研究者業績

道下 正貴

ミチシタ マサキ  (Masaki Michishita)

基本情報

所属
日本獣医生命科学大学 獣医学部 准教授
学位
博士(獣医学)(東京大学)

J-GLOBAL ID
201501014744797435
researchmap会員ID
B000250308

外部リンク

委員歴

 3

受賞

 1

論文

 154
  • Yuyo Yasumura, Takahiro Teshima, Tomokazu Nagashima, Masaki Michishita, Yoshiaki Taira, Ryohei Suzuki, Hirotaka Matsumoto
    Frontiers in Veterinary Science 11 2024年8月8日  査読有り
    Introduction The therapeutic efficacy of mesenchymal stromal cells (MSCs) in inflammatory bowel disease is not completely known and is not consistent. Priming with inflammatory cytokines has been proposed to adapt MSCs to an inflammatory environment to have them ready to counteract it, but may have undesirable effects on MSCs, such as increased immunogenicity. In this study, we hypothesized that priming MSCs with inflamed intestinal tissue would more effectively enhance their therapeutic effect on intestinal inflammation. Methods The capacity of canine adipose-derived MSCs (cADSCs) primed with colon tissue homogenates from mice with experimentally induced colitis or a combination of tumor necrosis factor-α and interferon-γ to inhibit T-cell proliferation was analyzed, along with their own apoptosis, proliferation, cell surface marker expression, and transcriptome. In addition, colitis mice were treated with the primed cADSCs to assess colitis severity and immune cell profile. Results Priming with cytokines induced apoptosis, decreased cell proliferation, and major histocompatibility complex-II gene expression in cADSCs, but these adverse effects were mild or absent with colitis-tissue priming. cADSCs primed with colitis tissue reduced the severity of colitis via the induction of M2 macrophages and T-regulatory cells and suppression of T-helper (Th)1/Th17-cell responses, and their effects were comparable to those of cytokine-primed cells. Discussion Our results emphasize the importance of the activation of MSCs by the appropriate microenvironment to maximize their therapeutic effect.
  • Tomokazu Nagashima, Shohei Tsumoto, Daisuke Yazawa, Miki Omura, Kazuhiko Ochiai, Karin Yoshida, Kayoko Sugibayashi, Yukino Machida, Ryoichi Suzuki, Koh Igarashi, Koichi Makimura, Yasushi Hara, Masaki Michishita
    Journal of comparative pathology 213 73-77 2024年8月  査読有り責任著者
    A 10-year-old spayed mixed breed dog presented with severe neurological signs. Computed tomography revealed a cranial mediastinal mass, osteolysis of the right second rib and second thoracic vertebra, tracheobronchial and mesenteric lymph node enlargement, pneumonia and pleural effusion. Magnetic resonance imaging detected lesions in the white matter of the right frontal lobe and left cerebral hemisphere with contrast-enhanced T1-weighted images showing demarcated enhancement. On cut section, the surface of the right cerebral frontal lobe and left cerebral hemisphere corticomedullary junctions were indistinct and the white matter was discoloured. Microscopically, multicentric granulomatous inflammation was seen in the brain, cranial mediastinal mass, masses on the right second rib, tracheobronchial and mesenteric lymph nodes, heart, kidneys, lungs and oesophagus. Necrosis and hyaline fungal structures were frequently observed in the centre of the granulomas. These fungi had septae, Y-shaped branching and were 2-3 μm in width. Sequence analysis of DNA from formalin-fixed paraffin-embedded samples identified the fungi as Schizophyllum commune. Based on these findings, this case was diagnosed as disseminated S. commune infection. This is the first report of granulomatous encephalitis caused by S. commune in a dog.
