1991 年度実績報告書

遺伝子レベルにおける自己免疫性甲状腺疾患の成因の究明

研究課題

研究課題/領域番号	03454519
研究機関	長崎大学
研究代表者	長瀧重信長崎大学, 医学部, 教授 (70010311)
研究分担者	山下俊一長崎大学, 医学部, 教授 (30200679) 和泉元衛長崎大学, 医学部, 助教授 (80039552)
キーワード	自己免疫性甲状腺疾患 / バセドウ病 / TSH受容体 / 遺伝子発現
研究概要	臓器特異性自己免疫疾患の代表であるバセドウ病と橋本病の成因を明らかにする目的でTSH受容体遺伝子を用いたtransfectionならびに抗原・抗体相互作用の解明を行なっている。すでに永山,Dr.Rapopurt(UCSF)らによってクロ-ン化されたヒトTSH受容体cDNAを用いて遺伝子レベルの研究をupーregulationとの関係で証明した。ヒト甲状腺癌細胞以外,CHO細胞,PC12細胞にTSH受容体を過剰発現させたstable transfectantを作製した。次にこれらの細胞表面にTSH受容体が発現していることを ^<125>IーTSH結合能ならびにNorthern gel分析によって証明した。しかし、TSH刺激によるcAMP産生については明らかな上昇反応を見出せていない。更に数10種類の異なるクロ-ンを完成させている。現在TSH受容体の刺激情報伝達系について解析中であるが、今後、免疫担当細胞側の反応性についてこれらTSH受容体の過剰発現細胞を用いて,すなわち立体構造が保持され抗原決定基を有する細胞を用いて検討する。TSH受容体が発現した抗原提示細胞に対して,auitologous,albbgousの組み合せによるT,Bリンパ球のcoーurltneを行ないTSH受容体抗体の産生を刺激活性や刺激阻害活性を指標に検索していく。すなわち患者血中のTSH受容体抗体の多様性の分類とそれらに対応する抗原の特異性について特定部位の同定へと応用していく予定である。最終的にはTSH受容体発現ベクタ-を用いたトランスジェニックマウス作製のための基礎的研究を行なう.マウス単核球細胞膜上に特異的にTSH受容体を発現させ,反応性にT,B細胞がら産生されるTSH受容体抗体が病因的役割を果しているか否かを検討する為,モデルマウスの作製を試みる予定である。

研究成果
(21件)

すべてその他

すべて文献書誌 (21件)

