Profile

Name

Isao Ishii

Affiliation

Health Chemistry

Subjects

Sulfur amino acid metabolism (homocysteine, H2S, glutathione)
Lysophospholipid signaling (S1P and LPA)

Official title

Professor

Degree

PhD

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Books

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• 2D-DIGE Proteomic Analysis of Mouse Liver Within 1 Week. In: Ohlendieck, K. (eds) Difference Gel Electrophoresis. Methods in Molecular Biology, vol 2596.　Shotaro Kamata, Isao Ishii　　217–230　Humana, New York, NY.　2023　978-1-0716-2831-
• Methionine: Biosynthesis, Chemical Structure and Toxicity　Kamata S，Ishii I　Protective roles of transsulfuration against methionine toxicity.　143-153　Nova Science Publishers　2013　978-1-62618-292-9

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Papers

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• [Original Article]　Competitive Ligand-Induced Recruitment of Coactivators to Specific PPARα/δ/γ Ligand-Binding Domains Revealed by Dual-Emission FRET and X-Ray Diffraction of Cocrystals　Kamata S, Honda A , Yashiro S, Kaneko C, Komori Y, Shimamura A, Masuda R, Oyama T, Ishii I　Antioxidants　14　494　2025　
• [Original Article]　Different coactivator recruitment to human PPARα/δ/γ ligand-binding domains by eight PPAR agonists to treat nonalcoholic fatty liver disease　Kamata S, Honda A, Kashiwagi N, Shimamura A, Yashiro S, Komori Y, Hosoda A, Akahoshi N, Ishii I　Biomedicines　12　624　2024　
• [Review]　Sphingosine 1-phosphate regulates obesity and glucose homeostasis　Kajita K, Ishii I, Mori I, Asano M, Fuwa M, Morita H　Int J Mol Sci　25　932　2024　
• [Original Article]　Pharmacological Inhibition and Genetic Deletion of Cystathionine Gamma-Lyase in Mice Protects against Organ Injury in Sepsis: A Key Role of Adhesion Molecules on Endothelial cells　Manandhar S, Chambers S, Miller A, Ishii I, Bhatia M　Int J Mol Sci　24　13650　2023　
• [Review]　Current clinical trial status and future prospects of PPAR-targeted drugs for treating nonalcoholic fatty liver disease　Kamata S, Honda A, Ishii I　Biomolecules　13　1264　2023　
• [Original Paper]　Functional and structural insights into the human PPARα/δ/γ targeting preferences of anti-NASH investigational drugs, lanifibranor, seladelpar, and elafibranor　Kamata S, Honda A, Ishikawa R, Akahane M, Fujita A, Kaneko C, Miyawaki S, Habu Y, Shiiyama Y, Uchii K, Machida Y, TOyama T, Ishii I　Antioxidants　12　1523　2023　
• [Original Paper]　Synthesis of sulfides and persulfides Is not impeded by disruption of three canonical enzymes in sulfur metabolism　Zainol Abidin, Q. H. Ida, T. Morita, M. Matsunaga, T. Nishimura, A. Jung, M. Hassan, N. Takata, T. Ishii, I. Kruger, W. Wang, R. Motohashi, H. Tsutsui, M. Akaike, T.　Antioxidants　12　868　2023　
• [Review]　Amino acids in health and disease: The good, the bad, and the ugly　Ishii I, Bhatia M　Int J Mol Sci　24　4931　2023　
• [Original paper]　Differential roles of cystathionine gamma-lyase and mercaptopyruvate sulfurtransferase in hapten-induced colitis and contact dermatitis in mice.　Akahoshi N, Hasegawa R, Yamamoto S, Takemoto R, Yoshizawa T, Kamichatani W, Ishii I.　Int J Mol Sci　24(3)　2659　2023　
• [Original paper]　Opposing roles of sphingosine 1-phosphate receptors 1 and 2 in fat deposition and glucose tolerance in obese male mice　Asano M, Kajita K, Fuwa M, Kajita T, Mori I, Akahoshi N, Ishii I, Morita H　Endocrinology　164　1-13　2023　
