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Biomedical subjects

J F Bach

Publications and source records attributed to J F Bach.

At least 217 records · Page 12Linked to original sources
PubMed1992

Autoantibodies against pancreatic beta-cells: characterization by western blot analysis in the non-obese diabetic (NOD) mouse.

The NOD mouse is a relevant model for studying autoimmune diabetes. As in human insulin-dependent diabetes mellitus, the nature of the autoantigen towards which the immune system is directed remains to be clarified. It has been shown that T cells are central to the disease process. However, autoantibodies may be used as a probe to identify islet autoantigens to which self tolerance is defective. Using Western blot analysis, we characterized autoantibodies which are specific for a 58 kDa islet antigen and a 29 kDa antigen. The 58 kDa autoantigen was present in cellular extracts prepared from rat tumoral insulin-secreting cells (Rin5F) and NOD islets but not from most other non-insulin-secreting cell lines. By contrast the 29 kDa antigen was a ubiquitous antigen expressed in all cell lines tested and was not further characterized since it is very likely to be responsible for secondary immunization rather than play any role in the NOD disease process. Anti-58 kDa autoantibodies were detected in all diabetic male and female NOD animals as well as in sera from old non-diabetic NOD animals. Anti-58 kDa antibodies were not detected in sera from young NOD mice (less than 6 weeks of age) or in sera from other conventional laboratory strains of mice including autoimmune prone animals such as MRL/lpr and (NZB x NZW)F1 mice. A monoclonal antibody (72.2) specific for the 58 kDa structure was obtained, which allowed further characterization of the corresponding islet cell antigen. The expression of the 58 kDa antigen was evidenced by Western blot analysis in normal islets and in a mouse neuroblastoma cell line.

Animals↗
PubMed1992

Passive immunotherapy in AIDS: a randomized trial of serial human immunodeficiency virus-positive transfusions of plasma rich in p24 antibodies versus transfusions of seronegative plasma.

To assess the place of passive immunotherapy in the treatment of AIDS, a randomized study was conducted that evaluated the safety and short-term efficacy of serial transfusions of human immunodeficiency virus type 1 (HIV-1) seropositive plasma in 18 patients. Heat-inactivated anti-HIV antibody-rich plasma was compared with seronegative fresh-frozen seronegative plasma given in addition to zidovudine and other conventional prophylactic treatments. Seven transfusions every 2 weeks of immune plasma significantly reduced (2 vs. 8, P = .016) the number of opportunistic infections. Antigenemia became undetectable. When transfusions were stopped, positive p24 antigenemia returned at a level higher than before treatment and was correlated with a severe clinical deterioration, suggesting a rebound effect. This trial suggests that passive immunotherapy is promising in AIDS treatment. It confirms also that plasma donation does not affect donors' CD4 cell count over a 1-year period. In patients with severe immunodeficiency, special attention should be paid to withdrawal of an effective therapy as virologic relapse may be explosive and poorly tolerated.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Prediction of successful allograft rejection retreatment with OKT3.

OKT3 is considered to be effective in the prophylaxis and treatment of rejection. However, anti-OKT3 immunization is still a major side-effect. Only the IgG antiidiotypic component of the response is responsible for neutralization of OKT3 therapeutic activity by inhibiting OKT3's binding to T cells (i.e., blocking antibodies). It has recently been reported that successful OKT3 retreatment could be performed in patients showing circulating anti-OKT3 antibodies assessed by ELISA, which does not distinguish between blocking and nonblocking antibodies. The aim of this study was to investigate the role of these two types of anti-OKT3 antibodies for their capacity to interfere with effective OKT3 retreatment. Twelve cadaver renal allograft recipients who received OKT3 inducing therapy, were given a second 10 day-course of OKT3 for treatment of rejection. Circulating CD3+ cells were sequentially monitored. Anti-OKT3 antibodies were detected by using both conventional ELISA and an immunofluorescence inhibition test specifically detecting blocking antibodies. OKT3 and the patient's serum were incubated for 30 min at 4 degrees C, and 2 x 10(5) normal T cells were added (30 min at 4 degrees C). After washing, the cells were incubated with FITC goat antimouse antiserum. Fluorescent cells were counted using a FACS analyzer. In 10 patients, at the end of the 10-day second course, less than 10% circulating CD3+ cells were detected. None of these patients had detectable antibodies in the IF inhibition assay at the beginning of retreatment, irrespective of anti-OKT3 antibody titers detected by ELISA. In contrast, in two patients, OKT3 therapy was ineffective: more than 50% circulating CD3+ cells were detected and OKT3 treatment had to be interrupted soon after it was initiated. In both of them, blocking antibodies were detected by the IF-inhibition assay. These results suggest that specific detection of blocking antiidiotypic antibodies by the IF inhibition assay is a reliable parameter for predicting the feasibility of OKT3 retreatment, avoiding misuse of this expensive therapy.

