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Biomedical subjects

B Lewis

Publications and source records attributed to B Lewis.

At least 235 records · Page 13Linked to original sources
PubMed1982

Heritability of the low density lipoprotein receptor activity of human blood mononuclear cells: studies in normolipidaemic adult male twins.

1. The concordance of low density lipoprotein (LDL) receptor activity of blood mononuclear cells was examined in 26 pairs of monozygotic and 17 pairs of dizygotic normolipidaemic young adult male twins. 2. Receptor activity was quantified as the degradation of 125I-labelled LDL during a 6 h incubation, after derepression of the cells for 72 h in lipoprotein-deficient medium. 3. The total variance of receptor activity was similar in the two groups of twins. In contrast, within-pair variance was five times greater in dizygotic twins than in monozygotic twins (P less than 0.001). 4. Estimates of heritability, mostly based on the intra-class correlation coefficients (monozygotic, r = 0.83; dizygotic, r = 0.39), ranged from 0.72 to 1.05. 5. These results suggest that the maximal LDL receptor activity of peripheral cells in normolipidaemic subjects is largely genetically determined.

Adolescent↗
PubMed1982

Relationships between the metabolism of high-density and very-low-density lipoproteins in man: studies of apolipoprotein kinetics and adipose tissue lipoprotein lipase activity.

In order to gain further insight into the relationship between high-density lipoprotein (HDL) metabolism and plasma triglyceride transport, measurements were made of HDL cholesterol concentration, apoprotein (apo) AI and AII metabolism, very-low-density-lipoprotein (VLDL) apo B metabolism, and heparin-elutable adipose tissue lipoprotein lipase (LPL) activity in seventeen subjects with a wide range of plasma triglyceride concentrations (0.8-25 mmol/l). The fractional catabolic rate (FCR) of VLDL apo B was directly related to LPL activity (r = +0.80), providing evidence that the activity of the enzyme in adipose tissue is a determinant of the rate of lipolysis of VLDL in man. HDL cholesterol concentration was a positive function of both VLDL apo B FCR (r = +0.74) and LPL activity, a finding consistent with previous evidence for the origin of a proportion of HDL cholesterol from 'surface remnants' liberated during VLDL catabolism. THe FCRs of both apo AI and apo AII were inversely related to VLDL apo B FCR (AI, r = -0.52; AII, r = -0.69) and to LPL activity. The synthetic rate of ap AII, but not that of apo AI, was positively correlated with VLDL apo B synthesis (r = +0.7 1). Thus, the metabolism of the major proteins of HDl in man appears to be closely associated with VLDL metabolism.

Adipose Tissue↗
PubMed1982

Prevalence of ischaemic heart disease and associations with serum lipoproteins in subjects aged 45 to 64 years. The Speedwell study.

A longitudinal study has been set up to examine the incidence of ischaemic heart disease and its associations with serum lipoproteins including high density lipoprotein cholesterol and its subfractions, certain haemostatic factors, and other "risk' factors. We report here on our pilot study findings. Cross-sectional data were available on 283 men and 68 women aged 45 to 64 representing 85% of the available population randomly selected from the lists of 16 general practitioners. Reproducibility of the measurements of total serum cholesterol, triglyceride, and low density lipoprotein cholesterol was acceptable. The reproducibility of some of the other serum lipid fractions, for example high density lipoprotein cholesterol, was less good, in part because of the small range of the values found for these components. Univariate associations of physical and behavioural characteristics and serum lipoproteins of men and women, with and without ischaemic heart disease, disclosed small and statistically nonsignificant differences except for levels of blood pressure. In particular, there was no significant difference in mean levels of serum high density lipoprotein cholesterol between men with ischaemic heart disease (0.91 mmol/l) and men without it (0.94 mmol/l). In examining our data for the determinants of serum high density lipoprotein cholesterol using a linear multiple regression model, sex, serum high density lipoprotein cholesterol, and very low density lipoprotein triglyceride were the major factors, each individually explaining about 7% of the variance of serum high density lipoprotein cholesterol levels. In addition, alcohol intake and obesity each explained a further 2% of the variance. The experience of the pilot study has led to modifications in the collection of blood samples and the subsequent estimation of lipid fractions.

Cholesterol↗
PubMed1981

Towards an improved lipid-lowering diet: additive effects of changes in nutrient intake.

To identify diets that are more effective than existing ones in reducing lipoprotein-mediated risk of atherosclerotic heart disease, the serum lipids and lipoprotein response to three modified diets was studied in twelve normal men living in an institution. The "Western" reference diet (40% energy from fat, P/S ratio 0.27) was compared in Latin square design with a fat-modified diet (diet B, 27% energy from fat, P/S 1.0, reduced cholesterol content); with a fat-modified diet supplemented with fruit, vegetable, and cereal fibre (diet C); and with a diet providing 40% energy from fat, having P/S ratio 1.0 and supplemented by fibre (diet D). The effects of fat modification and fibre-supplementation (diets C and D) were strongly additive-a fall serum cholesterol by 24-29%, in low-density-lipoprotein (LDL) cholesterol by 31-34%, and in serum triglyceride by 21-26%; and the reduction, by diet C, of the ratio of serum cholesterol to high-density-lipoprotein (HDL)-cholesterol by 21%, and that of LDL-cholesterol to HDL2-cholesterol by 26%. The additive effects of multiple changes in nutrient intake, each moderate in extent, permits the design of diets which are remarkably effective in reducing serum-cholesterol level.

