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Biomedical subjects

J C Fruchart

Publications and source records attributed to J C Fruchart.

At least 397 records · Page 22Linked to original sources
PubMed1988

Effects of fenofibrate on lipoprotein metabolism and fatty acid distribution in Zucker rats.

The short term effects of fenofibrate (150 mg/kg per day), administered by gavage, on lipoprotein and fatty acid distribution have been investigated in an hypertriglyceridemic model, the Zucker rat. Lean rats were compared to control obese and treated obese rats, and control obese animals to treated obese littermates. Classically, plasma cholesterol and triacylglycerol increased by 1.8- and 7.9-fold, respectively, in control obese versus lean rats. Treatment of the Zucker obese rats with fenofibrate reduced their plasma cholesterol by 10% and raised triacylglycerol by 47% (P less than 0.001) in comparison to untreated control obese rats. These effects were accompanied by a change in the composition of all plasma lipoproteins. The cholesterol/triacylglycerol ratio in VLDL rose by 32% while that in LDL and HDL fell by 43 and 47%, respectively. Drug therapy altered the fatty acid profile in both plasma and liver; the percentage of polyunsaturated fatty acids fell while monounsaturated fatty acids increased. The increased proportion of monounsaturated fatty acids in plasma suggests that the fatty acid composition of circulating lipoproteins is modified, particularly in VLDL. This, in association with the altered lipid distribution in VLDL may reflect an abnormal metabolism of this lipoprotein. In view of these abnormalities, we conclude that this rat is not an appropriate model for the short-term study of clofibrate analogues.

Animals↗
PubMed1988

Human apolipoprotein B. Evidence for its immunochemical heterogeneity using monoclonal antibodies and an immunoenzymometric assay.

Predefined monoclonal antibodies (Mabs) were used in an immunoenzymometric assay to study the immunochemical heterogeneity of lipoproteins and to search for potential epitopes with pathological importance. By measuring apolipoprotein B (apo B) epitopes in patients with and without angiographically documented coronary artery disease and in patients with type IIa hyperlipoproteinemia, we have found that both types of patients have a significant increase in Apo B-containing particles specifically recognized by one Mab (BL3). We have also observed that the effects of fenofibrate on type IIa patients vary greatly depending on the plasma concentrations of various Apo B-containing lipoproteins. The greatest effects occurred in patients with epitopes recognized by BL3. Lastly, by sequential precipitation of specific epitopes by BL3, we have obtained evidence that the residual epitope(s) may be related to one or more lipoprotein particles.

Antibodies, Monoclonal↗
PubMed1988

Characterization of a monoclonal antibody that binds to apolipoprotein E and to lipoprotein of human plasma containing apo E. Applications to ELISA quantification of plasma apo E.

This study describes the development of an enzyme-linked immunosorbent assay for human apolipoprotein E (apo E). A mouse monoclonal IgG1 antibody named E01 against apolipoprotein E was selected from five antibodies secreted by hybridomas. This antibody had a high affinity for apo E [K = 1.2 x 10(7) L.M-1 for purified apo E and K = 1.05 x 10(7) L.M-1 for native apo E in very low density lipoproteins) in liquid phase and recognized every isoform of apo E but not other proteins in VLDL. Competition experiments with 125I apo E showed that its binding affinity for the E in every density class (VLDL, HDL, LDL) and in serum was the same. This antibody was used for the quantification of human apo E in serum by enzyme linked immunoassay. E01 was coated on microtiter plates and a polyclonal peroxidase-conjugate was used as second antibody. A good correlation was observed between the values obtained for apo E using both monoclonal and polyclonal antibodies.

Animals↗
PubMed1988

Association between epitopes detected by monoclonal antibody BIP-45 and the XbaI polymorphism of apolipoprotein B.

