2021/10/25 更新

写真a

アベ リイチロウ
阿部 理一郎
ABE Riichiro
所属
教育研究院 医歯学系 医学系列 教授
医歯学総合研究科 分子細胞医学専攻 細胞機能 教授
職名
教授
外部リンク

学位

  • 医学博士 ( 2001年9月   北海道大学 )

研究キーワード

  • GVHD

  • 細胞・組織

  • 色素細胞

  • 自己免疫性疾患

  • 分化

  • 表皮水疱症

  • 免疫

  • 人工真皮

  • 白髪

  • 毛包

  • 色素幹細胞

  • 幹細胞

  • 再生学

  • 組織間幹細胞

  • 骨髄細胞

  • 皮膚生理学

  • 皮膚性理学

  • 皮膚炎症

  • 表皮細胞

  • 再生医療

  • トランスジェニックマウス

  • 創傷治癒

  • 生体機能利用

  • 皮膚免疫

  • 免疫学

  • Bcl2

  • transdifferentiation

  • 臨床

  • トレランス

  • T細胞

  • VII型コラーゲン

  • 遺伝子

研究分野

  • ライフサイエンス / 皮膚科学

経歴(researchmap)

  • 新潟大学大学院医歯学総合研究科分子細胞医学専攻細胞機能講座 皮膚科学分野 教授

    2015年

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  • 北海道大学大学院医学研究科   准教授

    2010年

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経歴

  • 新潟大学   医歯学総合研究科 分子細胞医学専攻 細胞機能   教授

    2015年9月 - 現在

所属学協会

委員歴

  • 日本皮膚科学会 代議員  

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    団体区分:学協会

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  • 日本アレルギー協会北海道支部   幹事  

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    団体区分:学協会

    日本アレルギー協会北海道支部

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  • 日本研究皮膚科学会 理事  

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    団体区分:学協会

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留学歴

  • Picower医学研究所   研究員

    1998年11月 - 2000年9月

 

論文

  • Late-onset Cutaneous Hydrophilic Polymer Embolism: A Case Occurring Two Years after Endovascular Procedures. 国際誌

    Yukino Kase, Ryota Hayashi, Izumi Takei, Osamu Ansai, Takeo Suzuki, Akihiko Yuki, Mitsuhiro Watanabe, Takao Yanagawa, Riichiro Abe

    Acta dermato-venereologica   2021年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2340/00015555-3881

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  • Extra-palmoplantar skin lesions of palmoplantar keratoderma with deafness caused by a mitochondrial mutation. 国際誌

    Tatsuya Katsumi, Ryota Hayashi, Rei Yokoyama, Osamu Ansai, Shuji Izumi, Tatsuya Yamagishi, Arata Horii, Riichiro Abe

    The Journal of dermatology   2021年7月

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  • Acquired ichthyosis disclosing intravascular large B-cell lymphoma. 国際誌

    Risa Hagiwara, Satoru Shinkuma, Rei Yokoyama, Osamu Ansai, Ryota Hayashi, Takayuki Katagiri, Riichiro Abe

    The Journal of dermatology   2021年7月

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  • Neutrophils initiate and exacerbate Stevens-Johnson syndrome and toxic epidermal necrolysis. 国際誌

    Manao Kinoshita, Youichi Ogawa, Natsumi Hama, Inkin Ujiie, Akito Hasegawa, Saeko Nakajima, Takashi Nomura, Jun Adachi, Takuya Sato, Schuichi Koizumi, Shinji Shimada, Yasuyuki Fujita, Hayato Takahashi, Yoshiko Mizukawa, Takeshi Tomonaga, Keisuke Nagao, Riichiro Abe, Tatsuyoshi Kawamura

    Science translational medicine   13 ( 600 )   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening mucocutaneous adverse drug reactions characterized by massive epidermal detachment. Cytotoxic T cells and associated effector molecules are known to drive SJS/TEN pathophysiology, but the contribution of innate immune responses is not well understood. We describe a mechanism by which neutrophils triggered inflammation during early phases of SJS/TEN. Skin-infiltrating CD8+ T cells produced lipocalin-2 in a drug-specific manner, which triggered the formation of neutrophil extracellular traps (NETs) in early lesional skin. Neutrophils undergoing NETosis released LL-37, an antimicrobial peptide, which induced formyl peptide receptor 1 (FPR1) expression by keratinocytes. FPR1 expression caused keratinocytes to be vulnerable to necroptosis that caused further release of LL-37 by necroptotic keratinocytes and induced FPR1 expression on surrounding keratinocytes, which likely amplified the necroptotic response. The NETs-necroptosis axis was not observed in less severe cutaneous adverse drug reactions, autoimmune diseases, or neutrophil-associated disorders, suggesting that this was a process specific to SJS/TEN. Initiation and progression of SJS/TEN keratinocyte necroptosis appear to involve a cascade of events mediated by innate and adaptive immune responses, and understanding these responses may contribute to the identification of diagnostic markers or therapeutic targets for these adverse drug reactions.

    DOI: 10.1126/scitranslmed.aax2398

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  • The role of IL-8 in skin lesions of a patient with erythema elevatum diutinum. 国際誌

    H Kimura, R Hayashi, Y Tsuchida, A Hasegawa, Y Kabata, M Tamura, R Abe

    Journal of the European Academy of Dermatology and Venereology : JEADV   35 ( 6 )   e396-e399   2021年6月

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    記述言語:英語  

    DOI: 10.1111/jdv.17179

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  • Alopecia areata and psoriasis vulgaris associated with Turner syndrome. 国際誌

    Rei Yokoyama, Ryota Hayashi, Osamu Ansai, Akito Hasegawa, Satoru Shinkuma, Yutaka Shimomura, Riichiro Abe

    The Australasian journal of dermatology   2021年5月

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    記述言語:英語  

    DOI: 10.1111/ajd.13597

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  • Massive perianal skin ulcer due to long-standing amoebic infection in an HIV-negative, heterosexual man. 国際誌

    Jin Sasaki, Hiroki Fujikawa, Tatsuya Katsumi, Yuki Saito, Akihiko Yuki, Hitoshi Kameyama, Masato Nakano, Yoshifumi Shimada, Toshifumi Wakai, Riichiro Abe

    The Journal of dermatology   48 ( 4 )   e198-e200   2021年4月

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  • Risk factors for lymph node metastasis in cutaneous squamous cell carcinoma: a long-term retrospective study of Japanese patients.

    Yuki Saito, Hiroki Fujikawa, Sumiko Takatsuka, Riichiro Abe, Tatsuya Takenouchi

    International journal of clinical oncology   26 ( 3 )   606 - 612   2021年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) is one of the most common skin cancers. Prognosis is favorable following surgical resection of early-stage disease, but the management of the metastatic disease is challenging. Several prognostic risk factors have been described in the American Joint Committee on Cancer/the Union for International Cancer Control (UICC) 8th edition staging and the Brigham and Women's Hospital T classification system. However, their clinical validity in Asian populations is unclear because of racial differences in the clinical characteristics of CSCC. This study aimed to identify factors that could predict lymph node metastasis in Asian patients. METHODS: This retrospective single-center study evaluated 540 patients with primary CSCC between 1989 and 2013. Five factors were evaluated for their ability to predict lymph node metastasis: maximum tumor diameter, tumor thickness, depth of invasion, degree of differentiation, and infiltrative growth pattern (INF). RESULTS: Tumor diameter > 2 cm (p < 0.0001), tumor thickness > 6 mm (p < 0.0001), invasion beyond the subcutaneous fat (p < 0.0001), poor differentiation (p = 0.042), and INFc infiltration (p < 0.0001) were associated with lymph node metastasis in the univariate analyses. In the multivariate analysis, lymph node metastasis was independently associated with tumor size > 2 cm [hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.4-6.2; p = 0.006], tumor thickness > 6.0 mm (HR 2.9, 95% CI 1.3-6.4; p = 0.007), and invasion beyond the subcutaneous fat (HR 2.3, 95% CI 1.0-5.1; p = 0.045). CONCLUSION: Larger tumor diameter, greater tumor thickness, and deeper invasion included in the UICC T classification system are associated with increased risks of lymph node metastasis from CSCC in Japanese patients.

    DOI: 10.1007/s10147-020-01830-7

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  • Risankizumab for treating chronic plaque psoriasis complicated by recurrent diverticulitis: A case report. 国際誌

    Yuko Tsuchida, Atsushi Fujimoto, Yohya Shigehara, Natsumi Hama, Atsunori Tsuchiya, Riichiro Abe

    The Journal of dermatology   48 ( 3 )   e124-e125   2021年3月

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  • Plasma exosomal miR-375-3p regulates mitochondria-dependent keratinocyte apoptosis by targeting XIAP in severe drug-induced skin reactions. 国際誌

    Chen Zhang, ZhenLai Zhu, JiXin Gao, LuTing Yang, ErLe Dang, Hui Fang, Shuai Shao, ShaoLong Zhang, ChunYing Xiao, Xu Yuan, Wei Li, Riichiro Abe, HongJiang Qiao, Gang Wang, Meng Fu

    Science translational medicine   12 ( 574 )   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug-induced cutaneous reactions characterized by keratinocyte apoptosis. Exosomes are nanometer-sized membranous vesicles in body fluids. They contain functional proteins, mRNAs, and miRNAs, which induce immune dysfunction and influence disease progression. However, their roles and mechanisms in SJS/TEN remain unknown. Our results demonstrate that exosomes isolated from the plasma of patients with SJS/TEN were 30 to 200 nm in diameter and expressed CD9, CD63, CD81, and TSG101 exosome marker proteins. miR-375-3p was markedly up-regulated in 35 patients with SJS/TEN and correlated with clinical severity. Plasma exosomes were internalized by human primary keratinocytes and promoted keratinocyte apoptosis in vitro. Furthermore, miR-375-3p overexpression promoted intrinsic (mitochondria-dependent) apoptosis of human primary keratinocytes via down-regulation of the X-linked inhibitor of apoptosis protein (XIAP), a key apoptosis regulator in primary human keratinocytes. In sum, our study indicates that the circulating exosomal miR-375-3p enters keratinocytes, down-regulates XIAP, and induces keratinocyte apoptosis in patients with SJS/TEN.

    DOI: 10.1126/scitranslmed.aaw6142

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  • Seborrheic dermatitis-like metastatic breast cancer. 国際誌

    Mahoko Oginezawa, Satoru Shinkuma, Osamu Ansai, Riichiro Abe

    The Journal of dermatology   47 ( 12 )   e440-e442   2020年12月

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  • The nationwide epidemiological survey of Stevens-Johnson syndrome and toxic epidermal necrolysis in Japan, 2016-2018. 国際誌

    Yuma Sunaga, Michiko Kurosawa, Hirotaka Ochiai, Hideaki Watanabe, Hirohiko Sueki, Hiroaki Azukizawa, Hideo Asada, Yuko Watanabe, Yukie Yamaguchi, Michiko Aihara, Yoshiko Mizukawa, Manabu Ohyama, Natsumi Hama, Riichiro Abe, Hideo Hashizume, Saeko Nakajima, Takashi Nomura, Kenji Kabashima, Mikiko Tohyama, Hayato Takahashi, Hiroki Mieno, Mayumi Ueta, Chie Sotozono, Hiroyuki Niihara, Eishin Morita, Akatsuki Kokaze

    Journal of dermatological science   100 ( 3 )   175 - 182   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening severe cutaneous adverse reactions (SCARs). The first national epidemiological survey of SJS/TEN was carried out in 2008. We conducted a new survey to identify changes from the previous survey. OBJECTIVE: The present survey aimed to estimate the number of SJS/TEN patients in Japan between 2016 and 2018 (primary survey) and to clarify clinical epidemiological profiles (secondary survey). METHODS: A primary survey asking for numbers of SJS/TEN patients during the study period was sent to 1205 institutions nationwide. A secondary survey was sent to institutions reporting SJS/TEN patients, seeking detailed information. RESULTS: Yearly prevalence per million was 2.5 for SJS and 1 for TEN. The secondary survey allowed analysis of 315 SJS cases and 174 TEN cases from 160 institutions. Mean age was 53.9 years in SJS, and 61.8 years in TEN. Mortality rate was 4.1 % for SJS and 29.9 % for TEN. In TEN, mean age and mortality rates had increased from the previous survey. The ratio of expected to observed mortality calculated by SCORTEN score was lowest with high-dose steroid therapy (0.40), followed by steroid pulse therapy (0.52). CONCLUSION: The present findings suggest that the mortality rate of TEN has increased because of increases in mean ages of patients and patients with malignant neoplasm as underlying disease. When comparing the ratio of expected mortality to actual mortality, high-dose steroid therapy achieved the greatest reduction in mortality.

    DOI: 10.1016/j.jdermsci.2020.09.009

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  • Pregnancy‐triggered atypical extrapalmoplantar erythematous hyperkeratotic lesions in palmoplantar keratoderma with mitochondrial mutations

    O. Ansai, R. Hayashi, A. Nakamura, A. Arimatsu‐Sato, A. Hasegawa, A. Yuki, A. Fujimoto, N. Hama, S. Shinkuma, Y. Shimomura, R. Abe

    Journal of the European Academy of Dermatology and Venereology   2020年11月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1111/jdv.17020

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  • Neutrophilic myositis with Sweet's syndrome leading to rhabdomyolysis: A case report. 査読 国際誌

    Haruna Shimagaki, Yudai Kabata, Anna Nakamura, Shingo Takei, Izumi Takei, Kiyoto Kimura, Tokiko Deguchi, Naokata Yuki, Riichiro Abe

    The Journal of dermatology   47 ( 11 )   e415-e417   2020年11月

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  • Seronegative Oligoarthritis Preceding Psoriasis by 9.5 Years.

    Junpei Tsuchiya, Naoki Kondo, Atsushi Fujimoto, Rie Kondo, Masahiko Yamada, Tatsuya Kuraishi, Takuya Yoda, Riichiro Abe, Naoto Endo

    Acta medica Okayama   74 ( 5 )   449 - 453   2020年10月

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    記述言語:英語  

    We report a case of psoriatic arthritis where oligoarthritis preceded the skin lesions. A 57-year-old man complained of left third-finger pain. Laboratory examinations were negative for anti-cyclic citrullinated peptide antibodies and rheumatoid factor; he was treated for suspected rheumatoid arthritis. Six years later, X-ray revealed enthesitis of his fingers and wrist joint. At 9.5 years after the initial visit, skin lesions appeared in the left auricular region and buttock and dermatopathology findings indicated psoriasis vulgaris. The final diagnosis was psoriatic arthritis. In cases of seronegative oligoarthritis, psoriatic arthritis must be considered because some patients demonstrate osteoarticular lesions preceding skin lesions.

    DOI: 10.18926/AMO/60807

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  • Inhibition of Endoglin Exerts Antitumor Effects through the Regulation of Non-Smad TGF-β Signaling in Angiosarcoma. 査読 国際誌

    Ryoko Sakamoto, Ikko Kajihara, Hitomi Miyauchi, Saki Maeda-Otsuka, Saori Yamada-Kanazawa, Soichiro Sawamura, Hisashi Kanemaru, Katsunari Makino, Jun Aoi, Takamitsu Makino, Satoshi Fukushima, Mamiko Masuzawa, Mikio Masuzawa, Yasuyuki Amoh, Daichi Hoshina, Riichiro Abe, Hironobu Ihn

    The Journal of investigative dermatology   140 ( 10 )   2060 - 2072   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Angiosarcoma is a rare malignant tumor derived from endothelial cells, and its prognosis is poor because advanced angiosarcoma is often resistant to taxane therapy. Endoglin (CD105) acts as a coreceptor for TGF-β signaling and is overexpressed in tumor-associated endothelial cells and enhances tumor angiogenesis. Numerous clinical trials are testing the effectiveness of anti-endoglin antibodies in various types of malignancies. Here, we investigated the role of endoglin in the pathogenesis of angiosarcoma and whether endoglin inhibition results in antitumor activity. Endoglin was overexpressed in angiosarcoma, and its inhibition was effective in promoting apoptosis and the suppression of migration, invasion, tube formation, and Warburg effect in angiosarcoma cells. Knockdown of endoglin activated caspase 3/7 that is essential for apoptosis, reduced survivin levels, and decreased paxillin and vascular endothelial cadherin phosphorylation and matrix metalloproteinase 2 and matrix metalloproteinase 9 activities in angiosarcoma cells. Although endoglin is a coreceptor that regulates TGF-β signaling, the antitumor effect of endoglin in angiosarcoma was not based on Smad signaling regulation but on non-Smad TGF-β signaling. Taken together, these results indicated that endoglin could be a novel therapeutic target for angiosarcoma.

    DOI: 10.1016/j.jid.2020.01.031

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  • Exploration of biomarkers to predict clinical improvement of atopic dermatitis in patients treated with dupilumab: A study protocol. 査読 国際誌

    Takeshi Nakahara, Kenji Izuhara, Daisuke Onozuka, Satoshi Nunomura, Risa Tamagawa-Mineoka, Koji Masuda, Susumu Ichiyama, Hidehisa Saeki, Yudai Kabata, Riichiro Abe, Mamitaro Ohtsuki, Koji Kamiya, Tatsuro Okano, Tomomitsu Miyagaki, Yozo Ishiuji, Akihiko Asahina, Hiroshi Kawasaki, Keiji Tanese, Hiroshi Mitsui, Tatsuyoshi Kawamura, Takuya Takeichi, Masashi Akiyama, Emi Nishida, Akimichi Morita, Kyoko Tonomura, Yukinobu Nakagawa, Koji Sugawara, Chiharu Tateishi, Yoko Kataoka, Rai Fujimoto, Sakae Kaneko, Eishin Morita, Akio Tanaka, Michihiro Hide, Natsuko Aoki, Shigetoshi Sano, Haruna Matsuda-Hirose, Yutaka Hatano, Motoi Takenaka, Hiroyuki Murota, Norito Katoh, Masutaka Furue

    Medicine   99 ( 38 )   e22043   2020年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Atopic dermatitis (AD) is a common eczematous skin disorder that profoundly reduces the quality of life due to intractable pruritus. Excellent therapeutic success of the anti-interleukin 4 receptor-α antibody dupilumab in clinical trials and a real-world clinical context indicates the crucial roles of interleukin (IL)-4 and IL-13 in the pathogenesis of AD. Along with the clinical improvement in skin scores and pruritus, dupilumab significantly and progressively reduces and normalizes the upregulated expression of T helper type 2 signatures such as Chemokine (C-C motif) ligand (CCL)17, CCL18, CCL22, and CCL26 in the lesional skin of AD. However, no blood/serum biomarkers are known to predict good or poor outcome in patients with AD treated with dupilumab. METHODS: Patients are at least 18 years of age and have moderate-to-severe AD with Eczema Area and Severity Index (EASI) ≥16, Investigator's Global Assessment ≥3, and body surface area ≥10%. We are going to enroll more than 130 subjects from 18 medical facilities. Clinical objective findings will be evaluated by EASI. Subjective symptoms will be assessed by Patient-Oriented Eczema Measure, Numerical Rating Scale for Pruritus (Pruritus-NRS), Skin Comfort-NRS, and Treatment Satisfaction-NRS. We will measure 18 blood/serum biomarkers including % eosinophils in blood cell count, lactate dehydrogenase, total IgE, soluble interleukin 2 receptor, CCL17, CCL18, CCL22, CCL26, CCL27, IL-13, IL-22, IL-24, IL-25, IL-31, IL-33, thymic stromal lymphopoietin, periostin, and squamous cell carcinoma antigen-2. The clinical evaluation and biomarker sampling will be performed at 0, 2, 4, 8, and 16 weeks of dupilumab treatment. We will also perform proteomic analysis (of roughly 300 proteins) of the patients' sera obtained at 0 and 2 weeks of treatment. The primary endpoint is the association between "baseline levels of 18 biomarkers" and "% change from baseline of EASI at 16 weeks of dupilumab treatment." DISCUSSION: This is the first clinical trial to explore the biomarkers, including potential proteomic markers, most strongly associated with improvement in EASI in patients with moderate-to-severe AD treated with dupilumab for 16 weeks (B-PAD study). A limitation is that we will only enroll Japanese patients.

