by Kwan Yiu Wing. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves 167-187). / Abstracts in English and Chinese. / ACKNOWLEDGMENTS --- p.IV / ABSTRACT --- p.1 / Chapter CHAPTER 1. --- INTRODUCTION --- p.5 / Chapter I. --- Epidemiology of Prostate Cancer --- p.5 / Chapter II. --- The Normal Prostate - Prostatic Anatomy --- p.9 / Chapter III. --- Pathology of Prostatic Cancers --- p.12 / Chapter CHAPTER 2. --- PROSTATIC INTRAEPITHELIAL NEOPLASIA --- p.16 / Chapter I. --- Introduction --- p.16 / Chapter II. --- "Definition, Characteristics and Grading" --- p.16 / Chapter III. --- Incidence and Prevalence of PIN --- p.26 / Chapter IV. --- Evidence Linking PIN with Prostatic Carcinoma --- p.27 / Chapter V. --- Conclusion --- p.37 / Chapter CHAPTER 3. --- HISTOLOGIC BIOMARKERS --- p.39 / Chapter I. --- p53 Protein --- p.39 / Chapter II. --- Proliferating Cell Nuclear Antigen (PCNA) --- p.44 / Chapter III. --- Ki-67 Antigen --- p.48 / Chapter IV. --- Epidermal Growth Factor Receptor --- p.49 / Chapter V. --- E-Cadherin --- p.51 / Chapter VI. --- CD44 --- p.54 / Chapter VII. --- nm23 --- p.58 / Chapter CHAPTER 4. --- OBJECTIVES OF STUDY --- p.62 / Chapter CHAPTER 5. --- MATERIALS AND METHODS --- p.63 / Chapter I. --- Materials --- p.63 / Chapter II. --- Methods --- p.71 / Chapter III. --- Interpretation of Immunostaining Results --- p.78 / Chapter IV. --- Statistical Analysis --- p.82 / Chapter CHAPTER 6. --- RESULTS --- p.83 / Chapter I. --- Immunohistochemical Results for p53 Protein --- p.83 / Chapter II. --- Results of Immunostaining of PCNA --- p.90 / Chapter III. --- Immunostaining and Quantitation of Ki-67 Expression --- p.97 / Chapter IV. --- Immunohistochemical Expression of EGFr --- p.105 / Chapter V. --- E-Cadherin --- p.110 / Chapter VI. --- CD44 --- p.115 / Chapter VII. --- Expression of nm23 in Prostatic Lesions --- p.122 / Chapter VIII. --- Correlation and Association of Expressions of All Biomarkers in Prostatic Lesions --- p.128 / Chapter CHAPTER 7. --- DISCUSSION --- p.132 / Chapter I. --- p53 Protein --- p.135 / Chapter II. --- PCNA --- p.137 / Chapter III. --- Ki-67 --- p.140 / Chapter IV. --- EGFr --- p.143 / Chapter V. --- E-Cadherin --- p.146 / Chapter VI. --- CD44 --- p.148 / Chapter VII. --- nm23 --- p.151 / Chapter VIII. --- Association between Biomarkers and Prostate lesions --- p.154 / Chapter CHAPTER 8. --- SUMMARY AND CONCLUSION --- p.157 / APPENDICES --- p.164 / Chapter I. --- Table of incidence and mortality rates of prostate cancer in the United States from 1973 to 1995 by race --- p.164 / Chapter II. --- Table of leading cancer deaths in Hong Kong from 1971 to 1996 --- p.165 / Chapter III. --- Table of incidence and mortality rate caused by prostate cancer in Hong Kong --- p.166 / Chapter IV. --- Reagents --- p.167 / REFERENCES --- p.169

The intestinal tissue is charged with a delicate immunological task. The intestinal immune system needs to be tolerant towards nutrients and microbiota present in the intestinal lumen, while simultaneously detecting and responding to dangers such as pathogens. A single-cell layer of intestinal epithelial cells (IECs) acts as a first line of defence. There is a T cell population located between the IECs that have been named intraepithelial lymphocytes (IELs). As the main lymphoid population within the intestinal barrier, IELs are thought to have an important role in intestinal homeostasis maintenance, as well as a role in intestinal inflammatory and autoimmune diseases such as inflammatory bowel disease and celiac disease. Despite extensive research on IEL biology, there are still questions remaining in terms of the development, maintenance and activation of IELs. Furthermore, IELs survive poorly in vitro, which hinders mechanistic insights. In this thesis, a co-culture system between IELs and intestinal organoids, "mini-guts", provides an in vitro model for IELs. With this IEL-organoid co-culture system, IELs associated with the organoids survive for at least 4 days. Additional findings suggest that IELs are kept in a poised state of activation due to differences in their mitochondria compared to other T cells found in spleen, lung and skin. Upon activation or intestinal inflammation, the mitochondrial mass in IELs increases. This increase correlates with effector functions such as cytokine production and proliferation. In addition, the composition of the mitochondria-specific lipid, cardiolipins, alters drastically in IELs after activation. These data support a model of mitochondria-dependent activation of IELs. The mitochondria-dependent activation in IELs appears to have at least two pathways: one T cell receptor-dependent and one microbiota-dependent. The latter pathway suggests a model in which IELs can become activated regardless of the cause of intestinal epithelial barrier damage.

