A dissertation submitted to the Faculty of Health Sciences, University of Witwatersrand, School of Physiology in fulfilment of the requirements for the degree of Master of Science in Medicine. Johannesburg, 2014 / Sedentary lifestyles and poor dietary choices are the major cause of the global increase in the prevalence of obesity and metabolic dysfunction in children. The high cost and limited access to conventional drugs by poor communities make them depend on ethnomedicines. Terminalia sericea (T. sericea) contains phytochemicals that give its extracts hypolipidaemic and hypoglycaemic properties hence its use in ethnomedicine to treat diabetes mellitus. Using weanling Wistar rat pups fed a high fructose diet to model growing children exposed to high-sugar diets, this study sought to evaluate the effects of aqueous T. sericea leaf extracts on their growth performance, glucose homeostasis, visceral morphometry and their general health profile. Forty 21-day old male Wistar pups were randomly allocated to five treatment regimens. Each group had ad libitum access to a commercially supplied rat chow. Group 1 pups were given plain drinking water and plain gelatine cubes, group 2: 12% fructose solution and plain gelatine cubes, group 3: 12% fructose solution and gelatine cubes containing fenofibrate at a dosage of 100 mg.kg-1 per day, group 4: 12% fructose solution and gelatine cubes with a low dose (100 mg.kg-1 per day) of the T. sericea extract and group 5: 12% fructose solution and gelatine cubes with a high dose (400 mg.kg-1 per day) of the T. sericea extract. The pups were maintained on the regimens for 12 weeks after which they under went an oral glucose tolerance test. Fasting blood metabolite content was then determined after which the rats were killed and tissues collected for visceral morphometrical, linear growth and surrogate markers’ of health determinations. T. sericea extracts had no negative effect on growth performance (body mass and indexes of long bone growth) but rats given fenofibrate had lighter empty carcasses and shorter tibiae. vi The administration of T. sericea extracts neither improved glucose homeostasis nor caused derangement of glucose handling by rats given a high fructose diet following an oral glucose challenge. However, the administration of fenofibrate to rats given a high fructose diet resulted in decreased glucose handling following an oral glucose challenge. With the exception of the administration of fenofibrate which resulted in a significantly high (P < 0.05) fasting blood glucose concentration, treatment regimens had no effect on fasting blood glucose, triglyceride and cholesterol concentrations. Rats given fructose with either plain gelatine cubes or low T. sericea dose had significantly higher (P < 0.05) liver lipid content compared with the control treatment. Administration of T. sericea extracts to rats given a high fructose diet had no effect on the GIT, other abdominal viscera and markers of general health. The administration of fenofibrate to rats given a high fructose diet caused increased relative mass of GIT organs (stomach, small intestine and caecum), increased absolute mass of other viscera (liver and kidney); increased serum phosphorus and alkaline phosphatase concentration. Results from the study revealed that administration of a high dose of aqueous T. sericea leaf extracts has potent phytochemicals properties that has helped to prevent high fructose diet-induced deposition of fat in the in the liver (non-alcoholic fatty liver disease), without compromising growth, visceral morphometry and general health of growing Wistar rats.

