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  2. 伊藤 弘康

伊藤 弘康

イトウ ヒロヤス  (Ito Hiroyasu)

基本情報

所属
藤田医科大学 医学部 臨床検査科 教授
学位
医学博士(岐阜大学)
研究者番号
80373075
J-GLOBAL ID
201601000738827795
researchmap会員ID
7000014447
近年、Toll用受容体のリガンドやNKT細胞の活性化分子などが同定され、宿主免疫系の修飾により様々な疾患に応用されつつある。また、免疫チェックポイント分子の同定も盛んに行われており、特に癌への治療応用が期待さえている。現在、このような免疫修飾技術を持ちいて、1）完全ウイルス排除を目指したHBV感染症治療法の開発、2）癌免疫療法の開発、3）臓器再生（肝再生・皮膚創傷治癒など）方法の確立に向けて基礎的実験を行っている。

研究キーワード

 29

研究分野

 4

経歴

 10
もっとみる

学歴

 1

受賞

 3

論文

 212
  • Hiroya Menjo, Midori Hasegawa, Hidetsugu Fujigaki, Takuma Ishihara, Shun Minatoguchi, Shigehisa Koide, Hiroki Hayashi, Midori Saito, Kazuo Takahashi, Hiroyasu Ito, Yukio Yuzawa, Kuniaki Saito, Naotake Tsuboi
    Internal medicine (Tokyo, Japan) 2023年9月29日  
    Objective The objective of this study was to estimate the humoral immune response evaluated by immunoglobulin G (IgG) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD-IgG) following the third mRNA COVID-19 vaccination in patients with kidney disease who received immunosuppressive treatment. Methods The primary outcome was RBD-IgG levels after the third SARS-CoV-2 vaccination. The primary comparison was the RBD-IgG levels between patients with kidney disease who received immunosuppressive treatment (n=124) and those who did not (n=33). Results The RBD-IgG levels were significantly lower in the patients with kidney disease who received immunosuppressive treatment than in those who did not receive immunosuppressive treatment. The RBD-IgG levels were lower in patients treated with glucocorticoid monotherapy than in those who did not receive immunosuppressive treatment. Even in patients who received ≤ 5 mg prednisolone, the RBD-IgG levels were significantly lower. Nine of the 10 patients who received rituximab within one year before the first vaccination did not experience seroconversion after the third vaccination. Meanwhile, all nine patients who received rituximab only after the second vaccination experienced seroconversion, even if B cell recovery was insufficient. Patients treated with mycophenolate mofetil plus glucocorticoid plus belimumab had significantly lower RBD-IgG levels than those treated with mycophenolate mofetil plus glucocorticoid. Conclusions The RBD-IgG levels were lower in patients with kidney disease who received immunosuppressive treatment than in those who did not receive immunosuppressive treatment. Low-dose glucocorticoid monotherapy affected the humoral immune response following the third mRNA COVID-19 vaccination.
  • Nanaka Morita, Masato Hoshi, Hiroyuki Tezuka, Tatsuya Ando, Sayaka Yoshida, Fumiaki Sato, Hiroyuki Yokoi, Hiroyasu Ito, Kuniaki Saito
    ImmunoHorizons 7(5) 353-363 2023年5月1日  
    Sepsis is a systemic inflammatory disease caused by a bacterial infection that leads to severe mortality, especially in elderly patients, because of an excessive immune response and impaired regulatory functions. Antibiotic treatment is widely accepted as the first-line therapy for sepsis; however, its excessive use has led to the emergence of multidrug-resistant bacteria in patients with sepsis. Therefore, immunotherapy may be effective in treating sepsis. Although CD8+ regulatory T cells (Tregs) are known to have