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Biomedical subjects

J F Bach

Publications and source records attributed to J F Bach.

At least 379 records · Page 21Linked to original sources
PubMed1987

Stimulatory effects of cyclosporin A on human and mouse thymic epithelial cells.

When injected daily into normal young or aging mice, cyclosporin A (CsA) induces a significant stimulation of thymic hormone (thymulin) secretion, as measured by the peripheral level of the hormone and the number of thymulin-producing cells in the thymus. This stimulation is dose dependent and reversible after the end of treatment. Similar findings have been made in primary cultures of human thymic epithelial cells in which CsA increases the percentage of thymulin-producing cells evaluated by immunofluorescence, as well as the amount of hormone released into the supernatants. No effect of CsA is observed on the expression of class II major histocompatibility complex antigens. CsA also increases the proliferation of cultured human thymic epithelial cells, as assessed by bromodeoxyuridine and [3H]thymidine incorporation. The present study strongly suggests that CsA can stimulate the proliferation and endocrine function of thymic epithelial cells. Its action on the immune system is thus not restricted to lymphoid cells and might be partially mediated by its effect on the thymic epithelium.

Animals↗
PubMed1987

Myasthenic sera recognize the human acetylcholine receptor bound to thymopoietin.

The thymic hormone, thymopoietin (Tpo), from human (HTpo), bovine (BTpo) and from synthetic (sHTpo) origins bound to the acetylcholine receptor (AChR) solubilized by Triton 1.5% from human muscle. This binding was demonstrated either by inhibition of formation of radiolabeled alpha bungarotoxin (alpha Bgt)-AChR complexes measured after precipitation by ammonium sulfate or by a myasthenic serum containing a high concentration of anti-AChR antibodies, or directly by incubating the human AChR with radiolabeled sHTpo or BTpo. The 125I-labeled alpha Bgt-AChR complexes were totally inhibited by 10(-6) M sHTpo or BTpo. The complexes formed by AChR and the radiolabeled Tpo were recognized specifically by sera containing anti-AChR antibodies from myasthenic patients. The active pentapeptide derivative of Tpo, thymopentin, another thymic hormone, thymulin, as well as bovine insulin did not interfere with the specific binding of alpha Bgt to human AChR. Tpo and anti-AChR antibodies could participate together in the inhibition of neuromuscular conduction with Tpo modulating the depressive effect of the antibodies on the neuromuscular junction in myasthenia gravis.

Autoantibodies↗
PubMed1987

The cytosolic free calcium in anti-mu-stimulated human B cells is derived partly from extracellular medium and partly from intracellular stores.

The inositol phospholipid metabolism and the increase in cytosolic free Ca2+ concentration ([Ca2+]i) into the cell are recognized as two important events in the anti-mu-induced B cell activation. The anti-mu stimulation caused the [3H]inositol incorporation and also a rapid increase in [Ca2+]i from 85 nM to 285 nM. This signal returned to baseline a few minutes after stimulation. By using the fluorescent indicator quin-2 we demonstrated that this [Ca2+]i uptake was derived part from extracellular medium and part from intracellular stores. Both EGTA (a calcium chelator) and TMB.8 (a drug which interferes with Ca2+ sequestration by smooth endoplasmic reticulum) partially suppressed the intracellular Ca2+ uptake and were fully inhibitory when added together. The role of Ca2+ from intracellular stores may also be evidenced in calcium-free experiments, or in permeabilized experiments using exogenous inositol 1,4,5-trisphosphate (IP3, the putative mobilizer of intracellular Ca2+). Preventing the increase in [Ca2+]i also prevents the apparition of early activation makers. These results are consistent with the hypothesis that the Ca2+ increase in B cells stimulated by anti-mu is caused by the generation of IP3 during the phosphatidyl-inositol metabolism and also by the entry of extracellular Ca2+ through the plasma membrane.

Antibodies, Anti-Idiotypic↗
PubMed1987

Splenocytes from MRL/Mp-lpr/lpr mice spontaneously produce antibodies against a cell-surface protein cross-reacting with DNA.

