Chan Ming Lok. / Thesis submitted in: December 1999. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 93-108). / Abstracts in English and Chinese. / Ackowledgments --- p.i / Abstract in English --- p.ii / Abstract in Chinese --- p.iii / List of Abbreviations --- p.iv / List of Tables --- p.v / List of Figures --- p.vi / Chapter Chapter 1 --- Introduction and Objectives / Chapter 1.1 --- Hepatocellular Carcinoma --- p.1 / Chapter 1.1.1 --- Epidemiology --- p.1 / Chapter 1.1.2 --- Geographical Distribution --- p.1 / Chapter 1.1.3 --- Sex and Age --- p.1 / Chapter 1.1.4 --- Etiology --- p.2 / Chapter 1.1.5 --- Molecular Basis of HCC --- p.3 / Chapter 1.1.6 --- Situation in China and Hong Kong --- p.4 / Chapter 1.2 --- The Hepatitis B Virus --- p.5 / Chapter 1.2.1 --- Morphology --- p.5 / Chapter 1.2.2 --- Structure of the HBV Genome --- p.6 / Chapter 1.2.3 --- Functional Domains of the HBV Genome --- p.9 / Chapter 1.2.4 --- Pathogenesis of HBV Infection --- p.11 / Chapter 1.3 --- HBx --- p.12 / Chapter 1.3.1 --- The HBV x Gene --- p.12 / Chapter 1.3.2 --- The HBX Protein --- p.13 / Chapter 1.3.3 --- "Preferential HBX Expression in Sera, Hepatitis, Cirrhosis and HCC" --- p.13 / Chapter 1.3.4 --- Cellular Localization of HBX --- p.14 / Chapter 1.3.5 --- Animal Studies --- p.15 / Chapter 1.3.6 --- Functional Studies on HBX --- p.15 / Chapter 1.3.7 --- Variations in the HBx Gene --- p.21 / Chapter 1.4 --- Objectives of this Study --- p.24 / Chapter Chapter 2 --- Methods and Materials Methods / Chapter 2.1 --- Paraffin Embedding of Patient Tissue Samples --- p.26 / Chapter 2.1.1 --- Tissue Processing --- p.26 / Chapter 2.1.2 --- Paraffin Embedding of Tissue Samples --- p.26 / Chapter 2.2 --- Sectioning of Paraffin Embedded Tissue Sections --- p.26 / Chapter 2.3 --- Immunohistochemical Staining of Paraffin Embedded Tissue Sections --- p.26 / Chapter 2.3.1 --- Dewaxing of Paraffin-Embedded Tissue Sections --- p.26 / Chapter 2.3.2 --- Rehydration of Tissue Sections --- p.27 / Chapter 2.3.3 --- Antigen Retrieval --- p.27 / Chapter 2.3.4 --- Quenching of Endogenous Hydrogen Peroxidase --- p.27 / Chapter 2.3.5 --- Blocking of Endogenous Biotin and Non-Specific Protein Binding --- p.27 / Chapter 2.3.6 --- Antibody Incubation and Color Development --- p.27 / Chapter 2.3.7 --- Counterstaining and Coverslip Mounting --- p.28 / Chapter 2.3.8 --- Interpretation of Immunostaining Results --- p.28 / Chapter 2.4 --- DNA Extraction from HCC Tissues --- p.28 / Chapter 2.4.1 --- Sectioning of Frozen HCC Specimens --- p.28 / Chapter 2.4.2 --- Proteinase K Digestion and Phenol Chloroform Extraction --- p.29 / Chapter 2.4.3 --- Ethanol Precipitation and Re-suspension in Tris-EDTA (TE) Buffer --- p.29 / Chapter 2.5 --- Quantitation and Purity Check of Extracted DNA --- p.29 / Chapter 2.6 --- Quality Check for Extracted Genomic DNA --- p.30 / Chapter 2.6.1 --- Agarose Gel Electrophoresis --- p.30 / Chapter 2.6.2 --- Polymerase Chain Reaction (PCR) of the β-globin Gene --- p.30 / Chapter 2.6.3 --- Analysis of PCR Fragments by Agarose Gel Electrophoresis --- p.30 / Chapter 2.7 --- Polymerase Chain Reaction Amplification of HBs and HBx Genes of the Hepatitis B Virus --- p.31 / Chapter 2.8 --- Southern Blot of HBx PCR Fragments --- p.31 / Chapter 2.8.1 --- Immobilization of DNA onto a Positively Charged Nylon Membrane and Pre-hybridization --- p.31 / Chapter 2.8.2 --- Radio-labeling of an HBV Probe --- p.32 / Chapter 2.8.3 --- Hybridization of a 32P-labeled HBV Probe and Film Exposure --- p.32 / Chapter 2.9 --- Cloning of PCR Fragments into pGEM®-T Vector for Sequencing --- p.33 / Chapter 2.9.1 --- Gel Extraction and Purification --- p.33 / Chapter 2.9.2 --- Ligation --- p.33 / Chapter 2.10 --- Transformation of Competent DH5a cells --- p.34 / Chapter 2.10.1 --- Preparation of Competent DH5α Using Calcium Chloride --- p.34 / Chapter 2.10.2 --- Heat Shock of Competent DH5α Cells --- p.34 / Chapter 2.10.3 --- Plating of Transformed Cells onto LB Agar Plates --- p.34 / Chapter 2.10.4 --- Screening of Transformants for Inserts --- p.35 / Chapter 2.11 --- Miniprep of Plasmid DNA --- p.35 / Chapter 2.11.1 --- Inoculation of Bacterial Clones --- p.35 / Chapter 2.11.2 --- DNA Extraction by Alkaline Lysis and Phenol/Chloroform --- p.35 / Chapter 2.11.3 --- Ethanol Precipitation and Re-suspension in TE Buffer --- p.35 / Chapter 2.11.4 --- Confirmation of Positive Clones --- p.36 / Chapter 2.12 --- Sequencing of pGEM®-T Cloned HBx PCR Fragments --- p.36 / Chapter 2.13 --- Construction of the HBx-GFP Plasmid --- p.36 / Chapter 2.13.1 --- PCR Amplification of HBx Gene Inserts --- p.36 / Chapter 2.13.2 --- Confirmation of HBx Insert Sequence by DNA Sequencing --- p.37 / Chapter 2.13.3 --- Restriction Digest of HBx-pGEM®-T Plasmids to Obtain HBx Inserts --- p.37 / Chapter 2.13.4 --- Restriction Digest of pEGFP-Nl Cloning Vector for Cloning --- p.37 / Chapter 2.13.5 --- Ligation of HBx Inserts into the pEGFP Cloning Vector --- p.37 / Chapter 2.14 --- Large Scale Plasmid DNA Preparation --- p.38 / Chapter 2.15 --- Cell Culture --- p.39 / Chapter 2.16 --- Transfection using LipofectAminéёØ --- p.39 / Chapter 2.16.1 --- Seeding of Cells for Coverslip Growth --- p.39 / Chapter 2.16.2 --- Transfection using LipofecAminéёØ --- p.39 / Chapter 2.17 --- Cell Fixation and DAPI Staining Materials --- p.40 / Chapter 2.18 --- Chemicals --- p.41 / Chapter 2.19 --- Antibodies --- p.41 / Chapter 2.20 --- "Formalin-fixed, Paraffin Embedded