A thesis submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfillment of the requirements for the degree of Doctor of Philosophy of Science. Johannesburg, 2013 / Chemotherapy, while representing a vital component of cancer treatment modalities, has so far not fulfilled basic expectations with unsatisfactory cure rates and frequent relapse due to limited effectiveness of the therapeutic drugs, severe side effects and resistance problems. The platinumcontaining drugs used in present clinical practice are no exception to this generalized finding. While highly effective against a small number of malignancies, they generally share in the deficiencies of other anticancer agents. To address this issue, intense research is being undertaken to develop novel platinum-compounds offering enhanced therapeutic effectiveness. To accomplish this, several new avenues of development are being pursued world-wide, and one of these involving the binding of monomeric anticancer drug systems to water-soluble, biocompatible and biodegradable polymeric carriers, was utilized in the current research. As part of the ongoing research, this dissertation demonstrates the preparation of several water-soluble polymeric carriers bearing pre-synthesized monomers aimed to anchor the platinum drug. The monomers of interest were aspartic acid, p-aminobenzoic acid and p-aminosalicylic acid derivatives; while the water-soluble carriers were polyaspartamides, prepared by an aminolytic ring-opening process of polysuccinimide. The platination agents were conjugated to the polymer backbone both via amine and via leaving-group ligands, such as dihydroxylato, dicarboxylato and carboxylatohydroxylato. In order to demonstrate the multidrug-binding capacity of the carriers, platinum complexes were co-conjugated to polymeric conjugates containing ferrocene. The in vitro studies against a human breast cancer (MCF-7) cell line showed IC50 values ranging from 48.92 μg.mL-1 to 281.37 μg.mL-1 for the platinum conjugates, 13.18 μg.mL-1 to 149.67 μg.mL-1 for ferrocene conjugates and 6.22 μg.mL-1 to 83.86 μg.mL-1 for platinum/ferrocene co-conjugates; and these values were on average 4 fold more active than the parent drug. The results of these preliminary tests provide proof of the principle that polymer-drug conjugates can play a role in future cancer therapy.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfillment of the requirements for the degree of Masters of Science in Medicine in Emergency Medicine. Johannesburg, 2013 / To determine the types of uropathogens encountered in patients presenting to a busy private emergency department in Johannesburg and compare sensitivity patterns of the bacteria identified with current antimicrobial prescribing patterns.

University of Macau / Institute of Chinese Medical Sciences

Despite numerous studies have demonstrated an association of type 2 diabetes mellitus (T2DM) and osteoporosis, the underlying mechanism connecting these two conditions remains elusive. Clinically, combined calcium and vitamin D supplement is the commonest osteoporosis therapy; however, recent studies have suggested an increase in cardiovascular risks associated with calcium plus vitamin D supplementation. Therefore, an alternative strategy in treating osteoporosis patients with T2DM is urgently needed. In this study, we hypothesized that combined administration of menaquinone-4 (vitamin K₂, biologically active form of vitamin K) and 1α,25-dihydroxyvitamin D₃ (vitamin D₃, biologically active form of vitamin D) as a novel therapy in treating osteoporosis of T2DM patients. Anabolic effect of vitamin