Search PubMed⌕ Search

Biomedical subjects

J Davignon

Publications and source records attributed to J Davignon.

At least 145 records · Page 8Linked to original sources
PubMed1990

Influence of a triphasic oral contraceptive preparation on plasma lipids and lipoproteins.

The influence of a triphasic oral contraceptive preparation on plasma lipid, lipoprotein, and apolipoprotein levels was studied in 20 women during 12 treatment cycles. Multiple blood samples representing all phases of the therapeutic cycle as well as posttherapy were obtained. Total and low-density lipoprotein (LDL) cholesterol fluctuated transiently in the earlier part of the study but after 9 and 12 cycles of therapy did not differ from baseline. Cyclic elevations in total cholesterol corresponding to changes in LDL cholesterol were noted twice. Total high-density lipoprotein (HDL) cholesterol remained remarkably stable over the entire study while HDL2 cholesterol decreased and HDL3 cholesterol increased. Triglycerides (total and lipoprotein fractions) increased during treatment and fell to baseline levels within one posttreatment cycle. Very low-density lipoprotein (VLDL) cholesterol was also elevated during the study. Apolipoprotein (apo) AI, apo AII, and apo B rose under therapy, the latter increase producing a lowered LDL cholesterol/apo B ratio. Apolipoprotein E showed a temporary decrease early in the study but otherwise remained unchanged.

Adolescent↗
PubMed1990

Common low-density lipoprotein receptor mutations in the French Canadian population.

Familial hypercholesterolemia (FH) has a frequency of 0.2% in most populations of the world. In selected populations such as the Afrikaners in South Africa, the Christian Lebanese, and the French Canadians, the disease is more frequent due to the founder effect. Previous studies demonstrated that a single mutation at the LDL receptor locus, the so-called French Canadian deletion, makes up 60% of the mutant genes responsible for FH in the French Canadian population. In this study, efforts were directed to determine if there were other common LDL receptor mutations in this population. Three missense mutations were identified and each mutation was reproduced and expressed in vitro. Two of the three mutations result in the production of an LDL receptor protein that is not processed to its mature form at a normal rate. Molecular assays were developed to detect the mutations directly, and the LDL receptor genes of 130 French Canadian FH heterozygotes were screened for the presence of the three missense mutations as well as two deletions. LDL receptor mutations were detected in 76% of individuals and 14% had one of the three missense mutations.

Base Sequence↗
PubMed1990

Familial defective apolipoprotein B-100: a mutation of apolipoprotein B that causes hypercholesterolemia.

Familial defective apolipoprotein B-100 is a genetic disorder of apolipoprotein B-100 that causes moderate to severe hypercholesterolemia. A single amino acid mutation in apolipoprotein B diminishes the ability of low density lipoproteins to bind to the low density lipoprotein receptor. Low density lipoproteins accumulate in the plasma because their efficient receptor-mediated catabolism is disrupted. This mutation has been identified in the United States, Canada, and Europe and is estimated to occur at a frequency of approximately 1/500 in these populations. Thus, it appears that this newly described disorder may be a significant genetic cause of hypercholesterolemia in Western societies.

Apolipoprotein B-100↗
PubMed1990

Analytical isoelectric focusing with immobilized pH gradients of human apolipoprotein E from very low density lipoproteins and total plasma.

A method for analytical isoelectric focusing (IEF) of apolipoprotein E (apoE) in immobilized pH gradients (IPG) and immunodetection of the separated isoforms has been developed for use with either very low density lipoproteins (VLDL) or whole plasma. Both VLDL and plasma were sequentially delipidated with 1,4-dioxane, acetone-ethanol, and ether. Neuraminidase treatment preceded the delipidation when required. Using preformed plates, pH 5.0-6.0 (LKB, Bromma) after rehydration with 6 M urea and dextran T-10, the IPG focusing pattern of the common isoforms (E2, E3, E4) was found to be equivalent to conventional IEF with the added resolution of the E4 disialo form. The use of self-poured narrower gradients permitted the further resolution of the E4 monosialo form, a previously unrecognized heterogeneity of the E2, E3, and E4 monosialo isoforms and differentiation of the apoE2** mutant; all of these forms comigrate with the common isoproteins in conventional IEF. Finally, the conditions for IPG of whole plasma using apoE monoclonal antibodies and enzyme-conjugated anti-mouse IgG for detection were established. Thus, IPG focusing is shown to be a powerful method for resolution of the apoE sialoforms and apoE mutant forms. The method has important implications in accurate and diagnostic phenotyping. Moreover, it is a convenient method for phenotyping which requires only very small volumes of plasma.