immunomodulatory effects in various inflammatory diseases, their role during sepsis remains unclear. In this study, we investigated the role of CD8+ Tregs in an LPS-induced endotoxic shock model in young (8-12 wk old) and aged (18-20 mo old) mice. The adoptive transfer of CD8+ Tregs into LPS-treated young mice improved the survival rate of LPS-induced endotoxic shock. Moreover, the number of CD8+ Tregs in LPS-treated young mice increased through the induction of IL-15 produced by CD11c+ cells. In contrast, LPS-treated aged mice showed a reduced induction of CD8+ Tregs owing to the limited production of IL-15. Furthermore, CD8+ Tregs induced by treatment with the rIL-15/IL-15Rα complex prevented LPS-induced body wight loss and tissue injury in aged mice. In this study, to our knowledge, the induction of CD8+ Tregs as novel immunotherapy or adjuvant therapy for endotoxic shock might reduce the uncontrolled immune response and ultimately improve the outcomes of endotoxic shock.
  • Daisuke Ito, Hiroyasu Ito, Tatsuya Ando, Yasuhiro Sakai, Takayasu Ideta, Ken J. Ishii, Tetsuya Ishikawa, Masahito Shimizu
    Hepatology Communications 7(4) 2023年3月24日  
  • Tatusya Ando, Daisuke Ito, Kazuya Shiogama, Yasuhiro Sakai, Masato Abe, Takayasu Ideta, Ayumu Kanbe, Masahito Shimizu, Hiroyasu Ito
    Biochemical and Biophysical Research Communications 648 44-49 2023年3月12日  査読有り
    A previous study revealed that treatment with the anticoagulant heparin attenuated concanavalin A (ConA)-induced liver injury. The administration of spermidine (SPD) increased urokinase-type plasminogen activator (uPA) levels in the serum. uPA is clinically used for the treatment of some thrombotic diseases such as cerebral infarction. Therefore, SPD may attenuate ConA-induced liver injury that is exacerbated by blood coagulation. The present study investigated the effect of SPD on liver injury in mice with autoimmune hepatopathy induced by ConA. A model of liver injury was created by intravenous injection of ConA into mice. SPD was administered in free drinking water and was biochemically and pathologically examined over time. The administration of SPD to ConA-treated mice significantly reduced liver injury. However, SPD treatment upregulated the mRNA expression of TNF-α and IFN-γ in the livers of ConA-treated mice. In contrast, the mRNA expression of tissue factor in the livers of SPD-treated mice was decreased after ConA injection. The frequency of lymphocytes and lymphocyte activation were not affected by SPD administration in ConA-treated mice. SPD treatment increased uPA levels in the serum and decreased the level of D-dimer in ConA-treated mice. Moreover, SPD decreased fibrin in the livers of ConA-treated mice. These results indicated that SPD treatment increased anticoagulant ability by increasing of uPA and attenuated ConA-induced liver injury.
  • 石田 秀和, 稲垣 薫乃, 長谷川 瞳, 土井 洋輝, 和久田 光毅, 東本 祐紀, 水谷 謙明, 藤田 孝, 竹村 正男, 齋藤 邦明, 伊藤 弘康
    医療検査と自動化 48(1) 75-80 2023年2月  
    厚生労働省より承認された重症急性呼吸器症候群コロナウイルス-2(SARS-CoV-2)抗原検査キットのうち6種の性能比較を行った。その結果,1キットのみが突出した検出感度を有していることが観察されRT-PCRのCt値28.0までの検体が検出可能であった。それ以外はほぼ同等の結果であり,Ct値25.0の検体の検出が16.7～100%で可能であった。SARS-CoV-2抗原検査キットは検出感度に若干の差異があるため,導入にあたっては検査キットの性能特性や操作性を踏まえて選定する必要がある。(著者抄録)
もっとみる