K₂ and vitamin D₃, alone or in combination, was assessed on primary osteoblasts harvested from the iliac crests of C57BL/KsJ lean (db⁺/m⁺) and obese/diabetic (db⁺/db⁺, leptin receptor-deficient) mice. Furthermore, the underlying cellular mechanism was also investigated. Serum undercarboxylated osteocalcin (an indication of vitamin K₂ level) level was higher whereas vitamin D₃ level was lower in db⁺/db⁺ mice, and sections of the iliac crests of db⁺/db⁺ mice illustrated extensive porous structures filled with enlarged adipocytes compared with db⁺/m⁺ mice. Lower levels of bone anabolic markers and bone formation transcription factors (osteocalcin, Runx2, Dlx5, ATF4, type I collagen, OSX, alkaline phosphatase (ALP) activity, p-Smad1/5/8 and p-ERK1/2) were observed in the osteoblasts of db⁺/db⁺ mice. Acute vitamin D₃ (10 nM) application elicited a more sustained and greater magnitude of increase of [Ca²⁺]ᵢ in osteoblasts of db⁺/m⁺ mice when compared with db⁺/db⁺ mice. A significantly higher level of calcium deposits in osteoblasts was observed in db⁺/m⁺ mice when compared to db⁺/db⁺ mice. Co-administration of vitamin K₂ (10 nM) and vitamin D₃ (10 nM) caused an enhancement of calcium deposits in osteoblasts in both strains of mice. Vitamins K₂ and D₃ co-administration time-dependently (7, 14 and 21 days) increased the levels of bone anabolic markers and transcription factors for bone formation, with a greater magnitude of increase observed in osteoblasts of db⁺/db⁺ mice. Suppressed expression of calcium-sensing receptor (CaSR), F-actin, V-ATPase, vitamin D receptor (VDR) and pregnane X receptor (PXR) observed in osteoblasts of db⁺/db⁺ mice were partially reversed by combined vitamins treatment. Moreover, combined vitamins K₂ plus D₃ treatment significantly enhanced migration and the appearance of surface microvilli and ruffles of osteoblasts of db⁺/db⁺ mice. Effects of combined vitamins K₂ plus D₃ treatment observed in osteoblasts of db⁺/db⁺ and db⁺/m⁺ mice were eradicated by warfarin (20 µM, a vitamin K epoxide reductase inhibitor). Thus, our results illustrate that vitamins K₂ plus D₃ supplementation is a novel therapeutic strategy in treating osteoporosis of T2DM patients. / 儘管大量研究已證明第二類型糖尿病和骨質疏鬆症的關聯，連接這兩個病症的基本機制仍然是難以捉摸的。在臨床上，鈣和維生素D的綜合補充劑是最常見的骨質疏鬆症治療，然而最近的研究卻表明服用鈣和維生素D的綜合補充劑會增加患者的心血管風險，因此急切需要尋找可以給予同時患有骨質疏鬆症和第二類型糖尿病患者的替代治療。在本研究中，我們假設甲萘醌-4（維生素K₂，維生素K生物活性形式）和1α，25 - 二羥基維生素D₃（維生素D₃，維生素D的生物活性形式）可以嘗試在同時患有骨質疏鬆症和第二類型糖尿病患者身上作為一種革新的療法。本研究從C57BL/KsJ瘦削/非糖尿病 (db⁺/m⁺) 的小鼠和肥胖/帶有第二類型糖尿病基因 (db⁺/db⁺) 兼有瘦素受體缺陷的小鼠的髂嵴原始成骨細胞上對維生素K₂和維生素D₃單獨或組合使用的合成代謝作用進行了評估。此外，我們也對該成骨細胞的底層機制進行了一系列的研究。 / 在肥胖/帶有第二類型糖尿病基因的小鼠血清內低羧骨鈣素水平（維生素K₂水平的指標）較高而維生素D水平較低，另外，它們的髂嵴的部分與瘦削/非糖尿病的小鼠相比，呈現出比較廣泛的多孔結構並填滿了擴大的脂肪細胞。從肥胖/帶有第二類型糖尿病基因的小鼠的成骨細胞中，可以觀察到它們的骨合成代謝的標誌物和骨骼形成的轉錄因子 (骨鈣蛋白，Runx2，Dlx5，ATF4，第一類型骨膠原，OSX，鹼性磷酸酶 (ALP) 活性，p-Smad1/5/8和p-ERK1/2) 的水平比較低。急性維生素D₃ (10 nM) 的應用在瘦削/非糖尿病小鼠的成骨細胞比起在肥胖/帶有第二類型糖尿病基因的小鼠的成骨細胞引起更持續和更大幅度的細胞內鈣變化增加。在瘦削/非糖尿病小鼠的成骨細胞中比起在肥胖/帶有第二類型糖尿病基因的小鼠的成骨細胞有顯著較高的鈣沉積形成。維生素K₂ (10 nM) 和維生素D₃ (10 nM) 的綜合藥在兩種小鼠的成骨細胞中可以有效地增強鈣沉積的形成。維生素K₂和維生素D₃的綜合藥對增加骨合成代謝的標誌物和骨形成轉錄因子的水平有時間依賴性 (7，14和21日)，療程越長至21日，在肥胖/帶有第二類型糖尿病基因小鼠的成骨細胞中有更大的幅度的增加。合併維生素治療能部分有效地逆轉在肥胖/帶有第二類型糖尿病基因小鼠的成骨細胞中被抑制表達的鈣敏感受體 (CASR)，F-肌動蛋白，V-ATP酶，維生素D受體 (VDR) 和孕烷X受體 (PXR)。此外，結合維生素K₂加維生素D₃治療顯著增強了肥胖/帶有第二類型糖尿病基因小鼠的成骨細胞的細胞遷移和增加了成骨細胞表面外觀的微絨毛和褶皺。在瘦削/非糖尿病小鼠的成骨細胞及肥胖/帶有第二類型糖尿病基因的小鼠的成骨細胞上結合維生素K₂加維生素D₃的治療效果被華法林 (20 μM，維生素K環氧化物還原酶抑製劑) 根除。因此，我們的結果証明了維生素K₂加維生素D₃補充劑的結合使用可有效地作為治療第二類型糖尿病患者並患有骨質疏鬆症的一種新的治療策略。 / Poon, Chui Wa Christina. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2014.n5203 / Includes bibliographical references (leaves 135-151). / Abstracts also in Chinese. / Title from PDF title page (viewed on 26, October, 2016). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