Tissues of HCC Tissues from Xiamen" --- p.41 / Chapter 2.21 --- Frozen Liver Tissues --- p.41 / Chapter 2.22 --- PCR Reagents --- p.43 / Chapter 2.23 --- Primers --- p.43 / Chapter 2.24 --- Plasmid --- p.43 / Chapter 2.25 --- Enzymes --- p.43 / Chapter 2.26 --- Ligation Reagents --- p.43 / Chapter 2.27 --- Cloning Vectors --- p.45 / Chapter 2.28 --- Competent Cell --- p.45 / Chapter 2.29 --- Hela and HepG2 Cell Line --- p.45 / Chapter Chapter 3 --- Results / Chapter 3.1 --- Hepatitis B Virus Status of HCC Patients from Hong Kong and Xiamen --- p.46 / Chapter 3.2 --- Immunohistochemical Studies of the HBx Protein in Hong Kong and Xiamen HCC --- p.46 / Chapter 3.2.1 --- Cross Reaction of Anti-99 with Cytokeratin 18 (CK18) --- p.46 / Chapter 3.2.2 --- HBx Expression in HCC Patient Tissue Samples from Hong Kong --- p.50 / Chapter 3.2.3 --- HBxAg Staining in HCC Tissue Samples from Xiamen --- p.50 / Chapter 3.3 --- Agarose Gel Electrophoresis of DNA Extracted from Frozen Liver Tissues --- p.50 / Chapter 3.4 --- PCR Amplification of the β-globin Gene --- p.55 / Chapter 3.5 --- PCR Amplification of the HBs Gene from Liver Samples of HCC Patients from Hong Kong --- p.55 / Chapter 3.6 --- PCR Amplification of the HBx Gene from Liver Samples of HCC Patients from Hong Kong --- p.55 / Chapter 3.7 --- Amplification of the HBx Gene from Serum Samples of Chronic Hepatitis B Virus from Hong Kong Using Nested PCR --- p.61 / Chapter 3.8 --- Southern Blot of HBx PCR Fragments --- p.61 / Chapter 3.9 --- Cloning and Sequencing of the HBx Gene in HCC and Chronic Hepatitis B Patient Samples from Hong Kong --- p.61 / Chapter 3.10 --- Expression Pattern of Wild-type HBx-GFP Fusion Protein in Transiently Transfected HeLa and HepG2 Cells --- p.73 / Chapter 3.11 --- Expression Patterns of HBx-GFP with and without Mutations at Codons 130 and 131 in HeLa and HepG2 Cell Line --- p.78 / Chapter 3.12 --- Growth Kinetics of HeLa Cells Transfected with GFP and Wild-type HBx-GFP with and without Mutations in Codons 130 and131 --- p.81 / Chapter Chapter 4 --- Discussion / Chapter 4.1 --- HBxAg Expression in Tumorous and Surrounding Non-tumorous Tissues --- p.83 / Chapter 4.2 --- "Detection of the HBx Gene in Sera, Non-tumorous and Tumorous Tissues" --- p.84 / Chapter 4.3 --- HBx Gene Mutations in Chronic Hepatitis and HCC --- p.85 / Chapter 4.3.1 --- Codon 127 (HBV nt 1752-1754) --- p.85 / Chapter 4.3.2 --- Codons 130 and 131 (HBV nt 1761-1766) --- p.86 / Chapter 4.3.3 --- Lack of Correlation between HBx Gene Mutations and Lack of HBxAg Expression --- p.87 / Chapter 4.4 --- Cellular Localization of HBxAg in Transiently Transfected Cells Lines --- p.88 / Chapter 4.5 --- Functional Difference Between Wild-type and Mutant HBX Protein --- p.89 / Chapter Chapter 5 --- Conclusions and Directions for Further Studies / Chapter 5.1 --- Conclusions --- p.91 / Chapter 5.2 --- Directions for Further Studies --- p.92 / References --- p.93 / Appendix / Chapter A1 --- Recipes of Reagents Used in this Study --- p.109 / Chapter A2 --- Schematic Setup of Downward Capillary Transfer of DNA --- p.112 / Chapter A3 --- Circle Map of the pGEM®-T Cloning Vector and Construct of the HBx-pGEM®-T Plasmid --- p.113 / Chapter A4 --- Circle Map of the pEGFP-Nl Cloning Vector and Construct of the HBx-GFP Plasmid --- p.114

Yeung Sau-Man. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 139-172). / Abstracts in English and Chinese. / Title page --- p.i / Acknowledgements --- p.ii / Table of Content --- p.iv / List of Figures --- p.viii / List of Graphs --- p.x / List of Tables --- p.xi / Abbreviations --- p.xiv / Abstract --- p.xv / Chinese Abstract --- p.xvii / Chapter Chapter 1 --- General Introduction --- p.1 / Chapter 1.1 --- Diabetes Mellitus --- p.2 / Chapter 1.1.1 --- Type 1 diabetes mellitus --- p.3 / Chapter 1.1.2 --- Type 2 diabetes mellitus --- p.5 / Chapter 1.1.3 --- Maturity onset diabetes of the young (MODY) --- p.6 / Chapter 1.1.4 --- Gestational diabetes --- p.7 / Chapter 1.2 --- Effect of Diabetes on Pregnancy --- p.9 / Chapter 1.3 --- Suggested Causes of Diabetic Embryopathy --- p.10 / Chapter 1.3.1 --- Glucose --- p.10 / Chapter 1.3.2 --- Ketone bodies --- p.11 / Chapter 1.3.3 --- Somatomedin inhibitors --- p.12 / Chapter 1.3.4 --- TNF-α --- p.12 / Chapter 1.3.5 --- Oxidative stress --- p.13 / Chapter 1.4 --- Animal Model of Diabetes --- p.15 / Chapter 1.4.1 --- Chemically-induced --- p.15 / Chapter 1.4.2 --- Mutants --- p.17 / Chapter 1.5 --- Gene-teratogen Interaction under Diabetic Pregnancy --- p.19 / Chapter 1.6 --- Strategy of the Thesis --- p.21 / Chapter Chapter 2 --- General Materials and Methods --- p.24 / Chapter 2.1 --- Mouse Maintenance and Mating Method --- p.25 / Chapter 2.2 --- Induction of Diabetes --- p.25 / Chapter 2.3 --- Preparation of All-trans Retinoic Acid --- p.26 / Chapter 2.4 --- Dissection of Embryos --- p.26 / Chapter 2.5 --- DNA Extraction from Yolk Sac for Genotyping --- p.27 / Chapter 2.6 --- Genotyping of Embryos --- p.28 / Chapter 2.7 --- Preparation of RNA Probes for In Situ Hybridization --- p.29 / Chapter 2.7.1 --- Mini-scale preparation of plasmid DNA --- p.29 / Chapter 2.7.2 --- Linearization of plasmid DNA --- p.30 / Chapter 2.7.3 --- In vitro transcription --- p.31 / Chapter 2.8 --- Whole Mount In Situ Hybridization --- p.33 / Chapter 2.8.1 --- Fixation and dehydration of embryos --- p.33 / Chapter 2.8.2 --- Hybridization --- p.33 / Chapter 2.8.3 --- Post-hybridization wash --- p.34 / Chapter 2.8.4 --- Antibody wash and color development --- p.35 / Chapter 2.8.5 --- Embryo powder preparation --- p.36 / Chapter 2.8.6 --- Pre-absorption of antibody --- p.35 / Chapter 2.9 --- Whole Mount TUNEL Staining --- p.36 / Chapter Chapter 3 --- "Maternal Diabetes, Sp2H and RA Interaction" --- p.39 / Chapter 3.1 --- Introduction --- p.40 / Chapter 3.1.1 --- Neural tube defects --- p.41 / Chapter 3.1.2 --- Retinoic acid as environmental factor --- p.41 / Chapter 3.1.3 --- Sp2H as genetic factor --- p.44 / Chapter 3.1.4 --- Experimental design of this chapter --- p.46 / Chapter 3.2 --- Material and Methods --- p.47 / Chapter 3.2.1 --- Sp2H mice --- p.47 / Chapter 3.2.2 --- Mating and RA injection protocol --- p.47 / Chapter 3.2.3 --- Dissection of fetuses and analysis of neural tube development --- p.48 / Chapter 3.3 --- Results --- p.49 / Chapter 3.3.1 --- Maternal diabetes alone --- p.50 / Chapter 3.3.2 --- Sp2H mutation alone --- p.51 / Chapter 3.3.3 --- RA alone --- p.52 / Chapter 3.3.4 --- Maternal diabetes and RA interaction --- p.53 / Chapter 3.3.5 --- Sp2H mutation and RA interaction --- p.55 / Chapter 3.3.6 --- Sp2H mutation and maternal diabetes interaction --- p.57 / Chapter 3.3.7 --- "Maternal diabetes, Sp2H mutation and RA interaction" --- p.59 / Chapter 3.4 --- Discussion --- p.62 / Chapter 3.4.1 --- Maternal diabetes alone does not cause neural tube defects --- p.62 / Chapter 3.4.2 --- RA induces neural tube defects --- p.63 / Chapter 3.4.3 --- Interaction of maternal diabetes with RA in increasing the susceptibility to neural tube defects --- p.64 / Chapter 3.4.4 --- Embryos with Sp2H allele show increased susceptibility to neural tube defects when triggered by maternal diabetes and RA --- p.67 / Chapter Chapter 4 --- Molecular and Cellular Bases of Interaction --- p.71 / Chapter 4.1 --- Introduction --- p.72 / Chapter 4.1.1 --- Mechanism of diabetic embryopathy --- p.72 / Chapter 4.1.2 --- Mechanism of Sp2H mutation in development of neural tube defects --- p.74 / Chapter 4.1.3 --- Mechanism of RA teratogenicity --- p.75 / Chapter 4.1.4 --- "Possible common pathways shared by maternal diabetes, RA and Sp2H mutation" --- p.76 / Chapter 4.1.5 --- Experimental design of this chapter --- p.78 / Chapter 4.2 --- Materials and Methods --- p.80 / Chapter 4.2.1 --- Sample collection for studying Pax3 expression in Sp2H/+ And +/+ embryos in response to maternal diabetes or RA by whole mount in situ hybridization --- p.80 / Chapter 4.2.2 --- "Sample collection for studying the level of apoptosis in response to the interaction of maternal diabetes, Sp2H mutation and RA by whole mount TUNEL staining" --- p.82 / Chapter 4.3 --- Results --- p.86 / Chapter 4.3.1 --- Expression levels of Pax3 mRNA detected by whole mount in situ hybridization / Chapter 4.3.1.1 --- Expression of Pax3 in Sp2H/+/- and +/+ embryos --- p.86 / Chapter 4.3.1.2 --- Effect of maternal diabetes on Pax3 expression in Sp2H/+ and +/+ embryos --- p.87 / Chapter 4.3.1.3 --- Effect of RA on Pax3 expression in Sp2H /+ and +/+ embryos --- p.88 / Chapter 4.3.2 --- Level of apoptosis detected by whole mount TUNEL --- p.89 / Chapter 4.3.2.1 --- Effect of Sp2H allele on apoptosis --- p.94 / Chapter 4.3.2.2 --- Effect of maternal diabetes on apoptosis in Sp2H/+ and +/+ embryos --- p.95 / Chapter 4.3.2.3 --- Effect of RA on apoptosis in Sp2H/+ and +/+ embryos --- p.96 / Chapter 4.3.2.4 --- Effect of maternal diabetes and RA on apoptosis in Sp2H/+ and +/+ embryos --- p.97 / Chapter 4.4 --- Discussion --- p.99 / Chapter 4.4.1 --- Underexpression of Pax3 and increases in apoptosis under maternal diabetes --- p.99 / Chapter 4.4.2 --- "RA does not down regulate Pαx3, but increases apoptosis" --- p.102 / Chapter 4.4.3 --- Interaction of maternal diabetes and RA in increasing apoptosis --- p.104 / Chapter Chapter 5 --- "Maternal Diabetes, NOD and RA Interaction" --- p.108 / Chapter 5.1 --- Introduction --- p.109 / Chapter 5.1.1 --- Diabetic embryopathy in NOD mice --- p.109 / Chapter 5.1.2 --- Experimental design of this chapter --- p.110 / Chapter 5.2 --- Materials and Methods --- p.112 / Chapter 5.2.1 --- NOD mice --- p.112 / Chapter 5.2.2 --- Mating and RA Injection Protocol --- p.112 / Chapter 5.2.3 --- Sample Collection for the Study of Pax3 Expression --- p.113 / Chapter 5.3 --- Results --- p.115 / Chapter 5.3.1 --- Maternal diabetic alone --- p.116 / Chapter 5.3.2 --- NOD mutation alone --- p.117 / Chapter 5.3.3 --- RA alone --- p.118 / Chapter 5.3.4 --- Maternal diabetes and RA interaction --- p.119 / Chapter 5.3.5 --- NOD mutation and RA interaction --- p.121 / Chapter 5.3.6 --- NOD mutation and maternal diabetes interaction --- p.123 / Chapter 5.3.7 --- "Maternal diabetes, NOD mutation and RA interaction" --- p.125 / Chapter 5.3.8 --- Expression of Pax3 in embryos with different copies of NOD alleles --- p.128 / Chapter 5.4 --- Discussion --- p.130 / Chapter 5.4.1 --- Maternal diabetes interacts with NOD mutation to increase susceptibility to neural tube defects --- p.130 / Chapter 5.4.2 --- Interaction of maternal diabetes with NOD mutation is greatly exacerbated when exposed to RA --- p.131 / Chapter 5.4.3 --- Pax3 is not involved in the interaction --- p.133 / Chapter Chapter 6 --- Conclusion and Future Perspectives --- p.134 / References --- p.139 / Figures / Graphs

Choi, Pui Wah. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 202-232). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese.

