2006 Fiscal Year Final Research Report Summary
Mechanism of diphenylarsinic acid intoxication and the treatment method
Project/Area Number |
16209021
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Hygiene
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Research Institution | Osaka City University |
Principal Investigator |
ENDO Ginji Osaka City University, Graduate School of Medicine, Professor (20160393)
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Co-Investigator(Kenkyū-buntansha) |
ISHII Kazuhiro University of Tsukuba, Graduate School of Comprehensive Human Sciences, Assistant Professor (70323293)
FUSHIKI Shinji Kyoto Prefectural University of Medicine, Graduate School, Professor (80150572)
SUZUKI Tsutomu Hoshi University, The Faculty of Pharmaceutical Sciences, Professor (90130757)
YAMANAKA Kenzo Nihon University, College of Pharmacy, Associate Professor (50182572)
WANIBUCHI Hideki Osaka City University, Graduate School of Medicine, Professor (90220970)
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Project Period (FY) |
2004 – 2006
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Keywords | diphenylarsinic acid / oreano-arsenic / chemical weanon / environmental nollution / cerebellar-brainstem symptoms / cerebral symptoms / Poisoning / mental retardation |
Research Abstract |
1. We noted a new clinical syndrome with prominent cerebellar-brainstem symptoms such as ataxic gait, titubation and scanning speech, myoclonus and tremor, and cerebral symptoms such as upward gaze-evoked nystagmus, sleep disorder, and memory impairment in residents who had drunk well water contaminated by diphenylarsinic acid (DPAA). Mental retardation associated with brain atrophy in magnetic resonance images was evident in some infants. 2. Motor impairment and the down -regulation of the dopamine receptor function in striatum were observed in adult mice treated with DPAA. Motor learning impairment was observed in neonatal mice exposed to a low dose of DPAA. 3. Administration of 20 ppm DPAA for 6 weeks significantly increased the number and areas of glutathione S-transferase placental form positive foci induced by diethylnitrosamine in rats. These results indicated the DPAA exerts promoting hepatocarinogenesis in rats. 4. Pathogenetic observations of DPAA intoxication were the vacuolation of glomerulus in granular layer of cerebellum by microscope, and the axonal degeneration by electron microscope. 5. Significantly positive staining with malondialdehyde and 3-nitrotyrosine was observed in the cerebellar Purkinje cells by repeated administration (5 mg/kg/day) with DPA for 5 weeks that led to the cerebellar symptoms from a behavioral pharmacology standpoint. These results suggest that DPAA associated novel active species may be a factor underlying the oxidative and nitrosative stress in Purkinje cells, and the damage lead to the cerebellar symptpms. 6. A selective and efficient clean-up method with solvent extraction and solid phase extraction for DPAA in fat and brain was developed. 7. We measured urinary arsenic compounds in 142 workers by HPLC-ICP-MS. DPAA peaks were detected in none of the workers.
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[Journal Article] Oral administration of diphenylarsinic acid,a degradation product of chemical warfare agents,induces oxidative and nitrosative stress in cerebellar Purkinje cells2007
Author(s)
Kato K, Mizoi M, An Y, Nakano M, Wanibucbi H, Endo G, Endo Y, Hoshino M, Okada S, Yamanaka K
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Journal Title
Life Sci 87(21-22)
Pages: 1518-25
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Yamanaka, K Oral administration of diphenylarsinic acid, a degradation product of chemical warfare agents, induces oxidative and nitrosative stress in cerebellar Purktnle cells2007
Author(s)
Kato, K., Mizoi, M., An, Y., Nakano, M., Wanibuchi, H., Endo, G., Endo, Y., Hoshmo, M., Okada, S
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Journal Title
Life Sci 81(21-22)
Pages: 1518-25
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Promoting effects of diphenylarsinic acid on hepatocarcinogenesis induced by diethelnitrosamine in rats2007
Author(s)
Wei, M., Mortmura, K., Kinoshita, A, Kitano, M., Doi, K, Fukushima, S., Wanibuchi, H
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Journal Title
Proc Jpn Soc Pathol 96(1)
Pages: 233
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Effect of organo-arsinic compounds on central nervous systems2006
Author(s)
Ishu, K., Takeda, T., Iwasakt, N., Ishn, K., Tsukada, H., Tamaoka, A
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Journal Title
J Pharmacol Set 100
Pages: 27
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Detection of bis(diphenylarsine) oxide,diphenylarsinic acid and phenylarsonic acid,compounds probably derived from chemical warfare agellts,in drinking well water2005
Author(s)
Ishizaki M, Yanaoka T, Nakamura M, Hakuta T, Ueno S, Komuro M, Shibata M, Kitamura T, Honda A, Doy M, Ishii K, Tamaoka A, Shimojo N, Ogata T, Nagasawa E, Hanaoka S
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Journal Title
J Health Science 51(2)
Pages: 130-137
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[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
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Journal Title
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Hanaoka S Detection of bis(diphenylarsine) oxide, diphenylarsinic acid and phenylarsonic acid, compounds probably derived from chemical warfare agents, in drinking well water2005
Author(s)
Ishtzakt, M., Yanaoka, T., Nakamura, M., Hakuta, T., Ueno, S., Komuro, M., Shibata, M., Kitamura, T., Honda, A., Doy, M., Ishn, K., Tamaoka, A., Shimojo, N., Ogata, T., Nagasawa, E
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Journal Title
J Health Science 51(2)
Pages: 130-137
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Diphenylarsinic acid poisoning from chemical weapons in Kamisu,Japan2004
Author(s)
Ishii K, Tamaoka A, Otsuka F, Iwasaki N, Shin K, Matsui A, Endo G, Kumagai Y, Ishii T, Shoji S, Ogata T, Ishizaki M, Doi M, Shimojo N.
