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DEVELOPMENTAL STUDY OF PELVIC FLOOR MUSCLES IN ANORECTAL MALFORMATIONS

Research Project

Project/Area Number 13557146
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Pediatric surgery
Research InstitutionKYOTO PREFECTURAL UNIVERSITY OF MEDICINE

Principal Investigator

SHIMOTAKE Takashi  KYOTO PREFECTURAL UNIVERSITY OF MEDICINE, CHILDREN RESEARCH HOSPITAL, DIVISION OF SURGERY, 医学研究科, 助手 (90254341)

Co-Investigator(Kenkyū-buntansha) 岩井 直躬  京都府立医科大学, 医学部, 教授 (90128695)
Project Period (FY) 2001 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥10,200,000 (Direct Cost: ¥10,200,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2001: ¥4,700,000 (Direct Cost: ¥4,700,000)
KeywordsANORECTAL MALFORMATIONS / DEVELOPMENT / EMBRYOGENESIS / PELVIC FLOOR MUSCLE / 骨盤底 / 筋細胞 / 発生
Research Abstract

Recent biological studies have elucidated the molecular mechanism of muscle development, in which various regulatory factors (MRFs) play key roles during embryogenesis. To investigate the development of anorectal malformations (ARM), we studied MRF expressions in myogenic cells in the pelvic floor using murine embryos affected with ARM. ARM embryos were obtained from the 10.5th embryonal day (E10.5) to the 7.0th postnatal day (D7.0) in a natural mutant strain (Sd/+,RSV/Le). Serial frozen sections were prepared for immunohistochemistry using specific antibodies to M-cadherin, myoD, Myogenin, myosin heavy chain, and α-actin molecule. In normal mice, embryonal caudal somites differentiated into myogenic stem cells and migrated to the pelvic floor between E11.0 and E14.0. In the ARM mice, however, caudal somites were irregularly arranged and MRF expressions in myogenic cells were markedly decreased in the dorsocaudal region at E11.5-13.0, leading to hypoplastic pelvic floor muscles. The maldevelopment of pelvic floor muscles in ARM is derived from a deficient supply of myogenic stem cells, with impaired MRF expression. These results suggest that myogenic stem cells, available from bone marrow contents, may be utilized for postnatal muscle regeneration to reinforce the pelvic floor muscle function in children with ARM.

Report

(5 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (32 results)

All 2005 2004 Other

All Journal Article (16 results) Publications (16 results)

  • [Journal Article] Impaired expression of myogenic regulatory molecules in the pelvic floor muscles of murine embryos with anorectal malformations2005

    • Author(s)
      Aoi S, Shimotake T, Tsuda T, Deguchi E, Iwai N
    • Journal Title

      J Pediatr Surg (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Morphology of the Enteric Nervous System in the Hindgut of an Infant With Cloacal Exstrophy : A Preliminary Report.2005

    • Author(s)
      Shimotake T, Tsuda T, Aoi S, Tomiyama H, Iwai N
    • Journal Title

      Eur J Pediatr Surg (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Infrared spectrophotometry of intraluminal meconium calculi in a neonate with imperforate anus and rectourethral fistula.2005

    • Author(s)
      Shimotake T, Tsuda T, Aoi S, Kohji Higuchi, Iwai N
    • Journal Title

      J Pediatr Surg (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Neurocutaneous melanosis associated with Hirschsprung's disease in a male neonate.2005

    • Author(s)
      Iwabuchi T, Shimotake T, Furukawa T, Tsuda T, Aoi S, Iwai N
    • Journal Title

      J Pediatr Surg (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Intestinal malrotation with midgut volvulus in a 10-year-old girl.2005

    • Author(s)
      Kume Y, Fumino S, Shimotake T, Iwai N
    • Journal Title

      J Pediatr Surg (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] ^<123>I-MIBG radio-guided navigation surgery for recurrent medullary thyroid carcinoma in a girl with multiple endocrine neoplasia type 2B2005

    • Author(s)
      Shimotake T, Aoi S, Fumino S, Iwai N
    • Journal Title

      J Pediatr Surg (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Impaired expression of myogenic regulatory molecules in the pelvic floor muscles of murine embryos with anorectal malformations.2005

    • Author(s)
      Aoi S, Shimotake T, Tsuda T, Deguchi E, Iwai N
    • Journal Title

      J Pediatr Surg (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ^<123>I-MIBG radio-guided navigation surgery for recurrent medullary thyroid carcinoma in a girl with multiple endocrine neoplasia type 2B.2005

    • Author(s)
      Shimotake T, Aoi S, Fumino S, Iwai N
    • Journal Title

      J Pediatr Surg (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Intestinal malrotation with midgut volvulus in a 10-year-old girl..2004

    • Author(s)
      Kume Y, Fumino S, Shimotake T, Iwai N
    • Journal Title

      J Pediatr Surg 39

      Pages: 783-784

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Impaired expression of myogenic regulatory molecules in the pelvic floor muscles of murine embryos with anorectal malformations.

    • Author(s)
      Aoi S, Shimotake T, Tsuda T, Deguchi E, Iwai N
    • Journal Title

      J Pediatr Surg (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Morphology of the Enteric Nervous System in the Hindgut of an Infant With Cloacal Exstrophy : A Preliminary Report..

