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Biomedical subjects

J M Bard

Publications and source records attributed to J M Bard.

At least 73 records · Page 4Linked to original sources
PubMed1993

Sequential ultracentrifugation micromethod for separation of serum lipoproteins and assays of lipids, apolipoproteins, and lipoprotein particles.

We describe a fast sequential separation of very-low-density, low-density, and high-density lipoproteins from 400 microL of serum, using the Beckman TL100 ultracentrifuge. The cumulative centrifugation time is 9.5 h. The purity of lipoprotein fractions was verified by a gel-filtration procedure. The major contaminant is the serum albumin, which can be eliminated by a second centrifugation at the same density. Enzymatic measurement of lipids shows good recovery (> 91%) and weak within-sample variation (< 7%). In comparison with a density-gradient procedure, the deleterious effects on the lipoprotein structure appear to be limited, as shown by the low concentrations of apolipoprotein (apo) E and apo A-I in the fraction > 1.21 kg/L. Furthermore, the micro-ultracentrifugation also gives a better recovery rate. Finally, we have studied the distribution of lipids, apolipoproteins, and lipoprotein particles (LpA-I:A-II, LpB:C-III, LpB:E) in each fraction separated from 10 serum samples from healthy subjects.

Adult↗
PubMed1992

Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction.

Factors involved in the pathogenesis of atherosclerosis, thrombosis and vasoconstriction contribute to the development of coronary heart disease. In a study comparing patients after myocardial infarction with controls, we have explored a possible association between coronary heart disease and a variation found in the gene encoding angiotensin-converting enzyme (ACE). The polymorphism ACE/ID is strongly associated with the level of circulating enzyme. This enzyme plays a key role in the production of angiotensin II and in the catabolism of bradykinin, two peptides involved in the modulation of vascular tone and in the proliferation of smooth muscle cells. Here we report that the DD genotype, which is associated with higher levels of circulating ACE than the ID and II genotypes, is significantly more frequent in patients with myocardial infarction (n = 610) than in controls (n = 733) (P = 0.007), especially among subjects with low body-mass index and low plasma levels of ApoB (P < 0.0001). The ACE/ID polymorphism seems to be a potent risk factor of coronary heart disease in subjects formerly considered to be at low risk according to common criteria.

Adult↗
PubMed1992

Isolation and characterization of two sub-species of Lp(a), one containing apo E and one free of apo E.

Lipoprotein Lp(a) was isolated by immunoaffinity chromatography using anti apolipoprotein B and anti apolipoprotein (a) immunosorbents. Besides apolipoproteins (a) and B, this fraction was shown to contain apolipoproteins C and E. Therefore, it was decided to further purify this crude Lp(a) into particles containing apolipoprotein E and particles free of apo E, using chromatography with an anti apolipoprotein E immunosorbent. Lp(a), free of apolipoprotein E was cholesterol ester rich and triacylglycerol poor and was found mainly in the LDL size range. In contrast, Lp(a) containing apolipoprotein E was triacylglycerol rich and was distributed mainly in the VLDL and IDL size range. Binding of these two fractions, one containing apo E and one free of it, to the apo B/E receptor of HeLa cells was studied. Both fractions bound to the receptor but the one containing apo E had a better affinity than the one free of apo E. Further studies are needed to identify the clinical importance of these two different entities.

Apolipoproteins↗
PubMed1992

Low-density lipoprotein for delivery of an acrylophenone antineoplastic molecule into malignant cells.

In vitro and in vivo data have indicated that tumor cells actively internalize the low-density lipoprotein (LDL) from the circulation. A family of 2-(aminomethyl) acrylophenones (AMA) possesses an in vitro antileukemic activity but is devoid of any in vivo antineoplastic activity, because the compounds are actively captured by proteins in solution in the blood. In order to achieve a selective delivery of these drugs via the LDL pathway, we have incorporated an AMA drug, 2-morpholinomethyl-2',3',4'- trimethoxy acrylophenone hydrochloride (ILE) into LDL particles. ILE spontaneously associated with LDL to produce an LDL-ILE complex containing 200 +/- 100 molecules of drug per LDL particle. The LDL-ILE complex was highly electronegative as detected by electrophoresis. Further, this complex presented an immunologically detected over expression of the ligand-binding domain to the LDL receptor. In spite of these modifications, the LDL receptor processing bound, internalized, and degraded the LDL-ILE complex. Nevertheless, these biological properties were reduced by 32, 20, and 40%, respectively, in comparison to native LDL. Despite its high electronegativity, the LDL-ILE complex was not recognized by the macrophagic scavenger receptor. The LDL-ILE complex showed specific LDL receptor mediated in vitro cytotoxicity as judged from the growth inhibition of neoplastic A549 cells and of normal fibroblasts, but no activity on defective LDL receptor cells. Further, the pharmacological activity of the complex against A549 cells has been demonstrated to be equally potent as that of the free drug (median inhibitory dose, 5 microM). It is suggested that LDL drug targeting of AMA molecules could specifically deliver active molecules to cancer cells, avoiding their entrapment by other blood proteins and their rapid clearance by the reticuloendothelial system.