Adolescent↗
PubMed1992

Evidence that antihuman tumor necrosis factor monoclonal antibody prevents OKT3-induced acute syndrome.

We have used an antihuman tumor necrosis factor monoclonal antibody, CB006 (murine IgG1), to prevent the OKT3-induced acute clinical syndrome. This syndrome is due to the massive, although transient release in the circulation of various cytokines (TNF, interferon gamma, interleukin 2, interleukin 6) and represents one important side effect linked to in vivo use of OKT3. Fourteen kidney allograft recipients undergoing prophylactic OKT3 therapy were treated with CB006 in a single i.v. injection of either 0.4 mg/kg (group I, 7 patients) or 2 mg/kg (group II, 7 patients), 1 hr before the first OKT3 administration. Nineteen consecutive patients formed a historical control group. None of the CB006-pretreated patients showed any of the common, severe OKT3-associated symptoms (hypotension, respiratory distress, or neurotoxicity), which were observed in 10% of the historical controls. In addition, CB006-treated patients showed a lower frequency of pyrexia (> or = 39 degrees C) and gastrointestinal symptoms. None of the CB006-treated patients presented severe vomiting or diarrhea, defined as repeated episodes inducing significant fluid and electrolyte loss. Two out of the 7 patients in group I and group II had mild transitory diarrhea. Mild single vomiting episodes occurred in 2 group I patients and 3 group II patients. At variance in all controls, gastrointestinal symptoms were long lasting and associated with major prostration due to electrolyte and fluid loss. Importantly, CB006-treated patients who presented mild symptoms had detectable bioactive circulating TNF, showing incomplete inactivation of OKT3-induced TNF by CB006. CB006 was perfectly well tolerated, did not induce xenosensitization, and did not affect the biological or clinical effectiveness of OKT3.

Acute Disease↗
PubMed1992

The prevalence of selective IgA deficiency in type 1 diabetes mellitus.

A significant increase in the prevalence of selective IgA deficiency has been observed in patients with autoimmune disorders such as systemic lupus erythematosus and rheumatoid arthritis. Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease and susceptibility to both IDDM and IgA deficiency is associated with HLA DQB1 alleles encoding non-Asp amino acids at position 57. In order to assess whether the prevalence of selective IgA deficiency is increased in IDDM, we have screened a homogeneous series of adult patients with IDDM for selective IgA deficiency. One patient (1:261) was found to have a selective IgA deficiency. The prevalence of selective IgA deficiency among adult French blood donors is 1:1400. Thus, although IDDM and selective IgA deficiency are both associated with the presence of non-Asp amino acids at position 57 of the HLA DQ beta chain, the frequency of this immunodeficiency in adult IDDM patients is not significantly increased.

Autoimmune Diseases↗
PubMed1992

Selective IgA deficiency and autoimmunity.

Selective IgA deficiency is the most common primary immunodeficiency. Selective IgA deficiency, as most other immunodeficiencies, is frequently associated with autoimmune phenomena. In this article the authors critically review the literature concerning this association, and discuss the possible mechanisms leading to the increased frequency of autoimmune disorders in subjects with selective IgA deficiency.

Autoantibodies↗
PubMed1992

Age-dependent HLA genetic heterogeneity of type 1 insulin-dependent diabetes mellitus.

The association of insulin-dependent diabetes mellitus (IDDM) with certain HLA alleles is well documented in pediatric patients. Whether a similar association is found in adult-on-set IDDM is not clear, although the disease occurs after the age of 20 in 50% of cases. HLA class II DRB1, DQA1, and DQB1 alleles were studied in 402 type I diabetics and 405 healthy controls (all Caucasian) using oligonucleotide typing after gene amplification. Alleles DRB1*03, DRB1*04, DQB1*0201, DQB1*0302, DQA1*0301, and DQA1*0501 were indeed enriched in diabetics and the highest relative risk was observed in patients carrying both the DRB1*03-DQB1*0201 and the DRB1*0402 or DRB1*0405-DQB1*0302 haplotypes. However none of these alleles, or specific residues, could alone account for the susceptibility to IDDM. Furthermore, there were major differences in HLA class II gene profiles according to the age of onset. Patients with onset after 15 yr (n = 290) showed a significantly higher percentage of non-DR3/non-DR4 genotypes than those with childhood onset (n = 112) and a lower percentage of DR3/4 genotypes. These non-DR3/non-DR4 patients, although presenting clinically as IDDM type 1 patients, showed a lower frequency of islet cell antibodies at diagnosis and a significantly milder initial insulin deficiency. These subjects probably represent a particular subset of IDDM patients in whom frequency increases with age. The data confirm the genetic heterogeneity of IDDM and call for caution in extrapolating to adult patients the genetic concepts derived from childhood IDDM.

Adolescent↗
PubMed1992

Growth hormone and insulin-like growth factor-I stimulate hormonal function and proliferation of thymic epithelial cells.

