Updated on 2025/04/03

写真a

 
YASHIRO Masato
 
Organization
Scheduled update Special-Appointment Assistant Professor
Position
Special-Appointment Assistant Professor
External link

Degree

  • Ph.D ( 2012.12   Graduate School of Medicine, Dentistry and Pharmaceutical Sciences )

Research Interests

  • Rediatric rheumatology

  • inflammation

  • 酸化ストレス

  • Pediatrics

Research Areas

  • Life Science / Embryonic medicine and pediatrics

Education

  • Okayama University    

    2006.4 - 2012.12

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    Country: Japan

    Notes: 岡山大学大学院医歯薬学総合研究科

  • Okayama University   大学院医歯薬学総合研究科   病態制御科学

    2006.4 - 2012.12

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    Country: Japan

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  • Ehime University   医学部   医学科

    1996.4 - 2002.3

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    Country: Japan

Research History

  • Okayama University   Assistant Professor

    2012.10

Committee Memberships

  • 小児アレルギー学会   研究推進委員会委員  

    2021.11   

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    Committee type:Academic society

  • Japanese Society of Pediatric Allergy and Clinical Immunology   Research Promotion Committee  

    2021.11   

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    Committee type:Academic society

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  • 日本小児リウマチ学会   ガイドライン委員  

    2021.4   

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    Committee type:Academic society

  • 日本小児リウマチ学会   教育委員会チューター  

    2021.1   

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    Committee type:Academic society

    チューター

  • 岡山県保健福祉部健康推進課   岡山県アレルギー疾患連絡協議会委員  

    2020.4   

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    Committee type:Municipal

  • 岡山県   アレルギー疾患連絡協議会 委員  

    2019.4   

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    Committee type:Municipal

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  • 日本小児リウマチ学会   専門認定医制度委員  

    2018.6   

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    Committee type:Academic society

  • 日本小児リウマチ学会   規則等制定ワーキンググループ委員  

    2018.4   

  • 日本リウマチ学会   小児リウマチ調査検討小委員会委員 ぶどう膜炎ワーキンググループ  

    2017.4 - 2019.3   

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Papers

  • Impact of Birth Order on Paediatric Allergic Diseases: A National Birth Cohort in Japan. International journal

    Mitsuro Kobayashi, Masanori Ikeda, Naomi Matsumoto, Mitsuru Tsuge, Masato Yashiro, Takashi Yorifuji, Hirokazu Tsukahara

    Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology   2025.1

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    DOI: 10.1111/cea.14626

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  • Maternal smoking during infancy increases the risk of allergic diseases in children: a nationwide longitudinal survey in Japan. International journal

    Kenji Shigehara, Naomi Matsumoto, Mitsuru Tsuge, Kazuhiro Uda, Yukie Saito, Masato Yashiro, Takashi Yorifuji, Masanori Ikeda, Hirokazu Tsukahara

    Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology   21 ( 1 )   4 - 4   2025.1

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    BACKGROUND: The incidence of allergic diseases has been increasing in Japan. In particular, a serious decline in the age of onset of allergic rhinitis has been observed. Passive smoking from parental smoking has a significant impact on children's health; however, it is difficult to restrict smoking in the home. While various studies have previously reported on the relationship between passive smoking and the development of allergic diseases in children. However, there have been no reports on passive smoking and allergic diseases on a national scale. METHODS: Using Japanese national longitudinal survey data (n = 38,444) for newborns born between May 10 and 24, 2010, we assessed parental smoking habits when their children were 6 months old and investigated the association with the development of allergic diseases until the age of 5.5 years. The risk ratios and 95% confidence intervals for the development of different allergic diseases were analyzed after adjusting for potential confounders using Poisson regression with a robust error variance. RESULTS: The risk ratio for developing allergic rhinitis/allergic conjunctivitis (AR/AC) in children was significantly higher in the maternal smoking groups ( ≦ 10 cigarettes/day; RR 1.15, 95% CI 1.02-1.30; ≧11 cigarettes/day; RR 1.16, 95% CI 0.93-1.44). Furthermore, associations were found between the maternal smoking group in the presence of paternal smoking and the risk of developing bronchial asthma ( ≦ 10, RR 1.33 95% CI 1.17-1.52; ≧11, RR 1.71 95% CI 1.38-2.1), food allergy ( ≦ 10, RR 1.36 95% CI 1.12-1.63; ≧11, RR 1.25 95% CI 0.84-1.86), atopic dermatitis ( ≦ 10, RR 1.42 95% CI 1.22-1.66; ≧11, RR 1.6 95% CI 1.2-2.13), and AR/AC ( ≦ 10, RR 1.21 95% CI 1.07-1.36; ≧11, RR 1.35 95% CI 1.09-1.67). CONCLUSIONS: Maternal smoking during infancy increases the risk of developing AR/AC in children. Considering paternal smoking, maternal smoking further increased the risk of developing allergic diseases in children, suggesting that reducing parental smoking at home may reduce the risk of developing allergic diseases in children.

    DOI: 10.1186/s13223-025-00952-9

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  • 後頭部可逆性白質脳症を合併した肢端紅痛症の1例

    武川 真也, 鈴木 健吾, 宇田 和宏, 茂原 研司, 荒川 恭佑, 齋藤 有希惠, 宮原 宏幸, 長谷川 高誠, 小原 隆史, 塚原 紘平, 八代 将登, 津下 充, 塚原 宏一

    日本小児科学会雑誌   128 ( 7 )   1004 - 1005   2024.7

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  • 後頭部可逆性白質脳症を合併した肢端紅痛症の1例

    武川 真也, 鈴木 健吾, 宇田 和宏, 茂原 研司, 荒川 恭佑, 齋藤 有希惠, 宮原 宏幸, 長谷川 高誠, 小原 隆史, 塚原 紘平, 八代 将登, 津下 充, 塚原 宏一

    日本小児科学会雑誌   128 ( 7 )   1004 - 1005   2024.7

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  • Efficacy and safety of abatacept for systemic juvenile idiopathic arthritis: a systematic review. International journal

    Kenichi Nishimura, Takashi Ishikawa, Nami Okamoto, Keiji Akamine, Natsumi Inoue, Hitoshi Irabu, Kentaro Kato, Hiroshi Keino, Masayo Kojima, Hiroshi Kubo, Kazuichi Maruyama, Mao Mizuta, Kosuke Shabana, Masaki Shimizu, Yuko Sugita, Yukiko Takakuwa, Satoshi Takanashi, Hiroshi Takase, Hiroaki Umebayashi, Natsuka Umezawa, Shingo Yamanishi, Kazuko Yamazaki, Masato Yashiro, Takahiro Yasumi, Masaaki Mori

    Modern rheumatology   2024.5

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    OBJECTIVES: This systematic review assessed the efficacy and safety of abatacept in patients with systemic juvenile idiopathic arthritis (JIA). METHODS: Studies published between 2000 and 2021 were searched using PubMed, Embase, Cochrane, Ichushi-Web and clinical trial registries. The risk of bias was assessed according to the manual for development clinical practice guidelines by Minds, a project to promote evidence-based medicine in Japan. RESULTS: Seven observational studies were included. American College of Rheumatology pediatric 30/50/70 responses at 3, 6 and 12 months were 64.8%/50.3%/27.9%, 85.7%/71.4%/42.9% and 80.0%/50.0%/40.0%, respectively. Outcomes on systemic symptoms, joint symptoms and activities of daily living were not obtained. No macrophage activation syndrome or infusion reaction occurred. Serious infection occurred in 2.6% of cases. CONCLUSIONS: Abatacept improved the disease activity index. In addition, abatacept was as safe as interleukin-6 (IL -6) and IL-1 inhibitors. However, both the efficacy and safety data in this systematic review should be reviewed with caution because their quality of evidence is low or very low. Further studies are needed to confirm the efficacy and safety of abatacept for systemic JIA, especially its efficacy on joint symptoms.

    DOI: 10.1093/mr/roae046

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  • Successful use of dupilumab for egg-induced eosinophilic gastroenteritis with duodenal ulcer: a pediatric case report and review of literature. International journal

    Mitsuru Tsuge, Kenji Shigehara, Kazuhiro Uda, Seiji Kawano, Masaya Iwamuro, Yukie Saito, Masato Yashiro, Masanori Ikeda, Hirokazu Tsukahara

    Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology   19 ( 1 )   103 - 103   2023.12

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    BACKGROUND: Non-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the esophagus; however, the number of patients with non-EoE-EGID has been increasing in recent years. Owing to its chronic course with repeated relapses, it can lead to developmental delays due to malnutrition, especially in pediatric patients. No established treatment exists for non-EoE-EGID, necessitating long-term systemic corticosteroid administration. Although the efficacy of dupilumab, an anti-IL-4/13 receptor monoclonal antibody, for eosinophilic esophagitis, has been reported, only few reports have demonstrated its efficacy in non-EoE EGIDs. CASE PRESENTATION: A 13-year-old boy developed non-EoE-EGID with duodenal ulcers, with chicken eggs as the trigger. He was successfully treated with an egg-free diet, proton pump inhibitors, and leukotriene receptor antagonists. However, at age 15, he developed worsening upper abdominal pain and difficulty eating. Blood analysis revealed eosinophilia; elevated erythrocyte sedimentation rate; and elevated levels of C-reactive protein, total immunoglobulin E, and thymic and activation-regulated chemokines. Upper gastrointestinal endoscopy revealed a duodenal ulcer with marked mucosal eosinophilic infiltration. Gastrointestinal symptoms persisted even after starting systemic steroids, making it difficult to reduce the steroid dose. Subcutaneous injection of dupilumab was initiated because of comorbid atopic dermatitis exacerbation. After 3 months, the gastrointestinal symptoms disappeared, and after 5 months, the duodenal ulcer disappeared and the eosinophil count decreased in the mucosa. Six months later, systemic steroids were discontinued, and the duodenal ulcer remained recurrence-free. The egg challenge test result was negative; therefore, the egg-free diet was discontinued. Blood eosinophil count and serum IL-5, IL-13, and eotaxin-3 levels decreased after dupilumab treatment. The serum levels of IL-5 and eotaxin-3 remained within normal ranges, although the blood eosinophil counts increased again after discontinuation of oral prednisolone. CONCLUSIONS: Suppression of IL-4R/IL-13R-mediated signaling by dupilumab may improve abdominal symptoms and endoscopic and histologic findings in patients with non-EoE-EGID, leading to the discontinuation of systemic steroid administration and tolerance of causative foods.

    DOI: 10.1186/s13223-023-00859-3

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  • Acute Switchitis: A New Subtype of Nintendinitis. International journal

    Hiroyoshi Takahashi, Kazuhiro Uda, Masato Yashiro

    The Journal of pediatrics   113852 - 113852   2023.11

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  • アトピー性皮膚炎に対するデュピルマブ投与によって全身ステロイド投与を中止しえた好酸球性胃腸炎の1例

    津下 充, 茂原 研司, 宇田 和宏, 斎藤 有希惠, 八代 将登, 池田 政憲, 塚原 宏一

    日本小児アレルギー学会誌   37 ( 4 )   382 - 382   2023.10

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  • アトピー性皮膚炎に対するデュピルマブ投与によって全身ステロイド投与を中止しえた好酸球性胃腸炎の1例

    津下 充, 茂原 研司, 宇田 和宏, 斎藤 有希惠, 八代 将登, 池田 政憲, 塚原 宏一

    日本小児アレルギー学会誌   37 ( 4 )   382 - 382   2023.10

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  • Idiopathic Pulmonary Hemosiderosis. Reply. International journal

    Kazuhiro Uda, Masato Yashiro

    The New England journal of medicine   389 ( 10 )   962 - 963   2023.9

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  • 好酸球性消化管疾患・好酸球性肺炎 アトピー性皮膚炎に対するデュピルマブ投与によって全身ステロイド投与を中止しえた好酸球性胃腸炎の1例

    津下 充, 茂原 研司, 宇田 和宏, 斎藤 有希惠, 八代 将登, 池田 政憲, 塚原 宏一

    アレルギー   72 ( 6-7 )   881 - 881   2023.8

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  • 好酸球性消化管疾患・好酸球性肺炎 アトピー性皮膚炎に対するデュピルマブ投与によって全身ステロイド投与を中止しえた好酸球性胃腸炎の1例

    津下 充, 茂原 研司, 宇田 和宏, 斎藤 有希惠, 八代 将登, 池田 政憲, 塚原 宏一

    アレルギー   72 ( 6-7 )   881 - 881   2023.8

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  • Idiopathic Pulmonary Hemosiderosis. International journal

    Kazuhiro Uda, Masato Yashiro

    The New England journal of medicine   2023.6

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    DOI: 10.1056/NEJMicm2214160

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  • 初診時,手足口病様皮疹を呈した新生児水疱性類天疱瘡の1例

    別木 祐介, 徳田 真優, 前 琴絵, 妹尾 春佳, 立花 宏太, 三宅 智子, 平井 陽至, 川上 佳夫, 森実 真, 宇田 和宏, 斎藤 友希恵, 茂原 研司, 津下 充, 八代 将登

    日本皮膚科学会雑誌   133 ( 4 )   715 - 715   2023.4

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  • Treatment for macrophage activation syndrome associated with systemic juvenile idiopathic arthritis in Japan. International journal

    Masaki Shimizu, Kenichi Nishimura, Naomi Iwata, Takahiro Yasumi, Hiroaki Umebayashi, Yasuo Nakagishi, Yuka Okura, Nami Okamoto, Noriko Kinjo, Mao Mizuta, Masato Yashiro, Junko Yasumura, Hiroyuki Wakiguchi, Tomohiro Kubota, Mariko Mouri, Utako Kaneko, Masaaki Mori

    International journal of rheumatic diseases   2023.3

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    OBJECTIVES: To clarify how pediatric rheumatologists treat systemic juvenile idiopathic arthritis (s-JIA) associated macrophage activation syndrome (MAS) in the real world and to assess the efficacy and safety of dexamethasone palmitate (DEX-P) in the treatment of s-JIA-associated MAS. METHODS: This multicenter, retrospective study was conducted at 13 pediatric rheumatology institutes in Japan. This study included 28 patients with s-JIA-associated MAS. Clinical findings, such as treatment details and adverse events, were evaluated. RESULTS: Methylprednisolone (mPSL) pulse therapy was selected as the first-line treatment in more than half of the patients with MAS. Cyclosporine A (CsA) was used as first-line therapy in combination with corticosteroids in half of the patients with MAS. DEX-P and/or CsA were selected as the second-line therapy in 63% of patients with corticosteroid-resistant MAS. Plasma exchange was selected as the third-line therapy for DEX-P and CsA-resistant MAS. All patients improved and there were no characteristically severe adverse events associated with DEX-P. CONCLUSIONS: The first-line treatment for MAS in Japan is mPSL pulse therapy and/or CyA. DEX-P could be an effective and safe therapeutic option for patients with corticosteroid-resistant MAS.

    DOI: 10.1111/1756-185X.14681

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  • Evaluation of the association of birth order and group childcare attendance with Kawasaki disease using data from a nationwide longitudinal survey. Reviewed International journal

    Takahiro Namba, Akihito Takeuchi, Naomi Matsumoto, Mitsuru Tsuge, Masato Yashiro, Hirokazu Tsukahara, Takashi Yorifuji

    Frontiers in pediatrics   11   1127053 - 1127053   2023

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    BACKGROUND: Kawasaki disease (KD) is a form of pediatric systemic vasculitis. Although the etiology remains unclear, infections have been identified as possible triggers. Children with a later birth order and those who attend childcare are at a higher risk of infections due to exposure to pathogens from their older siblings and other childcare attendees. However, longitudinal studies exploring these associations are limited. Thus, we aimed to elucidate the relationship between birth order, group childcare attendance, and KD, using a nationwide longitudinal survey in Japan. METHODS: In total, 36,885 children born in Japan in 2010 were included. The survey used questionnaires to identify hospitalized cases of KD. We evaluated the relationship between birth order classification, group childcare attendance, and KD prevalence every year, from 6 to 66 months of age. For each outcome, odds ratios (ORs), and 95% confidence intervals (CIs) were estimated after adjusting for child factors, parental factors, and region of residence. RESULTS: Children with higher birth orders were more likely to be hospitalized with KD at 6-18 months of age (second child OR: 1.77, 95% CI: 1.25-2.51; third child OR: 1.70, 95% CI: 1.08-2.65). This trend was stronger for children who did not attend group childcare (second child OR: 2.51, 95% CI: 1.57-4.01; third child OR: 2.41, 95% CI: 1.30-4.43). An increased risk of KD hospitalization owing to the birth order was not observed in any age group for children in the childcare group. CONCLUSIONS: Children with higher birth orders were at high risk for hospitalization due to KD at 6-18 months of age. The effect of birth order was more prominent among the children who did not attend group childcare.