Antibodies, Monoclonal↗
PubMed1992

Increased triglyceride levels in shift workers.

PURPOSE: To assess an independent relationship between shift work and serum lipid levels. DESIGN: Cross-sectional survey. SETTING: Two plants of northern France: a chemical one and a nuclear power station. PARTICIPANTS: All the shift workers of the chemical plant and of one part of the nuclear station. One hundred nine persons were selected, 25 were excluded or absent during the study, and 11 refused to participate. Day workers matched with shift workers according to age, educational level, birthplace, and occupational physical activity level served as controls; 109 were selected, 26 were excluded or absent, and 10 refused to participate. MAIN OUTCOME MEASURES: Fasting venous plasma concentration of total cholesterol, triglyceride, and high-density lipoprotein (HDL) cholesterol; dietary intake assessed by a 3-day record, smoking habits, and body mass index (BMI). RESULTS: Shift workers had significantly higher levels of serum triglyceride (1.26 versus 1.03 mmol/L, p = 0.01). Cholesterol and HDL cholesterol levels were similar for the two groups. There was no difference in energy and nutrient intake, but day workers had a higher alcohol intake (15.64 g/d versus 9.3 g/d, p = 0.03). Multivariate analysis conducted with triglycerides as dependent variable and shift work, BMI, smoking, age, leisure time physical activity level, energy intake, and alcohol intake as independent variables confirmed that shift work has a significant explanatory power for triglyceride levels (beta = 0.134, p = 0.0005). CONCLUSION: This study confirms that shift work is associated with an increase of triglyceride levels independent of dietary intake. We did not find any influence of shift work on cholesterol and HDL cholesterol. Despite this latter fact, our findings are to be considered in the explanation of coronary risk among shift workers. Further studies are needed to elucidate the mechanism of this relative hypertriglyceridemia: stress induced by shift work or diurnal rhythm disturbances.

Adult↗
PubMed1992

A multicenter comparison of the effects of simvastatin and fenofibrate therapy in severe primary hypercholesterolemia, with particular emphasis on lipoproteins defined by their apolipoprotein composition.

This multicenter, double-blind, randomized study was designed to compare the effects of simvastatin (20 mg/d and 40 mg/d) and fenofibrate (400 mg/d) on plasma lipids, lipoproteins, apolipoproteins (apo), and lipoprotein particles defined by their apo composition (Lp A-I, Lp A-II:A-I, Lp E:B, Lp C-III:B) in primary hypercholesterolemia. After 6 and 10 weeks of therapy, both drugs lowered plasma cholesterol, low-density lipoprotein (LDL) cholesterol, and apo B. The effect on LDL and apo B was significantly more pronounced for simvastatin (P = .01). Simvastatin increased Lp A-I, but did not change Lp A-II:A-I, while fenofibrate decreased Lp A-I and increased Lp A-II:A-I. Lp E:B and Lp C-III:B were decreased with both drugs, but fenofibrate was significantly more effective in reducing these particles than simvastatin. This study demonstrates that both drugs have beneficial effects on the parameters positively or negatively correlated with the atherosclerotic risk, with simvastatin being more effective in reducing some of them. These results suggest that the drugs led to different structural modifications of the lipoproteins, which would not be revealed by examination of lipoprotein density classes. These differences are probably related to the different mechanisms of action of the agents.

Adolescent↗
PubMed1992

Identification of apoB-containing lipoprotein families in NIDDM.

