypertension. 2006.

Researcher : Wong MS

List of Research Outputs

Carnley B.P., Prior J.F., Gilbert A., Lim E., Devenish R., Sing H., Sarin E., Guhadasan R., Sullivan S.G., Wise C.A., Bittles A.H., Chan K., Wong M.S., Chan V.N.Y. and Erber W.N., The prevalence and molecular basis of hemoglobinopathies in Cambodia., Hemoglobin. Taylor and Francis, 2006, 4: 463-470.

Researcher : Wong PC

List of Research Outputs

Chan M.M.W., Mak J.C.W., Ho S.P., Cheung A.H.K., Wong P.C., Chan K.K. and Ip M.S.M., Glutathione S-transferase (GST) polymorphisms and GST activity in Hong Kong Chinese COPD patients., International Journal of Tuberculosis and Lung Disease. 2007, 11: 508-14.

Lam B., Wong M.P., Fung S.L., Lam C.L., Wong P.C., Wong T.Y.W., Lam F.M., Ip M.S.M., Ooi C.G.C. and Lam W.K., The clinical value of autofluorescence bronchoscopy for the diagnosis of lung cancer , European Respiratory Journal. 2006, 28(5): 915-919.

Researcher : Wong RWM

List of Research Outputs

Hu H.C., Lam S.K., Lam C.L.K., Wong R.W.M., Lam K.F., Lai K.C., Wong Y.H., Wong B.C.Y., Chan O.O., Chan C.K., Leung G.M. and Hui W.M., Comparison between Empirical Prokinetics, Helicobacter Test-and-Treat and Empirical Endoscopy in Primary-Care Patients Presenting with Dyspepsia: A One-Year Study, World Journal of Gastroenterology. 2006, 12(31): 5010-5016.

Wang W.H., Huang J., Zheng G., Xia H.H.X., Wong R.W.M., Liu X.G., Karlberg J.P.E. and Wong B.C.Y., Effects of proton-pump inhibitors on function dyspepsia: A meta-analysis of randomized placebo-controlled trails, Clinical Gastroenterology & Hepatology. 2007, 5(2): 178-185.

Wong R.W.M., Lai K.C., Yiu M.W.C., Wong B.C.Y., Chan F.L. and Lai C.L., Intestinal tuberculosis mimicking fistulizing Crohn's disease, Journal of Gastroenterology and Hepatology. 2007, 22: 137-139.

Researcher : Wong RWS

List of Research Outputs

Mok T.M.Y., Tsang P.L., Lo Y., Wong R.W.S., Lau W.C.S. and Lam Y.M., Bosentan Use in Systemic Lupus Erythematosus Patients with Pulmonary Arterial Hypertension, Lupus. England, SAGE, 2007, 16(4): 279-285.

Mok T.M.Y., Chan E.Y.T., Wong R.W.S. and Lau W.C.S., Intrathecal Immunoglobulin Production in Patients with Systemic Lupus Erythematosus with Neuropsychiatric Manifestations, Annals of Rheumatic Diseases. 2007, 66: 846-847.

Mok T.M.Y., Wong S.S.Y., Chan D.T.M., Fong D.Y.T., Wong R.W.S. and Lau W.C.S., Non-tuberculous mycobacterial infection in patients with systemic lupus erythematosus, Rheumatology. Switzerland, Karger, 2007, 46(2): 280-284.

Mok T.M.Y., Wong S.S.Y., Chan D.T.M., Fong D.Y., Wong R.W.S. and Lau W.C.S., Non-tuberculous mycobacterial infection in patients with systemic lupus erythematosus, Rheumatology (Oxford). 2007, 46: 280-284.

Researcher : Wong SY

List of Research Outputs

Chan A.O.O., Jim M.H., Lam K.F., Siu D.C.W., Tong S.M., Ng F.H., Wong S.Y., Hui W.M., Lam S.K. and Wong B.C.Y., Aspirin does not prevent recurrence of colorrectal adenomas in patients with coronary artery disease. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A194.

Chan A.O.O., Jim M.H., Lam K.F., Siu D.C.W., Tong S.M., Ng F.H., Wong S.Y., Hui W.M., Chan C.K., Lai K.C., Cheung T.K., Chan P., Wong G., Yuen R.M.F., Lau Y.K., Lee S.W.L., Seto M.L., Lam S.K. and Wong B.C.Y., Patients with coronary artery disease had high prevalanece of colorectal cancer and adenoma: END-results of metabolic syndrome and smoking. Digestive Disease Week 2007, Washington DEc, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A65.

Chan A.O.O., Ng F.H., Chang P.C.M., Wong S.Y., Chu W.M., Yuen W.C., Lau Y.K., Cheung T.K. and Wong B.C.Y., Prevalence and prediction of gastrointestinal events in patients receiving a combination of aspirin plus clopidogrel. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A135.

Chan A.O.O., Loo C.K., Leung C.M., Wong S.Y., Ng F.H., Li M.K.W., Lam K.M., Lam S.K. and Wong B.C.Y., Prevalence of colonic lesions after a negative screening colonscopy in a population with rapidly rising colorectal cancer incidence: A prospective multi-center analysis. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A189.

Researcher : Wong W

List of Research Outputs

Wong W., Lam C.L.K., Sham J.S.T., Leung K.F., Leung K.F. and Zhao L., Effectiveness of Traditional Chinese Medicine in Primary Care, 13th Annual Conference of the International Society for Quality of Life Research. October 10 - 14, 2006.

Researcher : Wong WM

List of Research Outputs

Cheung T.K., Lam K.F., Hu H.C., Wong W.M., Hui W.M., Lam C.L.K., Lai K.C., Lam S.K. and Wong B.C.Y., Positive association between gastro-oesophageal reflux disease and irritable bowel syndrome in a Chinese population, Alimentary Pharmacology & Therapeutics. Blackwell Publishing, 2007, 25: 1099-1104.

Researcher : Wong WM

List of Research Outputs

Researcher : Wong WS

List of Research Outputs

Ho S., Yang W., Lau W.C.S., Chen T.M., Wong W.S. and Lau Y.L., Polymorphisms of Tumour Suppressor P53 Gene with Systemic Lupus Erythematosus in Hong Kong Chinese Patients, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006. 79.

Researcher : Wong Y

List of Research Outputs

Ho E.T., Tang S.C.W., Chui W.H., Tang A.W., Wong S.S., Wong Y., Lam W.O., Cheng Y.Y., Chau W.S. and Ho Y.W., Video-assisted thoracoscopic TALE pleurodesis for pleuroperitoneal communication in peritoneal dialysis, Peritoneal Dialysis International . 2006, Suppl 26: S118.

Shiu W.M.S., Huang Y., Wong Y. and Tan K.C.B., Type 2 diabetes and endothelial lipase, Second International Symposium on Healthy Aging, Mar 2007, Hong Kong. 2007.

Tan K.C.B., Shiu S.W.M., Chow W.S., Wong Y., Bucala R. and Betteridge D.J., Arterial stiffness and advanced glycation end products in type 2 diabetes mellitus, The International Diabetes Federation 19th World Diabetes Congress, Cape Town, Dec 2006.

Tan K.C.B., Shiu W.M.S., Wong Y., Tam S. and Bucala R., Increased serum soluble lectin-like oxidized LDL receptor-1 level in type 2 diabetes is associated with circulating advanced glycation end products, The Endocrine Society’s 89th Annual Meeting, June 2007, Toronto. 2007.

Tang A.W., Wong S.S., Tang S.C.W., Wong Y., Kwok M.W., Lam W.O., Cheng Y.Y. and Ho Y.W., Simultaneous removal and reinsertion of Tenckhoff catheters for the treatment of malfunctioning catheters, Peritoneal Dialysis International . 2006, Suppl 26: S64.

Zhou H., Shiu S.W.M., Wong Y. and Tan K.C.B., Impaired serum cholesterol efflux potential is associated with endothelial dysfunction in type 2 diabetes patients, Fourth International Huaxia congress of Endocrinology, Hong Kong, Dec 2006.

Researcher : Wong YF

List of Research Outputs

Ong K.L., Cheung B.M.Y., Man Y.B., Wong Y.F., Wat N.M.S., Tan K.C.B. and Lam K.S.L., Treatment and control of diabetes mellitus in the United States National Healthy and Nutrition Examination Survey 1999-2002, Journal of Cardiometabolic Syndrome. 2006, 1: 301-7.

Researcher : Wong YH

List of Research Outputs

Chan A.O.O., Hui W.M., Leung Y.C., Wong Y.H., Chan P., Hung I.F.H., Hsu A., But D., Lam S.K. and Wong B.C.Y., Better efficacy of tegaserod in constipated patients with slow colonic transit, absent pelvic floor dyssynergy and absent impaired rectal sensation. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A194.

Chan A.O.O., Hui W.M., Wong Y.H., Leung Y.C., Lam S.K. and Wong B.C.Y., Decreased cortical activation during rectal distention in patients with functional constipation with normal rectal compliance. Digestive Disease Week 2007, Washington DC, USA, May 19-24, Gastroenterology. 2007, 132(4) Suppl 2: A23.

Chan A.O.O., Lam K.F., Hui W.M., Leung G.K.L., Wong Y.H., Lam S.K. and Wong B.C.Y., Influence of Positive Family History on Clinical Characteristics of Functional Constipation, Clinical Gastroenterology and Hepatology. Elsevier, 2007, 5(2): 197-200.

Cheung T.K., Lam B., Ip M.S.M., Wong Y.H., Chan A.O.O., Lam S.K. and Wong B.C.Y., Nocturnal Reflux Symptoms Correlate with Respiratory Events in Patients with Obstructive Sleep Apnea. , AGA Digestive Digestive Disease Week 2007.

Cheung T.K., Lam B., Ip M.S.M., Wong Y.H., Chan A.O.O., Lam S.K. and Wong B.C.Y., Nocturnal reflux symptoms correlate with respiratory events in patients with obstructive sleep apnea. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132 (4) Supp 2: A482.

Hu H.C., Lam S.K., Lam C.L.K., Wong R.W.M., Lam K.F., Lai K.C., Wong Y.H., Wong B.C.Y., Chan O.O., Chan C.K., Leung G.M. and Hui W.M., Comparison between Empirical Prokinetics, Helicobacter Test-and-Treat and Empirical Endoscopy in Primary-Care Patients Presenting with Dyspepsia: A One-Year Study, World Journal of Gastroenterology. 2006, 12(31): 5010-5016.

Researcher : Wu D

List of Research Outputs

Cheng K.Y., Lam K.S.L., Wang Y., Yu H., Carling D., Wu D., Wong C.W. and Xu A., Adiponectin-induced eNOS activation and Nitric Oxide Production are Mediated by APPL1 in Endothelial Cells, Diabetes. 2007, 56: 1387-94.

Wang Y., Lam J.B.B., Lam K.S.L., Liu J., Lam C.W., Hoo R.L.C., Wu D., Cooper G.J. and Xu A., Adiponectin modulates the glycogen synthase kinase-3beta/beta-catenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice, Cancer Res. 2006, 66: 11462-70.

Researcher : Xia HHX

Project Title:	Homeobox genes in gastric carcinogenesis: an in vivo and in vitro study
Investigator(s):	Xia HHX, Wong BCY
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	01/2003

Abstract:

To investigate the expression of gastric-related homeobox genes in human normal, precancerous and cancerous gastric tissues in vivo, and in non-malignant and malignant gastric cancer cell lines in vitro; to determine the effect of gastric-related homeobox genes on the secretion of gastric endocrine hormones.

Project Title:	Role of cyclooxygenase in helicobacter pylori-induced gastric carcinogenesis
Investigator(s):	Xia HHX, Wong BCY
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2004

Abstract:

To reveal the precise mechanism of COX and interrelationship between COX and H. pylori infection in the pathogenesis of gastric cancer; to provide insights into whether specific targets can be dealth with by new drugs, or a combination of drugs on different cellular targets to potentiate the chemoprevention effects; to develop effective strategies in the prevention of gastric cancer, for which no active agent or drug is available at present.

Project Title:	Role of macrophage migration inhibitory factor in Helicobacter pylori-induced gastric carcinogenesis
Investigator(s):	Xia HHX, Wong BCY
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	05/2005

Abstract:

To determine the effect of MIF deficiency on H. pylori-induced inflammation and expression of inflammatory cytokines, cell proliferation and apoptosis and expression of related genes; to determine the difference in the incidence of gastric precancerous and cancerous lesions between MIF-knockout mice and wild-type mice after long-term infection with H. pylori.

Project Title:	Expression and role of homeobox gene PDX1 in gastric carcinogenesis
Investigator(s):	Xia HHX, Wong BCY
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	04/2006

Abstract:

Homeobox genes encoding homeodomain transcription factors are involved in establishing gradients of differentiation during development of embryo and in maintaining these patterns in adult tissue [1,2]. Dysregulation of homeobox gene expression in cancer conforms to a simple rule: homeobox genes that are upregulated in cancer are normally expressed during development and/or in undifferentiated cells, whereas homeobox genes that are downregulated in cancer are normally expressed in adulthood and/or in differentiated tissues [3]. For example, two genes, CDX1 and CDX2, are normally expressed only in the intestine, and downregulation of CDX1 and CDX2 expression is associated with colorectal cancer. Pancreatic duodenal homeobox-1 protein (PDX-1), also known as IPF-1, STF1, or IDX-1 is one transcription factor in the ParaHox gene family. Generally, PDX1 gene is found normally in endocrine glands such as pancreatic beta-cells, Brunner's glands of the duodenum, and pyloric glands of the stomach [4,5]. PDX1 was confirmed to be a key regulator of pancreatic islet development and insulin gene transcription in beta-cells [6]. Recently, the association between PDX1 and gastric development is paid attention. Similar to expression of CDX2, PDX1 which is found in gastric endocrine glands, may be aberrantly expressed in hyperplasia, pancreatic or/and intestinal metaplasia and even gastric cancer.However, few recent studies involving PDX1 and gastric precancerous and cancer lesions produced different results. Whereas our previous study showed that, gastric expression of PDX1 was down-regulated in H pylori infected gastric mucosa and intestinal metaplasia with compared to normal mucosa [7], another recent study reported that PDX1 was frequently expressed in pseudopyloric glands and intestinal metaplasia [8]. Moreover, the exact regulatory function of PDX1 gene in gastric carcinogenesis is unknown.Purpose:1. To investigate the expression of PDX1 gene in human normal, precancerous and cancerous gastric tissues in vivo;2. To investifgate the expression of PDX1 gene in non-malignant and malignant gastric cancer cell lines in vitro. 3. To determine the effect of PDX1 gene on the secretion of gastric endocrine cells since PDX1 has been implicated in the regulation of G (gastrin-producing), D (somatostatin-producing) and EC (serotonin producing) cells in gastric antral mucosa [9].Key issues and problems addressed1. Whether PDX1 expression is dysregulaetd in gastric carcinogenesis;2. Whether PDX1 plays an role in gastric carcinogenesis.Reference1.Byrd JC, Yan P, Sternberg L, Yunker CK, Scheiman JM, Bresalier RS. Gastroenterology 1997;113:455-64.2.Pitera JE, Smith VV, Thorogood P, Milla PJ. Gastroenterology 1999;117:1339-51.3.Cory Abate-Shen. Nature Reviews/Cancer.2002;2:777-785.4.Stoffers DA, Heller RS, Miller CP, et al. Endocrinology 1999;140:5374-81.5.Larsson LI, Madsen OD, Serup P, et al. Mech Dev 1996;60:175-84.6. Wang XP, Li Zh.J, Magnusson J, Brunicardi FC. World J. Surg. 2005;29:334-338.7. Zhu S, Xia HHX., Lam SK, et al. Gastroenterology 2005, 128(4 Suppl 2): A598.8. Sakai H, Eishi Y, Li XL, et al. Gut 2004;53:323-330.9. Larsson LI, Madsen OD, Seraph P, Jonsson J, Edlundc H. Mech evelopment.1996;60:175-184.

