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Studies on the pathogenesis, treatment and prevention of brain damage in the perinatal period.

Research Project

Project/Area Number 62480226
Research Category

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

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionNagoya University

Principal Investigator

WATANABE Kazuyoshi  Nagoya Univ. Med. Professor, 医学部, 教授 (80135368)

Co-Investigator(Kenkyū-buntansha) MAEHARA Mitsuo  Nagoya Univ. Med. Assistant, 医学部, 助手 (10192329)
NEGORO Tamiko  Nagoya Univ. Med. Assistant, 医学部, 助手 (40172754)
MIZUTZNI Naoki  Nagoya Univ. Med. Assistant, 医学部, 助手 (10115636)
MORISHIMA Tsuneo  Nagoya Univ. Med. Assist. Prof., 医学部, 講師 (90157892)
KEINO Hiroomi  Aichi Colony. Section Chief, 周生期, 室長 (30090426)
Project Period (FY) 1987 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1989: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1988: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1987: ¥2,800,000 (Direct Cost: ¥2,800,000)
KeywordsPerinatal period / Developmental disabilities / Intrauterine infection / Hypoxic-ischemic encephalopathy / Hyperbilirubinemia / Hyperarginemia / Lactic acidosis / Carnitine / 周生期脳障害 / 新生児脳波 / NSE / 神経ペプチド / ホモアルギニン / サイトメガロウイルス / 持続感染 / 新生児期脳波 / 周生期低酸素性虚血性脳症 / Tin-Protoporphyrin / Gunn-rat
Research Abstract

Among numerous causes of developmental disabilities, we addressed fetal and perinatal viral infections, perinatal hypoxic-ischemic encephalopathy, neonatal hyperbilirubinemia, and primary and secondary metabolic disturbances in the newborn and infants.
Pathogenetic, diagnostic and therapeutic aspects of herpes simplex virus(HSV) and cytomegalovirus(CMV) infection were investigated at the organ, tissue, cell and molecular level. The detection of HSV and CMV DNA in various specimens was made possible using Southern blot analysis and polymerase chain reaction.
Early detection and determination of the timing of perinatal brain injury was made possible by serial polygraphiv recordings including EEG and ultrasonographic examinations in high-risk term and early preterm infants.
Serial recordings disclosed that the prognosis of post-hemorrhagic hydrocephalus was more closely corrclated with the brain damage existing before the development of hydrocephalus than hydrocephalus per sc.
The pharmacolog … More ical and biological effects of tin-protoporphy (Snpp) was examined using Gunn rats to investigate its possible application in the treatment of neonatal hyperbilirubinemia. Although it is promising, further investigations are necessary in view of the demonstrated danger of this drug when used in combination with phototherapy in the animal experiment.
Various guanidino compounds were measured in the urine, serum and cerebrospinal fluids in patients with hyperarginemia and found to be abnormally clevated, suggesting a possible role in the pathogenesis of brain damage in this disorder. In order to develop efficient enzyme replacement therapy in this disease, purification and characterization of arginase and detection of the enzyme protein was performed using Western immunoblotting.
A new simple method was developed for the determination of pyruvate dehydrogenase activity by measuring acetyl CoA, separated by high-performance liquid chromatography and found useful in the diagnosis of various neonatal and infantile disorders with lactic acidoses. We also developed a simple and sensitive method to determine serum free carnitine and applied this method to the detection of secondary deficiency of this substance in the newborn and young infants. Less

Report

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

    (42 results)

All Other

All Publications (42 results)

