Search PubMed⌕ Search

Biomedical subjects

J Arnaud

Publications and source records attributed to J Arnaud.

At least 55 records · Page 3Linked to original sources

Expression and signal transduction of T-cell antigen receptor (TCR)/CD3 complexes on fresh or in vitro expanded T lymphocytes from patients with Hodgkin's and non-Hodgkin's lymphomas.

T-cell responses against soluble antigens, alloantigens and mitogens are frequently diminished in patients with certain types of cancer. In the present study, the authors investigated possible mechanisms for the partial T-cell immunodeficiency in patients with Hodgkin's or non-Hodgkin's lymphomas. It was found that T-cells from lymphoma patients had significantly reduced proliferative responses to EBV-transformed B-cell lines and to anti-TCR/CD3 MoAb; a 30-50% reduction of cells expressing membrane T-cell receptor (TCR) complexes; and a significantly reduced signal transduction function. Long-term in vitro culture conditions were developed to expand T cells in TCR/CD3-dependent or TCR/CD3-independent manners. With such methods, it was found that the decreased T-cell responses in patients with Hodgkin's and non-Hodgkin's lymphomas appeared to be an intrinsic T-cell defect (not at the antigen presenting cell level), and the T-cell responses could be recovered after only a few days in culture. Thus, it is suggested that the T-cell response-defect in Hodgkin or non-Hodgkin lymphoma patients is a reversible phenomenon, dependent on the patient's tumour-bearing environment.

B-Lymphocytes↗

Effect of a two-year supplementation with low doses of antioxidant vitamins and/or minerals in elderly subjects on levels of nutrients and antioxidant defense parameters.

BACKGROUND: Eighty-one elderly hospitalized subjects (> 65 years) were recruited for a double-blind placebo-controlled study to examine low dose supplementation of antioxidant vitamins and minerals on biological and functional parameters of free radical metabolism. Subjects were randomly assigned to one of the four treatment groups, daily receiving for 2 years: placebo group; mineral group: 20 mg zinc, 100 micrograms selenium; vitamin group: 120 mg vitamin C (Vit C), 6 mg beta-carotene (beta CA), 15 mg vitamin E (Vit E); mineral and vitamin group: Zn 20 mg, Se 100 micrograms, Vit C 120 mg, beta CA 6 mg, Vit E 15 mg. RESULTS: Fifty-seven subjects completed the study. A large frequency of Vit C, Zn and Se deficiencies were observed at baseline. As early as 6 months of treatment, a significant increase in vitamin and mineral serum levels was observed in the corresponding groups. The increases ranged from 1.1-4.0 fold depending on the nutrient. Antioxidant defense, studied in vitro with a test using red blood cells in presence of 2,2'-azo-bis (2-amidinopropane) by hydrochloride, showed an increase of cell resistance in patients receiving vitamins (p = 0.002); it was positively correlated with serum Vit C (p < 0.0001), alpha-tocopherol/cholesterol (p = 0.06), beta CA (p = 0.0014), serum Cu and Se (p < 0.05). Moreover, red blood cell antioxidant defense was reduced in elderly compared with young control subjects (50% hemolysis time: 69 +/- 14 mn and 109 +/- 12 mn, respectively). Erythrocyte glutathione peroxidase activity was enhanced in groups receiving minerals, whereas no significant change was observed for other indicators of oxidative stress (erythrocyte superoxide dismutase activity, thiobarbituric acid-reactive substances, total glutathione, reduced and oxidized forms). DISCUSSION: Our results provide experimental evidence that a low dose supplementation with vitamins and minerals was able to normalize biological nutrient status as early as 6 months of treatment. In addition, our data indicate that antioxidant defense in elderly subjects was improved with low doses of vit C, vit E and beta CA as studied by means of a functional test utilizing red blood cells challenged in vitro with free radicals.

Aged↗

The interchain disulfide bond between TCR alpha beta heterodimers on human T cells is not required for TCR-CD3 membrane expression and signal transduction.