MISC

 93
  • 仲本 賢太郎, 大橋 葉津希, 足立 真理子, 牛丸 星子, 宮崎 崇, 星 雅人, 稲垣 勇夫, 太田 浩敏, 古田 伸行, 竹村 正男, 和田 淳, 伊藤 弘康, 安田 満, 清島 満, 出口 隆
    臨床病理 60(補冊) 209-209 2012年10月  
  • 牛丸 星子, 稲垣 勇夫, 足立 真理子, 星 雅人, 古田 伸行, 竹村 正男, 伊藤 弘康, 清島 満
    医学検査 : 日本臨床衛生検査技師会誌 = The Japanese journal of medical technology 61(4) 736-740 2012年7月25日  
  • 林 麻実, 星 雅人, 牛丸 星子, 足立 真理子, 古田 伸行, 伊藤 弘康, 清島 満
    Sysmex Journal 35(Suppl.1) 45-56 2012年6月  
    凝固線溶検査は,出血性および血栓性疾患の病因や病態把握,治療のモニタリングなど臨床上極めて有用な検査であり,迅速で一括した結果報告が望まれる.今回新たに開発された全自動血液凝固測定装置CS-5100は,多検体・多項目における処理能力や試薬架設部の冷却性能,操作性が向上し,迅速かつ効率的な検査が期待される装置である.本検討においてCS-5100の基本的性能およびSTA-R Evolutionとの比較を行った.CS-5100の基本的性能は良好で,全自動凝固線溶測定装置STA-R Evolutionと比較し処理能力および試薬の安定性が優れていた.したがって,CS-5100は日勤帯および夜間・休日における試薬安定性の改善と多検体処理時における臨床への迅速な結果報告が十分期待できると考えられた.(著者抄録)
  • 星 雅人, 足立 真理子, 林 麻実, 牛丸 星子, 稲垣 勇夫, 伊藤 弘康, 清島 満
    医学検査 61(学会特集号) np290-np290 2012年4月  
  • 林 麻実, 星 雅人, 牛丸 星子, 足立 真理子, 古田 伸行, 伊藤 弘康, 清島 満
    医学検査 61(学会特集号) np308-np308 2012年4月  
  • 星 雅人, 斉藤 邦明, 大瀧 博文, 大澤 陽介, 伊藤 弘康, 清島 満
    アミノ酸研究 5(2) 113-114 2012年3月  
  • 大瀧 博文, 斉藤 邦明, 星 雅人, 大澤 陽介, 伊藤 弘康, 清島 満
    アミノ酸研究 5(2) 114-115 2012年3月  
  • 足立 真理子, 星 雅人, 牛丸 星子, 服部 高幸, 林 麻実, 稲垣 勇夫, 伊藤 弘康, 清島 満
    医学検査 : 日本臨床衛生検査技師会誌 = The Japanese journal of medical technology 61(1) 133-139 2012年1月25日  
  • 安藤達也, 大瀧博文, 伊藤弘康, 星雅人, 石川哲也, 斎藤邦明, 清島満
    臨床病理 60 2012年  
  • 星 雅人, 井上 里奈, 宮崎 崇, 太田 浩敏, 竹村 正男, 稲垣 勇夫, 伊藤 弘康, 清島 満
    医学検査 : 日本臨床衛生検査技師会誌 = The Japanese journal of medical technology 60(5) 741-745 2011年7月25日  
  • Tsuneo Watanabe, Tsuneo Watanabe, Tsuneo Watanabe, Hiroyasu Ito, Ayako Sekine, Ayako Sekine, Yuriko Katano, Yuriko Katano, Takashi Nishimura, Takashi Nishimura, Yoshihiro Kato, Jun Takeda, Mitsuru Seishima, Toshio Matsuoka
    Journal of Ultrasound in Medicine 29(5) 697-708 2010年5月  
    Objective. Early detection of nerve dysfunction is important to provide appropriate care for patients with diabetic polyneuropathy. The aim of this study was to assess the echo intensity of the peripheral nerve and to evaluate the relationship between nerve conduction study results and sonographic findings in patients with type 2 diabetes mellitus. Methods. Thirty patients with type 2 diabetes (mean ± SD, 59.8 ± 10.2 years) and 32 healthy volunteers (mean, 53.7 ± 13.9 years) were enrolled in this study. The cross-sectional area (CSA) and echo intensity of the peripheral nerve were evaluated at the carpal tunnel and proximal to the wrist (wrist) of the median nerve and in the tibial nerve at the ankle. Results. There was a significant increase in the CSA and hypoechoic area of the nerve in diabetic patients compared with controls (wrist, 7.1 ± 2.0 mm2, 62.3% ± 3.0%; ankle, 8.9 ± 2.8 mm2, 57.6% ± 3.9%; and wrist, 9.8 ± 3.7 mm2, 72.3% ± 6.6%; ankle, 15.0 ± 6.1 mm2, 61.4% ± 5.3% in controls and diabetic patients, respectively; P < .05). Cross-sectional areas were negatively correlated with reduced motor nerve conduction velocity and delayed latency. Conclusions. These result
  • 清島 満, 伊藤 弘康
    日本臨床 68 46-49 2010年1月  
  • Ryo Tanaka, Masao Takemura, Masao Sato, Yasunori Yamada, Takahito Nakagawa, Takuro Horibe, Masato Hoshi, Hirofumi Otaki, Hiroyasu Ito, Mitsuru Seishima, Katsuji Shimizu
    Clinica Chimica Acta 411(1-2) 22-25 2010年1月  
