2022/01/27 更新

写真a

シミズ ヒロシ
清水 宏
SHIMIZU Hiroshi
所属
脳研究所 准教授
職名
准教授
外部リンク

学位

  • 博士(医学) ( 2010年3月   新潟大学 )

研究キーワード

  • 認知症

  • 脳腫瘍病理

  • 筋疾患

  • 神経変性疾患

  • 神経病理学

研究分野

  • ライフサイエンス / 神経形態学

  • ライフサイエンス / 神経内科学

  • ライフサイエンス / 腫瘍診断、治療学

  • ライフサイエンス / 病態神経科学

経歴(researchmap)

  • 新潟大学脳研究所   病理学分野   准教授

    2019年4月 - 現在

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  • 新潟大学脳研究所   病理学分野   助教

    2011年4月 - 2019年3月

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    国名:日本国

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経歴

  • 新潟大学   脳研究所   准教授

    2019年4月 - 現在

  • 新潟大学   脳研究所 病態神経科学部門   助教

    2011年4月 - 2019年3月

学歴

  • 新潟大学   医歯学総合研究科   生体機能調節医学専攻

    2006年4月 - 2010年3月

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    国名: 日本国

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  • 北海道大学   医学部

    1994年 - 2000年

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所属学協会

  • 日本神経病理学会

    2005年4月 - 現在

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  • 日本神経学会

    2002年6月 - 現在

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  • 日本内科学会

    2000年12月 - 現在

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論文

  • Autoimmune glial fibrillary acidic protein astrocytopathy resembling isolated central nervous system lymphomatoid granulomatosis. 国際誌

    Akio Kimura, Shinei Kato, Akira Takekoshi, Nobuaki Yoshikura, Narufumi Yanagida, Hiroshi Kitaguchi, Daisuke Akiyama, Hiroshi Shimizu, Akiyoshi Kakita, Takayoshi Shimohata

    Journal of neuroimmunology   361   577748 - 577748   2021年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We report two patients with meningoencephalomyelitis without evidence of extra central nervous system (CNS) involvement. Brain MRI showed linear perivascular radial gadolinium enhancement patterns and spinal cord MRI showed longitudinal extensive T2-hyperintensity lesions. Pathological findings from brain biopsies were angiocentric T-cell predominant lymphoid infiltrates that lacked Epstein-Barr virus-positive atypical B cells. The patients were initially suspected to have isolated CNS-lymphomatoid granulomatosis (LYG). Thereafter, glial fibrillary acidic protein (GFAP)-immunoglobulin G were detected in their cerebrospinal fluid. This finding suggested autoimmune GFAP astrocytopathy. We speculate there is a link between isolated CNS-LYG and autoimmune GFAP astrocytopathy.

    DOI: 10.1016/j.jneuroim.2021.577748

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  • Hemiplegic-type ALS: clinicopathological features of two autopsied patients. 国際誌

    Makoto Sainouchi, Hidetomo Tanaka, Hiroshi Shimizu, Takuya Mashima, Takao Fukushima, Yuya Hatano, Tomohiko Ishihara, Kunihiko Makino, Osamu Onodera, Akiyoshi Kakita

    Journal of neurology, neurosurgery, and psychiatry   92 ( 9 )   1014 - 1016   2021年9月

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    担当区分:責任著者   記述言語:英語  

    DOI: 10.1136/jnnp-2021-326257

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  • Progressive supranuclear palsy: Neuropathology of patients with a short disease duration due to unexpected death

    Lu Zhang, Yasuko Toyoshima, Akari Takeshima, Hiroshi Shimizu, Itsuro Tomita, Osamu Onodera, Hitoshi Takahashi, Akiyoshi Kakita

    Neuropathology   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/neup.12707

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  • Oculopharyngodistal myopathy with coexisting histology of systemic neuronal intranuclear inclusion disease: Clinicopathologic features of an autopsied patient harboring CGG repeat expansions in LRP12. 査読 国際誌

    Rie Saito, Hiroshi Shimizu, Takeshi Miura, Norikazu Hara, Naomi Mezaki, Yo Higuchi, Akinori Miyashita, Izumi Kawachi, Kazuhiro Sanpei, Yoshiaki Honma, Osamu Onodera, Takeshi Ikeuchi, Akiyoshi Kakita

    Acta neuropathologica communications   8 ( 1 )   75 - 75   2020年6月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1186/s40478-020-00945-2