by Lee Wai Chi, Edwin. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1993. / Includes bibliographical references (leaves 115-125). / Acknowledgments --- p.I / List of figures --- p.II / List of tables --- p.III / List of graphs --- p.III / Abstract --- p.VIII / Chapter I.CHAPTER ONE --- Introduction --- p.1 / Chapter 1.1 --- Electromagnetic / Magnetic field in biological interventions --- p.1 / Chapter 1.2 --- Objective of the study --- p.4 / Chapter 1.3 --- Hypothesis of the study --- p.5 / Chapter II.CHAPTER TWO --- Literature Review --- p.6 / Chapter 2.1 --- Inflammation / Chapter 2.1.1 --- Models of studying tendon injuries --- p.6 / Chapter 2.1.2 --- Methods of measuring inflammation --- p.7 / Chapter 2.1.3 --- Treatments of soft tissue inflammation --- p.9 / Chapter 2.2 --- Aspects of electromagnetic and magnetic fields / Chapter 2.2.1 --- Applications of electromagnetic / magnetic fields in soft tissue inflammation --- p.12 / Chapter 2.2.2 --- Physiological effects of electromagnetic/magnetic fields / Chapter 2.2.2.1 --- Experiments on inflammation --- p.16 / Chapter 2.2.2.2 --- Experiments on soft tissue / tendon injuries --- p.16 / Chapter 2.2.2.3 --- Experiments on blood circulation --- p.18 / Chapter 2.2.3 --- Experiments with different parameter settings of PEMF / PMF in soft tissue inflammation --- p.19 / Chapter 2.2.4 --- Proposed mechanisms of electromagnetic/magnetic fields --- p.22 / Chapter III.CHAPTER THREE --- Methods and Materials --- p.23 / Chapter 3.1 --- Animal models --- p.23 / Chapter 3.2 --- Apparatus --- p.24 / Chapter 3.3 --- Treatment Regimen --- p.27 / Chapter 3.4 --- Assessments --- p.29 / Chapter IV.CHAPTER FOUR --- Histological Assessment --- p.30 / Chapter 4.1 --- Introduction --- p.30 / Chapter 4.2 --- Methods --- p.31 / Chapter 4.3 --- Results --- p.31 / Chapter 4.4 --- Discussions --- p.45 / Chapter V.CHAPTER FIVE --- Morphometrical analysis on tissue sections with immunochemical staining --- p.51 / Chapter 5.1 --- Introduction / Chapter 5.1.1 --- Different approaches in identification of macrophages --- p.51 / Chapter 5.1.2 --- Avidin-biotin enzyme complex assay --- p.52 / Chapter 5.2 --- Methods --- p.54 / Chapter 5.2.1 --- ABC method --- p.54 / Chapter 5.2.2 --- Morphometric analysis of tissue sections --- p.55 / Chapter 5.2.3 --- Statistical method --- p.56 / Chapter 5.3 --- Results / Chapter 5.3.1 --- Immunochemical results --- p.56 / Chapter 5.3.2 --- Morphometric results --- p.60 / Chapter 5.4 --- Discussions --- p.64 / Chapter VI.CHAPTER SIX --- Biochemical Assessments --- p.67 / Chapter 6.1 --- Water content / Chapter 6.1.1 --- Introduction --- p.67 / Chapter 6.1.2 --- Methods --- p.68 / Chapter 6.1.2.1 --- Water content measurement --- p.68 / Chapter 6.1.2.2 --- Statistical method --- p.69 / Chapter 6.1.3 --- Results --- p.72 / Chapter 6.1.4 --- Discussions --- p.77 / Chapter 6.2 --- Total collagen content / Chapter 6.2.1 --- Introduction --- p.81 / Chapter 6.2.1.1 --- Hydroxyproline as an indicator for collagen content assay --- p.81 / Chapter 6.2.2 --- Methods / Chapter 6.2.2.1 --- Hydrolysis method --- p.82 / Chapter 6.2.2.2 --- Standard-curve preparation --- p.83 / Chapter 6.2.2.3 --- Statstical method --- p.84 / Chapter 6.2.3 --- Results --- p.84 / Chapter 6.2.4 --- Discussions --- p.89 / Chapter VII.CHAPTER SEVEN --- Discussion --- p.92 / Chapter VIII.CHAPTER EIGHT --- Summary and Conclusions --- p.103 / Appendix A : Histological reagents preparations --- p.106 / Appendix B : Staining procedures for standard H & E --- p.107 / Appendix C : Immunochemical staining reagents preparations --- p.108 / Appendix D : Staining procedure for StreptABComplex / HRP --- p.110 / AppendixE : Biochemical reagents and preparations --- p.111 / Appendix F : Hydrolysis method for the tendon --- p.112 / Appendix G : Standard-curve of hydroxyproline --- p.113 / Appendix H : Determination of optimal hours for collagen hydrolysis --- p.114 / REFERENCES --- p.115

