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E W Sutherland

Publications and source records attributed to E W Sutherland.

At least 19 recordsLinked to original sources
PubMed1988

Documenting the activity and effectiveness of a regional drug information center.

The methods of data collection, storage, and retrieval used by the Rocky Mountain Drug Consultation Center (RMDCC) are described. To substantiate that drug information services provided by RMDCC are clinically useful and have a beneficial effect on therapy, data on medication-related problems and case outcomes, as well as demographic data, are stored in an IBM PC-XT using a system that allows searching and linkage of any number of recorded categories. Data were compiled on 28,081 inquiries from health-care professionals and consumers during 1985 and 1986. Analysis revealed that (1) medication-related problems are common (involving 34% of consumer inquiries), especially among the elderly; (2) a positive effect on therapy was made in the majority (76%) of problem cases; and (3) consumers were given drug information by their physician or pharmacist in fewer than half of the cases in which medications were prescribed and dispensed. A computer-based system to assist in analyzing information can be an important asset in documenting the activity and effectiveness of a regional drug information center.

Colorado↗
PubMed1985

Exercise and beta-blocking agents.

Beta-adrenoceptor-blocking agents produce noticeable effects on exercise performance. In patients with coronary heart disease, exercise capacity may in some cases increase during beta-blockade. Training effects (increased functional capacity, increased maximal oxygen uptake) may be somewhat attenuated in relatively healthy individuals taking beta-blockers, although with vigorous exercise programs, physiologic adaptations to exercise probably do occur.

Adrenergic beta-Antagonists↗
PubMed1976

Adenosine 3':5'-monophosphate content and actions in the division cycle of synchronized HeLa cells.

The involvement of adenosine 3':5'-monophosphate (cAMP) in the regulation of the cell cycle was studied by determining intracellular fluctuations in cAMP levels in synchronized HeLa cells and by testing the effects of experimentally altered levels on cell cycle traverse. Cyclic AMP levels were lowest during mitosis and were highest during late G-1 or early S phase. These findings were supported by results obtained when cells were accumulated at these points with Colcemid or high levels of thymidine. Additional fluctuations in cAMP levels were observed during S phase. Two specific effects of cAMP on cell cycle traverse were found. Elevation of cAMP levels in S phase or G-2 caused arrest of cells in G-2 for as long as 10 h and lengthened M. However, once cells reached metaphase, elevation of cAMP accelerated the completion of mitosis. Stimulation of mitosis was also observed after addition of CaCl2. The specificity of the effects of cAMP was verified by demonstrating that: (a) intracellular cAMP was increased after exposure to methylisobutylxanthine (MIX) before any observed effects on cycle traverse; (b) submaximal concentrations of MIX potentiated the effects of isoproterenol; and (c) effects of MIX and isoproterenol were mimicked by 8-Br-cAMP. MIX at high concentrations inhibited G-1 traverse, but this effect did not appear to be mediated by cAMP. Isoproterenol slightly stimulated G-1 traverse and partially prevented the MIX-induced delay. Moreover, low concentrations of 8-Br-cAMP (0.10-100 muM) stimulated G-1 traverse, whereas high concentrations (1 mM) inhibited. Both of these effects were also observed with the control, Br-5'-AMP, at 10-fold lower concentrations.

Calcium↗
PubMed1975

Hydrolysis of guanosine and adenosine 3',5'-monophosphates by rat blood.