    DOI: 10.3389/fped.2023.1127053

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  • Need for re-evaluating the risk of coronavirus disease 2019 transmission to neonates. International journal

    Kazuhiro Uda, Mitsuru Tsuge, Masato Yashiro, Tomoyuki Honda, Hirokazu Tsukahara

    Pediatrics international : official journal of the Japan Pediatric Society   65 ( 1 )   e15460   2022.12

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    DOI: 10.1111/ped.15460

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  • RSウイルス感染症の全国サーベイランスとGoogle Trendsの相関性に関する検討

    宇田 和宏, 萩谷 英大, 頼藤 貴志, 小山 敏広, 茂原 研司, 津下 充, 八代 将登, 本田 知之, 塚原 宏一

    日本小児感染症学会総会・学術集会プログラム・抄録集   54回   194 - 194   2022.11

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  • Neonatal hemochromatosis with εγδβ-thalassemia: a case report and analysis of serum iron regulators. International journal

    Mitsuru Tsuge, Aya Kodera, Hiromi Sumitomo, Tooru Araki, Ryuichi Yoshida, Kazuya Yasui, Hiroki Sato, Yosuke Washio, Kana Washio, Kenji Shigehara, Masato Yashiro, Takahito Yagi, Hirokazu Tsukahara

    BMC pediatrics   22 ( 1 )   622 - 622   2022.10

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    BACKGROUND: Neonatal hemochromatosis causes acute liver failure during the neonatal period, mostly due to gestational alloimmune liver disease (GALD). Thalassemia causes hemolytic anemia and ineffective erythropoiesis due to mutations in the globin gene. Although neonatal hemochromatosis and thalassemia have completely different causes, the coexistence of these diseases can synergistically exacerbate iron overload. We report that a newborn with εγδβ-thalassemia developed neonatal hemochromatosis, which did not respond to iron chelators and rapidly worsened, requiring living-donor liver transplantation. CASE PRESENTATION: A 1-day-old Japanese boy with hemolytic anemia and targeted red blood cells was diagnosed with εγδβ-thalassemia by genetic testing, and required frequent red blood cell transfusions. At 2 months after birth, exacerbation of jaundice, grayish-white stool, and high serum ferritin levels were observed, and liver biopsy showed iron deposition in hepatocytes and Kupffer cells. Magnetic resonance imaging scans showed findings suggestive of iron deposits in the liver, spleen, pancreas, and bone marrow. The total amount of red blood cell transfusions administered did not meet the criteria for post-transfusion iron overload. Administration of an iron-chelating agent was initiated, but iron overload rapidly progressed to liver failure without improvement in jaundice and liver damage. He underwent living-donor liver transplantation from his mother, after which iron overload disappeared, and no recurrence of iron overload was observed. Immunohistochemical staining for C5b-9 in the liver was positive. Serum hepcidin levels were low and serum growth differentiation factor-15 levels were high prior to living-donor liver transplantation. CONCLUSIONS: We reported that an infant with εγδβ-thalassemia developed NH due to GALD, and that coexistence of ineffective erythropoiesis in addition to erythrocyte transfusions may have exacerbated iron overload. Low serum hepcidin levels, in this case, might have been caused by decreased hepcidin production arising from fetal liver damage due to neonatal hemochromatosis and increased hepcidin-inhibiting hematopoietic mediators due to the ineffective hematopoiesis observed in thalassemia.

    DOI: 10.1186/s12887-022-03706-3

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  • 巨大胃十二指腸潰瘍を伴った卵黄による好酸球性胃腸炎の1例

    津下 充, 茂原 研司, 宇田 和宏, 斎藤 有希惠, 八代 将登, 池田 政憲, 塚原 宏一

    日本小児アレルギー学会誌   36 ( 4 )   418 - 418   2022.9

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  • Neck Pain with Abdominal Distention in a Patient with Systemic Lupus Erythematosus. International journal

    Kazuhiro Uda, Kenji Shigehara, Masato Yashiro

    Gastroenterology   2022.8

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    DOI: 10.1053/j.gastro.2022.08.022

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  • Correlation between national surveillance and search engine query data on respiratory syncytial virus infections in Japan. International journal

    Kazuhiro Uda, Hideharu Hagiya, Takashi Yorifuji, Toshihiro Koyama, Mitsuru Tsuge, Masato Yashiro, Hirokazu Tsukahara

    BMC public health   22 ( 1 )   1517 - 1517   2022.8

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    BACKGROUND: The respiratory syncytial virus (RSV) disease burden is significant, especially in infants and children with an underlying disease. Prophylaxis with palivizumab is recommended for these high-risk groups. Early recognition of a RSV epidemic is important for timely administration of palivizumab. We herein aimed to assess the correlation between national surveillance and Google Trends data pertaining to RSV infections in Japan. METHODS: The present, retrospective survey was performed between January 1, 2018 and November 14, 2021 and evaluated the correlation between national surveillance data and Google Trends data. Joinpoint regression was used to identify the points at which changes in trends occurred. RESULTS: A strong correlation was observed every study year (2018 [r = 0.87, p < 0.01], 2019 [r = 0.83, p < 0.01], 2020 [r = 0.83, p < 0.01], and 2021 [r = 0.96, p < 0.01]). The change-points in the Google Trends data indicating the start of the RSV epidemic were observed earlier than by sentinel surveillance in 2018 and 2021 and simultaneously with sentinel surveillance in 2019. No epidemic surge was observed in either the Google Trends or the surveillance data from 2020. CONCLUSIONS: Our data suggested that Google Trends has the potential to enable the early identification of RSV epidemics. In countries without a national surveillance system, Google Trends may serve as an alternative early warning system.

    DOI: 10.1186/s12889-022-13899-y

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  • 巨大胃十二指腸潰瘍を伴った卵黄による好酸球性胃腸炎の1小児例

    津下 充, 茂原 研司, 宇田 和宏, 斎藤 有希恵, 八代 将登, 池田 政憲, 塚原 宏一

    アレルギー   71 ( 6-7 )   858 - 858   2022.8

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  • 巨大胃十二指腸潰瘍を伴った卵黄による好酸球性胃腸炎の1小児例

    津下 充, 茂原 研司, 宇田 和宏, 斎藤 有希恵, 八代 将登, 池田 政憲, 塚原 宏一

    アレルギー   71 ( 6-7 )   858 - 858   2022.8

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  • Author Correction: Thioredoxin interacting protein protects mice from fasting induced liver steatosis by activating ER stress and its downstream signaling pathways. International journal

    Hiroyuki Miyahara, Kosei Hasegawa, Masato Yashiro, Toshiaki Ohara, Masayoshi Fujisawa, Teizo Yoshimura, Akihiro Matsukawa, Hirokazu Tsukahara

    Scientific reports   12 ( 1 )   8026 - 8026   2022.5

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  • Decreased Levels of Histidine-Rich Glycoprotein and Increased Levels of High-Mobility Group Box 1 are Risk Factors for Refractory Kawasaki Disease. International journal

    Takahiro Namba, Masato Yashiro, Yosuke Fujii, Mitsuru Tsuge, Keyue Liu, Masahiro Nishibori, Hirokazu Tsukahara

    Modern rheumatology   33 ( 3 )   599 - 607   2022.4

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    OBJECTIVES: Histidine-rich glycoprotein (HRG) and high-mobility group box 1 (HMGB1) regulate the activation of neutrophils and vascular endothelium. The aim of this study was to quantify HRG and HMGB1 levels in patients with Kawasaki disease (KD) and evaluate their use in the clinical management of KD. METHODS: This study was prospectively performed. Patients were divided into two groups and analyzed depending on whether KD symptoms improved by day 10 of illness. HRG, HMGB1, and other laboratory variables were measured before the first treatment in all cases and, in most cases, afterwards, for assessing trends. RESULTS: In this prospective study, we enrolled 60 patients with KD and 48 healthy controls. The HRG level in the KD group was significantly lower than that in the healthy control group; HMGB1 levels showed no obvious differences. In the KD group, HRG levels were negatively correlated with white blood cell and neutrophil counts. In the poor responders and responders groups, a tendency for a decrease in HRG and HMGB1 levels, respectively, was observed from pretreatment to post-treatment. CONCLUSIONS: HRG and HMGB1 are related to the pathogenesis of KD; low HRG and high HMGB1 levels cause resistance against KD treatment.

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  • 水疱性類天疱瘡に合併した偽性低アルドステロン症の乳児例

    宮原 宏幸, 村上 美智子, 二川 奈都子, 長谷川 高誠, 茂原 研司, 宇田 和宏, 津下 充, 八代 将登, 平井 陽至, 森実 真, 塚原 宏一

    日本小児科学会雑誌   126 ( 4 )   728 - 728   2022.4

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  • Thioredoxin interacting protein protects mice from fasting induced liver steatosis by activating ER stress and its downstream signaling pathways. Reviewed International journal

    Hiroyuki Miyahara, Kosei Hasegawa, Masato Yashiro, Toshiaki Ohara, Masayoshi Fujisawa, Teizo Yoshimura, Akihiro Matsukawa, Hirokazu Tsukahara

    Scientific reports   12 ( 1 )   4819 - 4819   2022.3

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    Under normal conditions, fasting results in decreased protein disulfide isomerase (PDI) activity and accumulation of unfolded proteins, leading to the subsequent activation of the unfolded protein response (UPR)/autophagy signaling pathway to eliminate damaged mitochondria. Fasting also induces upregulation of thioredoxin-interacting protein (TXNIP) expression and mice deficient of this protein (TXNIP-KO mice) was shown to develop severe hypoglycemia, hyperlipidemia and liver steatosis (LS). In the present study, we aimed to determine the role of TXNIP in fasting-induced LS by using male TXNIP-KO mice that developed LS without severe hypoglycemia. In TXNIP-KO mice, fasting induced severe microvesicular LS. Examinations by transmission electron microscopy revealed mitochondria with smaller size and deformities and the presence of few autophagosomes. The expression of β-oxidation-associated genes remained at the same level and the level of LC3-II was low. PDI activity level stayed at the original level and the levels of p-IRE1 and X-box binding protein 1 spliced form (sXBP1) were lower. Interestingly, treatment of TXNIP-KO mice with bacitracin, a PDI inhibitor, restored the level of LC3-II after fasting. These results suggest that TXNIP regulates PDI activity and subsequent activation of the UPR/autophagy pathway and plays a protective role in fasting-induced LS.

    DOI: 10.1038/s41598-022-08791-z

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  • SLEにおけるTAC、MMF併用中の下痢と急性腎障害

    奥村 美紗, 宮原 宏幸, 茂原 研司, 斎藤 有希恵, 津下 充, 八代 将登, 塚原 宏一

    小児科診療   85 ( 2 )   253 - 255   2022.2

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    症例は全身性エリテマトーデスの18歳女性。タクロリムス(TAC)、ミコフェノール酸モフェチル(MMF)併用下に寛解状態にあった。急性胃腸炎を機に腎機能が低下し、いったん軽快した下痢の再燃および血球減少を認めた。TAC、MMF相互の副作用により両薬剤の血中濃度が上昇し有害事象が出現したと考えられ、TAC減量により症状は改善した。TAC、MMF2剤併用中に胃腸炎に罹患したときには、特異な血中濃度の変動に注意する必要がある。(著者抄録)

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  • Bilateral Optic Disc Swelling as a Plausible Common Ocular Sign of Autoinflammatory Diseases: Report of Three Patients with Blau Syndrome or Cryopyrin-Associated Periodic Syndrome. International journal

    Toshihiko Matsuo, Masato Yashiro, Osamu Yamasaki, Takehiro Tanaka, Akira Manki

    Life (Basel, Switzerland)   11 ( 12 )   2021.12

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    The aim of this study is to describe bilateral optic disc swelling in three consecutive patients with Blau syndrome or cryopyrin-associated periodic syndrome at a single institution. Case 1 was a 30-year-old woman receiving 25 mg etanercept twice weekly who had been diagnosed as early-onset sarcoidosis by biopsy of skin rashes at 5 months old and genetically diagnosed with Blau syndrome with CARD15/NOD2 mutation (N670K) at 13 years old. At 10 years old, she began to have uveitis with optic disc swelling in both eyes, resulting in macular degeneration and optic disc atrophy at 17 years old only when etanercept was introduced. Case 2 was a 21-year-old man receiving adalimumab every 2 weeks who had been diagnosed as early-onset sarcoidosis by biopsy of skin rashes at 1.5 years old and genetically diagnosed as Blau syndrome with CARD15/NOD2 mutation (C495Y) at 5 years old. At 8 years old, around the time of adalimumab introduction, he began to show bilateral optic disc swelling which continued until the age of 16 years when the dose of adalimumab was increased. Case 3 was a 20-year-old woman receiving canakinumab every 8 weeks for systemic symptoms such as fever, headache, vomiting, and abdominal pain and later for sensorineural hearing disturbance on both sides. She had been diagnosed genetically with cryopyrin-associated periodic syndrome with NLRP3 mutation (Y859C) at 7 years old. At 5 years old, she was found to have bilateral optic disc swelling, which continued until the age of 10 years when she began receiving canakinumab (IL-1β inhibitor). Bilateral optic disc swelling might be tentatively designated as a plausible common ocular feature, if it occurred, in autoinflammatory diseases to pay more attention to ophthalmic complications in rare diseases.

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  • Bilateral Optic Disc Swelling as a Plausible Common Ocular Sign of Autoinflammatory Diseases: Report of Three Patients with Blau Syndrome or Cryopyrin-Associated Periodic Syndrome.

    Life (Basel).   1 ( 12 )   1433 - 1433   2021.12

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    DOI: 10.3390/life111

  • Anti-high mobility group box 1 monoclonal antibody suppressed hyper-permeability and cytokine production in human pulmonary endothelial cells infected with influenza A virus. International journal

    Takahiro Namba, Mitsuru Tsuge, Masato Yashiro, Yukie Saito, Keyue Liu, Masahiro Nishibori, Tsuneo Morishima, Hirokazu Tsukahara

    Inflammation research : official journal of the European Histamine Research Society ... [et al.]   70 ( 10-12 )   1101 - 1111   2021.12

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    OBJECTIVE: High mobility group box-1 (HMGB1) has been reported to be involved in influenza A virus-induced acute respiratory distress syndrome (ARDS). We studied the efficacy of an anti-HMGB1 mAb using an in vitro model of TNF-α stimulation or influenza A virus infection in human pulmonary microvascular endothelial cells (HMVECs). METHODS: Vascular permeability of HMVECs was quantified using the Boyden chamber assay under tumor necrosis factor-α (TNF-α) stimulation or influenza A virus infection in the presence of anti-HMGB1 mAb or control mAb. The intracellular localization of HMGB1 was assessed by immunostaining. Extracellular cytokine concentrations and intracellular viral mRNA expression were quantified by the enzyme-linked immunosorbent assay and quantitative reverse transcription PCR, respectively. RESULTS: Vascular permeability was increased by TNF-α stimulation or influenza A infection; HMVECs became elongated and the intercellular gaps were extended. Anti-HMGB1 mAb suppressed both the increase in permeability and the cell morphology changes. Translocation of HMGB1 to the cytoplasm was observed in the non-infected cells. Although anti-HMGB1 mAb did not suppress viral replication, it did suppress cytokine production in HMVECs. CONCLUSION: Anti-HMGB1 mAb might be an effective therapy for severe influenza ARDS.

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  • Terry's nails in an infant with liver cirrhosis. International journal

    Kazuhiro Uda, Mitsuru Tsuge, Kenji Shigehara, Masato Yashiro, Hirokazu Tsukahara

    Archives of disease in childhood   107 ( 5 )   485 - 485   2021.9

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    DOI: 10.1136/archdischild-2021-322953

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  • Terry's nails in an infant with liver cirrhosis. Reviewed

    Uda K, Tsuge M, Shigehara K, Yashiro M, Tsukahara H.

    Arch Dis Child.   2021.9

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  • 医学部学生に対する予防接種記録判定方法の現状と問題点

    茂原 研司, 八代 将登, 宇田 和宏, 塚原 宏一

    日本環境感染学会総会プログラム・抄録集   36回   253 - 253   2021.9

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  • 医学部学生に対する予防接種記録の判定方法に関する検討

    八代 将登, 茂原 研司, 宇田 和宏, 塚原 宏一

    日本環境感染学会総会プログラム・抄録集   36回   253 - 253   2021.9

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  • Anti-high mobility group box 1 monoclonal antibody suppressed hyper-permeability and cytokine production in human pulmonary endothelial cells infected with influenza A virus. Reviewed

    Namba T, Tsuge M, Yashiro M, Saito Y, Liu K, Nishibori M, Morishima T, Tsukahara H.

    1 - 11   2021.8

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  • 食物アレルゲン 経口負荷試験で診断に至った食用クラゲアレルギーの1小児例

    津下 充, 茂原 研司, 斎藤 有希恵, 八代 将登, 池田 政憲, 塚原 宏一

    アレルギー   70 ( 6-7 )   788 - 788   2021.8

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  • Influenza Encephalopathy: What Is Encephalopathy?