青少年特發性脊柱側凸(Adolescent Idiopathic Scoliosis, AIS) 是一種脊柱三維結構性畸形，其病因至今未明。它主要出現於11-13歲的青少年女性，其發病率為4%。由於目前此病的臨床治療效果未能盡如人意，因此必須明確其發病機制，以便能夠制定更有效的治療方案及預防措施。 / 既往有研究指出30%AIS患者存在系統性骨密度減低，且已證實骨密度的減少能夠預測其病情進展的情況。之前的研究主要通過傳統的雙能量X光骨質密度吸收儀（DXA）檢測骨密度，其測量結果僅局限於面積骨密度。然而，三維容積骨密度以及骨質微結構的分析對於深入了解患者的骨質量及其與發病機制的聯繫尤為重要。通過現代影像掃描技術發展，使我們可以通過高分辨率外周骨定量X-線斷層掃描儀（HR-pQCT）進行人體骨品質的無創定量檢測。其參數包括骨形態，容積骨密度以及鬆質骨的微結構。 / 本研究分為兩部分，研究目的為： 1）研究AIS患者與年齡，性別匹配的正常青少年骨品質的差異；2）評估及比較在AIS患者及其對照組中骨品質跟骨密度減少之關係。 / 未經治療AIS 患者214例，正常對照組187例，均為11-13歲的女性。 AIS患者及正常對照組均採用DXA掃描評估股骨頸的面積骨密度。此外，所有參加計劃者通過非優勢側橈骨遠端HR-pQCT 掃描，定量測量其骨形態，容積骨密度以及鬆質骨的微結構。 / 第一部分的結果顯示在校正年齡後AIS患者的皮質骨面積(p=0.048)，皮質骨容積骨密度(p=0.014)及鬆質骨骨小樑數目(p=0.003) 低於對照組，並且存在較高的骨小樑分離度(p=0.006)。通過多元線性回歸分析校正了年齡，鈣攝入量及體育活動後，仍顯示AIS患者皮質骨容積骨密度(p=0.032)及鬆質骨骨小樑數目(p=0.005) 顯著低於對照組，骨小樑分離度（p=0.010）顯著高於對照組。而皮質骨週長的比較則未見顯著差異。皮質骨中骨質量的異常提示AIS患者內皮質成骨時可能存在骨礦堆積障礙。並且這種較低的皮質骨面積及容積骨密度預示著較弱的骨機械強度，從而誘發AIS患者脊柱的不隱定以至畸形。此外，AIS中較少的骨小樑數目反映了骨小樑形成的缺陷，這可能是由於患者存在軟骨內成骨及骨礦化的異常調節。 / 在第二部分，根據DXA測量及計算的Z值，參加者被分為骨量偏低組（Z值≤-1)及正常骨量組（Z值>-1)。研究結果顯示，AIS的骨量偏低組與對照組具有顯著差異。通過骨量偏低組及正常骨量組的比較，結果顯示鬆質骨品質與骨量偏低的關係只存在於AIS組中。本研宄發現，在AIS患者中的骨量偏低組存在鬆質骨容積骨密度，骨體積分數顯著減少及骨小梁變薄。並且結果顯示AIS患者骨小梁模型指數（SMI）較大（p<0.001)，提示骨小梁更接近柱收結構，而先前研究已經證明柱狀結構較板狀結構在力學上更不穩定。通常鬆質骨對於代謝及生物力學的改變更加敏感。骨量偏低的AIS患者松質骨中骨品質的異常改變提示AIS患者可能存在骨代謝功能障礙，從而導致異常的骨形成及重塑。鬆質骨中骨微結構的改變可能會引起骨強度的下降，從而導致脊柱在機械力學上的不穩定及側凸進展。因此本研究的重要臨床意義在於需要形成一個融合了骨品質及骨密度相關指標的複合預測因素，在AIS的臨床治療過程中預測側凸進展。 / 此體內研究首次對AIS患者的骨品質進行了報導。研究結果表明AIS患者存在骨品質異常，並且首次提出骨量下降的AIS患者存在鬆質骨的異常改變。骨品質異常的本質和原因及其在AIS的發病機制中的作用值得進一步研究。 / Adolescent Idiopathic Scoliosis is a three-dimensional spinal deformity of unknown etiology. It occurs mainly in girls between 11 to 13-year-old with a prevalence rate of 4%. This common spinal condition can be associated with significant cosmetic and clinical morbidities in severe cases. Since the treatment for AIS remains unsatisfactory, it is imperative to elucidate the etiopathogenesis of AIS so that effective therapeutic and preventive measures can be devised. Towards this end, Cheng et al. investigated and noted that osteopenia was present in 30% of AIS subjects. Osteopenia was found to be a significant prognostic factor for curve progression in AIS. In previous studies, only Dual energy X-ray Absorptiometry (DXA) was available and the measurement was confined to areal-BMD (aBMD). For in-depth understanding of the bone quality and its link to the etiopathogenesis of AIS, three-dimensional volumetric evaluation of bone mass and measurement of key parameters of bone quality would be important. With the advancement of imaging techniques and the availability of high-resolution pQCT (HR-pQCT), it is now possible to have in vivo measurement of bone quality including Bone Morphometry, Volumetric BMD (vBMD) and Trabecular Bone Micro-architecture in human subjects. / The current study utilized HR-pQCT with the following objectives: 1) to investigate bone quality in AIS vs. age- and sex-matched normal controls and 2) to evaluate and compare the correlation of bone quality with osteopenia between AIS and non-AIS control subjects. / 214 untreated AIS and 187 non-AIS healthy girls between 11-13 years old were recruited. aBMD of bilateral femoral necks was measured by DXA. Bone Morphometry, vBMD and Trabecular Bone Micro-architecture were measured at the non-dominant distal radius using HR-pQCT. / In the first part, our findings demonstrated that AIS was associated with lower Cortical Bone Area (p=0.048), Cortical Bone vBMD (p=0.014), Trabecular Number (p=0.003) and greater Trabecular Separation (p=0.006) after adjustment for age. With multivariate linear regression analysis, after adjusted for age, calcium intake and physical activity levels, the association of AIS with lower Cortical Bone vBMD, (p=0.032), Trabecular Number (p=0.005) and greater Trabecular Separation (p=0.010) remained. In contrast, no difference was found in the Cortical Perimeter between AIS and controls. / The abnormalities in cortical bone quality in AIS suggested the possibility of defects in mineral accretion during endocortical apposition. We speculated that lower Cortical Area and vBMD could be associated with reduced bone mechanical strength thus predisposing to the development or progression of spinal deformity in AIS. Furthermore, the association between AIS and lower Trabecular Number reflected a defect in trabecular formation, which might be due to abnormal regulation and modulation of endochondral ossification and bone mineralization in AIS. / In the second part, subjects were classified into the osteopenic (Z-score≤-1) and non-osteopenic (Z-score>-1) group. Interestingly, we found that osteopenia in AIS was distinctly different from osteopenia in non-AIS controls. Alterations in trabecular bone quality in association with osteopenia were only detected in AIS. Osteopenic AIS was uniquely associated with lower Trabecular Bone vBMD, BV/TV, Trabecular Thickness (all p<0.001) and greater SMI (p=0.008) indicating predominance of rod-like trabeculae when compared with non-osteopenic AIS. / The trabecular compartment is generally more vulnerable and responsive to changes in the metabolic and biomechanical environment. The unique alterations of trabecular bone quality in osteopenic AIS suggested the presence of metabolic dysfunction resulting in abnormal modeling and remodeling processes in AIS. These altered trabecular bone micro-architecture might lead to reduced bone strength thus resulting in mechanical weakness of the spine and subsequent curve progression. Another clinical significance of the present study was the call for developing a composite prognostic factor incorporating both BMD and bone quality parameters for more accurate prediction of curve occurrence and progression in AIS in clinical practice. / In conclusion, this is the first series of in vivo studies evaluating bone quality in AIS. Our findings demonstrated abnormal bone quality in AIS and unique alteration of trabecular bone profile in osteopenic AIS. Further studies are warranted to better define the nature, origin and abnormal metabolic pathways and processes leading to the derangement in bone quality and its link to the etiopathogenesis of AIS. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Yu, Wing Sze. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 122-134). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese; appendixes includes Chinese. / ABSTRACT --- p.i / ABSTRACT (in Chinese) --- p.iv / ACKNOWLEDGEMENT --- p.vi / TABLE OF CONTENTS --- p.vii / LIST OF TABLES --- p.x / LIST OF FIGURES --- p.xi / LIST OF ABBREVIATIONS --- p.xii / Chapter Chapter 1 --- INTRODUCTION --- p.1 / Chapter 1.1. --- General overview of scoliosis --- p.1 / Chapter 1.1.1. --- Classification of scoliosis --- p.1 / Chapter 1.1.2. --- Prevalence of AIS --- p.2 / Chapter 1.2. --- Natural History of AIS --- p.3 / Chapter 1.3. --- Curve progression --- p.4 / Chapter 1.4. --- Current treatment modalities --- p.5 / Chapter 1.5. --- Etiology of AIS --- p.6 / Chapter 1.5.1. --- Bone mass and bone development --- p.9 / Chapter 1.5.2. --- Measurement of bone mineral density --- p.10 / Chapter 1.5.3. --- Osteopenia in AIS --- p.11 / Chapter 1.6. --- Bone quality --- p.13 / Chapter 1.6.1. --- Limitation of two-dimensional BMD measurement by DXA --- p.13 / Chapter 1.6.2. --- Bone quality assessment --- p.14 / Chapter Chapter 2 --- METHODOLOGY --- p.22 / Chapter 2.1. --- Research questions and Objectives --- p.22 / Chapter 2.2. --- Study Design --- p.23 / Chapter 2.2.1. --- Study Flowchart --- p.24 / Chapter 2.3. --- Subject Recruitment --- p.29 / Chapter 2.3.1. --- AIS patients --- p.29 / Chapter 2.3.2. --- Normal Controls --- p.29 / Chapter 2.4. --- Patients Consents --- p.30 / Chapter 2.5. --- Radiological Assessment --- p.30 / Chapter 2.5.1. --- Curve severity --- p.30 / Chapter 2.6. --- Anthropometric and pubertal assessments --- p.31 / Chapter 2.6.1. --- Body weight --- p.31 / Chapter 2.6.2. --- Body height --- p.31 / Chapter 2.6.3. --- Arm span --- p.32 / Chapter 2.6.4. --- Sitting height --- p.32 / Chapter 2.6.5. --- Body mass index --- p.32 / Chapter 2.7. --- Menstrual status and pubertal maturity --- p.33 / Chapter 2.8. --- Dietary calcium intake --- p.33 / Chapter 2.9. --- Physical activities --- p.34 / Chapter 2.10. --- Bone mineral density (BMD) measurements --- p.34 / Chapter 2.10.1. --- Areal BMD measured by Dual energy X-ray Absorptiometry (DXA) --- p.34 / Chapter 2.10.2. --- Definition of osteopenia or low bone mass --- p.35 / Chapter 2.11. --- Bone quality assessment --- p.36 / Chapter 2.11.1. --- Positioning --- p.36 / Chapter 2.11.2. --- Standardization of the Region of Interest (ROI) for Scan Acquisition --- p.36 / Chapter 2.11.3. --- Analysis of the Scan Results --- p.38 / Chapter 2.12. --- Statistical analysis --- p.41 / Chapter Chapter 3 --- RESULTS --- p.55 / Chapter 3.1. --- Subject characteristics --- p.55 / Chapter 3.2. --- Age of menarche, breast development and pubic hair development --- p.55 / Chapter 3.3. --- Anthropometric assessment --- p.55 / Chapter 3.4. --- Dietary calcium intake --- p.56 / Chapter 3.5. --- Physical activities --- p.56 / Chapter 3.6. --- aBMD and prevalence of osteopenia in AIS and controls --- p.56 / Chapter 3.7. --- Comparison of bone quality between AIS and controls --- p.57 / Chapter 3.7.1. --- Bone Morphometry --- p.57 / Chapter 3.7.2. --- Volumetric BMD --- p.58 / Chapter 3.7.3. --- Trabecular Bone Micro-architecture --- p.59 / Chapter 3.7.4. --- Short summary --- p.59 / Chapter 3.8. --- Comparison of bone quality Vs. Osteopenia between AIS and Controls --- p.61 / Chapter 3.8.1. --- Demographic characteristic of osteopenic and non-osteopenic AIS and controls --- p.61 / Chapter 3.8.2. --- Bone quality Vs Osteopenia in AIS and controls --- p.62 / Chapter 3.8.3. --- Short summary --- p.64 / Chapter Chapter 4 --- OVERALL DISCUSSION and CONCLUSION --- p.81 / Chapter 4.1. --- Low bone mineral density in AIS --- p.82 / Chapter 4.2. --- Comparison of bone quality between AIS and controls --- p.83 / Chapter 4.2.1. --- Alterations of Cortical Bone Morphometry and vBMD in AIS --- p.84 / Chapter 4.2.2. --- Lower Trabecular Number and greater Trabecular Separation in AIS --- p.88 / Chapter 4.3. --- Correlation between bone quality and osteopenia in AIS Vs normal controls --- p.90 / Chapter 4.3.1. --- Unique alteration of bone quality of trabecular bone in osteopenic AIS subjects --- p.90 / Chapter 4.3.2. --- Effect of the alterations in trabecular bone quality on bone strength in osteopenic AIS and its possible relationship with curve progression --- p.92 / Chapter 4.4. --- Justification of the Methodology --- p.95 / Chapter 4.4.1. --- Site of BMD measurement --- p.95 / Chapter 4.5. --- Summary and clinical significance --- p.97 / Chapter 4.6. --- Limitations and further studies --- p.99 / APPENDIX --- p.101 / BIBLIOGRAPHY --- p.122 / CONFERENCES AND PUBLICATIONS --- p.136