Cyclic nucleotide phosphodiesterase activity was measured in whole blood, plasma, and suspensions of platelets and erythrocytes from rats. In fresh whole blood, apparent phosphodiesterase activity was low, but it rose strikingly during the hour after blood withdrawal. The apparent phosphodiesterase activity in platelet-free plasma showed no such increase, but that in platelet-enriched plasma increased in parallel with that in whole blood. The apparent phosphodiesterase activity of blood or of platelet-enriched plasma also was increased markedly by sonication. The increase in rat blood phosphodiesterase activity with aging thus appeared to be due to damage of platelets. Most of the phosphodiesterase activity in rat erythrocytes and platelets was located in the soluble fraction of sonicated preparations, but the total enzyme activities from the two sources exhibited marked differences in substrate specificity. With erythrocyte preparations, the rate of hydrolysis of muM concentrations of cyclic AMP was approx. 50 times that of cyclic GMP, while with platelet preparations, cyclic GMP was hydrolyzed about 20 times faster than cyclic AMP at muM levels. The activity of phosphodiesterase in platelets was much greater than that in erythrocytes at all concentrations of both substrates.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1975

Cellular levels of feedback regulator of adenylate cyclase and the effect of epinephrine and insulin.

We have obtained direct evidence that shows the cellular formation and subsequent release of a potent inhibitor (feedback regulator) of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] by adipocytes, upon stimulation with epinephrine. The appearance of such a feedback regulator in adipocytes preceded its release into the medium. During a 30 min incubation, intracellular regulator levels rose rapidly and reached 39-61 units/g of adipocyte at 10 min. Release of inhibitor into the medium increased slowly and was 11-16 units/g of adipocyte at 10 min. Upon continued incubation, the cells at 30 min contained 30-41 units/g of ingibitor, slightly less than the content at 30 min; meanwhile, the medium content rose more than 3-fold. The inhibitor from both locations appeared to have the same characteristics, judging from the purification procedures and the biological activities on hormone-stimulated adenylate cyclase. Adenylate cyclase was inhibited by the feedback regulator in vitro when either epinephrine, corticotropin (ACTH), or glucagon was used as activator. The site of action of this inhibitor is therefore most likely beyond the specific hormone receptors. A new in vitro action of insulin has been found. Insulin, 50-500 microunits/ml, inhibited the formation and release of this factor from isolated rat or hamster adipocytes by 29-81% after these cells were stimulated by hormones that raise intracellular adenosine 3':5'-cyclic monophosphate. This factor enhaced the effect of insulin in lowering the adenosine 3':5'-cyclic monophosphate levels in fresh rat adipocytes. A reduced formation of such a factor may modify the metabolic events in adipocytes, and some as yet unexplained effects of insulin could therefore be linked to the metabolic effects of this factor.

Adenylyl Cyclases↗
PubMed1975

Action of feedback regulator on adenylate cyclase.

A factor [the feedback regulator (FR)] formed by adipocytes after the stimulation of a cAMP raising hormone has been found to be a potent inhibitor of membrane-bound adenylate cyclase [EC 4.6.1.1.; ATP pyrophosphate-lyase (cyclizing)]. In a standard assay system using rat adipocyte plasma membrane as the source of adenylate cyclase, the FR inhibited adenylate cyclase by lowering the Vmax without affecting the apparent Km for ATP (0.3-0.6 mM). The apparent Ka for epinephrine (5-6 muM) was also not affected by FR. The inhibitory action of FR was partially countered by Mg2+ ions. An increase in phosphorylation of plasma membrane was observed when FR was present in the incubation system. The concentration required for a 50% inhibition was four times higher when adenosine 5-(beta,gamma-imino) triphosphate [AMP-P(NH)P] replaced ATP as the substrate for adenylate cyclase, implying that adenylate cyclase was inactivated by phosphorylation caused by FR. Increase in FR inhibition obtained by adding low concentrations of adenosine 5-(alpha,beta-methylene) triphosphate or ATP to AMP-(NH)P as the substrate supports this view. The inhibitory action was reversible. These results are consistent with the previously reported phenomena that (1) the undue to the formation of FR, and (2) the recovery of responsiveness of the stimulated cells by washing the cells with regular buffer medium is a result of the removal of FR. The hormone-initiated biphasic curve of cAMP levels in adipocytes is believed to be due to the negative feedback action of FR on adenylate cyclase. The mechanism of action of FR on inhibition of adenylate cyclase appears to be related to the phosphorylation of certain membrane components.

