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Biomedical subjects

G Durand

Publications and source records attributed to G Durand.

At least 163 records · Page 9Linked to original sources
PubMed1992

Modifications of hepatic alpha-1-acid glycoprotein and albumin gene expression in rats treated with phenobarbital.

The serum level of alpha 1-acid glycoprotein (alpha 1-AGP) is significantly increased in various animal species by treatment with cytokines, glucocorticoids and phenobarbital. The mechanisms responsible for the cytokine-induced and glucocorticoid-induced increases are now well documented, but not so in the case of phenobarbital. The main purpose of this study was to assess whether phenobarbital acts on alpha 1-AGP synthesis in the liver at the transcriptional or translational level. Male Dark Agouti rats received 70 mg phenobarbital/kg daily for 7 days. The analysis of total hepatic RNA showed that a single injection of phenobarbital induced an 11-fold increase in phenobarbital-dependent cytochrome P450IIB mRNA, whereas seven injections of phenobarbital were required to induce a maximum 5.5-fold increase in alpha 1-AGP mRNA. Concurrently, the transcription rate of the alpha 1-AGP gene rose 3.5-fold. Hepatocytes isolated after the seventh injection of phenobarbital showed a threefold increased capacity to secrete alpha 1-AGP, corresponding to a 3.2-fold increased alpha 1-AGP mRNA content in the liver. In conditions in which its effect on the induction of alpha 1-AGP synthesis was maximum, phenobarbital caused a 30% reduction in liver albumin mRNA and in albumin secretion by isolated hepatocytes, resulting from a 60-70% reduction in the rate of transcription of the albumin gene measured in isolated nuclei. We conclude that the effect of phenobarbital on alpha 1-AGP and albumin gene expression occurs at the transcriptional rather than the translational level.

Albumins↗
PubMed1992

Differential rates of glycoprotein secretion by isolated rat hepatocytes studied in terms of concanavalin A binding.

Using a concanavalin-A-based method which respects cell function, we have shown that the kinetics of glycoprotein secretion appear to depend on the nature of the oligosaccharide moiety. In 37 degrees C pulse/chase experiments using freshly isolated normal rat hepatocytes, we found that except for transferrin, whose rate of secretion was independent of its concanavalin A reactivity, the secretion of the concanavalin-A-retained forms of alpha 1 acid glycoprotein, T-kininogen, alpha 1 protease inhibitor and alpha 1 inhibitor III was slower than that of the concanavalin-A-non-retained forms. When hepatocytes were incubated at 20 degrees C, secretion was blocked with the accumulation of mainly endoglycosidase-H-sensitive forms. The secretion kinetics of the concanavalin-A-differentiated forms were still different when the temperature was shifted back to 37 degrees C. The divergence between the secretion rates of the concanavalin-A-differentiated forms would appear to be due to a late event in intracellular protein trafficking, which may depend on the sugar content and/or the number of carbohydrate chains of the glycoproteins.

Acute-Phase Proteins↗
PubMed1992

Alpha 1-acid glycoprotein potentiates lipopolysaccharide-induced secretion of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha by human monocytes and alveolar and peritoneal macrophages.

Although the physiological role of alpha 1-acid glycoprotein (AGP), an acute-phase protein, is poorly understood, several lines of evidence support a modulatory action on the immune response. In this study, we investigated the effect of AGP on the production of interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF)-alpha by human monocytes, macrophages and the monocytic THP-1 cell line. AGP significantly enhanced (2- to 7-fold) the production of these cytokines in monocytes induced by suboptimal concentrations of lipopolysaccharide [E. coli lipopolysaccharide (LPS): 100 ng/ml] in serum-free conditions, whereas it had little or no effect in the absence of LPS. The potentiating effect of AGP was inhibited by specific antibodies. It was concentration dependent and the greatest enhancement was observed with 250-500 micrograms/ml. Moreover, AGP only potentiated the effect of suboptimal concentrations of LPS. AGP did not alter the time course of LPS-induced IL-1 beta, IL-6 or TNF-alpha secretion. AGP acts as a co-inducer and could also potentiate cytokine secretion triggered by Neisseria meningitidis LPS and muramyl dipeptide. The glycan moiety of AGP did not seem to be involved in its potentiating effect, since both its major glycoforms and asialo-AGP potentiated the effect of LPS to the same extent as native AGP. Possible differences in the effect of AGP according to cell maturation were investigated using isolated human macrophages: AGP potentiated LPS-induced cytokine production by both peritoneal and alveolar macrophages. These data suggest that AGP can modulate monocyte/macrophage functions, thereby contributing to the amplification and regulation of immune and inflammatory responses.