List of Research Outputs

Chan A.O.O., Chu K.M., Huang C.Y., Lam K.F., Leung S.Y., Sun Y., Ko S., Xia H.H.X., Cho C.H., Hui W.M., Lam S.K. and Rashid A., Association between Helicobacter pylori infection and interleukin 1beta polymorphism predispose to CpG island methylation in gastric cancer, GUT. 2007, 56: 595-597.

Cheung T.K., Xia H.H.X. and Wong B.C.Y., Helicobacter pylori Eradication for Gastric Cancer Prevention., Journal of Gastroenterology. 2007, 42 (Suppl 17): 10-15.

Dai Y., Qiao L., Gu Q., Xia H.H.X., Cheung T.K., Ma J., Zou B. and Wong B.C.Y., Activation of Pparc and inhibition of Xiap in human cancer cells: Synergistic effects on cell proliferation, apoptosis, and tumorigensis. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A425.

Ge R., Sun X., Gu Q., Watt R.M., Tanner J.A., Wong B.C.Y., Xia H.H.X., Huang J.D., He Q.Y. and Sun H., A proteomic approach for the identification of bismuth-binding proteins in Helicobacter pylori, Journal Biol Inorg Chem. 2007, 12: 831.

Ng S.M., Cheung Y.T., An X.M., Chen Y.C., Li M., Li H.Y., Cheung K.C., Sze J., Lai L., Peng Y., Xia H.H.X., Wong B.C.Y., Leung S.Y., Xie D., He M.L., Kung H.F. and Lin M.C., Cell Cycle-related Kinase: A Novel Candidate Oncogene in Human Glioblastoma, Journal of the National Cancer Institute. 2007, 99(12): 936-948.

Sun H., Ge R., Sun X., Xia H.H.X. and Huang J., Identification of Metal-binding Proteins/Motifs in Microorganisms by Metalloproteome: an Example for Bismuth, Gordon Research Conference, Metal in Medicine, Oxford, United Kingdom, July 9-14, 2006.

Tang L.P., Cho C.H., Hui W.M., Huang C., Chu K.M., Xia H.H.X., Lam S.K., Rashid A., Wong B.C.Y. and Chan O.O., An inverse correlation between IL-6 and select gene promoter methylation in patients with gastric cancer, Digestion. 2006, 74: 85-90.

Wang J., Yang Y., Xia H.H.X., Gu Q., Lin M.C., Jiang B., Peng Y., Li G., An X., Zhang Y., Zhuang Z., Zhang Z., Kung H.F. and Wong B.C.Y., Suppression of FHL2 Expression Induces Cell Differentiation and Inhibits Gastric and Colon Carcinogenesis , Gastroenterology. 2007, 132: 1066-1076.

Wang W.H., Huang J., Zheng G., Xia H.H.X., Wong R.W.M., Liu X.G., Karlberg J.P.E. and Wong B.C.Y., Effects of proton-pump inhibitors on function dyspepsia: A meta-analysis of randomized placebo-controlled trails, Clinical Gastroenterology & Hepatology. 2007, 5(2): 178-185.

Wong L.W., Zhu S.L., Zhang S.Y., Lan X.R., Chung A.C.K., Zhang R., Lam S.K., Wong B.C.Y., Xia H.H.X. and Lan H.Y., Macrophage Migration Inhibitory Factor (MIF) Knockout Mice Are Protected Against Helicobacter Pylori Induced Gastritis., 12th Medical Research Conference (Hong Kong, 3/2/2007). 2007.

Yu L., Wang J., Zou B., Lin M.C., Wu Y.L., Xia H.H.X., Sun Y., Gu Q., He H., Lam S.K., Kung H.F. and Wong B.C.Y., XAF1 Mediates Apoptosis Through an Extracellular Signal-Regulated Kinase Pathway in Colon Cancer , Cancer. 2007, 109(10): 1996-2003.

Researcher : Xu A

Project Title:	Characterization of the receptor and postreceptor events that underlie the anti-atherogenic and anti-diabetic actions of adiponectin
Investigator(s):	Xu A, Lam KSL
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2005

Abstract:

The proposal seeks to address the following three questions: (1) how does adiponectin activate its receptors? (2) what are the membrane proximal down-stream signaling events of adiponectin receptors? how does adiponectin exert its anti-atherogenic actions via macrophage cells?

Project Title:	Angiopoitein-like protein 4 (ANGPTL4) as a novel therapeutic target for the treatment of insulin resistance and hyperglycemia
Investigator(s):	Xu A, Lam KSL
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	12/2005

Abstract:

To investigate the direct metabolic effects of angiopoietin-like protein 4 on liver and muscle, the two major organs involved in the regulation of systemic energy metabolism and insulin sensitivity; to elucidate the detailed metabolic pathways and signal transduction events that mediate the hypoglycemia and insulin-sensitizing effects of angiopoietin-like protein 4.; to study whether oligomerization and/or proteolysis plays a role in modulating the biological activities of angiopoietin-like protein 4.

Project Title:	The use of adiponectin as a biomarker to identify novel anti-diabetic and anti-atherogenic agents from Chinese herbs
Investigator(s):	Xu A, Qin GW, Lam KSL
Department:	Medicine
Source(s) of Funding:	NSFC/RGC Joint Research Scheme
Start Date:	01/2006

Abstract:

To determine and optimize the chemical structures for the three bioactive compounds isolated from Rhizoma Dioscoreae and Radix Astragali; to study the molecular mechanisms by which the three bioactive compounds induce adiponectin production from fat cells; to explore the therapeutic potentials of the three bioactive compounds in the treatment of T2DM, endothelial dysfunction, atherosclerosis and other obesity-related metabolic disorders in several well-established animal models.

Project Title:	Inflammation in adipose tissue as a novel mechanism that link obesity with insulin reistance and type 2 diabetes
Investigator(s):	Xu A, Lam KSL, Chung SK
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2006

Abstract:

Obesity and its associated pathologies, including Type 2 Diabetes Mellitus (T2DM) and atherosclerosis, are chronic inflammatory diseases, characterized by elevated plasma concentrations of pro-inflammatory biomarkers, such as C-reactive proteins, TNF alpha and interleulin (IL) 6 (Bouloumie, Curat et al. 2005). Recent studies have found that adipose tissue (fat) is the predominant site that contributes to obesity-associated systemic inflammation and metabolic disorders (Wellen and Hotamisligil 2005). Macrophage infiltration and up-regulation of the inflammation-related genes in obese adipose tissue occur at the early phase of obesity and precede the development of insulin resistance (Xu, Barnes et al. 2003). It is suggested that activated macrophages in obese adipose tissue, in concert with the enlarged adipocytes, secrete a variety of pro-inflammatory adipokines/cytokines, which either act locally to perpetuate adipose tissue inflammation, or are released into the blood stream to induce systemic inflammation, insulin resistance and metabolic disorders in the periphery organs. Nevertheless, the mechanism responsible for triggering and perpetuating macrophage infiltration into obese adipose tissue remains poorly understood. It is also unclear whether inhibition of local inflammation in adipose tissue is sufficient to alleviate obesity-induced systemic inflammation and insulin resistance. Hypoxia inducible factor (HIF) 1alpha, a major transcription factor involved in the cellular response to hypoxia, has recently neen shown to be an important player in the inflammatory process (Paul, Simons et al. 2004). Studies in both human subjects and rodents have found that the expressions of HIF 1alpha in obese adipose tissue are substantially elevated (Trayhurn and Wood 2004; Cancello, Henegar et al. 2005). Weight loss, on the other hand, results in decreased expression of this transcription factor as well as reduced adipose tissue inflammation. Our in vitro studies showed that hypoxia, via induction of HIF 1alpha, could inhibit the production of the anti-inflammatory hormone adiponectin, but increase the expression of a cluster of pro-angiogenic and pro-inflammatory mediators from adipocytes, including leptin, VEGF, PAI-1 and IL6 (Chen, Wang et al.). In addition, we also demonstrated that HIF 1alpha activation could significantly enhance adipocyte-mediated adhesion and transmigration of human blood monocytes to/through the endothelial cells, the key step involved in macrophage tissue infiltration. Based on these evidences, we propose that HIF 1alpha plays a key role in initiating and/or maintaining chronic inflammation of adipose tissue and in triggering aberrant production of adipokines in obesity. As obesity develops, enlarged fat mass causes local micro-hypoxia and oxidative stress, both of which can induce HIF 1alpha accumulation and activation. Activated HIF 1alpha can decrease production of adiponectin and increase expression of macrophage attractants (such as leptin, VEGF, PAI-1, IL6, proteases and other chemokines). These changes can stimulate transport of monocytes to adipose tissue and promote adhesion and transmigration of monocytes to/through endothelial cells. Infiltrated monocytes in adipose tissue can be differentiated into macrophages by other locally produced inflammatory mediators. Activated macrophages in turn secrete a cluster of pro-inflammatory cytokines (such as IL1, TNFalpha and MCP1), which can act in a paracrine manner to induce further accumulation of HIF 1alpha in adipocytes, macrophage infiltration and aberrant production of adipokines. The macrophage-adipocyte interaction will perpetuate a viscous cycle that aggravates inflammatory responses in adipose tissue, and eventually induces systemic inflammation and insulin resistance. To test this hypothesis, the major objectives of this study are:1. To generate the transgenic mice with adipose tissue specific over-expression of dominant negative or constitutively active forms of HIF 1alpha; 2. To investigate the role of HIF 1alpha in obesity-induced macrophage infiltration and aberrant production of adipokines in adipose tissue, systemic inflammation and insulin resistance in the transgenic mouse models;3. To elucidate the molecular mechanisms by which HIF 1alpha induces endothelial cell activation and monocyte recruitment in adipose tissue; 4. To evaluate whether berberine, a compound with potent HIF 1alpha inhibitor activity, has therapeutic effects on obesity-associated chronic inflammation, insulin resistance and other metabolic abnormalities in mice.

Project Title:	Hypoxia inducible factor 1α as a mediator of obesity-induced chronic inflammation, aberrant production of adipokines, and insulin resistance
Investigator(s):	Xu A, Lam KSL, Chung SK
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2007

Abstract:

To generate the transgenic mice with adipose tissue specific over-expression of the dominant negative form of HIF 1α to investigate the role of HIF 1α in obesity-induced macrophage infiltration and aberrant production of adipokines in adipose tissue, systemic inflammation and insulin resistance in the transgenic mouse models; to evaluate whether berberine, a compound with potent HIF 1α inhibitor activity, has therapeutic effects on obesity-associated chronic inflammation, insulin resistance and other metabolic abnormalities in mice.

Project Title:	Endoplasmic reticulum (ER) stress alleviators as the novel therapeutic agents for treatment of obesity-related metabolic diseases
Investigator(s):	Xu A, Lam KSL, Hoo RLC, Wang Y
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	05/2007

Abstract:

The dramatic increase in the incidence of obesity becomes a major public health concern worldwide. Obesity is the main risk factor for a cluster of inter-related metabolic and cardiovascular diseases, including insulin resistance, dyslipidemia, type 2 diabetes, non-alcoholic steatohepatitis (NASH), hypertension and coronary heart diseases, which are the major contributors to the mortality and morbidity in our aging population. Although the detailed mechanisms that link obesity with its associated pathologies is not fully understood, growing evidence suggest that chronic inflammation within adipose tissue is a key culprit (1,2). Both clinical and experimental studies have demonstrated that obese adipose tissue is characterized by increased macrophage infiltration and activation of the inflammatory pathways, such c-Jun NH2-terminal kinase (JNK) and NF-kB (3-5). The number of macrophages present in adipose tissue is closely correlated with adiposity and adipocyte size in both humans and animal models (4). Notably, inflammation in adipose tissue preceded the development of hyperinsulinemia in high fat diet-induced obese mice, suggesting that adipose inflammation is causally linked with systemic insulin resistance (3). The causal link between inflammation of adipose tissue and insulin resistance is also supported by the findings that weight reduction and anti-inflammatory drugs can reduce adipose macrophage infiltration and currently improve systemic insulin sensitivity (3,6). Adipose tissue is a major endocrine organ that secretes a wide spectrum of bioactive molecules (such as adipokines, cytokines and acute phase proteins) into the blood stream (7). Some of the “good” adipokines, such as adiponectin, visfatin and recently characterized vaspin, can increase insulin sensitivity, improve glucose tolerance and vascular reactivity. We and others have demonstrated that adiponectin possesses potent anti-diabetic, anti-atherogenic and anti-inflammatory activities, and also protects against obesity-associated nonalcoholic fatty liver diseases (8-10). On the other hand, “noxious” adipokines and cytokines, such as TNFa, PAI-1, resistin, adipocyte-fatty acid binding protein (A-FABP) and lipocalin-2, possesses adverse effects. As obesity develops, macrophage infiltration and interactions between macrophages and adipocytes cause abnormal production of these secretory proteins from adipose tissue, such as decreased adiponectin and increased TNFa, lipocalin-2, A-FABP, IL6 and PAI-1 (1,2). Discordant production of adipokines/cytokines from inflamed adipose tissue is a central mediator in the pathogenesis of obesity-related insulin resistance and metabolic abnormalities. Endoplasmic reticulum (ER) stress has recently been shown to play a central role in triggering inflammation in obese adipose tissue (11,12). The ER is a critical organelle where all secreted and transmembrane proteins are synthesized, folded into their correct three-dimensional structures, posttranslationally modified, and transported to their final cellular destinations. Pathological conditions, such as nutrient overloads, viral infections, hypoxia and metabolic stress, cause the accumulation of misfolded or unfolded proteins in the ER lumen which known as ER stress. The unfolded protein response (UPR) is the mechanism to alleviate ER stress by activating the synthesis of proteins that can facilitate folding of protein in ER lumen. On the other hand, ER stress can induce activation of several major inflammatory pathways, including JNK and NF-kB (11). In both dietary and genetic animal models of obesity, the biochemical parameters of ER stress were detected in both adipose tissue and liver (12). Transgenic studies have demonstrated that the ER stress responses might be responsible for activation of the JNK inflammatory pathway in obese adipose tissue and causation of obesity-linked insulin resistance (12), suggesting that alleviation of ER stress may offer novel therapeutic or preventive strategies for obesity-related metabolic diseases, especially type 2 diabetes. Indeed, a latest study published in Science has identified two small chemical compounds (4-phenyl butyric acid (PBA) and taurine-conjugated ursodeoxycholic acid (TUDCA)) that can alleviate the ER stress in cells and whole animals(13). Remarkably, oral administration of PBA or TUDCA into obese and diabetic mice leads to the normalization of hyperglycemia, restoration of the systemic insulin sensitivity and resolution of fatty liver disease within 4 days after treatment (13). This exciting finding suggests that ER chemical chaperones, such as PBA and TUDCA, represent a novel class of drugs for the treatment of obesity-related disorders. In this study, we will further explore the therapeutic potentials of these two ER chemical chaperones (PBA and TUDCA), and investigate the detailed cellular mechanisms underlying the therapeutic actions of PBA and TUDCA. Our specific objectives are: 1. To evaluate the therapeutic effects of PBA and TUDCA in both dietary and genetic obese mouse models, with particular focus on their roles in alleviation of adipose tissue inflammation; 2. To comprehensively analyze the effects of PBA and TUDCA on circulating levels of adipokines, cytokines and metabolic hormones using antibody suspension array-based multiplex immunoassays. 3. To elucidate the cellular pathways by which the two ER chemical chaperones (PBA and TUDCA) increase insulin sensitivity in liver and muscle tissues. PLEASE REFER TO SECTION VII for the references cited.

List of Research Outputs

Chen J., Sun M., Liang B., Xu A., Zhang S. and Wu D., Cloning and expression of PDK4, FOXO1A and DYRK1A from the hibernating greater horseshoe bat (Rhinolophus ferrumequinum). , Comp Biochem Physiol B Biochem Mol Biol. 2007, 142: 166-71.

Cheng K.Y., Lam K.S.L., Wang Y. and Xu A., Adiponectin as a key player of inflammation, In: Fantuzzi G, Biomedical Reviews. 2006, 17: 11-22.

Cheng K.Y., Lam K.S.L., Wang Y., Yu H., Carling D., Wu D., Wong C.W. and Xu A., Adiponectin-induced eNOS activation and Nitric Oxide Production are Mediated by APPL1 in Endothelial Cells, Diabetes. 2007, 56: 1387-94.

Chow W.S., Cheung B.M.Y., Xu A., Wat N.M.S., Fong H.Y., Ong L.H.Y., Tam S., Tan K.C.B., Janus E.D., Lam T.H. and Lam K.S.L., Hypoadiponectinemia as a predictor for the development of hypertension: a 5-year prospective study. , Hypertension. 2007, 49: 1455-61.

Fayad R., Pini M., Selleno J.A., Cabay R.J., Chan L., Xu A. and Fantuzzi G., Adiponectin deficiency protects mice from chemically induced colonic inflammation. , Gastroenterology. 2007, 132: 601-14.

Hoo R.L.C., Lam C.W., Xu A., Chen B. and Lam K.S.L., ENDOPLASMIC RETICULUM STRESS DOWN-REGULATES THE ADIPOCYTE PRODUCTION OF THE ANTI-DIABETIC AND ANTI-ATHEROGENIC HORMONE ADIPONECTIN, XIV International Symposium on Atherosclerosis,Italy 2006. 2007.

Hoo R.L.C., Chow W.S., Yau M.H., Xu A., Tse H.F., Tso A.W.K., Fong H.Y., Tam S., Chan L. and Lam K.S.L., PPAR-γ agonist induced-suppression of plasminogen activator inhibitor-1 production is mediated through adiponectin. , 2nd International Symposium on Healthy Aging, 3-4 March 2007, Hong Kong. 2007.

Lam J.C., Lam C.L., Xu A., Yan S.W., Lam B., Lam K.S.L. and Ip M.S.M., Serum adipocyte-fatty acid binding protein (AFABP) level correlates with the duration of oxygen desaturation in obstructive sleep apnea (OSA) patients, American Thoracic Society International Conference, San Francisco, USA 2007. American Journal of Respiratory and Critical Care Medicine. 2007, 175: A55.

Lam K.S.L., Tso A.W.K., Chow W.S., Hoo R.L.C., Zhang J., Lam C.W. and Xu A., Adipocyte fatty acid binding protein as a potential circulating metabolic hormone: clinical and functional studies. , The Endocrine Society’s 88th Annual Meeting, June 24-27, 2006, Boston, USA. 2007.

Mullig M.A., Chen X.Y., Hickey A.J., Crossman D., Xu A., Wang Y., Greenwood D.R., Choong Y.-.S., Schönberger S.J., Middleditch M.J. and Phillips A.R., Reversal of diabetes-evoked changes in mitochondrial protein expression of cardiac left ventricle by treatment with a copper(II)-selective chelator , PROTEOMICS - Clinical Applications. Wiley, 2007, 1: 387-99.

Ng K.Y., Xu A., Lam K.S.L. and Cheung R.T.F., Aggravated cerebral infarction in diabetic mice following photothrombotic ischemia, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population. 2007, 57.

Ng K.Y., Xu A., Lam K.S.L. and Cheung R.T.F., Increased susceptibility of diabetic transgenic mice to photothrombotic stroke, 11th Research Postgraduate Symposium. 2006, 66.

Ong L.H.Y., Chow W.S., Tso A.W.K., Wat N.M.S., Xu A., Fong H.Y., Janus E.D. and Lam K.S.L., Hypoadiponectinaemia predicts the development of hypertension in Chinese. , The 19th World Diabetes Congress, 3-7 December 2006, Cape Town, South Africa. 2006.

Rong R., Tao Y., Cheung B.M.Y., Xu A., Cheng K.Y. and Lam K.S.L., Identification and functional characterization of three novel human melanocortin-4 receptor gene variants in an obese Chinese population. , Clinical Endocrinology. 2006, 65: 198-205.

Shore S.A., Terry R.D., Flynt L., Xu A. and Hug C., Adiponectin attenuates allergen-induced airway inflammation and hyperresponsiveness in mice, J Allergy Clin Immunol. Elsever, 2006, 118: 389-95.

Tso A.W.K., Wat N.M.S., Xu A., Tam S., Fong H.Y., Janus E.D., Tan K.C.B. and Lam K.S.L., Adiponectin/C-reactive protein ratio is an independent surrogate marker predictive of the development of metabolic risks and the metabolic syndrome over 5 years in Chinese, The 6th International Diabetes Federation Western Pacific Region Congress, Bangkok. 2006.

Tso A.W.K., Sham P.C., Wat N.M.S., Xu A., Cheung B.M.Y., Rong R., Fong H.Y., Xu J., Cheng K.Y., Janus E.D. and Lam K.S.L., Polymorphisms of the gene encoding adiponectin and glycaemic outcome of Chinese subjects with impaired glucose tolerance: a 5-year follow-up study, Diabetologia. 2006, 49: 1806-15.

Tso A.W.K., Xu A., Wat N.M.S., Fong H.Y., Janus E.D. and Lam K.S.L., Serum adipocyte fatty acid-binding protein is a predictor of the development of type 2 diabetes mellitus over 5 years. , The Endocrine Society's 89th Annual Meeting, 2-5 June2007, Toronto. 2007.

Wang Y., Lam J.B.B., Liu J., Lam K.S.L., Cooper G.J.S. and Xu A., Adiponectin Plays Inhibitory Roles in the Proliferation and Tumor Development of Human MDA-MB-231 Breast Cancer Cells, 2nd Modern Drug Discovery & Development Summit. 2006.

Wang Y., Lam K.S.L. and Xu A., Adiponectin as a negative regulator in obesity-related mammary carcinogenesis. , Cell Research. 2007, 17: 280-2.

Wang Y., Lam K.S.L. and Xu A., Adiponectin as a therapeutic target for obesity-related metabolic and cardiovascular diseases., Drugs Development Research. 2006, 67: 677-686.

Wang Y., Lam J.B.B., Lam K.S.L., Liu J., Lam C.W., Hoo R.L.C., Wu D., Cooper G.J. and Xu A., Adiponectin modulates the glycogen synthase kinase-3beta/beta-catenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice, Cancer Res. 2006, 66: 11462-70.

Wang Y., Lam K.S.L., Kraegen E.W., Sweeney G., Zhang J., Tso A.W.K., Chow W.S., Wat N.M.S., Xu J., Hoo R.L.C. and Xu A., Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans, Clin Chem. 2007, 53: 34-41.

Wang Y., Lam K.S.L. and Xu A., Lipocalin-2, a small lipid binding protein as an important mediator at the crossroad of obesity, inflammation and metabolic syndrome, Second International Symposium on Healthy Aging. 2007.

Wang Y., Lam K.S.L., Lam J.B.B., Lam C.W., Leung P.T.Y., Zhou M.Y. and Xu A., Overexpression of Angiopoietin-like Protein 4 Alters Mitochondria Activities and modulates methionine metabolic cycle in the liver tissues of db/db diabetic mice, Mol Endocrinol. 2007, 21: 972-86.

Wang Y., Xu L., Lam K.S.L., Lu G., Cooper G.J. and Xu A., Proteomic characterization of human serum proteins associated with the fat-derived hormone adiponectin. , Proteomics. 2006, 6: 3862-70.

Wang Y., Lam K.S.L., Cooper G.J. and Xu A., Proteomic characterization of human serum proteins associated with the fat-derived hormone adiponectin. , Proteomics. 2006, 6: 3862-70.

Xu A., Adipokines as a novel linker between obesity, type 2 diabetes and cardiovascular diseases, The Second Chinese American Diabetes Association Conference. Chicago, USA, 2007.

Xu A., Wang Y. and Lam K.S.L., Adiponectin, In: Fantuzzi G & mazzone T, Adipose tissue and adipokines in health and disease. Totowa, New Jersey, Human press, 2007, 47-59.

Xu A., Tso A.W., Cheung B.M.Y., Wang Y., Wat N.M.S., Fong H.Y., Yeung C.Y., Janus E.D., Sham P.C. and Lam K.S.L., Circulating adipocyte-fatty acid binding protein levels predict the development of the metabolic syndrome: a 5-year prospective study, Circulation. 2007, 115: 1537-43.

Xu A., Tso A.W.K., Cheung B.M.Y., Wang Y., Wat N.M.S., Fong H.Y., Yeung C.Y., Janus E.D., Sham P.C. and Lam K.S.L., Circulating levels of adipocyte-fatty acid binding protein correlate with its adipose tissue expression and predict the development of the metabolic syndrome. , The Endocrine Society's 89th Annual Meeting, 2-5 June 2007, Toronto. 2007.

Xu A., I am serving as an editor for Biochemical journal handling over 50 manuscript each year., Biochemical Journal. 2007.

Xu A., Oligomerization of adiponectin: Mechanisms and functional implications, In: The Second International Diabetes and Immunology forum in Xiangyia , 2007.

Xu A., Outstanding Young Researcher Awards, The University of Hong Kong. 2006.

Xu J., Sham P.C., Xu A., Tso A.W.K., Wat N.M.S., Cheng K.Y., Fong H.Y., Janus E.D. and Lam K.S.L., Resistin gene polymorphisms and progression of glycaemia in southern Chinese: a 5-year prospective study, Clin Endocrinol (Oxf). 2007, 66: 211-7.

Yeung C.Y., Xu A., Cheung C.W., Wat N.M.S., Yau M.H., Fong H.Y. and Lam K.S.L., Circulating serum adipocyte-fatty acid-binding protein (A-FABP) levels correlate with carotid intima-media thickness (IMT) in Southern Chinese women. , 89th Annual Meeting of Endocrine Society, 2-5 June 2007, Toronto, Canada. 2007.

Zhang H., Hui C.K., Lee P.Y., Chan W., Yueng Y.H., Leung K.W., Lu L., Leung N., Lo C.M., Fan S.T., Luk J.M.C., Xu A., Lam K.S.L., Kwong Y.L. and Lau G., Serum adiponectin is increased in advancing liver fibrosis and decline with reduction in fibrosis in chronic hepatitis B, The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007, Hepatology International. 2007, 242: 7.

Zhang X., Yeung C.Y., Wong L.C., Chow W.S., Xu A. and Lam K.S.L., Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans, Second Symposium on Healthy Aging: "Meeting the Challenges of an Aging Population" . 2007.

Researcher : Xu J

Project Title:	Search for susceptibility gene loci for maturity-onset diabetes of the young in Southern Chinese
Investigator(s):	Xu J, Lam KSL, Sham PC
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004

Abstract:

To further study the extended MODYX families recruited from our previous project and screen for MODY loci in Southern Chinese, starting with MODY loci reported in other populations; to investigate whether there is overlap between MODY loci and reported T2DM loci in Chinese, based on studies with predilection of early onset T2DM diagnosed before 40 years of age.

