KINDAI UNIVERSITY


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平野 牧人ヒラノ マキト

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所属部署名医学科
職名准教授
学位博士(医学)
専門臨床神経遺伝学
ジャンル科学・技術/遺伝子・DNA技術
コメンテータガイドhttp://www.kindai.ac.jp/meikan/497-hirano-makito.html
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Last Updated :2017/11/22

コミュニケーション情報 byコメンテータガイド

コメント

    神経難病の原因遺伝子について研究しています。特に筋萎縮性側索硬化症(ALS)や多系統萎縮症(MSA)などの神経変性疾患での遺伝子検査、スクリーニング検査を施行しております。

報道関連出演・掲載一覧

    <報道関連出演・掲載一覧>
    ●2016/3/15
     読売新聞
     パーキンソン病について

学歴・経歴

学歴

  •  - 1998年, 大阪大学, 医学研究科, 医学
  •  - 1990年, 大阪大学, 医学部, 医学科

経歴

  •   2002年, -  奈良県立医科大学助手

研究活動情報

研究分野

  • 神経科学, 神経科学一般

研究キーワード

  • 遺伝子治療, 小脳失調, パーキンソン病

論文

  • Unexpectedly mild phenotype in an ataxic family with a two-base deletion in the APTX gene., Hirano M, Matsumura R, Nakamura Y, Saigoh K, Sakamoto H, Ueno S, Inoue H, Kusunoki S., J Neurol Sci, 378, 75, 79,   2017年07月, 査読有り
  • Time Course of Radiological Imaging and Variable Interindividual Symptoms in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Associated with p.Arg487His Mutation in the VCP Gene., Hirano M, Yamagishi Y, Yanagimoto S, Saigoh K, Nakamura Y, Kusunoki S., Eur Neurol, 78, 1-2, 78, 83,   2017年, 査読有り
  • Histopathological features of a patient with Charcot-Marie-Tooth disease type 2U/ AD-CMTax-MARS., Hirano M, Oka N, Hashiguchi A, Ueno S, Sakamoto H, Takashima H, Higuchi Y, Kusunoki S, Nakamura Y, Journal of the peripheral nervous system : JPNS,   2016年10月, 査読有り
  • Valosin-containing protein-related amyotrophic lateral sclerosis in Japan., Hirano M, Nakamura Y, Kusunoki S, Rinsho shinkeigaku = Clinical neurology, 56, 4, 285, 286,   2016年04月, 査読有り
  • Chondroitin sulfate β-1,4-N-acetylgalactosaminyltransferase-1 (ChGn-1) polymorphism: Association with progression of multiple sclerosis., Saigoh K, Yoshimura S, Izumikawa T, Miyata S, Tabara Y, Matsushita T, Miki T, Miyamoto K, Hirano M, Kitagawa H, Kira JI, Kusunoki S, Neuroscience research, 108, 55, 59,   2016年01月, 査読有り
  • Analyses of the VCP gene in Japanese patients with sporadic amyotrophic lateral sclerosis identify the novel mutation that increases susceptibility to oxidative stress., Makito Hirano, Yusaku Nakamura, Kazumasa Saigoh, , Hikaru Sakamoto, Shuichi Ueno, Chiharu Isono, Susumu Kusunoki, Ann Neurol, 78, S, 103, 104,   2015年10月, 査読有り
  • Rotigotine Transdermal Patch Improves Swallowing in Dysphagic Patients with Parkinson's Disease., Hirano M, Isono C, Sakamoto H, Ueno S, Kusunoki S, Nakamura Y, Dysphagia, 30, 4, 452, 456,   2015年08月, 査読有り
  • VCP gene analyses in Japanese patients with sporadic amyotrophic lateral sclerosis identify a new mutation., Hirano M, Nakamura Y, Saigoh K, Sakamoto H, Ueno S, Isono C, Mitsui Y, Kusunoki S, Neurobiology of aging, 36, 3, 1604.e1, 6,   2015年03月, 査読有り
  • The first Japanese familial case of spinocerebellar ataxia 23 with a novel mutation in the PDYN gene., Saigoh K, Mitsui J, Hirano M, Shioyama M, Samukawa M, Ichikawa Y, Goto J, Tsuji S, Kusunoki S, Parkinsonism & related disorders, 21, 3, 332, 334,   2015年03月, 査読有り
  • Binding specificity of anti-HNK-1 IgM M-protein in anti-MAG neuropathy: possible clinical relevance., Hamada Y, Hirano M, Kuwahara M, Samukawa M, Takada K, Morise J, Yabuno K, Oka S, Kusunoki S, Neuroscience research, 91, 63, 68,   2015年02月, 査読有り
  • The First Nationwide Survey and Genetic Analyses of Bardet-Biedl Syndrome in Japan., Hirano M, Satake W, Ihara K, Tsuge I, Kondo S, Saida K, Betsui H, Okubo K, Sakamoto H, Ueno S, Ikuno Y, Ishihara R, Iwahashi H, Ohishi M, Mano T, Yamashita T, Suzuki Y, Nakamura Y, Kusunoki S, Toda T, PloS one, 10, 9, e0136317,   2015年, 査読有り
  • Differential Progression of Dysphagia in Heredity and Sporadic Ataxias Involving Multiple Systems., Isono C, Hirano M, Sakamoto H, Ueno S, Kusunoki S, Nakamura Y, European neurology, 74, 5-6, 237, 242,   2015年, 査読有り
  • A case of Bardet-Biedl syndrome complicated with intracranial hypertension in a Japanese child., Saida K, Inaba Y, Hirano M, Satake W, Toda T, Suzuki Y, Sudo A, Noda S, Hidaka Y, Hirabayashi K, Imai H, Kurokawa T, Koike K, Brain & development, 36, 8, 721, 724,   2014年09月, 査読有り
  • Multiple system involvement in a Japanese patient with a V31A mutation in the SOD1 gene., Sakamoto H, Akamatsu M, Hirano M, Saigoh K, Ueno S, Isono C, Kusunoki S, Nakamura Y, Amyotrophic lateral sclerosis & frontotemporal degeneration, 15, 3-4, 312, 314,   2014年06月, 査読有り
  • Eyelid tremor in a patient with anti-caspr2 antibody-related encephalitis., Ueno S, Hirano M, Sakamoto H, Kusunoki S, Nakamura Y, Case reports in neurology, 6, 2, 222, 225,   2014年05月, 査読有り
  • A case of anti-N-methyl-d-aspartate receptor encephalitis with multiple sclerosis-like demyelinated lesions., Takeda A, Shimada H, Tamura A, Yasui M, Yamamoto K, Itoh K, Ataka S, Tanaka S, Ohsawa M, Hatsuta H, Hirano M, Sakamoto H, Ueno S, Nakamura Y, Tsutada T, Miki T, Multiple sclerosis and related disorders, 3, 3, 391, 397,   2014年05月, 査読有り
  • Overlapping demyelinating syndromes and anti–N-methyl-D-aspartate receptor encephalitis., Titulaer MJ, Höftberger R, Iizuka T, Leypoldt F, McCracken L, Cellucci T, Benson LA, Shu H, Irioka T, Hirano M, Singh G, Cobo Calvo A, Kaida K, Morales PS, Wirtz PW, Yamamoto T, Reindl M, Rosenfeld MR, Graus F, Saiz A, Dalmau J, Annals of neurology, 75, 3, 411, 428,   2014年03月, 査読有り
  • Clinical features in Guillain-Barré syndrome with anti-Gal-C antibody., Samukawa M, Hamada Y, Kuwahara M, Takada K, Hirano M, Mitsui Y, Sonoo M, Kusunoki S, Japanese GBS Study Group, Journal of the neurological sciences, 337, 1-2, 55, 60,   2014年02月, 査読有り
  • Ophthalmologic involvement in Japanese siblings with chorea-acanthocytosis caused by a novel chorein mutation., Ogawa I, Saigoh K, Hirano M, Mtsui Y, Sugioka K, Takahashi J, Shimomura Y, Tani Y, Nakamura Y, Kusunoki S, Parkinsonism & related disorders, 19, 10, 913, 915,   2013年10月, 査読有り
  • Differences in dysphagia between spinocerebellar ataxia type 3 and type 6., Isono C, Hirano M, Sakamoto H, Ueno S, Kusunoki S, Nakamura Y, Dysphagia, 28, 3, 413, 418,   2013年09月, 査読有り
  • Triple A syndrome in Japan., Ikeda M, Hirano M, Shinoda K, Katsumata N, Furutama D, Nakamura K, Ikeda S, Tanaka T, Hanafusa T, Kitajima H, Kohno H, Nakagawa M, Nakamura Y, Ueno S, Muscle & nerve, 48, 3, 381, 386,   2013年09月, 査読有り
  • Mutations in the gene encoding p62 in Japanese patients with amyotrophic lateral sclerosis., Hirano M, Nakamura Y, Saigoh K, Sakamoto H, Ueno S, Isono C, Miyamoto K, Akamatsu M, Mitsui Y, Kusunoki S, Neurology, 80, 5, 458, 463,   2013年01月, 査読有り
  • Details of treatment-related difficulties in men with anti-N-methyl-D-aspartate receptor encephalitis., Sakamoto H, Hirano M, Samukawa M, Ueno S, Maekura S, Fujimura H, Kuwahara M, Hamada Y, Isono C, Tanaka K, Kusunoki S, Nakamura Y, European neurology, 69, 1, 21, 26,   2013年, 査読有り