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Journal Title
Ann Neurol 56(5)
Pages: 741-5
Description
「研究成果報告書概要(和文)」より
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[Journal Article] ジフェニルアルシン酸等化合物中毒における小児の臨床的検討2004
Author(s)
岩崎 信明, 石井 一弘, 玉岡 晃, 宮本 信也, 武田 徹, 新健 治, 家島 厚, 土田 昌宏, 大戸 達之, 斎藤 貴志, 向田 壮一, 松井 陽, 緒方 剛, 土井 幹夫, 石崎 睦雄
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Journal Title
脳と発達 36(Suppl.)
Pages: S392
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Shimojo N Diphenylarsinic acid poisoning from chemical weapons to Kamisu. Japan2004
Author(s)
Ishu, K., Tamaoka, A., Otsuka, F., Iwasakt, N., Shin, K., Matsui, A., Endo, G., Kumagai, Y., Ishu, T., Shoji, S., Ogata, T., Ishtzakt, M., Doi, M
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Journal Title
Ann Neurol 56(5)
Pages: 741-5
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Behavioral analysis of chronic exposure to diphenylarsinic acid associated with influence on central nervous systems
Author(s)
Miyagawa, K, Narita, M, Miyatake, M, Kato, K, Yamanaka, K, Suzuki, T
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Journal Title
Jpn. J. Nouropsychopharmacol 2007 27(5-6)
Pages: 181-189
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Pathogenetic mechanisms of dtphenylarsme intoxication
Author(s)
Itoh, K, Yaoi, T, Tsujimoto, Y, Yamanaka, K, Endo, G, Fushiki, S
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Journal Title
Japanese Medical Society of Alcohol and Drug Studies 2006 41(3)
Pages: 286-287
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Induction of oxidative stress in cerebellar Purkinje cells associated with tnfluence on central nervous systems exposed to diphenylarsinic acid in mice
Author(s)
Kato, K, Mizoi, M, An, Y, Nakano, M, Okada, S, Yamanaka, K
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Journal Title
Proc 126th Ann Meeting of Pharmaceutical Soc Jpn 2006 3
Pages: 176
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] FDG-PET findings in cases exposed to diphenylarsinic acid
Author(s)
Ishu, K, Ishu, K, Kawasaki, K, Oda, K, Takeda, T, Tsukada, H, Iwasaki, N, Tamaoka, A, Kimura, Y, Ishtwatari, Y
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Journal Title
Kaku Igaku 2006 43(3)
Pages: 235
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] FDG-PET findings in cases exposed to diphenylarsinic acid
Author(s)
Ishu, K, Ishu, K, Kawasaki, K, Takeda, T, Tsukada, H, Iwasaki, N, Tamaoka, A
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Journal Title
Rinsho Shinkeigaku 2006 46(12)
Pages: 1115
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Development of cerebral blood flow in cases exposed to diphenylarsinic acid
Author(s)
Ishu, K, Takeda, T, Ishu, K, Otuka, H, Iwasaki, N, Tamaoka, A
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Journal Title
Rinsho Shinkeigaku 2006 46(12)
Pages: 1115
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Clinical and neurological features of organoarsenic compound(dtphenylarsmtc acid)intoxication in Kamisu, Japan
Author(s)
Ishu, K, Tamaoka, A, Takeda, T, Ishii, K, Iwasaki, N, Shoji, S
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Journal Title
Rinsho Shinkeigaku 2006 46(11)
Pages: 768
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Analysis of cerebral Blood flow in cases exposed to organo-arsentc compounds, in Kamisu
Author(s)
Ishu, K, Tamaoka, A, Takeda, T, Ishii, K, Iwasaki, N, Shoji, S
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Journal Title
Rinsho Shinkeigaku 2005 45(12)
Pages: 1010
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Abnormal cerebral perfusion in cases exposed to diphenylarsinic acid, a chemical weapon raw material
