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P N Demacker

Publications and source records attributed to P N Demacker.

At least 145 records · Page 8Linked to original sources
PubMed1986

Studies on the relationship between the cholesterol content in total high density lipoprotein and its subfractions, HDL2 and HDL3 in normo- and hyperlipidemic subjects.

Total high density lipoprotein (HDL) cholesterol and cholesterol in its main subfractions, HDL2 and HDL3, were determined in 160 normo- and 90 hyperlipidemic subjects by density gradient ultracentrifugation (range of HDL-cholesterol: 0.05-2.85 mmol/l). Both in the normolipidemics and in the combined group HDL3-cholesterol (HDL3-chol) as well as HDL2-cholesterol (HDL2-chol) showed a parabolic relationship with total HDL-chol. The results indicate, that at low total HDL-chol values almost all cholesterol is present in the HDL3 fraction, which shows a linear increase with total HDL-chol from 0 to 0.75 mmol/l. At a further increase of total HDL-chol, cholesterol is increasingly isolated in the HDL2-fraction, especially when HDL3-chol has reached its maximum (about 1.25 mmol/l). Thus, the magnitude of the absolute intra-individual variation of either HDL3-chol or HDL2-chol (in mmol/l) is related to the total HDL-chol concentration. Given the strong correlation between cholesterol in both HDL-subfractions with total HDL-chol and the inverse relationship of total HDL-chol with the risk for coronary heart disease, a rise in HDL3-chol or in HDL2-chol may be equally favorable.

Adult↗
PubMed1986

A study of the hypolipidemic effect of estrogen in type III hyperlipoproteinemia.

Ethinylestradiol (1 microgram/kg/day during 15 days) resulted in a gradual decrease of serum cholesterol, serum triglycerides (TG), very low density lipoprotein (VLDL) cholesterol and VLDL-TG in 2 postmenopausal women and 2 men with type III hyperlipoproteinemia (HLP). The turnover rate of VLDL-TG did not change. These findings contrast with previous observations in normal subjects and patients with type IV HLP. Thus, the catabolism of VLDL and VLDL-remnants increased during treatment with estrogen in type III HLP, probably by direct degradation of VLDL-remnants because in the initial days of treatment no increase of LDL-cholesterol was observed.

Adult↗
PubMed1986

Evaluation of the dual-precipitation method for determination of cholesterol in high-density lipoprotein subfractions HDL2 and HDL3 in serum.

We compared the dual-precipitation method for measurement of cholesterol in high-density lipoprotein subfractions HDL2 and HDL3 (Gidez et al., J Lipid Res 1982;23:1206-33) with density-gradient ultracentrifugation in a swinging-bucket rotor (Demacker et al., Clin Chem 1983;29:656-63). The concentration of dextran sulfate 15,000 (DS) needed for optimal accuracy of the HDL2-chol and HDL3-chol values was established empirically. At a DS concentration of 0.87 g/L, the values for HDL2-chol as well as for HDL3-chol in 88 sera did not differ significantly from those obtained by ultracentrifugation. The precision of the method was satisfactory and was related to the concentration. Nevertheless, the dual-precipitation method lacks specificity inasmuch as it produces no fractions that contain only one HDL subfraction. HDL2 and HDL3 each contained an equivalent amount of cholesterol from the other. At increasing DS concentrations, some radiolabeled HDL3 appeared to have precipitated prior to complete precipitation of HDL2. This lack of specificity can be tolerated in large-scale epidemiological studies for screening, but not in small-scale intervention studies or in assay of clinical samples, where better accuracy is needed and ultracentrifugation is preferred.

Centrifugation, Density Gradient↗
PubMed1985

A comparative study of the effects of acipimox and clofibrate in type III and type IV hyperlipoproteinemia.

