Biomedical subjects
Publications and source records attributed to L L Mitchell.
In a healthcare organization, an internal control system segregates duties by function within the organization's financial operations. But segregating duties by function can result in poor internal communication that, in turn, can undermine an organization's internal processes and procedures. Effective communication can serve as an essential link between internal controls and operational effectiveness.
The active site of human immunodeficiency virus reverse transcriptase (HIV1-RT) was probed using three group-specific reagents: phenylglyoxal (PG), N-ethylmaleimide (NEM), and pyridoxal 5'-phosphate (PLP). The inactivation of HIV1-RT by arginine-specific PG was found to be completely protected against by adding primer-template. The potential active site arginine was localized to position 277 in the primary structure, suggesting that the polymerase domain of the enzyme should be considered as extending at least this far from the N terminus. The sulfhydryl-modifying reagent NEM completely inhibits NY5-HIV1-RT, which contains a cysteine at position 162, and such inhibition is protected against by primer-template. However, it does not strongly inhibit LAV-HIV1-RT, in which C162 is replaced by S162, indicating that while C162 may be at or near the active site or interact allosterically with primer-template, it is not essential for activity. The lysine-specific reagent PLP was found to be a noncompetitive inhibitor with respect to both primer-template [poly(rA).oligo(dT)] and dTTP. The latter result differentiates HIV1-RT from other RTs, for which PLP has been shown to be a competitive inhibitor with respect to dTTP.
Prostaglandin synthesis shows dependence on lipid hydroperoxides and resultant oxygen derived radical formation. In view of the importance of dietary copper in cytosolic copper dependent superoxide dismutase (Cu/Zn SOD) activity and the role of SOD in oxygen radical formation, the influence of dietary copper on prostacylin (PGI2) synthesis and SOD activity in rat aorta was examined. Copper deficient (0.5 micrograms Cu/g diet) rats showed a significant 47% reduction in PGI2 synthesis rates by aortic ring incubations in comparison to copper adequate (6.0 micrograms Cu/g diet) animals. Aortic SOD activity was reduced by 46% in copper deficiency in comparison to copper adequate animals. Marginal dietary copper (1.6 micrograms Cu/g diet) significantly reduced aortic SOD activity by 32% but was without effect on aortic ring incubation PGI2 synthesis. These results indicate that dietary copper deficiency, and the resultant decrease in SOD activity, depresses aortic PGI2 synthesis.