Konnal Satoru

Faculty of Veterinary Medicine Veterinary Medicine Disease ControlProfessor
International Institute for Zoonosis ControlProfessor
Institute for Integrated Innovations Institute for Vaccine Research and DevelopmentProfessor
One Health Research CenterProfessor
Last Updated :2026/01/07

■Researcher basic information

Researchmap personal page

Research Keyword

  • 感染免疫
  • 臨床免疫
  • 腫瘍免疫
  • ウイルス学
  • 感染症学
  • マダニ
  • 節足動物媒介性疾患

Research Field

  • Life sciences, Veterinary medicine

Educational Organization

■Career

Career

  • Apr. 2025 - Present
    Hokkaido University, 国際感染症学院, 学院長
  • Jul. 2022 - Present
    北海道大学大学院獣医学研究院, 病原制御学分野, 教授
  • Jul. 2022 - Mar. 2025
    北海道大学大学院獣医学研究院, 先端創薬分野, 分野長・教授
  • Jul. 2018 - Jun. 2022
    北海道大学大学院獣医学研究院, 先端創薬分野, 分野長・准教授
  • Apr. 2017 - Jun. 2022
    北海道大学大学院獣医学研究院, 病原制御学分野, 准教授
  • Dec. 2008 - Mar. 2017
    Hokkaido University, Graduate School of Veterinary Medicine, 准教授
  • Apr. 2007 - Nov. 2008
    Hokkaido University, Graduate School of Veterinary Medicine, 助教
  • Dec. 2004 - Mar. 2007
    Hokkaido University, Graduate School of Veterinary Medicine, 助手

Educational Background

  • Mar. 2003, Hokkaido University, Graduate School of Veterinary Medicine

Committee Memberships

  • 2019 - Present
    農政推進協議会 家畜防疫対策緊急プロジェクト, 委員, Autonomy
  • 2015 - Present
    公益社団法人日本獣医学会, 国際会議組織委員会 委員, Society
  • 2014 - Present
    プロダクションメディスン研究会, 委員, Society
  • 2014 - Present
    大動物臨床研究会, 特別理事, Society
  • 2013 - Present
    北海道獣医師会, 牛白血病対策検討委員会 委員, Society
  • 2010 - Present
    動物用ワクチン-バイオ医薬品研究会, 幹事, Society
  • 2005 - 2010
    動物サイトカイン研究会, 事務局長, Society

■Research activity information

Awards

  • Dec. 2019, 農林水産省, 農業技術 2019年10大ニュース               
    牛白血病の新たな制御方法、抗ウイルス効果の確認に成功 -牛の難治性疾病に対する応用に期待-
    今内 覚
  • Jun. 2019, 伊藤記念財団, 第4回伊藤記念財団賞               
    今内 覚
  • Jan. 2017, 北海道大学, 平成28年度北海道大学研究総長賞               
    今内 覚
  • Sep. 2015, 日本獣医学会, 日本獣医学会賞               
    Satoru Konnal
  • Feb. 2014, 北海道, 平成25年度北海道科学技術奨励賞               
    今内 覚
  • Jun. 2005, 森永奉仕会, 森永奉仕会賞               
    今内覚
  • Oct. 2003, 日本獣医学会, 獣医学奨励賞               
    今内覚
  • Oct. 2003, 日本獣医学会, 日本獣医学会会長賞               
    今内覚