by Wu Che-yuen Justin. / "September 2000 (amendment)." / Thesis (M.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (p. 237-267). / 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.

A coledocolitíase residual representa grande desafio na avaliação diagnóstica e proposta terapêutica. Neste contexto, realizamos estudo retrospectivo com o objetivo de avaliar critérios clínicos, laboratoriais e métodos de imagem para o seu diagnóstico; avaliar o resultado do tratamento através de procedimentos endoscópicos e cirúrgicos, bem como a ocorrência de complicações e sua repercussão no período de internação. Foram estudados 32 (trinta e dois) pacientes portadores de coledocolitíase residual internados na Clínica Cirúrgica do Hospital das Clínicas da Faculdade de Medicina da Universidade Federal de Goiás, no período de janeiro de 1995 a julho de 2001. Foram incluídos pacientes submetidos previamente a colecistectomia, nos quais o diagnóstico de coledocolitíase foi feito posteriormente (pela não realização de colangiografia trans-operatória) ou no próprio curso da colecistectomia, porém postergando-se o tratamento. Pudemos concluir: a maioria dos pacientes portadores de coledocolitíase residual tem como sintoma principal a icterícia; a ultra-sonografia não é um método diagnóstico eficaz, uma vez que demonstrou alteração de via biliar em cerca de 50% dos pacientes; tanto o procedimento endoscópico como o cirúrgico mostraram alto índice de clareamento da via biliar (acima de 90%), sendo a morbidade baixa e mortalidade nula em ambos os procedimentos; o período de internação foi menor quando o procedimento endoscópico foi realizado / Choledocholithiasis represents a great challenge in diagnostic evaluation and therapeutics. Because of it we\'ve proposed a retrospective study to analise the clinical and laboratorial criteria and image studies to the diagnosis of such condition. It was possible to evaluate the treatment (endoscopic or surgical) and complications with these information. Thus, with this aim, 32 (thirty-two) patients were evaluated. They were suffering from residual choledocholithiasis and were admitted on the Surgical Unit of the General Hospital of the Medical School of University of Goiás, from january 1995 to july 2001. It was included patients that were performed on a previous cholecistectomy. The diagnose of choledocholithiasis was get either during the surgery, although the definitive treatment had been postponed, or on the follow-up. We concluded that most part of the patients with residual choledocholithiasis were icteric and that the ultrasound study is not an effective method to detect residual choledocholithiasis (positive around 50%). Besides, both therapeutic procedures (endoscopic and surgical) were successful in the cleaning of biliary ducts (above 90%), had low morbidity and no mortality. The discharge of the patient was faster in case of endoscopic procedure

Hung Wing Yin Vivian. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 128-142). / Abstracts in English and Chinese ; appendix in Chinese. / ABSTRACT --- p.i / ABSTRACT (in Chinese) --- p.iv / ACKNOWLEDGMENT --- p.vii / TABLE OF CONTENTS --- p.viii / LIST OF TABLES --- p.xiv / LIST OF FIGURES --- p.xvi / LIST OF ABBREVIATIONS --- p.xix / Chapter I. --- INTRODUCTION --- p.1 / Chapter 1.1. --- Scoliosis --- p.1 / Chapter 1.1.1. --- Classification of scoliosis --- p.1 / Chapter 1.1.2. --- Idiopathic scoliosis --- p.1 / Chapter 1.1.3. --- Clinical examination --- p.2 / Chapter 1.1.4. --- Curve pattern --- p.2 / Chapter 1.2. --- Etiology of AIS --- p.3 / Chapter 1.2.1. --- Prevalence of AIS --- p.5 / Chapter 1.2.2. --- Anthropometric Measurement in AIS --- p.5 / Chapter 1.2.3. --- Bone mass --- p.6 / Chapter 1.2.4. --- Bone mineral density measurements --- p.6 / Chapter 1.2.5. --- Osteopenia in AIS --- p.7 / Chapter 1.3. --- Natural history ofAIS --- p.8 / Chapter 1.3.1. --- Curve progression --- p.9 / Chapter 1.3.2. --- Treatment of scoliosis --- p.11 / Chapter 1.4. --- Research questions --- p.12 / Chapter 1.5. --- Objectives --- p.13 / Chapter II. --- METHODOLOGY --- p.20 / Chapter 2.1 --- Study Design --- p.20 / Chapter 2.2 --- Subject recruitment --- p.20 / Chapter 2.2.1 --- AIS patients --- p.20 / Chapter 2.2.2 --- Inclusion criteria --- p.20 / Chapter 2.2.3 --- Exclusion criteria --- p.20 / Chapter 2.2.4 --- Informed consent --- p.21 / Chapter 2.3 --- Grouping for chronological age --- p.21 / Chapter 2.4 --- Radiography assessments --- p.21 / Chapter 2.4.1 --- Cobb angle measurement --- p.21 / Chapter 2.4.2 --- Curve pattern --- p.22 / Chapter 2.4.3 --- Risser grade --- p.22 / Chapter 2.5 --- Definition of curve progression --- p.22 / Chapter 2.6 --- Bone mineral density (BMD) measurements --- p.23 / Chapter 2.6.1 --- Dual energy X-ray Absorptiometry (DXA) --- p.23 / Chapter 2.6.2 --- Peripheral quantitative computed tomography (pQCT) --- p.24 / Chapter 2.6.3 --- Definition of osteopenia or low bone mass --- p.24 / Chapter 2.7 --- Anthropometric measurements --- p.25 / Chapter 2.7.1 --- Body height --- p.25 / Chapter 2.7.2 --- Body weight --- p.26 / Chapter 2.7.3 --- Arm span --- p.26 / Chapter 2.7.4 --- Sitting