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Biomedical subjects

J F Bach

Publications and source records attributed to J F Bach.

At least 469 records · Page 26Linked to original sources
PubMed1984

Immune lysis of hepatocytes in culture: accurate detection by aspartate aminotransferase release measurement.

Determination of the immune lysis of epithelial cells, especially of hepatocytes, in short term culture is dealt with inadequately because of the lack of accuracy inherent in most classical methods of measurement of cell lysis or because of the high spontaneous release of the lytic marker. We have studied different methods of detection of lysis of rat hepatocytes cultured for a short term (24-48 h) at a concentration of 10 000 cells/50 microliters. The determination of aspartate aminotransferase (ASAT) release, measured with a centrifugal analyser parallels lactate dehydrogenase (LDH) release and trypan blue dye staining which are indisputable markers of cell death, but ASAT release is a more sensitive determination. Surprisingly, 51chromium release (1.72%/h) is much higher than ASAT release (0.51%/h) for an experimental period of 24 h. In cell mediated cytotoxicity tests, the ASAT content of lymphocytes, in contrast to that of LDH, is much lower than that of hepatocytes and this makes determination of ASAT release a sensitive marker of cytotoxicity under these conditions.

Animals↗
PubMed1984

Studies on the zinc binding site to the serum thymic factor.

Gel filtration studies of 65Zn2+ binding to thymulin show that the nonapeptide can strongly bind one zinc metal ion. At pH 7.5, thymulin binds one zinc ion with an apparent affinity constant Kd of 5 +/- 2 X 10(-7) M. Binding is pH dependent. No binding is observed below pH 6.0. Ga3+, Al3+, Mn2+ and Cu2+ can compete with the binding of Zn2+ at pH 7.5. A good correlation between the competition potencies of metal ions used and the extent of biological activity of thymulin in the presence of these metal ions in an in vitro rosette assay is observed. Structural analogs of thymulin and non-thymulin-related peptides were used in a gel filtration technique to tentatively define the nature of amino acids present in the Zn2+-binding site of thymulin.

Binding Sites↗
PubMed1984

In vivo and in vitro studies of thymulin in marginally zinc-deficient mice.

Thymulin (or serum thymic factor, FTS-Zn), a well-defined thymic hormone previously shown to be a nonapeptide binding the metal zinc, was studied in mice subjected to a long-term marginally Zn-deficient diet. In spite of the absence of thymic atrophy, we observed a significant decrease in the serum levels of thymulin as early as two months after the onset of treatment. However, these levels could be consistently restored after in vitro addition of ZnCl2. The analysis of thymuses from Zn-deficient mice showed that, despite the apparently normal network of epithelial cells, there was a progressive increase in the number of thymulin -containing cells (assessed by immunofluorescence with anti- thymulin monoclonal antibodies) that was already significant after two months of treatment. These results are in keeping with those of previous investigators, showing a specific, altered, thymic endocrine function following Zn deprivation. Nonetheless, our results strongly suggest that the nonactive Zn-deprived peptide is secreted under these experimental conditions. Furthermore, the fact that the augmented numbers of thymulin -containing cells were observed in the thymuses following a decrease in the peripheral thymulin (biologically active) brings further evidence for the existence of a feedback mechanism for the secretion of this hormone.

Animals↗
PubMed1984

Unusually restricted anti-isotype human immune response to OKT3 monoclonal antibody.

The unusual anti-mouse immunoglobulin (Ig) sensitization of a renal allograft recipient who was treated prophylactically with the anti-T cell monoclonal antibody OKT3 (IgG2a) is reported. Whereas in most patients, the injection of OKT3 (5 mg/day, i.v. for 13 days) induces the rapid appearance of neutralizing anti-OKT3 antibodies, the patient reported here did not show the signs of conventional anti-OKT3 sensitization. High levels of circulating OKT3 persisted and no OKT3+ lymphocytes reappeared during the whole treatment period. Moreover, no IgG or IgM anti-OKT3 antibodies were detected at any time, using a specific enzyme-linked immunosorbent assay. However, an atypical anti-isotype response was evidenced in this subject whose Ig were shown by indirect fluorescence to bind to normal T cells coated with OKT3 or with other anti-T cell murine monoclonal antibodies carrying the IgG2a isotype (no reactivity was observed with IgG1 or IgG2b molecules). The patient's Ig did not bind to normal T cells coated with F(ab')2 fragments of OKT3 and did not inhibit the binding of OKT3 to its target antigen indicating that they reacted with the Fc fragment of the OKT3 molecule. Additionally, and probably explained by this unusual anti-OKT3 response, the patient's Ig were shown to inhibit the phytohemagglutinin-induced proliferation of normal lymphocytes, to bind under selected in vitro conditions to normal T cells and lastly to enhance the antigenic modulation induced in vitro by OKT3 on its membrane receptor.

Antibodies, Monoclonal↗
PubMed1984

The in vivo effects of corticosteroids on thymocyte subsets in myasthenia gravis.

The in vivo effects of corticotherapy on thymocyte subpopulations have been evaluated in patients with myasthenia gravis (MG). Ten patients receiving high-dose, long-term treatment were studied and compared with two control groups (MG untreated patients and normal age-matched subjects). In the treated group, the thymus was generally involuted; the percentage of OKT6+ or OKT4+T8+ thymocytes was profoundly decreased compared to controls. A significant percentage of OKT10 - cells was detected particularly among older patients, suggesting steroid-induced immigration. Conversely the percentage of more mature OKT3+ cells was increased. The balance between OKT4+T8- and OKT4-T8+ cells was unchanged in young patients (less than 40 years old) and increased in the older group. These data show that, as in the mouse, corticosteroids profoundly alter human thymocyte subsets.

