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Biomedical subjects

J F Bach

Publications and source records attributed to J F Bach.

At least 451 records · Page 25Linked to original sources
PubMed1985

Monoclonal antibodies raised against Lewy bodies in brains from subjects with Parkinson's disease.

Monoclonal antibodies which immunocytochemically label Lewy bodies on sections of substantia nigra from subjects with Parkinson's disease were produced by immunization of mice with substantia nigra and locus coeruleus containing Lewy bodies from parkinsonian subjects post-mortem. Tests of specificity indicate that the antibodies do not recognize the same antigen. One of the antibodies (G7) immunocytochemically labels only Lewy bodies, the other (G9) also faintly labels the cell bodies of nigral dopaminergic neurons and cerebellar Purkinje cells in both normal and parkinsonian brains. Absorption experiments show, however, that the G7 antigen is present in normal substantia nigra and the G9 antigen in normal substantia nigra and Purkinje cells. Neither of the antibodies seems to be directed against neurofilament protein. Immunoblots after two-directional electrophoresis indicate that antibody G7 labels a protein with an iso-electric point around 5.6 and a mol. wt. of approximately 40 kdalton, whereas the protein labeled by antibody G9 has an iso-electric point of near 8 and a mol. wt. above 70 kdalton.

Antibodies, Monoclonal↗
PubMed1985

[Present and future value of monoclonal antibodies in nephrology].

Many monoclonal antibodies directed against human T-lymphocytes have been produced in mice. Some of these, such as OKT 3, recognize all T-cells which can thus be counted in the blood; they have been used for the prevention of renal transplant rejection. Despite unexpected problems, such as antigenic modulation and anti-mouse sensitization, the first results obtained are promising. Other antibodies produced are directed against T-lymphocyte subsets, notably T-helpers (OKT4+) and T-suppressors or cytotoxic T-cells (OKT8+). Studies of the OKT4+/OKT8+ ratio have shown an imbalance in T-cell subsets in 2 types of glomerulonephritis: Berger's disease and membranous glomerulonephritis; they have also contributed to a better understanding of renal allograft rejection, where this ratio is often elevated.

Animals↗
PubMed1985

Thymus hormones do not induce proliferative ability or cytolytic function in PNA+ cortical thymocytes.

A variety of thymus hormone preparations, as well as drugs known to perturb cell differentiation, were tested for their ability to induce nonfunctional cortical thymocytes to become functional precursor cells. Murine cortical thymocytes, defined as the high peanut agglutinin (PNA) binding or as the low H-2K, major [86%] thymocyte subpopulation, were isolated by fluorescence-activated cell sorting. Their function was assessed in a high cloning efficiency, growth factor saturated, concanavalin A-stimulated limit-dilution culture system, determining the number of precursors of extended clones (PTL-p), or determining with a lectin-mediated tumor-lysis readout the number of precursors of cytolytic clones (CTL-p). The hormone preparations tested were crude or partially purified culture supernatants from thymus "epithelial" monolayers (TES), soluble extracts of thymic nonlymphoid tissue (STF), semipure thymus humoral factor (THF), and the pure peptides thymopoietin 32-36 (TP5) and "facteur thymique sérique" (FTS). These preparations were either added directly to the limit dilution cultures, or were first preincubated with the cells, which were then subjected to limit-dilution culture. In no case did the hormone preparations cause any increase in the level of PTL-p or CTL-p in the PNA+ or low H-2K thymocyte population, even though a conversion of only a few percent to functional cells could have been detected. Two possible explanations are considered. One is that the main function of these materials is to control post-thymic peripheral T cells, rather than to induce intrathymic differentiation. Another is that the typical cortical thymocyte is beyond the stage at which thymocytes can be induced by hormones, a view that is strengthened by the failure of either 5-azacytidine or the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate to activate these cells. In this latter explanation the true intrathymic target of hormone action may be an earlier, and very minor, thymus subpopulation.

Animals↗
PubMed1985

Metabolic and immunological effects of cyclosporin in recently diagnosed type 1 diabetes mellitus.

Cyclosporin 5-10 mg/kg daily was given for 2-8 months to twelve recently diagnosed type 1 diabetics from a mean of 49 +/- SE 14 days after the start of insulin therapy, which was regulated to give near-normal blood glucose and haemoglobin A1c values. Mean insulin dosage dropped from 46 +/- 5 U/day before cyclosporin treatment to 16 +/- 4 U/day by the 7th month. Four patients had a complete remission and the insulin needs of four more were cut by half. The remaining four did not have remissions. Initial basal and glucagon-stimulated C peptide concentrations were higher in those who went into remission than in those who did not; they rose during cyclosporin treatment in the former but not in the latter. OKT4+ lymphocyte functions were suppressed in all patients and OKT4/OKT8 ratios declined. Anti-beta-cell autoimmunity, as indicated by lymphocyte-induced inhibition of insulin release from mouse islet cells, declined in all patients who went into remission. No consistent trend was observed for anti-islet cell antibodies. In forty-four similar, but non-randomised, recently diagnosed diabetics treated with insulin alone, the incidence of remission was 6%.