Papers

  • Clinical efficacy of anti-PD-L1 antibody HFC-L1/c4G12 in dogs with malignant tumors: an exploratory study               
    Takagi S., Tagawa M., Maekawa N., Konnai S., Kagawa Y., Hosoya K., Yamauchi A., Kudo A., Kamo S., Kim S., Kinoshita R., Deguchi T., Owaki R., Tachibana Y., Yokokawa M., Takeuchi H., Nakamura H., Kato Y., Kanazawa S., Abe T., Furuta T., Yamamoto K., Suzuki Y., Okagawa T., Murata S., Ohashi K.
    J Vet Med Sci., 87, 12, 1419, 1425, Dec. 2025, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Enhancement of Vaccine-Induced T-cell Responses by Probiotics in Calves               
    Ikehata M., Okagawa T., Nakamura H., Maekawa N., Suzuki Y., Murata D., Ohashi K., Konna S.
    Vaccines, 13, 11, 1120, Oct. 2025, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Development of a multiplex real-time PCR assay for bovine immunodeficiency virus and bovine leukemia virus and its application to a large-scale survey in Kyushu, Japan               
    Yamamoto M., Okagawa T., Konnai S., Mekata H.
    J Vet Med Sci., 87, 10, 1164, 1169, Oct. 2025, [Peer-reviewed]
    English, Scientific journal
  • Two distinct polymorphisms in the basic region of Meq protein of marek's disease virus alter pathological progression and clinical manifestations               
    Sato J., Kurokawa A., Motai Y., Yamagami S., Win SY, Horio F., Saeki H., Maekawa N., Okagawa T., Kaufer BB, Osterrieder N., Parcells MS, Konnai S., Ohashi K., Murata S.
    Virol J., 22, 1, 303, Sep. 2025, [Peer-reviewed]
    English, Scientific journal
  • Genetic diversity and phylogenetic relationships among western and Asian honey bees, and Eristalis tenax collected in Myanmar               
    Bawm S., Khaing A.P.P., Oo H.M., Mu M.M., Hmuu N.C., Zaw A.N.S., Lwin N., Chel H.M., Khaing Y., Win S.Y., Htun L.L., Murata S., Konnai S., Ohashi K., Nonaka N., Nakao R., Tun T. N.
    J Asia Pac Entomol., in press, Sep. 2025, [Peer-reviewed]
    English, Scientific journal
  • Rhipicephalus microplus triosephosphate isomerase dimer interface is stabilized by a key cysteine residue               
    Saramago L., Cabrera N., Aguirre B., Gomes H., Moraes B., Itabajara da S.V., Marques M.A., Silva J.L., Okagawa T., Konnai S., Montfor R.P., Logullo C., Moraes J.
    Biochim Biophys Acta Gen Subj., 1869, 12, 130857, Sep. 2025, [Peer-reviewed]
    English, Scientific journal
  • Exploratory, randomized, dose-response study of the anti-PD-L1 antibody HFC-L1/c4G12 in dogs with pulmonary metastatic oral malignant melanoma               
    Hosoya K., Kim S., Kinoshita R., Maekawa N., Konnai S., Takagi S., Tagawa M., Kagawa Y., Deguchi T., Owaki R., Tachibana Y., Yokokawa M., Takeuchi H., Nakamura H., Yamauchi A., Kudo A., Kamo S., Kato Y., Kanazawa S., Abe T., Furuta T., Yamamoto K., Suzuki Y., Okagawa T., Murata S., Ohashi K.
    Vet Sci., 12, 9, 850., Sep. 2025, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • Evaluation of PD-L1 and TIM-3 pathways in T cells during experimental bovine leukemia virus infection in sheep               
    Tiyamanee W., Okagawa T., Yamada S., Ikehata M., Nakamura H., Inoue M., Maekawa N., Kato Y., Murata S., Ohashi K., Murakami K., Konnai S.
    Vet Sci., 12, 9, 810, Aug. 2025, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • Amino acid insertion in the Meq protein of Marek's disease virus, an avian oncogenic herpesvirus, accelerates tumorigenesis               
    Sato J., Murata S., Motai Y., Win SY, Seo H., Yamagami S., Maekawa N., Okagawa T., Konnai S., Ohashi K.
    Microbiol Spectr., 13, 8, e0336824, Aug. 2025, [Peer-reviewed]
    English, Scientific journal
  • Development of Blood-Brain Barrier-Penetrating Antibodies for Neutralizing Tick-Borne Encephalitis Virus in the Brain               
    Fukuta M., Fukano S., Maekawa N., Kobayashi S., Okamoto S., Hirano M., Nio-Kobayashi J., Kariwa H., Kawakami S., Konnai S., Yoshii K.
    mSphere, 10, 7, e0018425., Jul. 2025, [Peer-reviewed]
    English, Scientific journal
  • Amino Acid Polymorphisms in the Basic Region of Meq of Vaccine Strain CVI988 Drastically Diminish the Virulence of Marek's Disease Virus               
    Sato J., Motai Y., Yamagami S., Kurokawa A., Win SY, Horio F., Saeki H., Maekawa N., Okagawa T., Konnai S., Ohashi K., Murata S.
    Viruses, 17, 7, 907, Jun. 2025, [Peer-reviewed]
    English, Scientific journal
  • Comprehensive Analysis of Immune Checkpoint Molecules Profiles Phenotype and Function of Exhausted T Cells in Enzootic Bovine Leukosis               
    Nakamura H, Konnai S, Okagawa T, Maekawa N, Tiyamanee W, Ikehata M, Matsubara M, Watari K, Kamitani K, Saito M, Kato Y, Suzuki Y, Murata S, Ohashi K.
    J. Immunol., 214, 10, 2600, 2616, 27 May 2025, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • Development of caninized anti-CTLA-4 antibody as salvage combination therapy for anti-PD-L1 refractory tumors in dogs               
    Maekawa N., Konnai S., Watari K., Takeuchi H., Nakanishi T., Tachibana T., Hosoya K., Kim S., Kinoshita R., Owaki R., Yokokawa M., Kagawa Y., Takagi S., Deguchi T., Ohta, Kato Y., Yamamoto S., Yamamoto K., Suzuki Y., Okagawa T., Murata S., Ohashi K.
    Front Immunol., 16, 1570717, 20 May 2025, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • Genomic characteristics and distinctive genetic polymorphisms of Marek's disease virus strains circulating in Japan.
    Shunsuke Yamagami, Jumpei Sato, Yoshinosuke Motai, Naoya Maekawa, Tomohiro Okagawa, Satoru Konnai, Kazuhiko Ohashi, Shiro Murata
    The Journal of veterinary medical science, 87, 5, 517, 531, 15 May 2025, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, Marek's disease virus (MDV) is an oncogenic herpesvirus that causes malignant lymphomas in chickens (Marek's disease, MD). Although MD is currently well controlled by vaccination, field strains of MDV tend to increase in virulence, and sporadic outbreaks have been reported worldwide, including in Japan. Previously, we determined the whole-genome sequence of a Japanese MDV strain, Kgs-c1, isolated in 2014, and analyzed its genetic characteristics. However, to date, Kgs-c1 is the only MDV strain that has been subjected to whole-genome sequencing, leaving the possibility that the key genetic features of the Japanese strains remain undiscovered. Therefore, we conducted whole-genome sequencing of two MDV strains, Kgs-c2 and Sg-c1, isolated in 2016 and 2019, respectively, and analyzed their genetic characteristics. Consistent with our previous findings, the genomic sequences of the Japanese strains were classified into the Eurasian cluster, suggesting that the Japanese strains are genetically closer to the European and Chinese strains than they are to the US strains. In contrast, the Japanese strains exhibited genetic features different from those of pathogenic European and Chinese strains. Furthermore, polymorphisms in the meq and infected cell protein 4 (ICP4) genes, which are candidates involved in the enhanced virulence of MDV, were observed among the newly isolated strains and Kgs-c1. Thus, three MDV strains isolated in Japan had different genetic features from those in other countries. These findings emphasize the necessity of periodic monitoring of MDV field strains in order to determine shifts in their characteristics and effectively control MD.
  • Performance evaluation of an improved RAISING method for clonality analysis of bovine leukemia virus-infected cells: a collaborative study in Japan               
    Okagawa T., Nojiri N., Yoshida-Furihata H., Nao N., Tominaga M., Kohara J., Gondaira S., Higuchi H., Takeda Y., Ogawa H., Yamada S., Murakami K., Suzuki Y., Takai S., Maezawa M., Inokuma H., Shimizu K., Inoshima Y., Usui T., Tagawa M., Yamamoto M., Mekata H., Esaki M., Ozawa M., Matsudaira T., Maekawa N., Murata S., Ohashi K., Saito M., Konnai S.
    J. Vet. Med. Sci., 87, 5, 551, 558, 15 May 2025, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Programmed Cell Death-1 Expression in T-Cell Subsets in Chickens Infected with Marek's Disease Virus               
    Sato J., Motai Y., Yamagami S., Win SY, Horio F., Saeki H., Maekawa N., Okagawa T., Konnai S., Ohashi K., Murata S.
    Pathogens, 14, 5, 431, 29 Apr. 2025, [Peer-reviewed]
    English, Scientific journal
  • Characterization of a lipocalin-like molecule from Dermanyssus gallinae as a potential vaccine antigen.
    Fumiya Horio, Hikari Seo, Shwe Yee Win, Jumpei Sato, Yoshinosuke Motai, Shunsuke Yamagami, Takumi Sato, Eiji Ohishi, Naoya Maekawa, Tomohiro Okagawa, Satoru Konnai, Kazuhiko Ohashi, Shiro Murata
    Veterinary immunology and immunopathology, 283, 110921, 110921, 24 Mar. 2025, [International Magazine]
    English, Scientific journal, Poultry red mites (PRMs, Dermanyssus gallinae) are hematophagous ectoparasites of chickens that pose a significant threat to the egg-laying industry. The emergence of acaricide-resistant PRMs raises the demand for alternative control approaches such as vaccination. However, several vaccine antigens have failed to suppress the growth of PRM populations in field trials due to difficulties in maintaining antibody levels. In ticks, the molecules exposed to the host, such as lipocalins, can facilitate antibody production, and are therefore considered advantageous as vaccine antigens. Therefore, we focused on a lipocalin-like molecule (Dg-Lipocalin) identified from an RNA-seq analysis reported by Fujisawa et al. (2020) and analyzed its exposure to the host and potential as a vaccine antigen. Western blotting using 500-fold diluted plasma of chickens from PRM-contaminated farms revealed the presence of antibodies against Dg-Lipocalin, suggesting its exposure to the host. To evaluate its potential as a vaccine antigen, PRMs were artificially fed immune plasma with 32,000- to 64,000-fold antibody titers or plasma from PBS-inoculated control chickens, and their mortality was observed for 7 days. In experiment 1, the immune plasma significantly increased PRM mortality compared to the control plasma. However, these effects were not observed in experiment 2, although the total mortality was significantly increased in immune plasma-fed PRMs. Thus, the efficacy of Dg-Lipocalin appears to be limited; however, its exposure to the host may result in sustained antibody titers. Further investigation is required to evaluate its feasibility.
  • Enhancement of radio-sensitivity by inhibition of Janus kinase signaling with oclacitinib in canine tumor cell lines.
    Ryo Owaki, Kenji Hosoya, Tatsuya Deguchi, Satoru Konnai, Naoya Maekawa, Tomohiro Okagawa, Hironobu Yasui, Sangho Kim, Takafumi Sunaga, Masahiro Okumura
    Molecular therapy. Oncology, 33, 1, 200946, 200946, 20 Mar. 2025, [International Magazine]
    English, Scientific journal, A combination of irradiation and oclacitinib, a Janus kinase (JAK) inhibitor used in dogs, could lead to synergistic anticancer effects in canine tumors. However, the anti-tumor effects of oclacitinib remain unclear. This study investigated the radio-sensitizing effect of oclacitinib in canine tumors and determined its underlying mechanisms using osteosarcoma (HMPOS), malignant melanoma (CMeC), and thyroid adenocarcinoma (CTAC) cell lines. A clonogenic assay and a tumor growth assessment in a xenograft mouse model (BALB/cAJcl-nu/nu) were performed to evaluate the radio-sensitizing effects of oclacitinib. Oclacitinib enhanced the radio-sensitivity of tumor cells both in vitro and in vivo. The signal transducer and activator of transcription (STAT)3 expression was activated and suppressed by oclacitinib in X-irradiation-exposed cells. Oclacitinib enhanced radiation-induced apoptosis only in HMPOS cells by inhibiting anti-apoptotic genes. In addition, oclacitinib inhibited the transcription of cell-cycle-regulating genes and arrested cell cycle progression from the G1 phase to subsequent phases. In conclusion, oclacitinib enhanced radio-sensitivity both in vitro and in vivo by triggering apoptosis and impeding cell cycle progression via STAT3 inhibition in canine tumor cell lines. This study suggested the clinical therapeutic potential of oclacitinib and radiation therapy in enhancing treatment efficacy and outcomes in canine tumors.
  • Host Skin during Tick Infestation: Unearthing the Local Immunity to Lead an Anti-Tick Vaccine               
    Joao BC, Parizi LF, Zhou J., Konnai S., Termignoni C., da Silva Vaz I J.
    Acta Scientiae Veterinariae, 53, 1982, Mar. 2025, [Peer-reviewed]
    English, Scientific journal
  • Potential of histamine release factor for the utilization as a universal vaccine antigen against poultry red mites, tropical fowl mites, and northern fowl mites.
    Shwe Yee Win, Fumiya Horio, Jumpei Sato, Yoshinosuke Motai, Hikari Seo, Sotaro Fujisawa, Takumi Sato, Eiji Oishi, Lat Lat Htun, Saw Bawm, Tomohiro Okagawa, Naoya Maekawa, Satoru Konnai, Kazuhiko Ohashi, Shiro Murata
    The Journal of veterinary medical science, 87, 1, 1, 12, 01 Jan. 2025, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, Poultry red mites (PRMs, Dermanyssus gallinae), tropical fowl mites (TFMs, Ornithonyssus bursa), and northern fowl mites (NFMs, Ornithonyssus sylviarum) are hematophagous mites that are distributed worldwide which pose a serious challenge to the poultry industry and negatively impact poultry production and welfare. Vaccines represent a promising approach for controlling avian mites, and the identification of antigens with broad efficacy against multiple avian mite species is advantageous for vaccine control. This study aimed to identify histamine release factor (HRF), which was previously reported as a candidate vaccine antigen against PRMs, from TFMs and NFMs and to analyze its cross-reactivity and acaricidal effects on different avian mite species. The deduced amino acid sequences of the HRFs identified in the TFMs and NFMs were highly homologous to those of the PRMs. We generated recombinant HRF (rHRF) of TFMs, NFMs, and PRMs, and immune plasma against each rHRF was produced by immunization with each antigen. The immune plasma contained antibodies specific to each antigen and showed cross-reactivity with rHRFs from different avian mites. Moreover, PRM nymphs (protonymphs) artificially fed each immune plasma showed higher mortality rates than those fed the control plasma. These results suggest that HRFs can be used as candidate antigens for a universal vaccine with broad efficacy across avian mites.
  • Starvation Metabolism Adaptations in Tick Embryonic Cells BME26               
    Nogueira CL, Arcanjo AF, Lima ME, Moraes B., da Silva RM, Gondim KC, Konnai S., Ramos I., Santos S., Filardy AD, Pinto KG, Vaz Junior IDS, Logullo C.
    Int J Mol Sci., 26, 1, 87, Dec. 2024, [Peer-reviewed]
    English
  • Effect of C-to-T transition at CpG sites on tumor suppressor genes in tumor development in cattle evaluated by somatic mutation analysis in enzootic bovine leukosis               
    Nishimori A, Andoh K, Matsuura Y, Okagawa T, Konnai S
    mSphere, e0021624, Oct. 2024, [Peer-reviewed], [Last author]
    English, Scientific journal
  • 子牛における地方病性牛伝染性リンパ腫発症は母牛由来の腫瘍細胞が原因か?               
    廣瀬 海凪, 今内 覚, 岡川 朋弘, 富永 みその, 松原 幸芽, 前川 直也, 村田 史郎, 大橋 和彦
    北海道獣医師会雑誌, 68, 8, 278, 278, (公社)北海道獣医師会, Aug. 2024
    Japanese
  • An Ixodes persulcatus inhibitor of plasmin and thrombin hinders keratinocyte migration, blood coagulation, and endothelial permeability.               
    Berger M, Rosa da Mata S, Pizzolatti NM, Parizi LF, Konnai S, da Silva Vaz I Jr, Seixas A, Tirloni L
    J Invest Dermatol., 144, 5, 1112, 1123, May 2024, [Peer-reviewed]
    English
  • Chimeric provirus of bovine leukemia virus/ SMAD family member 3 in cattle with enzootic bovine leukosis               
    Nao N, Okagawa T, Nojiri N, Konnai S, Shimakura H, Tominaga M, Yoshida-Frihata H, Nishiyama E, Matsudaira T, Maekawa N, Murata S, Muramatsu M, Ohashi K, Saito M
    Archi Virol., 169, 3, 47, Feb. 2024, [Peer-reviewed]
    English, Scientific journal
  • In Vivo Characterization of the Anti-Glutathione S-Transferase Antibody Using an In Vitro Mite Feeding Model               
    Win SY, Seo H, Horio F, Fujisawa S, Sato J, Motai Y, Sato T, Oishi E, Taneno A, Htun LL, Bawn S, Okagawa T, Maekawa N, Konnai S, Ohashi K, Murata S
    Vaccines (Basel), 12, 2, 148, Jan. 2024, [Peer-reviewed]
    English, Scientific journal
  • Characterization of a Very Short Meq Protein Isoform in a Marek's Disease Virus Strain in Japan               
    Motai Y, Murata S, Sato J, Nishi A, Maekawa N, Okagawa T, Konnai S, Ohashi K
    Vet Sci., 11, 1, 43, Jan. 2024, [Peer-reviewed]
    English, Scientific journal
  • G6PDH as a key immunometabolic and redox trigger in arthropods               
    Moraes B, Martins R, Lopes C, Martins R, Arcanjo A, Nascimento J, Konnai S, da Silva Vaz I Jr, Logullo C
    Front Physiol., 14, 1287090, Nov. 2023, [Peer-reviewed]
    English, Scientific journal
  • Safety and clinical efficacy of an anti-PD-L1 antibody (c4G12) in dogs with advanced malignant tumours
    Maekawa N, Konnai S, Hosoya K, Kim S, Kinoshita R, Deguchi T, Owaki R, Tachibana Y, Yokokawa M, Takeuchi H, Kagawa Y, Takagi S, Ohta H, Kato Y, Yamamoto S, Yamamoto K, Suzuk Y, Okagawa T, Murata S, Ohashi K
    PLOS ONE, 18, 10, e0291727, Oct. 2023, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Immune checkpoint inhibitors (ICIs) have been developed for canine tumour treatment, and pilot clinical studies have demonstrated their antitumour efficacy in dogs with oral malignant melanoma (OMM). Although ICIs have been approved for various human malignancies, their clinical benefits in other tumour types remain to be elucidated in dogs. Here, we conducted a clinical study of c4G12, a canine chimeric anti-PD-L1 antibody, to assess its safety and efficacy in dogs with various advanced malignant tumours (n = 12) at the Veterinary Teaching Hospital of Hokkaido University from 2018 to 2023. Dogs with digit or foot pad malignant melanoma (n = 4), osteosarcoma (n = 2), hemangiosarcoma (n = 1), transitional cell carcinoma (n = 1), nasal adenocarcinoma (n = 1), B-cell lymphoma (n = 1), or undifferentiated sarcoma (n = 2) were treated with 2 or 5 mg/kg c4G12 every 2 weeks. Treatment-related adverse events of any grade were observed in eight dogs (66.7%), including elevated aspartate aminotransferase (grade 3) in one dog (8.3%) and thrombocytopenia (grade 4) in another dog (8.3%). Among dogs with target disease at baseline (n = 8), as defined by the response evaluation criteria for solid tumours in dogs (cRECIST), one dog with nasal adenocarcinoma and another with osteosarcoma experienced a partial response (PR), with an objective response rate of 25.0% (2 PR out of 8 dogs; 95% confidence interval: 3.2-65.1%). These results suggest that c4G12 is safe and tolerable and shows antitumor effects in dogs with malignant tumours other than OMM. Further clinical studies are warranted to identify the tumour types that are most likely to benefit from c4G12 treatment.
  • Development of a high-affinity anti-bovine PD-1 rabbit–bovine chimeric antibody using an efficient selection and large production system
    Okagawa T, Konnai S, Goto S, Sajiki Y, Ganbaatar O, Watari K, Nakamura H, Wang CX, Tachibana T, Kato Y, Kameda Y, Kohara J, Terasaki N, Kubota M, Takeda A, Takahashi H, Suzuki Y, Maekawa N, Murata S, Ohashi K
    Vet Res., 54, 1, 82, 82, Sep. 2023, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Immune checkpoint molecules PD-1/PD-L1 cause T-cell exhaustion and contribute to disease progression in chronic infections of cattle. We established monoclonal antibodies (mAbs) that specifically inhibit the binding of bovine PD-1/PD-L1; however, conventional anti-PD-1 mAbs are not suitable as therapeutic agents because of their low binding affinity to antigen. In addition, their sensitivity for the detection of bovine PD-1 is low and their use for immunostaining PD-1 is limited. To address these issues, we established two anti-bovine PD-1 rabbit mAbs (1F10F1 and 4F5F2) and its chimeric form using bovine IgG1 (Boch1D10F1), which exhibit high binding affinity. One of the rabbit mAb 1D10F1 binds more strongly to bovine PD-1 compared with a conventional anti-PD-1 mAb (5D2) and exhibits marked inhibitory activity on the PD-1/PD-L1 interaction. In addition, PD-1 expression in bovine T cells could be detected with higher sensitivity by flow cytometry using 1D10F1. Furthermore, we established higher-producing cells of Boch1D10F1 and succeeded in the mass production of Boch1D10F1. Boch1D10F1 exhibited a similar binding affinity to bovine PD-1 and the inhibitory activity on PD-1/PD-L1 binding compared with 1D10F1. The immune activation by Boch1D10F1 was also confirmed by the enhancement of IFN-γ production. Finally, Boch1D10F1 was administered to bovine leukemia virus-infected cows to determine its antiviral effect. In conclusion, the high-affinity anti-PD-1 antibody developed in this study represents a powerful tool for detecting and inhibiting bovine PD-1 and is a candidate for PD-1-targeted immunotherapy in cattle.
  • Characterization of cysteine proteases from poultry red mite, tropical fowl mite, and northern fowl mite to assess the feasibility of developing a broadly efficacious vaccine against multiple mite species
    Win SY, Murata S, Fujisawa S, Seo H, Sato J, Motai Y, Sato T, Oishi E, Taneno A, Htun LL, Bawm S, Okagawa T, Maekawa N, Konnai S, Ohashi K
    PLoS One, 18, 7, e0288565, Jul. 2023, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Infestation with poultry red mites (PRM, Dermanyssus gallinae) causes anemia, reduced egg production, and death in serious cases, resulting in significant economic losses to the poultry industry. As a novel strategy for controlling PRMs, vaccine approaches have been focused upon and several candidate vaccine antigens against PRMs have been reported. Tropical (TFM, Ornithonyssus bursa) and northern (NFM, Ornithonyssus sylviarum) fowl mites are also hematophagous and cause poultry industry problems similar to those caused by PRM. Therefore, ideal antigens for anti-PRM vaccines are molecules that cross-react with TFMs and NFMs, producing pesticidal effects similar to those against PRMs. In this study, to investigate the potential feasibility of developing vaccines with broad efficacy across mite species, we identified and characterized cysteine proteases (CPs) of TFMs and NFMs, which were previously reported to be effective vaccine antigens of PRMs. The open reading frames of CPs from TFMs and NFMs had the same sequences, which was 73.0% similar to that of PRMs. Phylogenetic analysis revealed that the CPs of TFMs and NFMs clustered in the same clade as CPs of PRMs. To assess protein functionality, we generated recombinant peptidase domains of CPs (rCP-PDs), revealing all rCP-PDs showed CP-like activities. Importantly, the plasma obtained from chickens immunized with each rCP-PD cross-reacted with rCP-PDs of different mites. Finally, all immune plasma of rCP-PDs reduced the survival rate of PRMs, even when the plasma was collected from chickens immunized with rCP-PDs derived from TFM and NFM. Therefore, CP antigen is a promising, broadly efficacious vaccine candidate against different avian mites.
  • Enhanced systemic antitumour immunity by hypofractionated radiotherapy and anti-PD-L1 therapy in dogs with pulmonary metastatic oral malignant melanoma
    Deguchi T, Maekawa N, Konnai S, Owaki R, Hosoya K, Morishita K, Nakamura M, Okagawa T, Takeuchi H, Kim S, Kinoshita R, Tachibana Y, Yokokawa M, Takagi S, Kato Y, Suzuk Y, Murata S, Ohashi K
    Cancers, 15, 11, 3013, Jun. 2023, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Although immune checkpoint inhibitors (ICIs), such as the anti-programmed death-ligand 1 (PD-L1) antibody, have been developed for the treatment of canine malignant melanoma, desirable clinical efficacies have not been achieved. Recent studies in humans have suggested that radiation therapy (RT) combined with ICIs induces robust systemic antitumour immunity in patients with cancer. This study retrospectively examined the therapeutic efficacy of combination therapy (hypofractionated RT and anti-PD-L1 antibody [c4G12]) in dogs with pulmonary metastatic oral malignant melanoma. The intrathoracic clinical benefit rate (CBR)/median overall survival (OS) in the no RT (n = 20, free from the effect of RT), previous RT (n = 9, received RT ≤8 weeks prior to the first c4G12 dose), and concurrent RT (n = 10, c4G12 therapy within ±1 week of the first RT fraction) groups were 10%/185 days, 55.6%/283.5 days (p < 0.05 vs. no RT group), and 20%/129 days (p > 0.05 vs. no RT group), respectively. The adverse events were considered to be tolerable in the combination therapy. Thus, hypofractionated RT before the initiation of c4G12 therapy can be an effective approach for enhancing the therapeutic efficacy of immunotherapy, with acceptable safety profiles. Further prospective clinical studies are required to confirm the findings of this study.
  • Molecular characterization of immunoinhibitory factors PD-1/PD-L1 in sheep
    Tiyamanee W, Konnai S, Okagawa T, Nojima Y, Ganbaatar O, Maekawa N, Hasebe R, Kagawa Y, Kato Y, Suzuki Y, Murata S, Ohashi K
    Vet Immunol Immunopathol., 11, 261, 110609, 110609, May 2023, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Sheep have been used as a large animal experimental model for studying infectious diseases. However, due to a lack of staining antibodies and reagents, immunological studies on sheep have not progressed. The immunoinhibitory receptor programmed death-1 (PD-1) is expressed on T lymphocytes. The interaction of PD-1 with its ligand PD-ligand 1 (PD-L1) delivers inhibitory signals and impairs proliferation, cytokine production, and cytotoxicity of T cells. We previously reported that the PD-1/PD-L1 pathway was closely associated with T-cell exhaustion and disease progression in bovine chronic infections using anti-bovine PD-L1 monoclonal antibodies (mAbs). Furthermore, we found that blocking antibodies against PD-1 and PD-L1 restore T-cell functions and could be used in immunotherapy of cattle. However, the immunological role of the PD-1/PD-L1 pathway in chronic diseases of sheep remains unknown. In this study, we identified cDNA sequences of ovine PD-1 and PD-L1 and examined the cross-activity of anti-bovine PD-L1 mAbs against ovine PD-L1 as well as the expression of PD-L1 in ovine listeriosis. The amino acid sequences of ovine PD-1 and PD-L1 share a high degree of identity and similarity with homologs from ruminants and other mammalian species. Anti-bovine PD-L1 mAb recognized ovine PD-L1 on lymphocytes in the flow cytometric assay. Furthermore, an immunohistochemical staining confirmed the PD-L1 expression on macrophages in the brain lesions of ovine listeriosis. These findings indicated that our anti-PD-L1 mAb would be useful for analyzing the ovine PD-1/PD-L1 pathway. Further research is needed to determine the immunological role of PD-1/PD-L1 in chronic diseases such as BLV infection through experimental infection of sheep.
  • Analysis of gene expression in poultry red mite, Dermanyssus gallinae, by RNAscope in situ hybridization
    Seo H, Murata S, Ichii O, Namba T, Win SY, Sato T, Oishi E, Taneno A, Maekawa N, Okagawa T, Konnai S, Ohashi K
    J Vet Med Sci., 85, 5, 532, 535, May 2023, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, The poultry red mite (PRM; Dermanyssus gallinae) is a hematophagous ectoparasite that mainly infests chickens, and its infestation causes significant economic losses to the poultry industry. In this study, we examined the use of RNAscope-based in situ hybridization (ISH) to characterize gene expression in PRM. We analyzed the mRNA expression of Dermanyssus gallinaecathepsin D-1 (Dg-CatD-1) and Dermanyssus gallinae cystatin (Dg-Cys). RNAscope ISH analysis revealed that mRNA expression of Dg-CatD-1 was observed in the digestive tract, and Dg-Cystatin mRNA was expressed in the ovaries in addition to the digestive tract. RNAscope ISH could be applicable for the analysis of gene expression in each tissue of PRM and is an effective method to investigate the characteristics of target genes.
  • Investigation of peripheral blood responses in chickens infested with Dermanyssus gallinae
    Fujisawa S, Murata S, Sato T, Oishi E, Taneno A, Konnai S, Ohashi K
    Parasitol Int., 95, 102754, 102754, Apr. 2023, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Among haematophagous ectoparasites that infest chickens, poultry red mite (Dermanyssus gallinae, PRM) is one of the most serious threats to poultry farms. Mass PRM infestation causes various health problems in chickens, resulting in significant productivity reduction in the poultry industry. Despite the efficiency of acaricides for controlling PRMs, the emergence of acaricide-resistant PRMs represents a challenging setback. Infestation with haematophagous ectoparasites, such as PRMs, induces inflammatory and haemostatic reactions in the host. Therefore, we aimed to explore the gene expression in chicken peripheral blood cells to elucidate host responses against PRM infestation in detail. RNA sequencing of blood-fed PRMs was performed, and the levels of the chicken-derived transcripts obtained from the ingested blood cells were analysed. Genes encoding haemoglobin subunits were found to be significantly more expressed, suggesting that PRM infestation causes anaemia in chickens. Additionally, the mRNA and plasma concentrations of CC chemokine ligand 4 and β2 microglobulin among the immune-related molecules were found to be significantly higher in PRM-infested chickens compared with non-infested animals. These results suggest that PRM infestation induce inflammation in chicken. Further studies are warranted to better understand the influence of PRM infestation on the host physiological states, including immunity.
  • Potential of ferritin 2 as an antigen for the development of a universal vaccine for avian mites, poultry red mites, tropical fowl mites, and northern fowl mites
    Win SY, Murata S, Fujisawa S, Seo H, Sato J, Motai Y, Sato T, Oishi E, Taneno A, Htun LL, Bawn S, Okagawa T, Maekawa N, Konnai S, Ohashi K
    Front Vet Sci., 10, 1182930, 1182930, Apr. 2023, [Peer-reviewed], [International Magazine]
    English, Scientific journal, INTRODUCTION: Poultry red mites (PRMs, Dermanyssus gallinae), blood-sucking ectoparasites, are a threat to the poultry industry because of reduced production caused by infestation. In addition, tropical fowl mites (TFMs, Ornithonyssus bursa) and northern fowl mites (NFMs, Ornithonyssus sylviarum) are hematophagous, distributed in various regions, genetically and morphologically close to PRMs, and cause similar problems to the poultry industry. Vaccine approaches have been studied for PRM control, and several molecules have been identified in PRMs as candidates for effective vaccine antigens. The development of an anti-PRM vaccine as a universal vaccine with broad efficacy against avian mites could improve the productivity of poultry farms worldwide. Molecules that are highly conserved among avian mites and have critical functions in the physiology and growth of mites could be ideal antigen candidates for the development of universal vaccines. Ferritin 2 (FER2), an iron-binding protein, is critical for the reproduction and survival of PRMs and has been reported as a useful vaccine antigen for the control of PRMs and a candidate for the universal vaccine antigen in some tick species. METHOD AND RESULTS: Herein, we identified and characterized FER2 in TFMs and NFM. Compared with the sequence of PRM, the ferroxidase centers of the heavy chain subunits were conserved in FER2 of TFMs and NFMs. Phylogenetic analysis revealed that FER2 belongs to clusters of secretory ferritins of mites and other arthropods. Recombinant FER2 (rFER2) proteins from PRMs, TFMs, and NFMs exhibited iron-binding abilities. Immunization with each rFER2 induced strong antibody responses in chickens, and each immune plasma cross-reacted with rFER2 from different mites. Moreover, mortality rates of PRMs fed with immune plasma against rFER2 from TFMs or NFMs, in addition to PRMs, were higher than those of control plasma. DISCUSSION: rFER2 from each avian mite exhibited anti-PRM effects. This data suggests that it has the potential to be used as an antigen candidate for a universal vaccine against avian mites. Further studies are needed to access the usefulness of FER2 as a universal vaccine for the control of avian mites.
  • In vitro evaluation of Lactiplantibacillus plantarum HOKKAIDO strain, effective lactic acid bacteria for calf diarrhea
    Ikehata M, Konnai S, Okagawa T, Abe K, Honma M, Kitamura T, Maekawa N, Suzuki Y, Murata S, Ohashi K
    Front Vet Sci., 10, 1145445, Apr. 2023, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Calf diarrhea adversely affects growth and sometimes results in mortality, leading to severe economic losses to the cattle industry. Antibiotics are useful in the treatment against bacterial diarrhea, but not against viral, protozoan, and antibiotic-resistant bacterial diarrhea. Therefore, there are growing requirements for a novel control method for calf diarrhea. Probiotics have been considered promising candidates for preventive and supportive therapy for calf diarrhea for many years. A recent study has revealed that Lactiplantibacillus plantarum HOKKAIDO strain (Lp-HKD) reduces intestinal pathology and the severity of diarrhea in bovine rotavirus (BRV)-infected calves. Lp-HKD is known to enhance the function of human immune cells and expected to be used as probiotics for humans. Therefore, it is hypothesized that Lp-HKD modulates antiviral immune response in cattle and provide the clinical benefits in BRV-infected calves. However, the detailed mechanism of Lp-HKD-induced immunomodulation remains unknown. Thus, this study aimed to elucidate the immunomodulatory and antiviral effects of Lp-HKD in cattle. Cultivation assay of bovine peripheral blood mononuclear cells (PBMCs) showed that live and heat-killed Lp-HKD stimulates the production of interleukin-1β (IL-1β), IL-6, IL-10, and interferon-γ (IFN-γ) from PBMCs. Stimulation by heat-killed Lp-HKD yielded stronger cytokine production than stimulation by the live Lp-HKD. Additionally, CD14+ monocytes were identified as major producers of IL-1β, IL-6, and IL-10 under Lp-HKD stimulation; however, IFN-γ was mainly produced from immune cells other than CD14+ monocytes. Depletion of CD14+ monocytes from the PBMCs cultivation strongly decreased cytokine production induced by heat-killed Lp-HKD. The inhibition of toll-like receptor (TLR) 2/4 signaling decreased IL-1β and IL-6 production induced by live Lp-HKD and IL-1β, IL-6, and IFN-γ production induced by heat-killed Lp-HKD. Furthermore, live or heat-killed Lp-HKD also activated T cells and their production of IFN-γ and tumor necrosis factor-α. Then, culture supernatants of bovine PBMCs treated with heat-killed Lp-HKD demonstrated antiviral effects against BRV in vitro. In conclusion, this study demonstrated that Lp-HKD activates the functions of bovine immune cells via TLR2/4 signaling and exerts an antiviral effect against BRV through the induction of antiviral cytokines. Lp-HKD could be useful for the prevention and treatment of calf diarrhea through its immune activating effect.
  • Enhancement of vaccine-induced T-cell responses by PD-L1 blockade in calves
    Okagawa T, Konnai S, Nakamura H, Ganbaatar O, Sajiki Y, Watari K, Noda H, Honma M, Kato Y, Suzuki Y, Maekawa N, Murata S, Ohashi K
    Vaccines, 11, 3, 559, Mar. 2023, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Interactions between programmed death 1 (PD-1) and PD-ligand 1 (PD-L1) cause functional exhaustion of T cells by inducing inhibitory signals, thereby attenuating effector functions of T cells. We have developed an anti-bovine PD-L1 blocking antibody (Ab) and have demonstrated that blockade of the interaction between PD-1 and PD-L1 reactivates T-cell responses in cattle. In the present study, we examined the potential utility of PD-1/PD-L1-targeted immunotherapy in enhancing T-cell responses to vaccination. Calves were inoculated with a hexavalent live-attenuated viral vaccine against bovine respiratory infections in combination with treatment with an anti-PD-L1 Ab. The expression kinetics of PD-1 in T cells and T-cell responses to viral antigens were measured before and after vaccination to evaluate the adjuvant effect of anti-PD-L1 Ab. PD-1 expression was upregulated in vaccinated calves after the administration of a booster vaccination. The activation status of CD4+, CD8+, and γδTCR+ T cells was enhanced by the combination of vaccination and PD-L1 blockade. In addition, IFN-γ responses to viral antigens were increased following combinatorial vaccination with PD-L1 blockade. In conclusion, the blockade of the PD-1/PD-L1 interaction enhances T-cell responses induced by vaccination in cattle, indicating the potential utility of anti-PD-L1 Ab in improving the efficacy of current vaccination programs.
  • Regulation of programmed death ligand 1 expression by interferon-γ and tumour necrosis factor-α in canine tumour cell lines
    Owaki R, Deguchi T, Konnai S, Maekawa N, Okagawa T, Hosoya K, Kim S, Sunaga T, Okumura M
    Vet Comp Oncol., 1, 12, 21 Feb. 2023, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Expression of programmed death ligand 1 (PD-L1) on tumor cells provides an immune evasion mechanism by inducing suppression of cytotoxic T cells. Various regulatory mechanisms of PD-L1 expression have been described in human tumours, however, little is known in canine tumours. To investigate whether inflammatory signaling is involved in PD-L1 regulation in canine tumours, the effects of interferon (IFN)-γ and tumour necrosis factor (TNF)-α treatment were examined in canine malignant melanoma cell lines (CMeC and LMeC) and an osteosarcoma cell line (HMPOS). The protein level of PD-L1 expression was upregulated by IFN-γ and TNF-α stimulation. Upon IFN-γ stimulation, all cell lines showed an increase in expression of PD-L1, signal transducer and activator of transcription (STAT)1, STAT3 and genes regulated by STAT activation. Upregulated expression of these genes was suppressed by the addition of a JAK inhibitor, oclacitinib. Contrastingly, upon TNF-α stimulation, all cell lines exhibited higher gene expression of the nuclear factor kappa B (NF-κB) gene RELA and genes regulated by NF-κB activation, whereas expression of PD-L1 was upregulated in LMeC only. Upregulated expression of these genes was suppressed by the addition of an NF-κB inhibitor, BAY 11-7082. The expression level of cell surface PD-L1 induced by IFN-γ and TNF-α treatment was reduced by oclacitinib and BAY 11-7082, respectively, indicating that upregulation of PD-L1 expression by IFN-γ and TNF-α stimulation is regulated via the JAK-STAT and NF-κB signaling pathways, respectively. These results provide insights into the role of inflammatory signaling in PD-L1 regulation in canine tumours. This article is protected by copyright. All rights reserved.
  • Suppressive modulation of host immune responses by Dermanyssus gallinae infestation
    Fujisawa S, Murata S, Isezaki M, Win SY, Sato T, Oishi E, Taneno A, Maekawa N, Okagawa T, Konnai S, Ohashi K
    Poult Sci., 102, 4, 102532, 102532, Feb. 2023, [Peer-reviewed], [International Magazine]
    English, Scientific journal, The poultry red mite (Dermanyssus gallinae, PRM) is a blood-sucking ectoparasite in chickens and is one of the most serious threats to poultry farms. Mass infestation with PRMs causes various health problems in chickens, resulting in significant productivity reduction in the poultry industry. Infestation with hematophagous ectoparasites, such as ticks, induces host inflammatory and hemostatic reactions. On the other hand, several studies have reported that hematophagous ectoparasites secrete various immunosuppressants from their saliva to suppress host immune responses to maintain blood sucking. Here, we examined the expression of cytokines in peripheral blood cells to investigate whether PRM infestation affects immunological states in chickens. In PRM-infested chickens, anti-inflammatory cytokines, IL-10 and TGF-β1, and immune checkpoint molecules, CTLA-4 and PD-1, were highly expressed compared to noninfested chickens. PRM-derived soluble mite extracts (SME) upregulated the gene expression of IL-10 in peripheral blood cells and HD-11 chicken macrophages. In addition, SME suppressed the expression of interferons and inflammatory cytokines in HD-11 chicken macrophages. Moreover, SME induces the polarization of macrophages into anti-inflammatory phenotypes. Collectively, PRM infestation could affect host immune responses, especially suppress the inflammatory responses. Further studies are warranted to fully understand the influence of PRM infestation on host immunity.
  • Characterization of SpsQ from Staphylococcus pseudintermedius as an affinity chromatography ligand for canine therapeutic antibodies
    Takeuchi H, Nakajima C, Konnai S, Maekawa N, Okagawa T, Usui M, Tamura U, Suzuki Y, Murata S, Ohashi K
    PLOS One, 18, 1, e0281171, Jan. 2023, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Coagulase-positive Staphylococci express protein A, which binds to host antibodies, to evade the immune system. Taking advantage of its specific binding to antibodies, protein A from Staphylococcus aureus, which is called SpA, is commonly used as an affinity chromatography ligand for human therapeutic antibodies. However, among four canine IgG subclasses (A, B, C, and D), only IgG-B binds to SpA strongly and establishing an efficient and robust purification scheme for canine therapeutic antibodies whose IgG subclass is A, C, or D remains difficult and depends on finding a suitable substitute to SpA. S. pseudintermedius, a major coagulase-positive Staphylococci found in dogs, expresses spsQ gene which is orthologous to S. aureus spa. We hypothesized that to serve S. pseudintermedius to better adapt to the dog immune system, SpsQ would bind to canine IgGs stronger than SpA, making it a better affinity chromatography ligand for canine therapeutic antibodies. To characterize SpsQ, we first determined the spsQ nucleotide sequence from S. pseudintermedius isolates. Based on the identified sequence, we prepared recombinant proteins containing the immunoglobulin-binding domains of SpA (r-SpA) and SpsQ (r-SpsQ) and determined their binding capacity for each canine IgG subclass. The binding capacity of r-SpsQ for IgG-B was almost as high as that of r-SpA. Interestingly, while both r-SpsQ and r-SpA showed no binding to IgG-C, the binding capacity of r-SpsQ for IgG-A and IgG-D was significantly higher than that of r-SpA. Finally, we performed affinity chromatography using r-SpsQ- or r-SpA-immobilized resin and revealed that the recovery rates of IgG-A and IgG-D using r-SpsQ were significantly higher than those using r-SpA. Our findings indicate that SpsQ has a strong potential to be used as an affinity chromatography ligand for canine therapeutic antibodies of subclass A, B, and D.
  • Molecular characterization of feline immune checkpoint molecules and establishment of PD-L1 immunohistochemistry for feline tumors
    Maekawa N, Konnai S, Asano Y, Otsuka T, Aoki E, Takeuchi H, Kato Y, Kaneko M, Yamada S, Kagawa Y, Nishimura M, Takagi S, Deguchi T, Ohta H, Nakagawa T, Suzuki Y, Okagawa T, Murata S, Ohashi K
    PLOS One, 18, 1, e0281143, Jan. 2023, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Spontaneous tumors are a major cause of death in cats. Treatment of human tumors has progressed dramatically in the past decade, partly due to the success of immunotherapies using immune checkpoint inhibitors, such as anti-programmed death 1 (PD-1) and anti-PD-ligand 1 (PD-L1) antibodies. However, little is known about the PD-1 pathway and its association with tumor disease in cats. This study investigated the applicability of anti-PD-1/PD-L1 therapy in feline tumors. We first determined the complete coding sequence of feline PD-L1 and PD-L2, and found that the deduced amino acid sequences of feline PD-L1/PD-L2 share high sequence identities (66-83%) with orthologs in other mammalian species. We prepared recombinant feline PD-1, PD-L1, and PD-L2 proteins and confirmed receptor-ligand binding between PD-1 and PD-L1/PD-L2 using flow cytometry. Next, we established an anti-feline PD-L1 monoclonal antibody (clone CL1Mab-7) to analyze the expression of PD-L1. Flow cytometry using CL1Mab-7 revealed the cell surface expression of PD-L1 in a feline macrophage (Fcwf-4) and five mammary adenocarcinoma cell lines (FKNp, FMCm, FYMp, FONp, and FONm), and showed that PD-L1 expression was upregulated by interferon-γ stimulation. Finally, immunohistochemistry using CL1Mab-7 also showed PD-L1 expression in feline squamous cell carcinoma (5/5, 100%), mammary adenocarcinoma (4/5, 80%), fibrosarcoma (5/5, 100%), and renal cell carcinoma (2/2, 100%) tissues. Our results strongly encourage further investigations of the PD-1/PD-L1 pathway as a potential therapeutic target for feline tumors.
  • Combined immune checkpoint blockade enhances antiviral immunity against bovine leukemia virus
    Nakamura H, Konnai S, Okagawa T, Maekawa N, Sajiki Y, Watari K, Kamitani K, Saito M, Kato Y, Suzuki Y, Murata S, Ohashi K
