Apolipoprotein B gene DNA polymorphisms are associated with macro- and microangiopathy in non-insulin-dependent diabetes mellitus.

The relationship between diabetic macroangiopathy or microangiopathy and apolipoprotein B (apoB) polymorphism was studied in 139 male and 129 female patients with non-insulin-dependent diabetes (NIDDM) mellitus, comprising consecutive patients with poor diabetic control (HBA1 13.2% +/- 2.7 (SD)) referred to our hospital.

A comparative study of 1H NMR lineshape fitting analyses and biochemical lipid analyses of the lipoprotein fractions VLDL, LDL and HDL, and total human blood plasma.

The purpose of this work was two-fold. In the first instance, 1H NMR spectra of the ultracentrifuged lipoprotein fractions (VLDL, LDL and HDL) from six volunteers with different clinical conditions were measured. The methylene regions of the experimental spectra were modelled in the frequency domain using non-linear lineshape fitting analyses.

Evaluation of plasma cholesteryl ester transfer protein (CETP) activity as a marker of alcoholism.

Plasma cholesteryl ester transfer protein (CETP) activity was measured in 52 alcoholics and 38 controls and compared with conventional laboratory markers of alcoholism. Mean daily alcohol intake was 180 g/day among the alcoholics and 10 g/day among the controls. Plasma CETP activity was 26% lower in the alcoholics (P < 0.

Reduction in the concentration and activity of plasma cholesteryl ester transfer protein by alcohol.

Plasma cholesteryl esters, synthesized within high density lipoproteins (HDL), may be transferred from HDL particles to other lipoproteins by plasma cholesteryl ester transfer protein (CETP). Alcohol consumption is associated with increased HDL cholesterol concentration and reduced plasma CETP activity. The alcohol-induced decrease in CETP activity may be due to a low concentration of CETP in plasma or the inhibition of CETP by specific inhibitor proteins or alterations in the composition of plasma lipoproteins.

Carbamylation-induced alterations in low-density lipoprotein metabolism.

Low-density lipoprotein was derived from carbamyl (carbamyl-LDL) by incubating LDL in potassium cyanate (KCNO). The proportion of free amino groups in the carbamyl-LDL was negatively correlated (r = -0.95) with the time of incubation in potassium cyanate (ranged from 5 to 360 min).

Prevalence and geographical distribution of major LDL receptor gene rearrangements in Finland.

In order to determine the prevalence of major rearrangements of the low density lipoprotein (LDL) receptor gene in Finland, DNA samples of 199 unrelated Finnish patients with the heterozygous form of familial hypercholesterolaemia (FH) were examined by Southern blot analysis. The FH-Helsinki mutation, characterized by a 9.5-kb deletion in the 3'-end of the LDL receptor gene, was found in 75 (38%) of the patients.

Low density lipoprotein derivatization by acetaldehyde affects lysine residues and the B/E receptor binding affinity.

Acetaldehyde (AcA), the first metabolite in ethanol oxidation, forms covalent adducts with the free amino groups of various proteins. In this study, we examined how acetaldehyde modification affects the chemical and biological properties of the atherogenic low density lipoprotein (LDL). AcA modification did not alter the protein and lipid composition of LDL, but the AcA concentration used in the incubation correlated strongly with the electrophoretic mobility of acetaldehyde-treated LDL (AcA-LDL) (r = 0.

Multiple changes in apoprotein B containing lipoproteins after ethanol withdrawal in alcoholic men.

The plasma concentrations and chemical compositions of the apolipoprotein B containing lipoproteins (VLDL, IDL and LDL) were studied in 29 male alcoholic subjects at the end of a drinking period and in 17 healthy controls. No difference was found in the concentrations of plasma total cholesterol and triglyceride between the alcoholics and the controls, whereas plasma HDL cholesterol and VLDL triglycerides were 90% and 73%, respectively, higher in the alcoholics. The VLDL cholesterol:triglyceride ratio was reduced by 32%, whereas VLDL protein:cholesterol and phospholipid:cholesterol ratios were increased by 36% and 46%, respectively.

A lineshape fitting model for 1H NMR spectra of human blood plasma.

A lineshape fitting model was constructed for classifying the overlapping information in the 1H NMR spectrum of human blood plasma. A reliable assignment of the overlapping fatty acid (-CH2-)n and -CH3 resonances of the various lipoproteins (VLDL, very low density lipoprotein; LDL, low density lipoprotein; HDL high density lipoprotein) is introduced, and for the first time detailed characteristics (chemical shifts, half linewidths, and relative intensities) of the individual lipoprotein components were obtained directly from the whole plasma spectrum. This was achieved by combining the constructed lineshape fitting model and the proper 400 MHz proton NMR measurements from blood plasma of a healthy donor, from fractions of the different lipoproteins, and from plasma samples in which the lipoprotein fractions were separately added.

Screening for a prevalent LDL receptor mutation in patients with severe hypercholesterolaemia.

A rapid new method for the diagnosis of familial hypercholesterolaemia (FH) detects the deletion extending from intron 15 to exon 18 in the low density lipoprotein (LDL) receptor gene, i.e. the FH-Helsinki mutation responsible for a major portion of FH in Finland.

Magnitude of dietary effects on plasma cholesterol concentration: role of sex and apolipoprotein E phenotype.

