• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

1997 Fiscal Year Final Research Report Summary

ANALYSIS OF 3-OXO-DELTA^4-BILE ACIDS IN URINE OF NEONATES AND CONGENITAL DISORDERS OF BILE ACID BIOSYNTHESIS.

Research Project

Project/Area Number 08672484
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
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) KIMURA Akihiko  KURUME UNIVERSITY,SCHOOL OF MEDICINE,DEPT.OF PEDIATRICS & CHILD HEALTH,ASSISTANT, 医学部, 助手 (00211201)
YOSHIMURA Teruki  HEALTH SCIENCES UNIV.OF HOKKAIDO,FAC.PHARMACEUTICAL SCIENCES,INSTRUCTOR, 薬学部, 講師 (60220737)
MURAI Tsuyoshi  HEALTH SCIENCES UNIV.OF HOKKAIDO,FAC.PHARMACEUTICAL SCIENCES,ASSISTANT, 薬学部, 助手 (50260823)
Project Period (FY) 1996 – 1997
KeywordsBILE ACID BIOSYNTHESIS / CONGENITAL DISORDER / CHOLESTASIS / GAS CHROMATOGRAPHY-MASS SPECTROMETRY / HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY / ENZYME IMMUNOASSAY / 3-OXO-DELTA^4-BILE ACID / 3-OXO-DELTA^4-STEROID 5beta-REDUCTASE / 3-オキソ-Δ^4-ステロイド5β-還元酵素
Research Abstract

The estsablishment of the diagnosis for congenital liver disease 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 3-oxo-DELTA^4-bile acids by GC-MS,HPLC and immunological assay, the elucidation of the bile acid profiles in neonatal cholestatic diseases, and the establishment of the diagnosis for the congenital bile acid disorder.
1.The 3-oxo-DELTA^4-bile acids were synthesized chemically from cholic and chenodeoxycholic acids, and their conjugates were also prepared as the authentic samples by condensation with glycine, taurine and/or sulfuric acid.
2.A highly sensitive determination method of the 3-oxo-DELTA^4-bile acids and related bile acids in neonatal urine has been developed by GC-MS using selected ion monitoring with their characteristic fragment ions. Diagnostic bile acid analysis for neonatal liver disease was performed by GC-MS.
3.An improved quantitative analysis of the conjugated 3-oxo-DELTA^4-bile acids in neonatal urine has been developed by HPLC employing the dual wavelength UV detection at 245 and 280nm for 3-oxo-DELTA^4- and 3-oxo-DELTA^<4,6>-bile acids, respectively. These bile acids were predominantly excreted in urine of patients as the glycine and taurine conjugates.
4.An enzyme immunoassay of conjugated 7alpha-hydroxy-3-oxo-DELTA^4-cholanoic acid has been developed using horse radish peroxidase labeled antigen. The conjugated bile acid in urine from patients were significantly higher than that of normal newborns.