  • A case of severe ganciclovir-induced encephalopathy., Sakamoto H, Hirano M, Nose K, Ueno S, Oki T, Sugimoto K, Nishioka T, Kusunoki S, Nakamura Y, Case reports in neurology, 5, 3, 183, 186,   2013年, 査読有り
  • Refractory acute disseminated encephalomyelitis with anti-galactocerebroside antibody., Samukawa M, Hirano M, Tsugawa J, Sakamoto H, Tabata E, Takada K, Kuwahara M, Suzuki S, Kitada M, Yamada T, Hara H, Tsuboi Y, Nakamura Y, Kusunoki S, Neuroscience research, 74, 3-4, 284, 289,   2012年12月, 査読有り
  • Risks of inappropriate secretion of antidiuretic hormone in multiple system atrophy., Samukawa M, Hirano M, Sakamoto H, Kitada M, Kusunoki S, Nakamura Y, Movement disorders : official journal of the Movement Disorder Society, 26, 14, 2572, 2573,   2011年12月, 査読有り
  • A case of chemotherapy-responsive paraneoplastic rubral tremor., Kiriyama T, Hirano M, Kitauchi T, Saito K, Kataoka H, Ueno S, Clinical neurology and neurosurgery, 113, 8, 693, 695,   2011年10月, 査読有り
  • A novel mutation in the calcium channel gene in a family with hypokalemic periodic paralysis., Hirano M, Kokunai Y, Nagai A, Nakamura Y, Saigoh K, Kusunoki S, Takahashi MP, Journal of the neurological sciences, 309, 1-2, 9, 11,   2011年10月, 査読有り
  • Proteasome assembly defect due to a proteasome subunit beta type 8 (PSMB8) mutation causes the autoinflammatory disorder, Nakajo-Nishimura syndrome., Arima K, Kinoshita A, Mishima H, Kanazawa N, Kaneko T, Mizushima T, Ichinose K, Nakamura H, Tsujino A, Kawakami A, Matsunaka M, Kasagi S, Kawano S, Kumagai S, Ohmura K, Mimori T, Hirano M, Ueno S, Tanaka K, Tanaka M, Toyoshima I, Sugino H, Yamakawa A, Tanaka K, Niikawa N, Furukawa F, Murata S, Eguchi K, Ida H, Yoshiura K, Proceedings of the National Academy of Sciences of the United States of America, 108, 36, 14914, 14919,   2011年09月, 査読有り
  • Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia., Deng HX, Chen W, Hong ST, Boycott KM, Gorrie GH, Siddique N, Yang Y, Fecto F, Shi Y, Zhai H, Jiang H, Hirano M, Rampersaud E, Jansen GH, Donkervoort S, Bigio EH, Brooks BR, Ajroud K, Sufit RL, Haines JL, Mugnaini E, Pericak-Vance MA, Siddique T, Nature, 477, 7363, 211, 215,   2011年08月, 査読有り
  • Serial neuroimaging in tolosa-hunt syndrome with acute bilateral complete ophthalmoplegia., Sugie K, Morikawa M, Taoka T, Hirano M, Ueno S, Journal of neuroimaging : official journal of the American Society of Neuroimaging, 21, 1, 79, 82,   2011年01月, 査読有り
  • Abnormal cystatin C levels in two patients with bardet-biedl syndrome., Hirano M, Ohishi M, Yamashita T, Ikuno Y, Iwahashi H, Mano T, Ishihara R, Tanaka I, Yanagihara K, Isono C, Sakamoto H, Nakamura Y, Kusunoki S, Clinical medicine insights. Case reports, 4, 17, 20,   2011年, 査読有り
  • Artery-to-artery embolism with a mobile mural thrombus due to rotational vertebral artery occlusion., Saito K, Hirano M, Taoka T, Nakagawa H, Kitauchi T, Tanizawa E, Yoshida K, Sakurai Y, Tamura K, Nakase H, Yoshioka A, Sakaki T, Kichikawa K, Ueno S, Journal of neuroimaging : official journal of the American Society of Neuroimaging, 20, 3, 284, 286,   2010年07月, 査読有り
  • Naturally- and experimentally-designed restorations of the Parkin gene deficit in autosomal recessive juvenile parkinsonism., Asai H, Hirano M, Kiriyama T, Ikeda M, Ueno S, Biochemical and biophysical research communications, 391, 1, 800, 805,   2010年01月, 査読有り
  • Juvenile Bow Hunter's Stroke without Hemodynamic Changes., Saito K, Hirano M, Taoka T, Nakagawa H, Kitauchi T, Ikeda M, Tanizawa E, Kichikawa K, Ueno S, Clinical medicine insights. Case reports, 3, 1, 4,   2010年, 査読有り
  • Protein kinase C gamma, a protein causative for dominant ataxia, negatively regulates nuclear import of recessive-ataxia-related aprataxin., Asai H, Hirano M, Shimada K, Kiriyama T, Furiya Y, Ikeda M, Iwamoto T, Mori T, Nishinaka K, Konishi N, Udaka F, Ueno S, Human molecular genetics, 18, 19, 3533, 3543,   2009年10月, 査読有り
  • Cerebrospinal fluid-orexin levels and sleep attacks in four patients with Parkinson's disease., Asai H, Hirano M, Furiya Y, Udaka F, Morikawa M, Kanbayashi T, Shimizu T, Ueno S, Clinical neurology and neurosurgery, 111, 4, 341, 344,   2009年05月, 査読有り
  • Treatable fluctuating mental impairment in a patient with Bardet-Biedl syndrome., Tonomura Y, Hirano M, Shimada K, Asai H, Ikeda M, Kataoka H, Tanaka I, Konishi N, Ueno S, Clinical neurology and neurosurgery, 111, 1, 102, 104,   2009年01月, 査読有り
  • Peripheral neuropathy in chromosome16q22.1 linked autosomal dominant cerebellar ataxia., Furiya Y, Hirano M, Nomura M, Asai H, Kiriyama T, Ueno S, BMJ case reports, 2009,   2009年, 査読有り
  • Subthalamic nucleus stimulation in Parkinson's disease is associated with a risk of fixed epiglottis., Kataoka H, Yanase M, Kawahara M, Hirabayashi H, Yamanaka T, Hirano M, Ueno S, BMJ case reports, 2009,   2009年, 査読有り
  • Acute autonomic, sensory and motor neuropathy associated with meningoencephalitis., Kinoshita S, Sugie K, Kataoka H, Sugie M, Hirano M, Ueno S, Clinical medicine. Case reports, 2, 17, 20,   2009年, 査読有り
  • Asymmetrical weakness associated with central nervous system involvement in a patient with guillain-barrè syndrome., Kiriyama T, Hirano M, Kusunoki S, Morita D, Hirakawa M, Tonomura Y, Kitauchi T, Ueno S, Clinical medicine. Case reports, 2, 51, 54,   2009年, 査読有り
  • Cerebral infarction associated with heparin-induced thrombocytopenia in a patient with encephalitis., Saito K, Hirano M, Kajitani M, Taoka T, Kichikawa K, Ueno S, Internal medicine (Tokyo, Japan), 48, 1, 71, 74,   2009年, 査読有り
  • Comparative study of nucleotide excision repair defects between XPD-mutated fibroblasts derived from trichothiodystrophy and xeroderma pigmentosum patients., Nishiwaki T, Kobayashi N, Iwamoto T, Yamamoto A, Sugiura S, Liu YC, Sarasin A, Okahashi Y, Hirano M, Ueno S, Mori T, DNA repair, 7, 12, 1990, 1998,   2008年12月, 査読有り
  • Complete recovery of an aged patient with Guillain-Barré syndrome associated with multiple IgM anti-ganglioside antibodies., Furiya Y, Hirano M, Kusunoki S, Ueda M, Sugie K, Nishiwaki T, Ueno S, Muscle & nerve, 38, 6, 1630, 1633,   2008年12月, 査読有り
  • Restoration of nuclear-import failure caused by triple A syndrome and oxidative stress., Kiriyama T, Hirano M, Asai H, Ikeda M, Furiya Y, Ueno S, Biochemical and biophysical research communications, 374, 4, 631, 634,   2008年10月, 査読有り
  • Molecular dissection of ALS-associated toxicity of SOD1 in transgenic mice using an exon-fusion approach., Deng HX, Jiang H, Fu R, Zhai H, Shi Y, Liu E, Hirano M, Dal Canto MC, Siddique T, Human molecular genetics, 17, 15, 2310, 2319,   2008年08月, 査読有り
