A comprehensive immunohistochemical study was carried out to investigate the phenotypes and prevalence of intraepithelial lymphocytes in NPC samples semi-quantitatively. CD25+/FOXP3+ T-cells were highly prevalent in primary NPCs, suggesting the presence of the immunosuppressive Tregs in tumor microenvironments. The low abundance of CD4+ T-cells, and the positive correlation between FOXP3 and CD8 staining in NPC samples imply that CD8+FOXP3+ Tregs may be present and play role in the suppression of anti-tumor immune response in NPC patients. The involvement of chemokine in the migration of tumor-infiltrating lymphocytes was studied. Chemokine ligand 20 (CCL20) was overexpressed in all EBV-positive NPC cell lines and xenografts compared to EBV-negative NPC, and immortalized normal nasopharynx epithelial cell lines. The presence of CCL20 was also found in primary tumors but not in normal epithelium. Furthermore, the ability of LMP1 to upregulate CCL20 expression in epithelial cells indicates that EBV may induce the production of chemokine involved in lymphocyte migration. / Epstein-Barr virus (EBV) is invariably associated with the development of nasopharyngeal carcinoma (NPC). Although the association of EBV and cancer has been reported for about four decades, it is still not clear how EBV latent infection contributes to the transformation of nasopharyngeal epithelial cells. The aims of this study are to identify EBV-regulated cellular genes and pathways and to determine the potential role of EBV in the modulation of anti-tumor immune responses in NPC. / In summary, EBV plays critical roles in the development of NPC by regulation of multiple cellular genes and pathways such as the Notch signaling cascade, and modulation of anti-tumor immune responses through the induction of chemokine important in migration of immune cells. / Notch signaling pathway functions in diverse cellular processes such as proliferation, apoptosis, adhesion, and epithelial to mesenchymal transition. In the current study, aberrant expression of activated Notch1 receptor (NICD), Notch ligand (Jagged1), negative regulator of Notch ( NUMB) and Notch downstream effector (HEY1) was detected in NPC cell lines and xenografts. Overexpression of NICD, Jagged1 and HEY1 proteins was also commonly found in primary tumors of NPC. / Transfection of Jagged1 to normal nasopharynx epithelial cells resulted in increased cell proliferation. Moreover, EBERs, which is abundantly expressed in EBV-positive NPC tumors, was capable of inducing the expression of Jagged1 in epithelial cells. The current data shows that Notch signaling pathway is aberrantly activated by the deregulated expression of multiple Notch components in NPC. The induction of Jagged1 by EBERs also implies the potential role of EBV in the activation of Notch signaling cascade in NPC. / Using high-density oligonucleotide microarray, expression profiles of EBV-infected NPC cell lines, HK1+EBV and HONE1+EBV, and their uninfected counterparts, HK1 and HONE, were generated. From the microarray results, six EBV-upregulated (JDP2, IL8, ATP6V0E2L, PLAP, PIK3C2B and AKR1B10 ) and three EBV-downregulated genes (BACE2, PADI3 and MMP1) were identified in both HK1 and HONE1 cells upon EBV latent infection. One hundred and thirty-eight and seventy-six genes were also found to be differentially modulated by EBV in HK1 and HONE1 cells, respectively. This study shows that cellular genes involved in wide range of biological processes and cellular functions are differentially regulated by EBV, which suggest that EBV modulates multiple pathways and processes during NPC tumorigenesis. / Hui, Wai Ying. / Adviser: Kw Lo. / Source: Dissertation Abstracts International, Volume: 69-02, Section: B, page: 0806. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 166-204). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / School code: 1307.

