Man, Cheuk Him. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 219-263). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgements --- p.vi / Table of Contents --- p.vii / List of Figures --- p.xii / List of Tables --- p.xvi / List of Publications --- p.xvii / Chapter Ch.l --- Introduction --- p.1 / Chapter 1.1 --- Aim of study --- p.1 / Chapter 1.2 --- Literature review --- p.3 / Chapter 1.2.1 --- Nasopharyngeal carcinoma (NPC) --- p.3 / Chapter 1.2.1.1 --- Structure and function of nasopharynx --- p.3 / Chapter 1.2.1.2 --- Histopathology of NPC --- p.3 / Chapter 1.2.1.3 --- Epidemiology of NPC --- p.4 / Chapter 1.2.2 --- Etiology of NPC --- p.6 / Chapter 1.2.2.1 --- Genetic factors --- p.6 / Chapter 1.2.2.2 --- Environment factors --- p.13 / Chapter 1.2.2.3 --- Epstein-Barr virus (EBV) infection --- p.14 / Chapter 1.2.3 --- Therapeutic treatment of NPC --- p.24 / Chapter 1.2.3.1 --- Radiotherapy (RT) --- p.24 / Chapter 1.2.3.2 --- Chemotherapy --- p.25 / Chapter 1.2.4 --- Notch signaling pathway --- p.26 / Chapter 1.2.4.1 --- Notch receptors and their ligands --- p.26 / Chapter 1.2.4.2 --- Activation of Notch signaling pathway --- p.29 / Chapter 1.2.4.3 --- Regulators of Notch signaling pathway --- p.32 / Chapter 1.2.4.4 --- Effectors of Notch signaling pathway --- p.32 / Chapter 1.2.5 --- Role of Notch signaling pathway in tumorigenesis --- p.33 / Chapter 1.2.5.1 --- Cell proliferation --- p.34 / Chapter 1.2.5.2 --- Cell survival --- p.35 / Chapter 1.2.5.3 --- Angiogenesis --- p.36 / Chapter 1.2.5.4 --- Cell invasion and metastasis --- p.36 / Chapter 1.2.6 --- Notch and oncogenic virus --- p.37 / Chapter 1.2.7 --- Crosstalk between Notch and other signaling pathways --- p.38 / Chapter 1.2.7.1 --- NFkB signaling pathway --- p.38 / Chapter 1.2.7.2 --- Ras signaling pathway --- p.39 / Chapter 1.2.7.3 --- Wnt signaling pathway --- p.40 / Chapter 1.2.7.4 --- Akt signaling pathway --- p.40 / Chapter 1.2.7.5 --- ErbB2 signaling pathway --- p.41 / Chapter 1.2.8 --- Notch as therapeutic target for cancer --- p.41 / Chapter Ch.2 --- Materials and Methods --- p.45 / Chapter 2.1 --- "Cell lines, xenografts and primary tumors" --- p.45 / Chapter 2.1.1 --- Cell lines --- p.45 / Chapter 2.1.2 --- Xenografts --- p.46 / Chapter 2.1.3 --- Primary tumors --- p.48 / Chapter 2.2 --- Reverse-transcription polymerase chain reaction (RT-PCR) --- p.50 / Chapter 2.2.1 --- Sample preparation for RT-PCR --- p.50 / Chapter 2.2.1.1 --- RNA extraction --- p.50 / Chapter 2.2.1.2 --- Quantitation of total RNA --- p.50 / Chapter 2.2.2 --- Conventional RT-PCR --- p.51 / Chapter 2.2.3 --- Quantitative RT-PCR --- p.51 / Chapter 2.3 --- Western immunoblot --- p.55 / Chapter 2.3.1 --- Protein extraction --- p.55 / Chapter 2.3.2 --- SDS-PAGE and immunoblotting --- p.55 / Chapter 2.4 --- Immunohistochemistry --- p.59 / Chapter 2.5 --- Cloning and plasmid DNA preparation --- p.62 / Chapter 2.5.1 --- Polymerase chain reaction (PCR) and purification of PCR products --- p.62 / Chapter 2.5.2 --- Restriction enzyme double digestion --- p.65 / Chapter 2.5.3 --- Ligation of plasmid and insert sequence --- p.65 / Chapter 2.5.4 --- Bacterial transformation --- p.66 / Chapter 2.5.5 --- Plasmid DNA extraction --- p.66 / Chapter 2.5.6 --- DNA sequencing --- p.67 / Chapter 2.6 --- Transient transfection of NPC cell lines --- p.67 / Chapter 2.7 --- Drug treatment on NPC cell lines --- p.69 / Chapter 2.8 --- Cell proliferation assays --- p.71 / Chapter 2.8.1 --- WST-1 assay --- p.71 / Chapter 2.8.2 --- BrdU assay --- p.71 / Chapter 2.9 --- Flow cytometry analysis --- p.72 / Chapter 2.9.1 --- Sample preparation --- p.72 / Chapter 2.9.2 --- Cell cycle analysis by propidium iodide staining --- p.73 / Chapter 2.9.3 --- Apoptosis analysis by AnnexinV-PI staining --- p.73 / Chapter 2.10 --- Apoptosis analysis by Caspase-3 activity assay --- p.74 / Chapter 2.11 --- RBP-Jk reporter assay --- p.75 / Chapter 2.12 --- NFKB1 reporter assay --- p.77 / Chapter 2.13 --- Dual luciferase reporter assay --- p.77 / Chapter 2.14 --- Expression array --- p.78 / Chapter 2.15 --- Statistical analysis --- p.79 / Chapter Ch.3 --- Characterization of Notch Signaling Molecules in NPC --- p.80 / Chapter 3.1 --- Introduction --- p.80 / Chapter 3.2 --- Results --- p.81 / Chapter 3.2.1 --- "Expression of Notch ligands, receptors, effectors and regulators in NPC cell lines and xenografts" --- p.81 / Chapter 3.2.2 --- "Expression of Notch ligands, receptors, regulators and effectors in NPC primary tumors" --- p.104 / Chapter 3.3 --- Discussion --- p.111 / Chapter 3.3.1 --- Overexpression of Jagl and D114 in NPC --- p.112 / Chapter 3.3.2 --- Overexpression of Notch receptors in NPC --- p.114 / Chapter 3.3.3 --- "Downregulation of Negative regulator, Numb, in NPC" --- p.116 / Chapter 3.3.4 --- Overexpression of Notch effectors in NPC --- p.117 / Chapter 3.4 --- Summary --- p.119 / Chapter Ch.4 --- Mechanisms of Activation of Notch Signaling Pathway in NPC --- p.120 / Chapter 4.1 --- Introduction --- p.120 / Chapter 4.2 --- Results --- p.122 / Chapter 4.2.1 --- EBV mediated Notch activation --- p.122 / Chapter 4.2.1.1 --- No effect of EBERs and EBNA1 on the expression of Notch Components --- p.122 / Chapter 4.2.1.2 --- LMP1 induces expression of Notch components --- p.129 / Chapter 4.2.1.3 --- LMP2A induces expression of Notch components --- p.133 / Chapter 4.2.2 --- Effect of CXCR4 on Notch signaling pathway in C666-1 --- p.137 / Chapter 4.3 --- Discussion --- p.139 / Chapter 4.3.1 --- EBV-mediated induction of Notch components --- p.139 / Chapter 4.3.2 --- Regulation of Notch expression by CXCR4 signaling pathway --- p.142 / Chapter 4.4 --- Summary --- p.145 / Chapter Ch.5 --- Investigation of the Oncogenic Role of Notch3 --- p.146 / Chapter 5.1 --- Introduction --- p.146 / Chapter 5.2 --- Results --- p.148 / Chapter 5.2.1 --- Effect of knockdown Notch 1 by siRNA on the growth of C666-1 --- p.148 / Chapter 5.2.2 --- Effect of knockdown Notch3 by siRNA on the growth of C666-1 --- p.151 / Chapter 5.2.2.1 --- Effect of knockdown Notch3 by siRNA on the RBP-Jk promoter activity of C666-1 --- p.153 / Chapter 5.2.2.2 --- Effect of knockdown Notch3 by siRNA on the proliferation of C666-1 --- p.155 / Chapter 5.2.2.3 --- Effect of knockdown Notch3 by siRNA on cell cycle progression of C666-1 --- p.158 / Chapter 5.2.2.4 --- Effect of knockdown Notch3 by siRNA on resistant to apoptosis in C666-1 --- p.160 / Chapter 5.2.3 --- Investigation of the anti-proliferation effect of therapeutic agents targeting Notch signaling pathway in NPC cells --- p.168 / Chapter 5.2.3.1 --- "Effect of DAPT on the proliferation of HEK293T, C666-1 and HK-1" --- p.168 / Chapter 5.2.3.2 --- Effect of AMD3100 on Notch signaling pathway and proliferation of NPC cells --- p.172 / Chapter 5.2.4 --- Study of downstream targets of Notch3 in NPC cells --- p.178 / Chapter 5.3 --- Discussion --- p.200 / Chapter 5.3.1 --- Oncogenic role of Notch3 in C666-1 --- p.200 / Chapter 5.3.2 --- Potential therapeutic approach in treating NPC via Notch inhibition --- p.206 / Chapter 5.3.2.1 --- "Gamma secretase inhibitor, DAPT" --- p.206 / Chapter 5.3.2.2 --- "CXCR4 antagonist, AMD3100" --- p.207 / Chapter 5.4 --- Summary --- p.209 / Chapter Ch.6 --- General Discussion --- p.210 / Chapter Ch.7 --- Conclusion --- p.217 / Reference --- p.219 / Appendices --- p.263 / Appendix 1 Summary of immunohistochemical staining results on 23 primary NPC samples --- p.264 / Appendix 2 Summary of 581 selected genes from the expression array --- p.265

by Chan Ping Lung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 108-118). / Abstracts in English and Chinese. / Abstract (in Chinese) --- p.ii / Abstract (in English) --- p.iv / Acknowledgements --- p.vii / Table of Contents --- p.viii / List of Tables --- p.xiii / List of Figures --- p.xiv / List of Appendices --- p.xv / List of Abbreviations --- p.xvi / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Epidemiology of catheter associated infections --- p.1 / Chapter 1.1.1 --- Catheter associated infections --- p.1 / Chapter 1.1.2 --- Risk and mortality of CAI --- p.2 / Chapter 1.1.3 --- Etiology of CAI --- p.3 / Chapter 1.1.3.1 --- Venous catheters --- p.4 / Chapter 1.1.3.2 --- Urinary catheters --- p.4 / Chapter 1.2 --- Pathogenesis of CAI --- p.5 / Chapter 1.2.1 --- Central venous catheters (CVC) --- p.6 / Chapter 1.2.2 --- Urinary catheters --- p.7 / Chapter 1.3 --- Adhesion mechanisms --- p.7 / Chapter 1.3.1 --- Definition of adhesion --- p.7 / Chapter 1.3.2 --- Adhesion mechanism --- p.8 / Chapter 1.3.2.1 --- The phase one --- p.8 / Chapter 1.3.2.2 --- The phase two --- p.10 / Chapter 1.4 --- Catheters --- p.10 / Chapter 1.5 --- Biology of Candida albicans --- p.11 / Chapter 1.5.1 --- Taxonomy of Candida albicans --- p.11 / Chapter 1.5.2 --- Morphology --- p.12 / Chapter 1.5.3 --- Genome --- p.13 / Chapter 1.5.4 --- Biology of Candida albicans cell wall --- p.14 / Chapter 1.5.4.1 --- Constituting molecules of Candida albicans cell wall --- p.14 / Chapter 1.5.4.2 --- Organization of Candida albicans cell wall --- p.15 / Chapter 1.6 --- Agglutinin like sequence gene family --- p.16 / Chapter 1.6.1 --- Gene structure of agglutinin like sequence genes --- p.16 / Chapter 1.6.2 --- Sequence similarity --- p.17 / Chapter 1.6.3 --- Sequence variability --- p.18 / Chapter 1.6.4 --- Expression of ALS genes --- p.19 / Chapter 1.6.5 --- The Als proteins --- p.20 / Chapter 1.6.6 --- Functions of Als proteins --- p.21 / Chapter 1.7 --- Adhesion assay --- p.23 / Chapter 1.7.1 --- Adhesion model --- p.24 / Chapter 1.7.2 --- Factors affecting static adhesion model --- p.25 / Chapter 1.7.3 --- Quantitation methods of adherent cells --- p.27 / Chapter 1.7.3.1 --- Sonication --- p.27 / Chapter 1.7.3.2 --- Staining methods --- p.28 / Chapter 1.7.3.3 --- ATP bioluminescence --- p.28 / Chapter 1.8 --- Research model --- p.29 / Chapter Chapter 2 --- Aim of study --- p.31 / Chapter Chapter 3 --- Materials and Methods --- p.32 / Chapter 3.1 --- Preparation of bacteriological reagents --- p.32 / Chapter 3.2 --- Confirmation of identity of Candida albicans and of Saccharomyces cerevisiae --- p.33 / Chapter 3.3 --- Cell culture of fibroblasts --- p.36 / Chapter 3.3.1 --- Preparation of cell culture reagents --- p.36 / Chapter 3.3.2 --- Recovery of freezing fibroblasts --- p.37 / Chapter 3.3.3 --- Establishment of cell line --- p.37 / Chapter 3.4 --- Preliminary study of adherence of Candida albicans to fibroblasts and to catheters --- p.38 / Chapter 3.4.1 --- Adherence to fibroblasts --- p.38 / Chapter 3.4.1.1 --- Preparation of fibroblasts --- p.38 / Chapter 3.4.1.2 --- Preparation of culture of Candida albicans and of Saccharomyces cerevisiae --- p.39 / Chapter 3.4.1.3 --- Adhesion assay --- p.41 / Chapter 3.4.2 --- Adherence to catheters --- p.42 / Chapter 3.4.2.1 --- Preparation of catheters --- p.42 / Chapter 3.4.2.2 --- Adhesion assay --- p.42 / Chapter 3.5 --- "Confirmation of expression of ALS1, ALS5 smaller allele, and ALS6 of Candida albicans in YPD broth" --- p.44 / Chapter 3.5.1 --- RNA extraction of Candida albicans --- p.45 / Chapter 3.5.2 --- "RT-PCR of ALS1, ALS5 smaller allele, and ALS6" --- p.46 / Chapter 3.5.2.1 --- Primers --- p.46 / Chapter 3.5.2.2 --- RT-PCR --- p.47 / Chapter 3.6 --- Establishment of quantitation system of adhesion assay --- p.49 / Chapter 3.6.1 --- Absorbance measurement of Candida albicans stained with safranin --- p.49 / Chapter 3.6.1.1 --- Preparation of Candida albicans culture --- p.49 / Chapter 3.6.1.2 --- Staining of Candida albicans --- p.50 / Chapter 3.6.1.3 --- Viable count of Candida albicans adhered on the 6-well plate --- p.51 / Chapter 3.6.2 --- ATP bioluminescence --- p.52 / Chapter 3.7 --- Effect of inoculum size on adhesion to catheters --- p.53 / Chapter 3.7.1 --- Preparation of adhesion chambers --- p.53 / Chapter 3.7.2 --- Preparation of catheters --- p.54 / Chapter 3.7.3 --- Preparation of Candida albicans culture --- p.54 / Chapter 3.7.4 --- Adhesion assay --- p.55 / Chapter 3.8 --- "Transformation of Saccharomyces cerevisiae with ALS1, ALS5 smaller allele, and ALS6" --- p.57 / Chapter 3.8.1 --- DNA extraction of Candida albicans --- p.58 / Chapter 3.8.2 --- "PCR of ALS1, ALS5 smaller allele, and ALS6" --- p.59 / Chapter 3.8.3 --- Gel extraction --- p.60 / Chapter 3.8.4 --- Restriction digestion of PCR products of ALS genes and cloning plasmids --- p.61 / Chapter 3.8.5 --- "Ligation of ALS1, ALS5 smaller allele, ALS6 with pYES6CT cloning plasmids" --- p.62 / Chapter 3.8.6 --- Transformation of ligated plasmid into Escherichia coli --- p.63 / Chapter 3.8.7 --- Miniprep of plasmids --- p.64 / Chapter 3.8.8 --- DNA sequencing --- p.65 / Chapter 3.8.9 --- Transformation of Saccharomyces cerevisiae --- p.66 / Chapter 3.8.10 --- "Detection of Alsl，Als5, and Als6 protiens expression" --- p.68 / Chapter 3.8.10.1 --- Preparation of cultures in SC synthetic medium --- p.68 / Chapter 3.8.10.2 --- Protein extraction --- p.69 / Chapter 3.8.10.3 --- Dot blot of cell wall lysates --- p.69 / Chapter 3.9 --- Adhesion of transformed Saccharomyces cerevisiae to fibroblasts --- p.71 / Chapter 3.9.1 --- Preparation of fibroblasts and of Saccharomyces cerevisiae cultures --- p.71 / Chapter 3.9.2 --- Adhesion assay --- p.72 / Chapter 3.10 --- "Adhesion of transformed Saccharomyces cerevisiae to FEP, polyurethane, and silicone catheters" --- p.72 / Chapter 3.10.1 --- "Preparation of catheters, adhesion chambers and transformed Saccharomyces cerevisiae cultures" --- p.73 / Chapter 3.10.2 --- Adhesion to catheter fragments --- p.73 / Chapter 3.11 --- Statistical analysis --- p.74 / Chapter Chapter 4 --- Results --- p.75 / Chapter 4.1 --- Confirmation of identity of Candida albicans and of Saccharomyces cerevisiae --- p.75 / Chapter 4.1.1 --- Candida albicans --- p.75 / Chapter 4.1.2 --- Saccharomyces cerevisiae --- p.75 / Chapter 4.2 --- Cell culture of fibroblasts --- p.76 / Chapter 4.3 --- "Preliminary studies of adherence of Candida albicans to fibroblasts and to FEP, polyurethane, and silicone catheters" --- p.76 / Chapter 4.3.1 --- Adherence to fibroblasts --- p.76 / Chapter 4.3.2 --- Adherence to catheters --- p.77 / Chapter 4.4 --- "Confirmation of expression of ALSl, ALS5 smaller allele, and ALS6 of Candida albicans in YPD broth" --- p.78 / Chapter 4.5 --- Establishment