  • Odor abnormalities caused by bilateral thalamic infarction., Asai H, Udaka F, Hirano M, Ueno S, Clinical neurology and neurosurgery, 110, 5, 500, 501,   2008年05月, 査読有り
  • Peripheral neuropathy in chromosome16q22.1 linked autosomal dominant cerebellar ataxia., Furiya Y, Hirano M, Nomura M, Asai H, Kiriyama T, Ueno S, Journal of neurology, neurosurgery, and psychiatry, 78, 9, 1009, 1011,   2007年09月, 査読有り
  • Diffusivity and diffusion anisotropy of cerebellar peduncles in cases of spinocerebellar degenerative disease., Taoka T, Kin T, Nakagawa H, Hirano M, Sakamoto M, Wada T, Takayama K, Wuttikul C, Iwasaki S, Ueno S, Kichikawa K, NeuroImage, 37, 2, 387, 393,   2007年08月, 査読有り
  • SPECT revealed cortical dysfunction in a patient who had genetically definite megalencephalic leukoencephalopathy with subcortical cysts., Kiriyama T, Tanizawa E, Hirano M, Shinkai T, Asai H, Furiya Y, Ueno S, Clinical neurology and neurosurgery, 109, 6, 526, 530,   2007年07月, 査読有り
  • Short half-lives of ataxia-associated aprataxin proteins in neuronal cells., Hirano M, Asai H, Kiriyama T, Furiya Y, Iwamoto T, Nishiwaki T, Yamamoto A, Mori T, Ueno S, Neuroscience letters, 419, 2, 184, 187,   2007年05月, 査読有り
  • Interferon causes no myasthenia in a seropositive patient with multiple sclerosis., Shimizu H, Kataoka H, Kawahara M, Hirano M, Furiya Y, Ueno S, Clinical neurology and neurosurgery, 109, 3, 277, 278,   2007年04月, 査読有り
  • Sympathetic disturbances increase risk of sudden cardiac arrest in sporadic ALS., Asai H, Hirano M, Udaka F, Shimada K, Oda M, Kubori T, Nishinaka K, Tsujimura T, Izumi Y, Konishi N, Matsumoto S, Kameyama M, Ueno S, Journal of the neurological sciences, 254, 1-2, 78, 83,   2007年03月, 査読有り
  • DNA single-strand break repair is impaired in aprataxin-related ataxia., Hirano M, Yamamoto A, Mori T, Lan L, Iwamoto TA, Aoki M, Shimada K, Furiya Y, Kariya S, Asai H, Yasui A, Nishiwaki T, Imoto K, Kobayashi N, Kiriyama T, Nagata T, Konishi N, Itoyama Y, Ueno S, Annals of neurology, 61, 2, 162, 174,   2007年02月, 査読有り
  • Treatable fluctuating Parkinsonism and dementia in a patient with a dural arteriovenous fistula., Kajitani M, Yagura H, Kawahara M, Hirano M, Ueno S, Fujimoto K, Sakaki T, Taoka T, Nakagawa H, Kichikawa K, Movement disorders : official journal of the Movement Disorder Society, 22, 3, 437, 439,   2007年02月, 査読有り
  • White matter T2 hyperintensity development and clinical deterioration after status epilepticus in a patient with dentatorubral-pallidoluysian atrophy., Takamure M, Hirano M, Taoka T, Ueno S, Clinical neurology and neurosurgery, 108, 5, 482, 485,   2006年07月, 査読有り
  • A case of post-Japanese encephalitis with partial hypothalamic dysfunction showing repetitive hyperthermia in summertime., Furiya Y, Hirano M, Nakamuro T, Kataoka H, Ueno S, The Journal of infection, 52, 5, e143, 6,   2006年05月, 査読有り
  • ALADINI482S causes selective failure of nuclear protein import and hypersensitivity to oxidative stress in triple A syndrome., Hirano M, Furiya Y, Asai H, Yasui A, Ueno S, Proceedings of the National Academy of Sciences of the United States of America, 103, 7, 2298, 2303,   2006年02月, 査読有り
  • Cytoprotective effect of novel histone deacetylase inhibitors against polyglutamine toxicity., Kariya S, Hirano M, Uesato S, Nagai Y, Nagaoka Y, Furiya Y, Asai H, Fujikake N, Toda T, Ueno S, Neuroscience letters, 392, 3, 213, 215,   2006年01月, 査読有り
  • Humanin expression in skeletal muscles of patients with chronic progressive external ophthalmoplegia., Kin T, Sugie K, Hirano M, Goto Y, Nishino I, Ueno S, Journal of human genetics, 51, 6, 555, 558,   2006年, 査読有り
  • Increased gastric motility during 5-HT4 agonist therapy reduces response fluctuations in Parkinson's disease., Asai H, Udaka F, Hirano M, Minami T, Oda M, Kubori T, Nishinaka K, Kameyama M, Ueno S, Parkinsonism & related disorders, 11, 8, 499, 502,   2005年12月, 査読有り
  • Alpha-1-antichymotrypsin gene polymorphism and susceptibility to multiple system atrophy (MSA)., Furiya Y, Hirano M, Kurumatani N, Nakamuro T, Matsumura R, Futamura N, Ueno S, Brain research. Molecular brain research, 138, 2, 178, 181,   2005年08月, 査読有り
  • Lack of association between polymorphic microsatellites of the VMAT2 gene and Parkinson's disease in Japan., Kariya S, Hirano M, Takahashi N, Furiya Y, Ueno S, Journal of the neurological sciences, 232, 1-2, 91, 94,   2005年05月, 査読有り
  • Effect of humanin on decreased ATP levels of human lymphocytes harboring A3243G mutant mitochondrial DNA., Kariya S, Hirano M, Furiya Y, Ueno S, Neuropeptides, 39, 2, 97, 101,   2005年04月, 査読有り
  • Humanin detected in skeletal muscles of MELAS patients: a possible new therapeutic agent., Kariya S, Hirano M, Furiya Y, Sugie K, Ueno S, Acta neuropathologica, 109, 4, 367, 372,   2005年04月, 査読有り
  • Humanin attenuates apoptosis induced by DRPLA proteins with expanded polyglutamine stretches., Kariya S, Hirano M, Nagai Y, Furiya Y, Fujikake N, Toda T, Ueno S, Journal of molecular neuroscience : MN, 25, 2, 165, 169,   2005年, 査読有り
  • Proton MR spectroscopy of adult-onset dentatorubral-pallidoluysian atrophy., Kin T, Hirano M, Taoka T, Takamure M, Furiya Y, Kichikawa K, Ueno S, Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine, 4, 3, 123, 127,   2005年, 査読有り
  • Increased vulnerability to L-DOPA toxicity in dopaminergic neurons From VMAT2 heterozygote knockout mice., Kariya S, Takahashi N, Hirano M, Ueno S, Journal of molecular neuroscience : MN, 27, 3, 277, 279,   2005年, 査読有り
  • Loss of function mechanism in aprataxin-related early-onset ataxia., Hirano M, Furiya Y, Kariya S, Nishiwaki T, Ueno S, Biochemical and biophysical research communications, 322, 2, 380, 386,   2004年09月, 査読有り
  • Novel splice variants increase molecular diversity of aprataxin, the gene responsible for early-onset ataxia with ocular motor apraxia and hypoalbuminemia., Hirano M, Nishiwaki T, Kariya S, Furiya Y, Kawahara M, Ueno S, Neuroscience letters, 366, 2, 120, 125,   2004年08月, 査読有り
  • Humanin improves impaired metabolic activity and prolongs survival of serum-deprived human lymphocytes., Kariya S, Takahashi N, Hirano M, Ueno S, Molecular and cellular biochemistry, 254, 1-2, 83, 89,   2003年12月, 査読有り
  • Two novel spliced presenilin 2 transcripts in human lymphocyte with oxidant stress and brain., Takahashi N, Kariya S, Hirano M, Ueno S, Molecular and cellular biochemistry, 252, 1-2, 279, 283,   2003年10月, 査読有り
  • A family with Campylobacter enteritis: Anti-GD1a antibody with/without Guillain-Barré syndrome, M. Hirano, S. Kusunoki, H. Asai, Y. Tonomura, D. Morita, Satoshi Ueno, Neurology, 60, 1719, 1720,   2003年05月27日
  • Erratum: The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis (Nature Genetics (2001) 29 (160-165)), Y. Yang, A. Hentati, H. X. Deng, O. Dabbagh, T. Sasaki, M. Hirano, W. Y. Hung, K. Ouahchi, J. Yan, A. C. Azim, N. Cole, G. Gascon, A. Yagmour, M. Ben-Hamida, M. Pericak-Vance, F. Hentati, T. Siddique, Nature Genetics, 29,   2001年12月10日