Thesis (Ph. D.)--University of Washington, 1997. / Vita. Includes bibliographical references (leaves [114]-135).

Thesis (Ph.D.)--University of Tennessee Health Science Center, 2009. / Title from title page screen (viewed on August 27, 2009). Research advisor: Donna Hathaway, PhD. Document formatted into pages (ix, 43 p. : ill.). Vita. Abstract. Includes bibliographical references (p. 34-37).

Orientador: Paulo Traiman / Resumo: Objetivando estudar a prevalência de neoplasia intra-epitelial cervical (NIC) em mulheres soro-positivas para o vírus da imunodeficiência humana (HIV) ao compará-las com um grupo controle de mulheres soro-negativas, foi realizado um trabalho retrospectivo em que foram avaliadas 86 mulheres HIV positivas e 86 mulheres HIV negativas, que freqüentaram um serviço público de acompanhamento em DST/AIDS na cidade de Campo Grande, Mato Grosso do Sul, Brasil. Foram realizadas avaliações citológicas pelo Papanocolaou, colposcopias e biópsias quando indicadas. Encontrou-se uma prevalência maior de NIC no grupo de mulheres HIV positivas em comparação ao grupo de mulheres HIV negativas, e esta diferença foi estatisticamente significativa. Conclui o autor que, sendo o câncer do colo uterino uma patologia previnível e com o atual aumento da expectativa de vida das pacientes HIV positivas, este grupo de mulheres merece atenção ginecológica diferenciada com consultas mais frequentes e livre acesso à colposcopia. / Abstract: Objetiving to study the prevalence of cervical intraepithelial neoplasia (CIN) in human immunodeficiency virus (HIV) - infected women and to compar with a group control of seronegative women, it was realized a retrospective study being assessed 86 HIV - infected and 86 HIV - unifected women, who were attended in a public service of accompaniment in TSD/AIDS in Campo Grande City, Mato Grosso do Sul, Brazil. Were realized evolution cytologic for the Papanicolaou test, colposcopy and biopsies, when indicated. It was found a prevalence of CIN significantly greater in HIV - seropositive women than in seronegative women. In conclusion, being the cervical cancer a pathology that can be prevented and with the current increase of the life's expectative of the HIV - seropositive women, this group of women needs a better gynecologic atenttion with visits and Papanicolaou smears more often and free access to colposcopy. / Mestre

Impact of the chromatin remodeller SMARCAD1 on murine intestinal intraepithelial lymphocyte and white adipose tissue biology. Chromatin remodelling factors use the energy of ATP hydrolysis to drive the movement of and/or affect molecular changes to the nucleosome. One such factor, SMARCAD1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1), has been previously shown to restore heterochromatin at the replication fork in vitro. This project aimed to assess the impact of SMARCAD1 on mammalian biology, utilising an animal model in which the catalytic ATPase domain of murine SMARCAD1 had been deleted using Cre/lox technology. Preliminary results had implicated SMARCAD1 in adaptive-immunity and white adipose tissue biology, and SMARCAD1 expression in these tissues/cells was confirmed by tissue-panel western blot. This project therefore aimed to build on these results to understand better the impact of SMARCAD1 on adaptive immune development and white adipose tissue biology. In addition, fewer than expected viable Smarcad1-/- homozygous offspring were produced during Smarcad1+/- x +/- matings, which both confirmed the observation from a previous knockout model of Smarcad1, and limited the number of knockout animals available for this study. Investigation of systemic B- and T-cells in the bone marrow, thymus and spleen had previously suggested there was no significant defect in adaptive immune development in Smarcad1-/- mice, however a tissue-specific and age-related loss of intra-epithelial (IEL) T-lymphocytes was found in the small intestine by flow cytometry. Analysis by qPCR of duodenal RNA suggested that differentiation rather than inflammation may underpin any loss-of-IEL phenotype, although further examination of cell-proliferation and crypt/villus anatomy by EdU incorporation and immunofluorescence revealed no overt cell-anatomical or proliferative difference in the knockout mice. The requirement for large numbers of aged mice made further investigation of the intestinal IEL phenotype logistically prohibitive. The reduction of epididymal white adipose tissue (eWAT) size had also been observed in male Smarcad1-/- mice, and serum from these mice showed elevated triglyceride (TG) and free fatty acids (FFA) levels. Transcriptomic analysis by RNA-seq of whole-WAT revealed an elevation in macrophage-related markers in knockout mice, which was confirmed by flow cytometry. As a number of reports have implicated SMARCAD1 in stem cell biology, putative adipose stem cells were isolated from +/+ and -/- mice by FACS and used for adipogenic differentiation assays ex-vivo In parallel, mouse embryonic fibroblasts from +/- and -/- mice were also assayed for adipogenic differentiation. While no significant differences in adipogenesis were observed, Smarcad1-/- mice challenged with a (60%) high fat diet did show increased weight gain over +/+ mice, and measurements of adipocyte size and cell cycle/cell proliferation analysis suggested hyperplasia rather than defects in adipogenesis may drive any WAT-related pathology in these mice.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.