    J Virol., 97, 1, e0143022, Jan. 2023, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Bovine leukemia virus (BLV) is a retrovirus that causes enzootic bovine leukosis (EBL) in cattle and is widespread in many countries, including Japan. Recent studies have revealed that the expression of immunoinhibitory molecules, such as programmed death-1 (PD-1) and PD-ligand 1, plays a critical role in immunosuppression and disease progression during BLV infection. In addition, a preliminary study has suggested that another immunoinhibitory molecule, T-cell immunoglobulin domain and mucin domain-3 (TIM-3), is involved in immunosuppression during BLV infection. Therefore, this study was designed to further elucidate the immunoinhibitory role of immune checkpoint molecules in BLV infection. TIM-3 expression was upregulated on peripheral CD4+ and CD8+ T cells in BLV-infected cattle. Interestingly, in EBL cattle, CD4+ and CD8+ T cells infiltrating lymphomas expressed TIM-3. TIM-3 and PD-1 were upregulated and coexpressed in peripheral CD4+ and CD8+ T cells from BLV-infected cattle. Blockade by anti-bovine TIM-3 monoclonal antibody increased CD69 expression on T cells and gamma interferon (IFN-γ) production from peripheral blood mononuclear cells from BLV-infected cattle. A syncytium formation assay also demonstrated the antiviral effects of TIM-3 blockade against BLV infection. The combined inhibition of TIM-3 and PD-1 pathways significantly enhanced IFN-γ production and antiviral efficacy compared to inhibition alone. In conclusion, the combined blockade of TIM-3 and PD-1 pathways shows strong immune activation and antiviral effects and has potential as a novel therapeutic method for BLV infection. IMPORTANCE Enzootic bovine leukosis caused by bovine leukemia virus (BLV) is an important viral disease in cattle, causing severe economic losses to the cattle industry worldwide. The molecular mechanisms of BLV-host interactions are complex. Previously, it was found that immune checkpoint molecules, such as PD-1, suppress BLV-specific Th1 responses as the disease progresses. To date, most studies have focused only on how PD-1 facilitates escape from host immunity in BLV-infected cattle and the antiviral effects of the PD-1 blockade. In contrast, how T-cell immunoglobulin domain and mucin domain-3 (TIM-3), another immune checkpoint molecule, regulates anti-BLV immune responses is rarely reported. It is also unclear why PD-1 inhibition alone was insufficient to exert anti-BLV effects in previous clinical studies. In this study, the expression profile of TIM-3 in T cells derived from BLV-infected cattle suggested that TIM-3 upregulation is a cause of immunosuppression in infected cattle. Based on these results, anti-TIM-3 antibody was used to experimentally evaluate its function in influencing immunity against BLV. Results indicated that TIM-3 upregulation induced by BLV infection suppressed T-cell activation and antiviral cytokine production. Some T cells coexpressed PD-1 and TIM-3, indicating that simultaneous inhibition of PD-1 and TIM-3 with their respective antibodies synergistically restored antiviral immunity. This study could open new avenues for treating bovine chronic infections.
  • Diagnosis and early prediction of lymphoma using high-throughput clonality analysis of bovine leukemia virus-infected cells
    Okagawa T, Shimakura H, Konnai S, Saito M, Matsudaira T, Nao N, Yamada S, Murakami K, Maekawa N, Murata S, Ohashi K
    Microbiol Spectr., 10, 2, e0259522, American Society for Microbiology, Oct. 2022, [Peer-reviewed], [Corresponding author]
    English, Scientific journal, Bovine leukemia virus (BLV) infection causes aggressive B-cell lymphoma in cattle and sheep. The virus has spread to farms around the world, causing significant economic damage to the livestock industry.
  • 乳酸菌Lactobacillus plantarum HOKKAIDO株による免疫制御機序の解明               
    池端 麻里, 今内 覚, 岡川 朋弘, 阿部 健太郎, 本間 満, 北村 亨, 前川 直也, 村田 史郎, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 165回, [DI1A, 01], (公社)日本獣医学会, Sep. 2022
    Japanese
  • ネコ腫瘍組織におけるprogrammed death ligand 1(PD-L1)の発現解析               
    青木 絵理, 今内 覚, 前川 直也, 岡川 朋弘, 竹内 寛人, 佐藤 純平, 浅野 裕美恵, 大塚 拓海, 賀川 由美子, 加藤 幸成, 高木 哲, 鈴木 定彦, 村田 史郎, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 165回, [DI1A, 04], (公社)日本獣医学会, Sep. 2022
    Japanese
  • 鼻疽の診断抗原の探索               
    市川 世識, 飯沼 由希帆, 岡川 朋弘, 前川 直也, 村田 史郎, 今内 覚, 木下 優太, 丹羽 秀和, 青島 圭佑, 小林 篤史, 大橋 和彦, 木村 享史
    日本獣医学会学術集会講演要旨集, 165回, [DI1A, 09], (公社)日本獣医学会, Sep. 2022
    Japanese
  • ダニ媒介性脳炎の治療法開発に向けた血液脳関門透過性分子の研究               
    福田 美津紀, 深野 紗代, 小林 進太郎, 前川 直也, 高橋 侑嗣, 平野 港, 苅和 宏明, 今内 覚, 好井 健太朗
    日本獣医学会学術集会講演要旨集, 165回, [F1P, 12], (公社)日本獣医学会, Sep. 2022
    Japanese
  • 広範な有効性を示すワクチン開発のための鳥類寄生ダニ由来システインプロテアーゼの特性解析(Characterization of cysteine proteases from avian mites to develop a vaccine with broad efficacy)               
    Win Shwe Yee, 村田 史郎, 藤澤 宗太郎, 瀬尾 光里, 佐藤 純平, 佐藤 匠, 大石 英司, 種子野 章, 岡川 朋弘, 前川 直也, 今内 覚, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 165回, [E3P, 02], (公社)日本獣医学会, Sep. 2022
    English
  • ワクモ(Dermanyssus gallinae)由来シスタチン様分子の抗ワクモワクチン抗原としての評価               
    藤澤 宗太郎, 村田 史郎, 伊勢崎 政美, 有泉 拓馬, 佐藤 匠, 大石 英司, 種子野 章, 前川 直也, 岡川 朋弘, 市居 修, 今内 覚, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 165回, [E3P, 01], (公社)日本獣医学会, Sep. 2022
    Japanese
  • ワクモ由来の2種類のアスパラギン酸ペプチダーゼの性状解析               
    瀬尾 光里, 村田 史郎, Shwe Yee Win, 藤澤 宗太郎, 北條 巧, 伊勢崎 政美, 佐藤 匠, 大石 英司, 種子野 章, 市居 修, 前川 直也, 岡川 朋弘, 今内 覚, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 165回, [E3P, 03], (公社)日本獣医学会, Sep. 2022
    Japanese
  • 乳酸菌Lactobacillus plantarum HOKKAIDO株による免疫制御機序の解明               
    池端 麻里, 今内 覚, 岡川 朋弘, 阿部 健太郎, 本間 満, 北村 亨, 前川 直也, 村田 史郎, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 165回, [DI1A, 01], (公社)日本獣医学会, Sep. 2022
    Japanese
  • ネコ腫瘍組織におけるprogrammed death ligand 1(PD-L1)の発現解析               
    青木 絵理, 今内 覚, 前川 直也, 岡川 朋弘, 竹内 寛人, 佐藤 純平, 浅野 裕美恵, 大塚 拓海, 賀川 由美子, 加藤 幸成, 高木 哲, 鈴木 定彦, 村田 史郎, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 165回, [DI1A, 04], (公社)日本獣医学会, Sep. 2022
    Japanese
  • ダニ媒介性脳炎の治療法開発に向けた血液脳関門透過性分子の研究               
    福田 美津紀, 深野 紗代, 小林 進太郎, 前川 直也, 高橋 侑嗣, 平野 港, 苅和 宏明, 今内 覚, 好井 健太朗
    日本獣医学会学術集会講演要旨集, 165回, [F1P, 12], (公社)日本獣医学会, Sep. 2022
    Japanese
  • ワクモ(Dermanyssus gallinae)由来シスタチン様分子の抗ワクモワクチン抗原としての評価               
    藤澤 宗太郎, 村田 史郎, 伊勢崎 政美, 有泉 拓馬, 佐藤 匠, 大石 英司, 種子野 章, 前川 直也, 岡川 朋弘, 市居 修, 今内 覚, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 165回, [E3P, 01], (公社)日本獣医学会, Sep. 2022
    Japanese
  • 広範な有効性を示すワクチン開発のための鳥類寄生ダニ由来システインプロテアーゼの特性解析(Characterization of cysteine proteases from avian mites to develop a vaccine with broad efficacy)               
    Win Shwe Yee, 村田 史郎, 藤澤 宗太郎, 瀬尾 光里, 佐藤 純平, 佐藤 匠, 大石 英司, 種子野 章, 岡川 朋弘, 前川 直也, 今内 覚, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 165回, [E3P, 02], (公社)日本獣医学会, Sep. 2022
    English
  • ワクモ由来の2種類のアスパラギン酸ペプチダーゼの性状解析               
    瀬尾 光里, 村田 史郎, Shwe Yee Win, 藤澤 宗太郎, 北條 巧, 伊勢崎 政美, 佐藤 匠, 大石 英司, 種子野 章, 市居 修, 前川 直也, 岡川 朋弘, 今内 覚, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 165回, [E3P, 03], (公社)日本獣医学会, Sep. 2022
    Japanese
  • 鼻疽の診断抗原の探索               
    市川 世識, 飯沼 由希帆, 岡川 朋弘, 前川 直也, 村田 史郎, 今内 覚, 木下 優太, 丹羽 秀和, 青島 圭佑, 小林 篤史, 大橋 和彦, 木村 享史
    日本獣医学会学術集会講演要旨集, 165回, [DI1A, 09], (公社)日本獣医学会, Sep. 2022
    Japanese
  • Prostaglandin E2-induced immune suppression viacytotoxic T-lymphocyte antigen-4 in paratuberculosis
    Sajiki Y, Konnai S, Watari K, Okagawa T, Tanaka A, Nagata R, Kawaji S, Maekawa N, Suzuki Y, Kato Y, Murata S, Mori Y, Ohashi K
    Infect Immun., 90, 10, e0021022, Sep. 2022, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Paratuberculosis is a chronic enteritis of ruminants caused by the facultative intracellular pathogen Mycobacterium avium subsp. paratuberculosis. The Th1 response inhibits the proliferation of M. avium subsp. paratuberculosis during the early subclinical stage. However, we have previously shown that immune inhibitory molecules, such as prostaglandin E2 (PGE2), suppress M. avium subsp. paratuberculosis-specific Th1 responses as the disease progresses. To date, the mechanism underlying immunosuppression during M. avium subsp. paratuberculosis infection has not been elucidated. Therefore, in the present study, we investigated the function of cytotoxic T-lymphocyte antigen 4 (CTLA-4) expressed by peripheral blood mononuclear cells (PBMCs) from cattle with paratuberculosis because CTLA-4 expression is known to be elevated in T cells under an M. avium subsp. paratuberculosis experimental infection. M. avium subsp. paratuberculosis antigen induced CTLA-4 expression in T cells from cattle experimentally infected with M. avium subsp. paratuberculosis. Interestingly, both PGE2 and an E prostanoid 4 agonist also induced CTLA-4 expression in T cells. In addition, a functional assay with a bovine CTLA-4-immunogobulin fusion protein (CTLA-4-Ig) indicated that CTLA-4 inhibited gamma interferon (IFN-γ) production in M. avium subsp. paratuberculosis-stimulated PBMCs, while blockade by anti-bovine CTLA-4 monoclonal antibody increased the secretion of IFN-γ and tumor necrosis factor alpha production in these PBMCs. These preliminary findings show that PGE2 has immunosuppressive effects via CTLA-4 to M. avium subsp. paratuberculosis. Therefore, it is necessary to clarify in the future whether CTLA-4-mediated immunosuppression facilitates disease progression of paratuberculosis in cattle.
  • RAISING is a high-performance method for identifying random transgene integration sites
    Wada Y, Sato T, Hasegawa H, Matsudaira T, Nao N, Coler-Reilly ALG, Tasaka T, Yamauchi S, Okagawa T, Momose H, Tanio M, Kuramitsu M, Sasaki D, Matsumoto N, Yagishita N, Yamauchi J, Araya N, Tanabe K, Yamagishi M, Nakashima M, Nakahata S, Iha H, Ogata M, Muramatsu M, Imaizumi Y, Uchimaru K, Miyazaki Y, Konnai S, Yanagihara K, Morishita K, Watanabe T, Yamano Y, Saito M
    Commun Biol., 5, 1, 535, 535, Jun. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Both natural viral infections and therapeutic interventions using viral vectors pose significant risks of malignant transformation. Monitoring for clonal expansion of infected cells is important for detecting cancer. Here we developed a novel method of tracking clonality via the detection of transgene integration sites. RAISING (Rapid Amplification of Integration Sites without Interference by Genomic DNA contamination) is a sensitive, inexpensive alternative to established methods. Its compatibility with Sanger sequencing combined with our CLOVA (Clonality Value) software is critical for those without access to expensive high throughput sequencing. We analyzed samples from 688 individuals infected with the retrovirus HTLV-1, which causes adult T-cell leukemia/lymphoma (ATL) to model our method. We defined a clonality value identifying ATL patients with 100% sensitivity and 94.8% specificity, and our longitudinal analysis also demonstrates the usefulness of ATL risk assessment. Future studies will confirm the broad applicability of our technology, especially in the emerging gene therapy sector.
  • Exploration of serum biomarkers in dogs with malignant melanoma receiving anti-PD-L1 therapy and potential of COX-2 inhibition for combination therapy
    Maekawa N, Konnai S, Asano Y, Sajiki Y, Deguchi T, Okagawa T, Watari K, Takeuchi H, Takagi S, Hosoya K, Kim S, Ohta H, Kato Y, Suzuki Y, Murata S, Ohashi K
    Sci Rep., 12, 1, 9265, 9265, Jun. 2022, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Immune checkpoint inhibitors (ICIs) such as anti-PD-L1 antibodies are widely used to treat human cancers, and growing evidence suggests that ICIs are promising treatments for canine malignancies. However, only some canine oral malignant melanoma (OMM) cases respond to ICIs. To explore biomarkers predictive of survival in dogs with pulmonary metastatic OMM receiving the anti-PD-L1 antibody c4G12 (n = 27), serum concentrations of prostaglandin E2 (PGE2), cytokines, chemokines, and growth factors were measured prior to treatment initiation. Among 12 factors tested, PGE2, interleukin (IL)-12p40, IL-8, monocyte chemotactic protein-1 (MCP-1), and stem cell factor (SCF) were higher in OMM dogs compared to healthy dogs (n = 8). Further, lower baseline serum PGE2, MCP-1, and vascular endothelial growth factor (VEGF)-A concentrations as well as higher IL-2, IL-12, and SCF concentrations predicted prolonged overall survival. These observations suggest that PGE2 confers resistance against anti-PD-L1 therapy through immunosuppression and thus is a candidate target for combination therapy. Indeed, PGE2 suppressed IL-2 and interferon (IFN)-γ production by stimulated canine peripheral blood mononuclear cells (PBMCs), while inhibition of PGE2 biosynthesis using the COX-2 inhibitor meloxicam in combination with c4G12 enhanced Th1 cytokine production by PBMCs. Thus, serum PGE2 may be predictive of c4G12 treatment response, and concomitant use of COX-2 inhibitors may enhance ICI antitumor efficacy.
  • Suppressive effects of Ixodes persulcatus sialostatin L2 against Borrelia miyamotoi-stimulated immunity
    Sajiki Y, Konnai S, Okagawa T, Maekawa N, Isezaki M, Yamada S, Ito T, Sato K, Kawabata H, Logullo C, da Silva Vaz I Jr, Murata S, Ohashi K
    Ticks Tick Borne Dis., 13, 4, 101963, 101963, Apr. 2022, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Borrelia miyamotoi infection is an emerging tick-borne disease that causes hard tick-borne relapsing fever. B. miyamotoi is transmitted through the bite of ticks, including Ixodes persulcatus. Although accumulating evidence suggests that tick salivary proteins enhance the infectivity of other tick-borne pathogens, the association of B. miyamotoi with tick-derived proteins remains unknown. In this study, the effect of I. persulcatus sialostatin L2 (Ip-sL2), a tick-derived cystatin, on specific immunity to B. miyamotoi was preliminarily investigated in vitro. Mice were immunized with heat-killed B. miyamotoi and in vitro analyses of the splenocytes of the immunized mice indicated that the expression levels of the activation markers of CD11c+ and CD3+ cells were significantly upregulated by B. miyamotoi stimulation. Spleen cells from B. miyamotoi-immunized mice were used to determine whether Ip-sL2 regulates murine immune responses against B. miyamotoi. Treatment with Ip-sL2 in vitro inhibited the activation of CD11c+ and CD3+ cells as well as inflammatory cytokine production by cultured splenocytes. These findings show that Ip-sL2 has modulatory effects on murine immune responses to B. miyamotoi. Therefore, it is necessary to clarify in the future whether Ip-sL2 is involved in the enhanced infectivity of B. miyamotoi.
  • Estradiol-induced immune suppression via prostaglandin E2 during parturition in bovine leukemia virus-infected cattle
    Sajiki Y, Konnai S, Okagawa T, Maekawa N, Goto S, Kohara J, Nitanai A, Takahashi H, Kubota K, Takeda H, Murata S, Ohashi K
    PLOS One, 17, 3, e0263660, e0263660, Public Library of Science (PLoS), Mar. 2022, [Peer-reviewed], [Corresponding author]
    English, Scientific journal, Immune suppression during pregnancy and parturition is considered a risk factor that is related to the progression of bovine chronic diseases, such as bovine leukosis, which is caused by bovine leukemia virus (BLV). Our previous studies have demonstrated that prostaglandin E2 (PGE2) suppresses BLV-specific Th1 responses and contributes to the disease progression during BLV infection. Although PGE2 reportedly plays important roles in the induction of parturition, PGE2 involvement in immune suppression during parturition is unknown. To investigate its involvement, we analyzed PGE2 kinetics and Th1 responses in BLV-infected pregnant cattle. PGE2 concentrations in sera were increased, whereas IFN-γ responses were decreased before delivery. PGE2 is known to suppress Th1 immune responses in cattle. Thus, these data suggest that PGE2 upregulation inhibits Th1 responses during parturition. We also found that estradiol was important for PGE2 induction in pregnant cattle. In vitro analyses indicated that estradiol suppressed IFN-γ production, at least in part, via PGE2/EP4 signaling. In vivo analyses showed that estradiol administration significantly influenced the induction of PGE2 production and impaired Th1 responses. Our data suggest that estradiol-induced PGE2 is involved in the suppression of Th1 responses during pregnancy and parturition in cattle, which could contribute to the progression of BLV infection.
  • Effect of Insertion and Deletion in the Meq Protein Encoded by Highly Oncogenic Marek’s Disease Virus on Transactivation Activity and Virulence               
    Sato J, Murata S, Yang Z, Kaufer BB, Fujisawa F, Seo H, Maekawa N, Okagawa T, Konnai S, Osterrider N, Parcells MS, Ohashi K
    Viruses, 14, 2, 382, Feb. 2022, [Peer-reviewed]
    English, Scientific journal
  • Hemangiosarcoma cells induce M2 polarization and PD-L1 expression in macrophages.               
    Gulay KCM, Aoshima K, Maekawa N, Suzuki T, Konnai S, Kobayashi A, Kimura T
    Sci Rep., 12, 1, 2124, Feb. 2022, [Peer-reviewed]
    English, Scientific journal
  • Redox imbalance induces remodeling of glucose metabolism in Rhipicephalus microplus embryonic cell line               
    Della Noce B, Martins da Silva R, de Carvalho, Uhl MV, Konnai S, Ohashi K, Calixto C, Arcanjo A, de Abreu LA, de Carvalho SS, da Silva Vaz I Jr, Logullo C
    J Biol Chem., 101599, Jan. 2022, [Peer-reviewed]
    Scientific journal
  • Enhancement of interleukin-2 production by bovine peripheral blood mononuclear cells treated with the combination of anti-programmed death-ligand 1 and cytotoxic T lymphocyte antigen 4 chimeric monoclonal antibodies
    Watari K, Konnai S, Okagawa T, Maekawa N, Sajiki Y, Kato Y, Suzuki Y, Murata S, Ohashi K
    J Vet Med Sci., 84, 1, 6, 15, Jan. 2022, [Peer-reviewed], [Corresponding author], [Domestic magazines]
    English, Scientific journal, Our previous studies demonstrate the therapeutic efficacy against bovine diseases of an anti-bovine programmed death-ligand 1 (PD-L1) chimeric antibody. In humans, PD-1 and PD-L1 antibodies are more effective when combined with an antibody targeting cytotoxic T lymphocyte antigen 4 (CTLA-4) and these combination therapies are therefore clinically used. Here we generated an anti-bovine CTLA-4 chimeric antibody (chAb) to enhance the therapeutic efficacy of the PD-L1 antibody. We further analyzed the effects of dual blockade of CTLA-4 and PD-1 pathways on T-cell responses. The established anti-bovine CTLA-4 chAb showed comparable blocking activity on the binding of bovine CTLA-4 to CD80 and CD86 as the anti-bovine CTLA-4 mouse monoclonal antibody. Anti-bovine CTLA-4 chAb also significantly increased IL-2 production from bovine peripheral blood mononuclear cells (PBMCs). Further, the combination of anti-CTLA-4 chAb with anti-PD-L1 chAb significantly upregulated IL-2 production by PBMCs. These results suggest that the combination of antibodies have higher potential to enhance immune responses against pathogens compared with single administration.
  • Characterization of a copper transporter 1 from Dermanyssus gallinae as a vaccine antigen
    Fujisawa S, Murata S, Isezaki M, Ariizumi T, Sato T, Oishi E, Taneno A, Maekawa N, Okagawa T, Ichii O, Konnai S, Ohashi K
    Parasitology, 149, 1, 105, 115, Jan. 2022, [Peer-reviewed]
    English, Scientific journal
  • In vitro evaluation of a cysteine protease from poultry red mites, Demanyssus gallinae, as a vaccine antigen for chickens               
    Ariizumi T, Murata S, Fujisawa S, Isezaki M, Sato T, Oishi E, Taneno A, Ichii O, Maekawa N, Okagawa T, Konnai S, Ohashi K
    Poult Sci, 101, 3, 101638, Dec. 2021, [Peer-reviewed]
    English, Scientific journal
  • Characterization of a Novel Cysteine Protease Inhibitor from Poultry Red Mites: Potential Vaccine for Chickens
    Fujisawa S, Murata S, Isezaki M, Ariizumi T, Sato T, Oishi E, Taneno A, Maekawa N, Okagawa T, Ichii O, Konnai S, Ohashi K
    Vaccines (Basel), 9, 12, 1472, 1472, MDPI AG, Dec. 2021, [Peer-reviewed]
    English, Scientific journal, Poultry red mite (PRM; Dermanyssus gallinae) is a hazardous, blood-sucking ectoparasite of birds that constitutes a threat to poultry farming worldwide. Acaricides, commonly used in poultry farms to prevent PRMs, are not effective because of the rapid emergence of acaricide-resistant PRMs. However, vaccination may be a promising strategy to control PRM. We identified a novel cystatin-like molecule in PRMs: Dg-Cys. Dg-Cys mRNA expression was detected in the midgut and ovaries, in all stages of life. The PRM nymphs that were artificially fed with the plasma from chickens that were immunized with Dg-Cys in vitro had a significantly reduced reproductive capacity and survival rate. Moreover, combination of Dg-Cys with other antigen candidates, like copper transporter 1 or adipocyte plasma membrane-associated protein, enhanced vaccine efficacies. vaccination and its application as an antigen for cocktail vaccines could be an effective strategy to reduce the damage caused by PRMs in poultry farming.
  • Programmed death-ligand 1 expression in swine chronic infections and enhancement of interleukin-2 production via programmed death-1/programmed death-ligand 1 blockade               
    Ganbaatar O, Konnai S, Okagawa T, Nojima Y, Maekawa N, Ichikawa I, Kobayashi A, Shibahara T, Yanagawa Y, Higuchi H, Kato Y, Suzuki Y, Murata S, Ohashi K
    Immun Inflamm Dis., 9, 4, 1573, 1583, Dec. 2021, [Peer-reviewed], [Corresponding author]
    English
  • Characterization of S-Meq containing the deletion in Meq protein's transactivation domain in a Marek's disease virus strain in Japan               
    Murata S, Yamamoto E, Sakashita N, Maekawa N, Okagawa T, Konnai S, Ohashi K
    Poult Sci., 100, 11, 101461, Nov. 2021, [Peer-reviewed]
    English, Scientific journal
  • In vitro characterization of adipocyte plasma membrane-associated protein from poultry red mites, Dermanyssus gallinae, as a vaccine antigen for chickens
    Fujisawa S, Murata S, Takehara M, Aoyama J, Morita A, Isezaki M, Win SY, Ariizumi T, Sato T, Oishi E, Taneno A, Maekawa N, Okagawa T, Ichii O, Konnai S, Ohashi K
    Vaccine, 39, 41, 6057, 6066, Elsevier BV, Oct. 2021, [Peer-reviewed]
    English, Scientific journal
  • ウシCTLA-4ならびにPD-L1を標的とした抗体併用法による免疫増強効果の検討               
    渡 慧, 今内 覚, 岡川 朋弘, 前川 直也, 村田 史郎, 鈴木 定彦, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 164回, [DIO, 4], (公社)日本獣医学会, Sep. 2021
    Japanese
  • 牛伝染性リンパ腫発症母牛における子宮内感染の解析               
    嶋倉 穂南, 今内 覚, 岡川 朋弘, 中村 隼人, 神谷 可菜, 齋藤 麻矢, 前川 直也, 村田 史郎, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 164回, [DVO, 5], (公社)日本獣医学会, Sep. 2021
    Japanese
  • マレック病ウイルスMeqタンパク質における挿入および欠損配列の病原性への影響               
    佐藤 純平, 村田 史郎, 藤澤 宗太郎, 瀬尾 光里, 前川 直也, 岡川 朋弘, 今内 覚, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 164回, [DVO, 25], (公社)日本獣医学会, Sep. 2021
    Japanese
  • イヌ腫瘍細胞株におけるProgrammed cell death-ligand 1の発現機序の解析               
    大脇 稜, 出口 辰弥, 今内 覚, 前川 直也, 細谷 謙次, 金 尚昊, 須永 隆文, 奥村 正裕
    日本獣医学会学術集会講演要旨集, 164回, [HSO, 19], (公社)日本獣医学会, Sep. 2021
    Japanese
  • ワクモ(Dermanyssus gallinae)由来システインプロテアーゼの抗ワクモワクチン抗原としての評価               
    有泉 拓馬, 村田 史郎, 藤澤 宗太郎, 伊勢崎 政美, 佐藤 匠, 大石 英司, 種子野 章, 市居 修, 前川 直也, 岡川 朋弘, 今内 覚, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 164回, [EO, 6], (公社)日本獣医学会, Sep. 2021
    Japanese
  • 鼻疽に対する診断用抗原の探索および血清診断法の確立               
    飯沼 由希帆, 岡川 朋弘, 市川 世識, 陸 拾七, 前川 直也, 村田 史郎, 今内 覚, 木村 亨史, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 164回, [DIO, 2], (公社)日本獣医学会, Sep. 2021
    Japanese
  • Expression and functional analysis of swine PD-1/PD-L1 pathway(和訳中)               
    Otgontuya Ganbaatar, 今内 覚, 岡川 朋弘, 野島 裕太郎, 前川 直也, 市川 世識, 小林 篤史, 芝原 友幸, 柳川 洋二郎, 鈴木 定彦, 村田 史郎, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 164回, [DIO, 3], (公社)日本獣医学会, Sep. 2021
    English
  • ウシCTLA-4ならびにPD-L1を標的とした抗体併用法による免疫増強効果の検討               
    渡 慧, 今内 覚, 岡川 朋弘, 前川 直也, 村田 史郎, 鈴木 定彦, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 164回, [DIO, 4], (公社)日本獣医学会, Sep. 2021
    Japanese
  • 牛伝染性リンパ腫発症母牛における子宮内感染の解析               
    嶋倉 穂南, 今内 覚, 岡川 朋弘, 中村 隼人, 神谷 可菜, 齋藤 麻矢, 前川 直也, 村田 史郎, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 164回, [DVO, 5], (公社)日本獣医学会, Sep. 2021
    Japanese
  • マレック病ウイルスMeqタンパク質における挿入および欠損配列の病原性への影響               
    佐藤 純平, 村田 史郎, 藤澤 宗太郎, 瀬尾 光里, 前川 直也, 岡川 朋弘, 今内 覚, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 164回, [DVO, 25], (公社)日本獣医学会, Sep. 2021
    Japanese
  • ワクモ(Dermanyssus gallinae)由来システインプロテアーゼの抗ワクモワクチン抗原としての評価               
    有泉 拓馬, 村田 史郎, 藤澤 宗太郎, 伊勢崎 政美, 佐藤 匠, 大石 英司, 種子野 章, 市居 修, 前川 直也, 岡川 朋弘, 今内 覚, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 164回, [EO, 6], (公社)日本獣医学会, Sep. 2021
    Japanese
  • イヌ腫瘍細胞株におけるProgrammed cell death-ligand 1の発現機序の解析               
    大脇 稜, 出口 辰弥, 今内 覚, 前川 直也, 細谷 謙次, 金 尚昊, 須永 隆文, 奥村 正裕
    日本獣医学会学術集会講演要旨集, 164回, [HSO, 19], (公社)日本獣医学会, Sep. 2021
    Japanese
  • Canine Transforming Growth Factor-β Receptor 2-Ig: A Potential Candidate Biologic for Melanoma Treatment That Reverses Transforming Growth Factor-β1 Immunosuppression
    Hiroto Takeuchi, Satoru Konnai, Naoya Maekawa, Satoshi Takagi, Hiroshi Ohta, Noboru Sasaki, Sangho Kim, Tomohiro Okagawa, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
    Frontiers in Veterinary Science, 8, 656715, 14 Jun. 2021, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • Molecular Epidemiology and Whole-Genome Analysis of Bovine Foamy Virus in Japan               
    Mekata H, Okagawa T, Konnai S, Miyazawa T
    Viruses, 13, 6, 1017, May 2021, [Peer-reviewed]
    English
  • Differential expression of PEPCK isoforms is correlated to Aedes aegypti oogenesis and embryogenesis               
    da Silva RM, Vital WO, Martins RS, Moraes J, Gomes H, Calixto C, Konnai S, Ohashi K, da Silva Vaz I Jr, Logullo C
    Comp Biochem Physiol B Biochem Mol Biol., 256, 110618, May 2021, [Peer-reviewed]
    English, Scientific journal
  • Prostaglandin-related immune suppression in cattle               
    Sajiki Y, Konnai S, Ikenaka Y, Okagawa T, Maekawa N, Logullo C, da Silva Vaz Jr I, Murata S, Ohashi K
    Vet Immunol Immunopathol, 236, 110238, Apr. 2021, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • Selection of reference genes for quantitative PCR analysis in poultry red mite (Dermanyssus gallinae)
    Ariizumi T, Murata S, Fujisawa S, Isezaki M, Maekawa N, Okagawa T, Sato T, Oishi E, Taneno A, Konnai S, Ohashi K
    J Vet Med Sci., 83, 4, 558, 565, Apr. 2021, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, Poultry red mites (PRMs, Dermanyssus gallinae) are harmful ectoparasites that affect farmed chickens and cause serious economic losses in the poultry industry worldwide. Acaricides are used for PRM control; however, some PRMs have developed acaricide-resistant properties, which have indicated the need for different approaches for PRM control. Therefore, it is necessary to elucidate the biological status of PRMs to develop alternative PRM control strategies. Quantitative polymerase chain reaction (qPCR) allows analysis of the biological status at the transcript level. However, reference genes are preferable for accurate comparison of expression level changes given the large variation in the quality of the PRM samples collected in each farm. This study aimed to identify candidate reference genes with stable expression levels in the different blood feeding states and life stages of PRMs. First, we selected candidates based on the following criteria: sufficient expression intensity and no significant expression difference between fed and starved states. We selected and characterized seven candidate reference genes. Among them, we evaluated the gene expression stability between the starved and fed states using RefFinder; moreover, we compared their expression levels in each life-stage and identified two reference genes, Elongation factor 1-alpha (ELF1A)-like and apolipophorins-like. Finally, we evaluated the utility of the candidates as reference genes, and the use of ELF1A-like and apolipophorins-like successfully normalized ATP synthase subunit g -like gene expression. Thus, ELF1A-like and apolipophorins-like could be suitable reference genes in PRMs.
  • Characterisation of a cysteine protease from poultry red mites and its potential use as a vaccine for chickens.
    Murata S, Taniguchi A, Isezaki M, Fujisawa S, Sakai E, Taneno A, Ichii O, Ito T, Maekawa N, Okagawa T, Konnai S, Ohashi K
    Parasite, 28, 9, 9, 9, Feb. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Poultry red mites (PRMs, Dermanyssus gallinae) are ectoparasites that negatively affect farmed chickens, leading to serious economic losses worldwide. Acaricides have been used to control PRMs in poultry houses. However, some PRMs have developed resistance to acaricides, and therefore different approaches are required to manage the problems caused by PRMs. Vaccination of chickens is one of the methods being considered to reduce the number of PRMs in poultry houses. In a previous study, a cysteine protease, Deg-CPR-1, was identified as a candidate vaccine against PRMs distributed in Europe. In this study, we investigated the characteristics of Deg-CPR-1. A phylogenetic analysis revealed that Deg-CPR-1 is closely related to the digestive cysteine proteases of other mite species, and it was classified into a cluster different from that of chicken cathepsins. Deg-CPR-1 of PRMs in Japan has an amino acid substitution compared with that of PRMs in Europe, but it showed efficacy as a vaccine, consistent with previous findings. Deg-CPR-1 exhibited cathepsin L-like enzyme activity. In addition, the Deg-CPR-1 mRNA was expressed in the midgut and in all stages of PRMs that feed on blood. These results imply that Deg-CPR-1 in the midgut may have important functions in physiological processes, and the inhibition of its expression may contribute to the efficacy of a Deg-CPR-1-based vaccine. Further research is required to fully understand the mechanisms of vaccine efficacy.
  • PD-L1 immunohistochemistry for canine cancers and clinical benefit of anti-PD-L1 antibody in dogs with pulmonary metastatic oral malignant melanoma
    Maekawa N, Konnai S, Nishimura M, Kagawa Y, Takagi S, Hosoya K, Ohta H, Kim S, Okagawa T, Izumi Y, Deguchi T, Kato Y, Yamamoto S, Yamamoto K, Toda M, Nakajima C, Suzuki Y, Murata S, Ohashi K
    NPJ Precis Oncol., 5, 1, 10, 10, Feb. 2021, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Immunotherapy targeting programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1) represents promising treatments for human cancers. Our previous studies demonstrated PD-L1 overexpression in some canine cancers, and suggested the therapeutic potential of a canine chimeric anti-PD-L1 monoclonal antibody (c4G12). However, such evidence is scarce, limiting the clinical application in dogs. In the present report, canine PD-L1 expression was assessed in various cancer types, using a new anti-PD-L1 mAb, 6C11-3A11, and the safety and efficacy of c4G12 were explored in 29 dogs with pulmonary metastatic oral malignant melanoma (OMM). PD-L1 expression was detected in most canine malignant cancers including OMM, and survival was significantly longer in the c4G12 treatment group (median 143 days) when compared to a historical control group (n = 15, median 54 days). In dogs with measurable disease (n = 13), one dog (7.7%) experienced a complete response. Treatment-related adverse events of any grade were observed in 15 dogs (51.7%). Here we show that PD-L1 is a promising target for cancer immunotherapy in dogs, and dogs could be a useful large animal model for human cancer research.
  • The enhancement of Th1 immune response by anti-PD-L1 antibody in cattle infected with Mycobacterium avium subsp. paratuberculosis
    Sajiki Y, Konnai S, Nagata R, Kawaji S, Nakamura H, Fujisawa S, Okagawa T, Maekawa N, Kato Y, Suzuki Y, Murata S, Mori Y, Ohashi K
    J Vet Med Sci., 83, 2, 162, 166, Feb. 2021, [Peer-reviewed], [Corresponding author], [Domestic magazines]
    English, Scientific journal, Johne's disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic enteritis of ruminants. Previous studies have shown that programmed death-ligand 1 (PD-L1) is associated with the disease progression, and PD-L1 blockade activates MAP-specific Th1 responses in vitro. Here, we performed anti-PD-L1 antibody administration using 2 MAP-infected cattle at the late subclinical stage of infection. After administration, bacterial shedding was reduced or maintained at a low level. Additionally, MAP-specific Th1 cytokine production was upregulated, and CD69 expression was increased in T cells. Collectively, the treatment has a potential as a novel control method against Johne's disease.
  • Cross-species reactivity of antibodies against Ixodes persulcatus ferritin 2 to Rhipicephalus microplus
    Xavier AM, Konnai S, Parizi FP, Githaka WN, Isezaki M, Goto S, Fujisawa S, Yamada S, Okagawa T, Maekawa N, Logullo C, Silva Vaz J r I, Murata S, Ohashi K
    Jpn J Vet Res., 69, 1, 57, 65, Feb. 2021, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • Intrauterine infection with Mycobacterium avium subsp. paratuberculosis in pregnant cattle diagnosed with Johne’s disease
    Taniguchi Y, Konnai S, Sakakibara S, Yamamoto A, Okagawa T, Maekawa N, Murata S, Ohashi K
    Jpn J Vet Res, 69, 1, 51, 55, Feb. 2021, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • The Role of Saliva in Arthropod-Host-Pathogen Relationships               
    Tirloni L, Calvo E, Konnai S, Silva Vaz Jr I
    Front Cell Infect Microbiol, 10, 630626, Jan. 2021, [Peer-reviewed], [Invited]
    English, Scientific journal
  • Direct evidence of the preventive effect of milk replacer–based probiotic feeding in calves against severe diarrhea
    Kayasaki F, Okagawa T, Konnai S, Kohara J, Sajiki Y, Watari K, Ganbaatar O, Goto S, Nakamura H, Shimakura H, Minato E, Kobayashi A, Kubota M, Terasaki N, Takeda A, Noda H, Honma M, Maekawa N, Murata S, Ohashi K
    Vet Microbiol., 254, 108976., 108976, Elsevier BV, Jan. 2021, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • Tick saliva-induced programmed death-1 and PD-ligand 1 and its related host immunosuppression
    Sajiki Y, Konnai S, Ikenaka Y, Gulay K, Kobayashi A, Parizi L, João B, Watari K, Fujisawa S, Okagawa T, Maekawa N, Logullo C, Silva Vaz Jr I, Murata S, Ohashi K
    Sci Rep., 11, 1, 1063, Springer Science and Business Media LLC, Jan. 2021, [Peer-reviewed], [Corresponding author]
    English, Scientific journal, AbstractThe tick Rhipicephalus microplus is a harmful parasite of cattle that causes considerable economic losses to the cattle breeding industry. Although R. microplus saliva (Rm-saliva) contains several immunosuppressants, any association between Rm-saliva and the expression of immunoinhibitory molecules, such as programmed death (PD)-1 and PD-ligand 1 (PD-L1), has not been described. In this study, flow cytometric analyses revealed that Rm-saliva upregulated PD-1 expression in T cells and PD-L1 expression in CD14+ and CD11c+ cells in cattle. Additionally, Rm-saliva decreased CD69 expression in T cells and Th1 cytokine production from peripheral blood mononuclear cells. Furthermore, PD-L1 blockade increased IFN-γ production in the presence of Rm-saliva, suggesting that Rm-saliva suppresses Th1 responses via the PD-1/PD-L1 pathway. To reveal the upregulation mechanism of PD-1/PD-L1 by Rm-saliva, we analyzed the function of prostaglandin E2 (PGE2), which is known as an inducer of PD-L1 expression, in Rm-saliva. We found that Rm-saliva contained a high concentration of PGE2, and PGE2 treatment induced PD-L1 expression in CD14+ cells in vitro. Immunohistochemical analyses revealed that PGE2 and PD-L1 expression was upregulated in tick-attached skin in cattle. These data suggest that PGE2 in Rm-saliva has the potential to induce the expression of immunoinhibitory molecules in host immune cells.
  • A TLR7 agonist activates bovine Th1 response and exerts antiviral activity against bovine leukemia virus
    Sajiki Y, Konnai S, Okagawa T, Maekawa N, Nakamura H, Kato Y, Suzuki Y, Murata S, Ohashi K
    Dev Comp Immunol., 114, 103847, 103847, Elsevier BV, Jan. 2021, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • Enhanced immunotherapeutic efficacy of anti-PD-L1 antibody in combination with an EP4 antagonist
    Sajiki Y, Konnai S, Cai Z, Takada K, Okagawa T, Maekawa N, Fujisawa S, Kato Y, Suzuki Y, Murata S, Ohashi K
    ImmunoHorizons, 4, 12, 837, 850, The American Association of Immunologists, Dec. 2020, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • The suppression of Th1 response by inducing TGF-β1 from regulatory T cells in bovine mycoplasmosis
    Sajiki Y, Konnai S, Goto S, Okagawa T, Ohira K, Shimakura H, Maekawa N, Gondaira S, Higuchi H, Tajima M, Hirano Y, Kohara J, Murata S, Ohashi K
    Front Vet Sci., 7, 609443, Frontiers Media SA, Dec. 2020, [Peer-reviewed], [Corresponding author]
    English, Scientific journal, Regulatory T cells (Tregs) regulate immune responses and maintain host immune homeostasis. Tregs contribute to the disease progression of several chronic infections by oversuppressing immune responses via the secretion of immunosuppressive cytokines, such as transforming growth factor (TGF)-β and interleukin-10. In the present study, we examined the association of Tregs with Mycoplasma bovis infection, in which immunosuppression is frequently observed. Compared with uninfected cattle, the percentage of Tregs, CD4+CD25highFoxp3+ T cells, was increased in M. bovis-infected cattle. Additionally, the plasma of M. bovis-infected cattle contained the high concentrations of TGF-β1, and M. bovis infection induced TGF-β1 production from bovine immune cells in in vitro cultures. Finally, we analyzed the immunosuppressive effects of TGF-β1 on bovine immune cells. Treatment with TGF-β1 significantly decreased the expression of CD69, an activation marker, in T cells, and Th1 cytokine production in vitro. These results suggest that the increase in Tregs and TGF-β1 secretion could be one of the immunosuppressive mechanisms and that lead to increased susceptibility to other infections in terms of exacerbation of disease during M. bovis infection.
  • Molecular detection and genetic characterization of infectious laryngotracheitis virus in poultry in Myanmar.
    Yang Z, Murata S, Fujisawa S, Takehara M, Katakura K, Hmoon MM, Win SY, Bawm S, Konnai S, Ohashi K
    BMC Vet Res., 16, 1, 453, Nov. 2020, [Peer-reviewed]
    English, Scientific journal
  • Genetic characterization of a Marek's disease virus strain isolated in Japan.               
    Murata S, Machida Y, Isezaki M, Maekawa N, Okagawa T, Konnai S, Ohashi K
    Virol J., 17, 1, 186, Nov. 2020, [Peer-reviewed]
    English, Scientific journal
  • PD-L1 expression in equine malignant melanoma and functional effects of PD-L1 blockade
    Ganbaatar O, Konnai S, Okagawa T, Nojima Y, Maekawa N, Minato E, Kobayashi A, Ando R, Sasaki N, Miyakoshi D, Ichii O, Kato Y, Suzuki Y, Murata S, Ohashi K
    PLOS ONE, 15, 11, e0234218, Nov. 2020, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Programmed death-1 (PD-1) is an immunoinhibitory receptor expressed on lymphocytes. Interaction of PD-1 with its ligand PD-ligand 1 (PD-L1) delivers inhibitory signals and impairs proliferation, cytokine production, and cytotoxicity of T cells. In our previous studies, we have developed anti-bovine PD-L1 monoclonal antibodies (mAbs) and reported that the PD-1/PD-L1 pathway was closely associated with T-cell exhaustion and disease progression in bovine chronic infections and canine tumors. Furthermore, we found that blocking antibodies that target PD-1 and PD-L1 restore T-cell functions and could be used in immunotherapy in cattle and dogs. However, the immunological role of the PD-1/PD-L1 pathway for chronic equine diseases, including tumors, remains unclear. In this study, we identified cDNA sequences of equine PD-1 (EqPD-1) and PD-L1 (EqPD-L1) and investigated the role of anti-bovine PD-L1 mAbs against EqPD-L1 using in vitro assays. In addition, we evaluated the expression of PD-L1 in tumor tissues of equine malignant melanoma (EMM). The amino acid sequences of EqPD-1 and EqPD-L1 share a considerable identity and similarity with homologs from non-primate species. Two clones of the anti-bovine PD-L1 mAbs recognized EqPD-L1 in flow cytometry, and one of these cross-reactive mAbs blocked the binding of equine PD-1/PD-L1. Of note, immunohistochemistry confirmed the PD-L1 expression in EMM tumor tissues. A cultivation assay revealed that PD-L1 blockade enhanced the production of Th1 cytokines in equine immune cells. These findings showed that our anti-PD-L1 mAbs would be useful for analyzing the equine PD-1/PD-L1 pathway. Further research is warranted to discover the immunological role of PD-1/PD-L1 in chronic equine diseases and elucidate a future application in immunotherapy for horses.
  • Identification and functional analysis of ferritin 2 from the Taiga tick Ixodes persulcatus Schulze
    Githaka N, Konnai S, Isezaki M, Goto S, Xavier M, Fujisawa S, Yamada S, Okagawa T, Maekawa N, Logullo C, da Silva Vaz Jr I, Murata S, Ohashi K
    Ticks Tick-Borne Dis, 11, 6, 101547, 101547, Elsevier BV, Nov. 2020, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • 牛白血病ウイルス感染症における免疫抑制受容体TIM-3の発現解析および機能解析               
    中村 隼人, 今内 覚, 岡川 朋弘, 佐治木 大和, 渡 慧, 神谷 可菜, 齋藤 麻矢, 前川 直也, 村田 史郎, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 163回, 221, 221, (公社)日本獣医学会, Oct. 2020
    Japanese
  • ネコCytotoxic T-lymphocyte antigen-4(CTLA-4)を標的とした新規免疫抑制剤の開発における基礎的検討               
    大塚 拓海, 今内 覚, 前川 直也, 渡 慧, 岡川 朋弘, 村田 史郎, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 163回, 221, 221, (公社)日本獣医学会, Oct. 2020
    Japanese
  • ワクモにおける定量的PCR法確立のための内在性コントロール遺伝子の探索               
    有泉 拓馬, 村田 史郎, 藤澤 宗太郎, 伊勢崎 政美, 前川 直也, 岡川 朋弘, 種子野 章, 大石 英司, 今内 覚, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 163回, 248, 248, (公社)日本獣医学会, Oct. 2020
    Japanese
  • Development and Characterization of Anti-Sheep Podoplanin Monoclonal Antibodies PMab-253 and PMab-260.
    Mika K Kaneko, Masato Sano, Junko Takei, Teizo Asano, Yusuke Sayama, Hideki Hosono, Atsushi Kobayashi, Satoru Konnai, Yukinari Kato
    Monoclonal antibodies in immunodiagnosis and immunotherapy, 39, 4, 144, 155, 16 Jul. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Anti-podoplanin (PDPN) monoclonal antibodies (mAbs) are needed as markers for lymphatic endothelial cells or type I alveolar cells in immunohistochemical analyses. We have developed anti-PDPN mAbs for many species, including humans, mice, rats, rabbits, dogs, cats, bovines, pigs, Tasmanian devils, alpacas, tigers, whales, goats, horses, and bears. This study develops and characterizes anti-sheep PDPN (sPDPN) mAbs using Cell-Based Immunization and Screening (CBIS) method. A RAP14 tag was added to the N-terminus of sPDPN, and an anti-RAP14 tag mAb (PMab-2) was used to measure the expression level of sPDPN in flow cytometry and Western blots. We immunized mice with sPDPN-overexpressing Chinese hamster ovary (CHO)-K1 (CHO/sPDPN) cells and screened mAbs against sPDPN using flow cytometry. Two of the mAbs, PMab-253 (immunoglobulin M [IgM], kappa) and PMab-260 (IgM, kappa), detected CHO/sPDPN cells specifically using flow cytometry and Western blots. Both PMab-253 and PMab-260 stained the renal glomerulus and Bowman's capsule, lymphatic endothelial cells of the lung and colon, and type I alveolar cells of the lung, suggesting PMab-253 and PMab-260, which were developed by CBIS method, can be applied to functional analyses of sPDPN. We also determined the binding epitope of PMab-253 and PMab-260 using flow cytometry. Analysis of sPDPN deletion mutants revealed that the N-terminus of the PMab-253 and PMab-260 epitope exists between amino acids 110 and 115 of sPDPN. Analysis of sPDPN point mutations revealed that the critical epitope of PMab-253 and PMab-260 includes Thr112 and Ser113 of sPDPN, indicating that the PMab-253 and PMab-260 epitope are independent of the platelet aggregation-stimulating (PLAG) domain or the PLAG-like domain of sPDPN.
  • Transcriptome dynamics of blood-fed and starved poultry red mites, Dermanyssus gallinae               
    Fujisawa S, Murata S, Isezaki M, Oishi E, Taneno A, Maekawa N, Okagawa T, Konnai S, Ohashi K
    Parasitol Int., 102156, 102156, Jun. 2020, [Peer-reviewed]
    English, Scientific journal
  • Expression Analysis of Canine CMTM6 and CMTM4 as Potential Regulators of the PD-L1 Protein in Canine Cancers
    Takeuchi H, Konnai S, Maekawa N, Minato E, Ichikawa Y, Kobayashi A, Okegawa T, Murata S, Ohashi K.
