徳島大学 / 教育研究者総覧 --- 鎌田正紀

検索:

徳島大学 ⟩ 大学院医歯薬学研究部 ⟩ 医学域 ⟩ 先端医学教育研究プロジェクト ⟩
徳島大学 ⟩ 大学院医歯薬学研究部 ⟩ 医学域 ⟩ 医科学部門 ⟩ 生理系 ⟩ 遺伝情報医学 ⟩
徳島大学 ⟩ 医学部 ⟩ 医学科 ⟩ 生体制御医学講座 ⟩ 遺伝情報医学分野 ⟩

(researchmapへのインポート用ファイル) [PDF解説] [researchmapへの自動反映について]

研究活動

専門分野

研究テーマ

著書・論文

学術論文(審査論文):

1.	Shunya Nakane, Koji Fujita, Shingo Azuma, Ryo Urushihara, Masaki Kamada, Masafumi Harada, Yuishin Izumi and Ryuji Kaji : CSF cystatin C and diffusion tensor imaging parameters as biomarkers of upper motor neuron degeneration in amyotrophic lateral sclerosis., Clinical Neurology and Neurosurgery, Vol.172, 162-168, 2018. (要約) MR findings indicated that decreased anisotropy, increased diffusion, and increased myo-inositol/creatine ratio were also significantly correlated with UMN involvement in patients with ALS. The CSF cystatin C levels were significantly lower in patients with ALS than in the other three groups. The reduction of CSF cystatin C levels was significantly correlated with clinical UMN involvement (r = -0.505, p = 0.023). (キーワード) Adult / Aged / Aged, 80 and over / Amyotrophic Lateral Sclerosis / Biomarkers / Cystatin C / Diffusion Magnetic Resonance Imaging / Diffusion Tensor Imaging / Female / Humans / Magnetic Resonance Spectroscopy / Male / Middle Aged / Motor Neurons / Multimodal Imaging / Nerve Degeneration (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.clineuro.2018.07.008 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30016754 ● Search Scopus @ Elsevier (PMID): 30016754 ● Search Scopus @ Elsevier (DOI): 10.1016/j.clineuro.2018.07.008 (DOI: 10.1016/j.clineuro.2018.07.008, PubMed: 30016754)
2.	Masaki Kamada, Toshitaka Kawarai, Ryosuke Miyamoto, Rie Kawakita, Yuki Tojima, Celeste Montecchiani, Laura D'Onofrio, Carlo Caltagirone, Antonio Orlacchio and Ryuji Kaji : Spastic paraplegia type 31: A novel REEP1 splice site donor variant and expansion of the phenotype variability., Parkinsonism & Related Disorders, Vol.46, 79-83, 2017. (要約) Mutations in REEP1 have been identified in three types of neurological disorders, autosomal dominant form of Hereditary Spastic Paraplegia type 31 (SPG31), autosomal dominant distal hereditary motor neuronopathy type VB (HMN5B), and autosomal recessive form of congenital axonal neuropathy and diaphragmatic palsy. Previous studies demonstrated different molecular pathogenesis in SPG31, including loss-of-function, gain-of-function and haploinsufficiency. A four-generation family from Japan, including 12 members, was investigated clinically and genetically. Seven affected members displayed pure spastic paraplegia. Impression of genetic anticipation was observed in the family, including tendency of earlier age-at-onset and increasing severity in subsequent generations. Genetic analysis revealed a heterozygous intronic variant, c.303+2T > A, in REEP1, which segregated with disease, and was also identified in one unaffected member. The variant causes exon 4 skipping leading to frame shift and a truncated transcript identified by complementary DNA sequencing of reverse transcription polymerase chain reaction products. Measurement of REEP1 transcripts in lymphocytes demonstrated a reduction through nonsense mediated mRNA decay (NMD). Our study demonstrated further evidence of allelic heterogeneity in SPG31, mutant REEP1 mRNA dosage effects through NMD and intra-familial phenotype variability. (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.parkreldis.2017.10.012 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29107646 ● Summary page in Scopus @ Elsevier: 2-s2.0-85032279469 (DOI: 10.1016/j.parkreldis.2017.10.012, PubMed: 29107646, Elsevier: Scopus)
