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ANALYSIS OF THE BILE ACID PROFILES AND APPLICATION TO THE CONGENITAL LIVER DISORDER

Research Project

Project/Area Number 02557089
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Physical pharmacy
Research InstitutionHIGASHI-NIPPON-GAKUEN UNIVERSITY

Principal Investigator

TOHMA Masahiko  HIGASHI-NIPPON-GAKUEN UNIV. FAC. PHARMACEUTICAL SCIENCES, PROFESSOR8., 薬学部, 教授 (30001043)

Co-Investigator(Kenkyū-buntansha) MAHARA Reijiro  HIGASHI-NIPPON-GAKUEN UNIV. DEPT. GENERAL EDU., ASSISTANT PROFESSOR, 教養部, 講師 (30192347)
KUROSAWA Takao  HIGASHI-NIPPON-GAKUEN UNIV. FAC. PHARM. SCIENCES, ASSOCIATE PROFESSOR, 薬学部, 助教授 (50103198)
IKEGAWA Shigeo  TOHOKU UNIV. FAC. PHARM. SCI., ASSOCIATE PROFESSOR, 薬学部, 助教授 (90111301)
荒島 真一郎  北海道教育大学, 教育学部・札幌分校, 教授 (90002344)
秦 温信  北海道大学, 医学部附属病院, 講師 (10113606)
Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1992: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1991: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1990: ¥3,200,000 (Direct Cost: ¥3,200,000)
KeywordsFETAL BILE ACID / BILE ACID BIOSYNTHETIC INTERMEDIATE / NEONATAL LIVER DESEASE / BILE ACID PROFILE / CAPILLARY GAS CHROMATOGRAPHY / CONGENITAL BILIARY ATRESIA / IMMUNOASSAY / ZELLWEGER SYNDROME / 先天性肝胆道疾患 / 抱合型胆汁酸 / 酵素免疫測定法 / マススクリーニング法 / C_<27>-胆汁酸 / マススクリ-ニング法 / キャピラリ-ガスクロマトグラフィ-
Research Abstract

The establishment of the diagnosis of congenital liver disorder is urgently required for the remedy of liver disorder in early life. The aim of this research is the development of quantitative analysis of fetal bile acids by GC-MS and immunological assay, elucidation of the change of bile acid profiles with growth, and establishment of the precise diagnosis and masscreening of congenital biliary atresia.
(1) The stereoisomeric C_<27>-bile acids and bile alcohols were chemically synthesized for the authentic specimens. The newly developed analysis of these intermediates was achieved by capillary gas chromatography.
(2) Highly sensitive radioimmunoassay and enzyme immunoassay were developed. By the established method, the change of conjugated fetal bile acids in urine of pregnant women and newborns was examined.
(3) The bile acid composition of neonatal periods changed with growth. In the case of preterm infants, the similar results were observed. The result of comparison of the ratio of 1beta-hydroxycholic acid to cholic acid indicated the activity of 1beta-hydroxylase decreased with growth.
(4) 1. Diagnostic analysis of congenital biliary atresia was accomplished by enzyme immunoassay. The possibility of masscreening using dried blood spots was also examined. 2. From the urine of Zellweger syndrome, THCA and varanic acid were identified and determined by GLC. 3. In addition to 1beta-hydroxycholic acid, 1beta-hydroxylated C_<23>- and C_<22>-bile acids were found in the urine of patients with cerebrotendinous xantomatosis.

Report

(4 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (56 results)

All Other

All Publications (56 results)

