Christine May Briton-Jones. / "May 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 149-171). / 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 Lam, Sau Hing. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 141-158). / Abstract also in Chinese. / Content / Acknowledgements / Abbreviation / Project Objectives / Abstract / Chapter Chapter One --- Introduction / Chapter 1.1 --- The definition of homeobox genes / Chapter 1.2 --- Homeobox genes as a transcription factor / Chapter 1.3 --- Homeobox in Drosophila / Chapter 1.3.1 --- The development of Drosophila / Chapter 1.3.2 --- Maternal genes / Chapter 1.3.3 --- Segmentation genes / Chapter 1.3.4 --- Homeobox genes / Chapter 1.4 --- Family of Hox genes in the mammalian system / Chapter 1.5 --- Some possible chemical mechanism in the cascade system of the Hox genes in the vertebrate / Chapter 1.6 --- Hox (Antp-Class homeobox gene) in mammal / Chapter 1.6.1 --- Labial Like homeobox genes / Chapter 1.6.2 --- Proboscipedia Like homeobox genes / Chapter 1.7 --- Divergent homeobox genes / Chapter 1.7.1 --- Paired (prd) Class / Chapter 1.7.2 --- Even-Skipped (Eve) Class / Chapter 1.7.3 --- Distal-less (Dll) Class / Chapter 1.7.4 --- Muscle-Specific Homeobox (Msx) Class / Chapter 1.8 --- Orphan homeobox gene / Chapter 1.8.1 --- The characteristic of Hox 11 sequence in human and mouse / Chapter 1.8.2 --- Novel homeobox genes related to hox 11 gene family / Chapter 1.8.3 --- The mechanism of HOX 11 inducing gene regulation and signal transduction pathways / Chapter 1.8.4 --- HOX 11 in human / Chapter 1.8.5 --- Hox11 in mouse / Chapter 1.8.6 --- Hox11 L1 in mouse / Chapter 1.9 --- Homeobox gene involved in haematopoiesis / Chapter 1.10 --- Some translocations of homeobox genes in blood lineage / Chapter 1.11 --- The development of mouse / Chapter 1.11.1 --- Early organogenesis / Chapter 1.11.2 --- Nervous system development / Chapter 1.11.3 --- Somite development / Chapter 1.11.4 --- Eye development / Chapter 1.11.5 --- Neural crest cell migration / Chapter 1.11.6 --- Branchial arches development / Chapter Chapter Two --- Materials and methods / Chapter 2.1 --- Mouse Embryos / Chapter 2.2 --- RNA extraction / Chapter 2.3 --- Large plasmid preparation / Chapter 2.4 --- The synthesis of cDNAs using Reverse Transcription / Polymerase Chain Reaction (RT-PCR) and ligation into Bluescript® II KS / Chapter 2.4.1 --- The synthesis of RT-PCR products / Chapter 2.4.2 --- The formation of blunt ends of cDNA / Chapter 2.4.3 --- The ligation of cDNA with plasmid vectors / Chapter 2.4.4 --- Transformation / Chapter 2.4.5 --- The miniprep plasmid purification / Chapter 2.5 --- T7 sequencing / Chapter 2.6 --- Double stranded DNA cycle sequencing of plasmid / Chapter 2.6.1 --- Gel electrophoresis / Chapter 2.7 --- Northern blot / Chapter 2.7.1 --- Preparation of Northern blot / Chapter 2.7.2 --- Hybridization of Northern blot / Chapter 2.8 --- DIG labeled probes in whole mount in situ hybridization / Chapter 2.8.1. --- Preparation of linear DNA to generate riboprobes / Chapter 2.8.2 --- Preparation of DIG labeled riboprobe / Chapter 2.8.3. --- Preparation of embryo powder / Chapter 2.8.4 --- Absorption of antibody / Chapter 2.8.5 --- Embryo preparation / Chapter 2.8.6 --- Embryos staining / Chapter 2.9 --- Sections from whole mount in situ hybridization / Chapter 2.10 --- The radiolabeled section in situ hybridization / Chapter 2.10.1 --- The preparation of paraffin wax block and sample sections / Chapter 2.10.2 --- Slide pretreatment / Chapter 2.10.3 --- Preparation of probe / Chapter 2.10.4 --- Hybridization / Chapter 2.10.5 --- Washing / Chapter 2.10.6 --- Emulsification and development / Chapter 2.11 --- DIG-label in situ hybridization of frozen / Chapter 2.12 --- H&E staining / Chapter Chapter Three --- Results and Discussion / Chapter 3.1 --- Synthesis of Tlx3 probes for use in the section and whole mount in situ hybridization / Chapter 3.1.1 --- Synthesis of the Tlx cDNA by RT-PCR method / Chapter 3.1.2 --- The Tlx3 genomic clone for detecting the developmental expression of Tlx3 by Northern Blot / Chapter 3.1.3 --- The characterization of Tlx3 cDNAs and the sonic hedgehog cDNA / Chapter 3.2 --- Section in situ hybridization using different probes / Chapter 3.2.1 --- Section in situ hybridization using the transcribed riboprobes of Pax2 cDNA / Chapter 3.2.2 --- The transcribed riboprobes of Tlx genomic clones were used to hybridize the section in situ hybridization / Chapter 3.2.3 --- The in situ hybridization of frozen sections of mouse embryos using the transcribed riboprobes from Tlx3 cDNA subclone / Chapter 3.3 --- Expression pattern of Tlx3 on whole mount embryos using both cDNA and genomic probes / Chapter 3.3.1 --- The expression of Tlx3 on whole mount in situ hybridization of the mouse embryos using the antisense probes from the Tlx3 genomic clone / Chapter 3.3.2 --- Whole mount in situ hybridization of mouse embryo using the transcribed riboprobes of Tlx3 cDNA / Chapter 3.3.3 --- The expression pattern of sonic hedgehog on embryos at 8.5 to9.5 dpc / Conclusion / Future prospective / Appendix / Reference / Acknowledgement

Leung Kim-chuen Andrew. / "August 2000." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (p. 168-200). / 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 Tse Kam Wah. / "September 1998." / Thesis (Ph.D.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (p. 123-145). / 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.

Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves [105]-131).

Chan Wai-Hon. / "September 2000." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (p. 137-156). / 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.

In this 15 year follow up study in a Chinese population, we confirmed that maternal gestational diabetic status significantly increased women’s future cardiometabolic risk. Glycaemic levels below the current criteria for a positive screening test for gestational diabetes and for the diagnosis of gestational diabetes still significantly predict women’s future risk. In utero hyperinsulinaemia, which caused by an intrauterine hyperglycaemic environment, was found to predict children’s AGT and adolescents’ overweight and MetS. The results had important implication that the current diagnostic criteria for gestational diabetes may not be discriminative in predicting both the mothers and their children’s future cardiometabolic risk. Although recent research has re-visited and emphasised on the diagnostic criteria of gestational diabetes which best predicted adverse pregnancy outcome, future study should also scrutinise on the optimal glycaemic threshold, either in screening or diagnostic test, that relate to the mothers’ and children offspring’s long term cardiometabolic risk. / Tam, Wing Hung. / Thesis (M.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 119-146). / Abstract also in Chinese. / LIST OF TABLES --- p.xxii / LIST OF FIGURES --- p.xxv / LIST OF ABBREVIATIONS --- p.xxvi / Chapter Chapter 1 --- Gestational diabetes & future cardiometabolic risk - an overview / Chapter 1.1 --- Historical background --- p.2 / Chapter 1.2 --- Pregnancy physiology vs. gestational diabetes --- p.5 / Chapter 1.3 --- Diabetes mellitus - a global epidemic --- p.6 / Chapter 1.4 --- History of gestational diabetes & progression to Type 2 DM --- p.7 / Chapter 1.5 --- History of gestational diabetes & cardiometabolic risk --- p.8 / Chapter 1.6 --- Type 2 DM among children and adolescents --- p.9 / Chapter 1.7 --- Type 2 DM among offspring of mothers with gestational diabetes --- p.10 / Chapter 1.8 --- Cardiometabolic risk in children exposed to maternal gestational diabetes --- p.12 / Chapter 1.9 --- Long term follow up on mothers & children cohort --- p.12 / Chapter Chapter 2 --- Research methodology / Chapter 2.1 --- Subjects --- p.16 / Chapter 2.2 --- Obstetric and neonatal information --- p.18 / Chapter 2.2.1 --- Maternal glycaemic indices at pregnancy --- p.18 / Chapter 2.2.2 --- Umbilical cord blood C-peptide & insulin levels --- p.18 / Chapter 2.2.3 --- Definition of antenatal variables --- p.19 / Chapter 2.3 --- Follow up assessment of the mothers --- p.19 / Chapter 2.4 --- Follow up assessment of the children and adolescents --- p.22 / Chapter 2.5 --- Definition of abnormal glucose tolerance and metabolic syndrome --- p.24 / Chapter 2.5.1 --- Definition of abnormal glucose tolerance --- p.24 / Chapter 2.5.2 --- Definition of metabolic syndrome in adult --- p.24 / Chapter 2.5.3 --- Definition of metabolic syndrome in adolescent --- p.25 / Chapter 2.6 --- Determination of insulin resistance and pancreatic beta cell function --- p.26 / Chapter 2.6.1 --- Definition of insulin resistance --- p.26 / Chapter 2.6.2 --- Definition of pancreatic beta cell function --- p.26 / Chapter 2.6.3 --- Measurement of insulin resistance and pancreatic β-cell function --- p.27 / Chapter 2.7 --- Statistical analysis --- p.31 / Chapter 2.7.1 --- Statistical programme --- p.31 / Chapter 2.7.2 --- Comparison between group differences --- p.31 / Chapter 2.7.3 --- General Linear Model --- p.32 / Chapter 2.7.4 --- Multivariate logistic regression --- p.33 / Chapter 2.7.5 --- Receiver operating characteristic analysis --- p.37 / Chapter 2.8 --- Ethics approval --- p.41 / Chapter 2.9 --- Funding --- p.42 / Chapter Chapter 3 --- History of gestational diabetes and women’s future cardiometabolic risk / Chapter 3.1 --- Maternal clinical parameters at the index pregnancy --- p.44 / Chapter 3.2 --- Maternal cardiometabolic status at 8 years post-delivery --- p.45 / Chapter 3.3 --- Maternal cardiometabolic status at 15 years post-delivery --- p.49 / Chapter 3.4 --- Prediction of cardiometabolic risk by maternal gestational diabetic status --- p.50 / Chapter 3.4.1 --- Abnormal glucose tolerance and metabolic syndrome at 8 years by maternal gestational diabetic status --- p.52 / Chapter 3.4.2 --- Abnormal glucose tolerance, DM, hypertension and metabolic syndrome at 15 years by maternal gestational diabetic status --- p.52 / Chapter 3.5 --- The role of insulin resistance in predicting women’s DM and metabolic syndrome --- p.55 / Chapter 3.6 --- Discussion --- p.57 / Chapter 3.7 --- Conclusion --- p.62 / Chapter Chapter 4 --- Glycaemic variables measured at mid-gestation of the index pregnancy predict women’s future cardiometabolic risk / Chapter 4.1 --- Glycaemic levels in pregnancy and perinatal outcome --- p.64 / Chapter 4.2 --- Glycaemic levels in pregnancy and women’s future cardiometabolic risk --- p.65 / Chapter 4.2.1 --- Prediction of women’s cardiometabolic risk at 8 and 15-year --- p.66 / Chapter 4.2.2 --- Optimal cut-off levels in predicting women’s future cardio- metabolic risk --- p.69 / Chapter 4.3 --- Discussion --- p.75 / Chapter 4.4 --- Conclusion --- p.78 / Chapter Chapter 5 --- Maternal gestational diabetes and offspring’s cardiometabolic risk / Chapter 5.1 --- Offspring’s cardiometabolic risk at 8 years age --- p.80 / Chapter 5.1.1 --- Baseline characteristics at pregnancy and delivery --- p.80 / Chapter 5.1.2 --- Children’s clinical and biochemical parameters at 8 years age --- p.82 / Chapter 5.2 --- Offspring’s cardiometabolic risk at 15 years age --- p.84 / Chapter 5.2.1 --- Adolescents’ clinical and biochemical parameters at 15 years age --- p.84 / Chapter 5.2.2 --- Clinical parameters of adolescents with abnormal glucose tolerance --- p.84 / Chapter 5.3 --- Discussion --- p.88 / Chapter 5.4 --- Conclusion --- p.90 / Chapter Chapter 6 --- In utero hyperinsulinaemia and offspring’s cardiometabolic risk / Chapter 6.1 --- Umbilical cord blood insulin and C-peptide --- p.92 / Chapter 6.1.1 --- Umbilical cord insulin and C-peptide concentrations in the original cohort --- p.92 / Chapter 6.1.2 --- Determination of in utero hyperinsulinaemia by umbilical cord insulin and C-peptide levels --- p.95 / Chapter 6.2 --- The effect of in utero hyperinsulinaemia on children’s abnormal glucose tolerance at 8 years of age --- p.98 / Chapter 6.2.1 --- Receiver operating characteristic analysis --- p.98 / Chapter 6.2.2 --- Logistic regression analysis --- p.98 / Chapter 6.3 --- The effect of in utero hyperinsulinaemia on adolescents’ cardio- metabolic risk at 15years of age --- p.102 / Chapter 6.3.1 --- Logistic regression analysis --- p.102 / Chapter 6.4 --- Discussion --- p.105 / Chapter 6.5 --- Conclusion --- p.108 / Chapter Chapter 7 --- Summary and conclusion / Chapter 7.1 --- Summary of the thesis --- p.110 / Chapter 7.1.1 --- Women’s long term cardiometabolic risk after a pregnancy with gestational diabetes --- p.110 / Chapter 7.1.2 --- The long term cardiometabolic risk of children born to mothers who had gestational diabetes --- p.111 / Chapter 7.1.3 --- New findings from the studies and their implications --- p.111 / Chapter 7.2 --- Strength and weakness in the study --- p.113 / Chapter 7.2.1 --- Unique cohort from universal screening --- p.113 / Chapter 7.2.2 --- Study design --- p.113 / Chapter 7.2.3 --- Response rate and loss to follow up --- p.114 / Chapter 7.2.4 --- Treatment effect of gestational diabetes --- p.115 / Chapter 7.3 --- Issues of future research --- p.115 / Chapter 7.3.1 --- Follow up study on the HAPO cohort --- p.115 / Chapter 7.3.2 --- Opportunity for international collaboration --- p.117 / Chapter 7.4 --- Conclusion --- p.118 / REFERENCES --- p.119

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 6 uppsatser.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2007. / Härtill 5 uppsatser.

The Hedgehog (Hh) family of proteins are secreted growth factors that play an essential role in the embryonic development of all organisms and the main components in the pathway are conserved from insects to humans. These proteins affect patterning and morphogenesis of multiple tissues. Therefore, mutations in the Hh pathway can result in a wide range of developmental defects and oncogenic diseases. Because the main components in the pathway are conserved from insects to humans, Drosophilahas been shown to provide a genetically tractable system to gain insight into the processes that Hh is involved in. In this study, the roles of Hh cholesterol modification and endocytosis during gradient fonnation are explored in the Drosophila larval wing imaginal disc. To exclude the possibility of looking at a redistribution of preexisting Hh instead of Hh movement, a spatially and temporally regulated system has been developed to induce Hh expression. Functional Hh-GFP with and without the cholesterol-modification was expressed in a wild-type or shi-tslendocytosis mutant background. The Gal80 system was used to temporally express (pulse) the Hh-GFP transgenes to look at the rate of Hh gradient formation over time and determine whether this process was affected by cholesterol modification and/or endocytosis. Hh with and without cholesterol were both largely detected in punctate structures and the spreading of the different forms of Hh was quantified by measuring distances of these particles from the expressing cells. Hh without cholesterol showed a greater range of distribution, but a lower percentage of particles near the source. Loss of endocytosis blocked formation of intracellular Hh particles, but did not dramatically alter its movement to target cells. Staining for Hh, its receptor Ptc and cortical actin revealed that these punctate structures could be classified into four types of Hh containing particles: cytoplasmic with and without Ptc, and cell surface with and without Ptc. Cholesterol is specifically required for the formation of cytoplasmic particles lacking Ptc. While previous studies have shown discrepancies in the localization of Hh following a block in endocytosis, Hh with and without cholesterol is detected at both apical and basolateral surfaces, but not at basal surfaces. In the absence of cholesterol and endocytosis, Hh particles can be observed in the extracellular space. Through three-dimensional reconstruction and quantitative analysis, this study concludes that the cholesterol modification is required to restrict Hh movement. In addition, the cholesterol modification promotes Ptc-independent internalization. This study also observes that Dynamin-dependent endocytosis is necessary for internalization but does not play an essential role in Hh distribution. The data in this thesis supports the model in which Hh movement occurs via planar diffusion.