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Molecular biological and clinocopathological study on the thymuses and lymph nodes of patients with myasthenia gravis

Research Project

Project/Area Number 06404049
Research Category

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

Allocation TypeSingle-year Grants
Research Field Thoracic surgery
Research InstitutionSaitama Madical School

Principal Investigator

YOSHITAKE Tsuyoshi  Saitama Medical School, Professor, 医学部, 教授 (60010261)

Co-Investigator(Kenkyū-buntansha) KAMETANI Yuichiro  Saitama Medical School, Instructor, 医学部, 助手 (30255129)
MASUNAGA Atsuko  Saitama Medical School, Instructor, 医学部, 助手 (60219350)
SUGAWARA Isamu  Saitama Medical School, Associate Professor, 医学部, 助教授 (10196701)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥24,500,000 (Direct Cost: ¥24,500,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1994: ¥23,100,000 (Direct Cost: ¥23,100,000)
KeywordsMyasthenia gravis / Thymus / Thmoma / Lymph node / Immunohistochemical stain / RT-PCR / Apoptosis / Tenascin / RT‐PCR / tenascin
Research Abstract

Several distinct immunohistochemical and molecular biological characeristics were shown using the thymic and lymph node tissues of patients with myasthenia gravis.
1. Thymic lymphoid follicles were surrounded by a fine matrix fiber tenascin, but these charcteisti compartmentalized structure was not found in the corresponding lymph nodes. In these thymic lymphoid follicles, immunohistochemically, expression of Fas antigen and p53 protein (apoptosis reacted factors) were less frequent than that in the other region of the thymus. Furthermore, Several densely but scatterd stained bc1-2 (apoptosis-depressing factor) positive B cells were observed in the thymic lymphoid follicles, although there were mostly no positive B cells in the lymph nodes. Expression of the antigen and protein were also confirmed at mRNA level through analysis using RT-PCR method.
2. Patients, who had several highly developed thymic lymphoid hyperplasia, have preoperatively maintained higher level of serum anti-Ach-R an … More tibody titer than that of patients with poorly developed hyperplasia or without it.
3. Population of memory and non-memory B cells of expression of adhesion molecules (LFA,ICAM) of the lymphoid follicles were similary recognized in both the thymus and lymph node.
4. Epitheital cells from the thymuses and thymomas were immunochemically shown using anti-CK-17mAB among several anti-cytokeratin mAB Series. In the thymus, only medullary epithelium was positively stained. In thymomas, about half of the cases possessed positive cells. CK-17 mRNA expression in these cases were also confirmed by RT-PCR method. Patients with thymomas possessing CK-17-positive cessl showed higher level of seurm anti-Ach-R antibody titer and more developing lymphoid follicles in the residual thymuses than those lacking positive cells.
CK-17-positive cell thymomas were both polygonal and polygonal-spindle shaped epithelial cell thypes, but contrary to out expection, spindle shaped epithelial cell type thymoma contained no positve cells.
These results indicate that some antibody producing B cells in the thymic lymphold follicles associated with myasthenia gravis could escape the entry of apoptosis. Thus, they might survive to produce auto-antibody. Thymomas containing CK-17-positive epithelial cells seem to have a promoting ability of thymic B cells to make auto-antibodies. Regarding epithelial cell differentiation toward subtype of thymomas, there were a discrepancy in the morphological and immunohistochemical observations. Less