  • Ichiro Yamamoto, Masaki Michishita, Koki Fujita, Tamami Sakai, Noriyasu Sasaki, Koh Kawasumi
    General and comparative endocrinology 353 114520-114520 2024年4月18日  査読有り
    G protein-coupled receptor 84 (GPR84) was cloned as an orphan receptor, and medium-chain fatty acids were then revealed as endogenous ligands. GPR84 is expressed in immune cells and is believed to protect liver function from lipotoxicity caused by overeating and high-fat diet intake. This study aimed to present the molecular characterization of GPR84 in domestic cats. The deduced amino acid sequence of the feline GPR84 shows high sequence homology (83-89 %) with the orthologues from other mammalians by cDNA cloning of feline GPR84. Remarkably high mRNA expression was observed in the bone marrow by Q-PCR analysis. The inhibition of intracellular cAMP concentration was observed in cells transfected with feline GPR84 and treated with medium-chain fatty acids. Immunostaining of GPR84 and free fatty acid receptor 2 (FFAR2)/GPR43 in the bone marrow, where high mRNA expression was observed, showed reactions in macrophages and myeloid cells. To clarify whether the receptor formed homo/hetero-merization, GPR84 and FFARs were analyzed using Nano-Luc binary technology and NanoLuc bioluminescence resonance energy transfer technologies, which revealed that GPR84 formed more heteromers with FFAR2 than homomers with each other. In addition, when GPR84 and FFAR2/GPR43 were cotransfected in the cell, their localization on the cell membrane was reduced compared with that when single receptors were transfected. These results indicated that GPR84 is a functional receptor protein that is expressed in cat tissues and may have a protein-protein interaction with FFAR2/GPR43 on the cell membrane.
  • Tomokazu Nagashima, Masanori Kobayashi, Yoshiaki Kubo, Katsuya Nagaho, Kayoko Sugibayashi, Takahiro Saito, Yukino Machida, Masaki Michishita
    Journal of Comparative Pathology 210 8-14 2024年4月  査読有り責任著者
  • Yoshihiko Yu, Tadashi Miyamoto, Yui Kimura, Kazuhito Itamoto, Masaki Michishita, Hitoshi Hatakeyama, Tomokazu Nagashima, Rikako Asada, Tomomi Yamaguchi, Daisuke Hasegawa, Yoshihiro Nomura, Leslie A Lyons, Tomoki Kosho
    The Canadian veterinary journal = La revue veterinaire canadienne 65(3) 227-233 2024年3月  査読有り
    A stray cat, an intact female Japanese domestic shorthair cat of unknown age (suspected to be a young adult), was rescued. The cat was lethargic and thin and had marked skin fragility, delayed wound healing without skin hyperextensibility, and hind limb proprioceptive ataxia and paresis. Survey radiography, computed tomography, and magnetic resonance imaging revealed congenital vertebral anomalies, including thoracolumbar transitional vertebrae, scoliosis resulting from a thoracic lateral wedge-shaped vertebra, and a kinked tail, and a dilated spinal cord central canal. Through nutritional support, the cat's general condition normalized, followed by a gradual and complete improvement of skin features. Whole-genome sequencing was completed; however, no pathogenic genetic variant was identified that could have caused this phenotype, including congenital scoliosis. A skin biopsy obtained 7 y after the rescue revealed no remarkable findings on histopathology or transmission electron microscopy. Based on clinical course and microscopic findings, malnutrition-induced reversible feline skin fragility syndrome (FSFS) was suspected, and nutritional support was considered to have improved the skin condition. Key clinical message: This is the second reported case of presumed malnutrition-induced reversible FSFS and was accompanied by long-term follow-up.

