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J M Lecerf

Publications and source records attributed to J M Lecerf.

At least 19 recordsLinked to original sources
PubMed2005

Nutritional intervention study with argan oil in man: effects on lipids and apolipoproteins.

AIM: To evaluate whether the consumption of virgin argan oil (VAO) is associated with a change in serum lipids and reduces the risk of cardiovascular disease in healthy Moroccans. METHODS: Sixty volunteers consumed butter (25 g/day) during 2 weeks (stabilization period) and were randomly divided into two groups: the treatment group received 25 g/day of VAO during 3 weeks (intervention period), and the control group received 25 g/day of extra virgin olive oil (EVO). Throughout the study, weight, blood pressure, and daily food intake were measured. Serum total cholesterol and low- and high-density lipoprotein cholesterol, triglycerides, and apolipoproteins A-I and B were measured at the end of each diet period. RESULTS: Analysis of food intake showed that the daily diet is isocaloric for the butter regimen (2,537 +/- 244 kcal/day) as well as for the VAO and EVO regimens (2,561+/- 246 and 2,560 +/- 253 kcal/day, respectively). Analysis of the lipid intake showed a reduction in saturated fatty acids with VAO and EVO regimens (27 +/- 1.4 and 26.4 +/- 3.4%, respectively) as compared with the stabilization period (41.6 +/- 2.4%). The analysis of serum lipids showed a significant increase in high-density lipoprotein cholesterol and apolipoprotein A-I in both VAO group (8.4%, p = 0.012, and 5.2%, p = 0.027, respectively) and EVO group (17.3%, p = 0.001, and 5.9%, p = 0.036, respectively). However, low-density lipoprotein cholesterol and apolipoprotein B (13.8%, p = 0.037, and 7.8%, p = 0.039, respectively) decreased significantly only in EVO group as compared with the stabilization period, while triglycerides decreased significantly by 17.5% (p = 0.039) only in VAO group. CONCLUSION: These results confirm the cholesterol-lowering effect of EVO and show for the first time the triglyceride-lowering effect of VAO in men.

Adult↗
PubMed2001

Human single-chain Fv intrabodies counteract in situ huntingtin aggregation in cellular models of Huntington's disease.

This investigation was pursued to test the use of intracellular antibodies (intrabodies) as a means of blocking the pathogenesis of Huntington's disease (HD). HD is characterized by abnormally elongated polyglutamine near the N terminus of the huntingtin protein, which induces pathological protein-protein interactions and aggregate formation by huntingtin or its exon 1-containing fragments. Selection from a large human phage display library yielded a single-chain Fv (sFv) antibody specific for the 17 N-terminal residues of huntingtin, adjacent to the polyglutamine in HD exon 1. This anti-huntingtin sFv intrabody was tested in a cellular model of the disease in which huntingtin exon 1 had been fused to green fluorescent protein (GFP). Expression of expanded repeat HD-polyQ-GFP in transfected cells shows perinuclear aggregation similar to human HD pathology, which worsens with increasing polyglutamine length; the number of aggregates in these transfected cells provided a quantifiable model of HD for this study. Coexpression of anti-huntingtin sFv intrabodies with the abnormal huntingtin-GFP fusion protein dramatically reduced the number of aggregates, compared with controls lacking the intrabody. Anti-huntingtin sFv fused with a nuclear localization signal retargeted huntingtin analogues to cell nuclei, providing further evidence of the anti-huntingtin sFv specificity and of its capacity to redirect the subcellular localization of exon 1. This study suggests that intrabody-mediated modulation of abnormal neuronal proteins may contribute to the treatment of neurodegenerative diseases such as HD, Alzheimer's, Parkinson's, prion disease, and the spinocerebellar ataxias.

Amino Acid Sequence↗
PubMed2000

Measurement of apolipoprotein B concentration in plasma lipoproteins by combining selective precipitation and mass spectrometry.

