Updated on 2025/04/25

写真a

 
Kuwamura Mitsuru
 
Organization
Graduate School of Veterinary Science Department of Veterinary Science Professor
School of Veterinary Science Department of Veterinary Science
Title
Professor
Affiliation
Institute of Veterinary Science
Contact information
メールアドレス

Position

  • Graduate School of Veterinary Science Department of Veterinary Science 

    Professor  2022.04 - Now

  • School of Veterinary Science Department of Veterinary Science 

    Professor  2022.04 - Now

Degree

  • 博士(獣医学) ( Others )

Research Interests

  • 自然発生病変

  • 疾患モデル

  • 獣医病理

Research subject summary

  • 神経疾患モデル動物の病態・遺伝解析

Professional Memberships

  • 日本実験動物学会

    2000.04 - Now

  • 日本獣医師会

    1999.04 - Now

  • 日本毒性病理学会

    1994.04 - Now

  • 日本獣医学会

    1991.04 - Now

Committee Memberships (off-campus)

  • 理事   日本獣医病理学専門家協会(JCVP)  

    2014.04 - Now 

  • 監事   日本獣医学会   

    2021.09 - Now 

  • 理事   日本毒性病理学会  

    2008.04 - Now 

Awards

  • 日本獣医学会賞

    2010.03   (社)日本獣医学会  

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    Country:Japan

  • 第126回日本獣医学会大会長賞

    1998.08   (社)日本獣医学会  

  • 獣医学奨励賞

    1998.08   (社)日本獣医学会  

Papers

  • PHF24 is expressed in the inhibitory interneurons in rats. Reviewed

    Numakura Y, Uemura R, Tanaka M, Izawa T, Yamate J, Kuramoto T, Kaneko T, Mashimo T, Yamamoto T, Serikawa T, Kuwamura M

    Exp Anim 雑誌   70 ( 1 )   137 - 143   2021

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    Kind of work:Joint Work  

  • Hashikawa Y, Hayashi R, Tajima M, Okubo T, Azuma S, Kuwamura M, Takai N, Osada Y, Kunihiro Y, Mashimo T, Nishida K. Reviewed

    Hashikawa Y, Hayashi R, Tajima M, Okubo T, Azuma S, Kuwamura M, Takai N, Osada Y, Kunihiro Y, Mashimo T, Nishida K.

    Sci Rep 雑誌   10 ( 1 )   2020

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    Kind of work:Joint Work  

  • Establishment of feline embryonic stem cells from the inner cell mass of blastocysts produced in vitro

    Yoshida T.

    Regenerative Therapy   28   63 - 72   2025.03

  • High mobility group box1 as a danger signal inducing the infiltration of neutrophils and macrophages in thioacetamide-induced rat liver injury(タイトル和訳中)

    Kuramochi Mizuki, Karim Mohammad Rabiul, Izawa Takeshi, Kuwamura Mitsuru, Yamate Jyoji

    Journal of Toxicologic Pathology   38 ( 1 )   49 - 58   2025.01( ISSN:0914-9198

  • A case of anaplastic oligodendroglioma in a rabbit (Oryctolagus cuniculus)(タイトル和訳中)

    Tokuno Hisaki, Tanaka Miyuu, Izawa Takeshi, Sasai Hiroshi, Kuwamura Mitsuru

    The Journal of Veterinary Medical Science   87 ( 1 )   86 - 89   2025.01( ISSN:0916-7250

  • High mobility group box1 as a danger signal inducing the infiltration of neutrophils and macrophages in thioacetamide-induced rat liver injury

    Kuramochi Mizuki, Karim Mohammad Rabiul, Izawa Takeshi, Kuwamura Mitsuru, Yamate Jyoji

    Journal of Toxicologic Pathology   38 ( 1 )   49 - 58   2025( ISSN:09149198 ( eISSN:1881915X

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:Domestic journal  

    <p> The liver, a major organ involved in substance metabolism, is highly susceptible to toxicity induced by chemicals and their metabolites. Although damage-associated molecular patterns (DAMPs) have been implicated in the development of sterile inflammation following cell injury, their involvement in chemically induced hepatocellular injury remains underexplored. This study aimed to determine the role of high-mobility group box 1 (HMGB1), a DAMP, in a rat model of liver injury treated with thioacetamide, a hepatotoxicant. The rats were administered thioacetamide and treated with HMGB1 neutralizing antibody. Histopathological analysis revealed the absence of significant differences between control rats and HMGB1 neutralizing antibody-treated rats. However, HMGB1 neutralizing antibody-treated rats showed a reduction in the hepatic devitalization enzymes, a decrease in the number of anti-inflammatory cluster of differentiation CD163<sup>+</sup> M2 macrophages and neutrophils in the injured area, and a decrease in cytokine expression. These results suggest that HMGB1 leads to the progression of inflammation after chemically induced hepatocyte injury and may represent a therapeutic target for mitigating such injury.</p>

    DOI: 10.1293/tox.2024-0055

    PubMed

  • Application of humanized mice to toxicology studies: properties of chimeric mice with humanized liver (PXB-mice) for hepatotoxicity

    Sultana Nazneen, Izawa Takeshi, Kamei Tomomi, Fujiwara Sho, Ito Yuri, Takami Yuki, Kuwamura Mitsuru

    Journal of Toxicologic Pathology   38 ( 2 )   183 - 189   2025( ISSN:09149198 ( eISSN:1881915X

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    <p> Chimeric mice with humanized liver are considered a useful tool to predict drug pharmacokinetics and <i>in vivo</i> toxicity in humans. The PXB-mouse is one of such chimeric (humanized) mouse models with more than 70% of human hepatocytes in their liver, which can produce human albumin with human-type bile secretion and express human xenobiotic metabolizing enzymes. However, data are limited regarding the properties of such humanized mice in hepatotoxicity studies. This study aimed to explore the distinctive characteristics of chimeric PXB-mice with humanized liver that can influence susceptibility to hepatotoxicity. Morphologically, the PXB-mice have a diffuse hepatic macrovesicular and microvesicular steatosis in the transplanted human hepatocytes, which can be suppressed after human growth hormone treatment. The humanized liver of the PXB-mice has a metabolic zonation of glutamine synthetase, cytochrome P450 2E1, and argininosuccinate synthase 1, similar to normal liver in rodents and humans. The transplanted human hepatocytes in the PXB liver have a markedly decreased N-cadherin expression compared with normal human liver. Scanning electron microscopy revealed formation of septum-like structures encircling the transplanted human hepatocytes in the PXB liver, which consists of an accumulation of fibers in the space of Disse under transmission electron microscopy and is immunolabeled for laminin. Overall, the present report demonstrated the morphological and immunohistochemical characteristics of the PXB-mice with humanized liver along with some abnormalities in the cell adhesion of the transplanted human hepatocytes. These findings would be useful for hepatotoxicity studies using humanized animal models.</p>

    DOI: 10.1293/tox.2024-0092

    PubMed

  • A case of anaplastic oligodendroglioma in a rabbit (<i>Oryctolagus cuniculus</i>)

    TOKUNO Hisaki, TANAKA Miyuu, IZAWA Takeshi, SASAI Hiroshi, KUWAMURA Mitsuru

    Journal of Veterinary Medical Science   87 ( 1 )   86 - 89   2025( ISSN:09167250 ( eISSN:13477439

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    <p>A 6-year-old male rabbit (<i>Oryctolagus cuniculus</i>) showed loss of appetite, right side rotating and the left side circling. The symptoms did not improve, and the rabbit died on the 2nd day after presentation. Histological evaluation of the brain revealed a non-demarcated high cellularity area of neoplastic cells in the midbrain. In the lesion, neoplastic proliferation of large pleomorphic cells with irregular nuclei and medium amount of cytoplasm with prominent atypia was observed. Most of the neoplastic cells were immunohistochemically positive for both Olig2 and vimentin, and filamentous structure was seen in the cytoplasm. To our knowledge, this is the first report of anaplastic oligodendroglioma in a pet rabbit.</p>

    DOI: 10.1292/jvms.24-0438

    PubMed

  • Canavan病の動物モデルであるアスパルトアシラーゼ(Aspa)遺伝子ノックアウトラットに伴うミエリン病変(Myelin lesion in the aspartoacylase(Aspa) knockout rat, an animal model for Canavan disease)

    Takeda Shuji, Hoshiai Rika, Tanaka Miyuu, Izawa Takeshi, Yamate Jyoji, Kuramoto Takashi, Kuwamura Mitsuru

    Experimental Animals   73 ( 3 )   347 - 356   2024.07( ISSN:1341-1357

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    Aspa遺伝子ノックアウトラット脳や脊髄で観察される病理学的/形態学的所見について報告した。なお、本報では、TALENを用いたゲノム編集で樹立したAspa遺伝子ノックアウトラットを用いて評価した。その結果、神経学的兆候はみられなかったが、軸索腫大を伴う空胞形成や髄鞘低形成および肥大活性化されたアストロサイトが、主に脳幹網様体や上行性/下行性運動ニューロン経路および嗅索で観察された。また、形態計測解析により、ニューロンの数に明確な変化がみられないことも明らかにされた。Aspa遺伝子ノックアウトラットに認められた中枢神経系での変化は、ヒトCanavan病(CD)と類似していたことから、Aspa遺伝子ノックアウトラットは、ヒトCD治療の研究と病態生理の理解に有用と判断された。

  • Deficiency of interleukin-19 exacerbates acute lung injury induced by intratracheal treatment of hydrochloric acid

    Nishiyama K.