    Mitsuru Tsuge, Masato Yashiro, Naoki Ohno, Hirokazu Tsukahara

    Respiratory Disease Series: Diagnostic Tools and Disease Managements   115 - 126   2020.11

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    DOI: 10.1007/978-981-15-9109-9_12

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  • Clinical Significance of Serum Soluble TNF Receptor I/II Ratio for the Differential Diagnosis of Tumor Necrosis Factor Receptor-Associated Periodic Syndrome From Other Autoinflammatory Diseases Reviewed

    Yasumura J, Shimizu M, Toma T, Yashiro M, Yachie A, Okada S.

    Front Immunol   11   2020.10

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    DOI: 10.3389/fimmu.2020.5

  • Clinical characteristics and treatment of 50 cases of Blau syndrome in Japan confirmed by genetic analysis of the NOD2 mutation Reviewed

    Matsuda T, Kambe N, Ueki Y, Kanazawa N, Izawa K, Honda Y, Kawakami A, Takei S, Tonomura K, Inoue M, Kobayashi H, Okafuji I, Sakurai Y, Kato N, Maruyama Y, Inoue Y, Otsubo Y, Makino T, Okada S, Kobayashi I, Yashiro M, Ito S, Fujii H, Kondo Y, Okamoto N, Ito S, Iwata N, Kaneko U, Doi M, Hosokawa J, Ohara O, Saito MK, Nishikomori R

    Annals of the Rheumatic Diseases   2020.7

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  • マルチターゲット療法で加療中、胃腸炎を機に急性腎障害に至った全身性エリテマトーデスの一例

    宮原 宏幸, 石井 雅人, 茂原 研司, 津下 充, 八代 将登, 塚原 宏一

    日本小児腎臓病学会雑誌   33 ( 1 )   106 - 106   2020.4

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  • Idiopathic Chondrolysis of the Hip Treated by Immunosuppressive Therapy and Arthroscopic Intervention. Reviewed

    Hirosuke Endo, Hirofumi Akazawa, Masato Yashiro, Kazuki Yamada, Tomoaki Sanki, Tomonori Tetsunaga, Keiichiro Nishida, Takayuki Furumatsu, Toshifumi Ozaki

    Acta medica Okayama   74 ( 1 )   77 - 81   2020.2

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    Idiopathic chondrolysis of the hip (ICH), a very rare disorder of unknown etiology, occurs mainly in female adolescents. Characterized by pain, limp, stiffness and radiological narrowing joint space from the rapid destruction of the articular cartilage, ICH sometimes results in ankyloses. We present the case of a 10-year-old girl diagnosed with ICH based on arthroscopic inspection and synovium biopsy. The femoral deformity appeared gradually, like a cam-type femoroacetabular impingement. She was treated with intensive rehabilitation and immunosuppressive drug. We later performed an arthroscopic bumpectomy for residual symptoms. She achieved a favorable outcome as a 15-year-old at the latest follow-up.

    DOI: 10.18926/AMO/57957

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  • Tocilizumab modifies clinical and laboratory features of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. Reviewed International journal

    Masaki Shimizu, Mao Mizuta, Nami Okamoto, Takahiro Yasumi, Naomi Iwata, Hiroaki Umebayashi, Yuka Okura, Noriko Kinjo, Tomohiro Kubota, Yasuo Nakagishi, Kenichi Nishimura, Mariko Mohri, Masato Yashiro, Junko Yasumura, Hiroyuki Wakiguchi, Masaaki Mori

    Pediatric rheumatology online journal   18 ( 1 )   2 - 2   2020.1

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    BACKGROUND: This study aimed to determine the influence of tocilizumab (TCZ) in modifying the clinical and laboratory features of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (s-JIA). Furthermore, we assessed the performance of the 2016 MAS classification criteria for patients with s-JIA-associated MAS while treated with TCZ. METHODS: A panel of 15 pediatric rheumatologists conducted a combination of expert consensus and analysis of real patient data. Clinical and laboratory features of s-JIA-associated MAS in 12 TCZ-treated patients and 18 untreated patients were evaluated. Possible MAS was defined as having characteristic laboratory features but lack of clinical features of MAS, or atypical MAS, or early treatment that prevented full-blown MAS. RESULTS: Clinically, the TCZ-treated patients with s-JIA-associated MAS were less likely febrile and had significantly lower ferritin, triglyceride, and CRP levels than the untreated patients with s-JIA-associated MAS. Other laboratory features of MAS including lower platelet counts and lower fibrinogen were more pronounced in TCZ-treated patients. The TCZ-treated patients with s-JIA-associated MAS were less likely to be classified as MAS based on the MAS classification criteria (25% vs 83.3%, p < 0.01). This is ascribed to the absence of fever or insufficient ferritin elevation, compared with the untreated patients. CONCLUSION: TCZ could modify the clinical and laboratory features of s-JIA-associated MAS. When evaluating the s-JIA patients while treated with TCZ, it is not applicable to use MAS classification criteria. Care must be taken to not underdiagnose MAS based on the MAS classification criteria.

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  • Tocilizumab modifies clinical and laboratory features of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. Reviewed

    Shimizu M, Mizuta M, Okamoto N, Yasumi T, Iwata N, Umebayashi H, Okura Y, Kinjo N, Kubota T, Nakagishi Y, Nishimura K, Mohri M, Yashiro M, Yasumura J, Wakiguchi H, Mori M.

    Pediatric Rheumatology Online Journal   18 ( 1 )   2   2020.1

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  • Long-Term Control of Macular Edema With Adalimumab After Cataract Surgery in a Japanese Child With Juvenile Idiopathic Arthritis: Case Report and Review of 26 Japanese Patients Reviewed

    Matsuo T, Yashiro M.

    J Investig Med High Impact Case Rep.   8   2020.1

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  • Clinical Significance of Serum Soluble TNF Receptor I/II Ratio for the Differential Diagnosis of Tumor Necrosis Factor Receptor-Associated Periodic Syndrome From Other Autoinflammatory Diseases. International journal

    Junko Yasumura, Masaki Shimizu, Tomoko Toma, Masato Yashiro, Akihiro Yachie, Satoshi Okada

    Frontiers in immunology   11   576152 - 576152   2020

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    Objectives: Genetic analysis of TNFRSF1A can confirm the diagnosis of tumor necrosis factor receptor-associated periodic syndrome (TRAPS), but interpretation of the pathogenesis of variants of unknown significance is sometimes required. The aim of this study was to evaluate the clinical significance of serum soluble tumor necrosis factor receptor type I (sTNFR-I)/II ratio to differentiate TRAPS from other autoinflammatory diseases. Methods: Serum sTNFR-I and sTNFR-II levels were measured using an enzyme-linked immunosorbent assay in patients with TRAPS (n = 5), familial Mediterranean fever (FMF) (n = 14), systemic juvenile idiopathic arthritis (s-JIA) (n = 90), and Kawasaki disease (KD) (n = 37) in the active and inactive phase, along with healthy controls (HCs) (n = 18). Results: In the active phase, the serum sTNFR-I/II ratio in patients with s-JIA, KD, and FMF was significantly elevated compared with that in HCs, whereas it was not elevated in patients with TRAPS. In the inactive phase, the serum sTNFR-I/II ratio in patients with s-JIA and FMF was significantly higher compared with that in HCs, and the ratio was lower in TRAPS patients than in patients with s-JIA and FMF. Conclusions: Low serum sTNFR-I/II ratio in the active and inactive phase might be useful for the differential diagnosis of TRAPS and other autoinflammatory diseases.

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  • トシリズマブ治療中に発症した全身型若年性特発性関節炎に合併したマクロファージ活性化症候群症例の臨床的特徴

    清水 正樹, 水田 麻雄, 岡本 奈美, 八角 高裕, 岩田 直美, 梅林 宏明, 大倉 有加, 金城 紀子, 久保田 知洋, 中岸 保夫, 西村 謙一, 毛利 万里子, 八代 将登, 安村 純子, 脇口 宏之, 森 雅亮

    日本小児リウマチ学会総会・学術集会プログラム・抄録集   29回   94 - 94   2019.10

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  • TOCILIZUMAB MODIFIES CLINICAL MANIFESTATIONS AND LABORATORY FEATURES OF SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS ASSOCIATED MACROPHAGE ACTIVATION SYNDROME Reviewed

    Shimizu Masaki, Mizuta Mao, Yasumi Takahiro, Iwata Naomi, Okura Yuka, Kinjo Noriko, Umebayashi Hiroaki, Kubota Tomohiro, Nakagishi Yasuo, Nishimura Kenichi, Yashiro Masato, Yasumura Junko, Wakiguchi Hiroyuki, Okamoto Nami, Mori Masaaki

    ANNALS OF THE RHEUMATIC DISEASES   78   1989   2019.6

  • Acute flaccid myelitis associated with enterovirus D68 in a non-epidemic setting Reviewed

    Kazuki Hatayama, Shinichiro Goto, Masato Yashiro, Harushi Mori, Tsuguto Fujimoto, Nozomu Hanaoka, Keiko Tanaka-Taya, Tomoka Zuzan, Masaru Inoue

    IDCASES   17   2019.5

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    Acute flaccid myelitis (AFM) is a recently defined clinical disease accompanied by the national outbreak of enterovirus D68 (EV-D68) in the United States during the late summer/fall of 2014; 258 cases of EV-D68 and 59 cases of AFM were reported in Japan during the late summer/fall of 2015. Subsequently, there have been no epidemics of AFM or EV-D68. However, we encountered a patient who had AFM associated with EV-D68 in 2017. This is the first case of AFM caused by EV-D68 after the 2015 epidemic, and the only reported case in 2017. This report indicates that AFM caused by EV-D68 can arise even in non-epidemic situations. If a patient presents with paralysis, AFM caused by EV-D68 should be included in the differential diagnosis, regardless of the absence of an epidemic of EV-D68 infection. (C) 2019 The Authors. Published by Elsevier Ltd.

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  • Clinical features and characteristics of uveitis associated with juvenile idiopathic arthritis in Japan: first report of the pediatric rheumatology association of Japan (PRAJ) Reviewed

    Yasumura J, Yashiro M, Okamoto N, Shabana K, Umebayashi H, Iwata N, Okura Y, Kubota T, Shimizu M, Tomiita M, Nakagishi Y, Nishimura K, Hara R, Mizuta M, Yasumi T, Yamaide F, Wakiguchi H, Kobayashi M, Mori M

    Pediatric Rheumatology Online Journal   17 ( 1 )   5   2019.4

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  • Clinical features and characteristics of uveitis associated with juvenile idiopathic arthritis in Japan: first report of the pediatric rheumatology association of Japan (PRAJ). Reviewed International journal

    Junko Yasumura, Masato Yashiro, Nami Okamoto, Kosuke Shabana, Hiroaki Umebayashi, Naomi Iwata, Yuka Okura, Tomohiro Kubota, Masaki Shimizu, Minako Tomiita, Yasuo Nakagishi, Kenichi Nishimura, Ryoki Hara, Mao Mizuta, Takahiro Yasumi, Fumiya Yamaide, Hiroyuki Wakiguchi, Masao Kobayashi, Masaaki Mori

    Pediatric rheumatology online journal   17 ( 1 )   15 - 15   2019.4

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    BACKGROUND: Although there are many reports on Juvenile Idiopathic arthritis-associated uveitis (JIA-U) from various countries, especially from Europe and North America, there are few reports from Asia. Our aim was to investigate the epidemiology, characteristics and predictors of JIA-U in Japan. METHODS: Data were retrospectively collected on 726 patients with JIA from medical records as of April 2016 at 15 medical centers specialized in pediatric rheumatic diseases. Of these, patients with uveitis were further investigated for the specific characteristics of this manifestation. RESULTS: The prevalence of uveitis was 6.1% in the 726 JIA patients examined. Incidence of uveitis was significantly higher in patients with an earlier arthritis onset (2.6-vs.-5.8 years, P < 0.0001), oligoarthritis (16.1%-vs.-1.6%, P < 0.001), or anti-nuclear antibodies. On the contrary, it was significantly less common in patients with rheumatoid factor or anti-cyclic citrullinated peptide antibodies. A history of using methotrexate (MTX), infliximab or adalimumab was also associated with uveitis occurrence. The median age at uveitis diagnosis was 5 years, and the median time from arthritis onset to uveitis diagnosis was 2 years. The occurrence of anterior and bilateral uveitis was 79.3 and 53.7%, respectively. There were no symptoms at uveitis diagnosis in 58.5% of cases. Complications arising between the time of uveitis diagnosis and the last observation increased from 31.7 to 56.1%; in particular, cataract was increased 3-fold. While no patients lost their vision, 61.9% did not recover normal vision (≥ 1.0), and in many cases active uveitis persisted, especially in males. In addition to steroid eye drops (97.6%) and MTX (15.4%), biological agents were used for treating the uveitis in 41.5% of patients. CONCLUSIONS: The epidemiology, characteristics and predictors of JIA-U in Japan are described here for the first time. Although the prevalence of JIA-U in Japan is lower than in predominantly Caucasian cohorts, as reported from North America and Europe, the epidemiology, characteristics and predictors were found to be similar.

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  • Combined effect of anti-high-mobility group box-1 monoclonal antibody and peramivir against influenza A virus-induced pneumonia in mice. Reviewed

    Hatayama K, Nosaka N, Yamada M, Yashiro M, Fujii Y, Tsukahara H, Liu K, Nishibori M, Matsukawa A, Morishima T.

    Journal of Medical Virology   91 ( 3 )   361 - 369   2019.3

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  • Combined effect of anti-high-mobility group box-1 monoclonal antibody and peramivir against influenza A virus-induced pneumonia in mice. International journal

    Kazuki Hatayama, Nobuyuki Nosaka, Mutsuko Yamada, Masato Yashiro, Yosuke Fujii, Hirokazu Tsukahara, Keyue Liu, Masahiro Nishibori, Akihiro Matsukawa, Tsuneo Morishima

    Journal of medical virology   91 ( 3 )   361 - 369   2019.3

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    Human pandemic H1N1 2009 influenza virus causes significant morbidity and mortality with severe acute lung injury due to the excessive inflammatory reaction, even with neuraminidase inhibitor use. The anti-inflammatory effect of anti-high-mobility group box-1 (HMGB1) monoclonal antibody (mAb) against influenza pneumonia has been reported. In this study, we evaluated the combined effect of anti-HMGB1 mAb and peramivir against pneumonia induced by influenza A (H1N1) virus in mice. Nine-week-old male C57BL/6 mice were inoculated with H1N1 and treated with intramuscularly administered peramivir at 2 and 3 days post-infection (dpi). The anti-HMGB1 mAb or a control mAb was administered at 2, 3, and 4 dpi. Survival rates were assessed, and lung lavage and pathological analyses were conducted at 5 and 7 dpi. The combination of peramivir with the anti-HMGB1 mAb significantly improved survival rate whereas the anti-HMGB1 mAb alone did not affect virus proliferation in the lungs. This combination therapy also significantly ameliorated histopathological changes, neutrophil infiltration, and macrophage aggregation by inhibiting HMGB1, inflammatory cytokines, and oxidative stress. Fluorescence immunostaining showed that the anti-HMGB1 mAb inhibited HMGB1 translocation from type I alveolar epithelial cells. In summary, combining anti-HMGB1 with conventional anti-influenza therapy might be useful against severe influenza virus infection.

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  • 小児の膠原病および若年性特発性関節炎 全国小児リウマチ中核施設の疫学調査結果を用いたMMP-3及び骨密度についての検討

    謝花 幸祐, 岡本 奈美, 梅林 宏明, 岩田 直美, 大倉 有加, 久保田 知洋, 清水 正樹, 中岸 保夫, 西村 謙一, 水田 麻雄, 八代 将登, 八角 高裕, 安村 純子, 脇口 宏之, 森 雅亮

    日本リウマチ学会総会・学術集会プログラム・抄録集   63回   424 - 424   2019.3

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  • 当院における播種性帯状疱疹の感染防止策

    宮村 純子, 木口 隆, 草野 展周, 八代 将登, 塚原 宏一

    日本環境感染学会総会プログラム・抄録集   34回   [P - 127]   2019.2

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  • Corrigendum to "Serum Procalcitonin Levels in Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion". International journal

    Yosuke Fujii, Masato Yashiro, Mutsuko Yamada, Tomonobu Kikkawa, Nobuyuki Nosaka, Yukie Saito, Kohei Tsukahara, Masanori Ikeda, Tsuneo Morishima, Hirokazu Tsukahara

    Disease markers   2019   4025694 - 4025694   2019

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    [This corrects the article DOI: 10.1155/2018/2380179.].

