Dept of Paediatrics & Adolescent Med

DEPT OF PAEDIATRICS & ADOLESCENT MED

Researcher : Bhatia I

List of Research Outputs

Wang Y., Cheung P.T., Shen G.X., Wu E.X., Qiu D., Khong P.L. and Bhatia I., Comparing diffusion-weighted and T2-weighted MR imaging for the quantification of infarct size in a neonatal rat hypoxic-ischemic model at 24 h post-injury, International Journal of Developmental Neuroscience. Elsevier, 2007, 25: 1-5.

Researcher : Chan GCF

Project Title:	Review of local experience in the management of childhood myelodysplastic syndrome
Investigator(s):	Chan GCF
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Other Funding Scheme
Start Date:	01/2001

Abstract:

To study the local incidence and outcome of this rare type of childhood maliquancy.

Project Title:	Treatment protocol for childhood medulloblastoma in Hong Kong
Investigator(s):	Chan GCF
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Other Funding Scheme
Start Date:	01/2001

Abstract:

To study the treatment outcome of this most common form of childhood brain tumour in Hong Kong.

Project Title:	Survey on the prevalence on use of alternative medical treatment in paediatric patients
Investigator(s):	Chan GCF
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Other Funding Scheme
Start Date:	09/2001

Abstract:

To study the prevalence, pattern of usage and the underlying predisposing factors on the use of alternative medicine in children.

Project Title:	Direct generation and functional characterization of human dendritic cells derived from bone marrow cells of leukemic origins
Investigator(s):	Chan GCF, Chiu CSW, Ma ESK, Huang F
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Other Funding Scheme
Start Date:	07/2002

Abstract:

To determine the implication of dentritic cells generated from leukaemic cellls on the host immune system.

Project Title:	Health-related quality of life measures for Hong Kong Chinese children with cancer
Investigator(s):	Chan GCF, Fielding R, Lam WWT, Ng MW
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Health and Health Services Research Fund - Full Grants
Start Date:	01/2005

Abstract:

Children under age 5 constiture >50% of new paediatric cancer cases. HRQoL impacts on these children are currently arbitrarily assessed (in HK) or use proxy measures which lack reliability and are subject to significant bias. A tool measuring changes in HRQoL would be of great value to paediatric oncologists to better and more consistently address HRQoL impacts, facilitating optimized paediatric cancer care. Such a tool is currently lacking and is badly needed

Project Title:	Influence of MYCN amplification on the response of neuroblastoma to arsenic trioxide (As₂O₃) in-vitro and in-vivo
Investigator(s):	Chan GCF
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	09/2005

Abstract:

To find out whether As₂O₃ can induce apoption on both MYCN amplified and non-amplified neuroblastoma cells; to identify the in reinstance pattern to As₂O₃ and replace whether resistant clones may generate faster from neuroblastoma cells with MYCN amplification; to established a dose limiting toxicity profile of As₂O₃ in vivo and study the toxicity, bio-availability and bio-distribution of arsenical compounds.

Project Title:	Comparing the effect of different purified beta-glucans on the maturation and function of human dendritic cells (DC) in vitro
Investigator(s):	Chan GCF
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	12/2005

Abstract:

We will investigate and compare the effect of different beta-glucans on human immune cells in particularly on the dendritic cells (DC) in vitro.

Project Title:	Exploring the mechanisms of microtubules toxins on human mesenchymal stem cells
Investigator(s):	Chan GCF
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	12/2006

Abstract:

We previously identified that human mesenchymal stem cells (MSC) are resistant to most chemotherapy tested but are particularly sensitive to microtubule toxins such as vincristine and paclitaxel (Li J, Chan GCF. 2004). We would like to explore this peculiar sensitivity pattern by looking at some of the possible mechanisms involved in this project. This can potentially help us to develop protective measure for the MSC during chemotherapy.

List of Research Outputs

Chan B.P., Cheung K.M.C., Chan G.C.F., Chan D. and Hui T.Y., Bioengineered intervertebral disc and Methods for Their Preparation., US Regular Patent Application No. 11/742,040 (filed on 30 April 2007). 2007.

Chan B.P., Chan G.C.F., Wong H.L., Cheung P.T., Cheah K.S.E. and Chan D., Cell-Matrix Microsphere, Associated Products, Methods for Preparation and Applications., US Regular Patent Application No. 11/750,863 (filed on 18 May 2007). 2007.

Chan B.P. and Chan G.C.F., Self-Assembled Collagen-Human mesenchymal stem cell (hMSCs) microspheres – novel bio-devices for cell delivery, International Society for Stem Cell Research 5th Annual Meeting. Jun 15-21 2007. Cairns, Queensland, Australia. 2007, p59.

Chan G.C.F., Management of the Pediatric Peripheral Solid Tumors: The Hong Kong Experience, 第二屆海峽兩岸兒童腫瘤研討會議, 台灣, 22-23 September 2006, 2006.

Chan G.C.F., Management of the Pediatric Peripheral Solid Tumours: The Hong Kong Experience, Second Cross Strait Symposium on Pediatric Oncology, Taiwan, 21-23 September 2006.

Chan G.C.F., Oral manifestations of children with acquired or congenital immunodeficiency, The 21^st Congress of International Association of Paediatric Dentistry (IAPD), 13-17 June 2007.

Chan G.C.F., Overview of Treatment of Childhood Cancers in Hong Kong, Hong Kong Paediatric Haematology & Oncology Study Group, Hong Kong, 3 March 2007. 2007.

Chan G.C.F., Chairperson for "第六節: 腎母細胞癗/橫紋肌肉瘤", Second Cross Strait Symposium on Pediatric Oncology, Taiwan, 21-23 September 2006. 2006.

Chan G.C.F., The clinical application of advanced genetic knowledge in chemotherapies, Pharmacogenomics & Pharmacogenetics in Paediatric Therapies. Organized by Hong Kong College of Paediatricians, Hong Kong, 6 May 2007.

Chan G.C.F., Update on the Management of Infantile Haemangiomas, The Hong Kong Medical Diary. 2007, 12(3): 8-10.

Chan W.K. and Chan G.C.F., Human Monocytic Leukemia Cells can be Differentiated to Immunoregulatory Dendritic Cells by Medicinal Mushroom Polysaccharides, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006.

Cheuk D.K.L., Lee T.L., Chiang A.K.S., Ha S.Y. and Chan G.C.F., Autologous Haematopoietic Stem Cell Transplantation for High Risk Brain Tumours in Children, 13^th Hong Kong International Cancer Congress, 3^rd Annual Meeting Centre for Cancer Research, HKU, 15-17 November 2006.

Cheuk D.K.L., Shek T.W.H., Chan G.C.F., Lau Y.L., Ha S.Y. and Chiang A.K.S., Parotid Acinic Cell Carcinoma in a Long-Term Survivor of Childhood Acute Lymphoblastic Leukemia, Pediatric Blood Cancer. 2006-7-1, InterScience, 2006, 24: 1-4.

Cheuk D.K.L., Lee T.L., Chiang A.K.S., Ha S.Y., Lau Y.L. and Chan G.C.F., Risk factors and treatment of hemorrhagic cystitis in children who underwent hematopoietic stem cell transplantation, Transplant International. 2007, 20: 73-81.

Cheung Y.F., Chow P.C., Chan G.C.F. and Ha S.Y., Carotid Intima-Media Thickness is Increased and Related to Arterial Stiffening in Patients With Beta-Thalassaemia Major, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 125.

Cheung Y.F., Chow P.C., Chan G.C.F. and Ha S.Y., Carotid intima-media thickness is increased and related to arterial stiffening in patients with beta-thalassaemia major, British Journal of Haematology. Blackwell Publishing Ltd, 2006, 135: 732-734.

Chiang A.K.S., Yuan X., Chan G.C.F., Kwong D.L.W., Chan T. and Ha S.Y., Treatment Outcome of Rhabdomyosarcoma in Hong Kong Chinese Children, 13^th Hong Kong International Cancer Congress, 3^rd Annual Meeting Centre for Cancer Research, HKU, 15-17 November 2006.

Chung B.H.Y., Lee T.L., Chan G.C.F., Chiang A.K.S., Chan K.W., Ha S.Y. and Lau Y.L., Haematopoietic stem cell transplant for Wiskott-Aldrich Syndrome, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 186-190.

Chung B.H.Y., Lee T.L., Chan G.C.F., Chiang A.K.S., Chan K.W., Ha S.Y. and Lau Y.L., Haematopoietic stem cell transplant for Wiskott-Aldrich syndrome, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 109.

Hui T.Y., Chan D., Cheung K.M.C., Chan G.C.F., Cheung W.L. and Chan B.P., Chondrogenic differentiation of human mesenchymal stem cells in three-dimensional collagen/chondroitin-6-sulfate gels: Influences of cell seeding density and collagen concentration, International Society for Stem Cell Research 5th Annual Meeting. Jun 15-21 2007. Cairns, Queensland, Australia. 2007, p155.

Lee T.L., Ho M.H.K., Ha S.Y., Chan G.C.F. and Lau Y.L., Autologous haemopoietic stem cell transplantation for severe autoimmune diseases in Hong Kong, 2nd Congress of Asian Society for Pediatric Research, Yokohama, Japan, 8-10 December 2006.

Lee T.L., Law H.K.W., Chan G.C.F., Ha S.Y., Ho M.H.K., Chan K.W. and Lau Y.L., Successful treatment of X-linked lymphoproliferative disease (XLP) with anti-CD20 monoclonal antibody (Rituximab) followed by Mismatched unrelated cord blood transfusion, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 210-214.

Li J., Kwong D.L.W. and Chan G.C.F., The effects of various irradiation doses on the growth and differentiation of marrow deerived human mesenchymal stromal cells, The 11^th Congress of the Asia Pacific Bone Marrow Transplantation (oral presentation), Nagoya, Japan, 27-29 October 2006.

Li J., Kwong D.L.W. and Chan G.C.F., The effects of various irradiation doses on the growth and differentiation of marrow-derived human mesenchymal stromal cells, Pediatric Transplantation. Blackwell Munksgaard, 2007, 11: 379-387.

Mo F.Y., Yip H.K., Law H.K.W., Lau Y.L. and Chan G.C.F., Effects of bacterial toxins on the growth, differentiation and toll-like receptor genes of human mesenchymal stem cells, Cytokine 2006. 17: 120.

Qiu D., Kwong D.L.W., Chan G.C.F., Leung L.H.T. and Khong P.L., Diffusion tensor MR imaging finding of discrepant fractional anisotropy between the frontal and parietal lobes after whole-brain irradiation in childhood medulloblastoma survivors: reflection of regional white matter radiosensitivity? , Internal Journal of Radiation Oncology Biology Physics. 2007, 69: 846-851.

Yang M., Cheung Y.F., Chan S. and Chan G.C.F., Tpo Has A Protective Effect On Iron-induced Apoptosis In Cardiomyocytes, Cytotherapy/international Society For Cellular Therapy Annual Meeting. 2007, 9: 76.

Researcher : Chan KW

List of Research Outputs

Chan K.W., Fong S.W., Mak H.S. and Chan S.Y., Expression of Tspyl2 in Transgenic Mice Reduces Cardiac Hypertrophy upon Hypertrophic Stress, 11^th Research Postgraduate Symposium, HKU, 7 December 2006. 169.

Chung B.H.Y., Lee T.L., Chan G.C.F., Chiang A.K.S., Chan K.W., Ha S.Y. and Lau Y.L., Haematopoietic stem cell transplant for Wiskott-Aldrich Syndrome, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 186-190.

Chung B.H.Y., Lee T.L., Chan G.C.F., Chiang A.K.S., Chan K.W., Ha S.Y. and Lau Y.L., Haematopoietic stem cell transplant for Wiskott-Aldrich syndrome, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 109.

Kwok H., Woo G.K.S., Chan K.W. and Chiang A.K.S., Characterization of Epstein-Barr Virus (EBV) Strains in Childhood Infectious Mononucleosis, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006. 72.

Kwok H., Woo G.K.S., Chan K.W. and Chiang A.K.S., Study of Epstein-Barr Virus (EBV) strains in childhood infectious mononucleosis, The Hong Kong Pediatric Society and Hong Kong Paediatric Nurses Association Ltd. - A Joint Annual Scientific Meeting for Paediatricians and Paediatric Nurses, QEH, Hong Kong, 25 November 2006. 40.

Lee P.P.W., Chan K.W., Lee T.L., Jiang L., Mak H.S., Fok S.F.S. and Lau Y.L., Clinical Characteristics and gp91phox Gene Mutations in Seventeen Chinese Children with X-linked Chronic Granulomatous Disease (Young Investigator Award), 2nd Congress of Asian Society for Pediatric Research. 2006.

Lee P.P.W., Chan K.W., Lee T.L., Jiang L., Mak H.S., Fok S.F.S., Hui Y.F., Li C., Yang X. and Lau Y.L., Clinical Characteristics and gp91phox Gene Mutations in Seventeen Chinese Children with X-linked Chronic Granulomatous Disease, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 96.

Lee P.P.W., Jiang L.P., Wang X.C., Chan K.W., Tu W. and Lau Y.L., Severe mycobacterial infections in two pairs of Chinese siblings with interleukin-12 receptor b1 deficiency, European Journal of Pediatrics. 2007-6-30, Springer-Verlag, 2007.

Lee P.P.W., Chan K.W., Tu W. and Lau Y.L., Severe mycobacterial infections in two pairs of Chinese siblings with interleukin-12 receptor 1 deficiency., Asia Pacific Primary Immune Deficiency (APPID) Summer School, 6-11th May 2007, Queensland, Australia. 2007.

Lee T.L., Chan K.W. and Lau Y.L., An 8-year-old girl with urticaria since birth, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 233-234.

Lee T.L., Law H.K.W., Chan G.C.F., Ha S.Y., Ho M.H.K., Chan K.W. and Lau Y.L., Successful treatment of X-linked lymphoproliferative disease (XLP) with anti-CD20 monoclonal antibody (Rituximab) followed by Mismatched unrelated cord blood transfusion, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 210-214.

Researcher : Chan KW

List of Research Outputs

Lee T.L., Chan K.W. and Lau Y.L., An 8-year-old girl with urticaria since birth, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 233-234.

Researcher : Chan S

List of Research Outputs

Yang M., Cheung Y.F., Chan S. and Chan G.C.F., Tpo Has A Protective Effect On Iron-induced Apoptosis In Cardiomyocytes, Cytotherapy/international Society For Cellular Therapy Annual Meeting. 2007, 9: 76.

Researcher : Chan SY

Project Title:	Functional studies of the role of NAP79 in the development of the heart
Investigator(s):	Chan SY, Zhang JCL
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	09/2003

Abstract:

To test the function of NAP79 in heart development by the generation of null-mutant mice. The focus of the phenotype analysis will be on cardiomyocyte proliferation and terminal differentitation.

Project Title:	Expression and function of NAP79 during brain development.
Investigator(s):	Chan SY, Yick LW
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2005

Abstract:

Background: Our group has identified a novel 79 kDa nucleosome assembly protein, NAP79, from human heart cDNAs. We have generated transgenic lines of mice expressing human NAP79 in the heart and brain. Nucleosome assembly proteins (NAPs) deposit histones onto DNA, which is important in nucleosome remodelling during DNA replication and gene transcription, and in controlling mitotic events. A role of NAPs in inhibiting cell proliferation is demonstrated by the inactivation of NAP1-like-2 in mice, which leads to an opened neural tube, and exposed brain. These defects are associated with overproduction of neuronal precursor cells. A few months ago, NAP79 is found to form a complex with CASK and Tbr-1 to modulate the expression of NMDA receptor subunit 2B (NR2b) in cultured hippocampal neurons. NAP79 encodes a novel protein containing a conserved NAP domain, potential phosphorylation sites for casein kinase II, cyclin-dependent kinases, and cAMP- and cGMP-dependent kinases. During postnatal development, we have found that NAP79 expression in cardiomyocytes changes as they exit from the cell cycle. Furthermore, NAP79 arrests cell proliferation when transfected into HeLa cells or yeast. These data suggest that NAP79 plays a role in regulating the proliferation and differentiation of cardiomyocytes. Also, our northern and western blot data has shown that NAP79 is highly expressed in the adult brain but not in other organs. Like the heart, the adult brain consists mostly of non-dividing post-mitotic cells. Objectives: We hypothesize that (1) NAP79 is essential for switching off cell proliferation during brain development; and/or (2) NAP79 controls brain function through controlling the expression of specific target genes. In this proposal we seek to investigate the expression and function of NAP79 during the development of the mammalian central nervous system (CNS). We shall also characterize the cell types expressing human NAP79 in the transgenic mouse brain. For elucidation of gene function, phenotype analysis of the NAP79 transgenic animals including expression of target genes (eg. NR2b), behavioural, learning and memory test will form the basis of a new RGC proposal.

Project Title:	Characterisation of NAP79 transgenic mice
Investigator(s):	Chan SY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	11/2006

Abstract:

Objective: To determine the function of NAP79 in cardiomyocyte proliferation by analysing transgenic mice with prolonged expression of NAP79. Key issues and problems being addressed: Our group has identified a novel 79 kDa nucleosome assembly protein, NAP79, from human heart cDNAs [1]. Nucleosome assembly proteins (NAPs) deposit histones onto DNA, which is important in nucleosome remodelling during DNA replication and gene transcription, and in controlling mitotic events. In mice, we found that Nap79 transcripts are mainly expressed in the neonatal heart and brain. We have raised antibodies against NAP79 and found that the cardiac expression of NAP79 decreases dramatically during the neonatal period. This is of great interest since cardiomyocytes permanently withdraw from the cell cycle within the first 2 weeks in mice and within 3-6 months in humans, and so the number of proliferating cardiomyocytes gradually decline during these periods. Is NAP79 expressed only in proliferating cardiomyocytes and switched off once the cells exit the cell cycle? Our preliminary experiments to knock down Nap79 expression by siRNA in the myoblast cell line C2C12 have shown an effect on the rate of cell proliferation and the cells can no longer undergo terminal differentiation. Based on its domain structure, expression pattern and the effect of siRNA, we hypothesize that NAP79 plays a role in regulating the proliferation/ terminal differentiation of cardiomyocytes. There are two possible mechanisms of how NAP79 may fuction in controlling cardiomyocyte proliferation: 1. Expression of NAP79 is required to keep cardiomyocyte in the cell cycle. 2. The peak cardiac expression of NAP79 during the neonatal period is a signal for cell cycle exit/ terminal differentiation. If the first situation is correct, then prolonging the expression of NAP79 may delay cell cycle exit of cardiomyocytes. By contrast, increasing the level of NAP79 may cause earlier exit of cardiomyocytes from the cell cycle if the second mechanism is correct. To test our hypothesis, we have generated transgenic mice with a HA-tagged human NAP79 cDNA driven by cardiomyocyte specific promoters. This can both increase and prolong the cardiac expression of NAP79. We have obtained two transgenic lines which express the transgene as measured by RT-PCR in the neonatal and adult heart samples. Given the complex nature of cell cycle control in vivo, it is not surprising that our transgenic mice do not show an overt change in heart to body weight ratio. As in other reports on transgenic mice of cell cycle regulators (eg. cyclin D1, D2 and A2), expression of positive cell cycle regulators or even mitosis may be increased in the postnatal myocardium. This proposal aims at analysing cardiomyocyte proliferation in the neonatal period of our transgenic animals. We shall perform immunostaining and analyse the percentage of proliferating cardiomyocytes at around day 2 and day 10 after birth. Reference: 1. Sun G et al. Isolation of differentially expressed genes in human heart tissues (2002) Biochimica et Biophysica Acta - Mechanisms of disease 1588, 241 -246.

List of Research Outputs

Chan K.W., Fong S.W., Mak H.S. and Chan S.Y., Expression of Tspyl2 in Transgenic Mice Reduces Cardiac Hypertrophy upon Hypertrophic Stress, 11^th Research Postgraduate Symposium, HKU, 7 December 2006. 169.

Chan S.Y., Adjudicator, 11^th Research Postgraduate Symposium, HKU, 7 December 2006. 2006.

Chan S.Y., Organizing Committee Member 2007-2008, Frontiers in Biomedical Research, HKU, Decembeer 2007. 2007.

Chan S.Y., Organizing Committee Member , Frontiers in Biomedical Research, HKU, 2006. 2006.

Yip K.Y. and Chan S.Y., Functional Characterization of a Neonatal Heart Expressing-Protein - Analysis of the Protein-interacting Partners of TSPYL-2, Joint Meeting of the Japanese Society of Developmental Biologists & the Japan Society for Cell Biology, Fukuoka, Japan, 28-30 May 2007.

Yip K.Y. and Chan S.Y., Functional Characterization of a Neonatal Heart Expressing-protein - Analysis of the Protein-interacting Partners of TSPYL-2, 11^th Research Postgraduate Symposium, HKU, 7 December 2006.

Researcher : Chan WK

List of Research Outputs

Chan W.K. and Chan G.C.F., Human Monocytic Leukemia Cells can be Differentiated to Immunoregulatory Dendritic Cells by Medicinal Mushroom Polysaccharides, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006.

Researcher : Chau AKT

List of Research Outputs

Chan S.Y., Lau W.Y., Wong W.H.S., Cheng L.C., Chau A.K.T. and Cheung Y.F., Chylothorax in Children After Congenital Heart Surgery, Annals of Thoracic Surgery. Elsevier Inc, 2006, 82: 1650-1657.

Chow P.C., Cheung E.W.Y., Chong` C.Y., Lun K.S., Yung T.C., Wong K.T., Chau A.K.T. and Cheung Y.F., Brain Natriuretic Peptide as a Biomarker of Systemic Right Ventricular Function in Patients After Atrial Switch Operation, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 126.

Chow P.C., Liang X., Cheung E.W.Y., Wong K.T., Lun K.S., Yung T.C., Chau A.K.T. and Cheung Y.F., Right Ventricular Dyssynchrony in Patients After Atrial Switch Operation for Transposition of the Great Arteries, Hong Kong College of Cardiology, Fifteenth Annual Scientific Congress Proceedings (Free Paper Session, Paediatric Cardiology I), Hong Kong, 4-6 May 2007. 15: 58.

Liang X., Cheung E.W.Y., Wong S.J., Chau A.K.T. and Cheung Y.F., Restrictive Right Ventricular Physiology after Biventricular Repair of Pulmonary Atresia with Intact Ventricular Septum, Hong Kong College of Cardioloyg, Fifteenth Annual Scientific Congress Proceedings (Free Paper Session, Paediatric Cardiology I), Hong Kong, 4-6 May 2007. 15: 58.

Researcher : Cheng M

Project Title:	The role of pro-inflammatory cytokines in matrix metalloproteinase (MMP) expression
Investigator(s):	Cheng M, Lau ASY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	10/2005
Completion Date:	09/2006

Abstract:

Objectives: 1. To characterize matrix metalloproteinases (MMPs) expression of tumor cell lines in response to various cytokines 2. To understand the effects of cytokine interactions on MMPs expression and tumor cell invasion Background and Significance: Matrix metalloproteinases (MMPs) (1) have gained considerable attention in cancer research due to their capabilities of degrading the ECM and thus facilitating tumor cell invasion (2). As excess MMPs production and activation have been implicated to play pathological roles in a variety of disease processes, including rheumatoid arthritis, atherosclerosis, and tumor invasion or metastasis (3-5), strict regulation of MMPs expression is therefore critical in maintaining the proper ECM homeostasis. Various tissue derived factors including cytokines have been implicated to play a role in the regulatory process. Cytokine including interferon (IFN) and tumor necrosis factor (TNF) are signaling molecules that are released in response to a diverse range of cellular stresses, including inflammation, infection, and immunity (6). Previous reports including ours have demonstrated that TNF functions as a tumor suppressor and an inducer of apoptosis (7, 8). Recently, several lines of evidence suggested that cytokines produced by infiltrating leukocytes can modulate tumor cells to produce more MMPs (9, 10). In addition, a growing evidence in clinical data suggested a correlation between leukocyte infiltration with poor outcome (11, 12) and cancer dissemination (13, 14). These observations suggested the possibility that host-derived cytokines may facilitate invasion and metastasis. Is it possible that the interaction of pro-inflammatory cytokines, produced in the tumor microenvironment, has an important role in cancer dissemination? If so, can therapies that are directed at reducing or inhibiting the function of inflammatory cytokines in attempts to reduce tumor cell invasion? Here, we hypothesize that (i) cytokines present in the microenvironment can facilitate the spread of tumor cells by induction of different MMPs. (ii) Therapeutic manipulations that are aimed to attenuate excessive cytokine action which might reduce the rate of tumor cell invasion. In delineating the interactions of this proteolytic system (i.e. MMP) and cytokines, we will gain better insights into the cause of cancer cell metastasis. In addition, the results can help us to clarify whether cytokine-mediated MMP-inhibition can be a part of future strategies against cancer invasion. References: 1. Brinckerhoff, C. E., and L. M. Matrisian. 2002. Matrix metalloproteinases: a tail of a frog that became a prince. Nat Rev Mol Cell Biol 3:207. 2. Friedl, P., and K. Wolf. 2003. Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer 3:362. 3. Ye, S., P. Eriksson, A. Hamsten, M. Kurkinen, S. E. Humphries, and A. M. Henney. 1996. Progression of coronary atherosclerosis is associated with a common genetic variant of the human stromelysin-1 promoter which results in reduced gene expression. J Biol Chem 271:13055. 4. Dayer, J. M., R. Graham, G. Russell, and S. M. Krane. 1977. Collagenase production by rheumatoid synovial cells: stimulation by a human lymphocyte factor. Science 195:181. 5. Lynch, C. C., and L. M. Matrisian. 2002. Matrix metalloproteinases in tumor-host cell communication. Differentiation 70:561. 6. Balkwill, F. R., and F. Burke. 1989. The cytokine network. Immunol Today 10:299. 7. Yeung, M. C., J. Liu, and A. S. Lau. 1996. An essential role for the interferon-inducible, double-stranded RNA-activated protein kinase PKR in the tumor necrosis factor-induced apoptosis in U937 cells. Proc Natl Acad Sci U S A 93:12451. 8. Clemens, M. J., and U. A. Bommer. 1999. Translational control: the cancer connection. Int J Biochem Cell Biol 31:1. 9. Warner, R. L., N. Bhagavathula, K. C. Nerusu, H. Lateef, E. Younkin, K. J. Johnson, and J. Varani. 2004. Matrix metalloproteinases in acute inflammation: induction of MMP-3 and MMP-9 in fibroblasts and epithelial cells following exposure to pro-inflammatory mediators in vitro. Exp Mol Pathol 76:189. 10. Witek-Zawada, B., and A. Koj. 2003. Regulation of expression of stromyelysin-1 by proinflammatory cytokines in mouse brain astrocytes. J Physiol Pharmacol 54:489. 11. Coussens, L. M., and Z. Werb. 2001. Inflammatory cells and cancer: think different! J Exp Med 193:F23. 12. Coussens, L. M., and Z. Werb. 2002. Inflammation and cancer. Nature 420:860. 13. Perissinotto, E., G. Cavalloni, F. Leone, V. Fonsato, S. Mitola, G. Grignani, N. Surrenti, D. Sangiolo, F. Bussolino, W. Piacibello, and M. Aglietta. 2005. Involvement of chemokine receptor 4/stromal cell-derived factor 1 system during osteosarcoma tumor progression. Clin Cancer Res 11:490. 14. Prime, S. S., J. W. Eveson, A. M. Stone, S. P. Huntley, M. Davies, I. C. Paterson, and C. M. Robinson. 2004. Metastatic dissemination of human malignant oral keratinocyte cell lines following orthotopic transplantation reflects response to TGF-beta 1. J Pathol 203:927. 15. Li, J. C., D. C. Lee, B. K. Cheung, and A. S. Lau. 2005. Mechanisms for HIV Tat upregulation of IL-10 and other cytokine expression: kinase signaling and PKR-mediated immune response. FEBS Lett 579:3055.

