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Biomedical subjects

J M Bard

Publications and source records attributed to J M Bard.

At least 91 records · Page 5Linked to original sources
PubMed1991

[Interaction between LDL receptor and lipoproteins containing apo B].

The physiocochemically defined lipoproteins such as VLDL, LDL are comprised of subpopulations with different lipid and apolipoprotein composition. In order to determine the respective roles of different apolipoproteins (B, C-III, E) in their metabolism, four species (LpB, LpB:E, LpB: C-III and LpB: C-III: E) have been separated by sequential immunoaffinity chromatography. We examined the binding characteristics of each lipoprotein to HeLa cells and expressed the results in relation to the number of moles of apo B. LpB particles which contained apo B as their sole apolipoprotein had lower affinity for the LDL receptor that did total LDL but an apparently higher number of binding sites. The presence of apo E of phenotype E3 or E4 on one particle increased the affinity for the receptor. The apparent number of binding sites decreased probably due to the fact that a particle containing multiple copies of apo E bound to more than one molecule of receptor. Interaction with several LDL receptors would also explain the higher binding affinity which we observed. When the apo E phenotype was E2/E2, the LpB: E particle did not bind to the receptor. We showed also that apo C-III, when present, diminished the binding of apo B containing lipoproteins. These data suggest that apolipoproteins E and C-III impaired the interaction of apo B with the LDL receptor. It is likely that in LpB: E only apo E (in the case of E3 or E4 phenotype) participates in the LDL receptor binding.

Apolipoproteins B↗
PubMed1991

Diverse effect of ethnicity on plasma lipoprotein[a] levels in heterozygote patients with familial hypercholesterolemia.

Plasma lipids, lipoproteins, and lipoprotein[a] (Lp[a]) levels were determined in 216 members of 14 families with familial hypercholesterolemia (FH). Ninety-nine subjects harbored a mutant low density lipoprotein (LDL) receptor allele as confirmed by molecular genetic analysis. Four different mutant alleles were identified, each in a defined genetic group, Druze, Christian-Arabs, and Ashkenazi and Sephardic Jews. The findings in FH subjects (cases) were compared with their nonaffected family members (controls). Plasma Lp[a] levels increased with age in the controls but not in cases and were different among the four genetic groups. Mean plasma Lp[a] levels were significantly higher in cases (33 mg/dl) than in controls (22 mg/dl). Plasma LDL cholesterol levels were raised in cases of the four genetic groups to a similar extent, in contrast to the mean plasma Lp[a] that varied. The Lp[a] level was higher by 30-33% in cases from the Druze, Christian-Arabs, and Jewish-Ashkenazi groups but by 110% in the Jewish-Sephardic group. Apo[a] isoform distribution was similar in cases and controls within each genetic group. Lp[a] levels were highest in subjects with LpS1 isoform, in particular in cases from the Jewish-Sephardic group. These data indicate that the higher Lp[a] levels in FH heterozygotes cannot be attributed solely to lack of functional LDL receptor molecules but possibly reflect multiple gene interactions.

Adolescent↗
PubMed1991

Heterozygous hypobetalipoproteinemia with fasting chylomicronemia.

We describe a disorder in which low-density lipoprotein (LDL)-cholesterol and apolipoprotein B are in low concentration (0.47 mmol/L and 0.28 g/L, respectively) and chylomicrons are still present in plasma after an 18-h fast. The d less than 1.006 fraction was isolated by flotation ultracentrifugation and the apolipoproteins were analyzed by electrophoresis, immunoblotting with anti-apolipoprotein B-100 antiserum, and isoelectric focusing. In the d less than 1.006 fraction of the fasting serum, we found an apolipoprotein B form with the same apparent molecular mass as apolipoprotein B-48 and similar in amount to apolipoprotein B-100 (respective percentages, 46% and 54%). The monosialylated form of the apolipoprotein C-III was severely decreased. After an oral fat load, the repartition of the two species of apolipoprotein B did not change greatly (respective percentages, 60% and 40%), and the concentration of serum triglyceride increased only from 1.20 to 1.65 mmol/L.

Adult↗
PubMed1990

Lipoprotein particles in homozygous familial hypercholesterolemic patients treated with portacaval shunt and LDL apheresis.

Lipoprotein particles containing apolipoproteins (Apo) were studied by enzyme-linked-immunosorbent assay in two homozygous familial hypercholesterolemic patients (1 male and 1 female) with portacaval shunts, and in controls. Total Apo B, total cholesterol and LDL cholesterol were increased in both patients while complex Apo B containing particles, Lp CIII: B, were not increased in these FH patients. The dextran-sulfate cellulose columns (Liposorber LA-40) had an excellent adsorption selectivity and adsorption capacity for lipoprotein particles containing Apo B and a minimum adsorption capacity in Apo AI and Apo AII-containing particles. This apheresis technique selectively depleted plasma of atherogenic Apo B-containing particles with a minimal loss of antiatherogenic Apo AI-containing particles.