    Journal of Pharmacological Sciences   155 ( 3 )   94 - 100   2024.07( ISSN:13478613

  • Generation of footprint-free, high-quality feline induced pluripotent stem cells using Sendai virus vector(タイトル和訳中)

    Kimura Kazuto, Tsukamoto Masaya, Sugisaki Hiroko, Tanaka Miyuu, Kuwamura Mitsuru, Matsumoto Yuki, Ishihara Genki, Watanabe Kei, Okada Mika, Nakanishi Mahito, Sugiura Kikuya, Hatoya Shingo

    Regenerative Therapy   26   708 - 716   2024.06

  • Generation of footprint-free, high-quality feline induced pluripotent stem cells using Sendai virus vector

    Kimura K.

    Regenerative Therapy   26   708 - 716   2024.06

  • L-アルギニン誘発性膵炎および関連する肺損傷のモデルマウスにおけるIL-19の機能的役割(Functional role of IL-19 in a mouse model of L-arginine-induced pancreatitis and related lung injury)

    Ono Naoshige, Horikoshi Joji, Izawa Takeshi, Nishiyama Kazuhiro, Tanaka Miyuu, Fujita Takashi, Kuwamura Mitsuru, Azuma Yasu-taka

    Experimental Animals   73 ( 2 )   175 - 185   2024.04( ISSN:1341-1357

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    野生型(WT)マウスとIL-19遺伝子欠乏(IL-19 KO)マウスにL-アルギニンを腹腔内注射して実験的膵炎を作成し、急性膵炎(AP)と関連肺損傷におけるIL-19の役割を解析した。IL-19 KOで血清アミラーゼ濃度が有意に高く、間質性浮腫が軽度悪化した。L-アルギニンによるTNF-αのmRNAの発現は、IL-19 KOにより有意に強く上方制御された。L-アルギニン誘発性膵炎マウスでは肺胞面積が著しく減少し、肺ミエロペルオキシダーゼの発現はIL-19 KOで有意に上昇した。肺ではIL-6と誘導型一酸化窒素シンターゼのmRNA発現は、IL-19 KOによって有意に増大した。以上より、IL-19はTNF-α産生を調節することによりL-アルギニン誘発性膵炎を緩和し、好中球遊走を抑制することによりAP関連肺損傷から保護すると考えられた。

  • Generation of canine induced pluripotent stem cells under feeder-free conditions using Sendai virus vector encoding six canine reprogramming factors

    Tsukamoto M.

    Stem Cell Reports   19 ( 1 )   141 - 157   2024.01( ISSN:22136711

  • Difference in the Mechanism of Iron Overload-Enhanced Acute Hepatotoxicity Induced by Thioacetamide and Carbon Tetrachloride in Rats.

    Yohei Inai, Takeshi Izawa, Tomomi Kamei, Sho Fujiwara, Miyuu Tanaka, Jyoji Yamate, Mitsuru Kuwamura

    Toxicologic pathology   52 ( 1 )   55 - 66   2024.01( ISSN:01926233

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    Iron overload has been recognized as a risk factor for liver disease; however, little is known about its pathological role in the modification of liver injury. The purpose of this study is to investigate the influence of iron overload on liver injury induced by two hepatotoxicants with different pathogenesis in rats. Rats were fed a control (Cont), 0.8% high-iron (0.8% Fe), or 1% high-iron diet (1% Fe) for 4 weeks and were then administered with saline, thioacetamide (TAA), or carbon tetrachloride (CCl4). Hepatic and systemic iron overload were seen in the 0.8% and 1% Fe groups. Twenty-four hours after administration, hepatocellular necrosis induced by TAA and hepatocellular necrosis, degeneration, and vacuolation induced by CCl4, as well as serum transaminase values, were exacerbated in the 0.8% and 1% Fe groups compared to the Cont group. On the other hand, microvesicular vacuolation induced by CCl4 was decreased in 0.8% and 1% Fe groups. Hepatocellular DNA damage was increased by iron overload in both models, whereas a synergistic effect of oxidative stress by excess iron and hepatotoxicant was only present in the CCl4 model. The data showed that dietary iron overload exacerbates TAA- and CCl4-induced acute liver injury with different mechanisms.

    DOI: 10.1177/01926233241235623

    PubMed

  • Myelin lesion in the aspartoacylase (<i>Aspa</i>) knockout rat, an animal model for Canavan disease

    Takeda Shuji, Hoshiai Rika, Tanaka Miyuu, Izawa Takeshi, Yamate Jyoji, Kuramoto Takashi, Kuwamura Mitsuru

    Experimental Animals   73 ( 3 )   347 - 356   2024( ISSN:13411357 ( eISSN:18817122

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:Domestic journal  

    <p> Canavan disease (CD) is a fatal hereditary neurological disorder caused by a mutation in the aspartoacylase (<i>ASPA</i>) gene and characterized by neurological signs and vacuolation in the central nervous system (CNS). The mutation inhibits the hydrolysis of N-acetyl-aspartate (NAA) resulting in accumulation of NAA in the CNS. A new <i>Aspa-</i>knockout rat was generated by transcription activator-like effector nuclease (TALEN) technology. Herein we describe the pathological and morphometrical findings in the brain and spinal cords of <i>Aspa</i>-knockout rats. Although <i>Aspa</i>-knockout rats did not show any neurological signs, vacuolation with swollen axons, hypomyelination, and activated swollen astrocytes were observed mainly in the brainstem reticular formation, ascending and descending motor neuron pathway, and in the olfactory tract. Morphometrical analysis revealed no obvious change in the number of neurons. These changes in the CNS are similar to human CD, suggesting that this animal model would be useful for further study of treatment and understanding the pathophysiology of human CD.</p>

    DOI: 10.1538/expanim.23-0089

    PubMed

  • Functional role of IL-19 in a mouse model of L-arginine-induced pancreatitis and related lung injury

    Ono Naoshige, Horikoshi Joji, Izawa Takeshi, Nishiyama Kazuhiro, Tanaka Miyuu, Fujita Takashi, Kuwamura Mitsuru, Azuma Yasu-Taka

    Experimental Animals   73 ( 2 )   175 - 185   2024( ISSN:13411357 ( eISSN:18817122

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    <p> IL-19 is a member of IL-10 family and is mainly produced by macrophages. Acute pancreatitis (AP) is an inflammatory disease characterized by acinar cell injury and necrosis. In the present study, the role of IL-19 in AP and AP-associated lung injury in mice was explored using L-arginine-induced pancreatitis. Experimental pancreatitis was induced by intraperitoneal injection of L-arginine in wild-type (WT) and <i>IL-19</i> gene-deficient (<i>IL-19</i> KO) mice. Among the mice treated with L-arginine, the serum amylase level was significantly increased in the <i>IL-19</i> KO mice, and interstitial edema, analyzed using hematoxylin and eosin-stained sections, was aggravated mildly in <i>IL-19</i> KO mice compared with WT mice. Furthermore, the mRNA expression of tumor necrosis factor-α was significantly upregulated in <i>IL-19</i> KO mice treated with L-arginine compared with WT mice treated with L-arginine. IL-19 mRNA was equally expressed in the pancreases of both control and L-arginine-treated WT mice. The conditions of lung alveoli were then evaluated in WT and <i>IL-19</i> KO mice treated with L-arginine. In mice with L-arginine-induced pancreatitis, the alveolar area was remarkedly decreased, and expression of lung myeloperoxidase was significantly increased in <i>IL-19</i> KO mice compared with WT mice. In the lungs, the mRNA expression of <i>IL-6</i> and inducible nitric oxide synthase was significantly increased in <i>IL-19</i> KO mice compared with WT mice. In summary, IL-19 was proposed to alleviate L-arginine-induced pancreatitis by regulating TNF-α production and to protect against AP-related lung injury by inhibiting neutrophil migration.</p>

    DOI: 10.1538/expanim.23-0094

    PubMed

  • A missense mutation in the Hspa8 gene encoding heat shock cognate protein 70 causes neuroaxonal dystrophy in rats

    Tanaka M.