    Background: Autoantibodies against cyclic citrullinated peptide (anti-CCP) are sensitive and highly specific markers for rheumatoid arthritis (RA). We evaluated the analytical and diagnostic accuracy of chemiluminescence enzyme immunoassay (CLEIA) for anti-CCP antibodies, and compared it with that of ELISA. Methods: Ninety-nine RA patients who were diagnosed according to the American College of Rheumatology criteria, 16 patients with osteoarthritis, and 94 healthy subjects were included. Sera were used to assess the precision, functional sensitivity, and linearity of anti-CCP antibody determination by CLEIA and the correlation of anti-CCP antibody values between CLEIA and ELISA. Results: For anti-CCP antibodies by CLEIA, the total CV was 4.0 and 5.3% at 21.17 and 90 U/ml, respectively, and the lower limit of detection was 0.1 U/ml. The correlation of CLEIA (x) with ELISA (y) for anti-CCP was: y = 1.08x + 4.171, r = 0.9178 (p < 0.0001). No difference was observed in the sensitivity and specificity between CLEIA and ELISA. Conclusions: The automated CLEIA processing system for determining anti-CCP antibodies showed a good analytical performance, and suggested that the CLEIA system ha
  • Osawa Y, Seki E, Adachi M, Suetsugu A, Ito H, Moriwaki H, Seishima M, Nagaki M
    Hepatology 51(1) 237-245 2010年  
  • 渡邉 恒夫, 伊藤 弘康, 松岡 敏男
    超音波techno 21(6) 105-110 2009年11月  
  • Hirofumi Ohtaki, Kiyofumi Ohkusu, Haruki Sawamura, Hirotoshi Ohta, Rina Inoue, Junpei Iwasa, Hiroyasu Ito, Nobuo Murakami, Takayuki Ezaki, Hisataka Moriwaki, Mitsuru Seishima
    Journal of Clinical Microbiology 47 3391-3393 2009年10月1日  
    Cellulomonas denverensis is a small and thin gram-positive rod-shaped bacterium that was proposed as a new species in 2005. Here we report a female case of acute cholecystitis and sepsis in which C. denverensis was determined to be causative. Copyright © 2009, American Society for Microbiology. All Rights Reserved.
  • 石田 秀和, 星 雅人, 小池 紀子, 長屋 昌幸, 古田 伸行, 竹村 正男, 伊藤 弘康, 清島 満
    日本臨床検査自動化学会会誌 34(4) 518-518 2009年9月  
  • 石田 秀和, 星 雅人, 小池 紀子, 長屋 昌幸, 古田 伸行, 竹村 正男, 伊藤 弘康, 清島 満
    日本臨床検査自動化学会会誌 34(4) 564-564 2009年9月  
  • 足立 真理子, 服部 高幸, 星 雅人, 林 麻実, 牛丸 星子, 大橋 葉津希, 竹村 正男, 大澤 陽介, 伊藤 弘康, 清島 満
    日本臨床検査自動化学会会誌 34(4) 671-671 2009年9月  
  • 星 雅人, 斉藤 邦明, 竹村 正男, 伊藤 弘康, 清島 満
    臨床化学 38(Suppl.1) 145-145 2009年7月  
  • 古田 伸行, 太田 浩敏, 服部 高幸, 小池 紀子, 星 雅人, 丸本 雅夫, 竹村 正男, 伊藤 弘康, 前田 悟司, 斉藤 邦明, 清島 満
    日本臨床検査自動化学会会誌 34(3) 349-353 2009年6月  
    病院経営や検査室を取り巻く環境は厳しく、特に診療報酬改定により検査室の効率性や経済性が強く求められている。国立大学病院は2004年4月より独立行政法人化として再スタートした。岐阜大学病院は、同年6月に完全電子カルテ化病院として新築移転し開院した。このような状況下において病院検査部としての存在価値を高めるために実施した改革の一つである経営管理(費用対効果)について紹介する。(著者抄録)
  • 足立 真理子, 星 雅人, 服部 高幸, 小林 沙織, 牛丸 星子, 古田 伸行, 丸本 雅夫, 竹村 正男, 金森 寛光, 大澤 陽介, 伊藤 弘康, 清島 満
    日本臨床検査自動化学会会誌 34(3) 365-370 2009年6月  
    凝固線溶検査の測定には種々の全自動血液凝固装置が用いられている。今回、CA-7000を基準にCS-2000i、COAPRESTA2000、STA-R Evolutionの機種間差を同一試薬を用いて調べた。各凝固装置における同時再現性のCV(%)は、コアグトロールI Xが0.21〜2.95%、コアグトロールII Xが0.39〜6.58%であった。相関係数においてはr=0.95以上を示し概ね良好であったが、項目により若干の改善点が必要と考えられた。今回、CA-7000と3機種同時に検討したことにより、機種間における凝固測定値の標準化への基礎的な知見の提供につながることが期待される。(著者抄録)
  • Tsuneo Watanabe, Tsuneo Watanabe, Hiroyasu Ito, Hiroyasu Ito, Ayako Morita, Yuriko Uno, Takashi Nishimura, Harumi Kawase, Yoshihiro Kato, Toshio Matsuoka, Jun Takeda, Mitsuru Seishima
    Journal of Ultrasound in Medicine 28(6) 727-734 2009年6月  
    Objective. Diabetes mellitus is becoming a major cause of premature disability in Japan, and peripheral neuropathy is a common complication of diabetes. The aim of this study was to evaluate the relationship between the results of nerve conduction studies (NCS) and the size of the nerve determined by sonography in diabetic patients. Methods. Twenty diabetic patients (mean age ± SD, 57.1 ± 13.6 years) and 20 healthy volunteers (mean, 61.1 ± 8.9 years) were enrolled in this study. Patients' wrists that had symptoms of carpal tunnel syndrome were not included in the study; those that were included had negative Phalen test results. We then divided