    Front Vet Sci, 7, 330, 330, Jun. 2020, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Cancer is one of the most significant causes of death in dogs. Antibody drugs targeting the PD-1/PD-L1 axis represent a promising immunotherapy for both human and canine cancers. However, the regulation mechanisms of PD-L1 expression in canine cancers require further investigation to better understand the resistance mechanisms to anti-PD-L1 therapy. Recent reports have shown that CMTM6 and CMTM4 are critical regulators of PD-L1 protein expression in human cancer cells. By preventing PD-L1 from lysosome-mediated degradation, CMTM6 maintains PD-L1 expression on the cell surface. However, the literature has not reported on CMTM6 and CMTM4 in dogs, and their functions are completely unknown. To reveal a regulation mechanism of PD-L1 in canine cancers, this study firstly identified the gene sequences of CMTM6 and CMTM4. Then, the expression analysis of these proteins was performed by immunohistochemistry. Furthermore, the functions of CMTM6 and CMTM4 in regulating PD-L1 expression were examined by gene knockdown of CMTM6 and CMTM4. Canine CMTM6 and CMTM4 displayed high amino acid sequence identities compared with those of humans and mice. An immunohistochemical analysis using cross-reactive antibodies revealed that canine malignant melanoma and osteosarcoma express CMTM6, CMTM4, and PD-L1 simultaneously. Gene knockdown of CMTM6 and CMTM4 with RNA interference significantly reduced the cell surface expression of PD-L1 in a canine cell line. These results suggest that CMTM6 and CMTM4 are regulators of PD-L1 expression in canine cancers and could serve as potential therapeutic targets to enhance antitumor immunity.
  • Rhipicephalus microplus cystatin as a potential cross-protective tick vaccine against Rhipicephalus appendiculatus               
    Parizi L, Rangel C, Sabadina G, Saggin B, Kiio I, Xavier M, Matos R, Camargo-Mathias M, Seixas A, Konnai S, Ohashi K, Githaka N, da Silva Vaz Jr I
    Ticks Tick-Borne Dis, 11, 3, 101378, May 2020, [Peer-reviewed]
    English, Scientific journal
  • Clinical efficacy of the combined treatment of anti-PD-L1 rat-bovine chimeric antibody with a COX-2 inhibitor in calves infected with Mycoplasma bovis
    Shinya Goto, Satoru Konnai, Yuki Hirano, Junko Kohara, Tomohiro Okagawa, Naoya Maekawa, Yamato Sajiki, Kei Watari, Erina Minato, Atsuhi Kobayashi, Satoshi Gondaira, Hidetoshi Higuchi, Masateru Koiwa, Motoshi Tajima, Eiji Taguchi, Masaru Ishida, Ryoko Uemura, Shinji Yamada, Mika K. Kaneko, Yukinari Kato, Keiichi Yamamoto, Mikihiro Toda, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 68, 2, 77, 90, May 2020, [Peer-reviewed]
    English, Scientific journal
  • Immunosuppressive effects of sialostatin L1 and L2 isolated from the taiga tick Ixodes persulcatus Schulze
    Yamato Sajiki, Satoru Konnai, Akie Ochi, Tomohiro Okagawa, Naftaly Githaka, Masayoshi Isezaki, Shinji Yamada, Takuya Ito, Shuji Ando, Hiroki Kawabata, Carlos Logullo, Itabajara da Silva Vaz, Naoya Maekawa, Shiro Murata, Kazuhiko Ohashi
    Ticks and Tick-borne Diseases, 11, 2, 101332, 101332, Elsevier BV, Mar. 2020, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • Immunosuppression in Cows following Intramammary Infusion of Mycoplasma bovis.
    Satoshi Gondaira, Koji Nishi, Takahiro Tanaka, Takashi Yamamoto, Takanori Nebu, Reina Watanabe, Satoru Konnai, Tomohito Hayashi, Yoshio Kiku, Mariko Okamoto, Kazuya Matsuda, Masateru Koiwa, Hidetomo Iwano, Hajime Nagahata, Hidetoshi Higuchi
    Infection and immunity, 88, 3, e00521, 19, 20 Feb. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Mycoplasma bovis is a destructive pathogen that causes large economic losses in rearing cattle for beef and dairy worldwide. M. bovis causes suppression of and evades the host immune response; however, the mechanisms of host immune function involved in M. bovis mastitis have not been elucidated. The purpose of this study was to elucidate the characteristics of the bovine immune response to mycoplasmal mastitis. We evaluated the responsiveness of the bovine mammary gland following infusion of M. bovis Somatic cell counts and bacterial counts in milk from the infected quarter were increased. However, the proliferation of peripheral blood mononuclear cells (blood MNCs) and mononuclear cells isolated from M. bovis-stimulated mammary lymph nodes (lymph node MNCs) did not differ from that in the unstimulated cells. Transcriptome analysis revealed that the mRNA levels of innate immune system-related genes in blood MNCs, complement factor D (CFD), ficolin 1 (FCN1), and tumor necrosis factor superfamily member 13 (TNFSF13) decreased following intramammary infusion of M. bovis The mRNA levels of immune exhaustion-related genes, programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), lymphocyte activation gene 3 (LAG3), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) of milk mononuclear cells (milk MNCs) in the infected quarter were increased compared with those before infusion. Increase in immune exhaustion-related gene expression and decrease in innate immune response-related genes of MNCs in quarters from cows were newly characterized by M. bovis-induced mastitis. These results suggested that M. bovis-induced mastitis affected the immune function of bovine MNCs, which is associated with prolonged duration of infection with M. bovis.
  • Upregulation of PD-L1 Expression by Prostaglandin E2 and the Enhancement of IFN-γ by Anti-PD-L1 Antibody Combined With a COX-2 Inhibitor in Mycoplasma bovis Infection.
    Shinya Goto, Satoru Konnai, Yuki Hirano, Junko Kohara, Tomohiro Okagawa, Naoya Maekawa, Yamato Sajiki, Kei Watari, Erina Minato, Atsuhi Kobayashi, Satoshi Gondaira, Hidetoshi Higuchi, Masateru Koiwa, Motoshi Tajima, Eiji Taguchi, Ryoko Uemura, Shinji Yamada, Mika K Kaneko, Yukinari Kato, Keiichi Yamamoto, Mikihiro Toda, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
    Frontiers in veterinary science, 7, 12, 12, 12, Feb. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Bovine mycoplasmosis caused by Mycoplasma bovis results in pneumonia and mastitis in cattle. We previously demonstrated that the programmed death 1 (PD-1)/PD-ligand 1 (PD-L1) pathway is involved in immune dysfunction during M. bovis infection and that prostaglandin E2 (PGE2) suppressed immune responses and upregulated PD-L1 expression in Johne's disease, a bacterial infection in cattle. In this study, we investigated the role of PGE2 in immune dysfunction and the relationship between PGE2 and the PD-1/PD-L1 pathway in M. bovis infection. In vitro stimulation with M. bovis upregulated the expressions of PGE2 and PD-L1 presumably via Toll-like receptor 2 in bovine peripheral blood mononuclear cells (PBMCs). PGE2 levels of peripheral blood in infected cattle were significantly increased compared with those in uninfected cattle. Remarkably, plasma PGE2 levels were positively correlated with the proportions of PD-L1+ monocytes in M. bovis-infected cattle. Additionally, plasma PGE2 production in infected cattle was negatively correlated with M. bovis-specific interferon (IFN)-γ production from PBMCs. These results suggest that PGE2 could be one of the inducers of PD-L1 expression and could be involved in immunosuppression during M. bovis infection. In vitro blockade assays using anti-bovine PD-L1 antibody and a cyclooxygenase 2 inhibitor significantly upregulated the M. bovis-specific IFN-γ response. Our study findings might contribute to the development of novel therapeutic strategies for bovine mycoplasmosis that target PGE2 and the PD-1/PD-L1 pathway.
  • PMab-241 Specifically Detects Bear Podoplanin of Lymphatic Endothelial Cells in the Lung of Brown Bear.
    Junko Takei, Shinji Yamada, Satoru Konnai, Tsuyoshi Ishinazaka, Michito Shimozuru, Mika K Kaneko, Yukinari Kato
    Monoclonal antibodies in immunodiagnosis and immunotherapy, 38, 6, 282, 284, Dec. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Podoplanin (PDPN)/T1alpha is utilized as a specific marker of lymphatic endothelial cells or type I alveolar cells of lung. Therefore, sensitive and specific monoclonal antibodies (mAbs) detecting PDPN are necessary for immunohistochemical analyses, especially using formalin-fixed paraffin-embedded tissues. Recently, we developed an anti-bear PDPN (bPDPN) mAb, PMab-247, which is useful for immunohistochemical analyses to detect both lymphatic endothelial cells and type I alveolar cells of lung. However, it is difficult to distinguish lymphatic endothelial cells from type I alveolar cells in the bear lung. In this study, we showed that a novel anti-bPDPN mAb, PMab-241 stained only lymphatic endothelial cells, not type I alveolar cells of the lung in immunohistochemical analyses. These findings suggest that PMab-241 could be useful for staining lymphatic endothelial cells specifically in the bear lung tissues.
  • Epitope Mapping of Anti-Bear Podoplanin Monoclonal Antibody PMab-247               
    Kato Y, Takei J, Furusawa Y, Sayama Y, Sano M, Konnai S, Kobayashi A, Harada H, Takahashi M, Suzuki H, Yamada S, Kaneko MK
    Monoclon Antib Immunodiagn Immunother., 38, 5, 230, 233, Sep. 2019, [Peer-reviewed]
    English, Scientific journal
  • Immune inhibitory function of bovine CTLA-4 and the effects of its blockade in IFN-γ production               
    Watari K, Konnai S, Maekawa N, Okagawa T, Suzuki Y, Murata S, Ohashi K
    BMC Vet Res, 15, 1, 380, Sep. 2019, [Peer-reviewed]
    English, Scientific journal
  • ミャンマーの養鶏場におけるマイコプラズマ、鶏伝染性気管支炎ウイルス、鶏伝染性喉頭気管炎ウイルスの分子学的検出と遺伝学的性状解析(Molecular detection and genetic characterization of mycoplasmas, infectious bronchitis virus and infectious laryngotracheitis virus in poultry farms in Myanmar)               
    Yang Zhiyuan, 藤澤 宗太郎, 村田 史郎, 竹原 昌生, 片倉 賢, Myint Myint Hmoon, Shwe Yee Win, Saw Bawm, Lat Lat Htun, Ye Htut Aung, Mar Mar Win, 今内 覚, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 162回, 411, 411, (公社)日本獣医学会, Aug. 2019
    English
  • イヌ腫瘍組織およびイヌ腫瘍由来細胞株におけるイヌHER2の発現解析               
    吉武 志江奈, 今内 覚, 前川 直也, 賀川 由美子, 西村 麻紀, 岡川 朋弘, 鈴木 定彦, 高木 哲, 中川 貴之, 村田 史郎, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 162回, 380, 380, (公社)日本獣医学会, Aug. 2019
    Japanese
  • イヌ腫瘍由来細胞株におけるCKLF-like MARVEL transmembrane domain containing protein 6(CMTM6)および4(CMTM4)の発現解析               
    竹内 寛人, 今内 覚, 岡川 朋弘, 前川 直也, 村田 史郎, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 162回, 380, 380, (公社)日本獣医学会, Aug. 2019
    Japanese
  • BLV感染症に対するCOX-2阻害剤と抗PD-L1抗体併用法の抗ウイルス効果の検討               
    佐治木 大和, 今内 覚, 岡川 朋弘, 前川 直也, 後藤 伸也, 小原 潤子, 山田 慎二, 加藤 幸成, 鈴木 定彦, 村田 史郎, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 162回, 381, 381, (公社)日本獣医学会, Aug. 2019
    Japanese
  • Mycoplasma bovis感染症に対する抗PD-L1キメラ抗体を用いた臨床試験               
    後藤 伸也, 今内 覚, 平野 佑気, 小原 潤子, 岡川 朋弘, 前川 直也, 鈴木 定彦, 加藤 幸成, 村田 史郎, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 162回, 381, 381, (公社)日本獣医学会, Aug. 2019
    Japanese
  • RNA-Seqを用いたワクモ(Dermanyssus gallinae)の吸血状態別における遺伝子発現解析               
    藤澤 宗太郎, 村田 史郎, 竹原 昌生, 伊勢崎 政美, 小川 遼, 宇野 有紀子, 種子野 章, 前川 直也, 岡川 朋弘, 今内 覚, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 162回, 412, 412, (公社)日本獣医学会, Aug. 2019
    Japanese
  • COX-2阻害剤の併用による抗PD-L1抗体を用いたイヌ腫瘍免疫療法の効果増強に向けた基礎的検討               
    前川 直也, 今内 覚, 浅野 裕美恵, 岡川 朋弘, 高木 哲, 村田 史郎, 大橋 和彦
    日本獣医学会学術集会講演要旨集, 162回, 460, 460, (公社)日本獣医学会, Aug. 2019
    Japanese
  • ネコのアクロメガリー関連インスリン抵抗性糖尿病のコントロールを目的とした成長ホルモン受容体/Fc融合タンパク質の作製               
    鈴木 理紗, 和泉 雄介, 前川 直也, 今内 覚, 高木 哲, 森下 啓太郎, 細谷 謙次, 滝口 満喜
    日本獣医学会学術集会講演要旨集, 162回, 469, 469, (公社)日本獣医学会, Aug. 2019
    Japanese
  • PMab-247 Detects Bear Podoplanin in Immunohistochemical Analysis
    Takei J, Furusawa Y, Yamada S, Nakamura T, Sayama Y, Sano M, Konnai S, Kobayashi A, Harada H, Kaneko MK, Kato Y
    Monoclon Antib Immunodiagn Immunother., 38, 4, 171, 174, Aug. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Podoplanin (PDPN) is utilized as a specific marker of type I alveolar cells of lung and lymphatic endothelial cells of every tissue. Therefore, sensitive and specific monoclonal antibodies detecting PDPN are necessary for immunohistochemical analyses, especially using formalin-fixed paraffin-embedded tissues. Recently, we developed an anti-bear PDPN (bPDPN) mAb, PMab-247, which is useful for Western blot, flow cytometry, and immunohistochemical analyses. In this study, immunohistochemical analyses showed that PMab-247 strongly detected bPDPN, which is expressed in type I alveolar cells and lymphatic endothelial cells of bear lung and podocytes of bear kidney. These findings suggest that PMab-247 could be useful for pathophysiological analyses using immunohistochemistry.
  • Prostaglandin E2 induced immune exhaustion and enhancement of anti-viral effects by anti-PD-L1 antibody combined with COX-2 inhibitor in bovine leukemia virus infection
    Sajiki Y, Konnai S, Okagawa T, Nishimori A, Maekawa N, Goto S, Watari K, Minato E, Kobayashi A, Kohara J, Yamada S, Kaneko M, Kato Y, Takahashi H, Terasaki N, Takeda A, Yamamoto K, Toda M, Suzuki Y, Murata S, Ohashi K
    J. Immunol, 203, 5, 1313, 1324, Aug. 2019, [Peer-reviewed]
    English, Scientific journal
  • Vector transmission of bovine leukemia virus during summer season in Northern Hokkaido
    Inagaki H, Konnai S, Kaburagi H, Murota H, Takabatake N, Watari K, Okagawa T, Maekawa N, Murata S, Ohashi K
    Jpn. J. Vet. Res, 67, 3, 235, 239, Aug. 2019, [Peer-reviewed]
    English, Scientific journal
  • Immunohistochemical Analysis of the Harbor Porpoise Using Antipodoplanin Antibody PMab-237.
    Shinji Yamada, Shunsuke Itai, Takuro Nakamura, Junko Takei, Masato Sano, Satoru Konnai, Atsushi Kobayashi, Shotaro Nakagun, Yoshiyasu Kobayashi, Mika K Kaneko, Yukinari Kato
    Monoclonal antibodies in immunodiagnosis and immunotherapy, 38, 3, 104, 107, Jun. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Podoplanin (PDPN)/T1 alpha is known as a specific marker of lymphatic endothelial cells and type I alveolar cells. Sensitive and specific monoclonal antibodies (mAbs) for PDPN are needed for immunohistochemical analyses. Recently, we developed an anticetacean PDPN mAb, PMab-237. Herein, immunohistochemical analyses showed that PMab-237 strongly detected pulmonary type I alveolar cells, renal podocytes, and lymphatic endothelial cells of the harbor porpoise. These findings suggest that PMab-237 may be useful for immunohistochemical analyses for cetacean tissues.
  • Haematophagous mites on poultry farms in the Republic of the Union of Myanmar
    Takehara M, Murata S, Katakura K, Fujisawa S, Hmoon MM, Win SY, Bawn S, Htun LL, Aung YH, Win MM, Isezaki M, Maekawa N, Okagawa T, Konnai S, Ohashi K
    Heliyon, 5, 4, e01544, Apr. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Haematophagous ectoparasites of poultry, such as Ornithonyssus sylviarum, northern fowl mites (NFMs), Dermanyssus gallinae, poultry red mites (PRMs), and Ornithonyssus bursa, tropical fowl mites (TFMs) are prevalent worldwide. Although poultry farming is a major industry in Southeast Asia, there are only a few reports concerning the prevalence of avian mites in this region. In this study, we sampled twenty farms in four major poultry farming areas in Myanmar. We detected the mites on six farms, and they showed morphological similarities to NFMs and TFMs. The nucleotide sequences of cytochrome c oxidase subunit I indicated that some mites were NFMs. This is the first report confirming the presence of NFMs and TFMs among the hematophagous mites infesting chickens on Myanmar poultry farms.
  • Carbohydrate Metabolic Compensation Coupled to High Tolerance to Oxidative Stress in Ticks               
    Noce BD, Uhl M, Machado J, Waltero C, Abreu L, Silva R, Fonseca R, Barros C, Sabadin G, Konnai S, Silva Vaz Jr. I, Ohashi K, Logullo C
    Scientific Rep., 9, 4753, Mar. 2019, [Peer-reviewed]
    English, Scientific journal
  • Effects of bovine tumor necrosis factor alpha decoy receptors on cell death and inflammatory cytokine kinetics: Potential for bovine inflammation therapy
    Fujisawa S, Konnai S, Okagawa T, Maekawa N, Tanaka A, Suzuki Y, Murata S, Ohashi K
    BMC Vet Res., 15, 1, 68, 68, Feb. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: Refractory diseases, including bacterial infections, are causing huge economic losses in dairy farming. Despite efforts to prevent and treat those diseases in cattle, including the use of antimicrobials, it is not well controlled in the field. Several inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), play important roles in disease progression; thus, blocking these cytokines can attenuate the acute and sever inflammation and may be a novel strategy for treatment. However, biological drugs targeting inflammatory cytokines have not been used in cattle. Therefore, in this study, bovine sTNFR1 and sTNFR2 IgG1 Fc-fusion proteins (TNFR1-Ig and TNFR2-Ig) were produced, and their anti-inflammatory functions were analyzed in vitro, to develop decoy receptors for bovine TNF-α. RESULTS: Both TNFR1-Ig and TNFR2-Ig were shown to bind with TNF-α, and TNFR2-Ig showed higher affinity toward TNF-α than TNFR1-Ig. We next stimulated murine fibroblast-derived cells (L929 cells) with TNF-α to induce cell death and analyzed cell viability in the presence of TNFR-Ig proteins. Both TNFR1-Ig and TNFR2-Ig suppressed TNF-α-induced cell death, significantly improving cell viability. In addition, cell death induced by TNF-α was suppressed, even at low TNFR2-Ig concentrations, suggesting TNFR2-Ig has higher activity to suppress TNF-α functions than TNFR1-Ig. Finally, to examine TNFR2-Ig's anti-inflammatory, we cultured peripheral blood mononuclear cells from cattle with TNF-α in the presence of TNFR2-Ig and analyzed the gene expression and protein production of the inflammatory cytokines IL-1β and TNF-α. TNFR2-Ig significantly reduced the gene expression and protein production of these cytokines. Our results suggest that TNFR2-Ig inhibits inflammatory cytokine kinetics by blocking TNF-α to transmembrane TNFR, thereby attenuating excessive inflammation induced by TNF-α. CONCLUSIONS: Collectively, the findings of this study demonstrated the potential of TNFR2-Ig as a novel therapeutic for inflammatory diseases, such as bovine clinical mastitis. Further investigation is required for future clinical application.
  • Anti-Horse Podoplanin Monoclonal Antibody PMab-219 is Useful for Detecting Lymphatic Endothelial Cells by Immunohistochemical Analysis               
    Kato Y, Yamada S, Itai S, Kobayashi A, Konnai S, Kaneko MK
    Monoclon Antib Immunodiagn Immunother., 37, 6, 272, 274, Dec. 2018, [Peer-reviewed]
    English, Scientific journal
  • Detection of Alpaca Podoplanin by Immunohistochemistry Using the Antibovine Podoplanin Monoclonal Antibody PMab-44               
    Kato Y, Yamada S, Itai S, Konnai S, Kobayashi A, Kaneko MK
    Monoclon Antib Immunodiagn Immunother., 37, 6, 269, 271, Dec. 2018, [Peer-reviewed]
    English, Scientific journal
  • Immunohistochemical Detection of Sheep Podoplanin Using an Antibovine Podoplanin Monoclonal Antibody PMab-44               
    Kato Y, Yamada S, Itai S, Kobayashi A, Konnai S, Kaneko MK
    Monoclon Antib Immunodiagn Immunother., 37, 6, 265, 268, Dec. 2018, [Peer-reviewed]
    English, Scientific journal
  • The mouse-canine chimeric anti-dog podoplanin antibody P38B exerts antitumor activity in mouse xenograft models               
    Kato Y, Ohishi T, Kawada M, Maekawa N, Konnai S, Itai S, Yamada S, Kaneko MK
    Biochem Biophys Rep., 17, 23, 26, Nov. 2018, [Peer-reviewed]
    English, Scientific journal
  • Identification of immuno-inhibitory molecules in Mongolian native cattle and yak
    Ochirkhuu N, Konnai S, Odbileg R, Okagawa T, Maekawa N, Murata S, Ohashi K
    Jpn J Vet Res, 66, 3, 177, 192, Aug. 2018, [Peer-reviewed]
    English, Scientific journal
  • Cattle with a low bovine leukemia virus proviral load are rarely an infectious source               
    Mekata H, Yamamoto M, Hayashi T, Kirino Y, Sekiguchi S, Konnai S, Horii Y, Norimine J
    Jpn J Vet Res, 66, 3, 157, 163, Aug. 2018, [Peer-reviewed]
    English, Scientific journal
  • Cooperation of PD-1 and LAG-3 in the exhaustion of CD4+ and CD8+ T cells during bovine leukemia virus infection.
    Tomohiro Okagawa, Satoru Konnai, Asami Nishimori, Naoya Maekawa, Shinya Goto, Ryoyo Ikebuchi, Junko Kohara, Yasuhiko Suzuki, Shinji Yamada, Yukinari Kato, Shiro Murata, Kazuhiko Ohashi
    Veterinary research, 49, 1, 50, 50, 19 Jun. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Bovine leukemia virus (BLV) is a retrovirus that infects B cells in cattle and causes bovine leukosis after a long latent period. Progressive exhaustion of T cell functions is considered to facilitate disease progression of BLV infection. Programmed death-1 (PD-1) and lymphocyte activation gene-3 (LAG-3) are immunoinhibitory receptors that contribute to T-cell exhaustion caused by BLV infection in cattle. However, it is unclear whether the cooperation of PD-1 and LAG-3 accelerates disease progression of BLV infection. In this study, multi-color flow cytometric analyses of PD-1- and LAG-3-expressing T cells were performed in BLV-infected cattle at different stages of the disease. The frequencies of PD-1+LAG-3+ heavily exhausted T cells among CD4+ and CD8+ T cells was higher in the blood of cattle with B-cell lymphoma over that of BLV-uninfected and BLV-infected cattle without lymphoma. In addition, blockade assays of peripheral blood mononuclear cells were performed to examine whether inhibition of the interactions between PD-1 and LAG-3 and their ligands by blocking antibodies could restore T-cell function during BLV infection. Single or dual blockade of the PD-1 and LAG-3 pathways reactivated the production of Th1 cytokines, interferon-γ and tumor necrosis factor-α, from BLV-specific T cells of the infected cattle. Taken together, these results indicate that PD-1 and LAG-3 cooperatively mediate the functional exhaustion of CD4+ and CD8+ T cells and are associated with the development of B-cell lymphoma in BLV-infected cattle.
  • Epitope mapping of anti-mouse podoplanin monoclonal antibody PMab-1               
    Yamada S, Itai S, Kaneko MK, Konnai S, Kato Y
    Biochem Biophys Rep., 15, 52, 56, Jun. 2018, [Peer-reviewed]
    English, Scientific journal
  • Evaluation of costimulatory molecules in dogs with B cell high grade lymphoma               
    Tagawa M, Kurashima C, Takagi S, Maekawa N, Konnai S, Shimbo G, Matsumoto K, Inokuma H, Kawamoto K, Miyahara K
    PLoS One, 13, 7, e0201222, Jun. 2018, [Peer-reviewed]
    English, Scientific journal
  • Prostaglandin E2 Induction Suppresses the Th1 Immune Responses in Cattle with Johne's Disease               
    Sajiki Y, Konnai S, Okagawa T, Nishimori A, Maekawa N, Goto S, Ikebuchi R, Nagata R, Kawaji S, Kagawa Y, Yamada S, Kato Y, Nakajima C, Suzuki Y, Murata S, Mori Y, Ohashi K
    Infect Immun., 86, 5, e00910-17, Apr. 2018, [Peer-reviewed]
    English, Scientific journal
  • Identification of an Atypical Enzootic Bovine Leukosis in Japan by Using a Novel Classification of Bovine Leukemia Based on Immunophenotypic Analysis               
    Nishimori A, Konnai S, Okagawa T, Maekawa N, Goto S, Ikebuchi R, Nakahara A, Chiba Y, Ikeda M, Murata S, Ohashi K
    Clin Vaccine Immunol., 24, 12, e00001-18, Apr. 2018, [Peer-reviewed]
    English, Scientific journal
  • New hematological key for bovine leukemia virus-infected Japanese Black cattle.
    Hirohisa Mekata, Mari Yamamoto, Yumi Kirino, Satoshi Sekiguchi, Satoru Konnai, Yoichiro Horii, Junzo Norimine
    The Journal of veterinary medical science, 80, 2, 316, 319, 20 Feb. 2018, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, The European Community's (EC) Key, which is also called Bendixen's Key, is a well-established bovine leukemia virus (BLV) diagnostic method that classifies cattle according to the absolute lymphocyte count and age. The EC Key was originally designed for dairy cattle and is not necessarily suitable for Japanese Black (JB) beef cattle. This study revealed the lymphocyte counts in the BLV-free and -infected JB cattle were significantly lower than those in the Holstein cattle. Therefore, applying the EC Key to JB cattle could result in a large number of undetected BLV-infected cattle. Our proposed hematological key, which was designed for JB cattle, improves the detection of BLV-infected cattle by approximately 20%. We believe that this study could help promote BLV control.
  • Molecular detection and phylogenetic analysis of Ehrlichia canis in a Philippine dog
    Maekawa N, Konnai S, Balbin MM, Mingala CN, Gicana KRB, Bernando FAEM, Murata S, Ohashi K
    Ticks Tick Borne Dis., 9, 2, 266, 269, Feb. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Canine monocytic ehrlichiosis (CME), caused by a rickettsial bacterium, Ehrlichia canis, is distributed worldwide, particularly in tropical and subtropical regions. Transmission of E. canis is primarily mediated by the vector tick, Rhipicephalus sanguineus sensu lato and the bacteria then infect and replicate in monocytes and macrophages. Many cases are seen in veterinary hospitals and treated routinely; however, the genetic variation of E. canis strains found in the Philippines has been poorly investigated to date. In this study, the 16S rRNA gene and the gp200 gene of E. canis were detected by polymerase chain reaction from an infected dog in the Philippines, and the deduced amino acid sequence of the gp200 gene was subjected to a phylogenetic analysis. The Philippine genotype formed a cluster with the Taiwan genotype, and was somewhat divergent from the USA and Brazil strains. This suggested that E. canis underwent evolution in East and Southeast Asia, confirming the utility of the gp200 gene for the assessment of genetic relationships among strains.
  • Expression profile of Rhipicephalus microplus vitellogenin receptor during oogenesis
    Adriana Seixas, Maria Fernanda Alzugaray, Lucas Tirloni, Luis Fernando Parizi, Antonio Frederico Michel Pinto, Naftaly Wang'ombe Githaka, Satoru Konnai, Kazuhiko Ohashi, John R. Yates, Carlos Termignoni, Itabajara da Silva Vaz
    TICKS AND TICK-BORNE DISEASES, 9, 1, 72, 81, Jan. 2018, [Peer-reviewed]
    English, Scientific journal
  • Intrauterine infection with bovine leukemia virus in pregnant dam with high viral load.
    Yamato Sajiki, Satoru Konnai, Asami Nishimori, Tomohiro Okagawa, Naoya Maekawa, Shinya Goto, Masashi Nagano, Junko Kohara, Nana Kitano, Toshihiko Takahashi, Motoshi Tajima, Hirohisa Mekata, Yoichiro Horii, Shiro Murata, Kazuhiko Ohashi
    The Journal of veterinary medical science, 79, 12, 2036, 2039, 22 Dec. 2017, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, Enzootic bovine leukemia is caused by the bovine leukemia virus (BLV). BLV is transmitted vertically or horizontally through the transfer of infected cells via direct contact, through milk, insect bites and contaminated iatrogenic procedures. However, we lacked direct evidence of intrauterine infection. The purpose of this study was to confirm intrauterine BLV infection in two pregnant dams with high viral load by cesarean delivery. BLV was detected in cord and placental blood, and the BLV in the newborns showed 100% nucleotide identity with the BLV-env sequence from the dams. Notably, a newborn was seropositive for BLV but had no colostral antibodies. In this study, we presented a direct evidence of intrauterine BLV transmission in pregnant dam with a high proviral load. These results could aid the development of BLV control measures targeting viral load.
  • Expression of Cat Podoplanin in Feline Squamous Cell Carcinomas
    Shunsuke Itai, Shinji Yamada, Mika K. Kaneko, Hiroyuki Harada, Yumiko Kagawa, Satoru Konnai, Yukinari Kato
    Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 36, 6, 243, 250, Mary Ann Liebert Inc., 01 Dec. 2017, [Peer-reviewed]
    English, Scientific journal
  • Detection and molecular characterization of equine infectious anemia virus in Mongolian horses
    Tumenjargal Sharav, Satoru Konnai, Nyamsuren Ochirkhuu, Erdene T. S. Ochir, Hirohisa Mekata, Yoshihiro Sakoda, Takashi Umemura, Shiro Murata, Tungalag Chultemdorj, Kazuhiko Ohashi
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 79, 11, 1884, 1888, Nov. 2017, [Peer-reviewed]
    English, Scientific journal
  • PMab-52: Specific and Sensitive Monoclonal Antibody Against Cat Podoplanin for Immunohistochemistry
    Shinji Yamada, Shunsuke Itai, Takuro Nakamura, Miyuki Yanaka, Noriko Saidoh, Yao-Wen Chang, Saori Handa, Hiroyuki Harada, Yumiko Kagawa, Osamu Ichii, Satoru Konnai, Mika K. Kaneko, Yukinari Kato
    Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 36, 5, 224, 230, Mary Ann Liebert Inc., 01 Oct. 2017, [Peer-reviewed]
    English, Scientific journal
  • Increase of cells expressing PD-1 and PD-L1 and enhancement of IFN-γ production via PD-1/PD-L1 blockade in bovine mycoplasmosis
    Goto S, Konnai S, Okagawa T, Nishimori A, Maekawa N, Gondaira S, Higuchi H, Koiwa M, Tajima M, Kohara J, Ogasawara S, Kato Y, Suzuki Y, Murata S, Ohashi K
    Immun Inflamm Dis., 5, 3, 355, 363, Sep. 2017, [Peer-reviewed], [International Magazine]
    English, Scientific journal, INTRODUCTION: Bovine mycoplasma, chiefly Mycoplasma bovis, is a pathogen that causes pneumonia, mastitis, arthritis, and otitis media in cattle. This pathogen exerts immunosuppressive effects, such as the inhibition of interferon production. However, the mechanisms involved in bovine mycoplasmosis have not been fully elucidated. In this study, we investigated the role of the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway in immunosuppression in bovine mycoplasmosis. METHODS: In the initial experiments, we used enzyme-linked immunosorbent assay to measure interferon-γ (IFN-γ) from peripheral blood mononuclear cells (PBMCs) isolated from cattle with mycoplasmosis. RESULTS: Expectedly, IFN-γ production significantly decreased in cattle with mycoplasmosis compared with that in clinically healthy cattle. Concomitantly, flow cytometric analysis revealed that the proportions of PD-1+ CD4+ and PD-L1+ CD14+ cells significantly increased in peripheral blood of the infected cattle. Interestingly, the number of PD-1+ CD4+ and PD-1+ CD8+ T cells were negatively correlated with IFN-γ production from PBMCs in bovine mycoplasmosis. Additionally, blockade of the PD-1/PD-L1 pathway in vitro by anti-bovine PD-1- and anti-bovine PD-L1 antibodies significantly upregulated the production of IFN-γ from anti-mycoplasma-specific cells. CONCLUSIONS: These results suggest that the PD-1/PD-L1 pathway could be involved in immune exhaustion of bovine mycoplasma-specific T cells. In conclusion, our study opens up a new perspective in the therapeutic strategy for bovine mycoplasmosis by targeting the immunoinhibitory receptor pathways.
  • Molecular Epidemiological Survey and Genetic Characterization of Anaplasma Species in Mongolian Livestock
    Nyamsuren Ochirkhuu, Satoru Konnai, Raadan Odbileg, Shiro Murata, Kazuhiko Ohashi
    VECTOR-BORNE AND ZOONOTIC DISEASES, 17, 8, 539, 549, Aug. 2017, [Peer-reviewed]
    English, Scientific journal
  • A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma
    Maekawa N, Konnai S, Takagi S, Kagawa Y, Okagawa T, Nishimori A, Ikebuchi R, Izumi Y, Deguchi T, Nakajima C, Kato Y, Yamamoto K, Uemura H, Suzuki Y, Murata S, Ohashi K
    Sci Rep., 7, 1, 8951, 8951, Aug. 2017, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Immunotherapy targeting immune checkpoint molecules, programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), using therapeutic antibodies has been widely used for some human malignancies in the last 5 years. A costimulatory receptor, PD-1, is expressed on T cells and suppresses effector functions when it binds to its ligand, PD-L1. Aberrant PD-L1 expression is reported in various human cancers and is considered an immune escape mechanism. Antibodies blocking the PD-1/PD-L1 axis induce antitumour responses in patients with malignant melanoma and other cancers. In dogs, no such clinical studies have been performed to date because of the lack of therapeutic antibodies that can be used in dogs. In this study, the immunomodulatory effects of c4G12, a canine-chimerised anti-PD-L1 monoclonal antibody, were evaluated in vitro, demonstrating significantly enhanced cytokine production and proliferation of dog peripheral blood mononuclear cells. A pilot clinical study was performed on seven dogs with oral malignant melanoma (OMM) and two with undifferentiated sarcoma. Objective antitumour responses were observed in one dog with OMM (14.3%, 1/7) and one with undifferentiated sarcoma (50.0%, 1/2) when c4G12 was given at 2 or 5 mg/kg, every 2 weeks. c4G12 could be a safe and effective treatment option for canine cancers.
  • Characterization of the Anti-Bovine Podoplanin Monoclonal Antibody PMab-44
    Shinji Yamada, Ryusuke Honma, Mika K. Kaneko, Takuro Nakamura, Miyuki Yanaka, Noriko Saidoh, Michiaki Takagi, Satoru Konnai, Yukinari Kato
    Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 36, 3, 129, 134, Mary Ann Liebert Inc., 01 Jun. 2017, [Peer-reviewed]
    English, Scientific journal
  • Anti-Bovine Programmed Death-1 Rat-Bovine Chimeric Antibody for Immunotherapy of Bovine Leukemia Virus Infection in Cattle
    Tomohiro Okagawa, Satoru Konnai, Asami Nishimori, Naoya Maekawa, Ryoyo Ikebuchi, Shinya Goto, Chie Nakajima, Junko Kohara, Satoshi Ogasawara, Yukinari Kato, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
    FRONTIERS IN IMMUNOLOGY, 8, 650, Jun. 2017, [Peer-reviewed]
    English, Scientific journal
  • Molecular characterization of the lymphocyte activation gene-3 (LAG-3, CD223) of swamp- and riverine-type water buffaloes (Bubalus bubalis)
    Shanemae M. Rivera, Ryan Bismark C. Padiernos, Evaristo A. Abella, Satoru Konnai, Claro N. Mingala
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 65, 2, 65, 74, May 2017, [Peer-reviewed]
    English, Scientific journal
  • Clinical and subclinical bovine leukemia virus infection in a dairy cattle herd in Zambia
    Girja S. Pandey, Edgar Simulundu, Danstan Mwiinga, Kenny L. Samui, Aaron S. Mweene, Masahiro Kajihara, Alfred Mangani, Racheal Mwenda, Joseph Ndebe, Satoru Konnai, Ayato Takada
    ARCHIVES OF VIROLOGY, 162, 4, 1051, 1056, Apr. 2017, [Peer-reviewed]
    English, Scientific journal
  • Development of mPMab-1, a Mouse-Rat Chimeric Antibody Against Mouse Podoplanin
    Shinji Yamada, Mika K. Kaneko, Takuro Nakamura, Osamu Ichii, Satoru Konnai, Yukinari Kato
    Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 36, 2, 77, 79, Mary Ann Liebert Inc., 01 Apr. 2017, [Peer-reviewed]
    English, Scientific journal
  • In vitro and in vivo antivirus activity of an anti-programmed death-ligand 1 (PD-L1) ratbovine chimeric antibody against bovine leukemia virus infection
    Asami Nishimori, Satoru Konnai, Tomohiro Okagawa, Naoya Maekawa, Ryoyo Ikebuchi, Shinya Goto, Yamato Sajiki, Yasuhiko Suzuki, Junko Kohara, Satoshi Ogasawara, Yukinari Kato, Shiro Murata, Kazuhiko Ohashi
    PLOS ONE, 12, 4, e0174916, Apr. 2017, [Peer-reviewed]
    English, Scientific journal
  • Isolation and purification of Gallid herpesvirus 2 strains currently distributed in Japan
    Yuka Machida, Shiro Murata, Ayumi Matsuyama-Kato, Masayoshi Isezaki, Akira Taneno, Eishi Sakai, Satoru Konnai, Kazuhiko Ohashi
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 79, 1, 115, 122, Jan. 2017, [Peer-reviewed]
    English, Scientific journal
  • Immune exhaustion during chronic infections in cattle
    Satoru Konnai, Shiro Murata, Kazuhiko Ohashi
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 79, 1, 1, 5, Jan. 2017, [Peer-reviewed], [Invited]
    English, Scientific journal
  • A novel mechanism of functional cooperativity regulation by thiol redox status in a dimeric inorganic pyrophosphatase
    Evenilton P. Costa, Arnoldo R. Facanha, Criscila S. Cruz, Jhenifer N. Silva, Josias A. Machado, Gabriel M. Carvalho, Mariana R. Fernandes, Renato Martins, Eldo Campos, Nelilma C. Romeiro, Naftaly W. Githaka, Satoru Konnai, Kazuhiko Ohashi, Itabajara S. Vaz, Carlos Logullo
    BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1861, 1, 2922, 2933, Jan. 2017, [Peer-reviewed]
    English, Scientific journal
  • Molecular and structural characterization of novel cystatins from the taiga tick Ixodes persulcatus
    Carolina K. Rangel, Luis F. Parizi, Gabriela A. Sabadin, Evenilton P. Costa, Nelilma C. Romeiro, Masayoshi Isezaki, Naftaly W. Githaka, Adriana Seixas, Carlos Logullo, Satoru Konnai, Kazuhiko Ohashi, Itabajara da Silva Vaz
    TICKS AND TICK-BORNE DISEASES, 8, 3, 432, 441, 2017, [Peer-reviewed]
    English, Scientific journal
  • Molecular epidemiological survey and genetic characterization of ovine gammaherpesvirus-2 in Mongolian livestock
    Nyamsuren Ochirkhuu, Satoru Konnai, Raadan Odbileg, Shiro Murata, Kazuhiko Ohashi
    Journal of Veterinary Medical Science, 79, 12, 2040, 2042, Japanese Society of Veterinary Science, 2017, [Peer-reviewed]
    English, Scientific journal
  • Podoplanin Expression in Canine Melanoma
    Satoshi Ogasawara, Ryusuke Honma, Mika K. Kaneko, Yuki Fujii, Yumiko Kagawa, Satoru Konnai, Yukinari Kato
    Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 35, 6, 304, 306, Mary Ann Liebert Inc., 01 Dec. 2016, [Peer-reviewed]
    English, Scientific journal
  • Cooperation of PD-1 and LAG-3 Contributes to T-Cell Exhaustion in Anaplasma marginale-Infected Cattle
    Tomohiro Okagawa, Satoru Konnai, James R. Deringer, Massaro W. Ueti, Glen A. Scoles, Shiro Murata, Kazuhiko Ohashi, Wendy C. Brown
    INFECTION AND IMMUNITY, 84, 10, 2779, 2790, Oct. 2016, [Peer-reviewed]
    English, Scientific journal
  • PMab-38 Recognizes Canine Podoplanin of Squamous Cell Carcinomas
    Mika K. Kaneko, Ryusuke Honma, Satoshi Ogasawara, Yuki Fujii, Takuro Nakamura, Noriko Saidoh, Michiaki Takagi, Yumiko Kagawa, Satoru Konnai, Yukinari Kato
    Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 35, 5, 263, 266, Mary Ann Liebert Inc., 01 Oct. 2016, [Peer-reviewed]
    English, Scientific journal
  • Molecular detection and characterization of bovine viral diarrhea virus in Mongolian cattle and yaks
    Nyamsuren Ochirkhuu, Satoru Konnai, Raadan Odbileg, Battogtokh Odzaya, Shura Gansukh, Shiro Murata, Kazuhiko Ohashi
    ARCHIVES OF VIROLOGY, 161, 8, 2279, 2283, Aug. 2016, [Peer-reviewed]
    English, Scientific journal
  • Specific Detection of Dog Podoplanin Expressed in Renal Glomerulus by a Novel Monoclonal Antibody PMab-38 in Immunohistochemistry
    Ryusuke Honma, Mika K. Kaneko, Satoshi Ogasawara, Yuki Fujii, Satoru Konnai, Michiaki Takagi, Yukinari Kato
    Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 35, 4, 212, 216, Mary Ann Liebert Inc., 01 Aug. 2016, [Peer-reviewed]
    English, Scientific journal
  • PMab-44 Detects Bovine Podoplanin in Immunohistochemistry               
    Honma R, Ogasawara S, Kaneko MK, Fujii Y, Oki H, Nakamura T, Takagi M, Konnai S, Kato Y
    Monoclon Antib Immunodiagn Immunother., Jun. 2016, [Peer-reviewed]
    English, Scientific journal
  • Immunohistochemical Analysis of PD-L1 Expression in Canine Malignant Cancers and PD-1 Expression on Lymphocytes in Canine Oral Melanoma
    Naoya Maekawa, Satoru Konnai, Tomohiro Okagawa, Asami Nishimori, Ryoyo Ikebuchi, Yusuke Izumi, Satoshi Takagi, Yumiko Kagawa, Chie Nakajima, Yasuhiko Suzuki, Yukinari Kato, Shiro Murata, Kazuhiko Ohashi
    PLOS ONE, 11, 6, e0157176, Jun. 2016, [Peer-reviewed]
    English, Scientific journal
  • Direct polymerase chain reaction from blood and tissue samples for rapid diagnosis of bovine leukemia virus infection
    Asami Nishimori, Satoru Konnai, Ryoyo Ikebuchi, Tomohiro Okagawa, Ayako Nakahara, Shiro Murata, Kazuhiko Ohashi
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 78, 5, 791, 796, May 2016, [Peer-reviewed]
    English, Scientific journal
  • Detection of bovine leukemia virus and identification of its genotype in Mongolian cattle
    Nyamsuren Ochirkhuu, Satoru Konnai, Raadan Odbileg, Asami Nishimori, Tomohiro Okagawa, Shiro Murata, Kazuhiko Ohashi
    ARCHIVES OF VIROLOGY, 161, 4, 985, 991, Apr. 2016, [Peer-reviewed]
    English, Scientific journal
  • Critical Epitope of Anti-Rabbit Podoplanin Monoclonal Antibodies for Immunohistochemical Analysis
    Ryusuke Honma, Yuki Fujii, Satoshi Ogasawara, Hiroharu Oki, Satoru Konnai, Yumiko Kagawa, Michiaki Takagi, Mika K. Kaneko, Yukinari Kato
    Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 35, 2, 65, 72, Mary Ann Liebert Inc., 01 Apr. 2016, [Peer-reviewed]
    English, Scientific journal
  • Evaluation of Costimulatory Molecules in Peripheral Blood Lymphocytes of Canine Patients with Histiocytic Sarcoma
    Michihito Tagawa, Naoya Maekawa, Satoru Konnai, Satoshi Takagi
    PLOS ONE, 11, 2, e0150030, Feb. 2016, [Peer-reviewed]
    English, Scientific journal
  • Identification and the preliminary in vitro characterization of IRIS homologue from salivary glands of Ixodes persulcatus Schulze
    Kochi Toyomane, Satoru Konnai, Ayano Niwa, Naftaly Githaka, Masayoshi Isezaki, Shinji Yamada, Takuya Ito, Ai Takano, Shuji Ando, Hiroki Kawabata, Shiro Murata, Kazuhiko Ohashi
    TICKS AND TICK-BORNE DISEASES, 7, 1, 119, 125, 2016, [Peer-reviewed]
    English, Scientific journal
  • Bovine leukemia virus reduces anti-viral cytokine activities and NK cytotoxicity by inducing TGF-β secretion from regulatory T cells
    Ohira K, Nakahara A, Konnai S, Okagawa T, Nishimori A, Maekawa N, Ikebuchi R, Kohara J, Murata S, Ohashi K
    Immun Inflamm Dis., 4, 1, 52, 63, Jan. 2016, [Peer-reviewed], [International Magazine]
    English, Scientific journal, CD4(+)CD25(high)Foxp3(+) T cells suppress excess immune responses that lead to autoimmune and/or inflammatory diseases, and maintain host immune homeostasis. However, CD4(+)CD25(high)Foxp3(+) T cells reportedly contribute to disease progression by over suppressing immune responses in some chronic infections. In this study, kinetic and functional analyses of CD4(+)CD25(high)Foxp3(+) T cells were performed in cattle with bovine leukemia virus (BLV) infections, which have reported immunosuppressive characteristics. In initial experiments, production of the Th1 cytokines IFN-γ and TNF-α was reduced in BLV-infected cattle compared with uninfected cattle, and numbers of IFN-γ or TNF-α producing CD4(+) T cells decreased with disease progression. In contrast, IFN-γ production by NK cells was inversely correlated with BLV proviral loads in infected cattle. Additionally, during persistent lymphocytosis disease stages, NK cytotoxicity was depressed as indicated by low expression of the cytolytic protein perforin. Concomitantly, total CD4(+)CD25(high)Foxp3(+) T cell numbers and percentages of TGF-β(+) cells were increased, suggesting that TGF-β plays a role in the functional declines of CD4(+) T cells and NK cells. In further experiments, recombinant bovine TGF-β suppressed IFN-γ and TNF-α production by CD4(+) T cells and NK cytotoxicity in cultured cells. These data suggest that TGF-β from CD4(+)CD25(high)Foxp3(+) T cells is immunosuppressive and contributes to disease progression and the development of opportunistic infections during BLV infection.
  • Molecular characterization of T-cell immunoglobulin mucin domain-3 and Galectin-9 genes of swamp- and riverine-type water buffaloes
    P. L. H. Duran, R. B. C. Padiernos, E. A. Abella, S. Konnai, C. N. Mingala
    INTERNATIONAL JOURNAL OF IMMUNOGENETICS, 42, 6, 469, 478, Dec. 2015, [Peer-reviewed]
    English, Scientific journal
  • A preliminary survey of the seroprevalence of Mycobacterium avium subspecies paratuberculosis in Mongolian cattle
    Nyamsuren Ochirkhuu, Satoru Konnai, Raadan Odbileg, Shiro Murata, Kazuhiko Ohashi
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 63, 4, 191, 194, Nov. 2015, [Peer-reviewed]
    English, Scientific journal
  • Metal extent in blood of livestock from Dandora dumping site, Kenya: Source identification of Pb exposure by stable isotope analysis
    Hokuto Nakata, Shouta M. M. Nakayama, Yoshinori Ikenaka, Hazuki Mizukawa, Chihiro Ishii, Yared B. Yohannes, Satoru Konnai, Wageh Sobhy Darwish, Mayumi Ishizuka
    ENVIRONMENTAL POLLUTION, 205, 8, 15, Oct. 2015, [Peer-reviewed]
    English, Scientific journal
  • Horizontal transmission and phylogenetic analysis of bovine leukemia virus in two districts of Miyazaki, Japan
    Hirohisa Mekata, Satoshi Sekiguchi, Satoru Konnai, Yumi Kirino, Yoichiro Horii, Junzo Norimine
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 77, 9, 1115, 1120, Sep. 2015, [Peer-reviewed]
    English, Scientific journal
  • Molecular epidemiological survey and genetic analysis of vector-borne infections of cattle in Luzon Island, the Philippines
    Nyamsuren Ochirkhuu, Satoru Konnai, Claro N. Mingala, Tomohiro Okagawa, Marvin Villanueva, Flor Marie Immanuelle R. Pilapil, Shiro Murata, Kazuhiko Ohashi
    VETERINARY PARASITOLOGY, 212, 3-4, 161, 167, Sep. 2015, [Peer-reviewed]
    English, Scientific journal
  • 組織球性肉腫罹患犬における末梢血中免疫状態の解析               
    田川 道人, 前川 直也, 今内 覚, 高木 哲
    日本獣医学会学術集会講演要旨集, 158回, 407, 407, (公社)日本獣医学会, Aug. 2015
    Japanese
  • Expression of regulatory dendritic cell-related cytokines in cattle experimentally infected with Trypanosoma evansi
    Hirohisa Mekata, Shiro Murata, Claro Niegos Mingala, Kazuhiko Ohashi, Satoru Konnai
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 77, 8, 1017, 1019, Aug. 2015, [Peer-reviewed]
    English, Scientific journal
  • Vaccination with cyclin-dependent kinase tick antigen confers protection against Ixodes infestation
    Helga Gomes, Jorge Moraes, Naftaly Githaka, Renato Martins, Masayoshi Isezaki, Itabajara da Silva Vaz, Carlos Logullo, Satoru Konnai, Kazuhiko Ohashi
    VETERINARY PARASITOLOGY, 211, 3-4, 266, 273, Jul. 2015, [Peer-reviewed]
    English, Scientific journal
  • CELLULAR IMMUNE RESPONSE TO INTERFERON-tau IN PERIPHERAL BLOOD MONONUCLEAR CELLS OF JAPANESE BLACK CATTLE WITH BOVINE LEUKEMIA VIRUS INFECTION