• [Review]　The perspective of PPAR dual/pan agonists as therapeutic drugs against NAFLD　Akihiro Honda, Isao Ishii　YAKUGAKUZASSHI　142　1335–1343　2022　[Related links]
• [Original Paper]　Hydrogen sulfide attenuates lymphedema via the induction of lymphangiogenesis through a PI3K/Akt-dependent mechanism　Suzuki J, Shimizu Y, Hayashi T, Che Y, Pu Z, Tsuzuki K, Narita S, Shibata R, Ishii I, Calvert JW, Murohara T　J Am Heart Assoc　11　e026889　2022　
• [Original Papaer]　Functional and Structural Insights into Human PPARα/δ/γ Subtype Selectivity of Bezafibrate, Fenofibric Acid, and Pemafibrate.　Honda, A.; Kamata, S.; Akahane, M.; Machida, Y.; Uchii, K.; Shiiyama, Y.; Habu, Y.; Miyawaki, S.; Kaneko, C.; Oyama, T.; Ishii, I. 　Int J Mol Sci　23　4726　2022　
• [Original Papaer]　The function of SARS-CoV-2 spike protein is impaired by disulfide-bond disruption with mutation at cysteine-488 and by thiol-reactive N-acetyl-cysteine and glutathione.　Murae, M., Shimizu, Y., Yamamoto, Y., Kobayashi, A., Houri, M., Inoue, T., Irie, T., Gemba, R., Kondo, Y., Nakano, Y., Miyazaki, S., Yamada, D., Saitoh, A., Ishii, I., Onodera, T., Takahashi, Y., Wakita, T., Fukasawa, M., Noguchi, K.　Biochem Biophys Res Commun　597　30–36　2022　
• [Original Papaer]　A high-methionine diet for one-week induces a high accumulation of methionine in the cerebrospinal fluid and confers bipolar disorder-like behavior in mice.　Ishii, I.; Kamata, S.; Ito, S.; Shimonaga, A.; Koizumi, M.; Tsushima, M.; Miura, A.; Nagata, T.; Tosaka, Y.; Ohtani, H.; Kamichatani, W.; Akahoshi, N.　Int. J. Mol. Sci.　23　928　2022　
• [Original Paper]　The gasotransmitter hydrogen sulfide (H2S) prevents pathologic calcification (PC) in cartilage　Nasi S, Ehirchlou D, Bertran J, Castelbianco M, Mitchell J, Ishii I, So A, Busso N　Antioxidants　10　1433　2021　
• [Review]　PPARalpha–Ligand Binding Modes Revealed by X-ray Crystallography　Kamata S, Ishii I　YAKUGAKUZASSHI　141　1267–1274　2021　[Related links]
• [Review]　Role of hydrogen sulfide producing and metabolizing enzymes: Insights from human genetic diseases and their mouse models.　Akahoshi N, Ishii I　J Jpn Biochem Soc　93　754–759　2021　
• [Original Paper]　Structural basis for anti-non-alcoholic fatty liver disease and diabetic dyslipidemia drug saroglitazar as a PPARalpha/gamma dual agonist　Honda A, Kamata S, Satta C, Machida Y, Uchii K, Terasawa K, Nemoto A, Oyama T, Ishii I　Biol Pharm Bull　44　1210–1219　2021　
• [Original Paper]　Crystal structures of the human peroxisome proliferator-activated receptor (PPAR) alpha ligand-binding domain in complexes with a series of phenylpropanoic acid derivatives generated by a ligand-exchanging soaking method　Oyama T, Kamata S, Ishii I, Miyachi H　Biol Pharm Bull　44　1202–1209　2021　
• [Original Paper]　Preparation of human PPARα ligand binding domain–ligand co-crystals for high-resolution X-ray crystallography　Kamata S, Oyama T, Ishii I　STAR Protocols　2　100364　2021　
• [Original paper]　PPARα ligand-binding domain structures with endogenous fatty acids and fibrates　Kamata S, Oyama T, Saito K, Honda A, Yamamoto Y, Suda K, Ishikawa R, Itoh T, Watanabe Y, Shibata T, Uchida K, Suematsu M, Ishii I　iScience　23　101727　2020　