Cell Line↗
PubMed1992

Structural and functional importance of dietary polyunsaturated fatty acids in the nervous system.

The nervous system is the organ with the second greatest concentration of lipids. These lipids participate directly in membrane functioning. Brain development is genetically programmed. It is therefore necessary to ensure that nerve cells receive an adequate supply of nutrients, especially of lipids, during their differentiation and multiplication, and throughout their lives. The effects of polyunsaturated fatty acid deficiency have been extensively studied; prolonged deficiency leads to death in animals. Linoleic acid is now universally recognized to be an essential nutrient. Until recently, however, alpha-linolenic acid was considered non-essential. Feeding animals with oils that have a low alpha-linolenic content results in all brain cells and organelles and various organs having reduced amounts of 22:6n-3, which is compensated for by an increase in 22:5n-6. The speed of recuperation from these anomalies is extremely slow for brain cells, organelles, and microvessels, in contrast to other organs. A decrease in alpha-linolenic series acids in the membranes results in a 40% reduction in the Na(+)-K(+)-ATPase of nerve terminals and a 20% reduction in 5'-nucleotidase. Some other enzymatic activities are not affected, although membrane fluidity is altered. A diet low in alpha-linolenic acid induces alterations in the electroretinogram which disappear with age; motor function and activity are little affected, but learning behavior is markedly altered. The presence of alpha-linolenic acid in the diet confers a greater resistance to certain neurotoxic agents (triethyl-lead). During the period of cerebral development, there is a linear relationship between brain content of n-3 acids and the n-3 content of the diet up to the point where alpha-linolenic levels reach 200 mg for 100 g of food intake. Beyond that level there is a plateau. For other organs, such as the liver, the relationship is also linear up to 200 mg/100 g, but then there is merely an abrupt change in slope and not a plateau. When dietary 18:2n-6 content was varied, it was noted that 20:4n-6 optimum values were obtained at 150 mg/100 g for all nerve structures, 300 mg for testicle and muscle, 800 mg for kidney, and 1200 mg for liver, lung and heart. A deficiency in alpha-linolenic acid and an excess of linoleic acid have the same main effect: an increase in 22:5n-6 levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Recombinant human interleukin 1 beta and tumor necrosis factor affect glycosylation of serum alpha 1-acid glycoprotein in rats.

Serum concentration and glycosylation of rat alpha 1-acid glycoprotein (alpha 1-AGP) were evaluated after the in vivo administration of recombinant human interleukin-1 beta (rhIL-1 beta) and tumor necrosis factor alpha (rhTNF-alpha), alone or associated. The effect of LPS and turpentine was also studied. In all models, serum alpha 1-AGP concentrations were increased and glycosylation was altered. The alpha 1-AGP levels reached 1.8 g/liter with cytokines alone, 2.1 g/liter with cytokines associated or LPS, and 3.4 g/liter with turpentine. Analysis by concanavalin A (Con A) affinoimmunoelectrophoresis (CAIE) revealed that the relative proportion of Con A unreactive form always decreased whatever the inducing agent. On the other hand, the resulting effect on the concentrations of Con A unreactive alpha 1-AGP concentrations was an increase with cytokines alone or LPS and a decrease with cytokines associated or turpentine. These results suggest a dissociation between the alteration in the level of alpha 1-AGP synthesis and in the pattern of its glycosylation in the various inflammatory models.

Acute-Phase Reaction↗
PubMed1992

Views of a general population on mass screening for colorectal cancer: the Burgundy Study.

BACKGROUND: The success of a screening program depends on a number of factors, including the validity of the test, its efficacy, its feasibility, and the rate of compliance. Thus, it is important to determine the factors influencing compliance to the screening test in order to obtain a high participation rate. METHODS: A mass screening campaign for colorectal cancer using the Hemoccult test was conducted in Burgundy, France. One year later, a questionnaire was mailed to a random sample of the population to assess the views of the general public (870 persons who had not completed the Hemoccult test, 750 persons who had a negative test, and 100 persons who had a positive test). The compliance rate of this survey was 32.2% among persons who had not completed the screening test, 88.2% among persons with a negative result, and 98.0% among persons with a positive result. RESULTS: The main reason for not participating was not wanting to know more about their health status (34.3%). Of the factors credited with encouraging persons to perform the test, the most important ones were the practitioner's explanations (55.7%) and the leaflet sent by mail (42.5%). The impact of the media campaign was weak. A small portion of the population (4.3%) said that they were very anxious while waiting for the results. Among persons with a positive screening test, only 1.2% regretted having taken it. Among those who took the test, 94.2% said they were ready to do it again; and among those who did not take it, 36.7% would accept it at a second screening. CONCLUSIONS: The data suggest that overall the Hemoccult is well accepted, that the campaign did not upset the population, and that it is worthwhile at the second screening to include those who did not participate in the first screening test.