    DOI: 10.1097/MD.0000000000022043

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  • Characteristic pathological features of keratinocyte death in a case of Stevens-Johnson syndrome manifested by an immune checkpoint inhibitor. 査読 国際誌

    H Kimura, A Hasegawa, I Takei, T Kawai, Y Tsuchida, Y Abe, R Hayashi, N Hama, R Abe

    Journal of the European Academy of Dermatology and Venereology : JEADV   2020年8月

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    記述言語:英語  

    A 71-year-old female was treated with pembrolizumab for lung cancer three months prior. However, pembrolizumab was discontinued, and prednisolone 50 mg/day and trimethoprim/sulfamethoxazole were started for immune checkpoint inhibitor (ICI)-induced interstitial pneumonia a month prior. She developed painful reddish erythema and blisters on palms and soles, sporadic erythema on trunk, and mucosal erosion when PSL was tapered to 27.5 mg/day (Fig. 1a-d). The skin biopsy showed keratinocyte death, which was dominant in basal layer, and remarkable interface change (Fig. 1e, f). Her symptoms improved with an increase in prednisolone to 50 mg/day.

    DOI: 10.1111/jdv.16872

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  • Loss of dynamin-related protein 1 (Drp1) does not affect epidermal development or UVB-induced apoptosis but does accelerate UVB-induced carcinogenesis. 査読 国際誌

    Teruki Yanagi, Shinya Kitamura, Keisuke Imafuku, Asuka Suto, Takuya Maeda, Shinya Tanaka, Hiromi Sesaki, Riichiro Abe, Hiroshi Shimizu

    Journal of dermatological science   99 ( 2 )   109 - 118   2020年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Mitochondrial morphology is controlled by fission and fusion. Dynamin-related protein 1 (Drp1, dynamin-1-like protein (Dnml1)) regulates mitochondrial fission, which is associated with cell division and apoptosis. We previously reported that DRP1 is indispensable for cell growth in cutaneous squamous cell carcinoma. However, little is known about Drp1 in normal epidermis/keratinocytes. OBJECTIVES: We investigated the function of Drp1 in normal epidermis/keratinocytes. METHODS: Epidermis-specific Drp1 knockout (EKO) mice were analyzed. RESULTS: Epidermal development in the EKO mice were indistinguishable from those in the wild-type (WT) mice. Ultrastructural analysis and immunohistochemistry revealed that the mitochondria of keratinocytes in the EKO mice were neither elongated nor constricted. Drp1 knockdown did not diminish the cell growth of normal human keratinocytes. Both in vivo and in vitro, UVB-induced apoptosis in the EKO epidermis and keratinocytes did not differ from that in the WT mice. In chronic UVB-irradiation, the loss of Drp1 sensitized the epidermis to the development of skin tumors. Clinically, DRP1 is expressed more highly in sun-exposed skin than in non-exposed skin in individuals under age 40, but not in those over age 60. CONCLUSION: EKO mice demonstrate that Drp1 is dispensable for the development and apoptosis of the epidermis. Drp1 plays critical roles in malignant tumors; thus, the molecular machinery of mitochondrial dynamics involving Drp1 could be a novel therapeutic target for malignant keratinocytic lesions. On the other hand, the anti-tumorigenic role of Drp1 in chronic UVB-induced carcinogenesis need to be further investigated.

    DOI: 10.1016/j.jdermsci.2020.06.009

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  • Case of toxic epidermal necrolysis successfully treated with repeated i.v. immunoglobulin. 査読 国際誌

    Koichi Tomii, Tokiko Deguchi, Tatsuya Katsumi, Takeo Suzuki, Atsushi Fujimoto, Hiroshi Miida, Riichiro Abe

    The Journal of dermatology   47 ( 7 )   e265-e266   2020年7月

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  • Mycoplasma pneumoniae-associated Stevens-Johnson syndrome: characteristic histological features of mucosal lesion. 査読 国際誌

    T Katsumi, N Hama, Y Iwai, K Kimura, O Ansai, T Suzuki, R Abe

    Journal of the European Academy of Dermatology and Venereology : JEADV   2020年6月

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    記述言語:英語  

    DOI: 10.1111/jdv.16796

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  • Diverse dystonin gene mutations cause distinct patterns of Dst isoform deficiency and phenotypic heterogeneity in Dystonia musculorum mice. 査読 国際誌

    Nozomu Yoshioka, Yudai Kabata, Momona Kuriyama, Norihisa Bizen, Li Zhou, Dang M Tran, Masato Yano, Atsushi Yoshiki, Tatsuo Ushiki, Thomas J Sproule, Riichiro Abe, Hirohide Takebayashi

    Disease models & mechanisms   13 ( 5 )   2020年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Loss-of-function mutations in dystonin (DST) can cause hereditary sensory and autonomic neuropathy type 6 (HSAN-VI) or epidermolysis bullosa simplex (EBS). Recently, DST-related diseases were recognized to be more complex than previously thought because a patient exhibited both neurological and skin manifestations, whereas others display only one or the other. A single DST locus produces at least three major DST isoforms: DST-a (neuronal isoform), DST-b (muscular isoform) and DST-e (epithelial isoform). Dystonia musculorum (dt) mice, which have mutations in Dst, were originally identified as spontaneous mutants displaying neurological phenotypes. To reveal the mechanisms underlying the phenotypic heterogeneity of DST-related diseases, we investigated two mutant strains with different mutations: a spontaneous Dst mutant (Dstdt-23Rbrc mice) and a gene-trap mutant (DstGt mice). The Dstdt-23Rbrc allele possesses a nonsense mutation in an exon shared by all Dst isoforms. The DstGt allele is predicted to inactivate Dst-a and Dst-b isoforms but not Dst-e There was a decrease in the levels of Dst-a mRNA in the neural tissue of both Dstdt-23Rbrc and DstGt homozygotes. Loss of sensory and autonomic nerve ends in the skin was observed in both Dstdt-23Rbrc and DstGt mice at postnatal stages. In contrast, Dst-e mRNA expression was reduced in the skin of Dstdt-23Rbrc mice but not in DstGt mice. Expression levels of Dst proteins in neural and cutaneous tissues correlated with Dst mRNAs. Because Dst-e encodes a structural protein in hemidesmosomes (HDs), we performed transmission electron microscopy. Lack of inner plaques and loss of keratin filament invasions underneath the HDs were observed in the basal keratinocytes of Dstdt-23Rbrc mice but not in those of DstGt mice; thus, the distinct phenotype of the skin of Dstdt-23Rbrc mice could be because of failure of Dst-e expression. These results indicate that distinct mutations within the Dst locus can cause different loss-of-function patterns among Dst isoforms, which accounts for the heterogeneous neural and skin phenotypes in dt mice and DST-related diseases.

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  • RIP3 as a diagnostic and severity marker for Stevens-Johnson syndrome and toxic epidermal necrolysis. 査読 国際誌

    Akito Hasegawa, Satoru Shinkuma, Ryota Hayashi, Natsumi Hama, Hideaki Watanabe, Manao Kinoshita, Youichi Ogawa, Riichiro Abe

    The journal of allergy and clinical immunology. In practice   8 ( 5 )   1768 - 1771   2020年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.jaip.2020.01.006

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  • Case of cutaneous botryomycosis in an 8-year-old immunocompetent boy with a review of the published work. 査読 国際誌

    Haruna Shimagaki, Akihiko Yuki, Kiyoto Kimura, Daisuke Yuki, Hiroki Fujikawa, Naoya Shimizu, Riichiro Abe

    The Journal of dermatology   47 ( 5 )   542 - 545   2020年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Botryomycosis is a rare chronic suppurative granulomatous infection caused by several genera of non-filamentous bacteria. The clinical and histopathological findings are similar to those of mycetoma caused by true fungi or aerobic actinomycetes. Botryomycosis is divided into cutaneous and visceral disease, with the cutaneous form being more common. Histopathology shows granules of etiologic bacteria called "sulfur granules". Botryomycosis occurs more commonly among immunocompromised patients, although some cases have also been reported in immunocompetent patients. We report the case of an 8-year-old immunocompetent boy who visited our hospital with a 4-mm diameter subcutaneous tumor with mild tenderness on his right heel for several months. We surgically removed the tumor with an initial diagnosis of epidermal cyst. Histopathology showed sulfur granules surrounded by an eosinophilic matrix, indicating the Splendore-Hoeppli phenomenon. The granules consisted of Gram-positive cocci, leading to a diagnosis of botryomycosis. The patient was successfully treated by excision and oral trimethoprim/sulfamethoxazole (240 mg b.i.d.) for 2 weeks as adjuvant therapy. No recurrence was noted following treatment. The subcutaneous tumor in this case was smaller than the typical in botryomycosis infections. We reviewed the infection duration and tumor size in reported cases of botryomycosis in immunocompetent patients. Small tumor size may suggest that the case is in an early stage; therefore, it is important to remove and investigate these lesions proactively.

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  • 凍瘡様皮疹を契機に診断しえたneuropsychiatric systemic lupus erythematosusの1例

    土田 裕子, 新熊 悟, 安齋 理, 出口 登希子, 片桐 隆幸, 浦部 陽香, 畠山 公大, 堅田 慎一, 小野寺 理, 阿部 理一郎

    臨床皮膚科   74 ( 6 )   395 - 400   2020年5月

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    記述言語:日本語   出版者・発行元:(株)医学書院  

    <文献概要>75歳,女性.当科初診の2ヵ月前から足趾の冷感,暗紫色調の変化を自覚するようになった.皮疹出現の1ヵ月後に意識障害が生じ,当院に緊急入院した.頭部画像検査で異常所見は認めず,意識障害の原因は不明であった.皮疹に関して当科を紹介され受診した.足趾に凍瘡様皮疹,頬部や耳介部に浸潤の触れる角化性紅斑を認めた.左頬部紅斑の病理組織検査で,表皮真皮境界部の液状変性および真皮付属器周囲にリンパ球を主体とした炎症細胞の浸潤を認めた.凍瘡状ループスに加え汎血球減少,低補体血症,抗核抗体陽性がみられたことから,neuropsychiatric systemic lupus erythematosus(NPSLE)を伴った全身性エリテマトーデスと診断した.意識障害はステロイド全身投与により改善した.エリテマトーデスを疑う皮疹をもつ原因不明の意識障害患者を診察した際,NPSLEを鑑別に挙げ全身を診察することが重要である.

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01559&link_issn=&doc_id=20200603050006&doc_link_id=10.11477%2Fmf.1412206068&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1412206068&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

  • Functional analysis of keratin filament network formation indicates clinical severity of epidermolysis bullosa simplex. 査読 国際誌

    O Ansai, S Shinkuma, R Hayashi, K Tomii, T Deguchi, A Aizawa, H Fujiwara, Y Shimomura, R Abe

    Journal of the European Academy of Dermatology and Venereology : JEADV   34 ( 10 )   e613-e616   2020年4月

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    記述言語:英語  

    DOI: 10.1111/jdv.16495

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  • Intracytoplasmic abnormality of corneocytes in circumscribed palmar or plantar hypokeratosis: ultrastructural observations. 査読 国際誌

    T Kawai, Y Kabata, S Shinkuma, M Oginezawa, R Hayashi, M Hayatsu, R Abe

    Journal of the European Academy of Dermatology and Venereology : JEADV   2020年4月

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    記述言語:英語  

    DOI: 10.1111/jdv.16518

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  • Refractory Bullous Pemphigoid Improved by Discontinuation of Phenytoin as an CYP3A4 Inducer. 査読 国際誌

    Rei Yokoyama, Ryota Hayashi, Yukie Umemori, Ami Arimatsu, Akihiko Yuki, Riichiro Abe

    Acta dermato-venereologica   100 ( 8 )   adv00108   2020年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2340/00015555-3472

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  • CADM1 expression of mast cells in mycosis fungoides. 査読 国際誌

    Akihiko Yuki, Osamu Ansai, Riichiro Abe

    Journal of the American Academy of Dermatology   82 ( 4 )   e143-e144   2020年4月

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  • SJS/TEN 2019: From science to translation. 査読 国際誌

    Wan-Chun Chang, Riichiro Abe, Paul Anderson, Wanpen Anderson, Michael R Ardern-Jones, Thomas M Beachkofsky, Teresa Bellón, Agnieszka K Biala, Charles Bouchard, Gianpiero L Cavalleri, Nicole Chapman, James Chodosh, Hyon K Choi, Ricardo R Cibotti, Sherrie J Divito, Karen Dewar, Ulrike Dehaeck, Mahyar Etminan, Diane Forbes, Esther Fuchs, Jennifer L Goldman, James H Holmes 4th, Elyse A Hope, Shuen-Iu Hung, Chia-Ling Hsieh, Alfonso Iovieno, Julienne Jagdeo, Mee Kum Kim, David M Koelle, Mario E Lacouture, Sophie Le Pallec, Rannakoe J Lehloenya, Robyn Lim, Angie Lowe, Jean McCawley, Julie McCawley, Robert G Micheletti, Maja Mockenhaupt, Katie Niemeyer, Michael A Norcross, Douglas Oboh, Cristina Olteanu, Helena B Pasieka, Jonathan Peter, Munir Pirmohamed, Michael Rieder, Hajirah N Saeed, Neil H Shear, Christine Shieh, Sabine Straus, Chonlaphat Sukasem, Cynthia Sung, Jason A Trubiano, Sheng-Ying Tsou, Mayumi Ueta, Simona Volpi, Chen Wan, Hongsheng Wang, Zhao-Qing Wang, Jessica Weintraub, Cindy Whale, Lisa M Wheatley, Sonia Whyte-Croasdaile, Kristina B Williams, Galen Wright, Sonia N Yeung, Li Zhou, Wen-Hung Chung, Elizabeth J Phillips, Bruce C Carleton

    Journal of dermatological science   98 ( 1 )   2 - 12   2020年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs.

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  • Multiple seborrheic keratosis-like lesions of mycosis fungoides masquerading as the Leser-Trèlat sign. 査読 国際誌

    Risa Hagiwara, Satoru Shinkuma, Koichi Tomii, Atsuko Aizawa, Riichiro Abe

    The Journal of dermatology   47 ( 3 )   e96-e97   2020年3月

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  • Localized bullous pemphigoid recurring at different sites: two case reports. 査読 国際誌

    Akito Hasegawa, Satoru Shinkuma, Tatsuya Katsumi, Naomi Kasahara, Kaoru Ito, Hideyuki Ujiie, Norito Ishii, Takashi Hashimoto, Riichiro Abe

    European journal of dermatology : EJD   2020年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Localized bullous pemphigoid is a relatively rare variant of bullous pemphigoid. Lesions develop only in localized sites including the legs or palms and soles and occasionally appear in trauma-affected body parts. In some cases, the skin lesions spread to the entire body, while in others, they remain localized and improve spontaneously or with treatment using topical corticosteroids. Rarely, the lesions recur at sites different from those of the original lesions, after the initial lesions have completely healed. OBJECTIVES: To investigate the clinical course of patients with localized bullous pemphigoid. MATERIALS AND METHODS: Two cases of localized bullous pemphigoid that recurred at sites distant from those of the initial lesions were reported. RESULTS: Case 1 involved a 62-year-old woman with mucous membrane pemphigoid. One year after the improvement of mucosal symptoms, new lesions appeared in the periumbilical area. The lesions resolved after topical corticosteroid treatment. This case is the first report of localized bullous pemphigoid occurring after an improvement of mucous membrane pemphigoid. Case 2 involved an 81-year-old man who bruised his right lower leg and developed erythematous plaques and tense bullae. The patient was diagnosed with localized bullous pemphigoid and was treated with topical corticosteroid. However, six months later, new lesions appeared on the palms and soles. The patient responded well to oral prednisolone. CONCLUSIONS: Since localized bullous pemphigoid may have a variable clinical course, clinicians should observe affected patients carefully over a long period of time.

    DOI: 10.1684/ejd.2019.3672

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  • sQuiz your knowledge! Cord-like erythematous plaques on the lower limbs of a patient with systemic lupus erythematosus. 査読 国際誌

    Yuki Iwai, Natsumi Hama, Riichiro Abe

    European journal of dermatology : EJD   30 ( 1 )   80 - 81   2020年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1684/ejd.2020.3739

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  • Confusion in determination of two types of cutaneous adverse reactions to drugs, maculopapular eruption and erythema multiforme, among the experts: A proposal of standardized terminology. 査読 国際誌

    Hideo Hashizume, Riichiro Abe, Hiroaki Azukizawa, Toshiharu Fujiyama, Natsumi Hama, Yoshiko Mizukawa, Eishin Morita, Yukinobu Nakagawa, Saeko Nakajima, Hiroyuki Niihara, Yuichi Teraki, Mikiko Tohyama, Hideaki Watanabe, Yoshiki Tokura

    The Journal of dermatology   47 ( 2 )   169 - 173   2020年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The clinical classification of cutaneous adverse reactions by drugs should be clearly distinguished to avoid conceptual confusion and inconsistency. Although dermatologists appear to have established a roughly common consensus for cutaneous adverse reactions, some types are more rigorously defined than other, possibly misleading classifications. To assess the consensus on the clinical classifications, we investigated the concordance rate of diagnosis by Japanese experts through a snap visual inspection of various clinical pictures exhibiting erythema multiforme and maculopapular eruption types of cutaneous adverse reactions. The experts were shown images on a screen and were then asked to decide whether to classify cases as maculopapular eruption or erythema multiforme type, and the concordance rates were calculated. Overall, the mean concordance rate was 71.6% (standard deviation, 17.3%), and only 33.8% of cases had a 90% or more concordance rate. Our study shows that the determinations of erythema multiforme and maculopapular eruption types by the existing classification criteria were confusing even among experts, which prompted us to standardize the terminology. We propose clinically defining erythema multiforme type as generalized macules mainly of 1 cm or more with a tendency of elevation and coalescence, and maculopapular eruption type as generalized erythema other than erythema multiforme type. Currently, the clinical definitions of cutaneous adverse reactions are poorly described, which may be problematic upon analyzing large volumes of data. Our proposal for a new terminology will enhance the accuracy and consistency of information for the correct analysis of cutaneous adverse reactions.

    DOI: 10.1111/1346-8138.15164

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  • Amino acid charge and epidermolysis bullosa simplex severity: genotype-phenotype correlations. 国際誌

    O Ansai, S Shinkuma, Y Kabata, T Katsumi, R Hagiwara, K Tomii, H Fujikawa, M Matsubara, R Abe

    Journal of the European Academy of Dermatology and Venereology : JEADV   34 ( 2 )   e87-e90   2020年2月

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    記述言語:英語  

    DOI: 10.1111/jdv.15990

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  • Recent advances in managing and understanding Stevens-Johnson syndrome and toxic epidermal necrolysis. 査読 国際誌

    Akito Hasegawa, Riichiro Abe

    F1000Research   9   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening diseases characterized by detachment of the epidermis and mucous membrane. SJS/TEN are considered to be on the same spectrum of diseases with different severities. They are classified by the percentage of skin detachment area. SJS/TEN can also cause several complications in the liver, kidneys, and respiratory tract. The pathogenesis of SJS/TEN is still unclear. Although it is difficult to diagnose early stage SJS/TEN, biomarkers for diagnosis or severity prediction have not been well established. Furthermore, optimal therapeutic options for SJS/TEN are still controversial. Several drugs, such as carbamazepine and allopurinol, are reported to have a strong relationship with a specific human leukocyte antigen (HLA) type. This relationship differs between different ethnicities. Recently, the usefulness of HLA screening before administering specific drugs to decrease the incidence of SJS/TEN has been investigated. Skin detachment in SJS/TEN skin lesions is caused by extensive epidermal cell death, which has been considered to be apoptosis via the Fas-FasL pathway or perforin/granzyme pathway. We reported that necroptosis, i.e. programmed necrosis, also contributes to epidermal cell death. Annexin A1, released from monocytes, and its interaction with the formyl peptide receptor 1 induce necroptosis. Several diagnostic or prognostic biomarkers for SJS/TEN have been reported, such as CCL-27, IL-15, galectin-7, and RIP3. Supportive care is recommended for the treatment of SJS/TEN. However, optimal therapeutic options such as systemic corticosteroids, intravenous immunoglobulin, cyclosporine, and TNF-α antagonists are still controversial. Recently, the beneficial effects of cyclosporine and TNF-α antagonists have been explored. In this review, we discuss recent advances in the pathophysiology and management of SJS/TEN.

