Search PubMed⌕ Search

Biomedical subjects

J Arnaud

Publications and source records attributed to J Arnaud.

At least 19 recordsLinked to original sources
PubMed1996

Defective interactions between TCR chains and CD3 heterodimers prevent membrane expression of TCR-alpha beta in human T cells.

The human TCR complex is composed of two clonotypic polypeptide chains, TCR-alpha and TCR-beta (or TCR-gamma and TCR-delta) associated with CD3 gamma-, delta-, and epsilon-chains and zeta 2 homodimers. All six polypeptide chains are indispensable for TCR membrane expression and signaling function. In the present paper is described the analysis of a new TCR membrane-negative Jurkat T cell variant: E6.R3. The defect in this variant bears on the interaction between TCR and CD3 chains. E6.R3 cells have deleted three nucleotides in the TCR-alpha transmembrane (TM) region, which consequently lacks a leucine. This defect causes 1) lack of association between TCR alpha-chains and CD delta epsilon heterodimers; 2) lack of formation of disulphide-linked, fully glycosylated TCR-alpha beta heterodimers; and 3) lack of interaction between TCR-alpha beta/CD3 complexes and zeta-chains. Despite these defective interactions, TCR alpha-chains appear to become fully glycosylated, i.e., they are not retained in the endoplasmic reticulum but are further processed in the Golgi apparatus without such interactions. The defect may be due to the observation that in the E6.R3 TCR alpha- chains TM region, the two charged amino acids are situated on the same side of the alpha-helix; these two amino acids are exposed on opposite faces of the TM alpha-helix in normal TCR alpha-chains, possibly allowing TCR alpha-chains to interact with both CD3 delta- and CD3 epsilon-chains. Further possible consequences of the leucine deletion in the E6.R3 TCR-alpha TM region are discussed.

Amino Acid Sequence↗
PubMed1996

Plasma and erythrocyte manganese concentrations. Influence of age and acute myocardial infarction.

This study was carried out to assess manganese (Mn) status after an acute episode of myocardial infarction. Plasma and erythrocyte Mn concentrations were measured from admission to hospital to day 15 postadmission in 21 patients suffering from acute myocardial infarction and in three control groups. The determination of Mn in these biological fluids was performed by electrothermal atomic absorption spectrometry. Plasma Mn was higher (p < 0.01) and erythrocyte Mn was similar in the acute myocardial infarction group compared to healthy age-matched control group. Plasma and erythrocyte Mn remained unchanged during the 2 wk after acute myocardial infarction and were not correlated to enzyme activities. A decrease of erythrocyte Mn with age, expressed in nmol/L, was noted (p < 0.02). These results suggest that plasma and erythrocyte Mn do not provide an indication of myocardial damage. Nonetheless, Mn status in elderly merits further attention.

Adult↗
PubMed1996

Increase in glutathione peroxidase activity in malaria parasite after selenium supplementation.

Glutathione peroxidase (GPx), a key enzyme involved in the detoxification of many peroxides, has been investigated in two malaria parasite species: P. yoelii in vivo (murine malaria) and P. falciparum in vitro (human malaria). We demonstrate the presence of an endogenous GPx activity in these two Plasmodia species. Enzymatic assays and the use of specific substrates and inhibitors allowed us to determine that the activity is selenium dependent. As this activity was shown to be lower in P. falciparum than in P. yoelii, and selenium levels were found to be low in culture medium and culture red blood cells, we hypothesized that a severe selenium deficiency could be responsible for this difference. After selenium supplementation, with either sodium selenite or selenocystine, we observed an increase in growth of P. falciparum only in with sodium selenite, whereas higher GPx activities were noted in parasites grown in media supplemented with both. An increase in GPx activities was also observed in parasites that had undergone an experimental oxidative stress with TBOOH. As the erythrocyte is unable to synthesize new proteins, these results provide further evidence for the existence of an endogenous parasitic selenium-dependent glutathione peroxidase.

Animals↗
PubMed1996

Analyzed dietary intakes, plasma concentrations of zinc, copper, and selenium, and related antioxidant enzyme activities in hospitalized elderly women.