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Yoshitake,Tsuyoshi: "Focal thymic hyperplasia in adult: Report of a case" Jpn J Surg. 24. 72-74 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masunaga,Atsuko: "Reduced expression of apoptosis-related antigens in thymuses from patitens with myasthenia gravis" Immunolog Letters. 39. 169-172 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 吉竹,毅: "胸腺腫(呼吸器症候群シリーズNo.4)" 下巻(別冊). 324-327 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 吉竹,毅: "胸腺腫瘍" 下巻(別冊). 328-330 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshitake,Tsuyoshi: "A comparative histological and immunohistochemical study of thymomas with and without myasthenia gravis" Jpn J Surg. 24. 1044-1049 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masunaga,Atsuko: "A case of encapsulated non-invasive thymoma(stage 1)with myasthenia gravis showing metastasis after a 2-year dormancy" Jpn J Surg. 25. 369-372 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 吉竹,毅: "重症筋無力症における胸腺Lymphoid hyperplasia" 胸部外科. 48. 447-451 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 吉竹,毅: "重症筋無力症胸腺濾胞の区画性および細胞調節に関する検討" 日本呼吸器外科学会誌. 10. 98-106 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sugawara,Isamu: "High-level bc1-2 and low-level p53 expression in thymuses from patients with myasthenia gravis" Immunolog Letters. in press. (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sugawara,Isamu: "Predominant expression of cytokeratin 17 in thymic medulla and its relevance to thymic tumors." Modern Patholog. in press. (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshitake T.: "Focal thymic hyperplasia in an abult ; Report of a case" Jpn J Surg. 24-1. 72-74 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masunaga A.: "Reduced expression of apoptosis-related antigens in thymuses from patients with myasathenis gravis." Immunolog Letters. 39-2. 169-172 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshitake T.: "Thymoma" Nippon rinsho. Suppl. -4. 324-327 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshitake T.: "Tumors of the Thymus" Nippon rinsho. Suppl. -4. 328-330 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshitake T.: "A comparative histological and immunohistochemical study of thymomas with and without myasthenia gravis." Jpn J Surg.25-12. 1044-1049 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masunaga A.: "A case fo encapsulated non-invasive Thymoma (stage I) with myasthenia gravis showing metastasis after a 2-year dormancy." Jpn J Surg. 25-4. 369-372 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshitake, T.: "Thymic lymphoid hyperplasia of myasthenia gravis patients ; Correlation with clinical fearures and efficacy of thymectomy." Jpn J Thorac Surg. 48-6. 447-451 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshitake T.: "Compartmentalization and cell regulation in lymphoid follicles of the thymus in patients with myasthenia gravis-Expression of extracellular matrix tenascin and bcl-2 protein." J Jpn Associat Chest Surg. 10-2. 98-106 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sugawara I.: "High-level bcl-2 and low-level p53 expression in thymues from patients with myasthenia gravis." Immunolog Letters. (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sugawara, I.: "Predominant expression of cytokeratin 17 in thymic maulla and its relevance to thymic tumors." Modern Patholog. (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tsuyoshi Yoshitake: "A comparative histological and immunohistochemical study of thymomas with and without myasthenia gravis" Jpn J Surg. 24. 1044-1049 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Atsuko Masunaga: "A case of encapsulated noninvasive thymoma (stage 1) with myastehnia gravis showing metastsis after a 2-year dormancy" Jpn J Surg. 25. 369-372 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 吉竹毅: "重症筋無力症における胸腺Lymphoid hyperplasia -臨床所見、胸腺切除効果との関連-" 胸部外科. 48. 447-451 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 福地義之助: "胸腔鏡の臨床応用の現状と展望" 治療学. 21. 1267-1275 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Isamu Sugawara: "High level bc1-2 and low level p53 express in thymuses from patients with myasthenia gravis" Immunolog Letters. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 吉竹毅: "重症筋無力症濾胞の区画性および細胞調節に関する検討" 日呼外会誌. 10(印刷中). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Masunaga,A,et al: "Reduced expression of apoptosis‐related antigens in thymuses from patients with myasthenia gravis." Immunolog Letters. 39. 169-172 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 吉竹 毅他: "胸腺腫(呼吸器症候群シリーズ No.4)" 日本臨床. 下巻(別冊). 324-327 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 吉竹 毅他: "胸腺腫瘍(呼吸器症候群シリーズ No.4)" 日本臨床. 下巻(別冊). 328-330 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshitake,T,et al: "Focal thymic hyperplasia in an adult:Report of a case" Jpn J Surg. 24. 72-74 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Masunaga,A,et al: "A case of encapsulated non‐invasive thymoma with myasthenia gravis showing metastasis after a two‐year dormancy." Jpn J Surg. (in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshitake,T.et al: "A comparative histological and immunohistochemical study of thymoma with and without myasthenia gravis." Jpn J Surg. (in press).

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2018-02-02  

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