    DOI: 10.12688/f1000research.24748.1

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  • Electron Microscopic and Immunohistochemical Findings of the Epidermal Basement Membrane in Two Families with Nail-patella Syndrome. 査読 国際誌

    Satoru Shinkuma, Hideki Nakamura, Manami Maehara, Shota Takashima, Toshifumi Nomura, Yasuyuki Fujita, Satoshi Hasegawa, Kazuko C Sato-Matsumura, Riichiro Abe, Hiroshi Shimizu

    Acta dermato-venereologica   99 ( 12 )   1110 - 1115   2019年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Nail-patella syndrome is an autosomal dominant disorder characterized by nail dysplasia and skeletal anomaly. Some patients have been shown to have ultrastructural abnormalities of the glomerular basement membrane that result in nephrosis. However, little has been reported on the epidermal basement membrane in this condition. This paper reports 2 families with nail-patella syndrome. Direct sequencing analysis of LMX1B revealed that family 1 and family 2 were heterozygous for the mutations c.140-1G>C and c.326+1G>C, respectively. To evaluate the epidermal basement membrane zone, ultrastructural and immunohistochemical analyses were performed using skin specimens obtained from the dorsal thumb. Electron microscopy showed intact hemidesmosomes, lamina lucida, lamina densa, and anchoring fibrils. Immunofluorescence studies with antibodies against components of the epidermal basement membrane zone revealed a normal expression pattern among the components, including type IV collagen. These data suggest that nail dysplasia in patients with nail-patella syndrome is not caused by structural abnormalities of the epidermal basement membrane.

    DOI: 10.2340/00015555-3318

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  • Cultured Epidermal Autografts from Clinically Revertant Skin as a Potential Wound Treatment for Recessive Dystrophic Epidermolysis Bullosa. 査読 国際誌

    Wakana Matsumura, Yasuyuki Fujita, Satoru Shinkuma, Shotaro Suzuki, Saki Yokoshiki, Hideki Goto, Hiroshi Hayashi, Kota Ono, Masukazu Inoie, Shota Takashima, Chihiro Nakayama, Toshifumi Nomura, Hideki Nakamura, Riichiro Abe, Norihiro Sato, Hiroshi Shimizu

    The Journal of investigative dermatology   139 ( 10 )   2115 - 2124   2019年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Inherited skin disorders have been reported recently to have sporadic normal-looking areas, where a portion of the keratinocytes have recovered from causative gene mutations (revertant mosaicism). We observed a case of recessive dystrophic epidermolysis bullosa treated with cultured epidermal autografts (CEAs), whose CEA-grafted site remained epithelized for 16 years. We proved that the CEA product and the grafted area included cells with revertant mosaicism. Based on these findings, we conducted an investigator-initiated clinical trial of CEAs from clinically revertant skin for recessive dystrophic epidermolysis bullosa. The donor sites were analyzed by genetic analysis, immunofluorescence, electron microscopy, and quantification of the reverted mRNA with deep sequencing. The primary endpoint was the ulcer epithelization rate per patient at 4 weeks after the last CEA application. Three patients with recessive dystrophic epidermolysis bullosa with 8 ulcers were enrolled, and the epithelization rate for each patient at the primary endpoint was 87.7%, 100%, and 57.0%, respectively. The clinical effects were found to persist for at least 76 weeks after CEA transplantation. One of the three patients had apparent revertant mosaicism in the donor skin and in the post-transplanted area. CEAs from clinically normal skin are a potentially well-tolerated treatment for recessive dystrophic epidermolysis bullosa.

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  • The significance of tumor cells-derived MFG-E8 in tumor growth of angiosarcoma. 査読 国際誌

    Chisako Fujiwara, Sei-Ichiro Motegi, Aoi Ohira, Sayaka Yamaguchi, Akiko Sekiguchi, Masahito Yasuda, Hideharu Nakamura, Takaya Makiguchi, Satoshi Yokoo, Daichi Hoshina, Riichiro Abe, Kenzo Takahashi, Osamu Ishikawa

    Journal of dermatological science   96 ( 1 )   18 - 25   2019年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    BACKGROUND: Previous studies have indicated that MFG-E8 enhances tumor cell survival, invasion and angiogenesis. However, the role of MFG-E8 in angiosarcoma (AS) has not been clarified. OBJECTIVE: Objective was to elucidate the mechanism of the regulation by MFG-E8 in AS and the association between MFG-E8 and clinicopathological features of AS. METHODS: The effects of the depletion of MFG-E8 by siRNA on tube formation, migration and proliferation in murine AS cells were examined. The effect of administration of anti-MFG-E8 antibody (Ab) on tumor growth of AS in mice was examined. The associations of MFG-E8 expression and clinicopathological features of human AS were assessed. RESULTS: The expressions of MFG-E8 in murine and human AS cells were significantly higher than those in melanoma cells, macrophages and endothelial cells. Depletion of MFG-E8 in murine AS cells by siRNA significantly inhibited the formation of capillary-like structures and migration, but not proliferation. Administration of anti-MFG-E8 Ab significantly inhibited tumor growth and decreased the number of tumor-associated macrophages (TAMs) in AS tumors. Tumor size and the number of TAMs in human AS with high expression of MFG-E8 were significantly increased compared to those of AS with low expression of MFG-E8. Progression-free survival and overall survival time of the patients of AS with high expression of MFG-E8 were significantly shorter than those of AS with low expression of MFG-E8. CONCLUSIONS: AS-derived MFG-E8 might enhance tumor growth via angiogenesis and the induction of TAMs in autocrine/paracrine manner, and administration of anti-MFG-E8 Ab could be a therapeutic potential for AS.

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  • Efficient Gene Reframing Therapy for Recessive Dystrophic Epidermolysis Bullosa with CRISPR/Cas9. 査読 国際誌

    Shota Takashima, Satoru Shinkuma, Yasuyuki Fujita, Toshifumi Nomura, Hideyuki Ujiie, Ken Natsuga, Hiroaki Iwata, Hideki Nakamura, Artem Vorobyev, Riichiro Abe, Hiroshi Shimizu

    The Journal of investigative dermatology   139 ( 8 )   1711 - 1721   2019年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system induces site-specific double-strand breaks, which stimulate cellular DNA repair through either the homologous recombination or non-homologous end-joining pathways. The non-homologous end-joining pathway, which is activated more frequently than homologous recombination, is prone to introducing small insertions and/or deletions at the double-strand break site, leading to changes in the reading frame. We hypothesized that the non-homologous end-joining pathway is applicable to genetic diseases caused by a frameshift mutation through restoration of the reading frame. Recessive dystrophic epidermolysis bullosa is a hereditary skin disorder caused by mutations in COL7A1. In this study, we applied gene reframing therapy to a recurrent frameshift mutation, c.5819delC, in COL7A1, which results in a premature termination codon. CRISPR/Cas9 targeting this specific mutation site was delivered to recessive dystrophic epidermolysis bullosa patient fibroblasts. After genotyping a large collection of gene-edited fibroblast clones, we identified a significant number (17/50) of clones in which the frameshift in COL7A1 was restored. The reframed COL7 was functional, as shown by triple-helix formation assay in vitro, and was correctly distributed in the basement membrane zone in mice. Our data suggest that mutation site-specific non-homologous end-joining might be a highly efficient gene therapy for inherited disorders caused by frameshift mutations.

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  • The morphology, size and density of the touch dome in human hairy skin by scanning electron microscopy. 査読 国際誌

    Yudai Kabata, Mari Orime, Riichiro Abe, Tatsuo Ushiki

    Microscopy (Oxford, England)   68 ( 3 )   207 - 215   2019年6月

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    記述言語:英語  

    The touch domes of mammalian hairy skin are mechanoreceptors characterized by the accumulation of Merkel cell-neurite complexes at the epidermal base. In this study, we examined the shape, size, and density of the touch dome of human skin of the forearm and the abdomen through scanning electron microscopy (SEM). Human skin samples were obtained from donated bodies, as well as a patient who underwent biopsy. Skin pieces were treated with a KOH-collagenase method for the separation of the epidermis from the dermis. The basal surface of the separated epidermis was then observed using SEM. The touch dome was clearly determined as a concave area bordered by a thick epidermal ridge, where neural components accumulated. The touch dome was rather independent from hair follicles, although they were sometimes located beside the touch dome. The average size and density of the touch dome were 0.06 mm2 and 3.82 cm2 in the forearm, and 0.10 mm2 and 1.30 cm2 in the abdomen, respectively. Our results suggested that the regional difference in size and density of the touch dome might be related to the sensation's sensitivity as touch spots in human hairy skin.

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  • Galectin-7 as a potential biomarker of Stevens-Johnson syndrome/toxic epidermal necrolysis: identification by targeted proteomics using causative drug-exposed peripheral blood cells. 査読

    Hama N, Nishimura K, Hasegawa A, Yuki A, Kume H, Adachi J, Kinoshita M, Ogawa Y, Nakajima S, Nomura T, Watanabe H, Mizukawa Y, Tomonaga T, Shimizu H, Abe R

    The journal of allergy and clinical immunology. In practice   2019年5月

  • Multiple yellowish white papules on the trunk and upper arms. 査読 国際誌

    Mami Nakajima, Satoru Shinkuma, Rei Yokoyama, Tokiko Deguchi, Atsuko Aizawa, Katsuhiro Tomiyama, Riichiro Abe

    International journal of dermatology   58 ( 5 )   543 - 544   2019年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/ijd.14273

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  • Reply. 査読 国際誌

    Akito Hasegawa, Riichiro Abe

    The Journal of allergy and clinical immunology   143 ( 5 )   1976 - 1977   2019年5月

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  • [Cutaneous Adverse Drug Reaction Caused by Antiepileptic Drug]. 査読

    Tokiko Deguchi, Riichiro Abe

    Brain and nerve = Shinkei kenkyu no shinpo   71 ( 4 )   401 - 406   2019年4月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug induced hypersensitivity syndrome (DIHS) are severe cutaneous adverse reactions, which can be life-threatening and lead to severe sequelae. Antiepileptic drugs frequently cause severe adverse reactions in the form of. It is important to understand the characteristics of each disease and attempt at early diagnosis.

    DOI: 10.11477/mf.1416201284

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  • Dental metal allergy is not the main cause of palmoplantar pustulosis 査読

    Y. Masui, A. Ito, Y. Akiba, K. Uoshima, R. Abe

    Journal of the European Academy of Dermatology and Venereology   33 ( 4 )   e180 - e181   2019年4月

  • Culprit Drugs Induce Specific IL-36 Overexpression in Acute Generalized Exanthematous Pustulosis. 査読 国際誌

    Barbara Meier-Schiesser, Laurence Feldmeyer, Dragana Jankovic, Mark Mellett, Takashi K Satoh, Daniel Yerly, Alexander Navarini, Riichiro Abe, Nikhil Yawalkar, Wen-Hung Chung, Lars E French, Emmanuel Contassot

    The Journal of investigative dermatology   139 ( 4 )   848 - 858   2019年4月

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    記述言語:英語  

    Acute generalized exanthematous pustulosis (AGEP) is a severe adverse cutaneous drug reaction. Although an involvement of drug-specific T cells has been reported, the physiopathology of AGEP and mechanism of neutrophilic skin inflammation remain incompletely understood. Recently, mutations in IL-36RN, the gene encoding the IL-36 receptor antagonist, have been reported to be more frequent in AGEP patients and pustular psoriasis. Here, we show that IL-36 cytokines, in particular IL-36γ, are highly expressed in lesional skin of AGEP patients, keratinocytes and macrophages being a major source of IL-36γ. Such an IL-36γ overexpression was not observed in patients with drug-induced maculopapular rash. In vitro, the causative drug specifically induced IL-36γ release either directly by the patient's peripheral blood monocytes or indirectly by keratinocytes in the presence of autologous peripheral blood mononuclear cells. Such culprit drug induction of IL-36γ secretion in vitro was specific for AGEP and involved toll-like receptor 4 sensing the drug/albumin complex as a danger signal. Our results suggest that IL-36γ secretion by monocytes/macrophages and keratinocytes in response to culprit drug exposure likely plays a key role in the pathogenesis of AGEP.

    DOI: 10.1016/j.jid.2018.10.023

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  • AIによる重症薬疹の早期診断

    藤本 篤, 岩井 由樹, 新熊 悟, 阿部 理一郎, 村松 正吾

    日本皮膚科学会雑誌   129 ( 4 )   556 - 556   2019年4月

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    記述言語:日本語   出版者・発行元:(公社)日本皮膚科学会  

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  • Generalized pustular psoriasis complicated with bullous pemphigoid. 査読 国際誌

    Yuko Tsuchida, Ryota Hayashi, Osamu Ansai, Mami Nakajima, Mahoko Oginezawa, Toru Kawai, Rei Yokoyama, Tokiko Deguchi, Natsumi Hama, Satoru Shinkuma, Riichiro Abe

    International journal of dermatology   58 ( 3 )   e66-e67 - e67   2019年3月

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    記述言語:英語  

    DOI: 10.1111/ijd.14332

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  • Hypoxia accelerates the progression of angiosarcoma through the regulation of angiosarcoma cells and tumor microenvironment. 査読 国際誌

    Saki Maeda-Otsuka, Ikko Kajihara, Yukino Tasaki, Saori Yamada-Kanazawa, Ryoko Sakamoto, Soichiro Sawamura, Mamiko Masuzawa, Mikio Masuzawa, Yasuyuki Amoh, Daichi Hoshina, Riichiro Abe, Yoshihiro Komohara, Hironobu Ihn

    Journal of dermatological science   93 ( 2 )   123 - 132   2019年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Angiosarcoma is a rare malignant tumor with a poor prognosis. It is known that hypoxic condition activates tumor progression in several cancers. Additionally, hypoxic tumor microenvironment accelerates immune escape. However, the presence and significance of hypoxia in angiosarcoma has not been adequately investigated. OBJECTIVE: To study the role of hypoxia in the progression of angiosarcoma. METHODS: The protein level of hypoxia inducible factor-1α (HIF-1α) in angiosarcoma was examined using immunohistochemistry and immunoblotting. To study the effect of hypoxia on tumor progression, cell proliferation, migration, invasion, and tube formation assays were performed in angiosarcoma cells. The influence of tumor cell supernatant in hypoxia from angiosarcoma cells on immune escape and angiogenesis was analysed to investigate the modulatory effect of hypoxia on tumor microenvironment of angiosarcoma. The molecular mechanism related to these results was investigated using immunoblotting and real time RT-PCR. RESULTS: HIF-1α protein was over-expressed in angiosarcoma tissues and cell lines under hypoxic conditions, and there was heterogeneity of oxygen supply in angiosarcoma. Hypoxia enhanced the proliferation, migration, and invasion abilities and inhibited tube formation in angiosarcoma cells. Tumor cell supernatant in hypoxia from angiosarcoma cells activated the monocyte invasion ability, facilitated its differentiation into M2-like macrophages, and suppressed cell-adhesion. These in vitro results were compatible to the pathological findings of angiosarcoma patients. CONCLUSION: Hypoxia plays a major role in progression of angiosarcoma cells by enhancing cell proliferation, migration, and invasion and by modulating the tumor microenvironment.

    DOI: 10.1016/j.jdermsci.2019.01.005

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  • Blockade of TNF receptor superfamily 1 (TNFR1)-dependent and TNFR1-independent cell death is crucial for normal epidermal differentiation. 査読 国際誌

    Xuehua Piao, Ryosuke Miura, Sanae Miyake, Sachiko Komazawa-Sakon, Masato Koike, Ryodai Shindo, Junji Takeda, Akito Hasegawa, Riichiro Abe, Chiharu Nishiyama, Tetsuo Mikami, Hideo Yagita, Yasuo Uchiyama, Hiroyasu Nakano

    The Journal of allergy and clinical immunology   143 ( 1 )   213 - 228   2019年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: A delicate balance between cell death and keratinocyte proliferation is crucial for normal skin development. Previous studies have reported that cellular FLICE (FADD-like ICE)-inhibitory protein plays a crucial role in prevention of keratinocytes from TNF-α-dependent apoptosis and blocking of dermatitis. However, a role for cellular FLICE-inhibitory protein in TNF-α-independent cell death remains unclear. OBJECTIVE: We investigated contribution of TNF-α-dependent and TNF-α-independent signals to the development of dermatitis in epidermis-specific Cflar-deficient (CflarE-KO) mice. METHODS: We examined the histology and expression of epidermal differentiation markers and inflammatory cytokines in the skin of CflarE-KO;Tnfrsf1a+/- and CflarE-KO;Tnfrsf1a-/- mice. Mice were treated with neutralizing antibodies against Fas ligand and TNF-related apoptosis-inducing ligand to block TNF-α-independent cell death of CflarE-KO;Tnfrsf1a-/- mice. RESULTS: CflarE-KO;Tnfrsf1a-/- mice were born but experienced severe dermatitis and succumbed soon after birth. CflarE-KO;Tnfrsf1a+/- mice exhibited embryonic lethality caused by massive keratinocyte apoptosis. Although keratinocytes from CflarE-KO;Tnfrsf1a-/- mice still died of apoptosis, neutralizing antibodies against Fas ligand and TNF-related apoptosis-inducing ligand substantially prolonged survival of CflarE-KO;Tnfrsf1a-/- mice. Expression of inflammatory cytokines, such as Il6 and Il17a was increased; conversely, expression of epidermal differentiation markers was severely downregulated in the skin of CflarE-KO;Tnfrsf1a-/- mice. Treatment of primary keratinocytes with IL-6 and, to a lesser extent, IL-17A suppressed expression of epidermal differentiation markers. CONCLUSION: TNF receptor superfamily 1 (TNFR1)-dependent or TNFR1-independent apoptosis of keratinocytes promotes inflammatory cytokine production, which subsequently blocks epidermal differentiation. Thus blockade of both TNFR1-dependent and TNFR1-independent cell death might be an alternative strategy to treat skin diseases when treatment with anti-TNF-α antibody alone is not sufficient.

    DOI: 10.1016/j.jaci.2018.02.043

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  • Two cases of hypohidrotic ectodermal dysplasia caused by novel deletion mutations in the EDA gene. 査読 国際誌

    Mami Nakajima, Ryota Hayashi, Satoru Shinkuma, Mio Watanabe, Yohya Shigehara, Yutaka Shimomura, Riichiro Abe

    The Journal of dermatology   46 ( 1 )   e21-e22 - e22   2019年1月

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  • 骨病変を有したLangerhans細胞組織球症の3例

    勝見 達也, 新熊 悟, 荻根沢 真帆子, 河合 亨, 加畑 雄大, 折目 真理, 伊藤 明子, 久保 暢大, 岩渕 晴子, 今井 千速, 阿部 理一郎

    臨床皮膚科   73 ( 1 )   78 - 84   2019年1月

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    記述言語:日本語   出版者・発行元:(株)医学書院  

    <文献概要>症例1:1歳5ヵ月,女児.頭部に脂漏性湿疹様皮疹,体幹四肢には紫斑,丘疹があり,Langerhans細胞の骨髄浸潤と,CT検査で蝶形骨の破壊像を認めた.症例2:5ヵ月,女児.下腹部や鼠径部に点状紫斑や丘疹があり,CT検査で右下顎骨の骨溶解を伴う腫瘤性病変を認めた.症例3:5歳,女児.鼠径部および大腿内側に褐色調の紅斑,丘疹があり,CT検査で第5頸椎の圧迫骨折を認めた.いずれの症例も皮疹からLangerhans細胞組織球症(Langerhans cell histiocytosis:LCH)を疑い,病理組織学的検査,電子顕微鏡検査にて多臓器型のLCHと診断した.化学療法もしくは経過観察で,皮疹は改善傾向である.LCHの皮疹は多彩であり,視診だけで診断することは困難である.LCHの皮膚病変を疑った場合は積極的に皮膚生検を行い,病型を確定する必要がある.

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01559&link_issn=&doc_id=20190201020017&doc_link_id=10.11477%2Fmf.1412205622&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1412205622&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

  • Erratum to "An Updated Review of the Molecular Mechanisms in Drug Hypersensitivity". 査読 国際誌

    Chun-Bing Chen, Riichiro Abe, Ren-You Pan, Chuang-Wei Wang, Shuen-Iu Hung, Yi-Giien Tsai, Wen-Hung Chung

    Journal of immunology research   2019   2489429 - 2489429   2019年

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    記述言語:英語  

    [This corrects the article DOI: 10.1155/2018/6431694.].

