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J C Fruchart

Publications and source records attributed to J C Fruchart.

At least 343 records · Page 19Linked to original sources
PubMed1990

Phosphatidylcholine breakdown in HDL3 stimulated platelets.

Low concentrations of HDL3 stimulate a transient biphasic increase in 1,2-diacylglycerol (DAG), with an early phase peaking at 30 seconds and a late phase at 60 seconds in (3H)-phosphatidylcholine prelabelled platelets. DAG generation is coupled to apolipoprotein AII or AI binding to specific surface receptors. Coincubations with HDL3 and 0.2 microM phorbol ester induced a significant rise in the second phase DAG indicating the involvement of protein kinase C in this late phase. The HDL3 induced production of DAG in platelets pretreated with 6 microM R 59022 is enhanced, while phosphatidic acid (PA) content was reduced, suggesting that DAG attenuation is derived at least in part from a pathway involving DAG-Kinase.

Blood Platelets↗
PubMed1990

Purification of an apolipoprotein A binding protein from mouse adipose cells.

A protein recognizing apolipoproteins AI, AII and AIV was purified from cultured mouse adipose cells of the Ob17MT18 clonal line. Apolipoprotein A binding sites were solubilized in the presence of proteinase inhibitors using the non-denaturating detergent CHAPS. Chromatography of the soluble extract on DEAE-Trisacryl was followed by immunoaffinity chromatography of the complex apolipoprotein AI-binding proteins on anti-(apolipoprotein AI) coupled to Sepharose 4B and then by h.p.l.c. on an RP-Select B column. A 1400-fold purification over the starting crude homogenate was achieved. The purified material contained two proteins that were both able to bind apolipoproteins AI, AII and AIV, but not low-density lipoprotein. Glycopeptidase F treatment showed the existence of a single protein bearing either N-linked high-mannose or complex oligosaccharide chains. The purified material showed an apparent molecular mass of 80 +/- 9 kDa by h.p.l.c. on a TSKG 3000 SW column. Rabbit polyclonal antibodies directed against the purified material revealed two protein bands of 80 and 92 kDa after SDS/PAGE under reducing conditions and immunoblotting. These bands were undetectable in growing Ob17PY cells previously shown not to bind the various apolipoproteins A and not to undergo cholesterol efflux, whereas they were conspicuous in growth-arrested Ob17PY cells which have recovered these properties.

Acrylic Resins↗
PubMed1990

Human apolipoprotein A-IV binds to apolipoprotein A-I/A-II receptor sites and promotes cholesterol efflux from adipose cells.

Cholesterol efflux was studied in cultured mouse adipose cells after preloading with low density lipoprotein cholesterol. Exposure to complexes containing human apolipoprotein A-IV and L-alpha-dimyristoylphosphatidylcholine (DMPC) as well as to human lipoprotein particles containing apolipoprotein A-IV but not apolipoprotein A-I and particles containing apolipoproteins A-IV and A-I showed that both artificial and native apolipoprotein A-IV-containing particles were able to promote cholesterol efflux at 37 degrees C as a function of time and concentration. The half-maximal concentration was found to be 0.3 X 10(-6) M for apolipoprotein A-IV.DMPC complexes. Binding experiments performed in intact cells at 4 degrees C with labeled apolipoprotein A-IV.DMPC complexes showed the existence of specific binding sites, with a Kd value of 0.32 x 10(-6) M and a maximal binding capacity of 223,000 sites/cell. By cross-competition experiments with labeled and unlabeled complexes containing apolipoprotein A-IV, A-I, or A-II, it appeared that all three apolipoproteins bind to the same cell-surface recognition sites. It is suggested that apolipoprotein A-IV, which is present in the interstitial fluid surrounding adipose cells in vivo at concentrations similar to those required in vitro for the promotion of cholesterol efflux, plays a critical role in cholesterol removal from peripheral cells.

Adipose Tissue↗
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

Use of bacterial expression cloning to localize the epitopes for a series of monoclonal antibodies against apolipoprotein B100.