    DOI: 10.1155/2019/4025694

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  • 子どもの痛みと付き合う 線維筋痛症と自閉スペクトラム症

    岡田 あゆみ, 椙原 彰子, 堀内 真希子, 藤井 智香子, 重安 良恵, 八代 将登, 塚原 宏一

    Locomotive Pain Frontier   7 ( 2 )   96 - 101   2018.12

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  • 熱性けいれん重積状態後に半球性の著明な脳血流低下を示し、その後典型的なけいれん重積型急性脳症に至った1歳女児

    土屋 弘樹, 井上 拓志, 原 成未, 西村 佑真, 竹内 章人, 塚原 紘平, 山本 浩継, 八代 将登, 佐藤 剛史, 久保 俊英

    脳と発達   50 ( 6 )   444 - 444   2018.11

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  • Early prediction for over two years efficacy of the first biologic agent for polyarticular juvenile idiopathic arthritis

    Tomohiro Kubota,Syuji Takei,Masaki Shimizu,Junko Yasumura,Yasuo Nakagishi,Toshitaka Kizawa,Masato Yashiro*,Hiroyuki Wakiguchi ,Yuichi Yamasaki,Yoshifumi Kawano

    Modern Rheumatology, Japanese Journal of Rheumatology   2018.9

  • Early prediction for over two years efficacy of the first biologic agent for polyarticular juvenile idiopathic arthritis: A multi-institutional study in Japan. Reviewed International journal

    Tomohiro Kubota, Syuji Takei, Masaki Shimizu, Junko Yasumura, Yasuo Nakagishi, Toshitaka Kizawa, Masato Yashiro, Hiroyuki Wakiguchi, Yuichi Yamasaki, Yoshifumi Kawano

    Modern rheumatology   28 ( 5 )   826 - 831   2018.9

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    OBJECTIVE: To estimate target of treatment for long-term efficacy of the first biologic agent used to treat polyarticular juvenile idiopathic arthritis (pJIA). METHODS: A retrospective cohort of patients with pJIA treated at six medical institutions in Japan between 1 March 2005 and 31 October 2014 was identified. The patients were divided by 2-year treatment periods with the first biologic agent into continuous treatment group and switching group. Three markers were examined: matrix metalloproteinase-3 (MMP-3), erythrocyte sedimentation rate (ESR), and disease activity score (DAS) 28-ESR. RESULTS: Thirty-two pJIA patients (8 boys, 24 girls) from 43 recruited patients were included in this study. The treatment periods with the first biologic agent in continuous treatment group (24 patients, 75%) was 40 months (median, range 24-119) and switching group (8 patients; 25%) was 9.5 months (median, 6-18). Markers [odds ratio (95% confidence interval)] at 3 months were MMP-3 [1.02 (0.99-1.05), p = .219], ESR [1.00 (0.78-1.30), p = .998], and DAS28-ESR [13.9 (2.08-409.82), p = .035]. The cut-off point for DAS28-ESR at 3 months to distinguish the two groups was 2.49 (sensitivity, 87.5%; specificity, 87.5%). CONCLUSION: DAS28-ESR of 2.49 at 3 months after initiating the first biologic agent can be a target of sustained treatment in pJIA patients.

    DOI: 10.1080/14397595.2017.1415628

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  • Epidemiology of Pediatric Acute Encephalitis/Encephalopathy in Japan Reviewed

    Shinichiro Goto, Nobuyuki Nosaka, Takashi Yorifuji, Tomoaki Wada, Yosuke Fujii, Masato Yashiro, Yosuke Washio, Kosei Hasegawa, Hirokazu Tsukahara, and Tsuneo Morishima

    Acta Med Okayama   72 ( 4 )   351 - 357   2018.8

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  • Serum Procalcitonin Levels in Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion

    Yosuke Fujii, Masato Yashiro, Mutsuko Yamada, Tomonobu Kikkawa, Nobuyuki Nosaka, Yukie Saito, Kohei Tsukahara, Masanori Ikeda, Tsuneo Morishima, and Hirokazu Tsukahara

    Disease markers   2018.3

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  • Anti-high mobility group box-1 monoclonal antibody treatment of brain edema induced by influenza infection and lipopolysaccharide. Reviewed International journal

    Nobuyuki Nosaka, Kazuki Hatayama, Mutsuko Yamada, Yousuke Fujii, Masato Yashiro, Hidenori Wake, Hirokazu Tsukahara, Masahiro Nishibori, Tsuneo Morishima

    Journal of medical virology   90 ( 7 )   1192 - 1198   2018

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    Encephalopathy is a major cause of influenza-associated child death and severe neurological sequelae in Japan, highlighting the urgent need for new therapeutic strategies. In this study, we evaluated the effects of anti-high mobility group box-1 monoclonal antibody (α-HMGB1) treatment on brain edema induced by influenza A virus (IAV) and lipopolysaccharide in 4-week-old BALB/c female mice. The results showed that administration of 7.5 mg/kg α-HMGB1 1 h after IAV (A/Puerto Rico/8/34) inoculation significantly alleviated brain edema at 48 h after IAV inoculation, as confirmed by the suppression of Evans Blue dye leakage and matrix metallopeptidase-9 mRNA expression in the brain. Moreover, we also observed suppression of oxidative stress and different cytokines in IAV-inoculated mice. The expression of plasminogen activator inhibitor-1 was also attenuated following treatment with α-HMGB1. Notably, α-HMGB1 treatment had no effect on virus propagation in the lung. In summary, anti-HMGB1 treatment may improve the prognosis in cases with influenza-associated encephalopathy by attenuating brain edema and reducing the inflammatory responses induced by HMGB1.

    DOI: 10.1002/jmv.25076

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  • Serum Procalcitonin Levels in Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion. Reviewed International journal

    Yosuke Fujii, Masato Yashiro, Mutsuko Yamada, Tomonobu Kikkawa, Nobuyuki Nosaka, Yukie Saito, Kohei Tsukahara, Masanori Ikeda, Tsuneo Morishima, Hirokazu Tsukahara

    Disease markers   2018   2380179 - 2380179   2018

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    Procalcitonin (PCT) is used as a biomarker in severe infections. Here, we retrospectively investigated levels of serum PCT, C-reactive protein (CRP), and inflammatory cytokines (IL-6, TNF-α, and IFN-γ) in the second phase of patients with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). Nine AESD pediatric patients (4 men, 5 women; AESD group) admitted to Okayama University Hospital from 2010 to 2016 were compared with 10 control patients with febrile seizures (FS) (3 men, 7 women; FS group). Mean PCT concentrations (ng/mL) in the AESD and FS groups were significantly different, at 9.8 ± 6.7 and 0.8 ± 0.9, respectively (p = 0.0011). CRP (mg/dL) were 0.79 ± 0.89 and 1.4 ± 1.0 (p = 0.21), respectively; IL-6 (pg/mL) were 449.7 ± 705.0 and 118.3 ± 145.4 (p = 0.20), respectively; TNF-α (pg/mL) were 18.6 ± 12.5 and 16.6 ± 6.0 (p = 0.67), respectively; and IFN-γ (pg/mL) were 79.6 ± 158.5 and 41.9 ± 63.7 (p = 0.56), respectively. Ratios of PCT to CRP were 27.5 ± 34.2 and 3.2 ± 6.8 (p < 0.0001), respectively. The sensitivity and specificity in the diagnosis of AESD using a cutoff of PCT/CRP ratio of 1.0 were 100% and 80%, respectively. These results suggest that PCT and the PCT/CRP ratio are useful in auxiliary diagnosis of the second stage of AESD, and in AESD, PCT is likely to increase through a different mechanism.

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  • Validation of classification criteria of macrophage activation syndrome in Japanese patients with systemic juvenile idiopathic arthritis. Reviewed

    Shimizu M, Mizuta M, Yasumi T, Iwata N, Okura Y, Kinjo N, Umebayashi H, Kubota T, Nakagishi Y, Nishimura K, Yashiro M, Yasumura J, Yamazaki K, Wakiguchi H, Okamoto N, Mori M.

    Arthritis Care & Research   2017.12

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  • 非もやもや病小児脳梗塞・脳虚血症例の治療におけるチーム医療の重要性 Reviewed

    安原 隆雄, 菱川 朋人, 亀田 雅博, 平松 匡文, 杉生 憲志, 野坂 宜之, 塚原 紘平, 八代 将登, 林 裕美子, 伊達 勲

    脳卒中の外科   45 ( 6 )   476 - 482   2017.11

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    症例1:9歳女児。左片麻痺で発症し、右内包後脚脳梗塞と診断された。aspirin内服を行い、24ヵ月再発なく外来加療中である。症例2:13歳男児。けいれん発作、意識障害、左片麻痺が生じ、動脈炎として加療開始された。右中大脳動脈領域に脳梗塞を認めたため外減圧術を施行したが、第62病日に頭蓋骨形成術を施行後に意識障害が生じ、けいれん重積状態となった。barbitalを用いた2週間にわたる鎮静・呼吸循環管理にて徐々に改善したが、左不全麻痺の悪化、右不全麻痺を生じた。17ヵ月経過現在、両杖をついた歩行訓練を行っている。症例3:10ヵ月女児。左不全片麻痺で発症し、3日後に意識障害が生じた。右側の血栓性脳梗塞と考えaspirin内服を開始したが、脳梗塞の再発、左側に新規の脳梗塞を来たした。warfarinとaspirinの内科加療を開始し、16ヵ月再発なく経過している。症例4:2歳女児。Klippel-Trenaunay症候群として経過観察されていた。繰り返す左片麻痺とけいれん発作が生じ、右内頸動脈の閉塞ないし狭窄に伴う脳虚血と診断し、aspirin内服加療を開始した。16ヵ月間再発なく経過している。

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  • Metabolic pathway catalyzed by Vanin-1 pantetheinase plays a suppressive role in influenza virus replication in human alveolar epithelial A549 cells Reviewed

    Nobuko Yamashita, Masato Yashiro, Hirohito Ogawa, Hikaru Namba, Nobuyuki Nosaka, Yousuke Fujii, Tsuneo Morishima, Hirokazu Tsukahara, Masao Yamada

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   489 ( 4 )   466 - 471   2017.8

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    Our previous analysis of gene expression profiles in the peripheral blood from patients with influenza A (H1N1) pdm09 pneumonia revealed elevated transcription levels of the vanin-1 (vascular non inflammatory molecule 1, VNN1) gene, which encodes an epithelial ectoenzyme with pantetheinase activity involved in recycling coenzyme A. Here, to elucidate the role of VNN1 in influenza A virus (IAV) H1N1 infection, we investigated the change of VNN1 expression in the context of IAV infection and the effects of its related substances, i.e., its direct substrate pantetheine and its two metabolites pantothenic acid and cysteamine on the replication of IAV in the human alveolar epithelial carcinoma cell line A549. The messenger RNA expression of VNN1 in A549 cells was significantly increased (by 4.9-fold) after IAV infection under an elevated concentration of pantetheine. Moreover, VNN1 mRNA levels were elevated by > 100-fold in response to pro-inflammatory cytokines, especially TNF-alpha and IL-1 beta. Pantetheine significantly reduced the IAV replication and IAV Matrix 1 (M1) mRNA levels when it was administered prior to and during infection. In addition, cysteamine treatment during IAV infection significantly reduced the viral replication and IAV M1 mRNA levels, whereas pantothenic acid did not. These findings suggest that the metabolic pathway catalyzed by VNNI pantetheinase plays a suppressive role in IAV infection in the respiratory tract, especially in severe conditions under hypercytokinemia. (C) 2017 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2017.05.172

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  • Local and Systemic Immune Responses to Influenza A Virus Infection in Pneumonia and Encephalitis Mouse Models. Reviewed

    Nagaoka Y, Nosaka N, Yamada M, Yashiro M, Washio Y, Baba K, Morishima T, Tsukahara H.

    Disease Markers   2017.8

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  • EBウイルス感染CD8陽性T細胞増殖で発症し、再燃時に感染B細胞が増殖した血球貪食性リンパ組織球症の1例 Reviewed

    北野 ひとみ, 藤井 洋輔, 野坂 宜之, 八代 将登, 嶋田 明, 塚原 宏一

    小児感染免疫   29 ( 2 )   165 - 170   2017.7

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    EBV関連血球貪食性リンパ組織球症(EBV-HLH)の児で初発時にCD8陽性T細胞に感染していたが、再燃時にB細胞内に増殖を認めた症例を経験したので報告する。症例は2歳の女児であり、発熱と汎血球減少からEBV-HLHと診断された。EBV-DNA量と感染細胞のプロファイリングを行い、診断時にはEBV-DNA量の増加とCD8陽性T細胞への感染を確認した。本児にはHLH-2004プロトコールに準じて治療を開始した。全血EBV-DNA量は一時的に検出感度未満まで低下したが、治療終了直後に再度増加した。感染細胞のプロファイリングによりB細胞内へのEBV感染が疑われた。EBV-HLHの再発例では造血幹細胞移植を行うこともあるが、感染細胞の同定によりB細胞への感染が考えられたためリツキシマブを使用し、EBV-DNA量は速やかに検出感度未満となった。EBV-DNA定量と感染細胞の同定はEBV-HLHの治療方針の決定に有用であると考えられた。(著者抄録)

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  • Intracranial Pressure Monitoring for Pediatric Acute Encephalopathy Reviewed

    Nosaka Nobuyuki, Tsukahara Kohei, Knaup Emily, Yabuuchi Toshihiko, Kikkawa Tomonobu, Fujii Yosuke, Yashiro Masato, Yasuhara Takao, Okada Ayumi, Ugawa Toyomu, Nakao Atsunori, Tsukahara Hirokazu, Date Isao

    Acta Medica Okayama   71 ( 2 )   179 - 180   2017.4

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    DOI: 10.18926/AMO/54987

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  • 長期保存的治療で改善した脊柱矯正固定術後発症の上腸間膜動脈症候群の1例 Reviewed

    籔内 俊彦, 渡邉 宏和, 吉川 知伸, 野坂 宜之, 藤井 洋輔, 八代 将登, 塚原 宏一

    小児科臨床   70 ( 4 )   479 - 484   2017.4

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    上腸間膜動脈症候群(superior mesenteric artery syndrome:SMAS)は、十二指腸の水平脚が上腸間膜動脈(superior mesenteric artery:SMA)と腹部大動脈あるいは椎体にはさまれて圧迫されることにより起こる十二指腸の通過障害の症候群である。保存的治療が第一選択とされ、無効の場合は外科的治療の適応となる。しかし、保存的治療の期間について明確な基準は確立されていない。今回、側彎症に対する脊柱矯正固定術後にSMASを発症し、76日間にわたる保存的治療が有効であった11歳女児の1例を経験した。体重の増加が確認できるならば長期の保存的治療は脊柱矯正固定術後に発症したSMASに有用であると考えられた。(著者抄録)

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  • Recurrent apnea in an infant with pertussis due to household transmission. Reviewed International journal

    Motoharu Ochi, Nobuyuki Nosaka, Emily Knaup, Kohei Tsukahara, Tomonobu Kikkawa, Yousuke Fujii, Masato Yashiro, Keiji Sato, Toyomu Ugawa, Ayumi Okada, Hirokazu Tsukahara

    Clinical case reports   5 ( 3 )   241 - 245   2017.3

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    Bordetella pertussis causes life-threatening apnea in infants. Lymphocytosis is an important clue for diagnosis and for determining the severity of pertussis. Antibiotics do not shorten or ameliorate the disease and only decrease the risk of transmission. Antepartum maternal immunization is important for preventing pertussis in infants.

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  • Recurrent apnea in an infant with pertussis due to household transmission.(共著) Reviewed

    Motoharu Ochi, Nobuyuki Nosaka, Emily Knaup, Kohei Tsukahara, Tomonobu Kikkawa, Yousuke Fujii, Masato Yashiro, Keiji Sato, Toyomu Ugawa, Ayumi Okada & Hirokazu Tsukahara

    Clinical Case Reports   5 ( 3 )   241 - 245   2017.1

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  • Local and Systemic Immune Responses to Influenza A Virus Infection in Pneumonia and Encephalitis Mouse Models. Reviewed International journal

    Yoshiharu Nagaoka, Nobuyuki Nosaka, Mutsuko Yamada, Masato Yashiro, Yosuke Washio, Kenji Baba, Tsuneo Morishima, Hirokazu Tsukahara

    Disease markers   2017   2594231 - 2594231   2017

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    OBJECTIVE: To compare local and systemic profiles between different disease pathologies (pneumonia and encephalitis) induced by influenza A virus (IAV). METHODS: An IAV pneumonia model was created by intranasal inoculation of C57BL/6 mice with influenza A/WSN/33 (H1N1) virus. Lung lavage and blood collection were performed on day 3 after IAV inoculation. Similarly, an IAV encephalitis mouse model was created by direct intracranial IAV inoculation. Cerebrospinal fluid (CSF) and blood collection were conducted according to the same schedule. Cytokine/chemokine profiles were produced for each collected sample. Then the data were compared visually using radar charts. RESULTS: Serum cytokine profiles were similar in pneumonia and encephalitis models, but local responses between the bronchoalveolar lavage fluid (BALF) in the pneumonia model and CSF in the encephalitis model differed. Moreover, to varying degrees, the profiles of local cytokines/chemokines differed from those of serum in both the pneumonia and encephalitis models. CONCLUSION: Investigating local samples such as BALF and CSF is important for evaluating local immune responses, providing insight into pathology at the primary loci of infection. Serum data alone might be insufficient to elucidate local immune responses and might not enable clinicians to devise the most appropriate treatment strategies.