List of Research Outputs

Tso A.W.K., Sham P.C., Wat N.M.S., Xu A., Cheung B.M.Y., Rong R., Fong H.Y., Xu J., Cheng K.Y., Janus E.D. and Lam K.S.L., Polymorphisms of the gene encoding adiponectin and glycaemic outcome of Chinese subjects with impaired glucose tolerance: a 5-year follow-up study, Diabetologia. 2006, 49: 1806-15.

Wang Y., Lam K.S.L., Kraegen E.W., Sweeney G., Zhang J., Tso A.W.K., Chow W.S., Wat N.M.S., Xu J., Hoo R.L.C. and Xu A., Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans, Clin Chem. 2007, 53: 34-41.

Xu J., Sham P.C., Xu A., Tso A.W.K., Wat N.M.S., Cheng K.Y., Fong H.Y., Janus E.D. and Lam K.S.L., Resistin gene polymorphisms and progression of glycaemia in southern Chinese: a 5-year prospective study, Clin Endocrinol (Oxf). 2007, 66: 211-7.

Researcher : Xue T

List of Research Outputs

Xue T., Siu C.W.D., Lieu D.K., Lau C.P., Tse H.F. and Li R.A., Mechanistic role of I(f) revealed by induction of ventricular automaticity by somatic gene transfer of gating-engineered pacemaker (HCN) channels., Circulation. 2007, 115(14): 1839-1850.

Researcher : Yam IYL

List of Research Outputs

Chan V.N.Y., Ng E.H.Y., Yam I.Y.L., Yeung W.S.B., Ho P.C. and Chan T.K., Experience in preimplantation genetic diagnosis for exclusion of homozygous a^o thalassaemia, Prenatal Diagnosis. 2006, 26: 1029-1036.

Researcher : Yam LYC

List of Research Outputs

Ip M.S.M., Yam L.Y.C., Lam C.L.K. and Sam K., Randomized controlled study of treatment for mild and moderate sleep apnoea, Hong Kong Medical Journal. 2007, 13 (suppl 3): S4-7.

Lam B., Sam K., Mok W.Y.W., Cheung M.T., Fong D.Y.T., Lam J.C.M., Lam C.L., Yam L.Y.C. and Ip M.S.M., Randomized study of three non-surgical treatments in mild to moderate obstructive sleep apnea, Thorax. 2007, 62: 354-359.

Researcher : Yang C

List of Research Outputs

Chan H.H.L., Yang C., Leung J.C.K., Wei W.I. and Lai K.N., An Animal Study of the Effects on p16 and PCNA Expression of Repeated Treatment with High-Energy Laser and Intense Pulsed Light Exposure, Lasers in Surgery and Medicine. 2007, 39: 8-13.

Researcher : Yang Y

List of Research Outputs

Wang J., Yang Y., Xia H.H.X., Gu Q., Lin M.C., Jiang B., Peng Y., Li G., An X., Zhang Y., Zhuang Z., Zhang Z., Kung H.F. and Wong B.C.Y., Suppression of FHL2 Expression Induces Cell Differentiation and Inhibits Gastric and Colon Carcinogenesis , Gastroenterology. 2007, 132: 1066-1076.

Zou B., Chim J.C.S., Zeng H., Leung S.Y., Yang Y., Tu S., Lin M.C., Wang J., He H., Jiang S.H., Sun Y., Yu L., Yuen S.T., Kung H.F. and Wong B.C.Y., Correlation Between the Single-site CpG Methylation and Expression Silencing of the XAF1 Gene in Human Gastric and Colon Cancers, Gastroenterology. 2006, 131(6): 1835-1843.

Researcher : Yeung CK

List of Research Outputs

Shek S.Y.N., Yu C.S., Yeung C.K., Kono T. and Chan H.H.L., Non-invasive body contouring with focused ultrasound technology., Lasers in Surgery and Medicine. 2007, S19: 60.

Shek S.Y.N., Yu C.S., Yeung C.K., Kono T. and Chan H.H.L., Non-thermal blue and near-infrared light system with glycolic acid peels and topical vitamin C for photorejuvenation., Lasers in Surgery and Medicine. 2007, S19: 252.

Shek S.Y.N., Yu C.S., Yeung C.K., Kono T. and Chan H.H.L., Treatment of pigmented lesions by Starlux-V handpiece., Lasers in Surgery and Medicine. 2007, S19: 253.

Yeung C.K., Shek S.Y.N., Pjerring P., Yu C.S., Kono T. and Chan H.H.L., A comparative study of intense pulsed light alone and its combination with photodynamic therapy for the treatment of facial acne in Asian skin, Lasers in Surgery and Medicine. 2007, 39(1): 1-6.

Yeung C.K., Tse K.C., Lam M.F., Chan D.T.M. and Lai K.N., A renal transplant recipient with mutiple facial nodules, Nephrology Dialysis Transplantation. 2006, 21: 3591-3592.

Yeung C.K., Shek S.Y.N., Yu C.S. and Chan H.H.L., Treatment of facial acne with 1450nm diode laser in Asians., Lasers in Surgery and Medicine. 2007, S19: 69.

Yu C.S., Shek S.Y.N., Yeung C.K., Kono T. and Chan H.H.L., Combined infrared light and bipolar radiofrequency for skin tightening in Asians., Lasers in Surgery and Medicine. 2007, S19: 65.

Researcher : Yeung CY

List of Research Outputs

Xu A., Tso A.W., Cheung B.M.Y., Wang Y., Wat N.M.S., Fong H.Y., Yeung C.Y., Janus E.D., Sham P.C. and Lam K.S.L., Circulating adipocyte-fatty acid binding protein levels predict the development of the metabolic syndrome: a 5-year prospective study, Circulation. 2007, 115: 1537-43.

Xu A., Tso A.W.K., Cheung B.M.Y., Wang Y., Wat N.M.S., Fong H.Y., Yeung C.Y., Janus E.D., Sham P.C. and Lam K.S.L., Circulating levels of adipocyte-fatty acid binding protein correlate with its adipose tissue expression and predict the development of the metabolic syndrome. , The Endocrine Society's 89th Annual Meeting, 2-5 June 2007, Toronto. 2007.

Yeung C.Y., Xu A., Cheung C.W., Wat N.M.S., Yau M.H., Fong H.Y. and Lam K.S.L., Circulating serum adipocyte-fatty acid-binding protein (A-FABP) levels correlate with carotid intima-media thickness (IMT) in Southern Chinese women. , 89th Annual Meeting of Endocrine Society, 2-5 June 2007, Toronto, Canada. 2007.

Zhang X., Yeung C.Y., Wong L.C., Chow W.S., Xu A. and Lam K.S.L., Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans, Second Symposium on Healthy Aging: "Meeting the Challenges of an Aging Population" . 2007.

Researcher : Yeung CY

List of Research Outputs

Researcher : Yew WW

List of Research Outputs

Chan M.M.W., Kam K.M., Leung C.C., Wang J., Yew W.W., Lam C.W. and Tam C.M., Population-based prospective molecular and conventional epidemiological study of tuberculosis in Hong Kong. , Respirology. 2006, 11(4): 442-8.

Researcher : Yik PY

List of Research Outputs

Chu L.W., Yik P.Y., Mok W. and Chung C.P., A two-year open-label study of galantamine therapy in Chinese Alzheimer’s disease patients in Hong Kong, Int J Clin Pract. 2007, 61: 403-10.

Li Y., Chu L.W., Cheung B.M.Y., Leung Y.H., Yik P.Y., Jin D. and Song Y., Association of ABCA1 Gene with Sporadic Alzheimer's Disease in Chinese Group and Potential Functional Importance for Novel Intronic Polymorphism., 11th Research Postgraduate Symposium, 7 Dec. 2006. The University of Hong Kong, Li Ka Shing Faculty of Medicine. 2006.

Li Y., Chu L.W., Chen Y., Cheung B.M.Y., Leung R.Y., Yik P.Y., Ng K.M.T., Mak W., Jin D., St. George-Hyslop P. and Song Y., Intron 2 (T/C) CYP46 polymorphism is associated with Alzheimer's disease in Chinese patients., Dement Geriatr Cogn Disord 2006. 2006, 22(5-6): 399-404.

Researcher : Yu CS

List of Research Outputs

Shek S.Y.N., Yu C.S., Yeung C.K., Kono T. and Chan H.H.L., Non-invasive body contouring with focused ultrasound technology., Lasers in Surgery and Medicine. 2007, S19: 60.

Shek S.Y.N., Yu C.S., Yeung C.K., Kono T. and Chan H.H.L., Non-thermal blue and near-infrared light system with glycolic acid peels and topical vitamin C for photorejuvenation., Lasers in Surgery and Medicine. 2007, S19: 252.

Shek S.Y.N., Yu C.S., Yeung C.K., Kono T. and Chan H.H.L., Treatment of pigmented lesions by Starlux-V handpiece., Lasers in Surgery and Medicine. 2007, S19: 253.

Yeung C.K., Shek S.Y.N., Pjerring P., Yu C.S., Kono T. and Chan H.H.L., A comparative study of intense pulsed light alone and its combination with photodynamic therapy for the treatment of facial acne in Asian skin, Lasers in Surgery and Medicine. 2007, 39(1): 1-6.

Yeung C.K., Shek S.Y.N., Yu C.S. and Chan H.H.L., Treatment of facial acne with 1450nm diode laser in Asians., Lasers in Surgery and Medicine. 2007, S19: 69.

Yu C.S., Shek S.Y.N., Yeung C.K., Kono T. and Chan H.H.L., Combined infrared light and bipolar radiofrequency for skin tightening in Asians., Lasers in Surgery and Medicine. 2007, S19: 65.

Yu C.S., Chan H.H.L. and Tse R.K., Radiosurgery versus carbon dioxide laser for dermatochalasis correction in Asians, Lasers in Surgery and Medicine. 2007, 39(2): 176-9.

Researcher : Yu L

List of Research Outputs

Yu L., Wang J., Zou B., Lin M.C., Wu Y.L., Xia H.H.X., Sun Y., Gu Q., He H., Lam S.K., Kung H.F. and Wong B.C.Y., XAF1 Mediates Apoptosis Through an Extracellular Signal-Regulated Kinase Pathway in Colon Cancer , Cancer. 2007, 109(10): 1996-2003.

Zou B., Chim J.C.S., Zeng H., Leung S.Y., Yang Y., Tu S., Lin M.C., Wang J., He H., Jiang S.H., Sun Y., Yu L., Yuen S.T., Kung H.F. and Wong B.C.Y., Correlation Between the Single-site CpG Methylation and Expression Silencing of the XAF1 Gene in Human Gastric and Colon Cancers, Gastroenterology. 2006, 131(6): 1835-1843.

Researcher : Yuen JCH

List of Research Outputs

Fung J.Y.Y., Lai C.L., Yuen J.C.H., Wong D.K.H., Tanaka Y., Mizokami M. and Yuen R.M.F., Adefovir dipivoxil monotherapy and combination therapy with lamivudine for the treatment of chronic hepatitis B in an Asian population, Antivir Ther. 2007, 12: 41-46.

Wong D.K.H., Yuen R.M.F., Poon R.T.P., Yuen J.C.H., Fung J.Y.Y. and Lai C.L., Quantification of hepatitis B virus covalently closed circular DNA in patients with hepatocellular carcinoma, Journal of hepatology : the journal of the European Association for the Study of the Liver. 2006, 45: 553-559.

Wong D.K.H., Yuen R.M.F., Poon R.T.P., Yuen J.C.H., Fung J.Y.Y. and Lai C.L., Quantitation of hepatitis B virus covalently closed circular DNA in patients with hepatocellular carcinoma, Journal of Hepatology. 2006, 45: 553-559.

Yuen R.M.F., Kim J., Kim C.R., Ngai W.S., Yuen J.C.H., Min C., Kang H.M., Shin B.S., Yoo S.D. and Lai C.L., A Randomized Placebo-controlled, Dose-finding Study of Oral LB80380 in HBeAg-positive Patients with Chronic Hepatitis B, Antivir Ther. 2006, 11(8): 977-983.

Yuen R.M.F., Wong D.K.H., Zheng B., Chan C.C.S., Yuen J.C.H., Wong B.C.Y. and Lai C.L., Difference in T Helper Responses During Hepatitis Flares in HBeAg-positive Patients with Genotypes B and C: Implication for Early HBeAg Seroconversion, Journal of Viral Hepatitis. 2007, 14: 269-275.

Yuen R.M.F., Tanaka Y., Shinkai N., Poon R.T.P., But D.Y.K., Fong D.Y.T., Fung J.Y.Y., Wong D.K.H., Yuen J.C.H., Mizokami M. and Lai C.L., Risk for hepatocellular carcinoma with respect to hepatitis B virus genotypes B/ C, specific mutations of enhancer II/ core promoter/ precore regions and HBV DNA levels, Gut. 2007, 57: 98-102.

Yuen R.M.F., Tanaka Y., Shinkai N., Poon R.T.P., Fung J.Y.Y., Wong D.K.H., Yuen J.C.H., Mizokami M. and Lai C.L., Role of HBV genotypes, core promoter/precore mutations and HBV DNA levels on hepatocarcinogenesis, Annual meeting, European Association for the Study of Liver (EASL), Barcelona, Spain, 11 - 15 April 2007.

Researcher : Yuen RMF

List of Research Outputs

Chan A.O.O., Hui W.M., Lam K.F., Leung G.K.L., Yuen R.M.F., Lam S.K. and Wong B.C.Y., Familial aggregation in constipated subjects in a tertiary referral center, American Journal of Gastroenterology. Blackwell Publishing, 2007, 102: 149-152.

Chan A.O.O., Jim M.H., Lam K.F., Siu D.C.W., Tong S.M., Ng F.H., Wong S.Y., Hui W.M., Chan C.K., Lai K.C., Cheung T.K., Chan P., Wong G., Yuen R.M.F., Lau Y.K., Lee S.W.L., Seto M.L., Lam S.K. and Wong B.C.Y., Patients with coronary artery disease had high prevalanece of colorectal cancer and adenoma: END-results of metabolic syndrome and smoking. Digestive Disease Week 2007, Washington DEc, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A65.

Chan O.O., Lam K.F., Tong T.P.H., Siu D.C.W., Jim M.H., Hui W.M., Lai K.C., Yuen R.M.F., Lam S.K. and Wong B.C.Y., Coexistence between colorectal cancer/adenoma and coronary artery disease: results from 1382 patients. , Alimentary Pharmacology and Therapeutics. 2006, 24(3): 535-9.