MISC

 39
  • 佐々木 紀彦, 五味 不二也, 吉村 久志, 山本 昌美, 松田 陽子, 道下 正貴, 畠山 仁, 川野 陽一, 板倉 陽子, 豊田 雅士, マレー・コーク, 石渡 俊行
    日本癌学会総会記事 80回 [J16-6] 2021年9月  
  • 志智 優樹, 南 風花, 佐々木 紀彦, 五味 不二也, 道下 正貴, 塚田 晃三, 豊田 雅士, 高橋 公正, 石渡 俊行
    日本癌学会総会記事 80回 [P14-7] 2021年9月  
  • 佐々木 紀彦, 五味 不二也, 吉村 久志, 山本 昌美, 松田 陽子, 道下 正貴, 畠山 仁, 川野 陽一, 豊田 雅士, コーク・マレー, 石渡 俊行
    膵臓 36(3) A299-A299 2021年8月  
  • 吉村久志, 山本昌美, 岸本拓也, 岸本拓也, 町田雪乃, 道下正貴, 落合和彦, 中川貴之, 松田陽子, 高橋公正, 石渡俊行
    日本獣医学会学術集会講演要旨集 164th (CD-ROM) 2021年  
  • 野中 基弘, 福士 昴, 保科 博, 近内 将記, 町田 雪乃, 塚田 晃三, 道下 正貴
    日本獣医師会雑誌 = Journal of the Japan Veterinary Medical Association 73(11) 665-668 2020年11月  
  • 高木 香奈, 呰上 大吾, 町田 雪乃, 落合 和彦, 道下 正貴
    日本獣医学会学術集会講演要旨集 162回 347-347 2019年8月  
  • 高添 夏希, 町田 雪乃, 野上 英, 原田 知享, 落合 和彦, 呰上 大吾, 道下 正貴
    日本獣医学会学術集会講演要旨集 162回 348-348 2019年8月  
  • 植村 光希, 落合 和彦, 森松 正美, 柏木 伸旭, 宇埜 友美子, 道下 正貴, 呰上 大吾, 小野沢 栄里, 近江 俊徳
    日本獣医学会学術集会講演要旨集 162回 479-479 2019年8月  
  • 石渡 俊行, 志智 優樹, 佐々木 紀彦, 道下 正貴, 長谷川 文雄, 松田 陽子, 新井 冨生, 五味 不二也, 相田 順子, 田久保 海誉, 豊田 雅士, 吉村 久志, 高橋 公正
    膵臓 34(3) A253-A254 2019年6月  
  • 石渡 俊行, 志智 優樹, 佐々木 紀彦, 道下 正貴, 長谷川 文雄, 松田 陽子, 高橋 公正, 田久保 海誉, 新井 冨生, 相田 順子
    日本病理学会会誌 108(1) 321-321 2019年4月  
  • 鈴木紗弥佳, 藤原亜紀, 道下正貴, 加納塁, 安田暁子, 浅田李佳子, 湯祥彦, 長谷川大輔, 藤田道郎
    第15回日本獣医内科学アカデミー学術大会 1 210-210 2019年2月  査読有り
  • Yuuki Shichi, Norihiko Sasaki, Masaki Michishita, Kimimasa Takahashi, Toshiyuki Ishiwata
    CANCER SCIENCE 109 1401-1401 2018年12月  
  • 唐谷 なな, 弥吉 直子, 増田 裕次, 阿部 大二郎, 関 瀬利, 久保 喜昭, 道下 正貴, 呰上 大吾
    動物臨床医学会年次大会プロシーディング 39回(2) 121-122 2018年11月  
  • 石渡 俊行, 佐々木 紀彦, 長谷川 文雄, 道下 正貴, 五味 不二也, 石川 直, 田久保 海誉, 松田 陽子, 新井 冨生, 相田 順子
    日本癌学会総会記事 77回 2113-2113 2018年9月  
  • 志智 優樹, 佐々木 紀彦, 道下 正貴, 高橋 公正, 石渡 俊行
    日本癌学会総会記事 77回 2228-2228 2018年9月  
  • 落合 和彦, 平間 日奈子, 森松 正美, 川上 翔太, 道下 正貴, 中川 貴之, 呰上 大吾, 稲垣 健志, 坂本 敦司, 近江 俊徳
    日本獣医学会学術集会講演要旨集 161回 431-431 2018年8月  
  • 石渡 俊行, 佐々木 紀彦, 長谷川 文雄, 道下 正貴, 石川 直, 田久保 海誉, 松田 陽子, 新井 冨生, 相田 順子
    膵臓 33(3) 468-468 2018年5月  
  • 石渡 俊行, 佐々木 紀彦, 長谷川 文雄, 道下 正貴, 石川 直, 田久保 海誉, 松田 陽子, 新井 冨生, 相田 順子
    膵臓 33(3) 468-468 2018年5月  
  • 石渡 俊行, 佐々木 紀彦, 長谷川 文雄, 道下 正貴, 石川 直, 田久保 海誉, 松田 陽子, 新井 冨生, 相田 順子
    日本病理学会会誌 107(1) 342-342 2018年4月  
  • K. Hagiwara, M. Michishita, H. Yoshimura, K. Ochiai, D. Azakami, T. Ishiwata, K. Takahashi
    JOURNAL OF COMPARATIVE PATHOLOGY 157(4) 266-269 2017年11月  
    A 21-year-old neutered female domestic shorthaired cat was presented with a history of inappetence, vomiting and haematuria. The cat was humanely destroyed at the owner's request and a necropsy examination was performed. A 0.8 x 0.5 x 0.5 cm mass was located in the left lobe of the pancreas. The mass was gelatinous in nature and the external and cut surfaces were pale yellow in colour. Microscopically, the mass was non-capsulated and comprised an accumulation of extracellular stromal mucin containing suspended neoplastic columnar epithelial cells forming tubular structures. Immunohistochemically, these cells diffusely expressed cytokeratin (CK) AE1/AE3, CK7 and carcinoembryonic antigen and were partially positive for CK19 and trypsin, but negative for vimentin. The tumour was diagnosed as a colloid carcinoma. The clinical presentation in this case was caused by chronic renal failure complicated by secondary renal hyperparathyroidism and associated metastatic calcinosis. To the best of our knowledge, this is the first report of colloid carcinoma arising from the pancreas in a cat. (C) 2017 Elsevier Ltd. All rights reserved.