Author(s)
Takeda, T, Ishu, K, Wu, J, Thet-Thet-Lwm, Minami, M, Tamaoka
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Journal Title
Jpn J Nuc Med 2005 42(3)
Pages: 303
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Diphenylarsinic acid poisoning in infants
Author(s)
Iwasaki, N, Ishti, K. Miyamoto, S, Takeda, T, Tanaka, R, Ooto T, Saito ,T Matui, A, Itarasni, K, Kinugasa, H, Tsuchida, M, Ieshima, A, Ogata, T, Sato, H
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Journal Title
NO TO HATTATSU 2005 37
Pages: 180
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Clinical aspect in infants intoxication of diphenylarsinic acid
Author(s)
Iwasaki, N, Ishu, K, Tamaoka, A, Niyamoto, S, Takeda, T, Atarashi, K, Ieshima, A, Tsuchida, M, Ooto, T, Saito, T, Mukaida, M, Matui, A, Ogata, T, Doi, M, Isozaki, M
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Journal Title
NO TO HATTATSU 2004 36(Suppl)
Pages: S392
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Clinical examination or organic-arsenic, diphenylarsinic acid, poisoning occurred in Kamisu, Ibaraki
Author(s)
Ishu, K, Tamaoka, A, Otsuka, F, Iwasaki, N, Atarasi, K, Syouji, S
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Journal Title
Rinsho Shinkeigaku 2004 44(12)
Pages: 1096
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Wanibuchi H Promoting effects of d,nh,n ,larsm,c ac,d on henatocarcmoeenests induced by diethelnitrosamine in rats2007
Author(s)
Wet, M., Kitano, M., Doi, K., Mortmura, K., Touma, K
Organizer
66th Jpn Cancer Assoc
Place of Presentation
Yokohama
Year and Date
20071003-05
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Wanibuchi H Promoting effects of diphenylarsinic acid on hepatocarcinogenesis induced by diethelnitrosamine in rats2007
Author(s)
Wei, M., Mortmura, K., Kinoshita, A., Kitano, M., Dot, K, Fukushtma, S
Organizer
96th Jpn Soc Pathol
Place of Presentation
Osaka
Year and Date
20070313-315
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Abnormal cerebral perfusion in cases exposed to diphenylarsinic acid, a chemical weapon raw material2006
Author(s)
Takeda, T., Ishii, K. Wu, J., Thet-Thet-Lwin, Minami, M, Tamaoka, A
Organizer
46th Jpn Soc Nuclear Medicine
Place of Presentation
Tokyo
Year and Date
20061111-13
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Ishtwatart Y FDG-PET findings in cases exposed to diphenylarsinic acid2006
Author(s)
Ishii, K., Ishn, K., Kawasaki, K., Oda, K., Takeda, T., Tsukada, H., Iwasaki, N., Tamaoka, A, Kimura, Y
Organizer
46th Jpn Soc Nuclear Medicine
Place of Presentation
kagosima
Year and Date
20061109-11
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Analysis of cerebral Blood flow SPECT in cases exposed to organo-arsenic compounds, in Kamisu2006
Author(s)
Ishii, K., Tamaoka, A., Takeda, T., Ishii, K., Iwasaki, N., Shoji, S
Organizer
46th Societas Neurologica Japonica
Place of Presentation
Kagoshima
Year and Date
20060525-27
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Development of cerebral Blood flow in cases exposed to diphenylarsinic acid2006
Author(s)
Ishu, K., Takeda, T., Ishn, K., Otuka, H., Iwasakt, N., Tamaoka, A
Organizer
47th Societas Neurologica Japonica
Place of Presentation
Tokyo
Year and Date
20060511-20660513
Description
「研究成果報告書概要(欧文)」より
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[Presentation] FDG-PET findings in cases exposed to diphenylarsinic acid2006
Author(s)
Ishii, K, Ishn, K, Kawasaki, K, Takeda, T, Tsukada, H, Iwasakt, N, Tamaoka, A
Organizer
47th Societas Neurologica Japonica
Place of Presentation