Chan O.O., Huang C.Y., Hui W.M., Cho C.H., Yuen R.M.F., Lam S.K., Rashid A. and Wong B.C.Y., Stability of E-cadherin methylation status in gastric mucosa associated with histology changes. , Alimentary Pharmacology and Therapeutics. 2006, 24(5): 831-6.

Cheung T.K., Lai C.L., Wong B.C.Y., Fung J.Y.Y. and Yuen R.M.F., Clinical Features, Biochemical Parameters, and Virological Profiles of Patients with Hepatocellular Carcinoma in Hong Kong, Aliment Pharmacol Ther . 2006, 24(4): 573-583.

Cheung T.K., Lai C.L., Wong B.C.Y., Fung J.Y.Y. and Yuen R.M.F., Clinical features, biochemical parameters, and virological profiles of patients with hepatocellular carcinoma in Hong Kong. , Alimentary Pharmacology and Therapeutics. 2006, 24(4): 573-83.

Fung J.Y.Y., Lai C.L., Yuen J.C.H., Wong D.K.H., Tanaka Y., Mizokami M. and Yuen R.M.F., Adefovir dipivoxil monotherapy and combination therapy with lamivudine for the treatment of chronic hepatitis B in an Asian population, Antivir Ther. 2007, 12: 41-46.

Fung J.Y.Y., Lai C.L., Wong D.K.H., Cheng C.T.K., But D.Y. and Yuen R.M.F., Large Population Study in Liver Stiffness Measurement: Prevalence of Significant Fibrosis and Correlation with Liver Biochemistry in Chronic Hepatitis B, Annual Meeting for European Association for the Study of the Liver (EASL 2007). 2007.

Fung J.Y.Y., Lai C.L., Wong D.K.H. and Yuen R.M.F., Large population study on the natural history of spontaneous hepatitis B e antigen seroconversion: risk of hepatocellular carcinoma. Annual meeting, European Association for the Study of Liver (EASL). Journal of Hepatology. 2007, 46 S1: S181.

Fung J.Y.Y., Lai C.L. and Yuen R.M.F., Overcoming the problem of chronic hepatitis B. Drug Discovery Today, Therapeutic Strategies. 2007, 3: 197-202.

Fung J.Y.Y., Lai C.L. and Yuen R.M.F., Telbivudine : A new treatment option in the management of chronic hepatitis B, Hepatitis B Annual. 2006, 3(1): 14-34.

Lee P.P.W., Lee W.Y., Yuen R.M.F., Poon R.T.P. and Lau Y.L., Gene association study on development of hepatic fibrosis in chronic hepatitis B among Hong Kong Chinese. , The 8th International Meeting on Human Genome Variation and Complex Genome Analysis, Hong Kong, 14 - 16 September 2006.

Lee W.Y., Lee P.P.W., Yuen R.M.F., Poon R.T.P. and Lau Y.L., Association of Interferon-gamma (IFN-g) Polymorphisms with Susceptibility of Hepatitis B Virus (HBV) Infection in the Hong Kong Chinese. , "European Human Genetics Conference, Nice, France, 16 - 19 June 2007.

Lee W.Y., Lee P.P.W., Wong W.H.S., Yuen R.M.F., Poon R.T.P., Lai C.L., Fan S.T. and Lau Y.L., Association of Transforming Growth Factor-Beta 1 (TGF-b1) Polymorphisms with Hepatitis B Virus (HBV) Related Fibrosis and Cirrhosis in the Hong Kong Chinese, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006.

Leung N., Sherman M., Peng C.Y., Sollano J.D., Lesmana L., Yuen R.M.F., Feffers L., Hann H.W., Menearini K., Colonno R., Cross A., Wilber R. and Lopez-Talavera J.C., Entecavir ETV) Results in Higher HBV-DNA Reduction vs Adefovir (ADV) In Chronically Infected HBeAg(+) Antiviral-Naive Adults: 48-Week Results (E.A.R.L.Y. STUDY), Digestive Disease Week. 2007.

Nerrault N., Kim W.R., Lim S.G., Papatheodoridis G., Alberti A., Yuen R.M.F., Goodman Z.D., Vaughan J., Wilber R. and Kreter B., Presence of Biopsy-Proven Histologic Damage (Necroinflammation And Fibrosis) is Common Even When ALT is Less Than 2X ULN in Patients With Chronic Hepatitis B (CHB), Digestive Disease Week. 2007.

Orito E., Fujiwara K., Tanaka Y., Yuen R.M.F., Lai C.L., Kato T., Sugauchi F., Kusakabe A., Sata M., Okanoue T., Niitsuma H., Sakugawa H., Hasegawa I. and Mizokami M., A case-control study of response to lamivudine therapy for 2 years in Japanese and Chinese patients chronically infected with hepatitis B virus of genotypes Bj, Ba and C, Hepatol Res. 2006, 35(2): 127-34.

Tanaka Y., Mukaide M., Orito E., Yuen R.M.F., Ito K., Kurbanov F., Sugauchi F., Asahina Y., Izumi N., Kato M., Lai C.L. and Ueda R., Specific mutations in enhancer II/core promoter of hepatitis B virus subgenotypes C1/C2 increase the risk of hepatocellular carcinoma [Epub ahead of print], Journal of hepatology : the journal of the European Association for the Study of the Liver. 2006, 10.

Tanaka Y., Mukaide M., Orito E., Yuen R.M.F., Ito K., Kurbanov F., Sugauchi F., Asahina Y., Izumi N., Kato M., Lai C.L., Ueda R. and Mizokami M., Specific mutations in enhancer II/core promoter of hepatitis B virus subgenotypes C1/C2 increase the risk of hepatocellular carcinoma, Journal of hepatology : the journal of the European Association for the Study of the Liver. 2006, 45: 646-653.

Tanaka Y., Mukaide M., Orito E., Yuen R.M.F., Ito K., Kurbanov F., Sugauchi F., Asahina Y., Izumi N., Kato M., Lai C.L., Ueda R. and Mizokami M., Ueda R, Mizokami M. Specific mutations in enhancer II/ core promoter of hepatitis B virus subgenotypes C1/C2 increase the risk of hepatocellular carcinoma, Journal of hepatology : the journal of the European Association for the Study of the Liver. 2006, 45(5): 646-653.

Wong D.K.H., Yuen R.M.F., Ngai W.S., Fung J.Y.Y. and Lai C.L., One-year entecavir or lamivudine therapy results in reduction of HBV intrahepatic covalently closed circular DNA levels, Antivir Ther . 2006, 11: 909-916.

Wong D.K.H., Yuen R.M.F., Ngai W.S., Fung J.Y.Y. and Lai C.L., One-year entecavir or lamivudine therapy results in reduction of hepatitis B virus intrahepatic covalently closed circular DNA levels., Antiviral Therapy. 2006, 11: 909-916.

Wong D.K.H., Yuen R.M.F., Poon R.T.P., Yuen J.C.H., Fung J.Y.Y. and Lai C.L., Quantification of hepatitis B virus covalently closed circular DNA in patients with hepatocellular carcinoma, Journal of hepatology : the journal of the European Association for the Study of the Liver. 2006, 45: 553-559.

Wong D.K.H., Yuen R.M.F., Poon R.T.P., Yuen J.C.H., Fung J.Y.Y. and Lai C.L., Quantitation of hepatitis B virus covalently closed circular DNA in patients with hepatocellular carcinoma, Journal of Hepatology. 2006, 45: 553-559.

Yuan H.J., Wong D.K.H., Doutreloigne J., Sablon E., Lai C.L. and Yuen R.M.F., Precore and core promoter mutations at the time of HBeAg seroclearance in Chinese patients with chronic hepatitis B., Journal of Infection. 2007, 54: 497-503.

Yuen R.M.F., Kim J., Kim C.R., Ngai W.S., Yuen J.C.H., Min C., Kang H.M., Shin B.S., Yoo S.D. and Lai C.L., A Randomized Placebo-controlled, Dose-finding Study of Oral LB80380 in HBeAg-positive Patients with Chronic Hepatitis B, Antivir Ther. 2006, 11(8): 977-983.

Yuen R.M.F. and Lai C.L., A new drug for chronic hepatitis B: entecavir, Medical Progress. 2006, 33(7): 343-346.

Yuen R.M.F., Assessment of liver fibrosis. The Hong Kong Medical Forum. 2007.

Yuen R.M.F. and Lai C.L., Combination therapy for chronic hepatitis B: Simultaneous or sequential, American Journal of Gastroenterology. 2007, 102: 105-106.

Yuen R.M.F., Determinants of Fibrosis progression in HBV Infection. Indian Association for the Study of Liver (INASL) – Asian Pacific Association for the Study of Liver (APASL) Single Theme Symposium, Kolkata, India. 2006.

Yuen R.M.F., Wong D.K.H., Zheng B., Chan C.C.S., Yuen J.C.H., Wong B.C.Y. and Lai C.L., Difference in T Helper Responses During Hepatitis Flares in HBeAg-positive Patients with Genotypes B and C: Implication for Early HBeAg Seroconversion, Journal of Viral Hepatitis. 2007, 14: 269-275.

Yuen R.M.F., Evolving therapy in HBV – future directions. Indian Association for the Study of Liver (INASL) – Asian Pacific Association for the Study of Liver (APASL) Single Theme Symposium, Kolkata, India. 2006.

Yuen R.M.F., First Awardee of Emerging Leader Lectureship Award , Asian Pacific Association of Gastroenterology (APAGE), Asian Pacific Society of Digestive Endoscopy (APSDE), Asian Pacific Association for the Study of Liver (APASL), International Society for Digestive Surgery (ISDS). 2006.

Yuen R.M.F. and Lai C.L., HBsAg seroclearance in the natural history of chronic hepatitis B infection, Current Hepatitis Reports. 2006, 5(1): 23-26.

Yuen R.M.F., Hepatitis B: markers for disease progression. The Importance of Viral Load and Hepatitis B Treatment Update. The Hong Kong Medical Association. 2007.

Yuen R.M.F., Keynote Lecture: Evolving options for hepatitis B therapy. National Conference on Liver Failure & Artificial Liver Support, Luo Yang, China. 2007.

Yuen R.M.F., Management of Chronic Hepatitis B: Consensus and Controversies. The 3rd Liver Update 2006, Jakarta, Indonesia. 2006.

Yuen R.M.F., Management of Difficult Chronic Liver Diseases. The 3rd Liver Update 2006, Jakarta, Indonesia. 2006.

Yuen R.M.F., Management of chronic hepatitis B in the era of potent antivirals. 6th Asian Pacific Digestive Week, Cebu, Philippines. 2006.

Yuen R.M.F., Markers for Disease Progression: The Importance of Viral Load. Annual Scientific Meeting of the Malaysian Society of Gastroenterology & Hepatology GUT 2006, Kuala Lumpur, Malaysia. 2006.

Yuen R.M.F., Natural history of hepatitis B related hepatocellular carcinoma. Macao Oncology Association, Macau . 2007.

Yuen R.M.F., Plenary Lecture: Revisit of the Natural History of Chronic Hepatitis B – Impact on the Old Theory. Emerging Leader Lecture, 6th Asian Pacific Digestive Week, Cebu, Philippines. 2006.

Yuen R.M.F. and Lai C.L., Recommendations and Potential Future Options in the Treatment of Hepatitis B, Expert Opin Pharmacother. 2006, 7(16): 2225-2231.

Yuen R.M.F., Revisiting the natural history of chronic hepatitis B: Impact of new concepts on clinical management., Journal of Gastroenterology and Hepatology. 2007, 22(7): 973-6.

Yuen R.M.F., Tanaka Y., Shinkai N., Poon R.T.P., But D.Y.K., Fong D.Y.T., Fung J.Y.Y., Wong D.K.H., Yuen J.C.H., Mizokami M. and Lai C.L., Risk for hepatocellular carcinoma with respect to hepatitis B virus genotypes B/ C, specific mutations of enhancer II/ core promoter/ precore regions and HBV DNA levels, Gut. 2007, 57: 98-102.

Yuen R.M.F., Tanaka Y., Shinkai N., Poon R.T.P., Fung J.Y.Y., Wong D.K.H., Yuen J.C.H., Mizokami M. and Lai C.L., Role of HBV genotypes, core promoter/precore mutations and HBV DNA levels on hepatocarcinogenesis, Annual meeting, European Association for the Study of Liver (EASL), Barcelona, Spain, 11 - 15 April 2007.

Yuen R.M.F., Sablon E., Libbrecht E., de Velde H.V., Wong D.K.H., Fung J.Y.Y., Wong B.C.Y. and Lai C.L., Significance of HBV viral load, core promoter/ precore mutations and specific sequences of polymerase gene in HBV-infected patients on 3-year lamivudine treatment, Antivir Ther. 2006, 11(6): 779-786.

Yuen R.M.F., Spontaneous or drug induced mutations in HBV: projection on treatment. 6th National Hepatology Meeting of the Turkish Association for the Study of Liver (TASL), Istanbul, Turkey. 2007.

Yuen R.M.F., Tam S., Fung J.Y.Y., Wong D.K.H., Wong B.C.Y. and Lai C.L., Traditional Chinese medicine causing hepatotoxicity in patients with chronic hepatitis B infection: A one-year prospective study, Alimentary Pharmacology and Therapeutics. 2006, 24(8): 1179-1186.

Yuen R.M.F., Treatment of Chronic Hepatitis B in Normal or Mild Elevation ALT. The 3rd Liver Update 2006, Jakarta, Indonesia. 2006.

Yuen R.M.F., Update on Hepatitis. Continued Medical Education Programme, Department of Anaesthesiology, Queen Mary Hospital, Hong Kong. 2007.

Yuen R.M.F., Viral suppression as a predictor of long term responses: part 1: evidence with lamivudine. The 10th Asia Pacific Advisory Board Meeting, Kyoto, Japan. 2007.

Zhou J., Lu L., Yuen R.M.F., Lam T.W., Chung C.P., Lam C.L., Zhang B., Wang S., Chen Y., Wu H.W., Poon K.M., Ng F., Chan C.S., Jiang S., Yuen K.Y. and Zheng B., Polymorphisms of type I interferon receptor 1 promoter and their effects on chronic hepatitis B virus infection, Journal of Hepatology. 2007, 46(2): 198-205.