List of Research Outputs

Cheng M., Xing B., Cheung B.K.W. and Li C.B., IFNg Inhibition of TNFa-enhanced Glioma Cell Invasion, 6th International Cytokine Conference Proceedings, Medimond International Proceedings, Bologna, Italy, 27-31 August 2006. 35-39.

Cheng M., Xing B., Cheung B.K.W., Li C.B. and Lau A.S.Y., IFNg regulation of TNF a-enhanced glioma cell migration through induction of matrix metalloproteinase expression, The 6th International Cytokine Conference 2006 (European Cytokine Network, Supplement Aug 2006, Vol 17 - as official journal of Cytokine 2006-Vienna), Vienna, Austria, 27-31 August 2006. 17: 02-21/P.

Cheng M., Xing B., Li C.B., Cheung B.K.W. and Lau A.S.Y., Interferon-gamma regulation of TNFalpha-induced matrix metalloproteinase 3 expression and migration of human glioma T98G cells, International Journal of Cancer. 2007, 121: 1190-1196.

Lau A.S.Y., Cheng M., Lin S.S. and Li C.B., Mechanism of HIV dysregulation of the interferon-gamma signal transduction: a role for transactivator tat in suppression of Jak/STAT pathways, 8th World Congress on Inflammation, Copenhagen, Bella Center, Copenhagen, Denmark, June 16-20. 2007.

Researcher : Cheuk DKL

List of Research Outputs

Cheuk D.K.L. and Wong V.C.N., Attention-deficit hyperactivity disorder and blood mercury level: a case-control study in Chinese children, Neuropediatrics. 2006, 37(4): 234-240.

Cheuk D.K.L., Lee T.L., Chiang A.K.S., Ha S.Y. and Chan G.C.F., Autologous Haematopoietic Stem Cell Transplantation for High Risk Brain Tumours in Children, 13^th Hong Kong International Cancer Congress, 3^rd Annual Meeting Centre for Cancer Research, HKU, 15-17 November 2006.

Cheuk D.K.L., Li Y.H. and Wong V.C.N., Exon 3 Polymorphisms of Dopamine D4 Receptor (DRD4) Gene and Attention Deficit Hyperactivity Disorder in Chinese Children, American Journal of Medical Genetics Part B (Neuropsychiatric Genetics). 2006, 141B: 907-911.

Cheuk D.K.L. and Wong V.C.N., Meta-analysis of association between a Catechol-O-Methyltransferase gene polymorphism and attention deficit hyperactivity disorder, Behavior Genetics. 2006, 36(5): 651-659.

Cheuk D.K.L., Shek T.W.H., Chan G.C.F., Lau Y.L., Ha S.Y. and Chiang A.K.S., Parotid Acinic Cell Carcinoma in a Long-Term Survivor of Childhood Acute Lymphoblastic Leukemia, Pediatric Blood Cancer. 2006-7-1, InterScience, 2006, 24: 1-4.

Cheuk D.K.L., Lee T.L., Chiang A.K.S., Ha S.Y., Lau Y.L. and Chan G.C.F., Risk factors and treatment of hemorrhagic cystitis in children who underwent hematopoietic stem cell transplantation, Transplant International. 2007, 20: 73-81.

Cheuk D.K.L., Wong V.C.N., Wraige E., Baxter P., Cole A., N'Diaye T. and Mayowe V., Surgery for scoliosis in Duchenne muscular dystrophy (Review), Cochrane Database of Systematic Reviews. 2007, 1: CD005373.

Xu Z.F., Xu Z.F., Cheuk D.K.L. and Lee S.L., Clinical Evaluation in Predicting Childhood Obstructive Sleep Apnea, Chest. 2006, 130(6): 1765-1771.

Researcher : Cheung BKW

List of Research Outputs

Cheng M., Xing B., Cheung B.K.W. and Li C.B., IFNg Inhibition of TNFa-enhanced Glioma Cell Invasion, 6th International Cytokine Conference Proceedings, Medimond International Proceedings, Bologna, Italy, 27-31 August 2006. 35-39.

Cheng M., Xing B., Cheung B.K.W., Li C.B. and Lau A.S.Y., IFNg regulation of TNF a-enhanced glioma cell migration through induction of matrix metalloproteinase expression, The 6th International Cytokine Conference 2006 (European Cytokine Network, Supplement Aug 2006, Vol 17 - as official journal of Cytokine 2006-Vienna), Vienna, Austria, 27-31 August 2006. 17: 02-21/P.

Cheng M., Xing B., Li C.B., Cheung B.K.W. and Lau A.S.Y., Interferon-gamma regulation of TNFalpha-induced matrix metalloproteinase 3 expression and migration of human glioma T98G cells, International Journal of Cancer. 2007, 121: 1190-1196.

Cheung B.K.W., Law H.Y. and Lau A.S.Y., Identification of a Viral Gene Responsible for SARS-Coronavirus-induced Chemokine Dysregulation, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006. 145.

Law H.Y., Lee D.C.W., Cheung B.K.W., Yim H.C.H. and Lau A.S.Y., Role for Nonstructural Protein 1 of Service Acute Respiratory Syndrome Coronavirus in Chemokine Dysregulation, Journal of Virology. 2007, 81(1): 416-422.

Researcher : Cheung EWY

List of Research Outputs

Cheung E.W.Y., Lam W.W.M., Cheung S.C.W. and Cheung Y.F., Functional Implications of the Right Ventricular Myocardial Performance Index in Patients After Surgical Repair of Tetralogy of Fallot, Hong Kong College of Cardioloyg, Fifteenth Annual Scientific Congress Proceedings (Free Paper Session, Paediatric Cardiology I), Hong Kong, 4-6 May 2007. 15: 60.

Chow P.C., Cheung E.W.Y., Chong` C.Y., Lun K.S., Yung T.C., Wong K.T., Chau A.K.T. and Cheung Y.F., Brain Natriuretic Peptide as a Biomarker of Systemic Right Ventricular Function in Patients After Atrial Switch Operation, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 126.

Chow P.C., Liang X., Cheung E.W.Y., Wong K.T., Lun K.S., Yung T.C., Chau A.K.T. and Cheung Y.F., Right Ventricular Dyssynchrony in Patients After Atrial Switch Operation for Transposition of the Great Arteries, Hong Kong College of Cardiology, Fifteenth Annual Scientific Congress Proceedings (Free Paper Session, Paediatric Cardiology I), Hong Kong, 4-6 May 2007. 15: 58.

Liang X., Cheung E.W.Y., Wong S.J., Chau A.K.T. and Cheung Y.F., Restrictive Right Ventricular Physiology after Biventricular Repair of Pulmonary Atresia with Intact Ventricular Septum, Hong Kong College of Cardioloyg, Fifteenth Annual Scientific Congress Proceedings (Free Paper Session, Paediatric Cardiology I), Hong Kong, 4-6 May 2007. 15: 58.

Researcher : Cheung PT

Project Title:	Delineation of molecular genetic basis for patients with idiopathic short stature
Investigator(s):	Cheung PT, Low LCK
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Low Budget High Impact Programme
Start Date:	11/2001

Abstract:

To determine the measurable biochemical profile in a group of patients with ISS and delineate the detailed genetic workup of the stated target genes.

List of Research Outputs

Chan B.P., Chan G.C.F., Wong H.L., Cheung P.T., Cheah K.S.E. and Chan D., Cell-Matrix Microsphere, Associated Products, Methods for Preparation and Applications., US Regular Patent Application No. 11/750,863 (filed on 18 May 2007). 2007.

Cheung P.T., Low L.C.K. and Kwan E.Y.W., Aldosterone synthetase (corticosterone methyloxidase) deficiency type II in a Chinese boy, 4th Biennial Scientific Meeting of the Asia Pacific Paediatric Endocrine Society, Pattaya, Thailand, 1 - 4 November . 2006.

Cheung P.T., Citrin deficiency – the Hong Kong experience. , Frequency and Pathophysiology of Citrin Deficiency. Seminar supported by AA Science Platform Program, Japan Society for the Promotion of Science. December 8, 2006, Vietnam-Hanoi. . 2006.

Cheung P.T., Presentation on the perspectives and leading discussion, Symposium on Citrin Deficiency at the 10th International Congress of Inborn Errors of Metabolism (ICIEM) 2006. September 12-16, 2006. Ciba, Japan. 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.

Poon G.W.K., Kwan E.Y.W., Cheung P.T. and Low L.C.K., Mutation analysis of the GLUT2 Gene in a Chinese patient with Fanconi-Bickel Syndrome, 4th Biennial Scientific Meeting of the Asia Pacific PaediatricEndocrine Society, Pattaya, Thailand, 1-4 November. 2006.

Shi J., Liu Y., Zheng Y., Guo Y., Zhang J., Cheung P.T., Xu R. and Zheng D., Therapeutic Expression of an Anti-Death Receptor 5 Single-Chain Fixed-Variable Region Prevents Tumor Growth in Mice, Research Article. 2006, 66(24): 11946-11953.

Wang S., Wu E.X., Wang Y., Lau H., Hui E., Cheung P.T. and Khong P.L., Axial and radial diffusivities as potential markers for characterization of white matter lesions and predicting lesion outcome in a neonatal rat hypoxia-ischemia model, ISMRM 15th Scientific Meeting & Exhibition, Berlin, Germany,19-25 May 2007. (Proc Intl Soc Mag Reson Med 2007;15:3075). 2007.

Wang Y., Cheung P.T., Shen G.X., Wu E.X., Qiu D., Khong P.L. and Bhatia I., Comparing diffusion-weighted and T2-weighted MR imaging for the quantification of infarct size in a neonatal rat hypoxic-ischemic model at 24 h post-injury, International Journal of Developmental Neuroscience. Elsevier, 2007, 25: 1-5.

Zhou Y., Bhata I., He Q.Y., Cheung P.T. and Chiu J., Hypoxia-ischemia induces dephosphorylation of collapsin mediator proteins ( CRMPs) in neonatal mice through down regulation of Cdk5/p35, 46th Annual meeting of The American Society for Cell Biology, December 9-13, 2006, San Diego, California, U. S. A. 2006.

Researcher : Cheung YF

Project Title:	CSX/NKX2.5 mutations in patients with pulmonary atresia and intact ventricular septum
Investigator(s):	Cheung YF, Chan SY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003

Abstract:

To determine the possible genetic cause of PAIVS, which is a relatively common cyanotic congenital heart disease in this locality.

Project Title:	Development of a multimedia tool for teaching of paediatric cardiology
Investigator(s):	Cheung YF
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Run Run Shaw Research and Teaching Endowment Fund - Teaching Grants
Start Date:	04/2004

Abstract:

To improve the knowledge on congenital heart disease of medical students; thier skills in the evaluation of children with congenital heart disease, and their skills in counseling of parents of paediatric cardiac patients.

Project Title:	Modulating effects of body defense molecule and inflammatory gene polymorphisms on arterial stiffness in Kawasaki disease
Investigator(s):	Cheung YF, Lau YL
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004

Abstract:

To test the hypothesis that polymorphisms of these candidate genes, in isolation or combination, modulate systemic arterial stiffness in patients with a history of KD.

Project Title:	Association and Linkage Studies Between Arterial Stiffness and the Fibrillin-1 Gene
Investigator(s):	Cheung YF, Lau YL, Sham PC
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	09/2005

Abstract:

Arterial stiffness is recently recognized as an independent cardiovascular risk factor. With arterial stiffening, the left ventricular afterload is increased while coronary perfusion is altered. The secondary increase in pulse pressure has further been shown to be an independent predictor of cardiovascular mortality and future cardiovascular events. Although arterial stiffening has traditionally been regarded as part of the normal aging process, there is growing evidence that it may precede clinical disease and predict a higher risk for developing atherosclerosis, hypertension and stroke. Recently, the genetic aspect of arterial stiffness is beginning to unveil. In particular, there is a growing body of evidence that suggests a contributory role of genetic variations in extracellular matrix proteins to arterial stiffening. Fibrillin-1, being a matrix glycoprotein and the principal constituent of microfibrils that provide load-bearing and anchoring functions within the arterial wall, is particularly relevant in this context. Indeed, mutation and polymorphism of the fibrillin-1 gene has been associated with aortic stiffening in patients with Marfan syndrome and brachial pulse pressure in a healthy middle-aged male population, respectively. Nonetheless, whether variations in the fibrillin-1 genotype contribute to arterial stiffness in the general population have hitherto remained unknown.The primary objective of the proposed study is to test the hypothesis that arterial stiffness in the general population is associated with variations in the fibrillin-1 genotype. To test the hypothesis, sibling pair association and linkage studies between arterial stiffness and fibrillin-1 gene will be performed. The central (aortic and carotid) and peripheral (brachio-radial) arterial stiffness will be related to demographic variables, cardiovascular risk factors and a variable nucleotide tandem repeat polymorphism in intron 28 of the fibrillin-1 gene. Additionally, the single nucleotide polymorphism at intron C in the upstream region of the fibrillin-1 gene will be determined. Based on findings of these studies, the following issues will be addressed:- heritability of central and peripheral conduit arterial stiffness- association between variations in fibrillin-1 genotypes and arterial stiffness- linkage between fibrillin-1 gene and arterial stiffness- gene-environment interaction of fibrillin-1 genotypic variations in relation to arterial stiffness

Project Title:	Impact of iron overloding on left ventricular torsion in patients with beta-thalassaemia major
Investigator(s):	Cheung YF, Chan GCF
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	09/2006

Abstract:

While cardiac dysfunction secondary to iron overload in patients with beta-thalassaemia major is well documented, the left ventricular (LV) function usually remains relatively normal as assessed by conventional echocardiograhic imaging until late in the cardiomyopathic process. These echocardiographic indices are derived primarily from the short- and long-axis function of the left ventricle. The relative insensitivity of these conventional, load-dependent indices of systolic and diastolic LV function is in part related to the fact that beta-thalassaemia major represents a high-output anaemic state, being generated by the volume-loaded ventricles to maintain a high cardiac output in the presence of a low systemic vascular resistance. Recent research in cardiac mechanics is moving from short- and long-axis LV function to three-dimensional ventricular deformation, notably LV torsional mechanics. The torsional deformation of the left ventricle is characterized by systolic twisting and diastolic untwisting about its long axis as a result of the opposite rotation of the cardiac apex and base. Left ventricular torsion plays an important role with respect to LV ejection and filling. More important, LV torsion has been shown to relate closely to alterations of sarcomeric proteins in experimental cardiomyopathy models. Ultrastructural alteration of the extracellular matrix proteins may result in subtle changes in myocardial function that are not evident with the conventional global ventricular function measurements. Hence, the effects of free iron increase within the cardimyocytes, which causes oxidative membrane damage and alterations in gene expression, may be reflected by changes in LV twisting and untwisting before the changes are apparent in indices of global LV function. We therefore hypothesized that iron-overloading in patients with beta-thalassaemia major has a negative impact on LV torsional mechanics both at rest and during exercise stress. The proposed study is to test the hypothesis by examining the LV torsion and torsional velocity by speckle tracking echocardiography in patients with beta-thalassaemia major at rest and during exercise stress and comparing the LV torsional mechanics to those of age and sex-matched controls. This proposed study would address the following issues:i) the impact of iron overloading on the resting and exercise-stressed LV torsional mechanics in patients with beta-thalassaemia major,ii) the relation between LV torsional indices and myocardial iron load,iii) the relation between indices of LV torsion and conventional and tissue Doppler indices of LV systolic and diastolic function, and iv) the impact of systemic arterial stiffening, demonstrated to occur in patients with beta-thalassaemia major previously by our group, on LV torsion.

List of Research Outputs

Chan S.Y., Lau W.Y., Wong W.H.S., Cheng L.C., Chau A.K.T. and Cheung Y.F., Chylothorax in Children After Congenital Heart Surgery, Annals of Thoracic Surgery. Elsevier Inc, 2006, 82: 1650-1657.

Cheung E.W.Y., Lam W.W.M., Cheung S.C.W. and Cheung Y.F., Functional Implications of the Right Ventricular Myocardial Performance Index in Patients After Surgical Repair of Tetralogy of Fallot, Hong Kong College of Cardioloyg, Fifteenth Annual Scientific Congress Proceedings (Free Paper Session, Paediatric Cardiology I), Hong Kong, 4-6 May 2007. 15: 60.

Cheung Y.F., "How does the LV react to changes in the arteries and vice versa?”, “Kawasaki disease: what happens to the blood vessels?”, and “Coarctation of the aorta: What are the late vascular implications”, 3rd Annual Toronto Symposium “Contemporary Questions in Congenital Heart Disease: The Left Heart”, organized by the Division of Cardiology, The Hospital for Sick Children, University of Toronto, Toronto, Canada . 2007.

Cheung Y.F., (Multimedia CD Rom) - Clinical Diagnosis of 'Congenital heart Disease: Heart Murmurs and Beyond'. Elsevier, 2006.

Cheung Y.F., Aortic root dilation and aortic elastic properties in children after repair of Tetralogy of Fallot, Hong Kong College of Cardiology, Fourteenth Annual Scientific Congress Proceedings, Hong Kong. 2006.

Cheung Y.F., Apply of Real Time 3D Echocardiography in Children with Congenital Heart Disease, Invited Talk in Children's Hospital of Chongqing Medical University, Chongqing, PR China, 23 November 2006. 2006.

Cheung Y.F., Arterial dysfunction in beta-thalassaemia major: implications on cardiac dysfunction and premature atherosclerosis, Hong Kong Society for the Study of Thalassaemia, Federation of Medical Societies of Hong Kong, Hong Kong. 2006.

Cheung Y.F., Chow P.C., Chan G.C.F. and Ha S.Y., Carotid Intima-Media Thickness is Increased and Related to Arterial Stiffening in Patients With Beta-Thalassaemia Major, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 125.

Cheung Y.F., Chow P.C., Chan G.C.F. and Ha S.Y., Carotid intima-media thickness is increased and related to arterial stiffening in patients with beta-thalassaemia major, British Journal of Haematology. Blackwell Publishing Ltd, 2006, 135: 732-734.

Cheung Y.F., Ou X. and Wong S.J., Central and Peripheral Arterial Stiffness in Patients After Surgical Repair of Tetralogy of Fallot: Implications for Aortic Root Dilation, American Heart Association, Scientific sessions 2006, Supplement II to Circulation (Journal of the American Heart Association), USA, 12-15 November 2006. 114(18): 780.

Cheung Y.F., Ou X. and Wong S.J., Central and peripheral arterial stiffness in patients after surgical repair of tetralogy of Fallot: implications for aortic root dilatation, Heart. 2006, 92: 1827-1830.

Cheung Y.F., Chairman - Oral Presentation, Carotid intima-media thickness is increased and related to arterial stiffening in patients with beta-thalassaema major, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 2006.

Cheung Y.F., Chairman, The 3^rd Interventional Symposium of Congenital Heart Disease (Continual Education for Non-Coronary Heart Disease Intervention, Shanghai, PR China, 9-11 October 2006. 2006.

Cheung Y.F., Chairperson of Session I: Current State-of-the-art in Echocardiography and Imaging Diagnosis, Biannual Scientific Meeting of the Shanghao Children's Medical Centre "Update on diagnosis and treatment for complex congenital heart disease", Shanghai, PR China, 22 May 2007. 2007.

Cheung Y.F., Chairperson of Session IV: Review of Difficult Cases, Biannual Scientific Meeting of the Shanghao Children's Medical Centre "Update on diagnosis and treatment for complex congenital heart disease", Shanghai, PR China, 22 May 2007. 2007.

Cheung Y.F., Coarctation: What are the late vascular implications? , SickKids - The 3rd Annual Toronto Symposium 2007, Contemporary Questions in Congenital Heart Disease, The Left Heart, Toronto, Canada. 2007.

Cheung Y.F., Editorial Board member, Hong Kong Journal of Paediatrics, 2007.

Cheung Y.F., Fundamentals of Congenital Heart Disease. Hong Kong, Elsevier, 2006, 1-205.

Cheung Y.F., Kawasaki disease: What happens to the blood vessels in the long term? , National Paediatric Cardiology meeting, Chinese Paediatric Cardiology Society, Huangshan, PR China . 2007.

Cheung Y.F., Long-term blood vessel complications in Kawasaki disease, National Paediatric Cardiology Meeting, Chinese Paediatric Cardiology Society, Huangshan, China. 2007.

Cheung Y.F., Long-term follow-up after surgical repair of complex congenital heart disease, The 3rd Interventional Symposium of Congenital Heart Disease (Continual Education for Non-Coronary Heart Disease Intervention) Shanghai, PR China . 2006.

Cheung Y.F., Member, Scientific Program Committee, China-Korea-Japan Pediatric Heart Forum 2006, Shanghai, PRC (hosted by Children's Hospital of Fudan University), 7 September 2006. 2006.

Cheung Y.F., Member, Scientific Program Committee, The 3^rd Interventional Symposium of Congenital Heart Disease (Continual Education for Non-Coronary Heart Disease Intervention, Shanghai, PR China, 9-11 October 2006. 2006.

Cheung Y.F., Paediatric Cardiac Emergency & CPR, Integrated Certificate Course, Grantham Hospital, Hong Kong. 2007.

Cheung Y.F., Programming of Vascular Function In-Utero, Joint Maternal Fetal Medicine Grand Round (Kwong Wah Hospital), 20 January 2007. 2007.

Cheung Y.F., Wong S.J. and Ho M.H.K., Relationship Between Carotid Intima-Media Thickness and Arterial Stiffness in Children After Kawasaki Disease, American Heart Association, Scientific sessions 2006, Supplement II to Circulation (Journal of the American Heart Association), USA, 12-15 November 2006. 114: 639-640.

Cheung Y.F., Wong S.J. and Ho M.H.K., Relationship between carotid intima-media thickness and arterial stiffness in children after Kawasaki disease, Archives of Disease in Childhood. 2007, 92: 43-47.

Cheung Y.F., Transesophageal Echocardiography, 食道超聲, Paediatric Cardiothoracic Surgery, in Chinese. 小兒胸心外科, 上海, 上海科學技藝文獻出版社, 2007, 132-135.

Cheung Y.F., What happens to the blood vessels? , Sickkids - The 3rd Annual Toronto Symposium 2007, Contemporary Questions in Congenital Heart Disease, The Left Heart, Toronto, Canada . 2007.

Chow P.C., Cheung E.W.Y., Chong` C.Y., Lun K.S., Yung T.C., Wong K.T., Chau A.K.T. and Cheung Y.F., Brain Natriuretic Peptide as a Biomarker of Systemic Right Ventricular Function in Patients After Atrial Switch Operation, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 126.

Chow P.C., Ho M.H.K., Lee T.L., Lau Y.L. and Cheung Y.F., Relation of Arterial Stiffness to Left Ventricular Structure and Function in Adolescents and Young Adults With Paediatric-onset Systemic Lupus Erythematosus, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 126.

Chow P.C., Ho M.H.K., Lee T.L., Lau Y.L. and Cheung Y.F., Relation of Arterial Stiffness to Left Ventricular Structure and Function in Adolescents and Young Adults with Pediatric-Onset Systemic Lupus Erythematosus, The Journal of Rheumatology. 2007, 34(6): 1345-1352.

Chow P.C., Liang X., Cheung E.W.Y., Wong K.T., Lun K.S., Yung T.C., Chau A.K.T. and Cheung Y.F., Right Ventricular Dyssynchrony in Patients After Atrial Switch Operation for Transposition of the Great Arteries, Hong Kong College of Cardiology, Fifteenth Annual Scientific Congress Proceedings (Free Paper Session, Paediatric Cardiology I), Hong Kong, 4-6 May 2007. 15: 58.

Ho M.H.K., Chow P.C., Lee T.L., Tam S., Wong W.H.S., Wong W.K.H.S., Lau Y.L. and Cheung Y.F., Carotid Intima-Media Thickening in Adolescents and Young Adults with Paediatric-Onset Systemic Lupus Erythematosus is Not Related to Traditional and Novel Cardiovascular Risk Factors, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 157.

Liang X., Cheung E.W.Y., Wong S.J., Chau A.K.T. and Cheung Y.F., Restrictive Right Ventricular Physiology after Biventricular Repair of Pulmonary Atresia with Intact Ventricular Septum, Hong Kong College of Cardioloyg, Fifteenth Annual Scientific Congress Proceedings (Free Paper Session, Paediatric Cardiology I), Hong Kong, 4-6 May 2007. 15: 58.

Wong M.L., Wong W.H.S. and Cheung Y.F., Fetal myocardial performance in pregnancies complicated by gestational impaired glucose tolerance, Ultrasound in Obstetrics and Gynaecology. 2007, 29: 395-400.

Yang M., Cheung Y.F., Chan S. and Chan G.C.F., Tpo Has A Protective Effect On Iron-induced Apoptosis In Cardiomyocytes, Cytotherapy/international Society For Cellular Therapy Annual Meeting. 2007, 9: 76.

Researcher : Chiang AKS

Project Title:	Experimental immunotherapy of tumours
Investigator(s):	Chiang AKS
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Research Initiation Programme
Start Date:	04/2001

Abstract:

To develop strategies in enhancing the host immune response against tumours.

Project Title:	Genetic studies of tubercubosis
Investigator(s):	Chiang AKS
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Other Funding Scheme
Start Date:	03/2002

Abstract:

To host susceptibility genes in tubercubosis; to study pharmacogenomics in anti-tubercubosis drug metabolism.

Project Title:	Prospective study of virologic and immunologic parameters of primary Epstein-Barr virus infection in Chinese children
Investigator(s):	Chiang AKS, Chan KH
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	10/2003

Abstract:

An unresolved issue in EBV immunology concerns the relationship between clinical IM-like symtoms, virus DNA load and CD8+ T cell lymphocytosis; Acute IM in adolescents is associated with large expansions of EBV lytic epitope reactivities which are followed by a later expansion of latent epitope responses. The magnitude of the EBV lytic and latent epitope reactivities would be studied and compared in both IM and non-IM patients; likewise, is there a difference in the rate of emergence of latent epitope responses bewteen the IM and non -IM patients? The kinetics and evolution of the EBV epitope-specific cytotoxic T-lymphocyte (CTL) responses from primary to persistent phases of EBV infection would be compared between the two groups of children.

