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Biomedical subjects

E J Schaefer

Publications and source records attributed to E J Schaefer.

At least 235 records · Page 13Linked to original sources

Plasma lipoprotein cholesterol and endogenous sex hormones in healthy young women.

Relationships between plasma levels of lipoproteins and sex hormones were studied in 24 healthy premenopausal women with no risk factors for coronary heart disease. The women were carefully selected to remove the effects of other environmental factors, such as smoking, drugs, alcohol, and exercise, which are known to influence lipid metabolism. They all ate precisely the same Western-style diet for 1 to 2 weeks before blood samples were obtained in the follicular phase of their menstrual cycle. After adjusting for other hormones by multiple regression, significant positive partial correlations were seen between high density lipoprotein cholesterol (HDL-C) and protein bound estradiol (r = .57, P = .02), as well as between very low density lipoprotein cholesterol (VLDL-C) and protein bound estradiol (r = .63, p = .01). A significant negative partial correlation was seen between VLDL-C and free estradiol (r = -.65 P = .01). Conversely, low density lipoprotein cholesterol (LDL-C) levels were negatively correlated with protein bound estradiol (r = -.77, P less than .001) and positively correlated with free estradiol (r = .71, P less than .001). No associations between plasma lipoproteins and testosterone were seen; however, androstenedione was positively correlated with VLDL-C (r = .59, P = .01). These findings show a close link between plasma lipoproteins and sex hormones, and may help to explain the lower risk of coronary heart disease in women.

Adult↗

Plasma lipoproteins in healthy octogenarians: lack of reduced high density lipoprotein cholesterol levels: results from the Framingham Heart Study.

Genetic low density lipoprotein (LDL) deficiency and high density lipoprotein (HDL) excess have been associated with enhanced longevity. This investigation assessed the prevalence of lipoprotein abnormalities in octogenarians free of clinical evidence of cardiovascular disease (CVD) in the Framingham Heart Study. Plasma lipid and lipoprotein cholesterol determinations were carried out by standard techniques between 1971 and 1974. Participants who were free of clinical evidence of CVD in an examination approximately 10 years later (1981 to 1982) had their lipoprotein values tabulated based on the earlier examination. There were 106 women and 57 men who met these criteria, with mean ages of 83.3 and 82.9 years, respectively, at examination 16 (called cases). Mean levels (+/- SEM) of LDL cholesterol in cases were 152 +/- 3 mg/dL for women, and 147 +/- 5 mg/dL for men. For HDL cholesterol, these values were 57 +/- mg/dL for women and 46 +/- 2 mg/dL for men. These values were not statistically different from those of other study subjects (who did not meet the CVD criteria or were decreased) or middle-aged controls. In contrast, HDL cholesterol levels below the tenth percentile of normal were not observed in any male cases and in only 1.0% of female cases (P less than .05) as compared with observations in control subjects. The data are consistent with the concept that there is not an overrepresentation of either decreased LDL cholesterol or elevated HDL cholesterol values in subjects who subsequently become healthy octogenarians, but that these subjects are exceedingly unlikely to have reduced HDL cholesterol levels.

Aged↗

Role of triglyceride-rich lipoproteins from the liver and intestine in the etiology of postprandial peaks in plasma triglyceride concentration.

Plasma triglyceride concentration in human subjects peaks once, twice or three times in the twelve-hour period following the ingestion of a fat-rich meal. Triglyceride-rich lipoproteins (TRL) containing apolipoprotein (apo)B-48 (of intestinal origin), and TRL containing apoB-100 (predominantly of hepatic origin) both contribute to postprandial changes in plasma triglyceride concentration. To test the hypothesis that earlier peaks in postprandial triglyceridemia are due predominantly to the secretion of TRL from the intestine, while later peaks are due to the secretion of TRL from the liver, TRL apoB-48, TRL apoB-100 and retinyl ester (a marker of intestinal lipoproteins) were measured in plasma samples from subjects fed a fat-rich meal (1 g fat/kg body wt). Data from seven subjects (four fed 40 retinol equivalents vitamin A/kg body wt, three fed 20 retinol equivalents vitamin A/kg body wt, with the fat meal), showed that postprandial peaks in plasma triglyceride were always associated with increases in plasma retinyl ester concentration. In four subjects, who were selected because they had two clearly defined postprandial triglyceride peaks, the plasma concentration of TRL triglyceride, apoB-48, apoE and apoC increased in conjunction with both the earlier (three hour) and later (nine hour) peaks in plasma triglyceride. Increase in TRL apoB-100 was associated with both peaks in two of the four subjects. Our data suggest that 1) TRL from the liver and intestine contribute to both earlier and later peaks in postprandial triglyceridemia; and 2) the rate of appearance of TRL from the intestine is not constant after dietary fat absorption.