    Frontiers in Neuroscience   18   1263724   2024( ISSN:16624548

  • The rat Downunder(Du) coat color mutation is associated with eye anomalies and embryonic lethality and maps to a 3.9-Mb region on chromosome 3(和訳中)

    Hieu Hoang Trung, Tanaka Miyuu, Kuwamura Mitsuru, Mashimo Tomoji, Serikawa Tadao, Kuramoto Takashi

    Experimental Animals   72 ( 1 )   88 - 94   2023.01( ISSN:1341-1357

  • The rat Downunder(Du) coat color mutation is associated with eye anomalies and embryonic lethality and maps to a 3.9-Mb region on chromosome 3(和訳中)

    Hieu Hoang Trung, Tanaka Miyuu, Kuwamura Mitsuru, Mashimo Tomoji, Serikawa Tadao, Kuramoto Takashi

    Experimental Animals   72 ( 1 )   88 - 94   2023.01( ISSN:1341-1357

  • L-arginine-induced pancreatitis aggravated by inhibiting Na<sup>+</sup>/Ca<sup>2+</sup> exchanger 1

    ONO Naoshige, HORIKOSHI Joji, IZAWA Takeshi, NISHIYAMA Kazuhiro, TANAKA Miyuu, KUWAMURA Mitsuru, AZUMA Yasu-Taka

    Journal of Veterinary Medical Science   advpub ( 0 )   2023( ISSN:09167250 ( eISSN:13477439

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    <p>Na<sup>+</sup>/Ca<sup>2+</sup> exchangers (NCX) are an exchange transporter of Na<sup>+</sup> and Ca<sup>2+</sup> ions on the plasma membrane. There are three types of NCX: NCX1, NCX2, and NCX3. We have been working for many years to understand the role of NCX1 and NCX2 in gastrointestinal motility. In this study, we focused on the pancreas, an organ closely related to the gastrointestinal tract, and used a mouse model of acute pancreatitis to investigate a possible role for NCX1 in the pathogenesis of pancreatitis. We characterized a model of acute pancreatitis induced by excessive doses of L-arginine. We administered the NCX1 inhibitor SEA0400 (1 mg/kg) 1 hr prior to L-arginine-induced pancreatitis and evaluated pathological changes. Mice treated with NCX1 inhibitors show exacerbation of the disease with decreased survival and increased amylase activity in response to L-arginine-induced experimental acute pancreatitis, and this exacerbation correlates with increased autophagy mediated by LC3B and p62. These results suggest that NCX1 has a role in regulating pancreatic inflammation and acinar cell homeostasis.</p>

    DOI: 10.1292/jvms.22-0569

    PubMed

  • Analyses of damage-associated molecular patterns, particularly biglycan, in cisplatin-induced rat progressive renal fibrosis

    NAKAGAWA Minto, IZAWA Takeshi, KUWAMURA Mitsuru, YAMATE Jyoji

    Journal of Toxicologic Pathology   advpub ( 0 )   2023( ISSN:09149198 ( eISSN:1881915X

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    <p>Damage-associated molecular patterns (DAMPs) and their receptors (TLR-2 and -4) may play important roles in renal fibrosis, of which the pathogenesis is complicated. We used rat renal lesions induced by a single intraperitoneal injection of cisplatin at 6 mg/kg body weigh; consisting of tissue damage of renal tubules on days 1 and 3, further damage and regeneration with inflammation mainly on days 5 and 7, and interstitial fibrosis on days 9, 12, 15, and 20. Microarray analyses on days 5 (the commencement of inflammation) and 9 (the commencement of interstitial fibrosis) showed that DAMPs increased by more than two-fold relative to control included common extra-cellular matrix (ECM) components such as laminin (Lamc2) and fibronectin, and heat shock protein family, as well as fibrinogen, although it was limited analysis; Lamc2, an element of basement membrane, may be regarded as an indicator for damaged renal tubules. In the real-time RT-PCR analyses, TLR-2 significantly increased transiently on day 1, whereas TLR-4 significantly increased on days 9 and 15, almost in agreement with the increased biglycan (a small leucine-rich proteoglycan as ubiquitous ECM component). As M1/M2 macrophages participated in renal lesions, such as inflammation and fibrosis, presumably, TLR-4, which may be expressed in immune cells, could play crucial roles in the formation of renal lesions in association with biglycan.</p>

    DOI: 10.1293/tox.2022-0148

  • L-arginine-induced pancreatitis aggravated by inhibiting Na<sup>+</sup>/Ca<sup>2+</sup> exchanger 1

    ONO Naoshige, HORIKOSHI Joji, IZAWA Takeshi, NISHIYAMA Kazuhiro, TANAKA Miyuu, KUWAMURA Mitsuru, AZUMA Yasu-Taka

    Journal of Veterinary Medical Science   advpub ( 0 )   2023( ISSN:09167250 ( eISSN:13477439

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    <p>Na<sup>+</sup>/Ca<sup>2+</sup> exchangers (NCX) are an exchange transporter of Na<sup>+</sup> and Ca<sup>2+</sup> ions on the plasma membrane. There are three types of NCX: NCX1, NCX2, and NCX3. We have been working for many years to understand the role of NCX1 and NCX2 in gastrointestinal motility. In this study, we focused on the pancreas, an organ closely related to the gastrointestinal tract, and used a mouse model of acute pancreatitis to investigate a possible role for NCX1 in the pathogenesis of pancreatitis. We characterized a model of acute pancreatitis induced by excessive doses of L-arginine. We administered the NCX1 inhibitor SEA0400 (1 mg/kg) 1 hr prior to L-arginine-induced pancreatitis and evaluated pathological changes. Mice treated with NCX1 inhibitors show exacerbation of the disease with decreased survival and increased amylase activity in response to L-arginine-induced experimental acute pancreatitis, and this exacerbation correlates with increased autophagy mediated by LC3B and p62. These results suggest that NCX1 has a role in regulating pancreatic inflammation and acinar cell homeostasis.</p>

    DOI: 10.1292/jvms.22-0569

    PubMed

  • Analyses of damage-associated molecular patterns, particularly biglycan, in cisplatin-induced rat progressive renal fibrosis

    NAKAGAWA Minto, IZAWA Takeshi, KUWAMURA Mitsuru, YAMATE Jyoji

    Journal of Toxicologic Pathology   advpub ( 0 )   2023( ISSN:09149198 ( eISSN:1881915X

     More details

    <p>Damage-associated molecular patterns (DAMPs) and their receptors (TLR-2 and -4) may play important roles in renal fibrosis, of which the pathogenesis is complicated. We used rat renal lesions induced by a single intraperitoneal injection of cisplatin at 6 mg/kg body weigh; consisting of tissue damage of renal tubules on days 1 and 3, further damage and regeneration with inflammation mainly on days 5 and 7, and interstitial fibrosis on days 9, 12, 15, and 20. Microarray analyses on days 5 (the commencement of inflammation) and 9 (the commencement of interstitial fibrosis) showed that DAMPs increased by more than two-fold relative to control included common extra-cellular matrix (ECM) components such as laminin (Lamc2) and fibronectin, and heat shock protein family, as well as fibrinogen, although it was limited analysis; Lamc2, an element of basement membrane, may be regarded as an indicator for damaged renal tubules. In the real-time RT-PCR analyses, TLR-2 significantly increased transiently on day 1, whereas TLR-4 significantly increased on days 9 and 15, almost in agreement with the increased biglycan (a small leucine-rich proteoglycan as ubiquitous ECM component). As M1/M2 macrophages participated in renal lesions, such as inflammation and fibrosis, presumably, TLR-4, which may be expressed in immune cells, could play crucial roles in the formation of renal lesions in association with biglycan.</p>

    DOI: 10.1293/tox.2022-0148

  • Dietary iron overload enhances Western diet induced hepatic inflammation and alters lipid metabolism in rats sharing similarity with human DIOS

    Fujiwara S.

    Scientific Reports   12 ( 1 )   21414   2022.12

  • Dietary iron overload enhances Western diet induced hepatic inflammation and alters lipid metabolism in rats sharing similarity with human DIOS

    Fujiwara S.

    Scientific Reports   12 ( 1 )   21414   2022.12

  • 側脳室発生時のラットにおける水頭症原因蛋白質CCDC85Cと中間径フィラメント蛋白質の発現(Expression of CCDC85C, a causative protein for hydrocephalus, and intermediate filament proteins during lateral ventricle development in rats)

    Hasan Md.Mehedi, Konishi Shizuka, Tanaka Miyuu, Izawa Takeshi, Yamate Jyoji, Kuwamura Mitsuru

    Experimental Animals   71 ( 1 )   100 - 108   2022.01( ISSN:1341-1357

  • 側脳室発生時のラットにおける水頭症原因蛋白質CCDC85Cと中間径フィラメント蛋白質の発現(Expression of CCDC85C, a causative protein for hydrocephalus, and intermediate filament proteins during lateral ventricle development in rats)

    Hasan Md.Mehedi, Konishi Shizuka, Tanaka Miyuu, Izawa Takeshi, Yamate Jyoji, Kuwamura Mitsuru

    Experimental Animals   71 ( 1 )   100 - 108   2022.01( ISSN:1341-1357

  • 低用量チオアセトアミド投与によるラット肝臓好中球の関与(Involvement of neutrophils in rat livers by low-dose thioacetamide administration)

    Kuramochi Mizuki, Izawa Takeshi, Kuwamura Mitsuru, Yamate Jyoji

    The Journal of Veterinary Medical Science   83 ( 3 )   390 - 396   2021.03( ISSN:0916-7250

  • 低用量チオアセトアミド投与によるラット肝臓好中球の関与(Involvement of neutrophils in rat livers by low-dose thioacetamide administration)

    Kuramochi Mizuki, Izawa Takeshi, Kuwamura Mitsuru, Yamate Jyoji

    The Journal of Veterinary Medical Science   83 ( 3 )   390 - 396   2021.03( ISSN:0916-7250

  • 鉄分を多く含む飼料を給餌したラットでみられる出血性素因の解析(Analyses of hemorrhagic diathesis in high-iron diet-fed rats)

    Inai Yohei, Izawa Takeshi, Mori Mutsuki, Atarashi Machi, Tsuchiya Seiichirou, Kuwamura Mitsuru, Yamate Jyoji

