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Biomedical subjects

Y Stein

Publications and source records attributed to Y Stein.

At least 109 records · Page 6Linked to original sources

Comparison of plasma lipids, lipoproteins and dyslipoproteinemia in Israel and the United States. The Lipid Research Clinics Program Prevalence Study.

Based on the common study design, protocol, and laboratory techniques used by the Lipid Research Clinics (LRCs), the study reported here compared the adult study populations examined by the U.S. LRCs and the LRC located in Jerusalem, Israel. A number of 2388 residents of Jerusalem were contrasted with 6528 examinees of the U.S. LRCs regarding their plasma lipid and lipoprotein cholesterol distributions. Marked differences between the U.S. and Jerusalem LRCs were observed in the plasma levels of lipids and lipoprotein cholesterol fractions. Mean total cholesterol concentrations were 2-8% higher in the U.S. compared to the Jerusalem sample. Low density lipoprotein cholesterol levels were higher by approximately 5-15% in the U.S. LRCs, a phenomenon more marked in men than women and in older compared to younger study participants. High density lipoprotein cholesterol values were also higher in the U.S. compared to the Jerusalem LRC, by approximately 10-14% in men and women. These differences were also more pronounced in older compared to younger participants. By contrast, median plasma total triglycerides (and by implication very low density lipoprotein cholesterol) were higher in the Jerusalem compared to the U.S. study participants. This difference ranged from 10-21% by age and sex. The correlations between the plasma lipid/lipoprotein measurements were similar in the two study populations. Only the degree of linear association between plasma total triglyceride and very low density lipoprotein cholesterol was different between the U.S. and Jerusalem, with a correlation coefficient of greater magnitude in the latter. Employing common cutpoints to define dyslipoproteinemia (DLP) observed differences in plasma lipid/lipoprotein distributions determined differences in the frequency of DLP categories between the U.S. and the Jerusalem samples. Higher proportions of Type IV and hypo-HDL were observed in Jerusalem compared to the U.S. By contrast, fewer individuals were classified as Type IIa, Type IIb, and hyper-HDL in Jerusalem relative to the U.S.

Adult↗

Analysis of risk factors in 532 survivors of first myocardial infarction hospitalized in Jerusalem.

During the period January 1979-March 1983, we have conducted in Jerusalem a case control study of all patients under the age of 65 surviving their first diagnosed myocardial infarction, in order to evaluate the importance of the conventional risk factors and to detect additional factors through quantifying plasma apolipoprotein concentrations. As a control group, we have chosen a sample from a previously studied Jewish population (LRC study), representative of the adult Jerusalemite population, parents of children born during 1958-1961. To complete the younger age group missing in the LRC population, we added a population studied in the Kiryat Yovel district of Jerusalem. We report here the results obtained from interviews and analysis of 532 cases (448 males and 84 females), and 869 controls (457 males and 412 females). In order to overcome the effects of age and ethnic origin on the risk factors, we have divided our populations according to age and country of origin of their fathers. Age, sex, smoking, history of high blood pressure, diabetes, elevated plasma triglycerides and/or cholesterol, and decrease in plasma HDL cholesterol, emerged as the most powerful and significant risk factors in this study. Other putative risk factors such as socioeconomic status, dietary habits, physical activity and obesity index were not found to be significantly different between cases and controls. It is noteworthy that smoking was more important as a risk factor in the younger age groups, whereas hypertension and diabetes were more important in the older age groups, particularly in females. The differences in lipid levels were considerably more prominent in the young age groups in both sexes. Myocardial infarction was observed more frequently in patients of European or American extractions. Apolipoproteins A-I, A-II, E and B determined in this study were shown to be affected partly by age and country of origin. Apo E and apo B levels were significantly higher and Apo A-I significantly lower in patients with myocardial infarction when compared to controls.

Aged↗

Religious orthodoxy and myocardial infarction in Jerusalem--a case control study.

