2002 年度実績報告書

バセドウ病緩解とCTLA-4・GD遺伝子異常/超高感度TSAb

研究課題

研究課題/領域番号	13671159
研究機関	琉球大学
研究代表者	高須信行琉球大学, 医学部, 教授 (20020927)
研究分担者	幸喜毅琉球大学, 医学部附属病院, 助手 (80273415) 島袋充生琉球大学, 医学部附属病院, 講師 (60271144)
キーワード	バセドウ病 / TSH受容体抗体(TRAb) / 甲状腺刺激抗体(TSAb) / CTLA-4 / 緩解 / 抗甲状腺剤 / CTLA-4遺伝子多型 / 放射線療法
研究概要	バセドウ病は難治疾患である。バセドウ病には緩解するものと緩解しにくいものがあり、両者を早期に区別することが大切である。バセドウ病患者治療の課題は「どのようにして緩解するものと緩解しにくいものを早期に区別するか」ということである。「緩解するものと緩解しにくいものを早期に区別すること」を中心にバセドウ病緩解をCTLA-4・GD遺伝子異常と超高感度TSAbから研究した。緩解するものと緩解しにくいものを早期に区別する方法を明らかにした。さらに遺伝子レベルで緩解するものと緩解しにくいものを早期に区別する方法を明らかにした。バセドウ病は自己免疫疾患である。バセドウ病発症は免疫制御機構の異常による。この免疫制御機構の異常には遺伝因子と環境因子が関与している。遺伝因子としてはCTLA-4遺伝子がある。CTLA-4遺伝子多形とバセドウ病緩解が関係していることを明らかにした(J Clin Endoclin Metab 87:2593,2002)。CTLA-4のExon 1の49A/G多形がバセドウ病緩解に関係している。Aが多いものでは緩解するが、Gが多いものは緩解しない。Aが多いものでは抗甲状腺剤で治療する。Gが多いものは放射線療法あるいは手術をする。緩解するものと緩解しにくいものを早期に区別する方法を明らかにした。TSH受容体抗体(TRAb)が早期にきれいに消失するものは緩解するが、TRAbが複雑な動きを示すものは緩解しにくい。さらに遺伝子レベルで緩解するものと緩解しにくいものを早期に区別する方法を明らかにした。CTLA-4遺伝子多形とバセドウ病緩解が関係していることを明らかにした(JCEM)。CTLA-4のExon 1の49A/G多形がバセドウ病緩解に関係している。Aが多いものでは緩解するが、Gが多いものは緩解しない。Aが多いものでは抗甲状腺剤で治療する。Gが多いものは放射線療法あるいは手術をする。

研究成果
(24件)

すべてその他

すべて文献書誌 (24件)

