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PROFILE OF FETAL BILE ACID IN FETUS AND NEONATE,AND DIAGNOSIS OF NEONATAL HEPATOBILIALY DISEASES

Research Project

Project/Area Number 05671788
Research Category

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

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

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) KIMURA Akihiko  KURUME UNIVERSITY SCHOOL OF MEDICINE,INSTRUCTOR, 医学部, 助手 (00211201)
YOSHIMURA Teruki  HEALTH SCIENCES UNIVERSITY OF HOKKAIDO,FAC.PHARM.SCIENCES,INSTRUCTOR, 薬学部, 助手 (60220737)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1993: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsFETAL BILE ACID / BILE ACID PROFILE / NEONATAL LIVER DISTEASE / GAS CHROMATOGRAPHY-MASS SPECTROMETRY / BILE ACID ENZYMATIC BIOSYNTHESIS / HYPERTYROSINEMIA CHOLESTASIS / 3-0X0 UNSATURATED BILE ACID / RAT LIVER MICROSOME / 未熟児 / 高速液体クロマトグラフィー / 胎児性胆汁酸合成 / カニクイザル肝ミクロゾーム / ガスクロマトグラフイー質量分析 / 高速液体クロマトグラフイー
Research Abstract

The metabolism of bile acids in fetus and neonate is thought to be different from that in adults. A highly sensitive analytical metod of bile acids by GC-MS has been required to elucidate the composition of fetal bile acids in serum for the diagnosis of neonatal hepatobiliary diseases.
(1) Symthesis of 4beta- and 6alpha-hydroxy bile acids were efficiently carried out for the identification of these acid in urine and serum from neonates by the comparison with the standards.
(2) A higly sensitive GC-MS determination of the fetal bile acid in neonatal serum and dry blood spot disc has been developed by capillary GC-MS using selected ion monitoring with negative ion chemical ionization.
(3) The fetal bile acids are usualy biosynthesized thrugh the hydroxylation at 1beta- or 6alpha-psition of the correspnding usual bile acids. The 1beta-hydroxylated C_<27>-bile acid were detected in the incubation mixture of the C_<27>-intermediates with rat liver microsome as a new biosynthetic route.
(4) Diagnostic analysis of neonatal liver diseases was accomplished by GC-MS.The 3-oxo unsaturated bile acids were identified and determined in the urine of patients with sevear cholestasis from hypertyrosinemia.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report

Research Products

(29 results)

All Other

All Publications (29 results)