    DOI: 10.1155/2019/2489429

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  • CADM1 is a diagnostic marker in early-stage mycosis fungoides: Multicenter study of 58 cases. 査読 国際誌

    Akihiko Yuki, Satoru Shinkuma, Ryota Hayashi, Hiroki Fujikawa, Taisuke Kato, Erina Homma, Yohei Hamade, Osamu Onodera, Masao Matsuoka, Hiroshi Shimizu, Hiroaki Iwata, Riichiro Abe

    Journal of the American Academy of Dermatology   79 ( 6 )   1039 - 1046   2018年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. Early-stage MF patches or plaques often resemble inflammatory skin disorders (ISDs), including psoriasis and atopic dermatitis. Cell adhesion molecule 1 gene (CADM1), which was initially identified as a tumor suppressor gene in human non-small cell lung cancer, has been reported as a diagnostic marker for adult T-cell leukemia/lymphoma. OBJECTIVE: We investigated CADM1 expression in MF neoplastic cells, especially during early stages, and evaluated its usefulness as a diagnostic marker for MF. METHODS: We conducted a retrospective study by using immunohistochemical staining and confirmed the expression of CADM1 in MF. In addition, we compared CADM1 messenger RNA expression in microdissected MF samples and ISD samples. RESULTS: In the overall study period, 55 of 58 MF samples (94.8 %) stained positive for CADM1. None of the 50 ISD samples showed positive reactivity (P < .0001). We found CADM1 messenger RNA expression in the intradermal lymphocytes of patients with MF but not in those of patients with an ISD. LIMITATIONS: We did not conduct a validation study for MF cases in other institutions. CONCLUSIONS: CADM1-positive cells can be identified in early stages with fewer infiltrating cells and may be useful as a diagnostic marker for early-stage MF.

    DOI: 10.1016/j.jaad.2018.06.025

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  • Hailey-Hailey disease patient with a novel missense mutation in ATP2C1 successfully treated with minocycline hydrochloride. 査読 国際誌

    Yohya Shigehara, Satoru Shinkuma, Atsushi Fujimoto, Shinobu Saijo, Riichiro Abe

    The Journal of dermatology   45 ( 11 )   e306-e308 - e308   2018年11月

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  • Successful treatment of psoriatic arthritis associated with adrenal hypoplasia congenita using infliximab. 査読 国際誌

    Kiyoto Kimura, Atsushi Fujimoto, Tokiko Deguchi, Osamu Ansai, Yuko Tsuchida, Natsumi Hama, Naoki Kondo, Keisuke Nagasaki, Waka Ishida, Riichiro Abe

    European journal of dermatology : EJD   28 ( 5 )   707 - 708   2018年10月

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    記述言語:英語  

    DOI: 10.1684/ejd.2018.3382

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  • Severe thrombocytopenia induced by intravenous immunoglobulin therapy in a patient with bullous pemphigoid 査読

    Yokoyama Rei, Hama Natsumi, Kimura Kiyoto, Hasegawa Akito, Kibune Natsuko, Kariya Naoyuki, Yuki Naokata, Abe Riichiro

    DERMATOLOGICA SINICA   36 ( 3 )   163 - 164   2018年9月

  • Novel COL7A1 mutation in a family with bullous dermolysis of the newborn: Phenotypic variability associated with a COL7A1 mutation within the same family. 査読 国際誌

    Shota Takashima, Satoru Shinkuma, Yasuyuki Fujita, Ken Natsuga, Toshifumi Nomura, Tokimasa Hida, Shuku Ishikawa, Hideki Nakamura, Riichiro Abe, Hiroshi Shimizu

    The Journal of dermatology   45 ( 9 )   e260-e261 - e261   2018年9月

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  • The development of induced pluripotent stem cell-derived mesenchymal stem/stromal cells from normal human and RDEB epidermal keratinocytes. 査読 国際誌

    Chihiro Nakayama, Yasuyuki Fujita, Wakana Matsumura, Inkin Ujiie, Shota Takashima, Satoru Shinkuma, Toshifumi Nomura, Riichiro Abe, Hiroshi Shimizu

    Journal of dermatological science   91 ( 3 )   301 - 310   2018年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Epidermolysis bullosa (EB) is a group of hereditary disorders caused by mutations in the genes encoding structural molecules of the dermal-epidermal junction (DEJ). Cell-based therapies such as allogeneic mesenchymal stem/stromal cell (MSC) transplantation have recently been explored for severe EB types, such as recessive dystrophic EB (RDEB). However, hurdles exist in current MSC-based therapies, such as limited proliferation from a single cell source and limited cell survival due to potential allogenic rejection. OBJECTIVES: We aimed to develop MSCs from keratinocyte-derived induced pluripotent stem cells (iPSCs). METHODS: Keratinocyte-derived iPSCs (KC-iPSCs) of a healthy human and an RDEB patient were cultured with activin A, 6-bromoindirubin-3'-oxime and bone morphogenetic protein 4 to induce mesodermal lineage formation. These induced cells were subjected to immunohistochemical analysis, flow cytometric analysis and RNA microarray analysis in vitro, and were injected subcutaneously and intravenously to wounded immunodeficient mice to assess their wound-healing efficacy. RESULTS: After their induction, KC-iPSC-induced cells were found to be compatible with MSCs. Furthermore, with the subcutaneous and intravenous injection of the KC-iPSC-induced cells into wounded immunodeficient mice, human type VII collagen was detected at the DEJ of epithelized areas. CONCLUSIONS: We successfully established iPSC-derived MSCs from keratinocytes (KC-iPSC-MSCs) of a normal human and an RDEB patient. KC-iPSC-MSCs may have potential in therapies for RDEB.

    DOI: 10.1016/j.jdermsci.2018.06.004

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  • A novel WRN mutation identified in a patient with Werner syndrome and acute generalized exanthematous pustulosis. 査読 国際誌

    Toru Kawai, Ryota Hayashi, Natsumi Hama, Satoru Shinkuma, Atsushi Fujimoto, Yutaka Shimomura, Riichiro Abe

    European journal of dermatology : EJD   28 ( 4 )   553 - 554   2018年8月

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    DOI: 10.1684/ejd.2018.3354

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  • PR3-ANCA: a potential biomarker of disease activity for propylthiouracil-induced ANCA-associated vasculitis. 査読 国際誌

    Akito Hasegawa, Atsushi Fujimoto, Daisuke Yuki, Ryota Hayashi, Atsuko Aizawa, Takako Ito, Riichiro Abe

    European journal of dermatology : EJD   28 ( 4 )   530 - 531   2018年8月

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    記述言語:英語  

    DOI: 10.1684/ejd.2018.3314

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  • Potential role of extracellular vesicle-mediated antigen presentation in Helicobacter pylori hypersensitivity during eradication therapy. 査読 国際誌

    Takamasa Ito, Takashi Shiromizu, Shunsuke Ohnishi, Shotaro Suzuki, Katsuhiro Mabe, Akito Hasegawa, Hideyuki Ujiie, Yasuyuki Fujita, Yuichi Sato, Shuji Terai, Mototsugu Kato, Masahiro Asaka, Takeshi Tomonaga, Hiroshi Shimizu, Riichiro Abe

    The Journal of allergy and clinical immunology   142 ( 2 )   672 - 676   2018年8月

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  • A case of allergic contact dermatitis caused by goalkeeper gloves. 査読 国際誌

    Atsuko Aizawa, Akiko Ito, Yukiko Masui, Kazumi Sasaki, Yutaka Ishimura, Mitsuru Numata, Riichiro Abe

    Contact dermatitis   79 ( 2 )   113 - 115   2018年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/cod.13011

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  • A heterozygous mutation in the SAM domain of p63 underlies a mild form of ectodermal dysplasia. 査読 国際誌

    Toru Kawai, Ryota Hayashi, Hiroyuki Nakai, Yutaka Shimomura, Mazen Kurban, Lamiaa Hamie, Hiroki Fujikawa, Atsushi Fujimoto, Riichiro Abe

    Journal of dermatological science   90 ( 3 )   360 - 363   2018年6月

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  • ATP2C1遺伝子に新規変異を同定したHailey-Hailey病の1例

    重原 庸哉, 新熊 悟, 藤本 篤, 阿部 理一郎, 西條 忍

    日本皮膚科学会雑誌   128 ( 4 )   614 - 614   2018年4月

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    記述言語:日本語   出版者・発行元:(公社)日本皮膚科学会  

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  • Delayed-onset heat intolerance in a Japanese patient with X-linked hypohidrotic ectodermal dysplasia associated with a large deletion involving four genes. 査読 国際誌

    Hironori Niizeki, Ryota Hayashi, Yasuhiro Naiki, Kazue Yoshida, Ryo Tanaka, Ai Shimizu, Hiroshi Terashima, Nobutaka Isogawa, Riichiro Abe, Yutaka Shimomura

    The Journal of dermatology   45 ( 3 )   376 - 378   2018年3月

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  • Establishment of integration-free induced pluripotent stem cells from human recessive dystrophic epidermolysis bullosa keratinocytes. 査読 国際誌

    Wakana Matsumura, Yasuyuki Fujita, Chihiro Nakayama, Satoru Shinkuma, Shotaro Suzuki, Toshifumi Nomura, Riichiro Abe, Hiroshi Shimizu

    Journal of dermatological science   89 ( 3 )   263 - 271   2018年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Induced pluripotent stem cell (iPSC) technology enables patient-specific pluripotent stem cells to be derived from adult somatic cells without the use of an embryonic cell source. To date, recessive dystrophic epidermolysis bullosa (RDEB)-specific iPSCs have been generated from patients using integrating retroviral vectors. However, vector integration into the host genome can endanger the biosafety and differentiation propensities of iPSCs. Although various integration-free reprogramming systems have been reported, their utility in reprogramming somatic cells from patients remains largely undetermined. OBJECTIVE: Our study aims to establish safe iPSCs from keratinocytes of RDEB patients using non-integration vector. METHOD: We optimized and infected non-integrating Sendai viral vectors to reprogram keratinocytes from healthy volunteers and RDEB patients. RESULTS: Sendai vector infection led to the reproducible generation of genomic modification-free iPSCs from these keratinocytes, which was proved by immunohistochemistry, reverse transcription polymerase chain reaction, methylation assay, teratoma assay and embryoid body formation assay. Furthermore, we confirmed that these iPSCs have the potential to differentiate into dermal fibroblasts and epidermal keratinocytes. CONCLUSION: This is the first report to prove that the Sendai vector system facilitates the reliable reprogramming of patient keratinocytes into transgene-free iPSCs, providing another pluripotent platform for personalized diagnostic and therapeutic approaches to RDEB.

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  • Rapid response to clinical symptoms in early psoriatic onycho-pachydermo-periostitis treated with infliximab. 査読 国際誌

    Keita Horie, Yasuyuki Fujita, Daichi Hoshina, Riichiro Abe, Hiroshi Shimizu

    The Australasian journal of dermatology   59 ( 1 )   e78-e79 - e79   2018年2月

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    記述言語:英語  

    DOI: 10.1111/ajd.12667

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  • SJS/TEN 2017: Building Multidisciplinary Networks to Drive Science and Translation. 査読

    White KD, Abe R, Ardern-Jones M, Beachkofsky T, Bouchard C, Carleton B, Chodosh J, Cibotti R, Davis R, Denny JC, Dodiuk-Gad RP, Ergen EN, Goldman JL, Holmes JH 4th, Hung SI, Lacouture ME, Lehloenya RJ, Mallal S, Manolio TA, Micheletti RG, Mitchell CM, Mockenhaupt M, Ostrov DA, Pavlos R, Pirmohamed M, Pope E, Redwood A, Rosenbach M, Rosenblum MD, Roujeau JC, Saavedra AP, Saeed HN, Struewing JP, Sueki H, Sukasem C, Sung C, Trubiano JA, Weintraub J, Wheatley LM, Williams KB, Worley B, Chung WH, Shear NH, Phillips EJ

    The journal of allergy and clinical immunology. In practice   6 ( 1 )   95 - 98.e3   2018年1月

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  • An Updated Review of the Molecular Mechanisms in Drug Hypersensitivity. 査読 国際誌

    Chun-Bing Chen, Riichiro Abe, Ren-You Pan, Chuang-Wei Wang, Shuen-Iu Hung, Yi-Giien Tsai, Wen-Hung Chung

    Journal of immunology research   2018   6431694 - 6431694   2018年

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    記述言語:英語  

    Drug hypersensitivity may manifest ranging from milder skin reactions (e.g., maculopapular exanthema and urticaria) to severe systemic reactions, such as anaphylaxis, drug reactions with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS), or Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Current pharmacogenomic studies have made important strides in the prevention of some drug hypersensitivity through the identification of relevant genetic variants, particularly for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs). The associations identified by these studies are usually drug, phenotype, and ethnic specific. The drug presentation models that explain how small drug antigens might interact with HLA and T cell receptor (TCR) molecules in drug hypersensitivity include the hapten theory, the p-i concept, the altered peptide repertoire model, and the altered TCR repertoire model. The broad spectrum of clinical manifestations of drug hypersensitivity involving different drugs, as well as the various pathomechanisms involved, makes the diagnosis and management of it more challenging. This review highlights recent advances in our understanding of the predisposing factors, immune mechanisms, pathogenesis, diagnostic tools, and therapeutic approaches for drug hypersensitivity.

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  • New Advances in Drug Hypersensitivity Research and Treatment. 査読

    Tsai YG, Chung WH, Abe R, Tassaneeyakul W

    Journal of immunology research   2018   9345078   2018年

  • Drp1 regulates mitochondrial morphology and cell proliferation in cutaneous squamous cell carcinoma. 査読 国際誌

    Shinya Kitamura, Teruki Yanagi, Keisuke Imafuku, Hiroo Hata, Riichiro Abe, Hiroshi Shimizu

    Journal of dermatological science   88 ( 3 )   298 - 307   2017年12月

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    記述言語:英語  

    BACKGROUND: Dynamin-related protein 1 (Drp1) mediates mitochondrial fission. Recently, several studies have shown that Drp1 plays an important role in some cancers. However, little is known about Drp1 in cutaneous squamous cell carcinoma (SCC). OBJECTIVE: To investigate the role of Drp1 in the tumorigenesis of cutaneous SCCs. METHODS AND RESULTS: We investigated cell proliferation, cell cycle, mitochondrial morphology, and MAPK signaling pathway using cutaneous SCC A431 and DJM1 cells that were transfected with shRNA vectors targeting Drp1. The Drp1 gene-knockdown SCC cells showed lower cell proliferation than scramble-control cells, as assessed by direct cell counting and clonogenic assays. DNA content analysis showed Drp1 knockdown to cause G2/M arrest. Morphologically, the depletion of Drp1 resulted in an elongated, hyper-fused mitochondrial network. The MEK inhibitor PD325901 suppressed cell proliferation, as well as inhibiting the phosphorylation of ERK1/2 and Drp1Ser616. Also, PD325901 caused the dysregulation of the mitochondrial network. In tumor xenografts of DJM1 cells, the knockdown of Drp1 suppressed tumor growth in vivo, and clinically, the expression levels of Drp1 were higher in cutaneous SCCs than in normal epidermis, and correlated positively with the advanced clinical stages. CONCLUSION: Our results reveal a crucial function for Drp1 in regulating tumor growth, mitochondrial morphology, and cell cycle in cutaneous SCC, suggesting that Drp1 could be a novel target for skin tumor therapies.

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  • Investigating the use of tie-over dressing after skin grafting. 査読 国際誌

    Akihiko Yuki, Tatsuya Takenouchi, Sumiko Takatsuka, Hiroki Fujikawa, Riichiro Abe

    The Journal of dermatology   44 ( 11 )   1317 - 1319   2017年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Tie-over bolster dressing after skin grafting can prolong operative time, and cause hematoma and seroma formation because of uneven pressure application. To describe the possibility of discontinuing the use of tie-over dressing, we carried out a retrospective comparative study of patients who underwent skin grafting at an institution between January 2009 and December 2014. We investigated and compared the take rate, healing period, wound infection rate and hematoma formation rate for the tie-over dressing group and the non-tie-over dressing group. Among 266 patients, 148 and 118 patients were included in the tie-over dressing group and non-tie-over dressing group, respectively. There were no significant differences between the take rate, healing period, wound infection rate and hematoma formation rate for the two groups. Multivariate analysis showed that the complete graft take rate was not significantly influenced by tie-over dressing, age, sex, graft site, graft procedure and skin graft diameter. Although the use of tie-over dressing might remain necessary on sites with a free margin, including the eyelids, lips or nostrils, because of the difficulty in using tape fixation, the present study showed that alternative dressing with polyurethane foam is also useful in most cases of skin grafting.

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  • A case of non-episodic angioedema with eosinophilia induced by influenza vaccine. 査読 国際誌

    Ryota Hayashi, Naoko Shimomura, Michihiro Hosojima, Akari Sakai, Yohya Shigehara, Riichiro Abe

    European journal of dermatology : EJD   27 ( 5 )   554 - 555   2017年10月

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    記述言語:英語   出版者・発行元:JOHN LIBBEY EUROTEXT LTD  

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  • Inhibition of heat shock protein 90 exerts an antitumour effect in angiosarcoma: involvement of the vascular endothelial growth factor signalling pathway 査読

    S. Yamada-Kanazawa, I. Kajihara, S. Fukushima, M. Jinnin, M. Masuzawa, M. Masuzawa, Y. Amoh, D. Hoshina, R. Abe, H. Ihn

    BRITISH JOURNAL OF DERMATOLOGY   177 ( 2 )   456 - 469   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Background Angiosarcoma is a rare malignant neoplasm derived from endothelial cells, and because advanced angiosarcoma is resistant to standard chemotherapy its prognosis is poor. Therefore, new therapies are urgently needed. Heat shock protein (HSP) 90 has been identified as a molecular chaperone that regulates various cancer-related proteins. Numerous clinical trials are currently testing the effectiveness of HSP90 inhibitors in various types of malignancies.
    Objectives To investigate the role of HSP90 in the pathogenesis of angiosarcoma and whether the inhibition of HSP90 may have antitumour activity.
    Methods The expression of HSP90 protein in angiosarcoma was examined using immunohistochemistry and immunoblotting. The effects of HSP90 inhibition were proven using proliferation, migration and invasion assay in angiosarcoma cells. The mechanism of antitumour effect by HSP90 inhibition was investigated by the transfection of small interfering RNA (siRNA).
    Results The levels of HSP90 protein expression in cultured angiosarcoma cell lines were markedly increased compared with those in normal tissue cell lines. Immunohistochemical analyses revealed that the expression of HSP90 protein was strongly detected in angiosarcoma tissues compared with that in normal dermal vessels or senile angioma tissues. Ganetespib, an HSP90 inhibitor, with or without taxanes, inhibited the proliferation of angiosarcoma cells via apoptosis in a dose-dependent manner. HSP90 siRNA suppressed the proliferation, migration and invasion of angiosarcoma cells. Knock-down of HSP90 did not suppress vascular endothelial growth factor receptor 2 directly, but selectively suppressed several downstream targets of vascular endothelial growth factor signalling in angiosarcoma cells.
    Conclusions HSP90 could be a novel therapeutic target for angiosarcoma.

