2007 Fiscal Year Final Research Report Summary
The analysis of PDGFR-β deficient brain
Project/Area Number |
17590338
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Experimental pathology
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Research Institution | University of Toyama |
Principal Investigator |
ISHII Yoko University of Toyama, University of Thyama, Graduate School of Medicine and Pharmaceutical Sciences for Education, Assistant Professor (00361949)
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Co-Investigator(Kenkyū-buntansha) |
SASAHARA Masakiyo University of Toyama, Graduate School of Medicine and Pharmaceutical Sciences for Education, Professor (20154015)
ISHIZAWA Shin University of Toyama, Graduate School of Medicine and Pharmaceutical Sciences for Education, Associate Professor (40222989)
|
Project Period (FY) |
2005 – 2007
|
Keywords | platelet-derived growth factor / receptor / conditional knockout / neurotrophic factor / injury / excitotoxicity / differentiation / cell culture |
Research Abstract |
Platelet-derived growth factors (PDGFs) and PDGF receptors (PDGFRs) are widely expressed in the mammalian CNS, though their functional significance remains unclear. To clarify PDGFR function in CNS, we developed novel mutant mice in which the gene encoding the b subunit of PDGFR (PDGFR-b) was genetically deleted in CNS neurons to elucidate the role of PDGFR-b, particularly in the post-natal stage and analyzed the mutant mice. 1) The cerebral damage after cryogenic injury was severely exacerbated in the mutants compared with controls. Furthermore, TdT-mediated dUTP-biotin nick end labeling (TUNEL)- positive neuronal cell death and lesion formation in the cerebral hemisphere were extensively exacerbated in our mutant mice after direct injection of NMDA without altered NMDA receptor expression. Our results clearly demonstrate that PDGFR-b expressed in neurons protects them from cryogenic injury and NMDA-induced excitotoxicity. 2) We examined the inhibitory effect of PDGF-BB on the AMPA rece
… More
ptor function in the nucleus tractus solitarius (NTS) by using slice patch-clamp techniques. PDGF-BB significantly reduced the amplitude of AMPA-induced currents in NTS neurons, which showed that PDGF-BB could suppress the AMPA receptor-mediated excitatory input via the postsynaptic mechanism. The inhibitory effect of PDGF-BB on EPSCs was not observed in mutant mice with conditional deletion of the PDGFR-β gene in neurons. These studies suggest that the PDGF-B/PDGFR-β axis inhibits the AMPA receptormediated synaptic transmission that comprises the major part of the primary afferent to the NTS second-order neuron. The detected inhibitory action may be involved in the CNS regulation of the respiratory response. 3) PDGFRB-/-neural stem cells showed a higher rate of apoptosis without any significant decrease in proliferation. They demonstrated reduced capacities of migration and neuronal differentiation in response to not only PDGF-BB but also bFGF. bFGF increased the activity of the PDGFRB promoter as well as the expression and phosphorylation of PDGFRB. These results suggest the presence of the signaling convergence between PDGF and FGF. PDGFRB is needed for survival, and the effects of bFGF in migration and neural differentiation of the cells may be potentiated by induction of PDGFRB. Less
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Research Products
(55 results)
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[Journal Article] PDGF Receptor β is a Potent Regulator of Mesenchymal Stromal Cell Function. 2008 .2008
Author(s)
Tokunaga A., Oya T., Ishii Y., Moto mura H, Nakamura C., Ishizawa S., Fujimori T., Nabeshima Y., Umezawa A., Kanamori M., Kimura T., Sasahara M.
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Journal Title
Journal of Bone and Mineral Research (In press)
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Characterization of neuroprogenitor cells expressing the PDGF 13-receptor within the subventricular zone of postnatal mice2008
Author(s)
Ishii, Y., Matsumoto, Y., Watanabe, R., Elmi, M., Fujimori, T., Nissen, J., Cao, Y., Nabeshima, Y., Sasahara, M., Funa, K
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Journal Title
Molecular and Cellular Neuroscience 37
Pages: 507-518
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] PDGF Receptor 13 is a Potent Regulator of Mesenchymal Stromal Cell Function2008
Author(s)
Tokunaga, A. Oya, T., Ishii, Y., Motomura, H, Nakamura, C., Ishizawa, S., Fujimori, T., Nabeshima, Y., Umezawa, A. Kanamori, M., Kimura, T., Sasahara, M
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Journal Title
Journal of Bone and Mineral Research (in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Neuroprotective Role of Transgenic PAF-Acetylhydrolase II in Mouse Models of Focal Cerebral Ischemia.2007
Author(s)
Umemura K., Kato I., Hirashima Y., Ishii Y., Inoue T., Aoki J., Kono N., Oya T. Hayashi N., Hamada H., Endo S., Oda M., Arai H., Kinouchi H., and Hiraga K.
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Journal Title
Stroke. 38
Pages: 1063-1068
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Neuroprotective Role of Transgenic PAF-Acetylhydrolase II in Mouse Models of Focal Cerebral Ischemia.2007
Author(s)
Umemura, K., Kato, I., Hirashima, Y., Ishii, Y., Inoue, T., Aoki, J., Kono, N., Oya, T., Hayashi, N., Hamada, H., Endo, S., Oda, M., Arai, H., Kinouchi, H., Hiraga, K
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Journal Title
Stroke 38
Pages: 1063-1068
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Platelet-derived growth factor(PDGF)-BB inhibits AMPA receptor-mediated synaptic transmission via PDGF receptor-beta in murine nucleus tractus solitarius2007
Author(s)
Ohi, Y., Ishii, Y., Haji, A. Noguchi, S., Sasaoka, T., Fujimori, T., Nabeshima, Y, Sasahara, M., Hattori, Y
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Journal Title
Brain research 1159
Pages: 77-85
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mouse brains deficient in neuronal PDGF receptor-beta develop normally but are vulnerable to injury.2006
Author(s)
Ishii Y., Oya T., Zheng L., Gao Z., Kawaguchi M., Sabit H., Matsushima T., Tokunaga A., Ishizawa S., Hori E., Nabeshima Y., Sasaoka T., Fujimori T., Mori H. and Sasahara M.
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Journal Title
J. Neurochem. 98
Pages: 588-600
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Mouse brains deficient in neuronal PDGF receptor-beta develop normally but are vulnerable to injury2006
Author(s)
Ishii, Y., Oya, T., Zheng, L., Gao, Z., Kawaguchi, M., Sabit, H., Matsushima, T., Tokunaga, A. Ishizawa, S., Hori, E., Nabeshima, Y., Sasaoka, T., Fujimori, T., Mori, H., Sasahara, M
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Journal Title
J. Neurochem 96
Pages: 588-600
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A Homeodomain-Zinc Finger Protein, ZFHX4, Is Expressed in Neuronal Differentiation Manner and Suppressed in Muscle Differentiation Manner2006
Author(s)
Hemmi, K., Ma, D., Miura, Y., Kawaguchi, M., Sasahara, M., Hashimoto-Tamaoki, T., Tamaoki, T., Sakata, N., Tsuchiya K
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Journal Title
Biol. Pharm. Bull 56
Pages: 1830-1835
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Absence of human herpesvirus-8 and Epstein-Barr virus in inflammatory myofibroblastic tumor with anaplastic large cell lymphoma kinase fusion gene2006
Author(s)
Yamamoto, H., Kohashi, K., Oda, Y., Tamiya, S., Takahashi, Y., Kinoshita, Y., Ishizawa, S., Kubota, M., Tsuneyoshi, M
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Journal Title
Pathol. Int 56
Pages: 584-590
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Deletion of The PDGFR-β gene affects key fibroblast functions important for wound healing.2005
Author(s)
Gao Z., Sasaoka T., Fujimori T., Oya T., Ishii Y., Sabit H., Kawaguchi M., Kurotaki Y., Naito M., Wada T., Ishizawa S., Kobayashi M., Nabeshima Y. I. and Sasahara M
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Journal Title
J. Biol. Chem. 280
Pages: 9375-9389
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Some biochemical and histochemical properties of human liver serine dehydratase.2005
Author(s)
Kashii T., Gomi T., Oya T., Ishii Y., Oda H., Maruyama M., Kobayashi M., Masuda T., Yamazaki M., Nagata T., Tsukada K., Nakajma A., tatsu K., Mori H., Takusagawa F., Owa H. and Pitot H. C.
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Journal Title
Int. J. Biochem. Cell Biol. 37
Pages: 574-589
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Deletion of The PDGFR-B gene affects key fibroblast functions important for wound healing2005
Author(s)
Gao, Z., Sasaoka, T., Fujimori, T., Oya, T., Ishii, Y., Sabit, H., Kawaguchi, M., Kurotaki, Y., Naito, M., Wada, T., Ishizawa, S., Kobayashi, M., Nabeshima, Y.I., Sasahara, M
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Journal Title
J. Biol. Chem 280
Pages: 9375-9389
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Some biochemical, and histochemical properties of human liver serine dehydratase2005
Author(s)
Kashii, T., Gomi, T., Oya, T., Ishii, Y., Oda, H., Maruyama, M., Kobayashi, M., Masuda, T., Yamazaki, M., Nagata, T., Tsukada, K., Nakajima, A. Tatsu, K., Mori, H., Takusagawa, F., Ogawa, H., Pitot, H.C
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Journal Title
Int. J. Biochem. Cell Biol 37
Pages: 574-589
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Cytoplasmic expression of c-erbB2 in non-small cell lung cancers2005
Author(s)
Cheng, C.M., Tsuneyama, K., Matsui, K., Takahashi, H., Ishizawa, S., Takano, Y
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Journal Title
Virchows Arch 446
Pages: 596-603
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Neuroprotection of PDGF-B against oxidative stress via the PI3K/Akt signal2007
Author(s)
Zheng, L., shii, Y., Oya, T., Tokunaga, A. Hamashima, T., Ishizawa, S., Sasahara, M
Organizer
Neuro 2007(The 29th Annual Meeting of the Japan Neuroscience Society, The 50th Annual Meeting of the Japanese Society for Neurochemistry
Place of Presentation
Yokohama
Year and Date
20070910-12
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Transgenic PAF-Acetylhydrolase II Protects Neurons in Mouse Models of Transient Focal Cerebral Ischemia.2007
Author(s)
Kato I., Umemura K., Ishii Y., Inoue T., Aoki J., Kono N., Oya T., Arai H., Hayashi N., Hamada H., Endo S., Hirashima Y. and Hiraga K.
Organizer
21COE Program Joint symposium of Peking University and University of Toyama. "Evidence-based approach to traditional medicine and modern medicine"
Place of Presentation
Beijing
Year and Date
20070600
Description
「研究成果報告書概要(和文)」より
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[Presentation] Transgenic PAF-Acetylhydrolase II Protects Neurons in Mouse Models of Transient Focal Cerebral Ischemia. 21COE Program Joint symposium of Peking University and University of Toyama2007
Author(s)
Kato, I., Umemura, K., Ishii, Y., Inoue, T., Aoki, J., Kono, N., Oya, T., Arai, H., Hayashi, N., Hamada, H., Endo, S., Hirashima, Y., Hiraga, K
Organizer
Evidence-based approach to traditional medicine and modern medicine
Place of Presentation
Beijing
Year and Date
20070600
Description
「研究成果報告書概要(欧文)」より
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[Presentation] PDGF-B protects neuron from oxidative stress via the PI3K/Akt signal2007
Author(s)
Zheng, L., Ishii, Y., Oya, T., Sabit, H., Matsushima, T., Kurashige, Y., Ishizawa, S., Sasahara, M
Organizer
The 96th Annual Meeting of the Japan Society of Pathology
Place of Presentation
Osaka
Year and Date
20070313-15
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The role of PDGFR-t3 in the activation of mouse stellate cells2007
Author(s)
Morita, S., Oya, T., Ishii, Y., Sabit, H., Tokunaga, A. Ishizawa, S., Matsushima, T., Kurashige, Y., Sasahara, M
Organizer
The 96th Annual Meeting of the Japan Society of Pathology
Place of Presentation
Osaka
Year and Date
20070313-15
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The analysis of the function of PDGFR-13 in fibroblast migration2007
Author(s)
Tokunaga, A. Oya, T., Ishii, Y., Sabit, H., Matsushima, T., Kurashige, Y., Ishizawa, S., Kanamori, M., Sasahara, M
Organizer
The 96th Annual Meeting of the Japan Society of Pathology
Place of Presentation
Osaka
Year and Date
20070313-15
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The role of platelet-derived growth factor receptor 13 in the process of mouse hepatic stellate cell activation2006
Author(s)
Morita, S., Sabit, H., Oya, T., Tokunaga, A. Kudo, H., Yata, Y., Takahara, T., Ishii, Y., Ishizawa, S., Tsukada, K., Sasahara, M
Organizer
13th International Symposium on Cells of the Hepatic Sinusoid
Place of Presentation
Niigata
Year and Date
20060900
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Study about PDGF receptors and their signaling in peripheral nervous regeneration2006
Author(s)
Sabit, H., Yamazaki, T., Oya, T., Ishii, Y., Furuta, I., Sasahara, M
Organizer
The 29th Annual Meeting of the Japan Neuroscience Society
Place of Presentation
Kyoto
Year and Date
20060700
Description
「研究成果報告書概要(欧文)」より
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[Presentation] A novel model for diabetic retinopathy.2006
Author(s)
Ichsan A. M., Kato I., Oya T., Tomi M., Takasawa S., Okamoto H., Sasahara M., Hayasaka S., Hosoya K. and Hiraga K.
