No description available.

No description available.

This thesis demonstrates a pulse-chase assay that describes the turnover of the .r J normal human oesophageal epithelium and Barretr~- metaplasia. to be approximately 11 days. This assay also identified the existence of label-retaining cells after 67 days within the basal layer of the human oesophagus and showed that these cells were epithelial in origin, capable of division yet are not frequently dividing. Furthermore, label-retaining cells were identified within the base of Barrett's glands and were also epithelial and primarily undifferentiated. This thesis suggests that these cells may represent a population of stem cells within the human oesophagus. Using mtDNA mutations as markers of clonal expansion, this thesis demonstrates the presence of a stem cell niche within the normal human oesophagus. Furthermore, clonal patches covering large areas of squamous epithelium were observed. In Barrett's oesophagus, partially-mutated glands were observed indicating that glands are maintained by multiple stem cells. Wholly-mutated Barrett's glands contain all the expected differentiated cell lineages; demonstrating multilineage differentiation from single stem cells. Patches of clonally-related Barrett's glands were also observed; indicating that glands can divide by fission. In one patient the squamous epithelium and the underlying glandular tissue were shown to be derived from a common progenitor cell. TNFa was shown to induce migration of Barrett's cells in vitro suggesting that the inflammatory environment contributes to the expansion of Barrett's lesion. Furthermore, data presented here shows that NSAIDs can act as TNFa inhibitors in the human oesophagus, by decreasing epithelial cell membrane TNFa levels in vivo. This suggests that anti-TNFa therapy may prevent further growth of Barrett's lesions. III

No description available.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 177-188).

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 159-174).

<p>Cancer is now the leading cause of death in developed countries. Despite advances in strategies aimed at the prevention and treatment of the disease, early detection of precancerous growths remains the most effective method of reducing associated morbidity and mortality. Pathological examination of physical tissues that are collected via systematic biopsy is the current "gold standard" in this pursuit. Despite widespread acceptance of this methodology and high confidence in its performance, it is not without limitations. Recently, much attention has been given to the development of optical biopsy techniques that can be used clinically and are able to overcome these limitations. This dissertation describes one such optical biopsy technique, angle-resolved low coherence interferometry (a/LCI), its adaptation to a clinical technology, and its evaluation in clinical studies.</p><p> The dissertation presents the theory that underlies the operation of the a/LCI technique, the design and validation of the clinical instrument, and its evaluation by means of two clinical trials. First, an account of the manner in which the depth-resolved angular scattering profiles that are collected by a/LCI can be used to determine nuclear characteristics of the investigated tissues is given. The design of the clinical system that is able to collect these scattering profiles through an optical fiber probe that can be passed through the accessory channel of an endoscope for <italic>in vivo</italic> use is presented. To demonstrate the ability of this system to accurately determine the size of cell nuclei, a set of validation experiments are described.</p><p> In order to evaluate the clinical utility of this a/LCI system, two clinical trials intended to assess the ability of a/LCI to detect the presence of early, pre-cancerous dysplasias in human tissues are presented. The first of these, an <italic>in vivo</italic> study of Barrett's esophagus (BE) patients undergoing routine surveillance for the early signs of esophageal adenocarcinoma, is described. This study represents the first use of the a/LCI technique in vivo, and confirms its ability to provide clinically useful information regarding the disease state of the tissue that it examines, with performance that compares favorably to other optical biopsy techniques. Next, an <italics>ex vivo</italics> study of resected intestinal tissue is presented. The results of this study demonstrate the ability of a/LCI to provide information that can be used to detect dysplasia in the lower gastrointestinal tract with high accuracy. This study will enable future development of the technology to allow conduction of <italic>in vivo</italic> trials of intestinal tissue. The results of these two clinical studies demonstrate the clinical utility a/LCI, illustrating its potential as an optical biopsy technique that has great potential to provide diagnostically relevant information during surveillance procedures. This is particularly relevant in the case of BE, where its successful use has been demonstrated <italic>in vivo</italic>.</p> / Dissertation

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Dissertation (PhD)--University of Stellenbosch, 2006. / Bibliography. Also available via the Internet.

No description available.