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Biomedical subjects

J S Cohn

Publications and source records attributed to J S Cohn.

53 records · Page 3Linked to original sources
PubMed1990

Postprandial plasma vitamin A metabolism in humans: a reassessment of the use of plasma retinyl esters as markers for intestinally derived chylomicrons and their remnants.

We investigated postprandial vitamin A metabolism by measuring retinyl ester, triglyceride, and apolipoprotein (apo)B-48 in the plasma lipoproteins of human subjects before and after fat-feeding. Following a 14-hour fast, eight healthy subjects (two men, six women, 28 to 79 years) were given a fat-rich meal (1 g fat/kg body weight) containing vitamin A (40 retinol equivalents per kilogram body weight). Blood was collected every 3 hours for 12 hours and lipoproteins were isolated by sequential ultracentrifugation. Mean plasma retinyl ester concentration peaked 6 hours after the fat-rich meal, whereas mean plasma triglyceride peaked at 3 hours. Data obtained from hourly samples in 3 subjects showed that changes in the postprandial plasma concentration of retinyl ester occurred 1 to 2 hours after changes in the plasma triglyceride concentration. In triglyceride-rich lipoproteins (TRL) of d less than 1.006 g/mL, retinyl ester similarly peaked at 6 hours, whereas triglyceride as well as apoB-48 peaked at 3 hours. Although retinyl esters were found mainly in TRL in the initial postprandial period (84%, 3 hours; 83%, 6 hours), in fasting and postprandial plasma, particularly 9 or more hours after fat-feeding, a large percentage of plasma retinyl esters were in low-density lipoproteins (LDL) (44%, fasting; 9%, 3 hours; 9%, 6 hours; 19%, 9 hours; 32%, 12 hours). A small percentage of retinyl esters were also found in postprandial high-density lipoproteins (HDL) (2% to 7%). ApoB-48 was not detected in LDL of fasting or postprandial plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Measurement of very low density and low density lipoprotein apolipoprotein (Apo) B-100 and high density lipoprotein Apo A-I production in human subjects using deuterated leucine. Effect of fasting and feeding.

Six normolipidemic male subjects, after an 8-h overnight fast, were given a bolus injection and then a 15-h constant intravenous infusion of [D3]L-leucine. Subjects were studied in the fasted state and on a second occasion in the fed state (small, physiological meals were given every hour for 15 h). Apolipoproteins were isolated by preparative gradient gel electrophoresis from plasma lipoproteins separated by sequential ultracentrifugation. Incorporation of [D3]L-leucine into apolipoproteins was monitored by negative ionization, gas chromatography-mass spectrometry. Production rates were determined by multiplying plasma apolipoprotein pool sizes by fractional production rates (calculated as the rate of isotopic enrichment [IE] of each protein as a fraction of IE achieved by VLDL (d less than 1.006 g/ml) apo B-100 at plateau. VLDL apo B-100 production was greater, and LDL (1.019 less than d less than 1.063 g/ml) apo B-100 production was less in the fed compared with the fasted state (9.9 +/- 1.7 vs. 6.4 +/- 1.7 mg/kg per d, P less than 0.01, and 8.9 +/- 1.2 vs. 13.1 +/- 1.2 mg/kg per d, P less than 0.05, respectively). No mean change was observed in high density lipoprotein apo A-I production. We conclude that: (a) this stable isotope, endogenous-labeling technique, for the first time allows for the in vivo measurement of apolipoprotein production in the fasted and fed state; and (b) since LDL apo B-100 production was greater than VLDL apo B-100 production in the fasted state, this study provides in vivo evidence that LDL apo B-100 can be produced independently of VLDL apo B-100 in normolipidemic subjects.

Adult↗
PubMed1990

Postprandial plasma retinyl ester response is greater in older subjects compared with younger subjects. Evidence for delayed plasma clearance of intestinal lipoproteins.