the patients into 2 groups (patients with and without diabetic symmetric polyneuropathy [DPN]). The cross-sectional area (CSA) was measured in the carpal tunnel 5 cm proximal to the wrist and elbow joint of the median nerve. Results. There was a significant increase in the CSA in patients with DPN in the carpal tunnel compared with the control participants (P < .01) and patients without DPN (P < .01). The CSA in the carpal tunnel showed a significant correlation with the motor nerve conduction velocity (r = -0.473). Conclusions. The CSA o
  • Yosuke Osawa, Masahito Nagaki, Hiroyasu Ito, Mitsuru Seishima, Hisataka Moriwaki
    GASTROENTEROLOGY 136(5) A819-A819 2009年5月  
  • 小林 沙織, 星 雅人, 大橋 葉津希, 竹村 正男, 伊藤 弘康, 清島 満, 油野 友二
    日本腎臓学会誌 51(3) 302-302 2009年4月  
  • 小林 沙織, 星 雅人, 稲垣 勇夫, 服部 高幸, 牛丸 星子, 大橋 葉津希, 古田 伸行, 丸本 雅夫, 竹村 正男, 伊藤 弘康, 清島 満
    臨床病理 57(3) 213-220 2009年3月  
    慢性腎臓病(CKD)における尿中の蛋白/クレアチニン比(P/C比)と尿沈渣の有用性を検討した。血清クレアチニンと尿検査の測定依頼のあった160検体について、アトラス試薬カートリッジPRO12によるP/C比(試験紙法)と各種生化学成分を比較した結果、試験紙法と定量法P/C比の相関は良好であり、P/C比の判定段階は腎機能障害を反映した妥当なものであった。また、試験紙法P/C比は従来の尿蛋白定性法より陽性率が高く、150mg/g・Cr群をカットオフ値とした場合の感度、特異度は良好で、300mg/g・Cr群の特異度は91.0%であった。一方、尿沈渣所見では病期の進行に伴って顆粒円柱やロウ様円柱などの多様な沈渣成分の増加を認め、硝子円柱は早期の腎障害を反映している可能性が示された。試験紙法P/C比と尿沈渣はCKDスクリーニングに有用である。
  • 星雅人, 斉藤邦明, 村上由希, 松本圭史, 有岡祐子, 田中領, 大澤陽介, 伊藤弘康, 松波英寿, 清島満
    アミノ酸研究 2(2) 167-167 2009年1月  
  • 星 雅人, 古田 伸行, 小池 紀子, 太田 浩敏, 服部 高幸, 小林 沙織, 足立 真理子, 大橋 葉津希, 長屋 昌幸, 丸本 雅夫, 前田 悟司, 伊藤 弘康, 竹村 正男, 清島 満
    日本臨床検査自動化学会会誌 33(5) 855-859 2008年11月  
    移植医療において拒絶反応の抑制はもっとも重要な課題である。移植技術の進歩はこの免疫抑制の発展と切り離すことはできず、簡便な測定系の開発が求められてきた。免疫抑制剤タクロリムスの測定における従来の測定系は操作性や経済性に問題があり、測定条件において制約を受けていた。今回、検討を行なった全自動化学分析装置ディメンション-RxL Maxによるタクロリムスの測定は日常の生化学検査と同様の操作で、リアルタイムに測定が可能となる迅速性を有していることが明らかになった。(著者抄録)
  • Kaori Sudo, Yasuhiro Yamada, Kuniaki Saito, Kuniaki Saito, Syogo Shimizu, Hazuki Ohashi, Tomohiro Kato, Hisataka Moriwaki, Hiroyasu Ito, Mitsuru Seishima
    Biochimica et Biophysica Acta - Molecular Basis of Disease 1782 671-679 2008年11月1日  
    In the present study, we used bone marrow transplanted mice and revealed the role of bone marrow derived cells in liver regeneration after partial hepatectomy (PH). Irradiated wild type (WT) mice received a bone marrow transplant from either WT, TNF (tumor necrosis factor)-α knockout (KO), or interleukin (IL)-6 KO donors. Both TNF-α KO- and IL-6 KO-transplanted mice compared with WT-transplanted mice showed decreased hepatocyte DNA synthesis after PH. TNF-α KO-transplanted mice showed no nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription (STAT) 3 binding after PH, while IL-6 KO-transplanted mice showed NF-κB, but not STAT3, binding. Lack of AP-1 or C/EBP binding or expression of c-jun or c-myc mRNA after PH was unrelated to the timing and amount of DNA replication. In conclusion, The TNF-α and IL-6 signals from the blood are necessary for liver regeneration and NF-κB and STAT3 binding are activated via TNF-α and IL-6 signal pathways. © 2008 Elsevier B.V. All rights reserved.
  • 牛丸 星子, 星 雅人, 服部 高幸, 小林 沙織, 信田 光明, 古田 伸行, 丸本 雅夫, 竹村 正男, 伊藤 弘康, 清島 満
    医療と検査機器・試薬 31(5) 569-574 2008年10月  
    新しいフィブリノゲン測定試薬として開発された「コアグピアFbg」の基本性能について、汎用の全自動血液凝固測定装置CA-7000を用いて検討した。その結果、再現性は良好であり、共存物質の影響は認めなかった。測定域は30〜600mg/dL付近まで認められ、試薬安定性については1ヵ月間は使用可能であった。オーレンベロナール緩衝液を用いた変法では、希釈直線性は得られるものの、従来法と比較すると低値に測定されており、専用の希釈液を用いるほうが良いと思われた。
  • 足立 真理子, 星 雅人, 服部 高幸, 小林 沙織, 牛丸 星子, 古田 伸行, 丸本 雅夫, 竹村 正男, 大澤 陽介, 伊藤 弘康, 清島 満
    日本臨床検査自動化学会会誌 33(4) 671-671 2008年9月  
  • 吉川 武志, 原 武志, 鶴見 寿, 後藤 尚絵, 星 雅人, 伊藤 弘康, 北川 順一, 兼村 信宏, 笠原 千嗣, 竹村 正男, 清島 満, 森脇 久隆
    臨床血液 49(9) 1176-1176 2008年9月  
  • 星 雅人, 斎藤 邦明, 高橋 健, 大山 正巳, 冨田 栄一, 竹村 正男, 伊藤 弘康, 清島 満
