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Biomedical subjects

G Siest

Publications and source records attributed to G Siest.

At least 109 records · Page 6Linked to original sources
PubMed1996

Apolipoprotein E genotype epsilon 4/epsilon 2 in the STANISLAS Cohort Study--dominance of the epsilon 2 allele?

Apolipoprotein (apo) E has been discussed as a marker for cardiovascular risk, but information about lipid traits in healthy individuals having one of the rare apoE genotypes (epsilon 4/epsilon 2, epsilon 2/epsilon 2 or epsilon 4/epsilon 4) is scarce. Our work was designed to answer the following questions: 1. Are the allelic effects of epsilon 2 and epsilon 4 on lipid traits additive or dominant? 2. If there is additivity, do the allelic effects of epsilon 2 and epsilon 4 have the same magnitude? 3. Are the allelic effects neutralised in epsilon 4/ epsilon 2 individuals who are under the influence of both rare alleles? Allelic effects on apoB and apoE serum levels were codominant. Allelic models are thus not adequate to study the influence of apoE polymorphism on these traits. Allelic effects were additive for total cholesterol, LDL-C, HDL-C and apoAI, with epsilon 2 having a greater impact than epsilon 4. Serum levels differed significantly between epsilon 4/epsilon 2 and epsilon 3/epsilon 3 individuals only for apoE (p < 0.001) and for apoB (p < 0.05).

Adult↗
PubMed1996

Weights at birth and in early infancy, systolic pressure, and left ventricular structure in subjects aged 8 to 24 years.

The objective of this study was to determine whether systolic pressure and left ventricular mass in children, adolescents, and young adults are related to fetal and infant growth. Blood pressure measurements and M-mode echocardiography were performed in 210 subjects aged 8 to 24 years whose information on weights at birth and in early infancy, written by physicians, was obtained from the children's health record booklets. Systolic pressure, adjusted for sex and current height or for sex, current age, weight, and height, was the highest in subjects with low birth weight. No association was observed between systolic pressure and weight at either 9 months or 2 years. Left ventricular mass, adjusted for sex and current height or for sex, current age, weight, and height, increased with decreasing weight at 9 months or 2 years, independent of systolic pressure. Increased ventricular mass associated with reduced infant growth was concentric, resulting from a proportionate thickening of the posterior wall and interventricular septum. Left ventricular mass was not related to birth weight. These findings were observed in both sexes and in all age subgroups and were independent of gestational age, birth order, and parental risk factors. This study supports the hypothesis that systolic pressure and left ventricular mass might be partly determined during fetal life and early infancy. The mechanisms that underlie the associations of blood pressure and left ventricular structure with weights at birth and in early infancy should be studied thoroughly.

Adolescent↗
PubMed1996

Apolipoprotein (apo) E genotype and apoE concentration determine binding of normal very low density lipoproteins to HepG2 cell surface receptors.

The clinical relevance of apoE concentration in lipoprotein fractions should be evaluated. We investigated the impact of the common apolipoprotein (apo) E polymorphism in conjunction with very low density lipoprotein (VLDL) apoE concentration on the receptor binding properties of VLDL preparations from 17 normolipidemic subjects of the HepG2 cell surface receptors. All six apoE genotypes were studied. When apoE genotype alone was considered, two subgroups could be distinguished: VLDL without apoE isoform E2 (VLDL-3/3, VLDL-3/4, and VLDL-4/4) showed significantly higher affinity than VLDL with apoE2 (VLDL-4/2, VLDL-3/2, and VLDL-2/2). Once we adjusted for VLDL apoE content, we observed that VLDL affinity to HepG2 cell surface receptors decreased, according to apoE genotype, in the following order: VLDL-4/4 (100%) > VLDL-3/4 (93%) > VLDL-3/3 (82%) > VLDL-4/2 (53%) > VLDL-3/2 (36%) > VLDL-2/2 (30%). Moreover, we found that VLDL apoE concentration could modify isoform-specific binding. An analysis in 47 subjects showed that the concentration of total VLDL protein and the VLDL apoE concentration varied considerably. The variation of VLDL apoE was independent of apoE genotype and corresponding serum apoE levels. We conclude that, in addition to apoE genotype, apoE content of VLDL is an important determinant of the receptor binding properties of VLDL.

Apolipoproteins E↗
PubMed1996

Changes in serum apolipoprotein and lipoprotein profile induced by chronic alcohol consumption and withdrawal: determinant effect on heart disease?

