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Biomedical subjects

J F Bach

Publications and source records attributed to J F Bach.

At least 361 records · Page 20Linked to original sources
PubMed1988

Neonatal myasthenia gravis: a new clinical and immunologic appraisal on 30 cases.

Anti-acetylcholine receptor (AChR) antibody titers, toxin binding blocking antibody, functional activity of serum on rat myotube cultures, IgG subclasses, and clinical data were studied in relation to the onset of neonatal myasthenia gravis (NMG) in 30 children of myasthenic mothers. Fourteen had NMG, including 4 atypical cases. Anti-AChR antibody titer was the best indication of NMG onset. NMG in a previous baby was also predictive. Pattern of IgG subclasses, presence of toxin-binding blocking antibodies, and serum functional activity were less predictive, but cast light on the mechanism of anti-AChR antibody pathogenicity.

Animals↗
PubMed1988

Inhibition of insulin release in vitro mediated by mononuclear cells from diabetic patients treated with cyclosporin A or placebo.

Anti-beta-cell-specific cell-mediated immunity was studied over a 12-mo period in 65 recently diagnosed diabetic patients randomly receiving either cyclosporin or placebo. Anti-beta-cell cellular immunity was assessed by an in vitro test based on the inhibition of insulin release from cultured rat islet cells by patients' mononuclear cells. This beta-cell-suppressive effect disappeared in cyclosporin A-treated patients within 1 mo and did not reappear during 12 mo of follow-up. Conversely, the suppressive effect persisted unchanged in placebo-treated patients during 12 mo of follow-up. These changes were predictive neither of cyclosporin A-induced remission nor of relapses. Results of the insulin-release inhibition test were not correlated to islet cell autoantibodies or HLA phenotype.

Adolescent↗
PubMed1988

Modulation of thymic endocrine function by thyroid and steroid hormones.

The thymic epithelium is responsible for the secretion of thymic hormones that intervene in some steps of intra- and extra-thymic T cell differentiation. In the present paper, we studied the in vivo and in vitro influences of thyroid and steroid hormones on the secretion of thymulin, one of the chemically-defined thymic hormones. Triodothyronine injected in young mice or applied into supernatants of cultured thymic epithelial cells resulted in an increase of thymulin synthesis and secretion, respectively evaluated by the analyses of thymulin containing cells and thymulin levels. The influence of steroids was investigated in vivo by steroid depletion (adrenalectomy and/or castration) and in vitro by the addition of various steroids and/or their specific antagonists to cultured thymic epithelial cells. Surgical ablation of adrenals and/or gonads induced a transient depletion of circulating thymulin and, by feedback mechanism, an increase in the numbers of thymulin containing cells. From the in vitro data we could conclude that the various steroid hormones (that exhibited a stimulatory effect) can act directly on the thymic epithelium, probably via specific receptors. The bulk of data above described represents a strong evidence for the physiological involvement of the neuroendocrine network, on the hormonal function of the thymic epithelium.

Adrenal Cortex Hormones↗
PubMed1988

[Immunology of transplantation].

Immunologic events leading to the acute rejection of a grafted organ follow three sequential stages: 1) recognition of the antigens fully specific expressed by the allograft; 2) proliferation and differentiation of the T lymphocytes; 3) destruction of the graft mediated by various cellular types: sensitized cytotoxic T lymphocytes, lymphokine activated lymphocytes or macrophage cells, and, more hypothetically, by the so-called "killer" cells. The T lymphocytes infiltrating the grafts during rejection include functionally distinct subsets: inducer T cells (CD4+ cells) and suppressor/cytotoxic cells, T cells (CD8+ cells). In reversible acute rejections the role of activated cytotoxic cells (CD3+ CD8+) seems to be predominant. The functional nature of the lymphoblasts infiltrating the allograft is heterogeneous. It includes cell-mediated cytotoxicity, the proliferative response to alloantigens and the production of lymphokines. Finally, the role of the T cell receptor for the recognition of the antigen appears to be essential. The necessity for the immune system to build up a large repertoire of different T receptors is dependent on a mechanism of genetic coding similar to the one used by immunoglobulins. In the near future, one may hope to alter specifically the repertory of the T receptors used by the lymphocytes responsible for rejection. This would represent the dawn of a new era in transplantation immunity with the beginning or specific immunosuppression.

Child↗
PubMed1988

Cell-mediated immunity to pancreatic islet cells in the non-obese diabetic (NOD) mouse: in vitro characterization and time course study.