of quantitation system of adhesion assay --- p.79 / Chapter 4.5.1 --- Absorbance measurement of Candida albicans stained with safranin --- p.79 / Chapter 4.5.2 --- ATP bioluminescence --- p.79 / Chapter 4.6 --- Effect of inoculum size on adhesion to catheters --- p.80 / Chapter 4.7 --- "Transformation of Saccharomyces cerevisiae with ALS1, ALS5 smaller allele, and ALS6" --- p.81 / Chapter 4.7.1 --- "PCR of ALSl, ALS5 smaller allele, and ALS6" --- p.81 / Chapter 4.7.2 --- Ligation of PCR products with pYES6CT plasmids --- p.82 / Chapter 4.7.3 --- "DNA sequencing results of ALS1, ALS5 smaller allele, and ALS6 ligated plasmids" --- p.83 / Chapter 4.7.4 --- "Detection of Alsl, Als5, and Als6 proteins expression" --- p.84 / Chapter 4.8 --- Adhesion of transformed Saccharomyces cerevisiae to fibroblasts --- p.84 / Chapter 4.9 --- "Adhesion of transformed Saccharomyces cerevisiae to FEP, polyurethane and silicone catheters" --- p.85 / Chapter Chapter 5 --- Discussion --- p.89 / Chapter 5.1 --- Limitations of static adhesion assay model --- p.89 / Chapter 5.2 --- Quantitation System --- p.90 / Chapter 5.2.1 --- Staining method --- p.90 / Chapter 5.2.2 --- ATP bioluminescence assay --- p.91 / Chapter 5.3 --- "Preliminary studies of adherence of Candida albicans to fibroblasts and to FEP, polyurethane, and silicone catheters" --- p.93 / Chapter 5.4 --- Effect of inoculum size on adhesion to catheters --- p.94 / Chapter 5.5 --- Selection of ALS genes --- p.96 / Chapter 5.6 --- Adhesion assay of transformed Saccharomyces cerevisiae to fibroblasts --- p.97 / Chapter 5.7 --- Adhesion assay of transformed Saccharomyces cerevisiae to catheters --- p.99 / Chapter 5.8 --- Alternative research model --- p.101 / Chapter 5.9 --- Implications and future work --- p.102 / Chapter Chapter 6 --- Conclusion --- p.107 / References --- p.108 / Tables --- p.119 / Figures --- p.123 / Appendices --- p.136

Made available in DSpace on 2015-07-15T13:31:41Z (GMT). No. of bitstreams: 1 Hyrlana Leal.pdf: 2114449 bytes, checksum: 1a7453f5f4cf5b54fa31a2de50b34c94 (MD5) Previous issue date: 2007-01-23 / Funda??o de Amparo a Pesquisa do Estado da Bahia / Lichen planus (LP) is a chronic inflammatory disease that affects skin and/or mucous and whose origin still is unknown. In the mouth the disease is called oral lichen planus (OLP). The association between OLP and the hepatitis C virus (HCV) infection has been widely argued in literature with controversial results. The aim of this age- and sex-matched case-control study was evaluate the association between OLP and HCV infection. Thirty individuals with OLP diagnosed in the Reference Center of Oral Disease of the State University of Feira de Santana, comprised of the test group (OLP group), and thirty healthy individuals proceeding from the same population were included in the control group. None out of the OLP group or control group were seropositive for anti-HCV. The results showed there is not association between OLP and HCV infection. Analyses add between the association of the LPB and the presence of systemic diseases, drugs use, menopause and habits to smoke and to consume alcoholic beverage did not shown significance statistics. On the basis of the results of the present study were not possible to establish the association between OLP and HCV infection. In conclusion, further new longitudinal studies may be performed in attempt to clarify this matter. / L?quen plano (LP) ? uma doen?a inflamat?ria cr?nica que afeta, principalmente, pele e/ou mucosas e cuja origem ainda ? desconhecida. Na boca a doen?a ? denominada de l?quen plano bucal (LPB). A associa??o entre o LPB e a infec??o pelo v?rus da hepatite C (VHC) tem sido amplamente discutida na literatura, com resultados controversos. Com o prop?sito de verificar a associa??o entre o LPB e a infec??o pelo VCH, foi conduzido um estudo tipo caso-controle, pareado por idade e selecionados trinta indiv?duos portadores de LPB, diagnosticados no Centro de Refer?ncia em Les?es Bucais da Universidade Estadual de Feira de Santana, que compuseram o grupo de casos, e outros trinta indiv?duos provenientes da mesma popula??o, que n?o apresentavam les?es bucais. Os resultados encontrados indicaram n?o haver associa??o entre o LPB e a infec??o pelo VHC visto que n?o foram encontrados indiv?duos com sorologia reagente para o v?rus. An?lises adicionais entre a associa??o do LPB e a presen?a de doen?as sist?micas e menopausa, uso de medicamentos e h?bitos de fumar e consumir bebidas alco?licas n?o mostraram signific?ncia estat?stica. Com base nos resultados do presente estudo n?o foi poss?vel estabelecer a associa??o entre o LPB e a VHC e, portanto, sugere-se a realiza??o de novos estudos longitudinais, que possam esclarecer tal poss?vel rela??o.

