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Biomedical subjects

J Davignon

Publications and source records attributed to J Davignon.

At least 181 records · Page 10Linked to original sources
PubMed1983

Fatty acid composition of tissue phospholipids and prostaglandin excretion in hyperlipidemia induced in rats by implantation of the mammotropic pituitary tumor MtT-F4.

A mammotropic pituitary tumor, MtT-F4, was implanted into male Fisher 344 rats for a period of 4 weeks. This tumor induced growth retardation, hyperlipidemia, hepatic hypertrophy and adrenal hyperplasia. Lipids were extracted from various tissues. In tumor-bearing rats, phospholipid concentration was found to be increased in plasma, spleen and testis. Distribution among the various phospholipid classes was similar to that of controls except in liver and heart, where phosphatidylcholine was increased at the expense of phosphatidylinositol and phosphatidylserine. The main difference was in the fatty acid composition of major phospholipids. The proportion of omega 6 fatty acids was lower and that of docosahexaenoic acid of the omega 3 series (22:6 omega 3) was higher in most tissues, especially in plasma, liver, heart and kidney. Concurrently, the urinary excretion of two endogenous metabolites of PGI2 (2,3-dinor-6-keto-PGF1 alpha and 6,15-diketo-13,14-dihydro-2,3-dinor-PGF1 alpha) was found to be increased significantly in tumor-bearing rats. The results raise the hypothesis that hormonal changes induced by the MtT-F4 tumor accelerate the conversion of arachidonic acid (20:4 omega 6) to prostaglandins. This effect, perhaps coupled with a diversion of linoleic acid (18:2 omega 6) towards other metabolic processes, would account for a partial depletion of membrane phospholipids in 18:2 omega 6 and for the reduced production of longer chain omega 6 unsaturated acids from 20:4 omega 6, creating a state of "relative essential fatty acid deficiency." As a result, the metabolism of omega 3 fatty acids is altered towards an enhanced production of 22:6 omega 3 which accumulates in the lipids of cell membranes to compensate for the depletion of unsaturated acids of the omega 6 series.

Animals↗
PubMed1983

Effect of methyl linoleate administration on phospholipid fatty acid composition and osmotic fragility of erythrocytes in essential fatty acid deficient rats.

Methyl linoleate (18:2 omega 6) was administered to rats deficient in essential fatty acids (EFA) and the effects on osmotic fragility and lipid composition of their red blood cells were studied. Even if they remained deficient in omega-3 fatty acids, the fragile red cells of EFA-deficient rats were remarkably strengthened by the linoleate treatment. It is concluded that omega-3 fatty acids are not essential for the maintenance of cell membrane integrity in rats. Since the cholesterol/phospholipid ratio in red cells was lower in untreated than in treated rats, it is suggested that this factor might be responsible in part for the higher fragility of red cells in EFA-deficient rats. Despite the prolonged administration of overload quantities of methyl linoleate, the proportion of 18:2 omega 6 in the red blood cell phospholipids of treated rats was actually lower than that in rats fed a regular stock diet, while the relative content of other omega-6 fatty acids (20:4 omega 6, 22:4 omega 6, and 22:5 omega 6) increased. These results indicate that the metabolic processes of omega-6 fatty acids in treated rats were stimulated, probably as a result of the lack of competition from omega-3 fatty acids for the same enzyme systems.

Animals↗
PubMed1983

Apolipoprotein E phenotyping with a single gel method: application to the study of informative matings.

Two-dimensional gel electrophoresis or isoelectric focusing before and after treatment with cysteamine are currently used to determine the six apolipoprotein E isomorphic phenotypes from isolated very low density lipoproteins. A technique is described that makes this possible by performing isoelectric focusing on a single polyacrylamide cylindrical gel under standardized conditions. The technique is simple and accurate enough to obtain 99.5% concordance when the gels are interpreted independently by four different skilled and unskilled observers in the absence of any knowledge of the origin of the samples. There was complete agreement between our technique and the bidimensional method carried out independently in another laboratory on 74 aliquots of plasma very low density lipoproteins. Its application to 16 informative matings involving 101 subjects confirmed the recent demonstration that the apolipoprotein E phenotype inheritance is autosomal and compatible with three common alleles acting at a single genetic locus. Analyses of the contribution of apoE polymorphism to lipid and lipoprotein variability demonstrated a recessive allelic effect of epsilon 2 on plasma very low density lipoprotein cholesterol and a dominant epsilon 4 effect on low density lipoprotein cholesterol. As much as 30% of the variability in low density lipoprotein cholesterol was attributable to this polymorphic gene locus. A simplified scheme is proposed for the symbolic representation of the six phenotypes for clinical and genetic applications.

