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DEVELOPMENT OF MASS SCREENING METHOD FOR CONGENITAL BILIARY ATRESIA.

Research Project

Project/Area Number 07557297
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section試験
Research Field Physical pharmacy
Research InstitutionHEALTH SCIENCES UNIVERSITY OF HOKKAIDO

Principal Investigator

TOHMA Masahiko  HEALTH SCIENCES UNIV.OF HOKKAIDO,FAC.PHARMACEUTICAL SCIENCES,PROFESSOR, 薬学部, 教授 (30001043)

Co-Investigator(Kenkyū-buntansha) MURAI Tsuyoshi  HEALTH SCIENCES UNIV.OF HOKKAIDO,FAC.PHARM.SCI., ASSISTANT, 薬学部, 助手 (50260823)
YOSHIMURA Teruki  HEALTH SCIENCES UNIV.OF HOKKAIDO,FAC.PHARM.SCI., INSTRUCTOR, 薬学部, 講師 (60220737)
KUROSAWA Takao  HEALTH SCIENCES UNIV.OF HOKKAIDO,FAC.PHARM.SCI., ASSISTANT PROFESSOR, 薬学部, 助教授 (50103198)
鈴木 三佳子  北海道医療大学, 薬学部, 助手 (60260824)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsFETAL BILE ACID / CONGENITAL BILIARY ATRESIA / NEONATAL LIVER DISORDER / GAS CHROMATOGRAPHY-MASS SPECTROMETRY / HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY / ENZYME IMMUNOASSAY / MASS SCREENING / DRIED BLOOD SPOTTED FILER PAPER
Research Abstract

The estsablishment of the diagnosis of congenital liver disorder is urgently required for the remedy of liver disorder in early life. The metabolism of bile acids in fetus and neonate is thought to be different from that in adults. The aim of this reaserch is the developement of quantitative analysis of fetal bile acids by GC-MS and immunological assay, elucidation of the profiles of bile acids with hepatobiliary diseases, and establishment of the precise diagnosis and mass screening of congenital biliary atresia.
1. A highly sensitive GC-MS determination of the fetal bile acids in neonatal serum and dried blood spot disc has been developed by capillary GC-MS using selected ion monitoring with negative ion chemical ionization. Diagnostic bile acid analysis of neonatal liver diseases was accomplished by GC-MS.
2. An improved quantitative analysis of the conjugated fetal bile acids in urine of newborns has been developed by HPLC employing labeling with 1-anthroyl cyanide and fluorescence detection.
3. A highly sensitive enzyme immunoassay of conjugated 1beta-hydroxycholic acid in heterologous combination has been developed using horse radish peroxidase labeled antigen. Concentrations of the conjugated bile acid in dried blood spotted onto filter paper in newborns with congenital biliary atresia were significantly higher than those of normal newborns, showing the possibility of mass screening for the disorder.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report

Research Products

(31 results)

All Other

All Publications (31 results)

