1989 Fiscal Year Annual Research Report

遺伝子レベルにおけるバセドウ病の成因の解明

Research Project

Project/Area Number	63480272
Research Institution	Nagasaki University
Principal Investigator	長瀧重信長崎大学, 医学部, 教授 (70010311)
Co-Investigator(Kenkyū-buntansha)	山下俊一長崎大学, 医学部, 助手 (30200679) 和泉元衛長崎大学, 医学部, 助教授 (80039552)
Keywords	バセドウ病 / 成因 / サイトカイン / 遺伝子
Research Abstract	自己免疾患であるバセドウ病の成因を明らかにする目的で、甲状腺特異遺伝子(ペルオキシダ-ゼ:TPO,サイログロブリン:Tg)さらにTSH受容体遺伝子の研究を行なった。マイクロゾ-ム抗原と考えられるTPO遺伝子の各種甲状腺疾患における疾患特異性はなく、バセドウ病甲状腺組織から得られた初代単層培養細胞を用いて実験した。サイトカインのうちインタ-フェロン(TFN)γはウイルス感染などにより誘導され甲状腺膜上に異所性自己抗原を発現させるが、同時に甲状腺ホルモンとサイログロブリン(Tg)の分泌を抑制する。この分子機構を明らかにする目的でペルオキシダ-ゼ(TPO)とTgcDNAを用いてそれらのnRNAレベルの検討を行なった。IFNーγはその濃度および時間依存性にTPOnRNA発現を抑制した。同様にインタ-ロイキン(IL)ー1α,β,ILーδ,腫瘍壊死因子(TNF)αを用いた場合も、TSHにより刺激誘導されるTPOmRNA,TgmRNAレベルを抑制した。とりわけILー1はTSHで刺激されるTgの転写活性を抑制した。これらサイトカイン受容体は甲状腺膜上に存在しその標的臓器の一つであることも証明された。さらにバセドウ病患者甲状腺およびリンパ球からDNAを抽出し、レトロウイルスの関与(とりこみ又はその相同性遺伝子の存在)を外来性にせよ内因性にせよgag-probeを用いて検討した。20例のバセドウ病患者中にはIFNγを誘導すると考えられるHIV-1 gag様の塩基配例は認められなかった。最近はTSH受容体遺伝子cDNAの塩基配例が決定され、その遺伝子を用いたバセドウ病の成因の解明についての研究も進行中である。

Research Products

(31 results)

All Other

All Publications (31 results)