The measurement of apolipoprotein B (apoB) in purified lipoproteins by immunological assays is subject to criticism because of denatured epitopes or immunoreactivity differences between purified lipoproteins and standard. Chemical methods have therefore been developed, such as the selective precipitation of apoB followed by quantification of the precipitate. In this study, we present the measurement of apoB concentration in lipoproteins purified by ultracentrifugation by combining isopropanol precipitation and gas chromatography/mass spectrometry. Very low density lipoprotein (VLDL; d < 1.006 g/mL); VLDL plus intermediate density lipoprotein (VLDL + IDL; d < 1.019 g/mL); and VLDL, IDL, and low density lipoprotein (VLDL + IDL + LDL; d < 1.063 g/mL) were purified by ultracentrifugation. Apolipoprotein B-100 was selectively precipitated by isopropanol. The leucine content of the pellet was then determined by gas chromatography/mass spectrometry, using norleucine as internal standard. Knowledge of the number of leucine molecules in one apoB-100 molecule makes it possible to calculate the plasma concentration of apoB in the various lipoprotein fractions. ApoB in IDL (d 1.006-1.019 g/mL) and LDL (d 1.019-1.063 g/mL) were then determined by subtracting VLDL-apoB from apoB in lipoproteins d < 1.019 and apoB in lipoproteins d < 1.019 g/mL from apoB in lipoproteins d < 1.063 g/mL, respectively. The isopropanol precipitate was verified as pure apoB (>97%) in lipoprotein fractions isolated from normo- and hyperlipidemic plasma and the method appeared reproducible. The combination of isopropanol precipitation and the GC/MS method appears therefore to be a precise and reliable method for kinetic and epidemiological studies.

2-Propanol↗
PubMed1999

Monocyte tissue factor response is decreased in patients with hyperlipidemia.

Monocytes are potent regulators of blood coagulation through the expression of tissue factor (TF) on stimulation and of tissue factor pathway inhibitor (TFPI), a selective inhibitor of TF pathway. As hyperlipidemia can modify some monocyte functions, we compared the TF and TFPI expression by circulating monocytes and the plasma TFPI levels between 65 healthy normolipemic controls and 38 nontreated hyperlipemic patients. TF and TFPI relationships with plasma lipoproteins are also examined. TF and TFPI expression were evaluated in peripheral mononuclear cells after isolation from blood by density gradient centrifugation and after short culture with or without lipopolysaccharide (LPS). TF and TFPI activity and antigen were measured in mononuclear cell lysates using amidolytic assay and enzyme-linked immunosorbent assay, respectively. TFPI activity and antigen were measured in plasma using the same methods. Plasma factor VII (FVII) activity and antigen were also determined. LPS-stimulated monocyte TF activity and antigen were lower in hyperlipidemic patients than in controls (0.0001<p<0.03). This decrease of monocyte TF expression in hyperlipidemic patients was not related to an increase of monocyte TFPI. Monocyte TF activity was negatively correlated to atherogenic fractions and positively correlated to protective fractions, specially after ex vivo LPS stimulation. Increased TFPI and FVII plasma levels were found in hyperlipidemic patients compared to controls. These results indicate an impairment of TF production by circulating monocytes from hyperlipidemic subjects, which is linked to the increase of atherogenic lipoprotein fractions. Further studies are required to elucidate the mechanism of this inhibition.

Adult↗
PubMed1998

Autoreactivity of human VH domains from cDNA libraries: analysis with a bacterial expression system.

Previous studies showed that VH domains of several anti-DNA Abs can bind DNA in the absence of VL. In the current work, we tested the VH autoreactive potential more generally, examining VH domains that did not come from known autoantibodies. Using a bacterial expression system, we produced 11 fusion proteins, each containing a VH domain and a B domain of staphylococcal protein A. The VH domains were coded in cDNA libraries from circulating B cells of healthy young adult humans. Thus, binding properties of the Ig molecules from which they came were unknown. The B cells had not been stimulated in vitro. Seven cDNA clones combined the frequently expressed VH3-23 gene segment with varied DH and JH segments. The other clones contained unmutated VH3-7, VH3-9, VH3-53, and VH4-39 segments. We compared these bacterial expression products with single-chain Fv, VH and VL domains of IgM mAb 18/2, a VH3-23-encoded, DNA-binding autoantibody. Submicromolar concentrations of 5 of the 11 VH domains bound to ssDNA. Those and one more also bound to immobilized poly(dT), and two bound to circular plasmid dsDNA. Soluble poly(dT) was the most potent inhibitor in competitive ELISA. Seven of the VH domains also bound to immobilized nuclear ribonucleoprotein, four to histone and none to thyroglobulin. Two interacted with the matrix of a Sephacryl S-100 column. The polyreactive autoantigen-binding properties of these VH domains raise the question of whether these properties may play a role in the formation of the VH repertoire of circulating B cells.

