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Dynamic analysis of Shh and specific receptor in embryologic process of anorectal malformations.

Research Project

Project/Area Number 15390534
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatric surgery
Research InstitutionKyoto Prefectural University of Mdicine

Principal Investigator

IWAI Naomi  Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Professor, 医学研究科, 教授 (90128695)

Co-Investigator(Kenkyū-buntansha) KIMURA Osamu  Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Associate Professor, 医学研究科, 講師 (10315963)
下竹 孝志  京都府立医科大学, 医学研究科, 助手 (90254341)
Project Period (FY) 2003 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2004: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥6,100,000 (Direct Cost: ¥6,100,000)
KeywordsAnorectal malformations / Embryology / Receptor / Shh / Morphology / 胎生学 / シグナル伝達系 / tethered cord syndrome
Research Abstract

The aim of this research was to determine the possible role of the retinoid-mediated signaling pathway in the pathogenesis of anorectal malformatins (ARM). We investigated whether all-trans retinoic acid (ATRA) affects the expression pattern of Sonic hedgehog (Shh) and Bone morphogenetic protein (BMP) 4, which play important roles in anorectal morphogenesis in vertebrates.
Pregnant ICR strain mice were fed 100mg/kg of ATRA on the ninth gestigational day (E9). Embryos with or without administration of ATRA were obtained from the uteri between El2 and E16 and were fixed immediately in a 4% paraformaldehyde solution. Frozen sections were evaluated for concentric layers around the endodermal epithelium by II & E stain and immunohistochemistry using antibodies created specifically to act against Shh and BMP4.
More than 95% of the embryos administered ATRA had ARM. In normal hindgut development, Shh from the epithelium induces BMP4 expression in the mesenchyme, which differenciates into the lamina propria and the submucosa. In ARM embryos, expressions of Shh and BMP4, which appear to play a crucial role in organogenesis of the hindgut, were disturbed in the cell signaling pathway between the epithelium and the mesenchyme layers.

Report

(5 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (33 results)

All 2007 2006 2005 2004 Other

All Journal Article (26 results) Book (3 results) Publications (4 results)

  • [Journal Article] Social quality of life for adult patients with anorectal malformations2007

    • Author(s)
      Iwai N, Deguchi E, Kimura O, Kubota Y, Ono S, Shimadera S
    • Journal Title

      Journal of Pediatric Surgery 42・2

      Pages: 313-317

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Social quality of life for adult patients with anorectal malformations2007

    • Author(s)
      Iwai N, Deguchi E, Kimura 0, Kubota Y, Ono S, Shimadera S
    • Journal Title

      Journal of Pediatric Surgery 42-2

      Pages: 313-317

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Infrared spectrophotometry of intraluminal meconiumcalculi in a neonate with imperforate anus and rectal fistula2006

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

      Journal of Pediatric Surgery 41・6

      Pages: 1173-1176

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Morphology of the enteric nervous system in the hindgut of an infant with cloacal extrophy2006

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

      Journal of Pediatric Surgery 41・12

      Pages: 1957-1961

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 高位鎖肛に対する腹腔鏡下腹会陰式肛門形成術後の排便機能2006

    • Author(s)
      木村 修, 岩渕敏久, 文野誠久, 嶋寺伸一, 佐々木康成, 岩井直躬
    • Journal Title

      京都府立医科大学雑誌 1151・1

      Pages: 13-17

    • NAID

      110002963957

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] 中間位および高位型の直腸肛門奇形術後の排便機能評価2006

    • Author(s)
      木村修, 津田知樹, 嶋寺伸一, 樋口恒司, 文野誠久, 岩井直躬
    • Journal Title

      小児外科 38・8

      Pages: 984-987

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Infrared spectrophotometry of intraluminal meconiumcalculi in a neonate with imperforate anus and rectal fistula2006

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

      Journal of Pediatric Surgery 41-6

      Pages: 1173-1176

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Morphology of the enteric nervous system in the hindgut of an infant with cloacal extrophy2006

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

      Journal of Pediatric Surgery 41-12

      Pages: 1957-1961

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Results of laparoscopic anorectal pull-through in infants with high type of anorectal malformations ( in Japanese)2006

    • Author(s)
      Kimura 0, Iwabuchi T, Fumino S, Shimadera S, Sasaki Y, Deguchi E, Iwai N
    • Journal Title

      Journal of Kyoto Prefectural University of Medicine 115-1

      Pages: 13-17

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Evaluation of postoperative anorectal function in children with intermediate and high type of anorectal malformations ( in Japanese)2006

    • Author(s)
      Kimura 0, Tsuda T, Shimadera S, Higuchi K, Fumino S, Ono S, Kubota T, Deguchi E, Iwai N
    • Journal Title