3.	Masaki Kamada, Yuishin Izumi, T Ayaki, Masataka Nakamura, Seiko Kagawa, Eiji Kudo, Wataru Sako, Hirofumi Maruyama, Y Nishida, Hideshi Kawakami, Hidefumi Ito and Ryuji Kaji : Clinicopathologic features of autosomal recessive amyotrophic lateral sclerosis associated with optineurin mutation, Neuropathology, Vol.34, No.1, 64-70, 2014. (要約) We performed clinicopathological analyses of two amyotrophic lateral sclerosis (ALS) patients with homozygous Q398X optineurin (OPTN) mutation. Clinically, both patients presented signs of upper and lower motor neuron degeneration, but only Patient 1 showed gradual frontal dysfunction and extrapyramidal signs, and temporal lobe and motor cortex atrophy. Neuropathological examination of Patient 1 revealed extensive cortical and spinal motor neuron degeneration and widespread degeneration of the basal ganglia. Bilateral corticospinal tracts exhibited degeneration. Loss of spinal anterior horn cells (AHCs) and gliosis were observed, whereas posterior columns, Clarke's columns, intermediate lateral columns, and the Onuf's nucleus were spared. In the brainstem, moderate neuronal loss and gliosis were noted in the hypoglossal and facial motor nuclei. No Bunina bodies were found in the surviving spinal and brainstem motor neurons. Transactivation response (TAR) DNA-binding protein 43 (TDP-43)-positive neuronal and glial cytoplasmic inclusions were observed throughout the central nervous system. The Golgi apparatus in motor neurons of the brainstem and spinal cord was often fragmented. Immunoreactivity for OPTN was not observed in the brain and spinal cord, consistent with nonsense-mediated mRNA decay of OPTN. The TDP-43 pathology of Q398X was similar to that of an autosomal dominant E478G mutation. This result suggests that the loss-of-function, but not the proteinopathy itself, of OPTN results in TDP-43 deposits in neuronal and glial cytoplasm and Golgi apparatus fragmentation, leading to multisystem neurodegeneration. (キーワード) Amyotrophic Lateral Sclerosis / Female / Genes, Recessive / Humans / Middle Aged / Mutation / Transcription Factor TFIIIA (出版サイトへのリンク) ● Publication site (DOI): 10.1111/neup.12051 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23889540 ● Summary page in Scopus @ Elsevier: 2-s2.0-84892808067 (DOI: 10.1111/neup.12051, PubMed: 23889540, Elsevier: Scopus)
4.	Toshitaka Kawarai, Pasco Matthew D. Paul, Teleg A. Rosalia, Masaki Kamada, Sakai Waka, Komei Shimozono, Makoto Mizuguchi, Tabuena Daisy, Orlacchio Antonio, Yuishin Izumi, Satoshi Goto, Lee V. Lillian and Ryuji Kaji : Application of long-range polymerase chain reaction in the diagnosis of X-linked dystonia-parkinsonism, Neurogenetics, Vol.14, No.2, 167-169, 2013. (キーワード) dystonia / genetic testing / long-range PCR (出版サイトへのリンク) ● Publication site (DOI): 10.1007/s10048-013-0357-x (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23435702 ● Search Scopus @ Elsevier (PMID): 23435702 ● Search Scopus @ Elsevier (DOI): 10.1007/s10048-013-0357-x (DOI: 10.1007/s10048-013-0357-x, PubMed: 23435702)
5.	Wataru Sako, Hidefumi Ito, Mari Yoshida, Hidetaka Koizumi, Masaki Kamada, Koji Fujita, Yoshio Hashizume, Yuishin Izumi and Ryuji Kaji : Nuclear factor B expression in patients with sporadic amyotrophic lateral sclerosis and hereditary amyotrophic lateral sclerosis with optineurin mutations, Clinical Neuropathology, Vol.31, No.6, 418-423, 2011. (要約) Nuclear factor κ B (NF-κB) is involved in the pathogenesis of a number of neurodegenerative disorders with neuroinflammation. In order to clarify the role of NF-κB in ALS, immunohistochemical studies with an antibody that recognizes the p65 subunit of NF-κB were performed on the spinal anterior horn of 4 patients with sporadic ALS (sALS), 1 patient with optineurin-mutated ALS (OPTN-ALS), and 3 normal controls (NC). In patients with sALS or OPTN-ALS, the expression pattern of NF-κB was altered when compared to that of NC; NF-κB immunoreactivity tended to be absent from neuronal nucleus and was increased in microglia. The down-regulation of NF-κB in neuronal nucleus might contribute to a loss of neuroprotection, or neurons with nuclear NF-κB might be lost immediately after its activation. The microglial induction of NF-κB might contribute to neuroinflammation. In conclusion, NF-κB signaling pathway could have a key role in the pathomechanism of ALS. (キーワード) Aged / Aged, 80 and over / Amyotrophic Lateral Sclerosis / Blotting, Western / Female / Humans / 免疫組織化学 (immunohistochemistry) / Male / Middle Aged / NF-kappa B / 脊髄 (spinal cord) / Transcription Factor TFIIIA (出版サイトへのリンク) ● Publication site (DOI): 10.5414/NP300493 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22762947 ● Summary page in Scopus @ Elsevier: 2-s2.0-84871831437 (DOI: 10.5414/NP300493, PubMed: 22762947, Elsevier: Scopus)

