著者

Keiko Nagata Kazuhiko Hayashi Keisuke Kumata Yukio Satoh Mitsuhiko Osaki Yuji Nakayama Satoshi Kuwamoto Yoshinori Ichihara Tsuyoshi Okura Kazuhiko Matsuzawa Junichiro Miake Shuji Fukata Takeshi Imamura

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ22-0609, (Released:2023-03-10)

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Epstein-Barr virus (EBV) is a human herpes virus that latently infects B lymphocytes. When EBV is reactivated, host B cells differentiate into plasma cells and produce IgM-dominant antibodies as well as many progeny virions. The aims of the present study were to confirm the IgM dominance of thyrotropin-receptor antibodies (TRAbs) produced by EBV reactivation and investigate the roles of TRAb-IgM in Graves’ disease. Peripheral blood mononuclear cells (PBMCs) containing TRAb-producing cells were stimulated for EBV reactivation, and TRAb-IgM and TRAb-IgG were measured by ELISA. TRAb-IgM were purified and TSH-binding inhibitory activities were assessed using a radio-receptor assay. Porcine thyroid follicular epithelial cells were cultured with TRAb-IgM and/or complements to measure the intracellular levels of cAMP and the amount of LDH released. TRAb-IgM/TRAb-IgG (the MG ratio) was examined in sequential serum samples of Graves’ disease and compared among groups of thyroid function. The results obtained showed that IgM-dominant TRAb production was induced by EBV reactivation. TRAb-IgM did not inhibit TSH binding to TSH receptors and did not transduce hormone-producing signals. However, it destroyed thyroid follicular epithelial cells with complements. The MG ratio was significantly higher in samples of hyperthyroidism or hypothyroidism than in those with normal function or in healthy controls. A close relationship was observed between TRAb-IgM produced by EBV reactivation and the development and exacerbation of Graves’ disease. The present results provide novel insights for the development of prophylaxis and therapeutics for Graves’ disease.

著者

Takeshi IMAMURA

出版者

Japanische Gesellschaft für Germanistik

雑誌

Neue Beiträge zur Germanistik (ISSN:24330906)

巻号頁・発行日

vol.114, pp.160-236, 2003 (Released:2018-03-31)

著者

今村 武史 イマムラ タケシ Takeshi IMAMURA

出版者

総合研究大学院大学

巻号頁・発行日

2018-03-23

著者

Tomio Okamura Masashi Tawa Ayman Geddawy Takashi Shimosato Hirotaka Iwasaki Haruo Shintaku Yuichi Yoshida Masahiro Masada Kazuya Shinozaki Takeshi Imamura

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.124, no.1, pp.76-85, 2014-01-20 (Released:2014-01-18)

参考文献数

41

被引用文献数

10 21

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Deficiency of tetrahydrobiopterin (BH4) in the vascular tissue contributes to endothelial dysfunction through reduced eNOS activity and increased superoxide anion (O2−) generation in the insulin-resistant state. We investigated the effects of atorvastatin, a 3-hydroxyl-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor; amlodipine, a calcium antagonist; and their combination on blood pressure, arterial relaxation and contraction, and vascular oxidative stress in aortas of high fructose–fed rats. Oral administration of atorvastatin for 8 weeks did not significantly lower blood pressure, but normalized angiotensin II–induced vasoconstriction and endothelial function in the fructose-fed rats. Atorvastatin treatment of fructose-fed rats increased vascular BH4 content, which was associated with an increase in endothelial NO synthase activity as well as a reduction in endothelial O2− production. On the other hand, administration of amlodipine did not affect the angiotensin II–induced vasoconstriction and endothelial function, but normalized the elevated blood pressure in the fructose-fed rats. The combined treatment did not show synergistic but additive beneficial effects. The present study suggests that combined therapy of HMG-CoA reductase inhibitors and calcium antagonists prevents functional vascular disorders in the insulin-resistant state, possibly resulting in the protection against or delay of development of hypertension, vascular dysfunction in diabetes, and thereafter atherosclerosis.