Project Title:	Prospective study of Epstein-Barr virus (EBV) strains in primary EBV infection
Investigator(s):	Chiang AKS
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004

Abstract:

To study the occurrence of Epstein-Barr virus (EBV) diversity and coinfection in a prospective study of primary Epstein-Barr virus infection in Chinese children.

Project Title:	Longitudinal study of Epstein-Barr virus specific antibody responses in childhood infectious mononucleosis
Investigator(s):	Chiang AKS
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	12/2005

Abstract:

The purpose of the proposed study is to compare the evolution of Epstein-Barr virus (EBV) specific antibody responses in a longitudinal followup study of symptomatic and asymptomatic primary EBV infection. What is known about EBV antibody responses in the literature? Epstein-Barr virus (EBV) infects greater than 90% of all human populations and establishes a lifelong persistence within the host. Primary infections by EBV may remain silent or induce a self-limiting lymphoproliferative disorder, infectious mononucleosis (IM). EBV-encoded antigens are divided into those expressed in the viral replicative cycle, i.e., the viral capsid antigen (VCA) and the early amtigens (EA) of the diffuse (D) and the restricted (R) varieties and those expressed in the viral latent cycle, the EBV-determined nuclear antigen (EBNA). The different timing of emergence between the antibodies to VCA and EA and those to EBNA indicates that the two sets of antigens are likely expressed on separate types of cells which become available to stimulate antibody responses under different circumstances. The laboratory diagnosis of EBV infection is based on serological tests to detect both specific antibodies to EBV antigens (1, 2) and heterophile antibodies (3, 4). At the onset of symptoms of IM, the humoral response to EBV infection is characterized by the presence of VCA IgM antibodies and the concurrent rise of VCA IgG antibodies (5). Antibodies to diffuse early antigen (anti-EA-D) are transitory and are detected in about 80% of infected persons. Antibodies to EA-R may become detectable in protracted cases of the disease after the anti-D titres have subsided. Anti-EBNA IgG can usually be detected at a later stage at several weeks to months after the the onset of symptoms. The majority of adult IM patients also develop IgM heterophile antibodies of the Paul-Bunnell type but the reason for their transient emergence is unknown. However, these heterophile antibodies are absent in the majority of children under 4 years of age (6). The antibody responses in silent primary EBV infections (more frequently occurred in children than adults) largely conform to those seen in IM except that antibodies to the EA complex are directed against R instead of D (7, 8). The early EBV-specific IgG antibody response after primary infection is made up of low avidity antibodies. The avidity increases in the few weeks to several months after the infection (9, 10). This property of the humoral IgG response has been employed in serological assays to distinguish between primary and re-infection or reactivation of different viruses such as rubella, CMV and parvovirus (11, 12, 13). Key issues: The pattern of antibody responses and the antibody levels to EBV-encoded antigens are largely derived from cross sectional studies of large number of individuals. Longitudinal serology data of persons recovering from IM is seldom available and information on the humoral response in asymptomatic EBV infection is scanty. I have followed a large number of Chinese children presenting with infectious mononucleosis and some children who are found to have asymptomatic primary EBV infection from the time of onset of infection through convalescence to persistence. It offers an opportunity to compare the natural evolution of antibody responses against EBV in symptomatic and asymptomatic infections. Project objectives: 1. To define the evolution of the humoral response against a human persistent virus. 2. To study the maturation of the humoral response against a persistent virus in terms of antibody avidity. 3. To compare the magnitude and the quality of the humoral response against viral lytic and latent EBV antigens from acute phase through convalescent to persistent phase in symptomatic and asymptomatic infections. References: 1.Henle W and Henle G: Epstein-Barr virus specific serology in immunologically compromized individuals. Cancer Res 41: 4222-4225, 1981 2.Henle W and Henle G: Immunology of Epstein-Barr virus. In: B, Roizman (Ed.), The Herpsesviruses, Vol. 1. Plenum Publishing Corp., Ne York, pp 209-252, 1982 3.Paul JR and Bunnell WW: The presence of heterophile antibodies in infecetious mononucleosis. Am J Med Sci 183: 90-104, 1932 4.Davidsohn I and Lee CL: The clinical serology of infectious mononucleosis. In: RL Carter and HG Penman (Eds.), Infectious Mononucleosis. Blackwell Scientific Publications, Ltd., Oxford, pp 177-200, 1969 5.Okano M, Thiele GM, Davis JR, Grierson HL, Purtilo DT: Epstein-Barr virus and human diseases: recent advances in disgnosis. Clin Microbiol Rev 1: 300-312, 1988 6.Sumaya CV: Infectious mononucleosis and other EBV infections: diagnostic factors. Lab Manag 24: 37-45, 1986 7.Biggar RJ, Henle G, Bocker J, Lennette ET, Fleisher G, Henle W: Primary Epstein-Barr virus infections in African infacnts. II. Clinical and serological obsevations during seroconversion. Int J cancer 22: 244-250, 1978 8.Fleisher G, Henle W, Henle G, Lennette ET, Biggar RJ: Primary Epstein-Barr virus infection in American infants: clinical and serological observations. J Infect Dis 139: 553-558, 1979 9.Inouye S, Hasegawa A, MAtsuno S, Katwo S: Changes in antibody avidity after virus infections: detection by an immunosorbent assay in which a mild protein-denaturing agent is employed. J Clin Microbiol 20: 525-529, 1984 10.Kocks C and Rajewsky K: Stepwise intracloncal maturation of antibody affinity through somatic hypermutation. Proc Nat Acad Sci USA 85: 8206-8210, 1988 11.Thomas HIJ and Morgan-Capner P: Rubella-specific IgG subclass avidity and its role in differenetiation between primary rubella and rubella reinfection. Epidemiol Infect 101: 591-598, 1988 12.Lutz E, Ward KN, Gray JJ: Maturation of antibody avidity after primary human cytomegalovirus infection is delayed in immunosuppressed solid organ transplant patients. J Med Virol 44: 317-322, 1994 13.Gray JJ, Cohen BJ, Dresselberger U: Detection of human parvirus B19-specific IgM and IgG sntibodies using a recombinant viral VP1 antigen expressed in insect cells and estimation of time of infection by testing for antibody avidity. J Virol Methods 44: 11-24, 1993

List of Research Outputs

Cheuk D.K.L., Lee T.L., Chiang A.K.S., Ha S.Y. and Chan G.C.F., Autologous Haematopoietic Stem Cell Transplantation for High Risk Brain Tumours in Children, 13^th Hong Kong International Cancer Congress, 3^rd Annual Meeting Centre for Cancer Research, HKU, 15-17 November 2006.

Cheuk D.K.L., Shek T.W.H., Chan G.C.F., Lau Y.L., Ha S.Y. and Chiang A.K.S., Parotid Acinic Cell Carcinoma in a Long-Term Survivor of Childhood Acute Lymphoblastic Leukemia, Pediatric Blood Cancer. 2006-7-1, InterScience, 2006, 24: 1-4.

Cheuk D.K.L., Lee T.L., Chiang A.K.S., Ha S.Y., Lau Y.L. and Chan G.C.F., Risk factors and treatment of hemorrhagic cystitis in children who underwent hematopoietic stem cell transplantation, Transplant International. 2007, 20: 73-81.

Chiang A.K.S., An unusual case of rapidly progressing obstructive jaundice in an 18 year old male, Masterclass in Paediatric Oncology, The European School of Oncology, Milan, Italy, 14-18 October 2006.

Chiang A.K.S., Childhood Non-Hodgkin Lymphoma: Subtypes, Clinical Presentation and Treatment, Hong Kong Paediatric Haematology and Oncology Study Group Annual Scientific Meeting, March 3. 2007.

Chiang A.K.S. and Chan K.H., Comparison of Serological and Virological Parameters Between Infectious Mononucleosis and Asymptomatic Primary Epstein-Barr Virus Infection, 12^th Biennial Conference of the International Association for Research on Epstein-Barr Virus and Associated Diseases (EBV 2006), Boston, USA, 8-12 July 2006.

Chiang A.K.S., Yuan X., Chan G.C.F., Kwong D.L.W., Chan T. and Ha S.Y., Treatment Outcome of Rhabdomyosarcoma in Hong Kong Chinese Children, 13^th Hong Kong International Cancer Congress, 3^rd Annual Meeting Centre for Cancer Research, HKU, 15-17 November 2006.

Chiang A.K.S., Lee P.P.W., Li C.K., Yuen H.L., Lee A.C.W. and Li C.K., Treatment outcome of hepatoblastoma and hepatocellular carcinoma in Hong Kong children, Second Cross Strait Symposium on Pediatric Oncology, Taiwan, 21-23 September 2006.

Chung B.H.Y., Lee T.L., Chan G.C.F., Chiang A.K.S., Chan K.W., Ha S.Y. and Lau Y.L., Haematopoietic stem cell transplant for Wiskott-Aldrich Syndrome, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 186-190.

Chung B.H.Y., Lee T.L., Chan G.C.F., Chiang A.K.S., Chan K.W., Ha S.Y. and Lau Y.L., Haematopoietic stem cell transplant for Wiskott-Aldrich syndrome, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 109.

Kwok H., Woo G.K.S., Chan K.W. and Chiang A.K.S., Characterization of Epstein-Barr Virus (EBV) Strains in Childhood Infectious Mononucleosis, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006. 72.

Kwok H., Woo G.K.S., Chan K.W. and Chiang A.K.S., Study of Epstein-Barr Virus (EBV) strains in childhood infectious mononucleosis, The Hong Kong Pediatric Society and Hong Kong Paediatric Nurses Association Ltd. - A Joint Annual Scientific Meeting for Paediatricians and Paediatric Nurses, QEH, Hong Kong, 25 November 2006. 40.

Lee A.C.W., Lau Y., Li C.H., Wong Y.C. and Chiang A.K.S., Intraspinal and Intracranial Hemorrhage After Lumbar Puncture, Pediatric Blood Cancer. Wiley InterScience, 2007, 48: 233-237.

To K.W., Wong O.H., Li H.B., Chen S.F., Lo C.K., Chiang A.K.S. and Huang F., Effects Of Bergapten On Dendritic Cell Functions, The 9th International Syposium on Dendritic Cells, Edinburgh, September 16-20 . 2006.

To K.W., Wong O.H., Li H.B., Chen S.F., Lo C.K., Chiang A.K.S. and Huang F., Immunomodulatory effects of Bergapten on dendritic cell functions, 9^th International Conference on Dendritic Cell, Edinburgh, England, 16-20 September 2006.

Xu X., Woo G.K.S., Chan K.H. and Chiang A.K.S., Characterization of EBV-specific CD8⁺ CTL Responses in Childhood Infectious Mononucleosis, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006. 158.

Xu X., Woo G.K.S., Chan K.H. and Chiang A.K.S., Longitudinal study of EBV-specific CD8⁺ CTL responses in childhood infectious mononucleosis, The Hong Kong Pediatric Society and Hong Kong Paediatric Nurses Association Ltd. - A Joint Annual Scientific Meeting for Paediatricians and Paediatric Nurses, QEH, Hong Kong, 25 November 2006. 43.

Researcher : Chik SCC

List of Research Outputs

Chik S.C.C., Lee D.C.W., Li C.B., Mak W.W., Tam P.K. and Lau A.S.Y., Immunomodulatory Effects of Ginseng on Human Monocytic Cells, The 6^th International Symposium on Natural Medicine and Microflora (6^th ISNMM), Seoul, Korea, 6-8 August 2006. 100-101.

Researcher : Chim S

List of Research Outputs

Chan G.S.W., Chim S., Fan Y.S. and Chan K.W., Focal segmental glomerulosclerosis after membranous glomerulonephritis in remission: temporal diversity of glomerulopathy after bone marrow transplantation, Human Pathology. 2006, 37(12): 1607-10.

Researcher : Chiu SSS

Project Title:	Streptococcus pneumoniae carriage in young children in Hong Kong
Investigator(s):	Chiu SSS, Ho PL
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Health Services Research Fund - Full Grants
Start Date:	10/1999

Abstract:

To study the serotypes and the incidence of antibiotic resistant Streptococcus pneumoniae in young children in the community.

Project Title:	A population based study of hospitalization disease burden for respiratory viral infections in children
Investigator(s):	Chiu SSS, Lau YL, McGhee SM, Peiris JSM
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	09/2003

Abstract:

To define the population based disease burden of influenzavirus and other respiratory viruses including RSV, adenovirus, parainfluenzae types I,II and III, rhinovirus, hMPV and the newly discovered SARS associated coronavirus in children hospitalized for acute respiratory infections; to define the role of influenza A in children hospitalized for febrile seizures and encephalopathy; to define the impact of these respiratory viruses on children with asthma exacerbations; to document the socio-economic impact of these respiratory viral infections on families with children hospitalized in Hong Kong; to perform phylogenetic analysis of hMPV in Asia.

List of Research Outputs

Chiu S.S.S., AIDS and vaccine update, Seminar on AIDS & Vaccine Update, organized by HK Paediatric Nurses Association Ltd., HK, 12 September 2006. 2006.

Chiu S.S.S., HIV Manual 2007. Chapter: HIV/AIDS in infants and children., Hong Kong, Stanley Ho Centre for Emerging Infectious Diseases, The Chin, 2007, 397-414.

Chiu S.S.S., Peiris J.S.M., Chan K.H., Wong W.H.S. and Lau Y.L., Immunogenicity and Safety of Intradermal Influenza Immunization at a Reduced Dose in Healthy Children, Pediatrics. 2007, 119: 1076-1082.

Chiu S.S.S., Is there anything new in vaccinating children against influenza?, The 2^nd Symposium of the Hong Kong Society for Paediatric Immunology and Infectious Diseases, HK, 19 September 2006. 2006.

Chiu S.S.S., Pediatrics & neonatal infection, 14^th Infection Control Course for Health Care Professionals 2006, 21 August - 2 September 2006. 2006.

Chiu S.S.S., Respiratory Infection I - Human Influenza, Rhinovirus, Human Metapneumovirus & Coronaviruses, Certificate Course in Infectious Diseases & Infection Control, Hong Kong, 13 December 2006. 2006.

Chiu S.S.S. and Lau Y.L., Update on preinatally acquired human immunodeficiency virus infection in children followed at one centre in Hong Kong, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 215-222.

Chiu S.S.S., Updates on the currently available vaccines in HK, Update Series on Child Health 2006, organized by The Hong Kong Paediatric Society, 4 November 2006. 2006.

Researcher : Chong WP

List of Research Outputs

Chong W.P. and Lau Y.L., Natural Killer Cells Interact with Apoptotic Cells to Show Anti-inflammatory Properties, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006. 146.

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.

Ng M.W., Zhou G., Chong W.P., Lee W.Y., Law H.K.W., Zhang H., Wong W.H.S., Fok S.F.S., Zhai Y., Yung R.W.H., Chow E.Y., Au K.L., Chan E.Y.T., Lim W., Peiris J.S.M., He F. and Lau Y.L., The association of RANTES polymorphism with severe acute respiratory syndrome in Hong Kong and Beijing Chinese, BMC Infectious Diseases. 2007, 7: 50.

Researcher : Chow PC

List of Research Outputs

Cheung Y.F., Chow P.C., Chan G.C.F. and Ha S.Y., Carotid Intima-Media Thickness is Increased and Related to Arterial Stiffening in Patients With Beta-Thalassaemia Major, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 125.

Cheung Y.F., Chow P.C., Chan G.C.F. and Ha S.Y., Carotid intima-media thickness is increased and related to arterial stiffening in patients with beta-thalassaemia major, British Journal of Haematology. Blackwell Publishing Ltd, 2006, 135: 732-734.

Chow P.C., Cheung E.W.Y., Chong` C.Y., Lun K.S., Yung T.C., Wong K.T., Chau A.K.T. and Cheung Y.F., Brain Natriuretic Peptide as a Biomarker of Systemic Right Ventricular Function in Patients After Atrial Switch Operation, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 126.

Chow P.C., Lee S.L., Tang M.H.Y., Chan K.L., Lee C.P., Lam B.C.C. and Tsoi N.S., Management and outcome of antenatally diagnosed congenital cystic adenomatoid malformation of the lung, Hong Kong Medical Journal. 2007, 13(1): 31-39.

Chow P.C., Ho M.H.K., Lee T.L., Lau Y.L. and Cheung Y.F., Relation of Arterial Stiffness to Left Ventricular Structure and Function in Adolescents and Young Adults With Paediatric-onset Systemic Lupus Erythematosus, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 126.

Chow P.C., Ho M.H.K., Lee T.L., Lau Y.L. and Cheung Y.F., Relation of Arterial Stiffness to Left Ventricular Structure and Function in Adolescents and Young Adults with Pediatric-Onset Systemic Lupus Erythematosus, The Journal of Rheumatology. 2007, 34(6): 1345-1352.

Chow P.C., Liang X., Cheung E.W.Y., Wong K.T., Lun K.S., Yung T.C., Chau A.K.T. and Cheung Y.F., Right Ventricular Dyssynchrony in Patients After Atrial Switch Operation for Transposition of the Great Arteries, Hong Kong College of Cardiology, Fifteenth Annual Scientific Congress Proceedings (Free Paper Session, Paediatric Cardiology I), Hong Kong, 4-6 May 2007. 15: 58.

Ho M.H.K., Chow P.C., Lee T.L., Tam S., Wong W.H.S., Wong W.K.H.S., Lau Y.L. and Cheung Y.F., Carotid Intima-Media Thickening in Adolescents and Young Adults with Paediatric-Onset Systemic Lupus Erythematosus is Not Related to Traditional and Novel Cardiovascular Risk Factors, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 157.

Researcher : Chow WC

List of Research Outputs

Chow W.C., Management of Atopic Eczema in Children, The Hong Kong Medical Diary. 2007, 12(3): 13-15.

Ho M.H.K., Lee T.L., Chow W.C. and Lau Y.L., Adrenaline auto-injector (EpiPenÒ) use in Hong Kong experience of Queen Mary Hospital, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 223-228.

Researcher : Chung BHY

Project Title:	Identification of TGFBR2 Mutations in Chinese patients with Marfan Syndrome (MFS) using DHPLC (Denaturing High Performance Liquid Chromatography)
Investigator(s):	Chung BHY, Lau YL, Lun KS
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	01/2007

Abstract:

Marfan syndrome (MFS) is an autosomal dominant mulit-systemic connective tissue disease with involvement of cardiovascular, musculo-skeletal, ocular and many other systems. It has an estimated incidence of up to 1: 5,000 (1). Among all the clinical features, progressive aortic root dilatation and aortic dissection is the most serious one and it represents the predominant cause of death in over 90% of patients. The first genetic defect identified for MFS is the fibrillin-1(FBN1) gene located in the long arm of chromosome 15. Up to date, there are at least 562 published FBN1 mutations (2) which scattered over the 200 kb FBN1 gene. In our previous study (3), 24 mutations in FBN1 gene could be identified in 66 probands with MPS (n=17 fulfil Ghent criteria, 14/17 FBN1 mutation positive) and marfan-like phenotypes (1). In 1991, a second disease-locus for MFS was mapped to 3p24.2-p25 in a large French family and later found to encode the transforming growth factor-beta-receptor type II (TGFBR2) gene in 2004 (4). This has provided the first genetic evidence of a link between abnormal TGF-beta signalling and human connective tissue disorders. Several functional studies have been performed following this discovery and have increased our understanding of the pathogenesis of MFS and its related disroders e.g. Loeys-Dietz syndrome (5). FBN1 mutations are shown to be positive in up to 90% probands who fulfil Ghent diagnostic criteria (2). And the study by Matyas et al, have shown that TGFBR2 mutations could be identified in ~10% of non-FBN1-patients with MFS-related disorders (6). Probands with TGFBR2 mutations have comparable clinical features with those with FBN1 mutations but often with milder ocular abnormalities and infrequent dural ectasia (2,4,7). From our local Chinese cohort, FBN1 mutations were detected only in 36% probands (76% in those fulfilling Ghent criteria) (3). Analysis of their phenotypic characteristics reveals that our patients have relatively infrequent ocular abnormalities (9%) and dural ectasia (6%) . We hypothesize that TGBFR2 mutations could be a major underlyinig genetic abnormality in Chinese MFS patients and our objective is to examine the mutation spectrum of TGFBR2 in non-FBN1 Chinese patients with MFS and its related phenotypes. References: 1. Pyeritz RE. The Marfan syndrome. Annu Rev Med 2000; 51: 481-510. 2. Boileau C, Jondeau G, Mizuguchi T, Matsumoto N. Molecular genetics of Marfan syndrome. Curr Opin Cardiol 2005; 20:194-200. 3. Chung B.H.Y., Lam S.T.S., Tong T.M.F., Li S., Lun K.S., Chan H.C., Or S.F., and Lau Y.L. Identification of 21 novel and 3 known FBN1 mutations in 66 unrelated Chinese probands with Marfan syndrome or Marfan-like phenotypes. Joint 6th Human Genome Organization (HUGO) Pacific Meeting and the 7th Asia-Pacific Human Genetics Conference, Taipei, Taiwan, 6-10 March 2006 (poster presentation). 4. Mizuguchi T, Collod-Beroud G, Akiyama T, Abifadel M, Harada N, Morisaki T, Allard D, Varret M, Claustres M, Morisaki H, Ihara M, Kinoshita A, Yoshiura K, Junien C, Kajii T, Jondeau G, Ohta T, Kishikno T, Furukawa Y, Nakamura Y, Niikawa N, Boileau C, Matsumoto N. Heterozygous TGFBR2 mutations in Marfan syndrome. Nat Gen 2004; 36(8):855-860. 5. Singh KK, Rommel K, Mishra A, Karck M, Haverich A, Schmidtke J, Arslan-Kirchner M. TGFBR1 and TGFBR2 mutations in patients with features of marfan syndrome and Loeys-Dietz syndrome. Hum Mutat 2006; 27(8):770-777. 6. Matyas G, Arnold E, Carrel T, Baumgartner D, Boileau C, Berger W, Steinmann B. Identification and in silico analyses of novel TGFBR1 and TGFBR2 mutations in marfan syndrome-related disorders. Hum Mutat 2006; 27(8):760-769. 7. Disabella E, Grasso M, Marziliano N, Ansaldi S, Lucchelli C, Porcu E, Tagliani M, Pilotto A, Diegoli M, Lanzarini L, Malattia C, Pelliccia A, Ficcadenti A, Gabrielli O, Arbustini E. Two novel and one known mutation of the TGFBR2 gene in marfan syndrome not associated with FBN1 gene defects. Eur J Hum Gen 2006;14:34-38.

List of Research Outputs

Chung B.H.Y., Application of Molecular Genetic in Patient Care, Certificate Course on Medical Genetics, The Federation of Medical Societies of Hong Kong, 28 April 2007. 2007.

Chung B.H.Y., Yang W., Lee P.P.W., Wong W.B. and Zhu Y.D., Clinical Quiz (case 21), http://www.hku.hk/paed/student area/clinical quiz. 2007.

Chung B.H.Y., Yang W., Lee P.P.W., Wong W.B. and Zhou Y.D., Clinical Quiz (case 22), http://www.hku.hk/paed/student area/clinical quiz. 2007.

Chung B.H.Y., Yang W., Lee P.P.W., Wong W.B. and Zhu Y.D., Clinical Quiz (case 23), http://www.hku.hk/paed/student area/clinical quiz. 2007.

Chung B.H.Y., General paediatrics (Clinical Quiz, case 19), http://www.hku.hk/paed/student area/clinical quiz. 2007.

Chung B.H.Y. and Tsang A.M.C., General paediatrics (Clinical Quiz, case 20), http://www.hku.hk/paed/student area/clinical quiz. 2007.

Chung B.H.Y., Lee T.L., Chan G.C.F., Chiang A.K.S., Chan K.W., Ha S.Y. and Lau Y.L., Haematopoietic stem cell transplant for Wiskott-Aldrich Syndrome, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 186-190.

Chung B.H.Y., Lee T.L., Chan G.C.F., Chiang A.K.S., Chan K.W., Ha S.Y. and Lau Y.L., Haematopoietic stem cell transplant for Wiskott-Aldrich syndrome, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 109.

Chung B.H.Y., Lam S.T.S., Tong T.M.F., Li Y.H., Lun K.S., Chan H.C., Or S.F. and Lau Y.L., Identification of 21 novel and 3 known FBN1 mutations in 66 unrelated Chinese probands with Marfan syndrome or Marfan-like phenotypes, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 96.

Chung B.H.Y. and Wong V.C.N., Relationship between five common viruses and febrile seizure in children, Archives of Disease in Childhood. 2007, 92: 589-593.

Wong V.C.N., Chung B.H.Y., Soo E. and Hardiner S.G., Interesting case presented in DK-Grandround "Look at these Facies" (Clinical Quiz, case 18), http://www.hku.hk/paed/student area/clinical quiz. 2007.

Wong V.C.N. and Chung B.H.Y., Interesting case seen during acute neurology consultation in 2002 (clinical quiz - case 12), http://www.hku.hk/paed/student area/clinical quiz. 2007.

Wong V.C.N., Chung B.H.Y. and Fung C.W., Interesting case seen in DK-Grandround December 2005 (Clinical Quiz, Case 16), http://www.hku.hk/paed/student area/clinical quiz. 2007.

Researcher : Fok SFS

List of Research Outputs

Lee P.P.W., Chan K.W., Lee T.L., Jiang L., Mak H.S., Fok S.F.S. and Lau Y.L., Clinical Characteristics and gp91phox Gene Mutations in Seventeen Chinese Children with X-linked Chronic Granulomatous Disease (Young Investigator Award), 2nd Congress of Asian Society for Pediatric Research. 2006.

Lee P.P.W., Chan K.W., Lee T.L., Jiang L., Mak H.S., Fok S.F.S., Hui Y.F., Li C., Yang X. and Lau Y.L., Clinical Characteristics and gp91phox Gene Mutations in Seventeen Chinese Children with X-linked Chronic Granulomatous Disease, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 96.

Ng M.W., Zhou G., Chong W.P., Lee W.Y., Law H.K.W., Zhang H., Wong W.H.S., Fok S.F.S., Zhai Y., Yung R.W.H., Chow E.Y., Au K.L., Chan E.Y.T., Lim W., Peiris J.S.M., He F. and Lau Y.L., The association of RANTES polymorphism with severe acute respiratory syndrome in Hong Kong and Beijing Chinese, BMC Infectious Diseases. 2007, 7: 50.

Researcher : Fong SW

List of Research Outputs

Chan K.W., Fong S.W., Mak H.S. and Chan S.Y., Expression of Tspyl2 in Transgenic Mice Reduces Cardiac Hypertrophy upon Hypertrophic Stress, 11^th Research Postgraduate Symposium, HKU, 7 December 2006. 169.

Researcher : Fung CW

List of Research Outputs

Wong V.C.N., Chung B.H.Y. and Fung C.W., Interesting case seen in DK-Grandround December 2005 (Clinical Quiz, Case 16), http://www.hku.hk/paed/student area/clinical quiz. 2007.