    • Author(s)
      Shimotake T, Tsuda T, Aoi S, Kohji Higuchi, Iwai N.
    • Journal Title

      Euro J Pediatr Surg (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Infrared spectrophotometry of intraluminal meconium calculi in a neonate with imperforate anus and rectourethral fistula

    • Author(s)
      Shimotake T, Tsuda T, Aoi S, Kohji Higuchi, Iwai N.
    • Journal Title

      J Pediatr Surg (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Neurocutaneous melanosis associated with Hirschsprung's disease in a male neonate..

    • Author(s)
      Iwabuchi T, Shimotake T, Furukawa T, Tsuda T, Aoi S, Iwai N
    • Journal Title

      J Pediatr Surg (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] ^<123>I-MIBG radio-guided navigation surgery for recurrent medullary thyroid carcinoma in a girl with multiple endocrine neoplasia type 2B...

    • Author(s)
      Shimotake T, Aoi S, Fumino S, Iwai N
    • Journal Title

      J Pediatr Surg (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Respiratory insufficiency in a newborn patient with mesenchymal hamartoma of the chest wall occupying the thoracic cavity

    • Author(s)
      Shimotake T, Fumino S, Aoi S, Tsuda T, Iwai N
    • Journal Title

      J Pediatr Surg (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mucoepidermal carcinoma of the lung detected by positron emission tomography in a 5-year-old girl

    • Author(s)
      Kinoshita H, Shimotake T, Furukawa T, Deguchi E, Iwai N
    • Journal Title

      J Pediatr Surg (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Shimotake T, Tomiyama H, Aoi S, Iwai N: "Discrepancy between macroscopic and microscopic transitional zones in Hirschsprung's disease with reference to the type of RET/GDNF/NTN gene mutation."Journal of Pediatric Surgery. 38(6). 698-701 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimotake T, Aoi S, Tomiyama H, Iwai N: "DPC-4 (Smad-4) and K-ras gene mutations in biliary tract epithelium in children with anomalous pancreaticobiliary ductal union."Journal of Pediatric Surgery. 38(6). 694-697 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimotake T, Go S, Tomiyama H, Aoi S, Iwai N.: "Proximal jejunostomy with or without myectomy-myotomy modification in five infants with total intestinal aganglionosis : An experience with surgical treatments in a single institution."Journal of Pediatric Surgery. 37(6). 835-839 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tomiyama H, Shimotake T, Ono S, Kimura O, Tokiwa K, Iwai N.: "Relationship between the type of RET/GDNF/NTN or SOX10 gene mutations and long-term results after surgery for total colonic aganglionosis with small bowel involvement."Journal of Pediatric Surgery. 36(11). 1685-1688 (2001)

    • Related Report
      2003 Annual Research Report
  • [Publications] Bitoh Y, Shimotake T, Sasaki Y, Iwai N.: "Development of the pelvic floor muscles of murine embryos with anorectal malformations."Journal of Pediatric Surgery. 37(2). 224-227 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Bitoh Y, Shimotake T, Kubota Y, Kimura O, Iwai N: "Impaired distribution of retinoic acid receptors in the hindgut-tailgut region of murine embryos with anorectal malformations"Journal of Pediatric Surgery. 36(2). 377-380 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Bitoh Y, Shimotake T, Sasaki Y, Iwai N: "Development of the pelvic floor muscles of murine embryos with anorectal malformations"Journal of Pediatric Surgery. 37(2). 224-227 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shimotake T, Go S, Inoue K, Tomiyama H, Iwai N.: "A homozygous missense mutation in the tyrosine E kinase domain of the RET proto-oncogene in an infant with total intestinal aganglionosis"American Journal of Gastroenterology. 96(4). 345-347 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tomiyama H, Shimotake T, Ono S, Kimura O, Tokiwa K, Iwai N.: "Relationship between the type of RET/GDNF/NTN or SOX10 gene mutations and long-term results after surgery for total colonic aganglionosis with small bowel involvement"Journal of Pediatric Surgery. 36(11). 1685-1688 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Pingault V, Girard M, Bondurand N, Dorkins H, Shimotake T, Verma I, Baumann C, Goossens M: "SOX10 mutations in chronic intestinal pseudo-obstruction suggest a complex physiopathological mechanism"Human Genetics. 111(2). 198-206 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Bitoh Y, Shimotake T, Sasaki Y, et al.: "Development of the pelvic floor muscles of murine embryos with anorectal malformations"Journal of Pediatric surgery. 37(2). 224-227 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Bitoh Y, Shimotake T, Kubota Y, et al.: "Impaired distribution of retioic acid receptors in the hindgut-tailgut regionof murine embryos with anorectal malformations"Journal of Pediatric Surgery. 36(2). 377-370 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tomiyama H, Shimotake T, Ono S, et al.: "Relationship between the type of RET/GDNF/NTN or SOX10 gene mutations and long-term results after surgery fortotal colonic aganglionosis with small bowel involvement"Journal of Pediatric Surgery. 36(11). 1685-1688 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shimotake T, Go S, Tomiyama H, et al.: "Proximal jejunostomy with or without myectomy-myotomy modification in 5 infants with total intestinal aganglionosis-an experience of surgical treatments in a single institution"Journal of Pediatric Surgery. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shimotake T, Go S, Inoue K, et al.: "A homozygous missense mutation in the tyrosine kinase domain of the RET proto-oncogene in an infant with total intestinal aganglionoses"American Journal of Gastroenterology. 96(4). 1286-1291 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Inoue K, Shimotake T, Tomiyama H, et al.: "Mutational analysis of the RET and GDNF genes in children with hypoganglionosis"European Journal of Pediatric Surgery. 11(2). 120-123 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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