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Profile Analysis of Fetal Bile Acids and Congenital Liver Diseases

Research Project

Project/Area Number 62570970
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  Higashi-Nippon-Gakuen University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (30001043)

Co-Investigator(Kenkyū-buntansha) IKEGAWA Shigeo  Higashi-Nippon-Gakuen University, Faculty of Pharmaceutical Sciences, Associate, 薬学部, 助教授 (90111301)
MAHARA Reijiro  Higashi-Nippon-Gakuen University, Faculty of Pharmaceutical Sciences, Assistant, 薬学部, 助手 (30192347)
KUROSAWA Takao  Higashi-Nippon-Gakuen University, Faculty of Pharmaceutical Sciences, Assistant, 薬学部, 講師 (50103198)
Project Period (FY) 1987 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1989: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1988: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1987: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsFetal bile acid / Congenital biliary atresia / Gas chromatography-mass spectrometry / High-performance liquid chromatography / Immunoassay / 1 beta-Hydroxylated bile acid / Neonate / Bile acid profile / ガスクロマトグラフィ-質量分析 / 1β-水酸化胆汁酸 / 6ー水酸化胆汁酸 / C_<27>ー胆汁酸 / ガスクロマトグラフィー / ガスクロマトグラフィー質量分析 / 免疫家的測定法 / 先天性胆汁酸代謝異常症 / 6-水酸化胆汁酸 / 胎便 / 新生児尿 / 高速液体クロマトグラフィ / ガスクロマトグラフィ質量分析
Research Abstract

(1) The 1 beta- and 6 alpha-hydroxylated and DELT^A5-unsaturated bile acids were synthesized from cholic acid as a starting material, and these unusual bile acids were identified from meconium, amniotic fluid and neonatal urine. A highly sensitive and specific quantitative assay of these bile acids was developed by selected ion monitoring in GC-MS. The conjugated fetal bile acids were determined by HPLC using 3alpha-hydroxysteroid dehydrogenase and chemical luminesscence.
(2) In profile analysis of fetal bile acids, 1 beta-hydroxylated cholic acid was predominant in full term amniotic fluid, and neonatal urine, while 6alpha-hydroxylated chenodeoxycholic acid constituted a main component in meconium. Quantity of these bile acids increased according to the progress of gestation and decreased with developmental age after birth. Taurine conjugates are main bile salts in meconium and were exchanged progressively for the glycine conjugates in neonatal biles.
(3) Anti-fetal bile acid antisera were prepared by immunizing rabbits with hapten-bovine serum albumin conjugates coupled at C-15alpha and C-24 positions on the bile acid molecule, and their properties were investigated by heterologous combination assay using ^<125>I-labeled tracer. The antisera raised against these conjugates showed satisfactory affinity constants and reasonable specificity.
(4) The metabolism of fetal bile acids was studied on congenital and cholestatic liver diseases. These results suggested that hydroxylation at C-1beta or C-6alpha position and conjugation with taurine in liver might be carried out for the elimination of bile acids in fetal period and cholestasis.

Report

(4 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • 1987 Annual Research Report
  • Research Products

    (44 results)

All Other

All Publications (44 results)