We examined the hypothesis that the degree of religious orthodoxy is an independent risk factor for coronary heart disease incidence in a study of 454 men and 85 women who experienced a first myocardial infarction. They were compared with a control group of 295 men and 391 women. All were Jewish residents of Jerusalem. The degree of religious orthodoxy was ascertained by interview of participants. Among the cases, 51% of the men and 50% of the women defined themselves as secular compared with 21% and 16%, respectively, among the controls. In a multivariate logistic model (including terms for age, ethnicity, education, smoking, physical exercise, body mass index and religious orthodoxy), the coefficients for age and smoking were positive and statistically significant, and those for education negative and significant. The risk for European born subjects was greater than for the other ethnic origin groups (statistically significant only in men). Secular subjects had a significantly higher risk of myocardial infarction compared to orthodox subject (odds ratio of 4.2 (95% confidence interval 2.6-6.6) for men and 7.3 (95% confidence interval 2.3-23.0 for women). This relationship was independent of the other variables in the model. The relation persisted in a subsample of cases who were examined 2-3 months after the acute phase of the infarction upon controlling for plasma cholesterol, high density lipoprotein cholesterol and hypertension. This finding should be substantiated. It would appear important to identify the components of religiosity associated with reduced risk.

Adolescent↗

Comparison of nutrient intakes of selected populations in the United States and Israel: the Lipid Research Clinics prevalence study.

Nutrient intakes of 2,772 US and 2,680 Jerusalem participants of the Lipid Research Clinics Program were assessed by 24-h dietary recall in men aged 15-19 and 40-59 yr and women aged 15-19 and 35-59 yr. Energy intake was higher in the US than in Jerusalem. In Jerusalem intake of total fat ranged between 32.2-33.7% of kcal, of saturated fatty acids (SFA) between 9.8-10.9%, of polyunsaturated fatty acids (PFA) between 7.9-8.6%, of carbohydrates between 50.5-53.9%, and of starch between 24.0-30.5%. The P:S ratio ranged between 0.80 and 1.01. The corresponding ranges for the US were 38.8-40.8% for fat, 14.3-15.9% for SFA, 5.9-6.8% for PFA, 38.9-46.2% for carbohydrates, 17.0-17.9% for starch, and 0.40-0.53 for the P:S ratio. Intake of cholesterol (mg/1000 kcal) was higher in Jerusalem than in the US. These data address the feasibility of reducing fat in diets of free-living, Western populations.

Adolescent↗

Biological and environmental sources of variation in plasma lipids and lipoproteins: the Jerusalem Lipid Research Clinic.

We have previously described a general pattern of homogeneity in genetic and cultural determinants of blood lipids and lipoproteins among the major origin groups in the Israeli population. This paper reports on these determinants of total plasma cholesterol (TC), triglyceride (TG), low- and high-density lipoprotein cholesterol (LDL-C, HDL-C), and of the HDL-C/TC ratio, estimated from the total sample of 4,000 families whose members were examined in the Jerusalem Lipid Research Clinic. Both genetic (h2) and cultural (c2) components of inheritance were significant for all lipid variables. Under the most parsimonious model genetic heritability (h2) ranges from 0.45 for LDL-C, 0.47 for HDL-C to 0.64 for HDL-C/TC ratio. Cultural heritability (c2) was 0.03 for LDL-C, 0.04 for TC, 0.05 for TG and 0.07 for HDL-C and HDL-C/TC ratio. Within this population, as in others, genetic factors appear to be the major determinants of lipid variation, suggesting relative homogeneity of environmental correlates of plasma lipids.

Adolescent↗

Blood group and height in a multiethnic population.

In a sample of 4,472 boys, aged 17-18 years, resident in Jerusalem, those with blood groups B or AB tended to be slightly shorter than groups O and A (p = 0.011). Participants were classified into 8 groups according to father's country of origin: Israel, Southern Europe/Balkans, rest of Europe, North Africa, Iraq, Iran, Yemen and the rest of Asia. The association of ABO blood group, classified according to the presence of the B antigen (groups B and AB) or its absence (O and A), with height differed in the 8 origin groups (p = 0.026 for interaction). In 7 of the 8 groups, subjects with the B allele were either shorter or of equal height to groups O and A and in only one instance were they taller. These findings do not support the generalizability of a positive association of the presence of the B antigen with height suggested by Borecki et al. [1985].

