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Clinical research and development of therapy for diphenylarsinic acid poisoning from a possible chemical warfare agent

Research Project

Project/Area Number 16590811
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionUniversity of Tsukuba

Principal Investigator

ISHII Kazuhiro  University of Tsukuba, Graduate School of Comprehensive Human Sciences, Assistant Professor, 大学院人間総合科学研究科, 講師 (70323293)

Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsOrganoarsinic compounds / Diphenylarsinic acid / Cerebral blood flow scintigraphy / Cerebellar signs / Myoclonus / Tremors / 脳血流シンチグラフ
Research Abstract

Diphenylarsinic acid (DPAA) is the chemical material of diphenylcyanoarsine and diphenylchloroarsine used to synthesize chemical weapons and it does not exist in nature. In March 2003, we noted a new clinical syndrome with prominent cerebellar symptoms in the residents of an apartment building in Kamisu, Japan. The well that provided drinking water for all of these apartments contained DPAA. Characteristics of the DPAA poisoning included temporo-occipital lobe symptoms such as sleep disturbance, memory impairment and visual disorder, and cerebellar-brainstem symptoms such as ataxia, myoclonus and tremors. Mental retardation associated with brain atrophy in magnetic resonance images was evident in some infants. DPAA was detected in urine, blood, nails and hair. Furthermore, phenylmethylarsinic acid (PMAA) and monophenylarsinic acid (PAA), which are biological metabolites from DPAA, were found by LC/MS/MS. DPAA could no longer be detected in the blood and urine at about 200 days and 300 days after termination of exposure, respectively. Animal experiment revealed that DPAA was easy to accumulate in the central nervous system(CNS), especially in the cerebellum-brainstem significantly. Elimination of DPAA from the central nervous system was very slow. DPAA tends to accumulate in the CNS more than in other organs. Cerebral functional imaging views such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) showed hypoperfusion and hypometabolism of glucose in related symptomatic regions. These facts explain the clinical CNS symptoms of DPAA poisoning, that is, the cerebellum and brainstem are the target regions of DPAA in CNS. It is thought that prolonged abnormality of functional imaging views in relevant regions reflect the long-term influence of DPAA against CNS. We believe that SPECT and PET can be used as a DPAA exposure index and biomarker for treatment or recovery.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (26 results)

All 2006 2005 2004

All Journal Article (24 results) Book (2 results)

  • [Journal Article] Upward gaze-evoked nystagmus with organoarsenic poisoning.2006

    • Author(s)
      Nakamagoe K, Ishii K, Tamaoka A, Shoji S
    • Journal Title

      Neurology. 66(1)

      Pages: 131-132

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] ジフェニルアルシン酸暴露者における脳FDG-PET所見2006

    • Author(s)
      石井賢二, 石井一弘, 川崎敬一, 織田圭一, 武田徹, 塚田秀夫, 岩崎信明, 玉岡晃, 木村裕一, 石渡喜一
    • Journal Title

      核医学 43巻3号

      Pages: 235-235

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 神栖市で発生した有機ヒ素化合物(ジフェニルアルシン酸)中毒の臨床神経学的所見2006

    • Author(s)
      石井一弘, 玉岡晃, 武田徹, 石井賢二, 岩崎信明, 庄司進一
    • Journal Title

      臨床神経学 46巻11号

      Pages: 768-768

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Upward gaze-evoked nystagmus with organoarsenic poisoning.2006

    • Author(s)
      Nakamagoe K, Ishii K, Tamaoka A, Shoji S.
    • Journal Title

      Neurology. 66(1)

      Pages: 13-2

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Brain FDG-PET views in a patients with diphenylarsinic acid poisoning.2006

    • Author(s)
      Ishii K, Ishii K, Kawasaki K, Oda K, Takeda T, Tsukada H, Iwasaki N, Tamaoka A, Kimura Y, Ishiwata K.
    • Journal Title

      Japanese Journal of Nuclear Medicine. 43(3)

      Pages: 235-235

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Clinical and Neurological features of Diphenylarsinic acid (DPAA) intoxication, in Kamisu, Japan.2006

    • Author(s)
      Ishii K, Tamaoka A, Takeda T, Ishii K, Iwasaki N, Shoji S.
    • Journal Title

      Clinical Neurology 46(11)

      Pages: 768-768

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] ジフェニルアルシン酸暴露者における脳 FDG-PET 所見2006

    • Author(s)
      石井賢二, 石井一弘, 川崎敬一, 織田圭一, 武田徹, 塚田秀夫, 岩崎信明, 玉岡晃, 木村裕一, 石渡喜一
    • Journal Title

      核医学 43巻3号

      Pages: 235-235

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 茨城県神栖町のジフェニルアルシン酸等による健康被害2005

    • Author(s)
      石井一弘
    • Journal Title

      環境ホルモン学会 講演会テキスト 14

      Pages: 46-56

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Detection of Bis(diphenylarsine)oxide, Diphenylarsinic Acid and Phenylarsonic Acid, compounds probably derived from chemical warfare agents, in drinking well water.2005