  • [Publications] Masahiko Tohma,et al.: "Determination of 3β,12α-Dihydroxy-5-cholen-24-oic Acid and Related Bile Acids in Human Serum by Gas Chromatography-Mass Spectrometry." J.Chromatogr.421. 9-19 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Reijiro Mahara,et al.: "Determination of 1β-Hydroxylated Bile Acids and Related Compounds in Human Biological Fluids by Gas Chromatography-Mass Spectrometry." Anal.Sci.3. 449-452 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Reijiro Mahara,et al.: "Profile Analysis of Bile Acids in Human Fetal and Neonatal Periods by Gas Chromatography-Mass Spectrometry." J.Pharm.Dyn.12. s-7 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Takao Kurosawa,et al.: "Synthesis of 6-Hydroxylated Bile Acids and Identification of 3α,6α,7α,12α-Tetra-hydroxy-5β-cholan-24-oic Acid in Human Meconium and Neonatal Urine." Chem.Pharm.Bull.37. 557-559 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Junichi Shoda,et al.: "Altered Metabolism of Bile Acids in Cholestasis:Determination of 1β-and 6α-Hydroxylated Metabolites." J.Chromatogr.488. 315-328 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Shigeo Ikegawa,et al.: "Preparation and Properties of Antisera against Lithocholic Acid Linked to Bovine Serum Albumin at the C-1β and C-6 Positions." Chem.Pharm.Bull.36. 994-999 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 池川繁男,他: "抗Glyco-3β-hydroxy-5-cholen-24-oic Acid C-3 Bovine Serum Albumin(BSA) 結合体抗血清の調製とradioimmunoassay(RIA)における特異性" 薬学雑誌. 108. 979-983 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Shigeo Ikegawa,et al.: "Preparation and Comparative Properties of Antisera against Glyco-3β,12α-dihydroxy-5-cholen-24-oic Acid Linked to Bovine Serum Albumin at the C-3,C-15 and C-24 positions." Chem.Pharm.Bull.37. 2147-2152 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Junichi Shoda,et al.: "Similarity of Unusaual Bile Acids in Human Umbilical Cord Blood and Amniotic Fluid from Newborns' and in Sera and Urine from Adult Patients with Cholestatic Liver Diseases." J.Lipid Res.29. 847-858 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 秦温信,他: "先天性胆道閉鎖症の肝における胎児性胆汁酸の生成" 肝臓. 33. 819-820 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 藤間貞彦,他: "胎児ー新生児期における胆汁酸の体内動態と先天性代謝異常" 薬物動態. 4. 607-617 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Junichi Shoda,et al.: "Concurrent Occurrence of 3β,12α-Dihydroxy-5-cholenoic Acid Associated with 3β-Hydroxy-5-cholenoic Acid and Their Preferntial Urinary Excretion in Liver Diseases." J.Lipid Res.30. 1233-1242 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Masahiko Tohma, Hiromi Takeshita, Reijiro Mahara, Takao Kurosawa and Isao Makino: "Determination of 3beta, 12alpha-Dihydroxy-5-cholen-24-oic Acid and Related Bile Acids in Human Serum by Gas Chromatography-Mass Spectrometry." J. Chromatogr., 421 (1), 9-19 (1987).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Reijiro Mahara, Hiromi Takeshita, Takao Kurosawa, Shigeo Ikegawa and Masahiko Tohma: "Determination of 1beta-Hydroxylated Bile Acids and Related Compounds in Human Biological Fluids by Gas Chromatography-Mass Spectrometry." Anal. Sci., 3 (10), 449-452 (1987).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Reijiro Mahara, Takao Kurosawa, Masahiko Tohma, Yoshinobu Hata and Seiichiro Fujimoto: "Profile Analysis of Bile Acids in Human Fetal and Neonatal Periods by Gas Chromatography-Mass Spectrometry." J. Pharm. Dyn., 12 (1), s-7 (1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Takao Kurosawa, Reijiro Mahara, Hiroshi Nittono, Masahiko Tohma: "Synthesis of 6-Hydroxylated Bile Acids and Identification of 3alpha, 6alpha, 7alpha, 12alpha-Tetra-hydroxy-5beta-cholan-24-oic Acid in Human Meconium and Neonatal Urine." Chem. Pharm. Bull., 37 (2), 557-559 (1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Junichi Shoda, Toshiaki Osuga, Reijiro Mahara, Masahiko Tohma, Kenji Matsuura, Naomi Tanaka, Yasushi Matsuzaki and Hiroshi Miyazaki: "Altered Metabolism of Bile Acids in Cholestasis: Determination of 1beta- and 6alpha-Hydroxylated Metabolites." J. Chromatogr., 488 (3), 315-328 (1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Reijiro Mahara, Takao Kurosawa, Masahiko Tohma: "Analysis of Fetal and Neonatal Bile Acids by Gas Chromatography-Mass Spectrometry." Proc. Jap. Soc. Med. Mass Spectrom., 14, 67-74 (1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Shigeo Ikegawa, Hiroyuki Onodera, Junko Kinoshita and Masahiko Tohma: "Preparation and Properties of Antisera against Lithocholic Acid Linked to Bovine Serum Albumin at the C-1beta and C-6 Positions." Chem. Pharm. Bull., 36 (3), 994-999 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Shigeo Ikegawa, Junko Kinoshita, Zhen-Zhi Xu, Masako Ohta, and Masahiko Tohma: "Preparation and Specificity of Anti Glyco-3beta-hydroxy-5-cholen-24-oic