The purpose of this study was to determine the concentrations and composition of apoB-containing lipoprotein families in whole plasma and major lipoprotein density classes of a selected group of Native Americans from northeastern Oklahoma with non-insulin-dependent diabetes mellitus. The measurement of lipoprotein density classes showed that the total lipoprotein mass of very-low-density lipoproteins was significantly higher and that of high-density lipoproteins significantly lower in diabetic patients than nondiabetic control subjects regardless of their plasma triglyceride levels. The VLDLs were enriched with TG, free cholesterol, and apolipoproteins C-III and E. HDLs were enriched with TG but depleted of apoC-III and apoE. There was no change in the levels of TG-enriched low-density lipoproteins. Fractionation of VLDL by sequential immunoprecipitation with antisera to apoE and apoC-III established that increased concentrations of this density class in diabetic patients are due to elevated levels of TG-rich lipoprotein LP-B:C and lipoprotein LP-B:C:E. The levels of LP-B:C particles were increased more than the levels of LP-B:C:E particles. The LDLs were characterized by a slight increase in TG-enriched lipoprotein B and no change in the levels of LP-B:C and LP-B:C:E. There was no difference between diabetic patients with or without vascular disease in the levels of LP-B and LP-B:C:E. However, patients with vascular disease had higher concentrations of LP-B:C particles in VLDL and whole plasma than patients without vascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Isolation and characterization of human Lp-B lipoprotein containing apolipoprotein B as the sole apolipoprotein.

A sequential immunoaffinity chromatography procedure was developed to isolate from whole normolipidemic human plasma a subpopulation of apoB containing particles (Lp-B) which is virtually free of non apoB protein. The absence of non apoB protein in Lp-B was assessed by enzyme immunoassay against apolipoproteins A-I, A-II, A-IV, E, C-III and (a). Electron microscopy and fractionation of the isolated particles by gel filtration demonstrated that these particles were heterogeneous in size. However, most of them had diameters between 18 and 26 nm. These particles were found to be rich in cholesterol (molar ratio cholesterol/apoB = 2246 +/- 995) poor in triacylglycerol (molar ratio triacylglycerol/apoB = 555 +/- 518) and had a phospholipids/apoB molar ratio of 713 +/- 348. Most of the cholesterol was esterified (66% +/- 5%). Lp-B particles bound to the apoB, E receptor of HeLa cells with a lower affinity than LDL prepared by ultracentrifugation (1.030 kg/l less than d less than 1.053 kg/l). (KD = 18.9 vs 10.5 nmol/l).

Apolipoproteins B↗
PubMed1991

Plasma apolipoprotein A-I, A-II, B, E and C-III containing particles in men with premature coronary artery disease.

Lipoprotein (Lp) cholesterol and apolipoproteins (apo) A-I and B levels have been shown to be better markers for the presence of coronary artery disease than total cholesterol. In this study, we determined the plasma levels of lipoprotein particles containing apo A-I only (LpA-I), apo A-I and A-II (LpA-I:A-II), apo B and C-III (LpB:C-III) and apo B and E (LpB:E) in 145 patients with coronary artery disease (mean age +/- SD, 51 +/- 7 years) and 135 healthy control men (mean age 49 +/- 11 years). Patients with CAD had lower high density lipoprotein (HDL) cholesterol and apo A-I levels and higher triglycerides and apo had lower high density lipoprotein (HDL) cholesterol and apo A-I levels and higher triglycerides and apo B levels than controls. In patients with CAD, LpA-I (0.341 +/- 0.093 vs. 0.461 +/- 148 g/l) and LpA-I:A-II (0.694 +/- 0.171 vs. 0.899 +/- 0.148 g/l) were lower, whereas LpB:E (0.372 +/- 0.204 vs. 0.235 +/- 0.184 g/l) were higher than in controls (cases vs. controls, all P less than 0.005). No significant differences were observed for LpB:C-III (0.098 +/- 0.057 vs. 0.107 +/- 0.061 g/l, p = 0.235) particles. Discriminant analysis indicates that LpA-II:A-I, LpE:B, LpA-I, and triglycerides best differentiate between cases and controls. Plasma apo C-III (0.027 +/- 0.008 vs. 0.036 +/- 0.020 g/l) and E (0.040 +/- 0.015 vs. 0.055 +/- 0.029 g/l) were lower in the CAD group (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1991

Lipoprotein particle analysis comparing simvastatin and fenofibrate.