[Publications] Y.Nagayama,M.Izumi and S.Nagataki: "The management of Hyperthyroidism Due to Graves' Disease in Japan in 1988" Endocrirol,Japan. 36. 299-314 (1989)
[Publications] Y.Kawabe,K.Eguchi,C.Shimomura,M.Mine,T.Otsubo,Y.Ueki,H.Tezuka,H.Nakao,A.Kawakami,K.Migita,S.Yamashita,M.Matsunaga,N,Ishikawa,K.Ito and S.Nagataki: "Interleukin-1 Production and Action in Thyroid Tissue" Journal of Clinical Endocrinology and Metabolism. 68. 1174-1183 (1989)
[Publications] H.Tamai,K.Kasagi,Y.Takaichi,J.Takamatsu,G.Komaki,S.Matsubayashi,J.Konishi,K.Kuma,L.F.Kumagai and S.Nagataki: "Development of Spontaneous Hypothyraidisn in Patients with Graves' Disease Treated with Antithyraidal Drugs:Clinical,Immunological,and Histological Findings in 26 Patients" Jounal of Clinical Endocrinology and Metabolism. 69. 49-53 (1989)
[Publications] Y.Nagayama,S.Yamashita,H.Hirayu,M.Izumi,T.Uga,N.Ishikawa,K.Ito and S.Nagataki: "Regulation of Thyroid Peroxidase and Thyrogbbulin Gere Expression by Thyrotropin in Cultcored Human Thyroid Cells" Journal of Clinical Endocrinology and Metabolism. 68. 1155-1159 (1989)
[Publications] K.Eguchi,Y.Ueki,C.Shimamura,T.Otsubo,H.Nakao,K.Migita,A.Kawakami,M.Matsunaga,H.Tezuka,N.Ishikawa,K.Ito and S.Nagataki: "Increment in the Tal^+ Cells in the Reripberal Blood and Thyroid Tissue of Patierts with Groves' Disease" Jounal of Immunology. 142. 4233-4240 (1989)
[Publications] Y.Nagayama,K.Ashizawa,K.Matuso,S.Inoue,S.Harakawa,H.Hirayu,S.Yamashita,M.Izumiand S.Nagataki: "Radioiodine(^<131>I)Therapy of Graves' diseas:Use of the New High Resolutional Ultrasonic Scanner for the Determinotion of the Accurate Weight of the Thyroid Gland" Endocrirol.Japon. 36. 359-365 (1989)
[Publications] S.Matsubayashi,H.Tamai,T.Morita,K.Mori,T.Katsuki,F.Matsuzuka,K.Kuma and S.Nagataki: "Malignant Lymphoma of the Thyroid and Epstein-Barr Virus" Endocrinol.Japan. 36. 343-349 (1989)
[Publications] S.Yamashita,H.Kimura,K.Ashizawa,Y.Nagayama,H.Hirayu,M.Izumi and S.Nagataki: "Interleukin-1 inhibits thyrotrophin-induced human thyroglobulin gene expression" Journal of Endocrinology. 122. 177-183 (1989)
[Publications] S.Nagataki,H.Hirayu,M.Izumi,S.Inoue,S.Okajima and K.Shimaoka: "High Prevalence of Thyroid Nodule in Area of Radioactive Falbut" The Larcet. 385-386 (1989)
[Publications] K.Ashizawa,S.Yamashita,T.Tobinaga,Y.Nagayama,H.Kimura,H.Hirayu,M.Izumi and S.Nagataki: "Inhibiton of human thyroid peroxidase gere expression by interleukin 1" Acta Erdocrinologica(Coperh). 121. 465-469 (1989)
[Publications] K.Ashizawa,S.Yamashita,H.Kimura,H.Hirayu,M.Izumi and S.Nagataki: "Interferon-r Inhibits Thyrotropin-induced Thyroidal Peroxidase Gere Expression In Cultured Human Thyrocytes" Journal of Clinical Encbcriolgy and Metabolism. 69. 475-477 (1989)
[Publications] S.Nagataki: "Highlight In The 4th Acta Meeting" Progress in Thyroidology. 5-8 (1989)
[Publications] K.Matsuo,S.Yamashita,M.Nina,M.Kurihara,K.Shigematus,S.Harakawa,M.Izumi,M.Ozaki and S.Nagataki: "Receptor Autoiadiographic Aralysis of Insulin-like Growth Factor I(IGF1)Binding Sites in Normal and Thyroidectomized Rats" Rrogress in Thyroidology. 227-230 (1989)
[Publications] K.Eshima,H.Hirayu,S.Harakawa,S.Yamashita,K.Ashizawa,K.Matsuo,Y.Nagayama,S.Inoue.T.Kiriyama,S.Morita,M.Izumi and S.Nagataki: "^<131>I Accumulation as a Good Progrostic Indicator and Sercun Thyroglobulin(Tg)Level as a Good Diagrostic Marker for Metastatic Thyroid Carciroma" Rrogress in Thyroidology. 541-544 (1989)
[Publications] Y.Ueki,K.Eguchi,T.Otsuba,Y.Kawabe,C.Shimomura,H.Tezuka,H.Nakao,A.Kawakami,K.Migita,N.Ishikawa,K.Ito and S.Nagataki: "Abnormal B Lymphocyte Fonction in Thyroid Glands from Patients with Graves' Disease" Jarnal of Clinical Endokrinology and Metabolism. 69. 939-945 (1989)
[Publications] K.Eguchi,A.Kawakami,K.Migita,H.Nagao,T.Otsubo,C.Shimamura,Y.Ueki,M.Matsunaga,N.Ishikawa,K.Ito and S.Nagataki: "The Autologous Mixed Lymphocyte Reaction in Five Identical Twins with Antoimmiure Thyroid Diseases" Rrogress in Thyroidology. 45-48 (1989)
