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Biomedical subjects

R S Clark

Publications and source records attributed to R S Clark.

At least 73 records · Page 4Linked to original sources
PubMed1990

Excessive sympathetic nervous system activity decreases myocardial contractility.

The objective of this study was to determine whether myocardial contractility is depressed by intense activation of the sympathetic nervous system. A massive sympathetic discharge was produced by injecting veratrine or sodium citrate into the cisterna magna of anesthetized rabbits (n = 10). Two and one-half hr later, the hearts were isolated and their left ventricular (LV) performance evaluated and compared with the LV performance of hearts isolated from control animals (n = 10). LV performance was evaluated from steady-state peak isovolumic systolic and end-diastolic pressures that were generated at various end-diastolic volumes (LV function curves). The relationship between peak LV systolic pressure (or the average peak developed LV wall stress) and LV end-diastolic volume was rotated downward (P less than 0.01) in the hearts removed from rabbits treated with veratrine or citrate. The LV end-diastolic pressure or LV end-diastolic wall stress of these hearts was not different from control at any end-diastolic volume. The diminished ability of the experimental hearts to develop systolic pressure or wall stress suggests that intense sympathetic activation depressed contractility. Severely damaged myofibers, located largely in the subendocardium, were found in these hearts. Furthermore, the depressed contractility was not related to pulmonary edema since only 2 of 10 rabbits developed edema.

Animals↗
PubMed1988

Excess of heterozygotes at albumin locus in American Standardbred horses.

Data from 5934 matings of American Standardbred horses provided evidence for an excess of heterozygotes at the albumin locus, statistically significant (P less than 0.01) in one mating class (A1-AB stallions x Al-A dams), primarily attributed to an excess of heterozygotes among male offspring.

Albumins↗
PubMed1986

Acetylation of decarboxylated S-adenosylmethionine by mammalian cells.

Decarboxylated S-adenosylmethionine was found to be a substrate for the nuclear acetyltransferases that act on polyamines and on histones. The rate of acetylation of decarboxylated S-adenosylmethionine was more than twice that of spermidine at saturating substrate concentrations, and decarboxylated S-adenosylmethionine was an active inhibitor of the acetylation of histones by nuclear extracts from rat liver. The acetylation of decarboxylated S-adenosylmethionine occurred in vivo in SV-3T3 cells exposed to the ornithine decarboxylase inhibitor 2-(difluoromethyl)ornithine. The decline in putrescine and spermidine brought about by exposure to 2-(difluoromethyl)ornithine was found to be accompanied by a large rise in the content of both decarboxylated S-adenosylmethionine and acetylated decarboxylated S-adenosylmethionine. These results indicate that decarboxylated S-adenosylmethionine is metabolized not only in the well-known reactions in which it serves as an aminopropyl donor for polyamine biosynthesis but also by acetylation in reaction with acetyl coenzyme A. Furthermore, the inhibition of histone acetylation by decarboxylated S-adenosylmethionine could contribute to the biological effects brought about by inhibitors of ornithine decarboxylase.

Acetyl Coenzyme A↗
PubMed1986

Effect of 1,3,6-triaminohexane and 1,4,7-triaminoheptane on growth and polyamine metabolism in SV-3T3 cells treated with 2-difluoromethylornithine.