We have investigated the role of GH and insulin-like growth factor-I (IGF-I) in controlling the secretion of thymulin, a hormone produced by thymic epithelial cells (TEC). Thymulin plasma concentrations (mean +/- SD) were increased in 21 patients with acromegaly compared to those in 30 controls, as assessed by bioassay (4.24 +/- 0.97 vs. 2.67 +/- 0.87; P less than 0.001) and RIA (561 +/- 241 vs. 315 +/- 113 pg/L; P less than 0.01). Good correlations were observed between plasma levels of thymulin and IGF-I (P less than 0.001). In vitro experiments demonstrated that both recombinant human GH and IGF-I significantly increased thymulin production in culture supernatants of normal human TEC and a rat TEC line. In parallel, IGF-I also significantly stimulated the proliferation of human TEC, as measured by bromodeoxyuridine incorporation. Additionally, the stimulatory effect of GH on thymulin production was abrogated by both an anti-IGF-I antibody and an anti-IGF-I receptor antibody. These results support a role for GH and IGF-I in the control of thymic hormonal function in man and suggest that the effect of GH may be mediated by local secretion of IGF-I within the thymus.

Acromegaly↗
PubMed1992

The frequency of selective IgA deficiency in myasthenia gravis.

The frequency of selective IgA deficiency is unknown in myasthenia gravis. We screened a series of 333 consecutive adult myasthenic patients for selective IgA deficiency and found only one patient with a selective IgA deficiency, which is not significantly different from the normal population. Organ-specific autoimmune diseases may differ from systemic autoimmune diseases concerning their frequency of association with selective IgA deficiency.

Adult↗
PubMed1992

Selective immunosuppression with anti-T cell monoclonal antibodies.

Murine monoclonal antibodies specifically directed at the CD3 molecular complex are widely used in clinical practice. They are potent inhibitors of immune function and may be administered in association to conventional immunosuppressants. The main purpose of this review is to summarize our present knowledge on the CD3 molecule, to discuss the available data on the clinical use of anti-CD3 MoAb (therapeutic effectiveness, mode of action and side effects) and the recent information derived from the use of anti-CD3 MoAb in experimental models that are opening new perspectives in the applications of anti-CD3 and will hopefully lead to the extension of its clinical use to settings different from transplantation.

Animals↗
PubMed1992

TAP1 and TAP2 transporter genes and predisposition to insulin dependent diabetes mellitus.

Genetic control of insulin dependent diabetes mellitus (IDDM) is mainly dependent on HLA genes in the major histocompatibility complex (MHC). The participation of TAP1 and TAP2 genes, located in the MHC region and coding for antigenic peptide transporters, was investigated in 116 IDDM patients and 98 normal controls using oligotyping after DNA amplification. The TAP2-B allele had a dominant protective effect, additive to that of the DR2 haplotype but antagonist to the susceptibility associated with the DR3 and/or DR4 haplotypes. The TAP2-A allele, in the homozygous state, had a predisposing effect. TAP1 allelic distribution did not differ among IDDM patients and controls. These data argue in favour of the role of peptide transporter gene in diabetogenesis.

Adult↗
PubMed1992

[Cancer immunotherapy: from fundamental concepts to clinical applications].

Cancer immunotherapy is based on the idea that anti-tumor immunity in its various aspects can usefully complement the effect of conventional treatments (surgery, chemotherapy, radiotherapy). Immunotherapy can be active when one stimulates the function of cells capable to contribute to tumor regression, notably by using interleukin-2 or immunomodulators. It can be adoptive when patients' lymphocytes are collected and incubated in vitro in the presence of cytokines to enhance their function and reinjected in the patients. It can be passive when one administers anti-tumor monoclonal antibodies.

Humans↗
PubMed1992

[Remission of established disease in diabetic NOD mice induced by anti-CD3 monoclonal antibody].

Anti-CD3 monoclonal antibodies are potent immunosuppressants widely used in clinical transplantation to prevent or treat acute allograft rejection. We have used a hamster monoclonal antibody (145 2C11) specific for the epsilon chain of the murine CD3 complex to treat autoimmune insulin-dependent diabetes appearing spontaneously by 15 to 30 weeks of age in female Non Obese Diabetic (NOD) mice. Mice showing overt disease (glycosuria and glycemia > or = 4 g/l) were randomized in two groups receiving either anti-CD3 (5 micrograms/day i.v. for 5 consecutive days) or an identical dose of hamster polyclonal immunoglobulins. Progressive remission of disease was observed, 3 to 6 weeks after the end of treatment, in 80% of anti-CD3 treated mice as compared to 6% of mice in the control group. This remission was maintained long term namely, during the 4 to 5 months (after the end of treatment) observation period. These results open interesting perspectives on the possibility to treat recently diagnosed diabetic patients with therapy showing long term efficacy and no chronic toxicity.

Animals↗