Acipimox, an analogue of nicotinic acid, is a hypolipidemic drug with antilipolytic activity. Ten patients with type III and 10 with type IV hyperlipoproteinemia participated in a comparative open cross-over study of the effect of acipimox (750 mg/day) and clofibrate (2 g/day) on lipoproteins, apoliproproteins and postheparin lipase activities during 6 weeks. During acipimox treatment 2 type III patients complained of flushing, resulting in one drop-out. In the type III patients serum cholesterol decreased 30% (P less than 0.01) during treatment with acipimox and 24% (P less than 0.01) with clofibrate, and serum triglycerides 48% (P less than 0.01) and 34% (P less than 0.01), respectively. In the type IV patients serum cholesterol remained unchanged and serum triglycerides decreased 34% (P less than 0.05) and 35% (P less than 0.01), respectively. HDL cholesterol increased during treatment with both drugs in both groups between 6 and 15% (P less than 0.05) mainly due to a rise in HDL3 cholesterol (d greater than 1.100 g/ml). LDL cholesterol increased significantly during treatment with clofibrate, but not with acipimox. There were no or slight changes in the apoproteins A and B. Postheparin lipoprotein lipase increased during clofibrate treatment and hepatic lipase decreased during acipimox treatment. We concluded that acipimox in a dose of 750 mg/day has a similar hypolipidemic effect as 2 g clofibrate daily in type III and IV hyperlipoproteinemia.

Adult↗
PubMed1985

A comparative study on serum lipids and atherosclerotic plaque formation in diet-induced and familial hypercholesterolemia in rabbits, and the effect of partial ileal bypass.

Aim of the present study was to compare an alimentary and a hereditary rabbit model for hypercholesterolemia. Serum lipids, serum lipoproteins and distribution and prevention of atherosclerotic plaque formation were studied in (1%) cholesterol-fed NZW rabbits and both heterozygous and homozygous WHHL rabbits. Cholesterol-fed NZW rabbits showed a hypercholesterolemia without hypertriglyceridemia, caused by accumulation of a spectrum of cholesterol ester-rich beta-migrating lipoproteins with a relatively low density. The WHHL rabbits displayed both a hypercholesterolemia with an elevation of LDL, and a hypertriglyceridemia. The hypertriglyceridemia in the WHHL homozygotes was due to accumulation of VLDL remnants and in the heterozygotes to a slight rise in normal pre-beta VLDL. Despite the pronounced quantitative and qualitative differences in lipoproteins, the location and extent of atherosclerotic plaques which had developed after 13 weeks cholesterol-rich diet in NZW rabbits and in 10 months old homozygous WHHL rabbits, was quite similar. Partial ileal bypass surgery lowered serum cholesterol in all three groups and also prevented atherogenesis.

Animals↗
PubMed1984

Partial ileal bypass reduces the production rate of low density lipoproteins in Watanabe heritable hyperlipidemic rabbits.

Partial ileal bypass surgery in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits resulted in a decrease of low density lipoproteins (LDL)-cholesterol from 14.2 +/- 2.4 to 7.0 +/- 1.2 mmol/l. To investigate the effect of partial ileal bypass on receptor-mediated and receptor-independent LDL catabolism, turnover studies were performed of radiolabeled native LDL and chemically modified LDL (methyl-LDL) in WHHL rabbits after partial ileal bypass, in WHHL control rabbits, and in New Zealand White ("normal") rabbits. The plasma LDL pool in WHHL control rabbits was increased 10-fold. The receptor-mediated LDL clearance was essentially zero in WHHL rabbits, both in controls and after ileal bypass surgery; the fractional catabolic rates for total LDL were equal in both WHHL groups and were also similar to that for methyl-LDL in the normal rabbits. Seventy percent of the total LDL clearance in the normal rabbits occurred via the LDL receptor pathway. In the animals with a partial ileal bypass, the plasma LDL-protein pool was appreciably lower than in WHHL controls (41.6 +/- 5.7 vs 73.4 +/- 9.9 mg/kg, P less than 0.02). The absolute catabolic rate was almost 50% lower in the PIB group (21.4 +/- 2.0 vs 40.0 +/- 7.5 mg X kg-1 X day-1, P less than 0.02). These results indicate that the decrease of LDL after partial ileal bypass surgery in WHHL rabbits is the result of a reduced production rate of LDL.