The possibility that one or both of the synthetic triamines, 1,3,6-triaminohexane and 1,4,7-triaminoheptane, could substitute for the naturally occurring polyamines in the growth of SV-3T3 cells was investigated. It was found that these triamines did lead to a restoration of growth in cells in which spermidine content had been depleted by exposure to the ornithine decarboxylase inhibitor 2-difluoromethylornithine. This resumption of a normal growth rate occurred prior to the reduction in the content of cellular decarboxylated S-adenosylmethionine, suggesting that this nucleoside (which increases in concentration several hundred-fold in cells treated with 2-difluoromethylornithine) does not cause the reduction of cell growth. However, unlike the increase in cell growth brought about by spermidine, which continued indefinitely, the increase produced by 1,3,6-triaminohexane or 1,4,7-triaminoheptane was transient. Cell growth in the presence of 2-difluoromethylornithine and these triamines stopped after about three or four population doublings. This corresponded to the time at which the intracellular spermine content of the cells was reduced to values less than 20% of normal. It is suggested that the increased growth rate of spermidine-depleted cells in response to these triamines is due to their uptake into the cell and ability to displace spermine from intracellular sites, thus making spermine available to fulfill the polyamine function(s) essential for growth. These results indicate that the naturally occurring polyamines spermidine or spermine are essential for continued cell growth and cannot be replaced by analogues containing only primary amino groups.

Animals↗
PubMed1985

Effect of intravenous infusion of insulin in diabetics with acute myocardial infarction.

Diabetes mellitus is associated with a high mortality after myocardial infarction. To see whether this may be decreased by improved diabetic control the effect of an insulin infusion regimen was studied in patients with acute myocardial infarction. From April 1982 to April 1983, 33 diabetics were admitted with acute myocardial infarction. Those being treated with diet alone or oral hypoglycaemic drugs continued with this unless control was poor, when they were changed to a "sliding scale" regimen of subcutaneous insulin injections thrice daily. Those already receiving insulin were maintained on thrice daily subcutaneous injections. From April 1983 to April 1984, 29 diabetics had acute myocardial infarction. Those receiving treatment with oral hypoglycaemic drugs or insulin were changed to continuous intravenous infusion of insulin, the aim being to maintain the blood glucose concentration at 4-7 mmol/I (72-126 mg/100 ml). Those being treated with diet alone continued with this if blood glucose concentrations were acceptable. Total mortality fell from 42% in the first year to 17% in the second (p less than 0.05). Over the same period mortality among non-diabetic patients with myocardial infarction did not change significantly. There was a significant fall in cardiac arrhythmias (expressed as the percentage of patients in whom arrhythmias were recorded) from 42% to 17% (p less than 0.05). The most significant fall in the incidence of complications occurred in those who had been receiving oral hypoglycaemic drugs on entry to the study (87% to 50%, p less than 0.05).

Aged↗
PubMed1985

Blood group and protein polymorphism gene frequencies for seven breeds of horses in the United States.

Gene frequencies at 20 blood group and protein polymorphism loci (A, C, D, K, P, Q, U, Al, Tf, Pi, Xk, Es, Gc, PGD, CA, Cat, PGM, AP, Hb and PHI) are given for seven horse breeds in the United States (Thoroughbred, Arabian, Standardbred, Morgan, Quarter Horse, Paso Fino and Peruvian Paso). These data are used to calculate that the battery of tests is at least 96% effective for recognizing incorrect paternity in these breeds. In addition to paternity testing, these tests can be applied to studies of breed relationships.

Animal Husbandry↗
PubMed1985

Interaction of paraquat and amine uptake by rat lungs perfused in situ.

The kinetics of [14C]paraquat (N,N-di[14C]methyl-4,4'-bipyridylium) uptake from the pulmonary circulation were investigated in rat lungs perfused in situ. During the 1st h of exposure to the herbicide paraquat entered the lungs primarily by diffusion; no evidence was obtained from concentrative uptake, saturation kinetics (1-3,500 microM paraquat), or inhibition by the amines methyl-glyoxal bis(guanylhydrazone) or spermidine, both of which were expected to compete for paraquat transport sites. In contrast, after 60 min of exposure, uptake rates increased two- to three-fold, and paraquat was accumulated to an apparent intracellular concentration greater than that in the perfusate. The latter phase of paraquat uptake was saturable and was inhibited by methylglyoxal bis(guanylhydrazone); it did not appear to reflect a progressive paraquat-induced alteration in cellular permeability but rather predominance of a rapid, carrier-mediated uptake pathway.