[文献書誌] KAWAKAMI A et al: "EFFECTS OF LOBENZARIT DISODIUM ON HUMAN ENDOTHELIAL CELLS Lobenzarit Disodium Inhibits Proliferative Response,HLAーDR Antigen Expression,and T Cell Adherence Toward" ARTHRITIS&RHEUMATISM. 34. 296-303 (1991)
[文献書誌] MIGITA K et al: "Detection of Leuー19(CD56)antigen on human thyroid epithelial cells by an immunohistochemical method" Immunolohy. 72. 246-249 (1991)
[文献書誌] NAGAYAMA Y et al: "ThyrotropinーIuteinizing hormone/chorionic gonadotropin receptor extracellular domain chimeras as probes for thyropin receptor function" Proc.Natl.Acad.Sci.USA. 88. 902-905 (1991)
[文献書誌] NAGAYAMA Y et al: "EXTRACELLULAR DOMAIN CHIMERAS OF THE TSH AND LH/CG RECEPTORS REVEAL THE MIDーREGION(AMINO ACIDS 171ー260)TO PLAY A VITAL ROLE IN HIGH AFFINITY TSH BINDING" BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATTIONS. 173. 1150-1156 (1990)
[文献書誌] IDA H et al: "Different BーCell Responses to Human TーCell Lynphotropic Virus Type I(HTLVーI)EnveLope Synthetic Peptides in HTLVーIーInfected Individuals" Journal of Clinical ImmunoLogy. 11. 143-151 (1991)
[文献書誌] KOHNO K et al: "Variations in radiiommunoscintigraphic detection of tumor showed by five monoclonal antibodies to carcinoembryonic antigen" Annals of Nuclear Medicine. 5. 69-75 (1991)
[文献書誌] YAMAGUCHI Y et al: "Production of islet cell antibodies from EpsteinーBarr Virusーtransformed peripheral blood Iymphocytes in Type 1 (insulinーdependent) diabetic patients" Diabetologia. 34. 511-514 (1991)
[文献書誌] Lernmark A et al: "The Fourth International Serum Exchange Workshop to standardixe cytoplasmic islet cell antibodies" Diabetologia Workshop report. 34. 534-535 (1991)
[文献書誌] MATSUOKA N et al: "Phenotypic Characteristics of T cells Interacted with Synovial Cells" The Journal of Rheumatology. 18. 1137-1142 (1991)
[文献書誌] YAMAMOTO H et al: "Effects of Cyclosporin A and Low Dosages of Steroid on Posttransplantation Diabetes in kidney Transplant Recipients" DIABETES CARE. 14. 867-870 (1991)
[文献書誌] TAMAI H et al: "The Incidence of Thyroid Stimulating Bloking Antibodies during the Hypothyroid Phase in Patients with Subacute Thyroiditis" Journal of Clinical Endocrinology and Metabolism. 73. 245-250 (1991)
[文献書誌] KAWAKAMI A et al: "Endothelial Cells stimulate proliferation of human tyroid epithelial cells" Acta Endocrinologica. 125. (1991)
[文献書誌] AKASHI M et al: "Original Articles Effects of Insulin and myoーInositol on Embryo Growth and Developement During Early organogenesis in StreptozocinーInduced Diabetic Rats" DIABETES. 40. 1574-1579 (1991)
[文献書誌] AKASHI M et al: "Effects of Insulin and myoーInositol on Embryo Growth and Development During Early Organogenesis in staptpzpcinーInduced Dabetic Rats" Diabetes. 40. 1574-1579 (1991)
[文献書誌] Tominaga T et al: "Lack of evidence fuv presence of human imnumock ficiency virus type 1ーrelated Sequences in patients with Graves chieare" Thyroid. 1. 307-314 (1991)
[文献書誌] Kimura H et al: "Interlenkinー1 inhibits human thyroid coreiwma cell growth" Jornal of clinical Endocrinolgy and metabolism. (1992)
[文献書誌] Okuno S et al: "International Congress series 963" Excerpta Medica,Amsterdan, 4 (1991)
[文献書誌] Maeda Y.et al: "International Congress series 963" Excerpta Medica,Amesterdam, 4 (1991)
[文献書誌] Shigenobu Nagataki: "THE THYROID" J.B.LIPPINCOTT COMPANY, 8 (1991)
[文献書誌] Shigenobu Nagataki: "PROGRESS IN THYROID RESEARCH" BALKEMA, 6 (1991)
[文献書誌] Shunichi Yamashita: "PROGRESS IN THYROID RESEARCH" BALKEMA, 4 (1991)

1991 年度 実績報告書

遺伝子レベルにおける自己免疫性甲状腺疾患の成因の究明

研究代表者

長瀧 重信 長崎大学, 医学部, 教授 (70010311)

研究成果

[文献書誌] KAWAKAMI A et al: "EFFECTS OF LOBENZARIT DISODIUM ON HUMAN ENDOTHELIAL CELLS Lobenzarit Disodium Inhibits Proliferative Response,HLAーDR Antigen Expression,and T Cell Adherence Toward" ARTHRITIS&RHEUMATISM. 34. 296-303 (1991)

[文献書誌] MIGITA K et al: "Detection of Leuー19(CD56)antigen on human thyroid epithelial cells by an immunohistochemical method" Immunolohy. 72. 246-249 (1991)

[文献書誌] NAGAYAMA Y et al: "ThyrotropinーIuteinizing hormone/chorionic gonadotropin receptor extracellular domain chimeras as probes for thyropin receptor function" Proc.Natl.Acad.Sci.USA. 88. 902-905 (1991)