  • The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis, Yi Yang, Afif Hentati, Han Xiang Deng, Omar Dabbagh, Toru Sasaki, Makito Hirano, Wu Yen Hung, Karim Ouahchi, Jianhua Yan, Anser C. Azim, Natalie Cole, Generoso Gascon, Ayesha Yagmour, Mongi Ben-Hamida, Margaret Pericak-Vance, Fayçal Hentati, Teepu Siddique, Teepu Siddique, Teepu Siddique, Nature Genetics, 29, 160, 165,   2001年10月22日
    概要:Amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) are neurodegenerative conditions that affect large motor neurons of the central nervous system. We have identified a familial juvenile PLS (JPLS) locus overlapping the previously identified ALS2 locus on chromosome 2q33. We report two deletion mutations in a new gene that are found both in individuals with ALS2 and those with JPLS, indicating that these conditions have a common genetic origin. The predicted sequence of the protein (alsin) may indicate a mechanism for motor-neuron degeneration, as it may include several cell-signaling motifs with known functions, including three associated with guanine-nucleotide exchange factors for GTPases (GEFs).
  • Current status of SOD1 mutations in familial amyotrophic lateral sclerosis, Gaudette Mara, Makito Hirano, Teepu Siddique, Teepu Siddique, Amyotrophic Lateral Sclerosis, 1, 83, 89,   2000年12月01日
    概要:Twenty percent of cases of familial amyotrophic lateral sclerosis (FALS) have identifiable mutations in the gene for Cu,Zn superoxide dismutase (SOD1) located on the long arm of chromosome 21. SOD1 mutations are thought to cause a yet unknown toxic gain of function resulting in motor neuron damage. Seventy-one mutations, located in all five exons of SOD1, have been reported. Identified mutations are predominantly heterozygous mis-sense mutations, although rare nonsense mutations, deletions, and insertions exist. While gene dosage has an effect on the age of onset, genotoype/phenotype correlation is better defined for progression of symptoms than for disease onset. (ALS 2000; 1:83-89) © 2000 Informa UK Ltd All rights reserved.
  • Multiple transcripts of the human Cu,Zn superoxide dismutase gene, M. Hirano, W. Y. Hung, N. Cole, A. C. Azim, H. X. Deng, T. Siddique, T. Siddique, T. Siddique, Biochemical and Biophysical Research Communications, 276, 52, 56,   2000年09月16日
    概要:We have identified five alternatively spliced transcripts of the gene for human Cu,Zn superoxide dismutase (SOD1), a causative gene for autosomal dominant amyotrophic lateral sclerosis (ALS). The splice variants of wild-type or mutant SOD1 were expressed in a tissue-specific manner; therefore, their expression may be regulated to modify SOD1 function. In addition, the expression in the brain implies that variants may play a role in the nervous system, the region involved in ALS. Immunoblot study of HeLa cells transfected with two variants encoding C-terminal truncated proteins did not show the proteins of expected size. However, this observation is consistent with the previous study of C-terminal truncated mutant proteins that cause ALS, suggesting that both variant and mutant proteins may share certain properties, such as instability or insolubility in the cytosol. These findings suggest that the splice variants may contribute to a physiological function of SOD1 or to a pathological mechanism in ALS. (C) 2000 Academic Press.
  • Missense mutants inactivate guanosine triphosphate cyclohydrolase I in hereditary progressive dystonia, Satoshi Ueno, Makito Hirano, Brain and Development, 22,   2000年09月01日
    概要:Hereditary progressive dystonia (HPD) with marked diurnal fluctuation is caused by mutant guanosine triphosphate (GTP) cyclohydrolase I (GCH). The clinical presentation of dominant HPD varies considerably. We proposed the hypothesis that a relative increase of mutant GCH capable of inhibiting normal GCH is responsible for heterogeneous phenotypic manifestations. In a Japanese family with a novel G90V mutation, an affected heterozygote had a higher mutant/normal mRNA ratio than an unaffected heterozygote. Co-expression analysis showed that mutant enzyme (GCH-G90V) inactivated the normal enzyme in the COS cells. Similarly, GCH-G203R showed the dominant negative effects. These results supported our proposed hypothesis. Copyright (C) 2000 Elsevier Science B.V.
  • Chronic fentanyl treatments induce the up-regulation of μ opioid receptor mRNA in rat pheochromocytoma cells, Mayumi Yoshikawa, Mayumi Yoshikawa, Hitoshi Nakayama, Satoshi Ueno, Makito Hirano, Hiroshi Hatanaka, Hitoshi Furuya, Brain Research, 859, 217, 223,   2000年03月24日
    概要:Chronic activation of adenylate cyclase-cAMP-cAMP-dependent protein kinase (PKA) systems by administration of opioid receptor agonists has been considered as one of the mechanisms of opioid tolerance and dependence. Although analysis of the μ opioid receptor (MOR) gene suggests that cAMP-related signal transduction systems regulate the expression of this gene, which transcription factors affect the MOR gene expression in brain and neural cells has not been clarified. This study deals with the effects of fentanyl on MOR mRNA levels in the rat pheochromocytoma cell line (PC12 cells). PC12 cells were cultured in medium with clinically relevant concentrations of fentanyl. The quantitative reverse transcription and polymerase chain reaction (RT-PCR) method was used for determination of MOR mRNA. Treatment of PC12 cells with fentanyl induced the MOR mRNA up-regulation in a concentration- and time-dependent manner. A cAMP analogue also up-regulated MOR mRNA. The intracellular cAMP level increased after fentanyl treatment. A PKA inhibitor blocked the MOR mRNA up-regulation by fentanyl and the cAMP analogue. Expression of a dominant inhibitory Ras also inhibited the MOR mRNA up-regulation. Fentanyl-induced up-regulation of MOR mRNA via activation of cAMP signaling may be important in compensating for the MOR reduction during long-term treatment of PC12 cells with fentanyl. The present study could be relevant to understanding the molecular mechanisms of opioids in a state of drug tolerance or dependence, and in patients under anesthesia or being treated for pain. Copyright (C) 2000 Elsevier Science B.V.
  • Current status of SOD1 mutations in familial amyotrophic lateral sclerosis, Mara Gaudette, Makito Hirano, Teepu Siddique, Teepu Siddique, Teepu Siddique, Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders, 1, 83, 89,   2000年03月01日