Aged↗
PubMed1992

Dietary alpha-linolenic acid deficiency and early uterine development in female rats.

Feeding rats a purified diet containing peanut oil with a low alpha-linolenic acid [18:3(n-3)] content resulted in lower amounts of (n-3) polyunsaturated fatty acids, mainly docosahexaenoic acid [22:6(n-3)], greater amounts of docosapentaenoic acid [22:5(n-6)] in uterus phospholipids, and altered postnatal uterus development when compared with rats fed a diet containing peanut and rapeseed oils. Maximal differences in uterine growth, as measured by uterine weight, protein and DNA content, occurred between d 24 and 30 postpartum and disappeared near the end of sexual development (d 40). The induction of the progesterone receptor was not affected, and serum estradiol concentrations were not significantly reduced in deficient animals. Moreover, growth response of the uterus to low doses of 17 beta-estradiol (less than 5 micrograms/kg) was significantly reduced in ovariectomized animals fed the diet containing only peanut oil. However, the maximal response of the uterus, observed with higher 17 beta-estradiol doses (5-50 micrograms/kg), was not affected. Because the two diets used differed in the content of alpha-linolenic acid, it is likely that alpha-linolenic acid deficiency in animals fed the diet containing only peanut oil was the cause of the affected uterine development.

Animals↗
PubMed1992

Variations in human liver fucosyltransferase activities in hepatobiliary diseases.

The hyperfucosylation of a number of glycoconjugates observed in liver diseases involves the action of several specific fucosyltransferases (F.T.) notably responsible for synthesizing histo-blood group antigens. We determined the activities of alpha 3, alpha 2 and alpha 3/4 F.T. in 35 liver biopsy samples from patients with fatty liver, alcoholic or post-hepatic liver cirrhosis, primary or secondary biliary cirrhosis, acute hepatitis or a normal liver. F.T. activities were measured by transfer of GDP [14C] fucose to asialotransferrin for alpha 3 F.T., to phenyl beta-D-galactoside for alpha 2 F.T. and to 2' fucosyllactose for alpha 3/4 F.T. The diseased liver extracts showed an early increase in non-Le gene-associated alpha 3 F.T. activity (p = 0.001), which was related to the number of steatosic hepatocytes and the degree of intralobular inflammatory infiltration. Overexpression of this alpha 3 F.T. provides an explanation for the strong expression of 3-fucosyl lactosamine structures described in several hepatobiliary diseases. alpha 2 F.T. levels were significantly elevated in the two groups of liver cirrhosis and acute hepatitis (p = 0.05), but not enough to consider alpha 2 F.T. as a sensitive feature of mesenchymal cell injury. All Lewis-positive biopsies displaying biliary alterations showed increased Le gene-encoded alpha 3/4 F.T. activity (p = 0.001), which was related to the intensity of neoductular proliferation. Elevated levels of alpha 3/4 F.T. may be a very early sign of biliary regeneration.

Bile Duct Diseases↗
PubMed1992

The in vivo systemic effect of human recombinant interleukin-1 beta on fibronectin in rats.

The in vivo systemic effect of interleukin (IL)-1 beta on plasma and cartilage fibronectin was studied in arthritic rats, as well as alpha 1-acid glycoprotein and albumin. Plasma fibronectin showed a 27% increase in the arthritic group, while alpha 1-acid glycoprotein increased 22-fold and albumin decreased by 46%. IL-1 effect depended on the administered dose. 2 micrograms injection significantly increased plasma fibronectin and alpha 1-acid glycoprotein. In cartilage, fibronectin was significantly modified in arthritic animals but increased in a dose-related manner after IL-1 treatment. As IL-1 increases fibronectin-degrading enzyme production and as some of these fragments can develop properties that do not possess the intact molecule, one can postulate a vicious circle in matrix degradation in the inflammatory process of the joint.

Animals↗
PubMed1992

Factors influencing the reaction of alpha 1-fetoprotein with concanavalin A and Lens culinaris agglutinin in crossed affinoimmunoelectrophoresis.