by Chun-kwok Wong. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1990. / Bibliography: leaves 181-196. / ABSTRACT --- p.i / ACKNOWLEDGEMENTS --- p.iii / ABBREVIATIONS --- p.iv / CHAPTER / Chapter 1. --- INTRODUCTION : An overview of Tumor Necrosis Factor ( TNF) / Chapter 1. --- The discovery of tumor necrosis factor (TNF) --- p.1 / Chapter 2. --- Production of tumor necrosis factor --- p.3 / Chapter 3. --- Physiochemical properties of TNF --- p.5 / Chapter 4. --- Biological activities of TNF on various cells in the mammal --- p.8 / Chapter 5. --- Mechanisms of anti-tumor action of TNF --- p.12 / Chapter 6. --- Clinical studies of Hr-TNF --- p.19 / Chapter 2. --- AIM OF INVESTIGATION --- p.23 / Chapter 3. --- MATERIALS AND METHODS / Chapter A. --- MATERIALS --- p.26 / Chapter B. --- METHODS / Chapter 1. --- Preparation of Reagents --- p.30 / Chapter 2. --- Cell Culture --- p.31 / Chapter 3. --- Lymphocytes proliferation --- p.32 / Chapter 4. --- In vitro production of tumor necrosis factor (TNF) by peritoneal macrophages of ICR mice --- p.33 / Chapter 5. --- Production of TNF in animals --- p.34 / Chapter 6. --- Determination of TNF titre --- p.35 / Chapter 7. --- Determination of TNF containing serum titre on EAT in vitro --- p.35 / Chapter 8. --- Mortality determination of mice --- p.36 / Chapter 9. --- "3H-Thymidine, 3H-uridine, 14C-leucine incorporation" --- p.36 / Chapter 10. --- Glucose uptake determination --- p.37 / Chapter 11. --- Whole body hyperthermic treatment of EAT bearing mice --- p.37 / Chapter 12. --- Lipolysis assay --- p.38 / Chapter 13. --- Statistical analysis --- p.39 / Chapter 4. --- IN VIVO PRODUCTION OF TUMOR NECROSIS FACTOR USING ZYMOSAN AND LIPOPOLYSACCHARIDE / INTRODUCTION --- p.40 / EXPERIMENTAL --- p.43 / RESULTS --- p.45 / DISCUSSION --- p.65 / Chapter 5. --- SIDE EFFECTS DURING IN VIVO PRODUCTION OF TUMOR NECROSIS FACTOR IN EHRLICH ASCITES TUMOR BEARING MICE / INTRODUCTION --- p.70 / EXPERIMENTAL --- p.72 / RESULTS --- p.74 / DISCUSSION --- p.93 / Chapter 6. --- MODIFIED PROCEDURE FOR THE IN VIVO PRODUCTION OF TUMOR NECROSIS FACTOR FOR THE TREATMENT OF EHRLICH ASCITES TUMOR BEARING MICE / INTRODUCTION --- p.98 / EXPERIMENTAL --- p.99 / RESULTS --- p.100 / DISCUSSION --- p.108 / Chapter 7. --- "COMBINED TREATMENTS OF IN VIVO PRODUCTION OF TUMOR NECROSIS FACTOR (TNF) WITH HYPERTHERMIA, METHOTREXATE (MTX), POLYRIBOINOSINIC-POLYRIBOCYTIDYLIC ACID (POLY I.C), N-(PHOSPHONACETYL)-L-ASPARTATE (PALA) ON EAT BEARING MICE" / INTRODUCTION --- p.111 / EXPERIMENTAL --- p.116 / RESULTS --- p.118 / DISCUSSION --- p.133 / Chapter 8. --- EFFECTS OF IN VIVO PRODUCTION OF TUMOR NECROSIS FACTOR ON EHRLICH ASCITES TUMOR CELLS CYTOTOXICITY / INTRODUCTION --- p.138 / EXPERIMENTAL --- p.140 / RESULTS --- p.142 / DISCUSSION --- p.151 / Chapter 9. --- SIDE EFFECTS OF TUMOR NECROSIS FACTOR AND LIPOPOLYSACCHARIDE ON RAT IN VITRO AND IN VIVO / INTRODUCTION --- p.154 / EXPERIMENTAL --- p.157 / RESULTS --- p.159 / DISCUSSION --- p.170 / Chapter 10. --- CONCLUSION AND OUTLOOK --- p.174 / BIBLIOGRAPHY --- p.181

by Yeung, Sai-mo, Simon. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1989. / Bibliography: leaves 189-207.