The effects of alcohol consumption on serum concentrations of apolipoproteins (apo) A-I, C-III, B, and E and of lipoproteins (Lp) A-I, A-I:A-II, C-III, C-III:B, and (a) were studied in 132 healthy subjects, including 55 low drinkers of alcohol (<20 g/day), 36 moderate drinkers (20-50 g/day), and 41 heavy drinkers (>50 g/day), and in 97 hospitalized alcoholic patients (> 100 g/day) without severe liver disease (especially functional insufficiency), before and after 21 days of withdrawal treatment. Serum concentrations of apo A-I, LpA-I, LpA-I:A-II, apo C-III, and LpC-III significantly (P </= 0.01) increased with alcohol intake (mean +/- SE in low drinkers vs in alcoholics)--1.45 +/- 0.03 vs 1.78 +/- 0.05 g/L; 0.45 +/- 0.02 vs 0.56 +/- 0.02 g/L; 0.99 +/- 0.02 vs 1.22 +/- 0.04 g/L; 27.6 +/- 1.5 vs 39.7 +/- 1.7 mg/L; and 8.4 +/- 0.9 vs 24.7 +/- 1.7 mg/L, respectively-whereas apo B and LpC-III:B concentrations tended to decrease--1.20 +/- 0.04 vs 1.06 +/- 0.04 g/L and 19.3 +/- 1.2 vs 14.9 +/- 1.0 mg/L, respectively. No significant difference between these four types of alcohol consumption was noticed for cholesterol, triglycerides, apo E, and Lp(a). After withdrawal, the concentrations of serum apo A-I, apo C-III, LpA-I, LpA-I:A-II, and LpC-III decreased significantly (P </= 0.01), reaching values comparable with those in low drinkers; concentrations of triglycerides, apo B, apo E, and Lp(a) rose; and cholesterol concentration was unaffected. In multiple regression analysis, after adjustment for serum concentrations of albumin, aspartate aminotransferase, and gamma-glutamyltransferase and for the Quetelet index, alcohol consumption remained positively correlated to apo A-I, LpA-I:A-II, apo C-III, and LpC-III concentrations. Study of other determinants of serum apo and lipoprotein concentrations suggests that alcohol-related variations in some of them, especially apo A-I, might depend on the metabolic ability of the liver to synthesize proteins and on induction phenomena. Finally, although the increase of antiatherogenic apo- and lipoproteins and the decrease of those known to be atherogenic were generally marked in alcoholics, alcohol-related modifications of these markers were very limited in our sample of French healthy men. We conclude, therefore, that moderate alcohol consumption (20-50 g/day) is unlikely to protect against ischemic heart disease through an effect on the proteins measured in this study.

Adult↗
PubMed1995

Glucuronidation in the Caco-2 human intestinal cell line: induction of UDP-glucuronosyltransferase 1*6.

The ability of the differentiated human intestinal cell line, Caco-2, to glucuronidate various endobiotic and xenobiotic molecules was investigated. Glucuronidation of hydroxylated or carboxylic acid compounds such as 1-naphthol, thymol, androsterone, estriol, hyodeoxycholic acid, lithocholic acid, chloramphenicol, paracetamol and morphine could be determined in microsomal fractions of Caco-2 cells. The activity toward 1-naphthol was the highest glucuronidation activity measured in Caco-2 cells. This activity was specifically increased four-fold upon addition of beta-naphthoflavone into culture medium but not by rifampicine or clofibrate and was related to a biosynthesis of UDP-glucuronosyltransferase 1*6 (UGT1*6). alpha-Naphthoflavone did not affect the inducing property of beta-naphthoflavone. 7-Ethoxyresorufin-O-dealkylation activity, supported by cytochrome P4501A1, was induced more than 1000-times in Caco-2 cells by beta-naphthoflavone treatment, and this effect was partially abolished by alpha-naphthoflavone treatment. The results suggest that several isoforms, including UGT1*6, are expressed in Caco-2 cells.

Benzoflavones↗
PubMed1995

gamma-Glutamyltransferase expression during all-trans retinoic acid-induced differentiation of hematopoietic cell lines.

gamma-Glutamyltransferase activity, genes transcripts and differentiation by all-trans retinoic acid have been investigated in cultured HL-60, U937, and K562 cells. Acquisition of morphological and functional characteristics confirmed the terminal differentiation of HL-60 and U937 cells. All-trans retinoic acid increased gamma-glutamyltransferase activity in a cell type- and time dependent manner. Treatments with all-trans retinoic acid isomers and structurally analogs showed that only retinoids with carboxylic acid group were able to induce enzyme activity in terminal differentiated cells. Additionally, the analysis of gamma-glutamyltransferase genes transcription products demonstrated clearly that, both in untreated and in RA treated cells, only mRNA type I transcribed from the gene 6, was expressed.

