Thesis (EDD)--University of Montana, 2009. / Contents viewed on December 28, 2009. Title from author supplied metadata. Includes bibliographical references.

Thèse de doctorat : Biologie Cellulaire et Nutrition : Nancy 1 : 2009. / Titre provenant de l'écran-titre.

Thesis (M.F.A.)--Kent State University, 2008. / Title from PDF t.p. (viewed Jan. 21, 2010). Advisor: Isabel Farnsworth. Keywords: Cognitive mapping; self and place; sculpture and geography; sculpture; geography. Includes bibliographical references (p. 20-21).

Thesis (Ph. D.)--University of Oregon, 2002. / Typescript. Includes vita and abstract. Includes bibliographical references (leaves 296-324). Also available for download via the World Wide Web; free to University of Oregon users. Address: http://wwwlib.umi.com/cr/uoregon/fullcit?p3061965.

Thesis (Ph. D.)--York University, 2001. Graduate Programme in Psychology. / Typescript. Includes bibliographical references (leaves 220-254). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://wwwlib.umi.com/cr/yorku/fullcit?pNQ67924.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Nursing Studies / Master / Master of Nursing

Although B cells are well-known for their functions in antibody production and antigen presentation, certain B cell subsets have been recently identified as regulatory B cells to modulate immune responses through cytokine production. However, the microenvironmental factors involved in the induction of regulatory B cells remain largely uncharacterized. B cell-activating factor (BAFF), a member of TNF family cytokines produced by myeloid cells, is a key regulator for B cell maturation and function. However, it remains unknown whether BAFF plays a role in modulating the generation of regulatory B cells and how regulatory B cells suppress autoimmune pathogenesis. In this study, treatment with BAFF significantly increased IL-10-producing B cells in culture of mouse splenic B cells, an effect specifically abrogated by neutralization with TACI-Fc. BAFF-induced IL-10-producing B cells showed a distinct CD1dhiCD5+(B10) phenotype. Phenotypic analysis further indicated that these BAFF-induced B10 cells were marginal-zone (MZ)-like B cells. Interestingly, BAFF treatment in vivo also increased the number of IL-10-producingB cells in splenic MZ regions. Moreover, chromatin immunoprecipitation analysis revealed that BAFF activated the transcription factor AP-1 for binding to IL-10 promoter, demonstrating a novel function for BAFF in inducing IL-10 production. Furthermore, those BAFF-induced B10 cells exhibited significant suppressive effects on CD4+T cell proliferation and Th1 cytokine production in culture. To explore whether these BAFF-induced B10 cells possess a regulatory function in suppressing autoimmune progression in vivo, collagen-induced arthritis (CIA) mouse model was employed. In vitro-expanded B10 cells and other control B cells were intravenously transferred into DBA/1J mice on the day of 2ndcollagen II (CII)-immunization. After adoptive transfer of BAFF-induced B10 cells, CII-immunized mice exhibited a delayed onset of arthritis and substantially reduced severity of clinical symptoms. The pathogenesis of IL-17-producing CD4+T cells (Th17) in the development of arthritis has been well-recognized, which has led me to test the hypothesis whether B10 cells ameliorate the development of arthritis via modulating Th17 cells. During the progression of CIA, IL-10-producing B cells were decreasedwhereasTh17 cells were significantly increased at the acute phase of CIA. Upon transfer of BAFF-induced B10 cells, a substantially reduction ofTh17 cells in both lymphoid organs and inflamed joints were detected. To verify whether B10 cells inhibit Th17 cell generation in culture, CFSE-labeled na?ve CD4+T cells were cocultured with B10 cells in Th17 cell polarization medium. It was found that B10 cells suppressed Th17 cell differentiation via reducing STAT3 phosphorylation and RORt expression. Although adoptive transfer of Th17 cells triggered the development of CIA in IL-17-/-DBA mice, cotransfer of B10 cells with Th17 cells profoundly delayed the onset of delayed the onset of arthritisand remarkably reduced the infiltration of Th17 cells in synovial fluid. Taken together, I have identified a novel function of BAFF in the induction of IL-10-producing regulatory B cells. My findings that adoptive transfer of BAFF-expanded B10 cells can effectively suppress the development of experimental arthritisin mice via the inhibition of Th17 cell generation may contribute to the development of new therapeutic strategies in treating human rheumatoid arthritis. / published_or_final_version / Pathology / Doctoral / Doctor of Philosophy

Not available / text

Traditional Chinese Medicine (TCM) has been criticized for being unscientific because the theory on which it is based involves entities like qi and ’meridians’ that appear ambiguous and because the internal ‘organs’ like the kidney and the spleen are very different from those of modern anatomy and physiology. Even more so, TCM methods of therapy based on the yin-yang principle, the model of the five elements, and the classification of illnesses according to standard constellations of symptoms (TCM “syndromes”) are largely unproven by the protocols of modern evidence-based medicine. This dissertation attempts to reconstruct TCM theory by: (a) providing explanations of TCM entities as abstractions and constructs that relate to observable body functions and illness symptoms and (b) interpreting TCM theory as comprising heuristic models that were constructed from clinical experience to fit empirical observations of illnesses and their treatments with herbal medications and acupuncture. It suggests that scientists should be less concerned with the ontological status of TCM entities and the epistemic credentials of TCM models than with the ability of these concepts and models to guide physicians in therapy. More importantly, it makes the argument that these models are testable using the methods of evidence-based medicine. There are methodological difficulties associated with randomized controlled trials partly because TCM treatments tend to be individualized and syndromes are dynamic in nature; observational trials may be more appropriate in some situations. It is also possible that, for patients who are more culturally attuned to TCM, the placebo effect is strongly at play and may render the real effects of TCM treatments harder to tease out in clinical trials. The dissertation concludes that the main postulates of TCM should be put to rigorous test. The result may be a leaner but more robust theory, with parts that do not stand up to the test being rejected or modified, and a possible acceptance of its more modest therapeutic claims for a limited range of pathological conditions like pain and chronic illnesses.