    臨床化学 37(Suppl.1) 138-138 2008年8月  
  • Hiroyasu Ito, Hiroyasu Ito, Kazuki Ando, Kazuki Ando, Tetsuya Ishikawa, Toshinori Nakayama, Masaru Taniguchi, Kuniaki Saito, Kuniaki Saito, Michio Imawari, Hisataka Moriwaki, Takashi Yokochi, Shinichi Kakumu, Mitsuru Seishima
    International Immunology 20 869-879 2008年7月1日  
    CTLs are thought to be major effectors for clearing viruses in acute infections including hepatitis B virus (HBV). Persistent HBV infection is characterized by a lack of or a weak CTL response to HBV, which is thought to reflect tolerance to HBV antigens. In the present study, we found that alpha-galactosylceramide (α-GalCer), a ligand for Vα14-positive NKT cells, strongly enhanced the induction and proliferation of HBV-specific CTLs by HBsAg. In HBsAg transgenic mice, which are thought to be tolerant to HBV-encoded antigens, administration of HBsAg or α-GalCer alone failed to induce HBsAg-specific CTLs, but they were induced by co-administration of both compounds. Furthermore, by limiting dilution analysis, we confirmed the existence of HBsAg-specific CTL precursors in the HBsAg transgenic mice immunized with HBsAg and α-GalCer. A blocking experiment using antibodies to cytokines and CD40 ligand showed that IL-2 and CD40-CD40L interaction mediate the enhancement of CTL induction caused by α-GalCer through NKT cell activation. Our results may open up a new method for clearing the virus from patients with persistent HBV infection. © The Japanese Society for Immunology. 2008. A
  • 小池 紀子, 古田 伸行, 服部 高幸, 星 雅人, 太田 浩敏, 丸本 雅夫, 竹村 正男, 伊藤 弘康, 清島 満
    医療と検査機器・試薬 31(1) 105-109 2008年2月  
    新しいシスタチンC測定試薬、FTラテックスシスタチンCについて基礎的性能評価を行った。日常検査としてクレアチニンクリアランス、尿素窒素およびクレアチニンを検査した150例を対象とした。日差再現性は良好な再現性を示した。ビリルビンF;18.1mg/dL、ビリルビンC;19.5mg/dL、溶血ヘモグロビン;490mg/dL、乳び;2290濁度、リウマチ因子;5001U/mLまで影響を認めなかった。有効測定範囲内での希釈直線性は良好であった。0.28〜0.41mg/L付近が実行検出限界濃度であった。腎・肝機能検査に異常を認めない男女99例で、性差は認めなかった。汎用機用の試薬との相関は、ネスコートGCシスタチン、イアトロCys-Cとは良好な相関を認めたが、N-ラテックスシスタチンCとイアトロCys-Cは、本法がやや高値傾向であった。Ccr(24時間)とは負、β2-ミクログロブリンとは正の相関が得られた。
  • 古田 伸行, 太田 浩敏, 服部 高幸, 小池 紀子, 星 雅人, 丸本 雅夫, 竹村 正男, 伊藤 弘康, 前田 悟司, 斉藤 邦明, 清島 満
    日本臨床検査自動化学会会誌 32(4) 605-605 2007年9月  
  • 内藤 智雄, 内木 隆文, 伊藤 弘康, 永木 正仁, 村上 啓雄, 森脇 久隆
    日本アフェレシス学会雑誌 21 75-75 2002年  
  • Hiroyasu Ito, Mitsuru Seishima
    Journal of Biomedicine and Biotechnology 2010  
    Cytotoxic T lymphocytes (CTLs) play a crucial role in the infections and the antitumor immunity. Induction and activation of antigen-specific CTLs is an important strategy in immunotherapy for various diseases, and several researchers have focused on the modulation of CTL induction and function. Natural killer T (NKT) cells are an important focus area of researchers studying immunomodulatory responses to tumors and infectious diseases. CD1d-restricted NKT cells consist of type I NKT cells and type II NKT cells. -galactosylceramide ( -GalCer)-activated type I NKT cells secrete both Th1 (e.g., IFN- ) and Th2 cytokines, affect the expression of costimulatory molecules in immune cells, and regulate the host immune system. Type II NKT cells, however, are stimulated by sulfatide, a self-glycolipid derived from myelin, and play an immunosuppressive role in animal model of autoimmune diseases. CTL generation, activation, and suppression are strongly affected by activated type I and type II NKT cells. Thus, the regulation of these NKT cells leads to the modification of CTL function. CTLs contribute to antimicrobial responses, antitumor immune and autoimmune responses. Understanding the role