Amino Acid Sequence↗
PubMed1997

Fasting during Ramadan induces a marked increase in high-density lipoprotein cholesterol and decrease in low-density lipoprotein cholesterol.

We demonstrated for the first time in a Moroccan population that fasting during Ramadan, the ninth lunar month of the Muslims' year, affected lipid and lipoprotein metabolism in a group of 32 healthy adult male volunteers. This investigation was conducted to study the changes in serum total cholesterol, triglycerides, cholesterol in high-density lipoprotein (HDL) and low-density lipoprotein (LDL), glucose, and body weight during Ramadan. The results showed a significant decrease (7.9%, p < 0.001) in serum total cholesterol concentration during Ramadan as compared with the prefasting period. Also, we obtained a significant decrease of serum triglyceride concentration (30%, p < 0.001) during Ramadan fasting as compared to the period before Ramadan. The reduction of both serum triglycerides and total cholesterol was maintained 1 month after Ramadan. By the end of Ramadan, serum HDL cholesterol had markedly increased (14.3%, p < 0.001) and remained elevated 1 month after Ramadan in contrast to LDL cholesterol which showed a significant decrease (11.7%, p < 0.0001) also maintained 1 month after Ramadan. Mean body weight declined by 2.6% (p < 0.01) on day 29 of Ramadan, whereas during Ramadan, the diet pattern used by our subjects showed an increase of total energy intake due to carbohydrates (+ 1.4% of total energy), proteins (+ 0.4% of total energy) but not fat (-0.7% of total energy) compared to a usual diet used throughout the rest of the year. Moreover, the fat diet is high in monounsaturated (p < 0.05) and polyunsaturated fatty acid in contrast to saturated fatty acid which significantly (p < 0.05) decreased during Ramadan. These findings suggest that feeding behavior that occurs during Ramadan beneficially affects plasma lipids and lipoproteins.

Adult↗
PubMed1996

Repertoire cloning of lupus anti-DNA autoantibodies.

To investigate the autoantibody repertoire associated with SLE, we have created phage display IgG Fab libraries from two clinically active SLE patients and from the healthy identical twin of one of these patients. The libraries from the lupus discordant twins were found to both include unusually large representations of the V(H)5 gene family. By panning with DNA, the SLE libraries each yielded IgG anti-double-stranded (ds) DNA autoantibodies, which are characteristic of lupus disease. These included a V(H)5 autoantibody from the affected twin, that has a targeted cluster of mutations that potentially improves binding affinity. The recovered IgG anti-dsDNA autoantibodies expressed the same idiotypes associated with the in vivo IgG anti-dsDNA response of the respective SLE donor. Heavy-light chain shuffling experiments demonstrated a case in which the in vitro creation of anti-dsDNA binding activity required restrictive pairing of a heavy chain with Vlambda light chains similar to those in circulating anti-dsDNA autoantibodies. By contrast, IgG anti-ds autoantibodies could not be recovered from the library from the healthy twin, or from shuffled libraries with heavy chains from the healthy twin. These repertoire analyses illustrate how inheritance and somatic processes interplay to produce lupus-associated IgG autoantibodies.

Amino Acid Sequence↗
PubMed1996

Heavy chain dominance in the binding of DNA by a lupus mouse monoclonal autoantibody.

