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T B Clarkson

Publications and source records attributed to T B Clarkson.

205 records · Page 12Linked to original sources
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Pregnancy-associated inhibition of coronary artery atherosclerosis in monkeys. Evidence of a relationship with endogenous estrogen.

We investigated the influence of repeated pregnancy on diet-induced atherosclerosis in cynomolgus monkeys and sought to determine if circulating endogenous reproductive steroid levels were associated with the extent of coronary artery atherosclerosis. At necropsy, females which were pregnant one or more times were found to have coronary artery atherosclerosis which was one-fourth as extensive as that of intact females which had not been pregnant. Extent of coronary artery atherosclerosis correlated positively with mean total plasma cholesterol (Rho = 0.52, p less than 0.01) and inversely with high density lipoprotein (HDL) cholesterol (Rho = -0.48, p less than 0.01) concentrations; both decreased during pregnancy. Additionally, the extent of coronary artery atherosclerosis was found to have a strong inverse association (Rho = -0.66, p less than 0.001) with an index (area-under-the-curve) of magnitude and duration of the pregnancy-induced elevation in plasma 17-beta estradiol concentration. This association could not be explained by an interrelationship between estradiol area-under-the-curve and either plasma total or HDL cholesterol concentrations. There was no relationship between atherosclerosis extent and a similar index of plasma progesterone concentrations. These findings provide evidence for an inhibitory effect of endogenous estrogen on the progression of coronary artery atherosclerosis.

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Atherosclerosis of cynomolgus monkeys hyper- and hyporesponsive to dietary cholesterol. Lack of effect of vasectomy.

A moderately atherogenic diet was fed to young adult cynomolgus macaque males that were observed to be either hypo- or hyperresponsive to dietary cholesterol and who were randomized into groups to be either vasectomized or sham-vasectomized. The extent of atherosclerosis was found to be considerably greater at all arterial sites studied for the monkeys that were hyperresponsive to dietary cholesterol. The differences in atherosclerosis development among the hyperresponder monkeys occurred primarily in the proximal portions of the coronary arteries, the proximal and distal portions of the common carotid arteries, and only in the most proximal portions of the femoral arteries. There were no significant effects of vasectomy or sham vasectomy on atherosclerosis extent in either the hyper- or the hyporesponding groups, although there was a suggestion of somewhat larger lesions in the left circumflex coronary artery of hyperresponder monkeys that were vasectomized and somewhat smaller atherosclerotic lesions in the left common carotid arteries of vasectomized monkeys. The data presented here do not support our first report of worsened atherosclerosis among cynomolgus monkeys fed diets high in cholesterol. The findings of the current study are consistent with recent epidemiological studies of vasectomized and nonvasectomized human males.

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Contraceptive steroid effects on lipids and lipoproteins in cynomolgus monkeys.

Seventy-three adult female cynomolgus monkeys fed an atherogenic diet were studied to determine the effect of two different combination contraceptive steroid preparations containing equivalent amounts of estrogen but different progestin components on plasma lipids and lipoproteins. Our hypothesis was that any high density lipoprotein (HDL) lowering effect of the contraceptive steroid preparations was proportional to the rise in total serum cholesterol caused by the progestins. For 2 years, one group (Ovral [Wyeth Laboratories], n = 23) received 75 micrograms norgestrel and 7.5 micrograms ethinyl estradiol daily, while another (Demulen [Searle & Co.], n = 25) received 150 micrograms ethynodiol diacetate and 7.5 micrograms ethinyl estradiol daily. The control group (n = 24) received no treatment. On average, the two oral contraceptive groups had higher total serum cholesterol and triglyceride concentrations but lower HDL cholesterol concentrations and smaller low density lipoproteins (LDL) compared with the control group. There was an inverse relationship between total serum cholesterol and HDL cholesterol for all three groups, but at any given total serum cholesterol concentration between 350 and 500 mg/dl, the Ovral group had HDL cholesterol concentrations that averaged 37% and 14% lower than the control and Demulen groups, respectively. The decrease in HDL concentrations with oral contraceptive treatment was associated with a sharp decrease in (HDL2b)gge protein (82% for Ovral and 59% for Demulen) and a corresponding increase in (HDL3b,c)gge protein as determined by gradient gel electrophoresis. Of 23 animals in the Ovral group, six had HDL subfractions greater than 10 nm diameter (HDL2b)gge compared with 22 of 24 animals in the control group. Although LDL size, on average, was smaller and plasma triglycerides were greater with oral contraceptive treatment compared with controls, there was no apparent relationship between LDL size and plasma triglyceride concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

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Prednisone increases low density lipoprotein in cynomolgus monkeys fed saturated fat and cholesterol.

Cynomolgus monkeys were given prednisone to determine its effects on lipoprotein metabolism and other risk factors for atherosclerotic cardiovascular disease. After 1 month of oral prednisone, the mean total plasma cholesterol (TPC) concentration increased from 240 +/- 36 to 476 +/- 78 mg/dl (p less than 0.01) in animals fed a diet containing 36% of calories as fat (polyunsaturated/monounsaturated/saturated, 1.0:3.9:4.1) and cholesterol (0.39 mg/kcal). The increase in TPC was due to higher concentrations of the apolipoprotein B (apo B)-containing lipoproteins, particularly low density lipoprotein (LDL). LDL cholesterol concentrations also increased in animals fed a diet containing saturated fat and 0.25 mg/kcal of cholesterol, as well as in animals fed monkey chow. Kinetic studies of LDL indicated both an increased flux of apo B into LDL and a decrease in the fractional catabolic rate of LDL. Mean high density lipoprotein cholesterol (HDL-C) concentration decreased from 48 +/- 8.2 to 14 +/- 4 mg/dl, p less than 0.001, in animals fed fat and cholesterol, but there was no significant change in HDL-C in animals fed monkey chow. Blood pressure, fasting serum glucose, and anthropometric measures did not change after 7 months of prednisone therapy. Prednisone increases LDL concentration in the cynomolgus monkey. This animal may be a good model for studying corticosteroid dyslipoproteinemia, and possibly atherosclerosis, in an immunosuppressed host.

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PubMedDate not supplied

Pathogenesis of carotid bifurcation atherosclerosis in cynomolgus monkeys.

We report here the effect of diet and social environment on the carotid bifurcation atherosclerosis of 60 adult male cynomolgus monkeys (Macaca fascicularis) fed either an atherogenic diet (AD) or a more "prudent" diet (PD). Animals within each dietary condition lived either in unstable social groupings (which had their memberships reorganized on a regular basis) or in stable groupings. The experiment lasted 22 months, after which animals were necropsied and the extent of atherosclerosis was measured both at the carotid bifurcation and at other arterial sites. Carotid bifurcation atherosclerosis (CBA) was significantly more extensive and severe among animals fed the AD diet. Among these animals, all of which were normotensive, lesion extent was positively associated with both plasma cholesterol concentrations and heart rate response to behavioral stress, and negatively associated with the ability to clear glucose. No experimental variables correlated with the CBA of the PD animals; these lesions, some of which were extensive, were probably pre-existing. The social conditions and individual behavior patterns of the animals had no effect on CBA in either group, despite a pronounced effect on the coronary arteries (CA) of the same animals. While the overall correlation between CBA and CA atherosclerosis was not high, animals with extensive CBA almost always had extensive CA atherosclerosis. The factors influencing CBA in the cynomolgus monkey may be similar to those affecting humans.

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