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Biomedical subjects

M Harigai

Publications and source records attributed to M Harigai.

66 records · Page 4Linked to original sources
PubMed1989

Heterogeneity of B cell responsiveness to interleukin 4, interleukin 6 and low molecular weight B cell growth factor in discrete stages of B cell activation in patients with systemic lupus erythematosus.

To investigate the differential stages of B cell activation in patients with systemic lupus erythematosus (SLE), the effects of recombinant interleukin-4 (rIL-4) interleukin-6 (rIL-6), and low mol. wt BCGF (1-BCGF) on B cell proliferation and differentiation were evaluated. In a co-stimulatory assay with anti-IgM, proliferative response to rIL-4 and 1-BCGF showed no significant differences between SLE patients and healthy controls. In a restimulation assay, after pre-activation with anti-IgM for 3 days, proliferative response to rIL-4 and 1-BCGF was significantly decreased in SLE patients compared with normal healthy controls (P less than 0.01). With regard to rIL-6 induced B cell differentiation, SAC-pre-activated low density, large B cells from both SLE patients and healthy controls differentiated well, whereas high density B cells did not differentiate at all. Of particular interest, low density B cells from active patients directly differentiated into Ig secreting cells in response to rIL-6 without SAC activation. These data indicate that heterogeneity of B cell responsiveness to B cell-tropic interleukins resulted from the discrete stages of B cell activation in SLE.

Adult↗
PubMed1988

Production of B cell stimulatory factor-2/interleukin-6 activity by human endothelial cells.

The effect of culture supernatants of endothelial cell (EC) lines on the immunoglobulin-M(IgM) synthesis by human B cell line, SKW6-CL4 cells, was investigated. Supernatants of human EC stimulated IgM synthesis, as high as 6-fold, but supernatants of bovine EC did not. This enhancing activity was completely blocked by addition of anti-human B cell stimulatory factor-2/interleukin-6 (BSF-2/IL-6) antibody. These data suggest that human EC might participate in the human antibody production system by producing soluble factor, BSF-2/IL-6.

Animals↗
PubMed1988

Stimulatory effect of CD5 antibody on B cells from patients with rheumatoid arthritis.

In order to clarify the role of CD5 antigen on B cell in autoimmunity, we examined B cells from patients with rheumatoid arthritis (RA). The percentages of CD5 positive B cells were increased in peripheral blood from RA compared with normal. Normal and RA B cells were stimulated with two kinds of monoclonal antibodies to CD5 (Leu-1, SL-1) which recognize different epitopes. RA B cells proliferated and secreted IgM by CD5 antibody stimulation in combination with IL-1. Our observations imply that CD5 positive B cells in RA are in their differentiation stage and that CD5 antigen might be one of the triggers to activate CD5 positive B cells in vivo to produce autoantibody.

Adjuvants, Immunologic↗
PubMed1988

Rheumatoid adherent synovial cells produce B cell differentiation factor activity neutralizable by antibody to B cell stimulatory factor-2/interleukin 6.

B cell differentiation factor (BCDF) activity assayed on SKW6-CL4 cells was found in adherent synovial cell (ASC) conditioned medium. ASC of patients with RA (n = 8) produced significantly larger amounts of BCDF than those of patients with osteoarthritis (n = 5) (219.0 +/- 212.1 vs 25.5 +/- 12.4 units/microgram.DNA, p less than 0.01). ASC clones, established by the limiting dilution technique, also produced this factor. Experiments with several neutralizing antibodies revealed that this BCDF is inhibited by anti-B cell stimulatory factor-2/interleukin 6 antibody (anti-BSF-2/IL-6 ab) up to 90%, but not by antiinterleukin 1, antiinterleukin 2 or antiinterferon-r antibodies. Our data suggest that ASC could participate in the B cell differentiation process in joint space by producing a molecule which has a similar active site to BSF-2/IL-6.

Aged↗
PubMed1987

Inhibitory effect of human recombinant interleukin-1 alpha and beta on growth of human vascular endothelial cells.

Endothelial cell growth factor (ECGF) is a potent polypeptide mitogen which stimulates the growth of endothelial cells. The mitogenic effect of ECGF was inhibited by addition of recombinant interleukin-1 (rIL-1) alpha or beta in a concentration dependent manner. The morphological change was not observed distinctly. In the condition without ECGF, both types of rIL-1 enhanced [3H]-thymidine uptake slightly, but failed to increase cell numbers. These data suggest the possibility that the effect of rIL-1 on EC is modulated by the presence of ECGF.

Cell Division↗
PubMed1987

Differential abnormality in cell-cycle stage of peripheral B cells from patients with systemic lupus erythematosus.

In order to clarify the stage of abnormal activation of systemic lupus erythematosus (SLE) B cells, we investigated the cell-cycle phase of SLE B cells by flow-cytometric analysis. This study uses the simultaneous flow-cytometric analysis of cellular DNA content and incorporated bromodeoxyuridine, an analogue of thymidine, as indicators for DNA synthesis to detect activated B cells in peripheral blood of patients with SLE. In active SLE, the percentage of B cells increased in the S and G2M phase and decreased in the G0G1 phase as compared with normal control subjects. In inactive SLE, the percentage of B cells in the S phase also increased. Active SLE B cells did not progress through the cell cycle with the stimulation of anti-IgM plus PMA or SAC plus BSF, although normal B cells transit into S and G2M phase with such stimulation. These data suggest that SLE B cells are already activated and shifted to a matured state and that for this reason the B cells were poorly responsive to mitogen.