height --- p.27 / Chapter 2.8 --- Family history --- p.27 / Chapter 2.9 --- Menstrual status --- p.27 / Chapter 2.10 --- Medication and fracture history --- p.27 / Chapter 2.11 --- Statistical analysis --- p.27 / Chapter 2.11.1 --- Sample size power calculation --- p.28 / Chapter 2.11.2 --- Student t test --- p.28 / Chapter 2.11.3 --- Paired t-test --- p.28 / Chapter 2.11.4 --- Predicting the incidence of curve progression --- p.28 / Chapter 2.11.4.1 --- Predictive outcome --- p.28 / Chapter 2.11.4.2 --- Potential risk factors --- p.28 / Chapter 2.11.4.3 --- Coding system for categorical variables --- p.29 / Chapter 2.11.4.4 --- Univariate analysis --- p.30 / Chapter 2.11.4.5 --- Logistic regression --- p.30 / Chapter 2.11.4.6 --- Receiver operating characteristics (ROC) curves --- p.32 / Chapter III. --- RESULTS --- p.54 / Chapter 3.1 --- Patients Characteristics --- p.54 / Chapter 3.1.1 --- Sample size --- p.54 / Chapter 3.1.2 --- Distribution of patient characteristics --- p.54 / Chapter 3.1.3 --- Drop out --- p.54 / Chapter 3.1.4 --- Prevalence of osteopenia (BMDage-adjusted ≤ -1) and low bone mass (BMCage-adjusted ≤ -1) --- p.55 / Chapter 3.1.5 --- Comparison between the BMD of the bilateral hip and tibia --- p.55 / Chapter 3.2 --- Comparison of AIS patients with osteopenia and with normal bone status --- p.55 / Chapter 3.3 --- Univariate analysis --- p.56 / Chapter 3.3.1 --- Growth related factors --- p.56 / Chapter 3.3.2 --- "Skeletal related parameters (areal BMD, volumetric BMD and BMC)" --- p.56 / Chapter 3.3.2.1 --- DXA lumbar spine --- p.56 / Chapter 3.3.2.2 --- DXA proximal femur at the convex-side hip --- p.56 / Chapter 3.3.2.3 --- DXA proximal femur at the concave-side hip --- p.57 / Chapter 3.3.2.4 --- pQCT at non-dominant distal radius --- p.57 / Chapter 3.3.2.5 --- pQCT - vBMD at convex-side distal tibia --- p.57 / Chapter 3.3.2.6 --- pQCT - vBMD at concave-side distal tibia --- p.58 / Chapter 3.3.3 --- Curve related factors --- p.58 / Chapter 3.3.4 --- Anthropometrics parameters --- p.58 / Chapter 3.3.5 --- Family history --- p.58 / Chapter 3.3.6 --- Summary of univariate analysis --- p.59 / Chapter 3.4 --- Logistic regression model (single factor) --- p.59 / Chapter 3.5 --- Logistic regression model (multiple factors) --- p.60 / Chapter 3.5.1 --- BMD inclusive model --- p.60 / Chapter 3.5.2 --- BMC inclusive model --- p.61 / Chapter 3.5.3 --- Conventional model --- p.63 / Chapter 3.6 --- ROC curve --- p.63 / Chapter 3.6.1 --- BMD inclusive model --- p.64 / Chapter 3.6.2 --- Conventional model --- p.64 / Chapter 3.7 --- Predictive equation obtained from different logistic regression models --- p.64 / Chapter 3.7.1 --- BMD inclusive model --- p.65 / Chapter 3.7.2 --- Conventional model --- p.65 / Chapter IV. --- DISCUSSION --- p.105 / Chapter 4.1 --- Prognostic factors for curve progression --- p.105 / Chapter 4.1.1 --- Well-known prognostic factors --- p.105 / Chapter 4.1.1.1 --- Growth-related factors --- p.106 / Chapter 4.1.1.2 --- Initial curve magnitude --- p.107 / Chapter 4.1.2 --- A new predictor 一 Osteopenia --- p.107 / Chapter 4.2 --- Non-significant prognostic factors for curve progression --- p.109 / Chapter 4.2.1 --- Anthropometric parameters --- p.109 / Chapter 4.2.2 --- Family History --- p.110 / Chapter 4.2.3 --- Curve pattern --- p.110 / Chapter 4.3 --- Predictive model --- p.111 / Chapter 4.4 --- Comparison of predictive models between BMD inclusive model and conventional model derived from our population --- p.115 / Chapter 4.5 --- Possible relationship between osteopenia and etiopathogensis of AIS --- p.116 / Chapter 4.6 --- Axial measurement has a better predictive power in curve progression than peripheral measurement --- p.117 / Chapter 4.7 --- Discordance of BMD in bilateral hips --- p.118 / Chapter 4.8 --- Method justifications --- p.119 / Chapter 4.8.1 --- Definition of curve progression --- p.119 / Chapter 4.8.2 --- Incidence of progression as the outcome of prediction --- p.119 / Chapter 4.8.3 --- Selection on bone densitometers --- p.119 / Chapter 4.9 --- Clinical significance --- p.121 / Chapter 4.10 --- Limitations and Future Studies --- p.122 / Chapter 4.10.1 --- Limited follow-up time --- p.122 / Chapter 4.10.2 --- No defined cutoff value for 226}0´ببosteopenia 226}0ح or low BMC in paediatric area --- p.122 / Chapter 4.10.3 --- Predictive model could only applied in local population --- p.122 / Chapter 4.10.4 --- Intrinsic error in Risser grade measurement --- p.123 / Chapter 4.10.5 --- Further studies --- p.123 / Chapter 4.10.5.1 --- Validation of the newly developed predictive model --- p.123 / Chapter 4.10.5.2 --- Possible intervention of osteopenia --- p.124 / Chapter 4.10.5.3 --- Long term follow-up BMD measurements and fracture risk in AIS patients --- p.124 / Chapter 4.10.5.4 --- Discordance of bilateral hips BMD contributed by the shift of center of gravity --- p.125 / Chapter 4.10.5.5 --- Axial QCT can be an alternative method in assessing BMDin scoliotic patients --- p.125 / Chapter V. --- CONCLUSION --- p.126 / Chapter VI. --- APPENDIX --- p.127 / Chapter VII. --- BIBLIOGRAPHY --- p.128 / Chapter VIII. --- CONFERENCE PUBLICATIONS --- p.142

Lam Wai-man Wynnie. / "April 2002." / Thesis (M.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 109-134). / 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.