For linkage region on chromosome 5, further fine mapping was performed on a total of three pedigrees. Linkage analysis revealed a maximum two point LOD score of 4.81 at marker D5S2505. Haplotype analysis narrowed the linkage region to 5p15.33-p15.2. Resequencing of five candidate genes, IRX2, IRX1, POLS, CCT5 and CTNND2 within the linkage region did not reveal any myopia mutation. They were therefore excluded as the myopia causative gene. Genotyping of 41 SNPs within this region in a Chinese cohort of 94 high myopia cases and 94 control subjects showed that the allele and genotypes distributions of rs370010 was significantly different between cases and controls (genotype P= 0.01176, allele P=0.00271 and trend P=0.00375). This SNP is located within a hypothetical gene LOC442129. After multiple testing corrections, none of the SNP remained significantly associated with high myopia. This is a novel myopia locus. Further work to identify the myopia gene in this region would involve candidate gene resequencing, family linkage analysis and gene-based SNPs association analysis. / High myopia is defined as refractive error below or equal to -6 dioptres (D). The prevalence of high myopia varies among different populations. The most common pathological structural abnormality in high myopia is the excessive lengthening of the posterior segment of the ocular globe. Apart from causing impaired vision, it may lead to severe ocular complications. The precise mechanistic role of genes and environmental factors in the development of high myopia is still uncertain. Studies of twins and families suggested that heredity is a major contributing factor. While no myopia gene has yet to be identified, 14 putative loci have been found on many chromosomes. In this study, we have utilized different approaches to map the myopia locus in the Chinese population. / In our family-based genome-wide scan program, the whole genome of Chinese high myopia pedigrees was screened by using microsatellite markers. Two point LOD scores > 1 were observed on chromosomes 12 and 5. Regions were further analyzed by fine mapping. For linkage region on chromosome 12, a maximum two point LOD score of 2.71 was obtained at marker D12S88 and suggested linkage region was narrowed at 12q21.31-q22 by haplotype analysis. Lumican located in this region was screened and no segregation of polymorphism was observed within the pedigree. The suggested locus in this study overlapped with the MYP3 but with a smaller interval than the one reported. Lumican was excluded to be the myopia gene in this locus. / In the candidate-gene program, the paired box gene 6 (PAX6) on 11p13, was first studied. Two dinucleotide repeats (AC)m and (AG)n in the promoter region were found to be highly polymorphic. Association was observed between these two repeats with high myopia in which patients had high repeat number in both (AC) m and (AG)n (p-value=0.0001317 and p-value=0.001). Our results indicated that the Chinese population does not show association between high myopia and polymorphisms in PAX6 coding region but the AC and AG dinucleotide repeats in the promoter region was significantly associated with high myopia. / Lam, Ching Yan. / "August 2007." / Source: Dissertation Abstracts International, Volume: 69-07, Section: B, page: 4103. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Lan Wei. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 260-301). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Photocopy. Ann Arbor, Mich. : UMI Dissertation Services, 2002. xx, 301 p. : ill. ; 22 cm. / Abstracts in English and Chinese.

Leung Yuk Fai. / "June 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 132-166). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