An epitope of Apolipoprotein B (ApoB), recognised by a monoclonal antibody BIP-45, is associated with the development of ischaemic heart disease (Duriez et al. 1988). We have examined the genetic relationships between this epitope and three Restriction Fragment Length Polymorphisms (RFLPs) of the gene for ApoB detected with the enzymes EcoRI, PvuII and XbaI in a sample of 53 unrelated individuals from France. There is an association between binding affinity to BIP-45 and the XbaI RFLP; the 8.6 kb XbaI allele (absence of cutting site) being associated with low-affinity binding to BIP-45. In this sample of individuals there is no significant association between serum cholesterol levels and BIP-45 binding affinity, but there is a significant correlation between serum cholesterol levels and XbaI genotype, with individuals of the genotype X1X1 having the highest and those with the genotype X2X2 having the lowest levels of serum cholesterol. This suggests that variation at the ApoB locus may be involved independently in the determination of serum lipid levels and in the development of ischaemic heart disease.

Adult↗
PubMed1988

Acylgalactosylceramides in developing dysmyelinating mutant mice.

Acylgalactosylceramides (AGC) from forebrains of normal and dysmyelinating (quaking and shiverer) mice were purified by Florisil column chromatography and preparative TLC. These procedures resolved the AGC on the basis of their Rf values into two main fractions which comigrate with their homologs from rat forebrains. In control animals, AGC were detectable in mouse forebrains from the eighth postnatal day and reached maximal values within 20 days. The same developmental pattern was obtained in dysmyelinating shiverer mice but the AGC content was reduced to approximately 30% of control values. In quaking mutants, the AGC were hardly detected. They were also present in sciatic nerve of normal mice and to a lesser extent in trembler mice. Gas chromatography-mass spectrometry analysis of both ester- and amide-linked fatty acids isolated from AGC of normal and shiverer mice shows that the shiverer mutant AGC display a chemical structure similar to that of normal AGC. AGC constituents of control myelin are reduced by approximately 70% in shiverer myelin, indicating that these molecules can be considered as early markers of oligodendrocyte differentiation. The early arrest of myelinogenesis in the quaking animals and the near absence of AGC are in good agreement with this proposal. Moreover, the reduced amount of AGC in the trembler PNS indicates that AGC could also be early markers for differentiation of the Schwann cell.

Animals↗
PubMed1988

Interaction of LDL, Lp[a], and reduced Lp[a] with monoclonal antibodies against apoB.

Five monoclonal antibodies (2A, 9A, 6B, L3, L7) produced in mice against human apolipoprotein B were investigated by competitive and inhibitive electroimmunoassay (EIA) for their reactivity with low density lipoprotein (LDL), lipoprotein[a] (Lp[a]), and reduced Lp[a]. All of the antibodies reacted with apoB of the different lipoproteins indicated by very similar slopes of the binding curves. None of them gave a positive reaction with apolipoprotein[a]. The amount of apoB required for 50% inhibition of antibody binding varied for the different antibodies and lipoproteins. Antibody 9A showed almost the same affinity for LDL, Lp[a], and reduced Lp[a]. Antibodies 2A and 6B bound about twofold better to LDL and reduced Lp[a] than to untreated Lp[a]. Antibodies L3 and L7 needed nearly threefold higher amounts of Lp[a]-apoB for 50% inhibition of antibody binding than of apoB of LDL and reduced Lp[a]. The amount of apoB required for 50% inhibition of antibody binding was somewhat higher in inhibitive assay than in competitive assay. We suggest that apo[a] covers certain epitopes of apoB in native Lp[a] leading to a reduced reaction with the monoclonal antibodies. However, it could also be that the binding of the [a]antigen to apoB via disulfide bridges causes profound conformational changes of the apoB region exposed to the surface.

Adolescent↗
PubMed1988

[Receptors and molecular heterogeneity of lipoprotein particles containing apolipoprotein A-I].