  • [Publications] Takako MIYARA: "Capillary Gas Chromatography/Negative Ion Chemical Ionization Mass Spectrometry for the Quantitation of Bile Acids Including 1β-Hydr-oxylated and Unsaturated Bile Acids in Serum and Urine." Biomed.Chromatogr.4. 56-60 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Taiju KURAMOTO: "Identification of Short Side Chain Bile Acids in Urine of Patients with Cerebrotendinous Xanthomatosis." J.Lipid Res.31. 1895-1902 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Shigeo IKEGAWA: "Quantitative Determination of Conjugated Fetal Bile Acids in Urine by Chemiluminescence High-Performance Liquid chromatography" Journal of Pharmacobio-Dyanamics. 14. S-92 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Akira HONDA: "Simultaneous Assay of the Activities of Two Key Enzymes in Cholesterol Metabolism by Gas Chromatography-Mass Spectrometry." J.Chromatogr.565. 53-66 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 日向 平明: "早期産児の新生児期における尿中胆汁酸のGC-MSにおける動態解析." 臨床小児医学. 39. 223-226 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Reijiro MAHARA: "Determination of Fetal Bile Acids in Human Neonates by Gas Chromatography-Negative Ion Chemical Ionization Mass Spectrometry." Anal.Sci.7-S. 983-986 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yoshinobu HATA: "Fetal Bile Acids in Congenital Biliary Atresia." Proc.5th Intern.Sympo.¨Biliary Atresia¨. 182-186 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Akihiko KIMURA: "Neonatal Dubin-Johnson Syndrome with Severe Cholestasis:Effective Phenobarbital Therapy." Acta Pediatr.Scand.80. 381-385 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Akihiko KIMURA: "Abnormal Low Ratio of Cholic Acid to Chenodeoxycholic Acid in a Cholestatic Infant with Severe Hypoglycemia." J.Pediatr.Gastroenterol.Nutr.12. 383-387 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yoshinobu HATA: "Fetal Bile Acids in Congenital Biliary Atresia-Production in the Liver and Clinical Significance." Pediatr.Surg.Int.6. 309-312 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yasumasa KOIBUCHI: "Study on Stereospecificity of Enzyme Reaction Related to Peroxisomal Bile Acid Synthesis in Rat Liver." Chem.Pharm.Bull.40. 446-448 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Shigeo IKEGAWA: "Measurement of Conjugated 1β-Hydroxycholic Acid in Urine of Newborns by Specific Radioimmunoassay." Chem.Pharm.Bull.40. 701-704 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Shigeo IKEGAWA: "Conjugated 1β-Hydroxycholic Acid in the Urine of Newborns and Pregnant Women measured by Radioimmunoassay using Antisera raised against N-(1β-Hydroxycholyl)-2-aminopropionic Accid-BSA Conjugate." Chem.Pharm.Bull.40. 1835-1838 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Shigeo IKEGAWA: "Determination of Conjugated Bile Acids in Human Urine by High-Performance Liquid Chromatography with Chemiluminescence Detection." J.Chromatogr.577. 229-238 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kaoru OBINATA: "1β-Hydroxylated Bile Acids in the Urine of Healthy Neonates." J.Pediatr.Gastroentrol.Nutr.15. 1-5 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Teruki YOSHIMURA: "An Efficient Synthesis of 4β-and 6α-Hydroxylated Bile Acids." Steroids. 57. 426-429 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 日本分析化学会北海道支部編: "膜と界面" 学会出版センター, 322 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Takako Miyara, Noriko Shindo, Masahiko Tohma, and Kimie Murayama: "Capillary Gas Chromatography/Negative Ion Chemical Ionization Mass Spectrometry for the Quantitation of Bile Acids Including 1beta-Hydroxylated and Unsaturated Bile Acids in Serum and Urine." Biomed. Chromatogr.4 (2). 56-60 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Shigeo Ikegawa, Takao Kurosawa, and Masahiko Tohma: "Synthesis of 4- and 16alpha-Hydroxylated Equine Estrogens." Steroids. 55. 250-255 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Taiju Kuramoto, Yukari Furukawa, Toshihiro Nishina, Tadao Sugimoto, Reijiro Mahara, Masahiko Tohma, Kenji Kihira, and Takehiko Hoshita: "Identification of Short Side Chain Bile Acids in Urine of Patients with Cerebrotendinous Xanthomatosis." J. Lipid Res.31. 