学術レター:

1.	Toshio Inui, Toshitaka Kawarai, Koji Fujita, Kazuyuki Kawamura, Takao Mitsui, Antonio Orlacchio, Masaki Kamada, Takashi Abe, Yuishin Izumi and Ryuji Kaji : A new CSF1R mutation presenting with an extensive white matter lesion mimicking primary progressive multiple sclerosis., Journal of the Neurological Sciences, 2013. (要約) HDLS (Hereditary Diffuse Leukodystrophy with Spheroids) is a hereditary leukodystrophy whose main clinical manifestations include parkinsonism, spasticity, and ataxia. Genetic defects in the colony-stimulating factor 1 receptor (CSF1R) gene have been reported in many HDLS cases. The present report describes a new missense mutation Arg777Gln involving exon 18 of the CSF1R gene in a sporadic patient presenting with tumor-like lesions mimicking primary progressive multiple sclerosis. The patient was initially diagnosed with a progressive variant of multiple sclerosis and received inadequate treatments. Although most HDLS cases have a positive family history, this disease should also be suspected in sporadic patients showing unusual white matter lesions at MRI. (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.jns.2013.08.020 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24034409 ● Search Scopus @ Elsevier (PMID): 24034409 ● Search Scopus @ Elsevier (DOI): 10.1016/j.jns.2013.08.020 (DOI: 10.1016/j.jns.2013.08.020, PubMed: 24034409)
2.	Hirofumi Maruyama, Hiroyuki Morino, Hidefumi Ito, Yuishin Izumi, Hidemasa Kato, Yasuhito Watanabe, Yoshimi Kinoshita, Masaki Kamada, Hiroyuki Nodera, Hidenori Suzuki, Osamu Komure, Shinya Matsuura, Keitaro Kobatake, Nobutoshi Morimoto, Koji Abe, Naoki Suzuki, Masashi Aoki, Akihiro Kawata, Takeshi Hirai, Takeo Kato, Kazumasa Ogasawara, Asao Hirano, Toru Takumi, Hirofumi Kusaka, Koichi Hagiwara, Ryuji Kaji and Hideshi Kawakami : Mutations of optineurin in amyotrophic lateral sclerosis., Nature, Vol.465, No.7295, 223-226, 2010. (要約) Amyotrophic lateral sclerosis (ALS) has its onset in middle age and is a progressive disorder characterized by degeneration of motor neurons of the primary motor cortex, brainstem and spinal cord. Most cases of ALS are sporadic, but about 10% are familial. Genes known to cause classic familial ALS (FALS) are superoxide dismutase 1 (SOD1), ANG encoding angiogenin, TARDP encoding transactive response (TAR) DNA-binding protein TDP-43 (ref. 4) and fused in sarcoma/translated in liposarcoma (FUS, also known as TLS). However, these genetic defects occur in only about 20-30% of cases of FALS, and most genes causing FALS are unknown. Here we show that there are mutations in the gene encoding optineurin (OPTN), earlier reported to be a causative gene of primary open-angle glaucoma (POAG), in patients with ALS. We found three types of mutation of OPTN: a homozygous deletion of exon 5, a homozygous Q398X nonsense mutation and a heterozygous E478G missense mutation within its ubiquitin-binding domain. Analysis of cell transfection showed that the nonsense and missense mutations of OPTN abolished the inhibition of activation of nuclear factor kappa B (NF-kappaB), and the E478G mutation revealed a cytoplasmic distribution different from that of the wild type or a POAG mutation. A case with the E478G mutation showed OPTN-immunoreactive cytoplasmic inclusions. Furthermore, TDP-43- or SOD1-positive inclusions of sporadic and SOD1 cases of ALS were also noticeably immunolabelled by anti-OPTN antibodies. Our findings strongly suggest that OPTN is involved in the pathogenesis of ALS. They also indicate that NF-kappaB inhibitors could be used to treat ALS and that transgenic mice bearing various mutations of OPTN will be relevant in developing new drugs for this disorder. (キーワード) Adolescent / Adult / Aged / Aged, 80 and over / Amino Acid Sequence / Amyotrophic Lateral Sclerosis / Asian Continental Ancestry Group / Base Sequence / 子ども (children) / Codon, Nonsense / Consanguinity / Cytoplasm / DNA-Binding Proteins / Exons / Female / Humans / 近代日本 (modern Japan) / Male / Middle Aged / Mutant Proteins / Mutation / Mutation, Missense / NF-kappa B / Pedigree / Polymorphism, Single Nucleotide / Protein Transport / Sequence Deletion / Superoxide Dismutase / Transcription Factor TFIIIA / Young Adult (出版サイトへのリンク) ● Publication site (DOI): 10.1038/nature08971 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20428114 ● Search Scopus @ Elsevier (PMID): 20428114 ● Search Scopus @ Elsevier (DOI): 10.1038/nature08971 (DOI: 10.1038/nature08971, PubMed: 20428114)