Animals↗
PubMed1984

Familial apolipoprotein CII deficiency: a preliminary analysis of the gene defect in two independent families.

We have used a cDNA clone for human apolipoprotein CII (apo CII) to study the apo CII genes in two independent individuals with familial apo CII deficiency. With all the restriction enzymes so far used, gene fragments hybridising with apo CII cDNA are observed that are indistinguishable from normal samples. This demonstrates that in neither of these individuals is the defect due to a major deletion of DNA in or around the apo CII gene. We have used a common polymorphism of the apo CII gene detected with the enzyme TaqI to follow the inheritance of the gene in the families of these apo CII deficient individuals. The pattern of inheritance that we observe is consistent with the defect causing apo CII deficiency being in, or closely linked to the apo CII structural gene.

Apolipoprotein C-II↗
PubMed1984

Serum lipids, lipoproteins and apolipoprotein E phenotypes in relatives of patients with type III hyperlipoproteinaemia.

Eighty-six relatives of nineteen probands with type III hyperlipoproteinaemia were studied to determine the occurrence of hyperlipidaemia and to investigate the relation between apo E phenotypes, the occurrence of hyperlipidaemia, and the composition of the very low density lipoprotein (VLDL) fraction. Thirty-nine relatives were hyperlipidaemic: four type IIa or IIb, nine type III and twenty-six type IV. The predisposition for hyperlipidaemia was independent of the apo E phenotype. Hyperlipidaemic relatives with apo E phenotype E2/2 had a significantly (P less than 0.01) higher VLDL-cholesterol/VLDL-triglycerides ratio (1.26 +/- 0.35, n = 9) than those heterozygous for apo E allele epsilon 2 (0.66 +/- 0.12, n = 23) or without apo E allele epsilon 2 (0.69 +/- 0.11, n = 7). Normolipidaemic homozygous apo E-2 relatives had also a significantly (P less than 0.05) higher ratio (0.97 +/- 0.19, n = 6) than those heterozygous for (0.77 +/- 0.19, n = 31) or without the apo E allele epsilon 2 (0.74 +/- 0.13, n = 10). Thus, both hyper- and normolipidaemic apo E2 homozygotes have higher concentrations of VLDL remnants than the subjects heterozygous or without allele epsilon 2.

Adult↗
PubMed1984

Five methods for determining low-density lipoprotein cholesterol compared.

We evaluated three precipitation methods for determination of low-density lipoprotein cholesterol in serum and an indirect method involving the Friedewald formula (Clin Chem 18: 499-502, 1972) by comparison with results by ultracentrifugation. The results of all methods for 83 sera, including 59 hyperlipidemic type IIA, IIB, and IV sera agreed very well, at least for concentrations of serum triglycerides below 8 mmol/L. The accuracy of the Friedewald formula was confirmed in 285 other sera, including 66 sera with triglycerides content between 4.52 and 8.0 mmol/L. For type III sera, the precipitation methods produced similar values to those obtained with the Friedewald formula, all being much higher than the ultracentrifugation values. Density-gradient ultracentrifugation showed that the very-low-density lipoprotein remnants in type III sera almost completely coprecipitated with the low-density lipoproteins. The precipitation methods are not only accurate but also very precise (CV less than 5%); they can therefore be used in clinical laboratories to measure atherogenic low-density lipoproteins plus the remnants of very-low-density lipoproteins. However, when serum triglycerides and high-density lipoprotein cholesterol also are determined, the Friedewald formula is a reliable alternative.

Centrifugation, Density Gradient↗
PubMed1984

Suitability of various control sera for use in testing the accuracy of cholesterol determination with enzymic kits.