Adolescent↗
PubMed1987

Production of thymocyte-stimulating activity by cultured human thyroid epithelial cells.

Since thyroid follicular epithelial cells (thyrocytes) have been shown to express a number of functions similar to monocytes, they were further examined for their potency in secreting thymocyte-stimulating activity (TSA). Although spontaneous production of TSA could not be detected when thyrocytes were cultured in the culture medium, TSA was demonstrated in the culture supernatants after stimulation with the immune adjuvant lentinan. The release of TSA was found in the culture supernatants collected 24 h after stimulation and was maintained for the 4 days of culture. Maximum levels of TSA release were achieved by 2 days. In addition, when culture supernatants of thyrocytes stimulated with lentinan or monocyte-derived interleukin 1 (IL-1) were incubated with a rabbit antibody to human IL-1, a parallel reduction in TSA was observed, suggesting that the active product in the thyrocyte culture supernatant shared a common antigenic site with IL-1. The demonstration of the production of IL-1 like activity by thyrocytes provides additional evidence that these cells, in addition to their functions as endocrine cells, may also participate in the local immune responses under appropriate conditions.

Animals↗
PubMed1987

Synovial fluids from patients with rheumatoid arthritis possessed B cell differentiation activity contributing to synthesis of rheumatoid factor in vitro.

B cell differentiation activity assayed on B cells preactivated by Staphylococcus aureus Cowan I was found in synovial fluids (SF) of patients with rheumatoid arthritis (RA) (n = 14), while little, if any, activity was found in SF of patients without RA (n = 13) including patients with osteoarthritis and traumatic arthritis. There was a positive correlation between the RA hemagglutination assay titer and B cell differentiation activity (r = 0.7438). This molecule with molecular weight ranges 15-20 kDa as well as supernatant from phytohemaglutinin stimulated normal T cells could promote not only polyvalent immunoglobulin synthesis but also rheumatoid factor synthesis by lymphocytes from patients with RA in vitro, and was considered to be distinct from interleukin-1, interleukin-2, interferon r, or proteolytic lysosomal enzymes which have been shown to modulate B cell activation.

Arthritis, Rheumatoid↗
PubMed1986

Measurement of spontaneous and stimulated anti-microsomal antibody synthesis in vitro by avidin-biotin enzyme immunoassay.

The spontaneous and stimulated anti-microsomal (anti-Mic) antibody synthesis in vitro by peripheral blood lymphocytes (PBL) from patients with Hashimoto's thyroiditis (HT) was studied by a highly sensitive and thyroid microsome-specific enzyme immunoassay using an avidin-biotin system (A-B EIA). Since the amount of the synthesized anti-Mic antibody by PBL in vitro is very small, it is difficult to study its kinetics and response to mitogens or the specific antigen by conventional assay systems. We applied the avidin-biotin system to conventional indirect EIA and established an assay system which was about four times as sensitive as indirect EIA. PBL from patients with HT synthesized significant amount of IgG anti-Mic antibody spontaneously but those from normal individuals and patients with rheumatoid arthritis did not. IgG anti-Mic antibody synthesis with pokeweed mitogen stimulation was increased in all HT patients and that with thyroid microsome stimulation was increased in three out of five patients. These results indicate that A-B EIA is a useful system to study the mechanism of anti-Mic antibody synthesis in vitro.

Animals↗
PubMed1986

Analysis of thyroglobulin antibody synthesis by cultured peripheral blood lymphocytes from patients with Hashimoto's thyroiditis using biotin-avidin solid phase enzyme immuno-assay.

The influence of bovine thyroglobulin (Tg) and/or staphylococcus aureus cowan I (SAC) on Tg antibody synthesis has been studied using cultures of 8 Hashimoto's and 5 normal peripheral blood lymphocytes (PBL). The detection of Tg antibody in the culture supernatants was performed by sensitive biotin-avidin solid phase enzyme immunoassay. By using this technique, we were able to detect small amounts of Tg antibody synthesized by cultured Hashimoto's PBL responsive to bovine Tg and/or SAC; PBL from three out of eight patients produced increased levels of Tg antibody in the presence of 0.02 microgram/ml bovine Tg. On the other hand, PBL from two other cases among them which were unresponsive to bovine Tg alone became responsive to bovine Tg following simultaneous stimulation with SAC. PBL from the other three cases failed to respond to bovine Tg or simultaneous stimulation with bovine Tg and SAC. The former five patients had serum Tg tanned red cell hemagglutination (TGHA) titers greater than 1:409,600 except in one case and the latter had serum TGHA titers less than 1:12,800. These results indicated the presence of the different functional stages of B cells to produce Tg antibody in the circulation of Hashimoto's patients and suggested that sufficient number of lymphocytes responsive to bovine Tg are present in the circulation of Hashimoto's patients with high titers of serum TGHA.

Adult↗