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Biomedical subjects

Y Stein

Publications and source records attributed to Y Stein.

At least 145 records · Page 8Linked to original sources

Hepatic retention and elimination of cholesteryl linoleyl ether after injection of labeled acetylated LDL or chylomicrons.

Rat mesenteric duct chylomicrons labeled with [3H]cholesteryl linoleyl ether and human acetylated low density lipoproteins labeled with [14C]cholesteryl linoleyl ether were injected simultaneously into rats. 3 h after injection 80-90% of the injected radioactivity were recovered in the liver and the ratio of 3H/14C in the liver was the same as in the injected material. The 3H/14C ratio declined gradually over a period of 18 days due to loss of [3H]cholesteryl ether which had been injected with the chylomicrons, and retention of the same compound injected bound to acetylated LDL. The loss from the liver of the chylomicron-bound cholesteryl linoleyl ether was shown to occur through the bile, and its elimination from the body was verified by monitoring fecal excretion. The present results provide evidence that hepatic persistence of a nonhydrolyzable analog of cholesteryl ester is a function of the cell type which has ingested the lipid. Thus, the uptake of labeled chylomicrons by hepatocytes results in a slow but progressive excretion of the nonhydrolyzable lipid through the bile, while the preferential uptake of acetylated LDL by nonparenchymal cells of liver and by the spleen leads to persistence of the lipid in the organ.

Acetylation↗

Transfer of cholesteryl linoleyl ether from phosphatidylcholine and phosphatidylethanolamine liposomes to cultured cells catalyzed by lipoprotein lipase.

Unilamellar liposomes prepared from purified phospholipids (phosphatidylcholine, phosphatidylethanolamine or sphingomyelin) and labeled cholesteryl linoleyl ether were used to study lipoprotein lipase-catalyzed transfer of cholesteryl ester into cells in culture. In mesenchymal rat heart cell cultures, the transfer of cholesteryl linoleyl ether and cholesteryl linoleate was similar and related to the activity of endogenously produced lipoprotein lipase. In human skin fibroblasts transfer of labeled cholesteryl linoleyl ether was proportional to the concentration of milk lipoprotein lipase added to the incubation medium. Liposomes prepared from phosphatidylcholine or phosphatidylethanolamine were much better donors of cholesteryl ether to normal and apolipoprotein E-B receptor-negative fibroblasts and to endothelial cells than those prepared from sphingomyelin. Lysophosphatidylcholine was formed during incubation with milk lipoprotein lipase but was not considered to be directly responsible for the lipoprotein lipase-catalyzed transfer of cholesteryl ether. This conclusion was drawn because in the absence of lipoprotein lipase addition of lysophosphatidylcholine to liposomes, or almost complete phospholipolysis by phospholipase A2, did not result in the transfer of cholesteryl linoleyl ether from liposomes to cells. Attachment of lipoprotein lipase to the cell surface was mandatory for the transfer of cholesteryl ether and could be prevented by heparin. High density apolipoprotein reduced also the transfer of cholesteryl linoleyl ether, even though it did not interfere with the binding of labeled milk lipoprotein lipase to cultured fibroblasts. The present results provide evidence that lipoprotein lipase, and not the products of phospholipid hydrolysis, is the ligand for the non-apolipoprotein E-B receptor-mediated transfer of cholesteryl ester to cells.

Animals↗

Risk factors for coronary heart disease among Jerusalem schoolchildren: preliminary findings.

The presence of risk factors for cardiovascular diseases were investigated in 7- and 11-year-old schoolchildren (808 subjects). Data analysis was performed according to sex, age, and country of origin of the father. The following variables were investigated: weight, height, total plasma cholesterol (TCH), high density lipoprotein cholesterol (HDL), plasma triglycerides, and systolic and diastolic blood pressure. Significant differences were found between sex, age, and origin groups for most variables. The prevalence of hypercholesterolemia (greater than 180 mg/dl) varied between 9.6 and 14.1%, in the different sex and age groups, and that of low HDL cholesterol (less than 40 mg/dl), 6.8-12.1%. Elevated systolic blood pressure (greater than 130 mm Hg) was found in 4.4-6.7% of the 7-year-old children, and in 13,4-18.6% of the 11 year-olds. Elevated diastolic blood pressure (greater than 85 mm Hg) was found predominantly in the 11-year-old children, 6.2-9.1%. These findings demonstrate the necessity to initiate health programs related to prevention of cardiovascular diseases in childhood.

Blood Pressure↗

Admixture analysis of high density lipoprotein cholesterol distribution in a Jerusalem population sample.

The distribution of high density lipoprotein cholesterol values (HDL-C) in 2003 nuclear families (including both parents and one child aged 17) participating in the Jerusalem Lipid Research Clinic survey, were analyzed by a maximum-likelihood procedure for evidence of bimodality. HDL-C was age-sex adjusted by the mean-variance method to 17 year old male levels. After covariance adjustment for Quetelet's index, season, education and social class, when using untransformed data a mixture of two distributions fitted the data significantly better than one distribution in both sexes. The results indicated that 4.7% of males and 14.1% of females came from an upper distribution with mean values of 2.15-3.15 standard deviations above the major mode. We next applied the MacLean et al. (1976) method of transformation and used a maximum-likelihood method in which the skewness parameter was estimated jointly with the other parameters of the model. When the data were transformed the mixture of two distributions fitted the data significantly better than one for males only. We tested a mixture of three normal distributions and estimated that 6% of both males and females belonged to a higher distribution, while 1% came from a lower distribution. This model did not provide a significantly better fit to the data than a mixture of two distributions. Our findings imply that in the Israeli population there is evidence for an admixture in the distribution of HDL-cholesterol. Segregation analysis is necessary in order to determine whether a major gene or some environmental factors are responsible for the commingling detected.

Adolescent↗

Binding of lipoprotein lipase to the cell surface is essential for the transmembrane transport of chylomicron cholesteryl ester.

Four cell types, F1 rat heart cells, rat preadipocytes, human skin fibroblasts and bovine endothelial cells, were used to investigate whether surface binding of lipoprotein lipase was essential in the transmembrane transport of chylomicron cholesteryl ester. Exposure of F1 heart cells to colchicine resulted in decrease in endogenous surface-bound lipoprotein lipase and a concomitant fall in the uptake of chylomicron cholesteryl linoleyl ether, a nondegradable analog of cholesteryl ester. Uptake of chylomicron cholesteryl linoleyl ether was enhanced by addition of milk lipoprotein lipase and this enhancement also persisted in the presence of colchicine. The drug did not reduce surface binding to the enzyme. Milk lipoprotein lipase was bound to the cell surface of the different cell types and its fate during chase in enzyme-free medium was determined. The t 1/2 of surface-bound enzyme in endothelial cells and in F1 heart cells was about 2 h; it was 4 h in skin fibroblasts. The decrease in surface-bound lipoprotein lipase was accompanied by a parallel fall in the binding and uptake of chylomicron cholesteryl linoleyl ether by the various cell types examined. This decrease in the uptake of cholesteryl linoleyl ether occurred even though lipoprotein lipase activity in the medium was present, as evidenced by the hydrolysis of [14C]triacylglycerol. Release of surface-bound endogenous or exogenous lipoprotein lipase by heparin was accompanied by almost complete elimination of uptake of cholesteryl linoleyl ether in presence of complete hydrolysis of [14C]triacylglycerol. The present results indicate that the transmembrane transport of cholesteryl ester is catalyzed by lipoprotein lipase only when the enzyme is bound to the cell membrane.

Adipose Tissue↗

Fate of milk 125I-labelled lipoprotein lipase in cells in culture. Comparison of lipoprotein lipase- and non-lipoprotein lipase-synthesizing cells.

Radioiodinated lipoprotein lipase, isolated from bovine milk (125I-labeled milk lipoprotein lipase) was shown to retain full hydrolytic activity towards its native substrate, i.e., chylomicron triacylglycerol. The 125I-labeled enzyme interacted with various cells in culture by being bound to the cellular surface, internalized and degraded. Cellular binding of the labeled enzyme occurred in the presence or absence of substrate and was related to enzyme concentration. Heparin reduced cellular binding by 50% but inhibited uptake and degradation more extensively. Cellular uptake was not affected by chloroquine or NH4Cl, but degradation of the labeled enzyme was blocked. Uptake and degradation were not inhibited by mannose 6-phosphate. The interaction between the exogenous enzyme and cells which do not synthesize lipoprotein lipase, i.e., fibroblasts and endothelial cells, resulted in a high ratio of surface binding to degradation. In heart cell cultures and preadipocyte cultures, which produce lipoprotein lipase, the ratio of enzyme catabolized to that bound was high at all time points examined. Since in the intact organism lipoprotein lipase acts at the luminal surface of vascular endothelium, it seems expedient that these cells are able to bind the enzyme, but will catabolize it only slowly. The rapid and extensive degradation of the 125I-labeled lipoprotein lipase in heart cells and preadipocytes may be related to the metabolism of the endogenously produced lipoprotein lipase.

Adipose Tissue↗

Long-lived labeling of phagocytic cells with analogs of atheroma lipids.