[文献書誌] Kinjyo Y, Takasu N, et al.: "Remission of Graves' Hyperthyroidism and A/G Polymorphism at Position 49 in Exon 1 of Cytotoxic T Lymphocyte Associated Molecule-4 (CTLA-4) Gene"J Clin Endocrinol Metab. 87(6). 2593-2596 (2002)
[文献書誌] Tomoyose T, Takasu N, et al.: "Cytotoxic T-Lymphocyte antigen-4 gene polymorphisms and human T-cell lymphotrophic virus-1 infection : their associations with Hashimoto's thyroiditis in Japanese patients"Thyroid. 12(8). 673-677 (2002)
[文献書誌] Ochi Y, Takasu N, et al.: "Sensitive thyroid stimulating antibody (TSAb) assay using polyethylene glycol (PEG)--a review"J Immunoassay Immunochem. 23(4). 461-470 (2002)
[文献書誌] Ikema T, Takasu N, et al.: "Identification of three new mutations of the HNF-1 alpha gene in Japanese MODY families"Diabetologia. 45(12). 1713-1718 (2002)
[文献書誌] Yamakaw K: "Galpha13 induces preproET-1 gene expression via JNK"Hypertens Res 2002. 25(3). 427-432 (2002)
[文献書誌] Miyagi J, Takasu N, et al.: "Acute myeloid leukemia (FAB-M2) with a masked type of t(8;21) translocation revealed by spectral karyotyping"Int J Hematol. 76(4). 338-343 (2002)
[文献書誌] Miyagi J, Takasu N, et al.: "Establishment of a primary effusion lymphoma cell line (RM-P1) and in vivo growth system using SCID mice"Int J Hematol. 76(2). 165-172 (2002)
[文献書誌] Takasu N, et al.: "TSBAb (TSH-stimulation blocking antibody) and TSAb (thyroid stimulating antibody) in TSBAb-positive patients with hypothyroidism and Graves, patients with hyperthyroidism"Horm Metab Res. 33(4). 232-237 (2001)
[文献書誌] Takasu N, et al.: "Remission of Graves' hyperthyroidism predicted by smooth decreases of thyroid-stimulating antibody and thyrotropin-binding inhibitor immunoglobulin during antithyroid drug treatment"Thyroid. 10(10). 891-896 (2001)
[文献書誌] Asahi T, Takasu N, et al.: "Cilazapril prevents cardiac hypertrophy and postischemic myocardial dysfunction in hyperthyroid rats"Thyroid. 11(11). 1009-1015 (2001)
[文献書誌] Matsushita M, Takasu N, et al.: "Co-expression of urotensin II and its receptor (GPR14) in human cardiovascular and renal tissues"J Hypertens. 19(12). 2185-2190 (2001)
[文献書誌] Ochi Y, Takasu N, et al.: "Sensitive assay to detect thyroid stimulating antibody (TSAb) in the presence of thyroid stimulation blocking antibody (TSBAb) in serum"Horm Metab Res. 33(2). 115-120 (2001)
[文献書誌] Ohshiro Y, Takasu N, et al.: "Triiodothyronine concomitantly inhibits calcium overload and postischemic myocardial stunning in diabetic rats"Life Sci. 69(16). 1907-1918 (2001)
[文献書誌] Ohshiro Y, Takasu N, et al.: "Analysis of 825C/T polymorphism of G proteinbeta3 subunit in obese/diabetic Japanese"Biochem Biophys Res Commun. 286(4). 678-680 (2001)
[文献書誌] Sugimoto J, Takasu N, et al.: "Transcriptionally active HERV-K genes : identification, isolation, and chromosomal mapping"Genomics. 72(2). 1137-1144 (2001)
[文献書誌] Miyagi J, Takasu N et al.: "Detection of Epstein-Barr virus and human T-cell lymphotropic virus type 1 in malignant nodal lymphoma, studied in Okinawa, a subtropical area in Japan"Int J Hematol. 75(1). 78-84 (2002)
[文献書誌] Higa M, Takasu N, et al.: "Atrophic change of rat salivary gland during adenovirus-induced hyperleptinemia"Biochem Biophys Res Commun. 291(3). 675-679 (2002)
[文献書誌] Miyagi J, Takasu N, et al.: "Increased risk of human herpesvirus-8 infection in patients with adult T cell leukemia/lymphoma in Okinawa"Leukemia. 16(9). 1881-1882 (2002)
[文献書誌] Fukuchi M, Takasu N, et al.: "Evidence for a deficient pancreatic beta-cell response in a rat model of hyperthyroidism"Life Sci. 71(9). 1059-1070 (2002)
[文献書誌] Ohshiro Y, Takasu N, et al.: "Sequence analysis of the pro-opiomelanocortin (POMC) gene in obese/diabetic Japanese"Int J Obes Relat Metab Disord. 26(5). 730-731 (2002)
[文献書誌] Kinjo Y, Takasu N, et al.: "Identification of nonsynonymous polymorphisms in the superantigen-coding region of JDDMKl,2 22 and a pilot study on the association between IDDMK1,2 22 and type 1 diabetes"J Hum Genet. 46(12). 712-716 (2001)
[文献書誌] Komiya I, Takasu N, et al.: "Remission and recurrence of hyperthyroid Graves' disease during and after methimazole treatment when assessed by IgE and interleukin 13"J Clin Endocrinol Metab. 86(8). 3540-3544 (2001)
[文献書誌] Shimajiri Y, Takasu N, et al.: "A missense mutation of Pax4 gene (R121W) is associated with type 2 diabetes in Japanese"Diabetes. 50(12). 2864-2869 (2001)
[文献書誌] 高須信行: "バセドウ病以外の甲状腺機能亢進症・甲状腺中毒症"日野原重明、井村裕夫監修「最新医学講座…代謝疾患・内分泌疾患」、中山書店、東京. 305-312 (2001)

2002 年度 実績報告書

バセドウ病緩解とCTLA-4・GD遺伝子異常/超高感度TSAb

研究代表者

高須 信行 琉球大学, 医学部, 教授 (20020927)

研究成果

[文献書誌] Kinjyo Y, Takasu N, et al.: "Remission of Graves' Hyperthyroidism and A/G Polymorphism at Position 49 in Exon 1 of Cytotoxic T Lymphocyte Associated Molecule-4 (CTLA-4) Gene"J Clin Endocrinol Metab. 87(6). 2593-2596 (2002)

[文献書誌] Tomoyose T, Takasu N, et al.: "Cytotoxic T-Lymphocyte antigen-4 gene polymorphisms and human T-cell lymphotrophic virus-1 infection : their associations with Hashimoto's thyroiditis in Japanese patients"Thyroid. 12(8). 673-677 (2002)

[文献書誌] Ochi Y, Takasu N, et al.: "Sensitive thyroid stimulating antibody (TSAb) assay using polyethylene glycol (PEG)--a review"J Immunoassay Immunochem. 23(4). 461-470 (2002)

[文献書誌] Ikema T, Takasu N, et al.: "Identification of three new mutations of the HNF-1 alpha gene in Japanese MODY families"Diabetologia. 45(12). 1713-1718 (2002)

[文献書誌] Yamakaw K: "Galpha13 induces preproET-1 gene expression via JNK"Hypertens Res 2002. 25(3). 427-432 (2002)

