Poon Kin-yan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 119-147). / Abstracts in English and Chinese. / ACKNOWLEDGMENT --- p.i / ABSTRACT --- p.iii / ABBREVIATIONS --- p.viii / TABLE OF CONTENTS --- p.x / Chapter CHAPTER I --- INTRODUCTION --- p.1 / Chapter 1.1 --- Cervical Intraepithelial Neoplasia (CIN) and Cervical Cancer --- p.1 / Chapter 1.1.1 --- Epidemiology --- p.3 / Chapter 1.1.1.1 --- Descriptive Epidemiology --- p.4 / Chapter 1.1.1.2 --- Risk Factors --- p.7 / Chapter 1.1.2 --- Pathology --- p.22 / Chapter 1.1.2.1 --- Macroscopic Appearance --- p.22 / Chapter 1.1.2.2 --- Symptoms and Diagnosis --- p.23 / Chapter 1.1.2.3 --- Staging Classification --- p.25 / Chapter 1.1.2.4 --- Histopathology --- p.29 / Chapter 1.2 --- Microsatellite Instability (MSI) --- p.35 / Chapter 1.2.1 --- Microsatellite --- p.35 / Chapter 1.2.2 --- Mismatch Repair --- p.37 / Chapter 1.2.3 --- Microsatellite Instability (MSI) --- p.38 / Chapter 1.2.4 --- MSI in Various Cancers --- p.42 / Chapter 1.2.5 --- The Role of MSI in Carcinogenesis --- p.49 / Chapter 1.2.6 --- MSI as a Diagnostic / Prognostic Tool --- p.50 / Chapter CHAPTER II --- AIMS OF THE STUDY --- p.53 / Chapter CHAPTER III --- MATERIALS AND METHODS --- p.56 / Chapter 3.1 --- Materials --- p.56 / Chapter 3.1.1 --- Patients and Specimens --- p.56 / Chapter 3.1.2 --- Microsatellite Markers --- p.57 / Chapter 3.2 --- Methods --- p.59 / Chapter 3.2.1 --- Preparation of OCT-embedded Specimen Sections --- p.59 / Chapter 3.2.2 --- Microdissection of Epithelial Cells and Neoplastic Cells from Specimen Sections --- p.60 / Chapter 3.2.3 --- DNA Extraction --- p.60 / Chapter 3.2.3.1 --- Normal Blood --- p.61 / Chapter 3.2.3.2 --- Dissected Cells --- p.62 / Chapter 3.2.4 --- DNA Amplification --- p.64 / Chapter 3.2.4.1 --- End-labeling of Primers --- p.64 / Chapter 3.2.4.2 --- Polymerase Chain Reaction --- p.65 / Chapter 3.2.5 --- Denaturing Polyacrylamide Gel Electrophoresis --- p.66 / Chapter 3.2.6 --- Autoradiography --- p.67 / Chapter 3.2.7 --- Determination of MSI --- p.67 / Chapter 3.2.8 --- HPV Detection --- p.68 / Chapter 3.2.9 --- Statistical Analysis --- p.69 / Chapter CHAPTER IV --- RESULTS --- p.70 / Chapter 4.1 --- Incidence of MSI in Cervix --- p.70 / Chapter 4.1.1 --- Incidence of MSI in Normal Cervix --- p.70 / Chapter 4.1.2 --- Incidence of MSI in CIN --- p.70 / Chapter 4.1.3 --- Incidence of MSI in Cervical Carcinoma --- p.71 / Chapter 4.1.4 --- Correlation of MSI-positive with the Evolution of Cervical Neoplasm --- p.77 / Chapter 4.2 --- Correlation of MSI-positive with Clinicopathological Characteristics in Cervical Carcinoma --- p.77 / Chapter 4.2.1 --- MSI and Age --- p.80 / Chapter 4.2.2 --- MSI and Clinical Stage --- p.80 / Chapter 4.2.3 --- MSI and Histological Grade --- p.80 / Chapter 4.2.4 --- MSI and Clinical Status --- p.81 / Chapter 4.3 --- Comparison between Two Panels of Microsatellite Markers used in MSI Detection --- p.84 / Chapter 4.4 --- Human Papilloma Virus (HPV) Infection in Cervical Neoplasm --- p.89 / Chapter 4.4.1 --- HPV Infection and Typing in CIN and Cervical Carcinoma --- p.89 / Chapter 4.4.2 --- Correlation of MSI-positive with HPV Infection in Cervical Carcinoma --- p.94 / Chapter CHAPTER V --- DISCUSSION --- p.96 / Chapter 5.1 --- MSI Detection --- p.96 / Chapter 5.1.1 --- Techniques in MSI Assays --- p.98 / Chapter 5.1.2 --- Choice of Microsatellite Markers --- p.101 / Chapter 5.1.3 --- Diagnostic Criteria of MSI --- p.105 / Chapter 5.2 --- The Role of MSI in the Carcinogenesis of Cervical Neoplasm --- p.107 / Chapter 5.3 --- The Clinical Significant of MSI in Cervical Carcinoma --- p.111 / Chapter 5.4 --- The Interaction between HPV Infection and MSI in Cervical Carcinoma --- p.113 / Chapter CHAPTER VI --- CONCLUSION --- p.116 / REFERENCES --- p.119