    Kakinuma Sei-Ichi, Izawa Tomohiro, Matsuda Kei-Ichi, Konnai Satoru, Maeda Yosuke, Ohtsuka Hiromichi
    ACTA VETERINARIA-BEOGRAD, 65, 2, 287, 296, Jun. 2015, [Peer-reviewed]
    English, Scientific journal
  • An investigation of binding ability of Ixodes persulcatus Schulze Salp15 with Lyme disease spirochetes
    Yusuke Murase, Satoru Konnai, Shinji Yamada, Naftaly Githaka, Masayoshi Isezaki, Takuya Ito, Ai Takano, Shuji Ando, Hiroki Kawabata, Siro Murata, Kazuhko Ohashi
    INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY, 60, 59, 67, May 2015, [Peer-reviewed]
    English, Scientific journal
  • Cytokine mRNA profiling and the proliferative response of bovine peripheral blood mononuclear cells to Mycoplasma bovis
    Satoshi Gondaira, Hidetoshi Higuchi, Hidetomo Iwano, Keiichi Nakajima, Kazuhiro Kawai, Shuhei Hashiguchi, Satoru Konnai, Hajime Nagahata
    VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 165, 1-2, 45, 53, May 2015, [Peer-reviewed]
    English, Scientific journal
  • Evaluation of the natural perinatal transmission of bovine leukaemia virus
    Hirohisa Mekata, Satoshi Sekiguchi, Satoru Konnai, Yumi Kirino, Kazuyuki Honkawa, Nariaki Nonaka, Yoichiro Horii, Junzo Norimine
    VETERINARY RECORD, 176, 10, 254, +, Mar. 2015, [Peer-reviewed]
    English, Scientific journal
  • Increased expression of the regulatory T cell-associated marker CTLA-4 in bovine leukemia virus infection
    Saori Suzuki, Satoru Konnai, Tomohiro Okagawa, Ryoyo Ikebuchi, Asami Nishimori, Junko Kohara, Claro N. Mingala, Shiro Murata, Kazuhiko Ohashi
    VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 163, 3-4, 115, 124, Feb. 2015, [Peer-reviewed]
    English, Scientific journal
  • Rhipicephalus microplus and Ixodes ovatus cystatins in tick blood digestion and evasion of host immune response
    Luis Fernando Parizi, Gabriela Alves Sabadin, Mara Fernanda Alzugaray, Adriana Seixas, Carlos Logullo, Satoru Konnai, Kazuhiko Ohashi, Aoi Masuda, Itabajara da Silva Vaz
    PARASITES & VECTORS, 8, 122, Feb. 2015, [Peer-reviewed]
    English, Scientific journal
  • Non-Classical Gluconeogenesis-Dependent Glucose Metabolism in Rhipicephalus microplus Embryonic Cell Line BME26
    Renato Martins da Silva, Barbara Della Noce, Camila Fernanda Waltero, Evenilton Pessoa Costa, Leonardo Araujo de Abreu, Naftaly Wang'ombe Githaka, Jorge Moraes, Helga Fernandes Gomes, Satoru Konnai, Itabajara da Silva Vaz, Kazuhiko Ohashi, Carlos Logullo
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 16, 1, 1821, 1839, Jan. 2015, [Peer-reviewed]
    English, Scientific journal
  • Bovine immunoinhibitory receptors contribute to suppression of Mycobacterium avium subsp. paratuberculosis-specific T-cell responses
    Tomohiro Okagawa, Satoru Konnai, Asami Nishimori, Ryoyo Ikebuchi, Seiko Mizorogi, Reiko Nagata, Satoko Kawaji, Shogo Tanaka, Yumiko Kagawa, Shiro Murata, Yasuyuki Mori, Kazuhiko Ohashi
    Infection and Immunity, 84, 1, 77, 89, American Society for Microbiology, 2015, [Peer-reviewed]
    English, Scientific journal
  • 北海道のsika deerおよびHaemaphysalis属ダニより検出されたRF Borrelia属(A RF Borrelia sp. found among wild sika deer and Haemaphysalis ticks in Hokkaido)               
    李 景利, 高野 愛, Taylor Kyle, 佐鹿 万里子, 下鶴 倫人, 今内 覚, 川端 寛樹, 坪田 敏男
    日本獣医学会学術集会講演要旨集, 157回, 548, 548, (公社)日本獣医学会, Aug. 2014
    English
  • Influence of PD-L1 cross-linking on cell death in PD-L1-expressing cell lines and bovine lymphocytes
    Ryoyo Ikebuchi, Satoru Konnai, Tomohiro Okagawa, Kazumasa Yokoyama, Chie Nakajima, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
    IMMUNOLOGY, 142, 4, 551, 561, Aug. 2014, [Peer-reviewed]
    English, Scientific journal
  • Expression analysis of programmed death ligand 2 in tumors caused by the avian oncovirus Marek's disease virus
    Ayumi Matsuyama-Kato, Shiro Murata, Masayoshi Isezaki, Sarah Takasaki, Rika Kano, Satoru Konnai, Kazuhiko Ohashi
    ARCHIVES OF VIROLOGY, 159, 8, 2123, 2126, Aug. 2014, [Peer-reviewed]
    English, Scientific journal
  • Reprolysin metalloproteases from Ixodes persulcatus, Rhipicephalus sanguineus and Rhipicephalus microplus ticks
    Abid Ali, Lucas Tirloni, Masayoshi Isezaki, Adriana Seixas, Satoru Konnai, Kazuhiko Ohashi, Itabajara da Silva Vaz Junior, Carlos Termignoni
    EXPERIMENTAL AND APPLIED ACAROLOGY, 63, 4, 559, 578, Aug. 2014, [Peer-reviewed]
    English, Scientific journal
  • Suppressive effects of neutrophil by Salp16-like salivary gland proteins from Ixodes persulcatus Schulze tick
    A. Hidano, S. Konnai, S. Yamada, N. Githaka, M. Isezaki, H. Higuchi, H. Nagahata, T. Ito, A. Takano, S. Ando, H. Kawabata, S. Murata, K. Ohahsi
    INSECT MOLECULAR BIOLOGY, 23, 4, 466, 474, Aug. 2014, [Peer-reviewed]
    English, Scientific journal
  • Differences in cellular function and viral protein expression between IgM(high) and IgM(low) B-cells in bovine leukemia virus-infected cattle
    Ryoyo Ikebuchi, Satoru Konnai, Tomohiro Okagawa, Asami Nishimori, Ayako Nakahara, Shiro Murata, Kazuhiko Ohashi
    JOURNAL OF GENERAL VIROLOGY, 95, Pt 8, 1832, 1842, Aug. 2014, [Peer-reviewed]
    English, Scientific journal
  • Human Infections with Borrelia miyamotoi, Japan
    Sato, Kozue, Takano, Ai, Konnai, Satoru, Nakao, Minoru, Ito, Takuya, Koyama, Kojiro, Kaneko, Minoru, Ohnishi, Makoto, Kawabata, Hiroki
    EMERGING INFECTIOUS DISEASES, 20, 8, 1391, 1393, Aug. 2014, [Peer-reviewed]
    English, Scientific journal
  • Tick Surveillance for Relapsing Fever Spirochete Borrelia miyamotoi in Hokkaido, Japan
    Takano, Ai, Toyomane, Kochi, Konnai, Satoru, Ohashi, Kazuhiko, Nakao, Minoru, Ito, Takuya, Andoh, Masako, Maeda, Ken, Watarai, Masahisa, Sato, Kozue, Kawabata, Hiroki
    PLOS ONE, 9, 8, e104532, Aug. 2014, [Peer-reviewed]
    English, Scientific journal
  • Identification and characterization of bovine programmed death-ligand 2
    Asami Nishimori, Satoru Konnai, Ryoyo Ikebuchi, Tomohiro Okagawa, Chie Nakajima, Yasuhiko Suzuki, Claro N. Mingala, Shiro Murata, Kazuhiko Ohashi
    MICROBIOLOGY AND IMMUNOLOGY, 58, 7, 388, 397, Jul. 2014, [Peer-reviewed]
    English, Scientific journal
  • Expression of PD-L1 on Canine Tumor Cells and Enhancement of IFN-gamma Production from Tumor-Infiltrating Cells by PD-L1 Blockade
    Naoya Maekawa, Satoru Konnai, Ryoyo Ikebuchi, Tomohiro Okagawa, Mami Adachi, Satoshi Takagi, Yumiko Kagawa, Chie Nakajima, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
    PLOS ONE, 9, 6, e98415, Jun. 2014, [Peer-reviewed]
    English, Scientific journal
  • 牛白血病ウイルスに感染した黒毛和種牛の臨床例における免疫状態
    伊澤 智宏, 田中 健一郎, 柿沼 清市, 杉山 由夏, 松田 敬一, 小比類巻 正幸, 今内 覚, 大塚 浩通
    日本獣医師会雑誌, 67, 5, 328, 332, (公社)日本獣医師会, May 2014
    Japanese
  • Identification and sequence characterization of novel Theileria genotypes from the waterbuck (Kobus defassa) in a Theileria parva-endemic area in Kenya
    Naftaly Githaka, Satoru Konnai, Richard Bishop, David Odongo, Isaac Lekolool, Edward Kariuki, Francis Gakuya, Lucy Kamau, Masayoshi Isezaki, Shiro Murata, Kazuhiko Ohashi
    VETERINARY PARASITOLOGY, 202, 3-4, 180, 193, May 2014, [Peer-reviewed]
    English, Scientific journal
  • Bovine Leukemia virus titer and leukocyte population associated with mastitis in periparturient dairy cows
    Seiichi Kakinuma, Yousuke Maeda, Hiromichi Ohtsuka, Satoru Konnai, Masa-aki Oikawa
    INTERNATIONAL JOURNAL OF APPLIED RESEARCH IN VETERINARY MEDICINE, 12, 3, 239, 244, 2014
    English, Scientific journal
  • A relapsing fever group Borrelia sp similar to Borrelia lonestari found among wild sika deer (Cervus nippon yesoensis) and Haemaphysalis spp. ticks in Hokkaido, Japan
    Kyunglee Lee, Ai Takano, Kyle Taylor, Mariko Sashika, Michito Shimozuru, Satoru Konnai, Hiroki Kawabata, Toshio Tsubota
    TICKS AND TICK-BORNE DISEASES, 5, 6, 841, 847, 2014, [Peer-reviewed]
    English, Scientific journal
  • Sequence characterization and immunogenicity of cystatins from the cattle tick Rhipicephalus (Boophilus) microplus
    Luís F. Parizi, Naftaly W. Githaka, Carolina Acevedo, Uruguaysito Benavides, Adriana Seixas, Carlos Logullo, Satoru Konnai, Kazuhiko Ohashi, Aoi Masuda, Itabajara Da Silva Vaz
    Ticks and Tick-borne Diseases, 4, 6, 492, 499, Dec. 2013, [Peer-reviewed]
    English, Scientific journal
  • Short communication: Horizontal transmission of bovine leukemia virus from lymphocytotic cattle, and beneficial effects of insect vector control
    M. Ooshiro, S. Konnai, Y. Katagiri, M. Afuso, N. Arakaki, O. Tsuha, S. Murata, K. Ohashi
    Veterinary Record, 173, 21, 527, 30 Nov. 2013, [Peer-reviewed]
    English, Scientific journal
  • Identification and Structural-Functional Analysis of Cyclin-Dependent Kinases of the Cattle Tick Rhipicephalus (Boophilus) microplus
    Helga Gomes, Nelilma C. Romeiro, Gloria R. C. Braz, Eduardo Alves Gamosa de Oliveira, Camilla Rodrigues, Rodrigo Nunes da Fonseca, Naftaly Githaka, Masayoshi Isezaki, Satoru Konnai, Kazuhiko Ohashi, Itabajara da Silva Vaz Jr., Carlos Logullo, Jorge Moraes
    PLoS ONE, 8, 10, e76128., 11 Oct. 2013, [Peer-reviewed]
    English, Scientific journal
  • Genotypic variations in field isolates of Theileria species infecting giraffes (Giraffa camelopardalis tippelskirchi and Giraffa camelopardalis reticulata) in Kenya
    Naftaly Githaka, Satoru Konnai, Robert Skilton, Edward Kariuki, Esther Kanduma, Shiro Murata, Kazuhiko Ohashi
    Parasitology International, 62, 5, 448, 453, Oct. 2013, [Peer-reviewed]
    English, Scientific journal
  • Expression analysis of Foxp3 in T cells from bovine leukemia virus infected cattle
    Saori Suzuki, Satoru Konnai, Tomohiro Okagawa, Ryoyo Ikebuchi, Tatsuya Shirai, Yuji Sunden, Claro N. Mingala, Shiro Murata, Kazuhiko Ohashi
    Microbiology and Immunology, 57, 8, 600, 604, Aug. 2013, [Peer-reviewed]
    English, Scientific journal
  • Expression analysis of Foxp3 in T-cells from bovine leukemia virus infected cattle.
    Suzuki S, Konnai S, Okagawa T, Ikebuchi R, Shirai T, Sunden Y, Mingala CN, Murata S, Ohashi K
    Microbiology and immunology, Jun. 2013, [Peer-reviewed]
  • 北海道の野生下におけるボレリア種の維持、小型哺乳類とダニの関係について(On the maintenance of Borrelia spp. among wildlife in Hokkaido: the relationship between small mammals and ticks)               
    カイル・テイラー, 川端 寛樹, 今内 覚, 下鶴 倫人, 高野 愛, 坪田 敏男
    衛生動物, 64, 2, 112, 112, 日本衛生動物学会, Jun. 2013
    English
  • Characterization of Meq proteins from field isolates of Marek's disease virus in Japan
    Shiro Murata, Tomoyuki Hashiguchi, Yuko Hayashi, Yuki Yamamoto, Ayumi Matsuyama-Kato, Sarah Takasaki, Masayoshi Isezaki, Misao Onuma, Satoru Konnai, Kazuhiko Ohashi
    INFECTION GENETICS AND EVOLUTION, 16, 137, 143, Jun. 2013, [Peer-reviewed]
    English, Scientific journal
  • Differential Tick Burdens May Explain Differential Borrelia afzelii and Borrelia garinii Infection Rates among Four, Wild, Rodent Species in Hokkaido, Japan
    Kyle R. Taylor, Ai Takano, Satoru Konnai, Michito Shimozuru, Hiroki Kawabata, Toshio Tsubota
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 75, 6, 785, 790, Jun. 2013, [Peer-reviewed]
    English, Scientific journal
  • 免疫抑制受容体PD-1のリガンドPD-L2の機能的特徴と臨床応用研究               
    西森朝美, 今内 覚, 池渕良洋, 岡川朋弘, 村田史郎, 大橋和彦
    動物用ワクチンーバイオ医薬品研究会ニュースレター, 7, 19, 20, Jun. 2013, [Invited]
    Japanese
  • Bovine whole-blood culture as a tool for the measurement of endotoxin activities in Gram-negative bacterial vaccines
    Saiki Imamura, Mari Nakamizo, Michiko Kawanishi, Nao Nakajima, Kinya Yamamoto, Mariko Uchiyama, Fumiya Hirano, Hidetaka Nagai, Mayumi Kijima, Ryoyo Ikebuchi, Hirohisa Mekata, Shiro Murata, Satoru Konnai, Kazuhiko Ohashi
    VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 153, 1-2, 153, 158, May 2013, [Peer-reviewed]
    English, Scientific journal
  • Isolation, cloning, and pathologic analysis of Trypanosoma evansi field isolates
    Hirohisa Mekata, Satoru Konnai, Claro N. Mingala, Nancy S. Abes, Charito A. Gutierrez, Alan P. Dargantes, William H. Witola, Noboru Inoue, Misao Onuma, Shiro Murata, Kazuhiko Ohashi
    PARASITOLOGY RESEARCH, 112, 4, 1513, 1521, Apr. 2013, [Peer-reviewed]
    English, Scientific journal
  • The conserved role of the AKT/GSK3 axis in cell survival and glycogen metabolism in Rhipicephalus (Boophilus) microplus embryo tick cell line BME26
    Leonardo Araujo de Abreu, Christiano Calixto, Camila Fernanda Waltero, Barbara Pitta Della Noce, Naftaly Wang'ombe Githaka, Adriana Seixas, Luis Fernando Parizi, Satoru Konnai, Itabajara da Silva Vaz, Kazuhiko Ohashi, Carlos Logullo
    BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1830, 3, 2574, 2582, Mar. 2013, [Peer-reviewed]
    English, Scientific journal
  • Prevalence of Lyme Borrelia in Ixodes persulcatus Ticks from an Area with a Confirmed Case of Lyme Disease
    Yusuke Murase, Satoru Konnai, Naftaly Githaka, Arata Hidano, Kyle Taylor, Takuya Ito, Ai Takano, Shuji Ando, Hiroki Kawabata, Toshio Tsubota, Shiro Murata, Kazuhiko Ohashi
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 75, 2, 215, 218, Feb. 2013, [Peer-reviewed]
    English, Scientific journal
  • Borrelia miyamotoi Infections among Wild Rodents Show Age and Month Independence and Correlation with Ixodes persulcatus Larval Attachment in Hokkaido, Japan
    Kyle R. Taylor, Ai Takano, Satoru Konnai, Michito Shimozuru, Hiroki Kawabata, Toshio Tsubota
    VECTOR-BORNE AND ZOONOTIC DISEASES, 13, 2, 92, 97, Feb. 2013, [Peer-reviewed]
    English, Scientific journal
  • Enhanced expression of LAG-3 on lymphocyte subpopulations from persistently lymphocytotic cattle infected with bovine leukemia virus
    Satoru Konnai, Saori Suzuki, Tatsuya Shirai, Ryoyo Ikebuchi, Tomohiro Okagawa, Yuji Sunden, Claro N. Mingala, Misao Onuma, Shiro Murata, Kazuhiko Ohashi
    COMPARATIVE IMMUNOLOGY MICROBIOLOGY AND INFECTIOUS DISEASES, 36, 1, 63, 69, Jan. 2013, [Peer-reviewed]
    English, Scientific journal
  • Identification and partial characterization of a gut Rhipicephalus appendiculatus cystatin
    Saiki Imamura, Satoru Konnai, Shinji Yamada, Luis F. Parizi, Naftaly Githaka, Itabajara da S. Vaz, Shiro Murata, Kazuhiko Ohashi
    TICKS AND TICK-BORNE DISEASES, 4, 1-2, 138, 144, 2013, [Peer-reviewed]
    English, Scientific journal
  • Blockade of bovine PD-1 increases T cell function and inhibits bovine leukemia virus expression in B cells in vitro
    Ryoyo Ikebuchi, Satoru Konnai, Tomohiro Okagawa, Kazumasa Yokoyama, Chie Nakajima, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
    Veterinary Research, 44, 1, 59, 2013, [Peer-reviewed]
    English, Scientific journal
  • The quest for a universal vaccine against ticks: Cross-immunity insights
    Luis F. Parizi, Naftaly W. Githaka, Carlos Logullo, Satoru Konnai, Aoi Masuda, Kazuhiko Ohashi, Itabajara da Silva Vaz
    VETERINARY JOURNAL, 194, 2, 158, 165, Nov. 2012, [Peer-reviewed]
    English, Scientific journal
  • Molecular detection and characterization of potentially new Babesia and Theileria species/variants in wild felids from Kenya
    Naftaly Githaka, Satoru Konnai, Edward Kariuki, Esther Kanduma, Shiro Murata, Kazuhiko Ohashi
    ACTA TROPICA, 124, 1, 71, 78, Oct. 2012, [Peer-reviewed]
    English, Scientific journal
  • EFFECTS OF ENVIRONMENTAL LEAD CONTAMINATION ON CATTLE IN A LEAD/ZINC MINING AREA: CHANGES IN CATTLE IMMUNE SYSTEMS ON EXPOSURE TO LEAD IN VIVO AND IN VITRO
    Yoshinori Ikenaka, Shouta M. M. Nakayama, Taro Muroya, John Yabe, Satoru Konnai, Wageh Sobhy Darwish, Kaampwe Muzandu, Kennedy Choongo, Geoffrey Mainda, Hiroki Teraoka, Takashi Umemura, Mayumi Ishizuka
    ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY, 31, 10, 2300, 2305, Oct. 2012, [Peer-reviewed]
    English, Scientific journal
  • Transcriptional profiling of inflammatory cytokine genes in African, buffaloes (Syncerus caffer) infected with Theileria parva
    Tomohiro Okagawa, Satoru Konnai, Hirohisa Mekata, Naftaly Githaka, Saori Suzuki, Edward Kariuki, Francis Gakuya, Esther Kanduma, Tatsuya Shirai, Ryoyo Ikebuchi, Yoshinori Ikenaka, Mayumi Ishizuka, Shiro Murata, Kazuhiko Ohashi
    VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 148, 3-4, 373, 379, Aug. 2012, [Peer-reviewed]
    English, Scientific journal
  • Effects of interferon-tau on cattle persistently infected with bovine viral diarrhea virus
    Junko Kohara, Yumiko Nishikura, Satoru Konnai, Motoshi Tajima, Misao Onuma
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 60, 2-3, 63, 70, Aug. 2012, [Peer-reviewed]
    English, Scientific journal
  • Surveillance of Marek's disease virus in migratory and sedentary birds in Hokkaido, Japan
    Shiro Murata, Yuko Hayashi, Ayumi Kato, Masayoshi Isezaki, Sarah Takasaki, Misao Onuma, Yuichi Osa, Mitsuhiko Asakawa, Satoru Konnai, Kazuhiko Ohashi
    VETERINARY JOURNAL, 192, 3, 538, 540, Jun. 2012, [Peer-reviewed]
    English, Scientific journal
  • Kinetics of regulatory dendritic cells in inflammatory responses during Trypanosoma evansi infection
    H. Mekata, S. Konnai, C. N. Mingala, N. S. Abes, C. A. Gutierrez, A. P. Dargantes, W. H. Witola, N. Inoue, M. Onuma, S. Murata, K. Ohashi
    PARASITE IMMUNOLOGY, 34, 6, 318, 329, Jun. 2012, [Peer-reviewed]
    English, Scientific journal
  • Molecular characterization of immunoinhibitory factors PD-1/PD-L1 in chickens infected with Marek's disease virus
    Ayumi Matsuyama-Kato, Shiro Murata, Masayoshi Isezaki, Rika Kano, Sara Takasaki, Osamu Ichii, Satoru Konnai, Kazuhiko Ohashi
    VIROLOGY JOURNAL, 9, 94, May 2012, [Peer-reviewed]
    English, Scientific journal
  • Increased bovine Tim-3 and its ligand expressions during bovine leukemia virus infection
    Tomohiro Okagawa, Satoru Konnai, Ryoyo Ikebuchi, Saori Suzuki, Tatsuya Shirai, Yuji Sunden, Misao Onuma, Shiro Murata, Kazuhiko Ohashi
    VETERINARY RESEARCH, 43, 45, May 2012, [Peer-reviewed]
    English, Scientific journal
  • Molecular cloning and characterization of Th1 and Th2 cytokines of African buffalo (Syncerus caffer)
    S. Suzuki, S. Konnai, T. Okagawa, N. W. Githaka, E. Kariuki, F. Gakuya, E. Kanduma, T. Shirai, R. Ikebuchi, Y. Ikenaka, M. Ishizuka, S. Murata, K. Ohashi
    INTERNATIONAL JOURNAL OF IMMUNOGENETICS, 39, 2, 170, 182, Apr. 2012, [Peer-reviewed]
    English, Scientific journal
  • The Leukocyte Population in the Peripheral Blood and the Colostrum of Cows Infected with Bovine Leukemia Virus is Skewed Towards Humoral Immunity
    Seiichi Kakinuma, Yousuke Maeda, Hiromichi Ohtsuka, Kaori Ohmae, Kyouko Ayabe, Satoru Konnai, Masa-aki Oikawa
    INTERNATIONAL JOURNAL OF APPLIED RESEARCH IN VETERINARY MEDICINE, 10, 4, 323, 327, 2012, [Peer-reviewed]
    English, Scientific journal
  • Identification of TROSPA homologue in Ixodes persulcatus Schulze, the specific vector for human Lyme borreliosis in Japan
    Satoru Konnai, Shinji Yamada, Saiki Imamura, Hideto Nishikado, Naftaly Githaka, Takuya Ito, Ai Takano, Hiroki Kawabata, Shiro Murata, Kazuhiko Ohashi
    TICKS AND TICK-BORNE DISEASES, 3, 2, 75, 77, 2012, [Peer-reviewed]
    English, Scientific journal
  • A novel relapsing fever Borrelia sp infects the salivary glands of the molted hard tick, Amblyomma geoemydae
    Takano, Ai, Sugimori, Chieko, Fujita, Hiromi, Kadosaka, Teruki, Taylor, Kyle R., Tsubota, Toshio, Konnai, Satoru, Tajima, Tomoko, Sato, Kozue, Watanabe, Haruo, Ohnishi, Makoto, Kawabata, Hiroki
    TICKS AND TICK-BORNE DISEASES, 3, 4, 259, 261, 2012, [Peer-reviewed]
    English, Scientific journal
  • Molecular cloning of bovine lymphocyte activation gene-3 and its expression characteristics in bovine leukemia virus-infected cattle
    Tatsuya Shirai, Satoru Konnai, Ryoyo Ikebuchi, Tomohiro Okagawa, Saori Suzuki, Yuji Sunden, Misao Onuma, Shiro Murata, Kazuhiko Ohashi
    VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 144, 3-4, 462, 467, Dec. 2011, [Peer-reviewed]
    English, Scientific journal
  • Characterization of reptile-associated Borrelia sp in the vector tick, Amblyomma geoemydae, and its association with Lyme disease and relapsing fever Borrelia spp.
    Ai Takano, Hiromi Fujita, Teruki Kadosaka, Satoru Konnai, Tomoko Tajima, Haruo Watanabe, Makoto Ohnishi, Hiroki Kawabata
    ENVIRONMENTAL MICROBIOLOGY REPORTS, 3, 5, 632, 637, Oct. 2011, [Peer-reviewed]
    English, Scientific journal
  • Increase of cells expressing PD-L1 in bovine leukemia virus infection and enhancement of anti-viral immune responses in vitro via PD-L1 blockade
    Ryoyo Ikebuchi, Satoru Konnai, Tatsuya Shirai, Yuji Sunden, Shiro Murata, Misao Onuma, Kazuhiko Ohashi
    VETERINARY RESEARCH, 42, 103, Sep. 2011, [Peer-reviewed]
    English, Scientific journal
  • Analysis of transcriptional activities of the Meq proteins present in highly virulent Marek's disease virus strains, RB1B and Md5
    Shiro Murata, Tsukasa Okada, Rika Kano, Yuko Hayashi, Tomoyuki Hashiguchi, Misao Onuma, Satoru Konnai, Kazuhiko Ohashi
    VIRUS GENES, 43, 1, 66, 71, Aug. 2011, [Peer-reviewed]
    English, Scientific journal
  • Molecular detection of Anaplasma phagocytophilum in cattle and Ixodes persulcatus ticks
    Yusuke Murase, Satoru Konnai, Arata Hidano, Naftali W. Githaka, Takuya Ito, Ai Takano, Hiroki Kawabata, Manabu Ato, Tomoko Tajima, Motoshi Tajima, Misao Onuma, Shiro Murata, Kazuhiko Ohashi
    VETERINARY MICROBIOLOGY, 149, 3-4, 504, 507, May 2011, [Peer-reviewed]
    English, Scientific journal
  • Multilocus Sequence Typing Implicates Rodents as the Main Reservoir Host of Human-Pathogenic Borrelia garinii in Japan
    Ai Takano, Minoru Nakao, Toshiyuki Masuzawa, Nobuhiro Takada, Yasuhiro Yano, Fubito Ishiguro, Hiromi Fujita, Takuya Ito, Xiaohang Ma, Yozaburo Oikawa, Fumihiko Kawamori, Kunihiko Kumagai, Toshiyuki Mikami, Nozomu Hanaoka, Shuji Ando, Naoko Honda, Kyle Taylor, Toshio Tsubota, Satoru Konnai, Haruo Watanabe, Makoto Ohnishi, Hiroki Kawabata
    JOURNAL OF CLINICAL MICROBIOLOGY, 49, 5, 2035, 2039, May 2011, [Peer-reviewed]
    English, Scientific journal
  • Molecular identification and expression analysis of lipocalins from blood feeding taiga tick, Ixodes persulcatus Schulze
    Satoru Konnai, Hideto Nishikado, Shinji Yamada, Saiki Imamura, Takuya Ito, Misao Onuma, Shiro Murata, Kazuhiko Ohashi
    EXPERIMENTAL PARASITOLOGY, 127, 2, 467, 474, Feb. 2011, [Peer-reviewed]
    English, Scientific journal
  • Peripheral Blood Leukocyte Populations in Dairy Cows Infected with Bovine Leukemia Virus
    Seiichi KAKINUMA, Hiromichi OHTSUKA, Kaori OHMAE, Kyouko AYABE, Motoharu KAKINUMA, Satoru KONNAI, Masaaki OIKAWA
    Journal of the Japan Veterinary Medical Association, 64, 5, 375, 380, Japan Veterinary Medical Association, 2011, [Peer-reviewed]
    Scientific journal
  • Characterization of CTLA-4, PD-1 and PDL-1 of swamp and riverine type water buffaloes
    Claro N. Mingala, Satoru Konnai, Ryoyo Ikebuchi, Kazuhiko Ohashi
    COMPARATIVE IMMUNOLOGY MICROBIOLOGY AND INFECTIOUS DISEASES, 34, 1, 55, 63, Jan. 2011, [Peer-reviewed]
    English, Scientific journal
  • Two novel Salp15-like immunosuppressant genes from salivary glands of Ixodes persulcatus Schulze tick
    A. Mori, S. Konnai, S. Yamada, A. Hidano, Y. Murase, T. Ito, A. Takano, H. Kawabata, M. Onuma, K. Ohashi
    INSECT MOLECULAR BIOLOGY, 19, 3, 359, 365, Jun. 2010, [Peer-reviewed]
    English, Scientific journal
  • Molecular cloning and expression analysis of bovine programmed death-1
    Ryoyo Ikebuchi, Satoru Konnai, Yuji Sunden, Misao Onuma, Kazuhiko Ohashi
    MICROBIOLOGY AND IMMUNOLOGY, 54, 5, 291, 298, May 2010, [Peer-reviewed]
    English, Scientific journal
  • Molecular detection of trypanosomes in cattle in South America and genetic diversity of Trypanosoma evansi based on expression-site-associated gene 6
    Hirohisa Mekata, Satoru Konnai, William H. Witola, Noboru Inoue, Misao Onuma, Kazuhiko Ohashi
    INFECTION GENETICS AND EVOLUTION, 9, 6, 1301, 1305, Dec. 2009, [Peer-reviewed]
    English, Scientific journal
  • PCR-based detection of blood parasites in cattle and adult Rhipicephalus appendiculatus ticks
    Shinji Yamada, Satoru Konnai, Saiki Imamura, Martin Simuunza, Mwelwa Chembensofu, Amos Chota, Andrew Nambota, Misao Onuma, Kazuhiko Ohashi
    VETERINARY JOURNAL, 182, 2, 352, 355, Nov. 2009, [Peer-reviewed]
    English, Scientific journal
  • Quantification of water buffalo (Bubalus bubalis) cytokine expression in response to inactivated foot-and-mouth disease (FMD) vaccine
    Claro N. Mingala, Satoru Konnai, Fe A. Venturina, Misao Onuma, Kazubliko Ohashi
    RESEARCH IN VETERINARY SCIENCE, 87, 2, 213, 217, Oct. 2009, [Peer-reviewed]
    English, Scientific journal
  • Classification of new BVDV isolates from Philippine water buffalo using the viral E2 region
    Claro N. Mingala, Satoru Konnai, Motoshi Tajima, Misao Onuma, Kazuhiko Ohashi
    JOURNAL OF BASIC MICROBIOLOGY, 49, 5, 495, 500, Oct. 2009, [Peer-reviewed]
    English, Scientific journal
  • Cloning and characterization of Rhipicephalus appendiculatus voraxin alpha and its effect as anti-tick vaccine
    Shinji Yamada, Satoru Konnai, Saiki Imamura, Takuya Ito, Misao Onuma, Kazuhiko Ohashi
    VACCINE, 27, 43, 5989, 5997, Oct. 2009, [Peer-reviewed]
    English, Scientific journal
  • Effect of vaccination with a recombinant metalloprotease from Haemaphysalis longicornis
    Saiki Imamura, Itabajara da Silva Vaz, Satoru Konnai, Shinji Yamada, Chie Nakajima, Misao Onuma, Kazuhiko Ohashi
    EXPERIMENTAL AND APPLIED ACAROLOGY, 48, 4, 345, 358, Aug. 2009, [Peer-reviewed]
    English, Scientific journal
  • Identification and characterization of antimicrobial peptide, defensin, in the taiga tick, Ixodes persulcatus
    Y. Saito, S. Konnai, S. Yamada, S. Imamura, H. Nishikado, T. Ito, M. Onuma, K. Ohashi
    INSECT MOLECULAR BIOLOGY, 18, 4, 531, 539, Aug. 2009, [Peer-reviewed]
    English, Scientific journal
  • Development and application of a quantitative real-time PCR for the diagnosis of Surra in water buffaloes
    Satoru Konnai, Hirohisa Mekata, Claro N. Mingala, Nancy S. Abes, Charito A. Gutierrez, Jesus Rommel V. Herrera, Alan P. Dargantes, William H. Witola, Libertado C. Cruz, Noboru Inoue, Misao Onuma, Kazuhiko Ohashi
    INFECTION GENETICS AND EVOLUTION, 9, 4, 449, 452, Jul. 2009, [Peer-reviewed]
    English, Scientific journal
  • Expression and activity of glycogen synthase kinase during vitellogenesis and embryogenesis of Rhipicephalus (Boophilus) microplus
    Carlos Logullo, William H. Witola, Caroline Andrade, Leonardo Abreu, Josiana Gomes, Itabajara da Silva Vaz, Saiki Imamura, Satoru Konnai, Kazuhiko Ohashi, Misao Onuma
    VETERINARY PARASITOLOGY, 161, 3-4, 261, 269, May 2009, [Peer-reviewed]
    English, Scientific journal
  • Comparative moleculo-immunological analysis of swamp- and riverine-type water buffaloes responses
    Claro N. Mingala, Satoru Konnai, Libertado C. Cruz, Misao Onuma, Kazuhiko Ohashi
    CYTOKINE, 46, 2, 273, 282, May 2009, [Peer-reviewed]
    English, Scientific journal
  • Microarray Analysis of Host Immune Responses to Marek's Disease Virus Infection in Vaccinated Chickens
    Rika Kano, Satoru Konnai, Misao Onuma, Kazuhiko Ohashi
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 71, 5, 603, 610, May 2009, [Peer-reviewed]
    English, Scientific journal
  • Cytokine profiles in chickens infected with virulent and avirulent Marek's disease viruses: Interferon-gamma is a key factor in the protection of Marek's disease by vaccination
    Rika Kano, Satoru Konnai, Misao Onuma, Kazuhiko Ohashi
    MICROBIOLOGY AND IMMUNOLOGY, 53, 4, 224, 232, Apr. 2009, [Peer-reviewed]
    English, Scientific journal
  • Suppression of cell proliferation and cytokine expression by HL-p36, a tick salivary gland-derived protein of Haemaphysalis longicornis
    Satoru Konnai, Chie Nakajima, Saiki Imamura, Shinji Yamada, Hideto Nishikado, Michi Kodama, Misao Onuma, Kazuhiko Ohashi
    IMMUNOLOGY, 126, 2, 209, 219, Feb. 2009, [Peer-reviewed]
    English, Scientific journal
  • Quantitative Analysis of Cytokine mRNA Expression and Protozoan DNA Load in Theileria parva-Infected Cattle
    Shinji Yamada, Satoru Konnai, Saiki Imamura, Martin Simuunza, Mwelwa Chembensofu, Amos Chota, Andrew Nambota, Misao Onuma, Kazuhiko Ohashi
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 71, 1, 49, 54, Jan. 2009, [Peer-reviewed]
    English, Scientific journal
  • Rhipicephalus appendiculatus: Characterization of a testis-associated protein
    Shinji Yamada, Yuko Ito, Saiki Imamura, Satoru Konnai, Takuya Ito, Misao Onuma, Kazuhiko Ohashi
    EXPERIMENTAL PARASITOLOGY, 120, 4, 337, 342, Dec. 2008, [Peer-reviewed]
    English, Scientific journal
  • Prevalence and Source of Trypanosome Infections in Field-Captured Vector Flies (Glossina pallidipes) in Southeastern Zambia
    Hirohisa Mekata, Satoru Konnai, Martin Simuunza, Mwelwa Chembensofu, Rika Kano, William H. Witola, Mwase E. Tembo, Harrison Chitambo, Noboru Inoue, Misao Onuma, Kazuhiko Ohashi
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 70, 9, 923, 928, Sep. 2008
    English, Scientific journal
  • Prevalence and Source of Trypanosome Infections in Field-Captured Vector Flies (Glossina pallidipes) in Southeastern Zambia
    Hirohisa Mekata, Satoru Konnai, Martin Simuunza, Mwelwa Chembensofu, Rika Kano, William H. Witola, Mwase E. Tembo, Harrison Chitambo, Noboru Inoue, Misao Onuma, Kazuhiko Ohashi
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 70, 9, 923, 928, Sep. 2008, [Peer-reviewed]
    English, Scientific journal
  • Detection of Trypanosoma brucei in field-captured tsetse flies and identification of host species fed on by the infected flies
    Satoru Konnai, Hirohisa Mekata, Raadan Odbileg, Martin Simuunza, Mwelwa Chembensof, William Harold Witola, Mwase Enala Tembo, Harrison Chitambo, Noboru Inoue, Misao Onuma, Kazuhiko Ohashi
    VECTOR-BORNE AND ZOONOTIC DISEASES, 8, 4, 565, 573, Aug. 2008, [Peer-reviewed]
    English, Scientific journal
  • Serological survey of Toxoplasma gondii in wild waterfowl in Chukotka, Kamchatka, Russia and Hokkaido, Japan
    Takehiro Murao, Yoshitaka Omata, Rika Kano, Shiro Murata, Tsukasa Okada, Satoru Konnai, Mitsuhiko Asakawa, Kazuhiko Ohashi, Misao Onuma
    JOURNAL OF PARASITOLOGY, 94, 4, 830, 833, Aug. 2008, [Peer-reviewed]
    English, Scientific journal
  • Effects of anti-tick cocktail vaccine against Rhipicephalus appendiculatus
    Saiki Imamura, Satoru Konnai, Itabajara da Silva Vaz Junior, Shinji Yamada, Chie Nakajima, Yuko Ito, Tomoko Tajima, Jun Yasuda, Martin Simuunza, Misao Onuma, Kazuhiko Ohashi
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 56, 2, 85, 98, Aug. 2008, [Peer-reviewed]
    English, Scientific journal
  • A survey of abortifacient infectious agents in livestock in Luzon, the Philippines, with emphasis on the situation in a cattle herd with abortion problems
    Satoru Konnai, Claro N. Mingala, Misako Sato, Nancy S. Abes, Fe A. Venturina, Charito A. Gutierrez, Takafumi Sano, Yoshitaka Omata, Libertado C. Cruz, Misao Onuma, Kazuhiko Ohashi
    ACTA TROPICA, 105, 3, 269, 273, Mar. 2008, [Peer-reviewed]
    English, Scientific journal
  • Cytokine responses in camels (Camelus bactrianus) vaccinated with Brucella abortus strain 19 vaccine
    Raadan Odbileg, Byambaa Purevtseren, Dorj Gantsetseg, Bazartseren Boldbaatar, Tumurjav Buyannemekh, Zagd Galmandakh, Janchivdorj Erdenebaatar, Satoru Konnai, Misao Onuma, Kazuhiko Ohashi
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 70, 2, 197, 201, Feb. 2008, [Peer-reviewed]
    English, Scientific journal
  • Establishment of a laboratory colony of taiga tick Ixodes persulcatus for tick-borne pathogen transmission studies
    Satoru Konnai, Yoichi Saito, Hideto Nishikado, Shinji Yamada, Saiki Imamura, Akina Mori, Takuya Ito, Misao Onuma, Kazuhiko Ohashi
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 55, 2-3, 85, 92, Jan. 2008, [Peer-reviewed]
    English, Scientific journal
  • Development of a nested polymerase chain reaction method to detect oncogenic Marek's disease virus from feather tips
    Shiro Murata, Kyung-Soo Chang, Sung-Il Lee, Satoru Konnai, Misao Onuma, Kazuhiko Ohashi
    JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION, 19, 5, 471, 478, Sep. 2007, [Peer-reviewed]
    English, Scientific journal
  • Detection of the virulent Marek's disease virus genome from feather tips of wild geese in Japan and the Far East region of Russia
    S. Murata, K.-S. Chang, Y. Yamamoto, T. Okada, S.-I. Lee, S. Konnai, M. Onuma, Y. Osa, M. Asakawa, K. Ohashi
    ARCHIVES OF VIROLOGY, 152, 8, 1523, 1526, Aug. 2007, [Peer-reviewed]
    English, Scientific journal
  • Attachment duration required for Rhipicephalus appendiculatus to transmit Theileria parva to the host
    Satoru Konnai, Shinji Yamada, Saiki Imamura, Martin Simuunza, Mwelwa Chembensof, Amos Chota, Andrew Nambota, Kazuhiko Ohashi, Misao Onuma
    Vector-Borne and Zoonotic Diseases, 7, 2, 241, 248, Jun. 2007, [Peer-reviewed]
    English, Scientific journal
  • Molecular cloning, sequencing and phylogenetic analysis of inflammatory cytokines of swamp type buffalo contrasting with other bubaline breeds
    Claro N. Mingala, Raadan Odbileg, Satoru Konnai, Kazuhiko Ohashi, Misao Onuma
    COMPARATIVE IMMUNOLOGY MICROBIOLOGY AND INFECTIOUS DISEASES, 30, 2, 119, 131, Mar. 2007, [Peer-reviewed]
    English, Scientific journal
  • Interferon-gamma expression associated with suppression of bovine leukemia virus at the early phase of infection in sheep
    Tatsufumi Usui, Satoru Konnai, Kazuhiko Ohashi, Misao Onuma
    VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 115, 1-2, 17, 23, Jan. 2007, [Peer-reviewed]
    English, Scientific journal
  • Comparative assessment of Th1 and Th2 cytokines of swamp type buffalo and other bubaline breeds by molecular cloning, sequencing and phylogenetics
    Claro N. Mingala, Raadan Odbileg, Satoru Konnal, Kazuhiko Ohashi, Misao Onuma
    VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 113, 3-4, 348, 356, Oct. 2006, [Peer-reviewed]
    English, Scientific journal
  • Complete cDNA sequences and phylogenetic analyses of the Th1 and Th2 cytokines of the bactrian camel (Camelus bactrianus)
    Raadan Odbileg, Byambaa Purevtseren, Zayat Batsukh, Satoru Konnaii, Kazuhiko Ohashi, Misao Onuma
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 68, 9, 941, 946, Sep. 2006, [Peer-reviewed]
    English, Scientific journal
  • Expression of tumor necrosis factor-alpha in IgM(+) B-cells from bovine leukemia virus-infected lymphocytotic sheep
    Tatsufumi Usui, Satoru Konnai, Kazuhiko Ohashi, Misao Onuma
    VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 112, 3-4, 296, 301, Aug. 2006, [Peer-reviewed]
    English, Scientific journal
  • Acquisition and transmission of Theileria parva by vector tick, Rhipicephalus appendiculatus
    Satoru Konnai, Saiki Imamura, Chie Nakajima, William Harold Witola, Shinji Yamada, Martin Simuunza, Andrew Nambota, Jun Yasuda, Kazuhiko Ohashi, Misao Onuma
    ACTA TROPICA, 99, 1, 34, 41, Aug. 2006, [Peer-reviewed]
    English, Scientific journal
  • Tumor necrosis factor-alpha genetic polymorphism may contribute to progression of bovine leukemia virus-infection
    Satoru Konnai, Tatsufumi Usui, Manabu Ikeda, Junko Kohara, Toh-ichi Hirata, Kosuke Okada, Kazuhiko Ohashi, Misao Onuma
    MICROBES AND INFECTION, 8, 8, 2163, 2171, Jul. 2006, [Peer-reviewed]
    English, Scientific journal
  • The effect of TAO expression on PCD-like phenomenon development and drug resistance in Trypanosoma brucei
    A Tsuda, WH Witola, S Konnai, K Ohashi, M Onuma
    PARASITOLOGY INTERNATIONAL, 55, 2, 135, 142, Jun. 2006, [Peer-reviewed]
    English, Scientific journal
  • A novel gene encoding a thrombin inhibitory protein in a cDNA library from Haemaphysalis longicornis salivary gland
    C Nakajima, S Imamura, S Konnai, S Yamada, H Nishikado, K Ohashi, M Onuma
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 68, 5, 447, 452, May 2006, [Peer-reviewed]
    English, Scientific journal
  • Experimental transmission of Bovine leukemia virus in cattle via rectal palpation
    Junko Kohara, Satoru Konnai, Misao Onuma
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 54, 1, 25, 30, May 2006, [Peer-reviewed]
    English, Scientific journal
  • Tumor necrosis factor-alpha up-regulation in spontaneously proliferating cells derived from bovine leukemia virus-infected cattle
    S Konnai, T Usui, M Ikeda, J Kohara, T Hirata, K Okada, K Ohashi, M Onuma
    ARCHIVES OF VIROLOGY, 151, 2, 347, 360, Feb. 2006, [Peer-reviewed]
    English, Scientific journal
  • Rapid detection and differentiation of Newcastle disease virus by real-time PCR with melting-curve analysis
    HM Pham, S Konnai, T Usui, KS Chang, S Murata, M Mase, K Ohashi, M Onuma
    ARCHIVES OF VIROLOGY, 150, 12, 2429, 2438, Dec. 2005, [Peer-reviewed]
    English, Scientific journal
  • Bovine leukemia virus high tax molecular clone experimentally induces leukemia/lymphoma in sheep
    K Okada, N Nakae, K Kuramochi, S Yin, M Ikeda, S Takami, T Hirata, M Goryo, S Numakunai, S Takeshima, M Takahashi, S Tajima, S Konnai, M Onuma, Y Aida
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 67, 12, 1231, 1235, Dec. 2005, [Peer-reviewed]
    English, Scientific journal
  • Random sequencing of cDNA library derived from partially-fed adult female Haemaphysalis longicornis salivary gland
    C Nakajima, ID Vaz, S Imamura, S Konnai, K Ohashi, M Onuma
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 67, 11, 1127, 1131, Nov. 2005, [Peer-reviewed]
    English, Scientific journal
  • Imbalance of tumor necrosis factor receptors during progression in bovine leukemia virus infection
    S Konnai, T Usui, M Ikeda, J Kohara, T Hirata, K Okada, K Ohashi, M Onuma
    VIROLOGY, 339, 2, 239, 248, Sep. 2005, [Peer-reviewed]
    English, Scientific journal
  • Molecular cloning and phylogenetic analysis of inflammatory cytokines of Camelidae (llama and camel)
    R Odbileg, S Konnai, K Ohashi, M Onuma
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 67, 9, 921, 925, Sep. 2005, [Peer-reviewed]
    English, Scientific journal
  • Immmohistochemical analysis of expression patterns of tumor necrosis factor receptors on lymphoma cells in enzootic bovine leukosis
    M Ikeda, S Konnai, M Onuma, N Ishiguro, M Goryo, K Okada
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 67, 4, 425, 432, Apr. 2005, [Peer-reviewed]
    English, Scientific journal
  • Quantification of llama inflammatory cytokine mRNAs by real-time RT-PCR
    R Odbileg, S Konnai, T Usui, K Ohashi, M Onuma
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 67, 2, 195, 198, Feb. 2005, [Peer-reviewed]
    English, Scientific journal
  • Ex vivo survival of peripheral blood mononuclear cells in sheep induced by bovine leukemia virus (BLV) mainly occurs in CD5- B cells that express BLV
    Masahiko Takahashi, Shigeru Tajima, Shin-Nosuke Takeshima, Satoru Konnai, Shan Ai Yin, Kosuke Okada, William C. Davis, Yoko Aida
    Microbes and Infection, 6, 6, 584, 595, May 2004, [Peer-reviewed]
    English, Scientific journal
  • Protective effects of vaccination with bovine leukemia virus (BLV) tax DNA against BLV infection in sheep
    T Usui, S Konnai, S Tajima, S Watarai, Y Aida, K Ohashi, M Onuma
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 65, 11, 1201, 1205, Nov. 2003, [Peer-reviewed]
    English, Scientific journal
  • Technical note: DNA typing for ovine MHC DRB1 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
    S Konnai, Y Nagaoka, S Takesima, M Onuma, Y Aida
    JOURNAL OF DAIRY SCIENCE, 86, 10, 3362, 3365, Oct. 2003, [Peer-reviewed]
    English, Scientific journal
  • Sequences and diversity of 17 new Ovar-DRB1 alleles from three breeds of sheep
    S Konnai, Y Nagaoka, S Takeshima, M Onuma, Y Aida
    EUROPEAN JOURNAL OF IMMUNOGENETICS, 30, 4, 275, 282, Aug. 2003, [Peer-reviewed]
    English, Scientific journal
  • The rapid quantitative analysis of bovine cytokine genes by real-time RT-PCR
    S Konnai, T Usui, K Ohashi, M Onuma
    VETERINARY MICROBIOLOGY, 94, 4, 283, 294, Jul. 2003, [Peer-reviewed]
    English, Scientific journal
  • 牛白血病ウイルス(BLV)Envに対する抗体反応性とウシMHCクラスII DR抗原との相関性               
    竹嶋 伸之輔, 嘉村 浩美, 若本 裕晶, 田島 茂, 今内 覚, 森田 裕, 小沼 操, 岡田 幸助, 間 陽子
    日本獣医学会学術集会講演要旨集, 135回, 123, 123, (公社)日本獣医学会, Mar. 2003
    Japanese
  • A mutant form of the Tax protein of bovine leukemia virus (BLV), with enhanced transactivation activity, increases expression and propagation of BLV in vitro but not in vivo
    S Tajima, M Takahashi, S Takeshima, S Konnai, SA Yin, S Watarai, Tana, Y Tanaka, M Onuma, K Okada, Y Aida
    JOURNAL OF VIROLOGY, 77, 3, 1894, 1903, Feb. 2003, [Peer-reviewed]
    English, Scientific journal
  • Seroprevalence of bovine immunodeficiency virus and bovine leukemia virus in dairy and beef cattle in Hokkaido
    T Usui, S Meas, S Konnai, K Ohashi, M Onuma
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 65, 2, 287, 289, Feb. 2003, [Peer-reviewed]
    English, Scientific journal
  • The influence of ovine MHC class II DRB1 alleles on immune response in bovine leukemia virus infection
    S Konnai, NS Takeshima, S Tajima, SA Yin, K Okada, M Onuma, Y Aida
    MICROBIOLOGY AND IMMUNOLOGY, 47, 3, 223, 232, 2003, [Peer-reviewed]
    English, Scientific journal
  • Effects of chlorpromazine, pentoxifylline and dexamethasone on mRNA expression of lipopolysaccharide-induced inflammatory cytokines in bovine peripheral blood mononuclear cells
    Y Kiku, H Matsuzawa, H Ohtsuka, N Terasaki, S Fukuda, S Kon-Nai, M Koiwa, Y Yokomizo, H Sato, TJ Rosol, H Okada, TO Yoshino
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 64, 8, 723, 726, Aug. 2002, [Peer-reviewed]
    English, Scientific journal
  • BLV-Tax発現DNAワクチンのウイルス増殖抑制効果               
    笛吹 達史, 今内 覚, 田島 茂, 渡来 仁, 大橋 和彦, 間 陽子, 小沼 操
    日本獣医学会学術集会講演要旨集, 133回, 95, 95, (公社)日本獣医学会, Mar. 2002
    Japanese
  • ヒツジMHC(OLA)-DRB1の塩基配列の決定と多型解析
    今内 覚, 長岡 淑子, 小沼 操, 間 陽子
    MHC: Major Histocompatibility Complex, 8, 2, 122, 122, (一社)日本組織適合性学会, Sep. 2001
    Japanese
  • 異なるMHCを有するBLV感染羊の免疫応答
    今内 覚, 竹嶋 伸之輔, 田島 茂, 岡田 幸助, 小沼 操, 間 陽子
    MHC: Major Histocompatibility Complex, 8, 2, 136, 136, (一社)日本組織適合性学会, Sep. 2001
    Japanese
  • Inflammatory Cytokines and Antigen-Responsive Mononuclear Cells in Peripheral Blood of Cattle Infected with Salmonella Takoradi
    KONNAI Satoru, OHTSUKA Hiromichi, SAKAMOTO Tetsuaki, NAKAOKA Yuji, KIKU Yukio, FUKUDA Sigeo, KOIWA Masateru, TAKAHASHI Junkichi, TANIYAMA Hiroyuki, YOKOMIZO Yuichi, OKADA Hiroyuki, YOSHINO Tomoo
    Journal of Veterinary Medical Science, 63, 8, 859, 865, Japanese Society of Veterinary Science, 25 Aug. 2001, [Peer-reviewed]
    English, Scientific journal, To determine the immunological response in lactating dairy cows infected with Salmonella (S.) Takoradi, the relationships among distributions of peripheral blood mononuclear cell (PBMC) subpopulations, endotoxin concentrations and dynamics of inflammatory cytokines in blood were investigated. The ratio of CD4+ T cells to CD8+ T cells was significantly lower in the affected cattle than in the control cattle (p<0.05) to decrease in the number of CD4+ T cells in the infected cattle. In contrast, the numbers of γδ-T cells, MHC class II-positive cells were significantly higher in the affected cattle than in the control cattle (p<0.01 respectively). Endotoxemia was found in all but one of the affected cattle. Serum IL-1 and IL-6 bioactivities were significantly higher in the affected cattle than in the control cattle (IL-1, p<0.05; IL-6, p<0.01). Serum TNF-α activities and levels were not detected in the control and affected cattle. The activities of proinflammatory cytokines determined by the bioassay are important to the relationships between concentration of endotoxin, cytokines and clinical signs, such as leukocytosis, leukopenia, fever or bacterial shedding. Serum IL-2 levels were lower in the affected cattle than in the control cattle. Serum IFN-γ was not detected in the affected cattle except one. These results by the ELISA seemed to reflect the condition of subpopulation in the PBMCs from the shedding cattle. The present results suggest that cellular immunity is suppressed while the humoral immunity is activated in acute bovine salmonellosis.
  • 牛白血病ウイルス(BLV)Tax変異体をコードする感染性分子クローン接種ヒツジにおけるウイルス動態の解析               
    田島 茂, 今内 覚, 竹嶋 伸之輔, 高橋 雅彦, 渡来 仁, 小沼 操, 岡田 幸助, 間 陽子
    日本獣医学会学術集会講演要旨集, 131回, 84, 84, (公社)日本獣医学会, Mar. 2001
    Japanese
  • ウシ白血病ウイルス(BLV)感染初期羊におけるCD4+T細胞のBLV抗原に対する反応性               
    尹 善愛, 池田 学, 御領 政信, 沼宮内 茂, 平田 統一, 今内 覚, 小沼 操, 間 陽子, 岡田 幸助
    日本獣医学会学術集会講演要旨集, 131回, 92, 92, (公社)日本獣医学会, Mar. 2001
    Japanese
  • 異なるMHCを有するBLV感染羊の免疫応答               
    今内 覚, 竹嶋 伸之輔, 田島 茂, 岡田 幸助, 小沼 操, 間 陽子
    日本獣医学会学術集会講演要旨集, 131回, 92, 92, (公社)日本獣医学会, Mar. 2001
    Japanese
  • Effects of Lipopolysaccharide on Production of Interleukin-1 and Interleukin-6 by Bovine Mammary Epithelial Cells in vitro
    Hiroyuki Okada, Hiromichi Ohtsuka, Satoru Kon-Nai, Rikio Kirisawa, Yuichi Yokomizo, Tomo-O. Yoshino, Thomas J. Rosol
    Journal of Veterinary Medical Science, 61, 1, 33, 35, Jan. 1999, [Peer-reviewed]
    English, Scientific journal
  • Effects of lipopolysaccharide on production of interleukin-1 and interleukin-6 by bovine mammary epithelial cells in vitro
    H Okada, H Ohtsuka, S Kon-Nai, R Kirisawa, Y Yokomizo, T Yoshino, TJ Rosol
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 61, 1, 33, 35, Jan. 1999, [Peer-reviewed]
    English, Scientific journal