Researcher : Yuen YM

List of Research Outputs

Leung J.C.K., Tang S.C.W., Chan L.Y., Yuen Y.M. and Lai K.N., Specific induction of neutrophil gelatinase-associated lipocalin in peritoneal mesothelial cells by interleukin-1, Journal of American Society of Nephrology. 2006, 17: 751A.

Researcher : Yueng YH

List of Research Outputs

Hui C.K., Zhang H., Shek T., Yao H., Yueng Y.H., Leung K.W., Lai S.T., Lai J.Y., Leung N. and Lau G., Disease progression in Chinese chronic hepatitis C patients with persistently normal alanin aminotransaminase levels, Alimentary Pharmacology Therapy. 2007, 25(11): 1283-92.

Hui C.K., Zhang H., Lee P.Y., Marin H., Yueng Y.H., Leung K.W., Lu L., Leung N., Luk J.M.C., Naoumov N., Huang F. and Lau G., Role of regulatory T cells in natural immunity and sustained pharmacological control hepatitis B infection, The Liver Meeting of The American Association for the Study of Liver, Hepatology. 2006, 44: 543A.

Hui C.K., Zhang H.Y., Lee P.Y., Mommeja-Marin H., Yueng Y.H., Leung K.W., Lu L., Leung N., Luk J.M.C., Naoumov N.N., Huang F.P. and Lau G., Role of regulatory T cells in natural immunity and sustained pharmacological control of chronic hepatitis B infection, Hepatology. 2006, 44(4): 543A-543A.

Zhang H., Hui C.K., Lee P.Y., Chan W., Yueng Y.H., Leung K.W., Lu L., Leung N., Lo C.M., Fan S.T., Luk J.M.C., Xu A., Lam K.S.L., Kwong Y.L. and Lau G., Serum adiponectin is increased in advancing liver fibrosis and decline with reduction in fibrosis in chronic hepatitis B, The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007, Hepatology International. 2007, 242: 7.

Researcher : Yung CY

List of Research Outputs

Siu C.W.D., Au W.Y., Yung C.Y., Kumana C.R., Lau C.P., Kwong Y.L. and Tse H.F., Effects of oral arsenic trioxide therapy on QT intervals in patients with acute promyelocytic leukemia: implications on long-term cardiac safety, Blood. 2006, 108(1): 103-106.

Researcher : Yung SSY

Project Title:	The role of thrombospondin-1 in the activation of TGF-beta1, and synthesis of matrix proteins in human proximal tubular epithelial cells under elevated glucose concentrations - implications in diabetic nephropathy
Investigator(s):	Yung SSY, Chan DTM
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2005
Completion Date:	01/2007

Abstract:

Background Nephropathy in patients with type I and II diabetes mellitus is a rapidly increasing problem worldwide, and is the most important cause of end-stage renal failure, accounting for 40% of new patients who require renal replacement therapy (1). The incidence of diabetic nephropathy (DN) will continue to increase, attributed in part by the improved survival of type II patients as the cardiovascular mortality in this group declines (2). DN is initiated by hyperglycaemia and characterized by cell proliferation, and thickening of tubular and glomerular basement membranes due to an excessive accumulation of extracellular matrix proteins that ultimately results in progressive scarring and fibrosis of the kidney (3). Clinically, DN manifests itself by the onset of continuous microalbuminuria followed by the appearance of persistent proteinuria. This is subsequently followed by a progressive decline in glomerular filtration rate leading to end-stage renal failure (4). Although DN was traditionally considered to be primarily a glomerular disease, recent studies have demonstrated that the rate of kidney function deterioration correlates best with the degree of tubulo-interstitial fibrosis (5). This therefore suggests that although glomerular changes are predominantly observed in diabetic patients, the long-term outcome is determined by events in the tubulo-interstitium. Proximal tubular epithelial cells (PTEC) constitutes the predominant cell type within the tubulo-interstitium. Although previously considered to be mainly involved in the transport of fluid and electrolytes, there is increasing evidence that they play a critical role in the immunopathogenesis of various renal parenchymal diseases, and act as a regulator/effector of immune-mediated inflammation and fibrosis (6). Thus, PTEC are not only affected secondary to glomerular injury, but are primary targets for pathological influences in DN. Animal and in vitro studies have shown that under elevated glucose concentrations, PTEC can directly contribute to the pathogenesis of renal fibrosis by induced synthesis of extracellular matrix proteins such as collagen type I and fibronectin through the enhanced secretion of the pro-fibrotic growth factor transforming growth factor-beta1 (TGF-beta1) (7-9). TGF-beta1 is normally synthesized and secreted in its latent form, and thus must be activated before it can bind to its receptors. Thus, changes in the expression of latent TGF-beta1 will have no biologic effect on the kidney parenchyma unless mechanisms are present to convert it to the active form. In the latent form, TGF-beta1 is non-covalently associated with a disulfide-linked dimer of the N-terminal part of the TGF-beta1 molecule, referred to as the latency-associated peptide (LAP). Physicochemical activation can occur by extreme pH or high temperature (10), limited proteolysis or deglycosylation of LAP (11), or binding to various membrane or extracellular matrix components. Activation in vivo is more complex and not well understood. Studies have documented that the extracellular matrix molecule thrombospondin-1 (TSP-1) is associated with TGF-beta1 as an active complex in stimulated platelets (12). Furthermore, TSP-1 has been shown to precede the development of tubulo-interstitial fibrosis in glomerular disease, and recent studies have shown TSP-1 to be the key activator of this pro-fibrotic peptide in human mesangial cells after exposure to elevated glucose concentrations (13-15). How TGF-beta1 is activated in PTEC in DN has not been investigated. We hypothesize that TSP-1 may activate TGF-beta1 in PTEC and contribute to tubulo-interstitial fibrosis. The objectives of this project are thus: 1. To assess PTEC proliferation and viability under physiological and elevated glucose concentrations pertaining to DN. 2. To assess gene expression and protein translation of TGF-beta1, matrix proteins (fibronectin, collagen type I, III and IV) and TSP-1 under different glucose concentrations, and correlate TSP-1 synthesis with TGF-beta1 activation and matrix protein synthesis. 3. To determine the bioactivity of TGF-beta1 secreted under control and elevated glucose concentrations. 4. To examine the effect of exogenous TSP-1 on TGF-beta1 bioactivity and matrix protein synthesis in PTEC, and to determine whether TSP-1 can directly modulate matrix synthesis or act only through induction of TGF-beta1 activation. References 1. Gilbert RE, Cooper ME. Kidney Int. 1999; 56: 1627-1637. 2. Ritz E, Stefanski A. Am J Kidney Dis. 1996; 27: 167-194. 3. Amos AF, McCarty DJ, Zimmet P. Diabet Med. 1997; 14: S1-S85. 4. Phillips AO, Steadman R. Histol Histopathol. 2002; 17: 247-252. 5. Bohle A, Wehrmann M, Bogenschutz O, Batz C, Muller CA, Muller GA. Pathol Res Pract. 1991; 187: 251-259. 6. Tang WW, Feng L, Xia Y, Wilson CB. Kidney Int. 45: 1994; 1077-1084. 7. Phillips AO, Steadman R, Topley N, Williams JD. Am J Pathol. 1995; 147: 362-374. 8. Phillips AO, Steadman R, Morrisey K, Martin J, Eynstone L, Williams JD. Kidney Int. 1997; 52: 973-984. 9. Morrisey K, Steadman R, Williams JD, Phillips AO. Kidney Int. 1999; 55: 2548-2572. 10. Brown PD, Wakefield LM, Levinson AD, Sporn MB. Growth Factors 1990; 3: 35-43. 11. Lyons R, Gentry LE, Purchio AF, Moses HL. J Cell Biol. 1990; 110: 1361-1367. 12. Murphy-Ullrich JE, Schultz-Cherry S, Hook M. Mol Biol Cell. 1992; 3: 181-188. 13. Poczatek MH, Hugo C, Darley-Usmar V, Murphy-Ullrich JE. Am J Pathol. 2000; 157: 1353-1363. 14. Yevdokimova N, Abdel Wahab N, Mason RM. J Am Soc Nephrol. 2001; 12: 703-712. 15. Hugo C, Shankland SJ, Pichler RH, Couser WG, Johnson RJ. Kidney Int. 1998; 53: 302-311.

Project Title:	The role of heparan sulfate proteoglycans in the pathogenesis of diabetic nephropathy and the effects of Sulodexide
Investigator(s):	Yung SSY, Chan DTM
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2007

Abstract:

To study the changes in heparan sulfare proteoglycan (HSPG) biosynthesis (including separate studies on its core protein, HS chain, and charge density), the expression of sulfotransferases (enzymes that add sulfate groups to the HS chains), and HSPG degradation in db/db mice; to examine whether the changes HSPG are related to altered sequestration of growth factors that are relevant to the progression of kidney damage, namely TGF-β1, VEGF, IGF and bFGF; to determine the relationship between altered PG expression and phenotypic manifestations of DN, including proteinuria and renal function impairment; to investigate the effects of Sulodexide on disease manifestation, renal histopathology, and PG expression in db/db mice with DN.

Project Title:	The effect of mycophenolic acid on the synthesis of matrix proteins and cytokines in proximal tubular epithelial cells
Investigator(s):	Yung SSY, Chan DTM
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2007

Abstract:

Background Lupus nephritis is a severe organ manifestation of systemic lupus erythematosus (SLE) and a major cause of morbidity worldwide. Anti-DNA antibodies are implicated in the pathogenesis of lupus nephritis since their levels correlate with disease activity, and they deposit in the glomerulus and tubular basement membrane of kidneys (1-3). To date, much of the research has focused on the immunopathogenesis of glomerular dysfunction in lupus nephritis whilst limited data is currently available on the consequence of tubulo-interstitial injury despite the frequent occurrence of tubulo-interstitial disease and their strong association with less favorable renal prognosis (4). Renal proximal tubular epithelial cells constitute the predominant cell type in the tubulo-interstitium. Although previously considered to be mainly involved in the transport of fluids and electrolytes, there is now compelling evidence to suggest a critical role of proximal tubular epithelial cells in the immunopathogenesis of various renal parenchymal diseases, undertaking an effector role during immune-mediated inflammation and fibrosis (5, 6). In this respect, our studies have demonstrated increased expression of IL-6 within the tubulo-interstitium of renal biopsies obtained from patients with lupus nephritis (7). The conventional treatment for severe lupus nephritis entails the use of corticosteroids and cyclophosphamide (8). Despite its efficacy, prolonged or repeated use of cyclophosphamide is associated with adverse effects, attributed in part to the metabolite acrolein, which has genotoxic and mutagenic properties (9). Mycophenolate mofetil (MMF) is a morpholinoethyl ester pro-drug that is converted after gastrointestinal absorption to its active metabolite mycophenolic acid (MPA) (10). It has established efficacy in the prevention and treatment of acute rejection after kidney transplantation. We have recently performed the first prospective randomized controlled study to determine the role of MMF in the treatment of severe proliferative lupus nephritis (11). We demonstrated that MMF is as effective as the regimen of cyclophosphamide and prednisolone in inducing remission, but has the distinct advantage of fewer side effects (11). Although the role of MMF/MPA on the inhibition of lymphocyte proliferation is well known, limited data is currently available on its effect on non-immune cells. Results from animal and in vitro studies show that MMF/MPA can inhibit platelet derived growth factor-induced proliferation of endothelial and vascular smooth muscle cells, decreases renal myofibroblast infiltration and collagen deposition, and inhibits cell proliferation and matrix synthesis in FCS-stimulated kidney mesangial cells (12-14). The mechanism by which MMF abrogates matrix synthesis has not been elucidated. In this regard, we and others have shown that chemical or inflammatory stimulation of mesothelial, epithelial, or mesangial cells can induce matrix protein synthesis through activation of protein kinase C (PKC) isomers (15-17). PKC has at least twelve isomeric forms and plays a pivotal role in intracellular signal transduction of hormones, cytokines and growth factors. We hypothesize that the PKC pathway may also be involved in the modulation of cellular functions by MPA. In an animal model of lupus nephritis, p38 MAPK contributes to autoimmune renal injury, and plays a pivotal role in cell proliferation and induction of cytokines (18). Whether MPA modulates MAPK in lupus nephritis remains to be determined. The Objectives of this project: 1. To assess the role of MPA on anti-DNA antibody mediated cell proliferation and viability in proximal tubular epithelial cells. 2. To assess the role of MPA on anti-DNA antibody mediated induction of cytokines, chemokines and matrix proteins in proximal tubular epithelial cells. 3. To ascertain the mechanisms through which anti-DNA antibodies and MPA mediate their actions on proximal tubular epithelial cells. References 1. Tan EM. Autoantibodies to nuclear antigens (ANA): Their immunobiology and medicine. Adv Immunol 1982; 33: 167-240. 2. Winfield JB, Faiferman I, Koffler D. Avidity of anti-DNA antibodies in serum and IgG glomerulate eluates from patients with systemic lupus erythematosus. J Clin Invest 1977; 59: 90-96. 3. Magil AB, Tyler M. Tubulo-interstitial disease in lupus nephritis. A morphometric study. Histopathology 1984; 8: 81-87. 4. Nath KA. Tubulointerstitial changes as a major determinant in the progression of renal damage. Am J Kidney Dis 1992; 20: 1-17. 5. Dai C, Liu Z, Zhou H, Li L. Monocyte chemoattractant protein-1 expression in renal tissue is associated with monocyte recruitment and tubulo-interstitial lesions in patients with lupus nephritis. Chin Med J 2001; 114: 864-868. 6. Tang WW, Feng L, Xia Y, Wilson CB. Extracellular matrix accumulation in immune-mediated tubulo-interstitial injury. Kidney Int 1994; 45: 1077-1084. 7. Yung S, Tsang RCW, Sun Y, Leung JKH, Chan TM. Effect of human anti-DNA antibodies on proximal renal tubular epithelial cell cytokine expression: implications on tubulointerstitial inflammation in lupus nephritis. J Am Soc Nephrol 2005; 16: 3281-3295. 8. Donadio JV Jr, Holley KE, Ferguson RH, Ilstrup DM. Treatment of diffuse proliferative lupus nephritis with prednisone and combined prednisone and cyclophosphamide. N Engl J Med 1978 299: 1151-1155. 9. Kehrer JP, Biswal SS. The molecular effects of acrolein. Toxicol Sci 2000; 57: 6-15. 10. Allison AC, Eugui EM. Immunosuppressive and other effects of mycophenolic acid and an ester prodrug, mycophenolate mofetil. Immunol Rev 1993; 136: 5-28. 11. Chan TM, Li FK, Tang CS, Wong RW, Fang GX, Ji YL, Lau CS, Wong AK, Tong MK, Chan KW, Lai KN. Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group. N Engl J Med 2000; 343: 1156-1162. 12. Dubus I, Vendrely B, Christophe I, Labouyrie JP, Delmas Y, Bonnet J, Combe C. Mycophenolic acid antagonizes the activation of cultured human mesangial cells. Kidney Int 2002; 857-867. 13. Hauser IA, Renders L, Radeke HH, Sterzel RB, Goppelt-Struebe M. Mycophenolate mofetil inhibits rat and human mesangial cell proliferation by guanosine depletion. Nephrol Dial Transplant. 1999; 14: 58-63. 14. Mohacsi PJ, Tuller D, Hulliger B, Wijngaard PL. Different inhibitory effects of immunosuppressive drugs on human and rat aortic smooth muscle and endothelial cell proliferation stimulated by platelet-derived growth factor or endothelial cell growth factor. J Heart Lung Transplant 1997; 16: 484-492. 15. Chan TM, Leung JKH, Tsang RCW, Liu ZH, Li LS, Yung S. Emodin ameliorates glucose-induced matrix synthesis in human peritoneal mesothelial cells. Kidney Int. 2003; 64: 519-533. 16. Page K, Li J, Zhou L, Iasvovskaia S, Corbit KC, Soh JW, Weinstein IB, Brasier AR, Lin A, Hershenson MB. Regulation of airway epithelial cell NF-kappa B-dependent gene expression by protein kinase C delta. J Immunol 2003; 170: 5681-5689. 17. Lin S, Sahai A, Chugh SS, Pan X, Wallner EI, Danesh FR, Lomasney JW, Kanwar YS. High glucose stimulates synthesis of fibronectin via a novel protein kinase C, Rap 1b, and B-Raf signaling pathway. J Biol Chem 2002; 277: 41725-41735. 18. Iwata Y, Wada T, Furuichi K, Sakai N, Matsushima K, Yokoyama H, Kobayashi K. p38 mitogen-activated protein kinase contributes to autoimmune renal injury in MRL-Faslpr mice. J Am Soc Nephrol 2003; 14: 57-67.