Adolescent↗
PubMed1990

The increased plasma Lp(a): B lipoprotein particle concentration in angina pectoris is not associated with hypofibrinolysis.

The structural homology between plasminogen and apolipoprotein (a), the specific glycoprotein of Lp(a) lipoprotein, raises the possibility of a relationship between this lipoprotein and the plasma fibrinolytic system. The present study examines this proposal by studying 66 patients with angina pectoris. As compared to normal controls, the patients had raised concentrations of Lp(a): B lipoprotein particles. No correlation was found between circulating Lp(a): B and the fibrinolytic system. The pathogenic role of Lp(a): B lipoprotein seems therefore not mediated by its effect on the plasma fibrinolytic system.

Aged↗
PubMed1990

Logistic discriminant analysis of lipids and apolipoproteins in a population of coronary bypass patients and the significance of apolipoproteins C-III and E.

The lipid and apolipoprotein states of 74 men (mean age 49.96 +/- 5.9 years) were studied 24 h before coronary bypass surgery and their results were compared with those of a control group of 78 men (mean age 48.88 +/- 5.41 years). Apolipoproteins C-III (apo C-III) and E (apo E) were determined in particles with (LpB) and without (nonLpB) apo B separated using a concanavalin A reagent. Apo C-III was significantly increased in LpB particles (P less than 0.001), and apo E in LpB (P less than 0.001) and nonLpB (P less than 0.001) particles. The significant variables selected in logistic discriminant stepwise analysis were total cholesterol/HDL-cholesterol, apo E-nonLpB and apo C-III-LpB. This last parameter, which is more discriminant than triglycerides, provides a more specific indication of dyslipoproteinemia in coronary bypass patients; in association with the other two variables, it significantly improved the percentage of correctly classified individuals.

Adult↗
PubMed1990

Effect of pravastatin, an HMG CoA reductase inhibitor, and cholestyramine, a bile acid sequestrant, on lipoprotein particles defined by their apolipoprotein composition.

This study compares the effects of cholestyramine (16 g/d) and pravastatin (40 mg/d) on lipoprotein particles defined by their apolipoprotein composition (Lp A-I, Lp A-II:A-I, Lp E:B, and Lp C-III:B). Analysis was performed after 4, 8, and 12 weeks of therapy. Low-density lipoprotein (LDL) cholesterol decreased by 25.1% to 35.0% with cholestyramine and 26.2% to 30.7% with pravastatin, while triglycerides decreased slightly with pravastatin therapy and increased slightly during cholestyramine administration. The fall in cholesterol was mainly due to a decrease in very-low-density lipoprotein (VLDL) and LDL cholesterol; high-density lipoprotein (HDL) cholesterol increased. Apolipoprotein B was reduced dramatically (by 21.7% to 30.5% with cholestyramine and 27.7% to 37.4% with pravastatin). No significant effect on apolipoproteins C-III and E was observed with cholestyramine, while pravastatin reduced these parameters slightly. Apolipoprotein A-I increased during therapy with both drugs, while apolipoprotein A-II was slightly decreased. Although the drugs had nearly the same effects on plasma lipids, their influence on lipoprotein particles defined by their apolipoprotein composition was substantially different. Lp A-II:A-I was increased by both drugs (+8.1% to +41.2% for cholestyramine and +7.2% to +32.6% for pravastatin). Lp A-I was also increased with both drugs, but cholestyramine had a more constant and pronounced effect than pravastatin (+15.1% to +21.7% for cholestyramine and +1.7% to +13.0% for pravastatin). Lp E:B and Lp C-III:B were consistently decreased by pravastatin (-10.2% to -36.5% for LP E:B and -7.2% to -20.9% for Lp C-III:B), while cholestyramine had variable effects on these particles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

[Determination of blood profile of atherogenic lipids using immunologic techniques].

Apolipoprotein B (Apo B) exists in different types of particles in human plasma: Lp B containing only Apo B, Lp B:E containing Apo B and Apo E, Lp B:C-III containing Apo B and Apo C-III, Lp B: (a) containing Apo B and Apo (a) and so on. The physicochemically defined lipoproteins were found to be heterogeneous with respect to this concept. A particle such as Lp B, for example, may occur in any segment of the density spectrum depending on the composition and content of its lipid complement. These particles are metabolically distinct and their quantification is essential for better understanding of lipid transport disorders. Using new immunological procedures, we have identified some subpopulations of Apo B containing lipoproteins which are more abondant in atherosclerotic patients and which characterize some dyslipoproteinemic states. Drugs decreasing Apo B act differently on these different types of particles. The results presented substantiate the usefulness of the study of lipoprotein particles defined by their apolipoprotein composition for future clinical, pharmacological and epidemiological studies.

Apolipoproteins B↗
PubMed1990

Differential electroimmunoassay of human LpA-I lipoprotein particles on ready-to-use plates.