Other Activities and Achievements

Books and other publications

  • 動物の感染症<第5版>               
    今内 覚, 総論;IV感染症の予防と治療;感染症の予防;各論;牛 19.免疫不全ウイルス感染症;めん羊・山羊 9.跳躍病;10.ウェッセルスブロン病;11.羊肺腺腫
    近代出版, Mar. 2025, [Contributor]
  • 哺育・育成牛の飼養管理ガイド               
    今内 覚, 岡川朋弘, 第4章 給餌と飼養管理のポイント ③下痢予防のための発酵代用乳のつくり方と給与
    DAIRYMAN, Oct. 2024, [Contributor]
  • 哺育・育成牛の飼養管理ガイド               
    今内 覚, 第3章 重要疾病の基礎知識と予防策 ①子牛の免疫とワクチン
    DAIRYMAN, Oct. 2024, [Contributor]
  • 動物衛生学 第2版               
    今内 覚, 分担執筆, 範囲:コラム 牛伝染性リンパ腫 (旧名:牛白血病)
    文永堂出版, Mar. 2024, [Joint work]
  • 周産期疾病から牛を守る               
    今内 覚 他, 第Ⅰ章 重要疾病の基礎知識と周産期免疫の新知見: 5 周産期に免疫が低下するメカニズムの一端を解明
    デーリィマン編集部, Nov. 2022, [Contributor]
  • 獣医内科学第3版 産業動物編               
    今内 覚, 第11章 血液・造血臓器疾患 5. 血液の感染症 1) 牛伝染性リンパ腫
    一般社団法人 日本獣医内科アカデミー 編・文永堂出版, Mar. 2022, [Contributor]
  • 主要症状を基礎にした牛の臨床3               
    今内 覚 他, トリパノソーマ病、悪性カタル熱
    デーリィマン社, May 2020, [Contributor]
  • Academic Fantasista 免疫療法で動物を救う               
    今内 覚, 免疫療法で動物を救う https://www.hokudai.ac.jp/pr/hokudai_af2018.pdf
    北海道大学, Apr. 2019, [Contributor]
  • 動物の感染症<第4版>               
    今内 覚, 総論:IV感染症の予防と治療: 1. 感染症の予防, 各論 : 11 アデノウイルス病, 19 牛免疫不全ウイルス感染症.
    近代出版, Mar. 2019, [Contributor]
  • 北大など、動物用の免疫チェックポイント阻害薬を開発 ー 目指すは病気の違いを越えた汎用免疫療法 ー               
    今内 覚
    日経バイオテクONLINE, Oct. 2017, [Others]
  • テレビ・ドクター4 よく分かる乳牛の病気100選               
    今内 覚, 近年の重大疾病と予防策 地方病型(流行型)牛白血病、皮膚に異常を示す病気 散発性牛白血病の項
    デーリィマン社, Oct. 2017, [Contributor]
  • 動物衛生学               
    今内 覚, コラム 牛白血病
    文永堂出版, Sep. 2017, [Contributor]
  • 動物用ワクチンとバイオ医薬品 -新たな潮流-               
    Satoru Konnal, 第1章 総論 4. 抗体医薬: 免疫チェックポイント阻害薬等
    文永堂出版, Jul. 2017, [Contributor]
  • 牛白血病防除の観点から               
    今内 覚, 検定検査乳S
    検定検査乳S 34:7, Jan. 2016, [Others]
  • 現代農業・牛白血病を出さない!尾鈴のBL対策               
    宮崎県JA尾鈴, 牛白血病を出さない!尾鈴のBL対策
    農山漁村文化協会, May 2015, [Others]
  • 獣医免疫学               
    今内 覚 ほか, 第13章 ワクチン
    緑書房, 2015, [Contributor]
  • 新製品の登場で注目集める動物用医薬品               
    今内 覚
    日経バイオテク, Sep. 2014, [Others]
  • 牛病学〈第三版〉               
    今内 覚, V. 感染症の制御 3) 免疫疲弊化と免疫賦活化
    近代出版, 2013, [Contributor]

Lectures, oral presentations, etc.