[3H]Trioleyl glyceryl ether and [3H]cholesteryl linoleyl ether were bound to Intralipid and injected intraperitoneally into mice. About 20% of the injected label was recovered from peritoneal macrophages up to 2 weeks after injection, and there was a gradual appearance of the label in the liver. Following injection of acetylated low density lipoprotein, labeled with [3H]trioleyl glyceryl ether, into rats, about 90% of the label appeared in the liver shortly after injection and all label was retained up to 73 days. The findings indicate that [3H]cholesteryl linoleyl ether and [3H]trioleyl glycerol can serve as non-degradable analogs of atheroma lipids, which are readily taken up by macrophages when presented in the form of appropriate substrates. These preliminary results serve as basis for experiments designed to study the role of macrophages in the transport of atheroma lipids.

Animals↗

Association arrays for comparing familial total cholesterol, high density lipoprotein cholesterol, and triglyceride similarity in the Israeli population by country of origin.

The method of association arrays is applied to plasma total cholesterol, triglyceride, and high density lipoprotein cholesterol concentrations measured for 2485 young men and women aged 17-18 years and living in Jerusalem, and for their parents. These triad families are divided into five groups according to whether they were of mixed "origins." Stronger associations are present for all lipid and lipoprotein cholesterol variables in Asian and African families relative to families of other origins, possibly reflecting the more disciplined life-style patterns in these families relative to other families. Parent and offspring values exhibit positive association for all lipid variables in all groups. Patterns of familial similarity revealed by the association arrays are discussed in relation to historic and cultural differences among groups.

Adolescent↗

Seasonal changes in plasma lipid and lipoprotein levels in Jerusalem.

Seasonal variations were observed for fasting total plasma cholesterol, high-density lipoprotein-cholesterol (HDL-C), estimated low-density lipoprotein-cholesterol (LDL-C), and the ratio of HDL-C to total cholesterol (TC), measured in 5,244 middle-aged men and women in Jerusalem. HDL-C was highest in winter and lowest in summer, and triglycerides showed a mirror image of this pattern. TC and LDL-C followed a more complex wave form, levels of these being high in the winter, decreasing to a trough in the summer and increasing rapidly to a peak in the autumn. The ratio of HDL-C to TC was lowest in early autumn and highest in winter and early spring. There were two- to fivefold changes in the prevalence of hypercholesterolemia, hypertriglyceridemia and high LDL-C according to the season of examination. These findings imply that clinicians should take season into account when diagnosing hyperlipidemia and when evaluating apparent success or failure in its treatment. Studies of lipid distributions and of interventions aimed at lipid modification need to consider the potentially confounding effects of season.

Cholesterol↗

The Jerusalem Lipid Research Clinic: sampling, response and selected methodological issues.

The Jerusalem Lipid Research Clinic examined 8,646 17-yr-old youngsters and 6,952 of their parents in order to obtain information on the distribution of plasma lipids and lipoproteins in the free-living multiethnic population of Jerusalem. Sampling procedures and recruitment methods are described, and the degree to which the study population was representative of the target population is addressed in detail. Sources of response bias, although not likely to have influenced the results of analyses to date, are identified, and biased portions of the sample will be excluded from further analyses. Selected methodological problems unique to the Jerusalem Lipid Research Clinic are discussed.

Adolescent↗

Plasma lipids and lipoproteins in adult Jews of different origins: the Jerusalem Lipid Research Clinic prevalence study.

Plasma cholesterol, triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C) were measured in a cross-sectional sample of 6,952 middle-aged Jerusalem residents in 1976-79, using the protocols and methods of the North American Lipid Research Clinics (LRC) prevalence studies. There were highly significant variations between groups of Jews of different origin. Age-adjusted levels of total cholesterol were about 10 mg/dl higher in European- and Israeli-born men and women than in immigrants from North Africa or Asia. TG levels showed a similar pattern in men, but the reverse in women. HDL-C levels were 2 to 4 mg/dl higher in European- and Israeli-born women than in female immigrants from Asia or North Africa. In men there was little variation of HDL-C by origin, but males showed significant ethnic differences in the proportion of HDL-C in total cholesterol, while females did not.

Adult↗

Plasma cholesterol, triglyceride and high-density lipoprotein-cholesterol levels in 17-year-old Jerusalem offspring of Jews from 19 countries of birth.