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  • Tufted angioma associated with hyperplasia of eccrine sweat glands 査読

    Y. Saito, Y. Shimomura, R. Abe

    CLINICAL AND EXPERIMENTAL DERMATOLOGY   42 ( 5 )   548 - 550   2017年7月

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    記述言語:英語   出版者・発行元:WILEY  

    DOI: 10.1111/ced.13122

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  • Late-onset skin involvement on the forehead in multicentric Castleman disease. 査読 国際誌

    Kazumasa Sato, Satoru Shinkuma, Katsuya Fujimoto, Kanako C Hatanaka, Hideyuki Ujiie, Toshifumi Nomura, Yasuyuki Fujita, Riichiro Abe, Yoshihiro Matsuno, Hiroshi Shimizu

    International journal of dermatology   56 ( 7 )   e152-e153 - E153   2017年7月

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    記述言語:英語   出版者・発行元:WILEY  

    DOI: 10.1111/ijd.13559

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  • Panniculitis as the initial manifestation of dermatomyositis with anti-MDA5 antibody 査読

    A. Hasegawa, Y. Shimomura, N. Kibune, J. Koshio, Y. Umemori, R. Abe

    CLINICAL AND EXPERIMENTAL DERMATOLOGY   42 ( 5 )   551 - 553   2017年7月

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    記述言語:英語   出版者・発行元:WILEY  

    DOI: 10.1111/ced.13128

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  • Case of infantile digital fibromatosis: Observation of its dermoscopic features. 査読 国際誌

    Koichi Tomii, Yutaka Shimomura, Hiroki Fujikawa, Naoyuki Kariya, Riichiro Abe

    The Journal of dermatology   44 ( 5 )   549 - 551   2017年5月

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    記述言語:英語   出版者・発行元:WILEY  

    DOI: 10.1111/1346-8138.13685

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  • Cross-reactivity of cephalosporins: allergic immediate hypersensitivity to ceftriaxone in a cefcapene pivoxil-sensitized patient. 査読 国際誌

    Tokiko Deguchi, Yutaka Shimomura, Ryota Hayashi, Mari Orime, Katsuhiro Tomiyama, Riichiro Abe

    European journal of dermatology : EJD   27 ( 2 )   187 - 189   2017年4月

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    記述言語:英語   出版者・発行元:JOHN LIBBEY EUROTEXT LTD  

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  • Photodynamic therapy with intradermal application of 5-aminolevulinic acid successfully improved tumor lesions of mycosis fungoides. 査読 国際誌

    Yudai Kabata, Yutaka Shimomura, Yoshie Matsuo, Hiroshi Fujiwara, Riichiro Abe

    International journal of dermatology   56 ( 4 )   e81-e82 - e82   2017年4月

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    記述言語:英語   出版者・発行元:WILEY  

    DOI: 10.1111/ijd.13483

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  • Beneficial effect of hydroxychloroquine on cutaneous vasculitis in a Japanese patient with systemic lupus erythematosus. 査読 国際誌

    Natsuko Kibune, Yutaka Shimomura, Akito Hasegawa, Takako Saeki, Yukie Umemori, Riichiro Abe

    The Journal of dermatology   44 ( 4 )   e52-e53 - E53   2017年4月

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    記述言語:英語   出版者・発行元:WILEY  

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  • Non-paraneoplastic autoimmune subepidermal bullous disease associated with fatal bronchiolitis obliterans. 査読 国際誌

    Mari Orime, Katsuhiro Tomiyama, Hideki Hashidate, Satoru Yoshida, Satoshi Hokari, Akiko Tsuda, Hisashi Yokoyama, Jun-Ichi Narita, Youhei Uchida, Takuro Kanekura, Riichiro Abe, Norito Ishii, Takashi Hashimoto, Kazuhiro Kawai

    The Journal of dermatology   44 ( 4 )   461 - 464   2017年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Bronchiolitis obliterans is a small-airway obstructive lung disease for which immunologically mediated pathogenesis is supposed. Frequent association of bronchiolitis obliterans with paraneoplastic pemphigus is well known, but its association with other autoimmune bullous diseases has not been reported except for a case of anti-laminin-332-type mucous membrane pemphigoid in a patient with chronic graft-versus-host disease. We report a case of non-paraneoplastic autoimmune subepidermal bullous disease associated with fatal bronchiolitis obliterans in a patient without transplantation. Although the patient's serum contained immunoglobulin (Ig)A antibodies to the 180-kDa bullous pemphigoid antigen/type XVII collagen and IgG antibodies to laminin-332, diagnosis of either linear IgA bullous dermatosis or mucous membrane pemphigoid could not be made because of the failure to detect linear IgA deposition at the basement membrane zone by direct immunofluorescence and the lack of mucous membrane lesions. Physicians should be aware that autoimmune bullous diseases other than paraneoplastic pemphigus can also associate with this rare but potentially fatal lung disease.

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  • Altered balance of epidermis-related chemokines in epidermolysis bullosa. 査読 国際誌

    Inkin Ujiie, Yasuyuki Fujita, Chihiro Nakayama, Wakana Matsumura, Shotaro Suzuki, Satoru Shinkuma, Toshifumi Nomura, Riichiro Abe, Hiroshi Shimizu

    Journal of dermatological science   86 ( 1 )   37 - 45   2017年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    BACKGROUND: Epidermolysis bullosa (EB) is a congenital, refractory skin disease and there are no fundamental treatments. Recently, allogenic cell therapies are beginning to be applied as potential treatments, that are based on the concept that the allogenic cells can migrate into the skin and reconstitute the skin components. Although the mechanisms of cell migration into skin are not fully understood, chemokines are regarded as key factors in recruiting bone marrow-derived cells. OBJECTIVES: Our study aims to elucidate the expression of chemokines in the EB patients. METHODS: We determined the expression of wound-healing related chemokines in the sera, keratinocytes, and skin tissues of EB patients and compared them to those of healthy volunteers by enzyme-linked immunosorbent assays, quantitative reverse transcription PCR, and immunofluorescence staining. RESULTS: The serum levels of CXCL12 and HMGB1 were found to be significantly elevated in the EB patients. Conversely, the serum levels of CCL21 were found to be lower in the EB patients than in healthy controls. In addition, the serum levels of CXCL12 tended to increase and the serum levels of CCL27 tended to decrease with an increase in the affected body surface areas. To detect the origin of the circulating chemokines, we performed immunofluorescence staining. CCL21, CCL27, HMGB1 and CXCL12 were stained more broadly in the EB patient tissues than those in the control tissues. CONCLUSIONS: These results suggest that fluctuations in chemokine levels may contribute in a coordinated way to the wound-healing process and lend clues toward efficient cell therapies for EB.

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  • Segmental lichen aureus in infancy 査読

    Y. Saito, Y. Shimomura, M. Orime, N. Kariya, R. Abe

    CLINICAL AND EXPERIMENTAL DERMATOLOGY   42 ( 2 )   215 - 217   2017年3月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    DOI: 10.1111/ced.13019

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  • Hypertrophic lupus erythematosus successfully treated with hydroxychloroquine. 査読 国際誌

    Norihiro Yoshimoto, Satoru Shinkuma, Hideyuki Ujiie, Toshifumi Nomura, Yasuyuki Fujita, Riichiro Abe, Hiroshi Shimizu

    The Journal of dermatology   44 ( 3 )   e48-e49 - E49   2017年3月

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    記述言語:英語   出版者・発行元:WILEY  

    DOI: 10.1111/1346-8138.13474

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  • Case of severe acneiform eruptions associated with the BRAF inhibitor vemurafenib. 査読 国際誌

    Osamu Ansai, Hiroki Fujikawa, Yutaka Shimomura, Riichiro Abe

    The Journal of dermatology   44 ( 3 )   e15-e16 - E16   2017年3月

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    記述言語:英語   出版者・発行元:WILEY  

    DOI: 10.1111/1346-8138.13534

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  • Linagliptin-associated bullous pemphigoid that was most likely caused by IgG autoantibodies against the midportion of BP180 査読

    A. Sakai, Y. Shimomura, O. Ansai, Y. Saito, K. Tomi, Y. Tsuchida, H. Iwata, H. Ujhe, H. Shimizu, R. Abe

    BRITISH JOURNAL OF DERMATOLOGY   176 ( 2 )   541 - 543   2017年2月

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    記述言語:英語   出版者・発行元:WILEY  

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  • First Japanese case of congenital generalized hypertrichosis with a copy number variation on chromosome 17q24. 査読 国際誌

    Ryota Hayashi, Kazue Yoshida, Riichiro Abe, Hironori Niizeki, Yutaka Shimomura

    Journal of dermatological science   85 ( 1 )   63 - 65   2017年1月

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    記述言語:英語   出版者・発行元:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.jdermsci.2016.10.010

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  • Case of pemphigus herpetiformis with immunoglobulin G autoantibodies against desmocollin-3. 査読 国際誌

    Osamu Ansai, Yutaka Shimomura, Atsushi Fujimoto, Akari Sakai, Yuko Tsuchida, Ryota Hayashi, Yohya Shigehara, Natsumi Hama, Riichiro Abe

    The Journal of dermatology   44 ( 1 )   104 - 105   2017年1月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

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  • Infiltration of PD-1-positive cells in combination with tumor site PD-L1 expression is a positive prognostic factor in cutaneous angiosarcoma. 査読 国際誌

    Yuki Honda, Atsushi Otsuka, Sachiko Ono, Yosuke Yamamoto, Judith A Seidel, Satoshi Morita, Masahiro Hirata, Tatsuki R Kataoka, Tatsuya Takenouchi, Kazuyasu Fujii, Takuro Kanekura, Yuko Okubo, Kenzo Takahashi, Teruki Yanagi, Daichi Hoshina, Hiroo Hata, Riichiro Abe, Taku Fujimura, Takeru Funakoshi, Koji Yoshino, Mamiko Masuzawa, Yasuyuki Amoh, Ryota Tanaka, Yasuhiro Fujisawa, Tetsuya Honda, Kenji Kabashima

    Oncoimmunology   6 ( 1 )   e1253657   2017年

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    記述言語:英語  

    Cutaneous angiosarcoma (CAS) is a malignant sarcoma with poor prognosis. Programmed cell death-1 (PD-1)/programmed cell death-1 ligand-1 (PD-L1) expression reflects antitumor immunity, and is associated with patient prognosis in various cancers. The purpose of this study is to investigate the relationship between PD-1/PD-L1 expression and CAS prognosis. CAS cases (n = 106) were immunohistochemically studied for PD-L1 and PD-1 expression, and the correlation with patient prognosis was analyzed. PD-L1 expression was assessed by flow cytometry on three CAS cell lines with or without IFNγ stimulation. A total of 30.2% of patients' samples were positive for PD-L1, and 17.9% showed a high infiltration of PD-1-positive cells. Univariate analysis showed a significant relationship between a high infiltration of PD-1-positive cells with tumor site PD-L1 expression and favorable survival in stage 1 patients (p = 0.014, log-rank test). Multivariable Cox-proportional hazard regression analysis also showed that patients with a high infiltration of PD-1-positive cells with tumor site PD-L1 expression were more likely to have favorable survival, after adjustment with possible confounders (hazard ratio (HR) = 0.38, p = 0.021, 95% confidence interval (CI) 0.16-0.86). Immunofluorescence staining of CAS samples revealed that PD-L1-positive cells were adjacent to PD-1-positive cells and/or tumor stroma with high IFNγ expression. In vitro stimulation with IFNγ increased PD-L1 expression in two out of three established CAS cell lines. Our results suggest that PD-1/PD-L1 expression is related to CAS progression, and the treatment with anti-PD-1 antibodies could be a new therapeutic option for CAS.

    DOI: 10.1080/2162402X.2016.1253657

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  • A novel splice site mutation in the ADAR gene leading to exon skipping and dyschromatosis symmetrica hereditaria in a Japanese patient 査読

    O. Ansai, Y. Shigehara, A. Ito, R. Abe, Y. Shimomura

    CLINICAL AND EXPERIMENTAL DERMATOLOGY   41 ( 8 )   933 - 934   2016年12月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    DOI: 10.1111/ced.12981

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  • Expression studies of nectin-1 in human hair follicles and identification of a p63-responsive element in the NECTIN1 promoter. 査読 国際誌

    Ryota Hayashi, Riichiro Abe, Yutaka Shimomura

    Journal of dermatological science   84 ( 2 )   221 - 224   2016年11月

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  • Generalized acute subcutaneous edema as a rare cutaneous manifestation of severe dermatomyositis 査読

    M. Watanabe, K. Natsuga, K. Arita, R. Abe, H. Shimizu

    JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY   30 ( 11 )   E151 - E152   2016年11月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Watanabe M, Natsuga K, Arita K, Abe R, Shimizu H, Journal of the European Academy of Dermatology and Venereology : JEADV, 2015

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  • Mutations in SDR9C7 gene encoding an enzyme for vitamin A metabolism underlie autosomal recessive congenital ichthyosis. 査読 国際誌

    Yohya Shigehara, Shujiro Okuda, Georges Nemer, Adele Chedraoui, Ryota Hayashi, Fadi Bitar, Hiroyuki Nakai, Ossama Abbas, Laetitia Daou, Riichiro Abe, Maria Bou Sleiman, Abdul Ghani Kibbi, Mazen Kurban, Yutaka Shimomura

    Human molecular genetics   25 ( 20 )   4484 - 4493   2016年10月

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    記述言語:英語  

    Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of hereditary skin disorder characterized by an aberrant cornification of the epidermis. ARCI is classified into a total of 11 subtypes (ARCI1-ARCI11) based on their causative genes or loci. Of these, the causative gene for only ARCI7 has not been identified, while it was previously mapped on chromosome 12p11.2-q13.1. In this study, we performed genetic analyses for three Lebanese families with ARCI, and successfully determined the linkage interval to 9.47 Mb region on chromosome 12q13.13-q14.1, which was unexpectedly outside of the ARCI7 locus. Whole-exome sequencing and the subsequent Sanger sequencing led to the identification of missense mutations in short chain dehydrogenase/reductase family 9C, member 7 (SDR9C7) gene on chromosome 12q13.3, i.e. two families shared an identical homozygous mutation c.599T > C (p.Ile200Thr) and one family had another homozygous mutation c.214C > T (p.Arg72Trp). In cultured cells, expression of both the mutant SDR9C7 proteins was markedly reduced as compared to wild-type protein, suggesting that the mutations severely affected a stability of the protein. In normal human skin, the SDR9C7 was abundantly expressed in granular and cornified layers of the epidermis. By contrast, in a patient’s skin, its expression in the cornified layer was significantly decreased. It has previously been reported that SDR9C7 is an enzyme to convert retinal into retinol. Therefore, our study not only adds a new gene responsible for ARCI, but also further suggests a potential role of vitamin A metabolism in terminal differentiation of the epidermis in humans.

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  • Localized heat urticaria: Positive reaction of preheated autologous serum skin test. 査読 国際誌

    Natsumi Hama, Yutaka Shimomura, Hiroshi Arinami, Ryoko Maruyama, Riichiro Abe

    The Journal of dermatology   43 ( 9 )   1099 - 100   2016年9月

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  • mTOR expression correlates with invasiveness and progression of extramammary Paget's disease 査読

    H. Hata, S. Kitamura, Y. Inamura, K. Imafuku, E. Homma, K. Muramatsu, K. Natsuga, R. Abe, H. Shimizu

    JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY   30 ( 7 )   1238 - 1239   2016年7月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Hata H, Kitamura S, Inamura Y, Imafuku K, Homma E, Muramatsu K, Natsuga K, Abe R, Shimizu H, Journal of the European Academy of Dermatology and Venereology : JEADV, 2015

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  • A case of drug-associated dermatomyositis following ipilimumab therapy. 査読 国際誌

    Yasuyuki Yamaguchi, Riichiro Abe, Naoya Haga, Hiroshi Shimizu

    European journal of dermatology : EJD   26 ( 3 )   320 - 1   2016年6月

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    DOI: 10.1684/ejd.2016.2770

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  • Massive petechiae as an initial symptom of Waldenström's macroglobulinemia. 査読 国際誌

    Shiba K, Abe R, Miyauchi T, Nomura T, Kondo T, Shimizu H

    International journal of dermatology   55 ( 6 )   e361-2 - 2   2016年6月

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    記述言語:英語  

    DOI: 10.1111/ijd.13189

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  • Allogeneic hematopoietic stem cell transplantation following reduced-intensity conditioning for mycosis fungoides and Sezary syndrome. 査読 国際誌

    Souichi Shiratori, Katsuya Fujimoto, Machiko Nishimura, Kanako C Hatanaka, Mizuha Kosugi-Kanaya, Kohei Okada, Junichi Sugita, Akio Shigematsu, Daigo Hashimoto, Tomoyuki Endo, Takeshi Kondo, Riichiro Abe, Satoshi Hashino, Yoshihiro Matsuno, Hiroshi Shimizu, Takanori Teshima

    Hematological oncology   34 ( 1 )   9 - 16   2016年3月

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    記述言語:英語  

    Advanced-stage mycosis fungoides and Sezary syndrome (MF/SS) have a poor prognosis. Allogeneic hematopoietic stem cell transplantation (HSCT), particularly using a reduced-intensity conditioning (RIC) regimen, is a promising treatment for advanced-stage MF/SS. We performed RIC-HSCT in nine patients with advanced MF/SS. With a median follow-up period of 954 days after HSCT, the estimated 3-year overall survival was 85.7% (95% confidence interval, 33.4-97.9%) with no non-relapse mortality. Five patients relapsed after RIC-HSCT; however, in four patients whose relapse was detected only from the skin, persistent complete response was achieved in one patient, and the disease was manageable in other three patients by the tapering of immunosuppressants and donor lymphocyte infusion, suggesting that graft-versus-lymphoma effect and 'down-staging' effect from advanced stage to early stage by HSCT improve the prognosis of advanced-stage MF/SS. These results suggest that RIC-HSCT is an effective treatment for advanced MF/SS.

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  • Prognostic Significance of Forkhead Box M1 (FOXM1) Expression and Antitumor Effect of FOXM1 Inhibition in Angiosarcoma. 査読 国際誌

    Takamichi Ito, Kenichi Kohashi, Yuichi Yamada, Takeshi Iwasaki, Akira Maekawa, Masaaki Kuda, Daichi Hoshina, Riichiro Abe, Masutaka Furue, Yoshinao Oda

    Journal of Cancer   7 ( 7 )   823 - 30   2016年

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    記述言語:英語  

    BACKGROUND: The prognosis of angiosarcoma is poor and a novel treatment option for the disease is desired. The aim of this study was to investigate the prognostic significance of Forkhead box M1 (FOXM1), a transcription factor that regulates cell-cycle progression and various crucial processes in tumor progression, and its potential as a new therapeutic target. METHODS: We investigated 125 angiosarcoma clinical samples (94 primary lesions and 31 metastatic lesions in 94 patients) and a human angiosarcoma cell line (HAMON) using immunohistochemical staining and molecular biological approaches. FOXM1 expression in angiosarcoma samples was also compared with that in Kaposi's sarcomas (n = 13), epithelioid hemangioendotheliomas (n = 13) and benign hemangiomas (n = 10). RESULTS: Patients with FOXM1-overexpressing angiosarcoma had significantly shorter survival (both for disease-specific survival [DSS] and event-free survival [EFS]) than other patients (5-year DSS, 23.5% vs. 47.1%, P = 0.013; and 5-year EFS, 5.5% vs. 28.7%, P = 0.004). FOXM1 overexpression was also an independent prognostic factor for both DSS and EFS in Cox multivariate analyses (hazard ratio [HR] 2.84, 95% confidence interval [CI] 1.10-5.81, P = 0.039; and HR 4.16, 95%CI 2.03-8.67, P = 0.0001, respectively). FOXM1 inhibition using both small interfering RNA and a specific inhibitor (thiostrepton) suppressed cell proliferation of the angiosarcoma cell line. Furthermore, FOXM1 inhibition improved the chemosensitivity to docetaxel in vitro. CONCLUSIONS: FOXM1 inhibition may be a potential therapeutic option for angiosarcoma.