    概要:Twenty percent of cases of familial amyotrophic lateral sclerosis (FALS) have identifiable mutations in the gene for Cu,Zn superoxide dismutase (SOD1) located on the long arm of chromosome 21. SOD1 mutations are thought to cause a yet unknown toxic gain of function resulting in motor neuron damage. Seventy-one mutations, located in all five exons of SOD1, have been reported. Identified mutations are predominantly heterozygous mis-sense mutations, although rare nonsense mutations, deletions, and insertions exist. While gene dosage has an effect on the age of onset, genotoype/phenotype correlation is better defined for progression of symptoms than for disease onset.
  • Effects of fentanyl on survival of serum-deprived rat pheochromocytoma cells, Mayumi Yoshikawa, Mayumi Yoshikawa, Satoshi Ueno, Makito Hirano, Hitoshi Nakayama, Hitoshi Furuya, Pharmacy and Pharmacology Communications, 5, 603, 607,   1999年11月19日
    概要:The effect of fentanyl, an opioid receptor agonist, on the survival of a rat pheochromocytoma cell line (PC12 cells) after serum deprivation was studied. PCR amplification of reverse-transcribed mRNA demonstrated the μ-opioid receptor transcripts in the PC12 cells. The metabolism of a tetrazolium dye (MTS) assay showed that cell viability was significantly reduced, and agarose electrophoresis of the DNA extracted from the cells resulted in a ladder-like pattern of fragmentation 18 h after serum withdrawal. The incubation with fentanyl prolonged cell survival in a dose-dependent manner. This effect was abolished by naloxone. There was a rapid and transient induction of the c-fos, c-jun and heat shock protein 70 genes, in PC12 cells after serum deprivation, which was not observed in fentanyl-treated PC12 cells.
  • A novel missense mutant inactivates GTP cyclohydrolase I in dopa- responsive dystonia, Makito Hirano, Osamu Komure, Satoshi Ueno, Neuroscience Letters, 260, 181, 184,   1999年02月05日
    概要:Dopa-responsive dystonia (DRD) due to mutant GTP cyclohydrolase I (GCH) shows the considerable heterogeneity of clinical phenotypic expression. To explain the clinical diversity, we studied a Japanese family with a novel mutant GCH (GCH-G90V), where an affected heterozygote had a higher mutant/normal mRNA ratio than an unaffected heterozygote. Coexpression experiments using the mutant with wild-type GCH showed that GCH-G90V inactivated the normal enzyme in a dose-dependent manner, suggesting that the dominant negative effect of a mutant GCH on the normal enzyme might be one of the molecular mechanisms for the clinical heterogeneity of DRD.
  • Mutant GTP cyclohydrolase I in autosomal dominant dystonia and recessive hyperphenylalaninemia, Makito Hirano, Satoshi Ueno, Satoshi Ueno, Neurology, 52, 182, 184,   1999年01月01日
    概要:Guanosine 5'-triphosphate cyclohydrolase I (GCH) mutants (H144P and T186K) associated with dominant dopa-responsive cystonia were enzymatically inactive and inhibited the normal enzyme, suggesting that GCH activity in a heterozygote was <50% of control. The M2311I mutant associated with recessive hyperphenylalaninemia was slightly active and had no inhibitory effects, so GCH activity in a heterozygote would be <50% of normal; therefore hyperphenylalaninemia would be evident only in homozygotes.
  • Dominant negative effect of GTP cyclohydrolase I mutations in dopa- responsive hereditary progressive dystonia, Makito Hirano, Makito Hirano, Makito Hirano, Takehiko Yanagihara, Satoshi Ueno, Satoshi Ueno, Annals of Neurology, 44, 365, 371,   1998年09月01日
    概要:Hereditary progressive dystonia (HPD) is caused by the mutant gene encoding GTP cyclohydrolase I (GCH). The clinical presentation of this disease varies considerably, and many cases appear to be sporadic. We have previously proposed that this clinical variation may be due to differential expression of the mutant and normal GCH mRNA, presumably at the protein level. To provide support for this proposal, we studied a new Japanese family with HPD, in which 2 members were heterozygous for an exon-skipping mutation. This mutation produced truncated GCH, which shared 180-amino acid residues at the amino terminus of the normal enzyme (GCH180). An affected heterozygote had a higher mutant/normal mRNA ratio than an unaffected heterozygote, consistent with our previous finding in the HPD family with GCH114. A further study, using coexpression of the mutant with wild-type GCH in COS-7 cells, showed that three mutant GCHs inactivated the normal enzyme. GCH114 was most effective in enzyme inactivation, which was followed by GCH180 and a normally occurring mutant GCH209. These results suggested that the dominant negative effect of a mutant GCH on the normal enzyme might be one of the molecular mechanisms determining the heterogeneity of clinical phenotypes of HPD.
  • Clinical and molecular genetic study in seven Japanese families with spinocerebellar ataxia type 6, Yoshitaka Nagai, Yoshitaka Nagai, Tsutomu Azuma, Masahiro Funauchi, Masashi Fujita, Masao Umi, Makito Hirano, Tsuyoshi Matsubara, Satoshi Ueno, Journal of the Neurological Sciences, 157, 52, 59,   1998年04月15日
    概要:We report on seven Japanese families with spinocerebellar ataxia type 6 (SCA6) carrying small CAG repeat expansions in the calcium channel α1A subunit gene. The number of the expanded CAG repeat, ranged from 22 to 25, showed no intergenerational instability and had a significant inverse correlation with the age of onset. The clinical features of these patients were late onset progressive pure cerebellar ataxia with dysarthria and nystagmus, and are consistent with autosomal dominant cerebellar ataxia type III (ADCA type III). Magnetic resonance imaging scan of the brain demonstrated cerebellar atrophy with no evidence of brainstem involvement. We propose that clinical phenotype of SCA6 is compatible with ADCA type III and SCA6 is one of the most common types of ADCA in Japan.
  • Clinical similarities of hereditary progressive/dopa responsive dystonia caused by different types of mutations in the GTP cyclohydrolase I gene, Yoshiko Tamaru, Yoshiko Tamaru, Makito Hirano, Makito Hirano, Hidefumi Ito, Junichiro Kawamura, Sadayuki Matsumoto, Terukuni Imai, Satoshi Ueno, Journal of Neurology Neurosurgery and Psychiatry, 64, 469, 473,   1998年04月01日