Base Sequence↗
PubMed1995

Dextromethorphan O-demethylase activity in rat brain microsomes.

CYP2D, a genetically variable isoform of cytochrome P450, has been characterized mainly in the liver and the brain of mammals by measurement of debrisoquine hydroxylase activity. Moreover, 'poor debrisoquine metabolizer' phenotype is significantly increased in Parkinson's disease patients. We present here the first demonstration that the activity of the CYP2D isoform can be characterized in rat brain microsomes by the measurement of dextromethorphan O-demethylase capacity. The cerebral formation of dextrorphan, an antagonist of the N-methyl-D-aspartate receptor, was inhibited by the presence of quinidine and N-methyl-4-phenylpyridinium (MPP+), a dopaminergic neurotoxin inducing a chemical parkinsonism in humans.

Animals↗
PubMed1995

Characterization of a new class of inhibitors of the recombinant human liver UDP-glucuronosyltransferase, UGT1*6.

The inhibitory effect of a series of novel structurally related compounds on the human UDP-glucuronosyltransferase UGT1*6 stably expressed in a V79 cell line was investigated. The inhibitors contain a lipophilic N-acyl phenylaminoalcohol residue and a uridine moiety connected by a spacer varying for each compound. The effects of these compounds on the glucuronidation reaction measured with 4-methylumbelliferone as substrate were determined. The best inhibitor of the series, D-DPMSU, had an IC50 of 39 microM in the assay conditions. Low Ki values were found toward both UDP-glucuronic acid and 4-methylumbelliferone (17 and 21 microM, respectively). The inhibition was competitive toward both substrates. A similar strong and competitive inhibitory effect was observed with two other inhibitors, DHPASU and DHPASiU. Another compound, D-DPASiU, showed a pure competitive inhibition towards UDP-glucuronic acid, but a non-competitive inhibition towards the acceptor substrate. These data and the optimization of the structures of the inhibitors by molecular modeling suggest that D-DPMSU and DHPASiU compounds may be transition state analog inhibitors of the recombinant UGT1*6 enzyme.

Binding Sites↗
PubMed1995

Segregation analysis and variance components analysis of bone mineral density in healthy families.

Bone mineral density (BMD) was measured in 1992-93 in 129 nuclear families, including 258 parents and 183 children, and was analyzed for familial resemblance factors. BMD measurements were adjusted on weight and age. Segregation analysis rejected the monogenic hypothesis and exhibited a strong polygenic component. Variance components analysis was then used to estimate the parameters of a multivariate normal model including an additive polygenic component, a common environment factor, and a residual specific to each individual. The genetic component was independent of sex and age. The common environmental factor was not significant. The variance of the residual specific factor appeared to be a quadratic function of age, reaching its minimum value at 26.4 years. Consequently, the maximum value for heritability (ratio of genetic variance to total variance) is observed at this age (h2 = 0.84). According to this model, the correlation between two relatives is a function of the ages of each individual in the pair.

Adolescent↗
PubMed1995

Lipid and lipoprotein genetic variability: an important contribution from the French health examination centers.

OBJECTIVE: To assess lipid and lipoprotein genetic variability in the French Population. METHODS: Many health examination centers are covering a great part of France (700,000 individuals are examined in 54 centers every year). Each citizen has the right to have a personal examination every 5 years. This unique system was modified in 1992, and we are presenting our 25-year experience focusing on the results we have more recently obtained in the lipid and lipoprotein field. RESULTS: First of all, the 600 items of information collected on every patient coming to our Center give us the data and facilitate the development of the theory of reference values. Having mastered the analytical variations, we studied the biological variations. Age, sex, overweight, tobacco, alcohol, and drugs are the main factors we should control for obtaining reference values. More recently, the genetic part in the production of reference values has become of greater importance, particularly for apolipoproteins. Apolipoprotein E is an important lipoprotein for which the two frequent mutations influence the level of circulating Apolipoprotein E. The risks linked to these alleles are also very different in cardiovascular disease and extremely important (for epsilon 4) in Alzheimer's Disease. Apolipoproteins B and A-IV also have interesting polymorphisms, but currently have no systematic applications in clinical chemistry. The familial recruitment we have in Nancy also permitted us to constitute a large tool "La Cohorte Stanislas." CONCLUSION: The thousand families recruited will be followed for 10 years. It is an open tool for collaboration.