  • Hirofumi Ohtaki, Hirofumi Ohtaki, Kiyofumi Ohkusu, Hirotoshi Ohta, Takashi Miyazaki, Jun Yonetamari, Taro Usui, Ichiro Mori, Hiroyasu Ito, Tatsuo Ishizuka, Mitsuru Seishima
    Journal of Infection and Chemotherapy 19 1206-1209  
    A 91-year-old dog-owning woman with a history of hypertension and femoral neck fracture consulted our hospital with fever and femur pain with redness. Laboratory test results showed leukocytosis with 85 % neutrophils and high values of C-reactive protein and procalcitonin. In addition, growth of Gram-positive streptococcus was observed in two independent blood culture sets. The isolated bacterium was identified as Streptococcus canis on the basis of biochemical properties and sequencing analyses of the 16S rRNA gene. The patient recovered completely without critical illness following prompt antimicrobial treatment with ceftriaxone. S. canis, a β-hemolytic Lancefield group G streptococcus, is in general isolated from various animal sources, but its isolation from a human clinical sample is extremely rare. Since β-hemolytic streptococci can cause severe infectious diseases such as necrotizing fasciitis, it is absolutely necessary to start antimicrobial treatment immediately. It is necessary to identify pathogenic bacteria carefully and to obtain information on a patient's background, including history of contact with an animal, when S. canis is isolated. © 2013 Japanese Society o
  • Yosuke Osawa, Yosuke Osawa, Hiromitsu Kanamori, Ekihiro Seki, Masato Hoshi, Hirofumi Ohtaki, Yoichi Yasuda, Hiroyasu Ito, Atsushi Suetsugu, Masahito Nagaki, Hisataka Moriwaki, Kuniaki Saito, Mitsuru Seishima
    Journal of Biological Chemistry 286 34800-34808  
    Nonalcoholic fatty liver disease is one of the most common liver diseases. L-Tryptophan and its metabolite serotonin are involved in hepatic lipid metabolism and inflammation. However, it is unclear whether L-tryptophan promotes hepatic steatosis. To explore this issue, we examined the role of L-tryptophan in mouse hepatic steatosis by using a high fat and high fructose diet (HFHFD) model. L-Tryptophan treatment in combination with an HFHFD exacerbated hepatic steatosis, expression of HNE-modified proteins, hydroxyproline content, and serum alanine aminotransaminase levels, whereas L-tryptophan alone did not result in these effects. We also found that L-tryptophan treatment increases serum serotonin levels. The introduction of adenoviral aromatic amino acid decarboxylase, which stimulates the serotonin synthesis from L-tryptophan, aggravated hepatic steatosis induced by the HFHFD. The fatty acid-induced accumulation of lipid was further increased by serotonin treatment in cultured hepatocytes. These results suggest that L-tryptophan increases the sensitivity to hepatic steatosis through serotonin production. Furthermore, L-tryptophan treatment, adenoviral AADC introduction, and ser
  • Masato Hoshi, Kuniaki Saito, Kuniaki Saito, Akira Hara, Ayako Taguchi, Hirofumi Ohtaki, Ryo Tanaka, Hidetsugu Fujigaki, Yosuke Osawa, Masao Takemura, Hidetoshi Matsunami, Hiroyasu Ito, Mitsuru Seishima
    Journal of Immunology 185 3305-3312  