Researcher : Goh WHS

List of Research Outputs

Goh W.H.S., Representative of HK West Cluster in HA Forum, in "Review of the Development of Community Paediatrics in HK" organized by HK College of Paediatricians & HM Lui Memorial Fund, 9 November 2006. 2006.

Ting J.Y., Wong K.Y., Goh W.H.S., Lee C.P. and Lam B.C.C., Changes in Mortality, Morbidity and Early Neurodevelopmental Outcomes among Extremely-low-birth-weight (ELBW) Infants Born in the Early and Recent Post-Surfactant Era, Hong Kong Journal of Paediatrics (new series). 2007, 12: 78-85.

Yung A.W.Y., Poon G.W.K., Qiu D., Chu J., Lam B.C.C., Leung C., Goh W.H.S. and Khong P.L., White matter volume and anisotropy in preterm children: a pilot study of neurocognitive correlates, Pediatric Research. 2007, 61: 732-736.

Researcher : Ha SY

List of Research Outputs

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.

Cheuk D.K.L., Lee T.L., Chiang A.K.S., Ha S.Y. and Chan G.C.F., Autologous Haematopoietic Stem Cell Transplantation for High Risk Brain Tumours in Children, 13^th Hong Kong International Cancer Congress, 3^rd Annual Meeting Centre for Cancer Research, HKU, 15-17 November 2006.

Cheuk D.K.L., Shek T.W.H., Chan G.C.F., Lau Y.L., Ha S.Y. and Chiang A.K.S., Parotid Acinic Cell Carcinoma in a Long-Term Survivor of Childhood Acute Lymphoblastic Leukemia, Pediatric Blood Cancer. 2006-7-1, InterScience, 2006, 24: 1-4.

Cheuk D.K.L., Lee T.L., Chiang A.K.S., Ha S.Y., Lau Y.L. and Chan G.C.F., Risk factors and treatment of hemorrhagic cystitis in children who underwent hematopoietic stem cell transplantation, Transplant International. 2007, 20: 73-81.

Cheung Y.F., Chow P.C., Chan G.C.F. and Ha S.Y., Carotid Intima-Media Thickness is Increased and Related to Arterial Stiffening in Patients With Beta-Thalassaemia Major, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 125.

Cheung Y.F., Chow P.C., Chan G.C.F. and Ha S.Y., Carotid intima-media thickness is increased and related to arterial stiffening in patients with beta-thalassaemia major, British Journal of Haematology. Blackwell Publishing Ltd, 2006, 135: 732-734.

Chiang A.K.S., Yuan X., Chan G.C.F., Kwong D.L.W., Chan T. and Ha S.Y., Treatment Outcome of Rhabdomyosarcoma in Hong Kong Chinese Children, 13^th Hong Kong International Cancer Congress, 3^rd Annual Meeting Centre for Cancer Research, HKU, 15-17 November 2006.

Chung B.H.Y., Lee T.L., Chan G.C.F., Chiang A.K.S., Chan K.W., Ha S.Y. and Lau Y.L., Haematopoietic stem cell transplant for Wiskott-Aldrich Syndrome, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 186-190.

Chung B.H.Y., Lee T.L., Chan G.C.F., Chiang A.K.S., Chan K.W., Ha S.Y. and Lau Y.L., Haematopoietic stem cell transplant for Wiskott-Aldrich syndrome, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 109.

Lam C.W., Tong S.F., Wong K., Luo Y.F., Tang H.Y., Ha S.Y. and Chan M.H.M., DNA-based diagnosis of malignant osteopetrosis by whole-genome scan using a single-nucleotide polymorphism microarray: standardization of molecular investigations of genetic diseases due to consangunity, Journal of Human Genetics. 2007, 52: 98-101.

Lee T.L., Ho M.H.K., Ha S.Y., Chan G.C.F. and Lau Y.L., Autologous haemopoietic stem cell transplantation for severe autoimmune diseases in Hong Kong, 2nd Congress of Asian Society for Pediatric Research, Yokohama, Japan, 8-10 December 2006.

Lee T.L., Law H.K.W., Chan G.C.F., Ha S.Y., Ho M.H.K., Chan K.W. and Lau Y.L., Successful treatment of X-linked lymphoproliferative disease (XLP) with anti-CD20 monoclonal antibody (Rituximab) followed by Mismatched unrelated cord blood transfusion, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 210-214.

Researcher : Ho MHK

List of Research Outputs

Cheung Y.F., Wong S.J. and Ho M.H.K., Relationship Between Carotid Intima-Media Thickness and Arterial Stiffness in Children After Kawasaki Disease, American Heart Association, Scientific sessions 2006, Supplement II to Circulation (Journal of the American Heart Association), USA, 12-15 November 2006. 114: 639-640.

Cheung Y.F., Wong S.J. and Ho M.H.K., Relationship between carotid intima-media thickness and arterial stiffness in children after Kawasaki disease, Archives of Disease in Childhood. 2007, 92: 43-47.

Chong C.Y., Lee T.L., Ho M.H.K., Lee S.L. and Lau Y.L., Review of IgG subclass and IgA deficiency in a tertiary center, Hong Kong Journal of Paediatrics (New series). 2006, 11: 205-209.

Chow P.C., Ho M.H.K., Lee T.L., Lau Y.L. and Cheung Y.F., Relation of Arterial Stiffness to Left Ventricular Structure and Function in Adolescents and Young Adults With Paediatric-onset Systemic Lupus Erythematosus, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 126.

Chow P.C., Ho M.H.K., Lee T.L., Lau Y.L. and Cheung Y.F., Relation of Arterial Stiffness to Left Ventricular Structure and Function in Adolescents and Young Adults with Pediatric-Onset Systemic Lupus Erythematosus, The Journal of Rheumatology. 2007, 34(6): 1345-1352.

Ho M.H.K., Lee T.L., Chow W.C. and Lau Y.L., Adrenaline auto-injector (EpiPenÒ) use in Hong Kong experience of Queen Mary Hospital, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 223-228.

Ho M.H.K., Chow P.C., Lee T.L., Tam S., Wong W.H.S., Wong W.K.H.S., Lau Y.L. and Cheung Y.F., Carotid Intima-Media Thickening in Adolescents and Young Adults with Paediatric-Onset Systemic Lupus Erythematosus is Not Related to Traditional and Novel Cardiovascular Risk Factors, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 157.

Ho M.H.K., Clinical Management of Childhood Food Allergy, The Hong Kong Medical Diary. 2007, 12(3): 3-7.

Lee P.P.W., Lee T.L., Ho M.H.K., Wong W.H.S. and Lau Y.L., Herpes Zoster in Juvenile-Onset Systemic Lupus Erythematosus, Pediatric Infectious Disease Journal. 2006, 25: 728-732.

Lee P.P.W., Lee T.L., Ho M.H.K., Wong W.H.S. and Lau Y.L., Recurrent Major Infections in Juvenile-Onset Systemic Lupus Erythematosus? A Close Link with Long-term Disease Damage, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 186.

Lee P.P.W., Lee T.L., Ho M.H.K., Wong W.H.S. and Lau Y.L., Recurrent major infections in juvenile-onset systemic Lupus erythematosus - a close link with long-term disease damage, Rheumatology. 2007, 1-7.

Lee T.L., Ho M.H.K., Ha S.Y., Chan G.C.F. and Lau Y.L., Autologous haemopoietic stem cell transplantation for severe autoimmune diseases in Hong Kong, 2nd Congress of Asian Society for Pediatric Research, Yokohama, Japan, 8-10 December 2006.

Lee T.L., Law H.K.W., Chan G.C.F., Ha S.Y., Ho M.H.K., Chan K.W. and Lau Y.L., Successful treatment of X-linked lymphoproliferative disease (XLP) with anti-CD20 monoclonal antibody (Rituximab) followed by Mismatched unrelated cord blood transfusion, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 210-214.

Researcher : Hui LH

List of Research Outputs

Wong V.C.N. and Hui L.H., Brief Report: Emerging Services for Children with Autistic Spectrum Disorders in Hong Kong (1960-2004), Journal of Autism and Developmental Disorders. 2007, Published online: 29 June 2007.

Researcher : Ip EWK

List of Research Outputs

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.

Thiel S., Steffensen R., Christensen I.J., Ip E.W.K., Lau Y.L., Reason I.J.M., Eiberg H., Gadjeva M., Ruseva M. and Jensenius J.C., Deficiency of mannan-binding lection associated serine protease-2 due to missense polymorphisms, Genes and Immunity. Nature Publishing Group, 2007, 1-10.

Researcher : Jiang L

List of Research Outputs

Lee P.P.W., Chan K.W., Lee T.L., Jiang L., Mak H.S., Fok S.F.S. and Lau Y.L., Clinical Characteristics and gp91phox Gene Mutations in Seventeen Chinese Children with X-linked Chronic Granulomatous Disease (Young Investigator Award), 2nd Congress of Asian Society for Pediatric Research. 2006.

Lee P.P.W., Chan K.W., Lee T.L., Jiang L., Mak H.S., Fok S.F.S., Hui Y.F., Li C., Yang X. and Lau Y.L., Clinical Characteristics and gp91phox Gene Mutations in Seventeen Chinese Children with X-linked Chronic Granulomatous Disease, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 96.

Researcher : Karlberg JPE

Project Title:	Long-term health consequences of insults in early life
Investigator(s):	Karlberg JPE, Low LCK
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Health Services Research Fund - Full Grants
Start Date:	11/1995

Abstract:

To understand the impact of early insults for health in adult-hood.

List of Research Outputs

Researcher : Kong KP

List of Research Outputs

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.

Researcher : Kwan EYW

List of Research Outputs

Cheung P.T., Low L.C.K. and Kwan E.Y.W., Aldosterone synthetase (corticosterone methyloxidase) deficiency type II in a Chinese boy, 4th Biennial Scientific Meeting of the Asia Pacific Paediatric Endocrine Society, Pattaya, Thailand, 1 - 4 November . 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.

Poon G.W.K., Kwan E.Y.W., Cheung P.T. and Low L.C.K., Mutation analysis of the GLUT2 Gene in a Chinese patient with Fanconi-Bickel Syndrome, 4th Biennial Scientific Meeting of the Asia Pacific PaediatricEndocrine Society, Pattaya, Thailand, 1-4 November. 2006.

Researcher : Kwok H

List of Research Outputs

Kwok H., Woo G.K.S., Chan K.W. and Chiang A.K.S., Characterization of Epstein-Barr Virus (EBV) Strains in Childhood Infectious Mononucleosis, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006. 72.

Kwok H., Woo G.K.S., Chan K.W. and Chiang A.K.S., Study of Epstein-Barr Virus (EBV) strains in childhood infectious mononucleosis, The Hong Kong Pediatric Society and Hong Kong Paediatric Nurses Association Ltd. - A Joint Annual Scientific Meeting for Paediatricians and Paediatric Nurses, QEH, Hong Kong, 25 November 2006. 40.

Researcher : Lam BCC

List of Research Outputs

Chow P.C., Lee S.L., Tang M.H.Y., Chan K.L., Lee C.P., Lam B.C.C. and Tsoi N.S., Management and outcome of antenatally diagnosed congenital cystic adenomatoid malformation of the lung, Hong Kong Medical Journal. 2007, 13(1): 31-39.

Ting J.Y., Wong K.Y., Goh W.H.S., Lee C.P. and Lam B.C.C., Changes in Mortality, Morbidity and Early Neurodevelopmental Outcomes among Extremely-low-birth-weight (ELBW) Infants Born in the Early and Recent Post-Surfactant Era, Hong Kong Journal of Paediatrics (new series). 2007, 12: 78-85.

Wong R.M.S., Wong K.Y. and Lam B.C.C., Atypical Presentation of Congenital Tuberculosis in a Preterm Infant, Hong Kong Journal of Paediatrics (new series). 2007, 12: 133-136.

Yung A.W.Y., Poon G.W.K., Qiu D., Chu J., Lam B.C.C., Leung C., Goh W.H.S. and Khong P.L., White matter volume and anisotropy in preterm children: a pilot study of neurocognitive correlates, Pediatric Research. 2007, 61: 732-736.

Researcher : Lau ASY

Project Title:	Mechanism of SARS-coronavirus pathogenesis - identification of viral genes implicated in immune dysregulation
Investigator(s):	Lau ASY, Peiris JSM
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	VCO SARS Research Fund
Start Date:	07/2003

Abstract:

To investigate the pathogenesis of SARS-Coronavirus-induced pulmonary injury and multi-organ dysfunctions in humans: (a) to identify the viral determinants of proinflammatory cytokine induction: candidate envelope genes to be examined include Spike (S), Envelope (E) and Membrane (M); (b) to investigate the signaling pathways including kinases and transcription factors involved in the cytokine induction.

Project Title:	A role for apoptogenic gene PKR in regulating TNF and cytokine expression in Avian influenza H5N1 infections
Investigator(s):	Lau ASY, Peiris JSM
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	10/2003

Abstract:

To investigate whether H5N1/97 is a potent inducer of specific signaling kinases, compared to H1N1 or H3N2, leading to enhanced cytotoxicity in the host cell; to investigate whether H5N1/97 induction of TNF-[alpha] and related proinflammatory cytokines is dependent on the expression of these signaling kinases; the mechanism of H5N1/97-induced TNF-[alpha] and related cytokine expression; to identify transcription factors (TF) operative in H5N1-induced and kinase-mediated pathways; the role of these signaling kinases in H5N1/97-induced cytotoxicity: to identify kinase-regulated downstream pathways and induction of apoptogenic genes.

Project Title:	Immune dysregulation in HIV infection - mechanism of mycobacterial pathogenesis
Investigator(s):	Lau ASY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2005

Abstract:

To confirm the role of HIV tat on monocytic cells in TH2 cytokine induction and TH1 reponse suppression; to identify the signaling pathways and transcription factors operative in Tat activation of IL-10 promoter; to investigate the effects of BCG or mycobacterial cell wall submits on IL-10 induction; to examine whether Tat interacts with TLR-associated kinases and factors directly or via PKR; to delineate whether exogenous IFN-[gamma] and other TH1 cytokines can counteract the effects of Tat and MTB in IL-10 induction.

Project Title:	Immunotherapy of mycobacterial infections: a cell and molecular model
Investigator(s):	Lau ASY, Lee DCW
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	02/2005

Abstract:

To examine the profile of cytokine expression including proinflammatory cytokines and anti-inflammatory cytokines in BCG and mycobacterial cell wall subunits-treated cells; to confirm the role of PKR and related kinases in signaling pathways operative in the BCG- and cell wall subunit-induced cytokine expression; to examine the role of IL-10 in inhibition of IFN signaling and macrophage functions; to examine whether IL-10 induces the expression of SOCS to inhibit IFN-gamma signaling; to delineate whether exogenous IFN-gamma and other TH1 cytokines can modulate and reverse the effects of BCG and IL-10 in SOCS induction and restore the effects of IFN-gamma macrophage function.

Project Title:	Cytokine Dysregulation and Virus-Induced Cell Death in Avian Influenza Virus Infections
Investigator(s):	Lau ASY, Peiris JSM
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	11/2005

Abstract:

Objectives: In this project, we will use H9N2 as prototypes to examine the cellular effects of TNF and IFN induction by avian influenza viruses. We will delineate whether there is differential induction of cytotoxicity by the avian viruses from the human ones. We will also examine the consequences of simultaneous induction of TNF and IFN on cell survival and expression of apoptotic genes. Our Specific Aims are 1) We will delineate whether there is a differential induction of cytotoxicity by the avian viruses (H9N2) compared to the human ones (H1N1 or H3N2). 2) We will examine the consequences of simultaneous induction of TNF and IFN on cell survival and expression of apoptotic genes. Background Influenza A virus infects a wide range of species, including poultry, swine, horses, seals and humans. Of the 15 hemagglutinins (HA) subtypes of influenza A, only H1, H2 and H3 had been known to cause significant morbidity and mortality in humans (1-3). The 1997 outbreak of avian influenza H5N1/97 in Hong Kong was the first documented cases of primary pneumonia rapidly progressing to adult respiratory distress syndrome and multiple organ dysfunctions in humans. In light of the high mortality of H5N1/97 infection, it would be desirable to understand the pathogenesis in order to enhance the development of novel therapy. Influenza A viruses are known to replicate in epithelial cells and leukocytes, resulting in induction of cytokines(4). During influenza virus infection, a multiple array of cytokines, including chemokines (Rantes, MIP-1), and interferons (IFN-α and –β), is induced (5,6). The biological actions of IFNs are mediated by multiple pathways resulting in mRNA degradation by ribonuclease L and inhibition of translation by a dsRNA-activated kinase, PKR. PKR is inducible by IFN, TNF-α, and dsRNA [viral RNA analogue] (7,8). We have previously shown that PKR mediates the cytotoxicity of TNF-α in cells of diverse tissue origins including fibroblasts and monocytes (9). It has been proposed that PKR serves as a common pattern-recognition molecule responsible for mediating these virus-induced antiviral effects (8-11). We previously demonstrated PKR serves multiple roles in the cell including the mediation of TNF-induced cytotoxicity, and induction of apoptotic gene p53 and IFN expression (9, 12-16). The signal transduction role of PKR is further confirmed by its effects on the induction of Fas and NF-kB, following TNF-α or endotoxin treatment. TNF-α is a potent, cytotoxic molecule induced in response to invasion by infectious pathogens or cancer cells. Elevated levels of TNF-α in the serum have been correlated to and predictive of morbidity and mortality in patients with meningococcemia. To unravel the pathogenesis of fulminant H5N1/97 disease in humans, we have developed a H5N1/97-blood macrophage (BMac) model to examine the interactions of H5N1/97-encoded genes and cellular factors which may result in immune dysregulation (17: Peiris as PI and Lau as co-I). Using our model, we have previously demonstrated that H5N1/97 induced dramatically higher levels of cytokine expression when compared to those elicited by “conventional” human H1N1 or H3N2 viruses (17). TNF-α protein levels in H5N1/97-infected macrophage culture supernatants were comparable to those induced by stimulation with E. coli endotoxin, and much higher than those in H1N1 or H3N2 infections (17). Recently, we further demonstrated that the TNF induction and its cytotoxicity are mediated, at least in part, by mitogen-activated protein (MAP) kinases including p38 and ERK (18: J Virol 2005, accepted May 2005, Lau as PI). Induction of proinflammatory cytokines is a major defense mechanism of the host to mobilize the immune system and to combat the invading pathogen. We hypothesize the high mortality associated with H5N1/97 infections may be due to an uncontrolled induction of IFN and TNF, consequent to virus interactions with cellular signaling pathways, leading to dysregulated immune response and differential effects on cell death.

Project Title:	Mechanisms of inteferon dysregulation and virus-induced cell death in avian influenza H5N1 virus infections
Investigator(s):	Lau ASY, Lee DCW
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	10/2006

Abstract:

To examine the signaling pathways in IFN-beta super-induction by avian influenza viruses including H5N1/97, as compared to human viruses including H1N1; to investigate whether there is a preferential activation of IFN regulatory factors (IRFs) during IFN induction in avian virus infections; to determine the transcriptional activation of IFNs by electrophorectic mobility shift, IFN promoter-driven luciferase and steady-state quantitative-PCR assays, in addition to Western blots; to delineate whether there is differential induction of cytotoxicity and apoptotic genes by the avian viruses from the human ones.

Project Title:	HIV dysregulation of the toll-like receptor system - implications for pathogenesis
Investigator(s):	Lau ASY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	10/2006

Abstract:

To investigate the effects of Tat on the expression of TLR2 in primary blood monocytes and identify whether there are other TLRs inducible by Tat; to identify the kinases and signaling pathways operative in Tat induction of TLR2 and its related receptors; to investigate whether the enhanced TLR plays a role in infection by HSV and the level of viral replication in monocytes; to examine the effects of Tat on astrocytic cells including TLR expression and infection by HSV.

Project Title:	Regulation of Matrix Metalloproteinases by Epstein-Barr Virus Latent Membrane Protein 1
Investigator(s):	Lau ASY, Chua DTT, Lee DCW
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	11/2006

Abstract:

Objectives: In this project, we will investigate the role of Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) in the expression of Matrix Metalloproteinases (MMPs) and their consequent effects on cell migration. Our Specific Aims are: 1) We will generate LMP1-expressing cells including fibroblasts or epithelial cells by transient transfection of the cells with LMP1 cDNA. 2) We will delineate the mechanisms of Epstein-Barr Virus, specifically LMP1 gene, in the regulation of MMPs induction and the promotion of cell invasion. Background Epstein-Barr Virus (EBV) is a human herpesvirus that infects a large percentage of the world’s population (1). EBV has been known to be highly associated with human malignancies, including Burkitt’s lymphoma, post-transplant lymphomas, AIDS-associated lymphoma, gastric carcinoma, and the highly invasive nasopharyngeal carcinoma (NPC), putatively related to and as a consequence of the latent infection state (1,2). Specific EBV latent genes including LMP1, 2A, and 2B, as well as EBV nuclear antigen-1 (EBNA1) and EBV non-polyadenylated RNAs (EBER) are expressed in NPC cells (1). LMP1 has been shown to have transforming properties in mouse fibroblasts (3). It also plays an important role in EBV-induced B-cell immortalization and association with metastasis in nasopharyngeal carcinoma (3, 4). In in vitro study, LMP1 regulates Matrix Metalloproteinase 1 (MMP1) expression in epithelial cells, as well as MMP2 and -9 in B-cells. The transmembrane component of the LMP1 C-terminal contains two important signaling domains, namely CTAR1 and CTAR2. The interactions of CTAR domains with TRAFs or TRADD result in the activation of NF-kB, p38 MAPK, JNK and/or JAK/STAT signaling pathways (5). Matrix Metalloproteinase, with a total of 23 family members, are endopeptidases involved in the degradation of extracellular matrix proteins and their upregulation in cancer samples implicates their role in tumor metastasis (6). Selected MMPs are highly expressed in malignant cancers, in particular in the areas of active invasion such as the interface of tumor and stroma. For example, MMP-3 induced by cytokines and cellular factors in cancer and non-cancerous stromal cells may result in the deregulation of E-cadherin, a prototype adhesion molecule in maintaining the intercellular matrix (3). Thus destruction of E-cadherin and associated proteins promotes tumor invasion. Our previous studies indicate that LMP1 regulates the expression of proinflammatory cytokines including TNF and IL-6 as well as anti-inflammatory cytokines including IL-10. In light of the role of LMP1 in cytokine regulation and the fact that MMPs are regulated by TNF, we hypothesize that LMP1 promotes the progression and metastasis of highly invasive NPC via the induction of MMPs.

List of Research Outputs

Cheng M., Xing B., Cheung B.K.W., Li C.B. and Lau A.S.Y., IFNg regulation of TNF a-enhanced glioma cell migration through induction of matrix metalloproteinase expression, The 6th International Cytokine Conference 2006 (European Cytokine Network, Supplement Aug 2006, Vol 17 - as official journal of Cytokine 2006-Vienna), Vienna, Austria, 27-31 August 2006. 17: 02-21/P.

Cheng M., Xing B., Li C.B., Cheung B.K.W. and Lau A.S.Y., Interferon-gamma regulation of TNFalpha-induced matrix metalloproteinase 3 expression and migration of human glioma T98G cells, International Journal of Cancer. 2007, 121: 1190-1196.

Cheung B.K.W., Law H.Y. and Lau A.S.Y., Identification of a Viral Gene Responsible for SARS-Coronavirus-induced Chemokine Dysregulation, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006. 145.

Chik S.C.C., Lee D.C.W., Li C.B., Mak W.W., Tam P.K. and Lau A.S.Y., Immunomodulatory Effects of Ginseng on Human Monocytic Cells, The 6^th International Symposium on Natural Medicine and Microflora (6^th ISNMM), Seoul, Korea, 6-8 August 2006. 100-101.

Lau A.S.Y., Biological Basis of Immune Dysregulation in Emerging Viral Infections: Implication for Treatment of SARS, Influenza and HIV, Hong Kong Doctors Union, Hong Kong, 29 November 2006. 2006.

Lau A.S.Y., Cytokine Signaling and Microbial Infections: Implications for TCM and Herbal Extracts Research, Institute of Chinese Medical Sciences, University of Macau, Macau, 3 March 2007. 2007.

Lau A.S.Y., Cytokines and microbial pathogenesis, Hosted by Prof Neil Reiner, Department of Medicine, Vancouver General Hospital, University of British Columbia, Canada, June 14. 2007.

Lau A.S.Y., Cytokines and signalling pathways in CNS viral infections: Implications for pathogenesis and treatment, Bimonthly Scientific Meeting, The Hong Kong Society of Child Neurology and Developmental Paediatrics, 19 January 2007. 2007.

Lau A.S.Y., Cytokines signalling and microbial infections: potential targets for natural products/TCM research, Coastal Marine Laboratory, Hong Kong University of Science & Technology, Hong Kong, 15 March 2007. 2007.

Lau A.S.Y., Host - Microbes Interaction, "Certificate course on infectious diseases & infection control for health care professionals", Organized by The Hong Kong Society for Infectious Diseases & Hong Kong Society for Paediatric Immunology & Infectious Diseases, Princess Margaret Hospital, Hong Kong, 17 March 2007. 2007.

Lau A.S.Y., Host-Microbes Interaction, Certificate course in Infectious Diseases & Infection Control, co-organize by PMH, HKSID and HKSPIID. 2007.

Lau A.S.Y., Interaction of Mycobacterium with the immune system, Toll like Receptor Conference, Melbourne, Australia, May 16. 2007.

Lau A.S.Y., Interplay between Mycobacteria and HIV in immune dysregulation, Hosted by Dr. Nick Gay, Reader, Department of Biochemistry, University of Cambridge, June 28. 2007.

Lau A.S.Y., Mechanism for HIV Suppression of the Interferon – gamma signaling – Tat and Jak/Stat interactions, Biannual World Congress on Inflammation, Copenhagen, Denmark, June 17-20. 2007.

Lau A.S.Y., Cheng M., Lin S.S. and Li C.B., Mechanism of HIV dysregulation of the interferon-gamma signal transduction: a role for transactivator tat in suppression of Jak/STAT pathways, 8th World Congress on Inflammation, Copenhagen, Bella Center, Copenhagen, Denmark, June 16-20. 2007.

Lau A.S.Y., Update on Cytokine Biology Research, British Columbia Cancer Research Institute, November 14. 2006.

Law H.Y., Lee D.C.W., Cheung B.K.W., Yim H.C.H. and Lau A.S.Y., Role for Nonstructural Protein 1 of Service Acute Respiratory Syndrome Coronavirus in Chemokine Dysregulation, Journal of Virology. 2007, 81(1): 416-422.

Lee D.C.W. and Lau A.S.Y., Avian influenza virus signaling: implications for the disease severity of H5N1 infection, Signal Transduction. Wiley InterScience, 2007, 7: 64-80.