Adult↗
PubMed1995

Apo B signal peptide insertion/deletion polymorphism is involved in postprandial lipoparticles' responses.

The changes in postprandial concentrations of five lipoparticles (LpC-III, LpC-III:B, LpC-IIInoB, LpA-I and LpA-I:A-II) were studied on 144 apparently healthy (71 male and 73 female) subjects during the 4 h following the ingestion of a 1.260 kJ milkshake. The influence of apo B signal peptide polymorphisms, apo E polymorphism, and other factors including age, gender, BMI, tobacco and alcohol consumption on the postprandial responses of lipoparticles was investigated. Apo-A-I-containing lipoparticles were not influenced during the 4 h following the test meal except for LpA-I:A-II, which decreased in women. LpA-I:A-II is the only particle that showed a gender-dependent change in postprandial concentration. Apo-CIII-containing lipoparticles showed significant postprandial variations. Particles containing both apo B and apo C-III (total LpC-III and LpC-III:B), mainly present in VLDL fraction, had significantly different postprandial responses among the genotypes of the apo B signal peptide polymorphism. Homozygotes for Del allele showed a decrease of LpC-III:B concentrations over the 4 h, whereas Ins/Ins homozygotes and Ins/Del heterozygotes had a peak in concentration at 2 h. The apo B signal peptide polymorphism explained 2.3% of the variance of LpCIII:B, whereas apo E polymorphism did not influence the postprandial concentrations of any lipoparticles.

Adult↗
PubMed1995

Reference limits of apolipoprotein A-I and apolipoprotein B using an IFCC standardized immunonephelometric method.

An important collaborative study organized by the IFCC enabled the selection of international reference materials and the standardization of commercially available methods by the use of common calibrators. In this paper, we report the reference limits of apolipoprotein A-I and apolipoprotein B in a selected healthy French population. The apolipoprotein measurements were performed on BNA Behring using reagents and protocols supplied by the manufacturer: the standard sera were calibrated using the IFCC-WHO reference preparations (SP1 and SP3). In addition, the apolipoprotein B protocol was modified by the addition of a supplementary reagent to reduce the interference by lipaemic samples on immunonephelometric measurement. In a sample of 115 random serum samples, there was a decrease in mean concentration between non-standardized and standardized methods: -4.8% for apolipoprotein A-I and -4.7% for apolipoprotein B. The reference limits for apolipoprotein A-I are unaffected by gender between 4 and 14 years, thereafter vary with age and gender until 40 years and with gender alone between 40 and 60 years. For apolipoprotein B, the variation with gender is only significant between 30 and 49 years.

Adolescent↗
PubMed1995

[Changes in blood cholesterol levels over a 10-year period; value of a single sample for predicting future blood cholesterol levels].

The aim of this study was to report the serum cholesterol changes over a 10 year period in 12,238 subjects aged 4 to 64 years (mean 28 +/- 14 years) based on 3 health check-ups at an average of 5.5 yearly intervals between 1973 and 1989, and to determine the value of a single sample for predicting the serum cholesterol level at 5 and 10 years, and the influence of blood pressure and Quetelet index on this predictability. After identification of the influencing factors, the different variables were adjusted using a step-by-step regression analysis. The correlation coefficients calculated between the adjusted cholesterol level at the first examination and that measured at 5 and 10 years, were all significant (0.38 to 0.59) and varied with age at the time of the first examination and gender. The positive predictive value of having a cholesterol level higher than the 90th centile at 5 and 10 years when it was already higher than this value at the first examination varied from 26 to 46% respectively with respect to the subgroups. The sensitivity of the test was 25 to 48%. The negative predictive value and specificity were 93 to 95%. The lowering of this threshold to the 80th centile increased the positive predictive value from 35 to 45% and decreased the specificity from 94 to 87% for the whole population. When the first two sampling results, five years apart, were taken into consideration simultaneously, the predictive value of having a raised cholesterol level at 10 years increased from 35 to 61%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Blood and plasma glutathione measured in healthy subjects by HPLC: relation to sex, aging, biological variables, and life habits.