Anti-double-stranded (ds) DNA autoantibodies are considered as pathogenic in systemic lupus erythematosus (SLE). Anti-DNA antibodies have been shown to be released by B cells from lupus mice or patients in vitro. A monoclonal anti-DNA antibody (PME 77) specific for dsDNA has previously been shown to react with a cell-surface protein called LAMP (lupus-associated membrane protein), which is present on the cell surface of various cell types involved in SLE pathogenesis. Using an immunoreplica analysis technique, we show here that spleen cells from MRL/Mp-lpr/lpr lupus mice, cultured in vitro, spontaneously produce anti-LAMP IgG antibodies. Conversely, anti-LAMP antibodies were not detected in spleen-cell culture supernatants from nonautoimmune CBA/Ca mice. Taken together with our previous reports, this result adds a new argument for a pathogenic role of anti-LAMP autoantibodies in SLE.

Animals↗
PubMed1987

Increased binding of anti-acetylcholine receptor antibodies to thymic antigen in patients with myasthenia gravis and other autoimmune diseases, as compared to those with myasthenia gravis alone.

We compared the binding activity against acetylcholine receptors solubilized from human muscle (AChRM) and human thymus (AChRT), of sera from patients with myasthenia gravis (MG) alone, to those of sera from patients with myasthenia gravis and associated autoimmune diseases (MG AD). The sera of the MG AD group bound relatively better to thymic antigen (86% vs. 62%). This group was found to contain a higher proportion of women over 40 years of age (more than 50% of the group). The expression of a particular AChR antigen in normal human thymus may be one of the factors involved in the pathogenesis of MG, especially when this disease is associated with other autoimmune disorders.

Adolescent↗
PubMed1987

Effects of cyclosporine in severe systemic lupus erythematosus.

Thirteen patients with severe steroid-resistant or steroid-dependent forms of systemic lupus erythematosus were treated with cyclosporine (average dose 5 mg/kg/d) for an average period of 12 months. In eight patients the disease activity decreased, as substantiated by the reduction in the amount of steroid required to control the clinical manifestations. Interruption of cyclosporine treatment was associated with relapse or worsening of disease in five subjects. These favorable clinical results occurred in the absence of changes in the levels of antinuclear, anti-double-stranded deoxyribonucleic acid autoantibodies or plasma complement components; plasma IgG concentration increased significantly. Six patients had signs of moderate cyclosporine nephrotoxicity that disappeared when the administration of the drug was discontinued. Hypertension was the most serious side effect observed in eight subjects; in every case it was controlled by antihypertensive medicine. These data indicate that cyclosporine may be beneficial in the treatment of some patients with severe forms of systemic lupus erythematosus.

Adolescent↗
PubMed1987

Insulin-dependent diabetes: strategy for immune intervention.

Increasingly, experimental results are underlining the role played by autoimmune mechanisms in the pathogenesis of type I insulin-dependent diabetes mellitus (IDDM). It has appeared logical to attempt to preclude the onset of IDDM by suppressing immune responses, but trials using steroids or azathioprine were unequivocal. Subsequently, a Canadian and a French group performed pilot studies to assay a new immunosuppressive drug, cyclosporine A (CyA) in human diabetes (Stiller et al., 1984; Assan et al., 1985). However, further testing is required to evaluate and confirm its potential benefits and possible risks.

Cyclosporins↗
PubMed1987

Altered cell-surface protein(s), crossreactive with DNA, on spleen cells of autoimmune lupic mice.

A murine monoclonal anti-DNA antibody, PME77, with specificity for double-stranded DNA, has previously been shown to react with a protein(s) present at the surface of such cells involved in lupus pathogenesis as human glomeruli, T and B lymphocytes, erythrocytes, and platelets. Mild elastase treatment of lymphoid cells from non-autoimmune (CBA/ca or BALB/c) mice releases a series of crossreactive polypeptides (34, 33, 17, 16, and 14 kDa) recognized by PME77. These polypeptides are not formed after treatment of the same cells with papain or trypsin. When lymphoid cells from autoimmune [MRL-lpr/lpr or (NZB X NZW)F1 B/W] mice are treated with elastase, trypsin, or papain, PME77 detects, in all supernatants, a single polypeptide of about 55 kDa. Antibodies present in the sera of autoimmune MRL-lpr/lpr and B/W mice and IgG eluted from kidneys of MRL-lpr/lpr mice react with the same polypeptides. Neither sera nor eluted IgG of normal BALB/c mice react with these polypeptides. These results suggest that an altered cell-surface protein(s), which we call LAMP [for lupus-associated membrane protein(s)], may be involved in lupus pathogenesis.