Antibodies H241 and 2C10 are lupus mouse IgG autoantibodies that bind native DNA. In previous experiments, oligonucleotide antigens affinity-labeled both H and L chains of H241 but only the H chain of antibody 2C10. Primary structures of the V regions of the 2C10 H and L chains and the H241 L chain, determined from cDNA, help to explain the previous affinity-labeling experiments. The 2C10 L chain CDRs had several Asp residues and a net negative charge of five, whereas the 2C10 H chain CDRs had four Arg residues and a net positive charge of five. The L chain CDRs of H241 had a net positive charge of one. [The H241 H chain cDNA sequence was published previously by Gangemi et al. (1993) J. Immun. 151, 4660-4671]. Plasmid vectors were used for bacterial expression of H and L chains of 2C10 alone and in combinations in single chain Fv (scFv) molecules. The H chain alone bound native DNA as well as or better than the H-plus-L chain scFv. The H chain alone also bound Z-DNA. Combination of the 2C10 H chain with the L chain of an anti-Z-DNA antibody maintained the selectivity for Z-DNA, whereas its combination with the 2C10 L chain (in the 2C10 Fab) yielded selective B-DNA binding. The results with 2C10 match other examples in which the H chain is sufficient for DNA binding but selectivity is modulated by the L chain. The H chain binding to autoantigen may reflect selective events in early stages of B cell development.

Amino Acid Sequence↗
PubMed1996

Serum Lp AI lipoprotein particles and other antiatherogenic lipid parameters in normolipidaemic obese subjects.

The android pattern of body fat distribution has been shown to increase the risk of metabolic and coronary heart disease. Protective lipid markers against cardiovascular disease were studied in 98 obese normolipidaemic, non diabetic, non-smoker subjects over 18 years of age according to regional distribution of adipose tissue as estimated by the waist ship ratio (WHR) and overall obesity as estimated by the body mass index (BMI). WHR was inversely correlated with Lp AI (r = 0.46) and HDL-cholesterol (r = 0.37). BMI was not correlated with protective lipid parameters but only with triglycerides. After adjustment, Lp AI was lower in men and in upper body obese women (p < 0.05). Lp AI is a better indicator of body fat distribution than HDL-cholesterol or apo AI, and its variations appear to be indirectly related to gender, menopause, and age, thereby influencing body fat distribution (the main factor accounting for Lp AI variation). Lp AI was inversely correlated with WHR in gluteal-femoral obese women but not in abdominally obese women or men, possibly because of a threshold effect.

Adult↗
PubMed1995

Kinetic analysis of the interactions of recombinant human VpreB and Ig V domains.

The surrogate light chain, composed of VpreB and lambda 5/14.1 proteins, is selectively expressed on B cell precursors, and is important for B cell development. The surrogate light chain associates with cell surface mu-chains on preB cells, but little is known about the ligand specificity and affinity of VpreB binding. To analyze its interactions with Igs, we made recombinant human VpreB protein and measured its affinity for H and L chain V domains using surface plasmon resonance. The recombinant VpreB protein existed as a homodimer in solution. VpreB chains associated with each other with an apparent Kd = 5 x 10(-7) M, and bound to a human VH domain, a mouse VH domain, and a human VL domain with a similar affinity. VpreB protein also bound to human Fab fragments of IgG with an apparent Kd = 6 x 10(-7) M, but showed a very low affinity for human Fc fragments of IgG. VpreB-Fab complex formation was reproduced by the formation of a trimolecular VpreB-VH-VL complex. Thus, VpreB proteins can associate with each other and also form complexes with Ig at sites different from those involved in VH-VL interaction. By flow cytometry, biotinylated VpreB protein bound to surface Ig-positive B cells but not T cells. Receptors that contain VpreB could be cross-linked by either Ig or by self-association.

Animals↗
PubMed1995

[Detection of the Arg 3500-->Gln mutation of B apolipoprotein. Value in clinical practice].

OBJECTIVE: Familial defective apolipoprotein B-100, caused by a mutation in position 3500 of apolipoprotein B, induces hypercholesterolaemia, a major risk factor of coronary artery disease. The objective is to evaluate the interest of the detecting subjects bearing the Arg3500-->Gln mutation and to observe the response of these subjects to different physiological and therapeutic situations, in clinical practice. METHODS: We performed a systematic screening among hypercholesterolaemic outpatients attending a lipid clinic. The heterozygote subjects were followed up during more than one year and, in some of them, we compared the efficiency of cholesterol-lowering drugs belonging to the different classes: fibrate and statine. RESULTS: Two probands and 3 related subjects were detected. Three patients were treated. For two patients, reduction of LDL-cholesterol plasma levels was observed with both drugs but was significantly higher with statine than with fibrate. For the third one, carrying the E2E4 phenotype, the statine did not seemed to have a major effect. CONCLUSION: The number of probands is in agreement with the frequency reported in literature. A possible interaction of the effect of statine with the apo E2 isoform is discussed.