Lee D.C.W., Chua D.T.T., Sham J.S.T., Wei W.I. and Lau A.S.Y., Differential induction of matrix metallo-proteinase 3 by Epstein-Barr virus latent membrane protein 1, Organisation for Oncology and Translational Research 3^rd Annual Conference, Hong Kong Academy of Medicine (Neoadjuvant & Molecular Therapy in Cancer), 22-23 September 2006.

Lee D.C.W., Chua D.T.T., Sham J.S.T. and Lau A.S.Y., Epstein-Barr virus latent membrane protein 1 enhances matrix metalloproteinase 3 induction in human fibroblast, The 6th International Cytokine Conference 2006 (European Cytokine Network, Supplement Aug 2006, Vol 17 - as official journal of Cytokine 2006-Vienna), Vienna, Austria, 27-31 August 2006. 17: 14-06/P.

Lee D.C.W., Chua D.T.T., Sham J.S.T. and Lau A.S.Y., Expression of Matrix Metallo-proteinase 3 by Epstein-Barr Virus Latent Membrane Protein 1, 6th International Cytokine Conference Proceedings, Medimond International Proceedings, Bologna, Italy, 27-31 August 2006. 101-104.

Li C.B. and Lau A.S.Y., A role for mitogen-activiated protein kinase and Ets-1 in the inductionof interleukin-10 transcription by human immunodeficiecny virus-1 Tat, Immunology. 2007, 121: 337-348.

Liu C., Cheung K., Cheng Y.C., Tilton R., Rong J., Ng K.M., Lau A.S.Y. and Tam P.K.H., An Ontology of Minimal Information for Quality Control of Botanical Drug Product and its Knowledge Base Implemented using the Entity-Attribute-Value Model. , Fifth Meeting of Consortium for Globalization of Chinese Medicine 5th (CGCM), ZhuHai, GuangDong, PRChina, 20-23 September 2006.

Mok K.P., Lee D.C.W., Cheung C.Y., Peiris J.S.M. and Lau A.S.Y., Differential onset of apoptosis in influenza A virus H5N1 - and H1N1 - infected human blood macrophages, Journal of General Virology. 2007, 88(Pt 4): 1275-1280.

Rong J., Shen J., Ng K.M., Liu C., Tam P.K.H. and Lau A.S.Y., Application Of Biological Response Fingerprinting (BioReF) To Define Marker Genes As Potential Quality Control Of Botanical Drug Products, 2006 World Congress on Chinese Medicine (CM2006). 2006.

Rong J., Shen J., Ng K.M., Liu C., Tam P.K.H. and Lau A.S.Y., Genome-wide biological response fingerprinting (BioReF) enables selection of multiple marker genes as potential quality control of botanical drug products, Fifth Meeting of Consortium for Globalization of Chinese Medicine (CGCM). 2006.

Rong J., Cheung Y.H., Shen J., Tam P.K.H. and Lau A.S.Y., Genome-wide biological response fingerprinting (BioReF) of Traditional Chinese Medicine formula ISF-1 reveals a potential role of heme oxygenase-1 pathway in the antioxidant therapy, The 7th International Conference of System Biology. 2006.

Rong J., Tilton R., Shen J., Ng K.M., Liu C., Tam P.K.H., Lau A.S.Y. and Cheng Y.C., Genome-wide biological response fingerprinting (BioReF) of the Chinese botanical formulation ISF-1 enables the selection of multiple marker genes as a potential metric for quality control, Journal of Ethnopharmacology. 2007, 113: 35-44.

Yim H.C.H., Li C.B. and Lau A.S.Y., Effects of HIV-1 Tat on Lipopolysaccharide Induced Cytokine Response, 6th International Cytokine Conference Proceedings, Medimond International Proceedings, Bologna, Italy, 27-31 August 2006. 163-166.

Yim H.C.H., Li C.B. and Lau A.S.Y., Impairment of lipopolysaccharide-activiated signalling pathway by HIV TAT protein, The 6th International Cytokine Conference 2006 (European Cytokine Network, Supplement Aug 2006, Vol 17 - as official journal of Cytokine 2006-Vienna), Vienna, Austria, 27-31 August 2006. 17: 12-17/P.

Researcher : Lau WY

List of Research Outputs

Chan S.Y., Lau W.Y., Wong W.H.S., Cheng L.C., Chau A.K.T. and Cheung Y.F., Chylothorax in Children After Congenital Heart Surgery, Annals of Thoracic Surgery. Elsevier Inc, 2006, 82: 1650-1657.

Researcher : Lau YL

Project Title:	A community-based educational program on thalassaemias to enhance awareness with the aim to reduce burden of thalassaemia related health problems in Hong Kong
Investigator(s):	Lau YL, Ha SY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Health Promotion Projects
Start Date:	09/1997

Abstract:

To enhance the awareness of the community regarding thalassaemias; to counsel, screen and/or refer clinets who come forward to the Unit after the educational sessions; to decrease the disease burden of thalassaemias in Hong Kong as well as to serve as a possible model for southern China.

Project Title:	Comparison of process upgrade varicella vaccine (Puvv) with VARILRIX-TM
Investigator(s):	Lau YL
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Other Funding Scheme
Start Date:	07/1999

Abstract:

To evaluate and provide information on the safety, tolerability, and immunogenicity of the Process Upgrade Varicella Vaccine (PUVV) at ~16,000 or ~50,000 PFU/0.5ml compared to VARILRIX ( estimated at a release dosage of ~50,000PFU/dose) when they are concomitantly with MMRII at separate injection sites.

Project Title:	Seroepidemiological prevalence survey of SARS-associated coronavirus antibody in children residing in Amoy Garden compared to a control group in southern district
Investigator(s):	Lau YL, Peiris JSM, Chiu SSS, Lam TH
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Health and Health Services Research Fund - Full Grants
Start Date:	05/2004

Abstract:

To define the seropositive rate of SARS-associated coronavirus (CV) infection among children who are household contacts or community contacts of SARS cases; to ascertain the full clinical spectrum of SARS-associated CV infection among chldren in Amoy Garden.

Project Title:	Joint Course on Molecular Medicine under the Joint Centre for Advanced Study
Investigator(s):	Lau YL
Department:	Medical Faculty
Source(s) of Funding:	Other Funding Scheme
Start Date:	07/2005

Abstract:

To carry out a joint course on molecular medicine under the Joint Centre for Advanced Study.

Project Title:	The role of dentritic cells in SARS coronavirus infection
Investigator(s):	Lau YL, Peiris JSM
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	08/2005

Abstract:

Despite the SARS epidemic being controlled by case isolation, neither an effective treatment nor an efficacious vaccine is available. Our study will shed lights on the pathogenesis and the immune evasion of SARS-CoV and the knowledge gained may facilitate the development of new treatment protocols and vaccines for SARS.

Project Title:	Immune response of cord blood macrophages and dendritic cells to the 1997 and 2004 strains of avian influenza viruses
Investigator(s):	Lau YL, Peiris JSM
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	09/2005

Abstract:

(1) To determine the host response against human/avian viruses infection. In particular, we will focus on: host immune responses; mechanism of lymphopenia;evolution of H5N1; (2) to campare the cytokine/chemokine expression in antigen presenting cell infected by different influenza viruses; (3) to determine the expression of death receptor ligands in influenza infected APCs and subsequent effect on T cell priming and polarisation.

Project Title:	Association of cytokine and chemokine genes polymorphism with susceptibility to SARS and severity of SARS
Investigator(s):	Lau YL, Peiris JSM
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	09/2005

Abstract:

To test the association of single nucleotide polymorphisms (SNPs) and microsatellites of 6 cytokine and chemokine genes, i.e. interferon-gamma (IFN-gamma), interluekin-12 (IL-12), interleukin-10 (IL-10), tumour necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), and interferon gamma-induced protein-10 (IP-10) with susceptibility to SARS; To test the association of these SNPs and microsatellites with mortality from SARS.

Project Title:	p21 gene polymorphism with systemic lupus erythematosus and rheumatoid arthritis
Investigator(s):	Lau YL, Lau WCS
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	09/2005

Abstract:

Systemic lupus erythematosus (SLE ) is a complex, multifactorial autoimmune disease that is characterized by the production of various autoantibodies. Dysregulated T cell-dependent induction of autoreactive B cells is considered to play a critical role in the development of SLE (1). The etiology and pathogenesis of SLE remain unclear, but the increased concordance rate in monozygotic twins, familial aggregation and high heritability suggested that the genetic factor is involved in the development of SLE (2-4). Cyclin-dependent kinase inhibitor 1A (also known as p21, WAF1 or CDKN1A) is a negative regulator of cyclin dependent kinases (CDKs) (5). The p21 protein encodes a 21 kDa cell cycle regulatory protein that forms quaternary complexes with the entire cyclin/CDK holoenzyme and acts as pancyclin inhibitors (6). It interacts with CDK2, CDK3, CDK4 and CDK6, thereby inhibiting the progression from the G1 to the S phase of the cell cycle (7-9). It can also bind to the replication factor proliferating cell nuclear antigen (PCNA) and inhibit DNA replication (10). The p21 gene contains the p53 binding site that is localized at 2.4 kb upstream from the translational start site and expression of p21 gene was found to be inducible by wild-type p53 gene expression (11). Moreover, several growth factors and cytokines, including interferon (IFN)-α and -γ, can modify p21 expression (12,13). As p21 is an important molecule in mediating cell cycle arrest, loss of function in p21 may favor cell proliferation. Mutations in the p21 gene have been reported to associate with development of various cancers (14-17). And cells lacking p21 gene are defective in DNA repair, which might induce impaired regulation in cell proliferation (18). Inactivating mutations of p21 lead to overexpression and hyperactivation of low-avidity, autoreactive T cells that are found in abundance in the peripheral lymphoid organs of normal individuals (19). These findings suggested that dysregulated p21 gene expression might contribute to defective cell cycle regulation and therefore lead to excessive cell proliferation and activation. The human p21 gene maps on chromosome 6p21.2 (11), which is a susceptibility region for SLE (20,21). A significant reduction in p21 gene expression is found in SLE patients as compared to controls (22). A lower expression in SLE patients is detected at various points from the G1 to G2/M phase through the S phase when compared with controls (22). Therefore, malfunction of p21 protein may contribute to the pathogenesis of systemic autoimmunity through a variety of primary or secondary mechanisms. Indeed, the p21-/- female mice with 129/Sv x C57BL/6 mixed backgrounds show development of severe lupus-like diseases followed by early mortality, high levels of anti-dsDNA antibodies and kidney immune complex deposits (23). However, the p21-/- lupus-prone BXSB mice show inhibition for the development of systemic autoimmunity (24). The p21-/- BXSB lupus-prone mice show enhancement of the Fas/FasL-mediated activation-induced T cell death and therefore promote the apoptosis of the accumulated autoreactive T and B cells, which inhibit spontaneous systemic autoimmunity (24). Although the above findings showed conflicting results for p21 deficiency, they suggested p21 gene is involved in the pathogenesis of SLE. Similar to SLE, rheumatoid arthritis (RA) is also a complex autoimmune diseases that involves genetic factors. Although disease pathogenesis remains unclear, we have previously identified the mannose binding lectin (MBL) gene as susceptibility gene in both SLE and RA (25-27) and recently, we have demonstrated that the low producing genotype of IL-10 promoter is associated with disease susceptibility and serositis in Hong Kong Chinese patients with SLE (28). The identification of susceptibility allele in SLE and RA by case-control study offers the potential for early prediction of risk of disease progression. This should also provide an approach to select the most appropriate candidate genes for intervention with new biological agents which may prevent or arrest disease progression in those at highest risk. References: Please refer to attachment [05-CRCG-SLE-References.doc]

Project Title:	Association of B Lymphocyte Stimulator (BLyS) gene polymorphisms with systemic lupus erythematosus (SLE)
Investigator(s):	Lau YL, Lau WCS
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	09/2006

Abstract:

Systemic lupus erythematosus (SLE ) is a complex, multifactorial autoimmune disease that is characterized by the production of various autoantibodies. Dysregulated T cell-dependent induction of autoreactive B cells is considered to play a critical role in the development of SLE (1). The etiology and pathogenesis of SLE remain unclear, but the increased concordance rate in monozygotic twins, familial aggregation and high heritability suggested that the genetic factor is involved in the development of SLE (2-4). BLyS (BAFF, TALL-1, THANK, zTNF-4 and TNFSF-13B) (NCBI gene ID: 10673) is one of the proteins controlling B cell homeostasis, tolerance and malignancy (5-8). It is critical for B cell survival and maturation. Excessive BLyS production has been shown to trigger severe autoimmune diseases in mice resembling SLE and Sjögren’s syndrome (SS) (9-12). BLyS is expressed by various types of cells including neutrophils, monocytes, macrophages, dendritic cells, follicular dendritic cells (FDCs) in germinal centres (GCs), activated T cells, malignant B cells and CD34+ cells from cord blood (13-20). Messenger RNA for BLyS is found in a variety of tissues, and its levels seem to be relatively constant, suggesting that the production rates for BLyS may be quite stable (21). Several pieces of evidence have suggestd that BLyS may be a candidate gene of SLE. BLyS is encoded on human chromosome 13q34 and murine chromosome 8 (5,7,22). As determined by previous genome-wide screening, this region is a susceptible locus of SLE (LOD score = 2.50) (23) Several polymorphisms have been identified in the human BLyS gene (24). These include four single nucleotide polymorphisms (SNPs) in the promoter region, -1283G/A, -871C/T, -514T/C and -353G/C and one SNP in the intron 1, IVS1-45C/G. Transgenic mice overexpressing BLyS have been well-studied (9-11). In general, BLyS overexpression creates a state of immune hyperreactivity that is skewed primarily towards peripheral B cell activation and terminal differentiation, including increased mature B cells in the periphery, enlarged lymphoid organs and spleens, and hypergammaglobulinemia with autoimmune-like manifestations, including anti-DNA antibodies and Ig-deposition in the kidneys leading to glomerulonephritis with proteinuria and decreased lifespan. In addition, a disproportional increase in the MZ B cells, and the presence of rheumatoid factors have been reported (9). Mice models for SLE, which include the NZBWF1 and the Fas-dependent MRL/lpr mice, were found to have elevated levels of circulating BLyS, which increases during disease progression (10, 25). In SLE patients, BLyS level is found to be elevated and fluctuate during the course of SLE (26). Significantly elevated serum BLyS levels correlated with higher levels of anti-dsDNA antibody titers among SLE patients has also been reported (27-28). In addition, the association of SNPs of BLyS, -1283G/A, -871C/, -514T/C, -353G/C and IVS1-45C/G, with SLE and RA has been demonstrated in a case-control study using 156 SLE patients, 221 RA patients and 227 healthy controls (24). It was found that -871TT genotype was over-represented in SLE patients with anti-Sm antibody (P = 0.082) and the -871 T allele was associated with higher BLyS mRNA level (P = 0.010). As pathogenesis of SLE involves the break of tolerance of B cells, whereas BLyS is essential for B cell survival when B cells progress from transient T1 to transitional T2 stages, MZ B cell formation, differentiation of MZ B cells, stable GC formation, proper humoral responses and immunoglobulin switch and T cell response. We hypothesize that BLyS is a candidate gene of SLE and we aimed to identify whether the BLyS gene polymorphisms are associated with SLE and disease phenotypes in our population. We also aimed to investigate the correlation between these BLyS gene polymorphisms and their circulating levels. Reference: Please refer to attachment [06-CRCG-BLyS-Reference.doc]

List of Research Outputs

Cheuk D.K.L., Shek T.W.H., Chan G.C.F., Lau Y.L., Ha S.Y. and Chiang A.K.S., Parotid Acinic Cell Carcinoma in a Long-Term Survivor of Childhood Acute Lymphoblastic Leukemia, Pediatric Blood Cancer. 2006-7-1, InterScience, 2006, 24: 1-4.

Cheuk D.K.L., Lee T.L., Chiang A.K.S., Ha S.Y., Lau Y.L. and Chan G.C.F., Risk factors and treatment of hemorrhagic cystitis in children who underwent hematopoietic stem cell transplantation, Transplant International. 2007, 20: 73-81.

Chiu S.S.S., Peiris J.S.M., Chan K.H., Wong W.H.S. and Lau Y.L., Immunogenicity and Safety of Intradermal Influenza Immunization at a Reduced Dose in Healthy Children, Pediatrics. 2007, 119: 1076-1082.

Chiu S.S.S. and Lau Y.L., Update on preinatally acquired human immunodeficiency virus infection in children followed at one centre in Hong Kong, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 215-222.

Chong C.Y., Lee T.L., Ho M.H.K., Lee S.L. and Lau Y.L., Review of IgG subclass and IgA deficiency in a tertiary center, Hong Kong Journal of Paediatrics (New series). 2006, 11: 205-209.

Chong W.P. and Lau Y.L., Natural Killer Cells Interact with Apoptotic Cells to Show Anti-inflammatory Properties, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006. 146.

Chow P.C., Ho M.H.K., Lee T.L., Lau Y.L. and Cheung Y.F., Relation of Arterial Stiffness to Left Ventricular Structure and Function in Adolescents and Young Adults With Paediatric-onset Systemic Lupus Erythematosus, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 126.

Chow P.C., Ho M.H.K., Lee T.L., Lau Y.L. and Cheung Y.F., Relation of Arterial Stiffness to Left Ventricular Structure and Function in Adolescents and Young Adults with Pediatric-Onset Systemic Lupus Erythematosus, The Journal of Rheumatology. 2007, 34(6): 1345-1352.

Chung B.H.Y., Lee T.L., Chan G.C.F., Chiang A.K.S., Chan K.W., Ha S.Y. and Lau Y.L., Haematopoietic stem cell transplant for Wiskott-Aldrich Syndrome, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 186-190.

Chung B.H.Y., Lee T.L., Chan G.C.F., Chiang A.K.S., Chan K.W., Ha S.Y. and Lau Y.L., Haematopoietic stem cell transplant for Wiskott-Aldrich syndrome, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 109.

Chung B.H.Y., Lam S.T.S., Tong T.M.F., Li Y.H., Lun K.S., Chan H.C., Or S.F. and Lau Y.L., Identification of 21 novel and 3 known FBN1 mutations in 66 unrelated Chinese probands with Marfan syndrome or Marfan-like phenotypes, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 96.

Ho M.H.K., Lee T.L., Chow W.C. and Lau Y.L., Adrenaline auto-injector (EpiPenÒ) use in Hong Kong experience of Queen Mary Hospital, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 223-228.

Ho M.H.K., Chow P.C., Lee T.L., Tam S., Wong W.H.S., Wong W.K.H.S., Lau Y.L. and Cheung Y.F., Carotid Intima-Media Thickening in Adolescents and Young Adults with Paediatric-Onset Systemic Lupus Erythematosus is Not Related to Traditional and Novel Cardiovascular Risk Factors, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 157.

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.

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.

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.

Kwok J.S.Y., Jones B.M., Lee T.L., Yau Y.S. and Lau Y.L., A young man with unusually severe eczema since childhood, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 229-232.

Kwok K.Y., Tang M.H.Y., Law H.K.W., Ngai C.S.W., Lau Y.L. and Lau E.T., Maternal plasma or human serum albumin in wash buffer enhances enrichment and ex vivo expansion of human umbilical cord blood CD34+ cells, British Journal of Haematology. Blackwell, 2007, 137 (5): 468-474.

Lau Y.L., 抵抗力有問題, 怎辦?, 120^th Anniversary Faculty of Medicine Public Lecture, Hong Kong, 7 April 2007. 2007.

Lau Y.L., Biological Agents - New Treatment Options for Chronic Inflammatory Diseases, Private Practising Paediatricians Study Group, Hong Kong, PRC, 25 October 2006. 2006.

Lau Y.L., Chairman, Emerging and re-emerging infectious diseases in Asian countries, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 2006.

Lau Y.L., Chairman, Oral Presentation on Infectious Diseases, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 2006.

Lau Y.L., Chairperson, Public Lecture I, East-West Alliance Meeting, Li Ka Shing Faculty of Medicine, HKU, 14 April 2007. 2007.

Lau Y.L., Dissemination of BCG infection, 14^th Congress of the Federation of Asia and Oceania Perinatal Societies (FAOPS), Bangkok, Thailand, 2-3 October 2006. 2006, 107-108.

Lau Y.L., Editorial on "Paediatric infectious diseases and immunology", Hong Kong Journal of Paediatrics (New Series). 2006, 11: 177-178.

Lau Y.L., Future development of paediatric immunology and infectious diseases, 兒科醫學發展論壇, 重慶醫科大學附屬兒童醫院, Chonqing, PR China, 21-24 July 2006, 2006.

Lau Y.L., GI Perspectives in Immunodeficiency Disorders, Seoul National University, Seoul, Korea, 23 October 2006. 2006.

Lau Y.L., Infections in Immunocompromised children, Certificate Course in Infectious Diseases & Infection Control, Hong Kong, 17 March 2007. 2007.

Lau Y.L., Keynote lecture on "Pediatric Research in Asia", 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 2006, 80.

Lau Y.L., New respiratory viral infections, 5^th World Congress on Pediatric Critical Care, Geneva, Switzerland, 24-28 June 2007. 2007.

Lau Y.L., 副主編, Pediatrics (Chinese Version), PR China, 2006. 2006.

Lau Y.L., Primary Immunodeficiency, 東京醫學會, 東京大學, Tokyo, Japan, 11 December 2006, 2006.

Lau Y.L., Rotavirus and pneumococcal vaccines - what should we know to support their use?, 2^nd Annual Scientific Meeting of Macau Pediatric Society, 20 May 2007. 2007.

Lau Y.L., Skin Manifestations in Primary Immunodeficiencies, Annual Scientific Meeting 2006, The Hong Kong Society of Dermatology & Venereology, Hong Kong, 9 July 2006. 2006.

Lau Y.L., Skin manifestations in primary immunodeficiencies, Hong Kong Journal of Dermatology & Venereology. 2006, 14(3): 155-156.

Lau Y.L., What should we know to support the use of rotavirus vaccine in Asia, The Korean Society of Pediatric Gastroenterology and Nutrition, Seoul, Korea, 21 Octoer 2006. 2006.

Lau Y.L., What we learned from SARS to face Avian Flu, 5^th World Congress on Pediatric Critical Care, Geneva, Switzerland, 24-28 June 2007. 2007.

Lau Y.L., Zhou J. and Tu W., 巨噬細胞活化綜合征基因相關性研究及治療構想, 中華兒科雜誌, Chinese Medical Association, 2006, 44(11): 803-805.

Lau Y.L., 第十三屆編輯會委員, 中華兒科雜誌, PRC, October 2006, 2006.

Lau Y.L., 編委會委員, 中華醫學雜誌 (英文版), 2006.

Law H.K.W. and Lau Y.L., Neonatal immune response to mycobacterium bovis bacillus Calmette-Guerin (BCG), Keystone Symposia on Molecular and Cellular Biology, Vancouver, Canada, 20-25 March 2007. 107.

Lee P.P.W., Chan K.W., Lee T.L., Jiang L., Mak H.S., Fok S.F.S. and Lau Y.L., Clinical Characteristics and gp91phox Gene Mutations in Seventeen Chinese Children with X-linked Chronic Granulomatous Disease (Young Investigator Award), 2nd Congress of Asian Society for Pediatric Research. 2006.

Lee P.P.W., Chan K.W., Lee T.L., Jiang L., Mak H.S., Fok S.F.S., Hui Y.F., Li C., Yang X. and Lau Y.L., Clinical Characteristics and gp91phox Gene Mutations in Seventeen Chinese Children with X-linked Chronic Granulomatous Disease, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 96.

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 P.P.W., Lee T.L., Ho M.H.K., Wong W.H.S. and Lau Y.L., Herpes Zoster in Juvenile-Onset Systemic Lupus Erythematosus, Pediatric Infectious Disease Journal. 2006, 25: 728-732.

Lee P.P.W., Lee T.L., Ho M.H.K., Wong W.H.S. and Lau Y.L., Recurrent Major Infections in Juvenile-Onset Systemic Lupus Erythematosus? A Close Link with Long-term Disease Damage, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 186.

Lee P.P.W., Lee T.L., Ho M.H.K., Wong W.H.S. and Lau Y.L., Recurrent major infections in juvenile-onset systemic Lupus erythematosus - a close link with long-term disease damage, Rheumatology. 2007, 1-7.

Lee P.P.W., Jiang L.P., Wang X.C., Chan K.W., Tu W. and Lau Y.L., Severe mycobacterial infections in two pairs of Chinese siblings with interleukin-12 receptor b1 deficiency, European Journal of Pediatrics. 2007-6-30, Springer-Verlag, 2007.

Lee P.P.W., Chan K.W., Tu W. and Lau Y.L., Severe mycobacterial infections in two pairs of Chinese siblings with interleukin-12 receptor 1 deficiency., Asia Pacific Primary Immune Deficiency (APPID) Summer School, 6-11th May 2007, Queensland, Australia. 2007.

Lee P.P.W., Lee T.L., Wong W.H.S. and Lau Y.L., The use of methotrexate in juvenile idiopathic arthritis: a single center experience, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 191-198.

Lee T.L., Chan K.W. and Lau Y.L., An 8-year-old girl with urticaria since birth, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 233-234.

Lee T.L., Ho M.H.K., Ha S.Y., Chan G.C.F. and Lau Y.L., Autologous haemopoietic stem cell transplantation for severe autoimmune diseases in Hong Kong, 2nd Congress of Asian Society for Pediatric Research, Yokohama, Japan, 8-10 December 2006.

Lee T.L., Law H.K.W., Chan G.C.F., Ha S.Y., Ho M.H.K., Chan K.W. and Lau Y.L., Successful treatment of X-linked lymphoproliferative disease (XLP) with anti-CD20 monoclonal antibody (Rituximab) followed by Mismatched unrelated cord blood transfusion, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 210-214.

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.

Mo F.Y., Yip H.K., Law H.K.W., Lau Y.L. and Chan G.C.F., Effects of bacterial toxins on the growth, differentiation and toll-like receptor genes of human mesenchymal stem cells, Cytokine 2006. 17: 120.

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.

Ng M.W., Zhou G., Chong W.P., Lee W.Y., Law H.K.W., Zhang H., Wong W.H.S., Fok S.F.S., Zhai Y., Yung R.W.H., Chow E.Y., Au K.L., Chan E.Y.T., Lim W., Peiris J.S.M., He F. and Lau Y.L., The association of RANTES polymorphism with severe acute respiratory syndrome in Hong Kong and Beijing Chinese, BMC Infectious Diseases. 2007, 7: 50.

Siu H.O., Yang W., Lau C.S., Chan T.M., Wong W.H.S., Lau Y.L. and Alarcon-Riquelme M.E., Association of Interferon Regulatory Factor 5 (IRF5) polymorphisms with systemic lupus erythematosus (SLE), European Human Genetics Conference, Nice, France, 16-19 June 2007. 279.

