基本情報
研究キーワード
23研究分野
1経歴
6-
2016年4月 - 現在
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2012年4月 - 2015年3月
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2007年4月 - 2012年3月
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2006年4月 - 2007年3月
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2004年4月 - 2006年3月
委員歴
3-
2019年9月 - 現在
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2017年10月 - 現在
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2017年4月 - 現在
受賞
1-
2014年4月
論文
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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.
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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.
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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.
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Journal of Comparative Pathology 210 8-14 2024年4月 査読有り責任著者
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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
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日本獣医師会雑誌 = Journal of the Japan Veterinary Medical Association 73(11) 665-668 2020年11月
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CANCER SCIENCE 109 1401-1401 2018年12月
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日本癌学会総会記事 77回 2113-2113 2018年9月
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日本病理学会会誌 107(1) 342-342 2018年4月
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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.
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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.
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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.
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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.
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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.
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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.
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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。
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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。
書籍等出版物
1講演・口頭発表等
44所属学協会
3共同研究・競争的資金等の研究課題
11-
日本学術振興会 科学研究費助成事業 2022年4月 - 2025年3月
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日本学術振興会 科学研究費助成事業 2021年4月 - 2024年3月
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日本学術振興会 科学研究費助成事業 基盤研究(C) 2019年4月 - 2022年3月
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基盤研究(B) 2015年4月 - 2018年3月
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日本学術振興会 科学研究費助成事業 2014年4月 - 2017年3月