UMLS:C0020473 - FACTA Search

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Query: UMLS:C0020473 (hyperlipidemia)
15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methods for quantitation of the major apoproteins of human serum very low density lipoprotein have been developed employing tetramethylurea, which delipidates the lipoprotein and selectively precipitates apolipoprotein B. Six soluble apoproteins are separated by electrophoresis in polyacrylamide gel. One of these is a previously unrecognized species of R-alanine (R4-alanine), more anionic than the R3-alanine polypeptide. Conditions of staining have been found which yield reproducibly linear chromogenic response with native lipoprotein and with each purified apoprotein. Recovery of protein in the seven species measured accounts for over 97% of the total in the very low density lipoprotein of normolipidemic individuals and in most samples from individuals with endogenous hyperlipemia. The mean content of apolipoprotein B in 43 samples from normolipidemic subjects was 36.9(+/-1.2 SEM)% of total protein, The distribution of the major soluble apoproteins as mean (+/-SEM) percentage of the soluble fraction was : R-serine, 5.3+/-o.5; arginine-rich, 20.6+/-1.0; R-glutamic, 10.6+/-0.4; R2-alanine, 28.3+/-0.7; R3-alanine, 26.9+/-0.5; and R4-alanine, 8.0+/-0.5. Distribution of the apoproteins was a function of particle diameter of very low density lipoprotein in fractions separated by gel permeation chromatography and by density gradient ultracentrifugation. In fractions below 700-800 A, apolipoprotein B comprised an increasing percentage of the total protein with decreasing particle diameter. Among the soluble proteins the percentage of the arginine-rich and R-serine polypeptides increased and that of the R-glutamic polypeptide declined progressively with decreasing particle size. Apoprotein distribution was similar in fractions of similar particle size from normolipidemic and hyperlipemic subjects with the exception that all fractions from the hyperlipemic subjects contained more R-serine and some, more arginine rich polypeptide. Even in the absence of chylomicrons, the distribution of soluble apoproteins in particles of diameters greater than 700-800 A was usually similar to that of the smallest particles. This suggests that the largest particles may include products of the partial catabolism of chylomicrons.
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PMID:Apoprotein composition of very low density lipoproteins of human serum. 17 34

We have shown that the circulating lipoproteins of the mouse contain a potent inhibitor of infectivity of the xenotropic type C virus. This virus neutralization does not involve immunoglobulins or complement. After fractionation of the lipoproteins on the basis of particle size, flotation properties, and electrostatic charge, virus neutralizing activity is found primarily in the triglyceride-rich lipoproteins (predominantly the chylomicrons) and in the HDL(2) subfraction of the high density lipoproteins. In fasted animals, activity resides chiefly in the high density lipoproteins. Neutralization titers increase strikingly during alimentary lipemia in both the lipoproteins of the rho < 1.006 g/cm(3) fraction and the high density lipoproteins. Increased activity persists in the high density lipoproteins after the lipemia recedes. Virus neutralizing activity is completely eliminated in all fractions by antiserum against high density lipoproteins and, in the triglyceride-rich fractions, by antiserum to murine apolipoprotein B. Complete removal of lipids markedly reduces the neutralizing activity of both classes of lipoproteins. Apolipoproteins delipidated with tetramethylurea retain some activity, which is enhanced by binding to a phospholipid-stabilized triglyceride emulsion and which is abolished by proteolytic digestion. We have demonstrated in vitro transfer of activity between high density and very low density lipoproteins of the mouse. These data indicate that xenotropic virus neutralization by normal mouse serum depends upon a protein that transfers among lipoprotein particles in a fashion analogous to the C apolipoproteins of other mammalian species.
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PMID:Apolipoprotein is responsible for neutralization of xenotropic type C virus by mouse serum. 23 Apr 95

Investigations performed in a patient with myeloma, hyperlipidemia, and xanthomatosis demonstrated the antilipoprotein activity of the monoclonal IgA directed against an antigenic site--called Ra.--different from those previously described. A complex IgA beta-lipoprotein has been firstly characterized. After isolation and purification of the IgA, it has been shown that the association between IgA and lipoprotein was immunologically mediated. The antibody is an IgA lambda bound via its Fab portion and in fixed combining ratio to an antigenic determinant shared only by LDL and VLDL of humans and some other mammalians to the exclusion of any other serum proteins. The results obtained with passive hemagglutination and inhibition of hemagglutination suggest that the antigenic site Ra. is not located on apoprotein B (major proteic moiety of LDL and VLDL), since the antigenic determinants of apolipoproteins are different in humans and in animals and since IgA Ra. fails to react with apolipoprotein B obtained by delipidation of LDL. On the other hand, the lack of reaction between IgA Ra. and HDL suggests that the antigenic determinant is not only present on the lipid hapten such as in the case of PG and AS determinants which are located on VLDL, LDL, and HDL from humans and animals. So the antigenic determinant revealed by IgA Ra. seems to be different from those previously described.
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PMID:[Monoclonal myelomatous IgA with antilipoprotein antibody activity of Ra specificity (author's transl)]. 51 6