Thiel S., Steffensen R., Christensen I.J., Ip E.W.K., Lau Y.L., Reason I.J.M., Eiberg H., Gadjeva M., Ruseva M. and Jensenius J.C., Deficiency of mannan-binding lection associated serine protease-2 due to missense polymorphisms, Genes and Immunity. Nature Publishing Group, 2007, 1-10.

Tsang H.Y.H., Lee S.L., Lee T.L., Wong K. and Lau Y.L., Prevalence of respiratory function abnormalities in asymptomatic Chinese patients wit juvenile onset systemic lupus erythematosus, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 199-204.

Tso H.W. and Lau Y.L., Interaction of Mesenchymal Stem Cells and Apoptotic Cells in Autoimmunity, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006. 156.

Tu W. and Lau Y.L., Antiviral Activities Of Human Gammadelta-t Cells Against Influenza A Viruses, Innate Immunity:receptors, Response, Regulation/society For Leukocyte Biology And International Endotoxin And Innate Immunity Society, Nov 9-11, 2006. San Antonio, TX, USA. 2006.

Tu W., Dionis K., Lewis D.B. and Lau Y.L., Ex vivo Generation of Alloantigen-specific Human Regulatory T cells by CD40-activated B cells, American Transplant Congress, May 5-9, 2007, San Francisco, USA. 2007.

Tu W., Mao H. and Lau Y.L., Immune defense mechanisms against human and avian influenza viruses, Chinese Journal of Pediatrics. 2007, 45(11): 831-834.

Yip M.S., Law H.K.W. and Lau Y.L., Comparison of Immune Responses Triggered by Human Metapneumovirus and Respiratory Syncytial Virus in Human Respiratory Epithelial Cells, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006. 83.

Zhou J., Law H.K.W., Tu W., Cheung C.Y., Ng I.H.Y., Peiris J.S.M. and Lau Y.L., Decreased T lymphocytes activation and Cytotoxic activity in avian influenza: an in vitro study, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 164.

Zhou J., Law H.K.W., Cheung C.Y., Ng I.H.Y., Peiris J.S.M. and Lau Y.L., Differential expression of chemokines and their receptors in adult and neonatal macrophages infected with human or avian influenza viruses, Journal of Infectious Diseases. Infectious Diseases Society of America, 2006, 194: 61-70.

Zhou J., Law H.K.W., Cheung C.Y., Ng I.H.Y., Peiris J.S.M. and Lau Y.L., Interaction of mannose binding lectin with H1N1 and H5N1 influenza A viruses, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 110.

Researcher : Law HKW

List of Research Outputs

Kwok K.Y., Tang M.H.Y., Law H.K.W., Ngai C.S.W., Lau Y.L. and Lau E.T., Maternal plasma or human serum albumin in wash buffer enhances enrichment and ex vivo expansion of human umbilical cord blood CD34+ cells, British Journal of Haematology. Blackwell, 2007, 137 (5): 468-474.

Law H.K.W., English Editor (Senior), The Journal of Clinical Pediatrics. 临床儿科杂志, 2006, July 2006 - Present.

Law H.K.W. and Lau Y.L., Neonatal immune response to mycobacterium bovis bacillus Calmette-Guerin (BCG), Keystone Symposia on Molecular and Cellular Biology, Vancouver, Canada, 20-25 March 2007. 107.

Law H.K.W., Real-time Quantitative Gene Expression Analysis for Infection and Immunity Research, Hong Kong Institute of Medical Laboratory Sciences 40th Anniversary Celebration - Annual Scientific Meeting and Annual General Meeting. 2006, 26.

Lee T.L., Law H.K.W., Chan G.C.F., Ha S.Y., Ho M.H.K., Chan K.W. and Lau Y.L., Successful treatment of X-linked lymphoproliferative disease (XLP) with anti-CD20 monoclonal antibody (Rituximab) followed by Mismatched unrelated cord blood transfusion, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 210-214.

Mo F.Y., Yip H.K., Law H.K.W., Lau Y.L. and Chan G.C.F., Effects of bacterial toxins on the growth, differentiation and toll-like receptor genes of human mesenchymal stem cells, Cytokine 2006. 17: 120.

Ng M.W., Zhou G., Chong W.P., Lee W.Y., Law H.K.W., Zhang H., Wong W.H.S., Fok S.F.S., Zhai Y., Yung R.W.H., Chow E.Y., Au K.L., Chan E.Y.T., Lim W., Peiris J.S.M., He F. and Lau Y.L., The association of RANTES polymorphism with severe acute respiratory syndrome in Hong Kong and Beijing Chinese, BMC Infectious Diseases. 2007, 7: 50.

Yip M.S., Law H.K.W. and Lau Y.L., Comparison of Immune Responses Triggered by Human Metapneumovirus and Respiratory Syncytial Virus in Human Respiratory Epithelial Cells, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006. 83.

Zhou J., Law H.K.W., Tu W., Cheung C.Y., Ng I.H.Y., Peiris J.S.M. and Lau Y.L., Decreased T lymphocytes activation and Cytotoxic activity in avian influenza: an in vitro study, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 164.

Zhou J., Law H.K.W., Cheung C.Y., Ng I.H.Y., Peiris J.S.M. and Lau Y.L., Differential expression of chemokines and their receptors in adult and neonatal macrophages infected with human or avian influenza viruses, Journal of Infectious Diseases. Infectious Diseases Society of America, 2006, 194: 61-70.

Zhou J., Law H.K.W., Cheung C.Y., Ng I.H.Y., Peiris J.S.M. and Lau Y.L., Interaction of mannose binding lectin with H1N1 and H5N1 influenza A viruses, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 110.

Researcher : Law HY

List of Research Outputs

Cheung B.K.W., Law H.Y. and Lau A.S.Y., Identification of a Viral Gene Responsible for SARS-Coronavirus-induced Chemokine Dysregulation, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006. 145.

Law H.Y., Lee D.C.W., Cheung B.K.W., Yim H.C.H. and Lau A.S.Y., Role for Nonstructural Protein 1 of Service Acute Respiratory Syndrome Coronavirus in Chemokine Dysregulation, Journal of Virology. 2007, 81(1): 416-422.

Researcher : Lee DCW

List of Research Outputs

Chik S.C.C., Lee D.C.W., Li C.B., Mak W.W., Tam P.K. and Lau A.S.Y., Immunomodulatory Effects of Ginseng on Human Monocytic Cells, The 6^th International Symposium on Natural Medicine and Microflora (6^th ISNMM), Seoul, Korea, 6-8 August 2006. 100-101.

Law H.Y., Lee D.C.W., Cheung B.K.W., Yim H.C.H. and Lau A.S.Y., Role for Nonstructural Protein 1 of Service Acute Respiratory Syndrome Coronavirus in Chemokine Dysregulation, Journal of Virology. 2007, 81(1): 416-422.

Lee D.C.W. and Lau A.S.Y., Avian influenza virus signaling: implications for the disease severity of H5N1 infection, Signal Transduction. Wiley InterScience, 2007, 7: 64-80.

Lee D.C.W., Chua D.T.T., Sham J.S.T., Wei W.I. and Lau A.S.Y., Differential induction of matrix metallo-proteinase 3 by Epstein-Barr virus latent membrane protein 1, Organisation for Oncology and Translational Research 3^rd Annual Conference, Hong Kong Academy of Medicine (Neoadjuvant & Molecular Therapy in Cancer), 22-23 September 2006.

Lee D.C.W., Chua D.T.T., Sham J.S.T. and Lau A.S.Y., Epstein-Barr virus latent membrane protein 1 enhances matrix metalloproteinase 3 induction in human fibroblast, The 6th International Cytokine Conference 2006 (European Cytokine Network, Supplement Aug 2006, Vol 17 - as official journal of Cytokine 2006-Vienna), Vienna, Austria, 27-31 August 2006. 17: 14-06/P.

Lee D.C.W., Chua D.T.T., Sham J.S.T. and Lau A.S.Y., Expression of Matrix Metallo-proteinase 3 by Epstein-Barr Virus Latent Membrane Protein 1, 6th International Cytokine Conference Proceedings, Medimond International Proceedings, Bologna, Italy, 27-31 August 2006. 101-104.

Mok K.P., Lee D.C.W., Cheung C.Y., Peiris J.S.M. and Lau A.S.Y., Differential onset of apoptosis in influenza A virus H5N1 - and H1N1 - infected human blood macrophages, Journal of General Virology. 2007, 88(Pt 4): 1275-1280.

Researcher : Lee PPW

List of Research Outputs

Chiang A.K.S., Lee P.P.W., Li C.K., Yuen H.L., Lee A.C.W. and Li C.K., Treatment outcome of hepatoblastoma and hepatocellular carcinoma in Hong Kong children, Second Cross Strait Symposium on Pediatric Oncology, Taiwan, 21-23 September 2006.

Chung B.H.Y., Yang W., Lee P.P.W., Wong W.B. and Zhu Y.D., Clinical Quiz (case 21), http://www.hku.hk/paed/student area/clinical quiz. 2007.

Chung B.H.Y., Yang W., Lee P.P.W., Wong W.B. and Zhou Y.D., Clinical Quiz (case 22), http://www.hku.hk/paed/student area/clinical quiz. 2007.

Chung B.H.Y., Yang W., Lee P.P.W., Wong W.B. and Zhu Y.D., Clinical Quiz (case 23), http://www.hku.hk/paed/student area/clinical quiz. 2007.

Lee P.P.W., Chan K.W., Lee T.L., Jiang L., Mak H.S., Fok S.F.S. and Lau Y.L., Clinical Characteristics and gp91phox Gene Mutations in Seventeen Chinese Children with X-linked Chronic Granulomatous Disease (Young Investigator Award), 2nd Congress of Asian Society for Pediatric Research. 2006.

Lee P.P.W., Chan K.W., Lee T.L., Jiang L., Mak H.S., Fok S.F.S., Hui Y.F., Li C., Yang X. and Lau Y.L., Clinical Characteristics and gp91phox Gene Mutations in Seventeen Chinese Children with X-linked Chronic Granulomatous Disease, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 96.

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 P.P.W., Lee T.L., Ho M.H.K., Wong W.H.S. and Lau Y.L., Herpes Zoster in Juvenile-Onset Systemic Lupus Erythematosus, Pediatric Infectious Disease Journal. 2006, 25: 728-732.

Lee P.P.W., Lee T.L., Ho M.H.K., Wong W.H.S. and Lau Y.L., Recurrent Major Infections in Juvenile-Onset Systemic Lupus Erythematosus? A Close Link with Long-term Disease Damage, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 186.

Lee P.P.W., Lee T.L., Ho M.H.K., Wong W.H.S. and Lau Y.L., Recurrent major infections in juvenile-onset systemic Lupus erythematosus - a close link with long-term disease damage, Rheumatology. 2007, 1-7.

Lee P.P.W., Jiang L.P., Wang X.C., Chan K.W., Tu W. and Lau Y.L., Severe mycobacterial infections in two pairs of Chinese siblings with interleukin-12 receptor b1 deficiency, European Journal of Pediatrics. 2007-6-30, Springer-Verlag, 2007.

Lee P.P.W., Chan K.W., Tu W. and Lau Y.L., Severe mycobacterial infections in two pairs of Chinese siblings with interleukin-12 receptor 1 deficiency., Asia Pacific Primary Immune Deficiency (APPID) Summer School, 6-11th May 2007, Queensland, Australia. 2007.

Lee P.P.W., Lee T.L., Wong W.H.S. and Lau Y.L., The use of methotrexate in juvenile idiopathic arthritis: a single center experience, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 191-198.

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.

Researcher : Lee SL

List of Research Outputs

Chong C.Y., Lee T.L., Ho M.H.K., Lee S.L. and Lau Y.L., Review of IgG subclass and IgA deficiency in a tertiary center, Hong Kong Journal of Paediatrics (New series). 2006, 11: 205-209.

Chow P.C., Lee S.L., Tang M.H.Y., Chan K.L., Lee C.P., Lam B.C.C. and Tsoi N.S., Management and outcome of antenatally diagnosed congenital cystic adenomatoid malformation of the lung, Hong Kong Medical Journal. 2007, 13(1): 31-39.

Tsang H.Y.H., Lee S.L., Lee T.L., Wong K. and Lau Y.L., Prevalence of respiratory function abnormalities in asymptomatic Chinese patients wit juvenile onset systemic lupus erythematosus, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 199-204.

Xu Z.F., Xu Z.F., Cheuk D.K.L. and Lee S.L., Clinical Evaluation in Predicting Childhood Obstructive Sleep Apnea, Chest. 2006, 130(6): 1765-1771.

Researcher : Lee TL

List of Research Outputs

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.

Cheuk D.K.L., Lee T.L., Chiang A.K.S., Ha S.Y. and Chan G.C.F., Autologous Haematopoietic Stem Cell Transplantation for High Risk Brain Tumours in Children, 13^th Hong Kong International Cancer Congress, 3^rd Annual Meeting Centre for Cancer Research, HKU, 15-17 November 2006.

Cheuk D.K.L., Lee T.L., Chiang A.K.S., Ha S.Y., Lau Y.L. and Chan G.C.F., Risk factors and treatment of hemorrhagic cystitis in children who underwent hematopoietic stem cell transplantation, Transplant International. 2007, 20: 73-81.

Chong C.Y., Lee T.L., Ho M.H.K., Lee S.L. and Lau Y.L., Review of IgG subclass and IgA deficiency in a tertiary center, Hong Kong Journal of Paediatrics (New series). 2006, 11: 205-209.

Chow P.C., Ho M.H.K., Lee T.L., Lau Y.L. and Cheung Y.F., Relation of Arterial Stiffness to Left Ventricular Structure and Function in Adolescents and Young Adults With Paediatric-onset Systemic Lupus Erythematosus, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 126.

Chow P.C., Ho M.H.K., Lee T.L., Lau Y.L. and Cheung Y.F., Relation of Arterial Stiffness to Left Ventricular Structure and Function in Adolescents and Young Adults with Pediatric-Onset Systemic Lupus Erythematosus, The Journal of Rheumatology. 2007, 34(6): 1345-1352.

Chung B.H.Y., Lee T.L., Chan G.C.F., Chiang A.K.S., Chan K.W., Ha S.Y. and Lau Y.L., Haematopoietic stem cell transplant for Wiskott-Aldrich Syndrome, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 186-190.

Chung B.H.Y., Lee T.L., Chan G.C.F., Chiang A.K.S., Chan K.W., Ha S.Y. and Lau Y.L., Haematopoietic stem cell transplant for Wiskott-Aldrich syndrome, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 109.

Ho M.H.K., Lee T.L., Chow W.C. and Lau Y.L., Adrenaline auto-injector (EpiPenÒ) use in Hong Kong experience of Queen Mary Hospital, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 223-228.

Ho M.H.K., Chow P.C., Lee T.L., Tam S., Wong W.H.S., Wong W.K.H.S., Lau Y.L. and Cheung Y.F., Carotid Intima-Media Thickening in Adolescents and Young Adults with Paediatric-Onset Systemic Lupus Erythematosus is Not Related to Traditional and Novel Cardiovascular Risk Factors, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 157.

Kwok J.S.Y., Jones B.M., Lee T.L., Yau Y.S. and Lau Y.L., A young man with unusually severe eczema since childhood, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 229-232.

Lee P.P.W., Chan K.W., Lee T.L., Jiang L., Mak H.S., Fok S.F.S. and Lau Y.L., Clinical Characteristics and gp91phox Gene Mutations in Seventeen Chinese Children with X-linked Chronic Granulomatous Disease (Young Investigator Award), 2nd Congress of Asian Society for Pediatric Research. 2006.

Lee P.P.W., Chan K.W., Lee T.L., Jiang L., Mak H.S., Fok S.F.S., Hui Y.F., Li C., Yang X. and Lau Y.L., Clinical Characteristics and gp91phox Gene Mutations in Seventeen Chinese Children with X-linked Chronic Granulomatous Disease, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 96.

Lee P.P.W., Lee T.L., Ho M.H.K., Wong W.H.S. and Lau Y.L., Herpes Zoster in Juvenile-Onset Systemic Lupus Erythematosus, Pediatric Infectious Disease Journal. 2006, 25: 728-732.

Lee P.P.W., Lee T.L., Ho M.H.K., Wong W.H.S. and Lau Y.L., Recurrent Major Infections in Juvenile-Onset Systemic Lupus Erythematosus? A Close Link with Long-term Disease Damage, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 186.

Lee P.P.W., Lee T.L., Ho M.H.K., Wong W.H.S. and Lau Y.L., Recurrent major infections in juvenile-onset systemic Lupus erythematosus - a close link with long-term disease damage, Rheumatology. 2007, 1-7.

Lee P.P.W., Lee T.L., Wong W.H.S. and Lau Y.L., The use of methotrexate in juvenile idiopathic arthritis: a single center experience, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 191-198.

Lee T.L., Chan K.W. and Lau Y.L., An 8-year-old girl with urticaria since birth, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 233-234.

Lee T.L., Approach to a child with limb pain, Hong Kong Bulletin on Rheumatic Diseases. 2007, 2(2): 68-71.

Lee T.L., Ho M.H.K., Ha S.Y., Chan G.C.F. and Lau Y.L., Autologous haemopoietic stem cell transplantation for severe autoimmune diseases in Hong Kong, 2nd Congress of Asian Society for Pediatric Research, Yokohama, Japan, 8-10 December 2006.

Lee T.L., Clinical Evaluation of a Patient with Familial Periodic Fever Syndrome, The Hong Kong Medical Diary. 2007, 12(5): 26-27.

Lee T.L., Current Management of Juvenile Idiopathic Arthritis, Medical Bulletin. 2006, 11(11): 17-19.

Lee T.L., Law H.K.W., Chan G.C.F., Ha S.Y., Ho M.H.K., Chan K.W. and Lau Y.L., Successful treatment of X-linked lymphoproliferative disease (XLP) with anti-CD20 monoclonal antibody (Rituximab) followed by Mismatched unrelated cord blood transfusion, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 210-214.

Tsang H.Y.H., Lee S.L., Lee T.L., Wong K. and Lau Y.L., Prevalence of respiratory function abnormalities in asymptomatic Chinese patients wit juvenile onset systemic lupus erythematosus, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 199-204.

Researcher : Lee WY

List of Research Outputs

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.

Ng M.W., Zhou G., Chong W.P., Lee W.Y., Law H.K.W., Zhang H., Wong W.H.S., Fok S.F.S., Zhai Y., Yung R.W.H., Chow E.Y., Au K.L., Chan E.Y.T., Lim W., Peiris J.S.M., He F. and Lau Y.L., The association of RANTES polymorphism with severe acute respiratory syndrome in Hong Kong and Beijing Chinese, BMC Infectious Diseases. 2007, 7: 50.

Researcher : Li CB

List of Research Outputs

Cheng M., Xing B., Cheung B.K.W. and Li C.B., IFNg Inhibition of TNFa-enhanced Glioma Cell Invasion, 6th International Cytokine Conference Proceedings, Medimond International Proceedings, Bologna, Italy, 27-31 August 2006. 35-39.

Cheng M., Xing B., Cheung B.K.W., Li C.B. and Lau A.S.Y., IFNg regulation of TNF a-enhanced glioma cell migration through induction of matrix metalloproteinase expression, The 6th International Cytokine Conference 2006 (European Cytokine Network, Supplement Aug 2006, Vol 17 - as official journal of Cytokine 2006-Vienna), Vienna, Austria, 27-31 August 2006. 17: 02-21/P.

Chik S.C.C., Lee D.C.W., Li C.B., Mak W.W., Tam P.K. and Lau A.S.Y., Immunomodulatory Effects of Ginseng on Human Monocytic Cells, The 6^th International Symposium on Natural Medicine and Microflora (6^th ISNMM), Seoul, Korea, 6-8 August 2006. 100-101.

Lau A.S.Y., Cheng M., Lin S.S. and Li C.B., Mechanism of HIV dysregulation of the interferon-gamma signal transduction: a role for transactivator tat in suppression of Jak/STAT pathways, 8th World Congress on Inflammation, Copenhagen, Bella Center, Copenhagen, Denmark, June 16-20. 2007.

Yim H.C.H., Li C.B. and Lau A.S.Y., Effects of HIV-1 Tat on Lipopolysaccharide Induced Cytokine Response, 6th International Cytokine Conference Proceedings, Medimond International Proceedings, Bologna, Italy, 27-31 August 2006. 163-166.

Yim H.C.H., Li C.B. and Lau A.S.Y., Impairment of lipopolysaccharide-activiated signalling pathway by HIV TAT protein, The 6th International Cytokine Conference 2006 (European Cytokine Network, Supplement Aug 2006, Vol 17 - as official journal of Cytokine 2006-Vienna), Vienna, Austria, 27-31 August 2006. 17: 12-17/P.

Researcher : Li J

List of Research Outputs

Li J., Kwong D.L.W. and Chan G.C.F., The effects of various irradiation doses on the growth and differentiation of marrow deerived human mesenchymal stromal cells, The 11^th Congress of the Asia Pacific Bone Marrow Transplantation (oral presentation), Nagoya, Japan, 27-29 October 2006.

Li J., Kwong D.L.W. and Chan G.C.F., The effects of various irradiation doses on the growth and differentiation of marrow-derived human mesenchymal stromal cells, Pediatric Transplantation. Blackwell Munksgaard, 2007, 11: 379-387.

Researcher : Li YH

List of Research Outputs

Cheuk D.K.L., Li Y.H. and Wong V.C.N., Exon 3 Polymorphisms of Dopamine D4 Receptor (DRD4) Gene and Attention Deficit Hyperactivity Disorder in Chinese Children, American Journal of Medical Genetics Part B (Neuropsychiatric Genetics). 2006, 141B: 907-911.

Chung B.H.Y., Lam S.T.S., Tong T.M.F., Li Y.H., Lun K.S., Chan H.C., Or S.F. and Lau Y.L., Identification of 21 novel and 3 known FBN1 mutations in 66 unrelated Chinese probands with Marfan syndrome or Marfan-like phenotypes, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 96.

Researcher : Liang X

List of Research Outputs

Chow P.C., Liang X., Cheung E.W.Y., Wong K.T., Lun K.S., Yung T.C., Chau A.K.T. and Cheung Y.F., Right Ventricular Dyssynchrony in Patients After Atrial Switch Operation for Transposition of the Great Arteries, Hong Kong College of Cardiology, Fifteenth Annual Scientific Congress Proceedings (Free Paper Session, Paediatric Cardiology I), Hong Kong, 4-6 May 2007. 15: 58.

Liang X., Cheung E.W.Y., Wong S.J., Chau A.K.T. and Cheung Y.F., Restrictive Right Ventricular Physiology after Biventricular Repair of Pulmonary Atresia with Intact Ventricular Septum, Hong Kong College of Cardioloyg, Fifteenth Annual Scientific Congress Proceedings (Free Paper Session, Paediatric Cardiology I), Hong Kong, 4-6 May 2007. 15: 58.

Researcher : Lin SS

List of Research Outputs

Lau A.S.Y., Cheng M., Lin S.S. and Li C.B., Mechanism of HIV dysregulation of the interferon-gamma signal transduction: a role for transactivator tat in suppression of Jak/STAT pathways, 8th World Congress on Inflammation, Copenhagen, Bella Center, Copenhagen, Denmark, June 16-20. 2007.

Researcher : Low LCK

Project Title:	IDF WPR Childhood and Adolescence Diabcare 2003 - an audit and benchmarking study on Type 2 diabetes management in childhood and adolescence in Western Pacific region countries
Investigator(s):
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Other Funding Scheme
Start Date:	06/2003

Abstract:

To describe diabetes control, diabetes management and complication status in children and adolescents with Type 2 diabetes mellitus in the WPR: a) to investigate the relationship between the above factors; b) to provide means of measuring the quality of diabetes management.

List of Research Outputs

Cheung P.T., Low L.C.K. and Kwan E.Y.W., Aldosterone synthetase (corticosterone methyloxidase) deficiency type II in a Chinese boy, 4th Biennial Scientific Meeting of the Asia Pacific Paediatric Endocrine Society, Pattaya, Thailand, 1 - 4 November . 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.

Low L.C.K., Advances in hypogonadism, National Pediatric Endocrinology (CME) Training Workshop, Wuhan, PR China. 13 - 17 November . 2006.

Low L.C.K., Advances in hypongonadism, Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology, Wuhan, PR China, 13-17 November 2006. 2006.

Low L.C.K., Advisor to Hong Kong Juvenile Diabetes Associaton, 2007. 2007.

Low L.C.K., Associate Editor, Hong Kong Journal of Pediatrics, 2006-2007. 2007.

Low L.C.K., Chairman Borad of Studies Master of Medical Science, 2006-2007. 2007.

Low L.C.K., Chairman of Subcommittee on Pediatric Endocrinology of Inherited Metabolic Disorder, 2007. 2007.

Low L.C.K., Chairperson of Kaichi Kida Oral Session 1, The 4^th Biennial Scientific Meeting Asia Pacific Paediatric Endocrine Society 2006, Rayong, Thailand, 28 October - 1 November 2006. 2006.

Low L.C.K., Childhood Obesity, Endocrine Division, Guangdong Medical Association of the Chinese Medical Association, Guangzhou, PR China. 8 November . 2006.

Low L.C.K., College V-President, till October 2006. 2006.

Low L.C.K., College, President, November 2006. 2006.

Low L.C.K., Disorders of Puberty in Pediatric Endocrinology, Pediatric Endocrinology, 2^nd Ed. 第九章:青春發育異常, 小兒內分泌學 (第二版) 顏純, 王慕逖 (主編), 人民衛生出版社, 北京 2007, 2007-6-30, 人民衛生出版社, 2007, 285-343.

Low L.C.K., Editorial Board Member, Expert Review of Endocrinology & Metabolism (March 2005-date). 2007.

Low L.C.K., Editorial Director, Journal of Obstetric, Paediatric and Gynecology, Pediatric Diabetes. 2007.

Low L.C.K., Global epidemic of obesity and diabetes. International Society for Pediatric and Adolescent Diabetes Science School (Fudan Children Hospital Medical Center), Shanghai, PR China. 29 November - 1 December 2006.

Low L.C.K., Growth Failure in Thalassaemia Major, 2nd National Thalassaemia Seminar 2006. Kuala Lumpur, Malaysia, 6-7 May 2006, 2006.

Low L.C.K., Hypogonadism (incl Thalassaemia), Asia Pacific Paediatric Endocrine Society Fellow's Course, Rayong Resort, Rayong, Thailand, 28 October - 1 November 2006.

Low L.C.K., Hypogonadism and its management in Thalassaemia Major, 2nd National Thalassaemia Seminar 2006. Kuala Lumpur, Malaysia, 6-7 May 2006, 2006.

Low L.C.K., Journal of Pediatric Endocrinology and Metabolism, Pediatric Endocrine Rev. 2007.

Low L.C.K., Licentitate Committee, Grant review board, 2006-2007. 2007.

Low L.C.K., Member of the Second Editorial Board of the Chinese Journal of Contemporary Pediatrics since (November 2003-date). 2006.

Low L.C.K., Member, Scientific Committee, Fourth International Huaxia Congress of Endocrinology, Hong Kong, 15-18 December 2006. 2006.