    Journal of Toxicologic Pathology   34 ( 1 )   33 - 41   2021.01( ISSN:0914-9198

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    これまでの研究に際して、ラットに鉄分を多く含む飼料(高Fe飼料)を与えると出血傾向がみられるという現象に予期せず遭遇した。本研究ではその機序を調査した。6週齢の雄性F344/DuCrlCrljマウスに、標準飼料(鉄を0.02%配合)(対照群)または高Fe飼料(1%配合)(高Fe群)を6週間与えた。各種検体を採取して分析したところ、血清中と肝組織中の鉄濃度は対照群に対し高Fe群で有意に上昇していた。同様にトランスフェリンの鉄飽和度も有意に上昇し、ほぼ飽和していた。その一方で、2種の肝トランスアミナーゼの濃度はいずれも上昇していなかった。高Fe群では血漿検体のプロトロンビン時間と活性化部分トロンボプラスチン時間は有意に延長していたが、それらは病理学的に評価した出血の有無とは関係していなかった。また高Fe群では凝固因子の第II因子と第VII因子の活性は有意に低下していたが、第VIII因子の活性は変化していなかった。血小板数には両群間で差はみられず、高Fe群の出血傾向は二次止血の障害に起因するものと示唆された。鉄を0.8%以上配合した飼料を与えられたラットでは多数の臓器に出血が観察された。本結果から、鉄の過剰負荷を受けるとビタミンK不足が不顕性に生じ、それが原因となって凝固異常への感受性が高まる可能性があることが示唆された。

  • ラットの抑制性介在ニューロンにおけるPHF24の発現(PHF24 is expressed in the inhibitory interneurons in rats)

    Numakura Yuki, Uemura Risa, Tanaka Miyuu, Izawa Takeshi, Yamate Jyoji, Kuramoto Takashi, Kaneko Takehito, Mashimo Tomoji, Yamamoto Takashi, Serikawa Tadao, Kuwamura Mitsuru

    Experimental Animals   70 ( 1 )   137 - 143   2021.01( ISSN:1341-1357

  • 鉄分を多く含む飼料を給餌したラットでみられる出血性素因の解析(Analyses of hemorrhagic diathesis in high-iron diet-fed rats)

    Inai Yohei, Izawa Takeshi, Mori Mutsuki, Atarashi Machi, Tsuchiya Seiichirou, Kuwamura Mitsuru, Yamate Jyoji

    Journal of Toxicologic Pathology   34 ( 1 )   33 - 41   2021.01( ISSN:0914-9198

     More details

    これまでの研究に際して、ラットに鉄分を多く含む飼料(高Fe飼料)を与えると出血傾向がみられるという現象に予期せず遭遇した。本研究ではその機序を調査した。6週齢の雄性F344/DuCrlCrljマウスに、標準飼料(鉄を0.02%配合)(対照群)または高Fe飼料(1%配合)(高Fe群)を6週間与えた。各種検体を採取して分析したところ、血清中と肝組織中の鉄濃度は対照群に対し高Fe群で有意に上昇していた。同様にトランスフェリンの鉄飽和度も有意に上昇し、ほぼ飽和していた。その一方で、2種の肝トランスアミナーゼの濃度はいずれも上昇していなかった。高Fe群では血漿検体のプロトロンビン時間と活性化部分トロンボプラスチン時間は有意に延長していたが、それらは病理学的に評価した出血の有無とは関係していなかった。また高Fe群では凝固因子の第II因子と第VII因子の活性は有意に低下していたが、第VIII因子の活性は変化していなかった。血小板数には両群間で差はみられず、高Fe群の出血傾向は二次止血の障害に起因するものと示唆された。鉄を0.8%以上配合した飼料を与えられたラットでは多数の臓器に出血が観察された。本結果から、鉄の過剰負荷を受けるとビタミンK不足が不顕性に生じ、それが原因となって凝固異常への感受性が高まる可能性があることが示唆された。

  • ラットの抑制性介在ニューロンにおけるPHF24の発現(PHF24 is expressed in the inhibitory interneurons in rats)

    Numakura Yuki, Uemura Risa, Tanaka Miyuu, Izawa Takeshi, Yamate Jyoji, Kuramoto Takashi, Kaneko Takehito, Mashimo Tomoji, Yamamoto Takashi, Serikawa Tadao, Kuwamura Mitsuru

    Experimental Animals   70 ( 1 )   137 - 143   2021.01( ISSN:1341-1357

  • ラットの正常肝臓とチオアセトアミド誘発性急性肝病変における肝臓マクロファージに対するデキサメタゾンの影響(Effects of dexamethasone on hepatic macrophages in normal livers and thioacetamide-induced acute liver lesions in rats)

    Hada Noa, Kuramochi Mizuki, Izawa Takeshi, Kuwamura Mitsuru, Yamate Jyoji

    Journal of Toxicologic Pathology   33 ( 4 )   237 - 246   2020.10( ISSN:0914-9198

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    正常な肝臓と化学的に誘発した肝損傷におけるマクロファージの影響を調べるため、正常ラットとチオアセトアミド(TAA)処理ラットに、免疫抑制剤のデキサメタゾン(DX)を投与し比較した。DX(0.5または1.0mg/kg体重)を3、7、11日間反復投与した。その結果、正常肝臓のCD163陽性肝臓常在マクロファージ(Kupffer細胞)の数が減少し、AST値とALT値が上昇した。DX(0.5mg/kg BW)前処理し、TAA(300mg/kg BW)処理したラットでは、M1およびM2マクロファージの数が、TAA処理のみのラットに比べて有意に低下していた。さらにTAA注射によって誘発された肝細胞損傷からの修復性線維化は、DX前処理によって抑制された。以上より、マクロファージは正常な肝臓の恒常性維持(AST、SLTに反映)に影響を与えるだけでなく、化学的に誘発された肝臓病変発生(修復性線維化の低下)にも影響を与えると考えられた。

  • インターロイキン19欠損はリポ多糖類/D-ガラクトサミン誘発性急性肝不全を悪化させる(Deficiency of interleukin-19 exacerbates lipopolysaccharide/D-galactosamine-induced acute liver failure)

    Fujimoto Yasuyuki, Kuwamura Mitsuru, Azuma Yasu-taka

    The Journal of Veterinary Medical Science   82 ( 10 )   1450 - 1455   2020.10( ISSN:0916-7250

  • ラットの正常肝臓とチオアセトアミド誘発性急性肝病変における肝臓マクロファージに対するデキサメタゾンの影響(Effects of dexamethasone on hepatic macrophages in normal livers and thioacetamide-induced acute liver lesions in rats)

    Hada Noa, Kuramochi Mizuki, Izawa Takeshi, Kuwamura Mitsuru, Yamate Jyoji

    Journal of Toxicologic Pathology   33 ( 4 )   237 - 246   2020.10( ISSN:0914-9198

     More details

    正常な肝臓と化学的に誘発した肝損傷におけるマクロファージの影響を調べるため、正常ラットとチオアセトアミド(TAA)処理ラットに、免疫抑制剤のデキサメタゾン(DX)を投与し比較した。DX(0.5または1.0mg/kg体重)を3、7、11日間反復投与した。その結果、正常肝臓のCD163陽性肝臓常在マクロファージ(Kupffer細胞)の数が減少し、AST値とALT値が上昇した。DX(0.5mg/kg BW)前処理し、TAA(300mg/kg BW)処理したラットでは、M1およびM2マクロファージの数が、TAA処理のみのラットに比べて有意に低下していた。さらにTAA注射によって誘発された肝細胞損傷からの修復性線維化は、DX前処理によって抑制された。以上より、マクロファージは正常な肝臓の恒常性維持(AST、SLTに反映)に影響を与えるだけでなく、化学的に誘発された肝臓病変発生(修復性線維化の低下)にも影響を与えると考えられた。

  • インターロイキン19欠損はリポ多糖類/D-ガラクトサミン誘発性急性肝不全を悪化させる(Deficiency of interleukin-19 exacerbates lipopolysaccharide/D-galactosamine-induced acute liver failure)

    Fujimoto Yasuyuki, Kuwamura Mitsuru, Azuma Yasu-taka

    The Journal of Veterinary Medical Science   82 ( 10 )   1450 - 1455   2020.10( ISSN:0916-7250

  • ゾニサミド投与イヌにおける顕著な再生反応を伴う肝細胞壊死(Hepatocellular necrosis with prominent regenerative reactions in a zonisamide administrated dog)

    Takami Yuki, Izawa Takeshi, Tanaka Miyuu, Hatoya Shingo, Nabetani Tomoyo, Yamate Jyoji, Kuwamura Mitsuru

    The Journal of Veterinary Medical Science   82 ( 6 )   704 - 706   2020.06( ISSN:0916-7250

  • ゾニサミド投与イヌにおける顕著な再生反応を伴う肝細胞壊死(Hepatocellular necrosis with prominent regenerative reactions in a zonisamide administrated dog)

    Takami Yuki, Izawa Takeshi, Tanaka Miyuu, Hatoya Shingo, Nabetani Tomoyo, Yamate Jyoji, Kuwamura Mitsuru

    The Journal of Veterinary Medical Science   82 ( 6 )   704 - 706   2020.06( ISSN:0916-7250

  • 肉腫様形態を示し軟骨化生がみられた大動脈体癌のフレンチブルドッグの1例(An aortic body carcinoma with sarcomatoid morphology and chondroid metaplasia in a French Bulldog)

    Morita Chiaki, Tanaka Miyuu, Noguchi Shunsuke, Shimamura Shunsuke, Wada Yusuke, Izawa Takeshi, Yamate Jyoji, Kuwamura Mitsuru