Postprandial vitamin A and intestinal lipoprotein metabolism was studied in 86 healthy men and women, aged 19-76 yr. Three independent experiments were carried out. In the first experiment, a supplement dose of vitamin A (3,000 retinol equivalents [RE]) was given without a meal to 59 subjects, aged 22-76 yr. In the second experiment, 20 RE/kg body wt was given with a fat-rich meal (1 g fat/kg body wt) to seven younger subjects (aged less than 50 yr) and seven older subjects (aged greater than or equal to 50 yr). In both experiments, postprandial plasma retinyl ester response increased significantly with advancing age (P less than 0.05). In the third experiment, retinyl ester-rich plasma was infused intravenously into nine young adult subjects (aged 18-30 yr) and nine elderly subjects (aged greater than or equal to 60 yr), and the rate of retinyl ester disappearance from plasma during the subsequent 3 h was determined. Mean (+/- SE) plasma retinyl ester residence time was 31 +/- 4 min in the young adult subjects vs. 57 +/- 8 min in the elderly subjects (P less than 0.05). These data are consistent with the concept that increased postprandial plasma retinyl ester concentrations in older subjects are due to delayed plasma clearance of retinyl esters in triglyceride-rich lipoproteins of intestinal origin.

Adult↗
PubMed1990

Comparison of deuterated leucine, valine, and lysine in the measurement of human apolipoprotein A-I and B-100 kinetics.

The production rates of apolipoprotein (apo)B-100 in very low density lipoprotein and in low density lipoprotein and apolipoprotein A-I in high density lipoprotein were determined using a primed-constant infusion of [5,5,5,-2H3]leucine, [4,4,4,-2H3]valine, and [6,6-2H2,1,2-13C2]lysine. The three stable isotope-labeled amino acids were administered simultaneously to determine whether absolute production rates calculated using a stochastic model were independent of the tracer species utilized. Three normolipidemic adult males were studied in the constantly fed state over a 15-h period. The absolute production rates of very low density lipoprotein apoB-100 were 11.4 +/- 5.8 (leucine), 11.2 +/- 6.8 (valine), and 11.1 +/- 5.4 (lysine) mg per kg per day (mean +/- SDM). The absolute production rates for low density lipoprotein apoB-100 were 8.0 +/- 4.7 (leucine), 7.5 +/- 3.8 (valine), and 7.5 +/- 4.2 (lysine) mg per kg per day. The absolute production rates for high density lipoprotein apoA-I were 9.7 +/- 0.2 (leucine), 9.4 +/- 1.7 (valine, and 9.1 +/- 1.3 (lysine) mg per kg per day. There were no statistically significant differences in absolute synthetic rates of the three apolipoproteins when the plateau isotopic enrichment values of very low density lipoprotein apoB-100 were used to define the isotopic enrichment of the intracellular precursor pool. Our data indicate that deuterated leucine, valine, or lysine provided similar results when used for the determination of apoA-I and apoB-100 absolute production rates within plasma lipoproteins as part of a primed-constant infusion protocol.

Adult↗
PubMed1990

Calculated values for low-density lipoprotein cholesterol in the assessment of lipid abnormalities and coronary disease risk.

Low-density lipoprotein (LDL) cholesterol concentrations are most commonly estimated by the formula LDL cholesterol = total cholesterol - [triglycerides (TG)/5 + high-density lipoprotein cholesterol], although alternative factors such as TG/6 have also been used. Using standardized, automated, enzymatic lipid assays, we analyzed 4797 plasma samples from normal and dyslipidemic adults, to compare LDL cholesterol concentrations obtained after ultracentrifugation with those calculated by several such methods (i.e., TG/4-TG/8). or TG concentrations less than or equal to 0.50 g/L, TG/4 agreed best with the direct assay; for TG of 0.51-2.00 g/L, TG/4.5 was best; and for TG of 2.01-4.00 g/L, TG/5 was best. Differences in estimated values were generally small, however. At TG greater than 4.00 g/L, none of the factors tested allowed a reliable estimate of LDL cholesterol. When TG were less than or equal to 4.00 g/L, 86% of estimated LDL cholesterol values were properly classified according to National Cholesterol Education Program cutpoints when the factor TG/5 was used. We conclude that a convenient direct method for measuring LDL cholesterol is needed but, until one is available, use of the factor TG/5 will assure that most individuals with TG less than or equal to 4.00 g/L, as measured in a standardized laboratory, can be reasonably well classified for risk of coronary artery disease.