Adult↗

Acute changes in lipid, lipoprotein, apolipoprotein, and low-density lipoprotein particle size after an endurance triathlon.

The effect of an endurance triathlon (2.4-mile swim, 112-mile bicycle ride, 26.2-mile run, in succession) on plasma total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, apolipoprotein (apo) A-I and B levels, and LDL particle size was determined in 34 male and six female participants 6 to 12 hours before and immediately after the completion of the triathlon. Plasma TG decreased significantly (70% decrease) in both men and women. In men the change in plasma TG was inversely associated with baseline TG values (P less than .0001). Plasma TC and LDL cholesterol did not change significantly in male athletes but decreased significantly in women. A significant increase in HDL cholesterol was observed in both men (18% increase, P less than .0001) and women (5% increase, P less than .01). In men the increase in HDL cholesterol was inversely correlated with the decrease in triglycerides (P less than .0002). Plasma apo A-I levels increased significantly only in the male group (P less than .005), whereas plasma apo B levels decreased significantly in both men and women (P less than .0005). LDL particle size increased in seven males, whereas in the remaining males and all females no change in LDL size was observed. The increase in LDL particle size in these seven subjects was associated with a greater decline in plasma TG compared with the remaining men (P less than .005) and women (P less than .03). These results indicate that prolonged strenuous physical exercise can induce acute modifications of plasma lipoproteins, which may in part be related to enhanced lipolysis.

Apolipoprotein A-I↗

Ascorbic acid, HDL cholesterol, and apolipoprotein A-I in an elderly Chinese population in Boston.

The relationships between plasma HDL cholesterol, apolipoprotein A-I, and plasma ascorbic acid were examined in 146 women and 92 men in a Chinese population in Boston, aged 60 and above. A significant partial correlation (r = 0.21, p = 0.015) between plasma ascorbic acid and plasma HDL cholesterol was observed among (predominantly nonsmoking) females after the effects of potentially confounding variables were taken into account. A similar relationship among 26 nonsmoking men was suggestive but inconclusive; there was no evidence of a relationship among 66 male smokers. The partial correlation between plasma apolipoprotein A-I and plasma ascorbic acid was marginally significant for women (r = 0.22, p = 0.057, n = 87) but was highly significant for men (r = 0.43, p = 0.007, n = 51). The correlation coefficient for men was highly dependent on smoking status, being 0.80 for those who never smoked and almost zero for current smokers.

Aged↗

Postprandial changes in the plasma concentration of alpha- and gamma-tocopherol in human subjects fed a fat-rich meal supplemented with fat-soluble vitamins.

The plasma concentrations of alpha (alpha)- and gamma (gamma)-tocopherol in 10 male and 15 female subjects (n = 14) received 1 g fat/kg body wt as soybean oil, and the meal was supplemented with 100% of the RDA for fat-soluble vitamins. In expt. 2, the subjects (n = 11) received 1 g fat/kg body wt as 50% soybean oil + 50% cream, and the meal was supplemented with 200% of the RDA for fat-soluble vitamins. The ratio of gamma- :alpha-tocopherol given in the test meal of expt. 1 was 2.8:1 and in expt. 2 was 0.9:1. Blood samples were obtained 0, 3, 6, 9 and 12 h after the meal. Tocopherol concentration was measured in plasma and lipoprotein fractions. In both studies, plasma triglyceride concentration increased significantly after the meal (P less than 0.001). Mean plasma cholesterol and alpha-tocopherol concentrations were unchanged, but plasma gamma-tocopherol concentration was significantly increased at 6, 9 and 12 h after the meal (P less than 0.05). The increase in plasma gamma-tocopherol was due to increases within the triglyceride-rich lipoprotein (TRL) fraction (d less than 1.006 g/ml) at earlier timepoints, followed by a sustained increase within low density lipoprotein (LDL) and high density lipoprotein (HDL) fractions at later timepoints. In contrast, alpha-tocopherol in LDL and HDL decreased postprandially, concomitant with a rise in TRL alpha-tocopherol. Our results are consistent with the concept that there are differences in the distribution of alpha- and gamma-tocopherol in postprandial lipoproteins.