ABO Blood-Group System↗

Effect of moderate isocaloric modification of dietary carbohydrate on high-density lipoprotein composition and apolipoprotein A-1 turnover in humans.

Plasma lipid and apolipoprotein (apo) levels were determined in five normolipidemic subjects and five patients with Type IV hypertriglyceridemia (HTG) who were fed for greater than or equal to 6 weeks on two isocaloric diets. The first diet contained carbohydrates (CHO) as 55% of total calories, 29% as fat and 16% as protein. The second diet contained 40% CHO, 45% fat and 15% protein in normolipidemic subjects and 40% CHO, 41% fat and 19% protein in patients with HTG. All diets had a cholesterol content of approximately 400 mg/day and a polyunsaturated/saturated fatty acid ratio of approximately 1:0. Apo A-1 kinetics were measured during the last 2 weeks of each dietary period. The composition and distribution of high-density lipoproteins (HDL), subclasses HDL2 and HDL3, were determined at the end of each dietary term. In the HTG patients, administration of a 40% compared with 55% CHO diet caused a significant decrease of plasma triglyceride levels and an increase of HDL-cholesterol; low-density lipoprotein (LDL) levels increased and very low-density lipoprotein (VLDL) levels decreased (P less than 0.01 and less than 0.07, respectively). Similar quantitative changes of VLDL and HDL levels were found in the normolipidemic subjects. No significant change in plasma levels of apo A-I, A-II and E occurred. Apo A-I kinetic studies revealed decreased synthetic rates and fractional catabolic rates on the low CHO diet. Separation of HDL subfractions by zonal ultracentrifugation in both groups revealed an increase in HDL3-cholesterol ester and protein, and a decrease in HDL2 protein, phospholipid and cholesterol. Our findings indicate that moderate changes in dietary CHO and fat content affect HDL levels, composition and apo A-I metabolism.

Adult↗

Endogenous plasma lipoprotein lipase activity in fed and fasting rats may reflect the functional pool of endothelial lipoprotein lipase.

In this study, a correlation was sought between the circulating lipoprotein lipase activity and nutritional state in the rat. In fed rats, the plasma lipoprotein lipase activity was between 30 and 120 munits/ml, whereas after an overnight fast in restraining cages, the lipoprotein lipase plasma levels were between 280 and 500 munits/ml. The plasma lipoprotein lipase activity was inhibited by a specific high titre goat antiserum to rat lipoprotein lipase. No effect of fasting was seen on the plasma hepatic triacylglycerol lipase. 6 h after fasting, adipose tissue lipoprotein lipase decreased maximally, but plasma lipoprotein lipase was not changed and rose only after 16 h. Thus, it seems that most of the lipoprotein lipase activity in the fasting plasma was related to the 3-fold rise in lipoprotein lipase activity in the heart, which may represent total muscle lipoprotein lipase. The increase in heart lipoprotein lipase was due in part to an increase in the t1/2 of the enzyme from 1.2 to 2.9 h. To determine whether the high plasma levels in the fasting rats might result from impaired clearance of the enzyme by the liver, functional hepatectomy was carried out. 15 min after hepatectomy, plasma lipoprotein lipase rose up to 20-fold in fed and about 6-fold in fasting rats. Lipoprotein lipase activity extracted by the liver was calculated to be 30-60 munits/ml in the fed and 171-247 munits/ml plasma per min in fasting rats. An increase in lipoprotein lipase activity in extrahepatic tissues (heart, lung, kidney, diaphragm and adrenal) occurred 30 min after hepatectomy in fed rats. The increase in heart lipoprotein lipase was due to an increase in heparin-releasable fraction. Since no impairment of hepatic clearance of circulating plasma lipoprotein lipase was found, the high fasting plasma lipoprotein lipase activity may be related to an increase in enzyme synthesis, decreased enzyme turnover and an expansion of the functional pool in tissues such as the heart and probably muscle. The present findings indicate that measurement of endogenous plasma lipoprotein lipase can provide information with respect to the size of the functional pool under normal and pathological conditions.