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  • Amyotrophic Lateral Sclerosis with Pallidonigroluysian Degeneration: A Clinicopathological Study. 査読 国際誌

    Junko Ito, Hiroshi Shimizu, Kentaro Ohta, Jiro Idezuka, Hajime Tanaka, Hiroshi Kondo, Takashi Nakajima, Hitoshi Takahashi, Kohei Akazawa, Osamu Onodera, Akiyoshi Kakita

    Annals of neurology   87 ( 2 )   302 - 312   2020年2月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: The pallidonigroluysian (PNL) system, the primary component of corticosubcortical circuits, is generally spared in amyotrophic lateral sclerosis (ALS). We evaluated the clinicopathological features of an unusual form of ALS with PNL degeneration (PNLD) and assessed whether ALS with PNLD represents a distinct ALS subtype. METHODS: From a cohort of 97 autopsied cases of sporadic ALS with phosphorylated 43kDa TAR DNA-binding protein (TDP-43) inclusions, we selected those with PNLD and analyzed their clinicopathological features. RESULTS: Eleven cases (11%) that showed PNLD were divided into 2 subtypes depending on the lesion distribution: (1) extensive type (n = 6), showing widespread TDP-43 pathology and multisystem degeneration, both involving the PNL system; and (2) limited type (n = 5), showing selective PNL and motor system involvement, thus being unclassifiable in terms of Brettschneider's staging or Nishihira's typing of ALS. The limited type showed a younger age at onset and predominant PNLD that accounted for the early development of extrapyramidal signs. The limited type exhibited the heaviest pathology in the subthalamus and external globus pallidus, suggesting that TDP-43 inclusions propagated via indirect or hyperdirect pathways, unlike ALS without PNLD, where the direct pathway is considered to convey TDP-43 aggregates from the cerebral cortex to the substantia nigra. INTERPRETATION: The PNL system can be involved in the disease process of ALS, either nonselectively as part of multisystem degeneration, or selectively. ALS with selective involvement of the PNL and motor systems exhibits unique clinicopathological features and TDP-43 propagation routes, thus representing a distinct subtype of ALS. ANN NEUROL 2020;87:302-312.

    DOI: 10.1002/ana.25652

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  • Fatal Progressive Meningoencephalitis Diagnosed in Two Members of a Family With X-Linked Agammaglobulinemia. 国際誌

    Yasushi Kasahara, Masaru Imamura, Chansu Shin, Hiroshi Shimizu, Jirou Utsumi, Ryosuke Hosokai, Haruko Iwabuchi, Takayuki Takachi, Akiyoshi Kakita, Hirokazu Kanegane, Akihiko Saitoh, Chihaya Imai

    Frontiers in pediatrics   8   579 - 579   2020年

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    記述言語:英語  

    Chronic enteroviral meningoencephalitis is a well-known complication in patients with X-linked agammaglobulinemia (XLA). However, progressive neurodegenerative disorders or chronic neuroinflammatory diseases with no causative microorganisms have been recognized as rare central nervous system (CNS) complications in XLA. We herein report a family in which two of three members with XLA had developed progressive meningoencephalitis with an unknown etiology. A 15-month-old male infant presented with left-sided ptosis. Initially, the family denied any family history of inherited diseases, but later disclosed a family history of agammaglobulinemia previously diagnosed in two family members. In the early 1980s, one of the elder brothers of the index patient's mother who had been treated with intramuscular immunoglobulin [or later intravenous immunoglobulin (IVIG)] for agammaglobulinemia deceased at 10 years of age after showing progressive neurological deterioration during the last several years of his life. The index patient was diagnosed with XLA caused by Bruton tyrosine kinase deficiency (654delG; Val219Leufs*9), and chronic meningoencephalitis with an unknown infectious etiology. Magnetic resonance imaging of the brain demonstrated inflammatory changes in the basal ganglia, hypothalamus, midbrain, and pons, with multiple nodular lesions with ring enhancement, which showed impressive amelioration after the initiation of IVIG replacement therapy. Pleocytosis, which was characterized by an increase in CD4-positive and CD8-positive T cells expressing an activation marker and an elevation in inflammatory cytokines in the cerebrospinal fluid, was identified. No microorganism was identified as a cause of CNS complications. He thereafter developed brain infarction at 19 months of age and fatal status epilepticus at 5 years of age, despite regular IVIG with high trough levels and regular intraventricular immunoglobulin administration. The etiology of this rare CNS complication in XLA is currently unknown. Previous studies have suggested a possible association of IVIG, which was clearly denied in our index case because of the demonstration of his neurological disorder at presentation. In the future, extensive and unbiased molecular methods to detect causative microorganisms, as well as to investigate the possible role of autoimmunity are needed to clarify the etiology of CNS complications.

