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C Boitard

Publications and source records attributed to C Boitard.

At least 145 records · Page 8Linked to original sources
PubMed1990

Comparative study of microencapsulated rat islets implanted in different diabetic models in mice.

Microencapsulated rat islets of Langerhans (alginatepolylysine microcapsules) were implanted into the peritoneal cavity of diabetic mice (500 rat islets per mouse) in order 1) to evaluate the ability of this xenograft in correcting hyperglycemia in different models of diabetes and 2) to examine the implanted material recovered from the recipients after several weeks. 1) In the high-dose streptozotocin model in Balb/c mice (n = 14), 6 had a sustained (over one month) decrease in plasma glucose concentration from 401 +/- 7 to 171 +/- 7 mg/dl, with no effect in the other. 2) In the low dose streptozotocin model in C57BL/6J mice (n = 17), plasma glucose levels decreased in 9 mice, from 439 +/- 27 to 180 +/- 30 mg/dl, and remained below 250 mg/dl up to 60 days. In 8 mice, only a transient effect was observed. Empty capsule transplantation had no effect. Plasma insulin in successfully transplanted mice was higher in fed than in fasted state. 3) Microencapsulated rat islets had no effect on plasma glucose in male NOD mice made diabetic by cyclophosphamide treatment (n = 10). Thus, microencapsulated rat islets can improve the diabetic state in some, but not all diabetic mice. In this study, microcapsules were consistently surrounded by an inflammatory reaction, which remains a major concern.

Animals↗
PubMed1990

[Hypertension induced by cyclosporin A in insulin-dependent diabetic patients. A one-year follow-up].

UNLABELLED: Forty-five recent insulin-dependent diabetics (IDD) were treated with cyclosporine A (CsA) 7.5 mg/kg b.i.d. as single immunosuppressive therapy to achieve remission of diabetes. Measurements of mean arterial pressure (MAP), glomerular filtration rate (GFR:inulin clearance), renal vascular resistance (RVR: MAP x [1-haematocrit] divided by PAH clearance), absolute (UNa.V) and fractional (FENa) urinary sodium excretion, were performed initially (M0) and after 3 (M3) and 12 (M12) months of treatment. Results were (mean +/- SD): [table: see text] Prevalence of hypertension defined as MAP greater than or equal to 107 mmHg was 12% at M3 and 24% at M12. Whereas the maximal changes in GFR and RVR occurred at M3, MAP increased further and sodium excretion decreased at M12. IN CONCLUSION: 1) CyA-induced increase in blood pressure paralleled that in RVR at M3 and decreased sodium excretion at M12. 2) There was a dissociation between MAP and GFR changes after 12 months of treatment with CyA.

Adult↗
PubMed1990

[Diabetes mellitus and autoimmunity].

Insulin-dependent diabetes is the direct consequence of an autoimmune reaction causing the destruction of the beta cells of the islets of Langerhans in the pancreas. The frequent association of diabetes with other diseases involving the immune system, the detection of circulating antibodies aimed at the islet cells, the occurrence of the disease in subjects with peculiar HLA antigens are as many arguments supporting the immunological hypothesis. The study of animal models of insulin-dependent diabetes (BB rats, NOD mice) now allows demonstrating the autoimmune process. The transient effectiveness of cyclosporin demonstrated in the human disease confirms these data. The prospects of transplantation of the pancreas, of islets or of islet cells in diabetic subjects to compensate for the insulin deficiency therefore raises the double immunological problem of allogenic rejection and of the risk of recurrence of the anti-islet autoimmune disease.

Animals↗
PubMed1990

Blood pressure changes induced by ciclosporin A in type I diabetes.

The determinants of ciclosporin A-induced blood pressure changes were analyzed initially and after 3 months in 30 recent type I diabetics submitted to chronic treatment with ciclosporin as single immunosuppressive drug. Prevalence of hypertension was 17% and relatively low as compared to those reported in organ transplantation. Ciclosporin induced a slight decrease in glomerular filtration rate and renal plasma flow, with unchanged filtration fraction, a mild average increase in blood pressure and a more pronounced increase in renal vascular resistance. There was a trend toward decrease in absolute urinary sodium excretion whereas fractional excretion of sodium was unchanged. Presence of familial history of essential hypertension was characterized by a slightly insignificantly lower renal plasma flow and did not affect the renal effect of ciclosporin except that the renal plasma flow was significantly lower in the groups of patients genetically predisposed.

Adult↗
PubMed1989

A new monoclonal antibody recognizing the amino-terminal consensus sequence of vertebrate intermediate filament proteins.