Animals↗
PubMed1985

Purification and characterization of some metabolic effects of S-neplanocylmethionine.

Our laboratory has previously demonstrated that treatment of mouse L929 cells with 1 microM neplanocin A results in the metabolic formation of S-neplanocylmethionine (Keller, B.T., and R.T. Borchardt, Biochem. Biophys. Res. Commun. 120:131-137 (1984]. The present study describes an efficient procedure for the purification of this analog from L cells based on its inherent chemical stability in alkaline conditions. Several metabolic effects of S-neplanocylmethionine are also reported. In L cells, S-neplanocylmethionine was determined to have an apparent half-life of 13 hr compared to 1 hr for S-adenosylmethionine during the initial 2 hr of a cycloleucine block. Analysis of polyamine levels in neplanocin A-treated cells showed a 3.8-fold decrease in putrescine and a 1.7-fold decrease in spermidine by 24 hr, reflecting a decrease in the cell growth rate in response to neplanocin A rather than a direct effect of S-neplanocylmethionine on the cellular S-adenosylmethionine decarboxylase. Consistent with these results are our findings that S-neplanocylmethionine does not significantly inhibit purified rat prostate or Escherichia coli S-adenosylmethionine decarboxylase and that [carboxy-14C]S-neplanocylmethionine exhibits no substrate activity with either enzyme. Purified S-neplanocylmethionine was observed to be a weak inhibitor of both S-adenosylmethionine-dependent protein carboxymethyltransferase and lipid methyltransferase in L cell extracts, having an IC50 value of 205 microM (S-adenosylmethionine = 10 microM). Similar studies with [methyl-3H]S-neplanocylmethionine indicate that the analog has little substrate activity in these two L cell methylation reactions and thus appears to act as a poor competitive inhibitor.

Adenosine↗
PubMed1984

Cold pressor induced changes in regional left ventricular wall motion: specific but insensitive for coronary artery disease.

The incidence of new regional abnormalities of left ventricular wall motion induced by a peripheral cold stimulus has been examined in 75 patients who all underwent coronary arteriography. When analysis was carried out from a cine loop display a new wall motion abnormality had a sensitivity of 12% and a specificity of 100% for coronary artery disease. From stroke volume images the sensitivity was 35% and the specificity 87%. It is concluded that cold pressor induced wall motion changes are too insensitive to be a useful method of screening for coronary artery disease.

Adult↗
PubMed1984

Apolipoprotein A and B (Sf 100-400) metabolism during bezafibrate therapy in hypertriglyceridemic subjects.

This study describes the effects of bezafibrate, an analogue of clofibrate, on the plasma lipid and lipoprotein profiles of 11 hypertriglyceridemic subjects and on their metabolism of apolipoproteins A-I, A-II, and B. The major action of the drug was to lower plasma triglyceride (by 58%; P less than 0.01). This was accompanied by a reduction in the level of very low density lipoprotein apoprotein B (Svedberg units of flotation [Sf] 60-400), whose mean residence time in the plasma fell threefold (from 3.4 to 1.0 h). Synthesis of the B protein in this fraction was not significantly altered, so the drug acts to accelerate the transit of very low density lipoprotein particles down the delipidation cascade. The metabolism of very low density lipoprotein remnant apoprotein B (Sf 12-100) changed little in response to treatment, although we detected a 30% increment (P less than 0.05) in the plasma concentration of this fraction. The mean residence time of these remnant particles in the plasma did not correlate with that of Sf 100-400 very low density lipoprotein apoprotein B, nor was this parameter altered by the drug. The most consistent and significant perturbation seen in the Sf 0-12 fraction (low density lipoprotein) was a reduction in the fractional catabolism of its apoprotein B moiety (26%; P less than 0.05). In those subjects who were grossly hypertriglyceridemic and who responded well to treatment, the level of this protein rose substantially owing to a combined increase in its synthesis and a reduction in its catabolism. In the group as a whole, high density lipoprotein cholesterol rose 13% (P less than 0.02), and detailed examination showed that this was associated with a small but significant increment in the plasma concentration of the high density lipoprotein subfraction 2. High density lipoprotein subfraction 3 also rose on the average, but this was not a consistent feature in all patients. The plasma concentrations and turnovers of the A proteins (A-I and A-II) were not significantly altered by bezafibrate therapy.