High density lipoproteins (HDL) are heterogeneous, with respect to their hydrated density (HDL2, HDL3), and to their apolipoprotein composition (Lp A-I : A-II contains both apolipoprotein A-I and A-II, Lp A-I contains apolipoprotein A-I but not apolipoprotein A-II). Lp A-I and Lp A-I and Lp A-I : A-II particles have different metabolic functions. Only Lp A-I particles seem to be involved in the antiatherogenic role of HDL. Alcohol consumption raises Lp A-I : A-II level but not Lp A-I. Different tissue possess specific binding sites for HDL: steroidogenic tissue, hepatocytes peripheral cells. Apolipoprotein A-I and/or A-II are possible ligands. HLD, after binding to the receptor, can provide the cells with cholesterol, or promote an efflux of cholesterol from the cells and the "reverse cholesterol transport" from the peripheral cells to the liver. The HDL subfractions possess different metabolic roles: binding of Lp A-I to mouse adipose cell receptors promotes cholesterol efflux. Apo A-II are antagonists for this effect.

Animals↗
PubMed1988

Lipoprotein abnormalities in chronic haemodialysis patients.

Measurement of lipids, apolipoproteins A-I, A-II, B, C-III, Lp(a) and cholesterol, phospholipids, apo C-III in lipoprotein with and without apolipoprotein B was made in 49 patients (18 women and 31 men; mean age 50 +/- 15 years) undergoing maintenance haemodialysis for chronic renal failure. A group of 49 healthy people, matched for sex and age, acted as controls. In the haemodialysis group, special attention was placed upon the comparison of patients who had evident cardiovascular alterations (n = 17) with the residual group (n = 32). The concentration of apo C-III in apolipoprotein B containing lipoproteins was statistically higher in the patients with arterial disease than in the remaining subjects, whereas the ratio apo C-III from Lp no B/apo C-III from Lp B was decreased. Compared to controls, haemodialysis patients had significantly higher values of triglycerides, apolipoproteins C-III, Lp(a), and apolipoprotein C-III from apolipoprotein B-containing lipoproteins (LpB); in contrast, concentrations of phospholipids and cholesterol from lipoproteins without apolipoprotein B (Lp no B) and apolipoprotein A-II were significantly reduced in patients. Discriminant analysis indicated that the levels of apolipoprotein C-III and apolipoprotein C-III from LpB were the best indicators of deranged lipid transport in patients with chronic renal failure. Our data suggest that chronic haemodialysis patients tend to exhibit qualitative abnormalities of serum apolipoprotein-B triglyceride rich particles containing apolipoprotein C-III or (a).

Adolescent↗
PubMed1988

Electroimmuno- and immunonephelometric assays of apolipoprotein A-I by using a mixture of monoclonal antibodies.

The use of mixtures of well-defined monoclonal antibodies may represent a step forward in the standardization of immunochemical assays. We developed and optimized working conditions for using such a mixture to determine apolipoprotein A-I in human sera by two independent techniques (electroimmuno- and immunonephelometric-assays). Six monoclonal antibodies, each addressed to distinct epitopes located at the surface of apolipoprotein A-I, were used in combination to permit a reproducible measurement of the protein, without prior delipidation of samples. Parallel standard curves for a high-density lipoprotein subfraction (HDL3, the primary standard) and a reference serum (the secondary standard) were obtained. Within- and between-run coefficients of variation were acceptable for both methods. Apolipoprotein A-I concentrations, as measured in 60 subjects selected to present a large range of apolipoprotein content by electroimmunoassay (y1) and immunonephelometric assay (y2) with monoclonal antibodies, compared well with those measured by the same techniques but with polyclonal antibodies (x): r1 = 0.96, r2 = 0.99; y1 = 1.19x - 0.11 g/L, y2 = 0.98x. Comparison of results obtained by electroimmunoassay and immunonephelometric assay performed with monoclonal antibodies was also good: r = 0.96; y2 = 1.08y1 + 0.13 g/L.

Antibodies, Monoclonal↗
PubMed1988

Effect of different APO A-I containing lipoprotein particles on reverse cholesterol transport in fat cells.