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  • 複数の原因が考えられた乳児期突発性危急事態の1例

    越智 元春, 野坂 宜之, 塚原 紘平, 佐藤 圭路, 鵜川 豊世武, 氏家 良人, 渡邉 宏和, 吉川 知伸, 藤井 洋輔, 八代 将登, 塚原 宏一

    日本小児科学会雑誌   120 ( 7 )   1128 - 1128   2016.7

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  • Letter to the Editor regarding the paper by Sun G et al Reviewed

    Nobuyuki Nosaka*,Kazuki Hatayama,Yousuke Fujii*,Masato Yashiro*,Hirokazu Tsukahara*,Tsuneo Morishima

    Journal of the Neurological Sciences, World neurology   364   2016.5

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    DOI: 10.1016/j.jns.2016.03.038

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  • Anti-high mobility group box-1 monoclonal antibody treatment provides protection against influenza A virus (H1N1)-induced pneumonia in mice. International journal

    Nobuyuki Nosaka, Masato Yashiro, Mutsuko Yamada, Yosuke Fujii, Hirokazu Tsukahara, Keyue Liu, Masahiro Nishibori, Akihiro Matsukawa, Tsuneo Morishima

    Critical care (London, England)   19 ( 1 )   249 - 249   2015.6

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    INTRODUCTION: Provision for the emergence of an influenza pandemic is an urgent issue. The discovery of a novel anti-influenza therapeutic approach would increase the effectiveness of traditional virus-based strategies. This study was undertaken to evaluate the therapeutic effects of anti-high mobility group box-1 (HMGB1) monoclonal antibody (mAb) treatment on influenza A virus (H1N1)-induced pneumonia in mice. METHODS: Nine-week-old male C57BL/6 mice were inoculated with H1N1, then anti-HMGB1 mAb or control mAb were administered intravenously at 1, 24 and 48 hours after H1N1 inoculation and the survival rate was analyzed. Lung lavage and histopathological analysis were performed on days 3, 5, 7 and 10 after inoculation. RESULTS: Anti-HMGB1 mAb significantly improved the survival rate of H1N1-inoculated mice (1 out of 15 versus 8 out of 15 deaths in the anti-HMGB1 mAb-treated group versus the control mAb-treated group, p < 0.01), although the treatment did not affect virus propagation in the lungs. The treatment also significantly attenuated histological changes and neutrophil infiltration in the lungs of H1N1-inoculated mice. This was associated with inhibition of HMGB1 and suppression of inflammatory cytokine/chemokine expression and oxidative stress enhancement, which were observed in H1N1-inoculated mice. The expression of receptor for advanced glycation end products and nuclear factor κB was attenuated by the treatment. CONCLUSIONS: Anti-HMGB1 mAb may provide a novel and effective pharmacological strategy for severe influenza virus infection in humans by reducing the inflammatory responses induced by HMGB1.

    DOI: 10.1186/s13054-015-0983-9

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  • Anti-high mobility group box-1 monoclonal antibody treatment provides protection against influenza A virus (H1N1)-induced pneumonia in mice.(共著) Reviewed

    Crtical Care   2015.6

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  • Gene expression analysis in children with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis(共著) Reviewed

    Tsuge M, Oka T, Yamashita N, Saito Y, Fujii Y, Yashiro M, Tsukahara H, Morishima T.

    Journal of neurovirology   20 ( 1 )   73 - 84   2014.2

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  • Gene expression analysis in children with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. Reviewed International journal

    Mitsuru Tsuge, Takashi Oka, Nobuko Yamashita, Yukie Saito, Yosuke Fujii, Yoshiharu Nagaoka, Masato Yashiro, Hirokazu Tsukahara, Tsuneo Morishima

    Journal of neurovirology   20 ( 1 )   73 - 84   2014.2

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    Viral infections have been implicated as a cause of complex seizures in children. The pathogenic differences in complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis remain unclear. This study analyzed the gene expression profiles in the peripheral whole blood from pediatric patients with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. The gene expression profiles of ten patients (five with seizures and five without) with influenza A(H1N1)pdm09 and six patients (three with seizures and three without) with rotavirus gastroenteritis were examined. Gene expression profiles in the whole blood were different in complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. Transcripts related to the immune response were significantly differentially expressed in complex seizures with influenza A(H1N1)pdm09, and transcripts related to the stress response were significantly differentially expressed in complex seizures with rotavirus gastroenteritis. Pathway analysis showed that the mitogen-activated protein kinases in the T cell receptor signaling pathway were activated in complex seizures due to influenza A(H1N1)pdm09. Dysregulation of the genes related to immune response or stress response could contribute to the pathogenic differences of the complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis.

    DOI: 10.1007/s13365-013-0231-5

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  • Somatic NLRP3 mosaicism in Muckle-Wells syndrome. A genetic mechanism shared by different phenotypes of cryopyrin-associated periodic syndromes. Reviewed International journal

    Kenji Nakagawa, Eva Gonzalez-Roca, Alejandro Souto, Toshinao Kawai, Hiroaki Umebayashi, Josep María Campistol, Jeronima Cañellas, Syuji Takei, Norimoto Kobayashi, Jose Luis Callejas-Rubio, Norberto Ortego-Centeno, Estíbaliz Ruiz-Ortiz, Fina Rius, Jordi Anton, Estibaliz Iglesias, Santiago Jimenez-Treviño, Carmen Vargas, Julian Fernandez-Martin, Inmaculada Calvo, José Hernández-Rodríguez, María Mendez, María Teresa Dordal, Maria Basagaña, Segundo Bujan, Masato Yashiro, Tetsuo Kubota, Ryuji Koike, Naoko Akuta, Kumiko Shimoyama, Naomi Iwata, Megumu K Saito, Osamu Ohara, Naotomo Kambe, Takahiro Yasumi, Kazushi Izawa, Tomoki Kawai, Toshio Heike, Jordi Yagüe, Ryuta Nishikomori, Juan I Aróstegui

    Annals of the rheumatic diseases   74 ( 3 )   603 - 10   2013.12

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    UNLABELLED: : Familial cold autoinflammatory syndrome, Muckle-Wells syndrome (MWS), and chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome are dominantly inherited autoinflammatory diseases associated to gain-of-function NLRP3 mutations and included in the cryopyrin-associated periodic syndromes (CAPS). A variable degree of somatic NLRP3 mosaicism has been detected in ≈35% of patients with CINCA. However, no data are currently available regarding the relevance of this mechanism in other CAPS phenotypes. OBJECTIVE: To evaluate somatic NLRP3 mosaicism as the disease-causing mechanism in patients with clinical CAPS phenotypes other than CINCA and NLRP3 mutation-negative. METHODS: NLRP3 analyses were performed by Sanger sequencing and by massively parallel sequencing. Apoptosis-associated Speck-like protein containing a CARD (ASC)-dependent nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB) activation and transfection-induced THP-1 cell death assays determined the functional consequences of the detected variants. RESULTS: A variable degree (5.5-34.9%) of somatic NLRP3 mosaicism was detected in 12.5% of enrolled patients, all of them with a MWS phenotype. Six different missense variants, three novel (p.D303A, p.K355T and p.L411F), were identified. Bioinformatics and functional analyses confirmed that they were disease-causing, gain-of-function NLRP3 mutations. All patients treated with anti-interleukin1 drugs showed long-lasting positive responses. CONCLUSIONS: We herein show somatic NLRP3 mosaicism underlying MWS, probably representing a shared genetic mechanism in CAPS not restricted to CINCA syndrome. The data here described allowed definitive diagnoses of these patients, which had serious implications for gaining access to anti-interleukin 1 treatments under legal indication and for genetic counselling. The detection of somatic mosaicism is difficult when using conventional methods. Potential candidates should benefit from the use of modern genetic tools.

    DOI: 10.1136/annrheumdis-2013-204361

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  • Pathogenic mechanisms of influenza A(H1N1)pdm09 infection elucidated on gene expression profiling.(共著) Reviewed

    Yamashita N, Tsukahara H, Tsuge M, Nagaoka Y, Yashiro M, Saito Y, Fujii Y, Oka T, Morishima T.

    Pediatrics international   55 ( 5 )   572 - 577   2013.10

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  • Pathogenic mechanisms of influenza A(H1N1)pdm09 infection elucidated on gene expression profiling. Reviewed International journal

    Nobuko Yamashita, Hirokazu Tsukahara, Mitsuru Tsuge, Yoshiharu Nagaoka, Masato Yashiro, Yukie Saito, Yosuke Fujii, Takashi Oka, Tsuneo Morishima

    Pediatrics international : official journal of the Japan Pediatric Society   55 ( 5 )   572 - 7   2013.10

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    BACKGROUND: The pathogenic mechanisms underlying influenza A(H1N1)pdm09-associated central nervous system (CNS) manifestations and pneumonia remain unclear. This study examined A(H1N1)pdm09 host responses using gene expression profiles of patients' peripheral blood. METHODS: Sixteen A(H1N1)pdm09-infected children in three groups were examined: a CNS group, with convulsion and altered consciousness (n = 6); a pneumonia (Pneu) group (n = 5); and a group of infected control patients (n = 5). The signal ratios of the acute to recovery phases in CNS or Pneu were analyzed versus those of the control. RESULTS: The CNS (619 transcripts) and Pneu (656 transcripts) groups had significantly increased signal ratios compared to the control group. Regarding the increased ratios of transcripts shown by multiple probes, contactin-associated protein-like 3 transcripts, oleoyl-ACP hydrolase transcripts, and interleukin 1 type 1 receptor were observed in CNS and Pneu. Increased ratios of prostaglandin-endoperoxide synthase 2 and α-synuclein were characteristic of CNS. Alkaline phosphatase and the Fc fragment of IgA receptor were characteristic of Pneu. Regarding enriched gene ontology terms, 'response to lipopolysaccharide', 'innate immune response', and 'intrinsic to membrane' were observed commonly in CNS and Pneu. Enriched gene ontology terms related to 'hemoglobin' and 'hemostasis' were, respectively, characteristic of CNS and Pneu. CONCLUSION: These symptom-associated transcripts might be some clues to the pathogenesis of the A(H1N1)pdm09 infection.

    DOI: 10.1111/ped.12139

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  • Prognostic value of brain injury biomarkers in acute encephalitis/encephalopathy.(共著) Reviewed

    Tsukahara H, Fujii Y, Matsubara K, Yamada M, Nagaoka Y, Saito Y, Yashiro M, Tsuge M, Goto S, Kitamura T, Hata A, Ichiyama T, Morishima T.

    Pediatrics international   55 ( 4 )   461 - 464   2013.8

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  • Prognostic value of brain injury biomarkers in acute encephalitis/encephalopathy. International journal

    Hirokazu Tsukahara, Yosuke Fujii, Kousaku Matsubara, Mutsuko Yamada, Yoshiharu Nagaoka, Yukie Saito, Masato Yashiro, Mitsuru Tsuge, Shinichiro Goto, Tetsuro Kitamura, Atsuko Hata, Takashi Ichiyama, Tsuneo Morishima

    Pediatrics international : official journal of the Japan Pediatric Society   55 ( 4 )   461 - 4   2013.8

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    BACKGROUND: Acute encephalitis/encephalopathy (AEE) is a devastating cause of severe neurodevelopmental sequelae or death in children. Assessing ongoing brain injury and predicting outcomes using bedside point-of-care testing is expected to be extremely valuable. METHODS: For this study, three brain injury markers, S-100B, glial fibrillary acidic protein (GFAP), and tau protein, were measured in early cerebrospinal fluid samples of children with AEE. Subjects comprised three groups: Group 1 (non-AEE control, n = 27); Group 2 (AEE with normal resolution or mild sequelae, n = 13); and Group 3 (AEE with severe sequelae or death, i.e. "poor outcome," n = 10). RESULTS: All marker levels were significantly higher in Group 3 than in Group 1 or 2. In Group 3, only S-100B was significantly higher in non-survivors than in survivors. For scoring assessment (range: 0-3 points), the predictive accuracies of 3 points for poor outcomes in children with AEE (i.e. Group 2 and 3, n = 23) were 91% (21/23) for S-100B, 74% (17/23) for GFAP, and 78% (18/23) for tau. When the scores were summed up for S-100B, GFAP, and tau (range: 0-9 points), and for S-100B and tau (range: 0-6 points), the patients with poor outcomes were identified more accurately using the respective thresholds of 6 points and 4 points (96% [22/23] and 100% [23/23], respectively). CONCLUSION: Our findings suggest that combined measurement and scoring assessment of the markers, especially S-100B and tau, show promise as predictors of clinical outcomes in children with AEE.

    DOI: 10.1111/ped.12094

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  • Redox-Active Protein Thioredoxin-1 Administration Ameliorates Influenza A Virus (H1N1)-Induced Acute Lung Injury in Mice Reviewed

    Yashiro Masato, Tsukahara Hirokazu, Matsukawa Akihiro, Yamada Mutsuko, Fujii Yosuke, Nagaoka Yoshiharu, Tsuge Mitsuru, Yamashita Nobuko, Ito Toshihiro, Yamada Masao, Masutani Hiroshi

    Critical Care Medicine   41 ( 1 )   171 - 181   2013.1

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    DOI: 10.1097/CCM.0b013e3182676352

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  • Therapeutic effects of redox-active protein thioredoxin(TRX)-1 in influenza-virus-induced pneumonia in mice

    YASHIRO MASATO, TSUKAHARA HIROKAZU, MATSUKAWA AKIHIRO, YAMADA MUTSUKO, FUJII YOSUKE, NAGAOKA YOSHIHARU, TSUGE MITSURU, YAMASHITA NOBUKO, ITO TOSHIHIRO, YAMADA MASAO, MASUTANI HIROSHI, YODOI JUNJI, MORISHIMA TSUNEO

    岡山医学会雑誌   125 ( 2 )   109-112 (J-STAGE)   2013

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  • Tumor necrosis factor-α can induce Langhans-type multinucleated giant cell formation derived from myeloid dendritic cells Reviewed

    YASUI Kozo, YASHIRO Masato, TSUGE Mitsuru, KONDO Yohichi, SAITO Yukie, NAGAOKA Yoshiharu, YAMASHITA Nobuko, MORISHIMA Tsuneo

    Microbiology and immunology   55 ( 11 )   809 - 816   2011.11

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    Other Link: http://search.jamas.or.jp/link/ui/2012230447

  • 抗TNF-α製剤による結核発症メカニズムに関する検討

    安井 耕三, 近藤 陽一, 山下 信子, 長岡 義晴, 齊藤 有希惠, 八代 将登, 津下 充, 森島 恒雄

    日本臨床免疫学会総会抄録集   39 ( 0 )   128 - 128   2011

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    生物学的製剤の治療導入により、リウマチ疾患群の治療予後は劇的に改善した。一方それに伴う副作用が問題となっている。なかでもinfliximab投与による結核発症の増加が関心を集めている。単球は種々のサイトカイン刺激によりマクロファージ・樹状細胞・破骨細胞・多核球に分化する。なかでもTNF-αはマクロファージ活性化や肉芽腫・多核巨細胞(Langhans-type)形成といった結核菌に対する単球の免疫防御発現にとって不可欠なサイトカインとされている。[目的]肉芽腫病変における多核巨細胞(MNGC; Langhans-type)への分化誘導のメカニズムの検討を行うことにより、生物学的製剤による結核発症のメカニズムの検討を行った。[方法]末梢血から単球を90%以上の純度で単離。GM-CSF(20ng/mL)・TNF-α(20ng/mL)・IL-4存在下に21日間培養。細胞分析プログラムを用いて多核細胞について形態および機能解析を行った。[結果]GM-CSF+IL-4は樹状細胞にさらにTNF-α刺激が単球を有効に集簇させ多核巨細胞へと分化させた。巨細胞はFAK・Rhoキナーゼの阻害により、細胞癒合が阻止された。また巨細胞形成は、抗TNF-α中和抗体により強力に抑制されたが、TNF-αRIIに対する抗体では影響が無かった。[結論]Langhans巨細胞形成とその維持は細胞内寄生菌である結核菌の免疫防御に重要であり、この機能低下が結核発症(潜在性感染の顕性化)に関与すると推察された。Etanercept/Tocilizmabでは細胞分化への影響は乏しく、結核発症率には影響が少ないと考えられた。各生物学的製剤使用中の結核発症症例数と併せ報告する。

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  • Increase of tumor necrosis factor-alpha in the blood induces early activation of matrix metalloproteinase-9 in the brain. Reviewed International journal

    Mitsuru Tsuge, Kozo Yasui, Takashi Ichiyawa, Yukie Saito, Yoshiharu Nagaoka, Masato Yashiro, Nobuko Yamashita, Tsuneo Morishima

    Microbiology and immunology   54 ( 7 )   417 - 24   2010.7

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    Increases of cytokine in the blood play important roles in the pathogenesis of influenza-associated encephalopathy. TNF-alpha was administered intravenously to wild-type mice, after which blood, CSF and brain tissue were obtained, and changes in BBB permeability, the amounts of MMP-9 and TIMP-1, and the localization of activated MMP were assessed. There was a significant increase in BBB permeability after 6 and 12 hr. MMP-9 was increased after 3 hr in the brain and cerebrospinal fluid, which was earlier than in the serum. TIMP-1 protein in the brain increased significantly after MMP-9 had increased. Activation of MMP-9 was observed in neurons in the cerebral cortex and hippocampus, and in vascular endothelial cells. These findings suggest that an increase in blood TNF-alpha promotes activation of MMP-9 in the brain, and may also induce an increase in permeability of the BBB. Early activation of MMP-9 in the brain may contribute to an early onset of neurological disorders and brain edema prior to multiple organ failure in those inflammatory diseases associated with highly increased concentrations of TNF-alpha in the blood, such as sepsis, burns, trauma and influenza-associated encephalopathy.

