M Sato

Kurume University, Куруме, Fukuoka, Japan

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Publications (7)15.42 Total impact

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    ABSTRACT: We used flow cytometry to investigate the effects of nicotinamide, an inhibitor of poly (ADP ribose) synthetase, on the cell-surface expression of cytokine-induced human leukocyte antigen (HLA)-A,B,C antigen, HLA-DR antigen, intercellular adhesion molecule 1, CD44, and Fas expression in cultured orbital fibroblasts from patients with thyroid-associated ophthalmopathy. After two to seven passages, cultured orbital fibroblasts were incubated for 3 days with interferon gamma or tumor necrosis factor alpha in the presence of nicotinamide. Nicotinamide inhibited the induction of both HLA-DR and intercellular adhesion molecule 1 expression by cytokines on fibroblasts but did not interfere with induction of HLA-A,B,C, or CD44 expression. Nicotinamide also inhibited the proliferation of orbital fibroblasts, as assessed by a [3H]-thymidine incorporation assay and cell counts. Nicotinamide also enhanced the expression of the apoptosis-mediating protein Fas on fibroblasts. Our data suggest that nicotinamide inhibits cytokine-induced activation of fibroblasts and thus may decrease the autoimmune injury to the orbit in thyroid-associated ophthalmopathy.
    Journal of Clinical Endocrinology &amp Metabolism 02/1998; 83(1):121-4. DOI:10.1210/jcem.83.1.4478 · 6.31 Impact Factor
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    ABSTRACT: The effect of FK506, an immunosuppressive agent, on phytohemagglutinin (PHA) or interferon gamma (IFN gamma)-induced intercellular adhesion molecule-1 (ICAM-1) expression on cultured human thyroid cells from patients with Graves' disease was investigated. Primary cultured thyroid cells were incubated for three days with IFN gamma (10 to 800 U/ml) or PHA (1 to 50 micrograms/ml) in the presence of FK506. The surface expression of ICAM-1 was measured by flow cytometry. In some experiments, polyclonal anti-IFN gamma antibody was added to the culture to determine whether ICAM-1 expression was blocked. FK506 inhibited the PHA-induced ICAM-1 expression in thyroid cells, but not the induction by IFN gamma. PHA-induced ICAM-1 expression was not inhibited by the polyclonal anti-IFN gamma antibody. FK506 did not affect the proliferation of thyroid cells. This data indicates that the inhibitory effect of FK506 on ICAM-1 expression in primary cultured thyroid cells may be due to actions on infiltrating lymphocytes in the thyroid gland. Further studies are necessary to elucidate whether the inhibition of ICAM-1 by FK506 results in the suppression of autoimmune reactions in the thyroid gland.
    The Kurume Medical Journal 02/1994; 41(2):73-9. DOI:10.2739/kurumemedj.41.73
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    ABSTRACT: We investigated the effects of FK506, a novel immunosuppressive agent, on the phytohemagglutinin (PHA) or interferon-gamma (IFN-gamma)-induced expression of HLA-DR antigen, accessory cell function and proliferation of primary cultured human thyroid cells. Primary cultured thyroid cells from patients with Graves' disease were incubated for 3 days with PHA in concentrations in the range 1-50 mg/l or with 200 kU/l of IFN-gamma, in the presence or absence of FK506. The surface expression of HLA-DR antigen was measured by flow cytometry. Accessory cell function of thyroid cells was assessed by the incorporation of [3H]thymidine to T cells in the presence of 0.1-1.0 micrograms/l staphylococcus enterotoxin B (SEB). The proliferation of thyroid cells was determined from [3H]thymidine incorporation assays. FK506 inhibited the induction of HLA-DR antigen expression by PHA on thyroid cells in a dose-dependent manner, but did not inhibit that by IFN-gamma. Polyclonal anti-IFN-gamma antibody partly inhibited the PHA-induced HLA-DR antigen expression on thyroid cells. Phytohemagglutinin enhanced the SEB-mediated accessory cell function of thyroid cells. FK506 inhibited the accessory cell function induced by PHA. FK506 alone did not directly affect the thyroid cell proliferation, although it ameliorated the thyroid cell growth suppressed by PHA. Our data suggest that FK506 suppresses the HLA-DR antigen expression induced by PHA and the subsequent accessory cell function on thyroid cells via the inhibition of T lymphocytes present in the primary culture.
    Acta endocrinologica 01/1994; 129(6):579-84. DOI:10.1530/acta.0.1290579
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    ABSTRACT: We investigated the effects of nicotinamide and 3-aminobenzamide (3-AB), inhibitors of poly (ADP ribose) synthetase, on phytohaemagglutinin (PHA)- or interferon-gamma (IFN-gamma)-induced intercellular adhesion molecule-1 (ICAM-1) expression on cultured thyroid cells from patients with Graves' disease. Primary cultured thyroid cells were incubated for 3 days with IFN-gamma (10-800 U/ml) or PHA (1-50 micrograms/ml) in the presence of nicotinamide, 3-AB, superoxide dismutase or catalase. The surface expression of ICAM-1 was measured by flow cytometry. Nicotinamide and 3-AB dose-dependently inhibited the induction of ICAM-1 expression by IFN-gamma or PHA on thyroid cells. Neither catalase nor superoxide dismutase, which are free-radical scavengers, inhibited the expression of ICAM-1 on thyroid cells. Our data suggest that the mechanism of the suppression of ICAM-1 expression on thyroid cells by nicotinamide is not likely to be due to the free radical scavenging. Further studies are indicated to elucidate whether the inhibition of ICAM-1 by these drugs may result in the suppression of autoimmune reaction in the thyroid gland.