Adult↗
PubMed1985

Hormonal modulation in systemic lupus erythematosus. Preliminary clinical and hormonal results with cyproterone acetate.

We prospectively studied the effects of hormonal modulation using the antigonadotropic drug, cyproterone acetate (CA), in 7 female patients who had moderately active systemic lupus erythematosus. CA was taken orally at a mean daily dose of 50 mg for 21-33 months by 6 patients (9 months by the seventh patient) without any side effects. The number of clinical lupus exacerbations during CA treatment was lower than that during the corresponding pretreatment period (15 of 170 patient-months versus 27 of 156 patient-months; P less than 0.05), despite a reduction in the daily maintenance dose of corticosteroids or antimalarial drugs. Mean plasma testosterone levels were low initially and remained unchanged (0.66 +/- 0.31 to 0.59 +/- 0.23 nmoles/liter), whereas plasma estradiol decreased markedly (from 0.6 +/- 0 38 to 0.11 +/- 0.03 nmoles/liter), resulting in a significant reduction in the estradiol:testosterone ratio (from 1.19 +/- 0.68 to 0.23 +/- 0.12) and in the plasma concentration of the sex hormone-binding protein. Thus, cyproterone acetate induced improvement in clinical lupus activity in parallel with the expected lower estradiol:testosterone balance.

Adult↗
PubMed1985

Effect of thymulin on intracellular cyclic nucleotides and prostaglandins E2 in peanut agglutinin-fractionated thymocytes.

Prostaglandin E2 (PGE2) and other selected agents which elevate intracellular cyclic AMP (cAMP) levels have been demonstrated to induce the appearance of surface markers in immature T lymphocytes. Thymic hormones, which are the natural inducers of these markers, have long been hypothesized to act through the increase of cAMP levels. We have approached this area of investigation by studying the effects of thymulin (a serum thymus-derived factor, coupled with Zinc) on intracellular cAMP and cyclic GMP (cGMP) levels (expressed as cAMP/cGMP ratio) and on the release of PGE2 in different thymocyte subpopulations. Thymocytes were fractionated by the peanut agglutinin (PNA) technique into cortical immature PNA+ and medullary mature PNA- thymocytes. The data presented in this report show that thymulin is able to increase the cAMP/cGMP ratio in PNA+ and in unfractionated thymocytes, depending on its concentration, but not in PNA- thymic cells. Conversely, it is able to increase the release of PGE2 by PNA- thymocytes but not by PNA+ and unfractionated thymic lymphocytes. These results are consistent with the hypothesis that thymulin could act through different mechanisms depending on the differentiation stage of its target cells. In fact, it could be suggested that immature T cells could be activated by thymulin thereby increasing the cAMP/cGMP ratio, whereas more mature T cells would be further differentiated by thymulin through enhanced release of PGE2.

Animals↗
PubMed1985

Production of a lymphocyte differentiating factor (ELDIF) by cultured human epidermal cells.

T lymphocyte maturation activity of supernatants from cultured human epidermal cells was investigated using a biological rosette assay based upon Thy 1 induction on T cell precursors. Between days 5 and 18 of keratinocyte cultures, supernatants exhibited Thy 1-inductive properties. Optimal activity was found between days 10 and 14 of culture, which correspond to the beginning of epidermal cell stratification. This activity was independent of the presence of prostaglandin E. Absorption experiments using monoclonal and polyclonal antibodies showed that ELDIF was different from other recognized thymic hormones (thymulin, thymopoietin, thymosin alpha 1), produced by thymic epithelial cells and known to induce T cell markers.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1985

Thymulin.

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Animals↗
PubMed1985

A zinc-dependent epitope on the molecule of thymulin, a thymic hormone.