[Publications] S.Yamashita,S.Morita,K.Ashizawa,K.Matsuo,K.Eishima,Y.Nagayama,S.Harakawa,S.Inoue,T.Kiriyama,H.Hirayu,M.Izumi and S.Nagataki: "Molecular Mechanism of Pituitary Cell Proliferation by Thyroid Humane" Rrogress in Thyroidology. 65-68 (1989)
[Publications] H.Tamai,K.Kasagi,G.Komaki,Y.Takaichi,J.Takamatsu,S.Matusbayashi,K.Kuma,J,Konishi and S.Nagataki: "Frequencies of Spontareous Hypothyroidism in Patients with Groves' Disease After Antithyroidal Drug Therapy" Rrogress in Thyroidology. 79-82 (1989)
[Publications] I.Otsubo,K.Eguchi,Y.Ueki,C.Shimomura,H.Nakao,K.Migita,A.Kawakami,M.Matsunaga,N.Ishikawa,K.Ito and S.Nagataki: "The Phenotypic Analysis of Activated T Cells in Thyroid Gland and Peripheral Blood From Patients with Graves' Disease" Progress in Thyroidology. 91-94 (1989)
[Publications] A.Kawakami,K.Eguchi,K.Migita,H.Nakao,T.Otsubo.C.Shimomura,Y.Ueki,M.Matsunaga,N.Ishikawa,K.Ito and S.Nagataki: "CD4^+ 2H4^+ T Cell Subset(Suppressor-Inducer T Cell)in Thyroid Tissue from Patients with Graves' Disease" Progress in Thyroidology. 95-98 (1989)
[Publications] C.Shimomura,K.Eguchi,T.Otsubo,Y.Ueki,H.Nakao,K.Migita,A.Kawakami,M.Matsunaga,N.Ishikawa,K.Ito and S.Nagataki: "Interferon-r Production of Intrathyroidal Gland Mononuclear Cells from Patients with Graves' Disease" Progress in Thyroidology. 103-106 (1989)
[Publications] K.Migita,K.Eguchi,H.Tezuka,T.Otsubo,A.Kawakami,H.Nakao,Y.Ueki,C.Shimomura,M.Matsunaga,N.Ishikawa,K.Ito and S.Nagataki: "Cytotoxic Activity of Interleukin-2 Activated Killer Cells Toward Thyroid Epithelial Cells." Progress in Thyroidology. 107-110 (1989)
[Publications] Y.Ueki,K.Eguchi,T.Otsubo,C.Shimomura,H.Nakao,A.Kawakami,K.Migita,N.Ishikawa,K.Ito,T.Yamaguchi and S.Nagataki: "B Cell Activation and Differentiation in Thyroid Glands from Patients with Graves' Disease" Progress in Thyroidology. 111-114 (1989)
[Publications] S.Harakawa,S.Yamashita,K.Ashizawa,K.Matsuo,K.Eshima,Y.Nagayama,S.Inoue,T.Kiriyama,S.Morita,H.Hirayu,M.Izumi and S.Nagataki: "Lew Iodine Diet Induces Thyroidal Proto-chcogere Expression" Progress in Thyroidology. 215-218 (1989)
[Publications] G.Komaki,H.Tomai,K.Kasagi,T.Morita,A.Hidaka,K.Kuma,J.Konishi and S.Nagataki: "Fellow-up Study of Euthyroid Relatives with Thyrotropin-binding Inhibitory Immunoglobulin(TB11)Who had Family History of Graves' Disease" Progress in Thyroidology. 387-390 (1989)
[Publications] T.Morita,H.Tamai,A.Oshima,G.Komaki,S.Fukata,S.Matsubayashi,K.Kuma,T.Nakagawa and S.Nagataki: "Changes of Thyroid Hormone,TSH,TBG and TG Concentrations After Suppressive Therapy in Nodular Goiter" Progress in Thyroidology. 503-506 (1989)
[Publications] S.Morita,K.Eishima,S.Iroue,S.Harakawa,S.Yamashita,H.Hirayu,M.Izumi and S.Nagataki: "The Thyroid Function and Analysis of Brain Computer Tomograms in Aged Subjects" Progress in Thyroidology. 557-559 (1989)
[Publications] S.Harakawa,S.Akazawa,M.Akazawa,M.Hashimoto,S.Yamashita,M.Izumi and S.Nagataki: "Changes of sercum thyraid hormone levels induce malformations on early embryogenesis in rats" Acta Endocrinologica. 121. 709-743 (1989)
[Publications] K.Matsuo,M.Niwa,M.Kunihara,K.Shigematsu,S.Yamashita,M.Ozaki and S.Nagataki: "Receptor Autoradiographic Aralysis of Ireulin-like Growth Factor I(IGF-1)Birding Sites in Rat Forebrain and Pititary Gland" Cellular and Molecular Neurobiology. 9. 357-367 (1989)
[Publications] S.Matsubayashi,H.Tawai,T.Morita,F.Matsuzaka,K.Kuma,T.Miyazaki,H.Matsumoto,S.Nagataki and R Volpe: "Possible Disolder of B-Cell-Related Surveillance and Malignant Lymphoma of the Thyroid" Cancer. 64. 2259-2261 (1989)
[Publications] K.Matsuo,S.Yamashita,M.Niwa,M.Kurihara,S.Harakawa,M.Izumi,S.Nagataki and S.Melwed: "Thyroid Hormone Regulates Rat Pituitary Insulin-like Growth Factor-I Receptors" Endocrirologe. 126. 550-554 (1989)

