Certain strains of mice, e.g. C57BL/6, are highly resistant to serious infections with the protozoan pathogen, Leishmania major, whereas other strains, e.g. BALB/c, are not. It has beenproposed that interferon gamma (IFN-y) is one of the most critical lymphokines produced in a protective response to these intracellular pathogens. IFN-y has been classified as a Thi lymphokine produced by the Thl subset of T lymphocytes which not only activates macrophages to kill the protozoa but also helps regulates the immune system overall to form a lasting immunity to the microorganism (4,19). Mice susceptible to L. major arethought to produce inadequate amounts of IFN-y and instead produce an excessive amount of a Th2 lymphokine, IL-4, produced by Th2 T cells. (6) We have previously found that prophylactic treatment with cyclosporine A (CsA), a T cell specific immunosuppressant, reduces the susceptibility of the BALB/c to L. major by either preventing disease entirely or delaying itsdevelopment significantly (19). In this murine model, it may be that CsA causes a switch from the production of the less protective Th2 lymphokines to the more protective Thl lymphokines. In order to test this hypothesis we examined the IFN-y produced by lymph node and spleen cells over time after infection in three groups of mice: C57BL/6, BALB/c and cyclosporine- protected BALB/c. Interestingly, cells taken from all three groups of mice were able to secrete IFN-y in vitro in response to co-culture with Leishmania, antigens. The pattern of secretion over time, however, varied and may indicate a significant difference in the animals' response to the pathogen. In addition to this work, we also examined the ability of another immunosuppressant, FK506, which is very similar in action to but much less toxic than CsA, to induce enhanced resistence to L. major. FK506 also appears to be effective in reversing the susceptibility of the BALB/c mice towards this pathogen with much less apparent toxicity. / Department of Biology

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Graduation date: 1994

Thesis (Ph.D.) -- University of Adelaide, Dept. of Clinical and Experimental Pharmacology, 2001. / Bibliography: leaves 234-257.

Thesis (M.A.)--Ball State University, 2009. / Title from PDF t.p. (viewed on Mar. 25, 2010). Research paper (M.A.), 3 hrs. Includes bibliographical references (p. [49]-53).

Bibliography: leaves 234-257. Three separate clinical studies in organ transplant recipients are presented. The aims are to examine fundamental questions regarding the clinically and economically important pharmokinetic interaction between diltiazem and cyclosporin, an interaction widely utilised in organ transplantation. The data contained should assist the development of soundly based policies that will ensure a benefit exists before a sparing agent is coprescribed, and that the lowest effective dose of sparing agent is used.

Bibliography: leaves 234-257. / xi, 277 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Three separate clinical studies in organ transplant recipients are presented. The aims are to examine fundamental questions regarding the clinically and economically important pharmokinetic interaction between diltiazem and cyclosporin, an interaction widely utilised in organ transplantation. The data contained should assist the development of soundly based policies that will ensure a benefit exists before a sparing agent is coprescribed, and that the lowest effective dose of sparing agent is used. / Thesis (Ph.D.)--University of Adelaide, Dept. of Clinical and Experimental Pharmacology, 2001

Thesis (Ph. D.)--University of Texas at Austin, 2006. / Vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Texas at Austin, 2006. / Vita. Includes bibliographical references.