This study compares the effects of fenofibrate and simvastatin in primary hypercholesterolemia, with particular regard to lipoprotein particles, as defined by their apolipoprotein composition: LpAI, LpAII: AI, LpE:B, LpCIII:B. This was a double-blind study in which patients were randomized to 2 groups, one receiving simvastatin 20 mg once daily and the other receiving fenofibrate 200 mg b.i.d., if their total cholesterol and their LDL cholesterol remained above 7.60 mmol/l (300 mg/dl) and 4.95 mmol/l (195 mg/dl) after a 4-week placebo period. Simvastatin dosage was doubled at the end of 6 weeks of therapy if the LDL-cholesterol level remained above 3.55 mmol/l (140 mg/dl). Analyses were done after 6 and 10 weeks of therapy. Apolipoprotein AI was increased significantly only at week 10 with fenofibrate (+7.4%). Simvastatin had a more pronounced effect than fenofibrate on apolipoprotein B. There was a significant difference between drugs at weeks 6 and 10. No change was observed in the LpAII:AI level with simvastatin, whereas fenofibrate increased these particles quite significantly (+13.9 and +22.3%). The drugs had opposite effects on LpAI (+2.5 and +5.6% with simvastatin; -12.8 and -15.1% with fenofibrate). LP E:B (-33.0 and -40.8% with simvastatin; -53.8 and -52.2% with fenofibrate) and LpCIII:B (-23.8 and -31.8% with simvastatin; -35.1 and -43.5% with fenofibrate) were decreased by both drugs, but fenofibrate was significantly more effective in reducing these particles than simvastatin at week 6. This study suggests that both drugs led to different structural modifications of the lipoproteins, which would not be revealed by total apolipoprotein analysis. These differences are probably related to the mechanisms of action of these drugs.

Adolescent↗
PubMed1991

High-density lipoprotein particles in octogenarians.

High-density lipoprotein (HDL) particles exhibit considerable heterogeneity, specifically in apolipoprotein (apo) composition. Thus, apo A-I, the major protein of HDL, is present in two types of particles: one species contains both apo A-I and apo A-II (Lp A-I/A-II) while in the other (Lp A-I), apo A-II is absent. We used the hypothesis that octogenarians, who survived periods in life when the incidence of coronary heart disease (CHD) is very high, have several protective factors. We compared HDL-cholesterol (HDL-C), HDL2-cholesterol (HDL2-C), HDL3-cholesterol (HDL3-C), apo A-I, and apo A-II in octogenarians and younger control subjects smoking less than 10 cigarettes/d and not taking drugs known to affect lipid metabolism. Using a new procedure, we also compared the levels of Lp A-I and Lp A-I/A-II. The cholesterol content of total HDL was similar in octogenarian and control (38 +/- 8 years) men while HDL2-C was higher and HDL3-C, apo A-I, and A-II were lower in octogenarian than in control men. In women, the level of HDL-C and apo A-I was similar in premenopausal and octogenarian subjects but higher in postmenopausal women than in octogenarians, while HDL2-C and apo A-II were similar in the three groups. In contrast, HDL3-C was higher in the two groups of control women (premenopausal and postmenopausal) than in octogenarians. However, Lp A-I was significantly elevated in octogenarian men and women (men: 61 +/- 14 mg/dL; women: 70 +/- 14 mg/dL) by comparison with younger control subjects (men: 48 +/- 12 mg/dL; premenopausal women: 53 +/- 11 mg/dL; postmenopausal women: 63 +/- 19 mg/dL).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

The effect of moderate alcohol intake on serum apolipoprotein A-I-containing lipoproteins and lipoprotein (a).

Two main types of lipoprotein particles are identified within high-density lipoprotein (HDL): those containing both apolipoprotein (apo) A-I and apo A-II (Lp A-I:A-II) and those containing only apo A-I (Lp A-I). To study the effects of prolonged moderate alcohol intake on apo A-I-containing lipoproteins in serum, 60 g/d of ethanol was administered to 10 healthy male volunteers (age, 27 to 45 years) during 3 weeks. The drinking period was preceded and followed by an abstinence period of 3 weeks. The HDL3 cholesterol level increased by 17% (P less than .01) and decreased by 22% (P less than .001) on and off alcohol, respectively. The HDL2 cholesterol increased by 17% (P = NS) during ethanol intake and decreased by 14% during the following abstention (P less than .01). The serum concentration of apo A-I increased by 17% (P less than .001) during drinking and came back to the starting level after 2 weeks of abstention. Ethanol intake caused an increase in the serum levels of both Lp A-I and Lp A-I:A-II, the former explaining one third of the total increase of apo A-I. The Lp (a) concentration decreased by 33% (P less than .05) during the first week of ethanol intake, but increased back to the starting level until the end of drinking. These data suggest that the increment of the antiatherogenic Lp A-I may be one beneficial effect provided by ethanol with respect to coronary heart disease.

