Three rolls of the early Septuagint: Genesis and Deuteronomy by Ludwig Koenen

By Ludwig Koenen

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3. To characterize the specific effects of CD8+ T cell recognition in the absence of IFN-gamma on antigen-presenting epithelial cells and the impact on progression to chronic pulmonary inflammation. ; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 21-SEP-2001; Project End 31-AUG-2004 Summary: (adapted from the application) Current treatment options for chronic hepatitis C infection remain limited and unsatisfactory. Treatment with interferon-alpha and ribavirin leads to a sustained response in the minority of patients, and many patients may not be eligible for treatment due to side effects associated with these medications.

Together, we now propose to identify and characterize MTB genes that control the formation of pulmonary cavities. We will use: 1) two different DNA microarrays to determine, on a genome wide scale, the presence and expression profile of all MTB genes; 2) a new mouse model that manifests the type of caseating granuloma that gives rise to cavities; and 3) conventional genetic approaches for gene knock-outs and complementation. We will build a matrix database of well characterized clinical isolates that records clinical cavity formation, results of assays of toxic lipids and whole genome DNA microarray identification of gene deletion and expression.

The principal investigator recently demonstrated that intratracheal (IT) injection of manganese superoxide dismutase-plasmid/liposomes (MnSOD-PL) protects the murine lung from irradiation-induced organizing alveolitis/fibrosis induced by single dose or fractionated irradiation. The proposed research will use validated, genetically modified animal models along with quantitative molecular methods to elucidate the cellular mechanism of irradiation lung fibrosis and the level(s) at which epitope-hemagglutinin (HA)-tagged MnSOD transgene therapy protects.

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