List of Research Outputs

Chan D.T.M., Tsang R.C.W., Chan K.W. and Yung S.S.Y., Anti-DNA antibodies stimulate hyaluronan synthesis in proximal tubular epithelial cells through the induction of IL-6 and IL-1b, Journal of the American Society of Nephrology. 2006, 17: 352A.

Chan D.T.M., Ho S.K.N., Tang C.S.O., Tse K.C., Lam M.F., Lai K.N. and Yung S.S.Y., Pilot study of pegylated interferon-alpha 2a in dialysis patients with chronic hepatitis C virus infection, Nephrology. 2007, 12: 11-17.

Chan D.T.M. and Yung S.S.Y., Studying the effects of new peritoneal dialysis solutions on the peritoneum, Peritoneal Dialysis International . 2007, 27: S87-S93.

Lui S.L., Chan K.W., Tsang R.C.W., Yung S.S.Y., Lai K.N. and Chan D.T.M., Effect of rapamycin on renal ischemia-reperfusion injury in mice, Transplant International. 2006, 19: 834-839.

Lui S.L., Yung S.S.Y., Tsang R.C.W., Chan K.W., Zhang Q., Tam S., Lai K.N. and Chan D.T.M., Rapamycin attenuates the severity of nephritis in NZB/NZW mice, Journal of the American Society of Nephrology. 2006, 17: 353A.

Lui S.L., Yung S.S.Y., Tsang R.C.W., Chan K.W., Zhang Q., Tam S., Lai K.N. and Chan D.T.M., Rapamycin reduces proteinuria and segmental glomerulosclerosis in murine adriamycin nephropathy, Journal of the American Society of Nephrology. 2006, 17: 743A.

Ng Y.C.C., Yung S.S.Y. and Chan D.T.M., Mycophenolic acid reduces anti-DNA antibody binding and cytokine secretion in renal proximal tubular epithelial cells - implications in lupus nephritis, Lupus. 2007, 16 (S1): 46.

Wan C.C., Yung S.S.Y., Tsang R.C.W. and Chan D.T.M., Fibrosis-related growth factors in peritoneal dialysate during peritonitis, Peritoneal Dialysis International. 2006, 26 (Suppl 2): S22.

Yung S.S.Y. and Chan D.T.M., Glycosaminoglycans and proteoglycans: overlooked entities?, Peritoneal Dialysis International. 2007, 27: S104-S109.

Yung S.S.Y. and Chan D.T.M., Hyaluronan - regulator and initiator of peritoneal inflammation and remodeling, International Journal of Artifical Organs. 2007, 30: 477-483.

Yung S.S.Y., Immunopathogenesis of lupus nephritis - the role of anti-DNA antibodies, The 8th International Congress on SLE, May 23-27. 2007.

Yung S.S.Y., Wan C.C., Tsang R.C.W., Mak J.C.W., Tsang K.W.T. and Chan D.T.M., Induction of IL-6 and matrix protein synthesis in human peritoneal mesothelial cells by Pseudomonas aeruginosa exotoxin pyocyanin, Journal of the American Society of Nephrology. 2006, 17: 305A.

Yung S.S.Y., Zhang Q., Tsang R.C.W., Mak J.C.W., Tsang K.W.T. and Chan D.T.M., Induction of interleukin-6 secretion and matrix protein synthesis in human peritoneal mesothelial cells (HPMCs) by Pseudomonas aeruginosa exotoxin pyocyanin, Peritoneal Dialysis International. 2006, 26 (Suppl 2): S22.

Yung S.S.Y., Mesothelial cells , 11th Congress of the International Society of Peritoneal Dialysis, 25-28 August. 2006.

Yung S.S.Y. and Chan D.T.M., Mesothelial cells, Peritoneal Dialysis International. 2007, 27: S110-S115.

Yung S.S.Y., Proteoglycans and glycosaminoglycans - overlooked entities, 11th Congress of the International Society of Peritoneal Dialysis, August 25-28. 2006.

Researcher : Zhang D

List of Research Outputs

Zhang D., Lau C.P. and Li G.R., Regulation of hERG channels by EGFR and Src-related tyrosine kinase, Journal of Hong Kong College Cardiology/The 10th Institute of Cardiovascular Science and Medicine . 2006, 14: 94.

Researcher : Zhang H

List of Research Outputs

Hui C.K., Zhang H., Shek T., Yao H., Yueng Y.H., Leung K.W., Lai S.T., Lai J.Y., Leung N. and Lau G., Disease progression in Chinese chronic hepatitis C patients with persistently normal alanin aminotransaminase levels, Alimentary Pharmacology Therapy. 2007, 25(11): 1283-92.

Hui C.K., Zhang H., Lee P.Y., Marin H., Yueng Y.H., Leung K.W., Lu L., Leung N., Luk J.M.C., Naoumov N., Huang F. and Lau G., Role of regulatory T cells in natural immunity and sustained pharmacological control hepatitis B infection, The Liver Meeting of The American Association for the Study of Liver, Hepatology. 2006, 44: 543A.

Zhang H., Jin Y., Chen X., Jin C., Law S.Y.K., Tsao G.S.W. and Kwong Y.L., Papillomavirus type 16 E6/E7 and human telomerase reverse transcriptase in esophageal cell immortalization and early transformation, Cancer Letters. 2007, 245(1-2): 184-194.

Zhang H., Hui C.K., Lee P.Y., Chan W., Yueng Y.H., Leung K.W., Lu L., Leung N., Lo C.M., Fan S.T., Luk J.M.C., Xu A., Lam K.S.L., Kwong Y.L. and Lau G., Serum adiponectin is increased in advancing liver fibrosis and decline with reduction in fibrosis in chronic hepatitis B, The 17th Asian Pacific Association for the Study of the Liver Conference, Kyoto, Japan, 27 - 30 March 2007, Hepatology International. 2007, 242: 7.

Researcher : Zhang H

List of Research Outputs

Researcher : Zhang J

List of Research Outputs

Lam K.S.L., Tso A.W.K., Chow W.S., Hoo R.L.C., Zhang J., Lam C.W. and Xu A., Adipocyte fatty acid binding protein as a potential circulating metabolic hormone: clinical and functional studies. , The Endocrine Society’s 88th Annual Meeting, June 24-27, 2006, Boston, USA. 2007.

Wang Y., Lam K.S.L., Kraegen E.W., Sweeney G., Zhang J., Tso A.W.K., Chow W.S., Wat N.M.S., Xu J., Hoo R.L.C. and Xu A., Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans, Clin Chem. 2007, 53: 34-41.

Researcher : Zhang Q

List of Research Outputs

Lui S.L., Yung S.S.Y., Tsang R.C.W., Chan K.W., Zhang Q., Tam S., Lai K.N. and Chan D.T.M., Rapamycin attenuates the severity of nephritis in NZB/NZW mice, Journal of the American Society of Nephrology. 2006, 17: 353A.

Lui S.L., Yung S.S.Y., Tsang R.C.W., Chan K.W., Zhang Q., Tam S., Lai K.N. and Chan D.T.M., Rapamycin reduces proteinuria and segmental glomerulosclerosis in murine adriamycin nephropathy, Journal of the American Society of Nephrology. 2006, 17: 743A.

Yung S.S.Y., Zhang Q., Tsang R.C.W., Mak J.C.W., Tsang K.W.T. and Chan D.T.M., Induction of interleukin-6 secretion and matrix protein synthesis in human peritoneal mesothelial cells (HPMCs) by Pseudomonas aeruginosa exotoxin pyocyanin, Peritoneal Dialysis International. 2006, 26 (Suppl 2): S22.

Researcher : Zhang R

Project Title:	Modulation of dedritic cell by tumor associate protein S100P
Investigator(s):	Zhang R, Lan HY
Department:	Medicine
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	05/2007

Abstract:

S100 is a multigenic family with intracellular and extracellular regulatory activities. S100P, a 95-amino-acid member of the S100 family of proteins that was first purified from placenta (1), is overexpressed in pancreatic cancer (2-4) and is consider to be an early developmental marker of pancreatic carcinogenesis (5). It was also found that S100P promotes pancreatic cancer growth, survival, and invasion (6). S100P is also expressed in other human cancers, including breast, colon, prostate, and lung. The elevated levels of S100P in breast cancer are associated with cellular immortalization (7). In colon cancer cell lines, its expression level was correlated with resistance to chemotherapy (8). In prostate tumors, S100P levels were found to be androgen sensitive (9). In lung cancer, S100P expression correlated with decreased patient survival (10). However, despite these observations, the extracellular immunological functions of S100P in tumorgenesis remain unknown. Dendritic cells (DCs) are professional antigen presenting cells which not only initiate T cell immunity by uptake, processing and presentation of specific antigens, but also induce immune tolerance by deletion of T cells and/or induction of regulatory T cells (T regs). (CD4+)CD25+ T regs maintain immune tolerance by suppressing the function of CD4+ and CD8+ T cells, B cells, macrophages, DCs and NK cells. Therefore, the crosstalk between DCs and (CD4+) CD25+ T regs play important role in balancing of immunity and tolerance. Transforming growth factor-beta (TGF-β) serving as a potential link between these two professionals cells (11). Recent studies show that colon tumor cell can convert immature dendritic cells into TGF-β-secreting cells inducing CD4+CD25+regulatory T cell proliferation (12). Recently, we found that BxPC-3, a S100P highly expressed human pancreatic cancer cell line, significantly supresse DC differentiation, maturation, antigen-presentation, and allostimulatory activity (Bharadwaj, U et al, unpublished results). However, mechnisims of how the cancer cell suppress DC function and convert DC inducing the T regulatory cell proliferation are yet unknown. We recently found that S100P modulate the DC surface molecules expression and cytokine production. This preliminary data indicates that the S100P may mediate tumor immune escape by modulating the function of DCs. Therefore, we hypothesize that S100P may play important role in inducing T regulatory cell proliferation and maintain immune tolerance to pancreatic cancer by modulating the function of DC and suppressing the function of CD4+ and CD8+ T cells. S100P could be a potential siRNA therapeutic target and vaccine candidate for cancer immunotherapy. There are two objectives in this proposed study. I, To determine the role of S100P in influencing DC activation and antigen presentation. Our working hypothesis in this specific aim is that S100P will influence the activation of DC, resulting in the changes in DC phenotypes and antigen presentation activities. II, To study the role of S100P in modulating DC cytokine profiles and inducing Foxp3+CD4+CD25+ T regulatory cell proliferation. Our working hypothesis in this specific aim is that S100P will change the cytokine profiles of DC, specifically enhancing TGF-β and/or IL-10 production, thereby inducing the Foxp3+CD4+CD25+ T regulatory cell-dependent immune tolerance. The future studies will focus on the in vivo studies in mouse. We will test the DC profiles and T regs proliferation in mouse (or S100P transgenic mouse) bearing with S100P overexpressed tumor cells and S100P silenced tumor cells. Reference: 1. Becker T, Gerke V, Kube E, Weber K. S100P, a novel Ca(2+)-binding protein from human placenta. cDNA cloning, recombinant protein expression and Ca2+ binding properties. Eur J Biochem. 1992; 207(2):541-7. 2. Logsdon CD, Simeone DM, Arumugam T, et al. Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancer. Cancer Res 2003;63:2649–57. 3. Crnogorac-Jurcevic T, Missiaglia E, Blaveri E, et al. Molecular alterations in pancreatic carcinoma: expression profiling shows that dysregulated expression of S100 genes is highly prevalent. J Pathol 2003;201:63–74. 4. Sato N, Fukushima N, Matsubayashi H, Goggins M. Identification of maspin and S100P as novel hypomethylation targets in pancreatic cancer using global gene expression profiling. Oncogene 2004;26:1531–8. 5. Ohuchida K, Mizumoto K, Egami T, Yamaguchi H, Fujii K, Konomi H, Nagai E, Yamaguchi K, Tsuneyoshi M, Tanaka M. S100P is an early developmental marker of pancreatic carcinogenesis. Clin Cancer Res. 2006;12(18):5411-6. 6. Arumugam T, Simeone DM, Van Golen K, Logsdon CD. S100P promotes pancreatic cancer growth, survival, and invasion. Clin Cancer Res. 2005; 11(15):5356-64. 7. Guerreiro DS, Hu YF, Russo IH, et al. S100P calcium-binding protein overexpression is associated with immortalization of human breast epithelial cells in vitro and early stages of breast cancer development in vivo. Int J Oncol 2000; 16:231–40 8. Bertram J, Palfner K, Hiddemann W, Kneba M. Elevated expression of S100P, CAPL and MAGE 3 in doxorubicin-resistant cell lines: comparison of mRNA differential display reverse transcription-polymerase chain reaction and subtractive suppressive hybridization for the analysis of differential gene expression. Anticancer Drugs 1998; 9:311–7. 9. Averboukh L, Liang P, Kantoff PW, Pardee AB. Regulation of S100P expression by androgen. Prostate 1996; 29:350–5. 10. Beer DG, Kardia SL, Huang CC, et al. Gene-expression profiles predict survival of patients with lung adenocarcinoma. Nat Med 2002;8:816–24. 11. Chen W. Dendritic cells and (CD4+)CD25+ T regulatory cells: crosstalk between two professionals in immunity versus tolerance. Front Biosci. 2006, 11:1360-70. 12. Ghiringhelli F, Puig PE, Roux S, Parcellier A, Schmitt E, Solary E, Kroemer G, Martin F, Chauffert B, Zitvogel L. Tumor cells convert immature myeloid dendritic cells into TGF-beta-secreting cells inducing CD4+CD25+ regulatory T cell proliferation. J Exp Med. 2005; 202(7):919-29.