Adult↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

Lipoprotein cholesterol concentrations in the plasma of human subjects as measured in the fed and fasted states.

Lipoprotein cholesterol concentrations in plasma are routinely estimated by using the Friedewald formula, whereby very-low-density lipoprotein cholesterol (VLDL-C) is estimated to be one-fifth the plasma triglyceride concentration. Ordinarily, this formula is applied only to plasma sampled from patients in the fasted state. To determine whether lipoprotein cholesterol measurements are altered substantially in plasma sampled from nonfasting subjects, we obtained postprandial blood samples from 22 healthy subjects (nine men, 13 women, ages 22-79 years) fed a fat-rich meal (1 g fat per kilogram body wt.). The plasma triglyceride concentration increased postprandially in all subjects (233 +/- 16% of baseline at 3 h). The mean cholesterol concentration in plasma was essentially unchanged. High-density lipoprotein cholesterol (HDL-C) was significantly decreased (94 +/- 2% at 3 h, P less than 0.001). VLDL-C and low-density lipoprotein cholesterol (LDL-C), estimated by the Friedewald formula, were compared with measurements obtained by modified Lipid Research Clinics (LRC) methodology. As measured by either method, VLDL-C increased and LDL-C decreased significantly after the fat-rich meal. These postprandial changes were significantly greater (P less than 0.01) when estimated by the Friedewald formula than by LRC methodology. We conclude that (a) lipoprotein cholesterol concentrations measured in the fed subject differ significantly from those measured in the fasted subject, and (b) plasma must be obtained after at least a 12-h fast if an individual's risk of coronary heart disease is to be accurately assessed.

Adult↗
PubMed1988

Postprandial plasma lipoprotein changes in human subjects of different ages.

Plasma lipoprotein changes were monitored for 12 hr after a fat-rich meal (1 g of fat/kg body weight) in 22 subjects (9 males, 13 females, 22-79 yr old). Plasma triglyceride, measured hourly, peaked once in some subjects, but twice or three times in others. The magnitude of postprandial triglyceridemia varied considerably between subjects (range: 650-4082 mg.hr/dl). Males tended to have greater postprandial triglyceridemia than females, and elderly subjects had significantly (P less than 0.05) greater postprandial triglyceridemia than younger subjects. Total plasma cholesterol, measured every three hr, increased significantly (6.0 +/- 2.1%) in 7 subjects, decreased significantly (7.1 +/- 1.2%) in 10 subjects, and remained unchanged in the remainder. Single spin ultracentrifugation and dextran sulfate precipitation procedures were used to quantitate triglyceride and cholesterol in triglyceride-rich lipoproteins (TRL, d less than 1.006 g/ml), low density lipoproteins (LDL), and high density lipoproteins (HDL). Plasma TRL and HDL triglyceride increased after the fat meal, while LDL triglyceride decreased at 3 hr but increased at 9 and 12 hr. TRL cholesterol increased postprandially, while LDL and HDL cholesterol decreased. Phospholipid (PL), free (FC) and esterified (EC) cholesterol measurements were carried out on the plasma and lipoprotein fractions of 8 subjects. Plasma PL increased significantly at 3, 6, and 9 hr after the fat-rich meal, due to increases in TRL and HDL PL. TRL CE increased postprandially, but a greater decrease in LDL and HDL CE caused plasma CE to be decreased. Plasma FC increased, predominantly due to an increase in TRL FC. Plasma concentrations of apolipoprotein A-I and apolipoprotein B both decreased after the fat-rich meal. The magnitude of postprandial triglyceridemia was inversely correlated with HDL cholesterol levels (r = -0.502, P less than 0.05) and positively correlated with age (r = -0.449, P less than 0.05), fasting levels of plasma triglyceride (r = 0.636, P less than 0.01), plasma apoB (r = 0.510, P less than 0.05), TRL triglyceride (r = 0.564, P less than 0.01), TRL cholesterol (r = 0.480, P less than 0.05) and LDL triglyceride (r = 0.566, P less than 0.01). Change in postprandial cholesterolemia was inversely correlated with fasting levels of HDL cholesterol (r = -0.451, P less than 0.05) and plasma apoA-I (r = -0.436, P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1988