    DOI: 10.3389/fped.2020.00579

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  • Two distinct prions in fatal familial insomnia and its sporadic form. 査読 国際誌

    Atsuko Takeuchi, Shirou Mohri, Hideaki Kai, Akira Tamaoka, Atsushi Kobayashi, Hidehiro Mizusawa, Yasushi Iwasaki, Mari Yoshida, Hiroshi Shimizu, Shigeo Murayama, Shigetoshi Kuroda, Masanori Morita, Piero Parchi, Tetsuyuki Kitamoto

    Brain Communications   1 ( 1 )   fcz045   2019年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/braincomms/fcz045

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  • Shrinkage of the myenteric neurons in the small intestine in patients with multiple system atrophy. 査読

    Tetsutaro Ozawa, Hiroshi Shimizu, Hideaki Matsui, Osamu Onodera, Akiyoshi Kakita

    Autonomic Neuroscience: Basic and Clinical   221   102583   2019年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.autneu.2019.102583.

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  • An autopsy case of peliosis hepatis with X-linked myotubular myopathy. 査読 国際誌

    Kazuhisa Funayama, Hiroshi Shimizu, Hidetomo Tanaka, Izumi Kawachi, Ichizo Nishino, Kou Matsui, Naoya Takahashi, Akihide Koyama, Rieka Katsuragi-Go, Ryoko Higuchi, Takashi Aoyama, Hiraku Watanabe, Akiyoshi Kakita, Hisakazu Takatsuka

    Legal medicine (Tokyo, Japan)   38   77 - 82   2019年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    This report describes the autopsy case of a 4-year-old boy who died from hepatic hemorrhage and rupture caused by peliosis hepatis with X-linked myotubular myopathy. Peliosis hepatis is characterized by multiple blood-filled cavities of various sizes in the liver, which occurs in chronic wasting disease or with the use of specific drugs. X-linked myotubular myopathy is one of the most serious types of congenital myopathies, in which an affected male infant typically presents with severe hypotonia and respiratory distress immediately after birth. Although each disorder is rare, 12 cases of pediatric peliosis hepatis associated with X-linked myotubular myopathy have been reported, including our case. Peliosis hepatis should be considered as a cause of hepatic hemorrhage despite its low incidence, and it requires adequate gross and histological investigation for correct diagnosis.

    DOI: 10.1016/j.legalmed.2019.04.005

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  • A case of cerebral amyloid angiopathy-type hereditary ATTR amyloidosis with Y69H (p.Y89H) variant displaying transient focal neurological episodes as the main symptom. 査読

    Yamada Y, Fukushima T, Kodama S, Shimizu H, Kakita A, Makino K, Sekijima Y

    Amyloid   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1080/13506129.2019.1632829.

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  • Clinicopathologic Features of Two Patients With Sporadic Amyotrophic Lateral Sclerosis Who Maintained Communication Ability for Over 30 Years. 査読 国際誌

    Junko Ito, Tetsuro Shimada, Mari Tada, Hiroshi Shimizu, Masatoshi Wakabayashi, Akio Yokoseki, Osamu Onodera, Hitoshi Takahashi, Akiyoshi Kakita

    Journal of neuropathology and experimental neurology   77 ( 11 )   981 - 986   2018年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We report the clinicopathologic features of 2 unrelated patients with sporadic amyotrophic lateral sclerosis (SALS) supported by tracheostomy and invasive ventilation (TIV) who were able to maintain communication ability for more than 30 years after disease onset. In both cases, the age at onset was younger than the mean, initially the progression of muscle weakness was consistent with that in the majority of SALS patients, and TIV became necessary several years after disease onset. Thereafter, however, their neurologic deterioration slowed and the patients were able to operate computers by facial movements for several decades. At autopsy, neuronal loss appeared to be confined to the motor neuron system. Furthermore, while Betz cells and lower motor neurons in the spinal anterior horns and hypoglossal nucleus were severely depleted, other pyramidal neurons in the motor cortex, and lower motor neurons in the other brainstem motor nuclei were retained. Neuronal and glial cytoplasmic inclusions immunoreactive for phosphorylated 43-kDa TAR DNA-binding protein (TDP-43) were evident in the CNS, but in extremely small numbers. The present patients may represent a distinct subgroup of patients with SALS who are able to maintain communication ability for an extremely long period, accompanied by very mild TDP-43 pathology.