We describe a method for directly measuring LpA-I lipoprotein particles containing apolipoprotein A-I (apo A-I) not associated with apolipoprotein A-II (apo A-II), by differential electroimmunoassay of plasma on ready-to-use plates. Lipoprotein particles containing both apo A-I and apo A-II (LpA-I:A-II) are retained close to the wells when a very high excess of anti-apo A-II is used as compared with anti-apo A-I, whereas the LpA-I particles migrate and react with anti-apo A-I. The method is specific, rapid, and precise. Within- and between-run CVs at three concentrations (high, medium, and low) ranged between 1.51% and 2.72% and 3.01% and 4.56%, respectively. Analytical recovery of isolated LpA-I was from 93% to 115%. Results correlate well with those obtained by two-phase electroimmunoassay, enzyme-linked differential-antibody immunosorbent assay, and immunoaffinity chromatography coupled to enzyme-linked immunosorbent assay. The average normolipidemic concentration of LpA-I was 600 mg/L in 45 women and 490 mg/L in 40 men (P less than 0.0001).

Adult↗
PubMed1989

Effect of simvastatin on plasma lipids, apolipoproteins and lipoprotein particles in patients with primary hypercholesterolaemia.

The effect of treatment with simvastatin, a new HMG-CoA reductase inhibitor, has been investigated in 27 patients with primary hypercholesterolaemia. It produced a significant decrease of cholesterol and phospholipids in plasma, LDL and apolipoprotein B-containing lipoproteins. Plasma apolipoproteins B, C-III and E were also significantly lowered. The concentration of lipoprotein particles recognized by monoclonal antibodies (BL3, BL5 and BL7), associated with atherosclerotic disease, was also lowered by the treatment. Lipoproteins LpA-II:A-I were not changed, while LpA-I, which has been suggested to be the protective fraction of the apo A-I-containing lipoproteins, was slightly and inconsistently increased.

Adolescent↗
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

Apolipoprotein B immunochemical heterogeneity in dialysed patients with chronic renal failure and patients with coronary artery stenosis.

Serum cholesterol, triglyceride, apolipoprotein B (apo B) and the cholesterol and phospholipid content of apo-B-containing particles was determined in 41 male patients on dialysis for chronic renal failure, in 41 male patients with coronary artery disease selected on the basis of a total cholesterol level below 6.72 mmol/l and in 41 male control subjects of similar age. Apo B was assessed as total B protein determined using polyclonal antibodies and also by measuring the expression of epitopes recognized by three different monoclonal antibodies (BL3, BL5 and BL7). Triglyceride was increased (p less than 0.01) and cholesterol was decreased (p less than 0.01) in the dialysed patients with chronic renal failure. Total apo B was similar in the three tested groups while the expression of the BL7 epitope was increased in the group of dialysed patients with chronic renal failure (p less than 0.001). The expression of BL3 and BL5 epitopes was increased in patients with coronary artery disease (BL3: p less than 0.05; BL5: p less than 0.02) but not in dialysed patients with chronic renal failure. These results suggest an abnormal composition and an immunological heterogeneity of apo-B-containing lipoprotein particles in patients with coronary artery stenosis and in dialysed patients with chronic renal failure.

Antibodies, Monoclonal↗
PubMed1989

Apolipoproteins in human amniotic fluid: concentrations, isoforms and polymorphism.

Apolipoproteins were determined in 50 human amniotic fluids obtained by amniocentesis during weeks 16 and 22 (n = 26) or 33 and 41 (n = 24) of gestation. Whereas apo A-I, A-II, A-IV, and E were identified at levels of 1, 0.7, 0.8 and 1% of normal human adult plasma, respectively, apo B levels were only 0.04% of plasma concentration and apo C-III levels were below the detection limits of the assay. Amniotic fluid levels of apo A-II, A-IV and E did not differ between early and late stages of pregnancy, but levels of apo B decreased and apo A-I increased significantly in late pregnancy. Isofocusing showed apo A-I, A-II and A-IV in identical positions as compared to human adult plasma. Furthermore the known genetic polymorphism of apo A-IV was detectable. Individuals heterozygous, for the variant form apo A-IV-2, showing the phenotype apo A-IV (2-1), had significantly higher levels of apo A-I and A-II as compared to the common phenotype apo A-IV (1-1). We conclude that human amniotic fluid contains the major plasma apolipoproteins at about 1% of plasma levels with the exception of apo B which shows a level at an order of magnitude less than high-density lipoprotein apoproteins in comparison to their plasma counterparts.

Amniotic Fluid↗
PubMed1987

Effect of fenofibrate treatment on type III hyperlipoproteinemia.

The effect of treatment with fenofibrate was investigated in nine patients (seven men) presenting with type III hyperlipoproteinemia. This therapy produced a statistically significant decrease in serum triglyceride, cholesterol, apolipoproteins B, CII, CIII, and E levels. Particular attention was focused on lipoproteins containing apolipoprotein B. The concentration of particles recognized by monoclonal antibodies (BL3, BL5, and BL7), associated with atherosclerotic disease, was lowered by the treatment. The most dramatic decrease was observed for lipoproteins LpE:B and LpCIII:B, which are particularly enhanced in type III hyperlipoproteinemia.

Adult↗