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Biomedical subjects

J M Lecerf

Publications and source records attributed to J M Lecerf.

30 records · Page 2Linked to original sources

[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↗

Comparison of dietary patterns between population samples in the three French MONICA nutritional surveys.

A nutritional survey was carried out from 1985 to 1987 in three French areas covered by the ischaemic heart disease registers: Bas-Rhin (BR), Haute-Garonne (HG) and the Urban Community of Lille (UCL). 1,128 men aged 45-64 were included in a survey, using the 3-day record method. The results, after adjustment for age, socio-economic status, residence and prescribed diet, showed differences, sometimes significant, between the three samples. Fat represented 37% of the total energy intake in BR, 36% in UCL, and 34% in HG. The P:S ratio ranged from 0.50 in HG, to 0.47 in BR, and 0.40 in UCL. These differences were due to a higher intake of vegetable fat and a lower intake of animal fat in HG. In spite of a very important alcohol intake, with no big differences between the centres (33 to 36 g/day), we noticed that HG drank mainly wine, whereas BR and UCL drank wine and beer in about the same proportions.

Alcoholic Beverages↗

Determination of the LDL receptor binding capacity of human lymphocytes by immunocytofluorimetric assay.

The determination of the LDL receptor binding capacity of human blood lymphocytes was assessed by indirect immunocytofluorimetric assay. To produce the maximal synthesis of the LDL receptor, the cholesterol efflux was enhanced by incubation of lymphocytes with HDL3 subfractions. The binding capacity of the LDL receptor was measured by incubation at 4 degrees C either with LDL and rabbit anti-LDL immunoglobulins or with peptide receptor antibody (ARP-Ig) raised against the NH2-terminal sequence of the LDL receptor. Thereafter complexes were incubated with fluorescein-labelled anti-rabbit immunoglobulin (FITC-Ig). Fluorescence flow cytometry was used to quantify the number of fluorescent lymphocytes and results were expressed as the percentage of lymphocytes with a fluorescent intensity above the threshold. Using preimmune rabbit immunoglobulin and then FITC-Ig, only 5-10% of cells were fluorescent. Neither LDL nor ARP-Ig could bind to homozygous familial hypercholesterolemia (FH) lymphocytes. Normal lymphocytes preincubated with HDL3 could bind LDL or ARP-Ig, the number of fluorescent cells being 59 and 39.2% respectively. Subjects with confirmed or suspected heterozygous FH demonstrated cell fluorescence at about half the normal level.

Female↗

Imbalance of MHC class I expression in 3LL tumour cells.

Cell lines and a clone established from the C57BL/6 (H-2b) Lewis lung (3LL) tumour were previously characterized with respect to tumour growth and metastatic spread in vivo, and to the expression of a 3LL tumour-specific antigen (3LL TA) using a monoclonal antibody raised in syngeneic mice immunized with 3LL cells. No correlation was observed between the presence of 3LL TA and the prevention of metastatic spread which suggests that the immune recognition of this tumour antigen requires the presence of a self H-2 molecule absent from these tumour cells. Indeed, radioimmunoassay (RIA) and cytofluorometric analysis using specific monoclonal antibodies have shown that the H-2Kb molecule was not expressed at the cell surface of all 3LL cell lines and clones, while the H-2Db molecule was present at normal levels. This defect, which was not the consequence of a lack of beta 2m expression, was accompanied by an absence or a marked reduction of the H-2K mRNA level (which has been reversed in the M4 cell line by in vitro gamma interferon treatment), while the H-2D class I gene was normally transcribed. Another defective transcription was also observed for a gene in the Tla region (gene 37). This low '37' phenotype was corrected by in vitro treatment of the M4 cell line with gamma interferon, which indicates that this class I gene of the Qa/Tla region has an interferon response sequence in the promoter.

Animals↗