Plasma cholesterol, triglyceride and apolipoprotein B were measured in healthy women during pregnancy. Hyperlipidaemia was most marked in the third trimester of pregnancy, but the increases in cholesterol, triglyceride and apolipoprotein-B were not identical (14, 74 and 36%, respectively). The increase in plasma cholesterol was due to a progressive rise in very low density (VLDL) and low density (LDL) lipoproteins. There was a change in composition and size of both VLDL and LDL, demonstrated by a reduction in the ratio of cholesterol to apolipoprotein-B and altered properties of both lipoproteins on polyacrylamide gradient gel electrophoresis. It is difficult to explain these changes but they did not appear to be related to growth hormone, oestrogens or progestogens.
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PMID:Plasma lipoproteins in pregnancy. 100 19

Experimental studies have demonstrated regression of atheromatous lesions with diet and lipid lowering drugs. In order to confirm these results clinically, reliable angiographic methods of analysis must be developed along two lines: quantitative by consensus between independent "blinded" experts, qualitative by digitalizing radiological images. Given the reproducibility of these methods, a variation of 17 to 20% in the size of the atheromatous plaques should be required to affirm a change. Five studies have been performed in patients with atherosclerosis associated with variable degrees of hyperlipidaemia and compared with a control group. NHLBI type II: 59 out of 146 patients with type II hyperlipoproteinaemia were treated with cholestyramine for 5 years with reduction of the progression of > 50% stenosis but no evidence of regression (6%). CLAS: 80 out of 160 coronary patients were treated with cholestipol and nicotinic acid for 2 years and a reduction of progression and a regression of lesions were observed in 16% of cases. Nikkila: 28 coronary patients with hyperlipidaemia were given clofibrate or nicotinic acid for a 7 year period, stabilising the evolution but with no signs of regression. FATS: 74 of 120 coronary patients with apolipoprotein B concentrations of over 1.25 g/l were given lovastatine-cholestipol or nicotinic acid-cholestipol for 2.5 years: regression of coronary lesions was observed in 32 to 39% of cases depending on the treatment administered. Olsson: reported the same results for femoral atheroma with treatments associating fenofibrate and nicotinic acid: 20% regression and reduction of progression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Evaluation of trials on regression of atheromatous lesions with hypolipemic drugs]. 128 2

Fenofibrate and other fibrate derivatives are commonly used to treat hyperlipidemia. It is not yet clear how they exert their modulatory effects on plasma lipoproteins. To investigate whether these drugs act on the liver to primarily inhibit very low density lipoprotein production, we utilized the highly differentiated human hepatoma cell line, Hep G2. At concentrations greater than 15 micrograms/mL, fenofibrate caused a 30% decrease in secreted apolipoprotein B (apo B) after 4 days of treatment. Pulse-chase studies demonstrated that this was not due to inhibition of apo B synthesis. Triglyceride synthesis by fenofibrate-treated Hep G2 cells was decreased by 30%, and the amount secreted into the medium was reduced by 50%. At a low concentration of drug (5 micrograms/mL), triglyceride secretion was reduced markedly while apo B secretion remained unchanged. Thus, apo B secretion is less sensitive to fenofibrate than the synthesis and secretion of triglyceride, and may be secondary to changes in the latter. Fenofibrate has also been shown to raise plasma high density lipoprotein concentrations. We found that low concentrations of fenofibrate caused a 20-101% increase in secreted apolipoprotein AI (apo AI), and pulse-chase immunoprecipitation studies showed that this was due to an increase in apo AI synthesis. Fenofibrate was compared to clofibrate to investigate whether their relative effects on lipoprotein production in Hep G2 cells were comparable to their relative effects on plasma lipoproteins. Both fibrates decreased the secretion of apo B to the same extent, but only fenofibrate increased apo AI secretion. Fenofibrate was more effective than clofibrate in inhibiting the secretion of lipids by these cells. Thus, the known effects of fenofibrate on plasma lipoproteins can be attributed to its direct modulation of lipoprotein synthesis in the liver cell. Hep G2 cells may thus be useful in testing the relative efficacy of fibric acid derivatives in vitro.
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PMID:Modulation of lipoprotein production in Hep G2 cells by fenofibrate and clofibrate. 131 85

Lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A inhibitor, was given to 14 patients with unremittent nephrotic syndrome (heavy proteinuria with hyperlipidaemia) for 6 months. Treatment was started at an initial dose of 20 mg/day, increasing to a maximum of 80 mg/day. Treatment was well tolerated except in two patients: one developed rhabdomyolysis and one severe hypertriglyceridaemia requiring an additional antihyperlipidaemic agent. Lovastatin was effective in reducing serum cholesterol, LDL-C and apolipoprotein B in the remaining 12 patients. Cholesterol was reduced by 31% from 8.24 +/- 0.49 mmol/l (mean +/- SEM) to 5.7 +/- 0.18 mmol/l after 6 months (P less than 0.001). LDL-C was normalized to 3.26 +/- 0.21 mmol/l from a pretreatment value of 5.76 +/- 0.48 mmol/l (P less than 0.001), a decrease of 43%. Serum apolipoprotein B was also normalized to 1.11 +/- 0.09 g/l from a basal level of 1.51 +/- 0.10 g/l (P less than 0.05). Triglyceride, HDL-C and apolipoprotein A1 concentrations were unchanged. Proteinuria as well as renal albumin clearance were unchanged. GFR by plasma radioisotope Cr-EDTA clearance for the whole group was unaltered by treatment. However, among those with relatively good pretreatment renal function (GFR greater than 70 ml/min per 1.73 m2), GFR increased at the end of 6 months' treatment (118.2 +/- 15 ml/min per 1.73 m2 versus 77.6 +/- 8.4 ml/min per 1.73 m2 in wash-out phase).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lovastatin in glomerulonephritis patients with hyperlipidaemia and heavy proteinuria. 131 86

1. The effect of inhibiting the rate-limiting enzyme (3-hydroxy-3-methylglutaryl-CoA reductase, EC 1.1.1.88) in cholesterol synthesis on plasma lipid and lipoprotein concentrations was investigated in 16 patients with primary glomerular disease, heavy proteinuria, well-preserved renal function and hypercholesterolaemia. 2. Detailed studies of low-density lipoprotein metabolism were performed on eight patients before and after 12 weeks of simvastatin therapy. Radioiodinated tracers were used to quantify the fractional catabolic rate of low-density lipoprotein by apolipoprotein B/E receptors and alternative pathways. 3. Simvastatin produced consistent reductions in total plasma cholesterol concentration (median 36.9%), plasma low-density lipoprotein-cholesterol concentration (43.6%) and apolipoprotein B pool size (29.9%). 4. In contrast, the changes in kinetic parameters of low-density lipoprotein metabolism showed no clear pattern. Although an increase in the receptor-mediated catabolism of low-density lipoprotein was demonstrated in five patients, no change or a slight decrease was seen in three patients. Production rates were not significantly altered, although there was a slight decrease in the median value (from 12.4 to 9.7 mg day-1 kg-1). Plasma lathosterol concentration was reduced in all eight patients (range 34-71%), indirectly confirming significant inhibition of cholesterol synthesis. 5. These results suggest that, as in patients with primary moderate hyperlipidaemia, the significant cholesterol-lowering effect of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors in the nephrotic syndrome is accompanied by variable changes in lipoprotein metabolism. The reasons for this heterogeneous response are unclear. This reflects our limited understanding of the metabolic basis of nephrotic hyperlipidaemia and the relationship between hepatic sterol synthesis and plasma lipoprotein kinetics.
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PMID:Effect of simvastatin on plasma lipid and lipoprotein concentrations and low-density lipoprotein metabolism in the nephrotic syndrome. 132 May 52

The purpose of this study was to examine the change in apolipoprotein and lipoprotein levels in patients with normolipidemic untreated non-insulin-dependent diabetes mellitus (NIDDM). Fifteen untreated, non-obese male NIDDM patients without hyperlipidemia were chosen, and 15 healthy subjects, matched for age, sex, body weight, alcohol consumption and cigarette smoking served as the control group. We observed that the concentrations of plasma total cholesterol (TC), triacylglycerol (TG) and very low density lipoprotein cholesterol (VLDL-C) were identical in both NIDDM and control groups. The levels of low-density lipoprotein cholesterol (LDL-C) were slightly increased in the diabetic group, but the difference did not reach statistical significance in our study. High-density lipoprotein cholesterol (HDL-C) was lower in the NIDDM group than in the controls. Significantly increased TC/HDL-C and LDL-C/HDL-C ratios were found in NIDDM patients compared with controls. The apolipoprotein A-I (apo A-I) and apolipoprotein A-II (apo A-II) levels were decreased in NIDDM patients, while the apolipoprotein B (apo B) level remained similar to that of the control subjects. The ratio of apo A-I/apo B was decreased significantly in the NIDDM group. Our results suggest that NIDDM patients are at higher risk of coronary heart disease, even if they remain normolipidemic.
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PMID:Apolipoprotein levels in normolipidemic non-insulin-dependent diabetes mellitus. 135 44

Three male patients with hyperlipidaemia were given daily infusions of dextran over a period of 10 days. Plasma levels of total cholesterol, LDL and HDL cholesterol, apolipoprotein B and AI and triglycerides were analysed after the infusion of dextrans different in dose and molecular size. Dextrans caused alterations of some plasma lipids and lipoproteins exceeding the haemodilution effect. The degree of lipid lowering depends on the volume and molecular size of the administered dextran.
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PMID:[Effect of low and high molecular weight dextrans on selected serum lipid parameters. 1]. 137 26

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