ClC-1 is the major skeletal muscle chloride channel and is essential for re-establishing the resting membrane potential of muscle cells after an action potential has occurred. Many mutations throughout the CLCN1 gene, which codes for the CIC-1 protein, have been demonstrated via characterisation in heterologous expression systems, to be causative mutations for either Dominant Myotonia Congenita or Recessive Generalised Myotonia. Recently, increasing numbers of myotonic mutations have been found in the carboxyl tail of CIC-1, which demonstrates its importance as a domain that is essential for the normal function of CIC-1 channels. Previous studies in our laboratory defined a region of 18 amino acids in the immediate post D13 segment of rat CIC-1, essential for the expression of functional channels. / thesis (PhDBiomedicalScience)--University of South Australia, 2002.

Title from spine / Includes bibliographies / 1 v. (various pagings) : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (D. Sc.)--University of Adelaide, 1988

Cataract is a leading cause of blindness throughout the world, yet the fundamental biochemical causes are unknown. A rodent model of the biochemical processes is selenite cataract. This cataract shows some of the features of human cataracts such as increased lens calcium, proteolysis of proteins, and insolubilization leading to lens opacity. The goals of the current experiments were: (1) To measure changes in transcript levels for calpains and caspase 3 and oxidation of epithelial proteins in selenite cataract. (2) To elucidate changes in calpain 10 and its interaction with other calpains in selenite cataract. (3) To investigate changes in stability of ��B1-crystallin caused by deamidation and truncation. These data would provide roles for apoptosis, protein insolubilization, proteolysis and deamidation observed in cataract. To induce cataract, 12-day old rats were injected with an overdose of Na���SeO���. Epithelium was analyzed by competitive RT-PCR, zymography, and thiol-blotting. Calpains were detected by western-blotting. For ��B1-crystallin stability studies, recombinant ��B1-crystallins were denatured by urea or heat. Urea stability was measured by circular dichroism and fluorescence spectrometry, and heat stability was measured by light scattering at 405 nm. During selenite cataract formation, calpains in epithelium were activated resulting in increased proteolysis of crystallins, but mRNA levels for calpains did not show appreciable changes. Oxidation of sulthydryls in epithelial proteins was minimal during cataract formation. These results suggested that calpain-induced proteolysis in the epithelium contribute to selenite cataract. In selenite cataract, calpain 10 proteins disappeared, which appeared to be due to degradation by calpain 2 and Lp82 calpain. Deamidated ��B1-crystallin was less stable in urea and heat, compared to wildtype. When the terminal extensions were removed, ��B1-crystallin was as stable as wild-type. However, without the extensions, truncated ��B1-crystallin caused accelerated precipitation in a complex with ��A-crystallin, suggesting that the extensions may contribute to proper association with other crystallins and to stability of the soluble complexes. In summary, proteolysis of proteins by calpains was more pronounced than protein oxidation in lens epithelium of selenite cataract. Deamidation and truncation caused instability of ��B1-crystallin and abnormal association with ��A-crystallin. Thus, proteolysis and deamidation may increase susceptibility of lenses to cataract. / Graduation date: 2003

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published_or_final_version / abstract / toc / Pharmacology / Doctoral / Doctor of Philosophy

published_or_final_version / Statistics / Master / Master of Philosophy

No description available.

No description available.