Animals↗

Importance of the different steps of glycosylation for the activity and secretion of lipoprotein lipase in rat preadipocytes studied with monensin and tunicamycin.

Lipoprotein lipase synthesized by cultured rat preadipocytes is present in three compartments: an intracellular, a surface-related 3-min heparin-releasable, and that secreted into the culture medium. 30 min after addition of 6 microM monensin, the lipoprotein lipase activity in the heparin-releasable compartment starts to decrease; by 4 h of monensin treatment the lipoprotein lipase activity in the heparin-releasable pool and in the culture medium is about 10% of that found in control dishes. The intracellular activity, which had been identified as lipoprotein lipase by an antiserum to lipoprotein lipase, increases slowly and doubles by 24 h. However, since the cellular compartment accounts for 10-25% of total activity, this increase does not account for the missing enzyme activity. To determine whether this enzyme molecule is synthesized but is not active, incorporation of labeled leucine, mannose and galactose into immunoadsorbable lipoprotein lipase was studied in control, monensin- or tunicamycin-treated cells. Addition of tunicamycin (5 micrograms/ml) for 24 h caused a 30-50% reduction in immunoadsorbable lipoprotein lipase, but the enzyme activity was reduced by 90%. On the other hand, 4 h monensin treatment reduced both incorporation of [3H]leucine into immunoadsorbable lipoprotein lipase and heparin-releasable and medium lipoprotein lipase activity by 57 to 77%. The immunoadsorbable lipoprotein lipase in the intracellular compartment has a [14C]mannose to [3H]galactose ratio of 0.15 and this ratio increased 6-fold in monensin-treated cells. The intracellular lipoprotein lipase in monensin-treated cells had the same affinity for both the native and synthetic substrate as the lipoprotein lipase in control cells, yet its spontaneous secretion into the culture medium and its release by 3 min heparin treatment was markedly decreased. The present results indicate that: the presence of asparagine-linked oligosaccharide (formation of which is inhibited by tunicamycin) is mandatory for the expression of lipoprotein lipase activity; lipoprotein lipase is active also in a high mannose form; and terminal glycosylation and oligosaccharide processing, which is inhibited by monensin, may be important for the appearance of heparin-releasable lipoprotein lipase and secretion of lipoprotein lipase into the medium.

Adipose Tissue↗

Coffee, tea, and plasma cholesterol: the Jerusalem Lipid Research Clinic prevalence study.

The association of intake of coffee and tea, assessed by 24 hour dietary recall, with plasma cholesterol and its lipoprotein fractions was studied in a sample of 1007 men and 589 women aged 35-64 resident in Jerusalem. These cross sectional data showed a significant linear association (p less than 0.001) between consumption of coffee in men and plasma cholesterol and low density lipoprotein cholesterol concentrations. Men who drank five cups of coffee or more had plasma cholesterol concentrations about 0.5 mmol/l (20 mg/100 ml) higher than non-drinkers after controlling for age, ethnicity, body mass, education, season of year, smoking, tea drinking, and dietary intake of fat and carbohydrates. In women adjusted mean plasma cholesterol concentration was 0.34 mmol/l (13 mg/100 ml) higher in coffee drinkers grouped together (p less than 0.01). The test for a linear trend was not significant. The association in both sexes was largely with the low density lipoprotein cholesterol fraction. High density lipoprotein cholesterol concentrations were somewhat increased in women who drank coffee (p less than 0.01 for a linear trend) but not in men. Tea drinking was not associated with unadjusted plasma cholesterol concentrations in either sex. Male tea drinkers, but not female, had slightly higher adjusted plasma cholesterol concentrations than non-drinkers (0.15 mmol/l (6 mg/100 ml), p = 0.04). No dose response relation was evident. In this population, characterised by a low intake of saturated fatty acids and relatively low mean plasma cholesterol concentrations, coffee drinking may be a determinant of low density lipoprotein cholesterol concentrations.

Adult↗

Angiotensin II stimulates receptor-mediated uptake of LDL by bovine adrenal cortical cells in primary culture.