Bacterial expression of apolipoprotein (apo) B cDNA constructs has been used to map a series of monoclonal antibodies (mAbs) to apoB by immunoblotting. In some cases assignments have been confirmed and refined by (i) semipurification of expressed protein, CNBr digestion, and assignment of the immunoreactive fragments; (ii) controlled digestion of the cDNA with the exonuclease Bal31 and bacterial expression of the truncated proteins that result; or (iii) expression of specific segments of cDNA amplified by the polymerase chain reaction. Forty mAbs were mapped to a minimum of 17 separate determinants on apoB. Tryptic fragments have been used to confirm the epitope assignments. In addition, this approach in conjunction with immunoassay, enables some deductions to be made about the trypsin-accessible regions in low density lipoprotein (LDL). The cleavage pattern obtained predicts retention of structure in the cysteine-rich domain of the amino terminus and also in the LDL receptor binding region. Trypsinized LDL was shown to bind to the LDL receptor by an authentic process, using monoclonal antibodies as competing ligands. In conjunction with the previous paper (Milne, R. W., Theolis, R., Maurice, R., Pease, R. J., Weech, P. K., Rassart, E., Fruchart, J.-C., Scott, J., and Marcel, Y. L. (1989) J. Biol. Chem. 265, 19754-19760) the mapped mAbs have been used to define the receptor-binding domain of apoB100 in LDL.

Antibodies, Monoclonal↗
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

An easier, reproducible, and mass-production method to study the blood-brain barrier in vitro.

To provide an "in vitro" system for studying brain capillary function, we have developed a process of coculture that closely mimics the "in vivo" situation by culturing brain capillary endothelial cells on one side of a filter and astrocytes on the other. Under these conditions, endothelial cells retain all the endothelial cell markers and the characteristics of the blood-brain barrier, including tight junctions and gamma-glutamyl transpeptidase activity. The average electric resistance for the monolayers was 661 omega cm2. The system is impermeable to inulin and sucrose but allows the transport of leucine. Arabinose treatment increases transcellular transport flux by 70%. The relative ease with which such monolayers can be produced in large quantities would facilitate the "in vitro" study of brain capillary functions.

Animals↗
PubMed1990

Variations in apolipoproteins serum amyloid A, A-I, A-II, and C-III in severely head-injured patients.

In five severely head-injured patients we determined the plasma concentrations of apolipoproteins serum amyloid A, A-I, A-II, C-III, and B, prealbumin and C-reactive protein on day 1, 5, 10 and 15 after head injury where possible. A dramatic increase in apolipoprotein serum amyloid A up to a mean plasma level of 0.764 g/l was accompanied by a considerable decrease in apolipoprotein A-I, apolipoprotein A-II and apolipoprotein C-III concentrations. The variations observed by immunological methods were confirmed by two-dimensional gel electrophoresis performed on plasma and different lipoprotein fractions. In addition to its association with high density lipoproteins, apolipoprotein serum amyloid A was also found with lipoproteins of low and very low density. Two-dimensional electrophoresis also showed the presence of several different serum amyloid A-peptides not seen in plasmas from healthy subjects. We propose that apolipoprotein serum amyloid A may be responsible for the decrease of the main HDL apolipoproteins in head-injured patients.

Apolipoprotein A-I↗
PubMed1990

Effect of alcohol intake on human apolipoprotein A-I-containing lipoprotein subfractions.

High-density lipoprotein comprises two main types of lipoprotein particles: (1) those that contain apolipoproteins A-I and A-II, designated LpA-I:A-II, and (2) those that contain apolipoprotein A-I but not apolipoprotein A-II, designated LpA-I. Both have been extensively studied and are believed to represent distinct metabolic entities that may confer differing protection against coronary artery disease risk. We have previously suggested that LpA-I might represent the antiatherogenic effect, which has been ascribed mainly to its effect on high-density lipoprotein cholesterol; we set out to investigate, in 344 men, the relation between LpA-I:A-II and LpA-I levels and alcohol consumption. As the alcohol intake rose, LpA-I:A-II levels increased, while LpA-I levels fell. On the assumption that LpA-I is the antiatherogenic fraction of high-density lipoprotein, the putative protective action of alcohol consumption against coronary artery disease should be reconsidered.

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

Lipoprotein heterogeneity and its effect on apolipoprotein assays.