Pregnancy loss, the demise of a pregnancy at any time between implantation and delivery, is a common event in women’s lives, affecting approximately one in three pregnancies. Pregnancy loss often causes profound psychological distress to women, their partners, and their families. However, despite its frequency and troubling nature, relatively little is known about the natural history of pregnancy loss, especially the multitude of signs and symptoms that precede a loss and distinguish it from an ongoing healthy pregnancy. One of the challenges in describing the natural history of pregnancy loss is that most losses occur very early, before entry to clinical care, necessitating the use of preconception cohort studies. Few such studies have ever been conducted worldwide. This dissertation aimed to describe the natural history of early pregnancy loss at <20 weeks gestation for the first time using a unique preconception cohort with daily prospective follow-up from the start of the pregnancy attempt through seven weeks post-conception. To accomplish this goal, three specific aims were undertaken. First, a systematic literature review was conducted to synthesize the existing literature on the relationships between the signs and symptoms and pregnancy loss. Two analytic aims were then undertaken to delineate thoroughly the relationships between prospectively ascertained signs and symptoms—namely, vaginal bleeding, lower abdominal cramping, nausea and vomiting (hereafter referred to as “signs and symptoms”)—and subsequent early pregnancy loss. The first analytic aim used a fixed covariate and fixed effect survival analytic approach to estimate the cumulative incidence of early pregnancy loss by the presence of individual, combinations, and patterns of signs and symptoms and the associations between signs and symptoms and the cumulative incidence of pregnancy loss. The second analytic aim used a time-varying covariate and time-varying effect survival analytic approach to estimate the weekly associations between signs and symptoms and pregnancy loss to determine if these relationships were consistent or divergent across gestational ages. The results of the first and second analytic aims were then compared to gain a more complete understanding of the natural history of early pregnancy loss. The literature review revealed a dearth of studies on the signs and symptoms of pregnancy loss. Two preconception and 16 pregnancy cohort studies were identified. The literature suggested that vaginal bleeding, particularly heavy vaginal bleeding, was associated with an increased risk of pregnancy loss while vomiting, and in some studies nausea, was associated with a decreased risk of pregnancy loss. However, reliance on care-seeking cohorts, maternal retrospective reports of signs and symptoms after pregnancy loss, and retrospective recall of signs and symptoms over long periods (e.g., entire trimesters) may have biased the observed associations between signs and symptoms and pregnancy loss leading to incorrect inferences regarding the relationships between signs and symptoms and pregnancy loss. The two analytic aims addressed the data gaps identified in the literature review. The preconception cohort design with prospective daily follow-up from the beginning of the pregnancy attempt facilitated the ascertainment of pregnancies at the earliest stages of gestation and losses prior to clinical care entry through the use of urine-based home pregnancy testing. The daily reporting of multiple signs and symptoms in the first five weeks after a positive home pregnancy test, or approximately two to seven weeks post-conception, allowed for a full description of the relationships between signs and symptoms of pregnancy loss without recall bias. Data for the two analytic aims come from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study, a population-based cohort with preconception recruitment of couples in 16 counties in Michigan and Texas followed for 12 months of trying for pregnancy and then through pregnancy loss or delivery for couples achieving an hCG pregnancy. 501 couples entered the study, and 347 achieved a pregnancy during the study period. Three hundred forty-one singleton pregnancies comprise the study population for the two analytic aims in this dissertation. Overall, 95 (28%) pregnancies in the study population ended in a pregnancy loss. Lower abdominal cramping, nausea, and vomiting were often reported during the early pregnancy period; vaginal bleeding was less common. The results of the fixed covariate fixed effect survival analysis from the first analytic aim demonstrated that vaginal bleeding, particularly heavy bleeding and bleeding accompanied by lower abdominal cramping, was associated with an increased risk of pregnancy loss. In contrast, the presence of vomiting, but not nausea alone, during the early pregnancy period was associated with a lower risk of loss. Analyses in the second analytic aim using weekly time-varying covariates and time-varying effects of signs and symptoms on pregnancy loss revealed some new findings. The first week after a positive pregnancy test appeared to be a vulnerable period. Vaginal bleeding and lower abdominal cramping were associated with an increased risk of loss in the first week but not in later weeks; conversely, nausea and/or vomiting were associated with lower risk of pregnancy loss but only after the first week. The observed weekly variations in the signs and symptoms of pregnancy loss may reflect changes in maternal adaptation to pregnancy across gestation. Overall, relatively little is known about the biological processes underlying healthy and unhealthy adaption to pregnancy as well as how embryo quality may affect these adaptive processes. More work is required from basic scientists, clinicians and epidemiologists to better understand the causes of signs and symptoms and their relationships to pregnancy loss, including genetic and environmental factors and their interactions. In the meantime, prognostic models developed from data in this dissertation using time-varying signs and symptoms may be useful to women and their health care providers for identifying pregnancies at increased risk for pregnancy loss. These models could prompt women to seek medical care when concerning patterns of signs and symptoms arise.