Apolipoproteins A↗
PubMed1984

The prognostic significance of dysrhythmias in the healthy elderly.

Fifty healthy, elderly subjects in whom a cardiovascular assessment, including 24-hour ambulatory electrocardiography had been performed, have been followed until death, or if surviving, for five years. Eight patients have died and 88 per cent of the survivors have had repeated 24-hour electrocardiography. Coronary death and the development of cardiovascular or neurological symptoms were not related to the presence in the original recording of significant dysrhythmias including frequent ventricular and supraventricular premature beats, R on T phenomena or sinus arrest. Treatment of these and other dysrhythmias in the asymptomatic elderly individual to prevent development of serious clinical sequelae is not justified.

Aged↗
PubMed1982

High density and low density lipoprotein subfractions in survivors of myocardial infarction and in control subjects.

The major lipoprotein classes (very low, low and high density lipoproteins, VLDL, LDL and HDL) and three lipoprotein subfractions (HDL2, HDL3 and LDL2) of 31 male survivors of myocardial infarction (MI) have been compared with those of 24 ostensibly normal subjects. The two groups had similar ages, relative weights, smoking and dietary habits, and physical activities. The MI survivors had significantly higher concentrations of total and VLDL-triglyceride and total and LDL-cholesterol than the control subjects. The differences in HDL-cholesterol, and total apolipoproteins A-1 and B were of borderline significance. HDL2 was significantly lower and LDL2 was higher in the MI survivors. There was no difference in HDL3. The differences in lipoprotein subfractions could be ascribed to differences in cholesterol, phospholipid and proteins, but not in triglyceride. The data suggest that the minor HDL2 subfraction shows a closer association with established coronary heart disease than does total HDL-cholesterol. The increased LDL-cholesterol concentration in the MI survivors can be ascribed at least partly to an increase in the major subfraction, LDL2.

Aged↗
PubMed1982

The effect of moderate physical exercise on the plasma lipoprotein subfractions of male survivors of myocardial infarction.

The effect of regular, moderate exercise on the lipoprotein subfractions of male survivors of myocardial infarction was studied. Nineteen men were randomly allocated to an incremental exercise program and 23 to a control group. Both groups were studied for 6 months. No change occurred in any lipoprotein class in the control group. In the trained group, total triglyceride and low-density lipoprotein (LDL) cholesterol concentrations decreased significantly (0.01 greater than p greater than 0.001 and 0.05 greater than p greater than 0.01, respectively) and high-density lipoprotein (HDL) cholesterol and apolipoprotein A-1 rose (both p less than 0.001). The concentration of the HDL2 subfraction increased with training (0.01 greater than p greater than 0.001) and HDL2 did not change. No relationship was found between changes in lipoproteins and treadmill exercise test performance. Thus, in survivors of myocardial infarction, exercise may alter plasma lipoprotein values beneficially.

Apolipoproteins↗
PubMed1981

Combined vasodilator therapy in the treatment of chronic heart failure.

Treatment of resistant congestive cardiac faiure by vasodilators is now well accepted. Twelve such patients were started on Isosorbide Dinitrate and Hydralazine therapy and monitored for 24 hours. Oral treatment was then continued indefinitely. This group responded well to combined therapy and four had their regimes altered in the light of haemodynamic observations. It was then concluded that this type of treatment can be tailored to the individual patient to produce the best effects on preload and afterload.

Blood Pressure↗