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Compounds with high affinity for LA, including polymyxin B (PMB) and derivatives, are capable of detoxifying LA nd protection a host against sepsis. By binding LA, these compounds also sensitize Gram-negative bacteria to hydrophobic antibiotics. However, therapeutic use of PMB is limited due to its toxicity. The aim of this research is to develop small molecules capable of strong and selective associating with LA for use in treatment of sepsis and as means of fighting bacterial infection. Taking the interactions of PMB with LA as a model, this research focuses on the preparation of simple compounds, based on cholic acid scaffolding, capable of mimicking the LA-binding behavior of PMB but lacking the toxicity of the antibiotic.

RNase H or RNase P can mediate inhibition of gene expression by Studies 25 degradation of mRNA in the presence of appropriate antisense molecules. The general strategy of this specific aim will consist of the utilization of two conceptually different approaches to identify regions in the mRNA available for interaction with oligonucleotides. With this information, oligodeoxynucleotides and analogues will be designed to inhibit the expression of aac(6')-Ib by inducing RNase H degradation of the mRNA.

Leukocytes in amniotic fluid and tracheal aspirates will be assessed by flow cytometry Postpartum, the mother will be treated with appropriate antibiotics to eradicate the GBS from the genital tract and returned to the colony. These studies will clarify the pathophysiology of infection-associated preterm labor and will suggest effective interventional strategies. Generate_Screen • Project Title: FORESPORE ENGULFMENT DURING B. ; Biology; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2003; Project Start 01-JAN-1998; Project End 31-DEC-2006 Summary: (provided by applicant): Bacteria from the genera Bacillus and Clostridium produce unusually durable and long-lived spores that are the infectious agent of Anthrax and Botulism, and which are assembled in the cytoplasm of another cell.

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