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The Global ETD Search service is a free service for researchers
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Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
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Showing 1 to 3 of 3 (0.082 seconds)Spelling suggestions: "subject:"thymocytes development""
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The Effects of Purine Nucleoside Phosphorylase (PNP) Deficiency on Thymocyte DevelopmentPapinazath, Taniya 27 July 2010 (has links)
PNP is a crucial enzyme in purine metabolism, and its inherited defects result in severe T-lineage immune deficiency in humans. I hypothesized that PNP deficiency disrupts the development of late CD4-CD8- double negative (DN) thymocytes and induces mitochondrial-mediated apoptosis of CD4+CD8+ double positive (DP) thymocytes. By using PNP-deficient (PNP-/-) mice as well as an OP9-DL1 co-culture system simulating PNP-deficient conditions, I demonstrated that PNP deficiency interferes with the maturation of DN thymocytes at the transition from DN3 to DN4 stage. Although PNP deficiency does not affect the generation or proliferation of DP thymocytes, PNP-/- DP thymocytes were observed to undergo apoptosis at a higher rate. My results suggest that apoptosis is induced through a mitochondrial mediated pathway. Additionally, re-introduction of PNP into PNP-/- thymocytes protected the cells from the toxic effects of deoxyguanosine by preventing the formation of deoxyguanosine triphosphate, indicating that the toxic metabolite in PNP deficiency is deoxyguanosine.
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| 2 |
The Effects of Purine Nucleoside Phosphorylase (PNP) Deficiency on Thymocyte DevelopmentPapinazath, Taniya 27 July 2010 (has links)
PNP is a crucial enzyme in purine metabolism, and its inherited defects result in severe T-lineage immune deficiency in humans. I hypothesized that PNP deficiency disrupts the development of late CD4-CD8- double negative (DN) thymocytes and induces mitochondrial-mediated apoptosis of CD4+CD8+ double positive (DP) thymocytes. By using PNP-deficient (PNP-/-) mice as well as an OP9-DL1 co-culture system simulating PNP-deficient conditions, I demonstrated that PNP deficiency interferes with the maturation of DN thymocytes at the transition from DN3 to DN4 stage. Although PNP deficiency does not affect the generation or proliferation of DP thymocytes, PNP-/- DP thymocytes were observed to undergo apoptosis at a higher rate. My results suggest that apoptosis is induced through a mitochondrial mediated pathway. Additionally, re-introduction of PNP into PNP-/- thymocytes protected the cells from the toxic effects of deoxyguanosine by preventing the formation of deoxyguanosine triphosphate, indicating that the toxic metabolite in PNP deficiency is deoxyguanosine.
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Regulation of Normal and Malignant T-cell Homeostasis by Protein Degradation AdaptorsUmphred-Wilson, Katharine 26 May 2023 (has links)
No description available.
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