    The Journal of Veterinary Medical Science   82 ( 5 )   576 - 579   2020.05( ISSN:0916-7250

  • 肉腫様形態を示し軟骨化生がみられた大動脈体癌のフレンチブルドッグの1例(An aortic body carcinoma with sarcomatoid morphology and chondroid metaplasia in a French Bulldog)

    Morita Chiaki, Tanaka Miyuu, Noguchi Shunsuke, Shimamura Shunsuke, Wada Yusuke, Izawa Takeshi, Yamate Jyoji, Kuwamura Mitsuru

    The Journal of Veterinary Medical Science   82 ( 5 )   576 - 579   2020.05( ISSN:0916-7250

  • ヒトのびまん性平滑筋腫症に類似した消化管壁の全周性肥厚を伴うびまん性平滑筋腫症の若齢ミニチュアダックスフントの1例(Diffuse leiomyomatosis with circumferential thickening of the gastrointestinal wall, resembling human diffuse leiomyomatosis, in a young miniature dachshund)

    Kuramochi Mizuki, Izawa Takeshi, Mori Mutsuki, Shimamura Shunsuke, Shimada Terumasa, Kuwamura Mitsuru, Yamate Jyoji

    The Journal of Veterinary Medical Science   82 ( 2 )   139 - 142   2020.02( ISSN:0916-7250

  • ヒトのびまん性平滑筋腫症に類似した消化管壁の全周性肥厚を伴うびまん性平滑筋腫症の若齢ミニチュアダックスフントの1例(Diffuse leiomyomatosis with circumferential thickening of the gastrointestinal wall, resembling human diffuse leiomyomatosis, in a young miniature dachshund)

    Kuramochi Mizuki, Izawa Takeshi, Mori Mutsuki, Shimamura Shunsuke, Shimada Terumasa, Kuwamura Mitsuru, Yamate Jyoji

    The Journal of Veterinary Medical Science   82 ( 2 )   139 - 142   2020.02( ISSN:0916-7250

  • 過分極活性化環状ヌクレオチド依存性チャネル1欠損ラットにおける筋力低下と運動協調障害(Muscle weakness and impaired motor coordination in hyperpolarization-activated cyclic nucleotide-gated potassium channel 1-deficient rats)

    Nishitani Ai, Yoshihara Toru, Tanaka Miyuu, Kuwamura Mitsuru, Asano Masahide, Tsubota Yuji, Kuramoto Takashi

    Experimental Animals   69 ( 1 )   11 - 17   2020.01( ISSN:1341-1357

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    細胞膜の過分極によって活性化される過分極活性化環状ヌクレオチド依存性チャネル1(HCN1)は心臓や脳に多く分布し、自発性リズム形成やペースメーカーの役割を担っている。最近、HCN1欠損ラットを用いた研究により、欠神てんかんや緩やかな筋肉の緊張と異常な歩行などが観察された。そこでHCN1欠損ラットの筋力と運動機能を評価したところ、ワイヤーハングテスト、傾斜面テスト、フットプリント分析など各種行動テストの結果により、HCN1欠損ラットは運動協調障害および筋力低下を呈したが、筋電図、筋組織学および深部腱反射では正常であった。これらの結果により、HCN1チャネルは運動協調能力および筋力に寄与していることが示され、HCN1欠損ラットの筋力低下は末梢神経系ではなく中枢神経系の関与により生じることが示唆された。

  • Ccdc85cノックアウトラットの病理学的特徴 遺伝的水頭症のラットモデル(Pathological characteristics of Ccdc85c knockout rats: a rat model of genetic hydrocephalus)

    Konishi Shizuka, Tanaka Natsuki, Mashimo Tomoji, Yamamoto Takashi, Sakuma Tetsushi, Kaneko Takehito, Tanaka Miyuu, Izawa Takeshi, Yamate Jyoji, Kuwamura Mitsuru

    Experimental Animals   69 ( 1 )   26 - 33   2020.01( ISSN:1341-1357

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    CCDC85C遺伝子欠損による出血性水頭症(hhy)マウスは、脳出血を伴う非閉塞性水頭症を発症し、皮質下異所性灰白質を形成する。CCDC85C蛋白質の生物学的機能は、マウス以外の動物において未だ不明であるため、ヒトに近い表現型を示すラットを用いてCCDC85C遺伝子ノックアウト(Ccdc85c KO)ラットを作製した。作製法はTranscriptional activator-like effector nuclease(TALEN)を用いたゲノム編集により、F344ラットのCcdc85cをノックアウトした。KOラットはCcdc85cに約350bpの欠失があり、CCDC85C蛋白質の発現が欠失していた。Ccdc85c KOラットを用いて病理組織学的解析を行ったところ、非閉塞性水頭症、皮質下異所性灰白質の形成および頭蓋内出血を呈した。KOラットは、hhyマウスと類似した多くの病理学的特徴を有していた。これらの結果により、CCDC85Cはラット脳の発達に重要な役割を果たしており、大脳におけるCCDC85Cの生物的機能はラットとマウスの種間においても類似していることが示唆された。

  • 過分極活性化環状ヌクレオチド依存性チャネル1欠損ラットにおける筋力低下と運動協調障害(Muscle weakness and impaired motor coordination in hyperpolarization-activated cyclic nucleotide-gated potassium channel 1-deficient rats)

    Nishitani Ai, Yoshihara Toru, Tanaka Miyuu, Kuwamura Mitsuru, Asano Masahide, Tsubota Yuji, Kuramoto Takashi

    Experimental Animals   69 ( 1 )   11 - 17   2020.01( ISSN:1341-1357

     More details

    細胞膜の過分極によって活性化される過分極活性化環状ヌクレオチド依存性チャネル1(HCN1)は心臓や脳に多く分布し、自発性リズム形成やペースメーカーの役割を担っている。最近、HCN1欠損ラットを用いた研究により、欠神てんかんや緩やかな筋肉の緊張と異常な歩行などが観察された。そこでHCN1欠損ラットの筋力と運動機能を評価したところ、ワイヤーハングテスト、傾斜面テスト、フットプリント分析など各種行動テストの結果により、HCN1欠損ラットは運動協調障害および筋力低下を呈したが、筋電図、筋組織学および深部腱反射では正常であった。これらの結果により、HCN1チャネルは運動協調能力および筋力に寄与していることが示され、HCN1欠損ラットの筋力低下は末梢神経系ではなく中枢神経系の関与により生じることが示唆された。

  • Ccdc85cノックアウトラットの病理学的特徴 遺伝的水頭症のラットモデル(Pathological characteristics of Ccdc85c knockout rats: a rat model of genetic hydrocephalus)

    Konishi Shizuka, Tanaka Natsuki, Mashimo Tomoji, Yamamoto Takashi, Sakuma Tetsushi, Kaneko Takehito, Tanaka Miyuu, Izawa Takeshi, Yamate Jyoji, Kuwamura Mitsuru

    Experimental Animals   69 ( 1 )   26 - 33   2020.01( ISSN:1341-1357

     More details

    CCDC85C遺伝子欠損による出血性水頭症(hhy)マウスは、脳出血を伴う非閉塞性水頭症を発症し、皮質下異所性灰白質を形成する。CCDC85C蛋白質の生物学的機能は、マウス以外の動物において未だ不明であるため、ヒトに近い表現型を示すラットを用いてCCDC85C遺伝子ノックアウト(Ccdc85c KO)ラットを作製した。作製法はTranscriptional activator-like effector nuclease(TALEN)を用いたゲノム編集により、F344ラットのCcdc85cをノックアウトした。KOラットはCcdc85cに約350bpの欠失があり、CCDC85C蛋白質の発現が欠失していた。Ccdc85c KOラットを用いて病理組織学的解析を行ったところ、非閉塞性水頭症、皮質下異所性灰白質の形成および頭蓋内出血を呈した。KOラットは、hhyマウスと類似した多くの病理学的特徴を有していた。これらの結果により、CCDC85Cはラット脳の発達に重要な役割を果たしており、大脳におけるCCDC85Cの生物的機能はラットとマウスの種間においても類似していることが示唆された。

  • Takami Y, Izawa T, Tanaka M, Hatoya S, Nabetani T, Yamate J, Kuwamura M Hepatocellular necrosis with prominent regenerative reactions in a zonisamide administrated dog. Reviewed

    Takami Y, Izawa T, Tanaka M, Hatoya S, Nabetani T, Yamate J, Kuwamura M

    J Vet Med Sci 雑誌   82 ( 6 )   704 - 706   2020

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    Kind of work:Joint Work  

  • Morita C, Tanaka M, Noguchi S, Shimamura S, Wada Y, Izawa T, Yamate J, Kuwamura M An aortic body carcinoma with sarcomatoid morphology and chondroid metaplasia in a French Bulldog. Reviewed

    Morita C, Tanaka M, Noguchi S, Shimamura S, Wada Y, Izawa T, Yamate J, Kuwamura M

    J Vet Med Sci 雑誌   82 ( 82 )   576 - 579   2020

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    Kind of work:Joint Work  

  • Downregulation of aspartoacylase during the progression of myelin breakdown in the dmy mutant rat with mitochondrial magnesium channel MRS2 defect. Reviewed

    Kuwamura M, Tanimura S, Hasegawa Y, Hoshiai R, Moriyama Y, Tanaka M, Takenaka S, Nagayoshi H, Izawa T, Yamate J, Kuramoto T, Serikawa T.

