[Trends in the measurement of body heights: correlation with lipoparticle LpA1 and insulinemia in the obese].
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Arteriosclerosis↗
Biomedical subjects
J M Lecerf
Publications and source records attributed to J M Lecerf.
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↗
The role of autoreactivity in B cell selection.
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Aging↗
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↗
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↗
Trp oxidation by copper-ascorbate under physiological conditions.
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Adult↗
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↗
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↗
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↗
[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↗
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↗
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↗
[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↗
[Nutritional aspects of cardiovascular prevention].
An outline of the points of impact of atherothrombosis on pathophysiological processes is followed by a review of nutritional trials concerning the prevention and regression of atherosclerosis. Unifactorial primary prevention studies, although favourable overall, are subject to methodological criticisms and would require far larger cohorts before conclusions can be drawn. Multifactorial primary prevention studies show evidence of efficacy proportional to the reduction in risk factors obtained. The OSLO study is the most conclusive in this respect. Secondary prevention studies concern patients with coronary disease or infarct survivors. They are extremely heterogeneous. Certain involve nutritional supplements in addition. Others, such as the Renaud study based upon a mediterranean-type diet, are spectacular. Trials of the prevention by n-3 fatty acids of restenosis after transluminal coronary angioplasty are also analysed: 5 out of 8 were effective. All studies devoted to the regression of atherosclerosis have revealed less progression or regression of the disease following nutritional measures, on the basis of both clinical and angiographic parameters. The role of nutrition in the prevention and treatment of atherothrombosis is worthy of greater consideration on a first-line basis, before being completed by drug treatment, the efficacy of which is then enhanced.
Cardiovascular Diseases↗
The relationship between the phospholipid fatty acid composition of red blood cells, plasma lipids, and apolipoproteins.
This study examined the relationship between the fatty acid composition of red blood cell phospholipids and lipid markers of atherosclerotic risk in an urban male population aged 45 to 66 years. There was a surprisingly significant positive association between the docosahexaenoic acid ([DHA] 22:6n-3) content of erythrocyte phospholipids and the following risk markers: plasma cholesterol (P < .01), low-density lipoprotein (LDL) cholesterol (P < .01), apolipoprotein (apo) B (P < .05), and apo B-containing lipoprotein particles (P < .05) recognized by a monoclonal antibody (LpBL3). On the other hand, phospholipid alpha-linolenate was positively correlated with apo A-I and high-density lipoprotein (HDL) cholesterol levels (P < .05), while arachidonate showed an inverse relationship with plasma cholesterol (P < .05). There was a negative association between palmitoleic acid and apo B (P < .01) and LpBL3 (P < .001); the latter showed a negative association with stearic acid (P < .001). These interesting findings emphasize the beneficial effect on atherosclerotic risk markers of dietary n-6 polyunsaturated and monounsaturated fatty acids, and suggest that long-chain n-3 polyunsaturated fatty acids (DHA) could have an adverse effect on some of the lipid risk markers.
Apolipoproteins↗
[Comparison of the efficacy between simvastatin and gemfibrozil in primary hypercholesterolemia].
The efficacy on plasma lipids, apo A1 and B of a HMG Co A Reductase inhibitor, simvastatin, and a fibrate derivative, gemfibrozil, were compared in 136 hypercholesterolemic patients. The study was randomized, double-blinded and the active drug was given after a 4 week period of placebo. Gemfibrozil (n = 69) was given at 900 mg q.p.m. during the entire study. The primary dose of simvastatin was 10 mg q.p.m. during the first 6-weeks of treatment. At the end of this period, the dose was doubled if the cholesterol level was above 2 g/l (5,16 mmol/l). The same modification was carried out 12 weeks after the beginning active drug treatment with the same criteria. The baselines of total cholesterol were 3.24 +/- 0.69 g/l (8.38 +/- 1.78 mmol/l) 3.21 +/- 0.72 g/l (8.31 +/- 1.87 mmol/l) for patients with simvastatin and those with gemfibrozil respectively. So, at the end of active treatment, 64% of patients in the simvastatin group (n = 67) received 40 mg q.p.m. After 18 weeks of treatment, 89% of patients treated with Simvastatin and 37% with gemfibrozil had more than 20% reduction in LDL cholesterol. Simvastatin was more efficient on total cholesterol, LDL-C and apo B. The increase of HDL-C is similar in both groups of patients. In contrast, the level of triglycerides was further decreased by gemfibrozil. The tolerance was good in the two groups of patients and no difference in the frequency of side effects was observed.
Adult↗
Energy-dependent accumulation of daunorubicin into subcellular compartments of human leukemia cells and cytoplasts.
Anthracycline accumulation was evaluated by flow cytometry or radiolabeled drug assays in cells and cytoplasts (enucleated cells) prepared from parental and multidrug-resistant human K562 leukemia cells. Treatment with energy inhibitors, such as dinitrophenol (DNP) or sodium azide/deoxyglucose, led to a marked decrease in daunorubicin accumulation in parental cells and cytoplasts. Another ionophore, monensin, also caused a significant decrease in daunorubicin accumulation; however, ATPase inhibitors ouabain, vanadate, and N-ethylamaleimide had little or no effect. The lysosomatropic agents chloroquine and methylamine caused a moderate decrease in anthracycline accumulation. Fluorescence microscopy showed that the DNP-sensitive daunorubicin uptake occurred in a nonnuclear subcellular compartment. Studies using increasing daunorubicin concentrations demonstrated fluorescence quenching that occurred in the nonnuclear, DNP-sensitive compartment. The effect of inhibitors on the accumulation of rhodamine 123 and acridine orange strongly implicated lysosomes as the principal compartment of this inhibitable daunorubicin accumulation. Cytoplasts from P-glycoprotein containing multidrug-resistant K562 cells demonstrated a verapamil-reversible, decreased daunorubicin accumulation that was observed in resistant whole cells. Verapamil pretreatment of cytoplasts from resistant cells revealed the subcellular DNP-sensitive uptake present in parental cytoplasts. These studies demonstrate that cytoplasts are an effective means to study drug transport in mammalian cells without nuclear drug binding. Parental K562 cells and cytoplasts exhibit an energy-dependent accumulation of daunorubicin into cytoplasmic organelles that is also present in resistant cells and cytoplasts when P-glycoprotein mediated efflux is inhibited.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Relationship between smoking and diet: the MONICA-France project.
The association between smoking habits and diet was examined in a sample of 1126 men, aged 45-64 years, from the general population living in the three French MONICA monitoring areas: Bas-Rhin (BR) (n = 346), Haute-Garonne (HG) (n = 400) and Urban Community of Lille (UCL) (n = 380). Diet was assessed by the 3-day record method. The energy and nutrient intakes were calculated for each of the 3 centres, using the same food composition tables. Alcohol consumption was higher among smokers (P less than 0.001). Taking into account alcohol consumption, age, body mass index, centre, educational level and family size, the analyses showed no difference in non-alcoholic energy intake, proteins, carbohydrates, and total fat. However, smokers had a lower intake of polyunsaturated fatty acids (P less than 0.05) and dietary fibre (P less than 0.01) than non-smokers. With regard to food items, smokers had a higher intake of sucrose (P less than 0.05) and a lower intake of vegetables (P less than 0.001), dairy products (P less than 0.05) and cheese (P less than 0.05). These results suggest that analyses in future epidemiological research regarding the role of diet in the aetiology of tobacco-related diseases should consider this association of potential risk factors.
Alcohol Drinking↗