  • 道下 正貴, 齋藤 那美香, 野澤 聡司, 古本 莉奈, 中川 貴之, 佐藤 稲子, 片山 欣哉, 田崎 弘之, 石渡 俊行, 高橋 公正
    日本癌学会総会記事 76回 P-1193 2017年9月  
  • 古本 莉奈, 道下 正貴, 斎藤 那美香, 野澤 聡司, 中川 貴之, 佐藤 稲子, 片山 欣哉, 田崎 弘之, 石渡 俊行, 高橋 公正
    日本獣医学会学術集会講演要旨集 160回 321-321 2017年8月  
  • 佐々木 悠, 吉村 久志, 道下 正貴, 塚田 晃三, 石渡 俊行, 高橋 公正
    日本獣医学会学術集会講演要旨集 160回 322-322 2017年8月  
  • R Furumoto, M Michishita, K Arai, S Soeta, K Takahashi
    Journal of comparative pathology 157(1) 11-14 2017年7月  
    A 13-year-old female Yorkshire terrier was presented with difficulty swallowing because of a lingual mass, which had grown to a size of 0.8 × 0.8 × 0.8 cm in 1 month. Grossly, the mass was located in the lingual frenulum and the cut surface was grey-white in colour. Microscopically, the mass was unencapsulated and composed of lobules of mature adipose tissue and cartilaginous tissue with abundant basophilic myxoid matrix separated by fibrous connective tissue. Immunohistochemically, almost all of these cells were positive for vimentin and S100. Chondroid cells and their adjacent spindle cells were also positive for SOX9. Based on these findings, a diagnosis of chondrolipoma was made. To the best of our knowledge, this is the first report of a chondrolipoma originating as a primary tumour in the lingual frenulum of a dog.
  • M. Michishita, Y. Katori, H. Sasaki, R. D. Obara, R. Furumoto, M. Kato, R. Nakahira, H. Yoshimura, S. Soeta, T. Ishiwata, K. Takahashi
    JOURNAL OF COMPARATIVE PATHOLOGY 157(1) 57-60 2017年7月  
    A 5-year-old male miniature dachshund was presented with a dermal nodule on the left forelimb that increased to 5 mm in diameter over a 2-month period. Grossly, the nodule was firm, and both the external and cut surfaces were homogeneously pale pink in colour. Microscopically, the nodule was comprised of mainly plump endothelial cells and inflammatory cells; among the latter, lymphocytes were predominant, with few scattered plasma cells, mast cells and macrophages. Lymphoid follicles with germinal centres were often observed. Mitotic figures were not observed amongst the endothelial cells. Immunohistochemically, the endothelial cells were positive for vimentin, factor VIII-related antigen and CD31, and the surrounding cells were positive for smooth muscle actin. Lymphocytes expressed CD3 or BLA36. These findings led to a diagnosis of cutaneous angiolymphoid hyperplasia. To the best of our knowledge, this is the first report of a cutaneous proliferative disorder comprising an admixture of proliferating vascular endothelial cells and lymphocytic infiltration with follicle formation in a dog. (C) 2017 Elsevier Ltd. All rights reserved.
