Search PubMed⌕ Search

Biomedical subjects

J F Bach

Publications and source records attributed to J F Bach.

At least 325 records · Page 18Linked to original sources
PubMed1989

Aberrant T cell-mediated immunity in untreated schizophrenic patients: deficient interleukin-2 production.

The authors examined the immune status at the cellular and humoral levels of 16 untreated schizophrenic patients. No abnormality in the distribution of T cell subsets (CD4+, CD8+) was detected. The proliferative response to the T cell mitogen phytohemagglutinin was normal. No increase in the number of T cells showing activation markers, such as human leukocyte antigens and interleukin-2 receptors, was noted. Conversely, function studies revealed a clear deficiency in interleukin-2 production by purified T cells. This lower production was probably intrinsic to the patients' T cells, since interleukin-2 production showed normal sensitivity to prostaglandin E2-mediated down-regulation by autologous monocytes.

Adolescent↗
PubMed1989

Neuroendocrine control of thymic hormonal production. I. Prolactin stimulates in vivo and in vitro the production of thymulin by human and murine thymic epithelial cells.

The thymic epithelium is responsible for the secretion of thymic peptides, which intervene in some steps of intra- and extrathymic T cell differentiation. Recent data suggest that thymic hormone secretion is modulated by the neuroendocrine network, comprising thyroid, adrenals, and gonads. However, the role of the pituitary gland in this regulation is still poorly understood. In the present paper we studied the in vivo and in vitro influences of PRL on the secretion of thymulin, one of the chemically defined thymic hormones, by thymic epithelial cells (TEC). When injected daily (20-100 micrograms/20 g) in young or old C57BL/6 mice, PRL induced a specific increase in thymulin synthesis and secretion, respectively, measured by the number of thymulin-producing cells in the thymus and the peripheral levels of the hormone. This stimulation was dose dependent and reversible after the end of treatment. Similar findings have been made in animals with pituitary dwarfism, known to have low levels of circulating thymulin. This stimulatory effect was also observed in primary cultures of human and mouse TEC when PRL (10(-7) to 10(-8) M) was applied to culture supernatants, thus suggesting that PRL could act directly on TEC. In addition, we induced in vivo experimental hypoprolactinemia, treating mice with bromocriptine, a dopamine receptor agonist that inhibits pituitary PRL secretion. Bromocriptine treatment (100-200 micrograms/20 g) yielded a significant decrease in thymulin secretion that could be reversed by coincident treatment with PRL. In the light of previous observations that bovine GH can also increase thymulin production in aged dogs, we performed a series of experiments in vitro to evaluate whether GH has a direct effect on TEC. We observed that only human GH preparations that are known to have a PRL-like effect were efficient in stimulating thymulin biosynthesis and release into the culture supernatants. The effects of PRL on TEC were not restricted to thymic hormone production. We observed that TEC proliferation, as well as the numbers of a TEC subset defined by the expression of cytokeratins 3 and 10, could also be increased by PRL treatment. All these findings show that the pituitary gland directly affects TEC in terms of cytoskeletal and secretory protein expression as well as cell cycle.

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↗
PubMed1989

[Evolution of the concept of autoimmunity and its therapeutic implications].

Autoimmunity is paradoxically a physiologic phenomenon. One finds in normal sera natural autoantibodies that are encoded by germ line genes. Autoimmunity is at the origin of common and severe diseases such as diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus and perhaps psoriasis and Crohn's disease. The disease may be due according to cases to exacerbation of physiologic autoimmunity or to appearance of autoreactive clones producing autoantibodies encoded by mutated genes. The respective role of triggering environmental factors and genetic predisposition (HLA and non HLA genes) is not determined. New immunotherapeutic methods, particularly cyclosporine, monoclonal antibodies (against T cells, CD4 and T cell receptor molecules and Ia antigens) and autoantigen-specific vaccination open new major therapeutic perspectives that presage major improvement in the prognosis of these diseases.