INTRODUCTION: Approximately 6 million couples in the United States experience infertility. Because few risk factors for infertility are known, identification of modifiable determinants is an important public health goal. Cervical intraepithelial neoplasia, CIN, occurs when the surface cells of the cervical tissue begin to change, and is caused by infection with a high-risk type of human Papillomavirus (HPV). CIN may affect the cervix’s immunological function, resulting in changes in mucus production, reduced protection against infections, and alterations in sperm transport through the cervical canal. CIN can also progress to invasive cervical cancer. There are four main CIN treatment procedures that aim to remove pre-cancerous cells from the cervix; loop excisions, commonly known as electrosurgical excision procedure (LEEP) or large loop excision of the transformative zone (LLETZ); cryosurgery; conization; and laser ablation. Because the goal of these procedures is to remove abnormal cells, healthy cervical cells may inadvertently be removed as well, leading to further changes in cervical mucus production, sperm motility, and reduced protection against infection. Because of the changes to the cervical tissue and its function, CIN and its surgical treatments may affect fecundability. METHODS: We analyzed data from Pregnancy Study Online (PRESTO), a preconception cohort of 5,594 North American pregnancy planners enrolled and followed between 2013 and 2018. At baseline, participants reported whether they had abnormal Pap tests and their age at their first abnormal Pap test, as well as cervical procedures and their age at the procedure. We estimated fecundability ratios (FR) and 95% confidence intervals (CI) using proportional probabilities models adjusted for sociodemographics, smoking, number of sexual partners, history of sexually transmitted infections/ pelvic inflammatory disease, and HPV vaccination. RESULTS: A history of abnormal Pap test, which we used as a proxy for cervical dysplasia, was positively associated with current and past smoking, gravidity, parity, irregular menses, number of sexual partners, history of chlamydia, genital warts and herpes, as well as a history of pelvic inflammatory disease. Of the women with an abnormal Pap test, the average age at first abnormal Pap test was 23.0 (std=4.5) years and the average number of abnormal Pap tests was 2.1 (std=1.7). We found little association overall between a history of abnormal Pap test and fecundability (FR=1.03, 95% CI: 0.96, 1.11). The results did not differ when the data were examined by number of abnormal Pap tests, or type of procedure. There was also little association between time since the diagnosis or procedure and pregnancy attempt and fecundability. There was however a slight decrease in fecundability within the first 2 years of diagnosis/ procedure, with FRs that tended to increase with increasing time since diagnosis/procedure. DISCUSSION: We found little association overall between a history of abnormal Pap test or cervical dysplasia, including excisional surgeries, and fecundability. These results are consistent with most other studies demonstrating no clear adverse effects of CIN and treatments. Recency of diagnosis or procedure did not appreciably affect these findings. Although we found a very slight decrease in fecundability within the first two years since diagnosis or procedure, fecundability became similar to that of undiagnosed/untreated women after 2 years, and then increased slightly. CONCLUSION: We found little association between a history of abnormal Pap and CIN treatments and fecundability. A major limitation of our study is that the data were self-reported, which may have resulted in non-differential exposure misclassification.

No description available.

BACKGROUND: Cervical cancer has historically been a major cause of mortality for women worldwide. Over the last 50 years, thanks to advances in screening technologies and the implementation of standardized management algorithms, the incidence of cervical cancer in the United States has been declining. LITERATURE REVIEW: In the most recent set of algorithms, the 2012 Updated Consensus Guidelines for the Management of Abnormal Cervical Cancer Screening Tests and Cancer Precursors, the authors conclude that there is high-level evidence to support extended screening intervals for women who are at average-risk for cervical cancer and who have a history of negative screening tests. However, there is large population of women with a history of abnormal screening tests, and their risk of recurrent disease is not well understood. Additionally, the predictive value of the available screening tests for this cohort of women is unknown. The authors of the 2012 Guidelines warn that there is insufficient evidence for optimal management of these women, the current guidelines are based on expert opinion only, and studies providing high-level evidence are lacking. PROPOSED PROJECT: This thesis proposes a systematic literature review of the existing evidence regarding to what extent women who are treated for cervical abnormalities at baseline are at an increased risk for persistent or recurrent disease in the future. Journal articles will be gathered from three different databases and abstracts will be screened for duplicity and relevancy. After article selection, the quality of evidence presented in each paper will be evaluated using the GRADE system to facilitate a methodical and accurate comparison of the existing evidence. Finally, a scheme for data abstraction from the articles will be outlined. CONCLUSIONS: The results of this systematic literature review will serve multiple purposes, including identifying what research has been done since the latest revision of management guidelines, and aiding in the revision of the algorithms for the population of women who have had abnormal screening test results. It will also identify persistent gaps in the body of knowledge regarding this cohort of patients, and guide the development of additional research studies to fill those gaps. SIGNIFICANCE: Determining the risk of recurrent disease in women with abnormal cervical cancer screening tests will serve to more optimally manage this cohort of women. This will allow providers to effectively monitor patients for the recurrence of cervical disease, while also minimizing the risks associated with overscreening.