  • 落合和彦, 加藤由比子, 中平嶺, 道下正貴, 呰上大吾, 高橋公正, 近江俊徳
    獣医臨床病理 14(1) 34 2015年12月30日  
  • H. Yoshimura, N. Kimura-Tsukada, Y. Ono, M. Michishita, K. Ohkusu-Tsukada, Y. Matsuda, T. Ishiwata, K. Takahashi
    VETERINARY PATHOLOGY 52(6) 1227-1234 2015年11月  
    Mammary tumors that spontaneously occurred in domestic Djungarian hamsters (Phodopus sungorus) were histologically examined. Forty-five mammary tumors included 14 adenomas, 18 adenocarcinomas, 1 lipid-rich carcinoma, 2 adenoacanthomas, 2 malignant adenomyoepitheliomas, 1 benign mixed tumor, and 7 balloon cell carcinosarcomas. The latter 4 types were newly recognized neoplasms in Djungarian hamsters. The relatively high incidence of spontaneous mammary carcinosarcomas in domestic Djungarian hamsters is intriguing. Carcinosarcomas exhibited anomalous histological features made up of a mixture of glandular cells, polygonal cells (including balloon cells), and sarcomatous spindle cells in varying proportions. Transitional features from glandular cells to polygonal cells and subsequently to sarcomatous spindle cells were observed. Using immunohistochemistry, we observed that glandular cells exhibited an epithelial phenotype (cytokeratin(+)/vimentin(-)), spindle cells exhibited a mesenchymal phenotype (cytokeratin(-)/vimentin(+)), and polygonal cells exhibited an intermediate phenotype (cytokeratin(+)/vimentin(+)). Reduction or loss of beta-catenin expression and gain of S100A4 expression were observed in polygonal and spindle cells. The polygonal cell population included a varying number of characteristic cells that were expanded by large intracytoplasmic vacuoles. Electron microscopy revealed that these balloon cells had large cytoplasmic lumens lined by microvilli. These observations suggest that epithelial-mesenchymal transition may account for the pathogenesis of mammary carcinosarcomas in Djungarian hamsters.
  • 加藤 由比子, 落合 和彦, 中平 嶺, 道下 正貴, 呰上 大吾, 高橋 公正, 近江 俊徳
    日本獣医学会学術集会講演要旨集 158回 422-422 2015年8月  
  • H. Yoshimura, M. Michishita, K. Ohkusu-Tsukada, Y. Matsuda, T. Ishiwata, Z. Naito, K. Takahashi
    VETERINARY PATHOLOGY 52(1) 92-96 2015年1月  
    Tenascin-C (Tn-C) is an extracellular matrix glycoprotein implicated in the progression of several human cancers. In canine mammary carcinomas, accumulation of Tn-C has been recognized in 3 different areas: regions of proliferating myoepithelial cells in complex carcinoma, basement membrane zone in low-grade simple carcinoma, and reactive stroma in high-grade simple carcinoma. To identify the Tn-C synthesizing cells in these areas, we utilized double-labeling immunohistochemistry, branched DNA in situ hybridization, and in situ hybridization-immunohistochemistry double-labeling techniques. In complex carcinomas, Tn-C was generated by proliferating myoepithelial cells. Tn-C in low-grade simple carcinomas was also derived from myoepithelial cells existing as a basal monolayer. However, stromal Tn-C in high-grade carcinomas was mainly synthesized by fibroblasts/myofibroblasts, similar to human breast cancer. Thus, the origin of Tn-C in canine mammary carcinomas differs between low- and high-grade malignancies. The role of myoepithelial cell-generated Tn-C is not yet understood.