OBJECTIVE: The purpose of the study was to assess the actual dietary intakes of zinc (Zn), copper (Cu) and selenium (Se) intakes in relation with some indicators of trace element status in a selected group of hospitalized elderly patients. SUBJECTS: 24 elderly women aged 76-99 years were recruited in the Geriatric Department of the Grenoble University Hospital. MEASURES OF OUTCOME: Zn, Cu, and Se dietary intakes were estimated by duplicate portion analysis. Plasma trace element concentrations, Cu-Zn superoxide dismutase (Cu-Zn SOD) and Se glutathione peroxidase (Se GSH-Px) activities were determined in parallel. RESULTS: Mean daily intakes of Zn (5.6 mg), Cu (0.67 mg), and Se (23 micrograms) were low, in relation with poor energy intake and nutrient densities. Zn and Se levels in plasma were lower and plasma Cu increased compared to reference values obtained from healthy younger subjects. Thirty-eight percent of the elderly patients had plasma Zn concentrations < 10.7 mumol/l, but Cu status appeared adequate as suggested by the lack of decline in Cu-Zn SOD activity. A high proportion of plasma Se concentrations < 0.76 mumol/l and the parallel decrease in erythrocyte and plasma GSH-Px activities suggest a Se deficiency in this population. CONCLUSION: Our findings indicate that French hospitalized elderly patients may be at risk of Zn and Se marginal status and present altered antioxidant defenses in relation with low dietary intakes. It underlines the interest of supplementation studies in this population.

Aged↗
PubMed1996

Micronutrient status in elderly people. Geriatrie/Min. Vit. Aux Network.

A biochemical assessment of the vitamin and trace element status of 756 institutionalized elderly men and women, 66-103 years old (average 83.5 +/- 7.6 y), was conducted in 26 nursing homes in different areas of France. Serum concentrations of beta- and alpha-carotene, beta-cryptoxanthin, lycopene, retinol, alpha- and gamma-tocopherol, vitamin C, zinc and selenium were measured. A difference in biochemical markers according to sex was observed for vitamins E and C: elderly women had higher levels of alpha-tocopherol and vitamin C than elderly men. When expressed as a ratio of cholesterol, the difference between sexes for alpha-tocopherol disappeared. Simple regression analysis showed that most vitamins and trace elements were significantly negatively correlated with age. A high prevalence of low concentrations of vitamin C, zinc and selenium was revealed.

Aged↗
PubMed1996

Effect of 6 month supplementation with different combinations of an association of antioxidant nutrients on biochemical parameters and markers of the antioxidant defence system in the elderly. The Geriatrie/Min.Vit.Aox Network.

OBJECTIVES: To study the effect of supplementation with an association of small physiological amounts of antioxidant nutrients upon biochemical parameters and indicators of oxidative stress and antioxidant enzymes. DESIGN: The study included a double-blind placebo-controlled design. SETTING: Nursing homes in different areas in France. SUBJECTS: 575 elderly long term hospitalized subjects aged 65-103 years. INTERVENTION: Four groups were compared. They received daily: (V) vitamins (vitamin E, 15 mg and vitamin C, 120 mg) and beta-carotene, 6 mg; (T) trace elements (zinc, 20 mg, selenium, 100 micrograms); (VT) vitamins associated with trace elements; or (P) a placebo. Biological markers of vitamin and trace element status, and free radical parameters were measured initially and after 6 months of supplementation. RESULTS: An analysis of variance indicated a significant effect of vitamin supplementation on serum alpha-tocopherol, beta-carotene and vitamin C, a significant effect of trace element supplementation on serum zinc and both a significant trace element and a vitamin-trace element interaction on serum selenium. We observed significant effects of both trace element and vitamin supplementation on GPx activity (P < 0.01), an effect of vitamin supplementation on SOD activity (P < 0.05). CONCLUSION: Our results indicate that short-term supplementation with moderate doses of antioxidant vitamins and trace elements in elderly subjects clearly improves both non-enzymatic (alpha-tocopherol, beta-carotene, vitamin C) levels and enzymatic antioxidant (GPx and SOD) activity.