The mouse monoclonal antibody ME 101 raised against human peripherin, an intermediate filament protein (IFP) specific to well defined neuronal populations, recognizes all the major classes of vertebrate IFP in immunoblotting assays. Desmin, GFAP, vimentin, peripherin and the lightest neurofilament protein (NF-L) were cleaved into carboxy- and amino-terminal halves by N-chlorosuccinimide at their unique trytophan residue. Whereas the antibody directed against the epitope common to every IFP (intermediate filament antigen or IFA) and located on the carboxy-terminal end of the rod domain recognizes the carboxy-terminal half, the ME 101 antibody, as the present study illustrates, recognizes specifically the amino-terminal half. From the amino acid sequence data of IFP, it is deduced that the cognate epitope is localized on the amino-terminal part of coil la.

Animals↗
PubMed1989

T cell-mediated inhibition of the transfer of autoimmune diabetes in NOD mice.

The nonobese diabetic (NOD) mouse has recently been introduced as a model for insulin-dependent diabetes mellitus. The role of regulatory T cells in the development of antipancreatic autoimmunity in this model remains unclear. To evaluate the presence of suppressive phenomena, we used disease transfer by spleen cells from diabetic NOD mice into preirradiated adult recipients as a model for accelerated disease. Suppressor phenomena were detected by testing the protection afforded by lymphoid cells from nondiabetic NOD mice against diabetes transfer in irradiated recipients. Transfer of diabetes was delayed by reconstituting recipients with spleen cells from nondiabetic NOD donors. The greatest protection against diabetes transfer was conferred by spleen cells from 8-wk-old nondiabetic female NOD mice. Depletion experiments showed that the protection was dependent on CD4+ cells. Protection was also detected within thymic cells from nondiabetic NOD mice and protection conferred by spleen cells was abrogated by thymectomy of nondiabetic female, but not male, NOD donors at 3 wk of age. These findings indicate that suppressive CD4+ T cells that are dependent on the presence of the thymus may delay the onset of diabetes in female diabetes-prone NOD mice.

Animals↗
PubMed1989

Neonatal induction of allogeneic tolerance prevents T cell-mediated autoimmunity in NOD mice.

Diabetes in the NOD mouse strain is a genetically programmed T cell-mediated autoimmune process that is directed against an as yet unknown antigen target(s) on pancreatic beta cells. To investigate whether the course of the autoimmune disease could be altered by immune manipulations of the T cell repertoire, we have induced allogeneic tolerance by injecting F1 semiallogeneic spleen cells into NOD neonates. This procedure resulted in a significant protection against both insulitis and diabetes. However, although it requires the induction of tolerance, as shown by the failure of non-tolerizing irradiated cells to prevent autoimmunity, protection appeared to be independent of the major histocompatibility complex haplotypes of the F1 spleen cells injected at birth, e.g. (C57BL/6 x NOD)F1, (CBA/Ca x NOD)F1 or (BALB/c x NOD)F1 cells. In addition, a similar degree of protection was induced, whether the tolerant state, as assessed by mixed lymphocyte reaction studies in vitro, was of short duration, approximately 6 weeks, or lasted for more than 12 weeks. Putative veto or suppressor functions of chimeric T cells were ruled out, since mice tolerized with T cell-depleted F1 spleen cells were equally protected. We conclude that the expression of spontaneous T cell-mediated autoimmunity can be modulated by immune manipulations at birth. Whether the protection observed in the present experiments resulted from the production of one or several specific holes in the autoimmune T cell repertoire, i.e. cross-tolerance, or whether it resulted from nonspecific disturbances of the emerging T cell repertoire remains to be elucidated.

Age Factors↗
PubMed1989

The role of class II major histocompatibility complex antigens in autoimmune diabetes: animal models.

Like human insulin-dependent diabetes, autoimmune diabetes in BB rats and NOD mice is under control of Class II genes of the major histocompatibility complex. The mechanisms of expression of these genes is still unclear. No aberrant expression of Class II antigens was found in BB rats at the onset of diabetes. The putative role of inadequate Class II-linked suppressor control is suggested, however, by the observation that in vivo treatment with anti-Class II monoclonal antibody prevents the onset of diabetes in NOD mice, and that this protection can be transfer by CD4+ T cells.

Animals↗
PubMed1989

Effect of cyclosporin on interleukin 2-related T-lymphocyte parameters in IDDM patients.