Adolescent↗
PubMed1984

The immunological basis of inflammatory diseases.

Most immunologically-mediated diseases are inflammatory in nature, as assessed by cellular infiltrates at the lesion site. Recent immunohistological studies using monoclonal antibodies on tissue sections and synovial or cerebrospinal fluid reveal that B- and T-lymphocytes (predominantly T) participate in this reaction, together with monocytes and macrophages. The etiopathogenesis of inflammatory diseases of immunological origin can be discussed at two levels. (1) Lesions may be secondary to the cytopathic effect of antibodies, either by direct cytolysis or by opsonization, antigenic modulation, or blockage of functionally-relevant molecules. Immune complexes formed in the circulation or locally at the lesion site may intervene. Direct cellular mechanisms are probably involved, as suggested by evidence in hepatitis (indirect) and in juvenile insulin-dependent diabetes (direct). K-cells may act by antibody-dependent cytotoxicity, particularly in autoimmune diabetes and thyroiditis where lymphocyte-dependent antibodies are demonstrated. Unfortunately, the absence of adequate markers does not permit adequate detection of K-cells in inflammatory reaction sites. (2) Etiological factors are multiple in a given disease and even in a single patient. Deficiency of suppressor T-cells, assessed using monoclonal anti T-cell antibodies, represents a major predisposing factor, although suppressor cell deficit may be restricted to some antigens (EBV) in certain patients. The deficiency of interleukin-2 production in lupus and rheumatoid arthritis is intriguing but the mechanism and its relationship to disease etiology are unknown. Other immunological factors include intrinsic B-cell hyperactivity, anti-T-cell auto-antibodies, and complement deficiencies, whereas non-immunological factors such as viruses, drugs or sex hormones are important but ill-defined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

The clinical use of monoclonal anti-T-cell antibodies.

Monoclonal anti-T-cell antibodies are progressively replacing other T-cell markers in clinical immunology. A number of problems persist however, that urge for caution in interpreting the data issued from their in vitro use. Several antibodies directed against the same molecule may give different results according to the subject (due to genetic variants) or according to stage T-cell differentiation. The expression of antigenic determinants (epitopes may vary under the effect of drugs, positively (cimetidine, thymic hormones) or negatively (indomethacin). Lastly the correlation between phenotype and function of T-cell subsets may be very poor in the same pathological settings. In spite of these pitfalls, monoclonal anti-T-cell antibodies have proven to be very useful in several circumstances. Thus, in renal allograft recipients immunological monitoring with monoclonals helps the diagnosis of rejection in patients treated with conventional immunosuppression and permits early detection of antigenic modulation and xenosensitization in patients treated with the anti-T-cell OKT3 antibody.

Antibodies, Monoclonal↗
PubMed1984

T-cell subsets in multiple sclerosis: a comparative study between cell surface antigens and function.

Pokeweed mitogen (PWM)-driven immunoglobulin synthesis (IgG, IgA, IgM) and concanavalin A (Con A)-stimulated suppression of allogeneic mixed leukocyte reaction (MLR) were studied and compared to T-cell subsets defined by monoclonal antibodies OKT4 and OKT8 in patients with multiple sclerosis (MS). The group of patients with active progressive MS showed diminished suppressor activity as measured by T-cell functional tests and also an elevated OKT4/OKT8 ratio. The group of MS patients in remission did not show these abnormalities. However, this correlation between functional tests and T-cell phenotypes was not found when separate individuals were considered within the subgroups of MS. Since neither OKT4 nor OKT8-reactive cells represent homogeneous functional subsets of T cells, the OKT4/OKT8 ratio does not account for the functional immunological status of separate individuals but rather provides a global evaluation of T-cell subset disturbances in different groups of diseases.

Adult↗
PubMed1984

Neonatal myasthenia gravis. Anti-acetylcholine receptor antibodies in the amniotic fluid.

Neonatal myasthenia gravis (NMG) with mild arthrogryposis was observed at birth in the newborn infant of a myasthenic mother. Anti-acetylcholine receptor (anti-AChR) antibodies were present in the serum of both mother and child, in umbilical cord serum and in the amniotic fluid. The presence of anti-AChR antibodies in the amniotic fluid may be one of the causes of the NMG.

Adult↗
PubMed1984

Evidence for the presence of immunoreactive acetylcholine receptors on human thymus cells.

Triton extracts from thymuses and thymomas from either normal subjects or MG patients specifically bind [125I] alpha-bungarotoxin (alpha Bgt). This binding is saturable (apparent Ks = 5.9 X 10(-9) M) and can be inhibited by cold alpha Bgt, acetylcholine or nicotinic agonists. These results demonstrate the presence on human thymus cells of acetylcholine receptor (ACh.R), 2.8% for normal human thymus in regard of ACh.R concentration in human muscle. Normal human thymic extracts were used as an antigen source in the radioimmunoassay for the detection of anti-ACh.R antibodies in positive MG patients' sera. 72% of these sera were also positive with the thymic antigen. The demonstration of ACh.R in human thymus brings further support to the hypothesis of intrathymic autosensitivity against ACh.R as a major factor in MG pathogenesis.

Antibodies↗