Cholesterol efflux was studied in cultured mouse adipose cells after preloading with LDL cholesterol. Long term exposure to LpA-I particles isolated from HDL2 and HDL3 promoted cholesterol efflux while LpA-I:A-II particles isolated from both fractions did not. However, LpA-I and LpA-I:A-II particles isolated from both HDL subfractions were effective in competing for the binding of 125I-HDL3 to apo A-I/A-II cell surface receptor sites. These results underline the role of LpA-I particles in the promotion of cholesterol efflux and suggest that the concentrations and/or the relative proportions of LpA-I and LpA-I:A-II particles might be critical for the regulation of cholesterol efflux from adipose cells.

Adipose Tissue↗
PubMed1988

Aspects of cholesterol metabolism in normal and hypercholesterolemic Syrian hamsters. Influence of fenofibrate.

This study reports the short-term effects of fenofibrate in golden Syrian hamsters receiving a standard or cholesterol enriched (0.5%) diet. In chow fed control animals, the plasma cholesterol (132 mg/dl) was transported essentially by LDL (27%) and HDL (56%). Conversely, the bulk of triglycerides (114 mg/dl) circulated in VLDL (54%). One week of hypercholesterolemic diet increased plasma cholesterol (+80%) and it is reflected in a 3.3-fold increase in VLDL, 2.8-fold in IDL, 1.6-fold in LDL and 1.5-fold in HDL, accompanied by a rise in cholesterol hepatic level by a factor of 4.5. 15 days of treatment with fenofibrate (300 mg/kg/d) produced a decrease in free plasma cholesterol (-21%) without modification in total cholesterol level in chow fed animals. In liver, cholesterol was reduced by 27% and triglycerides were raised by 58%. In animals receiving the hypercholesterolemic diet, fenofibrate increased hepatic and plasmatic triglyceride levels (55 and 54%, respectively), although it slightly reduced plasma cholesterol levels and more markedly the hepatic cholesterol content (-55%). In chow fed animals, cholesterol biosynthesis was decreased by fenofibrate treatment by 40%. The effects of fenofibrate on triglyceride levels are in contrast to experiences in other animal species, including man, and indicate a hypersecretion of chylomicrons and/or a hypersecretion of VLDL, although the explanations are not yet obvious. The results concerning cholesterol metabolism indicate similarities between man and hamster.

Animals↗
PubMed1988

Enzyme-linked immunosorbent assay for human proapolipoprotein A-I using specific antibodies against synthetic peptide.

Apolipoprotein A-I (apoA-I), the major protein component of human high density lipoprotein, appears intracellularly as an intermediate precursor (proapoA-I) with a hexapeptide extension (Arg-His-Phe-Trp-Gln-Gln) at its amino terminus. To investigate the regulation of processes that regulate plasma apoA-I levels, a sensitive and simple assay for proapoA-I is required. We describe a specific enzyme-linked immunosorbent assay (ELISA) for quantification of proapoA-I using monospecific rabbit antibodies raised against the peptide: Arg-His-Phe-Trp-Gln-Gln-Asp-Glu-Pro. The monospecificity of antibodies to propeptide has been checked and no cross-reaction with mature apoA-I has been found although three first mature apoA-I amino acids (Asp-Glu-Pro) were included in the immunizing peptide. The assay is a non-competitive sandwich ELISA in which polystyrene microtiter plates were used with antibodies to propeptide adsorbed on the wells. After incubation with plasma samples, the bound proapoA-I was revealed by labeled rabbit polyclonal antibodies directed against mature apoA-I. The working range was 10 to 100 ng/ml, recovery of proapoA-I added to plasma was 94.6 to 106.5%, and the intra- and interassay coefficients of variation were 3.8% and 7.9%, respectively. A delipidation step using diisopropylether-n-butanol was necessary to expose antigen sites of proapoA-I in native lipoproteins. Mean level of proapoA-I in normal subjects was 87 +/- 15 micrograms/ml. It represented 7.1% of total apoA-I while in Tangier serum it represented 29%.