    Brain Res 雑誌   1718   169 - 175   2019.09

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    Kind of work:Joint Work  

  • Muscle weakness and impaired motor coordination in Hcn1-deficient rats. Reviewed

    Nishitani A, Yoshihara T, Tanaka M, Kuwamura M, Asano M, Tsubota Y, Kuramoto T.

    Exp Anim 雑誌   2019.07

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    Kind of work:Joint Work  

  • Pathological characteristics of Ccdc85c knockout rats: a rat model of genetic hydrocephalus. Reviewed

    Konishi S, Tanaka N, Mashimo T, Yamamoto T, Sakuma T, Kaneko T, Tanaka M, Izawa T, Yamate J, Kuwamura M.

    Exp Anim 雑誌   2019.07

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    Kind of work:Joint Work  

  • Hepatic Myoepithelial Carcinoma in a Dog: Immunohistochemical Comparison With Other Canine Hepatic Carcinomas. Reviewed

    Tsuji Y, Kuramochi M, Izawa T, Akiyoshi H, Yamate J, Kuwamura M.

    Vet Pathol 雑誌   2019.06

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    Kind of work:Joint Work  

  • Late onset of cerebellar cortical degeneration in a Magellanic penguin (Spheniscus magellanicus). Reviewed

    Ioannidis M, Tanaka M, Yasui S, Kezuka C, Oyamada M, Hasegawa T, Izawa T, Yamate J, Kuwamura M.

    J Vet Med Sci 雑誌   81 ( 5 )   750 - 752   2019.05

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    Kind of work:Joint Work  

  • Spontaneous peripheral neuritis in two electric eels (Electrophorus electricus). Reviewed

    Rahman N, Kezuka C, Higashiguchi N, Kosaka N, Izawa T, Yamate J, Kuwamura M.

    J Vet Med Sci 雑誌   81 ( 5 )   744 - 746   2019.05

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    Kind of work:Joint Work  

  • イソプロテレノール誘発性ラット心筋線維化においてみられる筋線維芽細胞の免疫組織学的特徴(Immunohistochemical characterization of myofibroblasts appearing in isoproterenol-induced rat myocardial fibrosis)

    Koga Masaaki, Kuramochi Mizuki, Karim Mohammad Rabiul, Izawa Takeshi, Kuwamura Mitsuru, Yamate Jyoji

    The Journal of Veterinary Medical Science   81 ( 1 )   127 - 133   2019.01( ISSN:0916-7250

  • ラット結腸発達における体性幹細胞認識抗体(A3)により標識される細胞の局在性と分布 腸幹細胞微小環境を形成する新しい型の細胞が存在する可能性(The localization and distribution of cells labeled by a somatic stem cell-recognizing antibody(A3) in rat colon development: possible presence of a new cell type forming the intestinal stem cell niche)

    Nishina Hironobu, Katou-Ichikawa Chisa, Kuramochi Mizuki, Izawa Takeshi, Kuwamura Mitsuru, Yamate Jyoji

    Journal of Toxicologic Pathology   32 ( 1 )   37 - 48   2019.01( ISSN:0914-9198

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    発達中のラット腸管、特に結腸におけるA3に反応する細胞の分布について、A3陽性細胞の発達過程から検討した。ラット腸管では早期発生過程において、A3は粘膜下における紡錘状間質細胞と、粘膜固有層形成絨毛における毛細血管の内皮細胞を標識した。発達するに従って、A3陽性細胞は結腸陰窩周囲だけに局在するようになった。二重免疫蛍光法では、結腸陰窩周囲のA3陽性細胞はビメンチンおよびThy-1と反応したが、α-SMAまたはCD34とは反応せず、この細胞は未成熟間葉系細胞の特徴を備えていた。さらにA3は結腸陰窩基部の少数の上皮細胞を標識した。免疫電子顕微鏡観察では、A3陽性細胞は陰窩の上皮に隣接した筋線維芽細胞の内側に認められた。A3陽性細胞は陰窩周囲の未成熟間葉系細胞の新しい型で、上皮間葉相互作用を介して形成される結腸の幹細胞の微小環境に関与していると考えられた。

  • イソプロテレノール誘発性ラット心筋線維化においてみられる筋線維芽細胞の免疫組織学的特徴(Immunohistochemical characterization of myofibroblasts appearing in isoproterenol-induced rat myocardial fibrosis)

    Koga Masaaki, Kuramochi Mizuki, Karim Mohammad Rabiul, Izawa Takeshi, Kuwamura Mitsuru, Yamate Jyoji

    The Journal of Veterinary Medical Science   81 ( 1 )   127 - 133   2019.01( ISSN:0916-7250

  • ラット結腸発達における体性幹細胞認識抗体(A3)により標識される細胞の局在性と分布 腸幹細胞微小環境を形成する新しい型の細胞が存在する可能性(The localization and distribution of cells labeled by a somatic stem cell-recognizing antibody(A3) in rat colon development: possible presence of a new cell type forming the intestinal stem cell niche)

    Nishina Hironobu, Katou-Ichikawa Chisa, Kuramochi Mizuki, Izawa Takeshi, Kuwamura Mitsuru, Yamate Jyoji

    Journal of Toxicologic Pathology   32 ( 1 )   37 - 48   2019.01( ISSN:0914-9198

     More details

    発達中のラット腸管、特に結腸におけるA3に反応する細胞の分布について、A3陽性細胞の発達過程から検討した。ラット腸管では早期発生過程において、A3は粘膜下における紡錘状間質細胞と、粘膜固有層形成絨毛における毛細血管の内皮細胞を標識した。発達するに従って、A3陽性細胞は結腸陰窩周囲だけに局在するようになった。二重免疫蛍光法では、結腸陰窩周囲のA3陽性細胞はビメンチンおよびThy-1と反応したが、α-SMAまたはCD34とは反応せず、この細胞は未成熟間葉系細胞の特徴を備えていた。さらにA3は結腸陰窩基部の少数の上皮細胞を標識した。免疫電子顕微鏡観察では、A3陽性細胞は陰窩の上皮に隣接した筋線維芽細胞の内側に認められた。A3陽性細胞は陰窩周囲の未成熟間葉系細胞の新しい型で、上皮間葉相互作用を介して形成される結腸の幹細胞の微小環境に関与していると考えられた。

  • Rat polyomavirus 2 infection in a colony of X-linked severe combined immunodeficiency rats in Japan. Reviewed

    Tanaka M, Kuramochi M, Nakanishi S, Kuwamura M, Kuramoto T.

    J Vet Med Sci 雑誌   80 ( 9 )   1400 - 1406   2018.09

  • Expression of Ccdc85C, a causative protein for murine hydrocephalus, in the mammary gland tumors of dogs. Reviewed

    Tanaka N, Izawa T, Takenaka S, Akiyoshi H, Yamate J, Kuwamura M.

    Histol Histopathol 雑誌   32 ( 4 )   397 - 403   2018.04

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    Kind of work:Joint Work  

  • Ultrastructural features of canine neuroaxonal dystrophy in a Papillon dog. Reviewed

    Tanaka M, Yamaguchi S, Akiyoshi H, Tsuboi M, Uchida K, Izawa T, Yamate J, Kuwamura M.

    J Vet Med Sci 雑誌   79 ( 12 )   1927 - 1930   2017.12

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    Kind of work:Joint Work  

  • Tremor dominant Kyoto (Trdk) rats carry a missense mutation in the gene encoding the SK2 subunit of small-conductance Ca2+-activated K+ channel. Reviewed

    Kuramoto T, Yokoe M, Kunisawa N, Ohashi K, Miyake T, Higuchi Y, Yoshimi K, Mashimo T, Tanaka M, Kuwamura M, Kaneko S, Shimizu S, Serikawa T, Ohno Y.

    Brain Res 雑誌   1676   38 - 45   2017.12

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    Kind of work:Joint Work  

  • Identification of Candidate Genes for Generalized Tonic-Clonic Seizures in Noda Epileptic Rat. Reviewed

    Kuramoto T, Voigt B, Nakanishi S, Kitada K, Nakamura T, Wakamatsu K, Yoshihara M, Suyama M, Uemura R, Tanaka M, Kuwamura M, Shimizu S, Ohno Y, Sasa M, Serikawa T.

    Behav Genet 雑誌   47 ( 6 )   609 - 619   2017.11

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    Kind of work:Joint Work  

  • Spontaneous nephroblastoma with striated muscle differentiation in an F344 rat. Reviewed

    Tanaka N, Izawa T, Yamate J, Kuwamura M.

    J Toxicol Pathol 雑誌   30 ( 3 )   231 - 234   2017.07

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    Kind of work:Joint Work  

  • Identification of the PLA2G6 c.1579G>A Missense Mutation in Papillon Dog Neuroaxonal Dystrophy Using Whole Exome Sequencing Analysis. Reviewed

    Tsuboi M, Watanabe M, Nibe K, Yoshimi N, Kato A, Sakaguchi M, Yamato O, Tanaka M, Kuwamura M, Kushida K, Ishikura T, Harada T, Chambers JK, Sugano S, Uchida K, Nakayama H.

    PLoS One 雑誌   12 ( 1 )   2017.01

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    Kind of work:Joint Work  

  • Enhanced Expression of Trib3 during the Development of Myelin Breakdown in dmy Myelin Mutant Rats. Reviewed

    Shimotsuma Y, Tanaka M, Izawa T, Yamate J, Kuwamura M.