• [Original paper]　Cytotoxicity comparison of 35 developmental neurotoxicants in human induced pluripotent stem cells (iPSC), iPSC-derived neural progenitor cells, and transformed cell lines　Kamata S, Hashiyama R, Hana-ika H, Ohkubo I, Saito R, Honda A, Anan Y, Akahoshi N, Noguchi K, Kanda Y, Ishii I　Toxicol In Vitro　69　104999　2020　
• [Original paper]　Homocysteine hypothesis on the impaired peripheral but not central nervous system oxytocin responses in cystathionine γ-lyase-deficient dam mice　Akahoshi N, Kamichatani W, Ishii I　Biol Pharm Bull　43　1810–1813　2020　
• [Original Paper]　Hydrogen sulphide treatment improves post-infarct remodelling and long-term cardiac function in CSE knockout and wild-type mice　Ellmer LJ, Templeton EM, Pilbrow AP, Frampton C, Ishii I, Moore PK, Bhatia M, Richards AM, Cameron VA.　Int J Mol Sci　21　4284　2020　
• [Original Paper]　Repression of mercury accumulation and adverse effects of methylmercury exposure is mediated by cystathionine γ-lyase to produce reactive sulfur species in mouse brain.　Akiyama M, Unoki T, Yoshida E, Ding Y, Yamakawa H, Shinkai Y, Ishii I, Kumagai Y.M　Toxicol Lett　330　128–133　2020　
• [Original Paper]　Increased urinary 3-mercaptolactate excretion and enhanced passive systemic anaphylaxis in mice lacking mercaptopyruvate sulfurtransferase, a model of mercaptolactate-cysteine disulfiduria　Akahoshi N, Minakawa T, Miyashita M, Sugiyama U, Saito C, Takemoto R, Honda A, Kamichatani W, Kamata S, Anan Y, Ishii I.　Int J Mol Sci　21　818　2020　
• [Original Paper]　Preeclampsia-like features and partial lactation failure in mice lacking cystathionine γ-lyase—an animal model of cystathioninuria.　Akahoshi N, Handa H, Takemoto R, Kamata S, Yoshida M, Onaka T, Ishii I.　Int J Mol Sci　20　3057　2019　
• [Original Paper]　Cystathionine-gamma-lyase-derived hydrogen sulfide-regulated substance P modulates liver sieve fenestrations in caecal ligation and puncture-induced sepsis.　Gaddam RR, Chambers S, Fraser R, Cogger VC, Le Couture DG, Ishii I, Bhatia M.　Int J Mol Sci 　20　3191　2019　
• [Original Paper]　Environmental electrophile-mediated toxicity in mice lacking Nrf2, CSE, or both.　Akiyama M, Unoki T, Shinkai Y, Ishii I, Ida T, Akaike T, Yamamoto M, Kumagai Y.　Environ Health Perspect　127　67002　2019　
• [Original Paper]　Dietary selenium deficiency or selenomethionine excess drastically alters organ selenium contents without altering the expression of most selenoproteins in mice.　Akahoshi N, Anan Y, Hashimoto Y, Tokoro N, Mizuno R, Hayashi S, Yamamoto S, Shimada K, Kamata S, Ishii I.　J Nutr Biochem　69　120-129　2019　
• [Original Paper]　 Abnormal amino acid profiles of blood and cerebrospinal fluid from cystathionine beta-synthase-deficient mice, an animal model of homocystinuria.　Akahoshi N, Yokohama A, Nagata T, Miura A, Kamata S, Ishii I.　Biol Pharm Bull　42　1054-1057　2019　
• [Original Paper]　Mutations in homocysteine metabolism genes increase N-homocysteinylation and keratin damage in mice.　Borowczyk K, Wróblewski J, Maria Suliburska J, Akahoshi N, Ishii I, Jakubowski H.　Int J Genomics　2018　7570850　2018　
• [Original Paper]　2D DIGE proteomic analysis reveals fasting-induced protein remodeling through organ-specific transcription factor(s) in mice.　Kamata S, Yamamoto J, Ohtani H, Tosaka Y, Yoshikawa S, Akahoshi N, Ishii I.　FEBS Open Bio　8　1524-1543　2018　