[文献書誌] NAGAYAMA Y et al: "EXTRACELLULAR DOMAIN CHIMERAS OF THE TSH AND LH/CG RECEPTORS REVEAL THE MIDーREGION(AMINO ACIDS 171ー260)TO PLAY A VITAL ROLE IN HIGH AFFINITY TSH BINDING" BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATTIONS. 173. 1150-1156 (1990)

[文献書誌] IDA H et al: "Different BーCell Responses to Human TーCell Lynphotropic Virus Type I(HTLVーI)EnveLope Synthetic Peptides in HTLVーIーInfected Individuals" Journal of Clinical ImmunoLogy. 11. 143-151 (1991)

[文献書誌] KOHNO K et al: "Variations in radiiommunoscintigraphic detection of tumor showed by five monoclonal antibodies to carcinoembryonic antigen" Annals of Nuclear Medicine. 5. 69-75 (1991)

[文献書誌] YAMAGUCHI Y et al: "Production of islet cell antibodies from EpsteinーBarr Virusーtransformed peripheral blood Iymphocytes in Type 1 (insulinーdependent) diabetic patients" Diabetologia. 34. 511-514 (1991)

[文献書誌] Lernmark A et al: "The Fourth International Serum Exchange Workshop to standardixe cytoplasmic islet cell antibodies" Diabetologia Workshop report. 34. 534-535 (1991)

[文献書誌] MATSUOKA N et al: "Phenotypic Characteristics of T cells Interacted with Synovial Cells" The Journal of Rheumatology. 18. 1137-1142 (1991)

[文献書誌] YAMAMOTO H et al: "Effects of Cyclosporin A and Low Dosages of Steroid on Posttransplantation Diabetes in kidney Transplant Recipients" DIABETES CARE. 14. 867-870 (1991)

[文献書誌] TAMAI H et al: "The Incidence of Thyroid Stimulating Bloking Antibodies during the Hypothyroid Phase in Patients with Subacute Thyroiditis" Journal of Clinical Endocrinology and Metabolism. 73. 245-250 (1991)

[文献書誌] KAWAKAMI A et al: "Endothelial Cells stimulate proliferation of human tyroid epithelial cells" Acta Endocrinologica. 125. (1991)

[文献書誌] AKASHI M et al: "Original Articles Effects of Insulin and myoーInositol on Embryo Growth and Developement During Early organogenesis in StreptozocinーInduced Diabetic Rats" DIABETES. 40. 1574-1579 (1991)

[文献書誌] AKASHI M et al: "Effects of Insulin and myoーInositol on Embryo Growth and Development During Early Organogenesis in staptpzpcinーInduced Dabetic Rats" Diabetes. 40. 1574-1579 (1991)

[文献書誌] Tominaga T et al: "Lack of evidence fuv presence of human imnumock ficiency virus type 1ーrelated Sequences in patients with Graves chieare" Thyroid. 1. 307-314 (1991)

[文献書誌] Kimura H et al: "Interlenkinー1 inhibits human thyroid coreiwma cell growth" Jornal of clinical Endocrinolgy and metabolism. (1992)

[文献書誌] Okuno S et al: "International Congress series 963" Excerpta Medica,Amsterdan, 4 (1991)

[文献書誌] Maeda Y.et al: "International Congress series 963" Excerpta Medica,Amesterdam, 4 (1991)

[文献書誌] Shigenobu Nagataki: "THE THYROID" J.B.LIPPINCOTT COMPANY, 8 (1991)

[文献書誌] Shigenobu Nagataki: "PROGRESS IN THYROID RESEARCH" BALKEMA, 6 (1991)

[文献書誌] Shunichi Yamashita: "PROGRESS IN THYROID RESEARCH" BALKEMA, 4 (1991)

1991 年度実績報告書

長瀧重信長崎大学, 医学部, 教授 (70010311)