Organizer
20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
Place of Presentation
Kyoto
Year and Date
20060600
Description
「研究成果報告書概要(和文)」より
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[Presentation] A novel model for diabetic retinopathy2006
Author(s)
Ichsan, A.M., Kato, I., Oya, T., Tomi, M., Takasawa, S., Okamoto, H., Sasahara, M., Hayasaka, S., Hosoya, K., Hiraga, K
Organizer
The 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
Place of Presentation
Kyoto
Year and Date
20060600
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Expression of constitutively active form of CaM kinase II in pancreatic beta cells of transgenic mice leads to severe diabetes mellitus2006
Author(s)
Kato, I., Hiraga, K., Oya, T., Sasahara, M., Takasaki, I., Tabuchi, Y., Takasawa, S., Okamoto, H
Organizer
The 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
Place of Presentation
Kyoto
Year and Date
20060600
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The analysis of PDGF b receptor and its signaling in peripheral nervous regeneration2006
Author(s)
Yamazaki, T., Oya, T., Sabit, H. Ishii, Y., Ishizawa, S., Sasahara, M
Organizer
The 95th Annual Meeting of the Japan Society of Pathology
Place of Presentation
Tokyo
Year and Date
20060500
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Overexpression of PAF-acetylhydrolase II in transgenic mouse brain supresses ischemic stress-induced neuronal cell death.2006
Author(s)
Umemura K., Kato I., Hirashima Y., Ishii Y., Oya T., Hayashi N., Hamada H., Inoue T., Aoki J., Kinouchi H., Hiraga K. and Endo S
Organizer
2006 AANS Annual Meeting
Place of Presentation
San Francisco CA, America
Year and Date
20060400
Description
「研究成果報告書概要(和文)」より
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[Presentation] Overexpression of PAF-acetylhydrolase II in transgenic mouse brain supresses ischemic stress-induced neuronal cell death2006
Author(s)
Umemura, K., Kato, I., Hirashima, Y., Ishii, Y., Oya, T., Hayashi, N., Hamada, H., Inoue, T., Aoki, J., Kinouchi, H., Hiraga, K., Endo, S
Organizer
2006 AANS Annual Meeting
Place of Presentation
4 San Francisco CA, America
Year and Date
20060400
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Establishment of mutant mouse with neuron-specific PDGF receptor depletion.2005
Author(s)
Sasahara M., Gao Z., Oya T., Ishii Y., Sasaoka T., Ishizawa S., Matsushima T., Kurashige Y., Sabit H., Zheng L., Tokunaga A. and Fujimori T.
Organizer
第28回日本神経科学大会
Place of Presentation
横浜
Year and Date
20050700
Description
「研究成果報告書概要(和文)」より
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[Presentation] Establishment of mutant mouse with neuron-specific PDGF receptor depletion2005
Author(s)
Sasahara, M., Gao, Z., Oya, T., Ishii, Y., Sasaoka, T., Ishizawa, S., Matsushima, T., Kurashige, Y., Sabit, H., Zheng, L., Tokunaga, A. Fujimori, T
Organizer
The 28th Annual Meeting of the Japan Neuroscience Society
Place of Presentation
Yokohama
Year and Date
20050700
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The analysis of the PDGFR-I3 function in fibroblasts using Cre-loxP knockout system2005
Author(s)
Oya, T., Gao, Z., Ishii, Y., Sasaoka, T., Sabit, H. Tokunaga, A. Zheng, L., Ishizawa, S., Fujimori, T., Sasahara, M
Organizer
The 37th Annual Meeting of the Japan Connective Tissue Society
Place of Presentation
Toyama
Year and Date
20050500
Description
「研究成果報告書概要(欧文)」より
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[Presentation] A study on proliferation, migration and apoptosis after PDGF-13 knockout in dermal fibroblasts2005
Author(s)
Sasahara, M., Gao, Z., Sasaoka, T., Oya, T., Ishii, Y., Sabit, H., Ishizawa, S
Organizer
The 94th Annual Meeting of the Japan Society of Pathology
Place of Presentation
Yokohama
Year and Date
20050400
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The activation of ERK1/2 and JNK, but not p38, was attenuated after PDGFR-(3 depletion2005
Author(s)
Gao, Z., Sasahara, M., Sasaoka, T., Oya, T., Ishii, Y., Sabit, H., Ishizawa, S
Organizer
The 94th Annual Meeting of the Japan Society of Pathology
Place of Presentation
Yokohama
Year and Date
20050400
Description
「研究成果報告書概要(欧文)」より
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