Thesis (Ph. D.)--University of Texas at Austin, 2002. / Vita. Includes bibliographical references. Available also from UMI Company.

Cytotoxic T lymphocytes play an important role in mediating host immune reactions to viruses and other pathogens. Selective mechanisms operate during V(D)J recombination to enhance the diversity of the T cell repertoire that is generated, particularly in the CDR3 regions of the TCR, which mediate peptide recognition. The influence of V gene 3' sequences on the composition of the CDR3 loop in TCR β chains is analysed; in particular, A/T-rich coding termini are shown to be more susceptible to exonuclease "nibbling" during recombination. The recent development of peptide-MHC tetrameric complexes has enabled us to detect T lymphocytes according to their antigen specificity. Their use in detection and characterisation of EBV-specific CD8⁺ T cells during the primary acute phase of infection is described here. In particular, CTL responses to EBV lytic cycle antigens have only recently been reported and this study reveals unexpectedly high frequencies of activated, circulating CD8⁺ T lymphocytes which are directed towards lytic cycle epitopes, compared to well-characterised latent cycle antigens. In a second cohort of healthy long term asymptomatic donors, the frequency of CD8⁺ T cells recognising EBV lytic and latent cycle antigens was analysed by tetramer staining, ELISpot assays and limiting dilution assays; the tetramers detected antigen-specific CD8⁺ T lymphocytes with greater efficiency than other methods. Lytic cycle antigen-specific T lymphocytes were clearly detectable in all the asymptomatic donors, at higher frequencies than those specific for latent antigens. The final section of this thesis investigates the existence of enriched populations of EBV-specific T lymphocytes found within synovial joint fluid of rheumatoid arthritis patients. Although these cells do not appear to be directly involved in the initiation of disease, their ability to secrete proinflammatory cytokines within joints probably contributes to the maintenance of chronic inflammation in these patients.

Thesis (Ph. D.)--Virginia Polytechnic Institute and State University, 1991. / Vita. Abstract. Includes bibliographical references (leaves 358-379). Also available via the Internet.

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Thesis (Ph. D.)--University of Texas at Austin, 2004. / Supervisors: Serrine S. Lau and Shawn B. Bratton. Vita. Includes bibliographical references.

A dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfillment of the requirements of the degree of Masters of Science. February 2017. / Cancer has become a problematic fatal disease in developing and industrialised countries with pancreatic cancer as the seventh leading cause of cancer-related deaths, with an average survival rate of less than 5%. Environmental risk factors associated with pancreatic cancer include smoking, obesity, diet, alcohol etc. Furthermore, pancreatic cancer is commonly diagnosed at a late stage where its response to current anti-cancer agents is poor. Consequently, with South Africa being a 3rd world country and the cost of chemotherapy being so high, this has led to us trying to identify new, cheaper therapeutics for cancer cells. A majority (80%) of the South African population relies on traditional medicines, hence in this study we aimed to assess Lobostemon fruticosus for anti-proliferative effects on pancreatic cancer cell line (AsPC-1). This was achieved by the use of methanol and butanol extracts of L. fruticosus to screen for induction of apoptosis and inhibition of cell proliferation. The plant was collected, dried, crushed and dissolved in butanol and methanol to obtain experimental extracts. Cytotoxicity of the plant on Aspc-1 was determined using MTT Assay, xCELLigence and cell cycle analysis. MRC-5 cell line was used as a positive control cell line. L. fruticosus extracts induced cell death at IC50 of 60µg/ml (methanol extract) and 50µg/ml (butanol extract) at 48hour treatments on AsPC-1 cell line. Western Blots showed that the methanol and butanol extracts of L. fruticosus led to slight upregulation of the apoptotic gene p53 in AsPC-1 cell line, which was further confirmed by FACS apoptosis detection. Cell cycle analysis further showed the plant extracts do promote cell cycle arrest. LC/MS of the extracts gave spectra of active compounds presumed to play a role in induction of apoptosis on the pancreatic cancer cell line. The data obtained implies that the methanol and butanol extracts of L. fruticosus does have, to a certain extent, growth inhibiting and apoptosis inducing potential on the pancreatic cancer cell line. KEYWORDS: Lobostemon fruticosus, Pancreatic Cancer, methanol extract, butanol extract, AsPC-1 / LG2017

Tumor necrosis factor's (TNF) cytotoxic mechanism of action was examined using cultured cancer cell lines. TNF demonstrated cytolytic and cytostatic effects on L929 fibrosarcoma and MCF-7 adenocarcinoma cells. TNF failed to show any specific effects on RNA, DNA or protein synthesis or ATP content in tumor cells in vitro. It did not cause DNA single strand breaks. Decreased cellular levels of reduced thiols did not predict sensitivity to the cytotoxic effects of TNF. Depletion of cellular glutathione failed to increase the sensitivity of TNF-sensitive or resistant cells. However, various non-specific and specific lysosomotropic agents lead to an inhibition of TNF's cytotoxic action. Differences in enzyme activity, primarily lysosomal, were noted between TNF-sensitive and resistant cells. These changes involved a general halving of lysosomal proteins and enzymes in the TNF-resistant cells. The antitumor activity of TNF does not involve specific inhibition of macromolecular synthesis but may involve alterations in lysosomes.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Thesis (Ph. D.)--University of Hawaii at Manoa, 1994. / Includes bibliographical references (leaves 111-122). / Microfiche. / x, 122 leaves, bound ill. 29 cm

Thesis (M.Phil.)--Hong Kong University of Science and Technology, 2008. / Includes bibliographical references (leaves 57-69). Also available in electronic version.