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Biomedical subjects

M Fischbach

Publications and source records attributed to M Fischbach.

At least 109 records · Page 6Linked to original sources
PubMed1987

Interleukin 2, T cell receptor and sex hormone studies in autoimmune mice.

Systemic lupus erythematosus (SLE) is a disease of immune dysregulation in which B cell hyperactivity and T cell deficiency are important characteristics. Sex factors also play a major role in the pathogenesis based on the physiologic effects of estrogen in promoting immunologic hyperactivity. Our findings suggest that a posttranscriptional mechanism is responsible for the functional interleukin 2 (IL-2) defect since transcription of the IL-2 message occurs after mitogenic stimulation. The proliferating cell in the MRL/lpr mouse model of lupus may be an immature T cell. The T cell receptor in these mice has a lower molecular weight than normal. This aberrant T cell receptor might be explained by a defect in glycosylation. The administration of estrogen to pregnant mice late in gestation results in offspring with a permanently altered immune system. These mice develop features of autoimmunity similar to those that occur spontaneously in genetically susceptible autoimmune mice. This phenomenon may have etiopathological significance for familial SLE.

Animals↗
PubMed1986

Altered K+ channel expression in abnormal T lymphocytes from mice with the lpr gene mutation.

The observation that voltage-dependent K+ channels are required for activation of human T lymphocytes suggests that pathological conditions involving abnormal mitogen responses might be reflected in ion channel abnormalities. Gigaohm seal techniques were used to study T cells from MRL/MpJ-lpr/lpr mice; these mice develop generalized lymphoproliferation of functionally and phenotypically abnormal T cells and a disease resembling human systemic lupus erythematosus. The number and predominant type of K+ channels in T cells from these mice differ dramatically from those in T cells from control strains and a congenic strain lacking the lpr gene locus. Thus an abnormal pattern of ion channel expression has now been associated with a genetic defect in cells of the immune system.

Animals↗
PubMed1985

Monoclonal anti-poly(rA) hybridoma antibodies from an autoimmune MRL/MpJ-lpr/lpr mouse.

Three B cell hybridomas were produced by the fusion of spleen cells from a 5 month old MRL/Mp-lpr/lpr mouse with the myeloma cell line, NS-1. By competitive inhibition, all three monoclonal antibodies (MoAb) were specific for poly(rA) and were inhibited to a lesser extent by dDNA, nDNA, poly(rI) and poly(rC). Moreover, the three MoAb were not inhibited by mononucleosides and the nucleotide, ATP. Competitive inhibition, using poly(rA) of defined lengths, showed that the recognition site among the MoAb varied, one demonstrating binding of poly(rA) as small as two bases in length. This study suggests that the spontaneous autoimmune repertoire to poly(rA) is restricted as compared to other monoclonal autoantibodies to nucleic acids, but contains within itself microheterogeneity.

Animals↗
PubMed1985

Ability of isoprinosine to restore interleukin-2 production and T cell proliferation in autoimmune mice.

Autoimmune mice bearing the single autosomal recessive gene 1pr are unable to produce the T cell growth factor, interleukin-2 (IL-2). A physiological consequence of this defect is the inability of T cells from C57B1/6J-lpr/lpr mice to respond to antigen presented by macrophages. In an attempt to reverse these abnormalities, we administered the inosine containing drug isoprinosine. Injection of isoprinosine after antigen immunization restored both antigen presentation and IL-2 production.

Aging↗
PubMed1985

Interleukin-2 in rheumatoid arthritis: production of and response to interleukin-2 in rheumatoid synovial fluid, synovial tissue and peripheral blood.