Adult↗
PubMed1981

Relation of angiographically defined coronary artery disease to plasma lipoprotein subfractions and apolipoproteins.

The relation of coronary artery disease to plasma lipoproteins was examined in 104 men aged 35-65 years undergoing coronary angiography for suspected myocardial ischaemia. A score reflecting the number, degree, and length of stenoses in seven major coronary arteries was assigned to each angiogram. Lipid concentrations in lipoprotein subfractions were measured after preparative ultracentrifugation; plasma apolipoprotein concentrations were measured by electroimmunoassay. Men with high coronary scores tended to have lower plasma high-density lipoprotein (HDL) cholesterol concentrations and higher low-density lipoprotein (density 1.019-1.063 g/ml) cholesterol concentrations than subjects of similar age with low coronary scores (p approximately equal to 0.1). The strongest relation, however, was with the cholesterol concentration in the HDL2 subfraction (density 1.063-1.125 g/ml) of HDL, which averaged 44% lower in the severely affected patients (p less than 0.005). No associations were found between the coronary score and HDL3 cholesterol, the cholesterol content of lipoproteins of density less than 1.019 g/ml, plasma triglyceride, or the concentrations of apolipoproteins AI, AII, and E. The high coronary scores associated with low HDL2 concentrations reflected an increase in the number of both partial and complete stenoses distributed throughout the coronary tree. In contrast the sizes of the lesions and the proportion producing complete occlusion were unrelated to HDL2.

Adult↗
PubMed1981

Association of isoapolipoprotein-E3 deficiency with heterozygous familial hypercholesterolaemia: implications for lipoprotein physiology.

A prepubertal girl with both homozygous isoapolipoprotein-E3 deficiency (the genetic defect underlying type-III hyperlipoproteinaemia) and heterozygous familial hypercholesterolaemia (familial type-IIa hyperlipoproteinaemia) presented with severe hypercholesterolaemia and antecubital and popliteal planar xanthomas. She responded dramatically to clofibrate. Her mother was normolipidaemic and heterozygous for apo-E3-deficiency. Her father, an obligate apo-E3-deficient heterozygote, and his similarly affected brother died prematurely with severe hypercholesterolaemia which had been refractory to clofibrate. Her paternal grandfather, who had the same combination of disorders as the proband, also responded to clofibrate, whereas her grandmother was normolipidaemic. Hence homozygous apo-E3 deficiency may present during childhood as severe hypercholesterolaemia when combined with familial hypercholesterolaemia, suggesting that the low-density-lipoprotein receptor may represent one mechanism whereby apo-E3-deficient remnants of very-low-density lipoproteins and chylomicrons are cleared from the plasma compartment. The removal of such apo-E3-deficient remnants is especially facilitated by clofibrate.

Apolipoprotein E3↗
PubMed1981

Coronary artery reperfusion in acute myocardial infarction: beneficial effects of intracoronary streptokinase on left ventricular salvage and performance.

Coronary angiography was performed on hospital admission in 37 patients with acute myocardial infarction (AMI). Thirty patients had total occlusion of the infarct-related coronary artery and seven patients had severe proximal stenoses with poor distal flow. In 20 of 30 patients with total occlusion, intracoronary (IC) infusion of streptokinase (SK) resulted in reperfusion of the distal coronary artery. Left ventricular (LV) performance was assessed before coronary angiography and at discharge from the hospital by use of gated cardiac blood pool imaging techniques. In patients evidencing reperfusion of the infarct-related coronary artery, mean (+/- SD) left ventricular ejection fraction (LVEF) increased from admission through discharge (46% +/- 15% to 55% +/- 10%, p = 0.002). In contrast, LVEF did not change from admission through discharge in patients with severe proximal stenoses alone or in patients with total occlusion who did not demonstrate reperfusion following SK administration (47% +/- 17% vs 49% +/- 18%, p = ns). In an additional 14 control patients with AMI who were not evaluated with coronary angiography, LVEF did not change from admission through discharge (46% +/- 12% vs 48% +/- 14%, p = ns). Quantitative thallium-201 perfusion imaging demonstrated an increase (p less than 0.05) in thallium uptake in the infarct segment following coronary artery reperfusion. In contrast, thallium uptake did not change (p = ns) in the infarct segment in patients not evidencing angiographic coronary artery reperfusion. These data support the following : (1) Coronary artery thrombus occurs frequently in AMI and can be lysed by IC SK, and (2) reperfusion with IC SK in patients with evolving myocardial infarction results in myocardial salvage and improved LV performance through hospital discharge.