Autoimmune Diseases↗
PubMed1989

Potential pathogenic role of cell-surface polypeptides, cross-reactive with DNA, in systemic lupus erythematosus.

The authors report their studies on the cross-reactivity of certain anti-DNA antibodies with polypeptides expressed on the membrane of different cell types. These lupus associated membrane proteins (LAMPs) could play an important role in the pathophysiology of systemic lupus erythematosus (SLE) since anti-LAMP antibodies have been found in renal eluates of MRL/lpr/lpr mice and in the serum of patients with active SLE.

Animals↗
PubMed1989

In vitro and in vivo action of cyclosporin A on the induction of human interleukin-2 receptor alpha and beta chains.

To compare in vitro and in vivo cyclosporin A (CyA) effects on early events involved in human T cell activation, lymphocytes obtained from healthy donors and from diabetic patients undergoing CyA therapy were studied for their interleukin 2 (IL-2) responsiveness, surface IL-2 receptor (IL-2R) expression and IL-2R mRNA accumulation, following stimulation with mitogen or anti-CD3 monoclonal antibody. T cells recovered from eight in vivo CyA-treated patients and stimulated in vitro for 4 h with mitogen or anti-CD3 (in the absence of CyA) showed significant (50-60%) inhibition of Tac mRNA accumulation, as assessed and quantified by scanning densitometry. Conversely, these cells showed no modification in their expression of membrane alpha (p55, Tac) or beta (p70) chains of IL-2R in binding experiments performed with both iodinated anti-Tac and IL-2 following 18 h stimulation with either mitogen or anti-CD3. Normal lymphocytes treated in vitro with CyA showed significant inhibition of alpha chain IL-2R expression both at the mRNA and the membrane level. At variance, expression of the IL-2R beta chain was unaffected; a significant number of high-affinity IL-2 binding sites was still detectable after in vitro CyA treatment. These results suggest that: (1) a residual immunosuppressive effect of CyA on T cell activation may be evidenced in in vivo treated cells by measuring very early events triggered following short-term stimulation; (2) CyA activity on T cell activation seems similar in vivo and in vitro; and (3) the described approach would be potentially useful to monitor the individual in vivo immunosuppressive capacity of CyA.

Cells, Cultured↗
PubMed1989

[Myasthenia and pregnancy: a clinical and immunologic study of 42 cases (21 neonatal myasthenia cases)].

Forty-two pregnancies in 39 myasthenic mothers were studied between 1978 and 1987. In 4 cases myasthenia gravis began during pregnancy and for 20 patients the clinical condition exacerbated in 15 cases, usually during the first 3 months, or during the postpartum. Except for 1 case, clinical exacerbation was controlled by anticholinesterase drug adjustment. Obstetrical problems were uncommon: abortion in 1 case and premature delivery in 4 cases. In 2 babies with severe fetal involvement polyhydramnios was present. Twenty-one babies had neonatal myasthenia gravis (NMG). In 17 cases, transient symptoms were present at delivery or shortly afterwards and full recovery occurred from a few days to 4 months. In 4 babies the clinical presentation was atypical: 1 showed a long evolution (15 months) and residual facial bilateral weakness, and three others presented fetal involvement (arthrogryposis). In these latter cases, presentation was severe with polyhydramnios, respiratory failure and long standing evolution in 2 cases (4 months and 1 year). Antiacetylcholine receptor antibodies (anti-AChR Ab) were found in all myasthenic babies and in 19 out of 20 asymptomatic babies. Maternal antibody titers were usually slightly higher than umbilical cord titers. There was a good correlation between maternal titer and onset or severity of disorder in baby. Among the 15 high titer mothers (greater than 60 nM), 13 had a myasthenic baby, 6 of them with serious disease. Conversely all low titer mothers (less than 10 nM) had a symptom-free baby. Therefore, anti-AChR Ab titration in the mother is predictive for NMG onset. Mother's myasthenia gravis severity and treatment were not correlated to the clinical condition of the newborns.

Acetylcholine↗