Adult↗

Effect of exercise and menstrual cycle status on plasma lipids, low density lipoprotein particle size, and apolipoproteins.

Habitual physical exercise has been reported to have beneficial effects on plasma lipoproteins. To examine this question in women, plasma cholesterol, triglyceride, and apolipoprotein (apo) A-I and B levels, and low density lipoprotein (LDL) particle size were determined in 25 women runners (9 of whom had exercise-related secondary amenorrhea) and 36 age-matched nonexercising women (controls). The eumenorrheic runners had significantly lower apo B levels and significantly greater mean apo A-I/apo B ratios and LDL particle sizes than did the control women (P less than 0.05). Lower apo B levels were correlated with decreased body mass index, a known exercise effect (P less than 0.0001). In addition, normally menstruating runners had cholesterol and triglyceride levels that were 7.6% and 25.4% lower, respectively, and apo A-I levels that were 6.4% higher than control women (P = NS). In amenorrheic runners all parameters were similar to values in control women, except that apo B levels were 20% lower (P less than 0.05). Amenorrheic runners had lower plasma apo A-I levels (13%) and significantly lower apo A-I/apo B ratios and estradiol levels than eumenorrheic runners, and serum estradiol values in the runners were correlated with apo A-I levels (P less than 0.01). These data indicate that the beneficial effects of strenuous exercise on plasma apo A-I levels and apo A-I/apo B ratios in women runners can be reversed by exercise-induced amenorrhea and decreased serum estradiol levels, and that women runners have lower apo B levels than nonexercising women, regardless of menstrual status.

Adult↗

Screening for lipoprotein[a] elevations in plasma and assessment of size heterogeneity using gradient gel electrophoresis.

Plasma was screened for the presence of lipoprotein[a] using 2-16% nondenaturing, polyacrylamide gradient gel electrophoresis. Gels were scanned with a densitometer after staining with Sudan black B. Bands that migrated above low density lipoprotein bands were identified as lipoprotein[a] by immunoblotting with polyclonal and monoclonal antibodies to apolipoprotein[a]. Lipoprotein[a] was measured by gradient gel electrophoresis and by radioimmunoassay in 115 male patients with premature coronary artery disease and 132 control subjects. Lipoprotein[a] bands were detected in 96.7% of subjects with lipoprotein[a] values above 40 mg/dl; in 31.3% with values between 21 and 40 mg/dl, and in 6.5% with values below 20 mg/dl. This gel methodology is a simple and effective procedure for detecting elevated plasma lipoprotein[a] levels and for investigating size heterogeneity, but does not replace immunoassay for quantitation.

Coronary Disease↗

Effects of isradipine, a new calcium antagonist, versus hydrochlorothiazide on serum lipids and apolipoproteins in patients with systemic hypertension.

The effect of isradipine versus hydrochlorothiazide on the lipid profile of 44 hypertensive patients was investigated in a double-blind, randomized, 2-center trial. Lipid profiles included total cholesterol, serum triglycerides, high density lipoprotein (HDL) cholesterol, HDL subclasses, (HDL2 and HDL3), low density lipoprotein cholesterol, very low density lipoprotein cholesterol, apolipoprotein A-1 and apolipoprotein B. Isradipine had no effect on the lipid profile in short- (4 and 10 week) or long-term (52 week) studies. Hydrochlorothiazide increased serum triglycerides in 11 of 13 patients by a mean of 8% for the group (p less than 0.05) in long-term (52 week) studies, and total cholesterol by a mean of 9 and 16%, respectively (p less than 0.01) in 2 of 13 patients, with no difference in other lipid or lipoprotein parameters in short- or long-term studies.

Adult↗

Effect of hospitalization on high-density lipoprotein cholesterol in patients undergoing elective coronary angiography.