    概要:Objective - Hereditary progressive dystonia with pronounced diurnal fluctuation ((HPD)/dopa responsive dystonia (DRD)) is a childhood onset dystonia which responds to levodopa. Various clinical signs and symptoms of HPD/DRD have been recognised to date. Mutations in the GTP cyclohydrolase I (GTP-CH-I) gene were recently identified as the cause of HPD/DRD. In the present study, the GTP-CH-I gene and the clinical features of eight HPD/DRD patients from six families were analysed to determine the correlations between clinical expression and the mutations in the GTP-CH-I gene. Methods - The exons, exon-intron junctions, and an indispensable part of the 5' flanking region of the GTP-CH-I gene were sequenced in the eight clinically diagnosed patients with HPD/DRD and their asymptomatic parents. Results - Three independent mutations in the GTP-CH-I gene were found in three patients. One of the patients and her asymptomatic mother were heterozygous for a novel mutation at the initiation codon. The three patients with dissimilar GTP-CH-I mutations exhibited similar clinical features. The other five patients with normal sequences presented several features not manifested by the three patients with the mutations. No mutation was found in the 5' flanking region of any patients or their parents. Conclusions - A novel initiation codon mutation was found in a Japanese patient with HPD/DRD. The clinical manifestations common to the patients with HPD/DRD with a mutated GTP-CH-I gene were also identified. Although focal manifestations of HPD/DRD associated with the mutations of this gene will be broadened, it is inferred that these clinical features are fundamental to HPD/DRD caused by mutations in this gene.
  • A novel mutation of the GTP-cyclohydrolase I gene in a patient with hereditary progressive dystonia/dopa-responsive dystonia, Y. Imaiso, Y. Imaiso, T. Taniwaki, T. Yamada, T. Yoshimura, M. Hirano, S. Ueno, N. Kaneda, J. Kira, Neurology, 50, 517, 519,   1998年02月01日
    概要:We report a 37-year-old Japanese woman with hereditary progressive dystonia with marked diurnal fluctuation and dopa-responsive dystonia. She developed dystonia in the lower limbs at the age 11 years, followed by spasmodic torticollis and resting tremor of the feet, which responded remarkably to low doses of levodopa (100 mg/day). Concentrations of biopterin and neopterin in CSF were decreased. Polymerase chain reaction analysis of the guanosine 5'-triphosphate cyclohydrolase I gene revealed a novel mutation.
  • α-Tocopherol transfer protein gene: Exon skipping of all transcripts causes ataxia, Y. Tamaru, Y. Tamaru, M. Hirano, M. Hirano, H. Kusaka, H. Ito, T. Imai, S. Ueno, S. Ueno, Neurology, 49, 584, 588,   1997年08月01日
    概要:This report concerns the characterization of the α-tocopherol transfer protein (α-TTP) gene in a Japanese family affected by ataxia with isolated vitamin E deficiency (AVED). The sequence analysis revealed a G-to-A transition at the 3' end of exon 3 in both alleles, which predicts outsplicing of this exon from premessenger RNA and the concomitant frame shift in the ataxic patient. We used reverse transcriptase-polymerase chain reaction to analyze α-TTP gene transcripts. All transcripts in peripheral blood lymphocytes of the AVED patient, who was treated with large doses of vitamin E, lacked exon 3. The deduced truncated protein shares only 43% of the normal α-TTP. Normal control tissues and cells contained normal transcripts and, unexpectedly, also the same mutant transcripts as those of the patient, although with different transcription levels. Treatment of normal fibroblasts with clinically relevant concentrations of vitamin E increased production of transcripts in a dose-dependent manner. We propose that exon skipping of all transcripts through the complete inactivation of the splice site accounts for the clinical onset of AVED and for the clinical resistance to vitamin E in our patient.
  • Differential splicing of the GTP cyclohydrolase I RNA in dopa-responsive dystonia, Makito Hirano, Makito Hirano, Yasuyuki Imaiso, Satoshi Ueno, Biochemical and Biophysical Research Communications, 234, 316, 319,   1997年05月19日
    概要:We characterized the GTP cyclohydrolase I (GTP-CH-I) gene in a patient with hereditary progressive dystonia with marked diurnal fluctuation/dopa-responsive dystonia (HPD/DRD). The sequence analysis revealed a C to A transversion, which predicts a novel missense mutation (Thr186Lys). Unexpectedly, this base change, occurring in the middle of exon 5, resulted in a production of the novel transcript lacking exon 5 and a part of exon 6. Three different transcripts of the GTP-CH-I gene, previously reported in the human liver, were also present in the peripheral lymphocytes from the patient and controls. Quantitative comparison of the truncated-subunit mRNA and the wild-type one implied that differential splicing regulates the GTP-CH-I enzyme activity, leading to the clinical variations in HPD/DRD. The patient showed a unique clinical symptom, suggesting that the nigrostriatal dopaminergic system is more affected than previously thought in HPD/DRD.
  • Hereditary progressive dystonia with marked diurnal fluctuation--clinical features and GTP cyclohydrolase I gene mutations, Y. Tamaru, H. Ito, T. Imai, M. Hirano, S. Ueno, Nippon rinsho. Japanese journal of clinical medicine, 55, 135, 138,   1997年01月01日
    概要:Hereditary progressive dystonia with marked diurnal fluctuation (HPD) is a disorder characterized by childhood-onset dystonia and a dramatic and sustained response to low doses of levodopa. Recently the GTP cyclohydrolase I(GCH-I) gene was isolated as the first causative gene for HPD. We analyzed the GCH-I gene in 8 clinically diagnosed HPD patients and found different point mutations in GCH-I gene in 3 subjects. The clinical features of these patients considerably resembled each other. Our results imply that although clinically diagnosed HPD subjects could present diverse symptoms, patients with a mutant GCH-I gene might share homogeneous clinical manifestations.
  • α-Tocopherol Transfer Protein Gene: Exon Skipping of All Transcripts Causes Ataxia. Tmaru, Y.,Hrano, M., Kusaka, H., Ito, H., Imai, T., Ueno, S., Neurology, 49, 584-588,   1997年
  • Molecular cloning and expression of a novel peptide (LN1) gene: Reduced expression in the renal cortex of lupus nephritis in MRL/lpr mouse, Masayuki Iwano, Satoshi Ueno, Masanobu Miyazaki, Takashi Harada, Yoshitaka Nagai, Makito Hirano, Yoshiko Dohi, Yasuhiro Akai, Hideyuki Kurioka, Kazuhiro Dohi, Biochemical and Biophysical Research Communications, 229, 355, 360,   1996年12月04日
    概要:A gene has been identified by mRNA differential display whose expression is reduced in the renal cortex of MRL/lpr mouse, The nucleotide sequence of the cDNA contains an open reading frame that encodes a protein of 338 amino acids (termed LN1). In situ hybridization showed that LN1 mRNA is present in glomeruli, and a 39 kDa protein was detected in the kidney by immunoblot. A human LN1 cDNA was also isolated, the deduced amino acid sequence of which is 78% identical to that of mouse LN1. Although the function of LN1 remains to be elucidated, its reduced expression may contribute to the pathogenesis Of lupus nephritis.
  • Relationship of (CAG)nC configuration to repeat instability of the Machado-Joseph disease gene, Ryusuke Matsumura, Tetsuya Takayanagi, Kayoko Murata, Naonobu Futamura, Makito Hirano, Satoshi Ueno, Human Genetics, 98, 643, 645,   1996年12月01日