  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] 藤間 貞彦: "胎児性生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
  • [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
  • [Publications] Teruki Yoshimura: "High-Performance Liquid Chromtatographic Determination of Conjugated and Unconjugated 3-Oxo-Λ^4- and 3-Oxo-Δ^<4, 6>-Bile Acids in Human Urine." J. Liq,Chrom. & Rel. Technol,. 20(3). 923-934 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ryo Sumazaki: "Gene Analysis in Δ^4-3-Oxosteroid 5β-Reductase Deficiency." Lancet. 349. 329 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsuyoshi Murai: "Determination of Fetal Bile Acids in Biological Fluids from Neonates by GC-NICIMS." J. Chromatogr. B.691 (1). 13-22 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [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 GC-MS." J. Chromatogr. B. 693(1). 11-21 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Toshiro Inoue: " Developmental Pattern of 3-Oxo-Δ^4 Bile Acids in Neonatal Bile Acid Metabolism." Arch. Dis. Child.77(1). F52-56 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akihiko Kimura: "Perinatal Bile Acid Metabolism: Analysis of Urinary Bile Acids in Pregnant Women and Newborns." J. Lipid Res.38(l0). 1954-1962 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akihiko Kimura: "Urinary 7α-Hydroxy-3-oxochol-4-en-24-oic and 3-oxochola-4, 6-dien-24-oic Acids in Infants with Cholestasis." J. Hepatology. 28(1). 270-279 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akihiko Kimura: "Diagnosis of the First Japanese Patient with 3-Oxo-Δ^4-steroid 5β-Reductase Deficiency by Use of Immunoblot Analysis." Eur. J. Pediatr.(in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsuyoshi Murai: "Profile Analysis of 3-Oxo-Δ^4- and 3-Oxo-Δ^<4,6>-Bile Acids in BiologicalFluids from Infants with Cholestasis and Diagnosis of Matabolic Disorder." Trend. Anal. Chem.(in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [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
  • [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
  • [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
  • [Publications] Shigeo Ikegawa, Akiko Kinoshita, Kaori Kido, Tsuyoshi Murai, Teruki Yoshimura, and Masahiko Tohma: "Enzyme Immunoassay for Conjugated Cholic and 1beta-Hydroxy-cholic 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
  • [Publications] Ryo Sumazaki, Norimasa Nakamura, Junichi Shoda, Takao Kurosawa, and Masahiko Tohma: "Gene Analysis in DELTA^4-3-Oxosteroid 5beta-Reductase Deficiency." Lancet. 349. 329 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [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.691(1). 13-22 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mikako Suzuki, Tsuyoshi Murai, Teruki Yoshimura, Akihiko Kimura, Takao Kurosawa, and Masahiko Tohma: "Determination of 3-Oxo-DELTA^4- and 3-Ox-DELTA^<4,6>-bile Acids and Related Compounds in Biological Fluids of Patients with Ccholestasis by Gas Chromatography Mass Spectrometry." J.Chromatogr.B.693(1). 11-21 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Toshiro Inoue, Akihiko Kimura, Kumiko Aoki, Masahiko Tohma, and Hirohisa Kato: "Developmental Pattern of 3-Oxo-DELTA^4-Bile Acids in Neonatal Bile Acid Metabolism." Arch.Dis.Child.77(1). F52-56 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akihiko Kimura, Mikako Suzuki, Tsuyoshi Murai, Toshiro Inoue, Yukihiro Nomura, Teruki Yoshimura, Takao Kurosawa, and Masahiko Tohma: "Perinatal Bile Acid Metabolism : Analysis of Urinary Bile Acids in Pregnant Women and Newborns." J.Lipid Res.38(10). 1954-1962 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akihiko Kimura, Mikako Suzuki, Tsuyoshi Murai, Takao Kurosawa, Masahiko Tohma, Michio Sata, Toshiro Inoue, Atsuo Hoshiyama, Eisuke Nakashima, Yasuhiro Yamashita, Takuji Fujisawa, and Hirohisa Kato: "Urinary 7alpha-Hydroxy-3-oxochol-4-en-24-oic and 3-Oxochola-4,6-dien-24-oic Acids in Infants with Cholestasis." J.Hepatology. 28(1). 270-279 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akihiko Kimura, Kazu-Hiro Kondo, Kyu-Ichiro Okuda, Mikako Suzuki, Takao Kurosawa, Masahiko Tohma, Toshiro Inoue, Atsushi Nishiyori, Makoto Yoshino, and Toshiaki Setoguchi: "Diagnosis of the First Japanese Patient with 3-Oxo-DELTA^4-steroid 5beta-Reductase Deficiency by Use of Immunoblot Analysis." Eur.J.Pediatr.(in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuyoshi Murai, Teruki Yashimura, Akihiko Kimura, Takao Kurosawa and Masahiko Tohma: "Profile Analysis of 3-Oxo-DELTA^4- and 3-Oxo-DELTA^<4,6>-Bile Acids in Biological Fluids from Infants with Cholestasis and Diagnosis of Matabolic Disorder." Trend.Anal.Chem.(in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 1999-03-16  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi