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Biomedical subjects

I Beucler

Publications and source records attributed to I Beucler.

At least 37 records · Page 2Linked to original sources
PubMed1996

[Effects of rilmenidine (hyperium) on lipid balance in hyperlipidemic hypertensive patients. Randomized, controlled, double-blind 8-week study vs. captopril in parallel groups].

Rilmenidine (dose of 1 mg once or twice a day) is the first oxazoline compound with antihypertensive properties. Its effects on lipid parameters [total cholesterol, HDL and LDL fractions, triglycerides, apolipoprotein A1 and B, lipoprotein (a)] were compared under double-blind conditions and in parallel groups to those of captopril (50 to 100 mg per day, in 2 divided doses) over a period of 8 weeks, in 51 hyperlipidaemic hypertensive patients [age: 56.3 +/- 1.5 years, systolic and diastolic blood pressure (SBP/DBP): 165.1 +/- 2.0/99.1 +/- 0.6 mmHg, LDL cholesterol: 5.38 +/- 0.16 mmol/L]. No significant difference was demonstrated between the groups on inclusion for any of the clinical parameters (SBP, DBP, heart rate (HR)) and laboratory parameters, apart from apolipoprotein A1, for which the mean value was higher in the rilmenidine group than in the captopril group (p < 0.05). No difference between the groups was demonstrated during the 8 weeks of treatment for the course of blood pressure: SBP and DBP decreased by 20.5 and 13.9 mmHg, respectively, in the rilmenidine group and by 21.3 and 13.1 mmHg in the captopril group (no significant difference: NS). HR decreased by 0.3 beats per minute (bpm) in the rilmenidine group and by 4.1 bpm in the captopril group (NS). No statistically significant difference in lipid parameters was observed between the two groups. No clinically significant variation in any of the lipid parameters was observed after 8 weeks of treatment with rilmenidine or captopril. These results confirm the antihypertensive efficacy and neutrality of rilmenidine on lipid metabolism over a period of 8 weeks. Rilmenidine therefore represents a useful alternative in the first-line treatment of hypertension in hyperlipidaemic hypertensive patients.

Antihypertensive Agents↗
PubMed1995

Identification of a new apolipoprotein E variant (E2 Arg142-->Leu) in type III hyperlipidemia.

A new rare apolipoprotein E mutant was identified as we were investigating the apolipoprotein E genotype of patients with type III hyperlipidemia (HLP III). The unusual DNA restriction fragment length polymorphism profile and then the sequence analysis of a PCR amplified fragment of the proband's apo E gene revealed a simple base substitution (G-->T) at nucleotide 3836. This mutation leads to the replacement of arginine by leucine at position 142 of the mature protein. The proband carried the mutant allele at the heterozygous status with an epsilon 3 allele. Subsequently, analysis of the proband's father's apo E gene showed that same mutated allele associated with an epsilon 2 allele. The two subjects presented a dysbetalipoproteinemia in which this new apo E variant could be implicated.

Aged↗
PubMed1995

Familial isolated vitamin E deficiency. Extensive study of a large family with a 5-year therapeutic follow-up.

A major neurological deterioration, beginning with ataxia, led to the diagnosis of familial vitamin E deficiency in a girl. Based upon vitamin E determinations, 4/8 members of the (consanguineous) sibship were considered to be homozygous. Homozygosity was also found for the alleles of six markers linked to the AVED locus, recently identified in similar Tunisian or Sicilian families on chromosome 8q. Measures of vitamin E in lipoprotein fractions and in liver biopsy after vitamin E oral load suggested that free diffusion of vitamin E between the different compartments was possible and even increased. However, a high-affinity ligand seemed to be lacking, either in the hepatic recycling of vitamin E or in both the hepatic and the other vitamin E compartments. The 5-year substitutive treatment was successful only in the pre- or paucisymptomatic patients. Serum vitamin E must be measured in any unexplained progressive ataxia.