    概要:The mutation responsible for Machado-Joseph disease (MJD) has been identified as an expansion of a CAG trinucleotide repeat in a novel gene on chromosome 14q32.1. The CAG repeat tract is followed by C or G, and alleles are thereby divided into two types on the basis of molecular configuration, (CAG)nC and (CAG)nG. We have studied the relationship between the repeat length and the configuration in 38 patients from 28 Japanese families with MJD, and 31 unrelated normal Japanese subjects. The CAG repeat length in 100 normal alleles ranged from 13 to 37 repeats, while 38 MJD patients had one expanded allele with 64 to 84 repeats. Surprisingly, the expanded alleles had exclusively the (CAG)nC configuration, while both (CAG)nC and (CAG)nG were seen in normal alleles from MJD and control subjects. Furthermore, in normal alleles, the CAG repeat tract was significantly longer in (CAG)nC than in (CAG)nG. These findings suggest that the (CAG)nC configuration is related to repeat instability of the MJD gene.
  • Mutant GTP cyclohydrolase I mRNA levels contribute to dopa-responsive dystonia onset, Makito Hirano, Makito Hirano, Yoshiko Tamaru, Yoshiko Tamaru, Hidefumi Ito, Sadayuki Matsumoto, Terukuni Imai, Satoshi Ueno, Satoshi Ueno, Annals of Neurology, 40, 796, 798,   1996年11月01日
    概要:We present a new Japanese family with hereditary progressive dystonia with marked diurnal fluctuation/doparesponsive dystonia. The affected daughter and her asymptomatic father are heterozygous for a novel missense mutation that replaces His by Pro at codon 144 in the GTP cyclohydrolase I gene. Quantitative reverse transcription-polymerase chain reaction revealed a higher ratio of mutant/normal mRNA encoding GTP cyclohydrolase I in the patient. These results demonstrate the importance of mutant mRNA levels for phenotypic variability among cases with the same mutation.
  • Decrease of the D3 dopamine receptor mRNA expression in lymphocytes from patients with Parkinson's disease, Y. Nagai, Y. Nagai, S. Ueno, S. Ueno, Y. Saeki, F. Soga, M. Hirano, T. Yanagihara, Neurology, 46, 791, 795,   1996年03月01日
    概要:We investigated the dopamine receptor (DAR) mRNA expression in peripheral blood lymphocytes from 45 patients with Parkinson's disease (PD) and 21 age- matched controls using the quantitative reverse transcription and polymerase chain reaction method. β-actin mRNA was used as an internal control to evaluate the relative expression level of the DAR mRNA. There was a statistically significant decrease of the D3 dopamine receptor (D3R) mRNA expression in PD patients compared with that in controls. There was no change in expression of the D5 dopamine receptor mRNA in PD patients. A further binding study showed reduction of the D3R binding sites in PD lymphocytes. The decrease of the D3R mRNA expression correlated with the degree of clinical severity in PD patients.
  • Japanese triplets with cerebrotendinous xanthomatosis are homozygous for a mutant gene coding for the sterol 27-hydroxylase (Arg441Trp), Y. Nagai, Y. Nagai, M. Hirano, M. Hirano, T. Mori, Y. Takakura, S. Tamai, S. Ueno, S. Ueno, Neurology, 46, 571, 574,   1996年01月01日
    概要:We present the first case of triplets with cerebrotendinous xanthomatosis (CTX). A C-to-T base change identified in the genomic DNA and cDNA encoding the sterol 27-hydroxylase led to replacement of arginine by tryptophan at position 441 (Arg441Trp) in the triplets. The triplets were homozygous and their mother was heterozygous for this mutant gene. The triplets exhibited an identical phenotypic expression, which was different from that of a sporadic CTX case with the same mutation.
  • A case of carpal tunnel syndrome caused by a ganglion cyst. Diagnosis and follow-up study with magnetic resonance imaging, M. Hirano, K. Kuroda, M. Kunimoto, K. Tanohata, K. Inoue, Clinical Neurology, 35, 80, 82,   1995年01月01日
    概要:We report a case of carpal tunnel syndrome (CTS) caused by a ganglion cyst which was diagnosed by magnetic resonance (MR) imaging of the left wrist. MR images depicted a 10-mm ganglion cyst which pressed the median nerve toward the ulnar side. The ganglion cyst was punctured under direct endoscopic visualization in the carpal canal, subsequently the clinical and the electrophysiologic findings of CTS improved. The median nerve was delineated in its proper position. MR imaging of the wrist, a noninvasive means to observe median nerve, is useful for the diagnosis and the follow-up study of CTS.
  • Exon skipping caused by a base substitution at a splice site in the GTP cyclohydrolase I gene in a Japanese family with hereditary progressive dystonia/dopa responsive dystonia, M. Hirano, Y. Tamaru, Y. Nagai, H. Ito, T. Imai, S. Ueno, Biochemical and Biophysical Research Communications, 213, 645, 651,   1995年01月01日
    概要:We report a novel mutation at a splice site in the GTP cyclohydrolase I gene in a Japanese family with hereditary progressive dystonia with marked diurnal fluctuation (HPD)/dopa responsive dystonia (DRD). Reverse transcriptase-initiated PCR (RT-PCR) of lymphocyte mRNA showed both normal and small size fragments in the HPD patient and his asymptomatic mother. Sequence analysis revealed that skip splicing of exon 1 to exon 3 occurred in the small fragment. The patient and his mother were heterozygous for G→C substitution at conserved consensus sequence GT at 5' end of the intron 2. Quantitative RT-PCR showed that the expression of normal GTP cyclohydrolase I mRNA decreased in their lymphocytes, while the HPD patient had more expression of mutant GTP cyclohydrolase I mRNA than his asymptomatic mother.
  • A new variant Cu/Zn superoxide dismutase (Val7→Glu) deduced from lymphocyte mRNA sequences from Japanese patients with familial amyotrophic lateral sclerosis, M. Hirano, J. Fujii, Y. Nagai, M. Sonobe, K. Okamoto, H. Araki, N. Taniguchi, S. Ueno, Biochemical and Biophysical Research Communications, 204, 572, 577,   1994年01月01日
    概要:We have identified a new mutant Cu/Zn superoxide dismutase (SOD1) deduced from the nucleotide sequences of peripheral blood lymphocyte mRNA from Japanese patients with familial amyotrophic lateral sclerosis (FALS). Sequence analysis of reverse transcriptase-initiated PCR amplified mRNA revealed a heterozygosity indicative of one normal allele and one variant allele with a T→A transversion. This base change led to replacement of valine by glutamic acid at position 7 of 153-residue SOD1 molecule, and produced a new restriction site for Alu I in the exon I. Restriction fragment length polymorphism analysis confirmed the linkage of this mutation with this type of FALS. Both enzymatic activity and protein of the SOD1 were reduced in red blood cells from the patient.