  • [Publications] Teruki Yoshimura: "An Efficient Synthesis of 4β-and 6α-Hydroxylated Bile Acids." Steroids.58. 52-58 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hitoshi Chiba: "Determination of Urinary 18-Hydroxycortisol by Isocratic Normal-Phase High-Performance Liquid Chromatography." J. Chromatogr.613. 132-136 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hitoshi Chiba: "A Direct Enzyme Immunoassay for 18-Hydroxycortisol in Urine : A New Tool for Screening Primary Aldosteronism." J. Steroid Biochem. Molec. Biol.46. 85-89 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shigeo Ikegawa.: "Enzyme Immunoassay for Conjugated 1 β-Hydroxycholic Acid and Its Application to Dried Blood Spotted on Filter Paper." Anal. Sci.9. 791-794 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shigeo Ikegawa: "Radioimmunoassay of Conjugated 1 β-Hydroxycholic Acid in Dried Blood Spots for Diagnosis of Congenital Biliary Atresia." Biol. Pharm. Bull.17. 5-8 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mizuho Une: "Identification of (24E) -3α,7α-Dihydroxy-5β-cholest-24-enoic Acid and- (24R,25S) -3α,7α,24-Trihydroxy-5β-cholestanoic Acid as Intermediates in the Conversion of 3α,7α-Dihydroxy-5β-cholestanoic acid to Cheno-deoxycholic Acid in Rat Liver Homogenates." J. Lipid Res.35. 620-624 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Akihiko Kimura: "Fetal Bile Acid Metabolism During Infancy:Analysis of 1 β-Hydroxy-Iated Bile Acids in Urine,Meconium and Feces." Hepatorogy. 20. 819-824 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shigeo Ikegawa: "Simultaneous Fluorometric Determination of Conjugated Fetal Bile Acids in Urine of Newborns by High-Performance Liquid Chromatography." Anal. Sci.11. 91-96 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Teruki Yoshimura, Reijiro Mahara, Takao Kurosawa, Shigeo Ikegawa, and Masahiro Tohma: "An Efficient Synthesis of 4beta- and 6alpha-Hydroxylated Bile Acids." Steroids. 58 (2). 52-58 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hitoshi Chiba, Yoshito Ito, Kazuhiko Matsuno, Kunihiko Kobayashi, Takao Kurosawa, Shigeo Ikegawa, Reijiro Mahara, and Masahiko Tohma: "Determination of Urinary 18-Hydroxycortisol by Isocratic Normal-Phase High-Performance Liquid Chromatography." J.Chromatogr.613 (2). 132-136 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hitoshi Chiba, Shigeo Ikegawa, Takao Kurosawa, Teruki Yoshimura, Yoshito Ito, Kazuhiko Matsuno, Kunihiko Kobayashi, and Masahiko Tohma: "A Direct Enzyme Immunoassay for 18-Hydroxycortisol in Urine : A New Tool for Screening Primary Aldosteronism." J.Steroid Biochem.Molec.Biol.46 (1). 85-89 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shigeo Ikegawa, Tsuyoshi Murai, Kenji Nakamura, Tomoki Salaguchi, and Masahiko Tohma: "Enzyme Immunoassay for Conjugated 1beta-Hydroxycholic Acid and Its Application to Dried Bllod Spotted on Filter Paper." Anal.Sci.9 (6). 791-794 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shigeo Ikegawa, Tsuyoshi Murai, Akira Matsui, and Masahiko Tohma: "Radioimmunoassay of Conjugated 1beta-Hydroxycholic Acid in Dried Blood Spots for Diagnosis of Congenital Biliary Atresia." Biol.Pharm.Bull. 17 (1). 5-8 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mizuho Une, Akihumi Inoue, Takao Kurosawa, Masahiko Tohma, and Takahiko Hoshita.: "Identification of (24E)-3alpha, 7alpha-Dihydroxy-5beta-cholest-24-enoic Acid and (24R,25S)-3alpha, 7alpha, 24-Trihydroxy-5beta-cholestanoic Acid as Intermediates in the Conversion of 3alpha、7alpha-Dihydroxy-5beta-cholestanoic acid to Chenodeoxy-cholic Acid in Rat Liver Homogenates." J.Lipid Res.35. 620-624 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hiroaki Kohno, Seijiro Sato, Hitoshi Chiba, Kunihiko Kobayashi, Shigeo Ikegawa, Takao Kurosawa, Masahiko Tohma: "Monoclonal Antibodies Specific for 18-Hydroxycortisol and Their Use in an Enzyme Lmmunoassay for Human Urinary 18-Hydroxycortisol for Diagnosis of Primary Aldosteronism." Clin.Biochem.27 (4). 277-282 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Akihiko Kimura, Ryoichi Yamakawa, Kousuke Ushijima, Takuji Fujisawa, Norikazu Kuriya, Hirohisa Kato, Takahiro Inokuchi, Reijiro Mahara, Takao Kurosawa, Masahiko Tohma: "Fetal Bile Acid Metabolism During Infancy : Analysis of 1beta-Hydroxylated Bile ACid in Urine, Meconium and Feces." Hapatology. 20 (4). 819-824 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shigeo Ikegawa, Teruki Yoshimura, Kazuhiko Ito, Takao Kurosawa, 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
      1994 Final Research Report Summary
  • [Publications] Takao Kurosawa, Hiroyuki Nakano, Masahiro Sato, Masahiko Tohma: "Synthesis of 3alpha, 3alpha, 12alpha-Trihydroxy-and 3alpha, 7alpha-Dihydroxy-5beta-cholestan-26-oic Acid by the Use of beta-Ketosulfoxide." Steroids.(in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shigeo Ikegawa: "Redioimmunoassay of Conjugated 1β-Hydroxycholic Acid in Dried Blood Spots for Diagnosis of Congenital Biliary Atresia." Biol.Pharm.Bull.17. 5-8 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mizuho Une: "Identilication of (248)-3α,7α-Dihydroxy-5β-cholest-24-enoic Acid and (24R,25S)-3α,7α,24-Trihydroxy-5β-cholestanoic Acid as Intermediates in the Conversion of 3α,7α-Dihydroxy-5β-cholestanoic acid to Chenodooxycholic Acid in Rat Liver Homogenates." J.Lipid Res.35. 620-624 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hiroaki Kohno: "Monoclonal Antibodies Specific for 18-Hydroxycortisol and Their Use in an Enzyme Immunoassay for Human Urinary 18-Hydroxycortisol for Diagnosis of Primary Aldosteronisn." Clin.Biochem.27. 277-282 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Akihiko Kimura: "Fetal Bile Acid Metabolism During Infancy: Analysis of 1β-Hydroxylated Bile Acids in Urine,Meconium and Feces." Hepatorogy. 20. 819-824 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shigeo Ikegawa: "Simultaneous Fluorometric Determination of Conjugated Fetal Bile Acids in Urine of Newborns by High-Performance Liquid Chromatography." Anal.Sci.11. 91-96 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 井上寿郎: "胆汁酸代謝異常症-△^4-3-Oxosteroid 5β-Reductase 欠損症-" 小児科. 36. 101-105 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Teruki Yoshimura: "An Efficient Synthesis of 4beta-and 6alpha-Hydroxylated Bile Acids." Steroids.58. 52-58 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hitoshi Chiba: "Determination of Urinary 18-Hydroxycortisol by Isocratic Normal-Phase High-Performance Liquid Chromatography." J.Chromatogr.613. 132-136 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hitoshi Chiba: "A Direct Enzyme Immunoassay for 18-Hydroxycortisol in Urine:A New Tool for Screening Primary Aldosteronism." J.Steroid Biochem.Molec.Biol.46. 85-89 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Shigeo Ikegawa: "Enzyme Immunoassay for Conjugated 1beta-Hydroxycholic Acid and Its Application to Dried Blood Spotted on Filter Paper." Anal.Sci.9. 791-794 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Shigeo Ikegawa: "Radioimmunoassay of Conjugated 1beta-Hydroxycholic Acid in Dried Blood Spots for Diagnosis of Congenital Biliary Atresia." Biol.Pharm.Bull.17. 5-8 (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-03-31   Modified: 2016-04-21  

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