    Indoleamine 2,3-dioxygenase, the L-tryptophan-degrading enzyme, plays a key role in the powerful immunomodulatory effects on several different types of cells. Because modulation of IDO activities after viral infection may have great impact on disease progression, we investigated the role of IDO following infection with LP-BM5 murine leukemia virus. We found suppressed BM5 provirus copies and increased type I IFNs in the spleen from IDO knockout (IDO -/-) and 1-methyl-D-L-tryptophan-treated mice compared with those from wild-type (WT) mice. Additionally, the number of plasmacytoid dendritic cells in IDO-/- mice was higher in the former than in the WT mice. In addition, neutralization of type I IFNs in IDO-/- mice resulted in an increase in LP-BM5 viral replication. Moreover, the survival rate of IDO -/- mice or 1-methyl-D-L-tryptophan-treated mice infected with LP-BM5 alone or with both Toxoplasma gondii and LP-BM5 was clearly greater than the survival rate of WT mice. To our knowledge, the present study is the first report to observe suppressed virus replication with upregulated type I IFN in IDO-/- mice, suggesting that modulation of the IDO pathway may be an effective strategy fo
  • Masato Hoshi, Keishi Matsumoto, Hiroyasu Ito, Hirofumi Ohtaki, Yuko Arioka, Yosuke Osawa, Yasuko Yamamoto, Hidetoshi Matsunami, Akira Hara, Mitsuru Seishima, Kuniaki Saito
    Journal of Immunology 188 3980-3987  
    The activity of IDO that catalyzes the degradation of tryptophan (Trp) into kynurenine (Kyn) increases after diseases caused by different infectious agents. Previously, we demonstrated that IDO has an important immunomodulatory function in immune-related diseases. However, the pathophysiological role of IDO following acute viral infection is not fully understood. To investigate the role of IDO in the L-Trp-Kyn pathway during acute viral myocarditis, mice were infected with encephalomyocarditis virus, which induces acute myocarditis. We used IDO-deficient (IDO -/-) mice and mice treated with 1-methyl-D,L-Trp (1-MT), an inhibitor of IDO, to study the importance of Trp-Kyn pathway metabolites. Postinfection with encephalomyocarditis virus infection, the serum levels of Kyn increased, whereas those of Trp decreased, and IDO activity increased in the spleen and heart. The survival rate of IDO -/- or 1-MT-treated mice was significantly greater than that of IDO +/+ mice. Indeed, the viral load was suppressed in the IDO -/- or 1-MT-treated mice. Furthermore, the levels of type I IFNs in IDO -/- mice and IDO -/- bone marrow-transplanted IDO +/+ mice were significantly higher than those in I
  • Hiroyasu Ito, Masato Hoshi, Hirofumi Ohtaki, Ayako Taguchi, Kazuki Ando, Kazuki Ando, Tetsuya Ishikawa, Yosuke Osawa, Akira Hara, Hisataka Moriwaki, Kuniaki Saito, Mitsuru Seishima
    Journal of Immunology 185 4554-4560  
    IDO converts tryptophan to L-kynurenine, and it is noted as a relevant molecule in promoting tolerance and suppressing adaptive immunity. In this study, we examined the effect of IDO in α-galactosylceramide (α-GalCer)-induced hepatitis. The increase in IDO expression in the liver of wild-type (WT) mice administered α-GalCer was confirmed by real-time PCR, Western blotting, and IDO immunohistochemical analysis. The serum alanine aminotransferase levels in IDO-knockout (KO) mice after α-GalCer injection significantly increased compared with those in WT mice. 1-Methyl-D-tryptophan also exacerbated liver injury in this murine hepatitis model. In α-GalCer-induced hepatitis models, TNF-α is critical in the development of liver injury. The mRNA expression and protein level of TNF-α in the liver from IDO-KO mice were more enhanced compared with those in WT mice. The phenotypes of intrahepatic lymphocytes from WT mice and IDO-KO mice treated with α-GalCer were analyzed by flow cytometry, and the numbers of CD49b+ and CD11b+ cells were found to have increased in IDO-KO mice. Moreover, as a result of the increase in the number of NK cells and macrophages in the liver of IDO-KO mice in

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