[文献書誌] Miyagi J, Takasu N, et al.: "Acute myeloid leukemia (FAB-M2) with a masked type of t(8;21) translocation revealed by spectral karyotyping"Int J Hematol. 76(4). 338-343 (2002)

[文献書誌] Miyagi J, Takasu N, et al.: "Establishment of a primary effusion lymphoma cell line (RM-P1) and in vivo growth system using SCID mice"Int J Hematol. 76(2). 165-172 (2002)

[文献書誌] Takasu N, et al.: "TSBAb (TSH-stimulation blocking antibody) and TSAb (thyroid stimulating antibody) in TSBAb-positive patients with hypothyroidism and Graves, patients with hyperthyroidism"Horm Metab Res. 33(4). 232-237 (2001)

[文献書誌] Takasu N, et al.: "Remission of Graves' hyperthyroidism predicted by smooth decreases of thyroid-stimulating antibody and thyrotropin-binding inhibitor immunoglobulin during antithyroid drug treatment"Thyroid. 10(10). 891-896 (2001)

[文献書誌] Asahi T, Takasu N, et al.: "Cilazapril prevents cardiac hypertrophy and postischemic myocardial dysfunction in hyperthyroid rats"Thyroid. 11(11). 1009-1015 (2001)

[文献書誌] Matsushita M, Takasu N, et al.: "Co-expression of urotensin II and its receptor (GPR14) in human cardiovascular and renal tissues"J Hypertens. 19(12). 2185-2190 (2001)

[文献書誌] Ochi Y, Takasu N, et al.: "Sensitive assay to detect thyroid stimulating antibody (TSAb) in the presence of thyroid stimulation blocking antibody (TSBAb) in serum"Horm Metab Res. 33(2). 115-120 (2001)

[文献書誌] Ohshiro Y, Takasu N, et al.: "Triiodothyronine concomitantly inhibits calcium overload and postischemic myocardial stunning in diabetic rats"Life Sci. 69(16). 1907-1918 (2001)

[文献書誌] Ohshiro Y, Takasu N, et al.: "Analysis of 825C/T polymorphism of G proteinbeta3 subunit in obese/diabetic Japanese"Biochem Biophys Res Commun. 286(4). 678-680 (2001)

[文献書誌] Sugimoto J, Takasu N, et al.: "Transcriptionally active HERV-K genes : identification, isolation, and chromosomal mapping"Genomics. 72(2). 1137-1144 (2001)

[文献書誌] Miyagi J, Takasu N et al.: "Detection of Epstein-Barr virus and human T-cell lymphotropic virus type 1 in malignant nodal lymphoma, studied in Okinawa, a subtropical area in Japan"Int J Hematol. 75(1). 78-84 (2002)

[文献書誌] Higa M, Takasu N, et al.: "Atrophic change of rat salivary gland during adenovirus-induced hyperleptinemia"Biochem Biophys Res Commun. 291(3). 675-679 (2002)

[文献書誌] Miyagi J, Takasu N, et al.: "Increased risk of human herpesvirus-8 infection in patients with adult T cell leukemia/lymphoma in Okinawa"Leukemia. 16(9). 1881-1882 (2002)

[文献書誌] Fukuchi M, Takasu N, et al.: "Evidence for a deficient pancreatic beta-cell response in a rat model of hyperthyroidism"Life Sci. 71(9). 1059-1070 (2002)

[文献書誌] Ohshiro Y, Takasu N, et al.: "Sequence analysis of the pro-opiomelanocortin (POMC) gene in obese/diabetic Japanese"Int J Obes Relat Metab Disord. 26(5). 730-731 (2002)

[文献書誌] Kinjo Y, Takasu N, et al.: "Identification of nonsynonymous polymorphisms in the superantigen-coding region of JDDMKl,2 22 and a pilot study on the association between IDDMK1,2 22 and type 1 diabetes"J Hum Genet. 46(12). 712-716 (2001)

[文献書誌] Komiya I, Takasu N, et al.: "Remission and recurrence of hyperthyroid Graves' disease during and after methimazole treatment when assessed by IgE and interleukin 13"J Clin Endocrinol Metab. 86(8). 3540-3544 (2001)

[文献書誌] Shimajiri Y, Takasu N, et al.: "A missense mutation of Pax4 gene (R121W) is associated with type 2 diabetes in Japanese"Diabetes. 50(12). 2864-2869 (2001)

[文献書誌] 高須 信行: "バセドウ病以外の甲状腺機能亢進症・甲状腺中毒症"日野原重明、井村裕夫監修「最新医学講座…代謝疾患・内分泌疾患」、中山書店、東京. 305-312 (2001)

2002 年度実績報告書

高須信行琉球大学, 医学部, 教授 (20020927)

[文献書誌] 高須信行: "バセドウ病以外の甲状腺機能亢進症・甲状腺中毒症"日野原重明、井村裕夫監修「最新医学講座…代謝疾患・内分泌疾患」、中山書店、東京. 305-312 (2001)