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  • CD4/CD8 double-negative T-cell lymphoma: a variant of primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma? 査読 国際誌

    Toshinari Miyauchi, Riichiro Abe, Yusuke Morita, Maki Adachi, Keiko Shiba, Yohei Hamade, Nao Saito, Machiko Nishimura, Makoto Ibata, Kohei Okada, Akio Shigematsu, Tomoyuki Endo, Kazuhiro Kawai, Takanori Teshima, Hiroshi Shimizu

    Acta dermato-venereologica   95 ( 8 )   1024 - 5   2015年11月

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    記述言語:英語  

    DOI: 10.2340/00015555-2102

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  • Kimura disease associated with severe visual dysfunction due to remarkable periorbital involvement. 査読 国際誌

    Mika Watanabe, Hideyuki Ujiie, Nao Saito, Riichiro Abe, Hiroshi Shimizu

    The Journal of dermatology   42 ( 9 )   924 - 5   2015年9月

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  • Non-solar-induced elastotic bands on the forearm 査読

    Naoya Haga, Riichiro Abe, Yusuke Morita, Yu Fujimura, Ken Natsuga, Toshifumi Nomura, Masanobu Kumakiri, Hiroshi Shimizu

    EUROPEAN JOURNAL OF DERMATOLOGY   25 ( 5 )   508 - 509   2015年9月

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    記述言語:英語   出版者・発行元:JOHN LIBBEY EUROTEXT LTD  

    DOI: 10.1684/ejd.2015.2629

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  • Plasma cell cheilitis extending beyond vermillion border. 査読 国際誌

    Yu Fujimura, Ken Natsuga, Riichiro Abe, Yusuke Morita, Toshifumi Nomura, Hiroshi Shimizu

    The Journal of dermatology   42 ( 9 )   935 - 6   2015年9月

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  • Efficacy of additional i.v. immunoglobulin to steroid therapy in Stevens-Johnson syndrome and toxic epidermal necrolysis. 査読 国際誌

    Michiko Aihara, Yoko Kano, Hiroyuki Fujita, Takeshi Kambara, Setsuko Matsukura, Ichiro Katayama, Hiroaki Azukizawa, Yoshiki Miyachi, Yuichiro Endo, Hideo Asada, Fumi Miyagawa, Eishin Morita, Sakae Kaneko, Riichiro Abe, Toyoko Ochiai, Hirohiko Sueki, Hideaki Watanabe, Keisuke Nagao, Yumi Aoyama, Koji Sayama, Koji Hashimoto, Tetsuo Shiohara

    The Journal of dermatology   42 ( 8 )   768 - 77   2015年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and life-threatening cutaneous adverse drug reactions. While there is no established therapy for SJS/TEN, systemic corticosteroids, plasma exchange and i.v. immunoglobulin (IVIG) have been used as treatment. The efficacy of IVIG is still controversial because total doses of IVIG used vary greatly from one study to another. The aim of this study was to evaluate the efficacy of IVIG, administrated for 5 days consecutively, in an open-label, multicenter, single-arm study in patients with SJS or TEN. IVIG (400 mg/kg per day) administrated for 5 days consecutively was performed as an additional therapy to systemic steroids in adult patients with SJS or TEN. Efficacy on day 7 of IVIG was evaluated. Parameters to assess clinical outcome were enanthema including ophthalmic and oral lesions, cutaneous lesions and general condition. These parameters were scored and recorded before and after IVIG. We enrolled five patients with SJS and three patients with TEN who did not respond sufficiently to systemic steroids before IVIG administration. All of the patients survived and the efficacy on day 7 of the IVIG was 87.5% (7/8 patients). Prompt amelioration was observed in skin lesions and enanthema in the patients in whom IVIG therapy was effective. Serious side-effects from the use of IVIG were not observed. IVIG (400 mg/kg per day) administrated for 5 days consecutively seems to be effective in patients with SJS or TEN. IVIG administrated together with steroids should be considered as a treatment modality for patients with refractory SJS/TEN. Further studies are needed to define the therapeutic efficacy of IVIG.

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  • Serum granulysin levels as a predictor of serious telaprevir-induced dermatological reactions. 査読 国際誌

    Goki Suda, Yoshiya Yamamoto, Astushi Nagasaka, Ken Furuya, Mineo Kudo, Yoshimichi Chuganji, Yoko Tsukuda, Seiji Tsunematsu, Fumiyuki Sato, Katsumi Terasita, Masato Nakai, Hiromasa Horimoto, Takuya Sho, Mitsuteru Natsuizaka, Kouji Ogawa, Shunsuke Ohnishi, Makoto Chuma, Yasuyuki Fujita, Riichiro Abe, Miki Taniguchi, Mina Nakagawa, Yasuhiro Asahina, Naoya Sakamoto

    Hepatology research : the official journal of the Japan Society of Hepatology   45 ( 8 )   837 - 45   2015年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIM: Telaprevir-based therapy for chronic hepatitis C patients is effective; however, the high prevalence of dermatological reactions is an outstanding issue. The mechanism and characteristics of such adverse reactions are unclear; moreover, predictive factors remain unknown. Granulysin was recently reported to be upregulated in the blisters of patients with Stevens-Johnson syndrome (SJS). Therefore, we investigated the risk factors for severe telaprevir-induced dermatological reactions as well as the association between serum granulysin levels and the severity of such reactions. METHODS: A total of 89 patients who received telaprevir-based therapy and had complete clinical information were analyzed. We analyzed the associations between dermatological reactions and clinical factors. Next, we investigated the time-dependent changes in serum granulysin levels in five and 14 patients with grade 3 and non-grade 3 dermatological reactions, respectively. RESULTS: Of the 89 patients, 57 patients had dermatological reactions, including nine patients with grade 3. Univariate analysis revealed that grade 3 dermatological reactions were significantly associated with male sex. Moreover, serum granulysin levels were significantly associated with the severity of dermatological reactions. Three patients with grade 3 dermatological reaction had severe systemic manifestations including SJS, drug-induced hypersensitivity syndrome, and systemic lymphoid swelling and high-grade fever; all were hospitalized. Importantly, among the three patients, two patients' serum granulysin levels exceeded 8 ng/mL at onset and symptoms deteriorated within 6 days. CONCLUSION: Male patients are at high risk for severe telaprevir-induced dermatological reactions. Moreover, serum granulysin levels are significantly associated with the severity of dermatological reactions and may be a predictive factor in patients treated with telaprevir-based therapy.

    DOI: 10.1111/hepr.12421

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  • Erythema annulare centrifugum-like mycosis fungoides after unrelated bone marrow transplantation. 査読 国際誌

    Keisuke Imafuku, Yukiko Nomura, Chihiro Nakayama, Riichiro Abe, Tomoyuki Endo, Hiroshi Shimizu

    British journal of haematology   170 ( 2 )   140 - 140   2015年7月

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    記述言語:英語  

    DOI: 10.1111/bjh.13489

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  • Loss-of-function mutations in the gene encoding filaggrin underlie a Japanese family with food-dependent exercise-induced anaphylaxis 査読

    O. Mizuno, T. Nomura, Y. Ohguchi, S. Suzuki, Y. Nomura, Y. Hamade, D. Hoshina, A. Sandilands, M. Akiyama, W. H. I. McLean, R. Abe, H. Shimizu

    JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY   29 ( 4 )   805 - 808   2015年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    BackgroundFood-dependent exercise-induced anaphylaxis (FDEIA) is a serious food allergy in which anaphylaxis develops when exercise is performed within several hours after food intake. The precise mechanism underlying allergic sensitization in FDEIA has been an important issue but remains poorly understood.
    ObjectivesWe aimed to elucidate the pathomechanism including the route of allergen sensitization involved in FDEIA.
    MethodsA Japanese family with wheat-dependent exercise-induced anaphylaxis (WDEIA), a specific form of FDEIA, were clinically examined. Mutation analysis of the gene encoding filaggrin (FLG) was also performed.
    ResultsTwo of the family members were confirmed as WDEIA on the basis of their medical history and positive provocation test results. Notably, the two affected individuals in the family had concomitant ichthyosis vulgaris. Mutation analysis of FLG revealed that they carry one or more loss-of-function mutations that have not been described in the Japanese population.
    ConclusionThese results indicate that FLG mutations might be involved in the pathogenesis of WDEIA in the present case.

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  • Sequelae in 145 patients with drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms: survey conducted by the Asian Research Committee on Severe Cutaneous Adverse Reactions (ASCAR). 査読 国際誌

    Yoko Kano, Mikiko Tohyama, Michiko Aihara, Setsuko Matsukura, Hideaki Watanabe, Hirohiko Sueki, Masafumi Iijima, Eishin Morita, Hiroyuki Niihara, Hideo Asada, Kenji Kabashima, Hiroaki Azukizawa, Hideo Hashizume, Keisuke Nagao, Hayato Takahashi, Riichiro Abe, Chie Sotozono, Michiko Kurosawa, Yumi Aoyama, Chia-Yu Chu, Wen-Hung Chung, Tetsuo Shiohara

    The Journal of dermatology   42 ( 3 )   276 - 82   2015年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe adverse drug reaction caused by specific drug. It is characterized by visceral organ involvement and reactivation of various human herpesviruses. Although sporadic reports have documented certain conditions that appear after the resolution of DIHS/DRESS, little information is available on sequelae after resolution of DIHS/DRESS in a large patient population. The Asian Research Committee on Severe Cutaneous Adverse Reactions, comprised of doctors from Japan and Taiwan, conducted a survey on sequelae and deterioration of the underlying disease in patients with DIHS/DRESS. This was achieved by directly interviewing patients who had been followed-up by experts or through a questionnaire mailed to patients. Questions were asked about new onset cardiovascular disease, collagen disease or autoimmune disease, gastrointestinal disease, renal disease, respiratory disease, neoplasms, and other diseases such as herpes zoster and diabetes mellitus, as well as deterioration of the underlying disease. A total of 145 patients were analyzed in this study. The following newly developed diseases after recovery from DIHS/DRESS were observed: Graves' disease (n = 2), Hashimoto's disease (n = 3), painless thyroiditis (n = 2), fulminant type 1 diabetes mellitus (n = 5), and infectious diseases (n = 7). Several DIHS/DRESS patients with pre-existing renal dysfunction required lifelong hemodialysis. DIHS/DRESS is a condition that increases the risk of new onset of disease. Long-term observation of DIHS/DRESS can provide an opportunity to investigate substantial diseases from onset to the full-blown stage. Patients with DIHS/DRESS require careful long-term follow-up.

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  • MMP13 can be a useful differentiating marker between squamous cell carcinoma and benign hyperkeratotic lesions in recessive dystrophic epidermolysis bullosa 査読

    H. Hata, R. Abe, A. Suto, E. Homma, Y. Fujita, S. Aoyagi, H. Shimizu

    BRITISH JOURNAL OF DERMATOLOGY   172 ( 3 )   769 - 773   2015年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Recessive dystrophic epidermolysis bullosa (RDEB) is a severe hereditary mechanobullous disease resulting from mutations in the COL7A1 gene, coding for type VII collagen. Patients with RDEB tend to develop squamous cell carcinomas (SCCs) at sites of chronic ulceration or scarring on the whole body. Distinguishing SCC from benign hyperkeratotic lesions is often difficult, not only clinically but also histologically in patients with RDEB. We investigated several matrix metallopeptidase (MMP) subtypes by comparing the DNA amplification microarray findings between evident SCCs and benign hyperkeratotic lesions in the same patient with RDEB. We report that MMP13 was found to be strongly positive in SCCs but negative in benign hyperkeratotic lesions. We found that there is an evident difference in the transitional area between SCCs and benign hyperkeratotic lesions. We propose that MMP13 may be a useful differentiating marker between SCC and benign hyperkeratotic lesions in RDEB.

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  • Immunological response in Stevens-Johnson syndrome and toxic epidermal necrolysis. 査読 国際誌

    Riichiro Abe

    The Journal of dermatology   42 ( 1 )   42 - 8   2015年1月

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    記述言語:英語  

    Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening cutaneous adverse drug reactions that induce widespread epidermal necrosis. Recent advances in pharmacogenomic studies have provided evidence of genetic predispositions to SJS/TEN. Several concepts have been proposed to explain the pathogenesis of severe cutaneous adverse drug reactions. In the hapten concept, small molecules called haptens elicit an immune response only when attached to proteins. The "p-i" concept postulates that the causative drugs can stimulate cells by binding directly and reversibly to immune receptors. In addition, there is the idea that drugs alter the antigen by binding to the human leukocyte antigen pocket. With regard to keratinocyte death, several cell death mediators, such as FasL, granulysin and annexin A1, have been proposed as playing a role in SJS/TEN pathogenesis. A subset of T lymphocytes, including regulatory T cells, also may play a role in SJS/TEN.

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  • Randomized controlled trial on the skin toxicity of panitumumab in Japanese patients with metastatic colorectal cancer: HGCSG1001 study; J-STEPP. 査読 国際誌

    Yoshimitsu Kobayashi, Yoshito Komatsu, Satoshi Yuki, Hiraku Fukushima, Takahide Sasaki, Ichiro Iwanaga, Minoru Uebayashi, Hiroyuki Okuda, Takaya Kusumi, Takuto Miyagishima, Susumu Sogabe, Miki Tateyama, Kazuteru Hatanaka, Yasushi Tsuji, Michio Nakamura, Jun Konno, Fumiyasu Yamamoto, Manabu Onodera, Kazuhiro Iwai, Yuh Sakata, Riichiro Abe, Koji Oba, Naoya Sakamoto

    Future oncology (London, England)   11 ( 4 )   617 - 27   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIM: We planned a randomized, open-label trial to evaluate differences between pre-emptive and reactive skin treatment for panitumumab (Pmab)-associated skin toxicities in Japanese patients with metastatic colorectal cancer. PATIENTS & METHODS: Patients receiving third-line Pmab-containing regimens were randomized to pre-emptive or reactive treatment. The primary end point was the cumulative incidence of ≥grade 2 skin toxicities during 6 weeks. Retrospectively, a dermatologist reviewed skin toxicities, in a blinded manner. RESULTS: A total of 95 patients were enrolled (pre-emptive: 47, reactive: 48). The primary end point was achieved (21.3 and 62.5% [risk ratio: 0.34; p < 0.001], for pre-emptive and reactive treatment, respectively). A similar trend was observed in central review. CONCLUSION: Pre-emptive skin treatment could reduce the severity of Pmab-associated skin toxicities in Japanese metastatic colorectal cancer patients.

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  • p62/SQSTM1 plays a protective role in oxidative injury of steatotic liver in a mouse hepatectomy model. 査読 国際誌

    Sanae Haga, Takeaki Ozawa, Yuma Yamada, Naoki Morita, Izuru Nagashima, Hiroshi Inoue, Yuka Inaba, Natsumi Noda, Riichiro Abe, Kazuo Umezawa, Michitaka Ozaki

    Antioxidants & redox signaling   21 ( 18 )   2515 - 30   2014年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MARY ANN LIEBERT, INC  

    AIMS: Liver injury and regeneration involve complicated processes and are affected by various physio-pathological factors. We investigated the mechanisms of steatosis-associated liver injury and delayed regeneration in a mouse model of partial hepatectomy. RESULTS: Initial regeneration of the steatotic liver was significantly delayed after hepatectomy. Although hepatocyte proliferation was not significantly suppressed, severe liver injury with oxidative stress (OS) occurred immediately after hepatectomy in the steatotic liver. Fas-ligand (FasL)/Fas expression was upregulated in the steatotic liver, whereas the expression of antioxidant and anti-apoptotic molecules (catalase/MnSOD/Ref-1 and Bcl-2/Bcl-xL/FLIP, respectively) and p62/SQSTM1, a steatosis-associated protein, was downregulated. Interestingly, pro-survival Akt was not activated in response to hepatectomy, although it was sufficiently expressed even before hepatectomy. Suppression of p62/SQSTM1 increased FasL/Fas expression and reduced nuclear factor erythroid 2-related factor-2 (Nrf-2)-dependent antioxidant response elements activity and antioxidant responses in steatotic and nonsteatotic hepatocytes. Exogenously added FasL induced severe cellular OS and necrosis/apoptosis in steatotic hepatocytes, with only the necrosis being inhibited by pretreatment with antioxidants, suggesting that FasL/Fas-induced OS mainly leads to necrosis. Furthermore, p62/SQSTM1 re-expression in the steatotic liver markedly reduced liver injury and improved liver regeneration. INNOVATION: This study is the first which demonstrates that reduced expression of p62/SQSTM1 plays a crucial role in posthepatectomy acute injury and delayed regeneration of steatotic liver, mainly via redox-dependent mechanisms. CONCLUSION: In the steatotic liver, reduced expression of p62/SQSTM1 induced FasL/Fas overexpression and suppressed antioxidant genes, mainly through Nrf-2 inactivation, which, along with the hypo-responsiveness of Akt, caused posthepatectomy necrotic/apoptotic liver injury and delayed regeneration, both mainly via a redox-dependent mechanism.

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  • Solitary tumour on the neck: a quiz. Cutaneous Rosai-Dorfman disease. 査読 国際誌

    Keita Horie, Riichiro Abe, Erina Homma, Junko Murata, Toshifumi Nomura, Hiroshi Shimizu

    Acta dermato-venereologica   94 ( 5 )   619 - 22   2014年9月

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    記述言語:英語   出版者・発行元:ACTA DERMATO-VENEREOLOGICA  

    DOI: 10.2340/00015555-1792

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  • Recurrent course and CD30 expression of atypical T lymphocytes distinguish lymphomatoid papulosis from primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma. 査読 国際誌

    Masumi Tsujiwaki, Riichiro Abe, Yuka Ohguchi, Daichi Hoshina, Junko Murata, Yasuyuki Fujita, Toshifumi Nomura, Midori Ambo, Hiroshi Shimizu

    Acta dermato-venereologica   94 ( 5 )   613 - 4   2014年9月

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    記述言語:英語   出版者・発行元:ACTA DERMATO-VENEREOLOGICA  

    DOI: 10.2340/00015555-1806

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  • Tubular apocrine adenoma clinically and dermoscopically mimicking basal cell carcinoma. 査読 国際誌

    Takamasa Ito, Toshifumi Nomura, Yasuyuki Fujita, Riichiro Abe, Hiroshi Shimizu

    Journal of the American Academy of Dermatology   71 ( 2 )   e45-6 - E46   2014年8月

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    記述言語:英語   出版者・発行元:MOSBY-ELSEVIER  

    DOI: 10.1016/j.jaad.2014.01.873

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  • An annexin A1-FPR1 interaction contributes to necroptosis of keratinocytes in severe cutaneous adverse drug reactions. 査読 国際誌

    Nao Saito, Hongjiang Qiao, Teruki Yanagi, Satoru Shinkuma, Keiko Nishimura, Asuka Suto, Yasuyuki Fujita, Shotaro Suzuki, Toshifumi Nomura, Hideki Nakamura, Koji Nagao, Chikashi Obuse, Hiroshi Shimizu, Riichiro Abe

    Science translational medicine   6 ( 245 )   245ra95   2014年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC ADVANCEMENT SCIENCE  

    Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening, cutaneous adverse drug reactions that are accompanied by keratinocyte cell death. Dead keratinocytes from SJS/TEN lesions exhibited necrosis, by morphological criteria. Supernatant from peripheral blood mononuclear cells (PBMCs) that had been exposed to the causative drug from patients with SJS/TEN induced the death of SJS/TEN keratinocytes, whereas supernatant from PBMCs of patients with ordinary drug skin reactions (ODSRs) exposed to the same drug did not. Keratinocytes from ODSR patients or from healthy controls were unaffected by supernatant from SJS/TEN or ODSR PBMCs. Mass spectrometric analysis identified annexin A1 as a key mediator of keratinocyte death; depletion of annexin A1 by a specific antibody diminished supernatant cytotoxicity. The necroptosis-mediating complex of RIP1 and RIP3 was indispensable for SJS/TEN supernatant-induced keratinocyte death, and SJS/TEN keratinocytes expressed abundant formyl peptide receptor 1 (FPR1), the receptor for annexin A1, whereas control keratinocytes did not. Inhibition of necroptosis completely prevented SJS/TEN-like responses in a mouse model of SJS/TEN. Our results demonstrate that a necroptosis pathway, likely mediated by annexin 1 acting through the FPR1 receptor, contributes to SJS/TEN.

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  • MUC5AC expression correlates with invasiveness and progression of extramammary Paget's disease 査読

    H. Hata, R. Abe, D. Hoshina, N. Saito, E. Homma, S. Aoyagi, H. Shimizu

    JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY   28 ( 6 )   727 - 732   2014年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    BackgroundPatients with in situ extramammary Paget's disease (EMPD) tend to have a good prognosis, although dermal invasion and metastasis are associated with significantly increased morbidity and mortality. Previous studies have addressed mechanisms underlying the EMPD pathogenesis; however, no molecular markers that reflect invasiveness or progression have been established.
    ObjectiveThis study aims to identify a reliable marker for predicting the risk of invasion and metastasis in EMPD.
    MethodsWe performed an initial microarray screening for in situ, invasive or metastatic lymph node lesions of EMPD. We analysed 44 specimens from 38 primary EMPD cases by immunohistochemical staining.
    ResultsWe found that expressions of MUC5AC directly correlate with invasion and prognosis. Labelling rates of tumour cells were scored by staining intensity on a four-tiered scale (- to 3+) to investigate the correlation between the expression score of these molecular markers and the type of EMPD lesion. All the specimens scored positive (3+) for MUC1 and negative (-) for MUC6. MUC5AC expression was detected in 19 of 44 (43.2%) specimens. Invasive lesions and metastatic lymph nodes tended to express MUC5AC significantly higher than in situ lesions (P&lt;0.01). MUC2 was positive in 10 specimens (22.7%). There was no significant difference between the degree of MUC2 expression and invasiveness.
    ConclusionThe degree of MUC5AC expression may correlate with the invasiveness and progression of EMPD, and may be a useful marker for identifying high-risk EMPD cases.