Seventy patients aged 15-40 yr with recent-onset insulin-dependent diabetes mellitus (IDDM) were entered into a double-blind trial, in which they were randomly assigned to either cyclosporin (7.5 mg.kg-1.day-1) or to placebo and were monitored for 1 yr for various phenotypic and functional parameters of T-lymphocyte-mediated immunity. Before treatment, the proportions of total T-lymphocytes (CD3+) and helper-inducer T-lymphocytes (CD4+) were normal, whereas significantly decreased values of suppressor/cytotoxic T-lymphocytes (CD8+), as compared with normal controls, were found in 31% of the patients. The interleukin 2 (IL-2)-receptor expression was significantly increased in IDDM patients compared with control subjects, although the single values were low: patients, 2.02 +/- 0.41%; controls, 0.88 +/- 0.25% (means +/- SE). Circulating levels of soluble IL-2 receptor were also significantly increased in IDDM patients compared with controls: patients, 372.3 +/- 25.4 U/ml; controls, 235.5 +/- 29.3 U/ml (means +/- SE). However, no major abnormalities were found in mitogen (phytohemagglutinin)-induced IL-2 production, cell proliferation, or IL-2-receptor expression. After 6 mo of cyclosporin treatment, no major modifications of any of the parameters analyzed were noted, even in patients who had cyclosporin blood trough levels greater than 300 ng/ml, i.e., the threshold value associated with clinical efficacy. One explanation for the absence of a major effect of cyclosporin, in contrast with its demonstrated clinical effectiveness, is the reversibility of its activity. Our results preclude the use of the described tests to reliably monitor IDDM patients undergoing immunosuppressive therapy.

Adolescent↗
PubMed1989

Long-term complications of conventional immunosuppressive treatment.

Recent progress in understanding of the pathophysiologic mechanisms of an increasing number of diseases involving immunologic effector mechanisms and the broadening of indications for allograft transplantation have considerably expanded the use of immunosuppressive drugs in clinical medicine. A new therapeutic situation has thus been created that reproduces various aspects of pathologic conditions such as primary and secondary immunodeficiency disorders. This increasing use of immunosuppressive drugs raises the issue of careful evaluation of the risks involved balanced against the expected benefits. The present review will evaluate, through the literature, the long-term side effects of immunosuppressive drugs commonly used in clinical practice, including cyclophosphamide, azathioprine, and, more recently, cyclosporine A, which has increased the spectrum of allograft transplants, in particular, cardiac and hepatic. Other immunosuppressive drugs have been used less extensively. Their side effects are less well known or are analogous to those of the conventional immunosuppressive drugs just mentioned, in particular, chlorambucil, whose mode of action follows a pathway similar to that of cyclophosphamide. New developments in the spectrum of immunosuppressive drugs in clinical practice, such as those of monoclonal antibodies, await future evaluation. Their use is only recent, and a discussion of their side effects is beyond the scope of this review.

Autoimmune Diseases↗
PubMed1989

[Cross-reactivity between major histocompatibility complex class II antigens in mice NOD and an islet antigen with 58 kDA molecular weight].

The NOD mouse has been recently developed as a model for autoimmune insulin-dependent diabetes mellitus. The NOD mouse is further characterized by a genetic linkage with genes mapping within the major histocompatibility complex at the I-A locus. The present work demonstrates the presence in NOD mice of circulating autoantibodies specific for a 58 kDa antigen which is present in membrane extracts prepared from the murine insulin-secreting tumoral cell line Rin5F. This 58 kDa antigen shows a cross reactivity with NOD mouse class II antigens as indicated by its recognition by anti-I-A(NOD) monoclonal antibodies.

Animals↗
PubMed1989

Insulin autoantibodies in non-obese diabetic (NOD) mice.

Anti-insulin autoantibodies were detected in NOD mice using ELISA. The antibodies were detected as early as at 5 weeks of age, long before onset of clinically overt diabetes, especially in diabetes-prone female mice. The anti-insulin specificity was verified by passage on affinity chromatography insulin columns and demonstration that the anti-insulin activity was located on the F(ab')2 region of the immunoglobulins. The presence of anti-insulin antibodies in prediabetic NOD mice provides a unique possibility for studying their significance and their eventual pathogenic role in the development of insulin-dependent diabetes.

Animals↗
PubMed1988

Adoptive T cell transfer of autoimmune nonobese diabetic mouse diabetes does not require recruitment of host B lymphocytes.

The autoimmune nonobese diabetic mouse, a model of human juvenile type I diabetes mellitus, exhibits features of both B and T cell autoreactivity against insulin-producing cells. Using the neonatal cell transfer model of the disease, which we have described previously, we have shown that B cell suppression of newborn recipients by anti-mu treatment did not affect the transfer of diabetes by means of T cells. B cell-depleted, purified T cells from diabetic adults were injected into newborns treated with either IR-52, a control rat myeloma protein, or LOMM.9, a rat anti-mouse mu-chain mAb. Both groups developed diabetes over a similar time scale. Although the pancreases in both groups showed massive infiltration by T lymphocytes, B lymphocytes, presumably recruited in the host, were present in the IR-52-treated group, whereas they were absent in the LOMM.9-treated group. Anti-mu-treated diabetic animals showed substantial B cell suppression in vivo and in vitro when compared with IR-52-treated controls. These results suggest that B cell autoreactivity is a secondary phenomenon that is unimportant during the effector phase of diabetes in nonobese diabetic mice.

Animals↗