1989 Fiscal Year Annual Research Report

遺伝子レベルにおけるバセドウ病の成因の解明

Principal Investigator

長瀧 重信 長崎大学, 医学部, 教授 (70010311)

Research Products

[Publications] Y.Nagayama,M.Izumi and S.Nagataki: "The management of Hyperthyroidism Due to Graves' Disease in Japan in 1988" Endocrirol,Japan. 36. 299-314 (1989)

[Publications] Y.Kawabe,K.Eguchi,C.Shimomura,M.Mine,T.Otsubo,Y.Ueki,H.Tezuka,H.Nakao,A.Kawakami,K.Migita,S.Yamashita,M.Matsunaga,N,Ishikawa,K.Ito and S.Nagataki: "Interleukin-1 Production and Action in Thyroid Tissue" Journal of Clinical Endocrinology and Metabolism. 68. 1174-1183 (1989)

[Publications] Y.Nagayama,S.Yamashita,H.Hirayu,M.Izumi,T.Uga,N.Ishikawa,K.Ito and S.Nagataki: "Regulation of Thyroid Peroxidase and Thyrogbbulin Gere Expression by Thyrotropin in Cultcored Human Thyroid Cells" Journal of Clinical Endocrinology and Metabolism. 68. 1155-1159 (1989)

[Publications] K.Eguchi,Y.Ueki,C.Shimamura,T.Otsubo,H.Nakao,K.Migita,A.Kawakami,M.Matsunaga,H.Tezuka,N.Ishikawa,K.Ito and S.Nagataki: "Increment in the Tal^+ Cells in the Reripberal Blood and Thyroid Tissue of Patierts with Groves' Disease" Jounal of Immunology. 142. 4233-4240 (1989)

[Publications] S.Matsubayashi,H.Tamai,T.Morita,K.Mori,T.Katsuki,F.Matsuzuka,K.Kuma and S.Nagataki: "Malignant Lymphoma of the Thyroid and Epstein-Barr Virus" Endocrinol.Japan. 36. 343-349 (1989)

[Publications] S.Yamashita,H.Kimura,K.Ashizawa,Y.Nagayama,H.Hirayu,M.Izumi and S.Nagataki: "Interleukin-1 inhibits thyrotrophin-induced human thyroglobulin gene expression" Journal of Endocrinology. 122. 177-183 (1989)

