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Biomedical subjects
Publications and source records attributed to P McLaughlin.
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The activity of prolyl hydroxylase and the rate of collagen synthesis were examined in two anatomically different arterial segments of cholesterol-fold cynomolgus monkeys. In the aortic arch vessels the activity of prolyl hydroxylase was increased after six months on a high fat and high cholesterol diet. In this tissue the enzyme activity showed positive correlation with the levels of plasma and tissue cholesterol content. By contrast in the abdominal aortas of the same animals no significant increase of arterial tissue cholesterol or prolyl hydroxylase activity was seen. Despite the elevation of prolyl hydroxylase activity in the arch vessels of hyper cholesterolemic animals, no concomitant increase of collagen synthesis was seen. Neither cholesterolemia nor arterial cholesterol showed a positive correlation with the rate of arterial collagen synthesis. No significant changes of the rate of collagen metabolism were detected at the end of an 18 months intervention phase when the cholesterol content both in plasma and in the arterial tissue was substantially reduced.
Intestinal absorption of cholesterol was measured in control rats fed semipurified diets and in rats fed alfalfa meal, in which saponins had been previously extracted, or this extracted material plus alfalfa saponins. A dose of 2 mg radioactive cholesterol was administered intragastrically, and fecal excretion of labeled neutral steroids measured. Absorption of cholesterol was about 76% in control animals, and about 47% in alfalfa-red rats. Extraction of saponins from alfalfa eliminated the cholesterol absorption-lowering effect, while addition of 0.26% alfalfa saponins to the extracted alfalfa restored its activity. The results demonstrate that alfalfa saponins are responsible for the effect of alfalfa meal in reducing cholesterol absorption, and that alfalfa fiber is not involved in this activity.
A semipurified diet containing 1.2 mg of cholesterol/Cal was fed to cynomolgus monkeys (Macaca fascicularis). At the end of 6 months, a group of 18 animals was killed for evaluation of atherosclerosis in the aorta and the coronary arteries. The remaining monkeys were assigned to three groups of 18 animals each and fed, during the following 18 months, semipurified diets containing 0.34 mg of cholesterol/Cal with or without alfalfa meal, or a diet consisting entirely of Monkey Chow. a decrease in cholesterolemia and plasma phospholipid levels, normalization in the distribution of plasma lipoproteins, and reduction in the extent of aortic and coronary atherosclerosis were observed in monkeys fed the semipurified diet containing alfalfa, although the intake of cholesterol remained as high as in the usual American diet. These changes, also observed in monkeys fed a chow diet almost devoid of cholesterol, suggest that alfalfa counteracts the atherogenic effect of dietary cholesterol.
A semipurified diet containing 43% of the calories as fat and 1.2 mg of cholesterol/cal was fed to cynomolgus monkeys (Macaca fascicularis) for 6 months; the cholesterol content was reduced to 0.34 mg/cal for the next 18 months. During the latter period, the monkeys were assigned to 4 groups of 18 animals each and received the following dietary additions: A, none (controls); B, cholestyramine (5%, w/w); C, dextrothyroxine (0.003%); and D, Wy-14,643 (0.45%). Cholestyramine normalized plasma lipid levels and reduced the size of aortic and coronary atherosclerotic lesions in spite of the high-fat, high-cholesterol intake. Dextrothyroxine reduced cholesterolemia but did not modify the extent of arterial lesions. Wy-14,643 changed neither plasma cholesterol levels nor the extent of atherosclerosis.
Digitonin mixed in the diet was well tolerated by rats and cynomolgus monkeys (Macaca fascicularis), and prevented the expected rise in plasma cholesterol in monkeys fed a diet containing butter and cholesterol. Both digitonin and mildly hydrolyzed digitonin precipitated cholesterol dispersed in micellar suspensions and decreased intestinal absorption of cholesterol in rats, but only digitonin bound cholesterol in vitro. The hypocholesterolemic effect of digitonin may be secondary to decreased intestinal absorption of cholesterol associated with a disturbance in the micellar suspension of cholesterol in the intestinal content. Modification of other mechanisms that may be involved in membrane transport of cholesterol through the intestinal epithelium is not ruled out by the present findings.
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Five to 20 mg of saponins obtained from alfalfa tops or roots were introduced intragastrically in rats also receiving oral and intravenous ring-labeled cholesterol. The saponins were tested before and after partial acid hydrolysis. Absorption of cholesterol was determined by estimation of fecal sterols and by a dual isotope technique involving assay of plasma radioactivity. Alfalfa top saponins (nonhydrolyzed) reduced absorption of cholesterol. Acid hydrolysis of alfalfa top or root saponins enhanced their ability to inhibit cholesterol absorption.