The effects of time of sampling on plasma lipids and lipoprotein cholesterol concentrations were investigated in 88 patients undergoing elective coronary angiography. Patients with a myocardial infarction or major surgery within 6 weeks before catheterization were excluded. All subjects were sampled in the fasting state at the time of arteriotomy before systemic heparinization and at least 30 days after discharge from the hospital (mean 275 days) in the free living state. No statistically significant differences were noted in total cholesterol (220 +/- 51 vs 226 +/- 48 mg/dl), triglycerides (191 +/- 77 vs 191 +/- 113 mg/dl) and calculated low-density lipoprotein cholesterol levels (149 +/- 46 vs 150 +/- 43 mg/dl). High-density lipoprotein cholesterol values were significantly lower (p less than 0.0001) in subjects sampled before catheterization than in the free living state (32 +/- 10 vs 37 +/- 10 mg/dl, mean change 14%). Moreover, the frequency of high-density lipoprotein cholesterol less than 35 mg/dl was 77% before catheterization and 44% in the free living state. This effect was neither due to beta-adrenergic drugs nor to the length of time between samplings. In view of these findings, a screening lipid profile for patients with coronary artery disease should be performed in the free living state.

Adrenergic beta-Antagonists↗

Regulation of intestinal apolipoprotein B synthesis and secretion by Caco-2 cells. Lack of fatty acid effects and control by intracellular calcium ion.

To investigate the mechanism of control of intestinal apolipoprotein B (apoB) secretion, we studied the effects of fatty acids and calcium ionophores on the human intestinal model cell line Caco-2. Although treatment with various fatty acids (18:1w9, 18:2w6, and 20:5w3) complexed to bovine serum albumin resulted in a dramatic redistribution of apoB-100 from the low density and high density lipoproteins to the very low density lipoprotein fraction, there was no effect of any of the fatty acids on the overall rate of total apoB (apoB-100 and apoB-48) secretion. Treatment of differentiated monolayers with calcium ionophores A23187 or ionomycin caused dose-specific increases (125% at 1 microM) in the accumulation of total apoB, but not apoA-I, in conditioned medium as measured by specific immunoassays. Incubation studies with 35S-labeled Caco-2 apoB,E-containing low density lipoprotein particles revealed that treatment with ionomycin over a broad concentration range had no effect on the reuptake of secreted apoB-100. The effect on A23187 on total apoB secretion was blocked by prior chelation of medium calcium and was significantly enhanced by the addition of calcium (up to 50 mM) to the medium. The effect of A23187 was significantly blunted by treatment with the calmodulin antagonist trifluoperazine (10 microM). The time course of A23187 action on Caco-2 apoB secretion required at least 6 h to occur. In contrast to the concentration of apoB in the medium, cellular apoB content was not influenced by treatment with ionophore. Pulse-chase experiments demonstrated a significant reduction in the synthesis-secretion interval for apoB-100 and apoB-48 after 24 h of exposure to ionomycin. Neither fatty acid treatment nor stimulation with ionophore affected the ratio of apoB-100 to apoB-48 produced by the cells. These findings with calcium ionophores implicate the involvement of calcium ion in the mechanism of intestinal apoB secretion. A role for calcium-dependent processes in apoB production raises the possibility that, rather than fatty acid flux, calcium-evoked or calcium-dependent hormones may be important regulators of apoB secretion.

Adenocarcinoma↗

Clinical significance of hypertriglyceridemia.

Available data suggest that elevated triglyceride levels in plasma, associated with increased VLDL or chylomicron remnants, are associated with premature coronary artery atherosclerosis. Whether this is a direct effect or as a result of the association of hypertriglyceridemia with decreased HDL as well as decreased LDL particle size remains to be determined. Many families with premature coronary disease have a genetic form of hypertriglyceridemia associated with decreased HDL, or with both decreased HDL and increased LDL cholesterol concentrations. In addition, subjects with severe hypertriglyceridemia in excess of 1000 mg/dl associated with elevation of plasma chylomicrons are at increased risk of developing recurrent pancreatitis. Therefore, triglycerides have been implicated in the pathogenesis of both atherosclerosis and pancreatitis.

Chylomicrons↗