1895-1902 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Shigeo Ikegawa, Naoyuki Hirabayashi, Teruki Yoshimura, Masahiko Tohma, Masako Maeda, and Akio Tsuji: "Quantitative Determination of Conjugated Fetal Bile Acids in Urine by Chemiluminescence High-Performance Liquid Chromatography." J. Pharmacobio-Dyn.14. s-92 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Akira Honda, Junichi Shoda, Naomi Tanaka, Yasushi Matsuzaki, Toshiaki Osuga, Nobuharu Shigematsu, Masahiko Tohma, and Hiroshi Miyazaki: "Simultaneous Assay of the Activities of Two Key Enzymes in Cholesterol Metabolism by Gas Chromatography-Mass Spectrometry." J. Chromatogr.565. 53-66 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Akihiko Kimura, Kosuke Ushijima, Masayoshi Kage, Reijiro Mahara, Masahiko Tohma, Takahiro Inokuchi, Kyoko Shibao, Nobuko Tanaka, Takuji Fujisawa, Eiichiro Ono, and Fumio Yamashita: "Neonatal Dubin-Johnson Syndrome with Severe Cholestasis: Effective Phenobarbital Therapy." Acta Pediatr. Scand.80. 381-385 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Akihiko Kimura, Ken Yuge, Shigenori Yukizane, Masayoshi Kage, Hroshi Nittono, Reijiro Mahara, Takao Kurosawa, and Masahiko Tohma: "Abnormal Low Ratio of Cholic Acid to Chenodeoxycholic Acid in a Cholestatic Infant with Severe Hypoglycemia." J. Pediatr. Gastroenterol. Nutr.12 (3). 383-387 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yoshinobu Hata, Junichi Uchino, Fumiaki Sasaki, Tuyoshi Abe, Yoshinobu Koike, Saiful Alam, Kenji Kakuya, Shogo Nagano, Reijiro Mahara, and Masahiko Tohma: "Fetal Bile Acids in Congenital Biliary Atresia - Production in the Liver and Clinical Significance." Pediatr. Surg. Int.6. 309-312 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yoshinobu Hata, Fumiaki Sasaki, Hiromasa Takahashi, Hiromi Hamada, Motoshi Tamura, Yumi Ohkawa, Junichi Uchino, Toshiaki Hyuga, Reijiro Mahara, and Masahiko Tohma: "Fetal Bile Acids in Congenital Biliary Atresia." Pro. 5th Intern. Sympo."Biliary Atresia". 182-186 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Toshiaki Hyuga, Shin-ichiro Arashima, Reijiro Mahara, Masahiko Tohma, Takeo Nakajima, Satoshi Hattori, Yoshinori Wagatsuma, and Yoshinobu Hata: "Profile Analysis of Urine Bile Acids in Preterm Newborns of Neonatal Periods by Gas Chromatography-Mass Spectrometry." Rinsyosyoniigaku. 39(5). 223-226 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Reijiro Mahara, Takao Kurosawa, Teruki Yoshimura, Shigeo Ikegawa, and Masahiko Tohma: "Determination of Fetal Bile Acids in Human Neonates by Gas Chromatography-Negative Ion Chemical Ionization Mass Spectrometry." Anal. Sci.7, Suppl.983-986 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yasumasa Koibuchi, Junji Yamada, Takafumi Watanabe, Takao Kurosawa, Masahiko Tohma, and Tetsuya Suga: "Study on Stereospecificity of Enzyme Reaction Related to Peroxisomal Bile Acid Synthesis in Rat Liver." Chem. Pharm. Bull.40 (2). 446-448 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Shigeo Ikegawa, Tsuyoshi Murai, Teruki Yoshimura, Zhen-Zhi Xu, and Masahiko Tohma: "Measurement of Conjugated 1beta-Hydroxycholic Acid in Urine of Newborns by Specific Radioimmunoassay." Chem. Pharm. Bull.40 (3). 701-704 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Shigeo Ikegawa, Tsuyoshi Murai, Teruki Yoshimura, and Masahiko Tohma: "Conjugated 1beta-Hydroxycholic Acid in the Urine of Newborns and Pregnant Women Measured by Radioimmunoassay Using Antisera Raised against N-(1beta-Hydroxycholyl)-2-aminopropionic Acid-Bovine Serum Albumin Conjugate." Chem. Pharm. Bull.40 (7). 1835-1838 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Shigeo Ikegawa, Tsuyoshi Murai, Teruki Yoshimura, and Masahiko Tohma: "Determination of Conjugated Bile Acids in Human Urine by High-Performance Liquid Chromatography with Chemiluminescence Detection." J. Chromatogr.577 (2). 229-238 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Takao Kurosawa, Shigeo Ikegawa, Hitoshi Chiba, Yoshito Ito, Syoichi Nakagawa, Kunihiko Kobayashi, and Masahiko Tohma: "Convenient Synthesis of 18-Hydroxylated Cortisol and Predonisolone." Steroids. 57(9). 426-429 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kaoru Obinata, Hiroshi Nittono, Keijiro Yabuta, Reijiro Mahara, and Masahiko Tohma: "1beta-Hydroxylated Bile Acids in the Urine of Healthy Neonates." J. Pediatr. Gastroenterol. Nutr.15,(1). 