    DOI: 10.1093/jnen/nly082

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  • Ca2+-permeable AMPA receptors associated with epileptogenesis of hypothalamic hamartoma 査読

    Hiroki Kitaura, Masaki Sonoda, Sayaka Teramoto, Hiroshi Shirozu, Hiroshi Shimizu, Tadashi Kimura, Hiroshi Masuda, Yosuke Ito, Hitoshi Takahashi, Shin Kwak, Shigeki Kameyama, Akiyoshi Kakita

    Epilepsia   58 ( 4 )   E59 - E63   2017年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/epi.13700

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  • Familial amyotrophic lateral sclerosis with an I104F mutation in the SOD1 gene: Multisystem degeneration with neurofilamentous aggregates and SOD1 inclusions

    Haishan Jiang, Hiroshi Shimizu, Atsushi Shiga, Masami Tanaka, Osamu Onodera, Akiyoshi Kakita, Hitoshi Takahashi

    37 ( 1 )   69 - 77   2017年2月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/neup.12324

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  • Biallelic TBCD Mutations Cause Early-Onset Neurodegenerative Encephalopathy. 査読 国際誌

    Noriko Miyake, Ryoko Fukai, Chihiro Ohba, Takahiro Chihara, Masayuki Miura, Hiroshi Shimizu, Akiyoshi Kakita, Eri Imagawa, Masaaki Shiina, Kazuhiro Ogata, Jiu Okuno-Yuguchi, Noboru Fueki, Yoshifumi Ogiso, Hiroshi Suzumura, Yoshiyuki Watabe, George Imataka, Huey Yin Leong, Aviva Fattal-Valevski, Uri Kramer, Satoko Miyatake, Mitsuhiro Kato, Nobuhiko Okamoto, Yoshinori Sato, Satomi Mitsuhashi, Ichizo Nishino, Naofumi Kaneko, Akira Nishiyama, Tomohiko Tamura, Takeshi Mizuguchi, Mitsuko Nakashima, Fumiaki Tanaka, Hirotomo Saitsu, Naomichi Matsumoto

    American journal of human genetics   99 ( 4 )   950 - 961   2016年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We describe four families with affected siblings showing unique clinical features: early-onset (before 1 year of age) progressive diffuse brain atrophy with regression, postnatal microcephaly, postnatal growth retardation, muscle weakness/atrophy, and respiratory failure. By whole-exome sequencing, we identified biallelic TBCD mutations in eight affected individuals from the four families. TBCD encodes TBCD (tubulin folding co-factor D), which is one of five tubulin-specific chaperones playing a pivotal role in microtubule assembly in all cells. A total of seven mutations were found: five missense mutations, one nonsense, and one splice site mutation resulting in a frameshift. In vitro cell experiments revealed the impaired binding between most mutant TBCD proteins and ARL2, TBCE, and β-tubulin. The in vivo experiments using olfactory projection neurons in Drosophila melanogaster indicated that the TBCD mutations caused loss of function. The wide range of clinical severity seen in this neurodegenerative encephalopathy may result from the residual function of mutant TBCD proteins. Furthermore, the autopsied brain from one deceased individual showed characteristic neurodegenerative findings: cactus and somatic sprout formations in the residual Purkinje cells in the cerebellum, which are also seen in some diseases associated with mitochondrial impairment. Defects of microtubule formation caused by TBCD mutations may underlie the pathomechanism of this neurodegenerative encephalopathy.

