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Biomedical subjects

B McManus

Publications and source records attributed to B McManus.

27 records · Page 2Linked to original sources

Reversal of dietary-induced insulin resistance in muscle of the rat by adenosine deaminase and an adenosine-receptor antagonist.

Transfer of young rats from a maintenance diet to a breeding diet plus 10% sucrose in the drinking water for 4 weeks caused the development of insulin resistance. Inclusion of the enzyme adenosine deaminase or the adenosine-receptor antagonist 8-phenyltheophylline caused a marked increase in the sensitivity of the soleus-muscle strips isolated from the diet-induced insulin-resistant rats: the concentration of insulin giving 50% of maximum response of glycolysis shifted from 500 to less than 20 microunits/ml.

Adenosine Deaminase↗

Increased insulin sensitivity in soleus muscle from cold-exposed rats: reversal by an adenosine-receptor agonist.

The effect of 0.5, 2, 7 and 14 days cold exposure at 4 degrees C on insulin sensitivity was investigated in the stripped soleus muscle preparation incubated in vitro. Cold-exposure for 2 or 7 days increased the sensitivity of glycolysis, but did not affect the sensitivity of glycogen synthesis to insulin. Cold-exposure for 0.5 or 14 days had no effect on the sensitivity of either process to insulin. The increased sensitivity to insulin after exposure of animals to the cold for 2 days was completely reversed by addition of the adenosine receptor agonist, 2-chloroadenosine, to the incubation medium. This suggests that cold exposure may increase insulin sensitivity in the muscle, either by a decrease in the concentration of adenosine in the muscle, or by a decrease in the number or affinity of the adenosine receptors.

2-Chloroadenosine↗

Effects of an adenosine-receptor antagonist on insulin-resistance in soleus muscle from obese Zucker rats.

The decreased sensitivity of glycolysis to insulin seen in isolated soleus muscles from genetically obese Zucker rats was abolished by addition of the adenosine-receptor antagonist 8-phenyltheophylline to the incubation medium; 8-phenyltheophylline had no effect on the sensitivity of glycogen synthesis to insulin. These findings suggest that changes in the sensitivity of glucose utilization by muscles of genetically obese rats may be explained, in part, by a modification in either the concentration of adenosine or the affinity of adenosine receptors in skeletal muscle.

Animals↗

Cardiovascular features of homozygous familial hypercholesterolemia: analysis of 16 patients.

Familial hypercholesterolemia (FH) is characterized by an autosomal codominant inheritance, an abnormality in low-density lipoprotein (LDL) receptor function, elevated plasma cholesterol levels and premature atherosclerosis. Sixteen patients with homozygous FH were studied to correlate the extent of their atherosclerotic disease with their lipid levels and receptor function. The age range at initial presentation was 3 to 38 years (mean 12), and at the last examination, 6 to 43 years (mean 20). The mean pretreatment total plasma cholesterol concentration for all patients was 729 +/- 58 mg/dl (+/- standard error of the mean), and the mean LDL cholesterol level was 672 +/- 58 mg/dl (normal 60 to 176). High-density lipoprotein cholesterol was 28 +/- 3 mg/dl (normal 30 to 74). In the 7 patients with FH who had symptoms of myocardial ischemia (Group I), the mean pretreatment LDL cholesterol value (817 +/- 62 mg/dl) was higher than that of the 9 asymptomatic patients (Group II) (560 +/- 74 mg/dl). In Group I, 5 of 7 patients had left or right coronary ostial narrowing and 3 had significant left ventricular outflow obstruction. Most coronary arterial narrowing occurred in the right coronary and left anterior descending arteries and the least amount in the left circumflex coronary artery. A femoral bruit was the physical finding that correlated best with the Group I population; brother:sister pairs revealed a milder clinical course for the female. Seven of the 16 patients have survived into their third decade without symptoms. Comparison of these persons with those in whom angina developed reveals a marked heterogeneity in their clinical course, which appears to be associated with receptor negative/defective status.

Adolescent↗

Effects of analogues of adenosine and methyl xanthines on insulin sensitivity in soleus muscle of the rat.

The concentration of insulin that produces half-maximal stimulation of glycolysis by stripped soleus muscle preparations is markedly increased by the adenosine analogues, 2-chloroadenosine and N6-phenylisopropyladenosine, but is markedly decreased by the methyl xanthine analogue, 8-phenyltheophylline. 2-Chloroadenosine increases the concentration of insulin required to stimulate glycolysis half maximally, from about 100 to 2000 mu units/ml. 8-Phenyltheophylline decreases this concentration of insulin from about 100 to 10 mu units/ml, an effect which is similar to that produced either by addition of adenosine deaminase to the medium or to exercise-training of the donor animals for 4 weeks.

1-Methyl-3-isobutylxanthine↗

Cholesteryl ester crystals in a porcine aortic valvular bioprosthesis implanted for eight years.

Masses of crystals, which were largely composed of cholesteryl esters, were found in a porcine aortic valvular bioprosthesis removed eight years after implantation in the mitral position in a patient with rheumatic mitral valvular stenosis. Histologic sections of grossly raised and nonraised yellow lesions in the three cusps of this bioprosthesis revealed large clefts, which on frozen section contained lipid-positive, birefringent crystals. These crystals gave a positive reaction with the Schultz test for cholesterol. Biochemical analyses of isolated nodules revealed a cholesterol content of 40 nmole/mg of wet tissue. Of this cholesterol, 88 percent was esterified, and the remaining 12 percent was free cholesterol. These cholesterol deposits are most likely derived from blood lipids; however, they were not related to hyperlipidemia, since the patient had normal blood levels of cholesterol and triglycerides.

Aged↗