  • 動物も新薬で病気から救える時代に               
    今内 覚
    国民との科学・技術対話事業, 05 Dec. 2025, Japanese, Invited oral presentation
    [Invited]
  • 牛伝染性リンパ腫の現状から最後の砦:発症予測法について/プロバイオティクスを活用したワクチン効果の増強について               
    今内 覚
    令和7年度十勝獣医師会産業動物講習会・十勝管内家畜自衛防衛機推進協議会, 27 Nov. 2025, Japanese, Invited oral presentation
    [Invited]
  • 動物の難治性疾病に対する創薬研究 〜動物の免疫療法について〜               
    今内 覚
    日本実験動物医学会コラム(https://jalam.ne.jp/column/動物の難治性疾病に対する創薬研究-〜動物の免疫/), 12 Nov. 2025, Japanese, Others
    [Invited]
  • プロバイオティクスで子牛のワクチン応答を増強 ~既存のワクチンプログラムへの応用に期待~               
    今内 覚
    プレスリリース(https://www.hokudai.ac.jp/news/pdf/251031_pr3.pdf), 31 Oct. 2025
  • 牛伝染性リンパ腫の現状、発症早期診断法の開発とその実践               
    今内 覚
    公益社団法人福島県獣医師会令和7年度産業動物臨床講習会, 30 Oct. 2025, Japanese, Invited oral presentation
    [Invited]
  • 牛伝染性リンパ腫の現状、発症早期診断法の開発とその実践               
    今内 覚
    公益社団法人富山県獣医師会令和7年度家畜衛生対策事業, 15 Oct. 2025, Japanese, Invited oral presentation
    [Invited]
  • 動物難治性疾病に対する免疫療法の臨床研究               
    今内 覚
    日本実験動物医学会/JALAM特別講演「獣医領域における難治性疾患に対する新規治療法の開発」, 05 Sep. 2025, Japanese, Keynote oral presentation
    [Invited]
  • 牛伝染性リンパ腫の現状、発症早期診断法の開発とその実践               
    今内 覚
    宮城県農業共済組合令和7年度家畜診療等技術体験発表会及び診療技術研修会(第2班), 24 Jul. 2025, Japanese, Invited oral presentation
    [Invited]
  • 牛伝染性リンパ腫の現状、発症早期診断法の開発とその実践               
    今内 覚
    宮城県農業共済組合令和7年度家畜診療等技術体験発表会及び診療技術研修会(第1班), 23 Jul. 2025, Japanese, Invited oral presentation
    [Invited]
  • Recent topics on enzootic bovine leukosis               
    今内 覚
    27th Summer Retrovirus Conference, 10 Jul. 2025, Japanese, Invited oral presentation
    [Invited]
  • 牛伝染性リンパ腫を巡る情勢とRAISING               
    今内 覚
    令和7年度徳之島地区牛伝染性リンパ腫研修会, 27 Jun. 2025, Japanese, Invited oral presentation
    [Invited]
  • 牛伝染性リンパ腫ウイルス感染症の防疫戦略               
    今内 覚
    令和7年度家畜生産農場衛生対策事業に係る牛伝染性リンパ腫対策検討会, 26 Jun. 2025, Japanese, Invited oral presentation
    [Invited]
  • 牛伝染性リンパ腫を巡る情勢とRAISING               
    今内 覚
    令和7年度家畜生産農場衛生対策事業に係る牛伝染性リンパ腫対策検討会, 25 Jun. 2025, Japanese, Invited oral presentation
    [Invited]
  • 牛伝染性リンパ腫の発症予測診断法’RAISING’とは               
    今内 覚
    オホーツク獣医師会獣医新技術講習会, 22 May 2025, Invited oral presentation
    [Invited]
  • 古くて新しいプロバイオティクス ~最近の話題について~               
    今内 覚
    オホーツク獣医師会獣医新技術講習会, 22 May 2025, Japanese, Invited oral presentation
    [Invited]
  • イヌのがんに抗CTLA-4抗体治療が有効であることを初めて報告 ~イヌのがんへの免疫療法の適用拡大に期待~               
    今内 覚
    プレスリリース(https://www.hokudai.ac.jp/news/pdf/250520_pr2.pdf), 20 May 2025
  • 牛リンパ腫発症予測診断技術 RAISING の精度の高さを証明 ~国内初の 14 研究機関による多施設検証試験を実施~               
    今内 覚
    プレスリリース(https://www.hokudai.ac.jp/news/pdf/250328_pr.pdf), 28 Mar. 2025, Japanese
  • 牛伝染性リンパ腫を巡る情勢               
    今内 覚
    独立行政法人家畜改良センター新冠牧場 牛の飼養・衛生管理に関するセミナー, 26 Mar. 2025, Japanese, Invited oral presentation
    [Invited]
  • 抗菌剤に頼らない畜産物の生産体制の推進 薬剤耐性菌問題の克服も目指した新たな動物疾病制御法の実践研究               
    今内 覚
    知の集積と活用の場 産学官連携協議会, 14 Feb. 2025, Japanese, Public symposium
  • 牛伝染性リンパ腫の現状、発症早期診断法の開発とその実践               
    今内 覚
    第42回日本獣医師会獣医学術学会年次大会(令和6年度), 26 Jan. 2025, Japanese, Invited oral presentation
    [Invited]
  • 牛伝染性リンパ腫診断の新技術・早期発症予測診断法 RAISING とは               
    今内 覚
    第66回岐阜県家畜保健衛生業績発表会, 20 Dec. 2024, Japanese, Invited oral presentation
    [Invited]
  • 古くて新しいプロバイオティクス               
    今内 覚
    2024 アグリビジネス創出フェア in Hokkaido -北海道の食と農の明日へ-, 08 Nov. 2024, Japanese, Public symposium
  • 動物も新薬で病気から救える時代に               
    今内 覚
    国民との科学・技術対話事業, 25 Oct. 2024, Japanese, Invited oral presentation
    [Invited]
  • イヌの腫瘍に対する免疫療法の試み               
    今内 覚
    北海道獣医師会十勝支部小動物講習会, 19 Oct. 2024, Japanese, Invited oral presentation
    [Invited]
  • 牛伝染性リンパ腫発症牛の全部廃棄大幅削減による日本経済の活性化~前がん細胞検診技術RAISINGの実用化~               
    今内 覚
    鹿児島県家畜畜産物衛生指導協会令和6年度家畜生産農場衛生対策事業に係る牛伝染性リンパ種対策講習会, 26 Sep. 2024, Japanese, Invited oral presentation
    [Invited]
  • 牛伝染性リンパ腫発症牛の全部廃棄大幅削減による日本経済の活性化~前がん細胞検診技術RAISINGの実用化~               
    今内 覚
    第6回南九州畜産獣医学拠点(SKLV:すくらぶ)セミナー, 25 Sep. 2024, Japanese, Invited oral presentation
    [Invited]
  • 牛伝染性リンパ腫の現状と発症予測法               
    今内 覚
    第64回獣医疫学会学術集会シンポジウム, 31 Aug. 2024, Japanese, Invited oral presentation
    [Invited]
  • 古くて新しいプロバイオティクス 〜最近の話題について〜               
    今内 覚
    北海道獣医師会北海道地区学会セミナー, 29 Aug. 2024, Japanese, Invited oral presentation
    [Invited]
  • 牛伝染性リンパ腫について 感染・発症・診断の基本と最前線               
    今内 覚
    東京都芝浦食肉衛生検査所研修会, 23 May 2024, Japanese, Invited oral presentation
    [Invited]
  • Immune Checkpoint Inhibitors 〜Breakthrough Cancer Therapy and its Application to Veterinary Medicine 〜               
    Satoru KONNAI
    Seminario Especial in Universidade Federal do Rio Grande do Sul, 19 Mar. 2024, English, Invited oral presentation
    [Invited]
  • 牛伝染性リンパ腫の現状から最後の砦:発症予測法について               
    今内 覚
    新潟県獣医師会産業動物部会特別講習会, 01 Mar. 2024, Japanese, Invited oral presentation
    [Invited]
  • 動物も新薬で病気から救える時代に               
    今内 覚
    国民との科学・技術対話事業, 21 Feb. 2024, Japanese, Invited oral presentation
    [Invited]
  • 獣医学から生まれる医学への貢献 汎動物学(ズービキティ)とは?               
    今内 覚
    One Health リサーチセンター 開所記念 市民公開講座, 17 Feb. 2024, Japanese, Invited oral presentation
  • 牛伝染性リンパ腫ってどういう病気? 感染・発症・診断の基本と最前線               
    今内 覚
    細胞診クラブ主催 牛伝染性リンパ腫フォーラム【基本と最前線×東洋医学的解析×鍼灸治療】, 20 Jan. 2024, Japanese, Invited oral presentation
    [Invited]
  • 牛伝染性リンパ腫の現状から最後の砦:発症予測法について               
    今内 覚
    第41回日本獣医師会獣医学術学会年次大会(令和5年度)特別企画, 03 Dec. 2023, Japanese, Invited oral presentation
    [Invited]
  • 牛伝染性リンパ腫とは? 最後の砦!発症予測診断法RAISINGとは?               
    今内 覚
    2023アグリビジネス創出フェア in Hokkaido -北海道の食と農の明日へ-, 09 Nov. 2023, Japanese, Public symposium
  • 早期発症診断によって経済損失低減を実現する 牛のがん検診               
    今内 覚
    知の集積と活用の場 産学官連携協議会2023, 07 Nov. 2023, Japanese, Public symposium
  • Novel livestock disease prevention method using probiotics instead of antibiotics               
    Satoru KONNAI
    7th International Livestock Biotechnology Symposium, 19 Oct. 2023, English, Invited oral presentation
    17 Oct. 2023 - 20 Oct. 2023, [Invited]
  • 牛伝染性リンパ腫対策の最新知見               
    今内 覚
    令和5年岩手県獣医師会研修会, 13 Oct. 2023, Japanese, Invited oral presentation
    13 Oct. 2023, [Invited]
  • イヌの鼻腔内腺癌や骨肉腫に免疫チェックポイント阻害剤が有効であることを初めて報告 ~イヌ用抗PD-L1抗体による免疫療法の適用拡大に期待~               
    今内 覚ら
    プレスリリース(https://www.hokudai.ac.jp/news/pdf/231005_pr.pdf), 05 Oct. 2023, Japanese, Others
  • 酪農教育ファームにおける安全・衛生               
    今内 覚
    中央酪農会議 令和5年度酪農教育ファームスキルアップ研修会, 22 Sep. 2023, Japanese, Invited oral presentation
    [Invited]
  • 牛伝染性リンパ腫における最近の知見、新たな発症予測診断について               
    今内 覚
    北海道獣医師会留萌支部獣医新技術講習会, 20 Sep. 2023, Japanese, Invited oral presentation
    [Invited]
  • 牛伝染性リンパ腫への対策に向けて               
    今内 覚
    松前町肉牛改良センター特別講演会, 28 Jun. 2023, Japanese, Invited oral presentation
    [Invited]
  • Combination therapy effective against canine melanoma               
    Konnai S
    Research Press Release (https://www.global.hokudai.ac.jp/blog/combination-therapy-effective-against-canine-melanoma/), 23 Jun. 2023
  • イヌ悪性黒色腫に対して放射線治療との併用で 抗PD-L1抗体の効果が高まることをはじめて報告 ~イヌ用免疫チェックポイント阻害薬のより良い使用法の実現に期待~               
    今内 覚ら
    プレスリリース(https://www.hokudai.ac.jp/news/pdf/230602_pr.pdf), 02 Jun. 2023
  • 動物難治性疾病に対する新規予防・治療法の開発               
    今内 覚
    第15回大動物臨床研究会特別セミナー, 26 May 2023, Japanese, Invited oral presentation
    [Invited]
  • 動物難治性疾病に対する新規予防・治療法の開発               
    今内 覚
    北里大学第486回獣医学科セミナー<特別講演>, 18 May 2023, Japanese, Invited oral presentation
    [Invited]
  • 牛のリンパ腫発症を予測するがん検診技術               
    今内 覚
    岩手県中央家畜保健衛生所セミナー, 27 Apr. 2023, Japanese, Invited oral presentation
    [Invited]
  • PD-L1の阻害により既存のワクチン効果を増強 ~子牛のワクチンプログラムへの応用に期待~               
    今内 覚ら
    プレスリリース(https://www.hokudai.ac.jp/news/pdf/230316_pr2.pdf), 16 Mar. 2023
  • 動物も新薬で病気から救える時代に               
    今内 覚
    国民との科学・技術対話事業, 14 Mar. 2023, Japanese, Invited oral presentation
    [Invited]
  • 牛伝染性リンパ腫 (旧名:牛白血病)の現状と早期発症診断による経済損失低減の実現               
    今内 覚
    山口県畜産振興協会令和4年度家畜生産農場衛生対策事業, 21 Feb. 2023, Japanese, Invited oral presentation
    [Invited]
  • Development of effective preventive and therapeutic methods for animal diseases               
    Satoru KONNAI
    Special seminar in Mongolian University of Life Sciences, 15 Feb. 2023, English, Invited oral presentation
    [Invited]
  • 動物も新薬で病気から救える時代に               
    今内 覚
    国民との科学・技術対話事業, 09 Nov. 2022, Japanese, Invited oral presentation
    [Invited]
  • 牛のリンパ腫発症を予測するがん検診技術を開発~発症予測法の実用化による畜産被害の軽減に期待~               
    今内 覚ら
    プレスリリース(https://www.hokudai.ac.jp/news/2022/10/post-1113.html), 21 Oct. 2022
  • Breakthrough in cancer therapy               
    Satoru KONNAI
    Capability building of ASEAN biotechnology researchers for livestock resiliency and sustainability, 05 Jul. 2022, English, Invited oral presentation
    [Invited]
  • Importance of building global network for livestock resiliency and sustainability               
    Satoru KONNAI
    Capability building of ASEAN biotechnology researchers for livestock resiliency and sustainability, 04 Jul. 2022, English, Invited oral presentation
    [Invited]
  • Novel livestock disease prevention method using probiotics instead of antibiotics               
    Satoru KONNAI
    Capability building of ASEAN biotechnology researchers for livestock resiliency and sustainability, 04 Jul. 2022, English, Invited oral presentation
    [Invited]
  • 家畜伝染病ヨーネ病の現状と病態発生機序について               
    今内 覚
    第97回日本結核・非結核性抗酸菌症学会学術講演会エキスパートセミナー, 01 Jul. 2022, Japanese, Invited oral presentation
    [Invited]
  • 動物難治性疾病に対する治療と実際、未来               
    今内 覚
    北里大学第471回獣医学科セミナー<Cutting edge>, 16 May 2022, Invited oral presentation
    16 May 2022 - 16 May 2022, [Invited]
  • 母牛はわが身を削って子牛を出産する~牛伝染性リンパ腫と分娩との関係,周産期に疾病が多発するメカニズムの一端を証明~               
    今内 覚ら
    プレスリリース(https://www.hokudai.ac.jp/news/pdf/220310_pr.pdf)(https://www.hokudai.ac.jp/news/2022/03/post-1006.html), 10 Mar. 2022, Japanese, Others
  • 牛伝染性リンパ腫の防除戦略               
    今内 覚
    全国農業共済協会 令和3年度 家畜診療等技術全国研究集会, 22 Feb. 2022, Japanese, Invited oral presentation
    [Invited]
  • 動物用バイオ医薬品の開発と応用研究               
    今内 覚
    令和3年度日本薬剤師会農林水産薬事薬剤師部会動物薬事研修会, 18 Feb. 2022, Japanese, Invited oral presentation
    [Invited]
  • 動物難治性疾病に対する治療と実際、未来               
    今内 覚
    国民との科学・技術対話事業, 10 Feb. 2022, Japanese, Invited oral presentation
    [Invited]
  • 牛伝染性リンパ腫における免疫学的解析を基盤とした新制御法の試み               
    今内 覚
    日本獣医学会市民公開講座, 05 Feb. 2022, Japanese, Invited oral presentation
    [Invited]
  • 動物難治性疾病に対する治療と実際、未来               
    今内 覚
    国民との科学・技術対話事業, 04 Feb. 2022, Japanese, Invited oral presentation
    [Invited]
  • 牛伝染性リンパ腫の病態発生機序解析を基盤とする新制御法の試み               
    今内 覚
    日本家畜衛生学会 第94回大会・家畜衛生フォーラム2021, 03 Dec. 2021, Japanese, Invited oral presentation
    03 Dec. 2021, [Invited]
  • 牛伝性性リンパ腫の最新知見について               
    今内 覚
    令和3年度家畜保健衛生所病性鑑定技術検討会, 16 Nov. 2021, Japanese, Invited oral presentation
    16 Nov. 2021 - 16 Nov. 2021, [Invited]
  • 牛伝染性リンパ腫の現状と対策               
    今内 覚
    ささえや製薬学術セミナー, 27 Oct. 2021, Japanese, Invited oral presentation
    27 Oct. 2021 - 27 Oct. 2021, [Invited]
  • 動物の慢性感染症と免疫チェックポイント分子               
    今内 覚
    十勝家畜保健衛生所講演会, 30 Sep. 2021, Japanese, Invited oral presentation
    30 Sep. 2021 - 30 Sep. 2021, [Invited]
  • 牛伝染性リンパ腫の新たな知見               
    今内 覚
    北海道獣医師会十勝支部産業講習会, 29 Sep. 2021, Japanese, Invited oral presentation
    29 Sep. 2021 - 29 Sep. 2021, [Invited]
  • 牛伝染性リンパ腫の最新知見               
    今内 覚
    オホーツク獣医師会獣医新技術講習会, 20 Jul. 2021, Japanese, Invited oral presentation
    20 Jul. 2021 - 20 Jul. 2021, [Invited]
  • 免疫チェックポイント阻害薬による腫瘍免疫療法について 〜北海道大学動物医療センターにおける臨床研究成果から〜               
    今内 覚
    One Healthリサーチセンター キックオフシンポジウム, 29 May 2021, Japanese, Invited oral presentation
    29 May 2021 - 29 May 2021, [Invited]
  • Research Press Release: New therapy target for malignant melanomas in dogs               
    Konnai S
    Research Press Release (https://www.global.hokudai.ac.jp/blog/new-therapy-target-for-malignant-melanomas-in-dogs/), 22 Apr. 2021, English, Media report
  • Probiotics keep calves healthy, too!               
    Probiotics keep, calves healthy, too
    Research Press Release (https://www.global.hokudai.ac.jp/blog/probiotics-keep-calves-healthy-too/), 06 Apr. 2021, English, Media report
  • 続報・肺転移のあるイヌ悪性黒色腫に抗PD-L1抗体が有効であることをはじめて実証 ~イヌ用免疫チェックポイント阻害薬の実現に大きく前進~               
    今内 覚, 前川直也ら
    プレスリリース(https://www.hokudai.ac.jp/news/pdf/210215_pr.pdf) (https://www.hokudai.ac.jp/news/2021/02/pd-l1.html), 15 Feb. 2021, Japanese, Media report
  • Deeper insight into how tick spit suppresses cattle immunity               
    Konnai S
    Research Press Release (https://www.global.hokudai.ac.jp/blog/deeper-insight-into-how-tick-spit-suppresses-cattle-immunity/) (https://conexao.ufrj.br/2021/01/28/parceria-nipo-brasileira-estuda-como-carrapatos-afetam-bovinos/) (https://www.correiodopovo.com.br/especial/chance-de-al%C3%ADvio-para-bovinos-1.573426), 28 Jan. 2021, English, Media report
  • プロバイオティクスで子牛を下痢から守る~発酵哺乳飼料による子牛の腸炎防御効果を証明~               
    今内 覚, 茅先 史, 岡川朋弘ら
    プレスリリース (https://www.hokudai.ac.jp/news/pdf/210118_pr.pdf) (https://www.hokudai.ac.jp/news/2021/01/post-783.html), 18 Jan. 2021, Japanese, Media report
  • マダニ唾液が免疫チェックポイント因子の発現を誘導~マダニ媒介性病原体の伝播機序の解明に期待~               
    今内 覚, 佐治木大和ら
    プレスリリース (https://www.hokudai.ac.jp/news/pdf/210114_pr3.pdf)(https://www.hokudai.ac.jp/news/2021/01/post-779.html), 14 Jan. 2021, Japanese, Media report
  • プロスタグランジンE2を介した免疫チェックポイント阻害薬の新たな耐性獲得機構の解明~新たな免疫療法への応用に期待~               
    今内 覚, 佐治木大和ら
    プレスリリース(https://www.hokudai.ac.jp/news/pdf/201222_pr.pdf)(https://www.hokudai.ac.jp/news/2020/12/e2.html), 21 Dec. 2020, Japanese, Media report
  • 子牛の下痢症に対する発酵代用乳の腸炎抑制効果の検証               
    今内 覚
    令和2年度獣医療提供体制整備推進総合対策事業:新規獣医師臨床研修促進事業 実践実習, 28 Oct. 2020, Japanese, Invited oral presentation
    28 Oct. 2020, [Invited]
  • 家畜の慢性感染症制御の難しさ 〜免疫から逃れる病原体たち〜               
    今内 覚
    令和2年度獣医療提供体制整備推進総合対策事業:新規獣医師臨床研修促進事業, 28 Oct. 2020, Japanese, Invited oral presentation
    28 Oct. 2020, [Invited]
  • 牛伝染性リンパ腫(旧名:牛白血病) の最新知見 北海道大学による臨床検査診断結果に基づく実践的対策の紹介               
    今内 覚
    令和2年家畜診療等技術北海道地区研修会, 28 Oct. 2020, Japanese, Invited oral presentation
    28 Oct. 2020, [Invited]
  • 動物用バイオ医薬品実用化を可能とする大量生成技術の構築               
    今内 覚
    イノベーション創出強化研究推進事業研究紹介2020 (http://www.naro.affrc.go.jp/laboratory/brain/innovation/results/2019/26058BC.html), 23 Oct. 2020, Japanese, Media report
    [Invited]
  • 免疫療法 〜免疫チェックポイント阻害剤について〜               
    今内 覚
    北海道大学One Healthフロンティア卓越大学院プログラムOne Health Relay Report https://onehealth.vetmed.hokudai.ac.jp/news/220, 16 Mar. 2020, Japanese, Others
    [Invited]
  • 動物の難病(がん・感染症)に対する創薬研究               
    今内 覚
    日本学術振興会 科研費 研究成果トピックス https://www.jsps.go.jp/j-grantsinaid/37_topics/data/10101-40396304.pdf, 16 Mar. 2020, Japanese, Media report
    [Invited]
  • 動物用バイオ医薬品の開発と応用研究               
    今内 覚
    農林水産省動物医薬品検査所 令和元年度第1回特別講演会, 24 Jan. 2020, Japanese, Invited oral presentation
    [Invited]
  • 牛白血病の最新知見               
    今内 覚
    北海道獣医師会宗谷支部令和元年度新技術講習会, 19 Nov. 2019, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の最新知見〜北海道大学臨床検査診断結果に基づく実践的対策の紹介〜               
    今内 覚
    みなみ北海道農業共済組合南部家畜診療センター講習会, 05 Nov. 2019, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 抗生剤に頼らないプロバイオティクスを応用した新規家畜疾病予防法の開発 〜発酵哺乳飼料による子牛の下痢抑制効果〜               
    今内 覚
    みなみ北海道農業共済組合南部家畜診療センター講習会, 05 Nov. 2019, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 動物の難病(がん・感染症)に対する 創薬研究(新薬の開発)               
    今内 覚
    国民との科学・技術対話, 24 Oct. 2019, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 動物用抗体医薬品の開発および臨床研究               
    今内 覚
    公益社団法人日本動物用医薬品協会第51回学術講習会, 16 Oct. 2019, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 動物難治性疾病に対する創薬研究               
    今内 覚
    WISE特別セミナー2019, 08 Oct. 2019, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Effects of bovine tumor necrosis factor alpha decoy receptors on cell death and inflammatory cytokine kinetics: potential for bovine inflammation therapy               
    Fujisawa S, Konnai S, Okagawa T, Maekawa N, Goto S, Murata S, Ohashi K
    International Veterinary Immunology Symposium 2019, 16 Aug. 2019, English, Oral presentation
    [International presentation]
  • Functional analysis of bovine CTLA-4 in bovine leukemia virus infection               
    Watari K, Konnai S, Okagawa T, Maekawa N, Goto S, Murata S, Ohashi K
    International Veterinary Immunology Symposium 2019, 16 Aug. 2019, English, Oral presentation
    [International presentation]
  • Development of a sensitive PD-L1 immunohistochemistry of canine cancers and clinical efficacy of an anti-PD-L1 antibody in canine oral malignant melanoma with pulmonary metastasis               
    Maekawa N, Konnai S, Okagawa T, Murata S, Ohashi K
    International Veterinary Immunology Symposium 2019, 16 Aug. 2019, English, Invited oral presentation
    [International presentation]
  • Immunomodulatory effects of sialostatin L and sialostatin L2 from Ixodes persulcatus Schulze, Taiga tick               
    Satoru Konnai, Yamato Sajiki, Tomohiro Okagawa, Naoya Maekawa, Masayoshi Isezaki, Shiro Murata, Kazuhiko Ohashi
    International Veterinary Immunology Symposium 2019, 16 Aug. 2019, English, Oral presentation
    [International presentation]
  • The induction of immunosuppression via prostaglandin E2 and the enhancement of anti-bacterial effects by anti-PD-L1 antibody combined with COX-2 inhibitor in Mycoplasma bovis infection               
    Goto S, Konnai S, Okagawa T, Maekawa N, Murata S, Ohashi K
    International Veterinary Immunology Symposium 2019, 15 Aug. 2019, English, Oral presentation
    [International presentation]
  • Contribution of prostaglandin E2 to disease progression and enhancement of antiviral effects by anti-PD-L1 antibody combined with COX-2 inhibitor in bovine leukemia virus infection               
    Sajiki Y, Konnai S, Okagawa T, Maekawa N, Murata S, Ohashi K
    International Veterinary Immunology Symposium 2019, 14 Aug. 2019, English, Invited oral presentation
    [International presentation]
  • Establishment of anti-bovine PD-1 chimeric antibody and a pilot clinical study               
    Satoru Konnal, Tomohiro Okagawa, Naoya Maekawa, Shiro Murata, Kazuhiko Ohashi
    International Veterinary Immunology Symposium 2019, 14 Aug. 2019, English, Invited oral presentation
    [International presentation]
  • ウシマイコプラズマ感染症における免疫疲弊化               
    今内 覚
    日本マイコプラズマ学会第46会学術集会, 24 May 2019, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病臨床検査診断結果に基づく実践的対策               
    今内 覚
    上川青年獣医師会特別講演, 22 May 2019, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 獣医学領域における感染症の制御               
    今内 覚
    微生物化学研究所特別講演, 13 May 2019, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 免疫チェックポイントを標的としたイヌ免疫療法の試み               
    今内 覚
    麻布大学獣医学部臨床特別セミナー, 16 Apr. 2019, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Developing immunotherapy to save animals               
    Satoru Konnai
    Research Highlight: https://www.global.hokudai.ac.jp/blog/developing-immunotherapy-to-save-animals/, 08 Apr. 2019, English, Media report
    [Invited], [International presentation]
  • 動物難治性疾病に対する創薬研究               
    今内 覚
    東北大学大学院医学系研究院抗体創薬研究分野 第6回抗体創薬研究セミナー, 26 Mar. 2019, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Six scientists whose transformative work reaches across borders.               
    Satoru Konnai
    Nature index: https://www.nature.com/articles/d41586-019-00831-5, 20 Mar. 2019, English, Media report
    [Invited], [International presentation]
  • 牛白血病の最新知見とウイルス量を基盤とした対策について               
    今内 覚
    大分県畜産協会家畜生産農場清浄化支援事業講習会, 13 Mar. 2019, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 静かなる脅威・牛白血病 〜最新知見から〜               
    今内 覚
    日本中央競馬会(JRA)畜産振興事業シンポジウム 地方病性牛白血病・清浄化へのアプローチ ~牛白血病清浄化に向けて今しなければならないこと~, 06 Mar. 2019, Japanese, Keynote oral presentation
    [Invited], [Domestic Conference]
  • 家畜の慢性感染症制御の難しさ 〜免疫から逃れる病原体たち〜               
    今内 覚
    第9回大動物臨床研究会東京シンポジウム, 02 Mar. 2019, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 動物難治性疾病に対する創薬研究 〜免疫チェックポイントを標的としたイヌ免疫療法の試み〜               
    今内 覚
    第15回日本獣医内科学アカデミー学術大会, 16 Feb. 2019, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Immune checkpoint inhibitors-related diseases in animals: Application of immunotherapy targeting the immune checkpoints for veterinary medicine               
    Satoru KONNAI
    Seminario Especial in Universidade Federal do Rio Grande do Sul, 08 Feb. 2019, English, Invited oral presentation
    [Invited], [International presentation]
  • 動物の難病(がん・感染症)に対する 創薬研究(新薬の開発)               
    今内 覚
    国民との科学・技術対話, 26 Jan. 2019, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病臨床検査診断結果に基づく実践的対策               
    Satoru Konnal
    平成30年度小平町和牛生産改良組合牛白血病研修会, 16 Jan. 2019, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 動物難治性疾病に対する創薬研究 〜免疫チェックポイントを標的とした新規免疫療法の試み〜               
    Satoru Konnal
    大阪市立大学大学院工学研究科 医工・生命工学教育研究センター第1回セミナー, 27 Dec. 2018, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • イヌ難治性腫瘍疾患に対する免疫チェックポイントを 標的とした新規免疫療法の試み               
    今内 覚, 前川直也, 細谷謙次, 金 尚昊, 高木 哲, 賀川由美子, 岡川朋弘, 村田史郎, 大橋和彦
    北海道小動物獣医師会年次大会2018, 04 Nov. 2018, Japanese, Oral presentation
    [Domestic Conference]
  • 牛白血病の最新知見、現状と対策               
    今内 覚
    兵庫県畜産協会平成30年度食の安全・消費者の信頼確保対策事業平成30年度牛白血病講習会, 23 Oct. 2018, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 動物難治性疾病に対する創薬研究 〜免疫学的解析を基盤とした新規制御法の開発〜               
    今内 覚
    第161回日本獣医学会学術集会微生物学分科会シンポジウム「感染症対策の新たな突破口を探る」, 11 Sep. 2018, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の最新知見 〜臨床データーからの更新知見〜               
    今内 覚
    平成30年度みなみ北海道農業共済組合第1回診療等体験発表会 特別講演, 26 Jul. 2018, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 免疫チェックポイントを標的とした動物用抗体医薬の開発               
    今内 覚
    第2回ヒトと伴侶動物の比較医学研究会 ヒト医療と獣医療の先端技術を駆使した次世代のがん治療〜がん撲滅への新たな挑戦〜, 30 Jun. 2018, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛難治性疾病における免疫疲弊化機序の 解析と制御法への応用               
    今内 覚
    第74回九州・山口病性鑑定協議会, 21 Jun. 2018, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 動物難治性疾病に対する創薬研究               
    今内 覚
    北里大学獣医学部特定講義, 06 Jun. 2018, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の最新知見 現状と対策               
    今内 覚
    国立大学法人岐阜大学応用生物科学部附属家畜衛生地域連携教育研究センター家畜衛生講演会, 04 Jun. 2018, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の最新知見               
    今内 覚
    鹿児島県獣医師会 産業動物部会曽於・肝属地区獣医師講習会, 27 Mar. 2018, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の最新知見 帯広食肉衛生検査所との共同研究成果から               
    今内 覚
    北海道獣医師会十勝支部公衆衛生講習会, 07 Mar. 2018, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の疫学と公衆衛生分野での留意点               
    今内 覚
    北海道獣医師会平成29年度獣医公衆衛生講習会, 05 Mar. 2018, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 地方病性牛白血病対策 について               
    今内 覚
    平成29年度岩手県牛白血病防疫推進講習会, 26 Jan. 2018, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛の免疫応答を利用した難治性疾病の新規制御法開発 〜免疫チェックポイントを標的とした動物用抗体創薬〜               
    今内 覚
    家畜衛生フォーラム2017 「抗菌剤に頼らない新しい家畜疾病の制御法 -モデルとしての難治性・慢性疾病克服のための研究-」, 15 Dec. 2017, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Immune exhaustion during chronic diseases in animals               
    Satoru Konnal
    The 20th Joint Symposium Between Seoul National University and Hokkaido University, 16 Nov. 2017, English, Invited oral presentation
    [Invited], [International presentation]
  • 牛難治性疾病に対する多機能型バイオ医薬(抗体医薬)の創出と発展的応用               
    今内 覚
    農林水産業・食品産業科学技術研究推進事業 「知」の集積と活用の場ポスターセッション, 10 Nov. 2017, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 動物用バイオ医薬品の開発               
    今内 覚
    東北大学大学院医学系研究科抗体創薬研究分野 第二回抗体創薬研究セミナー, 02 Nov. 2017, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 増加している牛白血病 - 北海道での現状と対策について -               
    今内 覚
    第22回北海道肉牛研究会大会, 26 Oct. 2017, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Epidemiological and immunological study for intractable infectious diseases in Mongolian livestock               
    Satoru KONNAI
    JICA Project: Infectious Diseases Seminar 2017 in Mongolia, 10 Oct. 2017, English, Invited oral presentation
    [Invited], [International presentation]
  • 動物の難病に対する新規治療法の開発               
    今内 覚
    国民との科学・技術対話, 03 Oct. 2017, Japanese, Public discourse
    [Invited], [Domestic Conference]
  • Theileria parva感染症における免疫チェックポイント因子の動態解析               
    今内 覚, 岡川朋弘, 山田慎二, Martin Simuunza, Timothy Connelley, Ivan Morrison, 村田史郎, 大橋和彦
    第160回日本獣医学会学術集会, 13 Sep. 2017, Japanese, Oral presentation
    [Domestic Conference]
  • Role of Inhibitory Molecules in Bovine Chronic Infectious Diseases and as Target for Therapy               
    Satoru Konnal
    宮崎大学産業動物防疫リサーチセンター(CADIC)特別セミナー, 11 Sep. 2017, English, Invited oral presentation
    [Invited], [Domestic Conference]
  • Therapeutic intervention in cancer and chronic infections in animals: Antibody mediated manipulation of PD-1/PD-L1 interaction               
    Satoru Konnal
    Hokkaido University & Colorado State University Kick-off Symposium 2017, 26 Jul. 2017, English, Invited oral presentation
    [Invited], [International presentation]
  • 牛白血病の最新知見               
    Satoru Konnal
    平成29年度第108回上川家畜衛生研究会, 20 Jul. 2017, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 動物における免疫チェックポイント標的抗体による治療戦略               
    Satoru Konnal
    化学及血清療法研究所 三風会, 20 Jun. 2017, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • The role of tick saliva-derived factors in pathogen transmission               
    Satoru Konnal
    第90回日本細菌学会総会シンポジウム わが国におけるダニ媒介性細菌感染症研究の現状, 20 Mar. 2017, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 動物難治性疾病における免疫回避機序の解明 〜免疫チェックポイントを標的とした動物用医薬品開発〜               
    今内 覚
    第2回北海道大学・部局横断シンポジウム 『免疫・癌・感染』, 14 Mar. 2017, Japanese, Invited oral presentation
    [Domestic Conference]
  • Immune exhaustion during chronic infections in cattle               
    Satoru KONNI
    Seminar in the Loslin institute, University of Edinburgh, UK, 09 Feb. 2017, English, Public discourse
    [International presentation]
  • 牛白血病撲滅対策               
    Satoru Konnal
    公益社団法人千葉県畜産協会牛白血病感染拡大防止研修会 ー牛白血病の感染拡大防止を図るためー, 17 Jan. 2017, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 獣医療における抗体医薬の開発と現状               
    Satoru Konnal
    徳島大学先端酵素学研究所免疫制御学セミナー, 21 Dec. 2016, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛の感染免疫に関する最新の知見               
    Satoru Konnal
    平成28年度岩手県獣医師会職域部会合同研修会, 08 Dec. 2016, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 家畜法定伝染病ウシアナプラズマ病の免疫回避機構の解析               
    Satoru Konnal
    第23回 リケッチア研究会, 04 Dec. 2016, Japanese, Oral presentation
    [Domestic Conference]
  • 牛白血病の最新の知見について               
    Satoru Konnal
    神奈川県畜産技術協会生物科学安全研究所支部地方競馬益金補助事業主催講演会, 29 Nov. 2016, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Immunotherapy for canine malignant cancers               
    Satoru KONNAI
    The 19th Joint Symposium Between Seoul National University and Hokkaido University 〜Advanced Veterinary Sciences: From Bench to Clinic〜, 25 Nov. 2016, English, Invited oral presentation
    [Invited], [International presentation]
  • 牛白血病の現状と対策               
    Satoru Konnal
    日高町和牛生産改良組合防疫技術講習会, 15 Nov. 2016, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 免疫チェックポイントを標的とする免疫療法とは               
    Satoru Konnal
    平成28年宮崎大学テニュアトラック推進機構主催セミナー, 01 Nov. 2016, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病対策               
    Satoru Konnal
    八紘牧場衛生対策会議, 17 Oct. 2016, Japanese, Public discourse
    [Invited], [Domestic Conference]
  • 牛白血病について               
    Satoru Konnal
    平成28年度第3回標茶町技連学習会, 11 Oct. 2016, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Identification of immunomodulatory factors in Ixodes persulcatus Schulze ‘Taiga tick’, the vector for Lyme disease and relapsing fever in Japan               
    Satoru KONNAI
    XXV International Congress of Entomology (ICE-2016), 30 Sep. 2016, English, Invited oral presentation
    [Invited], [International presentation]
  • Development of novel strategy for disease control in animal-engineering animal antibodies for development of novel therapeutics               
    Satoru KONNAI
    Texas A&M University, College of Veterinary Medicine, Veterinary Pathology Seminar Series, 22 Sep. 2016, English, Invited oral presentation
    [Invited], [International presentation]
  • Engineering antibodies for development of novel therapeutics and vaccine for livestock               
    Satoru KONNAI
    1st International Symposium on Livestock Biotechnology, 26 Aug. 2016, English, Invited oral presentation
    [Invited], [International presentation]
  • Increases of cells expressing PD-1 and PD-L1 in bovine leukemia virus infection and enhancement of anti-viral immune responses in vitro via its blockade               
    Satoru KONNAI
    International Veterinary Immunology Symposium 2016, 17 Aug. 2016, English, Poster presentation
    [International presentation]
  • Research on immune checkpoint in veterinary medicine               
    Satoru KONNAI
    Joint Workshop on Livestock Disease Research in University of Sydney, 15 Aug. 2016, English, Public discourse
    [Invited], [International presentation]
  • むしからうつる感染症               
    Satoru Konnal
    札幌幌南ロータリークラブ市民講話, 05 Aug. 2016, Japanese, Public discourse
    [Invited], [Domestic Conference]
  • 牛白血病における免疫応答 〜免疫学的解析に基づく新規動物用バイオ医薬品の開発〜               
    今内 覚
    第20回大動物臨床教育セミナー, 21 May 2016, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病について               
    今内 覚
    平成28年度JA新はこだて酪農生産部会長万部支部講習会, 18 Apr. 2016, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牧野における牛白血病対策               
    今内 覚
    後志家畜自衛防疫推進協議会産業動物飼養管理講習会, 12 Apr. 2016, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の免疫学的解析               
    今内 覚
    理化学研究所シンポジウム, 15 Mar. 2016, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の制御法について               
    Satoru Konnal
    道東NOSAI牛白血病拡大防止事業教育講座, 10 Mar. 2016, Japanese, Public discourse
    [Invited], [Domestic Conference]
  • 牛白血病の感染防御対策               
    Satoru Konnal
    道東NOSAI牛白血病拡大防止対策事業教育講座, 09 Mar. 2016, Japanese, Public discourse
    [Invited], [Domestic Conference]
  • 牛白血病における免疫性状と制御方法の開発               
    Satoru Konnal
    平成27年度日本獣医師会獣医学術学会年次大会特別企画シンポジウム「牛白血病の現状と課題 -清浄化に向けて-」, 28 Feb. 2016, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の現状と対策について               
    Satoru Konnal
    静岡県東部家畜保健衛生推進協議会畜産講演会, 16 Feb. 2016, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病における免疫応答 〜免疫学的解析に基づく新規疾病予防法の開発〜               
    Satoru Konnal
    大動物臨床研究会第6回東京シンポジウム, 13 Feb. 2016, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 獣医医療における抗体医薬の開発と現状               
    Satoru Konnal
    東北大学大学院医学系研究科特別講義, 21 Jan. 2016, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Development of therapeutic antibodies targeting immunoinhibitory molecules in veterinary medicine               
    Satoru KONNAI
    IPR/CRED/PDIS Joint International Seminar -From protein structural science to development of therapeutics-, 12 Jan. 2016, English, Invited oral presentation
    [Invited], [International presentation]
  • 動物難治性疾病に対するバイオ医薬品の開発               
    Satoru Konnal
    JA全農家畜衛生研究所特別講演, 27 Nov. 2015, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の現状と対策の例               
    Satoru Konnal
    青森県上十三地区家畜衛生推進協議会H27年度畜産講習会, 24 Nov. 2015, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 初乳の衛生管理について 〜牛白血病防除の観点から〜               
    Satoru Konnal
    第23回乳房炎防疫対策研究会, 20 Nov. 2015, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の最新知見               
    Satoru Konnal
    第2回ミニ宮崎しゃくなげ会研修会, 17 Nov. 2015, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病における免疫応答               
    Satoru Konnal
    第39回大動物臨床研究会シンポジウム, 07 Nov. 2015, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病 最近の知見と対策について               
    今内 覚
    大分県畜産協会特別講演, 14 Sep. 2015, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の病態発生機序および制御法に関する研究               
    Satoru Konnal
    第158回日本獣医学会学術集会特別企画, 08 Sep. 2015, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病に認められる細胞性免疫の抑制 - PL牛を優先淘汰する意義 -               
    今内 覚
    2015年度 牛臨床寄生虫研究会・九州沖縄産業動物臨床研究会合同研究集会, 11 Jul. 2015, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 地方病型牛白血病の対策と新規制御法研究の現状               
    今内 覚
    長野県獣医師会産業動物臨床部会講習会, 21 Apr. 2015, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の対策               
    今内 覚
    北海道公共牧場会職員春期研修会, 14 Apr. 2015, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 慢性感染症における免疫応答と免疫回避機構               
    今内 覚
    新潟県農業共済組合連合会平成26年度家畜診療等技術講習会, 07 Mar. 2015, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病への対策について               
    今内 覚
    新潟県農業共済組合連合会平成26年度家畜診療等技術講習会, 06 Mar. 2015, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の現状について               
    今内 覚
    平成26年度放牧衛生技術検討会ならびに釧路地区家畜自衛防疫研修会, 27 Feb. 2015, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病ウイルス(BLV)感染症の現状と対策               
    今内 覚
    北海道獣医師会十勝支部産業動物講習会, 26 Feb. 2015, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 慢性感染症に認められる免疫疲弊               
    Satoru Konnal
    平成26年度日本獣医師会獣医学術集会年次大会特別企画 シンポジウム, 14 Feb. 2015, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Increases of cells expressing PD-1 and PD-L1 in bovine leukemia virus infection and enhancement of anti-viral immune responses in vitro via its blockade               
    Satoru Konnal
    Keystone Symposia on Immunity to Veterinary Pathogens: Informing Vaccine Development, 21 Jan. 2015, English, Invited oral presentation
    [Invited], [International presentation]
  • 牛白血病 ー最新知見・現状と対策ー               
    今内 覚
    平成26年度留萌和牛振興協議会研修会, 14 Jan. 2015, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 感染症と免疫細胞の役割               
    今内 覚
    中央畜産会平成26年度海外家畜伝染病等危機管理対策強化講習会 第一次診療臨床診断技術強化講習会, 19 Dec. 2014, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の現状と対策               
    今内 覚
    北海道獣医師会道南支部産業動物講習会, 11 Nov. 2014, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の現状と感染免疫               
    今内 覚
    平成26年度千葉県農業共済組合連合会紫葉会技術懇談会, 05 Nov. 2014, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の現状と北海道大学の取り組み               
    Satoru Konnal
    日本ウイルス学会北海道支部 第 48 回 夏季シンポジウム, 13 Jul. 2014, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛の難治性疾病に対する新規ワクチン戦略               
    今内 覚
    農業・食品産業技術総合研究機構 生物系特定産業技術研究支援センター 2013年度研究成果発表会, 05 Mar. 2014, Japanese, Invited oral presentation
    [Domestic Conference]
  • 牛白血病の新規制御法の開発と清浄化モデルの構築               
    今内 覚
    北海道の元気創出フォーラム~知的財産を活かした地域潜在力の発掘に向けて~, 20 Feb. 2014, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 獣医医療における免疫抑制機序を標的とした新規疾病制御法の開発               
    今内 覚
    大阪大学微生物病研究所セミナー, 09 Jan. 2014, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の病態発生機序の解明               
    今内 覚
    平成25年度動物衛生研究所北海道支所集談会, 17 Dec. 2013, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病 ー最新知見・現状と対策ー               
    今内 覚
    北海道しりべし獣医師会産業動物飼養管理講習会, 15 Nov. 2013, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病ウイルスの感染防御対策               
    今内 覚
    平成25年宮崎県畜産技術研修会特別講演, 13 Nov. 2013, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病ウイルス(BLV)感染症の現状と対策               
    今内 覚
    埼玉県獣医師会北支部・埼玉県八日会・しゃくなげ会埼玉県支部・埼玉県畜産技術振興会合同定例研修会, 08 Nov. 2013, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 家畜臨床免疫学研究: 牛白血病における病態発生機序の解明と新規制御法の確立               
    今内 覚
    岐阜大学大学院連合獣医学研究科 平成25年度若手研究者育成プログラム, 01 Nov. 2013, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病における病態発生機序の解明と新規制御法の確立に関する研究               
    今内 覚
    微生物化学研究所特別講演, 04 Oct. 2013, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の感染防御対策               
    今内 覚
    北海道獣医師会留萌支部平成25年度新技術講習会, 27 Sep. 2013, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • ウシ難治性感染症の現状と対策および新規制御法の開発               
    今内 覚
    ゼノアック 家畜感染症研修会, 19 Sep. 2013, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 気をつけよう 虫さされによる感染症               
    今内 覚
    札幌幌南ロータリークラブ市民講話, 23 Aug. 2013, Japanese, Public discourse
    [Invited], [Domestic Conference]
  • 牛白血病の現状と対策               
    今内 覚
    化学及血清療法研究所第30回家畜衛生講習会並びに研究協議会, 07 Aug. 2013, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の現状と対策について               
    今内 覚
    NOSAI山形平成25年度家畜診療所技術研究会, 25 Jul. 2013, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 農場の感染症リスクコントロール               
    今内 覚
    NOSAI山形平成25年度家畜診療所職員研修会, 24 Jul. 2013, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病 ー最新知見、現状と対策ー               
    今内 覚
    第104回上川家畜衛生研究会, 18 Jul. 2013, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 感染症(牛白血病)について 現状と対策               
    今内 覚
    第35回鹿児島・宮崎しゃくなげ会合同技術研修会, 12 Jul. 2013, Japanese, Keynote oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病清浄化対策について               
    今内 覚
    宮崎県尾鈴農業協同組合BL対策研修会, 04 Jun. 2013, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の対策について               
    今内 覚
    北海道獣医師会牛白血病対策検討委員会, 26 Mar. 2013, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病ウイルス(BLV)感染症の 現状と対策               
    今内 覚
    第51回愛知県獣医師会学術研究発表会特別講演, 03 Mar. 2013, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Role of Inhibitory Molecules in Bovine Chronic Infectious Diseases and as Target for Therapy               
    Satoru Konnal
    Philippines Carabao Center Special Seminar, 01 Mar. 2013, English, Invited oral presentation
    [Invited], [International presentation]
  • 牛難治性疾病に対する免疫抑制因子を標的とした新規制御法の開発               
    今内 覚
    日本大学生物資源科学部 動物医科学研究センター特別セミナー, 15 Jan. 2013, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病ウイルス感染症の伝播阻止トライアルについて               
    今内 覚
    本川牧場疾病対策講習会, 26 Dec. 2012, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病ウイルス感染症の現状と対策               
    今内 覚
    沖縄県獣医師会家畜衛生畜産部会沖縄畜産技術者協会特別講演, 06 Dec. 2012, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛の白血病について               
    今内 覚
    北海道獣医師会胆振支部特別講演, 30 Nov. 2012, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病ウイルス感染症の現状と対策               
    今内 覚
    宮崎県獣医師会学術委員会産業動物部門研修会, 16 Nov. 2012, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の現状と対策               
    今内 覚
    埼玉県獣医師会特別講演, 19 Oct. 2012, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛慢性疾患の新たなる治療法の可能性 -免疫抑制因子を標的とした新規治療薬の開発-               
    今内 覚
    酪農学園大学大動物研究セミナー, 18 Sep. 2012, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛の白血病について               
    今内 覚
    北海道獣医師会根室支部特別講演, 24 May 2012, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛難治性疾病に対する新規戦略(多機能型ワクチンによる牛疾病制御の試み)               
    今内 覚
    第153回日本獣医学会学術集会微生物分科会シンポジウム, 27 Mar. 2012, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病のコントロールについて〜ある農場における清浄化の取り組み事例から〜               
    Satoru Konnal
    平成23年度 北海道家畜保健衛生所病性鑑定技術検討会, 11 Jan. 2012, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の現状と感染予防対策について               
    今内 覚
    道央農業振興公社 畜産研修会, 16 Dec. 2011, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛の難治性疾病に対する多機能型ワクチン戦略               
    今内 覚
    第51回家畜衛生学会シンポジウム, 25 Nov. 2011, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 国内の牛白血病の現状と今後の対策について               
    今内 覚
    牛臨床寄生虫研究会・家畜臨床学会ジョイントシンポジウム, 29 Oct. 2011, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の現状とその対策               
    今内 覚
    栃木県獣医師会特別講演, 07 Oct. 2011, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛の難治性疾病に対する多機能型ワクチン戦略               
    今内 覚
    宮崎大学農学部特別シンポジウム(集談会), 03 Sep. 2011, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の現場でのコントロールについて               
    今内 覚
    宮崎大学農学部特別シンポジウム(教育プログラム), 02 Sep. 2011, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Research on host-pathogen interactions for establishment of novel strategies for disease control               
    Satoru Konnal
    Special seminar in Federal University of Rio Grande do Sul, 13 Aug. 2011, English, Invited oral presentation
    [Invited], [International presentation]
  • Research on host-pathogen interactions for establishment of novel strategies for disease control               
    Satoru Konnal
    Special seminar in Northern Fluminense State University Darcy Ribeiro (Campos campas), 28 Jul. 2011, English, Invited oral presentation
    [Invited], [International presentation]
  • Research on host-pathogen interactions for establishment of novel strategies for disease control               
    Satoru Konnal
    Special seminar in Northern Fluminense State University Darcy Ribeiro (Makae campus), 20 Jul. 2011, English, Invited oral presentation
    [Invited], [International presentation]
  • 牛白血病ウイルス感染症の現状と対策               
    今内 覚
    福岡県家畜保健衛生所講習会, 25 Feb. 2011, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病の感染防御対策               
    今内 覚
    第43回北海道しゃくなげ会, 18 Feb. 2011, Japanese, Oral presentation
    [Invited], [Domestic Conference]
  • 生産現場における白血病対策 —現状と課題—               
    今内 覚
    平成22年度日本獣医師会 獣医学術学会年次大会, 12 Feb. 2011, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 増加傾向にある牛白血病の現状と対策               
    今内 覚
    日本家畜臨床学会第41回学術集会, 06 Nov. 2010, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 原虫病疾病制御のための新戦略 -ダニワクチン開発-               
    今内 覚
    日本家畜衛生学会, 05 Nov. 2010, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 増加傾向にある牛白血病の現状と対策               
    今内 覚
    平成22年度北海道地区家畜診療技術研修会, 15 Sep. 2010, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • メガファームにおける取り組み紹介 —牛白血病ウイルス感染伝播阻止トライアルの実例—               
    今内 覚
    平成22年度獣医学術北海道地区学会シンポジウム, 10 Sep. 2010, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Pro-inflammatory cytokine storm in Theileria parva-infected cattle               
    Satoru Konnal
    The 9th International Veterinary Immunology Symposium (Concurrent Session), 17 Aug. 2010, English, Nominated symposium
    [Invited], [International presentation]
  • 牛白血病ウイルス感染症の現状と対策               
    今内 覚
    北海道獣医師会オホーツク支部大動物講習会2, 28 Jul. 2010, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病ウイルス感染症の現状と対策               
    今内 覚
    北海道獣医師会オホーツク支部大動物講習会1, 27 Jul. 2010, Japanese, Oral presentation
    [Invited], [Domestic Conference]
  • 新規動物用ワクチンならびに新規治療法の開発               
    今内 覚
    日本生物科学研究所シンポジウム, 29 Mar. 2010, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 新規動物用ワクチンならびに新規治療法の開発               
    今内 覚
    動物用ワクチンーバイオ医薬研究会改組設立記念シンポジウム, 25 Mar. 2010, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • PD-1/PD-L1システム制御による牛白血病ワクチン戦略               
    今内 覚
    平成21年度日本獣医師会学会年次大会・特別企画, 29 Jan. 2010, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛難治性慢性感染症における免疫疲弊化機序の解明と免疫賦活化の試み               
    今内 覚
    第4回日本家畜臨床感染症研究会総会・学術集会, 11 Dec. 2009, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病ウイルス感染症の現状と対策               
    今内 覚
    北海道獣医師会根室支部大動物臨床部会講演会, 20 Nov. 2009, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 牛白血病ウイルス(BLV)感染症対策               
    今内 覚
    第60回北海道獣医師大会産業動物獣医学会シンポジウム, 04 Sep. 2009, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • ダニのEST解析とダニワクチンの現状               
    今内 覚
    第15回 ダニと疾患のインタフェースに関するセミナー(SADI) 教育講演, 25 May 2007, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]