by Poon Lit Man. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1996. / Includes bibliographical references (leaves 97-113). / Title page --- p.i / Acknowledgements --- p.ii / Table of contents --- p.iii / List of tables --- p.vii / List of figures --- p.viii / Abbreviations --- p.x / Abstract --- p.xi / Chapter Chapter 1: --- General Introduction --- p.1 / Chapter 1.1 --- Sacral agenesis --- p.2 / Chapter 1.1.1 --- Skeletal anomalies --- p.3 / Chapter 1.1.2 --- Neurological anomalies --- p.4 / Chapter 1.1.3 --- Other anomalies --- p.5 / Chapter 1.1.4 --- Etiology --- p.5 / Chapter 1.1.5 --- Pathogenetic mechanism of SA --- p.7 / Chapter 1.2 --- Retinoids --- p.8 / Chapter 1.2.1 --- RA in embryonic development --- p.9 / Chapter 1.2.2 --- Teratogenic effect of RA in embryonic development --- p.10 / Chapter 1.3 --- Strategy of the thesis --- p.13 / Chapter Chapter 2: --- General Materials and Methods --- p.15 / Chapter 2.1 --- Mouse maintenance and mating method --- p.16 / Chapter 2.2 --- All-trans RA preparation and injection --- p.16 / Chapter 2.3 --- Dissection of embryos --- p.16 / Chapter 2.4 --- Preparation of histological sections --- p.17 / Chapter 2.4.1 --- Dehydration and embedding --- p.17 / Chapter 2.4.2 --- Sectioning --- p.18 / Chapter 2.4.3 --- Haematoxylin and eosin staining --- p.18 / Chapter 2.5 --- Plasmid preparation --- p.19 / Chapter 2.5.1 --- Competent cells preparation --- p.19 / Chapter 2.5.2 --- Bacterial transformation --- p.19 / Chapter 2.5.3 --- Mini-scale preparation of plasmid DNA --- p.20 / Chapter 2.6 --- In situ hybridization --- p.21 / Chapter 2.6.1 --- Sample preparation --- p.21 / Chapter 2.6.2 --- Probe synthesis --- p.21 / Chapter 2.6.3 --- Hybridization --- p.23 / Chapter 2.6.4 --- Post-hybridization wash and antibody labeling --- p.24 / Chapter 2.6.5 --- Post-antibody wash and colour development --- p.25 / Chapter 2.6.6 --- Embryo powder preparation --- p.25 / Chapter Chapter 3: --- Time and Dose Responses to RA --- p.26 / Chapter 3.1 --- Introduction --- p.27 / Chapter 3.1.1 --- Time response --- p.27 / Chapter 3.1.2 --- Dose response --- p.29 / Chapter 3.2 --- Materials and methods --- p.31 / Chapter 3.2.1 --- Dose response --- p.31 / Chapter 3.2.2 --- Time response --- p.31 / Chapter 3.2.3 --- Skeletal preparations and staining --- p.31 / Chapter 3.2.4 --- Early teratogenic responses to RA --- p.32 / Chapter 3.3 --- Results --- p.33 / Chapter 3.3.1 --- Dose response --- p.33 / Chapter 3.3.1.1 --- Tail length --- p.33 / Chapter 3.3.1.2 --- Vertebral pattern --- p.33 / Chapter 3.3.2 --- Time response --- p.36 / Chapter 3.3.2.1 --- Tail length --- p.36 / Chapter 3.3.2.2 --- Vertebral pattern --- p.36 / Chapter 3.3.2.3 --- Other anomalies associated with human SA --- p.40 / Chapter 3.3.3 --- Early teratogenic