by Tang Shengping. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 217-244). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Zhao Hailu. / "June 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 192-210). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Polyglutamine disease is a class of neurodegenerative diseases, which is manifested by the atrophy of nervous system that results in dementia and/or motor dysfunction. The major pathological characteristics include progressive loss of neuronal cells as well as the appearance of insoluble nuclear inclusions in degenerating neuronal cells. Polyglutamine disease is caused by CAG triplet expansion in the genome. When translated, such expansion leads to the formation of expanded polyglutamine domain within the respective disease proteins and promotes abnormal protein conformational changes. Owing to their misfolded nature, the expanded polyglutamine proteins form insoluble nuclear inclusions. These insoluble nuclear inclusions are heterogeneous in nature, in which polyglutamine protein and molecular chaperones are the recruited components. All eukaryotic cells express molecular chaperones which function to mediate the proper folding of proteins. The recruitment of molecular chaperones into nuclear inclusions that contain misfolded triplet-expanded proteins strongly suggests the involvement of molecular chaperones in polyglutamine disease progression. It has been shown that over-expression of molecular chaperones in polyglutamine disease models can lead to a suppression of polyglutamine toxicity and a concomitant increase in the solubility of disease proteins, i.e. the solubility of polyglutamine disease protein is related to its toxicity. Intrigued by these observations, I aimed at elucidating the mechanism of polyglutamine disease pathogenesis by first studying the cellular regulation of endogenous chaperone expression in neurodegeneration in a transgenic Drosophila model of polyglutamine disease. A biphasic regulation of Hsp70 expression was observed, which the regulation was at the transcription level. Moreover, over-expression of Hsp70 could alter the endogenous Hsp70 protein and mRNA level of polyglutamine disease fly model. The study may help the understanding of how the chaperone expression is regulated under the effects of polyglutamine expression and thus to find out the mechanism of pathogenesis. In addition, cellular proteins that change in solubility other than disease protein will also be identified. Small heat shock proteins, glutathione S transferase and alpha 4 proteasome subunit, etc., showed change in solubility or expression by 2D gel electrophoresis analysis. Identifying the proteins that change in solubility or expression may help the finding of the interplay of proteins and thus the pathways involve in the mechanism of polyglutamine disease pathogenesis. Understanding pathogenic pathways can give ideas on how polyglutamine lead to the disease, up- or down-regulation of those protein interplays may provide direction and therapeutic candidates to suppress polyglutamine disease. / Huen Ngar Yee. / "September 2006." / Advisers: Ho Yin Chan; Siu Kai Kong. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1465. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 134-146). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Depression is a highly prevalent clinical condition which has been estimated to affect a growing part of the population in western countries. Alongside expenditure on diagnostics and treatment, there is a high economic impact due to lost productivity. Although a range of treatments are available, diagnoses are currently costly and require subjective assessment by a specialist. Moreover, treatment selection can be lengthy and can involve trial and error. To develop better diagnostics, stratification, and treatments for depression, we need a better understanding of the condition across different levels - from neural mechanisms to cognition and behaviour. Computational modelling is an emergent theory-driven approach which can aid linking data across different levels of analysis - from neural mechanisms and computations in the brain, to cognitive algorithms and observable behaviour. Some models integrate diverse findings and make predictions, while others enable inference of clinical measures which are not obvious in raw data. Modelling can lead to better understanding of depression, and in turn to better stratification and treatments. On the other hand, machine learning and classification methods can help detect clinically-relevant patterns in experimental data in a purely data-driven manner. This can lead to development of better screening and diagnostic methods. In the current work, we first review some of the most prominent neurocognitive theories of depression, as well as existing studies which used computational modelling methods. Based