Several aspects of interleukin-2 (IL-2) generation and function were studied employing mononuclear cells from synovial fluid (SF), synovial tissue (ST) and peripheral blood (PB) of patients with rheumatoid arthritis (RA). Decreased PHA stimulated IL-2 production by lymphocytes from rheumatoid ST, SF (P less than 0.02), and PB (P less than 0.01) was observed when compared to normal blood and SF of patients with gout. The proliferative response of rheumatoid lymphocyte blasts exposed to exogenous IL-2 was also defective (P less than 0.05-0.001). This defect was greater in SF than in rheumatoid PB (P less than 0.05-0.001). In addition to the proliferative response, the effect of IL-2 on interferon-gamma (IFN-gamma) production was also examined. Rheumatoid lymphocytes from both PB and SF produced less IFN-gamma after overnight treatment with IL-2 than did normal PB lymphocytes. This decreased IFN-gamma induction was discordant with the excellent enhancement by IL-2 of natural killer activity. Removal of adherent cells in synovial fluid did not correct this deficit. Abnormalities in the biology of IL-2 and IFN-gamma suggest that impaired T cell function could contribute to the immunopathogenesis of RA.

Adult↗
PubMed1985

Anti-idiotypic antiserum to monoclonal anti-Sm inhibits the autoantigen-induced proliferative response.

Anti-idiotypic sera were produced in BALB/c mice against three established monoclonal anti-Sm antibodies. Inhibition assays showed that the anti-idiotypic antibodies recognized determinants that were present on all three monoclonal antibodies but not on normal mouse IgG from unimmunized BALB/c mice or myeloma proteins. Normal (+/+) and autoimmune (lpr/lpr) MRL/MpJ or C3H/HeJ mice were immunized with Sm in complete Freund's adjuvant. Immune T cells from the draining lymph nodes proliferated in response to the addition of Sm in vitro. Anti-idiotypic serum added to these cultures inhibited the proliferative response by 50 to 70%, whereas normal BALB/c serum had no effect. This inhibition of proliferation was antigen specific, because the anti-idiotypic serum did not inhibit the T cell proliferative response to an irrelevant antigen, TNP-KLH, or ovalbumin. Kinetic studies showed that the anti-idiotypic serum inhibited an early event in antigen-induced proliferative response, because the addition of serum late in culture did not cause any significant reduction in proliferation. The reduced proliferative response was due to direct action of the anti-idiotypic serum on the Lyt-1+, 2- T cell population.

Animals↗
PubMed1984

Characterization of the defective autologous mixed lymphocyte response in rheumatoid arthritis.

In order to characterize the autologous mixed lymphocyte response (AMLR) in patients with rheumatoid arthritis (RA) and to define the relationship with disease activity, peripheral blood T lymphocytes were stimulated with either a B lymphocyte-enriched (B cells) or a macrophage-enriched (macrophages) population. A significant reduction (P less than 0.01 to P less than 0.001) of T cell proliferation stimulated both by B cells and macrophages was observed in patients with active disease. The B lymphocytes were significantly less stimulatory (P less than 0.02 to P less than 0.001) than macrophages in the patients compared with the controls. In the normal controls, macrophages in higher concentrations were capable of suppressing the B lymphocyte-stimulated AMLR, but macrophages from patients with RA were not excessively suppressive. A significant association (P less than 0.02) was observed between disease activity and the AMLR. Using the B-enriched population, the AMLR proliferative response was significantly associated (P less than 0.001) with the production of interleukin-2. Defects in proliferation could only be partially restored by the addition of interleukin-2. These data indicate that the defective AMLR observed in patients with RA is related to disease activity and is associated with altered cellular interactions among T lymphocytes, macrophages, and the B lymphocyte-enriched population.

Arthritis, Rheumatoid↗
PubMed1984

Time course study of L-tyrosine aminotransferase induction in rat liver cell lines.

The enhancement of L-tyrosine aminotransferase activity by dexamethasone, an exclusive function of the liver, was serially measured at different passages of eight rat liver epithelial cell lines initiated and continuously grown in either a serum-supplemented medium or a serum-free medium. The enzyme basal activity was found to be 5.4 +/- 1.8 mU for cell lines in serum and 6.8 +/- 3.4 mU for cell lines without serum. Under the influence of dexamethasone (10(-6) mol/l for 5 hours) this basal level could be increased up to 2.9 fold in the presence of serum and 2.5 fold in its absence when investigations were carried out at early passages. During the following subcultures the induction ratio gradually declined and scarcely any induction could be detected after the 15th passage for cells grown in serum and after the 25th passage for cell lines grown without serum.

Animals↗