Thymulin is a nonapeptide hormone produced by thymic epithelial cells. Its biological activity is strictly dependent on the presence of the metal zinc in the molecule. Antithymulin monoclonal antibodies have been produced against either the synthetic (AS1) or the natural intraepithelial (AE1) molecule. These monoclonal antibodies were screened for their abilities to inhibit the zinc-dependent biological activity of the hormone and were shown to bind to thymic epithelial cells. By using biological and immunofluorescence assays, the two antibodies were shown to recognize exclusively the zinc-coupled thymulin molecule. Other antithymulin antibodies screened by RIA or ELISA (using a zinc-deprived substrate) recognized a zinc-independent epitope on the thymulin molecule. These data indicate the existence of a zinc-specific conformation on the thymulin molecule. They are in agreement with NMR studies showing that the zinc-containing hormone has a unique structure.

Animals↗
PubMed1985

Binding of a monoclonal anti-DNA autoantibody to identical protein(s) present at the surface of several human cell types involved in lupus pathogenesis.

A monoclonal anti-DNA antibody PME77, spontaneously produced in autoimmune B/W mice, has been found to recognize identical protein(s) present at the surface of several human cell types involved in the pathogenesis of systemic lupus erythematosus: glomeruli, platelets, erythrocytes, T and B cells, and neuronal tissue. Data indicate that protein(s) could represent a major stimulus or the target of anti-DNA autoimmunity and could account for tissue lesions observed in this disease.

Animals↗
PubMed1985

Thymoma epithelial cells secrete thymic hormone but do not express class II antigens of the major histocompatibility complex.

17 thymomas were studied by indirect immunofluorescence for the presence of thymic hormones and antigens of the major histocompatibility complex (MHC). The thymoma epithelial cells (specifically identified by their keratin content) contained thymic hormones (thymulin and thymosin alpha 1), a finding corroborated by the observation of elevated thymulin serum levels. In contrast with normal or hyperplastic thymuses, thymoma epithelial cells did not express HLA-DR and HLA-DC antigens as assessed by immunofluorescence as well as immunoblot analyses. Conversely, MHC class I antigens (HLA-ABC) were normally expressed. Thus, we conclude that thymoma epithelial cells are endocrinologically active but are defective for the expression of some MHC products (class II molecules) known to play an essential role in intrathymic T cell differentiation.

Adult↗
PubMed1985

Anti-islet cellular and humoral immunity, T-cell subsets, and thymic function in type I diabetes.

UNLABELLED: Peripheral lymphocyte subsets were enumerated, using OKT monoclonal sera, in 56 diabetic (43 adults and 13 children) and 20 control subjects. Concomitantly, anti-islet humoral and cellular immunity was tested in vitro and serum thymulin level was measured. In the newly diagnosed patients (less than 30 days; 18 cases), the percent of OKT4+ and OKT8+ cells was reduced, the OKT8+ depletion being particularly pronounced in children. Tests for cellular immunity were positive in 83% of the newly diagnosed diabetic subjects and anti-islet cytotoxic antibodies were detected in 50%. The serum thymulin level was decreased in 2 children. Later on in the course of the disease, a marked reduction in OKT3+, OKT4+, and OKT8+ cell percentage was observed, the mean OKT4/OKT8 ratio being normal or lower than normal. The percent of antibody-positive sera rose to 64%, while anti-islet cellular immunity was detectable in 54%. When extrapancreatic manifestations of probable autoimmune nature were present, anti-islet cellular immunity was detected in 100% of cases, accompanied by cytotoxic antibodies in 54%. CONCLUSIONS: (1) the magnitude of T-cell depletion and/or imbalance in diabetic subjects depended mainly on the duration of the disease, (2) anti-islet cellular immunity was the anomaly most frequently detectable, and (3) a decrease in serum thymulin level was infrequently detected.

Adolescent↗
PubMed1985

The wasted mutant mouse. I. An animal model of secretory IgA deficiency with normal serum IgA.

The wasted (wst) mutation was recently described as a spontaneous, recessive mutation leading to pathologic changes affecting both the neurologic and the immune systems of wst/wst homozygotes, which presented symptoms analogous to those observed in patients with ataxia-telangiectasia (A.T.). We studied the IgA system of wst/wst mutants and their normal littermates to determine whether IgA deficiency commonly found in A.T. patients was also affecting these mutants. Interestingly, although IgA plasma cells were totally absent from their entire (small and large) intestine, their serum contained a normal level of IgA with a normal ratio of monomeric vs polymeric IgA. The absence of gut IgA plasma cells was not due to malnutrition and was not compensated by the appearance of cells secreting any other isotypes. Studies at the precursor cell level showed the absence of IgA-specific B cell precursors in the Peyer's patches, whereas sIgA B cells and IgA plasma cells were found in normal numbers in the spleen of wasted mice. These data suggest that secretory and serum IgA may comprise distinct systems and that the wasted mutant mouse is a potential model for the study of the physiology and regulation of IgA production.

Animals↗