In the present paper, it was attempted to define the amino acids or regions on TCR beta molecules that determine the TCR alpha-TCR beta interaction. Sequence studies on HBP-ALL variant cells with an intrinsic deficiency in TCR alpha beta dimer formation elucidated a conserved amino acid motif in the TCR-C beta beta-strand E, = Y(C)(L)(S)SRLR(V)(S)(A); this motif seems to represent one interaction area for the TCR alpha-TCR beta interaction. In addition, amino acids in the connecting peptide may be shaped in a precise structure (by the interactions with CD3 molecules?) involved in TCR alpha-TCR beta dimerization. This result was supported by the finding that the interchain disulfide bond between TCR alpha and beta chains is not required for membrane expression or transmembrane signal transduction of TCR alpha beta-CD3 complexes. Finally, comparative results from two membrane TCR-CD3-negative Jurkat variants R4.9 and E6.E12 suggest that TCR-C beta exon 1- and 2-encoded amino acids are important for the TCR beta-CD3 gamma epsilon association.

Amino Acid Sequence↗

Effect of micronutrient supplementation on infection in institutionalized elderly subjects: a controlled trial.

To determine the impact of a trace element and vitamin supplementation on infectious morbidity, a double-blind controlled trial was performed on 81 elderly subjects in a geriatric center during a 2-year period. Subjects were randomly assigned to one of four treatment groups, and received daily: placebo; trace elements/zinc 20 mg; selenium 100 micrograms); vitamins (vitamin C 120 mg; beta-carotene 6 mg; alpha-tocopherol 15 mg); or a combination of trace elements and vitamins at equal doses. (1) Before supplementation, low serum values in vitamin C, folate, zinc and selenium were observed in more than two thirds of the patients. (2) After 6 months of supplementation, a significant increase in vitamin and trace element serum levels was obtained in the corresponding treatment groups: a plateau was then observed for the whole study. (3) Subjects who received trace elements (zinc and selenium) alone or associated with vitamins had significantly less infectious events during the 2 years of supplementation. These results indicate that supplementation with low doses of vitamins and trace elements is able to rapidly correct corresponding deficiencies in the institutionalized elderly. Moreover, zinc and selenium reduced infectious events.

Aged↗

[Evaluation of oxidative stress and antioxidant defences in malnourished Moroccan children].

In Morocco, malnutrition is a public health problem. Indeed, 25% of 6- to 60-month-old children suffer from malnutrition. Imbalance between antioxidant protection and prooxidant stress has been reported to accurately predict the survival of malnourished children. Therefore, we determined blood antioxidant vitamins (retinol, alpha-tocopherol and carotenoids), trace elements (serum zinc, copper and selenium) and enzymes (erythrocyte Se glutathione peroxydase and Cu-Zn superoxide dismutase) as well as blood oxidative stress index [ferritine, thiobarbituric-acid reactants (TBARS)] in 21 children suffering from severe malnutrition, 15 children suffering from mild malnutrition and in 20 healthy control children. Selenium, retionol, alpha-tocopherol and carotenoids were significantly decreased in malnourished children. These decreases were related to the severity of malnutrition. Moreover, the percentage of vitamin and trace element concentrations under deficient cutoff were high in malnourished children. On the contrary, TBARS, ferritin and prognostic inflammatory and nutritional index (PINI) were significantly increased in malnourished children. Except for TBARS, these increases were related to the severity of malnutrition. On the other hand, blood retional, alpha-tocopherol, beta-carotene and selenium were negatively related to alpha 1-acid glycoprotein. Blood beta-cryptoxanthin, lycopene, carotenes and copper were positively related to weight. Finally, blood lutein/zeaxanthin and copper were positively related to height. These results confirm the imbalance between antioxidant protective factors and oxidative stress index in malnourished children. Moreover, the decrease in antioxidant protective factors is related to inflammation or stature. These results suggest that antioxidant micronutrient supplementation of the refeeding diet could be required in the nutritional rehabilitation of malnourished children.

Antioxidants↗

Assessment of serum antioxidant micronutrients and biochemical indicators of nutritional status in children with cancer in search of prognostic factors.