Aged↗
PubMed1996

[Selenium, glutathione peroxidase, peroxides and platelet functions].

In the last five years, there has been a renewal of interest in the protective role of selenium in vascular disorders, inspired by experimental evidence that this trace element could modulate leukotriene and prostaglandin synthesis in both endothelial cells and platelets. In people living in low-selenium areas, a relationship has been established between a decrease in plasma selenium and an increase in the risk of coronary disease, atherosclerosis, platelet hyperaggregability and synthesis of proaggregant and proinflammatory compounds like thromboxane A2 and leukotrienes. Selenium, as an essential part of glutathione peroxidase, takes part in the reduction of hydrogen peroxides and lipid peroxides. The concentration of these peroxides, in turn, regulates the activities of cyclooxygenase and lipooxygenase pathways, ultimately influencing the production of eicosanoids and modulating the balance between a proaggregatory and antiaggregatory state. Recent evidence shows that selenium, via its action on glutathione peroxidase activity, may be primarily responsible for the regulation of the endogenous hydroperoxide level. In human platelets, the activity of glutathione peroxidase is particularly high and is very sensitive to the requirement of selenium. This sensitivity could explain why platelets of selenium-deficient subjects show increased aggregation, thromboxane B2 production and synthesis of the lipoxygenase-derived compounds. In these deficient subjects, selenium administration increases platelet glutathione peroxidase activity and inhibits platelet hyperaggregation and leukotriene synthesis. These results support the hypothesis that selenium supplementation has a positive effect on platelet aggregation in selenium-deficient subjects. In France, more than 10% of the population is selenium-deficient and long-term supplementation with low doses of selenium could have a beneficial effect on the prevention of both thrombosis and coronary heart disease in these subjects.

Animals↗
PubMed1996

The French interlaboratory quality assessment programme for copper, zinc and selenium in blood serum.

The group for quality assurance for trace elements of the Société Française de Biologie Clinique (SFBC) has operated an interlaboratory quality assessment programme for copper, zinc and selenium determinations in blood serum since 1988. The primary objective is to enable participants to maintain or improve the accuracy of their analytical performances by comparing their results with other laboratories, every two months, on the basis of three quality criteria: comparison to the mean value, recovery of added copper, zinc and selenium, between-run reproducibility for identical samples. A further aim of this scheme is to evaluate interlaboratory transferability of the results. The procedure for individual and overall evaluation is reported. For each participant a performance score is calculated for each quality criteria, and a global score is attributed. The analytical performances of the participants were considered "good", "acceptable" or "inadequate" according to their global scores. Some of the results observed in this scheme are interpreted on the basis of differences between the notions of quality control and total quality assurance.

Animals↗
PubMed1995

Effect of double-blind cross-over selenium supplementation on lipid peroxidation markers in cystic fibrosis patients.

Lipid peroxidation was assessed in 27 cystic fibrosis children during a double-blind selenium supplementation study (2.8 micrograms of sodium selenite per kg per day) with a placebo control and inversion of treatment periods. Simultaneously, 17 healthy children living in the same area were also investigated as control subjects. Before any treatment whatsoever and despite a selenium status close to those of control subjects, cystic fibrosis patients showed significant increase in plasma lipid peroxidation markers. Thiobarbituric acid reactants (TBARs) were normalized after the first treatment period of 5 months in both cystic fibrosis groups receiving either selenium supplementation or placebo. In this latter group, TBARs were reduced despite a significant decrease in plasma selenium concentrations as compared with the control group. Organic hydroperoxide concentrations were also simultaneously normalized in both cystic fibrosis groups at the end of the second treatment period. These results showed that improvement of lipid peroxidation markers was not related to the selenium supplementation. Nevertheless, oxidative stress sustained by cystic fibrosis children must be taken into account so that it does not aggravate the prognosis of the disease.

Adolescent↗
PubMed1995

Copper, iron, manganese and zinc contents in human colostrum and transitory milk of French women.