総説・解説:

1.	和泉唯信, 鎌田正紀, 梶龍兒 : 【日本発の神経疾患-発見の歴史からのメッセージ】遺伝性疾患 Optineurin 臨床の歴史, Clinical Neuroscience, Vol.41, No.1, 92-94, 2023年1月.

国際会議:

1.	Masaki Kamada, Toshitaka Kawarai, Ryosuke Miyamoto, Tojima Yuki, Orlacchio Antonio and Ryuji Kaji : Hereditary spastic paraplegia type 31: a novel splice site donor mutation and intra-familial phenotypic variability, The MDS 21th International Congress of Parkinsons Disease and Movement Disorders, Jun. 2017. (キーワード) hereditary spastic paraplegia / phenotypic variability

国内講演発表:

1.	鎌田正紀, 中根俊成, 松井尚子, 樋口理, 酒井和香, 藤田浩司, 和泉唯信, 松尾秀徳, 梶龍兒 : 抗MuSK抗体陽性の眼筋型重症筋無力症, 第28回日本神経免疫学会学術集会, 172, 2016年9月.
2.	宮﨑由道, 鎌田正紀, 藤田浩司, 松井尚子, 和泉唯信, 村山繁雄, 梶龍兒 : 急激な経過をたどったLymphomatosis cerebriの1例, 第109回日本内科学会四国地方会, 2013年12月.
3.	酒井和香, 松井尚子, 寺澤由佳, 藤田浩司, 佐藤健太, 鎌田正紀, 和泉唯信, 梶龍兒 : 50歳以上発症重症筋無力症における臨床像 64歳迄vs65歳以上, 第53回日本神経学会学術大会, 2012年5月.
4.	宮﨑由道, 中村和己, 佐藤健太, 鎌田正紀, 瓦井俊孝, 和泉唯信, 梶龍兒, 出口一志, 石川欽也, 水澤英洋 : 家族性脊髄小脳変性症(SCA15)の1家系, 臨床神経学, Vol.52, No.6, 450, 2012年. (キーワード) Wechsler知能検査血統活動電位 MRI *脊髄小脳変性症(診断) 体性感覚誘発電位遺伝学的検査ヒト中年(45~64) 女
5.	鎌田正紀, 中根俊成, 和泉唯信, 梶龍兒 : アルツハイマー病(AD)に正常圧水頭症(NPH)が合併していると考えられた1例, 日本老年医学会雑誌, Vol.47, No.4, 337, 2010年7月. (キーワード) Alzheimer病(合併症); 水頭症-正常圧(合併症) / ヒト; 高齢者(65∼79); 男
6.	宮﨑由道, 和泉唯信, 鎌田正紀, 浅沼光太郎, 野寺裕之, 梶龍兒 : 徳島大学病院の筋萎縮性側索硬化症(ALS)診療の現状と問題点, 臨床神経学, Vol.49, No.12, 1176, 2009年. (キーワード) *筋萎縮性側索硬化症大学病院ヒト

その他・研究会:

1.	松井尚子, 和泉唯信, 鎌田正紀, 川上秀史, 梶龍兒 : 骨Paget病と痙性対麻痺を併発したVCP遺伝子変異によるミオパチーの一例, 稀少難治性筋疾患に関する調査研究班「IBM分科会」(平成26年度), 2015年2月.

科学研究費補助金 (KAKEN Grants Database @ NII.ac.jp)

靴式下肢加重計を用いたパーキンソン病患者の歩行評価とアジリティーマットの有効性 (研究課題/領域番号: 24K15859 )
パーキンソン病の睡眠障害が夜間高血圧に及ぼす影響 (研究課題/領域番号: 16K09720 )
研究者番号（70612349）による検索