Concanavalin A (Con A) and lentil lectin (LCA) analysis of alpha-fetoprotein (AFP) glycosylation heterogeneity is used in a variety of clinical situations. We studied the influence of analytical conditions on the separation of AFP glycoforms by using lectin-crossed affinoimmunoelectrophoresis, regardless of the AFP concentration, which can vary over a wide range in biological fluids. We defined the optimal concentration of Con A (2 g/L) and LCA (0.35 g/L) in the first-dimension gel, together with the optimum antigen (AFP)/antibody ratio in the second-dimension gel. The presence of protein in the diluent used for AFP samples was found to change the shape of crossed affinoimmunoelectrophoresis patterns without changing the percentage composition of AFP fractions. The within-run CV was less than 4% for both lectins, and the between-run CV was less than 6.3%. The minimal quantity of AFP that provided a visible pattern with both lectins was 4 ng, corresponding to 50 microL of an 80 micrograms/L AFP sample. These technical conditions allow the cellular origin of AFP to be determined, regardless of the concentration in the sample. Typical AFP lectin patterns of secreting tumors are compared with fetal and cord serum AFP.

Amniotic Fluid↗
PubMed1992

Influence of dietary n-6/n-3 polyunsaturated fatty acid balance on the development of tolerance during chronic ethanol intoxication in rats.

The present study addresses the possible interacting effects of dietary n-6/n-3 polyunsaturated fatty acid (PUFA) balance and chronic ethanol intoxication on the synaptic membrane responses to ethanol and the development of tolerance in rats. Wistar rats were fed either a standard lab chow or various semi-synthetic diets: rich in PUFA (from soya oil: SO), deficient in linolenate (from sunflower oil: SFO) or rich in long-chain (n-3) PUFA (cod liver oil: CLO). Male adult rats from the second specially fed generation were submitted to a 3-week alcoholization by daily intubation. Functional tolerance was quantified by the hypothermic response to a challenge dose of ethanol. Synaptic fluidity and sensitivity to ethanol (variations after acute ethanol addition) were assessed by fluorescence polarization (FP) of DPH, TMA-DPH or PROP-DPH. Membrane fatty acid composition was determined by GLC. The fatty acid composition of the synaptic membranes was influenced by the diet, but rearrangements among the lipids occurred, resulting in an apparent stability in brain membrane fluidity parameters. Nevertheless, clear-cut differences were noted in response to ethanol intoxication according to the diet. In the same period of time, rats fed SFO or CLO diets were unable to develop tolerance to ethanol at the membrane level as well as functionally, contrarily to the rats fed SO or standard diets. The structurally specific roles of PUFA are suggested by the negative membrane effects of the alpha-linolenate deficient diet (SFO) and the positive ones of a diet (SO) rich and well balanced in (n-3 + n-6) PUFA. Furthermore, the n-6/n-3 PUFA balance in the synaptic membrane needs to be kept within very narrow limits to allow normal development of the adaptive response to ethanol.

Alcoholic Intoxication↗
PubMed1992

[Cost of a mass screening program for colorectal cancer using the occult blood test].

The Cancer Registry of Burgundy, France, set up a controlled study involving 91,000 people aged 45 to 74 to ascertain the cost-effectiveness of mass screening for colorectal cancer with the Hemoccult test. The aim of this study was to estimate the cost of the first part of the screening campaign, which took place in 1988 and 1989. The overall cost of the campaign was 2,275,589 FF. The cost for the GPs' instruction course was 3.9 percent and the press campaign, 8.4 percent of total costs. The cost related to the distribution or prescription of tests by the GPs was 60.3 percent of the total cost of the campaign. The average cost per test was 39.8 FF when it was distributed by the GPs. The average cost per test was 116.4 FF when bought individually in drugstores or pharmacies. The average cost per test was 70.1 FF when mailing was used. The average cost per test for the analysis was 12.7 FF that is to say 13.7 percent of the total cost. The cost of scientific follow-up and analysis was 13.8 percent. The cost for one person completing the test averaged 92.7 FF. The preliminary results of the cost-effectiveness analysis make it possible to estimate the cost of the mass screening campaign for colorectal cancer. Better cost/effectiveness ratios have already been made according to these results.

Aged↗
PubMed1992

[Auditory evoked potentials and tumor of the cerebellopontine angle].

The technique of auditory evoked potentials evaluates the auditory pathways along the vestibulocochlear nerve and in the brainstem. The authors stress the importance of this examination in the diagnosis of tumours of the cerebellopontine angle and they discuss its place in relation to radiological investigations.