    PLoS One 雑誌   11 ( 12 )   2016.12

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    Kind of work:Joint Work  

  • Involvement of aspartoacylase in tremor expression in rats. Reviewed

    Nishitani A, Tanaka M, Shimizu S, Kunisawa N, Yokoe M, Yoshida Y, Suzuki T, Sakuma T, Yamamoto T, Kuwamura M, Takenaka S, Ohno Y, Kuramoto T.

    Exp Anim 雑誌   65 ( 3 )   293 - 301   2016.07

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    Kind of work:Joint Work  

  • Ccdc85C, a causative protein for hydrocephalus and subcortical heterotopia, is expressed in the systemic epithelia with proliferative activity in rats. Reviewed

    Tanaka N, Izawa T, Takenaka S, Yamate J, Kuwamura M.

    Histol Histopathol 雑誌   30 ( 7 )   823 - 832   2015.07

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    Kind of work:Joint Work  

  • The VF rat with abnormal myelinogenesis has a mutation in Dopey1. Reviewed

    Tanaka M, Izawa T, Yamate J, Franklin RJ, Kuramoto T, Serikawa T, Kuwamura M.

    Glia 雑誌   62 ( 9 )   1530 - 1542   2014.09

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    Kind of work:Joint Work  

  • Primary cerebral T-cell lymphoma in a sea otter (enhydra lutris). Reviewed

    Tanaka N, Izawa T, Kashiwagi-Yamamoto E, Kuwamura M, Ozaki M, Nakao T, Yamate J.

    J Vet Med Sci 雑誌   75 ( 12 )   1667 - 1669   2013.12

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    Kind of work:Joint Work  

  • Amelioration of cisplatin-induced rat renal lesions by a cyclooxygenase (COX)-2 selective inhibitor. Reviewed

    Yamamato E, Izawa T, Sawamoto O, Juniantito V, Kuwamura M, Yamate J.

    Exp Toxicol Pathol   2011

  • A mutation in the gene encoding mitochondrial Mg²+ channel MRS2 results in demyelination in the rat. Reviewed

    Kuramoto T, Kuwamura M, Tokuda S, Izawa T, Nakane Y, Kitada K, Akao M, Guénet JL, Serikawa T.

    PLos Genet   7 ( 1 )   2011

  • Encapsulating Peritoneal Sclerosis Associated with Abnormal Liver Development in a Young Dog. Reviewed

    Izawa T, Murai F, Akiyoshi H, Ohashi F, Yamate J, Kuwamura M.

    J Vet Med Sci   2011

  • Successful Management with CHOP for Pulmonary Lymphomatoid Granulomatosis in a Dog. Reviewed

    Hatoya S, Kumagai D, Takeda S, Yamamoto E, Nakanishi M, Kuwamura M, Sugiura K, Sasai H, Yamate J, Inaba T.

    J Vet Med Sci   73 ( 4 )   527 - 530   2011

  • Evaluation of methods for cell harvesting and the biological properties at successive passages of canine bone marrow stromal cells Reviewed

    Nishida H, Shoji Y, Nakamura M, Hatoya S, Sugiura K, Yamate J, Kuwamura M, Kotani T, Nakayama M, Suzuki Y, Ide C, Inaba T

    Am J Vet Res   2011

  • A novel rat model of episodic ataxia type 1 shows persistent myokymia, neuromyothonia and spontaneous epileptic seizures. Reviewed

    Ishida S, Sakamoto Y, Nishio T, Baulac S, Kuwamura M, Ohno Y, Takizawa A, Kaneko S, Serikawa T, Mashimo T

    Brain Res   2011

  • A rhabdomyosarcoma arising in the larynx of a dog Reviewed

    Yamate J, Murai F, Izawa T, Akiyoshi H, Shimizu J, Ohashi F, Kuwamura M

    J Toxicol Pathol   2011

  • Immunohistochemical expressions of main PGE2 biosynthesis-related enzymes and PGE2 receptor in rat nephrogenesis. Reviewed

    Yamamoto E, Izawa T, Kuwamura M, Yamate J

    J Toxicol Pathol   2011

  • A collision tumor consisting of granular cell tumor and adenocarcinoma in the uterus of an aged djungarian hamster. Reviewed

    Golbar HM, Izawa T, Yano R, Kuwamura M, Okamura K, Fujita D, Tagami Y, Sasai H, Yamate J

    J Toxicol Pathol (in press)   2011

  • A rapid, targeted, neuron-selective, in vivo knockdown following a single intracerebroventricular injection of a novel chemically modified siRNA in the adult rat brain. Reviewed

    Nakajima H, Kubo T, Semi Y, Itakura M, Kuwamura M, Izawa T, Azuma YT, Takeuchi T.

    J Biotechnol.   2011

  • Ccdc85c Encodes a Protein at Apical Junctions of Radial Glia Is Disrupted in Hemorrhagic Hydrocephalus (hhy) Mice. Reviewed

    Mori N, Kuwamura M, Tanaka N, Hirano R, Nabe M, Ibuki M, Yamate J.

    Am J Pathol   2011

  • Immunohistochemical characterization of macrophages and myofibroblasts in α-Naphthylisothiocyanate (ANIT)--induced bile duct injury and subsequent fibrogenesis in rats. Reviewed

    Juniantito V, Izawa T, Yamamoto E, Murai F, Kuwamura M, Yamate J.

    Toxicol Pathol   145   378 - 389   2011

  • Heterogeneity of Macrophage Populations and Expression of Galectin-3 in Cutaneous Wound Healing in Rats. Reviewed

    Juniantito V, Izawa T, Yamamoto E, Murai F, Kuwamura M, Yamate J.

    J Comp Pathol   2011

  • Kyoto rhino rats derived by ENU mutagenesis undergo congenital hair loss and exhibit focal glomerulosclerosis. Reviewed

    Kuramoto T, Kuwamura M, Tagami F, Mashimo T, Nose M, Serikawa T.

    Exp Anim   60 ( 1 )   57 - 63   2011

  • Cardiac Hamartoma in a Young Squirrel Monkey Who Died Suddenly. Reviewed

    Golbar HM, Izawa T, Kuwamura M, Fujita D, Okamura K, Yamazaki R, Tagami Y, Sasai H, Yamate J.

    Vet Pathol   2010

  • The F gene of the Osaka-2 strain of measles virus derived from a case of subacute sclerosing panencephalitis is a major determinant of neurovirulence. Reviewed

    Ayata M, Takeuchi K, Takeda M, Ohgimoto S, Kato S, Sharma LB, Tanaka M, Kuwamura M, Ishida H, Ogura H.

    J Virol   84 ( 21 )   11189 - 11199   2010

  • PPARα contributes to colonic protection in mice with DSS-induced colitis. Reviewed

    Azuma YT, Nishiyama K, Matsuo Y, Kuwamura M, Morioka A, Nakajima H, Takeuchi T.

    Int Immunopharmacol   10 ( 10 )   1261 - 1267   2010

  • Immunohistochemical analyses of the kinetics and distribution of macrophages, hepatic stellate cells and bile duct epithelia in the developing rat liver. Reviewed

    Golbar HM, Izawa T, Murai F, Kuwamura M, Yamate J.

    Exp Toxicol Pathol   2010

  • Abnormal iron accumulation is involved in the pathogenesis of the demyelinating dmy rat but not in the hypomyelinating mv rat. Reviewed

    Izawa T, Yamate J, Franklin RJ, Kuwamura M.

    Brain Res   1349   105 - 114   2010

  • Relationship of heat shock protein 25 with reactive macrophages in thioacetamide-induced rat liver injury. Reviewed

    Fujisawa K, Miyoshi T, Tonomura Y, Izawa T, Kuwamura M, Torii M, Yamate J.

    Exp Toxicol Pathol   2010

  • Involvement of endogenous prostaglandin E2 in tubular epithelial regeneration through inhibition of apoptosis and epithelial-mesenchymal transition in cisplatin-induced rat renal lesions. Reviewed

    Yamamoto E, Izawa T, Juniantito V, Kuwamura M, Sugiura K, Takeuchi T, Yamate J.

    Histo Histopathol   25 ( 8 )   995 - 1007   2010

  • The kinetics and distribution of different macrophage populations in the developing rat skin. Reviewed

    Juniantito V, Izawa T, Yamamoto E, Kuwamura M, Yamate J.

    Histo Histopathol   25 ( 8 )   985 - 994   2010

  • Identification of the rat Rex mutation as a 7-bp deletion at splicing acceptor site of the Krt71 gene. Reviewed

    Kuramoto T, Hirano R, Kuwamura M, Serikawa T.

    J Vet Med Sci   72 ( 7 )   909 - 912   2010

  • Uterine adenocarcinoma with prominent desmoplasia in a geriatric miniature pig. Reviewed

    Golbar H, Izawa T, Kuwamura M, Ito S, Yamate J.

    J Vet Med Sci   72 ( 2 )   253 - 256   2010

  • Abnormal myelinogenesis both in the white and gray matter of the attractin-deficient mv rat. Reviewed

    Izawa T, Yamate J, Franklin RJ, Kuwamura M.

    Brain Res   1312   145 - 155   2010

  • Interleukin-19 protects mice from innate-mediated colonic inflammation. Reviewed

    Azuma YT, Matsuo Y, Kuwamura M, Yancopoulos GD, Valenzuela DM, Murphy AJ, Nakajima H, Karow M, Takeuchi T.