  • [Publications] Fumio Hayakawa: "Fz theta/alpha bnrsts:a transient EEG pattern in healthy newborns." Electroencephalography and clinical Neurophysiology. 67. 27-31 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kazuyoshi Watanabe: "Neurophysiological and Neuroradiological Features Preceding Infantile Spasms." Brain Dev.9. 391-8 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Naoki Mizutani: "Guanidino Compounds Hyperargininemia." Tohoku J.Med.153. 197-205 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mitsuo Maehara: "A simple fluorometric method for the determination of serum free carnitine." Clinica Chimica Acta. 171. 311-316 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Hidetoshi Nagae: "Pharmacological and Biological Effects of Tin-Protoporphyrin on Neonatal Hyperbilirubinemic Gunn Rats." PEDIATRIC RESEARCH. 24. 209-212 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Motohiro Shibata: "Enzymatic Amplification of Human Cytomegalovirus DNA by means of polymerase Chain Reaction." submitted to Pediatric Research.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 渡辺一功: "小児神経疾患診療ハンドブック、渡辺一功編" 南江堂, (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] J.Sluzuki: "Art and Science of Epilepsy." Elsevier, (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Fumio Hayakawa: "Fz theta/alpha bursts:a transient EEG pattern in healthy newborns." Electroencephalography and clinical Neurophysiology 67:27-31, 1987.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kazuyoshi Watanabe: "Neurophysilogical and Neuroradiological Features Preceding Infantile Spasms." Brain Dev.9:391-8, 1987.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] T.Kato: "Increased Urinary Excretion of Putrescine in Hyperargininaemia." J.Inher.Metab.Dis.10:391-396, 1987.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Naoki Mizutani: "Guanidino Compounds Hyperargininemia." Tohoku J.exp.Med.153:197-205, 1987.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mitsuo Maehara: "A simple fluorometric method for the determination of serum free carnitine." Clinica Chimica Acta 171:311-316, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Hidetoshi Nagae: "Pharmacological and Biological Effects of Tin-Protoporphyrin on Neonatal Hyperbilirubinemic Gunn Rats." PEDIATRIC RESEARCH 24(2):209-212, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] N.Hanada: "Non-invasive method for early diagnosis of herpes simplex encephalitis." Archives of Disease in Childhood. 63:1470-1473, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] H.Keino: "Dangerous effects of tin-protoporphyrin plus photoirradiation on neonatal rats." Eur J.Pediatr., 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Tatsuo Takeuchi: "The EEG Evolution and Neurological Prognosis of Neonates with Perinatal Hypoxia." Brain Dev.11:115-20, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Naoki Hanada: "Combined Effects of Acyclovir and Human Interferon-alpha on Herpes Simplex Virus Replication in Cultured Neural Cells." Journal of Medical Virology 29:7-12, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Naoki Mizutani: "Neurotoxicity of Guanidino Compounds in Hyperargininemia." Neurotoxic Guanidines in Hyperargininemia 233-243, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] T.Kato, et al.: "Homocitrullinuria and Homoargininuria in Lysinuric Protein Intolerance." J.Inher.Metab.Dis.12:157-161, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Shunji Mimura: "Lipid Peroxidation in vivo and in vitro in Nonjaundiced Gunn Rats Treated with Tin-protoporphyrin plus photoirradiation."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Hidetoshi Nagae: "Biological and Biochemical Effects of Tin-Protoporphyr in Plus Photoirradiation on Neonatal Rats."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Motohiro Shibata: "Enzymatic Amplification of Human Cytomegalovirus DNA by means ofpolymerase Chain Reaction."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kazuyoshi Watanabe: "The Evolution of EEG features before onset of childhood symptomatic epilepsy due to perinatal brain damage." in "Art and Science of Epilepsy" J.Suzuki, M.Seino, Y.Fukuyama, S.Komai. (eds), P.127-134, Elsevier, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] H.Keino,: "Dangerous effects of tin-protoporphyrin plus photoirradiation on neonatal rats." Eur J.Pediatr.(1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Tatsuo Takeuchi,: "The EEG Evolution and Neurological Prognosis of Neonates with Perinatal Hypoxia." Brain Dev.11. 115-20 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Naoki Hanada,: "Combined Effects of Acyclovir and Human Interferon- on Herpes Simplex Virus Replication in Cultured Neural Cells." Journal of Medical Virology. 29. 7-12 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Naoki Mizutani: "Neurotoxicity of Guanidino Compounds in Hyperargininemia." Neurotoxic Guanidines in Hyperargininemia. 233-243 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 渡辺一功: "胎内感染と脳障害" 神経研究の進歩. 33. 436-444 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 早川文雄: "新生児期出血後水頭症の管理-保存的治療法の有効性-" 新生児誌. (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] J.Suzuku,: "Art and Science of Epilepsy" Elsevier, (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 渡辺一功: 周産期医学、1988臨時増刊号. 18. 305-316 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 早川文雄: 小児科臨床. 41. 1801-1805 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Takeuchi,T.: Brain and Development. in Press.

    • Related Report
      1988 Annual Research Report
  • [Publications] 早川知恵美: 小児科臨床. 41. 907-910 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 水谷直樹: 小児科臨床. 41. 2093-2098 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Morishima,T.: Progress in Medical Reproductive Immunology. 2. 47-50 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Mizutani,N.: "Neurotoxcity of guanidine compounds in hyperargininemia in"Guanidines".edited by Lowenthal,BD et al." Plenum Press.,

    • Related Report
      1988 Annual Research Report
  • [Publications] Hayakawa Fumio: Electroencephalography and clinical Neurophysiology. 67. 27-31 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Nagae Hidetoshi: Pediatric Research.

    • Related Report
      1987 Annual Research Report
  • [Publications] 渡辺一功: 臨床脳波. 29. 19-24 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 森島恒雄: 周産期医学「周産期感染症」特集号. 337-342 (1987)

    • Related Report
      1987 Annual Research Report

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

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