Interference of barbiturates with pyrimidine incorporation. II. Structural specificity of the inhibition of orotate uptake in Bacillus cereus.
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Biomedical subjects
Publications and source records attributed to H G Mandel.
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Reich, Melvin (The George Washington University School of Medicine, Washington, D.C.), and H. George Mandel. Dissociation of cellular functions in Bacillus cereus by 5-fluorouracil. J. Bacteriol. 91:517-523. 1966.-5-Fluorouracil (FU) produced a marked inhibition of growth and deoxyribonucleic acid (DNA) synthesis in Bacillus cereus 569H. Protein and ribonucleic acid (RNA) synthesis were not specifically inhibited, and proceeded at the rate of turbidometric increase of the cells. Cell-wall synthesis, respiration, and penicillinase production continued in the presence of FU at essentially the control rate. The addition of equimolar concentrations of uracil and FU prevented growth inhibition but did not restore DNA synthesis. The addition of thymidine with FU did not relieve growth inhibition but did restore the DNA content to normal. Thymidine supplementation also increased the quantity of FU, but not uracil, incorporated into RNA and the acid-soluble fraction. The data indicate that inhibition of growth can be dissociated from inhibition of DNA synthesis and that more DNA is present in normal cells than is needed for growth and reproduction.
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The influence of carprofen and indomethacin on renal salt and water homeostasis was investigated. Carprofen is a new nonsteroidal antiinflammatory drug that is currently undergoing clinical trials in the United States. Both drugs were administered in usual clinical doses to steady state in six healthy individuals and in six individuals with rheumatoid arthritis. Blood pressure, weight, plasma renin activity, urine volume, creatinine clearance, fractional excretion of sodium and potassium, and free water reabsorption were determined. Both drugs were found to suppress plasma renin activity. Indomethacin suppressed plasma renin activity more than carprofen. Neither drug produced clinically significant changes in any of the other parameters. In healthy individuals and in patients with rheumatoid arthritis renal homeostatic mechanisms may compensate for the salt- and water-retaining effects of nonsteroidal antiinflammatory drugs.
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