A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the Degree of Master of Dentistry In the branch of Oral Pathology November 2012 / The giant cell lesions of the jaws are characterised histologically by scattered multinucleated giant cells (MNGCs) within a connective tissue stroma containing round and spindled mononuclear cells. Additional features include haemorrhage and haemosiderin deposition. Central giant cell granuloma (CGCG), peripheral giant cell granuloma (PGCG), cherubism and aneurysmal bone cyst (ABC) are thus encompassed by this term. The osteoclastic nature of the MNGCs within these lesions is well established. Microphthalmia-associated transcription factor (Mitf) is essential in the terminal differentiation of osteoclasts, the abnormal expression of which, results in dysfunctional osteoclast activity. Transcription factor E3 (Tfe3) belongs to the same transcription factor subfamily and is capable of forming co-immunoprecipitates with Mitf to function in a synergistic manner. It is abundantly expressed in physiological osteoclasts. Both factors are crucial for gene regulation in osteoclastic bone resorption. This study aimed to assess the expression of Mitf and Tfe3 within the stromal and MNGCs of the aforementioned giant cell lesions in order to enhance our understanding of the biological nature of these cells. The results showed positive nuclear staining within both the stromal and MNGCs in all four lesions with preferential expression noted in the MNGCs. This finding supports the concept of precursor stromal cell fusion. In addition, Mitf was consistently expressed at higher levels than Tfe3, in keeping with its reported principal role in the terminal differentiation process. The only exception to this was observed in ABC where Mitf and Tfe3 expression levels proved to be similar. It is thus apparent that the co-expression of Mitf and Tfe3 serves to confirm the osteoclast-like phenotype of the MNGCs within the giant cell lesions of the jaws. The degree of expression does not, however, correlate with the clinical behaviour of these cells, an observation substantiated by the minimal osteolytic potential of PGCG.

MINP solar cells ; Hoi Chi-sam. / Includes bibliographical references / Thesis (M.Phil.)--Chinese University of Hong Kong, 1983

by Poon Ming-cheong. / Bibliography: leaves 97-102 / Thesis (M.Phil.)--Chinese University of Hong Kong, 1983

Natural Killer (NK) cell, a crucial player of the human innate immune defense system, detects and kills virus-infected cells and cancer cells. Although the relevant molecular machineries involved in NK cell activation and NK-target cell interactions are largely known, how their collected dynamics regulate fast yet highly selective target cell killing in the complex environment of tissues is poorly understood. In traditional bulk killing assays, heterogeneity and kinetic details of individual NK-target cell interactions are masked, seriously limiting analysis of the underlying dynamic mechanisms. Therefore, the aim of my PhD study is to develop quantitative microscopy assays to elucidate, at the single cell level, real-time killing dynamics of epithelial cancer cells by primary NK cells purified from human blood. Results from my study not only identified the rate-limiting kinetics in NK-cancer cell interaction and mechanistically relevant heterogeneity in the process, but also characterized key molecular events and regulatory components of the NK cell machinery that were associated with the observed cytotoxic dynamics and heterogeneity. NK cells are considered promising candidate for cancer treatment, especially for eliminating residual cancer cells after conventional therapy. The fundamental knowledge acquired from my PhD study, in particular regarding how killing by primary NK cell varies between different target cancer cell types, provides new mechanistic insight that may help to develop this treatment strategy. And the quantitative microscopy assays that I developed are readily extendable to analysis of other cell-cell interaction dynamics, e.g., involved in cytotoxic T cell function.

archives@tulane.edu / I would like to thank the Tulane Department of Biomedical Engineering and the Tulane Center for Stem Cell Research and Regenerative Medicine for the support and means to conduct such meaningful research. I am also thankful for the continued support and encouragement from Dr. Bruce Bunnell, whose enthusiasm and inexhaustible drive is a source of inspiration. To my fellow lab members, and particularly Ben O’Donnell, I attribute the technical skills I have learned and the joy of coming to work every day in such a welcoming environment. I am grateful for the additional help from our cohort of research assistants, including Tia Monjure, Brooke Santagato, Michael L’Ecuyer, and Mitchell Couldwell. Additionally, much of my work is in part attributed to the team of specialized core personnel, Alan Tucker in flow cytometry and Dina Gaupp in histology. I am grateful for the American Association of University Women which provided funding for my master’s coursework. In affiliation with the University and Pittsburgh and Stanford University, this project is the collaborative effort of many great minds. It was financially supported by the National Institute of Health under the project number 1UG3TR002136-01. / 1 / Clara Ives

No description available.