    DOI: 10.1016/j.ajhg.2016.08.005

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  • Significant association of cadaveric dura mater grafting with subpial Aβ deposition and meningeal amyloid angiopathy. 査読

    Hamaguchi T, Taniguchi Y, Sakai K, Kitamoto T, Takao M, Murayama S, Iwasaki Y, Yoshida M, Shimizu H, Kakita A, Takahashi H, Suzuki H, Naiki H, Sanjo N, Mizusawa H, Yamada M

    Acta Neuropathologica   132 ( 2 )   313 - 315   2016年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s00401-016-1588-3

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  • Heterogeneity of cerebral TDP-43 pathology in sporadic amyotrophic lateral sclerosis: Evidence for clinico-pathologic subtypes 査読

    Ryoko Takeuchi, Mari Tada, Atsushi Shiga, Yasuko Toyoshima, Takuya Konno, Tomoe Sato, Hiroaki Nozaki, Taisuke Kato, Masao Horie, Hiroshi Shimizu, Hirohide Takebayashi, Osamu Onodera, Masatoyo Nishizawa, Akiyoshi Kakita, Hitoshi Takahashi

    Acta Neuropathologica Communications   4 ( 1 )   61   2016年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are types of major TDP-43 (43-kDa TAR DNA-binding protein) proteinopathy. Cortical TDP-43 pathology has been analyzed in detail in cases of FTLD-TDP, but is still unclear in cases of ALS. We attempted to clarify the cortical and subcortical TDP-43 pathology in Japanese cases of sporadic ALS (n = 96) using an antibody specific to phosphorylated TDP-43 (pTDP-43). The cases were divided into two groups: those without pTDP-43-positive neuronal cytoplasmic inclusions in the hippocampal dentate granule cells (Type 1, n = 63), and those with such inclusions (Type 2, n = 33). Furthermore, the Type 2 cases were divided into two subgroups based on semi-quantitative estimation of pTDP-43-positive dystrophic neurites (DNs) in the temporal neocortex: Type 2a (accompanied by no or few DNs, n = 22) and Type 2b (accompanied by abundant DNs, n = 11). Clinico-pathologic analysis revealed that cognitive impairment was a feature in patients with Type 2a and Type 2b, but not in those with Type 1, and that importantly, Type 2b is a distinct subtype characterized by a poor prognosis despite the less severe loss of lower motor neurons, the unusual subcortical dendrospinal pTDP-43 pathology, and more prominent glial involvement in cortical pTDP-43 pathology than other two groups. Considering the patient survival time and severity of motor neuron loss in each group, transition from Type 1 to Type 2, or from Type 2a to Type 2b during the disease course appeared unlikely. Therefore, each of these three groups was regarded as an independent subtype.

    DOI: 10.1186/s40478-016-0335-2

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  • Globular Glial Mixed Four Repeat Tau and TDP-43 Proteinopathy with Motor Neuron Disease and Frontotemporal Dementia. 査読 国際誌

    Ryoko Takeuchi, Yasuko Toyoshima, Mari Tada, Hidetomo Tanaka, Hiroshi Shimizu, Atsushi Shiga, Takeshi Miura, Kenju Aoki, Akane Aikawa, Shin Ishizawa, Takeshi Ikeuchi, Masatoyo Nishizawa, Akiyoshi Kakita, Hitoshi Takahashi

    Brain pathology (Zurich, Switzerland)   26 ( 1 )   82 - 94   2016年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Amyotrophic lateral sclerosis (ALS) may be accompanied by frontotemporal dementia (FTD). We report a case of glial mixed tau and TDP-43 proteinopathies in a Japanese patient diagnosed clinically as having ALS-D. Autopsy revealed loss of lower motor neurons and degeneration of the pyramidal tracts in the spinal cord and brain stem. The brain showed frontotemporal lobar degeneration (FTLD), the most severe neuronal loss and gliosis being evident in the precentral gyrus. Although less severe, such changes were also observed in other brain regions, including the basal ganglia and substantia nigra. AT8 immunostaining revealed that predominant occurrence of astrocytic tau lesions termed globular astrocytic inclusions (GAIs) was a feature of the affected regions. These GAIs were Gallyas-Braak negative. Neuronal and oligodendrocytic tau lesions were comparatively scarce. pS409/410 immunostaining also revealed similar neuronal and glial TDP-43 lesions. Interestingly, occasional co-localization of tau and TDP-43 was evident in the GAIs. Immunoblot analyses revealed band patterns characteristic of a 4-repeat (4R) tauopathy, corticobasal degeneration and a TDP-43 proteinopathy, ALS/FTLD-TDP Type B. No mutations were found in the MAPT or TDP-43 genes. We consider that this patient harbored a distinct, sporadic globular glial mixed 4R tau and TDP-43 proteinopathy associated with motor neuron disease and FTD.