    DOI: 10.1111/j.1348-0421.2010.00226.x

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  • Thalidomide dramatically improves the symptoms of early-onset sarcoidosis/Blau syndrome: its possible action and mechanism. Reviewed International journal

    Kozo Yasui, Masato Yashiro, Mitsuru Tsuge, Akira Manki, Kei Takemoto, Michiko Yamamoto, Tsuneo Morishima

    Arthritis and rheumatism   62 ( 1 )   250 - 7   2010.1

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    OBJECTIVE: Early-onset sarcoidosis (EOS), which occurs in children younger than 5 years of age, is associated with granulomatous lesions and a sporadic genetic mutation of the nucleotide-binding oligomerization domain 2 that causes constitutive NF-kappaB activation. The symptoms of EOS can be uncontrollable, progressive, and associated with profound complications. However, appropriate therapy is still under investigation. The aim of this study was to assess the efficacy of thalidomide in patients with severe EOS, based on etiology supporting an initial role of NF-kappaB in activation of this disease. METHODS: Thalidomide was given to 2 patients with EOS (a 16-year-old girl and an 8-year-old boy) at an initial dosage of 2 mg/kg/day, and the dosage was increased if necessary. To elucidate the mechanism of the drug, peripheral blood monocytes were isolated from the patients and stimulated with cytokines (macrophage colony-stimulating factor, tumor necrosis factor alpha, and interleukin-4), and their ability to form multinucleated giant cells (MGCs) and osteoclasts was measured. RESULTS: Both patients showed dramatic improvement of their clinical symptoms (alleviation of fever and optic nerve papillitis, achievement of a response according to the American College of Rheumatology Pediatric 50 and Pediatric 70 criteria) and laboratory findings. Monocytes from patients with EOS had a greater ability to survive and induce MGCs and osteoclasts than those from healthy control subjects. The formation of MGCs and osteoclasts was inhibited by the presence of thalidomide. CONCLUSION: The ability of thalidomide to improve clinical symptoms and laboratory findings in patients with EOS indicates a central role for NF-kappaB activity in this disorder. Inhibition of IKK might be a pharmacologic action by which thalidomide down-regulates NF-kappaB signaling. Thalidomide may be an effective medication in patients with severe complications of EOS, including ocular involvement.

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Books

  • 若年性特発性関節炎 カナキヌマブ治療の理論と実際 Reviewed

    森雅亮 武井修治( Role: Joint author ,  第2章 症例報告(経過良好))

    メディカルレビュー社  2021.4 

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    Total pages:107   Responsible for pages:2   Language:Japanese

  • 関節リウマチ診療ガイドライン2020

    一般社団法人 日本リウマチ学会(第4章 多様な患者背景に対応するために 関節型若年性特発性関節炎の成人移行期診療)

    診断と治療社  2021.4 

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  • 小児非感染性ぶどう膜炎初期診療の手引き

    一般社団法人 日本リウマチ学会 小児リウマチ調査検討小委員会 ぶどう膜炎ワーキンググループ( Role: Joint author ,  小児非感染性ぶどう膜炎の治療)

    羊土社  2020.12 

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  • JIAにおける生物学的製剤使用の手引き(2020年度版)

    森雅亮、梅林宏明ほか( Role: Joint author)

    羊土社  2020.6 

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  • 成人診療科医のための小児リウマチ性疾患移行支援ガイド

    森雅亮、梅林宏明ほか( Role: Joint author)

    羊土社  2020.6 

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  • 小児リウマチ学

    伊藤秀一 、森雅亮( Role: Joint author ,  第Ⅴ部 自己炎症性症候群 5. TNF受容体関連周期性症候群(TRAPS))

    朝倉書店  2020.5 

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  • 小児救命救急・ICUピックアップ 神経集中治療

    日本小児集中治療研究会、塚原紘平( Role: Joint author ,  pro-con:ステロイドパルス療法(pro))

    メディカル・サイエンス・インターナショナル  2019.12 

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  • レドックスUPDATE

    淀井淳司、平家俊男( Role: Joint author ,  インフルエンザ急性肺障害におけるチオレドキシン(TRX-1)の役割)

    医歯薬出版株式会社  2015.7 

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  • アクチュアル 脳・神経疾患の臨床 神経感染症を極める(インフルエンザ脳症)

    八代将登、森島恒雄( Role: Joint author)

    中山書店  2014.12 

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  • Oxidative Stress in Applied Basic Research and Clinical Practice Studies on Pediatric Disorders

    Hirokazu Tsukahara, Kazunari Kaneko

    2014.1 

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  • Oxidative Stress in Applied Basic Research and Clinical Practice Studies on Pediatric Disorders

    Hirokazu Tsukahara, Kazunari Kaneko( Role: Joint author ,  Thioredoxin Therapy: Challenges in Translational Research)

    Springer Link  2014.1 

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  • Oxidative Stress in Applied Basic Research and Clinical Practice

    Masato Yashiro, Hirokazu Tsukahara, Tsuneo Morishima( Role: Joint author)

    Springer Link  2014.1 

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  • 気管支肺胞洗浄により診断しえた特発性肺ヘモジデローシスの一例

    福田 花奈, 茂原 研司, 宇田 和宏, 斎藤 有希惠, 津下 充, 八代 将登, 塚原 宏一

    日本小児リウマチ学会総会・学術集会プログラム・抄録集   31回   143 - 143   2022.10

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  • 頸部痛を契機に腸管嚢胞様気腫症が判明したSLEの1例

    八代 将登, 茂原 研司, 宇田 和宏, 斎藤 有希惠, 津下 充, 塚原 宏一

    日本小児リウマチ学会総会・学術集会プログラム・抄録集   31回   163 - 163   2022.10

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  • 気管支肺胞洗浄により診断しえた特発性肺ヘモジデローシスの一例

    福田 花奈, 茂原 研司, 宇田 和宏, 斎藤 有希惠, 津下 充, 八代 将登, 塚原 宏一

    日本小児リウマチ学会総会・学術集会プログラム・抄録集   31回   143 - 143   2022.10

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  • 頸部痛を契機に腸管嚢胞様気腫症が判明したSLEの1例

    八代 将登, 茂原 研司, 宇田 和宏, 斎藤 有希惠, 津下 充, 塚原 宏一

    日本小児リウマチ学会総会・学術集会プログラム・抄録集   31回   163 - 163   2022.10

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  • 水疱性類天疱瘡に合併した偽性低アルドステロン症の乳児例

    宮原 宏幸, 村上 美智子, 二川 奈都子, 長谷川 高誠, 茂原 研司, 宇田 和宏, 津下 充, 八代 将登, 平井 陽至, 森実 真, 塚原 宏一

    日本小児科学会雑誌   126 ( 4 )   728 - 728   2022.4

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  • コロナ禍における鼻腔検体採取方法に関する検討

    八代 将登, 茂原 研司, 宇田 和宏, 斎藤 有希惠, 津下 充, 塚原 宏一

    日本小児感染症学会総会・学術集会プログラム・抄録集   53回   166 - 166   2021.10

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  • コロナ禍における鼻腔検体採取方法に関する検討

    八代 将登, 茂原 研司, 宇田 和宏, 斎藤 有希惠, 津下 充, 塚原 宏一

    日本小児感染症学会総会・学術集会プログラム・抄録集   53回   166 - 166   2021.10

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  • 医学部学生に対する予防接種記録の判定方法に関する検討

    八代 将登, 茂原 研司, 宇田 和宏, 塚原 宏一

    日本環境感染学会総会プログラム・抄録集   36回   253 - 253   2021.9

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  • 経口負荷経験で診断に至った食用クラゲアレルギーの1小児例

    津下 充, 茂原 研司, 宇田 和宏, 斎藤 有希惠, 八代 将登, 池田 政憲, 塚原 宏一

    日本小児アレルギー学会誌   35 ( 4 )   385 - 385   2021.9

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  • 医学部学生に対する予防接種記録判定方法の現状と問題点

    茂原 研司, 八代 将登, 宇田 和宏, 塚原 宏一

    日本環境感染学会総会プログラム・抄録集   36回   253 - 253   2021.9

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  • 経口負荷経験で診断に至った食用クラゲアレルギーの1小児例

    津下 充, 茂原 研司, 宇田 和宏, 斎藤 有希惠, 八代 将登, 池田 政憲, 塚原 宏一

    日本小児アレルギー学会誌   35 ( 4 )   385 - 385   2021.9

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  • 食物アレルゲン 経口負荷試験で診断に至った食用クラゲアレルギーの1小児例

    津下 充, 茂原 研司, 斎藤 有希恵, 八代 将登, 池田 政憲, 塚原 宏一

    アレルギー   70 ( 6-7 )   788 - 788   2021.8

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  • 重症神経疾患の病原体同定のための検体採取の実態解明

    八代 将登, 多屋 馨子, 茂原 研司, 津下 充, 塚原 宏一

    感染症学雑誌   95 ( 臨増 )   275 - 275   2021.4

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  • 心因性腹痛が疑われた小児好酸球性消化管疾患の1例

    國近 公介, 吉川 知伸, 宮原 大輔, 藤井 洋輔, 藤井 智香子, 八代 将登, 岡田 あゆみ, 塚原 宏一

    子どもの心とからだ   29 ( 3 )   281 - 285   2020.11

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    好酸球性消化管疾患は慢性の嘔吐や腹痛の原因となり、内視鏡検査所見で非特異的な所見を呈する症例や肉眼的な異常を呈さない症例では診断が難しい場合がある。今回、慢性の嘔吐・腹痛があり、心因性の腹痛と考えられていたが、アレルギー素因があることから好酸球性消化管疾患が疑われ、上部消化管内視鏡検査で粘膜生検をすることで、好酸球性消化管疾患と診断することができた症例を経験した。プロトンポンプ阻害薬およびロイコトリエン受容体拮抗薬による治療を開始し、症状の改善を認めた。慢性の消化器症状を有する患者でアレルギー素因がある場合には、好酸球性消化管疾患を鑑別に加える必要があると考えられた。(著者抄録)

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  • インフルエンザA(H1N1)pdm09による急性呼吸窮迫症候群に対して体外式膜型人工肺とペラミビル・バロキサビルマルボキシル併用療法で改善した一例

    津下 充, 茂原 研司, 斎藤 有希惠, 八代 将登, 塚原 宏一

    日本小児感染症学会総会・学術集会プログラム・抄録集   52回   206 - 206   2020.11

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  • 重症食物アレルギーにおける腸管上皮バリアに関連した血清バイオマーカーの検討

    津下 充, 茂原 研司, 斎藤 有希惠, 八代 将登, 池田 政憲, 塚原 宏一

    アレルギー   69 ( 臨時増刊号 )   290 - 290   2020.10

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  • 重症食物アレルギーにおける腸管上皮バリアに関連した血清バイオマーカーの検討

    津下 充, 茂原 研司, 斎藤 有希惠, 八代 将登, 池田 政憲, 塚原 宏一

    アレルギー   69 ( 臨時増刊号 )   290 - 290   2020.10

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  • 重症食物アレルギーにおける腸管上皮バリアに関連した血清バイオマーカーの検討

    津下 充, 茂原 研司, 斎藤 有希惠, 八代 将登, 池田 政憲, 塚原 宏一

    日本小児アレルギー学会誌   34 ( 4 )   484 - 484   2020.9

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  • 緊張性胸水症を呈した劇症型A群溶血性レンサ球菌の症例

    塚原 紘平, 山本 浩継, 尾迫 貴章, 中尾 篤典, 斎藤 有希惠, 茂原 研司, 八代 将登, 津下 充, 納所 洋, 谷本 光隆, 福田 花奈, 井上 勝

    日本小児科学会雑誌   124 ( 8 )   1298 - 1298   2020.8

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  • 小児リウマチ性疾患における酸化ストレスマーカーの有用性について

    八代 将登, 茂原 研司, 斎藤 有希惠, 藤井 洋輔, 津下 充, 池田 政憲, 塚原 宏一

    岡山医学会雑誌   132 ( 1 )   47 - 47   2020.4

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  • AFP症例の病原体診断には「周到な準備」と「現場の連携」が不可欠である-非流行期に診断されたEV-D68関連AFM症例の検討から-

    八代将登

    IASR   41   29 - 30   2020.2

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  • 肺血管内皮細胞を用いたインフルエンザ重症肺炎モデルの構築とhigh mobility group box 1抗体による肺血管透過性亢進の抑制効果

    難波 貴弘, 津下 充, 西堀 正洋, 斎藤 有希恵, 八代 将登, 塚原 宏一, 森島 恒雄

    日本小児感染症学会総会・学術集会プログラム・抄録集   51回   133 - 133   2019.10

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  • エトスクシミドにより誘発された膠原病類似疾患の検討

    茂原 研司, 八代 将登, 斎藤 有希惠, 津下 充, 塚原 宏一

    日本小児リウマチ学会総会・学術集会プログラム・抄録集   29回   88 - 88   2019.10

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  • 難治性真菌感染症、慢性心不全、慢性腎不全を有する児に発症した関節型若年性特発性関節炎に対する治療アプローチ

    八代 将登, 茂原 研司, 藤井 洋輔, 斎藤 有希惠, 津下 充, 塚原 宏一

    日本小児リウマチ学会総会・学術集会プログラム・抄録集   29回   114 - 114   2019.10

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  • ヒト脳血管内皮細胞を用いた高サイトカイン血症モデルにおけるhigh mobility group box 1抗体の血管透過性抑制効果

    津下 充, 難波 貴弘, 西堀 正洋, 斎藤 有希恵, 八代 将登, 塚原 宏一, 森島 恒雄

    日本小児感染症学会総会・学術集会プログラム・抄録集   51回   200 - 200   2019.10

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  • 小児重症喘息に対するオマリズマブの有効性と効果予測因子の探索

    津下 充, 茂原 研司, 齋藤 有希惠, 八代 将登, 池田 政憲, 塚原 宏一

    日本小児アレルギー学会誌   33 ( 4 )   538 - 538   2019.10

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  • 小児気管支喘息の治療・管理 小児重症喘息に対するオマリズマブの有効性と効果予測因子の探索

    津下 充, 茂原 研司, 斎藤 有希惠, 八代 将登, 池田 政憲

    アレルギー   68 ( 4-5 )   495 - 495   2019.5

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  • 当院におけるダニ舌下免疫療法と緩徐増量による副作用軽減の試み

    藤井 洋輔, 占部 智子, 板野 稔子, 茂原 研司, 齋藤 有希惠, 津下 充, 八代 将登, 池田 政憲, 塚原 宏一

    日本小児アレルギー学会誌   33 ( 4 )   620 - 620   2019

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  • 若年性特発性関節炎に対するアバタセプト治療の手引き

    木澤敏毅, 謝花幸祐, 井上なつみ, 大倉有加, 岡本奈美, 久保田知洋, 清水正樹, 中岸保夫, 西村謙一, 水田麻雄, 八代将登, 八角高裕, 安村純子, 山出晶子, 脇口宏之, 梅林宏明, 森雅亮

    小児リウマチ   9 ( 1 )   81‐87 - 87   2018.11

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  • 病原体検索のための急性期検体採取に対する当院の取り組み