    Inflamm Bowel DIs   16 ( 6 )   1017 - 1028   2010

  • The distribution and characterization of skeletal muscle lesions in dysferlin-deficient SJL and A/J mice. Reviewed

    Kobayashi K, Izawa T, Kuwamura M, Yamate J.

    Exp Toxicol Pathol   62 ( 5 )   509 - 517   2010

  • Macrophage populations and expressions of regulatory proinflammatory factors in the rat meninx under lipopolysaccharide treatment in vivo and in vitro. Reviewed

    Yamate J, Ishimine S, Izawa T, Kumagai D, Kuwamura M.

    Histo Histopathol   24 ( 1 )   13 - 24   2009

  • Gastrointestinal candidiasis in an Aldabra giant tortoise (Geochelone gigantea). Reviewed

    Juniantito V, Izawa T, Kuwamura M, Yonezawa M, Ito S, Yamate J.

    J Vet Med Sci   71 ( 9 )   1269 - 1272   2009

  • Late onset cerebellar cortical degeneration in a koala. Reviewed

    Kuwamura M, Murai F, Nishioka S, Aoki M, Ohashi F, Yamate J, Kotani T, Summers BA.

    Aust Vet J   87 ( 8 )   342 - 344   2009

  • Neuronal ceroid-lipofuscinosis in a Japanese domestic shorthair cat. Reviewed

    Kuwamura M, Nakagawa M, Nabe M, Yamate J, Inoue M, Satoh H, Yamato O.

    J Vet Med Sci   71 ( 5 )   665 - 667   2009

  • Malignant seminoma with multiple visceral metastases in a guinea fowl (Numida meleagris) kept in a zoo. Reviewed

    Golbar HM, Izawa T, Kuwamura M, Yonezawa M, Ito S, Yamate J.

    Avian Dis   53 ( 1 )   143 - 145   2009

  • Participation of functionally different macrophage populations and monocyte chemoattractant protein-1 in early stages of thioacetamide-induced rat hepatic injury. Reviewed

    Mori Y, Izawa T, Takenaka S, Kuwamura M, Yamate J.

    Toxicol Pathol   37 ( 4 )   463 - 473   2009

  • Vasoformative disorder, resembling littoral cell angioma, of the spleen in a geriatric Japanese macaque (Macaca fuscata). Reviewed

    Yamate J, Izawa T, Kuwamura M, Mitsunaga F, Nakamura S.

    Vet Pathol   46 ( 3 )   520 - 525   2009

  • Characterization of the Kyoto circling (KCI) rat carrying a spontaneous nonsense mutation in the protocadherin 15 (Pcdh15) gene.

    Naoi K, Kuramoto T, Kuwamura Y, Gohma H, Kuwamura M, Serikawa T.

    Exp Anim   58 ( 1 )   1 - 10   2009

  • Pancreatic metaplasia in the gastro-achlorhydria in WTC-dfk rat, a potassium channel Kcnq1 mutant. Reviewed

    Kuwamura M, Okajima R, Yamate J, Kotani T, Kuramoto T, Serikawa T.

    Vet Pathol   45 ( 4 )   586 - 591   2008

  • Cutaneous rhabdoid tumor in a cat.

    Izawa T, Yamate J, Takeda S, Kumagai D, Kuwamura M.

    Vet Pathol   45 ( 6 )   897 - 900   2008

  • Oligodendroglial pathology in the development of myelin breakdown in the dmy mutant rat. Reviewed

    Kuwamura M, Inumaki K, Tanaka M, Shirai M, Izawa T, Yamate J, Franklin RJ, Kuramoto T, Serikawa T.

    Brain Res   1389   161 - 168  

  • Relatioship of heat shock protein 25 with reactive macrophages in thioacetamide-induced rat liver injury. Reviewed

    Fujisawa K, Miyoshi T, Tonomura Y, Izawa T, Kuwamura M, Torii M, Yamate J

    Exp Toxicol Pathol  

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Books and Other Publications

  • 動物病理学各論第3版

    日本獣医病理学専門家協会( Role: Joint author)

    文永堂出版  2021.03 

  • 動物病理カラーアトラス第2版

    中山裕之 他( Role: Joint author)

    日本獣医病理学専門家協会  2018.01 

  • 脳神経外科医が知っておくべきニューロサイエンスの知識

    橋本信夫 他( Role: Joint author)

    文光堂  2015.10 

  • Hydrocephalus (Edt: Amaya Velazquez) Hemorrhagic hydrocephalus (hhy): a novel hydrocephalus mouse mutation with near-perfect penetrance

    Mori N et al( Role: Joint author)

    Nova Science Publishers, Inc  2013.04 

  • 動物病理学総論第3版

    中山裕之 他( Role: Joint author)

    日本獣医病理学会編  2013.03 

  • 動物病理学各論第2版

    林 俊春 他( Role: Joint author)

    日本獣医病理学会編  2010.03 

  • 獣医病理組織カラーアトラス5版

    桑村 充( Role: Joint author)

    文永堂出版  1998.04 

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    Responsible for pages:173  

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MISC

Presentations

Grant-in-Aid for Scientific Research

  • 比較病態モデルによる難治性ミエリン疾患のメカニズム解明

    2021

  • シャペロン介在性オートファジーと軸索輸送に着目した軸索ジストロフィーの病態解明

    Grant-in-Aid for Scientific Research(C)  2026

  • シャペロン介在性オートファジーと軸索輸送に着目した軸索ジストロフィーの病態解明

    Grant-in-Aid for Scientific Research(C)  2025

  • Elucidation of mechanism underlying toxicity resistance by human hepatocytes based on cell adhesion abnormality

    Grant-in-Aid for Challenging Research (Exploratory)  2025

  • Elucidating the mechanisms of intractable myelin disease using comparative pathological models

    Grant-in-Aid for Scientific Research(B)  2025

  • シャペロン介在性オートファジーと軸索輸送に着目した軸索ジストロフィーの病態解明

    Grant-in-Aid for Scientific Research(C)  2024

  • Elucidation of mechanism underlying toxicity resistance by human hepatocytes based on cell adhesion abnormality

    Grant-in-Aid for Challenging Research (Exploratory)  2024

  • Elucidating the mechanisms of intractable myelin disease using comparative pathological models

    Grant-in-Aid for Scientific Research(B)  2024

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Charge of on-campus class subject

  • 獣医病理学B

    2024   Weekly class   Undergraduate

  • 獣医病理診断学実習

    2024   Weekly class   Undergraduate

  • 小動物基礎臨床実習

    2024   Intensive lecture   Undergraduate

  • 自然科学特論

    2024   Intensive lecture   Graduate school

  • 毒性病理学

    2024   Intensive lecture   Undergraduate

  • 獣医科学英語演習

    2024   Intensive lecture   Undergraduate

  • 獣医病理組織学実習

    2024   Weekly class   Undergraduate

  • 獣医科学英語

    2024   Intensive lecture   Undergraduate

  • 獣医病理学A

    2024   Weekly class   Undergraduate

  • 生命環境科学概論

    2024   Intensive lecture   Undergraduate

  • 臨床基礎実習

    2024   Weekly class   Undergraduate

  • 学外特別実習

    2024   Intensive lecture   Undergraduate

  • 獣医病理学A

    2024   Weekly class   Undergraduate

  • 獣医病理組織学実習

    2024   Weekly class   Undergraduate

  • 獣医体験演習

    2024   Weekly class   Undergraduate

  • 獣医病理学B

    2024   Weekly class   Undergraduate

  • 生物学実験

    2024   Intensive lecture   Graduate school

  • 分子病理学特論

    2024   Intensive lecture   Graduate school

  • 統合生体学特別講義B

    2024   Intensive lecture   Graduate school

  • 先端獣医学研究法特別演習

    2024   Intensive lecture   Graduate school

  • 臨床基礎実習

    2024   Weekly class   Undergraduate

  • 学外特別実習

    2024   Intensive lecture   Undergraduate

  • 毒性病理学実習

    2024   Intensive lecture   Undergraduate

  • 疾患モデル動物学

    2024   Intensive lecture   Undergraduate

  • 獣医病理診断学実習

    2024   Weekly class   Undergraduate

  • Biology A

    2021    

  • Special Lecture: Integrated Structural Biosciences B

    2021    

  • Special Lecture: Animal Biotechnology

    2021    

  • Practice in Toxicologic Pathology

    2021   Practical Training  

  • Toxicologic Pathology

    2021    

  • Pathological Animal Model Science

    2021    

  • Veterinary Pathology A

    2021    

  • Veterinary Pathology B

    2021    

  • Introduction to Life, Environment, and Advanced Sciences

    2021    

  • Practice in Veterinary Pathological Diagnosis

    2021   Practical Training  

  • Biology B

    2021    

  • Basic clinical practices

    2021   Practical Training  

  • Practice in Veterinary Histopathology

    2021   Practical Training  

  • Veterinary English

    2021    

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Academic Activities

  • The Journal of Veterinary Medical Science誌 編集委員

    2014.04 - Now

  • 日本毒性病理学会誌(Journal of Toxicologic Pathology) 編集委員長

    2013.02 - Now

  • 日本実験動物学会 Experimental Animals誌 編集委員

    2017.05 - Now

  • Veterinary Pathology誌 Editor

    Role(s): Review, evaluation