Adult↗
PubMed1991

Quantitative determination of different apolipoprotein B containing lipoproteins by an enzyme linked immunosorbent assay: apo B with apo C-III and apo B with apo E.

A non competitive enzyme-linked immunosorbent assay (ELISA) for total apolipoprotein (apo) B, apo B with apo C-III (LpC-III:B), and apo B with apo E (LpE:B), was developed. Microtiter plates were used as solid-phase, and subdivided into three parts, coated respectively with affinity purified antibodies to apo B, to apo C-III and to apo E. After incubating the antigen with coated plates, a horseradish peroxidase-labelled antibody to apo B was added to all the plates to estimate total apo B, LpC-III:B and LpE:B.

Apolipoprotein C-III↗
PubMed1991

Lowering of HDL2-cholesterol and lipoprotein A-I particle levels by increasing the ratio of polyunsaturated to saturated fatty acids.

The protective role of high-density lipoproteins (HDLs) has been attributed to the subfractions HDL2 (according to the density) and lipoprotein A-I (LpA-I) (according to the composition in apolipoproteins). We investigated the effect of a high ratio of polyunsaturated to saturated fatty acids (P:S) on these subfractions in a homogeneous group of young adult males. Two prescribed diets were consumed successively at the subjects' homes for 3 wk each in a random order; one diet contained 70 g butter (P:S 0.2, diet B), the other contained 70 g sunflower margarine (P:S 1.1, diet M). Total calorie, fat, and cholesterol intakes were similar for the two diets. Cholesterol and apolipoprotein B in serum and in low-density lipoproteins (LDLs) were lower with diet M than with diet B. However, significant decreases in protective subfractions of HDL, HDL2, and LpA-I were observed. This undesirable effect of the diet with a high P:S could cancel the benefits of lowering the LDL-cholesterol concentrations.

Adult↗
PubMed1991

n-3 polyunsaturated fatty acids raise low-density lipoproteins, high-density lipoprotein 2, and plasminogen-activator inhibitor in healthy young men.

The effects of a moderate supplementation in n-3 polyunsaturated fatty acids (PUFAs) were investigated in 36 young healthy adult males. Factors investigated were lipoprotein (including HDL subfractions and apolipoproteins) and hemostasis indexes, assessed by platelet aggregation and plasminogen-activator-inhibitor (PAI) activity. Fat-controlled diets were prescribed, one with and one without a fish-oil supplement (control diet), successively during 3 wk in random order. Total calorie, fat, and cholesterol intakes were similar in the two diets. Triglycerides in serum and very-low-density lipoproteins were lower and high-density-lipoprotein 2 cholesterol was higher with the n-3 PUFA-supplemented diet. These effects as well as a significant decrease in platelet aggregation can be considered beneficial in terms of cardiovascular risk. However, significant increases in low-density-lipoprotein cholesterol and PAI activity occurred and were correlated. This latter effect could be detrimental.

Adult↗
PubMed1991

Apolipoprotein B polymorphism and altered apolipoprotein B concentrations in Congolese blacks.

The immunoreactivity of apolipoprotein B (apo B) in plasma obtained from 238 unrelated black African male subjects from the People's Republic of Congo was analysed by non-competitive Enzyme Linked-Immunosorbent Assay (ELISA) with monoclonal BIP 45 anti-LDL antibody. The polymorphism detected by BIP 45 monoclonal antibody is identical to the Ag(c,g) polymorphism. Antibody BIP 45 distinguishes three apo B allotypes (immunophenotypes) encoded by the two allelic genes apo B Ag(c) and apo B Ag(g). Because of co-dominant transmission, genotypes may be inferred from allotypes, and it has been shown that BIP 45 binds strongly to the Ag(c) factor and only weakly to the allelic Ag(g) factor. Analysis of the Congolese plasma samples indicated that 67.65% of them bound BIP 45 with low affinity (Ag(c-,g+) genotype), 28.15% with intermediate affinity (Ag(c+,g+) genotype) and 4.20% with high affinity (Ag(c+,g-) genotype). According to the Hardy-Weinberg equilibrium, this corresponds to gene frequencies of 0.817 and 0.183 for the type Ag(g)/Ag(c) alleles, respectively. After adjustment for age and body-mass index, it was found that the Ag(c) allele decreases the apo B level by 9.62 mg/dl and that the Ag(g) allele increases apo B by 0.43 mg/dl. Therefore, as much as 4.30% of the genetic variance for apo B level could be accounted for by the Ag(c,g) gene locus.

Alleles↗