    八代 将登, 茂原 研司, 斎藤 有希惠, 藤井 洋輔, 津下 充, 塚原 宏一

    日本小児感染症学会総会・学術集会プログラム・抄録集   50回   162 - 162   2018.11

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  • 病原体検索のための急性期検体採取に対する当院の取り組み

    八代 将登, 茂原 研司, 斎藤 有希惠, 藤井 洋輔, 津下 充, 塚原 宏一

    日本小児感染症学会総会・学術集会プログラム・抄録集   50回   162 - 162   2018.11

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  • 当院における散布疹を伴う帯状疱疹への感染防止策について

    橋本 倫子, 森田 幸子, 大野 貴司, 宮村 純子, 三宅 智子, 八代 将登, 塚原 宏一

    医療の質・安全学会誌   13 ( Suppl. )   450 - 450   2018.10

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  • 骨生検で診断し得たCRMOの男児例

    茂原 研司, 八代 将登, 二川 奈都子, 斎藤 有希惠, 藤井 洋輔, 津下 充, 池田 政憲, 塚原 宏一, 喜多村 哲朗

    日本小児リウマチ学会総会・学術集会プログラム・抄録集   28回   100 - 100   2018.10

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  • 先天性心疾患に合併した肺性肥大性骨関節症の1例

    八代 将登, 茂原 研司, 藤井 洋輔, 斎藤 有希惠, 津下 充, 塚原 宏一

    日本小児リウマチ学会総会・学術集会プログラム・抄録集   28回   109 - 109   2018.10

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  • 食物アレルギーと診断されることに伴う経済負担についての研究

    吉川 知伸, 三橋 利晴, 籔内 俊彦, 斎藤 有希惠, 藤井 洋輔, 津下 充, 八代 将登, 池田 政憲, 塚原 宏一

    日本小児アレルギー学会誌   32 ( 3 )   607 - 607   2018.8

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  • 気管支喘息病態・治療 エンテロウイルスD68感染症における小児アレルギー医の役割

    八代 将登, 茂原 研司, 斎藤 有希惠, 藤井 洋輔, 津下 充, 塚原 宏一, 池田 政憲, 多屋 馨子

    日本小児アレルギー学会誌   32 ( 3 )   512 - 512   2018.8

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  • 福山市小学生における食物アレルギー縦断調査から見た学童期の自然歴

    藤井 洋輔, 池田 政憲, 茂原 研司, 斎藤 有希惠, 津下 充, 八代 将登, 塚原 宏一

    日本小児アレルギー学会誌   32 ( 3 )   605 - 605   2018.8

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  • 食物アレルギーと診断されることに伴う経済負担についての研究

    吉川 知伸, 三橋 利晴, 籔内 俊彦, 斎藤 有希惠, 藤井 洋輔, 津下 充, 八代 将登, 池田 政憲, 塚原 宏一

    日本小児アレルギー学会誌   32 ( 3 )   607 - 607   2018.8

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  • オマリズマブからメポリズマブに変更し、呼吸症状の改善を認めた11歳男児の1例

    津下 充, 茂原 研司, 斎藤 有希惠, 八代 将登, 池田 政憲

    日本小児アレルギー学会誌   32 ( 3 )   533 - 533   2018.8

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  • 学童期における食物アレルギーの動向と果物アレルギーの増加 福山市と岡山市の比較

    斎藤 有希惠, 藤井 洋輔, 茂原 研司, 津下 充, 八代 将登, 塚原 宏一, 池田 政憲

    日本小児アレルギー学会誌   32 ( 3 )   604 - 604   2018.8

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  • Validation of 2016 ACR/EULAR Classification Criteria of Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis in Japanese Patients

    Masaki Shimizu, Mao Mizuta, Takahiro Yasumi, Naomi Iwata, Yuka Okura, Noriko Kinjo, Hiroaki Umebayashi, Tomohiro Kubota, Yasuo Nakagishi, Kenichi Nishimura, Masato Yashiro, Junko Yasumura, Kazuko Yamazaki, Hiroyuki Wakiguchi, Nami Okamoto, Masaaki Mori

    ARTHRITIS & RHEUMATOLOGY   69   2017.10

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  • 当科における過去10年のリアルタイムPCR法を用いたヘルペスウイルス感染症診断と病態解析

    八代 将登, 山田 陸子, 吉川 知伸, 野坂 宜之, 藤井 洋輔, 山下 信子, 塚原 宏一, 森島 恒雄

    日本小児科学会雑誌   120 ( 6 )   1034 - 1034   2016.6

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  • 中国四国地区における急性弛緩性麻痺を認める症例の網羅的調査

    八代 将登, 藤井 洋輔, 山下 信子, 塚原 宏一, 多屋 馨子, 森島 恒雄

    臨床とウイルス   44 ( 2 )   S61 - S61   2016.5

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  • 若年性特発性関節炎に対する生物学的製剤の効用と断薬を含めた予後に関する考察

    安井 耕三, 八代 将登, 津下 充, 山下 信子, 長岡 義晴

    日本小児リウマチ学会総会・学術集会プログラム・抄録集   25回   108 - 108   2015.10

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  • レドックス制御蛋白チオレドキシン(TRX)のインフルエンザ肺炎における治療的効果

    八代 将登, 野坂 宜之, 藤井 洋輔, 斎藤 有希惠, 山下 信子, 山田 雅夫, 塚原 宏一, 森島 恒雄

    臨床とウイルス   43 ( 2 )   S80 - S80   2015.5

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  • 結核免疫から考える生物学的製剤使用上の留意点

    安井 耕三, 八代 将登, 津下 充, 近藤 陽一

    日本小児リウマチ学会総会・学術集会プログラム・抄録集   24回   89 - 89   2014.10

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  • 急性脳症患者におけるCOX-2のDNAメチル化の関与

    藤井 洋輔, 齋藤 有希惠, 野坂 宜之, 八代 将登, 山下 信子, 塚原 宏一, 森島 恒雄

    日本小児科学会雑誌   118 ( 2 )   269 - 269   2014.2

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  • 岡山大学小児科関連施設における急性脳症66例の検討

    藤井 洋輔, 山田 睦子, 斎藤 有希恵, 野坂 宣之, 八代 将登, 後藤 振一郎, 長岡 義晴, 津下 充, 山下 信子, 塚原 宏一, 森島 恒雄

    小児感染免疫   26 ( 2 )   343 - 344   2014

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  • インフルエンザ感染における局所サイトカイン・ケモカインの動態

    藤井洋輔, 齋藤有希恵, 長岡義晴, 津下充, 八代将登, 塚原宏一, 森島恒雄

    日本小児科学会雑誌   117 ( 2 )   362 - 362   2013

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  • タクロリムスにより寛解導入を行った潰瘍性大腸炎の小児例

    藤井 洋輔, 小寺 亜矢, 長岡 義晴, 八代 将登, 山下 信子, 塚原 宏一, 森島 恒雄, 平岡 佐規子, 加藤 順

    小児科臨床   65 ( 6 )   1183 - 1188   2012.6

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    症例は14歳女児。発熱、腹痛、下痢で発症し、入院後の大腸内視鏡検査で潰瘍性大腸炎(ulcerative colitis:以下UC)と診断された。全大腸炎型UCであり、臨床的重症度分類では中等症であった。プレドニゾロン、5-アミノサリチル酸製剤により寛解導入を試みたが、治療中に重症化したため、経口タクロリムス療法を併用した。治療開始5日目ころから血便、腹痛が改善し、寛解に導入できた。タクロリムス使用中重大な副作用は認められなかった。また、経過中に酸化ストレスの指標である血清総ハイドロペルオキシド濃度を計測した。その値は病勢に一致して変動しており、UCの病態生理に酸化ストレス亢進が関与することが示唆された。タクロリムスは近年内科領域で難治性のUCに対し使用され、効果をあげている。今後、小児のUCに対する有効な治療選択の1つとして期待される。(著者抄録)

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  • インフルエンザ感染におけるThioredoxin binding protein 2(TBP-2)の役割

    八代 将登, 山田 睦子, 藤井 洋輔, 斉藤 有希恵, 長岡 義晴, 津下 充, 山下 信子, 塚原 宏一, 松川 昭博, 森島 恒雄

    日本小児科学会雑誌   116 ( 2 )   240 - 240   2012.2

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  • 中枢神経症状を示したロタウイルス及びインフルエンザの宿主遺伝子発現の解析

    津下 充, 藤井 洋輔, 長岡 義晴, 八代 将登, 山下 信子, 塚原 宏一, 森島 恒雄

    日本小児科学会雑誌   116 ( 2 )   238 - 238   2012.2

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  • 急性脳炎・脳症における脳神経障害マーカーの検討

    藤井 洋輔, 山田 睦子, 長岡 義晴, 八代 将登, 津下 充, 後藤 振一郎, 塚原 宏一, 市山 高志, 松原 康策, 森島 恒雄

    日本小児科学会雑誌   116 ( 2 )   238 - 238   2012

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  • 【疑問解決 小児の診かた】疾患別の診療 腎・泌尿器・生殖器疾患 急性腎盂腎炎の患者にはどのような形態・機能検査が必要ですか

    塚原 宏一, 八代 将登, 山下 信子

    小児内科   43 ( 増刊 )   756 - 759   2011.12

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  • 2009新型インフルエンザの宿主遺伝子発現の検討

    山下 信子, 津下 充, 斎藤 有希恵, 長岡 義晴, 藤井 洋輔, 八代 将登, 塚原 宏一, 森島 恒雄

    日本小児科学会雑誌   115 ( 5 )   976 - 976   2011

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  • インフルエンザ肺炎におけるレドックス制御蛋白チオレドキシン(TRX)の治療効果

    八代 将登, 藤井 洋輔, 齋藤 有希恵, 長岡 義晴, 津下 充, 山下 信子, 塚原 宏一, 松川 明博, 森島 恒雄

    日本小児科学会雑誌   115 ( 2 )   339 - 339   2011

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  • 水痘帯状疱疹ウイルスの再活性化により無疱性帯状疱疹と髄膜炎を発症した急性リンパ性白血病の1例

    藤井 洋輔, 宮村 能子, 茶山 公祐, 長岡 義晴, 津下 充, 八代 将登, 齊藤 有希恵, 森下 直人, 石田 敏章, 鷲尾 佳奈, 山下 信子, 塚原 宏一, 小田 慈, 森島 恒雄

    小児科臨床   64 ( 6 )   1111 - 1115   2011

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    無疱性帯状疱疹は皮疹を欠く無疱性の水痘帯状疱疹ウイルス(VZV)感染症であるが、その診断は困難であることが少なくない。今回、急性リンパ性白血病(ALL)の寛解期維持療法中にVZV再活性化により無疱性帯状疱疹と髄膜炎を発症した小児例を経験した。症例は15歳男児で、B前駆細胞性ALLの維持療法中に発熱、嘔吐を来して入院した。経過中、脳脊髄液細胞増加と左末梢性顔面神経麻痺が出現した。皮疹は出現しなかったが、髄液と唾液よりVZV-DNAが検出されたため、VZV再活性化による無疱性帯状疱疹および髄膜炎と診断した。プレドニゾロンとアシクロビルの併用により、諸症状は改善した。白血病の経過中に生じる顔面神経麻痺は、原病の再発と関連する場合が多いが、ウイルスの再活性化に伴う場合もあり、その鑑別診断は適切な治療を行ううえで重要である。(著者抄録)

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  • 抗TNF-α製剤による結核発症メカニズムに関する検討

    安井 耕三, 近藤 陽一, 山下 信子, 長岡 義晴, 齊藤 有希惠, 八代 将登, 津下 充, 森島 恒雄

    日本臨床免疫学会会誌   34 ( 4 )   302 - 302   2011

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  • 小児疾患における骨免疫学 その臨床応用

    安井 耕三, 八代 将登, 津下 充, 近藤 陽一, 長岡 義晴, 斎藤 有希恵, 山下 信子, 森島 恒雄

    日本小児科学会雑誌   115 ( 2 )   374 - 374   2011

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  • 小児の急性脳炎・脳症における宿主遺伝子発現の検討

    津下 充, 斎藤 有希恵, 長岡 義晴, 八代 将登, 山下 信子, 安井 耕三, 森島 恒雄

    日本小児科学会雑誌   114 ( 2 )   218 - 218   2010.2

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  • 新型インフルエンザ脳症と従来型インフルエンザ脳症の臨床像の比較

    長岡 義晴, 齋藤 有希恵, 津下 充, 八代 将登, 山下 信子, 安井 耕三, 森島 恒雄

    日本小児科学会雑誌   114 ( 2 )   216 - 216   2010

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  • HHV-6脳炎脳症の臨床的特徴-インフルエンザ脳症と比較して

    後藤振一郎, 津下充, 長岡義晴, 八代将登, 和田智顕, 森島恒雄

    日本小児感染症学会総会・学術集会プログラム・抄録集   42nd ( 1 )   82 - 82   2010

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  • 急性脳症における血液脳関門の障害のメカニズム

    津下 充, 長岡 義晴, 八代 将登, 和田 智顕, 山下 信子, 安井 耕三, 森島 恒雄

    日本小児科学会雑誌   113 ( 2 )   244 - 244   2009.2

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  • テオフィリンは末梢血単球の樹状細胞分化をアデノシンレセプター拮抗性に抑制する

    安井耕三, 近藤陽一, 和田智顕, 八代将登, 津下充, 森島恒雄

    日本小児アレルギー学会誌   23 ( 4 )   548 - 548   2009

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  • エタネルセプト投与により臨床症状の改善が得られたTRAPSの1例

    八代将登, 安井耕三, 長岡義晴, 津下充, 和田智顕, 萬木章, 森島恒雄

    日本小児科学会雑誌   113 ( 3 )   580 - 580   2009

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  • 小児における急性脳炎・脳症の現状-全国調査(2005-2006)の解析から-

    和田智顕, 津下充, 長岡義晴, 八代将登, 長尾隆志, 後藤振一郎, 萬木章, 安井耕三, 森島恒雄

    日本小児科学会雑誌   112 ( 2 )   262 - 262   2008

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  • 多核巨細胞形成を伴う肉芽腫性疾患(サルコイドーシスなど)に対する免疫抑制療法のin vitroでの検討および解析

    安井耕三, 津下充, 八代将登, 和田智顕, 萬木章, 長岡義晴, 森島恒雄

    日本臨床免疫学会会誌   31 ( 4 )   307 - 307   2008

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  • ヒト末梢血単球の多核巨細胞分化に関する研究

    安井耕三, 長岡義晴, 津下充, 八代将登, 和田智顕, 石田敏章, 鷲尾佳奈, 宮村能子, 茶山公祐, 小田慈, 森島恒雄

    臨床血液   49 ( 9 )   1139 - 1139   2008

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  • 小児における急性脳炎・脳症の病態解明と診断法および治療法の確立にむけて-急性脳炎・脳症全国調査(2005~2006)解析結果-

    和田智顕, 津下充, 長岡義晴, 八代将登, 長尾隆志, 後藤振一郎, 萬木章, 森島恒雄

    日本小児科学会雑誌   112 ( 4 )   781 - 781   2008

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  • 当科で経験した高IgE症候群の3例

    萬木 章, 八代 将登, 津下 充, 和田 智顕, 長尾 隆志, 宮村 能子, 茶山 公祐, 森島 恒雄

    日本小児科学会雑誌   111 ( 3 )   504 - 504   2007.3

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  • TNF受容体関連周期熱症候群の兄妹例

    萬木 章, 茶山 公祐, 宮村 能子, 長尾 隆志, 和田 智顕, 八代 将登, 西小森 隆太, 岡藤 郁夫, 森島 恒雄

    日本小児科学会雑誌   111 ( 2 )   198 - 198   2007.2

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  • インフルエンザ脳症の発症メカニズム 遺伝子多型の存在とその機能解析

    長尾 隆志, 津下 充, 八代 将登, 和田 智顕, 後藤 振一郎, 山下 信子, 萬木 章, 森島 恒雄

    日本小児科学会雑誌   111 ( 2 )   174 - 174   2007

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  • 半側空間無視を呈し、右大脳半球の広範な血流低下を認めたインフルエンザ脳症(特殊型)の女児例

    八代 将登, 中村 彩, 津下 充, 長尾 隆志, 和田 智顕, 山下 信子, 萬木 章, 森島 恒雄, 伊藤 美奈子, 岡 牧朗, 大塚 頌子, 吉田 匡人, 安井 雅人

    日本小児科学会雑誌   111 ( 3 )   501 - 501   2007

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Presentations

  • PRAJ Essential 〜エキスパートになろう2 不明熱・反復性発熱への診断アプローチ Invited

    八代将登

    日本小児リウマチ学会  2021.10.16  日本小児リウマチ学会

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    Event date: 2021.10.15 - 2021.10.16