The non-obese diabetic (NOD) mouse is an animal model of insulin-dependent diabetes mellitus (IDDM), in which 80% of the females become diabetic after the age of 12 weeks. Using an in vitro assay we investigated the capacity of spleen lymphocytes from NOD mice to inhibit the insulin secretion of normal islet cells after stimulation by theophylline plus arginine. Spleen cells from diabetic NOD mice inhibited the insulin release of DBA/2 islet cells. Depletion experiments using monoclonal antibodies demonstrated that inhibitory cells belonged to the Lyt2 positive T lymphocyte subset. The phenomenon was not restricted by the MHC class I K region, shared by NOD and DBA/2 mice, since lymphocytes from diabetic NOD mice also inhibited the insulin secretion of normal Wistar rat islet cells. Inhibitory T cells were detected in overtly diabetic mice but also in non-diabetic females aged 5-11 weeks indicating that they are not secondary to metabolic disturbances and might contribute to their onset. Conversely they were not found in male NOD mice although some of these mice show insulitis. The presence of these inhibitory T cells might thus represent an early and sensitive marker of anti-islet cell-mediated autoimmunity.

Aging↗
PubMed1988

[T lymphocyte activation induced in vivo by the first injection of OKT3 monoclonal antibodies].

One of the major side effects induced by the in vivo administration of the murine monoclonal antibody OKT3 is a spontaneously reversible clinical syndrome associating in variable proportions depending on the patient: fever, chills, headaches, diarrhea and seldomly meningismus. Sera from 3 renal allograft recipients treated with OKT3 were studied and showed that a massive although transient release of some cytokines namely, Tumor Necrosis Factor alpha, Interleukin 2 and Interferon gamma is observed following the first OKT3 injection.

Antibodies, Monoclonal↗
PubMed1988

Polyclonal and monoclonal antibodies directed against SK & F 94461, a specific H1 histamine receptor ligand.

SK & F 94461, an aminopentyl analogue of mepyramine, is a recently described H1 receptor antagonist. At variance with the other available H1 receptor ligands, SK & F 94461 offers the possibility of coupling to a protein carrier to render the molecule immunogenic. SK & F 94461 coupled to succinylated bovine serum albumin was used as an immunogen to raise polyclonal antibodies in rabbits and BALB/c mice. In parallel, spleen cells from immunized mice were used to produce hybridomas by somatic cell fusion. Thus, six different murine monoclonal antibodies sharing anti-SK & F 94461 specificity were selected for further detailed characterization of their binding properties. Pharmacologic studies of competitive inhibition using a set of 11 histaminergic agents allowed analysis of the fine specificity of anti-SK & F 94461 antibodies. Both polyclonal and monoclonal anti-SK & F 94461 antibodies showed very high affinity for the immunizing molecule (i.e., Ka values for monoclonal antibodies 8 and 12 were, respectively, 3 X 10(10) and 1.4 X 10(10) M-1). Both types of antibodies bound with high affinity (IC50 ranging from 10(-10) to 10(-12) M) to mepyramine, which has a chemical structure closely resembling that of SK & F 94461. Moreover, these antibodies displayed clear-cut stereoselectivity inasmuch as they bound the d-configuration of chlorpheniramine with significantly higher affinity than the l-form. Thus, all six monoclonal antibodies showed IC50 values 1 to 6 log units lower for d- than for l-chlorpheniramine. For some monoclonal antibodies, spectroscopic and fluorescence spectra studies showed that their different binding capacities correlated with their optical properties. Similarly, polyclonal anti-SK & F 94461 antibodies showed a 500-fold lower affinity for l- than for d-chlorpheniramine. All these results indicate that the polyclonal and the majority of monoclonal anti-SK & F 94461 antibodies recognized with high affinity structural configurations known to be important for the pharmacologic activity of H1 ligands, namely the presence of the dimethylaminoethyl side chain and, with stereochemical selectivity, the d-configuration of chlorpheniramine. These data extend for the first time to an H1 histamine receptor ligand results reported in other hormone systems.

Aminopyridines↗
PubMed1987

Syngeneic transfer of autoimmune diabetes from diabetic NOD mice to healthy neonates. Requirement for both L3T4+ and Lyt-2+ T cells.