Coronary Vessels↗
PubMed1981

Flux of plasma lipoproteins into human arterial intima. Comparison between grossly normal and atheromatous intima.

Arterial specimens were obtained from 12 patients during arterial repair surgery and 3 patients during nephrectomy following a bolus injection of autologous radio-iodinated very low density lipoprotein (VLDL) up to 30 h before surgery. Radioactivity in apoprotein B (apo B) was determined in lipoprotein fractions isolated from saline extracts of washed intima in the density ranges less than 1.006 g/ml, 1.006-1.019 g/ml and 1.019-1.063 g/ml [intimal VLDL, intermediate-(IDL) and low density lipoprotein (LDL), respectively]. Specific radioactivity of apo B was measured in corresponding plasma protein fractions. In atheromatous intima, minimum influx rates of VLDL-apo B [12.1 +/- 4.3 (SEM) ng . cm-1 . h-1] and IDL-apo B (13.6 +/- 5.1) over 24 h were significantly higher than fluxes of VLDL-apo B (1.2 +/- 0.34) and IDL-apo B (1.4 +/- 1.1) into normal intima (P less than 0.05). Minimum influx rate of LDL-apo B was also significantly higher in atheromatous intima (196 +/- 39) compared with normal intima (25.8 +/- 13.5, P less than 0.01) and was 16-18 fold higher than corresponding VLDL- and IDL-apo B fluxes in both types of intima. Collagenase digestion of intimal samples after saline extraction yielded further significant mass of VLDL but this fraction had little radioactivity compared with saline extractable VLDL.

Apolipoproteins↗
PubMed1981

Associations between sex hormones, thyroid hormones and lipoproteins.

1. A study of 150 middle-aged male industrial employees has shown significant positive correlations between plasma levels of high-density-lipoprotein (HDL) cholesterol and both serum testosterone and alcohol intake, and significant negative correlations between HDL cholesterol and both serum thyroxine and obesity. These associations persist when examined by multiple linear regression, indicating their independence. 2. Significant positive correlations are also shown between plasma triglyceride levels and both obesity and serum thyrotropic hormone (TSH) levels. 3. There are no evident relationships between serum oestrone or oestradiol and either HDL cholesterol or triglyceride levels, nor between any of the hormones and either total or low-density-lipoprotein (LDL) cholesterol. 4. Because of the potential importance in relation to coronary heart disease prevention, further studies are needed to try and understand the mechanisms of the associations between HDL cholesterol and obesity, alcohol intake and thyroid and sex hormone levels.

Alcohol Drinking↗
PubMed1981

Individual variation in the effects of dietary cholesterol on plasma lipoproteins and cellular cholesterol homeostasis in man. Studies of low density lipoprotein receptor activity and 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in blood mononuclear cells.

The effects of dietary cholesterol on plasma lipoproteins and cholesterol homeostasis in blood mononuclear cells have been examined in healthy adults. Addition of 1,500 mg of cholesterol to the daily diet of 37 subjects for 14 d was associated with a wide range of response of plasma total cholesterol concentration (from -6 to +75 mg/dl; mean change, +29 mg/dl; P < 0.001). Increases in plasma cholesterol reflected increased cholesterol concentrations in intermediate density lipoprotein (IDL; 1.006-1.019 g/ml), low density lipoprotein (LDL; 1.019-1.063 g/ml), and the HDL(2) subclass (1.063-1.125 g/ml) of high density lipoprotein, which on average accounted for 20, 58, and 22%, respectively, of the total increment. Similar responses occurred in 14 other subjects given 750 mg cholesterol per day for 28 d. Plasma apolipoprotein B concentrations in IDL and LDL also increased. THESE EFFECTS ON PLASMA LIPOPROTEINS WERE ACCOMPANIED BY THREE CHANGES IN FRESHLY ISOLATED BLOOD MONONUCLEAR CELLS: (a) an increase in cell cholesterol content (mean change, +17%; P < 0.01); (b) suppression of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity (-32%; P < 0.001); and (c) reduction of LDL receptor activity (-74%; P < 0.01), quantified as the rate of degradation of (125)I-LDL to noniodide trichloroacetic acid-soluble material. These results provide the first direct evidence for the modulation of LDL receptor activity and HMG CoA reductase activity in a peripheral cell type in response to a dietary perturbation of human lipoprotein metabolism.The percentage increase in LDL cholesterol was negatively correlated with the percentage decrease in HMG CoA reductase activity (r = -0.49, P < 0.01). An additional negative correlation existed between the increment in plasma cholesterol concentration and the capacity of cells to degrade (125)I-LDL after derepression by preincubation for 72 h in lipoprotein-deficient medium (r = -0.74, P < 0.001). Thus, differences between individuals in the responses of the plasma lipoproteins to dietary cholesterol appear to be related in part to differences in the capacity of peripheral cells to catabolize LDL and to down-regulate cholesterol synthesis.

Adult↗