    DOI: 10.1111/bpa.12262

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  • Sporadic ALS with compound heterozygous mutations in the SQSTM1 gene 査読

    Hiroshi Shimizu, Yasuko Toyoshima, Atsushi Shiga, Akio Yokoseki, Keiko Arakawa, Yumi Sekine, Takayoshi Shimohata, Takeshi Ikeuchi, Masatoyo Nishizawa, Akiyoshi Kakita, Osamu Onodera, Hitoshi Takahashi

    Acta Neuropathologica   126 ( 3 )   453 - 459   2013年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Accumulating evidence suggests that heterozygous mutations in the SQSTM1 gene, which encodes p62 protein, are associated with amyotrophic lateral sclerosis (ALS). Here, we report a Japanese patient with sporadic, late-onset ALS who harbored compound heterozygous SQSTM1 mutations (p.[Val90Met]
    [Val153Ile]). Autopsy examination revealed that although TDP-43 pathology was rather widespread, the selective occurrence of p62-positive/TDP-43-negative cytoplasmic inclusions in the lower motor neurons (LMNs) was a characteristic feature. No Bunina bodies were found. Ultrastructurally, p62-positive cytoplasmic inclusions observed in the spinal anterior horn cells were composed of aggregates of ribosome-like granules and intermingled bundles of filamentous structures. Another feature of interest was concomitant Lewy body pathology. The occurrence of distinct p62 pathology in the LMNs in this patient indicates the pathogenic role of SQSTM1 mutations in the development of a subset of ALS. © 2013 Springer-Verlag Berlin Heidelberg.

    DOI: 10.1007/s00401-013-1150-5

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  • Epstein-Barr virus-associated primary central nervous system cytotoxic T-cell lymphoma 査読

    Ryosuke Ogura, Hiroshi Aoki, Manabu Natsumeda, Hiroshi Shimizu, Tsutomu Kobayashi, Tomohisa Saito, Jun Takizawa, Kouichirou Okamoto, Go Hasegawa, Hajime Umezu, Kouichi Ohshima, Hitoshi Takahashi, Yukihiko Fujii, Akiyoshi Kakita

    NEUROPATHOLOGY   33 ( 4 )   436 - 441   2013年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Primary central nervous system lymphoma (PCNSL) expressing T-cell markers is rare, among which nasal-type extranodal NK/T-cell lymphoma is an extremely rare subtype associated with Epstein-Barr virus (EBV) infection. Here we report the clinicopathologic features of a case of EBV-associated PCNSL showing a cytotoxic T-cell phenotype. The patient, a 73-year-old woman, presented with rapidly progressive mental deterioration. Brain MRI revealed multiple lesions with swelling in the bilateral cerebral hemispheres, which were hypointense on T1-weighted images, hyperintense on T2-weighted and fluid-attenuated inversion recovery images, and slightly hyperintense on diffusion-weighted images. Biopsy specimens from the temporal region showed many medium-sized anaplastic lymphocytic cells with perivascular and angio-invasive patterns in the cortex. Immunohistochemically, the cells were positive for CD3, CD8, T-cell-restricted intracellular antigen-1 (TIA-1), granzyme B and perforin, but negative for CD56 and CD20. In situ hybridization revealed EBV-encoded RNAs in the tumor cell nuclei. A rearrangement study showed T-cell receptor g-chain gene rearrangement with a clonal appearance. The patient died 6 months after surgery, and a general autopsy revealed no lymphoma cells outside the brain. These cellular profiles are inconsistent with those of extranodal NK/T-cell lymphoma, and have not been previously described. This case appears to represent an unusual CNS manifestation of EBV-associated T-cell lymphoma.

    DOI: 10.1111/neup.12005

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  • Early adult-onset orbital apex Langerhans cell histiocytosis histologically confirmed during "truly spontaneous" regression 査読

    Keisuke Satoh, Masayoshi Tada, Hiroshi Shimizu, Yuichiro Yoneoka

    ACTA NEUROCHIRURGICA   154 ( 2 )   301 - 302   2012年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER WIEN  

    DOI: 10.1007/s00701-011-1250-8

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  • Involvement of Onuf's nucleus in Machado-Joseph disease: a morphometric and immunohistochemical study 査読

    Hiroshi Shimizu, Mitsunori Yamada, Yasuko Toyoshima, Takeshi Ikeuchi, Osamu Onodera, Hitoshi Takahashi