Acid C-3 Bovine Serum Albumin (BSA) Conjugate Antiserum in Radioimmunoassay (RIA)." YAKUGAKU ZASSHI, 108 (10), 979-983 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Shigeo Ikegawa, Junko Kinoshita, Masahiro Shimizu, and Masahiko Tohma: "Radioimmunological Characterization of Anti Lithocholic Acid Antisera Elicited by [C-6] Carboxylic Acid N-Succinimidyl Esters as Haptenic Derivatives." YAKUGAKU ZASSHI, 109 (5), 306-311 (1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Shigeo Ikegawa, Junko Kinoshita, Kohtaro Takeshita, Hirouki Sato and Masahiko Tohma: "Preparation and Comparative Properties of Antisera against Glyco-3beta, 12alpha-dihydroxy-5-cholen-24-oic Acid Linked to Bovine Serum Albumin at the C-3, C-15 and C-24 positions." Chem. Pharm. Bull., 37 (8), 2147-2152 (1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Junichi Shoda, Reijiro Mahara, Toshiaki Osuga, Masahiko Tohma, Shozo Ohnishi, Hiroshi Miyazaki, Naomi Tanaka and Yasushi Matsuzaki: "Similarity of Unusual Bile Acids in Human Umbilical Cord Blood and Amniotic Fluid from Newborns and in Sera and Urine from Adult Patients with Cholestatic Liver Diseases." J. Lipid Res., 29 (7), 847-858 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yoshinobu Hata, Fumiaki Sasaki, Takeshi Abe, Hiromi Hamada, Hajime Tamura, Junichi Uchino, Kenji Kakuya, Reijiro Mahara, and Masahiko Tohma: "Production of Fetal Bile Acids in The Liver of Patients with Congenital Biliary Atresia." Acta Hepatol. Jap., 33 (7), 819-820 (1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Junichi Shoda, Toshiaki Osuga, Kenji Matsuura, Reijiro Mahara, Masahiko Tohma, Naomi Tanaka, Yasushi Matsuzaki, and Hiroshi Miyazaki: "Concurrent Occurrence of 3beta, 12alpha-Dihydroxy-5-cholenoic Acid Associated with 3beta-Hydroxy-5-cholenoic Acid and Their Preferntial Urinary Excretion in Liver Diseases." J. Lipid Res., 30 (8), 1233-1242 (1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Akihiko Kimura, Reijiro Mahara, Masahiko Tohma, Kosuke Ushijima, Ken Yuge, Eiichiro Ono, and Fumio Yamashita: "Unusual 1beta-Hydroxy-lated Bile Acids in Children with a Paucity in Interlobular Bile Ducts." Clin. Chem. Acta, 185, 215-218 (1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Reijiro Mahara,et al.: "Profile Analysis of Bile Acids in Human Fetal and Neonatal Periods by Gas Chromatography-Mass Spectrometry." J.Pharm.Dyn.,. 12. s-7 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Takao Kurosawa,et al.: "Synthesis of 6-Hydroxylated Bile Acids and Identification of 3α,6α,7α,12α-Tetra-hydroxy-5β-cholan-24-oic Acid in Human Meconium and Neonatal Urine." Chem.Pharm.Bull.37. 557-559 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Junichi Shoda,et.al.: "Altered Metabolism of Bile Acids in Cholestasis:Determination of 1β-and 6α-Hydroxylated Metabolites." J.Chromatogr.488. 315-328 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Shigeo Ikegawa,et.al.: "Preparation and Comparative Properties of Antisera against Glyco-3β,12α-dihydroxy-5-cholen-24-oic Acid Linked to BovineSerum Albumin at the C-3,C-15 and C-24 positions." Chem.Pharm.Bull.37. 2147-2152 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Junichi Shoda,et.al.: "Concurrent Occurrence of 3β,12α-Dihydroxy-5-cholenoic Acid Associated with 3β-Hydroxy-5-Cholenoic Acid and Their Preferntial Urinary Excretion in Liver Diseases." J.Lipid Res.30. 1233-1242 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 藤間貞彦,et.al.: "胎児-新生児期における胆汁酸の体内動態と先天性代謝異常" 薬物動態. 4. 607-617 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 正田純一 他: 肝臓. 29. 409 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 藤間真彦 他: ぶんせき. 183-189 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Junichi Shoda;et al.: J.Lipid Res.36. 2993-2999 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 池川繁男 他: 薬学雑誌. 108. 978-983 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Reijiro Mahara;et al.: J.Phorm.Dyn.

    • Related Report
      1988 Annual Research Report
  • [Publications] Takao Kurosawa;et al.: Chem.Pharm.Bull.

    • Related Report
      1988 Annual Research Report
  • [Publications] 正田純一他: 肝臓. 28. 388 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 正田純一他: 日本消化器病学会誌. 84. 771 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Masahiko Tohma et al: J. Chromatogr.421. 9-19 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Reijiro Mahara et al.: Anal. Sci.3. 449-452 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Shigeo Ikegawa et al.: Chem. Pharm. Bull.36. 994-999 (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Junichi Shoda et al.: J. Lipid Res.(1988)

    • Related Report
      1987 Annual Research Report

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Published: 1987-04-01   Modified: 2016-04-21  

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