Apolipoproteins E↗
PubMed1989

Lipoprotein composition changes induced by fenofibrate in dysbetalipoproteinemia type III.

Fenofibrate (300 mg daily) was given to 9 subjects (7 men, 2 women) with dysbetalipoproteinemia type III. The treatment brought about important plasma level reductions in cholesterol (-35%), triglycerides (-56%), VLDL-cholesterol (-63%) and VLDL-triglycerides (-59%). The VLDL-C/TG ratio, which was 0.40 before treatment, was 0.30 after 4 weeks of fenofibrate, still suggestive of type III. LDL-C, when measured by conventional methods, was unchanged but isolation of the IDL (1.006-1.019 g/ml) fraction from the 1.006 g/ml infranatant revealed that true LDL-C levels actually increased in 6 individuals while IDL-C decreased considerably. The total HDL-C increase was mostly due to a 33% HDL3-C change. Apolipoprotein levels were considerably modified, notably apo B, C-III and E which were decreased, as well as the lipoprotein particles containing combinations of these apolipoproteins, namely LpE:B and LpC-III:B. Apo A-I was slightly modified as LpA-I: A-II particle levels increased and LpA-I decreased. There were marked compositional modifications of apo B-containing lipoproteins which corresponded to changes of the whole lipoprotein profile. Some abnormal classes of lipoproteins (e.g., beta-VLDL, dense LDL), characteristic of this disease, tended to disappear and were in some cases replaced by material of different size and density.

Adult↗
PubMed1989

Identification of a second "French Canadian" LDL receptor gene deletion and development of a rapid method to detect both deletions.

Hobbs et al. (N. Engl. J. Med. 317: 734-737, 1987) reported a large deletion of approximately 10 kilobases in the 5' portion of the human low-density lipoprotein (LDL) receptor gene. This deletion affects about 60% of familial hypercholesterolemia (FH) heterozygotes in the French Canadian population. We have developed a rapid, convenient method for the detection of the deletion using double digestion with the restriction enzymes XbaI and EcoRV, or triple digestion with XbaI, EcoRV and XmnI, and a 650 bp cDNA probe, radio-labeled using a random oligonucleotide primer technique. Eighty French Canadian FH heterozygotes were screened for the presence of the deletion. Forty-seven (59%) of them were found to carry the 10 kb deletion. Using the same method, we also identified a new mutation which was found in four of the 80 (5%) FH patients. This mutation has been found to be a 5 kb deletion removing exons 2 and 3 of the LDL receptor gene, which correspond to the first two repeats of the LDL receptor binding domain. Cosegregation of the 5 kb deletion and the FH phenotype was observed in one family. Possible structure-function relationship is discussed.

Canada↗
PubMed1988

Identification of the patient at risk in the physician's office and drug management of dyslipoproteinemia.

The wealth of convincing evidence favouring the major role of lipids in atherosclerosis and the benefit of lipid lowering therapy for its prevention now sets the stage for more practical questions: "Whom to treat? When to treat? How to treat?". Although each patient must be considered individually, there are general rules and specific guidelines that should be underlined. An isolated finding of abnormal lipid levels should by no means be a systematic starting point for initiating treatment. In a step by step approach, guidelines for individual risk assessment, systematic search for specific clinical clues and pertinence of complementary investigative measures are given. In addition to ensuring a correct diagnosis, these recommendations will orient the physician's decision with respect to the necessity of initiating treatment and, if warranted, the choice of an optimal treatment algorithm. Therapeutic modalities are discussed both in general and specific terms, focusing mostly on pharmacologic agents. Clinical indications, mechanisms of action, adverse effects and expected efficacy are seen for each drug or family of drugs, including those with a promising future. In summary, 10 easy rules of thumb are provided to ensure adequate diagnosis and management of hyperlipidemia.

Humans↗
PubMed1988

Sources of interindividual variation in the quantitative levels of apolipoprotein B in pedigrees ascertained through a lipid clinic.

The quantitative level of apolipoprotein (apo) B associated with low-density lipoprotein (LDL) varies among individuals within the population. This variation in level of the LDL receptor ligand appears to have predictive value, and may have an etiologic role, in coronary artery disease. Complex segregation analysis was used to compare eight different models of transmission. This study confirms the existence of allelic variations at a single genetic locus with large effects on the interindividual variation in the level of the serum apo B associated with LDL. This is the first study to consider the possible effects of inherited polymorphic variation in the apo E molecule when analyzing the components of variation in apo B associated with LDL. Our analyses suggest that the common alleles coding for the apo E polymorphism act independently of the unmeasured single-gene locus characterized by this study.

Age Factors↗