Apolipoprotein A-I↗
PubMed1988

Enzyme-linked immunosorbent assay for serum amyloid A apolipoprotein with use of specific antibodies against synthetic peptides.

We describe a noncompetitive enzyme-linked immunosorbent assay for amyloid A apolipoprotein in human serum (apo SAA) in which specific antibodies against synthetic peptides are used. Microtiter plates were used as solid phase and coated with affinity-purified antibodies raised against SAA1-(95-104) peptide. After incubation with delipidated plasmas, the bound apo SAA was revealed by labeled antibodies raised against SAA1-(58-69) peptide. The assay offers several advantages over existing techniques: sensitivity, specificity, simplicity, and non-use of radioisotopes. Results correlate well with those by a nephelometric method in which polyclonal antibodies are used.

Amino Acid Sequence↗
PubMed1987

Relationship in adipose cells between the presence of receptor sites for high density lipoproteins and the promotion of reverse cholesterol transport.

The role of a high-affinity receptor site for high-density lipoproteins (HDL) has been investigated in parental Ob1771 adipose cells and their transformed counterparts after transfer of the complete early region of polyoma virus (Ob17PY cells). Binding of ApoAI, ApoAII and HDL3 occurs in Ob1771 cells and derived membranes, whereas no binding is observed in Ob17PY cells and derived membranes. After thymidine block, growth-arrested Ob17PY cells become able to bind ApoAI, ApoAII and HDL3; this recovery is prevented in actinomycin D- or cycloheximide-treated cells. In contrast to ApoAI, ApoAII or HDL3 binding, both growing and growth-arrested Ob17PY cells do show receptor activities for low density lipoproteins and transferrin, respectively, which are similar in affinity and maximal capacity. Following cholesterol accumulation which takes place in the presence of LDL cholesterol, subsequent exposure to HDL3 or ApoAI promotes cholesterol efflux from Ob1771 cells and growth-arrested Ob17PY cells but not from growing Ob17PY cells. These results show that the presence of a high-affinity receptor site for HDL in intact adipose cells is required for the promotion of reverse cholesterol transport.

Adipose Tissue↗
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↗
PubMed1987

A monoclonal antibody (BIP 45) detects Ag(c,g) polymorphism of human apolipoprotein B.

A monoclonal antibody (BIP 45) against human apolipoprotein B (apo B) was used to study the polymorphism of apo B in families and in unrelated subjects. BIP 45 bound to apo B-containing lipoprotein particles in one of three distinct patterns of immunoreactivity (strong, weak and intermediate). Family studies showed that these binding patterns result from co-dominant transmission of apo B allelic pairs which are temporarily designated allele BIP- and allele BIP+; allele BIP+ would code for the apo B BIP 45 epitope. Analysis of plasma samples from 244 unrelated men randomly chosen from the North French population indicated that 46.7% of them bound BIP 45 with low affinity (weak reactors), 44.7% with intermediate affinity (intermediate reactors) and 8.6% with high affinity (strong reactors). According to the Hardy-Weinberg equilibrium, this corresponds to gene frequencies of 0.690/0.310 for the type BIP-/BIP+ alleles. This corresponds to the gene frequencies of 0.695/0.305 at the Ag(g)/Ag(c) locus previously found in a Caucasian population. Furthermore, the investigation of Ag(c,g) and of monoclonal BIP 45 antibody immunoaffinity for 30 individual plasma samples showed that BIP 45 bound strongly to Ag(c) factor, whereas it bound weakly to the allelic Ag(g) factor. This monoclonal antibody will be useful for the detection of the two corresponding apo B species designated apo B (Ag(c) factor, BIP+) and apo B (Ag(g) factor, BIP-).

Antibodies, Monoclonal↗