Adult↗
PubMed1995

Comparison between fat intake assessed by a 3-day food record and phospholipid fatty acid composition of red blood cells: results from the Monitoring of Cardiovascular Disease-Lille Study.

We investigated the relationship between assessment of fatty acid intake by a 3-day food record and by capillary gas chromatography of erythrocyte phospholipid fatty acid. The study was performed in a sample of 244 men aged 45 to 66 years from the general population who were participating in the Monitoring of Cardiovascular Disease (MONICA)-Lille survey. The relationship between each nutrient and food item and erythrocyte phospholipid fatty acid was investigated by a regression model on proportion including each food item and nutrient as a dependent variable and percentage of fatty acid and covariables (nonalcoholic energy intake, age, alcohol intake, and smoking) as independent variables. Polyunsaturated fat and linoleic acid intake were positively correlated with linoleic acid content of erythrocytes (beta = 0.641 and 0.604, respectively, P < .001). Monounsaturated and saturated fat intake were correlated with oleic acid (beta = 0.375 and 0.373, respectively, P < .01). Fish intake correlated positively with docosahexaenoic acid (DHA) (beta = 0.383, P < .001) and negatively with arachidonic acid (beta = -0.509, P < .01). These data confirm, on a group level, a good relationship between assessment of polyunsaturated fat intake by a 3-day record and linoleic acid content of erythrocyte membranes. These data suggest that erythrocyte oleic acid content is a marker of both saturated and monounsaturated fat intake.

Animals↗
PubMed1994

Overexpression of the multidrug resistance-associated protein (MRP) gene in vincristine but not doxorubicin-selected multidrug-resistant murine erythroleukemia cells.

Multidrug-resistant sublines of the murine erythroleukemia cell line PC4 were sequentially selected in increasing vincristine concentrations (5-160 ng/ml). The low- and intermediate-level resistant cell lines, selected in < or = 40 ng/ml of vincristine, demonstrated resistance to Vinca alkaloids and to an epipodophyllotoxin but little or none to an anthracycline. The expression of murine mdr genes, as analyzed by Northern blotting, revealed a baseline expression of murine mdr2 in parental cells that was unchanged in the drug-resistant cell lines. Overexpression of mdr3 was observed only in the highest-level resistant cell line, PC-V160, whereas mdr1 mRNA was not detected in any of the cell lines. The polymerase chain reaction, using mdr3-specific primers, excluded the possibility that low levels of P-glycoprotein expression contributed to the resistance phenotype in the low and intermediate-level resistant cell lines. Northern blot analysis using a human complementary DNA probe for the multidrug resistance-associated protein (MRP) demonstrated overexpression of murine mrp in each of the vincristine-selected sublines. Genomic amplification of the mrp gene was coincident with mrp overexpression. The expression of mrp was also examined in two series of previously characterized doxorubicin-selected cell lines derived from parental PC4 and C7D murine erythroleukemia cells. In contrast to the vincristine-selected cell lines, overexpression of mrp was not detected. These studies demonstrate that, in murine erythroleukemia cells selected for vincristine resistance, overexpression of murine mrp occurred prior to that for murine mdr. In contrast to human MRP, selection for vincristine, but not doxorubicin resistance, resulted in the overexpression of murine mrp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

[Vitamin E, antioxidants and atherosclerosis].

Atherosclerosis is a process in which lipid and factors are mixed. When LDL are oxydized, they are catabolized by the macrophage's pathway, leading to foam cells which constitute the fatty streak, the earliest lesion in atherogenesis, and they have cytotoxic, chemotactic effects. Many protective devices against free radicals and oxydation mechanisms exist, particularly antioxydant vitamins and other natural dietary antioxydants. After a brief recall of their mechanisms, epidemiological, experimental and clinical data are reviewed. To day it seems necessary to take into consideration these factors in prevention and therapeutic of atherosclerosis and dylipidaemia. Many inquiries keep going, particularly about susceptible of LDL to oxydation. One is waiting for intervention surveys in order to conclude about nutritional and medical treatments.

Antioxidants↗