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  • Randomized controlled trial on the skin toxicity of panitumumab in third-line treatment of KRAS wild-type metastatic colorectal cancer: HGSGl001 (Japanese Skin Toxicity Evaluation Protocol with Panitumumab: J-STEPP)-Additional analysis of antitumor effica 査読

    Kobayashi Yoshimitsu, Komatsu Yoshito, Yuki Satoshi, Nakatsumi Hiroshi, Fukushima Hiraku, Miyagishima Takuto, Ehira Nobuyuki, Iwanaga Ichiro, Okuda Hiroyuki, Kusumi Takaya, Tateyama Miki, Tsuji Yasushi, Hatanaka Kazuteru, Nakamura Michio, Kudo Mineo, Takagi Tomofumi, Hisai Hiroyuki, Abe Riichiro, Oba Koji, Sakata Yuh

    JOURNAL OF CLINICAL ONCOLOGY   32 ( 15 )   2014年5月

  • A novel NCSTN mutation alone may be insufficient for the development of familial hidradenitis suppurativa. 査読 国際誌

    Yukiko Nomura, Toshifumi Nomura, Shotaro Suzuki, Masae Takeda, Osamu Mizuno, Yuka Ohguchi, Riichiro Abe, Yozo Murata, Hiroshi Shimizu

    Journal of dermatological science   74 ( 2 )   180 - 2   2014年5月

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    記述言語:英語   出版者・発行元:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.jdermsci.2014.01.013

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  • Repeated skin sampling and prolonged incubation period identified cutaneous Mycobacterium chelonae infection on the face in an immunocompetent man 査読

    K. Muramatsu, T. Nomura, T. Ito, Y. Hamade, Y. Hirata, Y. Fujita, R. Abe, H. Shimizu

    British Journal of Dermatology   170 ( 2 )   471 - 473   2014年2月

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  • High survival rate of harlequin ichthyosis in Japan. 査読 国際誌

    Akitaka Shibata, Yasushi Ogawa, Kazumitsu Sugiura, Yoshinao Muro, Riichiro Abe, Tamio Suzuki, Masashi Akiyama

    Journal of the American Academy of Dermatology   70 ( 2 )   387 - 8   2014年2月

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    記述言語:英語   出版者・発行元:MOSBY-ELSEVIER  

    DOI: 10.1016/j.jaad.2013.10.055

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  • LC-MS/MS analysis of canine lipoproteins fractionated using the ultracentrifugation-precipitation method. 査読

    Asuka Suto, Masahiro Yamasaki, Yukari Takasaki, Yasuyuki Fujita, Riichiro Abe, Hiroshi Shimizu, Hiroshi Ohta, Mitsuyoshi Takiguchi

    The Journal of veterinary medical science   75 ( 11 )   1471 - 7   2013年11月

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    記述言語:英語   出版者・発行元:11  

    Due to the lack of a gold standard method in canine lipoprotein analysis, it is unclear whether canine high-density lipoprotein (HDL) and low-density lipoprotein (LDL) can be accurately evaluated by the lipoprotein analysis methods used for dogs. This study investigated whether the ultracentrifugation-precipitation (U-P) method was suitable as a gold standard method for analyzing canine lipoprotein. First, the U-P method was compared with a gel permeation high-performance liquid chromatography system (GP-HPLC). The concentrations of canine HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) determined by the U-P method correlated closely with those determined by GP-HPLC. However, the canine HDL-C concentration determined by the U-P method was lower than that determined by GP-HPLC, and the canine LDL-C concentration determined by the U-P method was higher than that determined by GP-HPLC. This study showed that some canine HDL could be precipitated with heparin manganese chloride solution. Second, the HDL and LDL fractions separated by the U-P method were analyzed by LC-MS/MS. The HDL fraction was found to contain only apolipoprotein A-I, which is an apolipoprotein of HDL, whereas the LDL fraction contained both apolipoprotein A-I and apolipoprotein B-100, which is an apolipoprotein of LDL. This data showed that a certain lipoprotein that includes apolipoprotein A-I might precipitate with canine LDL when using heparin manganese chloride solution. These results indicated that the U-P method is not currently a gold standard method for analyzing canine lipoproteins.

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  • Dermoscopy of pseudoxanthoma elasticum-like papillary dermal elastolysis. 査読 国際誌

    Takamasa Ito, Yasuyuki Fujita, Toshifumi Nomura, Riichiro Abe, Hiroshi Shimizu

    Journal of the American Academy of Dermatology   69 ( 4 )   e202-3 - 3   2013年10月

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    記述言語:英語   出版者・発行元:4  

    DOI: 10.1016/j.jaad.2013.04.059

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  • Coexistence case of bullous pemphigoid and pemphigus foliaceus 査読

    Masumi Tsujiwaki, Riichiro Abe, Yukiko Nomura, Machiko Nishimura, Daichi Hoshina, Satoru Shinkuma, Ken Natsuga, Hideyuki Ujiie, Ken Arita, Hiroshi Shimizu

    EUROPEAN JOURNAL OF DERMATOLOGY   23 ( 4 )   552 - 553   2013年7月

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    記述言語:英語   出版者・発行元:JOHN LIBBEY EUROTEXT LTD  

    DOI: 10.1684/ejd.2013.2084

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  • Disturbed balance in three subpopulations of CD4(+)Foxp3(+) regulatory T cells in Stevens-Johnson syndrome and toxic epidermal necrolysis patients. 査読 国際誌

    Naoya Yoshioka, Asuka Suto, Riichiro Abe, Nao Saito, Junko Murata, Inkin Hayashi-Ujiie, Daichi Hoshina, Yasuyuki Fujita, Hiroshi Shimizu

    Clinical immunology (Orlando, Fla.)   148 ( 1 )   89 - 91   2013年7月

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    記述言語:英語   出版者・発行元:1  

    DOI: 10.1016/j.clim.2013.04.002

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  • Infantile eczema caused by formula milk. 査読 国際誌

    Takamasa Ito, Wataru Nishie, Yasuyuki Fujita, Riichiro Abe, Hiroshi Shimizu

    Lancet (London, England)   381 ( 9881 )   1958 - 1958   2013年6月

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    記述言語:英語   出版者・発行元:9881  

    DOI: 10.1016/S0140-6736(13)60684-4

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  • Establishment of a novel experimental model of human angiosarcoma and a VEGF-targeting therapeutic experiment. 査読 国際誌

    Daichi Hoshina, Riichiro Abe, Naoya Yoshioka, Nao Saito, Hiroo Hata, Yasuyuki Fujita, Satoru Aoyagi, Hiroshi Shimizu

    Journal of dermatological science   70 ( 2 )   116 - 22   2013年5月

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    記述言語:英語   出版者・発行元:2  

    BACKGROUND: Angiosarcoma is one of the most life-threatening neoplasms with strong resistance to conventional chemotherapy/radiotherapy; consequently, alternative therapeutic agents are urgently required. One factor in delaying the therapy development is the limitation of experimental models. OBJECTIVE: We established a novel experimental angiosarcoma model. METHODS: From surgically resected tissue, human AS cell line was established. Using xenograft of AS cell line, we performed therapeutic experiments with the anti-human VEGF Ab or the receptor tyrosine kinase inhibitor. RESULTS: First we generated an angiosarcoma cell line, HAMON (human angiosarcoma, monoclonal), which expresses CD31 and produces tumors in immunodeficient mice. HAMON expresses VEGFR2 and that exogenous VEGF leads to HAMON proliferation in vitro. Anti-human VEGF Ab bevacizumab treatment failed to suppress HAMON proliferation in vitro and in vivo. Furthermore, the receptor tyrosine kinase inhibitor sunitinib did not suppress HAMON proliferation in vitro. Similarly, in in vivo therapeutic experiments, even high doses of sunitinib failed to inhibit tumor growth. Finally, we checked whether compensatory activation of VEGF signaling occurred after sunitinib addition. VEGF protein secretion, VEGF mRNA synthesis and VEGFR2 phosphorylation all were unaffected in HAMON after sunitinib treatment. CONCLUSION: A novel in vitro and in vivo experimental model of human angiosarcoma has been successfully established. With this model, we were able to perform therapeutic experiments. In addition, our angiosarcoma cell line, HAMON, is quite useful for identifying key molecules in angiosarcoma.

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  • Indomethacin for refractory infantile eosinophilic pustular folliculitis. 査読 国際誌

    Ellen Toyonaga, Riichiro Abe, Reine Moriuchi, Kei Ito, Yukiko Abe, Hiroshi Shimizu

    JAMA dermatology   149 ( 3 )   367 - 8   2013年3月

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    記述言語:英語   出版者・発行元:3  

    DOI: 10.1001/2013.jamadermatol.591

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  • A method for intravital monitoring of human cells using a far-red luminescent probe in graft-versus-host disease model mice. 査読 国際誌

    Hongjiang Qiao, Riichiro Abe, Nao Saito, Yasuyuki Fujita, Inkin Hayashi-Ujiie, Gang Wang, Sanae Haga, Chun Wu, Yoshihiro Ohmiya, Michitaka Ozaki, Hiroshi Shimizu

    The Journal of investigative dermatology   133 ( 3 )   841 - 843   2013年3月

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    記述言語:英語   出版者・発行元:3  

    DOI: 10.1038/jid.2012.345

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  • Stevens-Johnson syndrome/toxic epidermal necrolysis mouse model generated by using PBMCs and the skin of patients. 査読 国際誌

    Nao Saito, Naoya Yoshioka, Riichiro Abe, Hongjiang Qiao, Yasuyuki Fujita, Daichi Hoshina, Asuka Suto, Satoru Kase, Nobuyoshi Kitaichi, Michitaka Ozaki, Hiroshi Shimizu

    The Journal of allergy and clinical immunology   131 ( 2 )   434 - 41   2013年2月

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    記述言語:英語   出版者・発行元:2  

    BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening cutaneous reactions caused by drugs or infections and exhibiting widespread epidermal necrosis. Currently, there is no animal model that reproduces SJS/TEN symptoms. OBJECTIVE: We sought to develop a novel mouse model of SJS/TEN by using PBMCs and skin from patients who had recovered from SJS/TEN. METHODS: For our mouse model, patients' PBMCs were injected intravenously into immunocompromised NOD/Shi-scid, IL-2Rγ(null) (NOG) mice, followed by oral administration of a causative drug. Subsequently, to replace human skin, unaffected skin specimens obtained from patients who had recovered from SJS/TEN were grafted onto NOG mice, after which patient-derived PBMCs and the causative drug were applied. RESULTS: Mice injected with PBMCs from patients with SJS/TEN and given the causative drug showed marked conjunctival congestion and numerous cell death of conjunctival epithelium, whereas there were no symptoms in mice injected with PBMCs from patients with ordinary drug skin reactions. CD8(+) T lymphocyte-depleted PBMCs from patients with SJS/TEN did not elicit these symptoms. In addition, skin-grafted mice showed darkening of the skin-grafted areas. Cleaved caspase-3 staining showed that dead keratinocytes were more numerous in the skin-grafted mice than in the healthy control animals. CONCLUSION: We have established a novel human-oriented SJS/TEN mouse model and proved the importance of CD8(+) T lymphocytes in SJS/TEN pathogenesis. The mouse model promises to promote diagnostic and therapeutic approaches.

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  • A novel splice site mutation in NCSTN underlies a Japanese family with hidradenitis suppurativa 査読

    Y. Nomura, Toshifumi Nomura, K. Sakai, K. Sasaki, Y. Ohguchi, O. Mizuno, H. Hata, S. Aoyagi, R. Abe, Y. Itaya, M. Akiyama, H. Shimizu

    British Journal of Dermatology   168 ( 1 )   206 - 209   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:1  

    Background Hidradenitis suppurativa (HS) is a chronic follicular occlusive disease with characteristic recurrent draining sinuses, skin abscesses and disfiguring scars, mainly involving the axilla, groin, perianal and perineal regions. While most HS cases are nonfamilial, familial cases showing autosomal dominant inheritance have been reported. Recently, loss-of-function mutations in the genes encoding γ-secretase have been identified as a cause of familial HS in the Chinese and British populations. Objectives To identify mutations in the genes encoding γ-secretase in Japanese patients with familial and nonfamilial HS. Methods Two affected and three unaffected individuals from a Japanese family with familial HS and nine patients with nonfamilial HS were recruited. We conducted mutation analysis of the γ-secretase genes in Japanese patients with familial and nonfamilial HS. Results A novel splice site mutation in the nicastrin gene NCSTN, one of the six key component genes encoding γ-secretase, was identified in the patients with familial HS. Neither unaffected individuals in the family nor 100 ethnically matched control alleles carry this mutation. None of the nine patients with nonfamilial HS carry nonsense, frameshift or splice site mutations in this gene. Conclusions A novel splice site mutation, c.582+1delG, in NCSTN was identified in the familial patients with HS. We also reveal for the first time that a γ-secretase gene mutation is not linked to the development of nonfamilial HS. These results would further pave the way to a better understanding of the contribution of γ-secretase and other genes to the pathogenesis of HS and to the development of a new therapeutic strategy for HS. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

    DOI: 10.1111/j.1365-2133.2012.11174.x

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  • Pagetoid dyskeratosis with parallel ridge pattern under dermoscopy. 査読 国際誌

    Ellen Toyonaga, Daisuke Inokuma, Yukiko Abe, Riichiro Abe, Hiroshi Shimizu

    JAMA dermatology   149 ( 1 )   109 - 11   2013年1月

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    記述言語:英語   出版者・発行元:1  

    DOI: 10.1001/archdermatol.2012.3201

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  • Skin involvement in ALK-negative systemic anaplastic large-cell lymphoma. 査読 国際誌

    Daichi Hoshina, Ken Arita, Osamu Mizuno, Katsuya Fujimoto, Mitsufumi Nishio, Takeshi Kondo, Riichiro Abe, Hiroshi Shimizu

    Journal of the American Academy of Dermatology   67 ( 4 )   e159-60 - 60   2012年10月

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    記述言語:英語   出版者・発行元:4  

    DOI: 10.1016/j.jaad.2011.12.033

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  • Prolonged elevation of serum granulysin in drug-induced hypersensitivity syndrome 査読

    N. Saito, R. Abe, N. Yoshioka, J. Murata, Y. Fujita, H. Shimizu

    BRITISH JOURNAL OF DERMATOLOGY   167 ( 2 )   452 - 453   2012年8月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    DOI: 10.1111/j.1365-2133.2012.10921.x

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  • The β9 loop domain of PA-PLA1α has a crucial role in autosomal recessive woolly hair/hypotrichosis. 査読 国際誌

    Shinkuma S, Inoue A, Aoki J, Nishie W, Natsuga K, Ujiie H, Nomura T, Abe R, Akiyama M, Shimizu H

    The Journal of investigative dermatology   132 ( 8 )   2093 - 5   2012年8月

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    記述言語:英語   出版者・発行元:8  

    DOI: 10.1038/jid.2012.96

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  • Psoriatic onycho-pachydermo-periostitis progressing to generalized pustular psoriasis 査読

    M. Watanabe, H. Ujiie, M. M. Iitani, R. Abe, H. Shimizu

    CLINICAL AND EXPERIMENTAL DERMATOLOGY   37 ( 6 )   683 - 685   2012年8月

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    記述言語:英語   出版者・発行元:WILEY  

    DOI: 10.1111/j.1365-2230.2011.04328.x

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  • Conversion from human haematopoietic stem cells to keratinocytes requires keratinocyte secretory factors 査読

    Y. Fujita, D. Inokuma, R. Abe, M. Sasaki, H. Nakamura, T. Shimizu, H. Shimizu

    CLINICAL AND EXPERIMENTAL DERMATOLOGY   37 ( 6 )   658 - 664   2012年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Background. Recent studies have reported that bone-marrow-derived stem cells (BMSCs), including haematopoietic stem cells (HSCs) and mesenchymal stromal cells, differentiate in order to regenerate various cellular lineages. Based on these findings, it is known that BMSCs can be used clinically to treat various disorders, such as myocardial infarction and neurotraumatic injuries. However, the mechanism of HSC conversion into organ cells is incompletely understood. The mechanism is suspected to involve direct cellcell interaction between BMSCs, damaged organ cells, and paracrine-regulated soluble factors from the organ, but to date, there have been no investigations into which of these are essential for keratinocyte differentiation from HSCs. Aim. To elucidate the mechanism and necessary conditions for HSC differentiation into keratinocytes in vitro. Methods. We cultured human (h)HSCs under various conditions to try to elucidate the mechanism and necessary conditions for hHSCs to differentiate into keratinocytes. Result. hHSCs cocultured with mouse keratinocytes induced expression of human keratin 14 and transglutaminase I. Only 0.1% of the differentiated keratinocytes possessed multiple nuclei indicating cell fusion. Coculture of hHSCs with fixed murine keratinocytes (predicted to stabilize cellular components) failed to induce conversion into keratinocytes. Conversely, keratinocyte-conditioned medium from both human and mouse keratinocytes was found to mediate hHSC conversion into keratinocytes. Conclusions. Human HSCs are capable of differentiation into keratinocytes, and cell fusion is extremely rare. This differentiating is mediated by the plasma environment rather than by direct cellcell interactions.

    DOI: 10.1111/j.1365-2230.2011.04312.x

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  • Yellow nail syndrome: nail change reflects disease severity. 査読 国際誌

    Inkin Hayashi, Riichiro Abe, Teruki Yanagi, Yukiko Abe, Hiroshi Shimizu

    The Journal of dermatology   39 ( 4 )   415 - 6   2012年4月

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    記述言語:英語   出版者・発行元:4  

    DOI: 10.1111/j.1346-8138.2011.01293.x

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  • Intraepidermal neutrophilic IgA pemphigus successfully treated with dapsone 査読

    Yu Hirata, Riichiro Abe, Kazuhiro Kikuchi, Asuka Hamasaka, Satoru Shinkuma, Toshifumi Nomura, Wataru Nishie, Ken Arita, Hiroshi Shimizu

    EUROPEAN JOURNAL OF DERMATOLOGY   22 ( 2 )   282 - 283   2012年3月

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    記述言語:英語   出版者・発行元:JOHN LIBBEY EUROTEXT LTD  

    DOI: 10.1684/ejd.2012.1662

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  • Rapid immunochromatographic test for serum granulysin is useful for the prediction of Stevens-Johnson syndrome and toxic epidermal necrolysis. 査読 国際誌

    Yasuyuki Fujita, Naoya Yoshioka, Riichiro Abe, Junko Murata, Daichi Hoshina, Hirokatsu Mae, Hiroshi Shimizu

    Journal of the American Academy of Dermatology   65 ( 1 )   65 - 8   2011年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MOSBY-ELSEVIER  

    BACKGROUND: Life-threatening adverse drug reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) sometimes start with clinical features of ordinary drug-induced skin reactions (ODSRs) and it may be difficult to make a correct diagnosis before severe mucocutaneous erosions occur. We have reported that serum granulysin levels are elevated (cut off: 10 ng/mL) in patients with SJS/TEN before generalized blisters form. OBJECTIVE: We sought to develop a rapid detection system for elevated serum granulysin to predict the progression from ODSRs. METHODS: Serum samples from 5 patients with SJS/TEN at 2 to 4 days before mucocutaneous erosions formed were analyzed. Sera from 24 patients with ODSRs and 31 healthy volunteers were also investigated as control subjects. We developed a rapid immunochromatographic assay for the detection of high levels of serum granulysin using two different antigranulysin monoclonal antibodies. RESULTS: The immunochromatographic test showed positive results for 4 of 5 patients with SJS/TEN but only one patient of 24 with ODSRs. The results correlated closely with those of enzyme-linked immunosorbent assays. LIMITATIONS: The validation of the long-time stability in this test strip has not been investigated. CONCLUSION: This novel test enables the prediction of SJS/TEN occurrence in patients even when only features of ODSRs are noted clinically.