    ACTA NEUROPATHOLOGICA   120 ( 4 )   439 - 448   2010年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disease caused by an expansion of CAG repeats in the MJD1 gene, in which lower urinary tract dysfunction is known to be the most commonly encountered autonomic failure. However, it remains unclear whether Onuf's nucleus (ON), which plays major roles in the micturition reflex and voluntary continence, degenerates during the disease process. In the present study, we conducted a morphometric and immunohistochemical study of ON, together with the lateral nuclear group (LNG) of the sacral anterior horns, in seven patients with MJD. When compared with controls, the number of lower motor neurons in both ON and LNG was significantly smaller in the MJD patients, the former being inversely correlated with the size of the expanded CAG repeats. Notably, MJD patients with a large CAG-repeat expansion showed an ON-predominant pattern of neuronal loss, while in the remaining patients, ON and LNG were affected to a similar degree, or rather an LNG-predominant pattern of neuronal loss was evident. Moreover, when adjusted for age, the degree of neuronal loss in both ON and LNG was significantly correlated with the extent of expansion of the CAG repeats. In MJD, the remaining lower motor neurons in ON often exhibited ataxin-3- or 1C2-immunoreactive (ir) neuronal intranuclear inclusions, while no pTDP-43-ir neuronal cytoplasmic inclusions were present in these neurons. In conclusion, the present findings strongly suggest that neuronal loss in ON, the degree of which is highly influenced by the extent of expansion of CAG repeats, is a consistent feature in MJD.

    DOI: 10.1007/s00401-010-0699-5

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  • Creutzfeldt-Jakob disease with an M232R substitution: report of a patient showing slowly progressive disease with abundant plaque-like PrP deposits in the cerebellum 査読

    Hiroshi Shimizu, Mitsunori Yamada, Nae Matsubara, Hiroki Takano, Yoshitaka Umeda, Yasuhiro Kawase, Tetsuyuki Kitamoto, Masatoyo Nishizawa, Hitoshi Takahashi

    NEUROPATHOLOGY   29 ( 6 )   735 - 743   2009年12月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    Patients with genetic Creutzfeldt-Jakob disease in which arginine is substituted for methionine at codon 232 (M232R) of the prion protein gene (CJD232) have been described in Japan, and a recent study has revealed the presence of two clinical phenotypes: a rapidly progressive type (rapid-type) and a slowly progressive type (slow-type). Although the former is known to show pathologic features similar to those of classical CJD, the neuropathology of the latter still remains unclear. We report the autopsy findings of slow-type CJD232 of 37 months' duration in a 73-year-old man who had methionine homozygosity at codon 129 of the prion protein gene (129MM). His initial symptoms included agraphia and memory disturbance, followed by relatively slowly progressive dementia. Myoclonus and akinetic mutism became evident 5 and 23 months after disease onset, respectively. The electroencephalogram revealed periodic sharp wave complexes at 7 months before death. The neuropathologic features were partly reminiscent of those of MM2-cortical-type sporadic CJD, showing spongiform change of the large confluent vacuole type, neuronal loss with gliosis, and coarse, perivacuolar prion protein deposits, which were later shown to consist of protease-resistant type 2 prion protein, in the cerebral cortex and striatum. It was of considerable interest that not only was the medial thalamus severely involved, but also that the cerebellar cortex showed loss of Purkinje cells and abundant plaque-like prion protein deposits. These findings are not a feature of MM2-cortical-type sporadic CJD. Whether or not the M232R substitution, in combination with the genetic polymorphism and the molecular type of pathological prion protein, really participates in the development of CJD232 and its different phenotypes awaits further studies.

    DOI: 10.1111/j.1440-1789.2009.01019.x

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  • Spinal cord tau pathology in cervical spondylotic myelopathy 査読

    Hiroshi Shimizu, Akiyoshi Kakita, Hitoshi Takahashi

    ACTA NEUROPATHOLOGICA   115 ( 2 )   185 - 192   2008年2月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    We conducted an immunohistochemical and ultrastructural examination of the spinal cords from 11 cases of cervical spondylotic myelopathy (CSM), together with those from 11 age- and sex-matched control subjects. Immunostaining with AT8 antibody revealed various numbers of tau-positive neuropil thread-like structures (NTSs), often demonstrating a conspicuous astrocytic foot-like perivascular or subpial arrangement, and glial cells with short and thick processes, so-called thorn-shaped astrocytes (TSAs), in the affected cervical cords in 8 of the 11 CSM cases (73%). A number of tau-positive neuronal cytoplasmic pretangles/tangles were also found in the gray matter in all the CSM cases (100%). No such astrocytic or neuronal tau lesions were found in the control subjects. The tau deposited in the NTSs and TSAs was predominantly 4-repeat tau, whereas the neuronal cytoplasmic pretangles/tangles contained both 3-repeat and 4-repeat tau. Ultrastructurally, paired helical filaments about 20 nm wide, together with glial filaments, were detected occasionally in the astrocytic processes. In conclusion, the present findings indicate that astrocytic and neuronal tau lesions appear in the affected cervical cord during the disease process of CSM.

