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Biomedical subjects

L Chatenoud

Publications and source records attributed to L Chatenoud.

231 records · Page 13Linked to original sources

Abnormalities of T-cell subsets in glomerulonephritis and systemic lupus erythematosus.

In this study, three kinds of monoclonal antibodies directed at human T lymphocytes, produced by mouse hybridomas and termed OKT3, OKT4, and OKT8, were used in an indirect immunofluorescence assay, to analyze the distribution of peripheral T lymphocyte subsets in 41 patients with glomerulonephritis (GN) and 11 patients with systemic lupus erythematosus (SLE). As assessed by functional studies, OKT4 and OKT8 defined the helper and cytotoxic/suppressor T lymphocytes subsets, respectively, whereas OKT3 recognized all peripheral T-cells. Among GN patients, the ones presenting membranous GN (MGN), IgA disease, and lipoid nephrosis associated with segmental and focal hyalinosis (FGS) showed significant decrease of their peripheral cytotoxic/suppressive T cells. On the contrary, no significant alteration was found in the peripheral T cell distribution of patients with membranoproliferative GN (MPGN) and lipoid nephrosis associated with minimal-change GN (MCGN). Unexpectedly, there was a tendency for peripheral cytotoxic/suppressive T lymphocytes to be high in the majority of SLE patients, and only two of these subjects exhibited a relative decrease in peripheral OKT8 marked cells. The steroid therapy received by our patients might account for this discrepancy with previous reports of altered suppressor function in active SLE.

Adolescent↗

Studies on T cell subsets and functions in leprosy.

T cell subsets and T cell functions were explored in 31 leprosy patients with the following methods: determination of the percentages of the different T cell subpopulations defined by monoclonal antibodies directed at total T cells, helper T cells and suppressor/cytotoxic T cells; measurement of the in vitro proliferative responses to mitogens; study of the concanavalin A-induced suppressive activity, assessed on MLC; measurement of delayed-type hypersensitivity by skin testing. The confrontation between immunological lepromatous patients without type-2 reaction (erythema nodosum leprosum), (2) lepromatous patients without ENL (erythema nodosum leprosum), (2) lepromatous patients was recent ENL and (3) tuberculoid patients. Unexpectedly, groups 1 and 3, although differing strongly in their clinical status and their sensitivity to lepromin (absent in group 1 and strong in group 3), showed a similar immunological profile with a normal percentage of T cells and a normal distribution of T cells among the major T cell subset contrasting with a moderate decrease of proliferative responses to mitogens and impaired delayed-type hypersensitivity reactions. Concanavalin A-induced suppressive activity was type-2 reaction) strongly differed from both other groups, showing striking abnormalities other groups, showing striking abnormalities of the repartition of the T cell subsets, with increased percentages of helper T cells and decreased percentages of suppressor T cells, and elevated proliferative responses to mitogens. Concanavalin A-induced suppressive activity was reduced in most patients of this group. It is suggested that this imbalance between T cell subsets contributes to the occurrence of ENL reactions in lepromatous patients.

Adolescent↗

Deficit of suppressor T cells in active multiple sclerosis.

Suppressor T cells in forty-seven patients with multiple sclerosis (MS) were studied by indirect immunofluorescence by means of monoclonal antibodies directed at T-cell subsets. Suppressor cell numbers were depressed in patients with acute exacerbation of MS and in patients with continuous progressive deterioration. In one case the T-cell anomaly was observed one week before the onset of the acute phase; it had been absent 4 months before exacerbation.

Acute Disease↗

The epidemiology of multiple births.

On the basis of MEDLINE and manual searches, we examined the main papers in the English literature regarding risk factors for spontaneous (i.e. not related to fertility drug use) multiple births. The constant frequency of monozygotic (MZ) pregnancies over time and in different geographical areas suggests that the determination of MZ twins is largely unchanged over time, and that a genetic mechanism may have a role. In contrast, temporal and geographical trends observed in dizygotic (DZ) pregnancies suggest that environmental factors play a role in determining this condition. At present, maternal age and hereditary components are the best-defined determinants for spontaneous multiple births.