Tam Wing-yip. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 91-113). / Abstracts in English and Chinese. / Abstract --- p.i / Chinese Abstract --- p.iv / Acknowledgements --- p.vi / Table of Contents --- p.vii / Chapter Chapter 1 --- General Introduction --- p.1 / Chapter 1.1 --- Hirschsprung's disease --- p.1 / Chapter 1.2 --- Neural crest cells and enteric nervous system --- p.3 / Chapter 1.3 --- Genetics of Hirschsprun´gةs disease --- p.10 / Chapter 1.3.1 --- RET/GDNF/NTN signaling pathway --- p.10 / Chapter 1.3.2 --- EDNRB/EDN3/ECE-1 signaling pathway --- p.13 / Chapter 1.3.3 --- Dominant megacolon and Sox10 --- p.15 / Chapter 1.3.4 --- Other genes involved in intestinal aganglionosis --- p.16 / Chapter 1.4 --- Objectives of the present study --- p.19 / Chapter Chapter 2 --- Enteric Neural Crest Cells Migration in Dominant Megacolon Mouse Embryos --- p.21 / Chapter 2.1 --- Introduction --- p.21 / Chapter 2.2 --- Materials and Methods --- p.26 / Chapter 2.2.1 --- Animal --- p.26 / Chapter 2.2.2 --- Preparation of rat serum --- p.26 / Chapter 2.2.3 --- Isolation of embryos from pregnant mice --- p.27 / Chapter 2.2.4 --- Preparation of wheat germ agglutinin-gold (WGA-Au) --- p.28 / Chapter 2.2.5 --- Microinjection of WGA-Au conjugate --- p.28 / Chapter 2.2.6 --- Whole embryo culture --- p.29 / Chapter 2.2.7 --- Examination of cultured embryos --- p.30 / Chapter 2.2.8 --- Histological preparation of WGA-Au injected embryos --- p.30 / Chapter 2.2.9 --- Silver enhancement staining and histological examination of the sections --- p.31 / Chapter 2.2.10 --- Genotyping by polymerase chain reaction --- p.32 / Chapter 2.2.11 --- TUNEL assays --- p.33 / Chapter 2.3 --- Results --- p.35 / Chapter 2.3.1 --- In vivo development of Dominant megacolon mouse embryos of different genotypes --- p.35 / Chapter 2.3.2 --- In vitro development of embryos in control and experimental groups --- p.35 / Chapter 2.3.3 --- Migration of vagal neural crest cells in Dom embryos --- p.36 / Chapter 2.3.4 --- Apoptotic cells detection at the vagal region by TUNEL assay --- p.37 / Chapter 2.3.5 --- Migration of sacral neural crest cells in Dom embryos --- p.37 / Chapter 2.3.6 --- Apoptotic cells detection at the sacral region by TUNEL assay --- p.38 / Figures and Tables / Chapter 2.4 --- Discussion --- p.40 / Chapter 2.4.1 --- In vitro culture system supporting the normal development of mouse embryos --- p.40 / Chapter 2.4.2 --- WGA-Au as a cell marker for tracing the NCCs migration --- p.41 / Chapter 2.4.3 --- Vagal neural crest cells migration in Dom mouse embryos --- p.42 / Chapter 2.4.4 --- Apoptotic cell death does not contribute to the total aganglionosis in Dom homozygous embryos --- p.43 / Chapter 2.4.5 --- Sacral neural crest cells migration in Dom mouse embryos --- p.45 / Chapter 2.4.6 --- NCCs migration in zebrafish colourless mutant --- p.47 / Chapter 2.4.7 --- Limitation of the method used in this study --- p.49 / Chapter 2.4.8 --- Conclusions --- p.49 / Appendices / Chapter Chapter 3 --- Migration of Enteric Neural Crest-derived Cells in the Developing Gut of Dominant Megacolon Mouse Embryos --- p.51 / Chapter 3.1 --- Introduction --- p.51 / Chapter 3.2 --- Materials and Methods --- p.55 / Chapter 3.2.1 --- Isolation of the gut from Dom mouse embryos --- p.55 / Chapter 3.2.2 --- Whole mount immunohistochemistry --- p.55 / Chapter 3.3 --- Results --- p.57 / Chapter 3.3.1 --- PGP9.5 immunoreactivity in the 12.5 d.p.c. Dom embryos --- p.57 / Chapter 3.3.2 --- TH immunoreactivity in the 12.5 d.p.c. Dom embryos --- p.58 / Chapter 3.3.3 --- PGP9.5 immunoreactivity in the 14.5 d.p.c. Dom embryos --- p.59 / Figures and Tables / Chapter 3.4 --- Discussion --- p.61 / Chapter 3.4.1 --- The use of PGP9.5 and TH antibodies as markers for studying the migration of enteric neural crest-derived cells --- p.61 / Chapter 3.4.2 --- Incomplete migration of neural crest-derived cells within the gut of Dom heterozygous embryos --- p.62 / Chapter 3.4.3 --- Failure of sacral NCCs to invade the hindgut of Dom heterozygous embryos --- p.63 / Chapter 3.4.4 --- PGP9.5 and TH positive signals in the gut of Dom homozygous embryos --- p.64 / Chapter 3.4.5 --- Early differentiation of neural crest-derived cells into neurons due to haploinsufficiency of Sox10 --- p.65 / Chapter 3.4.6 --- Conclusions --- p.66 / Chapter Chapter 4 --- Localization of Interstitial Cells of Cajal in the Gut of Dominant Megacolon Mice --- p.67 / Chapter 4.1 --- Introduction --- p.67 / Chapter 4.2. --- Materials and Methods --- p.72 / Chapter 4.2.1 --- Isolation of the gut from mouse embryos and adult mice --- p.72 / Chapter 4.2.2 --- Cryosection and immunohistochemistry --- p.73 / Chapter 4.2.3 --- Whole-mount immunohistochemistry --- p.73 / Chapter 4.2.4 --- Total RNA extraction --- p.74 / Chapter 4.2.5 --- Reverse transcription for the first strand cDNA synthesis --- p.75 / Chapter 4.2.4 --- Reverse transcription-Polymerase chain reaction (RT-PCR) --- p.76 / Chapter 4.3 --- Results --- p.77 / Chapter 4.3.1 --- PGP9.5 and c-kit immunoreactivity in the Dom wild type colon --- p.77 / Chapter 4.3.2 --- c-kit immunoreactivity in the Dom heterozygous adult colon --- p.78 / Chapter 4.3.3 --- c-kit and SCF expression during gut development --- p.78 / Figures and Tables / Chapter 4.4 --- Discussion --- p.80 / Chapter 4.4.1 --- The importance in studying the development of ICCs in aganglionic gut --- p.80 / Chapter 4.4.2 --- ICCs development in Dominant megacolon mice --- p.81 / Chapter 4.4.3 --- The relationship between enteric neurons and ICCs development --- p.83 / Chapter 4.4.4 --- Advantages of using confocal microscopy and whole- mount preparations to study the ICCs development --- p.85 / Chapter 4.4.5 --- Conclusions --- p.86 / Chapter Chapter 5 --- General Discussion and Conclusions --- p.87 / References --- p.91