We report an HPLC method for measuring the concentrations of reduced (GSH) and total (GSHt) free glutathione in human plasma and whole blood. The chromatographic step was coupled with a postcolumn derivatization reaction and fluorometric detection. The linear range was 0.81-13.02 mumol/L, and the detection limit was 0.13 mumol/L. In healthy adults (ages 18-73 years), mean concentrations were 941 +/- 155 mumol/L for GSHt and 849 +/- 63 mumol/L for GSH in blood (107 men, 94 women), and 3.39 +/- 1.04 mumol/L for GSH in plasma (66 men, 58 women). Blood GSHt but not GSH was significantly lower in children (32 boys, 32 girls: 872 +/- 157 mumol/L) than in adults. Blood GSHt and GSH appeared to be correlated positively with the number of cigarettes smoked per day and the regular practice of physical exercise, and negatively with alcohol abstinence. We observed positive correlations between blood GSHt and cholesterol and calcium concentrations, and between blood GSH and cholesterol concentration.

Adolescent↗
PubMed1995

Cholesterol content of circulating immune complexes in patients with coronary stenosis and subjects without evidence of atherosclerosis.

The biological variation factors for cholesterol in circulating immune complexes (CIC-cholesterol) were studied in 941 unselected supposedly healthy volunteers, ages 4 to 78 years. We found a complex effect of age, including the existence of two peaks of CIC-cholesterol, one in males between 11 and 14 years and in females between 11 and 30 years, and in both sexes another peak between 41 and 60 years, and in both sexes a decrease between 31 and 40 years. By use of multiple regression analysis and after adjustment for age, CIC-cholesterol was positively related to plasma cholesterol concentration and leukocyte count, values being lower in females than in males and among subjects taking anti-inflammatory drugs. In addition, CIC-cholesterol was measured in 76 coronary angiography patients and in 100 supposedly healthy controls, ages 30 to 77 years. We noticed a significant increase (P < or = 0.05) of CIC-cholesterol when patients were affected by coronary stenosis between 20% and 50% (71.8 +/- 52.5 mumol/L vs 46.2 +/- 45.9 mumol/L in controls), but this was less pronounced in those with > 50% of obstruction (58.9 +/- 54.3 mumol/L); however, serum total cholesterol was not modified or even surprisingly slightly decreased in the coronary angiography individuals. Nevertheless, an important overlap of values in controls and patients makes questionable the usefulness of this variable in clinical practice.

Adolescent↗
PubMed1995

[Reference values of laboratory tests: a useful and important epidemiologic contribution of the Centers for health tests].

Since 1969 the Centre for Preventive Medicine in Nancy has been carrying out health examinations of the eastern region of France (Lorraine, Champagne-Ardenne). The clinical chemists at the Centre of Preventive Medicine have made a great contribution to the concept and the description of biochemical reference values for which the transferability to other health centres must be verified. Knowledge of reference values and biological variations facilitates the interpretation of weak modifications of biological constituents which are observed in preventive medicine. Reference values can be used to compare two populations (comparing reference values between to two) or to compare an individual observed value to the reference values obtained in the various population groups. In the long term, these reference values could become a useful education tool for patients coming for health examination. It should be possible for each subject to follow, throughout his life, the evolution of his biological constituents and to detect any deviation towards a pathology.

Diagnostic Tests, Routine↗
PubMed1995

Apolipoprotein E: an important gene and protein to follow in laboratory medicine.

The human apolipoprotein (apo) E gene is polymorphic, with three common alleles (epsilon 2, epsilon 3, epsilon 4) coding for three isoforms (E2, E3, E4). The isoforms differ from each other by a single amino acid substitution, and also differ in their binding affinity for the four apo E receptors. Apo E polymorphism is an important determinant of risk for the development of cardiovascular and Alzheimer diseases, the prevalence of the epsilon 4 allele being increased in both kinds of patients compared with control subjects. Furthermore, the prevalence of the epsilon 4 allele differs among populations (range 5-40%, respectively, for Taiwanese and Papua New Guineans). Genotyping or phenotyping needs to be introduced in clinical laboratories. The choice of the method should be based on the types of patients who are examined. The apo E genotype is also a determinant of apo E plasma concentration. Standardization of apo E measurement is an important prerequisite before investigating the clinical interest of plasma apo E concentration. Determination of apo E genotype/phenotype and later the plasma concentration are expected to yield useful clinical laboratory information.

Apolipoproteins E↗