    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

    Venue:東京   Country:Japan  

  • コロナ禍における鼻腔検体採取方法に関する検討

    八代将登

    第53回日本小児感染症学会総会・学術集会  2021.10.9 

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    Event date: 2021.10.9 - 2021.10.10

  • JIA Seminar for Young Pediatric Rheumatologists アドバンストミドルコース Invited

    八代将登

    小児リウマチ研修会  2021.9.23  日本小児リウマチ学会

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    Event date: 2021.9.23

    Presentation type:Public lecture, seminar, tutorial, course, or other speech  

    Country:Japan  

  • 医学部学生に対する予防接種記録の判定方法に関する検討

    八代将登

    第36回日本環境感染学会総会・学術集会  2021.9.19  日本環境感染学会

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    Event date: 2021.9.19 - 2021.9.20

    Venue:名古屋  

  • 当院における自己炎症性疾患の現状-免疫抑制薬タクロリムスの位置づけ- Invited

    八代将登

    第48回岡山膠原病研究会  2021.6.22 

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    Event date: 2021.6.22

    Language:Japanese  

  • FK506による腎障害を来したSLEの1例

    八代将登

    第48回岡山膠原病研究会  2021.6.22 

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    Event date: 2021.6.22

    Language:Japanese   Presentation type:Oral presentation (general)  

  • 重症神経疾患の病原体同定のための検体採取の実態解明

    八代将登

    第95回 日本感染症学会学術講演会 第69回 日本化学療法学会総会 合同学会  2021.5.7  日本感染症学会

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    Event date: 2021.5.7 - 2021.5.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  • レドックス制御蛋白チオレドキシン(TRX-1)は小児リウマチ性疾患の活動性を反映する

    八代将登

    第65回日本リウマチ学会総会学術集会  2021.4.26  日本リウマチ学会

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    Event date: 2021.4.26 - 2021.4.28

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  • 実臨床における若年性特発性関節炎治療 Invited

    八代将登

    2020.11.5 

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    Event date: 2020.11.5

    Language:Japanese  

  • 当院における自己炎症性疾患について Invited

    八代将登

    自己炎症性疾患フォーラム  2019.11.19 

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    Event date: 2019.11.19

    Language:Japanese  

  • First Multi-center Survey for the Treatment in Juvenile Idiopathic Arthritis-associated Uveitis (JIA-U) at Clinical Settings in Japan; the Report from Pediatric Rheumatology Association of Japan (PRAJ). International conference

    YASHIRO Masato

    Paediatric Rheumatology European Society:PRES 

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    Event date: 2018.9.5 - 2018.9.8

    Language:English   Presentation type:Poster presentation  

    Venue:Lisboa  

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  • 本邦の小児リウマチ専門施設における若年性特発性関節炎関連ぶどう膜炎の実態調査 - 治療-

    八代 将登, 安村 純子, 岡本 奈美, 大倉 有加, 梅林 宏明, 原 良紀, 西村 謙一, 岩田 直美, 清水 正樹, 水田 麻雄, 謝花 幸祐, 中岸 保夫, 脇口 宏之, 久保田 知洋, 金城 紀子, 山崎 和子, 森 雅亮

    第61回日本リウマチ学会総会学術集会 

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    Event date: 2017.4.20 - 2017.4.22

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:福岡国際会議場  

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  • ウイルスゲノム検出と定量価の有用性

    八代将登

    第7回広島小児腎と免疫研究会 

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    Event date: 2016.11.25

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Venue:広島  

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  • リアルタイムPCR法を用いたヘルペスウイルス定量評価の有用性

    八代将登

    第48回日本小児感染症学会総会  日本小児感染症学会

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    Event date: 2016.11.19 - 2016.11.20

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • 末梢性T細胞リンパ腫との鑑別を要したベーチェット病の1例

    八代将登

    第26回日本小児リウマチ学会総会学術集会  日本小児リウマチ学会

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    Event date: 2016.10.21 - 2016.10.23

    Language:Japanese   Presentation type:Poster presentation  

    Venue:千葉市民会館  

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  • 病因解明のためのウイルスゲノム検出の有用性と注意点

    八代将登

    第22回香川岡山感染免疫懇話会 

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    Event date: 2016.2.26

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:香川  

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  • レドックス制御蛋白チオレドキシン(TRX)のインフルエンザ肺炎における治療的効果

    八代将登、野坂宜之、藤井洋輔、斉藤有希恵、山下信子、山田雅夫、塚原宏一、森島恒雄

    第56回臨床ウイルス学会 

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    Event date: 2015.6.13 - 2015.6.14

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • マクロファージ活性化症候群を反復し治療に難渋している全身型若年性特発性関節炎の1例

    八代将登、吉川知伸、野坂宜之、藤井洋輔、齋藤有希惠、森島恒雄、塚原宏一

    第7回KOCS小児リウマチ研究会 

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    Event date: 2015.5.30

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • 抗TIF1抗体陽性若年性皮膚筋炎(JDM)の1例

    八代将登、山田睦子、野坂宜之、藤井洋輔、齋藤有希惠、塚原宏一、森島恒雄、森茂

    第87回日本小児科学会岡山地方会 

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    Event date: 2014.12.7

    Presentation type:Oral presentation (general)  

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  • マクロファージ活性化症候群(MAS)発症時に辺縁系脳炎を併発した全身型若年性特発性関節炎(sJIA)の1例

    八代将登、山田睦子、野坂宜之、藤井洋輔、齋藤有希惠、津下充、萬木章、塚原宏一、森島恒雄、林喬正、井上勝

    第37回岡山膠原病研究会 

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    Event date: 2014.11.4

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • 救命し得なかった劇症型肺炎球菌感染症の1例

    八代将登、藤井洋輔、塚原宏一、森島恒雄

    第84回日本感染症学会西日本地方会 

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    Event date: 2014.10.23 - 2014.10.25

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • マクロファージ活性化症候群(MAS)発症時に辺縁系脳炎を併発した全身型若年性特発性関節炎(sJIA)の1例

    八代将登

    第24回日本小児リウマチ学会 

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    Event date: 2014.10.3 - 2014.10.5

    Presentation type:Oral presentation (general)  

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  • Neonatal disseminated herpes simplex virus infection successfully treated with antiviral drug and corticosteroids International conference

    Masato Yashiro

    The 39th Annual International Herpesvirus workshop 2014 

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    Event date: 2014.7.19 - 2014.7.23

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  • ミゾリビンパルス療法が有効であった小児シェーグレン症候群の1例

    八代将登

    第36回岡山膠原病研究会 

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    Event date: 2014.6.3

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • 小児の重症感染症の診療;感染症の立場から

    八代将登

    大阪小児科医会 臨床カンファレンス 

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    Event date: 2014.5.11

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • 後遺症なく救命し得た重症全身型新生児ヘルペスの1例

    八代将登

    第117日本小児科学会 

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    Event date: 2014.4.11 - 2014.4.13

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • トシリズマブ(TCZ)を休薬後も寛解を維持している全身性若年性特発性関節炎の1例

    八代将登

    第45回岡山リウマチ研究会 

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    Event date: 2014.3.29

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • 救命し得た重症全身型新生児ヘルペスの1例

    八代将登

    第17回中国地区小児免疫薬物療法研究会 

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    Event date: 2014.3.1

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • インフルエンザ脳症の現状と課題

    八代将登

    第90回岡山小児てんかん懇話会 

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    Event date: 2014.2.26

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

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  • 岡山大学小児科関連施設における急性脳症66例の検討 International conference

    八代将登

    第19回香川岡山感染免疫懇話会 

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    Event date: 2014.2.23

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • トシリズマブ(TCZ)投与中に再燃を認めた若年性特発性関節炎(JIA)の1例

    八代将登

    第86回日本小児科学会岡山地方会 

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    Event date: 2013.12.1

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  • インフルエンザ脳症

    八代将登

    第61回日本ウイルス学会 

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    Event date: 2013.11.10 - 2013.11.12

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • トシリズマブ(TCZ)を休薬後も寛解を維持している全身性若年性特発性関節炎の1例

    八代将登

    第65回中国四国小児科学会 

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    Event date: 2013.11.2 - 2013.11.3

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  • 血栓性血小板減少症紫斑病(TTP)発症を契機に診断されたSLEの1例

    八代将登

    第23回日本小児リウマチ学会 

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    Event date: 2013.10.11 - 2013.10.13

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • 血栓性血小板減少症紫斑病(TTP)発症を契機に診断されたSLEの1例

    八代将登

    第34回岡山膠原病研究会 

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    Event date: 2013.6.4

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  • Difference in the profile of locally produced cytokines/chemokines in pneumonia and encephalitis of mice International conference

    Masato Yashiro

    16th US/Japan CMSP Acute Respiratory Infections Panel Meeting 

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    Event date: 2013.3.13

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Awards

  • 楷の木賞特別賞

    2022.3   岡山大学病院  

    COVID-ICT

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  • 楷の木賞特別賞

    2021.3   岡山大学病院  

    COVID-ICT

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  • 岡山医学会賞胸部・循環研究奨励賞(砂田賞)

    2013.6   Redox-Active Protein Thioredoxin-1 Administration Ameriorates Influenza A Virus(H1N1)-induced Acute Lung Injyury in Mice

  • Sunada Award

    2013.6   Redox-Active Protein Thioredoxin-1 Administration Ameriorates Influenza A Virus(H1N1)-induced Acute Lung Injyury in Mice

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  • 第7回友周会研究奨励賞(基礎部門)

    2013.3   レドックス制御蛋白チオレドキシンのマウスインフルエンザ重症肺炎モデルに対する治療的効果

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Research Projects

  • セシウムがインフルエンザウイルス・RSウイルス感染に及ぼす影響

    Grant number:20K08180  2020.04 - 2023.03

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

    山下 信子, 小川 寛人, 八代 将登, 難波 ひかる, 本田 知之

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    Grant amount:\4160000 ( Direct expense: \3200000 、 Indirect expense:\960000 )

    今年度は、安定同位体セシウム(Cesium;Cs)添加時の細胞毒性評価とインフルエンザウイルス(IAV)の増殖に及ぼす影響を検討した。細胞毒性評価はMTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)assayを用いた。MEM培地にCsClを0, 0.1, 0.3,1, 3, 10, 30mMで添加した場合の吸光度(A570- A650)で評価し、A549細胞とHEK293T細胞で検討を行った。添加48時間後ではCsCl 添加 0.1~3mMの生細胞率はA549細胞とHEK293T細胞のいずれも80%を超えていた(CsCl (-)を100%とした場合)。しかし、CsCl 10mMを超えると著しい細胞障害が認められた。次に、細胞障害を起こさない低濃度のCsCl添加時(0, 0.1, 0.5, 1mM)のポリメラーゼ活性への影響を検討するために、インフルエンザウイルスのミニゲノムアッセイ(pCAGGS-PB2,PB1,PA, NP (A/WSN/1933(H1N1))とNP分節NCRを持つルシフェラーゼ遺伝子をコードするpPolI-NP(0)Fluc(0) をHEK293T細胞にトランスフェクションし、転写・翻訳されるルシフェラーゼを測定)を行った。Relative Luciferase Activityは、CsCl 0mMを1とした場合、0.1mM 1.47、0.5mM 1.14、1mM 1.14(mean)であり有意差は認められなかった。このことから低濃度CsCl添加は、IAVのポリメラーゼ活性には影響を及ぼさないと考えられた。

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  • Development of biomarkers useful for evaluation of disease activity of pediatric rheumatic diseases

    Grant number:16K19646  2016.04 - 2020.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)  Grant-in-Aid for Young Scientists (B)

    Yashiro Masato

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    Grant amount:\3120000 ( Direct expense: \2400000 、 Indirect expense:\720000 )

    We established a measurement system for various oxidative stress markers (thioredoxin (TRX), High Mobility Group Box 1 (HMGB-1), d-ROMs) in pediatric rheumatic diseases.
    In juvenile idiopathic arthritis (JIA) other than systemic type, serum TRX increased during the acute phase and significantly decreased during the recovery phase. TRX was associated with d-ROMs and ferritin but not with MMP3. HMGB-1 did not show a certain tendency.
    TRX and d-ROMs were correlated with systemic inflammation in JIA but not with local inflammation (joint synovitis), suggesting that they may be useful biomarkers for monitoring the activity of pediatric rheumatic diseases.

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  • Therapeutic effects of anti-high mobility group box-1 monoclonal antibody for influenza A virus (H1N1)- induced pneumonia

    Grant number:15K21184  2015.04 - 2017.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)  Grant-in-Aid for Young Scientists (B)

    Nosaka Nobuyuki, MORISHIMA Tsuneo, NISHIBORI Masahiro, TSUKAHARA Hirokazu, MATSUKAWA Akihiro, LIU Keyue, YASHIRO Masato, YAMADA Mutsuko, HATAYAMA Kazuki

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    Grant amount:\2600000 ( Direct expense: \2000000 、 Indirect expense:\600000 )

    Provision for an influenza pandemic is an urgent issue. We aimed to evaluate the therapeutic effects of anti-high mobility group box-1 (HMGB1) monoclonal antibody (mAb) treatment on severe pneumonia induced by influenza A virus in mice. Anti-HMGB1 mAb significantly improved the survival rate of mice with severe influenza pneumonia with attenuated histological changes in the lungs. In addition, anti-HMGB1 mAb also improved the survival rate of mice with influenza pneumonia with 50% lethality even with anti-influenza drug administration. There were no adverse effects found by anti-HMGB1 mAb administration.

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  • Investigation of host factors for severe influenza virus infection

    Grant number:26461585  2014.04 - 2017.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Yamashita Nobuko

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    Grant amount:\4940000 ( Direct expense: \3800000 、 Indirect expense:\1140000 )

    Results: (i) Increased expression of IL-11, Fas L, Angiotensin II receptor genes was observed in vascular endothelial cells, when influenza virus infected the respiratory epithelium (in vitro). It was thought to be an influenza virus specific response. (ii) VNN1 was newly identified as a gene involved in influenza virus replication in the respiratory epithelium. VNN1 is an enzyme that hydrolyzes pantetheine, and it was found that cysteamine which is a degradation product of pantetheine, has a virus replication inhibiting action.

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  • Elucidation of the role of redox-active protein in severe influenza (pneumonia, encephalopathy)

    Grant number:25860865  2013.04 - 2016.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)  Grant-in-Aid for Young Scientists (B)

    Yashiro Masato, YAMADA Mutsuko, FUJII Yousuke, NOSAKA Nobuyuki, TSUKAHARA Hirokazu, MORISHIMA Tsuneo

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    Grant amount:\3900000 ( Direct expense: \3000000 、 Indirect expense:\900000 )

    TBP2KO mouse was suggested possibility of a metabolic disorder type influenza encephalopathy (Reye syndrome) model mice. In addition redox-active protein of TRX and anti-HMGB1 antibody has been shown to be effective in severe influenza pneumonia in mice. It is expected to confirm the therapeutic effect using a drug with anti-oxidative and anti-inflammatory effect in encephalopathy model mice.

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  • Biological response and therapeutic intervention in pediatric critical and intractable diseases

    Grant number:25461594  2013.04 - 2016.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Hirokazu Tsukahara, OKADA Ayumi, BABA Kenji, YASHIRO Masato, MIYAI Takayuki, YOSHIMOTO Junko, WASHIO Yosuke, FUJII Yosuke

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    Grant amount:\4940000 ( Direct expense: \3800000 、 Indirect expense:\1140000 )

    It is becoming increasingly apparent that reactive oxygen species (ROS) exert multiple biological effects over a wide spectrum, from physiological regulatory functions to the pathogenesis of diverse diseases. We sought for the clinical application of oxidative stress biomarkers in pediatric medicine. First, we explained important physiological and pathophysiological aspects of ROS and antioxidative defense systems. Second, we presented a list of clinically applicable biomarkers, along with pediatric diseases in which enhanced oxidative stress might be involved. Many good biomarkers are readily measurable using ELISA. Rapid diagnostic tests for measuring oxidative stress status (such as hydroperoxides, 8-OHdG, L-FABP) have been introduced. Third, we have evaluated the efficacy of antioxidative intervention for oxidative-stress related diseases using several animal models. Last, although not comprehensive, we provided a brief perspective of this particular area in pediatric research.

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Class subject in charge

  • 感染症の基礎病態学 (2021academic year) 3rd and 4th semester

  • 小児・発達系(臓器・系別統合講義) (2021academic year) 前期

  • 小児科学・小児神経学(基本臨床実習) (2021academic year) 通年

  • 小児科学(感染症) (2021academic year) 前期

 

Media Coverage

  • 新規バイオマーカーを用いて難治性川崎病の病態を解明 Internet

    国立大学法人岡山大学  国立大学法人岡山大学  2022.6.7

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    Author:Myself 

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  • 知ってうけよう、こどものワクチン Newspaper, magazine

    山陽新聞  山陽新聞  2021.9.4

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    Author:Myself 

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