Copper, iron, manganese and zinc were measured in breast milk samples collected from 82 healthy lactating mothers. Samples were collected from day of delivery to 7 days postpartum. Zn was analysed by flame atomic absorption spectrometry and the other elements by electrothermal atomic absorption spectrometry. Copper concentrations remained constant. Iron declined from 14.2 +/- 7.3 mumol/l at day 1 to 5.6 +/- 3.1 mumol/l at day 5 postpartum. Zinc and manganese declined from a maximum at 2 days postpartum (Zn: 183 +/- 70 mumol/l; Mn: 218 +/- 102 nmol/l) to 77 +/- 22 mumol/l (Zn) and 62 +/- 29 nmol/l (Mn) at 6 days postpartum. Copper concentrations are related to parity (r = 0.317, P < 0.001) and mother body mass index (r = 0.324, P < 0.001).

Adult↗
PubMed1995

Silica-associated connective tissue disease. A study of 24 cases.

We prospectively studied all patients hospitalized for connective tissue disease (CTD) in our French rheumatology clinic from January 1979 to December 1989. Our aims were 1) to determine if CTDs associated with occupational exposure to silica (Si) are currently observed in a rheumatology clinic, and, if so, 2) to describe the major features of Si-associated CTD, and 3) to specify which individuals are affected by Si-associated CTD. Patients were divided into 2 groups based on their responses to a questionnaire: those who had been exposed to Si, and those who had no occupational exposure to Si. Among the 764 patients with CTD studied, 24 (3%) were patients with Si-associated CTD and 740 (97%) were patients with non-Si-associated CTD. The sex ratio between the 2 groups was significantly different with a high frequency of men and of immigrants in the Si-associated CTD group. Two thirds of the patients exposed to Si were male miners or sandblasters, but the other third had more unusual exposures to Si, which may involve members of all socio-economics sectors and both sexes, such as sculpture or exposure to abrasive powders. Progressive systemic sclerosis (PSS) was significantly more prevalent in the Si-associated CTD group. This group also consisted of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), dermatomyositis (DM), and other autoimmune diseases. Si-associated CTD was characterized by the frequency of radiologic lung fibrosis, impaired pulmonary function tests, secondary Sjögren syndrome, and antinuclear antibodies. The number of mineral particles and crystalline Si content were raised in all the bronchoalveolar lavage specimens of Si-exposed patients but in none of those of nonexposed patients. In some cases of Si-associated CTD, the disease was reversible after early cessation of Si exposure. Epidemiologic studies are required to confirm our hypothesis that not only PSS and RA but also SLE and DM are associated with occupational exposure to Si. Pending such results, exposure to Si should be sought in the history of any patient with CTD, especially in a male patient with pulmonary signs, and if present, exposure should be stopped. In the meantime, steps should be taken to ensure that workers exposed to Si in all environments have adequate protection.

Adult↗
PubMed1994

Longitudinal changes in serum zinc concentration and distribution after acute myocardial infarction.

The authors studied the changes in serum zinc concentration and distribution during the 15 days following acute myocardial infarction in 21 patients. The method is based on ultrafiltration and electrothermal atomic absorption spectrometry. It is rapid and needs only 2.5 ml of serum. Serum and erythrocyte copper and zinc, serum zinc-binding ligands and serum enzyme activities were also determined. Serum zinc (P < 0.00001) and exchangeable zinc (mainly albumin-bound zinc, P = 0.01) declined within the first 3 days and then returned gradually to reference ranges. Exchangeable zinc was correlated with transthyretin (P = 0.00001) and total serum zinc (P < 0.00001). Exchangeable zinc accounted for virtually all of the differences in total serum zinc concentration after myocardial infarction. This result could be related to an increase of zinc uptake by tissues. Therefore, studies are needed to evaluate whether zinc supplementation in the early stages of acute myocardial infarction might improve prognosis.

Adult↗
PubMed1994

Functionally important amino acids in the TCR revealed by immunoselection of membrane TCR-negative T cells.