The present study is part of a project to develop a high productivity enzymatic process for (R)-phenylacetylcarbinol (PAC), a precursor for the pharmaceuticals ephedrine and pseudoephedrine, with recent interest for a low cost and more stable biocatalyst pyruvate decarboxylase (PDC) preparation. PDC initially added in the form of Candida utilis cells, viz. whole cell PDC, showed higher stability towards substrate benzaldehyde and temperature in comparison to the partially purified preparation in an aqueous/benzaldehyde emulsion system. Increasing the temperature from 4?? to 21??C for PAC production with whole cell PDC resulted in similar final PAC levels of 39 and 43 g/L (258 and 289 mM) respectively from initial 300 mM benzaldehyde and 364 mM pyruvate. However, the overall volumetric productivity was enhanced by 2.8-fold. Enantiomeric excess values of 98 and 94% for R-PAC were obtained at 4?? and 21??C respectively and benzylalcohol (a potential by-product from benzaldehyde) was not formed. The potential of whole cell PDC was also evident in an aqueous/octanolbenzaldehyde emulsion system at 21??C with a 3-fold higher specific production compared to partially purified PDC. At 2.5 U/mL, PAC levels of 104 g/L in the organic phase and 16 g/L in the aqueous phase (60 g/L total reaction volume, 15 h) and a 99.1% enantiomeric excess for R-PAC were obtained with whole cell PDC. The study of cell membrane components provided a better understanding for the enhanced performance of whole cell PDC in comparison to partially purified PDC. It was apparent that surfactants, both biologically-occurring (e.g. phosphatidylcholine) and synthetically manufactured (e.g. bis(2-ethyl-1-hexyl)sulfosuccinate (AOT)), enhanced PDC stability and/or PAC production in the aqueous/octanol-benzaldehyde biotransformation system with the partially purified enzyme. Addition of 50 mM AOT to the biotransformation with partially purified PDC enhanced the enzyme half-life by 13-fold (19 h) and increased specific PAC production by 2-fold (36 mg/U). Chemical modification studies targeting the amino and carboxyl groups were carried out to achieve increased stability of partially purified PDC. However these were not successful and future work could be directed at PDC protein engineering as well as optimization and scale up of the two-phase process using whole cell PDC.

114 leaves + / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D. 1972) from the Dept. of Pathology, University of Toronto & Dept. of Medicine, University of Adelaide

T cells are one of the key cells in the immune system. Although they are not the first line of defense against a pathogen, their functions can greatly enhance the phagocytosis and destruction of pathogens as well as the development of antibody responses. Furthermore, even when responding T cells have facilitated the clearance of the pathogen, they can avoid death to become long-lived cells that "remember" encountering the pathogen for years afterward. This long-term memory allows subsequent immune responses to improve with each exposure, ultimately preventing disease upon reinfection. The activation of these T cells depends on specific recognition of antigen along with a costimulatory signal. This activation process is well studied, but not completely understood. Additionally, the mechanism behind memory T cell development is still very much unknown. In the work presented in this thesis, delivery of costimulatory signals via CD4O and 0X40 were studied using an in vivo superantigen (SAg) model of T cell stimulation. In the context of this two-signal (SAg + costimulation) model, both CD4O and OX40 could deliver signals that enhanced SAg-reactive T cell clonal expansion, but they could only partially prevent T cell death. Coadministration of the inflammatory agent lipopolysaccharide (LPS), however, could keep increased responder T cell populations alive for at least two months. Interestingly, this three-signal (SAg + costimulation + LPS) induced survival was not dependent on proinflammatory cytokines or activation of the transcription factor NF-KB, but was sensitive to the immunosuppressant cyclosporin A (CsA). The mode of action of CsA may point to the mechanism driving long-term T cell survival. Additionally, examination of early time points after three-signal stimulation suggested more clues to the mechanism of survival induction. The cytokines IL-2 and TNF-�� seem to be involved early on, but for now, little is known about their complete role. Thus, the goal of this work was to investigate the costimulatory and adjuvant-mediated signals required for memory T cell development. Ultimately, an understanding of how memory T cells can be generated could be used to enhance vaccine efficacy or shut off autoimmune conditions. / Graduation date: 2002

No description available.