We used 20 different commercial enzymic kits to measure cholesterol in 19 commercial control sera and in a pooled specimen of human serum and compared the relative biases, with the Abell -Kendall procedure as reference. Our purpose was to select those sera in various enzymic kits showing behavior similar to that of human serum and which thus can be used to measure the accuracy of these kits. The overall mean relative biases obtained with each of the 20 kits for the pooled human serum on the one hand and for a given control serum on the other generally correlated significantly. On the basis of the correlation coefficients and regression equations, we could select the control sera best suited for measurement of accuracy. They were all human-serum based, with cholesterol concentrations greater than 5 mmol/L. Animal sera with above-normal lipid values produced by feeding special diets appeared to be less reliable control sera in this respect.

Animals↗
PubMed1983

Partial ileal bypass inhibits atherosclerosis in WHHL rabbits.

The effectiveness of partial ileal bypass (PIB) as a counter-measure against atherosclerosis was evaluated in WHHL rabbits. The effects of PIB and sham operation, each performed in five animals, on serum lipids, lipoproteins and plaque formation were investigated. PIB resulted in an immediate and sustained decrease of 52% (range 29-67%) in serum cholesterol, while sham operation had no effect. The main reduction was in LDL cholesterol; VLDL-cholesterol was lowered to a lesser extent. PIB also appeared to change the electrophoretic behaviour of total serum, very low density and low density lipoproteins. Plaque formation, measured 30 weeks after operation in various aortic segments and arteries, was significantly reduced after PIB. It is concluded that an induced lowering of serum cholesterol can prevent atherosclerosis in WHHL rabbits. Also, these animals must be considered as a model for the receptor-defective cellular phenotype of homozygous familial hypercholesterolemia, not for the receptor-negative type, which is the only truly genetically homozygous form.

Animals↗
PubMed1983

Ultracentrifugation in swinging-bucket and fixed-angle rotors evaluated for isolation and determination of high-density lipoprotein subfractions HDL2 and HDL3.

We evaluated the density-gradient ultracentrifugation method in a swinging-bucket rotor (Anal Biochem 111, 149-157, 1981) in a slightly modified version for isolation and determination of high-density lipoprotein (HDL) subfractions. We prestained the serum with Coomassie Brilliant Blue R, which did not change the hydrated densities of the lipoproteins, and after only 2.2 X 10(8) gav . min obtained an equilibrium distribution of the lipoproteins along the gradient. The density distribution of the HDL of 120 sera obtained from apparently healthy persons and from patients with different types of hyperlipoproteinemia was bimodal. The HDL2 could be isolated in the density range 1.072-1.098 kg/L and the HDL3 at 1.100-1.176 kg/L, the latter fraction being more heterogeneous. At a solvent density of 1.100 we obtained similar results for HDL2-and HDL3-cholesterol by ultracentrifugation in two different fixed-angle rotors with tube angles of 15 degrees or 35 degrees. Independent of the rotor and the ultracentrifugation technique, subfractionation at d = 1.100 resulted in more distinct stained entities than ultracentrifugation at d = 1.125. In the swinging-bucket rotor procedure, interference by sinking pre-beta-lipoproteins was minimized because, having hydrated densities between 1.058 and 1.075, they could be removed without aspirating the HDL2. The method is both accurate and precise. For HDL2- and HDL3-cholesterol determined in a thawed frozen serum pool, CVs were 8.8 and 6.3%, respectively (n = 18).

Centrifugation, Density Gradient↗
PubMed1983

Evaluation of accuracy of 20 different test kits for the enzymic determination of cholesterol.

We evaluated the accuracy of 20 different test kits for the enzymic determination of cholesterol. Using a selected set of standards, we found mean values differing by -9.9 to + 10.7% from values obtained by the Abell-Kendall procedure. Nine kits gave values with a relative bias of less than 2.5%. In the case of the other 11 kits, recalculation with secondary serum standards resulted in values within 5% of the reference values. Depending on the kit used, two different commercially available standard solutions produced results differing by, at most, 8.7%. We obtained indirect evidence that use of esterase of bacterial origin is associated with low values. We ascribe the high values obtained with some kits to positive interference by stabilizers or unspecified compounds in the reagents.

Cholesterol↗