  • [Publications] Takao Kurosawa: "Synthsis of 19-Hydroxylated Bile Acids and Identification of 3α,7α,12α,19-Tetrahydroxy-5β-cholan-24-oic Acid in Human Neonatal Urine." Chem.Pharm.Bull.43. 1551-1557 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 黒沢隆夫: "ガスクロマトグラフィー/質量分析法による新生児尿中の3β,4β,7α,12α-テトラヒドロキシ胆汁酸の同定と定量." 分析化学. 44. 777-782 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 吉村昭毅: "胎児性胆汁酸測定における3α-ヒドロキシステロイドデヒドゲナーゼの特異性." 分析化学. 44. 865-869 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akihiko Kimura: "Profile of Urinary Bile Acids in Familial intrahepatic Cholestasis with Coombs' Negative Haemolytic Anaemia." Acta Paediatr.84. 1119-1124 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tsuyoshi Murai: "Determination of Fetal Bile Acids in a Dried Blood Disc from Neonates by Gas Chrom atography-Negative Ion Chemical Ionization Mass Spectrometry." J.Mass Spectrom.& Rapid Commun.Mass Spectrom.S205-206 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 藤間貞彦: "胎児性胆汁酸及び関連ステロイドの高性能分析法の開発と体内動態の解析." 薬学雑誌. 116(10). 753-775 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shigeo Ikegawa: "Enzymeimmunoassay for Conjugated Cholic and 1β-Hydroxycholic Acids in Urine of Early Infancy." J.Immunoassay. 17(2). 105-118 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ryoichi Yamakawa: "Urinary 1β-Hydroxyursodeoxycholic Acid during Ursodeoxycholic Acid Therapy." J.Gastroenterol.31. 917-918 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shigeo Ikegawa, Teruki Yoshimura, Kazuhiko Ito, Takao Kurosawa, and Masahiko Tohma: "Simultaneous Fluorometric Determination of Conjugated Fetal Bile Acids in Urine of Newborns by High-Performance Liquid Chromatography." Anal.Sci.11 (1). 91-96 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takao Kurosawa, Yukihiro Nomura, Reijiro Mahara, Teruki Yoshimura, Akihiko Kimura, Shigeo Ikegawa, and Masahiko Tohma: "Synthsis of 19-Hydroxylated Bile Acids and Identification of 3alpha, 7alpha, 12alpha, 19-Tetrahydroxy-5beta-cholan-24-oic Acid in Human Neonatal Urine." Chem.Pharm.Bull.43 (9). 1551-1557 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takao Kurosawa, Yukihiro Nomura, Teruki Yoshimura, Tsuyoshi Murai, Reijiro Mahara, and Masahiko Tohma: "Identification and Determination of 3beta, 4beta, 7alpha, 12alpha-Tetrahydroxy-5beta-cholan-24-oic Acid by GC/MS in Neonatal Urine." BUNSEKI KAGAKU. 44 (10). 777-782 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Teruki Yoshimura, Takao Kurosawa, Shigeo Ikegawa, and Masahiko Tohma: "Substrate Specificity of 3alpha-Hydroxysteroid Dehydrogenase for the Oxidation of Fetal Bile Acids." BUNSEKI KAGAKU. 44 (10). 865-869 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akihiko Kimura, Kousuke Ushijima, Mikako Suzuki, Masahiko Tohma, Takahiro Inokuchi, and Hirohisa Kato: "Profile of Urinary Bile Acids in Familial Intrahepatic Cholestasis with Coombs' Negative Haemolytic Anaemia." Acta Paediatr.84. 1119-1124 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tsuyoshi Murai, Reijiro Mahara, Mikako Suzuki, Teruki Yoshimura, Takao Kurosawa, and Masahiko Tohma: "Determination of Fetal Bile Acids in a Dried Blood Disc from Neonates by Gas Chromatography-Negative Ion Chemical Ionization Mass Spectrometry." J.Mass Spectrom.& Rapid Commun.Mass Spectrom.S205-206 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shigeo Ikegawa, Akiko Kinoshita, Kaori Kido, Tsuyoshi Murai, Teruki Yoshimura, and Masahiko Tohma: "Enzyme Immunoassay for Conjugated Cholic and 1beta-Hydroxycholic Acids in Urine of Early Infancy" J.Immunoassay. 17 (2). 105-118 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Masahiko Tohma: "Determination of Fetal Bile Acids and Related Steroidal Compounds and Their Profile in Neonatal Biological Fluids." YAKUGAKU ZASSHI. 116 (10). 753-775 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ryoichi Yamakawa, Akihiko Kimura, Kumiko Aoki, Mikako Suzuki, Reijiro Mahara, and Masahiko Tohma: "Urinary 1beta-Hydroxyursodeoxycholic Acid during Ursodeoxycholic Acid Therapy." J.Gastroenterol.31. 917-918 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Teruki Yoshimura, Toshiyasu Taniguchi, Takao Kurosawa, Akihiko Kimura, and Masahiko Tohma: "High-Performance Liquid Chromatographic Determination of Conjugated and Unconjugated 3-Oxo-DELTA^4-and 3-Oxo-DELTA^<4,6>-Bile Acids in Human Urine" J.Liq.Chrom.& Rel.Technol.20 (6). 923-934 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tsuyoshi Murai, Reijiro Mahara, Takao Kurosawa, Akihiko Kimura, and Masahiko Tohma: "Determination of Fetal Bile Acids in Biological Fluids from Neonates by Gas Chromatography-Negative Ion Chemical Ionization Mass Spectrometry." J.Chromatogr.B.(in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 藤間貞彦: "胎児性胆汁酸及び関連ステロイドの高性能分析法の開発と体内動態の解析." 薬学雑誌. 116(10). 753-775 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shigeo Ikegawa: "Enzymeimmunoassay for conjugated Cholic and 1β-Hydroxycholic Acids in Urine of Early Infancy." J.Immunoassay. 17(2). 105-118 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ryoichi Yamakawa: "Urinary 1β-Hydroxyursodeoxycholic Acid during Ursodeoxycholic Acid Therapy." J.Gastroenterol.31. 917-918 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Teruki Yoshimura: "High-Performance Liquid Chromatographic Determination of conjugated and Unconjugated 3-Oxo-Δ^4- and 3-Oxo-Δ^<4,6>-Bile Acids in Human Urine." J.Liq.Chrom.& Rel.Technol. 20(3). 923-934 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tsuyoshi Murai: "Determination of Fetal Bile Acids in Biological Fluids from Neonates by Gas Chromatgraphy-Negative Ion Chemical Ionization Mass Spectrometry." J.Chromatogr.B. in press (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Mikako Suzuki: "Determination of 3-Oxo-Δ^4- and 3-Oxo-Δ^<4,6>-Bile Acids and Related Compounds in Biological Fluids of Patients with Ccholestasis by Gas Chromatography-Mass Spectrometry." J.Chromatogr.B. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takao Kurosawa: "Synthsis of 19-Hydroxylated Bile Acids and Identification of 3α, 7α, 12α, 19-Tetrahydroxy-5β-cholan-24-oic Acid in Human Neonatal Urine." Chem. Pharm. Bull.43. 1551-1557 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 黒沢隆夫: "ガスクロマトグラフィー/質量分析法による新生児尿中の3β,4β,7α,12β-テトラヒドロキシ胆汁酸の同定と定量." 分析化学. 44. 777-782 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 吉村昭毅: "胎児性胆汁酸測定における3α-ヒドロキシステロイドデヒドゲナーゼの特異性." 分析化学. 44. 865-869 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Akihiko Kimura: "Profile of Urinary Bile Acids in Familial Intrahepatic Cholestasis with Coombs' Negative Haemolytic Anaemia." Acta Paediatr.84. 1119-1124 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tsuyoshi Murai: "Determination of Fetal Bile Acids in a Dried Blood Disc from Neonates by Gas Chrom atography-Negative Ion Chemical Ionization Mass Spectrometry." J. Mass Spectrom. & Rapid Commun. Mass Spectrom.S205-206 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shigeo Ikegawa: "Enzymeimmunoassay for Conjugated Cholic and 1β-Hydroxycholic Acids in Urine of Early Infancy." J. Immunoassay. (in press.). (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1996-03-31   Modified: 2016-04-21  

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