    DOI: 10.1007/s00401-007-0321-7

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書籍等出版物

  • Neurodegeneration with brain iron accumulationの一剖検例

    村松一洋, 清水宏( 担当: 共著 ,  範囲: 小児神経学の進歩 第48集 p74-86)

    日本小児神経学会教育委員会(編集)  2019年5月 

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  • 運動失調のみかた、考えかた –小脳と脊髄小脳変性症−

    清水 宏, 柿田 明美( 担当: 共著 ,  範囲: 脊髄小脳変性症の神経病理)

    中外医学社  2017年9月  ( ISBN:9784498228900

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    総ページ数:358   担当ページ:300-307   記述言語:日本語 著書種別:学術書

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  • 神経内科 Clinical questions and pearls:認知症

    清水 宏, 柿田 明美( 担当: 共著 ,  範囲: プリオン病とは何ですか?)

    中外医学社  2017年1月  ( ISBN:9784498129863

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    総ページ数:435   担当ページ:374-378   記述言語:日本語 著書種別:教科書・概説・概論

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MISC

  • トリプレットリピート病(1)脊髄小脳失調症.連載‐変性疾患のみかた- 招待

    清水 宏

    病理と臨床   38 ( 1 )   67 - 71   2020年1月

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    担当区分:筆頭著者   記述言語:日本語   掲載種別:記事・総説・解説・論説等(その他)  

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  • ポリグルタミン病 招待

    清水 宏

    第13回神経病理コアカリキュラム教育セミナーハンドアウト   66 - 73   2017年6月

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    記述言語:日本語   掲載種別:講演資料等(セミナー,チュートリアル,講習,講義他)  

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  • 頭蓋咽頭腫 Craniopharyngioma 招待

    清水 宏, 柿田 明美

    病理と臨床(別冊、臨時増刊号、病理診断クイックリファレンス)   33   332 - 332   2015年4月

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    担当区分:筆頭著者   記述言語:日本語   掲載種別:記事・総説・解説・論説等(その他)   出版者・発行元:文光堂  

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  • 胚芽異形成性神経上皮腫瘍 Dysembryoplastic neuroepithelial tumor. 招待

    清水 宏, 柿田 明美

    病理と臨床(別冊、臨時増刊号、病理診断クイックリファレンス)   33   334 - 334   2015年4月

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    担当区分:筆頭著者   記述言語:日本語   掲載種別:記事・総説・解説・論説等(その他)   出版者・発行元:文光堂  

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講演・口頭発表等

  • 運動ニューロン疾患―臨床への還元のための病理確定診断の重要性 招待

    第62回日本神経学会  2021年5月 

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    会議種別:シンポジウム・ワークショップ パネル(公募)  

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  • リピート病 招待

    清水 宏

    第17回神経病理コアカリキュラム教育セミナー (第62回日本神経病理学会総会学術研究会).  2021年5月 

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  • ポリグルタミン病 招待

    清水 宏

    第13回神経病理コアカリキュラム教育セミナー (第58回日本神経病理学会総会学術研究会).  2017年6月 

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共同研究・競争的資金等の研究

  • パーキンソン病の多中心性病巣形成と伝播:剖検組織の透明化と三次元観察による検証

    研究課題/領域番号:19K07841  2019年4月 - 2022年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    清水 宏, 柿田 明美, 吉田 眞理, 宮原 弘明

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    担当区分:研究代表者 

    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

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  • 多系統萎縮症:乏突起膠細胞の鉄代謝異常と酸化ストレス亢進の病的意義の解明

    2015年4月 - 2018年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    清水 宏

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    担当区分:研究代表者  資金種別:競争的資金

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  • ブニナ小体を欠く筋萎縮性側索硬化症についての臨床病理学的研究

    2013年4月 - 2015年3月

    日本学術振興会  科学研究費助成事業  若手研究(B)

    清水宏

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    担当区分:研究代表者  資金種別:競争的資金

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