    • Author(s)
      Ishizaki M, Ishii K et al.
    • Journal Title

      Journal of Health Science 51(2)

      Pages: 130-137

    • NAID

      10016656872

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] 砒素中毒の病型分類と臨床症状と治療2005

    • Author(s)
      石井一弘
    • Journal Title

      内科 95巻,6号

      Pages: 1626-1630

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] 化学兵器原料diphenylarsinic acid暴露症例における脳血流異常2005

    • Author(s)
      武田徹, 石井一弘, 呉勁, LwinThet-Thet, 南学, 玉岡晃
    • Journal Title

      核医学 42 (3)

      Pages: 303-303

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 小児におけるジフェニルアルシン酸等化合物中毒2005

    • Author(s)
      岩崎信明, 石井一弘, 宮本信也, 武田徹, 田中竜太, 大戸達之, 斎藤貴志, 松井陽, 新健治, 絹笠英世, 土田昌宏, 家島厚, 緒方剛, 佐藤秀郎
    • Journal Title

      脳と発達 37巻Suppl

      Pages: 180-180

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Health hazard by diphenylarsinic acid in Kamisu, Ibaraki.2005

    • Author(s)
      Ishii K
    • Journal Title

      Environmental hormone society 14

      Pages: 46-56

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Detection of Bis (diphenylarsine)oxide, Diphenylarsinic Acid and Phenylarsonic Acid, compounds probably derived from chemical warfare agents, in drinking well water.2005

    • Author(s)
      Ishizaki M, Ishii K et al.
    • Journal Title

      Journal of Health Science 51(2)

      Pages: 130-137

    • NAID

      10016656872

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A classification of arsenic poisoning and clinical manifestations and treatment.2005

    • Author(s)
      Ishii K.
    • Journal Title

      Internal Medicine 35(6)

      Pages: 1626-30

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Characteristic of Cerebral blood flow in a patients with diphenylarsinic acid intoxication,2005

    • Author(s)
      Takeda T, Ishii K, Wu J, LwinThet-Thet, Minami M, Tamaoka A
    • Journal Title

      Japanese Journal of Nuclear Medicine. 42 (3)

      Pages: 303-303

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Satoh H. diphenylarsinic acids intoxication in infant.2005

    • Author(s)
      Iwasaki N, Ishii K, Miyamoto S, Takeda T, Tanaka R, OOto T, Saitoh T, Matsui A, Shin K, Kinugasa H, Tsuchida M, Ieshima A, Ogata T
    • Journal Title

      Brain & Development 37

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Chapter 3. Risks to Organisms and Risk Assessment, Actual examples of health hazards, Risk Assessment of Old and Abandoned Chemical Weapons and Development of Safe Advanced Destruction Technologies2005

    • Author(s)
      Ishii K
    • Journal Title

      Section of National Committee on Abandoned Chemical Weapons, National Committee for Restoration of Devastated Living Environments, Science Council of Japan

      Pages: 89-89

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 茨城県神栖町のジフェニルアルシン酸等による健康被害2005

    • Author(s)
      石井一弘
    • Journal Title

      環境ホルモン学会、講演会テキスト 14

      Pages: 46-56

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Diphenylarsinic acid poisoning derived from chemical weapons in Kamisu, Japan2004

    • Author(s)
      Ishii K et al.
    • Journal Title

      Annals of Neurology 56

      Pages: 741-745

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 茨城県神栖町で発生した有機ヒ素中毒について2004

    • Author(s)
      石井一弘, 玉岡晃, 岩崎信明
    • Journal Title

      中毒研究 17

      Pages: 125-131

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Iwasaki N. Intoxication of organic arsine in Kamisu, Japan.2004

    • Author(s)
      Ishii K, Tamaoka A
    • Journal Title

      The Japanese Journal of Toxicology 17

      Pages: 125-131

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Diphenylarsinic acid poisoning derived from chemical weapons in Kamise, Japan2004

    • Author(s)
      Ishii K et al.
    • Journal Title

      Annals of Neurology 56

      Pages: 741-745

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 茨城県神栖町で発生した有機ヒ素中毒について2004

    • Author(s)
      石井一弘, 玉岡 晃, 岩崎信明
    • Journal Title

      中毒研究 17

      Pages: 123-131

    • Related Report
      2004 Annual Research Report
  • [Book] 第3章 生体に対するリスクとリスク管理.健康被害の実例.老朽・遺棄化学兵器のリスク評価と安全な高度廃棄処理技術の開発.2005

    • Author(s)
      石井一弘
    • Total Pages
      65
    • Publisher
      日本学術会議.荒廃した生活環境の回復研究連絡委員会、遺棄化学兵器に対する高度処理技術の開発専門委員会.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] Chapter 3, Risks to Organisms and Risk Assessment, Actual examples of health hazards, Risk Assessment of Old and Abandoned Chemical Weapons and Development of Safe Advanced Destruction Technologies2005

    • Author(s)
      Ishii K
    • Total Pages
      89
    • Publisher
      Section of National Committee on Abandoned Chemical Weapons, National Committee for Restoration of Devastated Living Environments, Science Council of Japan
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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