Adolescent↗
PubMed1995

Lipid profile and antihypertensive efficacy in hyperlipidemic hypertensive patients: comparison of rilmenidine and captopril.

In hypertensive patients with lipid abnormalities, an ideal antihypertensive agent would control blood pressure without interfering with lipid metabolism. The aim of the present study was to assess whether in addition to angiotensin-converting enzyme inhibitors, calcium antagonists, and alpha 1-antagonists, rilmenidine (RIL), the first antihypertensive drug that is selective to imidazoline receptors, fulfills these requirements. To assess the effects of RIL (daily doses of 1 mg o.d. or b.i.d.) in comparison to captopril (CAP) (doses of 25 or 50 mg b.i.d.), an 8-week, double-blind, randomized, parallel-group study was carried out. Fifty-one patients (mean age: 56.3 +/- 1.5 years) with mild-to-moderate hypertension (supine systolic/diastolic blood pressure, 165.1 +/- 2.0/99.1 +/- 0.6 mm Hg) and type 2a or 2b hyperlipidemia (low-density lipoprotein (LDL) cholesterol: 5.38 +/- 0.16 mmol/L) were included in the study, and they were followed by their general practitioner at 4-week intervals. Twenty-six patients received RIL, and 25 received CAP. The permanence of hypercholesterolemia was checked twice before inclusion into the study, at 3-week intervals, for patients who had already been on a hypocholesterolemic diet for 6 weeks. Plasma lipid evaluation included total, LDL and high-density lipoprotein (HDL) cholesterol, triglycerides, apolipoproteins A1 and B, lipoprotein (a), and, last, a uric acid assay. Assays were centralized at the Lipid Laboratory, CHU Pitié-Salpétrière, Paris. In each group, 1 patient withdrew from the study for personal reasons, and four patients required a dose adjustment (double dose) at the week 4 visit. After 8 weeks of therapy, systolic blood pressure decreased significantly in both groups, with no statistically significant difference between groups (RIL, 20.5 mm Hg; CAP, 21.3 mm Hg; NS). Diastolic blood pressure also decreased (RIL, 13.9 mm Hg; CAP, 15.1 mm Hg; NS). No difference between groups was observed on the changes of lipid parameters between week 0 and week 8 visits. No severe adverse event occurred other than an asymptomatic atrial fibrillation in a CAP group patient at week 8. This study provides evidence that over a follow-up period of 8 weeks, both RIL and CAP are efficient and well-tolerated drugs in the first-line treatment of hypertensive patients with lipid abnormalities.

Adrenergic alpha-Agonists↗
PubMed1994

Chylomicron retention disease: exclusion of apolipoprotein B gene defects and detection of mRNA editing in an affected family.

Chylomicron retention disease (CRD) is a rare autosomal recessive disorder characterized by the absence of post-prandial chylomicrons and apolipoprotein (apo) B-48 in sera from affected individuals. Apo B-100 is synthesized, and apo B-100-containing lipoproteins are present in sera. A crucial difference between the synthesis and secretion of apo B-containing lipoproteins from the liver and gut in man is the generation of apo B-48 by editing of apo B mRNA in the gut to create a premature stop-translation codon. In this study the hypothesis that CRD may represent an absence of editing of apo B mRNA in the gut was investigated. Two affected sisters were identified as having low cholesterol levels and an absence of post-prandial chylomicronemia. Segregation analysis in the family showed that the apo B locus is not the site of the defect. Using reverse transcription-polymerase chain reaction (RT-PCR), duodenal biopsy-mRNA from the affected sisters was isolated and analyzed. The apo B editing site was amplified after cDNA synthesis, and the products analyzed by the primer extension assay. The results show that editing of apo B mRNA is normal in patients with CRD. The data provides strong confirmation that the primary defect in CRD is not in the synthesis, or editing of apo B mRNA in the gut. More likely, the disease arises from a defect in a gene crucial to the assembly and/or secretion of the chylomicron particle.