by Zhong Sheng. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1996. / Includes bibliographical references (p. 186-203). / 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.

Zheng Ping-pin. / Thesis submitted in: December 2001. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 118-159). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.i / ABSTRACT(ENGLISH/CHINESE) --- p.iii / CONTENTS --- p.viii / LIST OF TABLES --- p.xi / LIST OF FIGURES --- p.xii / PUBLICATION --- p.xiii / Chapter CHAPTER I --- INTRODUCTION / Chapter I.1. --- Preface --- p.1 / Chapter I.2. --- Overview of Carcinogenesis --- p.2 / Chapter I.3. --- Oncogene --- p.5 / Chapter I.4. --- Tumor Suppressor Genes (TSGs) --- p.6 / Chapter I.5 --- Detection of Oncogene and Tumor Suppressor Genes --- p.9 / Chapter I.5.1 --- Detaction of Oncogene --- p.9 / Chapter I.5.2. --- Detection of Tumor Suppressor Genes --- p.11 / Chapter I.6. --- Profiles of Oncogenes/TSGs and Molecular Subtype about Astrocytic Tumors --- p.17 / Chapter I.7. --- Intratumoral Heterogeneity and Microsatellite Instability --- p.20 / Chapter I.8. --- Outline of Ependymoma --- p.20 / Chapter I.9. --- Clinicopathological Factors and Prognosis --- p.22 / Chapter I.9.1. --- Histology and Grading (2000) --- p.22 / Chapter I.9.2. --- Prognosis Factors --- p.23 / Chapter I.9.2.1. --- Age/Sex/Location --- p.23 / Chapter I.9.2.2. --- Extent of Resection --- p.25 / Chapter I.9.2.3. --- Radiotherapy and Chemotherapy --- p.25 / Chapter I.9.2.4. --- Histology --- p.26 / Chapter I.10. --- "Cytogenetic, Molecular Genetic and Molecular Studies" --- p.27 / Chapter I.11. --- Advantages and Disadvantages of The Research Methods --- p.34 / Chapter CHAPTER II --- AIM OF STUDY --- p.36 / Chapter CHAPTER III --- MATERIALS AND METHODS --- p.37 / Chapter III.1. --- Tumor Samples and DNA Preparations --- p.37 / Chapter III.1.1. --- Tumor Samples --- p.38 / Chapter III.1.2. --- DNA Preparation --- p.38 / Chapter III.2. --- Comparative Genomic Hybridization --- p.42 / Chapter III.2.1. --- Metaphase Preparation --- p.42 / Chapter III.2.2. --- "DNA Labeling, Hybridization, and Detection" --- p.43 / Chapter III.2.3. --- Digital Image Analysis --- p.45 / Chapter III.3 --- High-Resolution Allelotying (Microsatellite Analysis) --- p.46 / Chapter III.3.1 --- General Outline --- p.46 / Chapter III.3.2 --- Multiplex PCR --- p.47 / Chapter III.3.3 --- Pooling of PCR Products --- p.49 / Chapter III.3.4 --- Electrophoresis --- p.50 / Chapter III.3.5. --- Assessment of Allelic Imbalance by Calculating Allelic Ratio --- p.52 / Chapter III.3.6 --- Standards of Evalution --- p.53 / Chapter III.3.7 --- Separating Allelic Loss from Allelic Duplication --- p.54 / Chapter III.3.8 --- Statistical Analyses --- p.54 / Chapter CHAPTER IV --- RESULTS --- p.54 / Chapter IV.1. --- CGH Study --- p.54 / Chapter IV.1.1 --- Overview --- p.54 / Chapter IV.1.2 --- Common Deletion Regions --- p.58 / Chapter IV.1.3 --- Common duplication Regions --- p.60 / Chapter IV.2. --- High-Resolution Allelotyping (Microsatellite Analysis) --- p.60 / Chapter IV.2.1. --- Overview of Results --- p.60 / Chapter IV.2.2. --- LOH profile of Individual Chromosome --- p.93 / Chapter IV.2.3. --- Overlapping Small Deletion Regions --- p.95 / Chapter CHAPTER V --- DISCUSSION --- p.97 / Chapter V.1. --- . General Outline --- p.98 / Chapter V.2. --- Chromosome 22 --- p.99 / Chapter V.3. --- Chromosome 17 --- p.102 / Chapter V.4. --- Chromosome 6 --- p.104 / Chapter V.5. --- Chromosome 16 --- p.105 / Chapter V.6. --- Chromosome 19 --- p.107 / Chapter V.7. --- Chromosome 20 --- p.108 / Chapter V.8. --- Chromosome 7 --- p.109 / Chapter V.9. --- Chromosome 12 --- p.110 / Chapter V.10. --- Chromosome 9 --- p.111 / Chapter V.11. --- Chromosome 5 --- p.112 / Chapter V.12. --- Chromosome 4 --- p.112 / Chapter V.13. --- Correlation of CGH with Allelotyping in the Study --- p.112 / Chapter V.14. --- Conclusion --- p.114 / Chapter CHAPTER VI --- LIMITATIONS OF THE STUDY --- p.115 / Chapter CHAPTER VII --- FUTURE STUDY --- p.116 / REFERENCES --- p.118