Animals↗
PubMed1987

Presence of antibodies against a cell-surface protein, cross-reactive with DNA, in systemic lupus erythematosus: a marker of the disease.

Antibodies against a cell-surface protein, cross-reactive with double-stranded DNA, were detected in the serum of 25 patients with active human systemic lupus erythematosus (SLE), defined on the basis of the revised American Rheumatism Association classification. Among these sera, two did not display anti-DNA antibodies, as shown by Farr assay, solid-phase radioimmunoassay, and Crithidia luciliae test. Five other SLE patients were consecutively studied in active and remission states. Antibodies against the protein were detected in the serum of the 5 SLE patients when they were in active phase but not in the serum of the same patients in inactive phase of the disease. The anti-protein antibodies were not found in the serum of 10 inactive SLE patients or in the sera of 10 normal human controls, 10 patients with rheumatoid arthritis, 5 patients with scleroderma, and 4 patients with primary sicca syndrome. Taken together, these results strongly suggest that antibodies against this cell-surface protein could provide a better diagnosis marker and activity index than anti-DNA antibodies in SLE.

Antigens, Surface↗
PubMed1987

Frequent lymphocytes infection by hepatitis B virus in haemophiliacs.

We have tested the different mononuclear blood cell populations of seven patients with severe haemophilia and one patient with F VII deficiency for the presence of HBV DNA. These subjects were all polytransfused with non-heated coagulation factors; three were HBsAg positive, five HBsAg negative but anti-HBc and anti-HBs positive; HBV DNA sequences were detected in six subjects including three without detectable serum HBsAg. Furthermore the viral DNA sequences were identified in the T lymphocyte subpopulations (OKT4+ and/or OKT8+ cells). This observation suggests that HBV infection of lymphocytes might be related to the immunological disorders observed in these patients.

Blood Coagulation Factors↗
PubMed1987

Nonathymulin in rheumatoid arthritis: two double blind, placebo controlled trials.

Two randomised double blind, placebo controlled trials have been carried out to assess the effectiveness of nonathymulin, a synthetic thymic peptide hormone, in the treatment of rheumatoid arthritis (RA) and to compare three different dosage schedules (1, 5, and 10 mg/day). Nonathymulin 5 mg proved to be the most efficient dose, providing significant clinical improvement as evaluated by the global assessment of all patients who entered the trials (56% v 17% in the placebo group) (p less than 0.02) and by four objective parameters. This effect was accompanied with minimal adverse effects and was not associated with clear changes in immunological parameters. A significant correlation was observed, however, in clinical response to nonathymulin, and T cell subset imbalance was assessed using monoclonal anti-T cell antibodies and a functional suppressor T cell assay.

Arthritis, Rheumatoid↗
PubMed1987

Effect of cyclosporin A treatment on the production of antibody in insulin-dependent (type I) diabetic patients.

Anti-islet cell and anti-insulin antibody production was studies over a 12-mo period in 82 recently diagnosed diabetics randomly receiving either cyclosporin or placebo. Cyclosporin had only minimal effects on the production of anti-islet cell antibodies whether directed to islet cytoplasmic (immunofluorescence) or membrane (cytotoxicity assay) antigens even in patients undergoing remission. These data suggest that these antibodies do not play a major role in the pathogenesis of the disease particularly since their (irregular) presence is not predictive of the clinical response to cyclosporin. Conversely, cyclosporin completely suppressed the synthesis of antibodies elicited by exogenous insulin irrespective of the insulin doses received, and decreased the autoantibody production against thyroid antigens, indicating that cyclosporin has variable effects on antibody production against various antigens.

Antibody Formation↗
PubMed1987

Synthesis and biological activity of eight thymulin analogues.

Eight analogues of thymulin, a thymic nonapeptide involved in several aspects of T-cell differentiation, were synthesized by the conventional method in solution. Four were modified in residue 7 (Ala, D-Ala, D-Leu or Sar instead of Gly) and two in residue 8 (D-Ser or Thr instead of Ser); in the others, the Gly6-Gly7 sequence was replaced either by a single glycyl residue or by a triglycyl sequence. The biological activity of the analogues was determined in the rosette assay: five exhibited a prolonged activity in vivo with respect to thymulin. All the analogues inhibited the binding of tritiated thymulin to thymulin receptors on three human lymphoblastoid T-cell lines (HSB2, 1301 and CEM) with the same order of magnitude as non-labelled thymulin.

Amino Acids↗