Bovine adrenal cells were isolated from the subcapsular region of the gland to obtain cultures enriched in cells of the zona glomerulosa. The cells kept in primary cultures were shown to respond to angiotensin II and adrenocorticorticotropin (ACTH) by a significant increase in aldosterone production. These primary adrenal cultures were used to study the effect of angiotensin II on LDL metabolism. Addition of angiotensin II for 48 h to the culture medium resulted in a 200-300% increase in LDL metabolism, and the lowest effective concentration was 10(-8) -10(-9) M. The angiotensin II effect became evident after 12-16 h of incubation. To compare the metabolism of the 125I-labeled protein moiety to that of cholesteryl ester of LDL, the lipoprotein was labeled also with cholesteryl linoleyl ether, a nonhydrolyzable analog of cholesteryl ester. Under basal conditions and in the presence of angiotensin II or ACTH the ratio of [3H]cholesteryl linoleyl ether to 125I indicate some preferential uptake of the cholesteryl ester moiety. Stimulation of specific LDL binding at 4 degrees C and LDL metabolism at 37 degrees C by 10(-7) M angiotensin II occurred at all concentrations of LDL studied. Linearization of the kinetic data showed that angiotensin II increased the LDL receptor number significantly but not the affinity of the LDL receptor for its ligand. The present findings indicate that in analogy to ACTH, angiotensin II can influence receptor-mediated uptake of LDL by adrenal cortical cells. It remains to be shown whether the angiotensin II effect on LDL metabolism is limited to adrenal cells or will affect other cells which express the angiotensin II receptor.

Adrenal Cortex↗

Putative role of cholesteryl ester transfer protein in removal of cholesteryl ester from vascular interstitium, studied in a model system in cell culture.

A model system to study the putative role of cholesteryl ester transfer protein in the egress of interstitial cholesteryl ester is described. Confluent cultures of bovine aortic smooth muscle cells were labeled for 24 h with [3H]cholesteryl linoleyl ether and [14C]cholesteryl linoleate by incubation with bovine milk lipoprotein lipase. This method of labeling results in the transfer of cholesteryl linoleyl ether and cholesteryl ester to three compartments: a trypsin-releasable, trypsin-resistant and catabolic compartment (Stein, O., Halperin, G., Leitersdorf, E., Olivecrona, T. and Stein, Y. (1984) Biochim. Biophys. Acta 795, 47-59). The efflux of labeled cholesteryl linoleyl ether and cholesteryl ester from the extracellular and cell-surface related compartments into a serum-free culture medium containing 1% bovine serum albumin was studied during 24 h of postincubation. The efflux was expressed as a percentage of pulse value, i.e., radioactivity retained by the cell culture at the end of the labeling period. The efflux of [3H]cholesteryl linoleyl ether, [14C]cholesteryl ester and 14C-labeled free cholesterol (formed by cellular hydrolysis of cholesterol ester) into the culture medium with 1% bovine serum albumin was about 5% of the pulse value. Addition of human lipoprotein-deficient serum resulted in a 3-10-fold increase in the efflux of [3H]cholesteryl linoleyl ether and [14C]cholesteryl ester, but did not change markedly the efflux of 14C-labeled free cholesterol. Rat lipoprotein-deficient serum which does not contain cholesteryl ester transfer protein did not increase the efflux of [3H]cholesteryl linoleyl ether or [14C]cholesteryl ester. The rate of cholesteryl ester efflux in the presence of human lipoprotein-deficient serum was linear for about 6 h and increased further up to 24 h. Addition of Intralipid to medium containing human lipoprotein-deficient serum further enhanced the efflux of [3H]cholesteryl linoleyl ether and, to a lesser extent, that of cholesteryl ester. A similar effect was observed also by addition of rat VLDL to medium containing human lipoprotein-deficient serum. Inhibition of cholesteryl linoleyl ether and cholesteryl ester efflux and marked enhancement of free cholesterol efflux occurred when rat HDL was added to medium containing human lipoprotein-deficient serum, while human HDL was only slightly inhibitory. The results obtained with human lipoprotein-deficient serum were reproduced with partially purified cholesteryl ester transfer protein. Using the partially purified cholesteryl ester transfer protein, the efflux of cholesteryl linoleate was compared to that of cholesteryl oleate and was found to be the same.

