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Biomedical subjects

R B Clark

Publications and source records attributed to R B Clark.

At least 217 records · Page 12Linked to original sources

Preoperative oral antacid therapy for patients requiring emergency surgery.

Preoperative oral antacid therapy has been used effectively to reduce the number of emergency obstetric patients "at risk" of developing acid-aspiration syndrome. Thirty-three nonobstetric adult patients requiring emergency surgery were selected to determine whether the protective effects of antacid therapy could also be derived in this high-risk group. Maalox-treated patients had a mean gastric pH of 6.46 +/- 0.5 and gastric volume 21.5 +/- 3.6 ml, with none at risk, whereas control patients had mean pH of 3.71 +/- 0.43, gastric volume 71.5 +/- 16.5 ml, and 42.1% at risk. This report suggests that preoperative antacid therapy should reduce the incidence of acid aspiration and subsequent morbidity and mortality in patients requiring emergency surgery.

Administration, Oral↗

Endogenous GTP and the regulation of epinephrine stimulation of adenylate cyclase.

Epinephrine increased adenylate cyclase activity 10 to 15 fold in lysates of the cultured human astrocytoma cell line 132-1N1. GTP had little effect on adenylate cyclase activity of lysed cell preparations either with or without added epinephrine. However, the epinephrine stimulation of adenylate cyclase was essentially lost (less than 90%) when a washed nuclei-free membrane preparation of the cyclase was assayed. A 10 to 15 fold epinephrine stimulation of the membrane adenylate cyclase could be demonstrated if cytosol of GTP were added to the assay with the hormone. The criteria of anion exchange, cation exchange, gel exclusion and paper chromatography indicated that the cytosolic agents which acted synergistically with hormones were GTP and GDP. The apparent Kact's for the synergistic action of GDP and GTP were essentially identical (1.0 muM) and of all the other nucleotides examined only GDP had a potency similar to GTP. However, the effect of GDP was apparently due to its rapid conversion to GTP even in the absence of a regenerating system. With epinephrine pretreatment of the intact 132-1N1 cells there was a specific loss of epinephrine stimulation of adenylate cyclase activity. The hormone pretreatment did not alter the capacity of the cytosol from these desensitized cells to potentiate epinephrine stimulation of the cyclase. Rather, the alteration was in the particulate fraction of the lysate. The desensitization of the membranous cyclase was stable and not reversed by GTP.

Adenylyl Cyclases↗

Disaster drills.

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Disaster Planning↗

Adenylylimidodiphosphate: effect of contaminants on adenylate cyclase activity.

Commercially available adenylylimidodiphosphate, APP(NH)P, appears to be contaminated with a variety of compounds. The effects of unpurified APP(NH)P on adenylate cyclase activity closely resembled the effects of guanylylimidodiphosphate (GPP(NH)P); that is, APP(NH)P alone caused a time-dependent, quasi-irreversible activation, and the stimulation of adenylate cyclase by APP(NH)P in combination with epinephrine was synergistic, eliminating the need for GTP. The GPP(NH)P-like activity of APP(NH)P could be separated from APP(NH)P by purification of the analogue on DEAE cellulose columns or by paper chromatography. The purified APP(NH)P does not appear to interest at the GTP site.

Adenosine Triphosphate↗

A conformational analysis for leucine-enkephalin using activity and binding data of synthetic analogues.

1. Leucine-enkephalin and some analogues were assayed for activity in vitro on the mouse vas deferens and for binding to opiate receptors from rat brain. 2. The experimental data were analysed in terms of the stringency for glycine, a D-amino acid or an L-amino acid at each position in the peptide. 3. The observed configurational specificity was compared with the stringency that would be predicted to occur if enkephalin adopted certain hydrogen-bonded conformations at the receptor. 4. A small subset of the conformations examined was found to be compatible with the experimental data.

Animals↗

Regulation of adenylate cyclase from cultured human cell lines by adenosine.

Broken cell particulate preparations of adenylate cyclase isolated from the human glioma cell line 132-1N1 were stimulated 2-to 3-fold by 30 muM adenosine. This concentration of adenosine produced a maximal stimulation of the cyclase while 3 to 5 muM adenosine produced half-maximal stimulation. Theophylline, at 40 muM, inhibited the adenosine stimulation of the adenylate cyclase by about 40% while 200 muM produced near complete inhibition. The inhibition by theophylline could be overcome by increasing adenosine to a concentration 10-fold that of theophylline, implying that the inhibition was competitive. Basal activity was not inhibited by even 1.0 mM theophylline, nor was the epinephrine stimulated activity. In contrast, 1.0 muM propranolol essentially completely inhibited the 8-fold stimulation of 1.0 muM epinephrine but had no effect on either basal or adenosine-stimulated activity. Adenosine and 2-chloroadenosine were equipotent in stimulating adenylate cyclase from the 132-1N1 line, whereas neither adenine nor guanosine had any detectable effect. GTP, 10 muM, produced a small variable stimulation of the adenylate cyclase while the GTP analogue, 5'-guanylylimidodiphosphate (Gpp(NH)p), produced a marked stimulation fo the cyclase. Preincubation of the adenylate cyclase preparation with the analogue greatly increased its potency and maximal effect. In contrast, both basal and adenosine-stimulated activity decreased markedly with preincubation. The effects of adenosine or epinephrine in combination with Gpp(NH)p were at least additive and often synergistic in comparison to the effects of the compounds alone. The effects of adenosine on intact and broken cell preparations of the human fibroblast lines WI-38 and VA13-2RA were also examined. In the intact VA13-2RA, adenosine produced rapid and large increases in intracellular and extracellular cyclic adenosine 3':5'-monophosphate (cAMP). In the parental fibroblast line, the WI-38, adenosine slightly elevated basal levels of cAMP, but only produced marked elevations in the presence of non-methylxanthine phosphodiesterase inhibitors. The effect of adenosine on the broken cell particulate preparations of adenylate cyclase from the fibroblasts was similar to its action on the cyclase from the 132-1N1; 30 muM adenosine produced a maximal stimulation of the adenylate cyclase, and the stimulation was inhibited by theophylline.

Adenosine↗