Age Factors↗

Aberrant function and long-term survival of mouse beta cells exposed in vitro to high glucose concentrations.

In vitro culture of murine Langerhans islets usually ends in islet death after 1-3 wk. Given contradictory published data, we studied the influence of glucose on the function and survival of islets from DBA/2 mice. Islets were cultured on plastic microwells, using 1, 2, or 11 g/l glucose concentrations. Using our routine technique, insulin secretion was evaluated after islet incubation for 15 min in basal medium [(sIS), 1 g/l glucose], followed by 15 min in stimulating medium [(sIS), 3 g/l glucose, 20 mM/l arginine, 5 mM/l theoophylline]. Insulin secretion of islets cultured in 1 g/l glucose remained stable and normal over a period of 2 mo [Day 7: bIS, 6.3 +/- 3.1 microU/50 microliters; sIS, 16.6 +/- 6.8 microU/50 microliters. Day 60: bIS, 6.0 +/- 4.0 microU/50 microliters; sIS, 21.3 +/- 10.5 microU/50 microliters]. Islet morphology also remained normal. Islets cultured in 2 g/l glucose showed elevated insulin response under basal and stimulating conditions during 2-3 wk, followed by a dramatic drop in insulin secretion [Day 7: bIS, 19.5 +/- 5.7 microU/50 microliters; sIS, 80.9 +/- 10.7 microU/50 microliters. Day 60: bIS, 5.4 +/- 5.0 microU/50 microliters; sIS, 2.7 +/- 1.4 microU/50 microliters]. Severe morphologic alterations appeared rapidly and islet destruction was nearly complete by 60 days. At 11 g/l glucose, functional and morphological islet alterations were accelerated [Day 7: bIS, 10.3 +/- 2.7 microU/50 microliters; sIS, 18.8 +/- 4.9 microU/50 microliters. Day 21: bIS and sIS almost undetectable].(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Follow-up of children included in the Italian Study on the Use of Low-Dose Aspirin During Pregnancy: development at 18 months of life and birth weight].

To assess the relationship between birthweight and the child's development at 18 months of age, we sent a postal questionnaire to the parents of 861 singleton children, born in the framework of the Italian Study of Aspirin in Pregnancy, 18 months after delivery. A total of 623 (72.4%) were returned. There were 94 children weighing < 2500-1500 g at birth and 19 < 1500 g. Children with weight and height less than the 10th percentile at 18 months were significantly more frequent in the low birthweight group (p < 0.01). Motor problems were about six times more common in children with birthweight less than 2500 g than in those with birthweight > or = 2500 g (p < 0.001). A larger proportion of children with birthweight < 2500 g than > or = 2500 g had respiratory problems (15% vs 11%, p = ns). Finally admission to hospital was more common in children with birthweight less than 2500 g (p < 0.01). This study confirms the differences in growth and development for children in low and normal birthweight groups.

Adult↗

The effects of interleukin-1 on pancreatic beta cell function in vitro depend on the glucose concentration.

Insulin-dependent diabetes mellitus is characterized by progressive autoimmune destruction of pancreatic Beta cells mediated by ill-defined effector mechanisms. Experimental data suggest that cytokines, e.g. interleukin 1 and tumor necrosis factor, could play a fundamental role. The aim of this study was to analyze the effect of recombinant IL-1 beta (rIL-1 beta) on both islet functional capacity and morphology, using long-term cultures and various glucose concentrations. Islet cultured with 1 g/l (5.5 mmol/l) glucose maintained normal insulin- secretion and morphology for more than two months. In contrast, islets cultured with 2 g/l (11 mmol/l) glucose showed an altered insulin secretion and a shorter survival (40 days). At 11 g/l (60 mmol/l) glucose, islets died by 2 weeks of culture. rIL-1 beta exerted a cytotoxic effect on islet cells only when added to cultures containing supraphysiological glucose concentrations. But, in the presence of 1 g/l glucose, the addition of rIL-1 beta (40 ng/ml) for prolonged periods (14 days), did not alter islet function. Our results suggest that in auto-immune type I diabetes, IL-1 beta represents an aggravating factor in lesion formation more than a primary pathogenic mechanism.