The distribution of plasma cholesterol, triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C) was examined in 6,654 17-yr-old young men and women who attended an army medical examination. There were highly significant differences among the four main groups, classified according to their father's place of birth: Israel, the Asian Near East, North Africa and Europe (including the Americas, Oceania and Southern Africa). Mean levels of plasma cholesterol in each group varied in males from 126.9 to 137.4 mg/dl, TG from 72.1 to 77.8 mg/dl and HDL-C from 41.3 to 44.4 mg/dl. In females, the cholesterol levels ranged from 144.6 to 154.8 mg/dl, TG from 72.7 to 76.3 and HDL-C from 47.3 to 50.5 mg/dl. In the various groups, subjects of North African origin consistently had the lowest lipid values, and subjects whose fathers were born in Europe or Israel, the highest. When the subjects were classified according to their fathers' specific country of origin, mean cholesterol values ranged from a low of 126.2 mg/dl in Moroccan males to a high of 143.0 in Austrian and Swiss males, and from 137.6 mg/dl in Tunisian females to 161.6 in those whose fathers had emigrated from North American countries. HDL-C ranged in males from 40.0 mg/dl in the Egyptian group to 47.0 in the Austrian-Swiss-Lichtenstein group; in females, the values ranged from 46.0 mg/dl in the Algerian group to 53.4 in the Austrian-Swiss-Lichtenstein group. These findings are discussed in light of published reports of lipid and lipoprotein levels in individuals living in different countries.

Adolescent↗

Contributions of different lipoprotein fractions to variations in total cholesterol between Israeli origin groups and social classes.

Total cholesterol, triglycerides and high-density lipoprotein (HDL)-cholesterol were measured in 2,306 boys, 1,716 girls, 2,479 fathers and 2,822 mothers examined on Visit 1 of the Jerusalem Lipid Research Clinics Prevalence Study in 1976-79. Low-density lipoprotein (LDL)-cholesterol levels were estimated from the other three measurements. Using multiple regression analysis to control for body mass index, social class, season of the year and (in parents) age, we compared the three origin groups (Asian, North African and European, depending on the birthplace of the parents) with the Israeli-born group. In both fathers and mothers, the lower total cholesterol levels in the North African group, and to a lesser extent in the Asian, were explained mainly by lower LDL-cholesterol in these groups. In youngsters, the origin groups were characterized by differences not only in LDL-cholesterol, but also in other lipoprotein fractions. Social class in youngsters and mothers was associated mainly with the HDL-cholesterol fraction; in fathers it was associated only with triglycerides. Possible relationships of these findings to smoking, alcohol, exercise and female sex hormones are discussed.

Adolescent↗

Familial aggregation of total cholesterol, triglyceride and high-density lipoprotein-cholesterol in an Israeli population sample.

An analysis of factors involved in the determination of cholesterol, triglyceride and high-density lipoprotein-cholesterol (HDL-C) variables is presented. The Jerusalem Lipid Research Clinic tested a population sample of 3,118 youngsters aged 17 to 18 yr and their parents. In 233 of these families, another sibling was examined at age 17 to 18 yr. Analysis was performed after adjustment of fasting lipid variables for age and sex effects. Since the Israeli population is heterogeneous, the families studied were classified by the parents' country of birth into four groups in which both parents had originated from the same country and one group in which each parent had originated from a different continent. Father-mother correlations for plasma lipid variables were relatively high in parents born in the same country and low in those from different continents. This result could be due to common genetic factors or perhaps to environmental factors shared by parents in early life. The midparent-child correlations were higher for cholesterol and HDL-C in all four groups where parents originated from the same country and lower in the heterogeneous group, but these differences were not statistically significant. The parent-child correlations for total cholesterol and HDL-C were between 0.21 and 0.32, and for triglyceride between 0.09 and 0.20. Sib-sib correlations were significantly positive for all three plasma lipids measured. Although mother-child correlations were stronger than those for father-child, this difference was only significant for HDL-C. The estimated heritability coefficients were between 0.30 and 0.54 for cholesterol and HDL-C and lower for triglyceride. These results provide evidence for familial aggregation of plasma cholesterol, triglyceride and HDL-C in an Israeli population, and they indicate that much of the variation in lipid variables can be explained by genetic factors.

Adolescent↗

Reported physical activity and blood lipids in Jerusalem adults.

The association of physical activity and fasting plasma lipids and lipoproteins was studied in an adult Jerusalem population consisting of 1,095 men and 614 women. Participants were questioned about habitual physical activity, and the relationship of their reported levels of activity of fasting lipid and lipoprotein values was examined. After adjustment was made for age, ethnic origin, body mass, season, cigarette smoking and alcohol consumption, the following associations were found: 1) an inverse association of reported physical activity with triglyceride, total cholesterol and very low-density lipoprotein-cholesterol (not significant), and 2) a significant positive association between reported activity and high-density lipoprotein-cholesterol in men. These findings generally confirm results found in other Western populations. Too few women reported moderate or strenuous physical activity to permit an examination of lipid associations in women.

Adult↗