The effects of fat-controlled, low-cholesterol and high-fat, high-cholesterol diets pursued for 4 weeks on plasma lipids and lipoproteins were studied in 44 healthy middle-aged subjects (22 women and 22 men). All the calories were supplied from the hospital kitchen. When the subjects were switched from the fat-controlled, low-cholesterol diet to the high-fat, high-cholesterol diet the average increase in total cholesterol was 1.

A rapid increase in lipoprotein (a) levels after ethanol withdrawal in alcoholic men.

Plasma concentrations of lipoprotein (a) (Lp(a)) were studied in 11 male alcoholics at the end of a drinking period and monitored during subsequent abstinence. Lp(a) levels showed a daily increase for four consecutive days after the beginning of abstinence, the values for the third and the fourth day being significantly higher than those of the first day (p less than 0.05 and p less than 0.

Increased high-density lipoprotein cholesterol concentration in alcoholics is related to low cholesteryl ester transfer protein activity.

Cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl esters from HDL to apoB-containing lipoproteins. Since alcoholics have high HDL cholesterol and low LDL cholesterol levels, a defect in cholesteryl ester transfer could be responsible for the alcohol-induced alteration in cholesterol distribution between lipoproteins. To test this hypothesis, we compared CETP activity in plasma from 30 alcoholics without severe liver damage and 16 control subjects.

Acetaldehyde binding increases the catabolism of rat serum low-density lipoproteins.

Acetaldehyde was found to form adducts with rat serum lipoproteins. The binding of [14C]acetaldehyde to lipoproteins was studied at low concentrations which are known to exist during ethanol oxidation. The amount of lipoprotein adducts was a linear function of acetaldehyde concentration up to 250 microM.

Pathogenesis of the hypertriglyceridemia at early stages of alcoholic liver injury in the baboon.

To study the mechanism of alcoholic hypertriglyceridemia, baboons were pair-fed liquid diets containing 50% of energy as ethanol or as additional carbohydrate for 5-16 months. Alcohol-fed animals developed hypertriglyceridemia and early stages of alcoholic injury, namely fatty liver with or without perivenular fibrosis. In the fasting state, the triglyceride content was sixfold higher in very low density (VLDL) and intermediate density (IDL) lipoproteins and twofold higher in low density (LDL) and high density (HDL) lipoproteins.

Effects of chronic ethanol intake on mobilization and excretion of cholesterol in baboons.

To investigate the effects of chronic ethanol administration on the mobilization and excretion of cholesterol, turnover and balance studies were carried out in baboons pair-fed cholesterol-free diets containing 50% of energy either as ethanol or as additional carbohydrate for several years. Ethanol feeding increased free cholesterol in all plasma lipoprotein fractions, and esterified cholesterol in very low density lipoprotein, intermediate density lipoprotein, and high density lipoprotein (HDL). The major increase occurred in HDL, mainly as esterified cholesterol.

Plasma HDL cholesterol and blood glucose in non-insulin-dependent diabetics related to liver lipids and microsomal enzyme activity.

The major lipid predictors of coronary events, plasma high density lipoprotein cholesterol (HDL-C) and the HDL-C/total cholesterol (T-C) ratio, and blood glucose (BG) in 12 subjects with non-insulin-dependent diabetes mellitus were related to hepatic lipids, proteins and microsomal enzyme activity assessed by liver cytochrome P-450 (P-450). Non-insulin-dependent diabetics had low HDL-C/T-C ratio, liver phospholipid (PL) and P-450 and high serum and liver triglyceride (TG) concentrations. Plasma HDL-C was decreased, and BG high, especially in subjects with reduced PL and P-450.

Relationship between lipid composition and drug metabolizing capacity of human liver.

The relationship between hepatic glycerolipids and microsomal drug-metabolizing enzymes was studied in liver biopsies from 41 subjects. The series included obese, diabetic, epileptic and chronic alcoholic patients, all of whom were hospitalized for suspected hepatic ailments (fatty liver, hepatitis or cirrhosis). Therapy with enzyme-inducing anticonvulsants was associated with high phospholipid and cytochrome P-450 and low triacylglycerol concentration in the liver.

Hepatic triacylglycerol synthesizing activity during progression of alcoholic liver injury in the baboon.

To study the effects of alcoholic liver injury on the ability of ethanol to promote hepatic fat accumulation and hyperlipemia, baboons were pair-fed liquid diets containing 50% of energy either as ethanol or as additional carbohydrate (controls) for 1 to 7 years. Alcohol consumption produced triacylglycerol accumulation in the liver, hypertriacylglyceridemia, and various degrees of liver injury, including cirrhosis. At the early stages of fatty liver (with or without perivenular fibrosis), there was increased activity of microsomal diacylglycerol acyltransferase and of both microsomal and cytosolic phosphatidate phosphohydrolase, with no changes in glycerol-3-phosphate acyltransferase.

Ethanol and lipids.

The interaction of ethanol with lipid metabolism is complex. When ethanol is present, it becomes a preferred fuel for the liver and displaces fat as a source of energy. This favors fat accumulation.

Plasma high-density lipoproteins and liver lipids and proteins in man. Relation to hepatic histology and microsomal enzyme induction.

The association of high-density lipoproteins (HDL) in plasma with liver lipids and proteins was investigated in 28 subjects with diagnostic liver biopsy. Lipids and proteins were evaluated in relation to hepatic histology and microsomal enzyme induction, assessed by liver cytochrome P-450. Moderate-severe hepatic parenchymal changes were associated with low liver phospholipids, protein and cytochrome P-450, low plasma HDL cholesterol (HDL-C), and high hepatic triglycerides.