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Stimulation Through Tlr4 Increases Fviii Inhibitor Formation In A Mouse Model Of Hemophilia A, Claire K. Holley
Stimulation Through Tlr4 Increases Fviii Inhibitor Formation In A Mouse Model Of Hemophilia A, Claire K. Holley
Dissertations & Theses (Open Access)
Hemophilia A is a clotting disorder caused by functional factor VIII (FVIII) deficiency. About 25% of patients treated with therapeutic recombinant FVIII develop antibodies (inhibitors) that render subsequent FVIII treatments ineffective. The immune mechanisms of inhibitor formation are not entirely understood, but circumstantial evidence indicates a role for increased inflammatory response, possibly via stimulation of Toll-like receptors (TLRs), at the time of FVIII immunization. I hypothesized that stimulation through TLR4 in conjunction with FVIII treatments would increase the formation of FVIII inhibitors. To test this hypothesis, FVIII K.O. mice were injected with recombinant human FVIII with or without concomitant doses …
Linking Obesity To Colorectal Cancer: Recent Insights Into Plausible Biological Mechanisms, Catherine Guffey
Linking Obesity To Colorectal Cancer: Recent Insights Into Plausible Biological Mechanisms, Catherine Guffey
Theses and Dissertations
Obesity has emerged as a leading environmental risk factor for the development of CRC. However, the mechanisms underlying this relationship have not yet been fully explained. Recent literature has focused on 1) inflammatory processes, 2) adipokines, and 3) estrogen. Obesity-enhanced inflammation is largely orchestrated by increases in adipose tissue macrophages leading to the secretion of TNF-alpha, MCP-1, and IL-6, all of which are linked to CRC. Adiponectin is decreased with obesity and has been reported to be negatively associated with CRC, while leptin, which is increased, is positively associated with the disease. Estrogen has been shown to influence CRC, although …