Plasma apolipoprotein changes in the triglyceride-rich lipoprotein fraction of human subjects fed a fat-rich meal.

Twenty two subjects (9 males, 13 females) were fed a fat-rich meal (1 g of fat/kg body weight). Triglyceride-rich lipoproteins (TRL) were isolated by ultracentrifugation (d less than 1.006 g/ml) from blood drawn 0, 3, 6, 9, and 12 hr after the meal. Plasma triglyceride increased then decreased postprandially, while plasma apoA-I and apoB concentrations decreased. TRL triglyceride, TRL total protein, and TRL apoB concentrations all increased then decreased after the fat-rich meal. Postprandial rise in plasma triglyceride was significantly correlated with fasting plasma triglyceride levels (r = 0.66, P less than 0.001); postprandial rise in TRL triglyceride was significantly correlated with fasting TRL triglyceride levels (r = 0.58, P less than 0.01); postprandial rise in TRL apoB was not, however, significantly correlated with fasting TRL apoB levels (r = 0.37, N.S.). TRL apolipoproteins were separated by polyacrylamide gradient (4-22.5%) gel electrophoresis and protein bands were scanned in two dimensions with a laser densitometer. Relative postprandial changes in the concentration of the TRL apolipoproteins were determined. TRL apoB-100, apoB-48, apoE, and apoC increased then decreased postprandially. The increase in TRL apoB-100 after the fat-rich meal was confirmed in 8 subjects by direct measurement of apoB-100 with a monoclonal antibody ELISA assay. ApoA-I concentration in TRL was unchanged. Albumin in the TRL fraction was significantly increased 12 hr after the meal. Subjects with a greater magnitude of postprandial triglyceridemia had a greater increase in TRL triglyceride and TRL apoB, but their TRL apoB-100/apoB-48 ratios were not different from subjects with less pronounced triglyceridemia. Assuming that plasma TRL containing apoB-100 are predominantly derived from the liver, our data suggest that triglyceride-rich lipoproteins from both the liver and intestine make a significant contribution to postprandial triglyceridemia.

Adult↗
PubMed1987

Metabolism of high-density lipoprotein in the hyperlipidemic, diabetic SHR/N-corpulent rat.

The SHR/N-corpulent rat is a new genetically obese strain that is both hyperlipidemic and diabetic. The high density lipoprotein (HDL) fraction from 12-week-old obese males contained significantly greater amounts of protein (+83%), free (+72%) and esterified (+76%) cholesterol, phospholipid (+94%), and triglyceride (+78%). HDL from obese rats were also enriched in C apolipoproteins (apo C-III0 and apo C-III3) but had similar relative amounts of both apo A-I and apo E compared to HDL from their lean littermates. HDL protein turnover, measured with 125I-labeled HDL, showed that obese rats had a smaller fractional catabolic rate (FCR) than lean rats, but due to their much larger HDL pool size, they had a significantly higher rate of HDL protein catabolism (obese, 1.98 +/- 0.07 mg/whole animal/h v lean, 1.32 +/- 0.05 mg/whole animal/h). Therefore, under steady-state conditions, HDL protein production must also have been increased in the obese animals. To determine whether the increased catabolism of HDL protein was associated with increased catabolism of cholesteryl ester (CE), tissue uptake of HDL CE was measured using the nonhydrolyzable ether analogue [3H]cholesteryl linoleyl ether. After four hours 41.6 +/- 1.6% of the injected dose was cleared from the plasma of lean rats compared with 37.0 +/- 1.1% from the plasma of obese rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Enzyme-linked immunosorbent assay for human plasma apolipoprotein B.