We have developed a model of syngeneic adoptive transfer for type I diabetes mellitus of NOD mice. This model consists in injecting spleen cells from diabetic adult mice into newborn NOD recipients. 50% of recipients inoculated with 20 X 10(6) cells develop diabetes within the first 10 wk of life, at a time when none of the control littermates have yet become diabetic. The earliest successful transfers are observed at 3 wk of age, at a time when controls do not even exhibit histological changes in their pancreas. In addition we have shown that: (a) both males and females can be adoptively transferred, despite the fact that males rarely develop spontaneous diabetes in our colony; (b) diabetes transfer is a dose-dependent phenomenon that provides an in vivo assay for comparing the autoimmune potential of spleen cells from mice at various stages of their natural history; (c) the susceptibility of the recipients to the transfer is limited in time and declines after 3 wk; and (d) both L3T4+ and Lyt-2+ T cell subsets are necessary for the successful transfer. The neonatal syngeneic transfer provides an effective model for studies of the cellular events involved at regulatory and effector stages of autoimmune type I diabetes.

Animals↗
PubMed1987

An enzyme immunoassay for synthetic thymulin.

Thymulin, a metallononapeptide with the following aminoacid sequence: pyroGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-AsnOH is a thymic hormone involved in T cell differentiation requiring zinc to express biological activity as measured by the rosette assay. We established an enzyme immunoassay (EIA) for synthetic zinc-free thymulin with a thymulin-acetylcholinesterase conjugate as tracer and specific polyclonal rabbit antithymulin antibodies. The assay is performed as a classical competition assay in microtiter plates previously coated with mouse monoclonal IgG to rabbit IgG. A quantitative thymulin assay more sensitive than radioimmunoassays (RIAs) previously described was obtained with a sensitivity (IC50) of 32.5 +/- 5 pg/ml and a detection limit of 5 pg/ml. Analysis in the EIA of synthetic thymulin analogs showed that the minimal peptidic structure necessary for enzymatic tracer competition is the C-terminal part Lys3 to Asn9. It was also shown that the biologically active form of thymulin (zinc-bound) has the same immunoreactivity as zinc-free thymulin and that other thymic hormones, thymosin alpha 1 and thymopoietin II (or TP5) and unrelated short peptides do not cross-react with thymulin. These data demonstrate the specificity of this EIA for thymulin and show its suitability for application in biological fluids.

Antibody Specificity↗
PubMed1987

Nonneoplastic circulating Sézary-like cells in cutaneous T-cell lymphoma. Ultrastructural, immunologic, and T-cell receptor gene-rearrangement studies.

Approximately 67% of peripheral blood lymphocytes in a case of nonmycosis fungoides-type cutaneous T-cell lymphoma, exhibited Sézary-like changes. Immunotyping showed a helper phenotype with an abnormally faint expression of the T3 membrane antigen, while quantitative electron microscopic study was suggestive of neoplasia. However, T-cell receptor gene study did not show any DNA rearrangement in Ficoll-separated blood lymphocytes, whereas clonal T-cell proliferation was simultaneously evidenced in cutaneous (non-Sézary-like) tumor cells. It is concluded that reactive nonneoplastic Sézary-like cells may be present not only in various benign conditions, as previously known, but also in T-cell lymphomas. This study provides further evidence for the nonspecificity of Sézary-like changes, and stresses the utility of T-cell receptor gene rearrangement study for diagnostic and prognostic procedures during the course of T-cell lymphoproliferative disorders.

DNA, Neoplasm↗
PubMed1987

Cortical thymocyte differentiation in thymomas: an immunohistologic analysis of the pathologic microenvironment.

Four monoclonal antibodies (BH11, T2/30, AG3, and BC3) were produced against different epithelial components of the normal thymus. An immunohistologic study was performed on 13 thymomas by the use of these and other stromal and lymphocyte-specific reagents. The aim of this study was to find possible relationships between the proliferating thymoma epithelial cell type and the T cell composition of thymomas. Our results indicate that cortical T cell differentiation is present in thymomas, and that this differentiation is induced in the absence of detectable levels of MHC class II antigens on the epithelial component in most cases. The role of the MHC class II antigens cannot be excluded, however, because these antigens were always present on macrophages. Analysis of the selected group of thymomas, each of which contained epithelial cells homogeneously stained by at least one of the described monoclonal antibodies, showed that the cortical type T cell inducer capacity of thymomas is independent of the epithelial type predominant in the tumor.

Antibodies, Monoclonal↗