Adult↗
PubMed1983

[Xanthoma and atherosclerosis in the presence of normal plasma lipids].

Normal plasma lipid levels do not prevent the infiltration of skin and arterial walls by cholesterol. This does not mean that lipoproteins do not play a role in tissue infiltration which takes place in subjects with normal lipids. Abnormal lipids, an abnormal distribution of atherogenic and non-atherogenic lipids in the blood, a latent hyperlipidemia, the relative proportions of apolipoproteins in circulation or an abnormal composition of the lipoproteins may contribute to this phenomenon. Our studies in subjects with normal lipid levels with xanthelasmata support the hypothesis that the apolipoprotein-B has atherogenic properties. In addition, they suggest that certain isomers of the apolipoprotein-E may also be involved. Preliminary studies in our laboratory using a simple technique of identifying the 6 phenotypes of the apolipoprotein-E suggest that the isomer E2 may favour the appearance of hyperlipidemia when another genetic or environmental factor is present.

Apolipoproteins↗
PubMed1983

Simple, reproducible procedure for selective measurement of lipoprotein lipase and hepatic lipase.

Existing methods for determining the release of lipoprotein lipase (EC 3.1.1.34) and hepatic lipase (EC 3.1.1.3) into plasma after heparin injection give highly variable results, primarily traceable to errors in the isolation of labeled oleate from the substrate, triolein. Methods involving anion-exchange resin to bind oleate show high variability and have a low yield. Introducing a strong base in the last step of the assay may spuriously increase the counts from oleate, whereas a detergent such as Triton X-100, used to minimize this problem, has a strong quenching effect. We report a simple and rapid method in which we eliminate rather than correct for the sources of variation. The substrate, tri[1-14C]oleoyl-glycerol, is sonicated under strictly standardized conditions with gum arabic, 50 g/L. Incubation is stopped by addition of a benzene/chloroform/methanol mixture and NaOH, 0.2 mol/L. Labeled oleic acid is extracted with hexane after acidification of the alkaline aqueous (upper) phase, so that no alkali is introduced into the scintillation liquid. For lipoprotein lipase measurement, hepatic lipase is inactivated by a specific antiserum, whereas hepatic lipase is measured after lipoprotein lipase is inactivated by NaCl, 1.0 mol/L. The method is efficient and specific, and quenching and chemiluminescence artifacts are avoided.

Animals↗
PubMed1982

Tissue lipids in acute acrylamide intoxicated rats.

A preliminary survey of tissue lipid composition in acrylamide intoxicated rats is reported. The animals were injected intraperitoneally with acrylamide 50 mg/kg body weight per day for 10 days. Liver cholesterol, mainly in the ester fraction, was decreased in treated rats. When fatty acid composition of liver cholesterol esters was examined, the proportions of linoleate and stearate were found to be decreased and were compensated by the increase of palmitate. Atrophy of epididymal fat pad resulted in severe triglyceride depletion and a relative increase in the proportion of phospholipids and cholesterol. There was also a reduction of linoleate, palmitate and palmitoleate in triglycerides and phospholipids of this tissue. There were, however, only minor changes in the fatty acid profile of the sciatic nerve.

Acrylamides↗
PubMed1982

Plasma lipoprotein lipase and hepatic lipase activities in Friedreich's ataxia.

Plasma triglycerides although within the normal range have been shown to be higher in Friedreich's ataxia than in control subjects. To determine whether this difference could be ascribed to a reduced catabolism of triglyceride-rich lipoproteins, the activities of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HL), released into plasma after an heparin injection, were measured in 13 cases of Friedreich's ataxia and 14 control subjects of comparable signs. LPL was found to be significantly lower in the ataxic patients. Moreover about half of the cases clustered below the normal range for both lipase activities. This subgroup of Friedreich's patients had significantly higher plasma triglycerides than those with normal lipase activities. Further studies are needed to relate these findings to other characteristics of the disease.