Low L.C.K., Paediatric Phaeochromocytoma, The 4^th Biennial Scientific Meeting Asia Pacific Paediatric Endocrine Society 2006, Rayong, Thailand, 28 October - 1 November 2006.

Low L.C.K., Pediatric Research (Nov 2003-date), Editorial Board Member, Combined Editorial Board . 2007.

Low L.C.K., Role of bisphosphonate in children, The 4^th Hong Kong International Orthopaedic Forum, Department of Orthopaedics and Traumatology, HKU, 21-22 April 2007. 47.

Low L.C.K., The metabolic syndrome - does it exist? International Society for Pediatric and Adolescent Diabetes Science School (Fudan Children Hospital Medical Center), Shanghai, PR China. 29 November - 1 December 2006.

Low L.C.K., Type II diabetes in Children and Adolescents, Endocrine Division, Guangdong Medical Association of the Chinese Medical Association, Guangzhou, PR China. 8 November . 2006.

Poon G.W.K., Kwan E.Y.W., Cheung P.T. and Low L.C.K., Mutation analysis of the GLUT2 Gene in a Chinese patient with Fanconi-Bickel Syndrome, 4th Biennial Scientific Meeting of the Asia Pacific PaediatricEndocrine Society, Pattaya, Thailand, 1-4 November. 2006.

Researcher : Lun KS

List of Research Outputs

Chow P.C., Cheung E.W.Y., Chong` C.Y., Lun K.S., Yung T.C., Wong K.T., Chau A.K.T. and Cheung Y.F., Brain Natriuretic Peptide as a Biomarker of Systemic Right Ventricular Function in Patients After Atrial Switch Operation, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 126.

Chow P.C., Liang X., Cheung E.W.Y., Wong K.T., Lun K.S., Yung T.C., Chau A.K.T. and Cheung Y.F., Right Ventricular Dyssynchrony in Patients After Atrial Switch Operation for Transposition of the Great Arteries, Hong Kong College of Cardiology, Fifteenth Annual Scientific Congress Proceedings (Free Paper Session, Paediatric Cardiology I), Hong Kong, 4-6 May 2007. 15: 58.

Chung B.H.Y., Lam S.T.S., Tong T.M.F., Li Y.H., Lun K.S., Chan H.C., Or S.F. and Lau Y.L., Identification of 21 novel and 3 known FBN1 mutations in 66 unrelated Chinese probands with Marfan syndrome or Marfan-like phenotypes, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 96.

Researcher : Mak HS

List of Research Outputs

Chan K.W., Fong S.W., Mak H.S. and Chan S.Y., Expression of Tspyl2 in Transgenic Mice Reduces Cardiac Hypertrophy upon Hypertrophic Stress, 11^th Research Postgraduate Symposium, HKU, 7 December 2006. 169.

Lee P.P.W., Chan K.W., Lee T.L., Jiang L., Mak H.S., Fok S.F.S. and Lau Y.L., Clinical Characteristics and gp91phox Gene Mutations in Seventeen Chinese Children with X-linked Chronic Granulomatous Disease (Young Investigator Award), 2nd Congress of Asian Society for Pediatric Research. 2006.

Lee P.P.W., Chan K.W., Lee T.L., Jiang L., Mak H.S., Fok S.F.S., Hui Y.F., Li C., Yang X. and Lau Y.L., Clinical Characteristics and gp91phox Gene Mutations in Seventeen Chinese Children with X-linked Chronic Granulomatous Disease, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 96.

Researcher : Mao H

List of Research Outputs

Tu W., Mao H. and Lau Y.L., Immune defense mechanisms against human and avian influenza viruses, Chinese Journal of Pediatrics. 2007, 45(11): 831-834.

Researcher : Mo FY

List of Research Outputs

Mo F.Y., Yip H.K., Law H.K.W., Lau Y.L. and Chan G.C.F., Effects of bacterial toxins on the growth, differentiation and toll-like receptor genes of human mesenchymal stem cells, Cytokine 2006. 17: 120.

Researcher : Mok KP

List of Research Outputs

Mok K.P., Lee D.C.W., Cheung C.Y., Peiris J.S.M. and Lau A.S.Y., Differential onset of apoptosis in influenza A virus H5N1 - and H1N1 - infected human blood macrophages, Journal of General Virology. 2007, 88(Pt 4): 1275-1280.

Researcher : Ng MW

List of Research Outputs

Ng M.W., Zhou G., Chong W.P., Lee W.Y., Law H.K.W., Zhang H., Wong W.H.S., Fok S.F.S., Zhai Y., Yung R.W.H., Chow E.Y., Au K.L., Chan E.Y.T., Lim W., Peiris J.S.M., He F. and Lau Y.L., The association of RANTES polymorphism with severe acute respiratory syndrome in Hong Kong and Beijing Chinese, BMC Infectious Diseases. 2007, 7: 50.

Researcher : Ou X

List of Research Outputs

Cheung Y.F., Ou X. and Wong S.J., Central and Peripheral Arterial Stiffness in Patients After Surgical Repair of Tetralogy of Fallot: Implications for Aortic Root Dilation, American Heart Association, Scientific sessions 2006, Supplement II to Circulation (Journal of the American Heart Association), USA, 12-15 November 2006. 114(18): 780.

Cheung Y.F., Ou X. and Wong S.J., Central and peripheral arterial stiffness in patients after surgical repair of tetralogy of Fallot: implications for aortic root dilatation, Heart. 2006, 92: 1827-1830.

Researcher : Poon GWK

List of Research Outputs

Poon G.W.K., Kwan E.Y.W., Cheung P.T. and Low L.C.K., Mutation analysis of the GLUT2 Gene in a Chinese patient with Fanconi-Bickel Syndrome, 4th Biennial Scientific Meeting of the Asia Pacific PaediatricEndocrine Society, Pattaya, Thailand, 1-4 November. 2006.

Yung A.W.Y., Poon G.W.K., Qiu D., Chu J., Lam B.C.C., Leung C., Goh W.H.S. and Khong P.L., White matter volume and anisotropy in preterm children: a pilot study of neurocognitive correlates, Pediatric Research. 2007, 61: 732-736.

Researcher : Siu HO

List of Research Outputs

Siu H.O., Yang W., Lau C.S., Chan T.M., Wong W.H.S., Lau Y.L. and Alarcon-Riquelme M.E., Association of Interferon Regulatory Factor 5 (IRF5) polymorphisms with systemic lupus erythematosus (SLE), European Human Genetics Conference, Nice, France, 16-19 June 2007. 279.

Researcher : Teoh KT

List of Research Outputs

Kien F.S., Millet J.K.G., Teoh K.T., Siu Y.L. and Nal-Rogier B.T.M., Identification Of Cellular Factors Which Regulate Early And/or Late Stages of Sars Cov Replication Cycle., Scientific conference of the 38th Board of Institutes Pasteur Directors, National Institute of Hygiene and Epidemiology. . 2006.

Nal-Rogier B.T.M., Kien F.S., Siu Y.L., Millet J.K.G., Teoh K.T. and Tse K.S., Tracking Virus-Host Cell Interactions: Example of the SARS coronavirus. , 1st RESPARI Workshop. Hong Kong . 2007.

Researcher : Tsang AMC

List of Research Outputs

Chung B.H.Y. and Tsang A.M.C., General paediatrics (Clinical Quiz, case 20), http://www.hku.hk/paed/student area/clinical quiz. 2007.

Tsang A.M.C., Representative of HK West Cluster in HA Forum, in "Review of the Development of Community Paediatrics in HK" organized by HK College of Paediatricians & HM Lui Memorial Fund, 9 November 2006. 2006.

Researcher : Tsang HYH

List of Research Outputs

Tsang H.Y.H., Lee S.L., Lee T.L., Wong K. and Lau Y.L., Prevalence of respiratory function abnormalities in asymptomatic Chinese patients wit juvenile onset systemic lupus erythematosus, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 199-204.

Researcher : Tso HW

List of Research Outputs

Tso H.W. and Lau Y.L., Interaction of Mesenchymal Stem Cells and Apoptotic Cells in Autoimmunity, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006. 156.

Researcher : Tsoi NS

List of Research Outputs

Chow P.C., Lee S.L., Tang M.H.Y., Chan K.L., Lee C.P., Lam B.C.C. and Tsoi N.S., Management and outcome of antenatally diagnosed congenital cystic adenomatoid malformation of the lung, Hong Kong Medical Journal. 2007, 13(1): 31-39.

Researcher : Tu W

Project Title:	The Role of Natural Killer Cells in Pathogenesis of Avian Influenza Virus Infection
Investigator(s):	Tu W, Lau YL, Peiris JSM
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2007

Abstract:

Introduction Influenza A (fluA) virus is a cause of substantial annual morbidity and mortality worldwide. Potential for the emergence of a new pandemic strain, through natural reassortment, e.g. avian fluA, is a major concern [1-6]. The innate immunity as the first line of host immune system is thought to be the main defense mechanism against this particular highly pathogenic virus infection. Natural killer (NK) cells function as a key factor in innate immune responses to intracellular pathogens, such as viruses [7, 8]. NK cells can directly lyse fluA virus-infected cells by exocytosis of perforin and granzymes and secrete cytokines, such as interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, which mediate their immune responses to virus infection [7-10]. The NK cell-mediated killing is controlled by activating and inhibitory receptors [11]. NK cell activating receptors include the natural cytotoxicity receptors (e.g. NKp30, NKp44 and NKp46), NKG2D, NKRP1 and CD16 [11]. Among of these, NKp46 and NK-44 have been demonstrated to play essential roles for the cytotoxic activities of NK cells against fluA viruses [11-14]. The inhibitory receptors include the killer cell Ig-like receptor (KIR) family, the C-type lectin family and the Ig-like transcript leukocyte Ig-like receptor (LIR) family [11]. The activity of NK cells is dependent on the balance of signals from the activating and inhibitory receptors [8, 11]. In addition, NK cells are activated by cytokines such as IL-12 and IFN-alpha, which are products of activated macrophage and dendritic cells [8, 11]. The distinctive features of avian fluA, in particular H5N1 affected patients include a primary viral pneumonia complicated acute respiratory distress, multiple organ dysfunction and haemophagocytosis [1, 15-18]. All of these are associated with the hyperinflammatory responses [1, 15-18]. Furthermore, the fatal outcome of H5N1 infection is associated with high viral load and hyperinflammatory cytokines [19]. Professor Peiris and our group have been demonstrated that these hyperinflammatory cytokines and chemokines are derived from H5N1-infected macrophages, and H5N1-infected macrophages are over-activated as compared with H1N1-infected cells [15-18]. However, the underlying mechanisms of macrophage over-activation and hyperinflammatory cytokines and chemokines are still unknown. It has been demonstrated that NK cell dysfunction is associated with systemic onset juvenile rheumatoid arthritis and macrophage activation syndrome [20]. Moreover, the overproduction of TNF-alpha, one of the hyperinflammatory cytokines found in H5N1 infected patients, was also indicated to associate with the low cytotoxic activity of NK cells in human [21]. Therefore, we speculate that hyperinflammatory cytokines and macrophage over-activation are associated with dysfunctions of NK cells in H5N1 infected-patients. Hypothesis We hypothesize that there are dysfunctions of NK cells in H5N1 infected-patients, and these dysfunctions are due to the increased apoptosis or decreased cytotoxicity of NK cells. We further hypothesize that H5N1-infected macrophages may induce the apoptosis or inhibit the cytotoxicity of NK cells through the cell-cell contact or the overproduction of inflammatory cytokines released from virus-infected macrophages. Aims 1. To determine whether H5N1 virus can induce an increased NK cell apoptosis or death, as compared to H1N1 virus. 2. To determine whether H5N1 virus can inhibit NK cell cytotoxicity, as compared to H1N1 virus. 3. To determine whether the increased apoptosis and death, or decreased cytotoxicity of NK cells is mediated by cell-cell contract or soluble molecules released from H5N1-infected cells. References: 1. Yuen KY, Chan PK, Peiris M, Tsang DN, Que TL, Shortridge KF, Cheung PT, To WK, Ho ET, Sung R, Cheng AF. Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus. Lancet. 1998;351(9101): 467-71 2. Guan Y, Poon LL, Cheung CY, Ellis TM, Lim W, Lipatov AS, Chan KH, Sturm-Ramirez KM, Cheung CL, Leung YH, Yuen KY, Webster RG, Peiris JS. H5N1 influenza: a protean pandemic threat. Proc Natl Acad Sci U S A. 2004, 101(21):8156-61. 3. Webby RJ, Webster RG. Are we ready for pandemic influenza? Science. 2003;302(5650):1519-22. 4. Zeitlin GA, Maslow MJ. Avian Influenza. Curr Infect Dis Rep. 2005;7(3):193-199. 5. Shortridge KF, Peiris JS, Guan Y. The next influenza pandemic: lessons from Hong Kong. J Appl Microbiol. 2003;94 Suppl:70S-79S. 6. Peiris JS, Yu WC, Leung CW, Cheung CY, Ng WF, Nicholls JM, Ng TK, Chan KH, Lai ST, Lim WL, Yuen KY, Guan Y. Re-emergence of fatal human influenza A subtype H5N1 disease. Lancet. 2004;363(9409):617-9. 7. Cerwenka A, Lanier LL. Natural killer cells, viruses and cancer. Nat Rev Immunol. 2001;1(1):41-9. 8. Lodoen MB, Lanier LL. Natural killer cells as an initial defense against pathogens. Curr Opin Immunol. 2006 Aug;18(4):391-8. 9. Trinchieri G. Biology of natural killer cells. Adv Immunol. 1989;47:187-376. 10. Robertson MJ, Ritz J. Biology and clinical relevance of human natural killer cells. Blood. 1990;76(12):2421-38. 11. Kirwan SE, Burshtyn DN. Regulation of natural killer cell activity. Curr Opin Immunol. 2007: 19:1-9. 12. Mandelboim O, Lieberman N, Lev M, Paul L, Arnon TI, Bushkin Y, Davis DM, Strominger JL, Yewdell JW, Porgador A. Recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells. Nature. 2001;409(6823):1055-60. 13. Gazit R, Gruda R, Elboim M, Arnon TI, Katz G, Achdout H, Hanna J, Qimron U, Landau G, Greenbaum E, Zakay-Rones Z, Porgador A, Mandelboim O. Lethal influenza infection in the absence of the natural killer cell receptor gene Ncr1. Nat Immunol. 2006; 7(5):517-23. 14. Arnon TI, Achdout H, Lieberman N, Gazit R, Gonen-Gross T, Katz G, Bar-Ilan A, Bloushtain N, Lev M, Joseph A, Kedar E, Porgador A, Mandelboim O. The mechanisms controlling the recognition of tumor- and virus-infected cells by NKp46. Blood. 2004;103(2):664-72. 15. Cheung CY, Poon LL, Lau AS, Luk W, Lau YL, Shortridge KF, Gordon S, Guan Y, Peiris JS. Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1)viruses: a mechanism for the unusual severity of human disease? Lancet. 2002;360(9348):1831-7. 16. To KF, Chan PK, Chan KF, Lee WK, Lam WY, Wong KF, Tang NL, Tsang DN, Sung RY, Buckley TA, Tam JS, Cheng AF. Pathology of fatal human infection associated with avian influenza A H5N1 virus. J Med Virol. 2001;63(3):242-6. 17. Zhou J, Law HK, Cheung CY, Ng IH, Peiris JS, Lau YL. Functional tumor necrosis factor-related apoptosis-inducing ligand production by avian influenza virus-infected macrophages. J Infect Dis. 2006;193(7):945-53. 18. Zhou J, Law HK, Cheung CY, Ng IH, Peiris JS, Lau YL. Differential expression of chemokines and their receptors in adult and neonatal macrophages infected with human or avian influenza viruses. J Infect Dis. 2006 Jul 1;194(1):61-70. 19. de Jong MD, Simmons CP, Thanh TT, Hien VM, Smith GJ, Chau TN, Hoang DM, Chau NV, Khanh TH, Dong VC, Qui PT, Cam BV, Ha do Q, Guan Y, Peiris JS, Chinh NT, Hien TT, Farrar J. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat Med. 2006;12(10):1203-7. 20. Villanueva J, Lee S, Giannini EH, Graham TB, Passo MH, Filipovich A, Grom AA. Natural killer cell dysfunction is a distinguishing feature of systemic onset juvenile rheumatoid arthritis and macrophage activation syndrome. Arthritis Res Ther. 2005; 7:R30-7. 21. Mysliwska J, Bryl E, Zorena K, Balon J, Foerster J, Mysliwski A. Overactivity of tumor necrosis factor-alpha but not interleukin 6 is associated with low natural killer cytotoxic activity in the elderly. Gerontology. 1997;43(3):158-67.

List of Research Outputs

Lau Y.L., Zhou J. and Tu W., 巨噬細胞活化綜合征基因相關性研究及治療構想, 中華兒科雜誌, Chinese Medical Association, 2006, 44(11): 803-805.

Lee P.P.W., Jiang L.P., Wang X.C., Chan K.W., Tu W. and Lau Y.L., Severe mycobacterial infections in two pairs of Chinese siblings with interleukin-12 receptor b1 deficiency, European Journal of Pediatrics. 2007-6-30, Springer-Verlag, 2007.

Lee P.P.W., Chan K.W., Tu W. and Lau Y.L., Severe mycobacterial infections in two pairs of Chinese siblings with interleukin-12 receptor 1 deficiency., Asia Pacific Primary Immune Deficiency (APPID) Summer School, 6-11th May 2007, Queensland, Australia. 2007.

Tu W. and Lau Y.L., Antiviral Activities Of Human Gammadelta-t Cells Against Influenza A Viruses, Innate Immunity:receptors, Response, Regulation/society For Leukocyte Biology And International Endotoxin And Innate Immunity Society, Nov 9-11, 2006. San Antonio, TX, USA. 2006.

Tu W., Chinese Journal of Pediatrics. Beijing, China, Chinese Medical Society, 2007.

Tu W., Dionis K., Lewis D.B. and Lau Y.L., Ex vivo Generation of Alloantigen-specific Human Regulatory T cells by CD40-activated B cells, American Transplant Congress, May 5-9, 2007, San Francisco, USA. 2007.

Tu W., Human Influenza Infections in Children, West China Second Hospital, University of Sichuan. 2007.

Tu W., Human and Avian Influenza Infections in Children, 14th National Conference of Chinese Pediatric Society. 2006.

Tu W., Immune Defenses against Human and Avian Influenza, 1st Zhongshan-Hong Kong Biomedical Research Symposia. 2007.

Tu W., Mao H. and Lau Y.L., Immune defense mechanisms against human and avian influenza viruses, Chinese Journal of Pediatrics. 2007, 45(11): 831-834.

Tu W., Potena L., Stepick-Biek P., Liu L., Dionis K.Y., Luikart H., Fearon W.F., Holmes T.H., Chin C., Cooke J.P., Valantine H.A., Mocarski E.S. and Lewis D.B., T-Cell Immunity to Subclinical Cytomegalovirus Infection Reduces Cardiac Allograft Disease, Circulation. 2006, 114: 1608-15.

Zeman A.M., Holmes T.H., Stamatis S., Tu W., He X.S., Bouvier N., Kemble G., Greenberg H.B., Lewis D.B., Arivin A.M. and Dekker C.L., Humoral And Cellular Immune Responses In Children Given Annual Immunization With Trivalent Inactivated Influenza Vaccine., Pediatr Infect Dis J. 2007, 26: 107-15.

Zhou J., Law H.K.W., Tu W., Cheung C.Y., Ng I.H.Y., Peiris J.S.M. and Lau Y.L., Decreased T lymphocytes activation and Cytotoxic activity in avian influenza: an in vitro study, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 164.

Researcher : Wong CL

List of Research Outputs

Wong C.L. and Wong V.C.N., Analysis of Children with Autism Spectrum Disorders Using Theories of Traditional Chinese Medicine (TCM), 11th Research Postgraduate Symposium, 7 December 2006). 2006.

Wong C.L. and Wong V.C.N., Study of Children with Autism Sepctrum Disorders Using Symptom Differentiation of Traditional Chinese Medicine (TCM), 2006 World Congress on Chinese Medicine: Charting the Course of Development, organized by School of Chinese Medicine, Hong Kong Baptist University (23-25 November, 2006). 2006.

Wong C.L. and Wong V.C.N., Use of Acupuncture in Stroke Rehabilitation - Two Case Reports, Second International Symposium on Healthy Aging (Hong Kong, March 3-4, 2007). 2007, OP19.

Researcher : Wong KT

List of Research Outputs

Chow P.C., Cheung E.W.Y., Chong` C.Y., Lun K.S., Yung T.C., Wong K.T., Chau A.K.T. and Cheung Y.F., Brain Natriuretic Peptide as a Biomarker of Systemic Right Ventricular Function in Patients After Atrial Switch Operation, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 126.

Chow P.C., Liang X., Cheung E.W.Y., Wong K.T., Lun K.S., Yung T.C., Chau A.K.T. and Cheung Y.F., Right Ventricular Dyssynchrony in Patients After Atrial Switch Operation for Transposition of the Great Arteries, Hong Kong College of Cardiology, Fifteenth Annual Scientific Congress Proceedings (Free Paper Session, Paediatric Cardiology I), Hong Kong, 4-6 May 2007. 15: 58.

Researcher : Wong KY

List of Research Outputs

Chen M., Lam Y.H., Ma E.S.K., Wong K.Y. and Tang M.H.Y., Intrauterine therapy in a fetus with severe congenital dyserythropoietic anaemia, The Third International Scientific Meeting of the International Society of Ultrasound in Obstetrics and Gynecology, Hong Kong Convention and Exhibition Centre, Hong Kong, February 25-28, 2007.

Kwok Y.L., Wong K.Y., Ying B.A., Yick K.L., Yi L. and Yeung C.Y., Anthropometric measurement of premature infants, International Journal of Clothing Science and Technology. Emerald Group, 2007, 19(5): 319-333.

Ting J.Y., Wong K.Y., Goh W.H.S., Lee C.P. and Lam B.C.C., Changes in Mortality, Morbidity and Early Neurodevelopmental Outcomes among Extremely-low-birth-weight (ELBW) Infants Born in the Early and Recent Post-Surfactant Era, Hong Kong Journal of Paediatrics (new series). 2007, 12: 78-85.

Wong R.M.S., Wong K.Y. and Lam B.C.C., Atypical Presentation of Congenital Tuberculosis in a Preterm Infant, Hong Kong Journal of Paediatrics (new series). 2007, 12: 133-136.

Researcher : Wong OH

List of Research Outputs

To K.W., Wong O.H., Li H.B., Chen S.F., Lo C.K., Chiang A.K.S. and Huang F., Effects Of Bergapten On Dendritic Cell Functions, The 9th International Syposium on Dendritic Cells, Edinburgh, September 16-20 . 2006.

To K.W., Wong O.H., Li H.B., Chen S.F., Lo C.K., Chiang A.K.S. and Huang F., Immunomodulatory effects of Bergapten on dendritic cell functions, 9^th International Conference on Dendritic Cell, Edinburgh, England, 16-20 September 2006.

Researcher : Wong RMS

List of Research Outputs

Wong R.M.S., Wong K.Y. and Lam B.C.C., Atypical Presentation of Congenital Tuberculosis in a Preterm Infant, Hong Kong Journal of Paediatrics (new series). 2007, 12: 133-136.

Researcher : Wong SJ

List of Research Outputs

Cheung Y.F., Ou X. and Wong S.J., Central and Peripheral Arterial Stiffness in Patients After Surgical Repair of Tetralogy of Fallot: Implications for Aortic Root Dilation, American Heart Association, Scientific sessions 2006, Supplement II to Circulation (Journal of the American Heart Association), USA, 12-15 November 2006. 114(18): 780.

Cheung Y.F., Ou X. and Wong S.J., Central and peripheral arterial stiffness in patients after surgical repair of tetralogy of Fallot: implications for aortic root dilatation, Heart. 2006, 92: 1827-1830.

Cheung Y.F., Wong S.J. and Ho M.H.K., Relationship Between Carotid Intima-Media Thickness and Arterial Stiffness in Children After Kawasaki Disease, American Heart Association, Scientific sessions 2006, Supplement II to Circulation (Journal of the American Heart Association), USA, 12-15 November 2006. 114: 639-640.

Cheung Y.F., Wong S.J. and Ho M.H.K., Relationship between carotid intima-media thickness and arterial stiffness in children after Kawasaki disease, Archives of Disease in Childhood. 2007, 92: 43-47.

Liang X., Cheung E.W.Y., Wong S.J., Chau A.K.T. and Cheung Y.F., Restrictive Right Ventricular Physiology after Biventricular Repair of Pulmonary Atresia with Intact Ventricular Septum, Hong Kong College of Cardioloyg, Fifteenth Annual Scientific Congress Proceedings (Free Paper Session, Paediatric Cardiology I), Hong Kong, 4-6 May 2007. 15: 58.