Animals↗

Latent hepatitis B virus (HBV) infection in systemic necrotizing vasculitis.

We have investigated hepatitis B virus (HBV) infection in systemic necrotizing vasculitis (SNV). Our approach included the detection of the viral surface antigen (HBsAg) with a radioimmunoassay employing monoclonal anti-HBs (m-RIA); in addition, HBV DNA was looked for in serum and peripheral mononuclear blood cells. Among 28 subjects with SNV, 12 were found to be positive for HBsAg with the conventional test (p-RIA) and 7 additional subjects had anti-HBc and/or anti-HBs. From the 16 HBsAg negative individuals, 9 had HBsAg epitopes identified in serum with the m-RIA test and 1 had a low amount of circulating viral DNA. In contrast, only 1 among 6 subjects with other systemic vasculitis showed a positive test for m-RIA and HBV DNA assays; this individual had acquired HIV infection through transfusions which were also probably the source of his HBV infection. HBV DNA sequences were identified in peripheral mononuclear blood cells of 9 from the 37 tested, including 2 individuals who were HBsAg positive only with m-RIA. Therefore, our study indicates a much higher rate of HBV infection in patients with polyarteritis nodosa than previously suspected.

Antibodies, Monoclonal↗

In vivo T cell activation properties of anti-T cell monoclonal antibodies.

Murine monoclonal antibodies specifically directed at the CD3 molecular complex are widely used in clinical transplantation. They are potent inhibitors of immune function and may be administered in association with conventional immunosuppressive drugs. However, their use has been complicated by the severe clinical syndrome that invariably follows the first injections of the antibody. We have shown that this reaction relates to transient T cell activation, with production of a cohort cytokines. This in vivo activating effect is unique to anti-CD3 MoAbs. Furthermore, this property is highly monocyte-dependent, engaging Fc receptors, and thus varies according to the isotype of the administered MoAb. Another anti-T cell MoAb such as the BMA031 directed towards monomorphic determinants of the T cell receptor (TCR) does not promote such massive in vivo activation.

Animals↗

Role of interleukin-2 receptors in the suppressive effect of spleen cells from anti-CD3-treated mice.

In the present study, we demonstrate that unresponsive spleen T cells from mice injected with a low dose of anti-CD3 mAb (single 10 micrograms i.v. injection) significantly inhibit Con A-induced proliferation of normal spleen cells. The induction of this phenomenon requires in vivo activation since spleen cells from mice injected with the F(ab')2 fragment of anti-CD3 mAb fail to promote it. Suppression of normal T cell proliferation is concomitant with increased expression of IL-2 receptor on spleen cells from anti-CD3-treated mice. It disappears within 3 days when IL-2R has returned to background levels. A normal proliferative response to Con A can be restored when high concentrations of IL-2 are added together with the "suppressor" cells. Taken together, these data support the notion that activated spleen cells from anti-CD3-injected mice exert their inhibitory effect by competing for the IL-2 generated during culture.

Animals↗

[Study of the reliability of a parenteral questionnaire used in a pediatric follow-up of 18-month-old children].

We are conducting a validation study of questionnaire to the parents according to the Griffiths Mental Developmental Scale, used in pediatric follow-up of obstetric studies among the Italian population. The questionnaire concerns the child's gross and fine motor and language development, swallowing, respiratory, hearing and vision problems, and hospital admissions within the first 18 months of life. The purpose of this study is to examine the degree of agreement between parental and professional assessment of normal and high-risk infants development at 18 months of life.

Child Development↗