Animals↗

Aggregation of plasma lipids and lipoproteins in families with and without coronary heart disease.

Familial aggregation of total plasma cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) was analyzed in 37 families with incidence cases of first myocardial infarction (MI), in 154 families of coronary heart disease (CHD) prevalence cases and in control families. Fasting plasma lipid levels were adjusted for age, sex, country of origin and season of year. Mean TC, LDL-C and TG levels were higher among cases, their spouses and among 17-year-old children of incidence cases than among control families. HDL-C was lower among cases and among wives of incidence cases than in their controls. No differences in HDL-C were noted among children. Mid parent-child correlations for TC and LDL-C were higher in 32 families of men who had a MI (r = 0.43 and r = 0.49) than for control families (r = 0.32 and r = 0.29, respectively). When the 5 families of mothers who had a first MI were included in the analysis, the case-child correlations for TC and LDL-C were 0.60 and 0.68, respectively. Father-child correlation for HDL-C was significantly lower (r = -0.17) among the MI incidence case families than among the control families (r = 0.22; P less than 0.05). No substantial differences in familial correlations for lipid variables were noted in the CHD prevalence families and their controls. These findings suggest that total cholesterol and LDL-C levels, but not HDL-C levels, may be a risk marker in adolescents. The associations evident in adolescent children of families with MI incidence cases were not apparent in children whose parents had CHD on entering the study. This could be due to the probably greater misclassification of CHD prevalence cases than MI incidence cases, the awareness in patients with CHD and subsequent behavioural changes, to possible differences in patterns of survival in the two categories, or may reflect a chance finding.

Adolescent↗

Endometrial carcinoma stage I--comparison of two different treatment regimes--evaluation of risk factors and its influence on prognosis; suggested step by step treatment protocol.

Two hundred twenty-four patients with stage I endometrial carcinoma were treated between the years 1964 and 1978. One hundred and fifteen patients were classified as clinical stage Ia (51.3%) and 109 patients as clinical state Ib (48.7%). For stage Ia the standard treatment protocol was total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH + BSO). In stage Ib disease, preoperative irradiation was performed followed by TAH + BSO after an interval of 4 to 6 weeks. Postoperative irradiation to the pelvis and vaginal vault was given when extrauterine spread was found and in cases of myometrial penetration beyond the inner one-third of the myometrium. At evaluation in May 1983, the rate of disease recurrence in stage Ia was 20% and in stage Ib 9.1%. Five-year survival in stage Ia was 77.3% and 72.4% in stage Ib. Preoperative irradiation was found justified for G3 disregarding the clinical stage, therefore the approach of routine preoperative irradiation in stage Ib is not recommended. The uterine cavity depth was found to be an inaccurate prognostic parameter. According to the data collected in our material the histological grade and myometrial invasion are much better prognostic parameter and should be taken into consideration while planning the treatment regime.

Adenocarcinoma↗

Coronary heart disease risk factors among religious groupings in a Jewish population sample in Jerusalem.

The hypothesis that plasma lipids, blood pressure, smoking and dietary intake differed according to degree of religiosity was examined in a sample of Jewish residents of Jerusalem. Religiosity was classified according to the subject's self-ranking of his perceived degree of religiosity. Prevalence of smoking, and plasma levels of cholesterol, triglycerides, and low-density lipoprotein cholesterol were higher in secular participants than in the orthodox group. No differences in blood pressure and in high-density lipoprotein cholesterol were observed. Secular subjects consumed more total fat, more saturated fatty acids and less carbohydrate than religious subjects. These differences in nutrient intake among the religious groups reflected differences in their food selection, notably consumption of dairy products. These findings of parallel differences in plasma lipids and in dietary intake are consistent with the differing incidence of myocardial infarction in the religious groups which has been shown in the Israeli population.

Adolescent↗