[Publications] S.Nagataki,H.Hirayu,M.Izumi,S.Inoue,S.Okajima and K.Shimaoka: "High Prevalence of Thyroid Nodule in Area of Radioactive Falbut" The Larcet. 385-386 (1989)

[Publications] K.Ashizawa,S.Yamashita,T.Tobinaga,Y.Nagayama,H.Kimura,H.Hirayu,M.Izumi and S.Nagataki: "Inhibiton of human thyroid peroxidase gere expression by interleukin 1" Acta Erdocrinologica(Coperh). 121. 465-469 (1989)

[Publications] K.Ashizawa,S.Yamashita,H.Kimura,H.Hirayu,M.Izumi and S.Nagataki: "Interferon-r Inhibits Thyrotropin-induced Thyroidal Peroxidase Gere Expression In Cultured Human Thyrocytes" Journal of Clinical Encbcriolgy and Metabolism. 69. 475-477 (1989)

[Publications] S.Nagataki: "Highlight In The 4th Acta Meeting" Progress in Thyroidology. 5-8 (1989)

[Publications] K.Matsuo,S.Yamashita,M.Nina,M.Kurihara,K.Shigematus,S.Harakawa,M.Izumi,M.Ozaki and S.Nagataki: "Receptor Autoiadiographic Aralysis of Insulin-like Growth Factor I(IGF1)Binding Sites in Normal and Thyroidectomized Rats" Rrogress in Thyroidology. 227-230 (1989)

[Publications] Y.Ueki,K.Eguchi,T.Otsuba,Y.Kawabe,C.Shimomura,H.Tezuka,H.Nakao,A.Kawakami,K.Migita,N.Ishikawa,K.Ito and S.Nagataki: "Abnormal B Lymphocyte Fonction in Thyroid Glands from Patients with Graves' Disease" Jarnal of Clinical Endokrinology and Metabolism. 69. 939-945 (1989)

[Publications] K.Eguchi,A.Kawakami,K.Migita,H.Nagao,T.Otsubo,C.Shimamura,Y.Ueki,M.Matsunaga,N.Ishikawa,K.Ito and S.Nagataki: "The Autologous Mixed Lymphocyte Reaction in Five Identical Twins with Antoimmiure Thyroid Diseases" Rrogress in Thyroidology. 45-48 (1989)

[Publications] S.Yamashita,S.Morita,K.Ashizawa,K.Matsuo,K.Eishima,Y.Nagayama,S.Harakawa,S.Inoue,T.Kiriyama,H.Hirayu,M.Izumi and S.Nagataki: "Molecular Mechanism of Pituitary Cell Proliferation by Thyroid Humane" Rrogress in Thyroidology. 65-68 (1989)

[Publications] H.Tamai,K.Kasagi,G.Komaki,Y.Takaichi,J.Takamatsu,S.Matusbayashi,K.Kuma,J,Konishi and S.Nagataki: "Frequencies of Spontareous Hypothyroidism in Patients with Groves' Disease After Antithyroidal Drug Therapy" Rrogress in Thyroidology. 79-82 (1989)

[Publications] I.Otsubo,K.Eguchi,Y.Ueki,C.Shimomura,H.Nakao,K.Migita,A.Kawakami,M.Matsunaga,N.Ishikawa,K.Ito and S.Nagataki: "The Phenotypic Analysis of Activated T Cells in Thyroid Gland and Peripheral Blood From Patients with Graves' Disease" Progress in Thyroidology. 91-94 (1989)

[Publications] A.Kawakami,K.Eguchi,K.Migita,H.Nakao,T.Otsubo.C.Shimomura,Y.Ueki,M.Matsunaga,N.Ishikawa,K.Ito and S.Nagataki: "CD4^+ 2H4^+ T Cell Subset(Suppressor-Inducer T Cell)in Thyroid Tissue from Patients with Graves' Disease" Progress in Thyroidology. 95-98 (1989)