on our review, we argue that modelling can provide a rich set of tools for a better understanding of the condition. We then develop two novel computational modelling accounts of depression. In the first account, we propose an explicit mechanistic link between a robust behavioural negative bias effect and some of the widely reported or theorised neural aspects of depression - hyperactive amygdala and inhibited dopamine release. In the second account, we attempt to better explain depressive cognitive deficits and show how they can arise from depression-relevant etiological factors - altered valuation and controllability estimates. Finally, in the third part of this work we attempt to develop a novel system for detecting depressive symptoms based on a combination of face-tracking, eye-tracking and cognitive performance measures. We evaluate the system in a pilot experiment and show that a combination of measures can achieve better results than measures from each domain separately.

Raymond Hiu Yeung, Li. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (leaves 51-69). / Acknowledgment --- p.iii / Abstract --- p.iv / List of Abbreviations --- p.vii / Chapter CHAPTER ONE: --- INTRODUCTION / Chapter 1.1. --- Parkinson's Disease --- p.1 / Chapter 1.1.1 --- Epidemiology --- p.1 / Chapter 1.1.2 --- Clinical symptoms --- p.2 / Chapter 1.1.3 --- Neuropathology --- p.3 / Chapter 1.2 --- Proposed mechanisms of Neuronal Cell Death in PD / Chapter 1.2.1 --- Oxidative Stress --- p.4 / Chapter 1.2.2 --- Mitochondrial Dysfunction --- p.5 / Chapter 1.2.3 --- Excitotoxicity --- p.6 / Chapter 1.2.4 --- Genetic Factor --- p.8 / Chapter 1.2.5 --- Aging --- p.9 / Chapter 1.3 --- "1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine as a PD model" / Chapter 1.3.1 --- The discovery of MPTP --- p.10 / Chapter 1.3.2 --- The mechanism of MPTP toxicity --- p.10 / Chapter 1.4 --- Reactive Oxygen Species (ROS) and Antioxidants in CNS / Chapter 1.4.1 --- Superoxide and Superoxide Dismutases --- p.13 / Chapter 1.4.2 --- "Hydrogen Peroxide, Catalase and Glutathione System" --- p.14 / Chapter 1.4.3 --- Hydroxyl Radicals --- p.15 / Chapter 1.4.4 --- Nitric Oxide (NO) --- p.16 / Chapter 1.5 --- Astrocytes / Chapter 1.5.1 --- Characteristics of astrocytes --- p.20 / Chapter 1.5.2 --- The role of astrocytes in PD --- p.21 / Chapter 1.6 --- The aim of this project --- p.24 / Chapter CHAPTER 2: --- MATERIALS AND METHODS / Chapter 2.1 --- Astrocyte cultures --- p.27 / Chapter 2.2 --- MPTP treatment --- p.28 / Chapter 2.3 --- Lactate Dehydrogenase Assay --- p.29 / Chapter 2.4 --- Determination of nitrite and nitrate levels in cultured astrocytes --- p.30 / Chapter 2.5 --- Assay for Cyclic GMP production --- p.32 / Chapter 2.6 --- Inhibition of NO by L-NAME and Dexamethasone --- p.33 / Chapter 2.7 --- NFkB immunostaining --- p.33 / Chapter 2.8 --- Superoxide Dismutase Assay --- p.34 / Chapter 2.9 --- Statistics --- p.36 / Chapter CHAPTER 3: --- RESULTS / Chapter 3.1 --- Lactate dehydrogenase (LDH) activities after MPTP treatment --- p.37 / Chapter 3.2 --- The effects of MPTP on nitrite levels --- p.37 / Chapter 3.2.1 --- Mesencephalic astrocytes --- p.37 / Chapter 3.2.2 --- Striatal astrocytes --- p.38 / Chapter 3.2.3 --- Cortical astrocytes --- p.38 / Chapter 3.3 --- The effects of L-NAME on nitrite levels after MPTP treatment --- p.38 / Chapter 3.4 --- The effects of dexamethasone on nitrite levels after MPTP treatment --- p.39 / Chapter 3.5 --- Change in intracellular cyclic GMP in astrocytes after MPTP treatment --- p.40 / Chapter 3.6 --- The effects of MPTP on NFkB distribution in astrocytes --- p.40 / Chapter 3.7 --- The effects of MPTP on SOD activity in astrocytes --- p.41 / Chapter 3.7.1 --- Mesencephalic astrocytes --- p.41 / Chapter 3.7.2 --- Striatal astrocytes --- p.41 / Chapter 3.7.3 --- Cortical astrocytes --- p.42 / Chapter CHAPTER 4: --- DISCUSSION AND CONCLUSION --- p.43 / REFERENCES --- p.51