Cerebellar Neoplasms↗
PubMed1991

Alterations of the glycan moiety of human alpha 1-acid glycoprotein in late-term pregnancy.

The carbohydrate moiety of purified alpha 1-acid glycoprotein (AGP) from healthy male adults (AGPn) and late-term pregnant women (AGPp) was analysed. Polyacrylamide gel electrophoresis with sodium dodecyl sulfate before and after N-glycanase treatment showed that AGPp had a slightly higher molecular mass due to an enriched carbohydrate moiety. BIO-GEL P-4 and Concanavalin A (Con A)-Sepharose chromatography of the oligosaccharides released by hydrazinolysis and fractionated by high-voltage electrophoresis indicated a progression towards Con A-unbound oligosaccharides and towards larger glycans in pregnancy. Carbohydrate analysis of purified AGPp and AGPn and of the most increased oligosaccharide fraction (F4A) evidenced a decrease in the fucosyl molar ratio and a slight increase in the galactosyl, N-acetyl-glucosaminyl and N-acetyl neuraminyl ratios. These results suggest that AGP contains more highly branched oligosaccharides and/or additional N-acetyllactosamine-type oligosaccharides in pregnancy.

Adult↗
PubMed1991

Changes in alpha 1-acid glycoprotein serum concentrations and glycoforms in the developing human fetus.

alpha 1-Acid glycoprotein concentrations and reactivity to concanavalin A were measured in maternal and fetal serum and amniotic fluid obtained from 24 women undergoing diagnostic cordocentesis at 20 to 33 wk gestation and in 30 additional fetal sera (19 to 34 weeks gestation). Maternal alpha 1-acid glycoprotein serum levels were five to ten times higher than fetal and amniotic levels. Fetal alpha 1-acid glycoprotein levels were found to increase with advancing gestational age. Using crossed immunoaffino electrophoresis with concanavalin A, alpha 1-acid glycoprotein patterns were identical in maternal serum and amniotic fluid but totally different in fetal serum. The fetal concanavalin A pattern changed progressively during fetal life towards that of the newborn. These data confirm earlier assumptions of fetal synthesis of alpha 1-acid glycoprotein and provide normal reference values for alpha 1-acid glycoprotein in fetal serum. In addition, the specific fetal concanavalin A pattern indicates that the alpha 1-acid glycoprotein glycosylation process during fetal life differs from that in post-natal life.

Amniotic Fluid↗
PubMed1991

Interactive effects of dietary (n-3) polyunsaturated fatty acids and chronic ethanol intoxication on synaptic membrane lipid composition and fluidity in rats.

The influence of dietary polyunsaturated fatty acids on fatty acid composition, cholesterol and phospholipid content as well as 'fluidity' (assessed by fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) probes) of brain synaptic plasma membranes (SPM) and their interactions with chronic ethanol effects were studied in rats fed for two generations with diets either devoid of (n-3) fatty acids (sunflower oil diet), rich in alpha-linolenic acid (soya oil diet) or in long chain (n-3) fatty acids (sunflower + cod liver oil diet). Results were compared with rats fed standard lab chow. Sunflower oil led to an increase in the (n-6)/(n-3) ratio in the membranes with an increase of the 'fluidity' at membrane apolar level; sunflower + cod liver oil decreased the (n-6)/(n-3) ratio without affecting membrane 'fluidity' while no difference was seen between the SPM of rats fed soya oil and standard diet. After 3 weeks alcohol intoxication in rat fed the standard diet: oleic alpha-linoleic acids and cholesterol levels were increased, arachidonic acid and the double bond index/saturated fatty acids were decreased and there was a decrease of 'fluidity' in the lipid core of the SPM. Soya oil almost totally abolished these usually observed changes in the SPM fatty acids composition but increased oleic acid and cholesterol without any change in fluidity. Sunflower oil led to the same general alterations of fatty acid as seen with standard diet but to a greater extent, with decrease of the 'fluidity" at the apolar level and in the region probed by TMA-DPH. When sunflower oil was supplemented with cod liver oil, oleic and alpha-linoleic acids were increased while the 'fluidity' of the apolar core of SPM was decreased. So, the small changes in fatty acid pattern seem able to modulate neural properties i.e. the responses to a neurotoxic like ethanol. A structurally specific role of PUFA is demonstrated by the pernicious effects of the alpha-linolenic acid deficient diet which are not totally prevented by the supply of long chain (n-3) PUFA.

Alcoholic Intoxication↗