The ability of low, clinically relevant levels of the chemotherapeutic drugs epirubicin and vinblastine to induce drug resistance was examined in the K562. U937, KG-la and HEL human leukaemia cell lines. Treatment with epirubicin and vinblastine induced the MDR phenotype and P-glycoprotein expression in K562 and U937 cells. However this treatment had no effect on drug resistance in the P-glycoprotein expressing KG-la and HEL cells. In the U937 cells, drug resistant cells were not only MDR but were also resistant to other drugs including cisplatinum and chlorambucil which are not normally associated with MDR. The drug resistant U937 sublines were also sensitised to doxorubicin, cisplatinum and chlorambucil by buthionine sulphoximine (BSO), suggesting that glutathione-related mechanisms also contributed to resistance in these sublines. The U937 sublines also had an increased DNA content and an increased ability to recover from DNA damage, as determined by cell cycle analysis, indicating that the broad cross-resistance exhibited by these cells was due to the co-existence of multiple resistance mechanisms. Drug treatment induced changes in expression of differentiation associated antigens in all four cell lines. Treatment with inducers of differentiation (TPA, sodium butyrate, granulocyte-macrophage colony-stimulating factor; GM-CSF). Treatment of K562 and K562/E15B cells with TPA induced megakaryocytic differentiation, with increases in drug resistance, and increased P-glycoprotein expression in the K562/E15B subline. TPA induced monocytic differentiation in the U937 cells but not the U937/EIS subline, with increased P-glycoprotein expression and function in the U937/E15 cells but not the U937 cells. Staurosporine, an inhibitor of PKC, inhibited differentiation in these cell lines, but did not inhibit increases in P-glycoprotein expression, suggesting drug resistance was not mediated by PKC. Sodium butyrate induced erythroid differentiation, and increased P-glycoprotein expression in the K562/E15B cells. However at a higher concentration (15 mM) this was not accompanied by increased drug resistance. Granulocyte monocyte colony stimulating factor (GM-CSF) did not induce differentiation in the K562 cells or K562/E15B subline, although the K562/E15B cells became more drug resistant after treatment with GM-CSF. Treatment with GM-CSF induced differentiation in the U937/E15 subline but did not change drug resistance in either the U937 cells or the U937/EI5 subline. Therefore the P-glycoprotein expressing K562/E15B and U937/E15 sublines were more responsive to inducers of differentiation than the parental cell lines. Induction of differentiation therefore induced increases in P-glycoprotein expression and drug resistance, suggesting that expression of P-glycoprotein or a multidrug resistance phenotype was associated with differentiation.

Tetracycline is a front line antibiotic for the treatment of chlamydial infections in both humans and animals, and the emergence of tetracycline resistant (tet[superscript R]) Chlamydia is of significant clinical importance. Recently, several tet[superscript R] chlamydial strains have been isolated from swine (Sus scrofa) raised in production facilities in Nebraska. Here, the intracellular development of two C. suis tet[superscript R] strains, R19 and R27, is characterized through the use of tissue culture and immunofluorescence. The strains grow in tetracycline up to 4 ��g/ml, while a tetracycline sensitive (tet[superscript S]) C. suis swine strain (S45) and a C. trachomatis strain of the human serovar L2 (LGV-434) grow in tetracycline up to 0.1 ��g/ml. Although inclusions form in the presence of tetracycline, many contain large aberrant RBs that do not differentiate into infectious EBs. The percentage of inclusions containing typical developmental forms decreases with increasing tetracycline concentrations, and at 3 ��g/ml of tetracycline, 100% of inclusions contain aberrant RBs. However, upon removal of the tetracycline, the aberrant RBs revert to typical RBs and a productive developmental cycle resumes. In addition, inclusions were found that contained both C. suis R19 and C. trachomatis L2 after sequential infection, demonstrating that two biologically distinct chlamydial strains could both develop within a single inclusion. / Graduation date: 2002

Thesis (Ph. D.)--Oregon State University, 2007. / Printout. Includes bibliographical references. Also available on the World Wide Web.

Thesis (Ph. D.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

Thesis (Ph. D.)--University of Missouri-Columbia, 2006. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file viewed on (March 5, 2007) Vita. Includes bibliographical references.

Thesis (Ph. D.)--Ohio State University, 2006. / Title from first page of PDF file. Includes bibliographical references (p. 122-140).

Thesis (M.S.)--Ohio State University, 2008. / Title from first page of PDF file. Includes bibliographical references (p. 65-71).

Thesis (Ph. D.)--Lehigh University, 2000. / Includes bibliographical references and vita.

Thesis (Ph. D.)--University of Texas at Austin, 2000. / Vita. Includes bibliographical references (leaves 107-111). Available also in a digital version from Dissertation Abstracts.

Thesis (Ph. D.)--Miami University, Dept. of Chemistry and Biochemistry, 2003. / Title from first page of PDF document. Document formatted into pages; contains xi, 150 p. : ill. Includes bibliographical references.