Adenosine Triphosphate↗
PubMed1975

Concepts for the rational selection of assays to be used in monitoring therapeutic drugs.

As the domain of monitoring therapeutic drugs rapidly expands from experimental investigations to everyday patient care, all clinical laboratory scientists, but especially clinical chemists, must learn to deal with their involvement in this expansion. First, the theoretical concepts underlying clinical pharmacology must be appreciated so that the laboratory's participation in it can succeed. Individual differences cause unpredictable variations of response to the customarily standardized drug dosage. Properly used, assays of drugs in blood can eliminate such variabilities. Second, the practical selection of which drug assays a laboratory intends to provide must be based on a rational evaluation of assay usefulness, integrating both clinical and laboratory considerations. Such a decision model is suggested; it is generally applicable in allocating priorities among an ever-increasing number of proposed tests under the constraint of finite resources.

Chemistry, Clinical↗
PubMed1973

The importance of calcium ions for the regulation of guanosine 3':5'-cyclic monophosphage levels.

Guanosine 3':5'-cyclic monosphosphate (cyclic GMP) levels in the ductus deferens of the rat were increased 2- to 3-fold by acetylcholine (10-1000 muM) or by 125 mM KCl, while adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels were not changed. After incubation for 30 min in the absence of Ca(++), cyclic GMP control levels were decreased by 85% and were not affected by acetylcholine or KCl. The readdition of Ca(++) (1.8 mM) for 3 min to Ca(++)-deprived tissue partially restored basal cyclic GMP levels and the effects of acetylcholine and KCl. The addition of Sr(++) (3.6 mM) or of Ba(++) (1.8 or 10 mM) also caused an increase in basal cyclic GMP in Ca(++)-deprived tissue. Cyclic AMP levels were not significantly changed under any of these conditions. The addition of the phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine (0.1 mM), to ductus deferentes increased the amount of cyclic AMP about 50% and that of cyclic GMP about 2-fold. The later effect also depended on the presence of Ca(++). 1-Methyl-3-isobutylxanthine (0.1 mM) increased cyclic GMP and cyclic AMP levels in slices of rat submaxillary glands. Methacholine increased cyclic GMP if added in the presence of methyl isobutylxanthine. Cyclic GMP control levels and the effect of methyl isobutylxanthine were unchanged by Ca(++) omission, but the effect of methacholine was abolished.These findings indicate that calcium ions are important for the control of cyclic GMP levels in these tissues.

Acetylcholine↗
PubMed1973

A new enzymatic assay for guanosine 3':5'-cyclic monophosphate and its application to the ductus deferens of the rat.

A sensitive enzymatic procedure has been developed for the determination of guanosine 3':5'-cyclic monophosphate (cyclic GMP). It is based on the conversion of cyclic GMP to GMP by cyclic nucleotide phosphodiesterase and on the transfer of (32)P from [gamma-(32)P]ATP to GMP by the action of a specific ATP:GMP phosphotransferase (EC 2.7.4.8). The [(32)P]GDP is separated from the remaining [(32)P]ATP by enzymatic degradation of ATP by myosin and by precipitation of the (32)P(i) formed. The reaction blank, which is mostly caused by the nucleotide content of the enzymes, is doubled by about 0.1 pmol of cyclic GMP. The procedure has advantages in speed and/or accuracy over other methods in current use. Cyclic nucleotide concentrations were studied in the ductus deferens of the rat; two agents were used, carbachol and norepinephrine, which cause contraction. Incubation with 0.1 mM carbachol caused a 3-fold increase in cyclic GMP content, which was maximal about 2 min after carbachol addition. Cyclic AMP concentrations were not significantly changed. Addition of 0.01 mM norepinephrine increased cyclic GMP content by about 25% within 1 min and by 40% within 3 min; cyclic AMP concentrations were only slightly increased. A 3-min incubation with the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine (0.1 mM) doubled the cyclic GMP content and increased cyclic AMP concentration by 50%.

Adenosine Diphosphate↗