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Semipurified diets whose cholesterol content varied from 34 to 120 mg/100 kcal were given to adult female cynomolgus monkeys (Macaca fascicularis) for 9 months. The intake of dietary fiber was increased through the addition of wheat, rice, or soya bran; 5% cholestyramine was given to one group of monkeys. None of the brans reduced plasma levels of cholesterol, whereas cholestyramine produced marked hypocholesterolemic effects. Triglyceride levels increased with higher cholesterol intake, but no additional changes were induced by any of the experimental diets. Plasma phospholipids were reduced by cholestyramine.
Twenty-six adult female cynomolgus monkeys (Macaca fascicularis) were randomly assigned to four groups which were fed on a standard laboratory diet or a semipurified diet containing cholesterol. In two of the groups, the monkeys were exposed intermittently to CO throughout the day for 14 months; the control animals breathed room air. No myocardial infarctions were observed, and the ECG showed a transitory injury current in only one animal. No differences in plasma cholesterol levels or in aortic and coronary atherosclerosis could be attributed to CO exposure.
A method for background subtraction is presented. The data are digitized scintigraphic images, stored in 64 X 64 frames. Within this array a rectangular area surrounding the target is defined. All data points outside of this area are set equal to zero. From each data point within the area, the computer subtracts a background value equal to the average of the two intersecting linear interpolations between the values at the edges of the rectangular area having the ordinate and abscissa values of the point of interest. The rationale for this approach is discussed and its application in myocardial perfusion studies is illustrated.
From the 15th day of birth, newborn rats were offered rat chow mixed with water or skim milk. The former also received tap water, the latter skim milk. In the latter group, plasma cholesterol was lowered in 43- and 64-day-old males and in 64-day-old females.
Experimental work has shown that technetium-99m (99mTc) pyrophosphate accumulates in recently infarcted myocardium and can be detected by external imaging techniques. Twenty-two 99mTc polyphosphate myocardial studies were performed in 17 patients (in 3 after cardiac surgery) 3 to 20 days after myocardial infarction. Seventeen myocardial studies were performed in 17 control patients (in 6 after cardiac surgery). Twenty millicuries of 99mTc polyphosphate was injected intravenously 60 to 120 minutes prior to gamma camera imaging in several views. Myocardial images were processed by the Gamma-11 computer system using standardized background subtraction and contrast enhancement. Results of 16 myocardial studies performed 4 to 20 days after transmural myocardial infarction in 12 patients were positive in 13 instances and questionable in 1. The location of the myocardial infarction by imaging corresponded to location by standard electrocardiograhic criteria in 8 of the 10 patients with positive findings. In five patients with nontransmural myocardial infarction, results of myocardial imaging were positive in two, questionable in one and normal in one. In one patient with questionable findings results were normal when imaging was repeated 16 days after nontransmural myocardial infarction. Results of 17 control myocardial imaging studies were normal in 16 and questionable in 1. Therefore, 99mTc polyphosphate myocardial imaging appears promising in the detection and location of transmural myocardial infarction. Its accuracy in detecting nontransmural myocardial infarction may be increased with greater experience and development of sophisticated digital analysis techniques. The method may prove useful in clinical situations such as cardiac surgery in which standard diagnostic aids are difficult to interpret.
A method is described to determine the mass of 7alpha-hydroxy cholesterol synthetized in vitro by liver microsomes without the use of a radioactive substrate.
From March 1969 to December 1972, 314 patients underwent elective aortocoronary saphenous vein bypass graft surgery at the Toronto General Hospital for the relief of stable disabling angina refractory to medical management. Inhospital mortality was 2.5%. Of these patients 100 agreed to return for follow-up hemodynamic and angiographic assessment at a mean interval of 19.7 months after operation. Seventy-four percent of patients were asymptomatic or had angina only with strenuous exertion at the time of follow-up. Seventy-five percent of the 142 grafts were patent, though a few had significant narrowings. Clinical improvement could be correlated with successful myocardial revascularization. Myocardial infarction was diagnosed by the presence of new Q waves after operation in 15% of patients. Many of these patients had patent grafts at follow-up and all were improved. Dyslipoproteinemia was not found to be a factor affecting late graft patency. Total left ventricular function was not shown to be improved by segmental revascularization. The trend toward improved survival in the intervening period for the total operated group is encouraging.