      Japanese Journal of Pediatric Surgery 38-8

      Pages: 984-987

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Postoperative electromanometric, myographic, and anal endosonographic evaluations2006

    • Author(s)
      Iwai N, Deguchi E, Shimotake T, Kimura 0
    • Journal Title

      Anorectal malformations in children, Springer, Heidelberg, Germany

      Pages: 345-349

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Infrared spectrophotometry of intraluminal meconium calculi in a neonate with imperforate anus and rectal fistula2006

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

      Journal of Pediatric Surgery 41・6

      Pages: 1173-1176

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Morphology of the enteric nervous system in the hindgut of an infant with cloacal extrophy2006

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

      Journal of Pediatric Surgery 41・12

      Pages: 1957-1961

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 中間位および高位型の直腸肛門奇形術後の排便機能評価2006

    • Author(s)
      木村 修, 津田知樹, 嶋寺伸一, 樋口恒司, 文野誠久, 岩井直躬
    • Journal Title

      小児外科 38・8

      Pages: 984-987

    • Related Report
      2006 Annual Research Report
  • [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

      Journal of Pediatric Surgery 40(5)

      Pages: 805-809

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Developmental study of the tethered spinal cord in murine embryos with anorectal malformations2005

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

      Journal of Pediatric Surgery 40(12)

      Pages: 1927-1930

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Preoperative bombesin administration can protect the rat small bowel allograft from ischemic reperfusion injury2005

    • Author(s)
      Kinoshita H, Kimura O, Furukawa T, Higuchi K, Chujo S, Iwai N
    • Journal Title

      Journal of Pediatric Surgery 40(12)

      Pages: 1877-1891

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Estrogen receptor expression in anomalous arrangement of the pancreaticobiliary duct2005

    • Author(s)
      Fumino S, Iwai N, Deguchi E, Kimura O, Ono S, Iwabuchi T
    • Journal Title

      Journal of Pediatric Surgery 40(11)

      Pages: 1716-1720

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Respiratory insufficiency in a newborn with mesenchymal hamartoma of the chest wall2005

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

      Journal of Pediatric Surgery 40(4)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Neuricutaneus melanosis associated with Hirschsprung's disease in a male neonate2005

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

      Journal of Pediatric Surgery 40(8)

    • Related Report
      2005 Annual Research Report
  • [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

      Journal of Pediatric Surgery (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Infrared spectrophotometry of intraluminal meconium calculi in a neonate with imperforate anus and rectourethral fistula2005

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

      Journal of Pediatric Surgery (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Morphology of the enteric nervous system in the hindgut of an infant with cloacal exstrophy2005

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

      European Journal of Pediatric Surgery (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Neurocutaneous melanosis associated with Hirschsprung's disease in a male neonate2005

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

      Journal of Pediatric Surgery (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Mucoepidermal carcinoma of the lung detected by positron emission tomography in a 5-year-old girl.2005

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

      Journal of Pediatric Surgery (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Sonic hedgehog and Bone morphogenetic protein 4 expressions in the hindgut region of murine embryo with anorectal malformations2004

    • Author(s)
      Sasaki Y, Iwai N, Tsuda T, Kimura O
    • Journal Title

      Journal of Pediatric Surgery 39(2)

      Pages: 170-173

    • Related Report
      2004 Annual Research Report
  • [Book] Anorectal malformations in children2006

    • Author(s)
      IwaiN, Deguchi E, Shimotake T, Kimura O
    • Publisher
      Springer, Heidelberg, Germany
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] Anorectal malformations in children2006

    • Author(s)
      Iwai N, Deguchi E, Shimotake T, Kimura O
    • Publisher
      Springer, Heidelherg, Germany
    • Related Report
      2006 Annual Research Report
  • [Book] Postoperative electromanometrical, myographical and imaging evaluations. Anorectmations in children(AM Holschneider ed)2006

    • Author(s)
      Iwai N, Deguchi E, Shimotake T, Kimura O
    • Publisher
      Springer(In press)
    • Related Report
      2005 Annual Research Report
  • [Publications] Sasaki Y, Iwai N, Tsuda T, Kimura O: "Sonic hedgehog and Bone morphogenetic protein 4 expressions in the hindgut region of murine embryo with anorectal malformations"Journal of Pediatric Surgery. 39(2). 170-173 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hibi M, Iwai N, Kimura O, Sasaki Y, Tsuda T: "Results of biofeedback therapy for fecal incontinence in children with encopresis and following surgery for anorectal malformations"Diseases of the Colon and Rectum. 46(10). S54-S58 (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, 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

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Published: 2003-04-01   Modified: 2016-04-21  

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