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Studies on thyroid grouth stimulating antibedies in autcimmura thyued disehses.

Research Project

Project/Area Number 04671475
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

KASAGI Kanji  Kyoto Univ.Dept, of Nuclear Medicine Associate Professor, 医学部, 助教授 (20115819)

Co-Investigator(Kenkyū-buntansha) MISAKI Takashi  Kyoto Univ.Dept.of Nuclear Med.Research Associate, 医学部, 助手 (60181872)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
Keywordsthyroid grouth / FRTL-5 aells / Cytochalasin B / TSH veceptor cutebodey / Graves' disease / Hashimoto's thyroiditis / TGI / TSH / 自己免疫性甲状腺疾患 / 甲状腺増殖刺激抗体 / サイトカイネーシスブロックアッセイ / PCNA / C-fon / C-myc
Research Abstract

In the present study, we have developed a novel bioassay for the assessment of thyroid growth stimulating activity using cytochalasin B (CB) and tested immunoglobulins (IgGs) form patients with autoimmune thyroid diseases. The assay is based on the principle that growing cells during incubation with CB show an increased number of nuclei in a cell (N/C index), since CB,at appropriate concentrations, is known to inhibit cytoplasmic cleavage without affecting nuclear mitosis.
FRTL-5 thyroid cells were incubated with various thyroid stimulators in TSH-free medium containing 2 mg/I CB for 3 days. After the incubation, the cells were harvested in trypsin/EDTA to obtain single cell suspension, fixed, dropped onto a glass slide, stained and observed under a microscope to determine the N/C index.
Bovine TSH,forskolin, cholera toxin, or (Bu) 2cAMP increased the N/C index up to approximately 2.0 in a dose-dependent manner, suggesting that thyroid cell proliferation is attributable, at least, to the … More increase in cAMP.IgGs not only from 27 patients with untreated goitrous Graves' disease but also from 14 patients with goitrous Hashimoto's thyroiditis elicited an increase in the N/C index, which exceeded the mean + 2SD of the values for 17 normal subjects (mean(]SY.+-。[))SD,1.063(]SY.+-。[))0.014). Four non-goitrous hypothyroid patients with primary myxedema displayd a normal N/C index. In Graves' disease, the N/C index did not correlate with TSAb activities but did correlate with estimated goiter size and TBII activities (both, P<0.05). IgGs containing blocking-type TSH-receptor antibody inhibited the TSH- or Graves' IgG-stimulated increase in N/C index, and the grade of inhibition correlated with TBII and TSBAb activities. The blocking-type antibody, however, did not influence the stimulatory effect of IgG from patients with Hashimoto's thyroiditis.
In conclusion, we have developed a sensitive and simple assay for thyroid growth simulating activity by using CB,and found that all tested patients with goitrous Graves' disease and goitrous Hashimoto's thyroiditis have thyroid growth stimulating immunoglobulin (TGI) whose activity does not correlate with TSAb. Less

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Shinichi Miyamoto: "Assessment of thyroid growth stimulating activity of immunoglobulins from patients with autoimmune thyroid diseaks by cytokinesis arrest Assay." European Journal of Endocinology. 136. 499-507 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 宮本 信一: "Cytokinesis arrest assayによる甲状腺増殖刺激抗体の測定" 厚生省特定疾患ホルモン受容機構異常調査研究班総括事業報告書. 101-104 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shinichi Miyamoto et al.: "Assessment of thyroid growth stimulating activity of immunoglobulins from patients with autoimmune thyroid diseases by cytokinesis arrest assay." European Journal of Endocrinology. 136. 499-509 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shinichi Miyamoto et al.: "Measurement of thyroid growth stimulating immunoglobulins by cytokinesis arrest assay" Report from a project team established by the Ministry of Health for hormone receptor diseases. 101-104 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kanji Kasagi: "Scintigraplnc findings of the thyroid in euthyroid Ophtpialmic Groves' dsaease." J.Nuil Med.35. 811-817 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Akinari Hidaka: "Stimulated iodiade uptake in PRTL-5 cells preincubeted with Graves immunoglobulins in NACL-free medium A sensitive assay for TSAB" Thyroid.4. 31-36 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kanji Kasagi: "Scintigraplnc findrngs of the thyroid in hypcthyroid Patieuts with blocking-typl TSH-receptor cmtipcdies." Eur. J.Nucl.Med.21. 962-967 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ryo Takeuchi: Eur.J,Endoainel. (印刷中).

    • Related Report
      1994 Annual Research Report
  • [Publications] Hiroto Hatabu: "Induction of c-fos and c-myc mRNA expression by immunoglobulin G from patients with Graves'disease in FRTL-5 cells." Clin Endocrinol. 34. 349-356 (1991)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kanji Kasagi: "Thyrotropin receptor antibodies in hypothyroid Graves'disease" J Clin Endocrinol Metab. 75. 504-508 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kanji Kasagi: "Scintigraphic findings of the thyroid in enthyroid ophthalmic Graves'disease" J Nucl Med. (印刷中).

    • Related Report
      1993 Annual Research Report
  • [Publications] Akinari Hidaka: "Stimulated iodide uptake in FRTL-5 cells preincubated with Groves'immunoglobulins in Nace free medium:A sensitive assay for thyroid stimulating antibodies." Thyroid. (印刷中).

    • Related Report
      1993 Annual Research Report
  • [Publications] Kanji Kasagi: "80 Years of Harhimoto Disease" Excepta Medica, 721 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 笠木寛治: "レセプタ 基礎と臨床" 朝倉書店, 944 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kanji Kasagi: "Thyrotropin peceptor antibodies is hypothynid Grauei disease" Jclin Endoainol Metab. 75. 504-508 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 日高 昭斉: "FRTL-5細胞へのI-125摂取を指標とした高感度甲状腺刺激抗体測定法の開発" 厚生省特定疾患ホルモン受容機構異常調査研究班・平成3年度総括研究事業報告書. 93-95 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hiroto Hatabu: "Indaction of C-fos and C-myc mRNA expresion by immcmoglobulin G from Patients with Gauis disease its thyntropin-depandunt rat thjhid cell linl(FlTL5)." Clin Endoainol. 34. 349-356 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kanji Kasagi: "Meawreweat of TSH-receptor Antibodies.The international Harhimito Symposium in Conjurtion with Satellite Meeting on TSH Receptor Antibcdies." Elsevier Science Publishey, (1994)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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