List of Research Outputs

Lan X.R., Zhang R. and Lan H.Y., Deletion of Smad3 Switches The TH1 to TH2 Immune Response in anti-GBM Glomerulonephritis., 12th Medical Research Conference of Department of Medicine (3/2/2007). 2007.

Wong L.W., Zhu S.L., Zhang S.Y., Lan X.R., Chung A.C.K., Zhang R., Lam S.K., Wong B.C.Y., Xia H.H.X. and Lan H.Y., Macrophage Migration Inhibitory Factor (MIF) Knockout Mice Are Protected Against Helicobacter Pylori Induced Gastritis., 12th Medical Research Conference (Hong Kong, 3/2/2007). 2007.

Researcher : Zhang SY

List of Research Outputs

Wong L.W., Zhu S.L., Zhang S.Y., Lan X.R., Chung A.C.K., Zhang R., Lam S.K., Wong B.C.Y., Xia H.H.X. and Lan H.Y., Macrophage Migration Inhibitory Factor (MIF) Knockout Mice Are Protected Against Helicobacter Pylori Induced Gastritis., 12th Medical Research Conference (Hong Kong, 3/2/2007). 2007.

Zhang S.Y., Lan X.R., Lau C.P. and Lan H.Y., Angiotensin II-induced Hypertensive Cardiac Fibrosis and Inflammation Are Enhanced in C-Reactive Protein Transgenic Mice., 12th Medical Research Conference of Department of Medicine (3/2/2007). 2007.

Researcher : Zhang X

List of Research Outputs

Siu C.W., Zhang X., Yung C., Kung A.W.C., Lau C.P. and Tse H.F., Hemodynamic Changes in Hyperthyroidism Related Pulmonary Hypertension: A Prospective Echocardiographic study, The American College of Cardiology 56th annual Scientific Sessions, New Orleans. 2007.

Siu C.W.D., Zhang X., Yung C., Kung A.W.C., Lau C.P. and Tse H.F., Hemodynamic Changes in Hyperthyroidism Related Pulmonary Hypertension: A Prospective Echocardiographic study, J Clin Endocrinol Metab. 2007, 92(5): 1736-42.

Siu D.C.W., Zhang X., Yung C., Kung A.W.C., Lau C.P. and Tse H.F., Hemodynamic changes in hyperthyroidism-related pulmonary hypertension: a prospective echocardiographic study, Journal of Clinical Endocrinology & Metabolism. 2007, 92: 1736-42.

Tse H.F., Kaufman C.L., Bank A.J., Zhang X., Siu C.W., Kaiser D.R. and Lau C.P., Right Ventricular Septal Pacing Upgrade Improves Left Ventricular Performance And Functional Capacity In Patients With Previous Permanent Right Ventricular Apical Pacing Independent Of Ventricular Dyssynchrony , 28th Annual Scientific Sessions of Heart Rhythm Socity, Denver. 2007.

Wang M.M., Lau C.P., Zhang X., Siu C.W., Tang M.O. and Tse H.F., Early Improvement Of Diastolic Dyschrony And Myocardial Relaxation Time After Upgrade Of Longstanding Right Ventricular Apical To Right Ventricular Septal Pacing (Oral presentation) , 28th Annual Scientific Sessions of Heart Rhythm Society, Denver, Colorado, May 9-12 2007.

Zhang X., Chen H., Tsang V.Y.C., Tang M.O., Lau C.P. and Tse H.F., Prevalence And Clinical Predictors For New-onset Heart Failure After Permanent Right Ventricular Apical Pacing In Patients With Aquired High-grade Atrioventricular Block, World Congress of Cardiology 2006, Barcelona. 2006.

Researcher : Zhao Y

Project Title:	Development of an in vitro assay for methylation-dependent genetic mutation based on linking in-frame CGA polynucleotides to the alpha-lacZ reporter gene system
Investigator(s):	Zhao Y, Epstein R
Department:	Medicine
Source(s) of Funding:	Small Project Funding
Start Date:	11/2005

Abstract:

CpG dinucleotides in human DNA can be uniquely modified by cytosine methyltransferases, yielding the 'fifth base' of DNA, 5-methylcytosine (5MC). 5MC residues clustered within CpG islands act as binding sites for linker proteins that recruit histone deacetylases, thus triggering chromatin condensation and transcriptional repression that is epigenetically transmissible via either germline or somatic cells. If the cell tolerates longterm transcriptional repression of such genes, 5MC residues within the coding sequence may persist in the absence of transcription-coupled repair; since oxidant deamination of 5MC yields thymidine (T), CpG methylation predisposes to a ten-fold excess of CG to TA transitional mutations within the coding sequence as a 'marker' or 'fossil' of repressed transcription (Rideout et al, 1990; Soussi, et al, 2003). Yet despite this insight, little is known as to the dynamics and function of CpG sites in the open reading frame of tumor suppressor genes (TSGs, e.g., p53; Rodin et al, 1998). Our recent work has confirmed that the CGA codon specifying arginine is specifically associated with a pronounced mutational asymmetry in TSGs associated with familial cancer syndromes, consistent with the observation that this codon is unique in its ability to undergo a single-base methylation-dependent mutation to a stop codon (viz., CGA  TGA; Table 1). Table 1 Asymmetry pattern of CGN germline mutations in human TSGs Gene CGA CGT CGC CGG TGA CAA TGT CAT TGC CAC TGG CAG APC 125** 0 0 0 1 0 3 0 TP53 10** 0 12 10 38 3 16 17 RB1 126** 0 0 0 0 0 0 0 MLH1 26** 0 0 0 0 0 0 0 VHL 18* 7 0 0 1 0 24 28 ATM 4 0 0 0 4 0 0 2 MSH2 6* 0 0 0 0 0 0 0 ** p < 0.001, p < 0.05, based on binomial distribution.Further evidence for the biological significance of the CGA codon is the finding that it is topographically clustered within TSGs such as p53, unlike other arginine-encoding codons: Table 2 Clustered CGA(CGN) codons in TP53 gene*Codons CGA CGG AGA AGG Codon position 196, 213, 306, 342 248, 267, 282 65, 209, 280 174, 249, 363 Cluster parameter h(2,4,392,18) h(3,3,392,99) h(2,3,392,145) h(2,3,392,76) and p value 0.0110 0.0157 0.2588 0.0904 h(2,4,392,37) h(2,3,392,72) h(2,3,392,114) 0.0432 0.0821 0.1797 h(4,4,392,147) h(3,3,392,216) h(3,3,392,189) 0.0193 0.1663 0.1112 (*Data calculated without assuming a hypergeometric distribution) Such CGA clustering is similarly evident in other TSGs such as RB1 and APC, with the distribution of clusters suggesting a 'mutational splicing' significance (data not shown). Hence, the position of the CGA clusters tends to separate the gene into loss-of-function subunits (e.g., in TP53, the 196/212 and 306/342 CGA clusters demarcate the DNA-binding domain, which also participates in mitochondrial apoptosis). We therefore speculate that CGA clustering represents a methylation-dependent genotype that is evolutionarily advantageous for the species (favouring adaptability) but hazardous for individuals (favouring genetic instability and, hence, loss of TSG function leading to clonal microevolution of cancer).Hence, in this small project application, we seek to explore a new hypothesis: namely, that the unique vulnerability of CGA codons to methylation-dependent nonsense (TGA) mutation can be exploited (i) to form the basis for a mutational assay based on the well-known alpha-lacZ reporter gene system used to investigate cancer and ageing in transgenic mouse models, and thus (ii) to clarify the oncogenetic role of CGA. The objectives of this funding application are:1. To exploit the foregoing insights regarding the CGA codon to develop a useful, and potentially patentable, in vitro assay system for methylation-dependent mutation;2. To exemplify the assay using conditions that will putatively favour or inhibit DNA methylation, forming the basis of a peer-reviewed publication in the epigenetic field;3. To use this assay (+/- patent) and submission/publication to compete for a 2006 RGC grant in which we will propose to develop an in vivo CGA-LacZ-based transgenic mouse model system of methylation-dependent mutation and/or ageing;4. To permit continuation of the laboratory programme over the next 12 months while awaiting publication of manuscripts to support external funding applications in 2006.References1. Soussi T, Beroud C. (2003) Significance of TP53 mutations in human cancer: a critical analysis of mutations at CpG dinucleotides. Hum Mutat. 21(3):192-200. 2. Rideout WM 3rd, Coetzee GA, Olumi AF, Jones PA.(1990) 5-Methylcytosine as an endogenous mutagen in the human LDL receptor and p53 genes. Science. 249(4974):1288-90. 3. Rodin SN, Rodin AS.(1998) Strand asymmetry of CpG transitions as indicator of G1 phase-dependent origin of multiple p53 mutations in stem cells. Proc Natl Acad Sci U S A. 95(20):11927-32.

List of Research Outputs

Tang S.M., Zhao Y., Smith D.K. and Epstein R., Intron length and accelerated 3' gene evolution., Genomics. 2006, 88: 682-89.

Researcher : Zheng G

List of Research Outputs

Wang W.H., Huang J., Zheng G., Xia H.H.X., Wong R.W.M., Liu X.G., Karlberg J.P.E. and Wong B.C.Y., Effects of proton-pump inhibitors on function dyspepsia: A meta-analysis of randomized placebo-controlled trails, Clinical Gastroenterology & Hepatology. 2007, 5(2): 178-185.

Researcher : Zhou H

List of Research Outputs

Zhou H., Shiu S.W.M., Wong Y. and Tan K.C.B., Impaired serum cholesterol efflux potential is associated with endothelial dysfunction in type 2 diabetes patients, Fourth International Huaxia congress of Endocrinology, Hong Kong, Dec 2006.

Researcher : Zhou L

List of Research Outputs

Zhou L., Fu P., Lan X.R. and Lan H.Y., Aristolochic Acid Induces Renal Tubular Epithelial Cell Apoptosis Via the P53 Pathway, Fifth Meeting of Consortium for Globalization of Chinese Medicine (Zhuhai, 20-23/9/2006). 2006.

Researcher : Zhu S

List of Research Outputs

Tse H.F., Siu C.W.D., Zhu S., Liao S., Zhang Q.Y., Lai K.W.H., Nicholls J.M. and Tse H.F., Paracrine effects of direct intramyocardial implantation of bone marrow derived cells for enhancement of neovascularization in chronic ischemic myocardium, European Journal Heart Fail. 2007, 9(8): 747-53.

Researcher : Zhuang Z

List of Research Outputs

Wang J., Yang Y., Xia H.H.X., Gu Q., Lin M.C., Jiang B., Peng Y., Li G., An X., Zhang Y., Zhuang Z., Zhang Z., Kung H.F. and Wong B.C.Y., Suppression of FHL2 Expression Induces Cell Differentiation and Inhibits Gastric and Colon Carcinogenesis , Gastroenterology. 2007, 132: 1066-1076.

Researcher : Zou B

List of Research Outputs

Dai Y., Qiao L., Gu Q., Xia H.H.X., Cheung T.K., Ma J., Zou B. and Wong B.C.Y., Activation of Pparc and inhibition of Xiap in human cancer cells: Synergistic effects on cell proliferation, apoptosis, and tumorigensis. Digestive Disease Week 2007, Washington DC, USA, 19-24 May, Gastroenterology. 2007, 132(4) Suppl 2: A425.

Yu L., Wang J., Zou B., Lin M.C., Wu Y.L., Xia H.H.X., Sun Y., Gu Q., He H., Lam S.K., Kung H.F. and Wong B.C.Y., XAF1 Mediates Apoptosis Through an Extracellular Signal-Regulated Kinase Pathway in Colon Cancer , Cancer. 2007, 109(10): 1996-2003.

Zou B., Chim J.C.S., Zeng H., Leung S.Y., Yang Y., Tu S., Lin M.C., Wang J., He H., Jiang S.H., Sun Y., Yu L., Yuen S.T., Kung H.F. and Wong B.C.Y., Correlation Between the Single-site CpG Methylation and Expression Silencing of the XAF1 Gene in Human Gastric and Colon Cancers, Gastroenterology. 2006, 131(6): 1835-1843.

Researcher : Zou L

List of Research Outputs

Cheung R.T.F., Tipoe G.L., Tam S., Ma E.S.K., Zou L. and Chan P.S., Preclinical evaluation of pharmacokinetics and safety of melatonin in propylene glycol for intravenous administration, Journal of Pineal Research. 2006, 41: 337-343.

Zou L., Cheung R.T.F., Liu S.R., Li G. and Huang L., Melatonin reduces infarction volume in a photothrombotic stroke model in the wild-type but not cyclooxygenase-1-gene knockout mice, Journal of Pineal Research. 2006, 41: 150-156.

Researcher : Zou L

List of Research Outputs

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