Apolipoprotein B-48↗
PubMed1994

[Pathology of the human apolipoprotein E gene].

Apolipoprotein E (apo E) is a polymorphic glycoprotein that plays an essential part in the binding to receptors for the uptake of chylomicrons and VLDL remnants and of LDL. The three major isoforms are E3 (Cys112/Arg158), E4 (Arg112/Arg158) and E2 (Cys112/Cys158). The apo E genetic variation has a great impact. In most of type III familial hyperlipoproteinemias (HLP), E2 is implicated at the homozygote status. In other cases, rare alleles are directly responsible for dominant type III HLP. Apo E polymorphism is an essential determinant in the interindividual variations of lipids in healthy subjects in various populations. Its influence can be significant on the efficacy of nutritional or therapeutic interventions. The allele epsilon 4 appears to be associated with an increased risk of premature atherosclerosis. Recently, epsilon 4 was demonstrated to be associated with an early Alzheimer's disease onset. Apo E polymorphism contributes to the lipid disorders in diabetes and obesity. The analysis of apo E polymorphism can be carried out with two conceptually different approaches. The first one is based on the separation of plasma isoforms of the protein by isoelectric focusing or bidimensional electrophoresis. The other one consists in the application of molecular biology techniques (PCR and endonuclease restriction profiles) for a detection of the common alleles and of several rare alleles, avoiding the possible errors of the phenotyping technique of the apo E protein. The application of genetic engineering allows a better understanding of the role played by apo E towards its receptors and in other molecular interactions which are not well known up to now.

Amino Acid Sequence↗
PubMed1993

Genetic exclusion of apo-B gene in recessive abetalipoproteinemia.

Abetalipoproteinemia is a recessive genetic disorder of unknown origin, which is characterized by absence of circulating apo-B-containing lipoproteins, malabsorption of intestinal fat, and degenerative neurological and retinal lesions. In this study, four families were analysed for genetic linkage between the abetalipoproteinemia phenotype and the apo-B genotype determined from polymorphisms of XbaI, MsPI, EcoRI and PvuII restriction sites and that of the 3'-minisatellite of the apo-B gene. The results definitively exclude mutation of the apo-B gene as a causal factor of abetalipoproteinemia in three families. Consanguinity of the parents in the fourth family made genotyping less conclusive.

Abetalipoproteinemia↗
PubMed1991

Anderson's disease: genetic exclusion of the apolipoprotein-B gene in two families.

Anderson's disease is a recessive disorder characterized by intestinal fat malabsorption, absence of postprandial chylomicrons, and reduced levels of cholesterol, triglycerides, and apoproteins B, AI, and C. We have studied two families with, respectively, three and two children with Anderson's disease. Intestinal apo-B and apo-AIV mRNAs from two Anderson's patients were normal in size but their concentration was decreased fivefold compared with controls. After DNA digestion with seven restriction enzymes, restriction fragment length polymorphisms of apo-B gene did not show conclusive information except for Xba1, which revealed a lack of cosegregation between the restriction fragment length polymorphism and the Anderson's phenotype. Linkage analysis was performed using the polymorphism of the apo-B gene 3'minisatellite. Genomic DNA from parents and children was amplified by polymerase chain reaction using oligonucleotide primers flanking the apo-B gene 3'hypervariable locus. In both families each child inherited different apo-B alleles from at least one parent. According to the recessive mode of transmission of the disease, our results are incompatible with the involvement of the apo-B gene. More likely a posttranslational defect or a mutation in another gene encoding a protein essential for lipoprotein assembly or secretion may be involved.

Adolescent↗
PubMed1990

[Use of 6 serum pools in standardization of the determination of apolipoproteins AI and B in the human serum].

The proliferation of commercial immunoassays for the determination of apolipoproteins AI and B as parameters of risk for coronary heart disease and the discordance between the values obtained with the systems have made more urgent than ever the need for standardization of these assays. The authors report here the results of a collaborative study on the standardization of the values between the "Comité Française de Coordination des Recherches sur l'Athérosclérose et le Cholestérol (ARCOL)" and 13 Companies providing 15 different analytical systems. The results show that standardized measurements are not possible using a "consensus international standard" and that the major problem is related to the enormous variability of the analytical systems. In contrast, the present study demonstrates that six different serum pools containing increasing amounts of apolipoproteins AI and B can be used to generate a common reference curve which permits calibration of all immunoassays and standardization of results.

Apolipoprotein A-I↗
PubMed1990

Description of two different patients with abetalipoproteinemia: synthesis of a normal-sized apolipoprotein B-48 in intestinal organ culture.

We describe here two patients, M. P. and S. L., with recessive abetalipoproteinemia. Analysis of restriction fragments of DNA from both patients using cDNA probes spanning the entire apolipoprotein B gene revealed no major insertions or deletions. Further, as defined by restriction fragment length polymorphism, abetalipoproteinemia, in these patients, did not appear associated with particular alleles of apolipoprotein B. Northern and dot blot analysis of intestinal mRNA of one patient (M. P.) revealed a normal-sized apolipoprotein B mRNA which was present in slightly reduced amounts. At the cellular level apolipoprotein B was detected in both intestinal and hepatic biopsies, of one patient (S. L.), by immunoenzymatic techniques using polyclonal and monoclonal antibodies to apolipoprotein B-48 and/or B-100. The level of apolipoprotein B-48 appeared to increase in the intestine after a fatty meal. In the other patient (M. P.), although no apolipoprotein B was detected in the enterocytes using similar immunoenzymatic techniques, organ culture experiments using [35S]methionine demonstrated the synthesis of a normal-sized apolipoprotein B-48 which appeared to be normally glycosylated. The glycosylation and processing of two intestinal membrane enzymes, sucrase-isomaltase and aminopeptidase N, were also normal. Although lipids and apolipoprotein B-48 were present intracellularly, no lipoprotein-like particles were observed by electron microscopy in the endoplasmic reticulum, the Golgi apparatus, or in the intercellular spaces of intestinal biopsies obtained in the fasted (M. P. and S. L.) or fed state (S. L.). The defect in these cases of abetalipoproteinemia, therefore, does not appear to involve the apolipoprotein B gene nor the synthesis or the glycosylation of the apolipoprotein but instead appears to involve some aspect of lipoprotein assembly or secretion.

Abetalipoproteinemia↗
PubMed1988

Electroimmunoassay of human serum lipoproteins containing Apo A-I by monoclonal antibodies.

Three monoclonal antibodies to human serum apolipoprotein (Apo) A-I (4A12, 4B11 and 2G11) were produced by Sanofi. They were directed to three distinct epitopes of the Apo A-I molecule, present on the surface of the lipoprotein particles. They were able to precipitate individually some lipoprotein units from the serum. Only the mixture of the three monoclonal antibodies could allow a precipitation of all Apo A-I containing particles. An electroimmunoassay using this oligoclonal mixture was assessed to standardize the Apo A-I measurement in serum. Results agreed well with those obtained by electroimmunoassays using polyclonal antisera. Moreover no pretreatment of serum samples with dissociating agents or detergents was required. Therefore, this specific, rapid (7-8 h), precise (within- and between-assay precisions were 4.25 and 3.1%, respectively) immunoassay is routinely available for apolipoprotein A-I measurement in serum.

Antibodies, Monoclonal↗
PubMed1987

Immunological detection of low-density lipoproteins modified by malondialdehyde in vitro or in vivo.

We describe an ELISA technique able to recognize malondialdehyde-modified low-density lipoproteins (LDL). For this purpose we produced antibodies to malondialdehyde-LDL, specific for the malondialdehyde modification of LDL; these antibodies recognized essentially malondialdehyde-LDL. Coating ELISA plates with the antibodies to malondialdehyde-LDL and using peroxidase-labelled antibodies to LDL, which reveal only apolipoprotein B, we obtained an accurate method of detecting malondialdehyde-modified apolipoprotein B. Preliminary studies demonstrated that this method allows the detection of lipoproteins containing malondialdehyde-modified apolipoprotein B in the serum of patients with cardiovascular diseases.

Animals↗
PubMed1986

Hypobetalipoproteinemia with accumulation of an apoprotein B-like protein in intestinal cells. Immunoenzymatic and biochemical characterization of seven cases of Anderson's disease.

We describe here seven cases (from five kindreds) of Anderson's disease, which is characterized by diarrhea, steatorrhea, hypobetalipoproteinemia with low levels of cholesterol, triglycerides, and phospholipids, and failure to secrete chylomicrons after a fat meal. Enterocytes isolated from intestinal biopsies of patients after overnight fast showed numerous fat droplets, a histological picture resembling that of abetalipoproteinemia. Immunoenzymatic staining of the enterocytes demonstrated large amounts of material that reacted with a polyclonal antiserum to apolipoprotein B. Further, the immunoreactive material was found to react with several different monoclonal antibodies capable of recognizing both the B100 and B48 forms of apoprotein B, but not with any of several monoclonal antibodies capable of recognizing only B100. This suggests that the material in the enterocytes is the B48 form of apoprotein B or a fragment thereof. Additional findings included decreased low density lipoprotein levels with an abnormal chemical composition, abnormal high density lipoprotein2 (HDL2) and HDL3 particle size distributions, and an abnormal HDL apoprotein composition. Increased amounts of proteins having electrophoretic mobilities similar to apo E and the E-AII complex were present. Finally, some cases exhibited additional protein components of apparent molecular weights between 17,000 and 28,000, which was similar to some cases of abetalipoproteinemia. These findings demonstrate that Anderson's disease is not due to the absence of synthesis of intestinal apo B and suggest that it is more complex than previously thought, affecting all the lipoprotein classes.

Abetalipoproteinemia↗
PubMed1986

[Structure and metabolism of lipoproteins].

Lipoproteins constitute in plasma a dynamic system allowing lipid transport. For this purpose, apolipoproteins play a very important part. They control and regulate lipid transfer between lipoproteins themselves and among cells, from their hepatic as intestinal synthesis sites to their hepatic as peripheral degradation sites. Enzymatic systems and specific receptors are involved to operate this metabolic pathway.

Chemical Phenomena↗
PubMed1984

[Dissociation of human serum low density lipoproteins in several immunologically distinct subunits. Isolation and characterization of a B-III subunit].

Low density lipoproteins (d = 1.030-1.055) were partially delipidated with ethyl-ether (LDLe). These LDLe exhibit a spontaneous dissociation several days after delipidation. Four different immunoprecipitation complexes (B-I to B-IV) are observed when using two dimensional immunoelectrophoresis against anti LDLe immunserum. The various subunits of LDLe have different behaviour upon electrophoresis. On disc gel electrophoresis containing urea three bands can be seen; all are phospholipoproteins. The apolipoprotein moiety of LDL and LDLe have the same apparent molecular weight around 550 000. With time several subunits appear in LDLe, the majority of them have a molecular weight around 370 000, 260 000 and 125 000. One of the components from dissociated LDLe containing the immunodeterminant B-III, has been separated by chromatography on heparin-agarose. This LDLe-B-III has the same phospholipid/protein ratio as total LDLe and a protein moiety with an apparent molecular weight of 110 000. This part of apolipoprotein B has no affinity for heparin. Immunocompetition studies by the ELISA technique indicated that sialic acid, one of terminal residues of LDL glycoprotein, is involved in the immunological recognition of LDL and of its derivatives by anti LDL and anti LDLe antisera.

Amino Acids↗