A noncompetitive enzyme-linked immunosorbent assay (ELISA) has been developed for measuring total plasma apolipoprotein (apo) B using affinity purified polyclonal and monoclonal antibodies. Microtiter plates from different manufacturers were tested with regard to their IgG binding characteristics; only one plate yielded consistent coefficients of variation of less than 5%. The optimal plasma dilution in this assay was 1:3000. IgG anti-apoB antisera conjugated to alkaline phosphatase was used as a second antibody. p-Nitrophenyl phosphate was utilized as substrate for color development, and the absorbance (410 nm) was read utilizing an ELISA reader interfaced with a microcomputer for data processing. Plasma apoB levels in plasma have been determined in 1115 male and female participants in the Framingham Offspring Study. Mean (+/- SD) plasma concentrations were 89 +/- 28 mg/dl. Significant age and sex related differences in apoB levels were noted.

Adult↗
PubMed1985

Initial plasma high-density lipoprotein distribution in the rat: effects of age, sex, and fasting.

The initial tissue distribution of high-density lipoprotein (HDL) was studied in the rat. Specific tissue-space measurements, calculated as the difference between HDL and albumin uptake in a tissue, 10 min after injecting radiolabeled lipoprotein, were taken to represent specific binding of HDL. Rat HDL (rHDL) and human HDL3 (hHDL3) were labeled directly with 125I or with prelabeled 125I-apolipoprotein A-I (125I-apoA-I). Specific tissue spaces were demonstrated for the liver and adrenals but not for spleen, jejunum, ileum, colon, muscle, or adipose tissue. The kidney showed a specific HDL space only when 125I-apoA-I-rHDL was injected. The adrenals bound rHDL to a greater extent than hHDL3, and the liver also bound from three to five times more rHDL than hHDL3. In male and female rats the liver accounted for about two-thirds of total HDL bound. Significantly more HDL was bound by adrenals of female than by male rats, but the reverse occurred for liver and kidney. The greater hepatic binding of HDL in males compared to females was consistent with measurements of HDL flux, calculated from constant infusions of labeled HDL; the fractional clearance of 125I-apoA-I-rHDL was 572 +/- 13 microliter plasma X h-1 X 100 g body wt-1 in males and 466 +/- 19 microliter plasma X h-1 X 100 g body wt-1 in females (P less than 0.01). Tissue-space measurements with 125I-rHDL were not affected by age. Fasting for 48 h increased HDL binding by liver but not by adrenals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1984

The effect of dietary casein and soy protein on cholesterol and very low density lipoprotein metabolism in the rat.

Rats fed a high-cholesterol semipurified diet containing casein developed higher levels of serum cholesterol than soy-fed animals. The hypercholesterolaemia of casein-fed rats was due to accumulation of very low density lipoproteins (VLDL), as measured by increased concentrations of serum VLDL cholesterol, protein and apoprotein B. High density lipoprotein (HDL) cholesterol was similar for the two dietary groups. Cholesterol absorption, as measured by the dual isotope ratio method and by direct measurement of cholesterol secretion into thoracic duct lymph, did not differ between the two groups. Cholesterol kinetics were derived from plasma cholesterol specific radioactivity curves and the casein-fed rats had a similar rate of plasma cholesterol production, but a significantly lower plasma cholesterol fractional catabolic rate (FCR) compared with the soy-fed rats. Kinetics of plasma VLDL apoprotein B, derived from analysis of reinjected 125I-labelled VLDL protein, also showed a lower fractional catabolic rate with casein feeding. This suggests that the accumulation of VLDL in the plasma of rats fed dietary casein is not due to excess VLDL production but to deficient VLDL removal. The hypercholesterolaemia appears to be a consequence of diminished VLDL catabolism.

Animals↗