    Immunology 11/1993; 80(2):330-2. · 3.74 Impact Factor
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    ABSTRACT: To investigate the efficacy of intravenous methylprednisolone pulse therapy on Graves' ophthalmopathy (GO), fifteen patients with severe GO were treated with large dose intravenous methylprednisolone (at a daily dosage of 1 g for 3 successive days). This treatment was repeated 3-5 times for 3-5 weeks. They were monitored before, 2 weeks after and 6 months after therapy by ophthalmological assessment, orbital magnetic resonance imaging (MRI), and by measuring serum antibodies to rat eye muscle (EMAB) in an enzyme linked immunosorbent assay and peripheral blood lymphocyte subsets by flow cytometry. Diplopia and periorbital edema markedly improved after treatment in 9 patients. Mean proptosis values and intraocular pressure measurements significantly decreased after pulse therapy. In 12 patients enlarged eye muscles significantly reduced in size after treatment, as determined by MRI. The overall ophthalmopathy index was improved from 4.8 +/- 2.4 to 2.5 +/- 1.6 at the end of pulse therapy (P < 0.01) and 2.4 +/- 1.5 six months after therapy (P < 0.01). Serum EMAB were detected in 8 out of 10 patients tested and their level significantly decreased after pulse therapy (from 3.3 +/- 1.4 to 2.5 +/- 1.2, P < 0.01). A significant increase in peripheral blood CD4+CD45RA+ cells was observed after pulse therapy. Increased numbers of CD11-CD8+ cells and decreased numbers of CD11+CD8++ cells were found prior to treatment and were normalized after pulse therapy. Our study indicates that methylprednisolone pulse therapy can be considered as a choice for the treatment of GO. The improvement in eye muscle involvement in these patients may be due to the effects of infused methylprednisolone on both humoral and cellular immune functions.
    Endocrine Journal 02/1993; 40(1):63-72. DOI:10.1507/endocrj.40.63 · 2.02 Impact Factor
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    ABSTRACT: We report the case of a 70-year-old man who developed hypothyroidism associated with TSH receptor antibodies and severe ophthalmopathy during lithium therapy. He had received lithium therapy for more than 20 years for manic depression, when ophthalmopathy (class VI of the American Thyroid Association classification) and mild hypothyroidism developed. Orbital magnetic resonance imaging indicated marked enlargement of the superior, medial and inferior rectus muscles in the left eye. He had anti-eye muscle antibodies in his serum, detected by Western blotting and quantified by chromatoscanning, as well as anti-TSH receptor antibodies. He was treated with supplementation of levothyroxine and four cycles of methylprednisolone pulse therapy. After the pulse therapy, both anti-eye muscle antibodies and anti-TSH receptor antibodies decreased and disappeared in parallel with the improvement in eye symptoms and signs. These observations suggest the importance of anti-eye muscle antibodies as clinical markers in the development of thyroid-associated ophthalmopathy.
    Endocrinologia japonica 01/1993; 39(6):593-600. DOI:10.1507/endocrj1954.39.593
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    ABSTRACT: We wished to investigate the effects of nicotinamide and 3-aminobenzamide, well known as inhibitors of poly(ADP ribose) synthetase, on interferon-gamma-induced HLA-DR antigen expression using cultured human thyroid cells from patients with Graves' disease. Cultured thyroid cells were incubated for 3 days with 10-400 U/ml of interferon gamma in the presence of nicotinamide, 3-aminobenzamide, superoxide dismutase or catalase. The surface expression of HLA-DR and HLA-A, B, C antigen was measured by flow cytometry. Nicotinamide and 3-aminobenzamide dose-dependently inhibited the induction of HLA-DR antigen expression by interferon gamma, but not HLA-A, B, C antigen expression on cultured thyroid cells. Neither catalase nor superoxide dismutase, which are free-radical scavengers, inhibited the expression of HLA antigens on thyroid cells. Our data suggest that inhibitors of poly(ADP ribose) synthetase may have differential effects on interferon-gamma-induced HLA-DR and HLA-A, B, C antigen expression, and suppress the autoimmune reactions associated with autoimmune thyroid disorders via the reduction of HLA-DR antigen expression on thyroid cells. The mechanism of the suppression of HLA-DR antigen expression is unlikely to be due to the free radical scavenging.
    Clinical Endocrinology 02/1992; 36(1):91-5. · 3.35 Impact Factor