responses in RA-treated embryos --- p.41 / Chapter 3.4 --- Discussion --- p.44 / Chapter Chapter 4: --- RA-induced Cell Death in Tail Bud --- p.51 / Chapter 4.1. --- Introduction --- p.52 / Chapter 4.1.1 --- Cell death --- p.52 / Chapter 4.1.2 --- Methods in cell death identification --- p.54 / Chapter 4.2 --- Materials and methods --- p.57 / Chapter 4.2.1 --- Histology of tail bud region --- p.57 / Chapter 4.2.2 --- Detection of internucleosomal DNA fragmentation --- p.57 / Chapter 4.2.2.1 --- Sample collection --- p.57 / Chapter 4.2.2.2 --- DNA extraction --- p.58 / Chapter 4.2.2.3 --- Analysis of DNA fragmentation pattern by ethidium bromide staining --- p.59 / Chapter 4.2.2.4 --- Analysis of DNA fragmentation pattern by autoradiography --- p.59 / Chapter 4.2.3 --- TUNEL --- p.61 / Chapter 4.2.3.1 --- Sample collection / Chapter 57 4.2.3.2 --- In situ end-labeling --- p.62 / Chapter 4.2.4 --- In situ hybridization of Wnt-5A --- p.63 / Chapter 4.2.4.1 --- Sample collection --- p.63 / Chapter 4.2.4.2 --- Probe preparation --- p.64 / Chapter 4.3 --- Results --- p.65 / Chapter 4.3.1 --- Histological examination of cell death in tail bud --- p.65 / Chapter 4.3.2 --- Analysis of DNA fragmentation of tail bud cells --- p.66 / Chapter 4.3.3 --- TUNEL --- p.67 / Chapter 4.3.4 --- Wnt-5A gene expression --- p.68 / Chapter 4.4 --- Discussion --- p.71 / Chapter Chapter 5: --- Retinoic Acid Receptors (RARs) --- p.75 / Chapter 5.1 --- Introduction --- p.76 / Chapter 5.1.1 --- RARs and their isoforms --- p.76 / Chapter 5.1.2 --- Expression pattern of RARs during embryogenesis --- p.77 / Chapter 5.1.3 --- RAR mutants and functional redundancy of RARs --- p.78 / Chapter 5.1.4 --- RARs and SA --- p.79 / Chapter 5.2 --- Materials and methods --- p.80 / Chapter 5.2.1 --- In situ hybridization of RAR-α --- p.80 / Chapter 5.2.1.1 --- Sample collection --- p.80 / Chapter 5.2.1.2 --- Probe preparation --- p.80 / Chapter 5.2.2 --- In situ hybridization of RAR-β --- p.81 / Chapter 5.2.2.1 --- Sample collection --- p.81 / Chapter 5.2.2.2 --- Probe preparation --- p.81 / Chapter 5.2.3 --- In situ hybridization of RAR-γ --- p.82 / Chapter 5.2.3.1 --- Sample collection --- p.82 / Chapter 5.2.3.2 --- Probe preparation --- p.82 / Chapter 5.3 --- Results --- p.83 / Chapter 5.3.1 --- RAR-α gene expression --- p.83 / Chapter 5.3.2 --- RAR-β gene expression --- p.84 / Chapter 5.3.3 --- RAR-γ gene expression --- p.86 / Chapter 5.4 --- Discussion --- p.88 / Chapter Chapter 6: --- Conclusion and Future Perspectives --- p.92 / Chapter 6.1 --- Conclusion and future perspectives --- p.93 / References --- p.97 / Appendices --- p.114 / Figures --- p.118

Hu, Baoguang. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 121-143). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.