1-5 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Teruki Yoshimura, Reijiro Mahara, Takao Kurosawa, Shigeo Ikegawa, and Masahiko Tohma: "An Efficient Synthesis of 4beta- and 6alpha-Hydroxylated Bile Acids." Steroids. 58 (1). 1-7 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 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.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 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 Tool Good for Screening Primary Aldosteronism." J. Steroid Biochem.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yasumasa Koibuchi: "Study on Stereospecificity of Enzyme Reaction Related to Peroxisomal Bile Acid Synthesis in Rat Liver." Chem.Pharm.Bull.40. 446-448 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Shigeo Ikegawa: "Measurement of Conjugated 1β-Hydroxycholic Acid in Urine of Newborns by Specific Radioimmunoassay." Chem.Pharm.Bull.40. 701-704 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Shigeo Ikegawa: "Conjugated 1β-Hydroxycholic Acid in the Urine of Newborns and Pregnant Women measured by Radioimmunoassay using Antisera raised against N-(1β-Hydroxycholyl)-2-aminopropionic Accid-BSA Conjugate." Chem.Pharm.Bull.40. 1835-1838 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Shigeo Ikegawa: "Determination of Conjugated Bile Acids in Human Urine by High-Performance Liquid Chromatography with Chemiluminescence Detection." J.Chromatogr.577. 229-238 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kaoru Obinata: "1β-Hydroxylated Bile Acids in the Urine of Healthy Neonates." J.Pediatr.Gastroentrol.Nutr.15. 1-5 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Teruki Yoshimura: "An Efficient Synthesis of 4β-and 6α-Hydroxylated Bile Acids." Steroids. 57. 426-429 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Akihiko Kimura: "Neonatal Dubin-Johnson Syndrome with Severe Cholestasis:Effective Phenobarbital Therapy." Acta Pediatr.Scand.80. 381-385 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Akihiko Kimura: "Abnormal Low Ratio of Cholic Acid to Chenodeoxycholic Acid in a Cholestatic Infant with Severe Hypoglycemia." J.Pediatr.Gastroenterol.Nutr.12. 383-387 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Yoshinobu Hata: "Fetal Bile Acids in Congenital Biliary Atresis-Production in the Liver and Clinical Significance." Pediatr.Surg.Int.6. 309-312 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Yoshinobu Hata: "Fetal Bile Acids in Congenital Biliary Atresia." Proc.5th Intern.Sympo."Biliary Atresia". 182-186 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Shigeo Ikegawa: "Measurement of Conjugated 1β-Hydroxycholic Acid in Urine of Newborns by Specific Radioimmunoassay." Chem.Pharm.Bull.40. 701-704 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Shigeo Ikegawa: "Conjugated 1β-Hydroxycholic Acid in the Urine of Newborns and Pregnant Women measured by Radioimmunoassay using Antisera raised against N-(1β-Hydroxycholyl)-2-aminopropionic Accid-BSA Conjugate." Chem.Pharm.Bull.40. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takako Miyara: "Capillary Gas Chromatography/Negative Ion Chemical Ionization Mass Spectrometry for the Quantitation of Bile Acids Including 1βーHydroxylated and Unsaturated Bile Acids in Serum and Urine." Biomed.Chromatogr.4. 56-60 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Shigeo Ikegawa: "Synthesis of 4ーand 16αーHydroxylated Equine Estrogens." Steroids. 55. 250-255 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Taiju Kuramoto: "Identification of Short Side Chain Bile Acids in Urine of Patients with Cerebrotendinous Xanthomatosis." J.Lipid Res.31. 1895-1902 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Shigeo Ikegawa: "Quantitative Determination of Conjugated Fetal Bile Acids in Urine by Chemiluminescence HighーPerformance Liquid Chromatography" Journal of PharmacobioーDyanamics. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Shigeo Ikegawa: "Radioimmunoassay of Conjugated 3β,12αーDihydroxyー5ーcholenー24ーoic Acid" Chemical & Pharmaceutical Bulletin. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Shigeo Ikegawa: "Concentration of Conjugated 1βーHydroxycholic Acid in Human Urine as determined by Specific RIA" Chemical & Pharmaceutical Bulletin. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 日本分析化学会北海道支部編: "膜と界画" 学会出版センタ-, 322 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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