書籍等出版物

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  • カラー版 内科学, 平野 牧人, 分担執筆, 末梢神経障害, 西村書店,   2012年08月

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  • COQ2遺伝子異常を有する多系統萎縮症の5症例, 平野 牧人, 阪本 光, 上野 周一, 西郷 和真, 楠 進, 中村 雄作, 臨床神経学,   2015年08月
  • Effect of combination of botulinum toxin treatment and rehabilitation in chronic stroke patients with functional MRI study., S Ueno, H Sakamoto, M Hirano, Y Nakamura, The 9th ICME International Conference,   2015年06月20日
  • 孤発性筋萎縮性側索硬化症の遺伝子解析による新規変異同定とカウンセリングの問題点, 平野牧人, 平野牧人, 中村雄作, 西郷和真, 阪本光, 上野周一, 上野周一, 鈴木秀和, 楠進, 第60回日本人類遺伝学会,   2015年10月17日

MISC

  • Fabry病における疼痛の実態と対策, 平野牧人, 平野牧人, 西郷和真, 中村雄作, 楠進, 日本末梢神経学会学術集会プログラム・抄録, 27th, 94,   2016年07月27日, http://jglobal.jst.go.jp/public/201602249939992460
  • 【筋萎縮性側索硬化症(ALS)の分子遺伝学update】 ALSとSQSTM1, 平野 牧人, 神経内科, 82, 4, 360, 365,   2015年04月
  • 頭部振戦と頭部MRIにて十字サインとを認めたSCA23の1家系, 西郷和真, 西郷和真, 三井純, 平野牧人, 塩山実章, 寒川真, 市川弥生子, 後藤順, 辻省次, 巽純子, 田村和朗, 楠進, 日本人類遺伝学会大会プログラム・抄録集, 60th, 262,   2015年, http://jglobal.jst.go.jp/detail.php?from=API&JGLOBAL_ID=201602213297286545
  • 多系統萎縮症および常染色体優性遺伝性脊髄小脳変性症におけるCOQ2遺伝子解析, 平野 牧人, 中村 雄作, 阪本 光, 上野 周一, 三井 良之, 西郷 和真, 楠 進, 臨床神経学, 54, Suppl., S47, S47,   2014年12月
  • 多系統の障害をきたしたSOD1変異例, 阪本 光, 平野 牧人, 上野 周一, 赤松 舞子, 中村 雄作, 楠 進, 臨床神経学, 54, Suppl., S149, S149,   2014年12月
  • 小児用注意障害評価プログラム「もぐらーず」を用いた成人の注意機能評価 健常成人における加齢の影響, 磯野 千春, 平野 牧人, 阪本 光, 上野 周一, 楠 進, 中村 雄作, 神経治療学, 31, 6, 713, 717,   2014年11月
    概要:注意欠陥多動性障害(attention deficit/hyperactivity disorder:ADHD)に対する補助診断として開発されたプログラムソフト「もぐらーず」を認知機能障害のスクリーニング検査として応用することを目的とし、小児用提示条件および難度を上げた成人用提示条件を検討した。また注意機能検査であるtrail making test(TMT、TMT-AとTMT-B)と比較検討した。その結果、成人用条件でのみ対象者の年齢と正答率とが負の相関を、見逃し率とは正の相関を認めた。またTMT-Bは正答率のばらつき、見逃し率と正の相関を認めた。ΔTMT(TMT-BとTMT-Aの差)は正答率と負の相関を、正答率のばらつきと見逃し率は正の相関を認めた。成人用条件下で、「もぐらーず」は注意維持や視覚探索、遂行機能を評価でき、認知機能の評価に有用であることが示された。(著者抄録)
  • 外来看護師によるapomorphine自己注射指導, 橘 紅丹子, 山本 亮子, 上野 周一, 阪本 光, 平野 牧人, 中村 雄作, 神経治療学, 31, 5, 642, 642,   2014年09月

受賞

  •   2016年, 近畿大学医学会, 近畿大学医学会賞

競争的資金

  • 日本ALS協会, ALS基金研究奨励金, ALS患者iPS細胞由来神経細胞に対するオートファジー促進薬や抗酸化薬による治療研究, 平野 牧人
  • 文部科学省, 科学研究費補助金(基盤研究(C)), 神経変性疾患の新規原因蛋白p62とユビキリン2の関連と治療的蛋白分解亢進, 平野 牧人, 1.患者iPS細胞の確立と神経への分化誘導すでに、予備実験で一部患者由来iPS細胞を確立していたが、本研究では、種々の異なる原因で生じる孤発性のALSや認知症も対象としており、できるだけ多くの患者のiPS細胞を樹立し、数種のiPS細胞で確認された知見を他の患者で確認する作業が必要である。このため、引き続き患者由来の線維芽細胞をiPS細胞に誘導し、新たに2例のiPS細胞を確立した。ALS患者から確立したiPS細胞を神経幹細胞さらに神経細胞へ分化誘導を行った。患者細胞では、神経突起伸展が阻害されていることが想定されていたが、実際には、明らかな伸展阻害は見られなかった。しかし、細胞内に凝集体が形成されていることが観察された。2.iPSから神経誘導におけるubiquilin2, p62の発現様式まず、基礎的情報収集のため行ったubiquilin2やp62発現に関して確認したが、iPS細胞においても、これら蛋白やそのmRNAは発現していることが証明された。また、凝集体はALS患者細胞でのみ観察された。
  • 文部科学省, 科学研究費補助金(若手研究(B)), 遺伝性小脳失調原因遺伝子アプラタキシンの野生型及びスプライス変異型蛋白の機能解析, 平野 牧人, 眼球運動失行と低アルブミン血症を伴う早発型小脳失調症(EAOH)は本邦では最も多い常染色体劣性小脳失調症である。原因遺伝子アプラタキシンには既報告の1種に加え、新たに6種のスプライス変異体が存在することが本研究の予備実験により明らかされた。野生型を含む8種のmRNAは4種の蛋白をコードする。本研究の目的はこれらの野生型および変異型蛋白の発現解析とアプラタキシン機能解析である。大腸菌内で合成した変異型蛋白において、アプラタキシンの生理活性に関与すると考えられるHIT活性を測定したところ、全ての変異型蛋白で著しく低下していた。昨年度作製したモノクローナル抗体が反応する唯一の変異型蛋白および野生型蛋白の動物細胞内における半減期を、モノクローナル抗体によるパルス・チェイス法で測定したところ、変異型では野生型に比べ短縮していた。また、種々の変異型蛋白の野生型への結合能力をGST pull down法で検討した結果、全ての変異型は野生型に結合した。一方、病的異常蛋白(689insT変異)への結合能は低下しており、この変異型の野生型への結合能は病態生理学的に重要である可能性が考えられる。以上から、変異型蛋白自身は活性を持たないが、野生型に結合することで、その活性を調整している可能性が示唆された。また半減期が短いことも活性調整の目的には適していると考えられる。以上の成果は今後、アプラタキシンの機能解明、さらにはEAOHの治療法開発に貢献できると考えられる。
  • 共同研究, 遺伝性小脳失調症の遺伝子治療
  • 共同研究, 神経疾患の細胞モデルの構築