Affiliated academic society

  • THE JAPANESE SOCIETY FOR VIROLOGY               
  • 大動物臨床研究会               
  • JAPANESE SOCIETY FOR CLINICAL INFECTIOUS DISEASE IN FARM ANIMALS               
  • 動物サイトカイン研究会               
  • 日本獣医寄生虫学会               
  • 動物用ワクチン-バイオ医薬品研究会               
  • 北海道獣医師会               
  • JAPAN VETERINARY MEDICAL ASSOCIATION               
  • JAPANESE SOCIETY OF VETERINARY SCIENCE               

Research Themes

  • 新規脳内分子輸送法を応用したウイルス性中枢神経疾患に対する発展的治療法の開発
    科学研究費助成事業
    01 Apr. 2023 - 31 Mar. 2027
    好井 健太朗, 平野 港, 今内 覚
    神経向性ウイルスは、脳に侵入・増殖することで重篤な神経症状を引き起こすが、有効な治療法は未開発である。これは、ウイルス感染による病態の進行に対応した治療の実施が困難である事、及び 血液脳関門(BBB)の存在のため、治療薬を病態の進行する脳に到達させる手法が無い事が大きな要因となっている。そこで本研究では、神経向性ウイルス感染症について、生体イメージングによるウイルス感染リアルタイム解析モデルを確立し、BBBを透過する分子を利用した治療候補分子の脳内輸送による治療応用の検証を行う。
    本年度の研究においては、神経向性ウイルスの一つでヒトや動物に致死率の高い脳炎を引き起こすダニ媒介性脳炎ウイルス(TBEV)に対する中和抗体について、血液脳関門(BBB)を透過する性質を付加させられるように改変した組換え抗体の検証を行った。我々の研究グループが構築してきたTBEVに対する組換え抗体について、ヒトBBB機能のモデルとなるhCMEC/D3細胞を用いて透過性試験を行った。hCMEC/D3細胞を単相培養したトランスウェルを用いて、抗体のBBBモデルの透過性を検証したところ、通常の抗体では透過性は観察されなかったが、BBBの透過性に関わる推定される外来性のペプチド配列を付加した組換え抗体は、トランスウェルを透過した抗体が優位に検出された。この事により、我々が作成した組換え抗体は、BBBモデルであるhCMEC/D3細胞の表面上のレセプターに結合し、トランスサイトーシスにより細胞内を輸送され脳側に放出される機能を持っている事が示され、今後の研究においてウイルス性中枢神経疾患に対する治療法へと応用していく上で有用であると考えられる。
    日本学術振興会, 基盤研究(B), 長崎大学, 23K27079
  • Development of cocktail vaccines against poultry red mites using the recombinant turkey herpesvirus
    Grants-in-Aid for Scientific Research
    01 Apr. 2023 - 31 Mar. 2027
    村田 史郎, 今内 覚, 大橋 和彦
    鳥類の外部寄生虫であるワクモによる吸血被害は、世界中の養鶏場で深刻な問題を引き起こしており、最近では薬剤に耐性を示すワクモの出現がその防除をさらに困難にさせている。そのため薬剤に変わる新たな防除法の開発研究が行われているが、その中でもワクチンによる防除法開発が注目されている。本ワクチンは、ワクモの生理機能に重要な分子を抗原として免疫し、血液に含まれる抗体を吸血したワクモに致死的影響を与えることを作用機序とする。しかし、単一の抗原による効果には限界があり、効果増強のためには複数抗原を用いたカクテルワクチンの開発が求められる。また実用化に際しては、従来のワクチンプログラムに抗ワクモワクチンを追加することになり、飼養者の負担が増えることになる。そこで本研究では、家禽の監視伝染病であるマレック病の予防に使用される七面鳥ヘルペスウイルス(HVT)をベクターとして用い、ウイルスゲノムに複数の抗原遺伝子を挿入することで、組換えHVT抗ワクモカクテルワクチンを開発することを目的とした。本年度は、ウイルスベクターとして用いるHVTの感染性クローンの作製に必要なベクター作製と、カクテルワクチンの作製に用いるワクチン抗原の評価を行なった。感染性クローン作製にはpBeloBac11ベクターを用い、ウイルスゲノム中のUS2遺伝子と相同組換えにより置換させることで行う。そのため、HVTのUS2遺伝子の両端の領域をpBeloBac11にクローニングした。さらに薬剤による組換えHVTの選抜のため、ecogpt遺伝子の発現カセットをクローニングした。カクテルワクチンの作製に用いるワクチン抗原として、複数の抗原候補の効果をin vitroにて評価した。その際には、ワクモと形態が類似するその他の家禽の吸血性ダニへの効果も期待される、ユニバーサルワクチンとしての応用の可能性を持つ抗原を選抜した。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 23K27063
  • Development of cocktail vaccines against poultry red mites using the recombinant turkey herpesvirus
    Grants-in-Aid for Scientific Research
    01 Apr. 2023 - 31 Mar. 2027
    村田 史郎, 今内 覚, 大橋 和彦
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 23H02370
  • Elucidation of the mechanism of tumorigenesis in bovine leukemia by comprehensive genomic analysis of proviral integration sites
    Grants-in-Aid for Scientific Research
    Apr. 2024 - Mar. 2027
    Tomohiro Okagawa, Satoru Konnai, Naoya Maekawa
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research (B), Hokkaido University, 24K01918
  • The roles of polymorphism in Meq on the pathogenicity of Marek's disease virus and their application for the vaccine development
    Grants-in-Aid for Scientific Research
    01 Apr. 2023 - 31 Mar. 2026
    大橋 和彦, 村田 史郎, 今内 覚
    マレック病ウイルス(MDV)の病原性進化の分子機構を明らかにして新規防除法を確立するために、MDVの病原性に最も重要なMeqについて、挿入や欠損を含むMeqアイソフォームを導入した組換えMDVを作出して、MDVの病原性発現機構を明らかにすることを目的として実施した。
    これまでMeqにおける挿入配列が病原性を増強することを明らかにしたが、その詳細について転写活性化能やmeq遺伝子をL-meq遺伝子に置換した組換えMDV(rMDV_L-Meq)を用いた感染実験等で検討した。L-MeqはMeqに比べ高い転写活性化能を示し、rMDV_Meq感染鶏群と比較して、rMDV_L-Meq感染鶏群ではがん関連因子の発現や末梢血におけるCD4+T細胞や制御性T細胞の増加が早期に認められた。一方で腫瘍病変部での発現遺伝子には両群に有意な差は認められなかった。以上よりMeqの挿入配列は、転写活性化能を増強させ早期に病態を形成させることが示唆された。
    当研究室では、野外株で欠損配列を持つmeq遺伝子(S-meq遺伝子)の同定・性状解析を報告したが、2022年に過去に報告例のない欠損配列を持つmeq遺伝子が同定されたため、その性状について解析を行なった。検出されたS-meq遺伝子よりも小さく(VS-meq遺伝子)、meq遺伝子と比べて転写活性化調節領域内に192bpの欠損が認められた。またMDV強毒株であるRB-1B株のMeqの配列と比べて、欠損以外に2箇所のアミノ酸配列の相違が認められた。RB-1B MeqとVS-Meqの転写活性化能に差は認められなかったが、欠損以外のアミノ酸配列をそろえたところ、VS-Meqの転写活性化能はRB-1B Meqより有意に高く、VS-Meqの欠損配列が転写活性化能を増加させることが示された。今後、組換えMDVを用いた感染実験により病原性への影響を調査する必要がある。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 23K27068
  • The roles of polymorphism in Meq on the pathogenicity of Marek's disease virus and their application for the vaccine development
    Grants-in-Aid for Scientific Research
    01 Apr. 2023 - 31 Mar. 2026
    大橋 和彦, 村田 史郎, 今内 覚
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 23H02375
  • Establishment of Animal Formy Viral Vectors and Development of a Vaccine for Bovine Leukemia Virus
    Grants-in-Aid for Scientific Research
    01 Apr. 2022 - 31 Mar. 2026
    目堅 博久, 齊藤 暁, 今内 覚, 岡川 朋弘
    牛伝染性リンパ腫は、牛伝染性リンパ腫ウイルス(BLV)の感染を原因とする牛の慢性致死性感染症である。畜産業の経済的被害が大きく、感染対策が難しいことから、ワクチンの実現が望まれている。1980および90年代の論文では、不活化ワクチンで2度免疫した後の中和抗体価が高い時期であれば、BLVの感染を阻止できることが報告されている。そこで本研究は、持続感染する牛フォーミーウイルスにBLV抗原を組み込むことで、中和抗体価を長期に渡って高い値で維持できるBLVワクチンを開発できると考えた。本研究は、研究項目①.組換え牛フォーミーウイルスの作成、研究項目②.BLVとの組換えウイルス作成とマウス感染モデルの構築、研究項目③.牛への組換えウイルス接種で構成される。2年目である2023年度は、研究項目①と②を実施した。①については、牛フォーミーウイルス全長を組み込んだウイルスベクターの構築に成功した。さらに、構築したベクターから牛フォーミーウイルスのアクセサリー蛋白質であるBorf-2領域を、BLVの主要な抗原であるgp51に置換した。その全長配列をロングリードシークエンスで確認し、変異や挿入等がないことを確認した。今後は組み換えウイルスの回収に取り組む。②については、過去の論文を参考にし、マウスに牛フォーミーウイルスを接種した。牛フォーミーウイルスを長期間培養した培養細胞上清をマウス(C57BL/6)に接種した場合に限り、一部のマウスの脾臓で感染が成立した。しかし、その感染率は低く、ワクチンの評価に用いるマウス感染モデルとしては不十分であるという結論に至った。そこで、現在はインターフェロン受容体ノックアウトマウスを使った、新たなマウス感染実験系に取り組んでいる。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), University of Miyazaki, 23K23765
  • Construction of animal foamy virus vector and development of enzootic bovine leukosis vaccine
    Grants-in-Aid for Scientific Research
    01 Apr. 2022 - 31 Mar. 2026
    目堅 博久, 齊藤 暁, 今内 覚, 岡川 朋弘
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), University of Miyazaki, 22H02500
  • The search for the candidate molecule for the vaccine to control a wide range of ectoparasite species of chickens
    Grants-in-Aid for Scientific Research
    01 Apr. 2020 - 31 Mar. 2023
    大橋 和彦, 村田 史郎, 今内 覚
    ワクモやトリサシダニは、鳥類の代表的な外部寄生虫であり、鶏に貧血や削痩、産卵率低下など養鶏産業に大きな経済的被害をもたらしている。現在、その防除 には主に駆虫剤が使用されているが、薬剤耐性個体の出現や駆虫剤残存による衛生環境の悪化などが問題となっており、抗ダニワクチンなど新規防除法の開発が必要となっている。そこで本研究では、ワクモとトリサシダニ及び近縁なミナミトリサシダニを同時に防除できるダニ種横断的な新規“ユニバーサル”ワクチン の開発を目指して、RNA-SEQ解析や全ゲノム解析と相同性検索により、これらのダニ間で共通の非暴露型抗原の探索・同定を行い、 吸血したダニ個体に致死的に作用して鶏舎内の寄生虫個体数を持続的に減少できるワクチンへの応用を検討することを目的とした。 今年度は、昨年度実施したRNA-SEQによる発現する遺伝子群の網羅的解析の結果を元にFER2など数種類の候補遺伝子を選抜して、その組換え抗原の調製や機能解析を行った。in vitro feeding assayによる今後交差防御試験を行いワクチン候補抗原としての有用性を確認する。またいくつかのワクモ由来分子の抗ワクモワクチンとしての有用性を検討し、抗ワクモ効果(持続的な個体数の減少)を示す新規抗原を同定した。さらに複数種の抗原を用いたカクテル抗原が単独抗原よりも有効な抗ワクモ効果を示すことも明らかとなった。今後、これらの抗原についても“ユニバーサル”ワクチンへの応用を検討していく。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 20H03137
  • 血液脳関門を透過する新規DDSによる神経向性ウイルス感染の治療法開発
    科学研究費助成事業
    01 Apr. 2020 - 31 Mar. 2023
    好井 健太朗, 小林 進太郎, 五十嵐 学, 今内 覚
    ダニ媒介性脳炎、日本脳炎、狂犬病など神経向性の人獣共通感染症ウイルスは、脳に侵入・増殖することで重篤な神経症状を引き起こし、致死率も高い。しかし血液脳関門:BBBの存在のため、抗ウイルス分子をウイルスの増殖する脳に到達させる手法が無く、治療法が未開発であった。BBBにはトランスサイトーシスと呼ばれる物質を血流から脳内へと輸送する機構があり、近年の研究により、このBBB透過に関わる分子の機構が明らかになってきている。本研究では、このBBB透過機構に着目し、組換え抗体等の抗ウイルス分子技術と融合させることで、BBBを透過する機能を利用した抗ウイルス分子の脳内導入法を構築し、神経向性ウイルス感染に対する治療応用を試みる。
    本年度における研究では、昨年度の研究で構築した、ダニ媒介性脳炎ウイルス(TBEV)の幅広いウイルス株に対して中和効果を示すモノクローナル抗体をベースとして、BBBのトランスサイトーシスへの関与が示されている狂犬病ウイルスのG蛋白上のアミノ酸配列を融合させた組換え抗体を用いての研究を進めた。本抗体に誘導させた、狂犬病ウイルスのG蛋白上のアミノ酸配列は、神経細胞やBBBの血管内皮細胞上に発現するアセチルコリンレセプターとの結合により細胞内輸送小胞に取り込まれて、これがトランスサイトーシスに関与する事が示されている。そこで本研究ではアセチルコリンレセプターを細胞膜上に豊富に発現している神経細胞由来の培養細胞等を用いて検証した所、作製した組換え抗体分子は細胞膜表面に結合している事が示され、これはアセチルコリンレセプターを介したものである事が示唆された。さらに抗体をマウスの末梢に投与した所、マウスの脳内から抗体が検出されたことから、抗体は脳内に移行していることが示され、本研究で検証した組換え抗体分子は、脳内で増殖するウイルスに対する治療応用に有効である可能性が示唆された。
    日本学術振興会, 基盤研究(B), 長崎大学, 20H03136
  • MHC クラスII DRB3*0902保有牛における牛白血病抵抗性機序
    科学研究費助成事業
    01 Apr. 2019 - 31 Mar. 2023
    乗峰 潤三, 佐藤 克明, 今内 覚
    BLV感染症において牛主要組織適合遺伝子複合体(bovine MHC: BoLA)クラスIIDRB3*0902遺伝子を保有する牛は、極めて低いプロウイルス量を維持し、リンパ球増多症への病態進行に対する抵抗性を持つ。本研究目的は、BLVに感染した牛のBLV抗原特異的CD4+T細胞を解析し、BoLA-DRB3*009:02遺伝子保有牛における抵抗性の免疫学的機序を解明する事である。そのためには、まずBoLA-DRB3*009:02拘束性のCD4+T細胞エピトープを同定する必要がある。これまで、CD4+T細胞エピトープ同定に使用する組換BLVgag及びenv 蛋白質(rBLVgag/env)を、全て発現ベクター(pET151)に組み込んだ。また、オリゴペプチドとして、全BLVgag/envをカバーする連続20アミノ酸ペプチドを合成した。さらに、多数のBoLA-DRB3テトラマーを作製し、tetramer-guided epitope mapping (TGEM)法によりBLV抗原特異的CD4+T 細胞エピトープの同定を行った。牛において、MHCクラスIIテトラマーを作製しているのは本研究室のみである。従って、牛のTGEM法によるCD4+T 細胞エピトープ同定の報告は世界初である。
    TGEM法によるCD4+T 細胞エピトープ同定に使用したのはフィールドBLV感染牛で、DRB3*009:02/DRB3*015:01ヘテロを保有する牛2頭、DRB3*009:02/DRB3*002:01ヘテロを保有する牛2頭、DRB3*015:01ホモを保有する牛2頭である。それぞれから回収した末梢血PBMCを利用してTGEM法により、BLV抗原特異的CD4+T 細胞エピトープを同定した。
    日本学術振興会, 基盤研究(B), 宮崎大学, 19H03128
  • Development of a method to control poultry red mites using recombinant Marek's disease virus that secretes a vaccine antigen
    Grants-in-Aid for Scientific Research
    01 Apr. 2018 - 31 Mar. 2021
    Murata Shiro
    Poultry red mites (PRMs, Dermanyssus gallinae) are haematophagous ectoparasites which causes serious economic losses to the poultry industry worldwide, and the development of novel methods to control PRMs is required. We have investigated the application of vaccination and have shown that immunization with vaccine antigens could contribute to the reduction in the number of PRMs. In addition, we investigate the application of virus vectors to develop easy-to-use vaccines for farmers. In this study, we designed the recombinant virus that secrets vaccine antigens to improve the efficiency of vaccines using the recombinant virus. To produce an antigen-secreting virus, we inserted the signal peptides of a virus-derived secretory protein to the virus genome. However, the secretion of antigens was not confirmed, although the expression was observed in infected cells. Further manipulation is required to generate effective vaccines using virus vectors for controlling PRMs.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 18H02332
  • Analysis of the molecular mechanism for the increase in the virulence of Marek's disease virus
    Grants-in-Aid for Scientific Research
    01 Apr. 2017 - 31 Mar. 2020
    Ohashi Kazuhiko
    Marek’s disease virus (MDV), a causative agents of Marek’s disease (MD), which is characterized by the formation of malignant lymphoma, appears to increase its virulence in the fields. To elucidate the molecular mechanisms for the increase in its virulence, we isolated MDVs from vaccinated chickens which still developed clinical MD, and analyzed their virological properties. MDV recently isolated in Japan caused clinical MD in inoculated chickens, although less virulent to chickens compared to virulent MDV strains isolated in United States. In addition, it is suggested that virus-derived factors other than polymorphisms in viral oncogene reported in the United States would be involved in the increase in MDV virulence.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 17H03911
  • Analysis of genetic polymorphism of poultry red mites in the world and search for candidate molecules of anti-mite vaccines
    Grants-in-Aid for Scientific Research
    01 Apr. 2016 - 31 Mar. 2019
    OHASHI Kazuhiko
    Poultry red mites (PRMs), Dermanyssus gallinae, are blood-sucking ectoparasites of chickens, which cause huge economic losses in the poultry industries worldwide. To establish a new effective control method for PRMs, we have searched for and identified candidate antigens which are not polymorphic among PRMs from different areas in the world to develop anti-PRM vaccines. Several antigens identified in this study showed anti-PRM effects determined by in vitro feeding assay using sera from immunized chickens.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 16H05804
  • Comprehensive analysis of molecules expressed on the midgut of poultry red mites for the development of new anti-mite vaccines
    Grants-in-Aid for Scientific Research
    01 Apr. 2016 - 31 Mar. 2018
    OHASHI Kazuhiko
    For the development of new vaccines against poultry red mite, Dermanyssus gallinae, a search was made for novel vaccine candidates expressed on the cell membrane of the midgut of the mite. Three kinds of molecules, whose expressions are predicted on the cell membrane, were identified, and their expressions on the midgut were confirmed by laser capture microdissection and RT-PCR. In addition, cathepsin D-like molecule, catD2, which was already identified in the course of the comprehensive analysis of genes expressed in the red mites done in our laboratory, was shown to be expressed in protonymph, deutonymph and adult and expressed regardless engorgement or starvation. The recombinant catD2 protein was not recognized by the sera from chickens fed by the red mites, suggesting that catD2 is a concealed antigen. Further analyses, including the detailed functions, the expression sites in red mites and the evaluation as vaccine antigens, are required to develop effective vaccines.
    Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, 16K15043
  • Intramammary infusion of food-grade lactic acid bacteria (Bifidobacterium breve) on cellular and immuno-modulatory functions in mammary glands and therapeutic trials on bovine mastitis in dairy cows.
    Grants-in-Aid for Scientific Research
    01 Apr. 2014 - 31 Mar. 2017
    NAGAHATA Hajime, ENDOU DAIJI
    The aim of this study was to evaluate the efficacy of lactic acid bacteria (LAB) by intramammary infusion for control of bovine mastitis. Methods: LAB, Bifidobacterium breve(3x10^9cells/ml) was infused quarters with mastitis of 48 lactating cows after milking once a day for 2 days. Pathogens, somatic cell counts (SCC), lactoferrin (LF) and IgG and A, chemiluminescence (CL), and mRNA expressions of Th1, 2- cytokines on milk cells were evaluated.
    Results: SCC and CL responses were increased (P<0.05) in quarters by LAB infusion. LF and IgG,A were also induced in milk on day 3 to day 7. Cytokines IL-1β,TNF-α and IL-6 were elevated in milk by LAB infusion. I Environmental mastitis pathogens, coagulase negative staphylococci and streptococci, were eliminated 50-60% by LAB infusion. In mastitis quarters with no pathogens, SCC in 80% quarters returned to the recovered normal range on day 14 by LAB infusion. The use of LAB appears to be a possible approach for controlling bovine mastitis.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Rakuno Gakuen University, 26450432
  • Influence of the immune status on the malignancy of canine histiocytic sarcoma
    Grants-in-Aid for Scientific Research
    01 Apr. 2014 - 31 Mar. 2017
    Takagi Satoshi, KONNAI Satoru, TAGAWA Michihito, YOSHIDA Hiromitsu, YOSHIMOTO Sho
    Histiocytic sarcoma (HS) is a progressive neoplastic disease in dogs. It is unclear whether costimulatory molecules, including CD28, CTLA-4, PD-1 are expressed on peripheral blood lymphocytes (PBLs) of canine patients with HS. The expression of CTLA-4 on CD8+ lymphocytes was significantly higher and the expression of PD-1 on CD8+ lymphocytes was significantly higher in the HS group than in the control group.
    On the other hand, we investigated the presence of tumor associated macrophages (TAMs) and fibroblasts (CAFs) in HS and other tumors. CAFs are rarely observed in HS tissues whereas relatively higher expressions were shown in epithelial tumors such as anal sac tumor and mammary gland tumor. CD204 positive TAMs were frequently observed in HS tissues which showed this tumor suppress host CTLs in situ. In conclusion, HS in dogs may have strong immunosuppressive ability and therapeutic agents such as anti-immune check point molecules can effective for the treatment of this tumor.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 26450420
  • Studies on the molecular mechanisms for the increase in MDV virulence in the field
    Grants-in-Aid for Scientific Research
    01 Apr. 2014 - 31 Mar. 2017
    Kazuhiko Ohashi
    Marek’s disease virus (MDV), a causative agent of Marek’s disease (MD), which is characterized by the formation of malignant lymphomas, tends to increase its virulence in the fields. To clarify the molecular mechanism for the increase in MDV virulence, recent MDV strains isolated from vaccinated chickens which developed clinical MD were virologically and molecular biologically characterized. Several new diversities/mutations were detected in viral genes of these strains, and a plaque-purified MDV strain was shown to be pathogenic to chicks. However, phylogenetic analysis of the whole genome of the MDV strain and reference strains showed that domestic MDV may increase its virulence through unknown mechanisms which are different from those suggested previously in MDV strains isolated in the United States.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 26292147
  • Defence mechanism against environmental chemicals in livestock animals
    Grants-in-Aid for Scientific Research
    01 Apr. 2012 - 31 Mar. 2016
    ISHIZUKA MAYUMI, IKENAKA Yoshinori, TSUBOTA Toshio, KONNAI Satoru
    In livestock animals, we identified the enzymatic characters of cytochrome P450 as typical phase I enzyme for xenobiotics. We also analyzed glucronyltrasnferase and sulfotransferase dependent metabolites in urine samples from mammalians including livestock animals, to elucidate the ability of xenobiotic conjugating detoxification. In field surveillance at Asia and African countries, heavy metals are major accumulated environmental pollutants in cattle, and the accumulating pattern is unique in ruminants. In case of poultry species, we clarify the expressed cytochrome P450 and phase II enzymes in liver using transcriptome analyses method and in silico analyses, and we compared the structure of xenobiotic metabolizing enzymes in poultry species to those of mammals.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, 24248056
  • Studies on the immunoinhibitory mechanisms of Marek's disease virus and its application for adjuvant
    Grants-in-Aid for Scientific Research
    01 Apr. 2011 - 31 Mar. 2014
    OHASHI KAZUHIKO, KONNAI Satoru, MURATA Shiro
    The programmed death 1 (PD-1) receptor and its ligands, programmed death ligand 1 (PD-L1) and 2 (PD-L2) are known to have an immunoinhibitory function which contribute to the pathogenesis of chronic infections and neoplastic diseases via the PD-1/PD-L pathway. In this study, it has been shown that chicken PD-1 and PD-L1/PD-L2 also have an immunoinhibitory function, such as inhibition of cytokine production. The expressions of PD-1 and PD-L2 were significantly higher in the spleens of infected chickens in the latent phase and in tumor lesions caused by Marek's disease virus (MDV). These results suggest that chicken PD-1/PD-L2 pathway is involved in the establishment of latency and tumor formation by MDV.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 23380176
  • Epidemiological and immunological analyzes of spread manner of bovine viral diarrhea virus in the herd
    Grants-in-Aid for Scientific Research
    01 Apr. 2010 - 31 Mar. 2014
    TAJIMA Motoshi, KADOHIRA Mutsuyo, KONNAI Satoshi
    In order to estimate the spread manner of bovine viral diarrhea virus (BVDV) in and among the dairy herd, epidemiological and immunological analyzes were done for the BVDV detected and free herd discriminated by the bulk tank milk tests. Although the correlation between the geographical place of farm and outbreak of BVDV was recognized, prevalent viruses were not common based on the genetical analysis of the detected virus gene. On the immunological analyzes, BVDV might prefer to localize in ovary fluid in the infected cattle. Moreover, it was strongly suspected that BVDV might bias the immune status of infected cattle for the easy transmission of virus in uterus.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), 22380169
  • Identification and characterization of factors involved in the resistance to Marek' s disease in chickens and wild waterfowls
    Grants-in-Aid for Scientific Research
    2009 - 2011
    OHASHI Kazuhiko, KONNAI Satoru
    To study the molecular mechanism(s) for the natural resistance to Marek' s disease (MD) in wild waterfowls and genetically resistant lines of chickens, the regulatory mechanisms of the expression of interferon y (IFNy), which plays an important role in the cell-mediated immunity against MD virus (MDV), were analyzed by using the conventional luciferase reporter assay system. The promoter activity was more strongly repressed in white-fronted geese than chickens when Meq, an MDV oncoprotein, was co-expressed. This result suggests that, in white-fronted geese, reduced expression of IFNy by Meq at early after MDV infection could result in the lower degree of T cell activation (activated T cells are targets for MDV) to reduce the chances for the birds to develop MD.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 21405034
  • Studies on the molecular mechanisms for Marek's disease virus to increase its virulence in the field
    Grants-in-Aid for Scientific Research
    2008 - 2010
    OHASHI Kazuhiko, OCHIAI Kenji, KONNAI Satoru
    To clarify the molecular mechanisms for Marek's disease virus (MDV) to increase its virulence, several viral genes of MDV strains recently isolated from the field were analyzed. Diversities/polymorphisms were identified in one of the MDV genes, meq, that could be potentially related to the increase in MDV virulence. When we analyzed the effects of these diversities/polymorphisms in the meq gene on the functions of the meq gene product (Meq), the amino acid substitutions resulted from the diversities/polymorphisms significantly altered the transactivation and transforming activities of Meq. These findings suggest that the diversities/polymorphisms in the meq gene could contribute to the recent increase in MDV virulence in the field.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 20380157
  • Genetic analysis of drug resistant trypanosomes
    Grants-in-Aid for Scientific Research
    2006 - 2008
    ONUMA Misao, OHASHI Kazuhiko, INOUE Noboru, KONNAI Satoru
    トリパノソーマ原虫は人、家畜および野生動物に感染し睡眠病、ナガナ病、スーラ病などを引き起こし、多大な被害を与えている。本症は、ワクチンによる制御が困難なうえ、近年、原虫薬剤耐性株の出現によって、その被害は深刻化している。そこで原虫遺伝子多型および薬剤耐性機序解明を目的として、ザンビア共和国およびフィリピン共和国における本症の分子疫学調査を行った。さらに、媒介昆虫であるツェツェバエの吸血宿主の同定、すなわち本症のレゼルボア動物の推定のために、トリパノソーマ感染ツェツェバエ由来のDNAサンプルに含まれる哺乳類動物のミトコンドリア遺伝子を検出し、その遺伝子配列解析から吸血宿主を同定した。その結果、ヒトおよびアフリカゾウ、アフリカバッファローなどの野生動物に加え、調査地区集落の主要な家畜であるヤギの遺伝子も検出されたことから、ヤギにおける本症の分子疫学調査も行い、同地区の高率な感染率を報告した。一方、フィリピン共和国において集団流産が認められた家畜の原因病原体の調査も実施するとともに、抗原虫薬剤治療歴を持つ家畜からトリパノソーマ原虫を分離し薬剤感受性ならびに病原性解析を行った。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 18405037
  • 抗糖脂質モノクローナル抗体のイヌ型抗体化とメラノーマ治療への応用
    科学研究費助成事業
    2006 - 2007
    大橋 和彦, 今内 覚, 奥村 正裕
    糖脂質を標的分子とした新規の抗腫瘍療法を開発することを目的として研究として研究を行った。今年度は、平成18年度に調製し、腫瘍細胞、特にイヌ由来メラノーマ細胞株との反応性を確認した各種糖脂質に対するマウスモノクローナル抗体(MAb)パネルのうち、細胞株に広範に反応した抗GM3 MAb(クローンNo.2-14)について、さらに解析を行った。その結果、このクローンMAbは、非常に多くのメラノーマ細胞株に対して試験管内で細胞傷害性を有していることを見出した。また種々のメラノーマ可移植性細胞株を皮下に移植したヌードマウスを用いた治療試験でも、MAbの連続投与により、移植腫瘍の生育が抑制されることが示された(ただし、対照群と治療群の間に統計学的有意差は検出されなかった)。以上より、in vivoにおいても抗GM3 MAbが抗腫瘍効果を発揮できることがマウスモデルで証明された。
    昨年度に、抗GM3 MAb(クローンNo.2-14)の抗原結合部位である超可変領域(抗原特異性決定部位)の塩基配列を決定し、イヌ型抗体化を目指して遺伝子発現ベクターへ挿入するため、遺伝子カセットをH鎖・L鎖それぞれにおいて作成したが、今年度は、さらに組み換えイヌ型抗糖脂質MAbの臨床応用を目的として、作成した遺伝子カセットをH鎖・L鎖のバキュロウイルス発現系を用いた組み換えイヌ型抗GM3 MAbの大量発現系の樹立を試みた。しかしながら、その発現量は、あまり高くないことが判明した。発現したL鎖とH鎖について、そのGM3との結合活性を確認したが、単独では結合せず、組み換えL鎖およびH鎖の会合した分子を調製する必要性が示唆された。今後、spacerなどでL鎖およびH鎖を結合した遺伝子を調製し共発現させる系を検討する。
    日本学術振興会, 萌芽研究, 北海道大学, 18658123
  • ダニの唾液由来免疫抑制因子を用いるダニ媒介性病原体の伝播阻止
    科学研究費助成事業
    2006 - 2007
    小沼 操, 大橋 和彦, 今内 覚
    ダニの発現遺伝子の網羅的解析のため吸血5日目のフタトゲチマダニ(Haemaphysalis longicornis)唾液腺を用いてEST解析(発現タグ解析)を行った。得られた653配列を米国NCBIのblastXプログラムを用いて蛋白データベースと比較したところ、232配列(36%)で有意な相関を示す類似遺伝子が見つかった。その大半は細胞の生存に必要な、いわゆるハウスキーピング遺伝子であったが、1/3は宿主の生理活性に何らかの影響を与え得る因子であると推察された。今回得られた遺伝子の一つは抗凝固因子であるmadanin1と塩基配列で88%、アミノ酸配列で66%の相同性を示した。そこで本因子の生物活性を解析したところ抗凝固活性が認められた。一方、免疫抑制作用が示唆される1配列について宿主免疫への影響を解析した。その結果、牛末梢血単核球(PBMC)やマウス脾臓細胞の増殖反応を濃度依存的に抑制し、サイトカイン(IL-2、IL-12p40およびTNF-α)の発現も強く抑制した。また、BALB/cマウスへの接種では、脾臓の萎縮が認められ、これらのマウス由来の脾臓細胞は各種Mitogenに対する増殖反応が著しく低下し、Microarray解析では免疫活性化因子の発現抑制も認められた。
    日本学術振興会, 萌芽研究, 北海道大学, 18658117
  • Tick vaccine development by using tick testis-derived factors
    Grants-in-Aid for Scientific Research
    2005 - 2007
    ONUMA Misao, OHASHI Kazuhiko, TAJIMA Tomoko, KONNAI Satoru
    From the cDNA library constructed from testis/vas deferens, we identified a novel gene of Rhipicephalus appendiculatus (Rappendiculatus) tick, male-specific factor, encoding a secretory component exclusively expressed in the testis/vas deferens. This molecule, tentatively named as Rappendiculatus Mating Factor (RAMF), contains a signal peptide and has 29% amino acid identity with male-specific Is5 gene of Ixodes scapularis. Gene expression studies revealed that RAMF mRNA was up-regulated in male ticks during blood feeding. RAMF was detected not only in the testis/vas deferens but also in the postcoitum female ticks by Western blotting, suggesting that this protein could be transferred into the female tick through copulation. The attachment duration had a tendency to prolong in the virgin female ticks microinjected with recombinant RAMF, but there was no obvious effect on blood feeding. These results suggest that RAMF is a male-specific molecule in spermatophore, and other factor(s) might be required for stimulation for female engorgement in R. appendiculatus tick.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 17380177

syllabus

  • 感染症学特別研究Ⅰ, 2024年, 博士後期課程, 国際感染症学院
  • 免疫学特論, 2024年, 博士後期課程, 獣医学院
  • 研究機器演習, 2024年, 博士後期課程, 国際感染症学院
  • 免疫学特論, 2024年, 博士後期課程, 国際感染症学院
  • 研究機器演習, 2024年, 博士後期課程, 獣医学院
  • 研究機器演習(総合成績), 2024年, 博士後期課程, 獣医学院
  • 研究機器演習(総合成績), 2024年, 博士後期課程, 国際感染症学院
  • 感染症学Ⅰ, 2024年, 学士課程, 獣医学部
  • 伝染病学実習, 2024年, 学士課程, 獣医学部
  • 獣医疫学演習, 2024年, 学士課程, 獣医学部
  • 感染症学Ⅱ, 2024年, 学士課程, 獣医学部
  • 動物衛生学実習, 2024年, 学士課程, 獣医学部
  • アドバンスト演習, 2024年, 学士課程, 獣医学部
  • アドバンスト演習, 2024年, 学士課程, 獣医学部