Tokyo
Year and Date
20060511-13
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Clinical and neurological features of organoarsenic compound (diphenylarsinic acid) intoxication in Kamisu, Japa2006
Author(s)
Ishii, K., Tamaoka, A., Takeda, T., Ishu, K., Iwasaki, N, Shoji, S
Organizer
47ths Societas Neurologica Japonica
Place of Presentation
Tokyo
Year and Date
20060511-0513
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 有機ヒ素中毒について2006
Author(s)
石井 一弘, 玉岡 晃
Organizer
東京薬科大大学院修士課程セミナー
Place of Presentation
八王子市
Year and Date
20060100
Description
「研究成果報告書概要(和文)」より
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[Presentation] ヒ素中毒について2005
Author(s)
石井 一弘
Organizer
持田製薬セミナー
Place of Presentation
土浦市
Year and Date
20051200
Description
「研究成果報告書概要(和文)」より
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[Presentation] Clinical and neurological features of organoarsenic compound (diphenylarsinic acid)intoxication in Kamisu,Japan2005
Author(s)
Ishu, K., Tamaoka, A., Takeda, T., Ishn, K., Iwasakt, N., Shoji, S
Organizer
Seninar to Mochtda Pharmaceutical Co, LTD
Place of Presentation
Tsuchiura
Year and Date
20051200
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Abnormal cerebral perfusion in cases exposed to diphenylarsinic acid, a chemical weapon raw material. Ishii K: Heath harmful on arsenic in well water2005
Author(s)
Takeda, T., Ishii, K., Wu, J., Thet-Thet-Lwin, Minami, M., Tamaoka
Organizer
45th Jpn Soc Nuclear Medicine
Place of Presentation
Tokyo
Year and Date
20051111-13
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Tamaoka A Abnormal cerebral perfusion by a chemical weapon raw material, diphenylarsinic acid intoxication in Kamisu, Japan2005
Author(s)
Takeda, T., Ishu, K., Wu, J., Thet-Thet-Lwin, Minami, M
Organizer
18th Annual Congress on the European Association of Nuclear Medicine
Place of Presentation
Istanbul
Year and Date
20051000
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 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
Organizer
第47回日本小児神経学会総会
Place of Presentation
熊本市
Year and Date
20050519-21
Description
「研究成果報告書概要(和文)」より
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[Presentation] diphenylarsinic acid2005
Author(s)
Iwasaki, N, Ishii, K. Miyamoto, S, Takeda, T, Tanaka, R, Ooto, T, Saito, T, Matui, A, Itarashi, K, Kinugasa, H, Tsuchida, M, Ieshima, A, Ogata, T, Sato, H
Organizer
49th Annual Meeting of Jpn Soc Child Neurology
Place of Presentation
Kumamoto
Year and Date
20050519-21
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Clinical neurological findings of organic-arsenic, diphenylarsinic acid, poisoning occurred in Kamisu Ibaraki2004
Author(s)
Ishii, K, Tamaoka, A, Takeda, T, Ishii, K, Iwasaki, N, Syouji, S
Organizer
45th Societas Neurologica Japonica
Place of Presentation
Tokyo
Year and Date
20040511-14
Description
「研究成果報告書概要(欧文)」より
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[Presentation] ジフェニルアルシン酸等化合物中毒における小児の臨床的検討2004
Author(s)
岩崎 信明, 石井 一弘, 玉岡 晃, 宮本 信也, 武田 徹, 新 健治, 家島 厚, 土田 昌宏, 大戸 達之, 斎藤 貴志, 向田 壮一, 松井 陽, 緒方 剛, 土井 幹夫, 石崎 睦雄
Organizer
第46回日本小児神経学会総会
Place of Presentation
東京都
Year and Date
2004-07-08
Description
「研究成果報告書概要(和文)」より
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[Presentation] diphenylarsinic acid poisoning in infants2004
Author(s)
Iwasaki, N, Ishii, K. Miyamoto, S, Takeda, T, Tanaka, R, Ooto, T, Saito, T, Matui, A, Itarashi, K, Kinugasa, H, Tsuchida, M, Ieshima, A, Ogata, T, Sato, H
Organizer
46th Annual Meeting of Jpn Soc Child Neurology
Place of Presentation
Tokyo
Year and Date
2004-07-08
Description
「研究成果報告書概要(欧文)」より
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