• [Original paper]　Cystathionine gamma-lyase-produced hydrogen sulfide controls endothelial NO bioavailability and blood pressure.　Szijarto IA, Marko L, Filipovic MR, Miljkovic JL, Tabeling C, Tsvetkov D, Wang N, Rabelo LA, Witzenrath M, Diedrich A, Tank J, Akahoshi N, Kamata S, Ishii I, Goulash M.　Hypertension　71　1210-1217　2018　
• [Original Paper]　Structural and functional insights into S-thiolation of human serum albumins.　Nakashima, F. Shibata, T. Kamiya, K. Yoshitake, J. Kikuchi, R. Matsushita, T. Ishii, I. Gimenez-Bastida, J. A. Schneider, C. Uchida, K.　Sci Rep　8　932　2018　
• [Original Paper]　Hydrogen sulfide inhibits the NLRP3 inflammasome and reduces cytokine production both in vitro and in a mouse model of inflammation.　Castelblanco, M. Lugrin, J. Ehirchiou, D. Nasi, S. Ishii, I. So, A. Martinon, F. Busso, N.　J Biol Chem　293　2546-2557　2018　
• [Original Paper]　Rapid 2D DIGE proteomic analysis of mouse liver.　Kamata, S. Ishii, I.　Methods Mol Biol　1664　153-166　2018　
• [Original Paper]　The Capture of cadmium by reactive polysulfides attenuates cadmium-induced adaptive responses and hepatotoxicity.　Akiyama, M. Shinkai, Y. Unoki, T. Shim, I. Ishii, I. Kumagai, Y.　Chem Res Toxicol　30　2209-2217　2017　
• [Original Paper]　Hydrogen sulfide-producing cystathionine gamma-lyase is critical in the progression of kidney fibrosis.　Han, S. J. Noh, M. R. Jung, J. M. Ishii, I. Yoo, J. Kim, J. I. Park, K. M.　Free Radic Biol Med　112　423-432　2017　
• [Original Paper]　Reactive sulfur species regulate tRNA methylthiolation and contribute to insulin secretion.　Takahashi N, Wei FY, Watanabe S, Hirayama M, Ohuchi Y, Fujimura A, Kaitsuka T, Ishii I, Sawa T, Nakayama H, Akaike T, Tomizawa K.　Nucleic Acids Res　45　435-445　2016　
• [Original paper]　Cystathionine-gamma-lyase gene deletion protects mice against inflammation and liver sieve injury following polymicrobial sepsis.　Gaddam R, Fraser R, Badiei A, Chambers S, Cogger V, Couture DL, Ishii I, Bhatia M.　PLoS One　11　e0160521　2016　
• [Original paper]　Immobilization of the Gas Signaling Molecule H2 S by Radioisotopes: Detection, Quantification, and In Vivo Imaging.　Sarkar S, Ha YS, Soni N, An GI, Lee W, Kim MH, Huynh PT, Ahn H, Bhatt N, Lee YJ, Kim JY, Park KM, Ishii I, Kang SG, Yoo J.　Angew Chem Int Ed Engl　55　9365-9370　2016　
• [Original paper]　Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).　Klionsky DJ, Ishii I, et al.　Autophagy　12　1-222　2016　
• [Original paper]　Blockade of sphingosine 1-phosphate receptor 2 signaling attenuates high-fat diet-induced adipocyte hypertrophy and systemic glucose intolerance in mice.　Kitada Y, Kajita K, Taguchi K, Mori I, Yamauchi M, Ikeda T, Kawashima M, Asano M, Kajita T, Ishizuka T, Banno Y, Kojima I, Chun J, Kamata S, Ishii I, Morita H.　Endocrinology　157　1839-1851　2016　
• [Original paper]　Improved tag-switch method reveals that thioredoxin acts as depersulfidase and controls the intracellular levels of protein persulfidation.　Wedmann R, Onderka C, Wei S, Szijártó IA, Miljkovic JL, Mitrovic A, Lange M, Savitsky S, Yadav PK, Torregrossa R, Harrer EG, Harrer T, Ishii I, Gollasch M, Wood ME, Galardon E, Xian M, Whiteman M, Banerjee R, Filipovic MR.　Chem Sci　7　3414-3426　2016　
• [Original paper]　Role of cystathionine gamma-lyase in immediate renal impairment and inflammatory response in acute ischemic kidney injury.　Markó L, Szijártó I, Filipovic MR, Kaßmann M, Balogh A, Park J-K, Przybyl L, N’diaye G, Kr?mer S, Anders J, Ishii I, Müller DN, Gollasch M　Sci Rep　8　27517　2016　