[Publications] C.Shimomura,K.Eguchi,T.Otsubo,Y.Ueki,H.Nakao,K.Migita,A.Kawakami,M.Matsunaga,N.Ishikawa,K.Ito and S.Nagataki: "Interferon-r Production of Intrathyroidal Gland Mononuclear Cells from Patients with Graves' Disease" Progress in Thyroidology. 103-106 (1989)

[Publications] K.Migita,K.Eguchi,H.Tezuka,T.Otsubo,A.Kawakami,H.Nakao,Y.Ueki,C.Shimomura,M.Matsunaga,N.Ishikawa,K.Ito and S.Nagataki: "Cytotoxic Activity of Interleukin-2 Activated Killer Cells Toward Thyroid Epithelial Cells." Progress in Thyroidology. 107-110 (1989)

[Publications] Y.Ueki,K.Eguchi,T.Otsubo,C.Shimomura,H.Nakao,A.Kawakami,K.Migita,N.Ishikawa,K.Ito,T.Yamaguchi and S.Nagataki: "B Cell Activation and Differentiation in Thyroid Glands from Patients with Graves' Disease" Progress in Thyroidology. 111-114 (1989)

[Publications] S.Harakawa,S.Yamashita,K.Ashizawa,K.Matsuo,K.Eshima,Y.Nagayama,S.Inoue,T.Kiriyama,S.Morita,H.Hirayu,M.Izumi and S.Nagataki: "Lew Iodine Diet Induces Thyroidal Proto-chcogere Expression" Progress in Thyroidology. 215-218 (1989)

[Publications] G.Komaki,H.Tomai,K.Kasagi,T.Morita,A.Hidaka,K.Kuma,J.Konishi and S.Nagataki: "Fellow-up Study of Euthyroid Relatives with Thyrotropin-binding Inhibitory Immunoglobulin(TB11)Who had Family History of Graves' Disease" Progress in Thyroidology. 387-390 (1989)

[Publications] T.Morita,H.Tamai,A.Oshima,G.Komaki,S.Fukata,S.Matsubayashi,K.Kuma,T.Nakagawa and S.Nagataki: "Changes of Thyroid Hormone,TSH,TBG and TG Concentrations After Suppressive Therapy in Nodular Goiter" Progress in Thyroidology. 503-506 (1989)

[Publications] S.Morita,K.Eishima,S.Iroue,S.Harakawa,S.Yamashita,H.Hirayu,M.Izumi and S.Nagataki: "The Thyroid Function and Analysis of Brain Computer Tomograms in Aged Subjects" Progress in Thyroidology. 557-559 (1989)

[Publications] S.Harakawa,S.Akazawa,M.Akazawa,M.Hashimoto,S.Yamashita,M.Izumi and S.Nagataki: "Changes of sercum thyraid hormone levels induce malformations on early embryogenesis in rats" Acta Endocrinologica. 121. 709-743 (1989)

[Publications] K.Matsuo,M.Niwa,M.Kunihara,K.Shigematsu,S.Yamashita,M.Ozaki and S.Nagataki: "Receptor Autoradiographic Aralysis of Ireulin-like Growth Factor I(IGF-1)Birding Sites in Rat Forebrain and Pititary Gland" Cellular and Molecular Neurobiology. 9. 357-367 (1989)

[Publications] S.Matsubayashi,H.Tawai,T.Morita,F.Matsuzaka,K.Kuma,T.Miyazaki,H.Matsumoto,S.Nagataki and R Volpe: "Possible Disolder of B-Cell-Related Surveillance and Malignant Lymphoma of the Thyroid" Cancer. 64. 2259-2261 (1989)

[Publications] K.Matsuo,S.Yamashita,M.Niwa,M.Kurihara,S.Harakawa,M.Izumi,S.Nagataki and S.Melwed: "Thyroid Hormone Regulates Rat Pituitary Insulin-like Growth Factor-I Receptors" Endocrirologe. 126. 550-554 (1989)

長瀧重信長崎大学, 医学部, 教授 (70010311)