A spontaneous TCR cell surface variant (3P11) of the Jurkat T cell line is described and characterized. 3P11 was selected by incubation of Jurkat cells with anti-TCR mAb followed by passage through Ig anti-Ig columns and cloning. 3P11 contained mRNA for both Ti alpha and Ti beta and CD3 gamma, delta, epsilon and zeta. Biochemical analyses demonstrated that all of the TCR components were produced in 3P11 cells. The Ti alpha beta/CD3 gamma delta epsilon zeta complex was assembled in the endoplasmic reticulum but the zeta did not associate with this complex. Epitopes recognized by the Ti beta chain specific mAb beta F1 and JOVI as well as anti-V beta 8 were affected in the 3P11 Ti beta chain indicating that the 3P11 Ti beta chain was mutated. Transfection of a wild-type Ti beta cDNA into 3P11 cells reconstituted TCR expression. Sequence analyses of the 3P11 Ti beta chain demonstrated a guanine to adenine change in the second nucleotide of the triplet coding for cysteine191 resulting in a cysteine to tyrosine exchange. Cysteine191 is the C-terminal cysteine involved in the intrachain disulfide bond in the C domain of the Ti beta chain; thus, the 3P11 Ti beta chain did not contain this disulfide bond. Transfection of a site-directed Ti beta chain containing the 3P11 mutation into a Ti beta negative variant of the Jurkat cell line resulted in a TCR phenotype identical with 3P11 demonstrating that the mutation identified in the 3P11 Ti beta chain was the sole cause for the 3P11 defect.

Amino Acid Sequence↗
PubMed1994

Zinc changes in blood and urine during cyclic parenteral nutrition: relationships with amino acid metabolism.

Serum Zn, ultrafiltrable Zn and amino acids in serum and urine samples of twenty-seven patients receiving cyclic (12 h/24 h) parenteral nutrition were measured. These samples were collected in patients after a 12 h period of parenteral nutrition, and in the evening after 12 h without parenteral nutrition. The same determinations were performed in ten control subjects who followed the same sampling scheme. Total serum ultrafiltrable Zn showed no significant variations in the patients during parenteral nutrition, and was not significantly different in the two groups although the proportion of the Zn present in the ultrafiltrable fraction was elevated. Serum cystine levels were significantly higher (P = 0.05) in the patients than the control subjects, and cystine excretion was also higher in patients (P < 0.05) and increased after parenteral nutrition (56.0 (SE 6.5) v. 147.1 (SE 20.6) mumol/12 h; P < 0.001). Histidine levels did not vary significantly in serum after parenteral nutrition and were not different in the patients in comparison with the control subjects. Histidine excretion was not different in the two groups but increased significantly during parenteral nutrition (P < 0.05). Serum albumin was significantly depressed in the patients compared with the control subjects (45.3 (SE 1.5) v. 33.9 (SE 1.5) g/l; P < 0.001). These results suggest that cystine infusion and excretion relate to the changes occurring in serum Zn and in urinary Zn excretion.

Adolescent↗
PubMed1994

Effect of alcohol consumption on blood antioxidant nutrients and oxidative stress indicators.

The effects of alcohol consumption on plasma concentrations of antioxidant vitamins (alpha-tocopherol and ascorbic acid), selenium, and markers of oxidative stress, especially malondialdehyde (MDA) and autoantibodies directed to MDA adducts to proteins (Ig-NH2-MDA) were investigated in a large population of 417 supposedly healthy men who consumed only low or moderate amounts of alcohol as compared with 102 alcoholic patients without severe liver disease, who were studied both before and after 21 d of withdrawal treatment. Plasma concentrations of alpha-tocopherol, ascorbic acid, and selenium were lower in alcoholics than in men who drank low amounts of alcohol (P < or = 0.001), whereas MDA and Ig-NH2-MDA were higher (P < or = 0.001). Plasma concentrations of alpha-tocopherol and selenium remained unchanged after the withdrawal period, whereas ascorbic acid (P < or = 0.01), MDA, and Ig-NH2-MDA concentrations decreased (P < or = 0.001). Adjustment of data for circulating lipids and nutritional intake suggests a specific effect of alcohol on antioxidant vitamins, independent of nutritional status.

Adult↗