A number of techniques have been proposed for separating lipoproteins according to their physicochemical properties. However, more recent evidence has pointed out that the physicochemically defined lipoproteins such as VLDL, IDL, LDL or HDL are both chemically and metabolically heterogeneous. According to Alaupovic concept, the plasma lipoprotein system consists of a mixture of particles, each of which is characterized by unique apolipoprotein composition. Using enzyme linked differential antibody immunosorbent assay and differential electroimmunoassay, we have discovered that the determination of lipoprotein particle profiles is essential for further clarification of the diagnostic value of measuring apo B and apo A-I. The metabolism of apo B and apo A-I containing lipoprotein particles seems to be affected primarily by their corresponding apolipoprotein composition. Some particular subpopulations of apo B containing lipoprotein particles, such as LpB containing only apo B, LpB:E containing apo B and (a), have been identified as important risk factors for atherosclerosis. We have also recently demonstrated that the protective effect of HDL is due to particles containing apo A-I but not apo A-II (LpA-I), while those containing apo A-I and apo A-II (LpA-I:A-II) have little or no effect. Dyslipoproteinemias are characterized by distinct profiles of apo B containing particles. Abnormalities in apo A-I containing particles distribution are related to the family history of coronary artery disease in young children and could explain differences in age standardized mortality from ischaemic heart diseases in different populations. Moreover hypolipidemic drugs seem to affect discrete apo B and apo A-I particles in a specific manner.

Apolipoprotein A-I↗
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↗
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

[Lipoprotein (a). An additional marker of atherosclerosis].

Lipoprotein Lp(a) is a plasma lipoprotein which possesses many similarities to low density lipoprotein (LDL) in its physical and chemical properties. The major protein constituent of both lipoproteins is apolipoprotein B100 (apo B100); however, Lp(a) is unique in that it contains an additional distinct antigen, the (a)-antigen, attached to apo B100 by one or more disulphide bridges. The (a)-glycoprotein has recently been shown to have a striking amino-acid sequence homology with plasminogen; so, Lp(a) seems to be a potential bridge between the fields of atherosclerosis and thrombosis. Metabolic studies have made it clear that Lp(a) is not a product derived from other apo B-containing lipoproteins, but is secreted by the liver as a distinct mature lipoprotein. Although a relationship between elevated serum Lp(a) levels and the occurrence of atherosclerotic diseases had been postulated by several investigators, little is known today about the role of this lipoprotein and/or the mechanism whereby it might predispose to atheroma. However, the new knowledge on the structure of Lp(a) being more and more rapidly acquired, should facilitate the understanding of the mechanism of its atherogenicity and its physiopathological role.

Animals↗
PubMed1990

[Serum amyloid A apolipoprotein (apo SAA). Implications in inflammation and in lipoprotein modifications].

The measurement of serum amyloid A apolipoprotein (apo SAA) during acute phase inflammation offers a high interest because of its specificity, sensitivity and early increase of its levels, compared to other acute phase proteins. Furthermore apo SAA is transported in serum in association with lipoproteins, in particular with their denser subpopulation, HDL3 thus inducing their modification. The decrease in Lp AI:AII concentrations in inflammatory diseases is the consequence of the decrease in HDL3. In general the HDL3 composition was changed with a displacement of apo AI by SAA. Another interest to this protein is its relationship with amyloidosis. Apo SAA is the presumed precursor of amyloid A protein, which can be deposited in various tissues, leading to secondary amyloidosis.

Animals↗
PubMed1990

[Application of the immunoenzyme technic in double determination of antibodies for the study of hyperlipoproteinemia].

Antibodies directed against designed apolipoprotein, were absorbed on microtiter plates, the other apolipoprotein present on the retained particles was evaluated by using corresponding peroxidase labeled antibodies. This differential antibody immunosorbent assay was applied to evaluate lipoprotein particles concentration in familial type IIa, IIb, III, IV, and in the type IV secondary to chronic renal failure. Type IIa and IIb, were characterized by the increasing plasma concentration of lipoprotein particles containing both apo B and apo E (LpE-B). Although type IIa have high level of apo CIII, the plasma concentration of lipoprotein containing both apo B and apo CIII was within the normal range. The high concentration of apo E in type III hyperlipoproteinemia, revealed the accumulation of LpB-CIII-E but mainly lipoproteins containing both apo B and apo E (LpE-B). The latter represents 0.94 +/- 0.51 g/l when compared to normolipidemic subjects: 0.29 +/- 0.06 g/l. The decrease concentration of apo AI affects essentially lipoprotein containing apo AI without apo AII (LpAI) in primary type IV hyperlipoproteinemic patients, while in chronic renal failure, both populations of apo AI (with and without apo AII) were affected. The differential antibody immunosorbent assay may be used in the future as a new approach to classify lipid transport disorders.

Apolipoproteins↗