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Biomedical subjects

J F Bach

Publications and source records attributed to J F Bach.

At least 397 records · Page 22Linked to original sources

Thymomatous epithelial cells and skeletal muscle share a common epitope defined by a monoclonal antibody.

Monoclonal antibodies have been raised against thymomatous epithelial cells with the use of fragments of a human thymoma as source of antigen. These monoclonals, which do not react with cultured epithelial cells or sections from normal thymus (except for some cells of Hassall's corpuscles), label a large number of cells in thymoma sections. In addition, they recognize cross-striations from skeletal muscle cells. Immunoblotting studies reveal that the proteins recognized on thymoma and muscle are in the same molecular weight range, suggesting that these proteins, which share a common epitope, are identical. These findings indicate that the production of circulating anti-cross-striational autoantibodies observed in most patients with thymoma could derive from immunization against a protein abnormally expressed by neoplastic epithelial cells.

Animals↗

[Early induction of diabetes in NOD mice by streptozotocin].

To clarify whether the non-obese diabetes prone (NOD) mouse has an unusual pancreatic sensitivity to damage, mice were administered streptozotocin in high dose (direct beta cell toxic) or multiple low-dose (autoimmune-insulitis generating) regimen. NOD mice were found to be less sensitive to the diabetogenic effects of high-dose streptozotocin than C57BL/6 mice, but were exquisitely responsive to the multiple low dose regimen when compared to C57BL/6 or C3H/HeJ mice. These results suggest that the basic defect in NOD mice resides in the immune system and that the NOD mouse may be a useful model to investigate the relationships between environmental factors and intrinsic genetic predisposition to diabetes.

Animals↗

[Preventive treatment of rejection by the prolonged administration of OKT3: decrease of the immune response of the host].

Clinical use of OKT3 for the treatment of ongoing rejection episodes has already been demonstrated as being highly effective. This work shows for the first time that combining azathioprine and OKT3 was able to delay as well as to decrease both the intensity and the quality of the anti-OKT3 immunization, allowing a 1-month prophylactic use of the MoAb. It also proves that OKT3 used prophylactically during one month can lead to 4-year first cadaver graft and patient survival rates better than those ever reported with any other immunosuppressive regimen. These results were obtained with lower doses of steroids and other immunosuppressive agents than in conventionally treated control patients. After the first two injections of OKT3, tolerance was perfect allowing out-hospital administration, and side effects consisted only in an increased number of viral infections instead of the bacterial infections observed in the conventional treatment groups. The prophylactic use of OKT3 should give even better results if it were possible to reach a 1-month administration schedule in all patients by modulating the dose of OKT3 according to the T3+ cell count and the monitoring of serum OKT3 levels.

Antibodies, Monoclonal↗

[Lupus associated membrane protein. Changes in the sensitivity of proteases during the life span of mice with lupus].

A murine monoclonal anti-DNA antibody, PME77, spontaneously produced in autoimmune B/W mouse, has been shown to react with a protein present at the surface of several cells involved in lupus pathogenesis. We have called this cell-surface protein LAMP (Lupus Associated Membrane Protein). Mild elastase treatment of lymphoid cells from non autoimmune (BALB/c or CBA/ca) mice releases five polypeptides (34, 33, 17, 16 and 14 kDa) recognized by PME77. These polypeptides are not found after treatment of these cells with papain or trypsin. When lymphoid cells from autoimmune mice (MRL/lpr/lpr and B/W) are treated with elastase, trypsin or papain, PME77 detected in all supernatants a single polypeptide of 55 kDa. It is demonstrated in the present work that: (1) this 55 kDa polypeptide is also detected in the elastase supernatant of glomeruli from MRL/lpr/lpr and B/W mice but not from BALB/c and CBA/ca mice. These results suggest that LAMP expressed at the surface of lymphoid and glomerular cells from lupus mice displays altered sensitivity to proteases. (2) The change in sensitivity to proteolytic enzymes appears between 1 and 3 weeks after birth in MRL/lpr/lpr mice. Such modifications might results in the appearance of a non-self antigen and elicit an anti-LAMP immune response.

Animals↗

[In vivo use of OKT3 monoclonal antibodies in recipients of renal allografts].

The OKT3 monoclonal antibody, that is specific for all mature human T lymphocytes represents a potent immunosuppressant when injected in vivo. The OKT3 antibody has been administered to more than 500 renal allograft recipients either to treat or prevent acute rejection episodes. OKT3 exerts its immunosuppressive effect by inducing rapid and important T cell depletion following the first injection. Then, OKT3 mediates the antigenic modulation of its T cell target antigen a phenomenon that is also related to the immunosuppressive effect exerted by the monoclonal antibody. The principal side effect observed following OKT3 administration, particularly if the antibody is injected alone, is the xenosensitisation against the foreign protein. Essentially, two sorts of anti-OKT3 antibodies are produced that respectively recognize the isotypic and the idiotypic determinants of the antibody molecule. The different strategies that may be envisaged to overcome this important side effect, that may totally neutralize the therapeutic effectiveness of OKT3 are discussed in detail.

Antibodies, Monoclonal↗

Protective effect of myasthenic immunoglobulins against the lethal toxicity of alpha bungarotoxin.

Using a radioimmunological method performed in the presence and absence of the acetylcholine agonist decamethonium (DC), it was demonstrated that 98% of myasthenia gravis (MG) patients' sera (positive for anti-acetylcholine receptor (anti-AChR) antibody titres in the conventional assay) contain antibodies that block the binding of alpha bungarotoxin (alpha Bgt) to human AChR. The positive effect of myasthenic immunoglobulins against the alpha Bgt toxicity was revealed by a test devised to investigate the biological significance of these blocking antibodies in vivo in Balb/c mice. IgG from sera containing blocking antibodies, detected either directly or in the presence of DC, protected the mice treated (24 of 25); nevertheless no overt clinical signs of a myasthenic syndrome were observed. Control IgG, from normal human sera or from a systemic lupus erythematosus patient, provided no protection (22 dead out of 26). IgG from MG sera devoid of anti-AChR antibodies (eight out of eight) and IgG from serum containing anti-AChR antibodies but devoid of blocking antibodies offered no defence against alpha Bgt toxicity (13 dead out of 15). The pathological role of blocking antibodies, cell mediated immunity or other mechanisms is discussed.

Animals↗