  • 道下 正貴
    日本獣医生命科学大学研究報告 (63) 23-26 2014年12月  
  • H. Yoshimura, Y. Matsuda, Y. Kawamoto, M. Michishita, K. Ohkusu-Tsukada, K. Takahashi, Z. Naito, T. Ishiwata
    JOURNAL OF COMPARATIVE PATHOLOGY 149(2-3) 225-228 2013年8月  
    Cystic tumours of the pancreas are heterogeneous lesions with a spectrum of morphology and biological behaviour in people. These are poorly characterized in animals. A multicystic tumour of the pancreas was identified in an 11-year-old, female, mixed breed cat. The tumour was 5.5 cm in diameter and the largest cysts were 1.5 cm in diameter. Microscopically, the cysts were lined by single layered or pseudostratified, flat, cuboidal or columnar epithelial cells that occasionally formed papillary structures with a thin fibrous core. The tumour cells had eosinophilic granules in the apical cytoplasm, similar to zymogen granules, and the nuclei were uniform in size and shape. Mitotic figures were not observed. Immunohistochemically, the tumour cells expressed trypsin, but not cytokeratin 7. A diagnosis of acinar cell cystadenoma of the pancreas was made and this is the first report of this tumour in a cat. (C) 2013 Elsevier Ltd. All rights reserved.
  • 道下 正貴, 鳥飼 和史, 吉村 久志, 寺沢 文男, 中平 嶺, 塚田 晃三, 髙橋 公正
    日本野生動物医学会誌 18(4) 129-132 2013年  
    飼育ゴマフアザラシ成雄(31歳)の全身性腫瘤を確認した。各腫瘤は有棘細胞由来の腫瘍細胞が充実胞巣状に増殖し,脈管内塞栓も認められた。免疫組織学化学的に腫瘍細胞はサイトケラチンAE1/AE3,ケラチン5,p63に陽性を示し,ビメンチン,サイトケラチンCAM5.2,カルレチニンに陰性であった。本症例は扁平上皮癌と診断し,肺原発と推察した。本例はゴマフアザラシにおける全身転移を伴う扁平上皮癌の初報告である。
  • 道下 正貴
    日本獣医生命科学大学研究報告 = Bulletin of Nippon Veterinary and Life Science University (58) 23-27 2009年12月  
    少数の細胞集団(癌幹細胞)が癌階層構造を形成するという癌幹細胞発生説が近年提唱されている。癌幹細胞は、自己複製能、分化能、異種移植による腫瘍形成能を有する細胞と定義される。癌幹細胞は、side population解析、細胞表面マーカーによるフローサイトメトリー解析、sphere assayおよびALDEFLUOR assayのようないろいろな方法で同定できる。癌幹細胞の理解は、癌形成機構の解明および新規治療を開発するために最も重要である。しかしながら、獣医学における癌幹細胞研究はほとんど行われていない。本稿では、犬乳腺腫瘍の癌幹細胞の分子生物学的解析および癌幹細胞を標的とする新規治療の展望について述べる。
  • 桑原孝幸, 長谷川大輔, 小林正典, 藤田道郎, 原康, 大村知之, 道下正貴, 高橋公正, 織間博光
    獣医画像診断 (20) 2009年  
  • 塚田 晃三, 戸田 正博, 鵜殿 平一郎, 河上 裕, 高橋 公正, 道下 正貴, 由井 克之
    日本獣医学会学術集会講演要旨集 146回 251-251 2008年9月  
  • 道下正貴, 池田敏男, 仲柴俊昭, 田代啓, 本庶佑, 土井邦雄, 糸原重美, 遠藤昌吾
    日本神経科学大会プログラム・抄録集 25th 199 2002年7月7日  
  • 道下正貴, 池田敏男, 仲柴俊昭, 田代啓, 本庶佑, 土井邦雄, 糸原重美, 遠藤昌吾
    日本獣医学会学術集会講演要旨集 133rd 172 2002年3月1日  
  • 道下正貴, 池田敏男, 仲柴俊昭, 田代啓, 本庶佑, 土井邦雄, 糸原重美, 遠藤昌吾
    日本神経科学大会プログラム・抄録集 24th 219 2001年9月26日  
  • 道下正貴, 池田敏男, 仲柴俊昭, 田代啓, 本庶佑, 土井邦雄, 糸原重美, 遠藤昌吾
    神経化学 40(2/3) 275 2001年9月1日  

書籍等出版物

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講演・口頭発表等

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担当経験のある科目(授業)

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共同研究・競争的資金等の研究課題

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