• [Original paper]　Hemizygosity of transsulfuration genes confers increased vulnerability against acetaminophen-induced hepatotoxicity in mice.　Hagiya Y, Kamata S, Mitsuoka S, Okada N, Yoshida S, Yamamoto J, Ohkubo R, Abiko Y, Yamada H, Akahoshi N, Kasahara T, Kumagai Y, Ishii I.　Toxicol Appl Pharmacol　282　195-206　2015　
• [Original paper]　Indispensable role of endothelial nitric oxide synthase in caloric restriction-induced cardioprotection against ischemia-reperfusion injury.　Shinmura K, Tamaki K, Ito K, Yan X, Yamamoto T, Katsumata Y, Matsuhashi T, Sano M, Fukuda K, Suematsu M, Ishii I.　Am J Physiol Heart Circ Physiol　308　894-903　2015　
• [Original paper]　Hyperhomocysteinemia abrogates fasting-induced cardioprotection against ischemia/reperfusion by limiting bioavailability of hydrogen sulfide anions.　Nakano S, Ishii I, Shinmura K, Tamaki K, Hishiki T, Akahoshi N, Ida T, Nakanishi T, Kamata S, Kumagai Y, Akaike T, Fukuda K, Sano M, Suematsu M.　J Mol Med (Berl)　93　879-889　2015　
• [Original paper]　Reactive Sulfur Species-Mediated Activation of the Keap1-Nrf2 Pathway by 1,2-Naphthoquinone through Sulfenic Acids Formation under Oxidative Stress.　Shinkai Y, Abiko Y, Ida T, Miura T, Kakehashi H, Ishii I, Nishida M, Sawa T, Akaike T, Kumagai Y.　Chem Res Toxicol　28　838-847　2015　
• [Original paper]　Involvement of reactive persulfides in biological bismethylmercury sulfide formation.　Abiko Y, Yoshida E, Ishii I, Fukuto JM, Akaike T, Kumagai Y.　Chem Res Toxicol　28　1301-1306　2015　
• [Original paper]　Differential adaptive responses to 1- or 2-day fasting in various mouse tissues revealed by quantitative PCR analysis.　Yamamoto J, Kamata S, Miura A, Nagata T, Kainuma R, Ishii I.　FEBS Open Bio　5　357-368　2015　
• [Original paper]　2D DIGE proteomic analysis highlights delayed postnatal repression of alpha-fetoprotein expression in homocystinuria model mice.　Kamata S, Akahoshi N, Ishii I.　FEBS Open Bio　5　535-541　2015　
• [Original paper]　The H2S-generating enzymes cystathionine beta-synthase and cystathionine gamma-lyase play a role in vascular development during normal lung alveolarization.　Madurga A, Golec A, Pozarska A, Ishii I, Mi?íková I, Nardiello C, Vadász I, Herold S, Mayer K, Reichenberger F, Fehrenbach H, Seeger W, Morty RE.　Am J Physiol Lung Cell Mol Physiol　309　710-724　2015　
• [Original paper]　Formation of sulfur adducts of N-acetyl-p-benzoquinoneimine, an electrophilic metabolite of acetaminophen in vivo: participation of reactive persulfides.　Abiko Y, Ishii I, Kamata S, Tsuchiya Y, Watanabe Y, Ihara H, Akaike T, Kumagai Y.　Chem Res Toxicol　28　1796-1802　2015　
• [Original paper]　Protective effects of hydrogen sulfide anions against acetaminophen-induced hepatotoxicity in mice.　Ishii I, Kamata S, Hagiya Y, Abiko Y, Kasahara T, Kumagai Y.　J Toxicol Sci　40　837-841　2015　
• [Original paper]　Dietary deprivation of each essential amino acid induces differential systemic adaptive responses in mice.　Kamata S, Yamamoto J, Kamijo K, Ochiai T, Morita T, Yoshitomi Y, Hagiya Y, Kubota M, Ohkubo R, Kawaguchi M, Himi T, Kasahara T, Ishii I.　Mol Nutr Food Res　58　1309-1321　2014　
• [Original paper]　Neutral aminoaciduria in cystathionine beta-synthase-deficient mice; an animal model of homocystinuria.　Akahoshi N, Kamata S, Kubota M, Hishiki T, Nagahata Y, Matsuura T, Yamazaki C, Yoshida Y, Yamada H, Ishizaki Y, Suematsu M, Kasahara T, Ishii I.　Am J Physiol Renal Physiol　306　1462-1476　2014　
• [Original paper]　The effect of CSE gene deletion in caerulein-induced acute pancreatitis in the mouse.　Ang AD, Rivers-Auty J, Hegde A, Ishii I, Bhatia M.　Am J Physiol Gastrointest Liver Physiol　305　712-721　2013　
• [Original paper]　Endogenous hydrogen sulfide protects pancreatic beta-cells from a high-fat diet-induced glucotoxicity and prevents the development of type 2 diabetes.　Okamoto M, Yamaoka M, Takei M, Ando T, Taniguchi S, Ishii I, Tohya K, Ishizaki T, Niki I, Kimura T.　Biochem Biophys Res Commun　442　227-233　2013　
• [Review]　Reconsideration of homocysteinemia.　Ishii I.　Seikagaku　85　1067-1071　2013　
• [Original paper]　Protein phosphorylation involved in the gene expression of the hydrogen sulphide producing enzyme cystathionine gamma-lyase in the pancreatic beta-cell.　Taniguchi S, Kimura T, Umeki T, Kimura Y, Kimura H, Ishii I, Itoh N, Naito Y, Yamamoto H, Niki I.　Mol Cell Endocrinol　350　31-38　2012　
• [Original paper]　TOF-SIMS imaging of halide/thiocyanate anions and hydrogen sulfide in mouse kidney sections using silver-deposited plates.　Akahoshi N, Ishizaki I, Naya M, Maekawa T, Yamazoe S, Horiuchi T, Kajimura M, Ohashi Y, Suematsu M, Ishii I.　Anal Bioanal Chem　402　1859-1864　2012　
• [Original paper]　Pyrvinium pamoate inhibits proliferation of myeloma/erythroleukemia cells by suppressing mitochondrial respiratory complex I and STAT3.　Harada Y, Ishii I, Hatake K, Kasahara T.　Cancer Lett　319　83-88　2012　
• [Original paper]　Hypoxic regulation of the cerebral microcirculation is mediated by a carbon monoxide-sensitive hydrogen sulfide pathway.　Morikawa T, Kajimura M, Nakamura T, Hishiki T, Nakanishi T, Yukutake Y, Nagahata Y, Ishikawa M, Hattori K, Takenouchi T, Takahashi T, Ishii I, Matsubara K, Kabe Y, Uchiyama S, Nagata E, Gadalla MM, Snyder SH, Suematsu M.　Proc Natl Acad Sci USA　109　1293-1298　2012　
• [Original paper]　Methionine excess in diet induces acute lethal hepatitis in mice lacking cystathionine gamma-lyase, an animal model of cystathioninuria.　Yamada H, Akahoshi N, Kamata S, Hagiya Y, Hishiki T, Nagahata Y, Matsuura T, Takano N, Mori M, Ishizaki Y, Izumi T, Kumagai Y, Kasahara T, Suematsu M, Ishii I.　Free Radic Biol Med　52　1716-1726　2012　
• [Review]　Reprofiling a classical anthelmintic, pyrvinium pamoate, as an anti-cancer drug targeting mitochondrial respiration.　Ishii I, Harada Y, Kasahara T.　Front Oncol　2　137　2012　
• [Original paper]　Triacylglycerol/phospholipid molecular species profiling of fatty livers and regenerated non-fatty livers in cystathionine beta-synthase-deficient mice, an animal model for homocysteinemia/homocystinuria.　Ikeda K, Kubo A, Akahoshi N, Yamada H, Miura N, Hishiki T, Nagahata Y, Matsuura T, Suematsu M, Taguchi R, Ishii I.　Anal Bioanal Chem　400　1853-1863　2011　
• [Original paper]　Frequent spontaneous seizures followed by spatial working memory/anxiety deficits in mice lacking sphingosine 1-phosphate receptor 2.　Akahoshi N, Ishizaki Y, Yasuda H, Murashima YL, Shinba T, Goto K, Himi T, Chun J, Ishii I.　Epilepsy Behav　22　659-665　2011　

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