Adolescent↗
PubMed1982

Plasma methyl sterol sulfates in familial hypercholesterolemia after partial ileal bypass.

We demonstrate, in this study, the presence of several unidentified components in the sterol sulfate fraction of familial hypercholesterolemia patients treated with partial ileal bypass surgery. The sterols obtained after solvolysis and derivatization of this fraction had a retention time, on gas-liquid chromatography, intermediate between cholesterol and beta-sitosterol. They were not present in the sterol sulfate fraction obtained from normal subjects, hypercholesterolemic patients, or ileal bypass subjects before surgery or after reanastomosis. The substances isolated from the sterol sulfate fraction were identified by combined gas-liquid chromatography and mass spectrometry to be 24,25-dihydrolanosterol, 4,4-dimethyl-5alpha-cholest-8-en-3beta-ol, 4,4-dimethyl-5alpha-cholest-9(11)-en-3beta-ol, 4alpha-methyl-5alpha-cholest-7-en-3beta-ol, and 4alpha-methyl-5alpha-cholest-8-en-3beta-ol. Their free forms are known to be biosynthetic intermediates in the transformation of lanosterol into cholesterol.

Gas Chromatography-Mass Spectrometry↗
PubMed1982

Increased Frequency of Apo E-ND phenotype and hyperapobeta-lipoproteinemia in normolipidemic subjects with xanthelasmas of the eyelids.

Apolipoprotein E isomorphs in very low density lipoproteins and apolipoprotein B of low density lipoproteins were measured in the plasma of normolipidemic subjects with xanthelasmas of the eyelids and in appropriate control groups. All patients tested in the experimental group had an apolipoprotein EII to apolipoprotein EIII ratio typical of the heterozygous state for familial dysbetalipoproteinemia, a hyperapobetalipoproteinemia, or both. Some patients had concomitant atherosclerosis. This is the first report of an increased frequency of the apolipoprotein E-ND phenotype in normolipidemic xanthelasma. This condition should not be dismissed as benign; tissue lipid deposition in the absence of hyperlipidemia might be related to the presence of lipoproteins of abnormal composition with an enhanced atherogenic potential.

Adult↗
PubMed1981

Cholesteryl sulfate: measurement with beta-sitosteryl sulfate as an internal standard.

A new method is described for the measurement of cholesteryl sulfate (CS) in plasma. Taking advantage of the use of beta-sitosteryl sulfate (SS) as an internal standard it is simpler and more rapid than the methods currently in use. It does not require the use of radioactive isotopes. A potential contamination of the CS band by free cholesterol is excluded by developing the thin-layer chromatography plate on which the sterols are first separated with a second solvent system which pushes free cholesterol to the solvent front without appreciably moving the CS band. The method is sensitive and reproducible and may be advantageous for the screening of large populations. The values obtained for plasma CS concentrations in normal subjects compare well with those measured by more elaborate techniques.

Cholesterol↗
PubMed1980

Usefulness of probucol in treating primary hypercholesterolemia.

Probucol (1 g per day) was administered in a double-blind crossover trial to 16 patients with familial hypercholesterolemia who had previously been tested for their response to clofibrate. Probucol led to a fall in the plasma cholesterol concentration of 15% or more (mean 20.2%) in 5 of the 12 clofibrate-resistant patients and between 8% and 15% in 3 others. The reduction was statistically significant in 7 of these 12 patients as well as in 3 of the 4 patients sensitive to clofibrate. Thus, probucol has a place in the treatment of patients with primary hypercholesterolemia who do not respond to clofibrate.

Adult↗
PubMed1980

Lecithin: cholesterol acyltransferase activity and fatty acid composition of erythrocyte phospholipids in Friedreich's ataxia.

In a study of the fatty acid composition of erythrocyte membrane phospholipids in Friedreich's ataxia, a lower percentage of linoleic acid in phosphatidylcholine was demonstrated. An enzyme involving the exchange of lipids between plasma and erythrocyte membrane, lecithin: cholesteryl acyltransferase (LCAT) was also studied. It was found that the LCAT activity had a trend towards low values. However, crossing-over studies indicated that when the LCAT enzyme of patients was exposed to its own substrate it gave low activity values but that the result reverted to normal when control substrate was used.

Acyltransferases↗