Serum vitamins A (retinol) and E (alpha-tocopherol), beta-carotene, zinc and selenium, and related proteins for 157 children with newly diagnosed and histologically proven malignancy were compared with those of 632 cancer-free controls. Incident cancer cases and controls were 1-16 years of age and recruited in 1986-1989. Age and sex-adjusted serum concentrations of beta-carotene and alpha-tocopherol were significantly inversely associated with cancer. No significant association with cancer was observed for serum values of selenium. Although low levels of antioxidants might in part be involved through a causality link, the reported decreased peripheral nutrient levels are considered rather as an impairment of the body's defence system, occurring during the cancer-related metabolic and nutritional disturbances and inflammation processes. The cancer cases group was followed-up and examined 6 months after diagnosis. Among the 157 subjects, 24 had died and 133 were reported to be alive. No substantial difference for any antioxidant or chemistry variable at onset was observed as a function of clinical outcome and health status.

Adolescent↗

Lipid peroxidation level and antioxidant micronutrient status in a pre-aging population; correlation with chronic disease prevalence in a French epidemiological study (Nantes, France).

OBJECTIVE: The general objective of the Etude du Viellissement Arterial (EVA) program is to follow vascular aging and the decline in cognitive functions at the cerebrovascular level longitudinally over a 4-year period. One of the specific objectives of this EVA study is to examine epidemiologically the relationship between the markers of oxidative stress (lipid peroxidation), the antioxidant micronutrient status (particularly of selenium, vitamin E, and the carotenoids) and the prevalence of chronic disorders occurring during the pre-aging period. METHODS: 1389 subjects aged from 59 to 71 years were studied. RESULTS: The concentration of plasma lipid peroxides was higher than in young adults (2.91 +/- 0.38, men; 2.97 +/- 0.40, women (mumol/l). On the other hand, plasma Se (1.09 +/- 0.21, men; 1.10 +/- 0.19, women (mumol/l)), erythrocyte vitamin E (5.32 +/- 1.29, men; 5.52 +/- 1.28, women (mumol/l)), and total plasma carotenoids (2.19 +/- 0.98, men; 3.07 +/- 1.33, women (mumol/l)) were comparable to values in young adults. In our cohort, 40% of subjects had unremarkable medical histories. The disorders most often encountered were lipemia (29.8% of men, 36.1% of women), and hypertension (28.9% of men, 30.4% of women). CONCLUSION: Se and vitamin E levels were raised in cases of lipemia, especially in those treated with fibrates. The mechanism of the increase is unknown. In hypertensives and diabetics, there was a decrease in total carotenoids associated with increased peroxidative risk.

Aged↗

Effects of trace element and/or vitamin supplementation on vitamin and mineral status, free radical metabolism and immunological markers in elderly long term-hospitalized subjects. Geriatric Network MIN. VIT. AOX.

A randomized double-blind trial was performed in order to assess the efficacity of differing combinations of antioxidant nutrients on biochemical parameters of vitamin and trace element status, immunological parameters and free radical metabolism in elderly long term hospitalized subjects. A total of 756 institutionalized elderly subjects were recruited in 26 nursing homes in different areas of France. Four groups were constituted, receiving daily, for 1 year, either vitamins (beta-carotene, 6 mg; vitamin C, 120 mg; and vitamin E, 15 mg), trace elements (zinc, 20 mg and selenium, 100 micrograms), trace elements associated with vitamins, or a placebo. Biochemical indicators of trace elements and vitamin status and free radical parameters were measured before and after 6 months and 1 year of supplementation. Some immunological markers were investigated initially and after 6 months of supplementation on a subsample of 134 subjects. Mean plasma levels of alpha-tocopherol, gamma-tocopherol, vitamin C, alpha-carotene, beta-carotene and copper increased significantly after 6 months of supplementation in groups receiving vitamins alone or associated with trace elements. Serum selenium concentrations were significantly increased at 6 months of supplementation, and serum zinc only after one year in the trace element groups. Serum lycopene levels were significantly decreased by trace element supplementation. A significant increase in Se-glutathione peroxidase (GPx) levels was observed in groups receiving trace elements alone or associated with vitamins. No effect was noted on superoxide dismutase (SOD) activity or TBARs production. No effect of supplementation was found for in vitro lymphocyte proliferative responses or most lymphocyte subsets, except for a significantly lower percentage of CD2 subsets observed in groups receiving mineral supplementation either alone or associated with vitamins. A significant difference in CD19 subsets was found in groups receiving trace elements. Mean IL-1 production was significantly higher after 6 months of supplementation in the vitamin groups.

Aged↗

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↗

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↗

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↗

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↗

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↗

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↗

[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↗

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↗

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↗

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↗