by Wang Wen. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 113-124). / Abstracts in English and Chinese. / ABSTRACT --- p.i / FLOWCHART --- p.vi / ACKNOWLEDGEMENT --- p.x / ABBREVIATIONS --- p.xi / INDEX FOR FIGURES --- p.xii / INDEX FOR TABLES --- p.xv / TABLE OF CONTENTS --- p.xvi / Chapter 1. --- INTRODUCTION --- p.1 / Chapter 1.1 --- PATELLAR TENDINOSIS --- p.1 / Chapter 1.1.1 --- Introduction --- p.1 / Chapter 1.1.2 --- Epidemiology of Patellar Tendinosis --- p.3 / Chapter 1.1.3 --- Etiology of Patellar Tendinosis --- p.3 / Chapter 1.1.4 --- Manifestations of Patellar Tendinosis --- p.4 / Chapter 1.1.5 --- Imaging Examination on Patellar Tendinosis --- p.4 / Chapter 1.1.6 --- Clinical Diagnosis of Patellar Tendinosis --- p.6 / Chapter 1.1.7 --- Management of Patellar Tendinosis … --- p.6 / Chapter 1.2 --- ANATOMY AND HISTOLOGY OF PATELLAR TCNDON --- p.7 / Chapter 1.3 --- STRUCTURE AND METABOLISM OF TENDON --- p.9 / Chapter 1.3.1 --- Tenocytes --- p.9 / Chapter 1.3.2 --- Extra-cellular Matrix --- p.11 / Chapter 1.3.2.1 --- Collagen --- p.11 / Chapter 1.3.2.2 --- Proteoglycans --- p.12 / Chapter 1.4 --- ROLES OF GROWTH FACTORS TENDON HEALING AND REPAIR --- p.14 / Chapter 1.4.1 --- Platelet-Derived Growth Factor --- p.14 / Chapter 1.4.2 --- Transforming Growth Factor-beta --- p.15 / Chapter 1.5 --- HISTOPATHOLOGY OF PATELLAR TENDINOSIS --- p.16 / Chapter 1.6 --- STUDY PLAN --- p.17 / Chapter 1.6.1 --- Characterization on Hypercellularity --- p.18 / Chapter 1.6.2 --- Characterization on Disorganization and Loosening of Collagen --- p.18 / Chapter 1.6.3 --- Characterization on Inflammatory Trace --- p.20 / Chapter 1.6.4 --- Characterization on Growth Factors in Tendinosis --- p.21 / Chapter 1.7 --- OBJECTIVES --- p.22 / Chapter 2. --- MATERIALS AND METHODS --- p.27 / Chapter 2.1 --- HUMAN TISSUES --- p.27 / Chapter 2.1.1 --- Patellar Tendinosis Tissues --- p.27 / Chapter 2.1.1.1 --- Diagnosis of patellar tendinosis --- p.27 / Chapter 2.1.1.2 --- Recruitment of patients --- p.27 / Chapter 2.1.4 --- Healthy Patellar Tendon tissues --- p.28 / Chapter 2.2 --- TISSUES COLLECTION AND PREPARATION --- p.28 / Chapter 2.3 --- HISTOLOGICAL STUDY ON HUMAN SPECIMENS --- p.28 / Chapter 2.3.1 --- Haematoxyline and Eosin Staining --- p.29 / Chapter 2.3.2 --- Safranin O Staining --- p.29 / Chapter 2.3.2.1 --- Reagents preparation --- p.29 / Chapter 2.3.2.2 --- Experimental procedure --- p.30 / Chapter 2.3.5 --- Polarization Microscopy --- p.30 / Chapter 2.4 --- IMMUNOHISTOCHEMICAL STAINING --- p.30 / Chapter 2.4.1 --- Reagents Preparation --- p.31 / Chapter 2.4.2 --- Experimental Procedure --- p.33 / Chapter 2.5 --- IMAGE ANALYSIS --- p.35 / Chapter 2.5.1 --- Equipment --- p.35 / Chapter 2.5.2 --- Procedures --- p.35 / Chapter 2.6 --- IN SITU ZYMOGRAPHY --- p.37 / Chapter 2.6.1 --- Reagents Preparation --- p.37 / Chapter 2.6.2 --- Experimental Procedure --- p.38 / Chapter 2.7 --- STATISTIC ANALYSIS.… --- p.39 / Chapter 3. --- RESULTS --- p.42 / Chapter 3.1 --- HUMAN SAMPLES --- p.42 / Chapter 3.1.1 --- Patellar tendinosis patients --- p.42 / Chapter 3.1.2 --- Healthy control group --- p.43 / Chapter 3.2 --- HISTOLOGICAL STUDY ON HUMAN SPECIMENS --- p.43 / Chapter 3.2.1 --- Gross Morphology --- p.43 / Chapter 3.2.2 --- Haematoxyline and Eosin Staining --- p.44 / Chapter 3.2.3 --- Safranin O Staining --- p.44 / Chapter 3.2.4 --- Polarization Microscopy --- p.44 / Chapter 3.3 --- IMAGE ANALYSIS --- p.45 / Chapter 3.3.1 --- Immunohistochemistry of PCNA --- p.45 / Chapter 3.3.2 --- Immunohistochemistry of hsp47 --- p.46 / Chapter 3.3.3 --- Immunohistochemistry of Procollogen Type I --- p.47 / Chapter 3.3.4 --- Immunohistochemistry of MMP1 --- p.47 / Chapter 3.3.5 --- Immunohistochemistry of TIMP1 --- p.48 / Chapter 3.3.6 --- Immunohistochemistry of COX-2 --- p.49 / Chapter 3.3.7 --- Immunohistochemistry of TGFP --- p.49 / Chapter 3.3.8 --- Immunohistochemistry of PDGFbb --- p.50 / Chapter 3.3.9 --- Immunohistochemistry of PDGFRβ --- p.51 / Chapter 3.3.10 --- Summary of Image Analysis of Immunohistochemical staining --- p.51 / Chapter 3.4 --- IN SITU ZYMOGRAPHY --- p.52 / Chapter 4. --- DISCUSSION --- p.93 / Chapter 4.1 --- DIAGNOSIS OF PATELLAR TENDINOSIS --- p.93 / Chapter 4.2 --- HYPERCELLULARITY IN PATELLAR TENDINOSIS --- p.95 / Chapter 4.3 --- COLLAGEN DISTURBANCE IN PATELLAR --- p.97 / Chapter 4.4 --- INFLAMMATORY RESPONSE IN PATELLAR TENDINOSIS --- p.100 / Chapter 4.5 --- THE EXPRESSION OF GROWTH FACTORS IN PATELLAR TENDINOSIS --- p.102 / Chapter 4.6 --- PROPOSED PATHOGENESIS FOR PATELLAR TENDINOSIS --- p.105 / Chapter 4.7 --- LIMITATION OF THIS STUDY --- p.108 / Chapter 4.8 --- FUTURE STUDY --- p.109 / Chapter 5. --- CONCLUSION --- p.111 / BIBLIOGRAPHY --- p.113