Results of the above studies thus suggested that immune dysregulation in SLE result in derangement of a spectrum of inflammatory mediators leading to possible multiple organs auto-inflammatory damages. However, the exact etio-pathogenic mechanism could not simply be explained by these phenomena. Infection has been invoked as an underlying etiology or trigger for the induction of autoimmune disease. Epstein-Barr virus (EBV) possesses multiple features that characterise its involvement in initiating or perpetuating SLE disease. Several research groups demonstrated that the peripheral blood EBV DNA load is significantly higher in SLE patients, yet cell-free viral DNA was also reported in other EBV-associated diseases such as nasopharyngeal carcinoma (NPC) and certain lymphomas, suggesting that relatively little is known about its biology and dynamic distribution in the blood circulation. In the second part of our study, we examined the cell-free and cell-associated distribution profile of EBV DNA load in SLE. Our data showed that the distribution of EBV DNA in the cell-free and cell-associated compartments exhibited a heterogeneous pattern in SLE patients. Contrary to the exclusive presence of circulating cell-free EBV DNA in NPC patients, both cell-free and cell-associated EBV DNA were detected in some SLE patients, while in others, no EBV DNA was measurable in either blood compartments. The level of cell-associated EBV viral load was significantly higher in SLE patients with active disease than those who presented with milder disease activity. This phenomenon indicated a possible association of EBV viral infection with the level of immune competence in SLE patients. It has been reported that EBV encodes proteins which shares significantly homology sequence with human IL-6, IL-8, IL-10, IL-12 and colony-stimulating factor (CSF)-1. This proposition brought our attention to the immune perturbation by EBV on the cytokine balance, possibly constitute in part, to the immune dysregulation and Th1 and Th2 dichotomy in SLE exacerbation. (Abstract shortened by UMI.) / The first section of this research study aimed to explore the messengers that influence Th1/Th2 cells differentiation, development, effector functions and hence their plausible contribution in SLE immunopathogenesis. We focused on studying the expression of cytokine and chemokine milieu that directs the traffic of T lymphocytes; co-stimulatory molecules in the activation of T lymphocytes; transcription factors T-bet and GATA-3 in regulating the differentiation of Th1 and Th2 cell lineage. We also investigated the involvement of the lymphocyte subpopulation, Th17 in the auto-inflammatory axis of SLE exacerbation. / Lit, Choi Wan. / Advisers: Christopher W.K. Lam; Y.M. Dennis Lo. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3358. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 203-235). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Tong Hung Man Joanna. / "June 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 137-149). / 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 conclusion, the current air pollution levels in Hong Kong had a risk for school children's respiratory and cardiovascular health. In comparison between the highly- and least-polluted districts, a rise of 8 mug/m 3 annual mean for PM10 concentration was significantly associated with increased risks for some respiratory symptoms such as wheezing, cough, and phlegm, with decreased lung function in FEF25-75% and FEF75%, and with decreased cardiopulmonary fitness in predicted VO2max, after adjustment for confounding factors. An increase of 13 mug/m3 annual mean for NO2 in the moderately-polluted district did not individually cause adverse effects on children's respiratory and cardiopulmonary health. Physical activity appears to have no positive health effects on the children's VO2max in moderately- and highly-polluted districts. / In the past year preceding the study (May 2003 to April 2004), the annual means for PM10, NO2, SO2 and O3 were respectively 55.1 mug/m3, 51.4 mug/m3, 15.4 mug/m3, and 42.5 mug/m3 in the least-polluted district (LPD); 56.3 mug/m3, 64.7 mug/m3, 15.2 mug/m3, and 35.2 mug/m3 in the moderately-polluted district (MPD); and 63.8 mug/m3, 64.1 mug/m3, 22.2 mug/m3, and 31.7 mug/m3 in the highly-polluted district (HPD). The 99th percentiles were 178 mug/m3, 158 mug/m 3, 104 mug/m3, and 140 mug/m3 in the LPD; 169 mug/m3, 181 mug/m3, 106 mug/m 3, and 113 mug/m3 in the MPD; and 226 mug/m 3, 177 mug/m3, 140 mug/m3, and 137 mug/m 3 in the HPD. The average daily 1-h maximum O3 (peak O 3) was 83.7 mug/m3 in the LPD, 73.6 mug/m 3 in the MPD, and 64.8 mug/m3 in the HPD. / Lung function indices included FVC, FEV1, FEV 1/FVC, FEF25-75%, FEF25%, and FEF75%. Children in the HPD had lower FEV 1/FVC, FEF25-75%, and FEF25% than those in both the LPD and MPD, after controlling for their corresponding confounders. In comparison between the LPD and HPD, the adjusted mean differences for FEV1/FVC, FEF25-75%, and FEF25% were respectively 1.39%, 85 ml, and 113 ml in boys, and 1.60%, 86 ml, and 225 ml in girls. In addition, the decreased FEF75% of HPD was found in boys (62 ml) but not in girls. When comparing the MPD with LPD, the increased FEF25% was observed in girls in the LPD (158 ml), whereas boys in the LPD had lower FEF75% than those in the MPD (81 ml). There were no significant differences in children's FVC and FEV1 between districts. / The multistage fitness test (MFT) with the Matsuzaka's function was employed to predict cardiopulmonary fitness (VO2max) of children. After adjustment for the factors, girls in the LPD had significantly higher VO 2max than those in the MPD and HPD by 0.19 and 0.75 ml&middot;kg -1 &middot;min-1 respectively. The VO 2max among boys in the LPD was 0.48 ml&middot;kg-1 &middot;min -1 higher than those in the HPD. When we compared the VO 2max between students in MPD and HPD, higher VO2max in both boys and girls in the MPD were observed---by 0.49 and 0.56 ml&middot;kg -1 &middot;min-1 respectively. In LPD, significantly higher VO2max values were observed in both boys and girls who were physically active (children who took part in sports and/or vigorous free play at least three times a week for at least 30 minutes each time) compared with those who were not (0.71 and 0.65 ml&middot;kg-1 &middot;min -1 respectively), but those differences in VO2max among students in MPD and HPD were small and insignificant. / There were totally 2,641 (82.9%) children who participated in the study, and 2,203 participants were involved in analyses. After adjustment for confounding factors, girls living in the HPD had significantly increased odds ratios (ORs) for wheezing without cold (4.75), cough at night (1.71), phlegm without cold (3.61), compared with those in the LPD. Boys in the HPD had increased OR only for phlegm without cold (1.88). When comparing the MPD with LPD, the adjusted OR for cough at night achieved significance in girls (1.74) and marginal significance in boys (1.40). Sneeze with itchy-watery eyes and current/ever allergic rhinitis had negative associations with district. In comparison with LPD, the decreased OR for sneeze with itchy-watery eye in girls in HPD (0.65) reached statistical significance. Both boys and girls in MPD had significantly decreased ORs for current allergic rhinitis (0.72 and 0.50 respectively) and for ever allergic rhinitis (0.74 and 0.55 respectively). There were no significant differences in the prevalence rates of asthma and bronchitis between districts. / To explore associations between air pollution and respiratory and cardiovascular health of school children, a cross-sectional study was conducted among 3,186 primary school children in P3 and P4 from three districts with different air pollution levels in Hong Kong during March to June in 2004. / Gao Yang. / "August 2005." / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6339. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 137-154). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Objetivo: Descrever os aspectos clínicos, etiológicos e terapêuticos da candidíase sistêmica em recém-nascidos. Casuística e Métodos: Estudo observacional, em 60 neonatos com candidíase sistêmica, durante 10 anos. Resultados: Freqüência global = 1,8%;sintomas: alterações respiratórias, febre, hipotermia, letargia, hepatomegalia. A C. albicans ocorreu em 83,3% dos casos. Conclusão: A freqüência global da candidíase foi alta, os fatores de risco observados concordam com os citados na literatura, os sinais e sintomas mais freqüentes foram alterações respiratórias, a espécie mais freqüentemente identificada foi C.albicans (83,3%). A mortalidade foi elevada (33,3%), a sobrevida foi maior nos neonatos tratados com formulação lipídica da anfotericina / Objetives: To describe the clinical, etiologic and therapeutical aspects of systemic candidiasis in newborns. Casuistic and methods: Observacional study in 60 neonates with systemic candidiasis during 10 years. Results: Global frequency = 1,8%,symptoms: respiratory alterations, fever, hipotermia, lethargy, hepatomegalia. The C.albicans occurred in 83,3% of the cases. Conclusions: The global frequency of candidiasis was high, the observed fators of risk agrees to the cited ones to literature, the signal and more frequent symptoms had been respiratory alterations, the species more frequently identified were C.albicans(83,3%).The mortality was high (33,3%), the survival was highest in neonates treated with lipid formulation of amphotericin

Em outubro de 2005 a notificação de 17 casos de doença ocular de etiologia desconhecida, envolvendo, em sua maioria, a população infantil da cidade de Araguatins/TO, levou as autoridades locais a pedirem ajuda a Secretaria de Estado da Saúde do Estado do Tocantins no intuito de descobrirem sua etiologia, tratamento e prevenção. Nos pacientes acometidos, os sinais freqüentemente observados foram: intensa hiperemia conjutival, granuloma, episclerite, infiltrado corneano periférico. Na anamnese realizada nos pacientes foi observado que todos tiveram contato com as águas do Rio Araguaia. Os resultados obtidos a partir do processamento das amostras de água, sedimentos e substratos particularmente na vegetação marginal inundada, permitiram confirmar a hipótese de que deveria haver uma fauna rica de esponjas no Araguaia, no trecho fronteiro à cidade de Araguatins A presença intraocular de espícula de esponja de água doce das espécies Drulia uruguayensis e Oncosclera navicela foi confirmada em material avaliado histopatologicamente proveniente de três pacientes que haviam sido submetidos a lensectomia, sugerindo que espículas de água doce poderiam ser um surpreendente novo agente etiológico de patologia ocular. Assim, neste estudo foram realizados ensaios de citotoxicidade com amostras de duas espécies de esponjas coletadas no local. Os resultados indicam que os extratos das esponjas após filtração em filtro Millipore 0,45 &mu;m continuaram apresentando atividade citotóxica, sugerindo haver um componente SOLÚVEL, e não somente espículas, capaz de induzir morte celular na população de células utilizadas. Os indivíduos acometidos foram na maioria do sexo masculino com idade entre 05 e 14 anos. / In October 2005 the notification of 17 cases of eyes disease of unknown etiology, involving, in its majority, the infant population of the city of Araguatins/TO, led the local authorities to ask help to the Secretariate of State of Health of the State of Tocantins in order to discover their etiology, treatment and prevention. In affected patients, the signs frequently observed were: intense hyperemia conjutival, granuloma, episclerite, peripheral cornea infiltrated. In the anamnesis performed in patients was observed that all of them had contact with the waters of the Araguaia river. The results obtained from processing samples of water, sediments and substrates particularly in the vegetation marginal flooded, allowed confirming the hypothesis that there should be a rich fauna sponges in Araguaia, close to the city of Araguatins The presence of spicula of intraocular sponge species of freshwater Drulia uruguayensis and Oncosclera navicela was confirmed in material evaluated histopathologically from three patients who had undergone lensectomy, suggesting that \"spikes freshwater could be a surprising new etiologic agent of pathology ocular\". Thus, in this study was performed cytotoxicity assays with samples from two species of sponges collected in place. The results indicate that the extracts of sponges after filtration Millipore 0.45 &mu;m continued presenting cytotoxic activity, suggesting there is a SOLUBLE component, and not only spikes, capable of inducing cellular death in the population of cells used. The individuals affected were the majority of males aged between 05 and 14 years.