Researcher : Wong VCN

Project Title:	Rett Syndrome :Systematic screening of MECP2 in children with autistic traits and or unexplained mental retardation/ encephalopathy to define the spectrum of Rett Syndrome phenotypes resulting from mutations in MECP2
Investigator(s):	Wong VCN
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	01/2006

Abstract:

Rett syndrome (RTT) is an X-linked dominant neurodegenerative disorder characterized by a period of early normal growth and development followed by regression with loss of speech, acquired motor skills, stereotypic hand movement, and seizures. RTT affects 1 in 15,000 females and is the second leading cause of profound mental retardation in females. RTT is a clinical syndrome without any diagnostic biologic markers and the pathophysiologic changes has not been identified. The diagnosis of RTT is still reliant on clinical criteria. Early diagnosis of RS in the normal developmental period is still impossible. The disease is caused by mutations in the methyl-CpG-binding protein 2 gene (MECP2), and various mutations have been reported. The phenotypic spectrum in both female and male patients is diverse, ranging from very mild to congenital encephalopathy and prenatal lethality. Methyl-CpG binding protein 2 (MECP2) The responible gene, encoding Methyl-CpG binding protein 2 (MECP2) is discovered (1999 Sept 30). (1,2) MECP2 mutations is detected in < 50% of girls with RS by PCR amplification of the coding region. The RTT phenotype of MECP2 mutation is broad with lethality and normality in the two extremes. Findings have suggested that X-Chromosome Inactivation (XCI) pattern is the major determinant of the phenotype in females. MECP2 is an abundant chromosome-binding protein that selectively binds 5-methyl cytosine residues in CpG dinucleotides of mammalian genome. MECP2 has a role as a global transcriptional repressor in vertebrate genome. However, how MECP2 mutation cause RTT is still unclear as only 50% of RS girls has the mutation. MECP2 mutations has been detected by PCR amplification of the coding region. As MECP2 mutations could also involve the highly conserved regions within the 8.5-kb 3’UTR, mutational analysis should expand to include this region as well. Until now, MECP2 mutations has been detected by PCR amplification of the coding region in 60% of girls with RS. Possibly MECP2 mutations in the highly conserved regions within the 8.5-kb 3’UTR are currently underway. Both nonsense and missense mutations have been found. Different single-nucleotide deletion or insertion was found in patients with RS. Others are the nucleotide substitutions, which involve C-T transitions at CpG hotspots except one variant (G-A). Clinical Spectrum of Rett syndrome: The spectrum of phenotypes of MECP2 mutations seems to be much broader. R168X mutation was found in 2 affected sisters and their normal mother. In one family, an 806 del G deletion causing a V288X stop in the transcription-repression domain was identified in a woman with mild neuropyschological problems and skewed X inactivation; in her sister and daughter with classic RS and in her hemizygous son, who died from congenital encephalopathy. This finding suggested that X-chromosome inactivation (XCI) pattern could be the major determinant of the phenotype in females. The severity of RS is believed to be a function of the percentage of cells with active, mutated MECP2 genes. MECP2 gene encodes a protein called MeCP2 that helps to orchestrate the “rests” that certain genes must take during the developmental symphony. If a defective MeCP2 protein is unable to “conduct” gene expression, then a neural chaos will result.MeCP2 is actually just a member of a family of methyl-binding proteins, all of which may help to regulate gene function. Mutations in any of these proteins or their interacting partners may be responsible for atypical RS, autism, severe neonatal encephalopathy, and non-syndromal mental retardation. The spectrum of phenotypes of MECP2 mutations is surprisingly wide with lethality to normality in the two extremes. (3) Even though the mutational types could have contributed to the phenotypes, some findings suggested that the X-chromosome inactivation (XCI) pattern may be the major determinant of the phenotype in females. We had reported MECP2 mutation in a cohort of Chinese girls with RS and autism (2000). (4, 5) We hope to explore the spectrum of phenotypes resulting from MECP2 mutations in the Chinese population. We hope to establish a systemic way of mutational analysis of the gene in RS and its possible variant including girls with autism or autistic features, developmental stagnancy or regression in girls with unknown etiology, and severe neonatal encephalopathy. XCI pattern will be examined in the family in which the mutation has been detected. We aim to study mutational analysis of the MECP2 gene in other related neurodevelopmental disorder with similar core autistic or neurological regression features, e.g. girls with autism or autistic features, developmental stagnancy or regression girls without unknown etiology, and newborn with unexplained severe encephalopathy and non-syndromal mental retardation. XCI pattern will be examined in family members if mutation is detected. Long term objective: We hope that prenatal test to detect RS families can be available in families with affected daughters (though the risk is < 1%). We hope to test for asymptomatic daughters in RTT families early on (prefebly in stage 1) (< 12 months) such that an early diagnosis can be made or refuted to alleviate parental anxiety. Objective: To detect MECP2 mutation in children with Autistic traits including Rett syndrome, atypical Rett Syndrome, Autism, unexplained mental retardation and infantile epileptic encephalopathy

List of Research Outputs

Cheuk D.K.L. and Wong V.C.N., Attention-deficit hyperactivity disorder and blood mercury level: a case-control study in Chinese children, Neuropediatrics. 2006, 37(4): 234-240.

Cheuk D.K.L., Li Y.H. and Wong V.C.N., Exon 3 Polymorphisms of Dopamine D4 Receptor (DRD4) Gene and Attention Deficit Hyperactivity Disorder in Chinese Children, American Journal of Medical Genetics Part B (Neuropsychiatric Genetics). 2006, 141B: 907-911.

Cheuk D.K.L. and Wong V.C.N., Meta-analysis of association between a Catechol-O-Methyltransferase gene polymorphism and attention deficit hyperactivity disorder, Behavior Genetics. 2006, 36(5): 651-659.

Cheuk D.K.L., Wong V.C.N., Wraige E., Baxter P., Cole A., N'Diaye T. and Mayowe V., Surgery for scoliosis in Duchenne muscular dystrophy (Review), Cochrane Database of Systematic Reviews. 2007, 1: CD005373.

Chu M.M.Y., Lee W.C., Leung J.L.S. and Wong V.C.N., Modified symbolic play test for Oriental children, Pediatrics International. 2006, 48(6): 519-524.

Chung B.H.Y. and Wong V.C.N., Relationship between five common viruses and febrile seizure in children, Archives of Disease in Childhood. 2007, 92: 589-593.

Wong C.L. and Wong V.C.N., Analysis of Children with Autism Spectrum Disorders Using Theories of Traditional Chinese Medicine (TCM), 11th Research Postgraduate Symposium, 7 December 2006). 2006.

Wong C.L. and Wong V.C.N., Study of Children with Autism Sepctrum Disorders Using Symptom Differentiation of Traditional Chinese Medicine (TCM), 2006 World Congress on Chinese Medicine: Charting the Course of Development, organized by School of Chinese Medicine, Hong Kong Baptist University (23-25 November, 2006). 2006.

Wong C.L. and Wong V.C.N., Use of Acupuncture in Stroke Rehabilitation - Two Case Reports, Second International Symposium on Healthy Aging (Hong Kong, March 3-4, 2007). 2007, OP19.

Wong S.S.N. and Wong V.C.N., Functional Independence Measure for Children: A Comparison of Chinese and Japanese Children, Neurorehabilitation and Neural Repair. 2007, 21(1): 91-96.

Wong V.C.N., Associate Member (Since 1995), American Association of Electrodiagnositic Medicine. 2007.

Wong V.C.N., Autism, Hong Kong Health Expo & International Conferences & 4th Pong Ding Yuen International Symposium on TCM, Hong Kong, 28-30 July, 2006.

Wong V.C.N. and Hui L.H., Brief Report: Emerging Services for Children with Autistic Spectrum Disorders in Hong Kong (1960-2004), Journal of Autism and Developmental Disorders. 2007, Published online: 29 June 2007.

Wong V.C.N., Chairman (Since 1997), Comprehensive Epilepsy Program, Queen Mary Hospital. 2007.

Wong V.C.N., Chairperson (2006-2010), Research Task Force of International Child Neurology Association. 2006.

Wong V.C.N., Coordinator of Hong Kong (Since 2005), Study Group in Pediatric Epilepsy in Asia. 2007.

Wong V.C.N., Deputy Chairman (Since 2003), HKU/HA HKW Institute Review Board, Queen Mary Hospital. 2007.

Wong V.C.N., Executive Board Member (2006-2010), International Child Neurology Association. 2006.

Wong V.C.N., Hong Kong Delegate (Since 1987), Asian Oceanean Child Neurology Association. 2007.

Wong V.C.N., Hong Kong Delegate (Since 1987), International Child Neurology Association. 2007.

Wong V.C.N., Honorary Advisor (Since 1999), Hong Kong Neuro-Muscular Disease Association. 2007.

Wong V.C.N., Honorary Advisor (Since 1999), The Hong Kong Epilepsy Association. 2007.

Wong V.C.N., Interactive teaching modules for medical Students and post-graduate medical doctors - children with brain disorders , LEARNet Conference 2005, organized by Centre of Advancment of University Teaching, HKU (13 December, 2006). 2006.

Wong V.C.N., Chung B.H.Y., Soo E. and Hardiner S.G., Interesting case presented in DK-Grandround "Look at these Facies" (Clinical Quiz, case 18), http://www.hku.hk/paed/student area/clinical quiz. 2007.

Wong V.C.N. and Chung B.H.Y., Interesting case seen during acute neurology consultation in 2002 (clinical quiz - case 12), http://www.hku.hk/paed/student area/clinical quiz. 2007.

Wong V.C.N., Chung B.H.Y. and Fung C.W., Interesting case seen in DK-Grandround December 2005 (Clinical Quiz, Case 16), http://www.hku.hk/paed/student area/clinical quiz. 2007.

Wong V.C.N., Member (Since 1985), Hong Kong Neurological Society. 2007.

Wong V.C.N., Member (Since 1989), Hong Kong Association for Child & Adolescent Psychology & Psychiatry. 2007.

Wong V.C.N., Member (Since 1990), World Federation of Neurology. 2007.

Wong V.C.N., Member (Since 1996), World Muscle Society. 2007.

Wong V.C.N., Member (Since 1997), American Academy of Neurology (Section of Child Neurology). 2007.

Wong V.C.N., Member (Since 1997), American Society of Neurorehabilitation. 2007.

Wong V.C.N., Member (Since 1997), European Society of Child Neurology. 2007.

Wong V.C.N., Member (Since 2007), Editorial Board of Child Neurology, Chinese Medical Association. 2007.

Wong V.C.N., Member, Editorial Board, Current Pediatric Reviews (Since 2005). 2007.

Wong V.C.N., Member, Editorial Board, Journal of Child Neurology (Since 2000). 2007.

Wong V.C.N., Member, Editorial Board, Journal of Pediatric Neurology (Since 2003). 2007.

Wong V.C.N., Member, Editorial Board, Pediatric Neurology (Since 2001). 2007.

Wong V.C.N., Organizer, Certificate Course on Intervention for Children with Autism Spectrum Disorder 2006 (Hong Kong, 15-20 July & 22-27 July, 2006). 2006.

Wong V.C.N., Reviewer (since 2005), Lancet. 2007.

Wong V.C.N., Reviewer, American Journal of Epidemiology (Since 2004). 2007.

Wong V.C.N., Reviewer, BMJ Pediatrics (Since 2003). 2007.

Wong V.C.N., Reviewer, Child: Care, Health and Development (Since 2003). 2007.

Wong V.C.N., Reviewer, Developmental Medicine and Child Neurology (Since 2003). 2007.

Wong V.C.N., Reviewer, Epilepsia (Since 2003). 2007.

Wong V.C.N., Reviewer, European Journal of Paediatric Neurology (Since 2003). 2007.

Wong V.C.N., Reviewer, Hong Kong Journal of Paediatrics (Since 1990). 2007.

Wong V.C.N., Reviewer, Journal of Paediatrics, Obstetrics & Gynaecology (Since 2003). 2007.

Wong V.C.N., Reviewer, Medical Progress (Since 2000). 2007.

Wong V.C.N., Reviewer, Medical Science Monitor (Since 2003). 2007.

Wong V.C.N., Reviewer, New England Journal of Medicine (Since 2005). 2007.

Wong V.C.N., Reviewer, Pediatrics (Since 2000). 2007.

Wong V.C.N., Reviewer, The Open Pediatric Medical Journal (Since 2007). 2007.

Wong V.C.N., 魔爪下的小英雄, Hong Kong, 紅出版, 2006, 1-159.

Researcher : Wong WHS

List of Research Outputs

Chan S.Y., Lau W.Y., Wong W.H.S., Cheng L.C., Chau A.K.T. and Cheung Y.F., Chylothorax in Children After Congenital Heart Surgery, Annals of Thoracic Surgery. Elsevier Inc, 2006, 82: 1650-1657.

Chiu S.S.S., Peiris J.S.M., Chan K.H., Wong W.H.S. and Lau Y.L., Immunogenicity and Safety of Intradermal Influenza Immunization at a Reduced Dose in Healthy Children, Pediatrics. 2007, 119: 1076-1082.

Fong D.Y.T., Lee C.F. and Wong W.H.S., Statistical Corner, Journal of Paediatric Respirology and Critical Care. 2007, 3(2): 16-17.

Ho M.H.K., Chow P.C., Lee T.L., Tam S., Wong W.H.S., Wong W.K.H.S., Lau Y.L. and Cheung Y.F., Carotid Intima-Media Thickening in Adolescents and Young Adults with Paediatric-Onset Systemic Lupus Erythematosus is Not Related to Traditional and Novel Cardiovascular Risk Factors, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 157.

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.

Lee C.F., Wong W.H.S. and Fong D.Y.T., Statistical Corner, Journal of Paediatric Respirology and Critical Care. 2007, 3(1): 13-15.

Lee P.P.W., Lee T.L., Ho M.H.K., Wong W.H.S. and Lau Y.L., Herpes Zoster in Juvenile-Onset Systemic Lupus Erythematosus, Pediatric Infectious Disease Journal. 2006, 25: 728-732.

Lee P.P.W., Lee T.L., Ho M.H.K., Wong W.H.S. and Lau Y.L., Recurrent Major Infections in Juvenile-Onset Systemic Lupus Erythematosus? A Close Link with Long-term Disease Damage, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 186.

Lee P.P.W., Lee T.L., Ho M.H.K., Wong W.H.S. and Lau Y.L., Recurrent major infections in juvenile-onset systemic Lupus erythematosus - a close link with long-term disease damage, Rheumatology. 2007, 1-7.

Lee P.P.W., Lee T.L., Wong W.H.S. and Lau Y.L., The use of methotrexate in juvenile idiopathic arthritis: a single center experience, Hong Kong Journal of Paediatrics (New Series). 2006, 11: 191-198.

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.

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.

Ng M.W., Zhou G., Chong W.P., Lee W.Y., Law H.K.W., Zhang H., Wong W.H.S., Fok S.F.S., Zhai Y., Yung R.W.H., Chow E.Y., Au K.L., Chan E.Y.T., Lim W., Peiris J.S.M., He F. and Lau Y.L., The association of RANTES polymorphism with severe acute respiratory syndrome in Hong Kong and Beijing Chinese, BMC Infectious Diseases. 2007, 7: 50.

Siu H.O., Yang W., Lau C.S., Chan T.M., Wong W.H.S., Lau Y.L. and Alarcon-Riquelme M.E., Association of Interferon Regulatory Factor 5 (IRF5) polymorphisms with systemic lupus erythematosus (SLE), European Human Genetics Conference, Nice, France, 16-19 June 2007. 279.

Wong M.L., Wong W.H.S. and Cheung Y.F., Fetal myocardial performance in pregnancies complicated by gestational impaired glucose tolerance, Ultrasound in Obstetrics and Gynaecology. 2007, 29: 395-400.

Wong W.H.S., Lee C.F. and Fong D.Y.T., Statistical Corner, Journal of Paediatric Respirology and Critical Care. 2006, 2(4): 14-16.

Wong W.H.S., Lee C.F. and Fong D.Y.T., Statistical Corner, Journal of Paediatric Respirology and Critical Care. Hong Kong, 2006, 2(3): 12.

Yip H.K., Guo J.H. and Wong W.H.S., Incipient caries lesions on cementum by mono- and co-culture oral bacteria, Journal of Dentistry. Elsevier Ltd., 2007, 35: 377-382.

Yip H.K., Guo J. and Wong W.H.S., Protection Offered by Root-surface Restorative Materials against Biofilm Challenge, Journal of Dental Research. 2007, 86(5): 431-435.

Researcher : Woo GKS

List of Research Outputs

Kwok H., Woo G.K.S., Chan K.W. and Chiang A.K.S., Characterization of Epstein-Barr Virus (EBV) Strains in Childhood Infectious Mononucleosis, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006. 72.

Kwok H., Woo G.K.S., Chan K.W. and Chiang A.K.S., Study of Epstein-Barr Virus (EBV) strains in childhood infectious mononucleosis, The Hong Kong Pediatric Society and Hong Kong Paediatric Nurses Association Ltd. - A Joint Annual Scientific Meeting for Paediatricians and Paediatric Nurses, QEH, Hong Kong, 25 November 2006. 40.

Xu X., Woo G.K.S., Chan K.H. and Chiang A.K.S., Characterization of EBV-specific CD8⁺ CTL Responses in Childhood Infectious Mononucleosis, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006. 158.

Xu X., Woo G.K.S., Chan K.H. and Chiang A.K.S., Longitudinal study of EBV-specific CD8⁺ CTL responses in childhood infectious mononucleosis, The Hong Kong Pediatric Society and Hong Kong Paediatric Nurses Association Ltd. - A Joint Annual Scientific Meeting for Paediatricians and Paediatric Nurses, QEH, Hong Kong, 25 November 2006. 43.

Researcher : Xu X

List of Research Outputs

Xu X., Woo G.K.S., Chan K.H. and Chiang A.K.S., Characterization of EBV-specific CD8⁺ CTL Responses in Childhood Infectious Mononucleosis, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006. 158.

Xu X., Woo G.K.S., Chan K.H. and Chiang A.K.S., Longitudinal study of EBV-specific CD8⁺ CTL responses in childhood infectious mononucleosis, The Hong Kong Pediatric Society and Hong Kong Paediatric Nurses Association Ltd. - A Joint Annual Scientific Meeting for Paediatricians and Paediatric Nurses, QEH, Hong Kong, 25 November 2006. 43.

Researcher : Yang M

List of Research Outputs

Li X.F., Wang Q.W., He Z.X., Chen H., Chen M.L., Chen J.L. and Yang M., Human cytomegalovirus induces apoptosis of human promyelocytic leukemic cells via direct infection in vitro, Journal of Experimental Hematology. 2007, 15 (1): 63-66.

Lin S., Liu S., Sun X. and Yang M., Studies on ex vivo expansion of megakaryocytic progenitor and its application--review, Journal Of Experimental Hematology. 2006, 14(4): 835-839.

Xiao D.W., Yang M., Yang J., Hon K.L. and Fok F.T., Lung damage may induce thrombocytopenia., Platelets. 2006, 17(5): 347-349.

Yang M., Li K., Ng P.C., Chuen C.K.Y., Lau T.K., Cheng Y.S., Liu Y.S., Li C.K., Yuan P.M.P., James A.E., Lee S.M. and Fok T.F., Promoting effects of serotonin on hematopoiesis: ex vivo expansion of cord blood CD34+ stem/progenitor cells, proliferation of bone marrow stromal cells, and antiapoptosis., Stem Cells. USA, AlphaMed Press, 2007, 25: 1800-1806.

Yang M., Stem Cells And Its Clinical Application, Zhongshan People's Hospital. 2007.

Yang M., Cheung Y.F., Chan S. and Chan G.C.F., Tpo Has A Protective Effect On Iron-induced Apoptosis In Cardiomyocytes, Cytotherapy/international Society For Cellular Therapy Annual Meeting. 2007, 9: 76.

周卓.妍., 宋燕.燕. and Yang M., 造血生長因子保護/修復新生兒缺氧缺血性腦損傷, 實用兒科臨床雜誌, 2007, 22 Ã¯Â¼Â6Ã¯Â¼Â: 462－465.

夏文.杰., Yang M., 羅廣.平., 付涌.水., 汪傳.喜. and 張麗.蓉., 促紅細胞生成素在缺氧缺血性腦病新生鼠模型中的神經保護作用, 實用兒科臨床雜誌, 2007, 22Ã¯Â¼Â6Ã¯Â¼Â: 416－418.

宋燕.燕., 孫新., 趙小.朋., 葉青.青., 李堅., 黃志.堅., 肖華., 李智.華. and Yang M., 促紅細胞生成素治療早産兒腦損傷的效果, 實用兒科臨床雜誌, 2007, 22 Ã¯Â¼Â6Ã¯Â¼Â: 454－455.

程源.山., 劉元.生., 吳映.娥. and Yang M., 血小板内容物5-羟色胺和血小板反应素-1对巨核细胞增殖及凋亡的生物学作用, 血栓與止血學, 2006, 12: 53-57.

肖大.衛., 謝澤.鋒., 黃偉.哲., 歐曉.敏. and Yang M., TPO對阿霉素誘導損傷小鼠心肌的保護, 中國心血管病研究雜志, 2007, 10: 20－24.

Researcher : Yang W

Project Title:	Linkage Analysis of Spondylo-Metaphyseal Dysplasia(SMD) using Pedigrees in Hong Kong
Investigator(s):	Yang W
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	12/2006

Abstract:

Small family cases of SMD "Corner Fracture" type have been reported around the world, but the genetic mutation and the linked genomic region have never been identified. A large pedigree for this disease and 5 smaller families have been collected in Hong Kong. The size of the large pedigree collected contains 14 informative individuals, sufficient to allow us to locate the genomic region containing the mutation for this disease for the first time using linkage analysis method (see Analysis of Human Genetic Linkage, 3rd edition, by Jurg Ott).

List of Research Outputs

Chung B.H.Y., Yang W., Lee P.P.W., Wong W.B. and Zhu Y.D., Clinical Quiz (case 21), http://www.hku.hk/paed/student area/clinical quiz. 2007.

Chung B.H.Y., Yang W., Lee P.P.W., Wong W.B. and Zhou Y.D., Clinical Quiz (case 22), http://www.hku.hk/paed/student area/clinical quiz. 2007.

Chung B.H.Y., Yang W., Lee P.P.W., Wong W.B. and Zhu Y.D., Clinical Quiz (case 23), http://www.hku.hk/paed/student area/clinical quiz. 2007.

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.

Siu H.O., Yang W., Lau C.S., Chan T.M., Wong W.H.S., Lau Y.L. and Alarcon-Riquelme M.E., Association of Interferon Regulatory Factor 5 (IRF5) polymorphisms with systemic lupus erythematosus (SLE), European Human Genetics Conference, Nice, France, 16-19 June 2007. 279.

Wong K.F., Lam T.W., Yang W. and Yiu S.M., Finding Alternative Splicing Patterns with Strong Support from Expressed Sequences , The 2007 International Conference on Bioinformatics and Computational Biology (BIOCOMP). 2007.

Yang W., Linkage Analysis With Dense Snp Genotyping, Joint Symposium on “New paradigms in Medical Genetics”. 2006.

Yu F., Chen M.H., Lynn K., Huang P. and Yang W., Bayesian Analysis Of Est Data With Multiple Libraries And Multiple Types Of Tissues, Joint Statistical Meetings. 2006.

Researcher : Yeung CY

List of Research Outputs

Kwok Y.L., Wong K.Y., Ying B.A., Yick K.L., Yi L. and Yeung C.Y., Anthropometric measurement of premature infants, International Journal of Clothing Science and Technology. Emerald Group, 2007, 19(5): 319-333.

Researcher : Yick LW

Project Title:	Defining the roles of epidermal growth factor (EGF) in the regulation of chondrocyte differentiation and endochondral bone formation
Investigator(s):	Yick LW, Chan SY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004

Abstract:

To understand the role of EGF in chondrocyte differentiation using our 'knock-in mice' with targeted expression of EGF in prehypertrophic chondrocytes.

List of Research Outputs

Researcher : Yim HCH

List of Research Outputs

Law H.Y., Lee D.C.W., Cheung B.K.W., Yim H.C.H. and Lau A.S.Y., Role for Nonstructural Protein 1 of Service Acute Respiratory Syndrome Coronavirus in Chemokine Dysregulation, Journal of Virology. 2007, 81(1): 416-422.

Yim H.C.H., Li C.B. and Lau A.S.Y., Effects of HIV-1 Tat on Lipopolysaccharide Induced Cytokine Response, 6th International Cytokine Conference Proceedings, Medimond International Proceedings, Bologna, Italy, 27-31 August 2006. 163-166.

Yim H.C.H., Li C.B. and Lau A.S.Y., Impairment of lipopolysaccharide-activiated signalling pathway by HIV TAT protein, The 6th International Cytokine Conference 2006 (European Cytokine Network, Supplement Aug 2006, Vol 17 - as official journal of Cytokine 2006-Vienna), Vienna, Austria, 27-31 August 2006. 17: 12-17/P.

Researcher : Yip KY

List of Research Outputs

Yip K.Y. and Chan S.Y., Functional Characterization of a Neonatal Heart Expressing-Protein - Analysis of the Protein-interacting Partners of TSPYL-2, Joint Meeting of the Japanese Society of Developmental Biologists & the Japan Society for Cell Biology, Fukuoka, Japan, 28-30 May 2007.

Yip K.Y. and Chan S.Y., Functional Characterization of a Neonatal Heart Expressing-protein - Analysis of the Protein-interacting Partners of TSPYL-2, 11^th Research Postgraduate Symposium, HKU, 7 December 2006.

Researcher : Yip MS

List of Research Outputs

Yip M.S., Law H.K.W. and Lau Y.L., Comparison of Immune Responses Triggered by Human Metapneumovirus and Respiratory Syncytial Virus in Human Respiratory Epithelial Cells, 11^th Research Postgraduate Symposium, Hong Kong, 7 December 2006. 83.

Researcher : Yuan X

List of Research Outputs

Chiang A.K.S., Yuan X., Chan G.C.F., Kwong D.L.W., Chan T. and Ha S.Y., Treatment Outcome of Rhabdomyosarcoma in Hong Kong Chinese Children, 13^th Hong Kong International Cancer Congress, 3^rd Annual Meeting Centre for Cancer Research, HKU, 15-17 November 2006.

Researcher : Yung AWY

List of Research Outputs

Yung A.W.Y., Epilepsy in Children, symposium on "Epilepsy", organized by The Society of Physicians of HK, 5 November 2006. 2006.

Yung A.W.Y., Poon G.W.K., Qiu D., Chu J., Lam B.C.C., Leung C., Goh W.H.S. and Khong P.L., White matter volume and anisotropy in preterm children: a pilot study of neurocognitive correlates, Pediatric Research. 2007, 61: 732-736.

Researcher : Yung TC

List of Research Outputs

Chow P.C., Cheung E.W.Y., Chong` C.Y., Lun K.S., Yung T.C., Wong K.T., Chau A.K.T. and Cheung Y.F., Brain Natriuretic Peptide as a Biomarker of Systemic Right Ventricular Function in Patients After Atrial Switch Operation, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 126.

Chow P.C., Liang X., Cheung E.W.Y., Wong K.T., Lun K.S., Yung T.C., Chau A.K.T. and Cheung Y.F., Right Ventricular Dyssynchrony in Patients After Atrial Switch Operation for Transposition of the Great Arteries, Hong Kong College of Cardiology, Fifteenth Annual Scientific Congress Proceedings (Free Paper Session, Paediatric Cardiology I), Hong Kong, 4-6 May 2007. 15: 58.

Researcher : Zhou J

List of Research Outputs

Lau Y.L., Zhou J. and Tu W., 巨噬細胞活化綜合征基因相關性研究及治療構想, 中華兒科雜誌, Chinese Medical Association, 2006, 44(11): 803-805.

Zhou J., Law H.K.W., Tu W., Cheung C.Y., Ng I.H.Y., Peiris J.S.M. and Lau Y.L., Decreased T lymphocytes activation and Cytotoxic activity in avian influenza: an in vitro study, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 164.

Zhou J., Law H.K.W., Cheung C.Y., Ng I.H.Y., Peiris J.S.M. and Lau Y.L., Differential expression of chemokines and their receptors in adult and neonatal macrophages infected with human or avian influenza viruses, Journal of Infectious Diseases. Infectious Diseases Society of America, 2006, 194: 61-70.

Zhou J., Law H.K.W., Cheung C.Y., Ng I.H.Y., Peiris J.S.M. and Lau Y.L., Interaction of mannose binding lectin with H1N1 and H5N1 influenza A viruses, 2^nd Congress of Asian Society for Pediatric Research (ASPR), Yokohama, Japan, 8-10 December 2006. 110.

Researcher : Zhou J

List of Research Outputs

Lau Y.L., Zhou J. and Tu W., 巨噬細胞活化綜合征基因相關性研究及治療構想, 中華兒科雜誌, Chinese Medical Association, 2006, 44(11): 803-805.

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