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  • Spontaneous remission of solitary-type infantile myofibromatosis. 査読 国際誌

    Kazuhiro Kikuchi, Riichiro Abe, Satoru Shinkuma, Erika Hamasaka, Ken Natsuga, Hiroo Hata, Yasuki Tateishi, Masahiko Shibata, Yuki Tomita, Yukiko Abe, Satoru Aoyagi, Makio Mukai, Hiroshi Shimizu

    Case reports in dermatology   3 ( 2 )   181 - 5   2011年5月

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    記述言語:英語   出版者・発行元:2  

    Infantile myofibromatosis is a rare fibrous tumor of infancy. The cutaneous solitary type has typically an excellent prognosis. However, histologically, it is important to rule out leiomyosarcoma, which has a poor prognosis. The low frequency of mitosis was definitive for a diagnosis of infantile myofibromatosis. We present a cutaneous solitary-type case of infantile myofibromatosis. Following incisional biopsy, the tumor remitted spontaneously.

    DOI: 10.1159/000331325

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  • Macrophage migration inhibitory factor is essential for eosinophil recruitment in allergen-induced skin inflammation. 査読 国際誌

    Yoko Yoshihisa, Teruhiko Makino, Kenji Matsunaga, Ayumi Honda, Osamu Norisugi, Riichiro Abe, Hiroshi Shimizu, Tadamichi Shimizu

    The Journal of investigative dermatology   131 ( 4 )   925 - 31   2011年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Macrophage migration inhibitory factor (MIF) is a pluripotent cytokine that has an essential role in the pathophysiology of experimental allergic inflammation. Recent findings suggest that MIF is involved in several allergic disorders, including atopic dermatitis (AD). In this study, the role of MIF in allergic skin inflammation was examined using a murine model of AD elicited by epicutaneous sensitization with ovalbumin (OVA). We observed the number of skin-infiltrating eosinophils to significantly increase in OVA-sensitized MIF transgenic (Tg) mice compared with their wild-type (WT) littermates. On the other hand, eosinophils were virtually absent from the skin of MIF knockout (KO) mice and failed to infiltrate their skin after repeated epicutaneous sensitization with OVA. The mRNA expression levels of eotaxin and IL-5 were significantly increased in OVA-sensitized skin sites of MIF Tg mice, but were significantly decreased in MIF KO mice in comparison with the levels in WT littermates. Eotaxin expression was induced by IL-4 stimulation in fibroblasts in MIF Tg mice, but not in MIF KO mice. These findings indicate that MIF can induce eosinophil accumulation in the skin. Therefore, the targeted inhibition of MIF might be a promising new therapeutic strategy for allergic skin diseases.

    DOI: 10.1038/jid.2010.418

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  • [Therapy for skin disease using bone marrow cells]. 査読

    Riichiro Abe

    Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology   34 ( 2 )   85 - 90   2011年

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    記述言語:英語   出版者・発行元:2  

    Attempts to treat congenital protein deficiencies using bone marrow-derived cells have been reported. These efforts have been based on the concepts of stem cell plasticity. We aimed to clarify whether bone marrow transplantation (BMT) treatment can rescue epidermolysis bullosa (EB) caused by defects in keratinocyte structural proteins. BMT treatment of adult collagen XVII (Col17) knockout mice induced donor-derived keratinocytes and Col17 expression associated with the recovery of hemidesmosomal structure and better skin manifestations, as well improving the survival rate. Furthermore, human cord blood CD34+ cells also differentiated into keratinocytes and expressed human skin component proteins in transplanted immunocompromised mice. The current conventional BMT techniques have significant potential as a systemic therapeutic approach for the treatment of human EB.

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  • Regenerative medicine for severe congenital skin disorders: restoration of deficient skin component proteins by stem cell therapy

    Fujita Yasuyuki, Abe Riichiro, Nishie Wataru, Shimizu Hiroshi

    Inflammation and Regeneration   31 ( 3 )   282 - 289   2011年

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    記述言語:英語   出版者・発行元:The Japanese Society of Inflammation and Regeneration  

    Some congenital skin disorders lacking structure proteins in the basement membrane zone carry severe prognosis because of severe erosion and skin dysfunction on the whole body. So far, several therapeutic strategies have been emerging for such disorders: 1. gene therapies, 2. protein therapies and 3. cell therapies. Cell therapies have a potential to affect skin systemically, and stem cell transplantation is one of the most hopeful candidates for treating severe congenital skin disorders such as epidermolysis bullosa, from a perspective of transdifferentiation and re-programming of stem cells. We review here the recent strategies and progress of stem cell transplantation for epidermolysis bullosa.

    DOI: 10.2492/inflammregen.31.282

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    その他リンク: http://search.jamas.or.jp/link/ui/2012198361

  • Japanese-specific filaggrin gene mutations in Japanese patients suffering from atopic eczema and asthma. 査読 国際誌

    Rinko Osawa, Satoshi Konno, Masashi Akiyama, Ikue Nemoto-Hasebe, Toshifumi Nomura, Yukiko Nomura, Riichiro Abe, Aileen Sandilands, W H Irwin McLean, Nobuyuki Hizawa, Masaharu Nishimura, Hiroshi Shimizu

    The Journal of investigative dermatology   130 ( 12 )   2834 - 6   2010年12月

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    記述言語:英語   出版者・発行元:12  

    DOI: 10.1038/jid.2010.218

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  • Protective effects of platinum nanoparticles against UV-light-induced epidermal inflammation. 査読 国際誌

    Yoko Yoshihisa, Ayumi Honda, Qing-Li Zhao, Teruhiko Makino, Riichiro Abe, Kotaro Matsui, Hiroshi Shimizu, Yusei Miyamoto, Takashi Kondo, Tadamichi Shimizu

    Experimental dermatology   19 ( 11 )   1000 - 6   2010年11月

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    記述言語:英語   出版者・発行元:11  

    Intracellular reactive oxygen species (ROS) and apoptosis play important roles in the ultraviolet (UV)-induced inflammatory responses in the skin. Metal nanoparticles have been developed to increase the catalytic activity of metals, which is because of the large surface area of smaller particles. Platinum nanoparticles (nano-Pt) protected by poly acrylic acid were manufactured by reduction with ethanol. A marked increase in ROS production was observed in UV-treated HaCaT keratinocytes cell lines, while a decrease in ROS production was observed in nano-Pt-treated cells. Pretreatment of the cells with nano-Pt also caused a significant inhibition of UVB- and UVC-induced apoptosis. Furthermore, we found that mice treated with nano-Pt gel prior to UV irradiation showed significant inhibition of UVB-induced inflammation and UVA-induced photoallergy compared to UV-irradiated control mice. These results suggest that nano-Pt effectively protects against UV-induced inflammation by decreasing ROS production and inhibiting apoptosis in keratinocytes.

    DOI: 10.1111/j.1600-0625.2010.01128.x

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  • Aleukemic leukemia cutis with extensive bone involvement. 査読 国際誌

    Maria Maroto Iitani, Riichiro Abe, Teruki Yanagi, Asuka Hamasaka, Yasuki Tateishi, Yukiko Abe, Miki Ito, Takeshi Kondo, Kanako Kubota, Hiroshi Shimizu

    Journal of the American Academy of Dermatology   63 ( 3 )   539 - 41   2010年9月

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    記述言語:英語   出版者・発行元:3  

    DOI: 10.1016/j.jaad.2009.05.040

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  • Chromosome 11q13.5 variant: No association with atopic eczema in the Japanese population. 査読 国際誌

    Yukiko Nomura, Masashi Akiyama, Toshifumi Nomura, Ikue Nemoto-Hasebe, Riichiro Abe, W H Irwin McLean, Hiroshi Shimizu

    Journal of dermatological science   59 ( 3 )   210 - 2   2010年9月

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    記述言語:英語   出版者・発行元:3  

    DOI: 10.1016/j.jdermsci.2010.06.010

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  • Bone marrow transplantation restores epidermal basement membrane protein expression and rescues epidermolysis bullosa model mice. 査読 国際誌

    Yasuyuki Fujita, Riichiro Abe, Daisuke Inokuma, Mikako Sasaki, Daichi Hoshina, Ken Natsuga, Wataru Nishie, James R McMillan, Hideki Nakamura, Tadamichi Shimizu, Masashi Akiyama, Daisuke Sawamura, Hiroshi Shimizu

    Proceedings of the National Academy of Sciences of the United States of America   107 ( 32 )   14345 - 50   2010年8月

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    記述言語:英語   出版者・発行元:32  

    Attempts to treat congenital protein deficiencies using bone marrow-derived cells have been reported. These efforts have been based on the concepts of stem cell plasticity. However, it is considered more difficult to restore structural proteins than to restore secretory enzymes. This study aims to clarify whether bone marrow transplantation (BMT) treatment can rescue epidermolysis bullosa (EB) caused by defects in keratinocyte structural proteins. BMT treatment of adult collagen XVII (Col17) knockout mice induced donor-derived keratinocytes and Col17 expression associated with the recovery of hemidesmosomal structure and better skin manifestations, as well improving the survival rate. Both hematopoietic and mesenchymal stem cells have the potential to produce Col17 in the BMT treatment model. Furthermore, human cord blood CD34(+) cells also differentiated into keratinocytes and expressed human skin component proteins in transplanted immunocompromised (NOD/SCID/gamma(c)(null)) mice. The current conventional BMT techniques have significant potential as a systemic therapeutic approach for the treatment of human EB.

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  • Topical application of dehydroxymethylepoxyquinomicin improves allergic inflammation via NF-kappaB inhibition. 査読 国際誌

    Asuka Hamasaka, Naoya Yoshioka, Riichiro Abe, Satoshi Kishino, Kazuo Umezawa, Michitaka Ozaki, Satoru Todo, Hiroshi Shimizu

    The Journal of allergy and clinical immunology   126 ( 2 )   400 - 3   2010年8月

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    DOI: 10.1016/j.jaci.2010.05.020

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  • The 1st JSID Kisaragi Juku: The junior tutors' perspective. 査読 国際誌

    Kenji Kabashima, Riichiro Abe, Satoshi Hirakawa, Naotomo Kambe, Manabu Ohyama, Manabu Fujimoto

    Journal of dermatological science   58 ( 3 )   167 - 70   2010年6月

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  • Prevalent LIPH founder mutations lead to loss of P2Y5 activation ability of PA-PLA1alpha in autosomal recessive hypotrichosis. 査読 国際誌

    Satoru Shinkuma, Masashi Akiyama, Asuka Inoue, Junken Aoki, Ken Natsuga, Toshifumi Nomura, Ken Arita, Riichiro Abe, Kei Ito, Hideki Nakamura, Hideyuki Ujiie, Akihiko Shibaki, Hiraku Suga, Yuichiro Tsunemi, Wataru Nishie, Hiroshi Shimizu

    Human mutation   31 ( 5 )   602 - 10   2010年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:5  

    Autosomal recessive hypotrichosis (ARH) is characterized by sparse hair on the scalp without other abnormalities. Three genes, DSG4, LIPH, and LPAR6 (P2RY5), have been reported to underlie ARH. We performed a mutation search for the three candidate genes in five independent Japanese ARH families and identified two LIPH mutations: c.736T>A (p.Cys246Ser) in all five families, and c.742C>A (p.His248Asn) in four of the five families. Out of 200 unrelated control alleles, we detected c.736T>A in three alleles and c.742C>A in one allele. Haplotype analysis revealed each of the two mutant alleles is derived from a respective founder. These results suggest the LIPH mutations are prevalent founder mutations for ARH in the Japanese population. LIPH encodes PA-PLA(1)alpha (LIPH), a membrane-associated phosphatidic acid-preferring phospholipase A(1)alpha. Two residues, altered by these mutations, are conserved among PA-PLA(1)alpha of diverse species. Cys(246) forms intramolecular disulfide bonds on the lid domain, a crucial structure for substrate recognition, and His(248) is one amino acid of the catalytic triad. Both p.Cys246Ser- and p.His248Asn-PA-PLA(1)alpha mutants showed complete abolition of hydrolytic activity and had no P2Y5 activation ability. These results suggest defective activation of P2Y5 due to reduced 2-acyl lysophosphatidic acid production by the mutant PA-PLA(1)alpha is involved in the pathogenesis of ARH.

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  • Topical application of anti-angiogenic peptides based on pigment epithelium-derived factor can improve psoriasis. 査読 国際誌

    Riichiro Abe, Sho-ichi Yamagishi, Yasuyuki Fujita, Daichi Hoshina, Mikako Sasaki, Kazuo Nakamura, Takanori Matsui, Tadamichi Shimizu, Richard Bucala, Hiroshi Shimizu

    Journal of dermatological science   57 ( 3 )   183 - 91   2010年3月

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    記述言語:英語   出版者・発行元:3  

    BACKGROUND: Psoriasis is a common chronic inflammatory skin disorder with a high prevalence (3-5%) in the Caucasian population. Although the number of capillary vessels increases in psoriatic lesions, there have been few reports that have specifically examined the role of angiogenesis in psoriasis. Angiogenic factors, such as vascular endothelial growth factor (VEGF), may dominate the activity of anti-angiogenic factors and accelerate angiogenesis in psoriatic skin. OBJECTIVE: We investigated to identify small peptide mimetics of PEDF that might show anti-angiogenic potential for the topical treatment for psoriasis. METHODS: We examined the expression of PEDF in skin by immunohistochemical staining, immunoblotting, and RT-PCR. To identify potential PEDF peptides, we screened peptides derived from the proteolytic fragmentation of PEDF for their anti-proliferative action. Anti-psoriatic functions of these peptides were analyzed using a mouse graft model of psoriasis. RESULTS: The specific low-molecular weight peptides (MW<850 Da) penetrated the skin and showed significant anti-angiogenic activity in vitro. Topical application of these peptides in a severe combined immunodeficient mouse model of psoriatic disease led to reduced angiogenesis and epidermal thickness. CONCLUSIONS: These data suggest that low-molecular PEDF peptides with anti-angiogenic activity may be a novel therapeutic strategy for psoriasis.

    DOI: 10.1016/j.jdermsci.2009.12.010

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  • Granulysin as a marker for early diagnosis of the Stevens-Johnson syndrome. 査読 国際誌

    Riichiro Abe, Naoya Yoshioka, Junko Murata, Yasuyuki Fujita, Hiroshi Shimizu

    Annals of internal medicine   151 ( 7 )   514 - 5   2009年10月

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  • Secondary syphilis mimicking warts in an HIV-positive patient 査読

    S. Shinkuma, R. Abe, M. Nishimura, K. Natsuga, Y. Fujita, T. Nomura, W. Nishie, H. Shimizu

    SEXUALLY TRANSMITTED INFECTIONS   85 ( 6 )   484 - 484   2009年10月

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    記述言語:英語   出版者・発行元:B M J PUBLISHING GROUP  

    DOI: 10.1136/sti.2008.035626

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  • Scleroedema adultorum associated with sarcoidosis 査読

    D. Inokuma, D. Sawamura, A. Shibaki, R. Abe, H. Shimizu

    CLINICAL AND EXPERIMENTAL DERMATOLOGY   34 ( 7 )   e428 - e429   2009年10月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    DOI: 10.1111/j.1365-2230.2009.03423.x

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  • Deficient deletion of apoptotic cells by macrophage migration inhibitory factor (MIF) overexpression accelerates photocarcinogenesis. 査読 国際誌

    Ayumi Honda, Riichiro Abe, Yoko Yoshihisa, Teruhiko Makino, Kenji Matsunaga, Jun Nishihira, Hiroshi Shimizu, Tadamichi Shimizu

    Carcinogenesis   30 ( 9 )   1597 - 605   2009年9月

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    記述言語:英語  

    Chronic ultraviolet (UV) exposure can increase the occurrence of p53 mutations, thus leading to a dysregulation of apoptosis and the initiation of skin cancer. Therefore, it is extremely important that apoptosis is induced quickly after UV irradiation, without any dysregulation. Recent studies have suggested a potentially broader role for macrophage migration inhibitory factor (MIF) in growth regulation via its ability to antagonize p53-mediated gene activation and apoptosis. To further elucidate the possible role of MIF in photocarcinogenesis, the acute and chronic UVB effect in the skin was examined using macrophage migration inhibitory factor transgenic (MIF Tg) and wild-type (WT) mice. The MIF Tg mice exposed to chronic UVB irradiation began to develop skin tumors after approximately 14 weeks, whereas the WT mice began to develop tumors after 18 weeks. A higher incidence of tumors was observed in the MIF Tg in comparison with the WT mice after chronic UVB irradiation. Next, we clarified whether the acceleration of photo-induced carcinogenesis in the MIF Tg mice was mediated by the inhibition of apoptosis There were fewer sunburned cells in the epidermis of the MIF Tg mice than the WT mice after acute UVB exposure. The epidermis derived from the MIF Tg mice exhibited substantially decreased levels of p53, bax and p21 after UVB exposure in comparison with the WT mice. Collectively, these findings suggest that chronic UVB exposure enhances MIF production, which may inhibit the p53-dependent apoptotic processes and thereby induce photocarcinogenesis in the skin.

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  • Collagen XVII participates in keratinocyte adhesion to collagen IV, and in p38MAPK-dependent migration and cell signaling. 査読 国際誌

    Hongjiang Qiao, Akihiko Shibaki, Heather A Long, Gang Wang, Qiang Li, Wataru Nishie, Riichiro Abe, Masashi Akiyama, Hiroshi Shimizu, James R McMillan

    The Journal of investigative dermatology   129 ( 9 )   2288 - 95   2009年9月

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    記述言語:英語   出版者・発行元:9  

    Collagen XVII (COL17) participates in keratinocyte adhesion and possibly migration, as COL17 defects disrupt keratinocyte-basal lamina adhesion and underlie the disease non-Herlitz junctional epidermolysis bullosa. Using small interference RNA (siRNA) to knock down COL17 expression in HaCaT cells, we assessed cell characteristics, including adhesion, migration, and signaling. Control and siRNA-transfected keratinocytes showed no difference in adhesion on plastic dishes after incubation for 8 hours in serum-free keratinocyte-growth medium; however, when grown on collagen IV alone or BD matrigel (containing collagen IV and laminin isoforms), COL17-deficient cells showed significantly reduced adhesion compared with controls (P<0.01), and mitogen-activated protein kinase (MAPK)/ERK kinase (MEK)1/2 and MAPK showed reduced phosphorylation. Furthermore, COL17-deficient HaCaT cells plated on plastic exhibited reduced motility that was p38MAPK-dependent (after addition of the p38MAPK inhibitor SB203580). Together, these results suggest that COL17 has significantly wider signaling roles than were previously thought, including the involvement of COL17 in keratinocyte adhesion to collagen IV, in p38MAPK-dependent cell migration, and multiple cell signaling events pertaining to MEK1/2 phosphorylation.

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  • DNA vaccination against macrophage migration inhibitory factor improves atopic dermatitis in murine models. 査読 国際誌

    Asuka Hamasaka, Riichiro Abe, Yoshikazu Koyama, Naoya Yoshioka, Yasuyuki Fujita, Daichi Hoshina, Mikako Sasaki, Tsutomu Hirasawa, Shin Onodera, Shigeki Ohshima, Lin Leng, Richard Bucala, Jun Nishihira, Tadamichi Shimizu, Hiroshi Shimizu

    The Journal of allergy and clinical immunology   124 ( 1 )   90 - 9   2009年7月

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    記述言語:英語   出版者・発行元:1  

    BACKGROUND: Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that has been implicated in the pathogenesis of AD. Recently, we developed a novel DNA vaccine that generates neutralizing endogenous anti-MIF antibodies. OBJECTIVE: This study explores the preventive and therapeutic effects of this MIF-DNA vaccine in mouse models of AD. METHODS: Two different AD model mice (DS-Nh and NC/Nga) received MIF-DNA vaccination to analyze preventive and therapeutic effects, as assessed by clinical skin scores, histologic findings, and serum IgE levels. RESULTS: In murine models of AD, MIF-DNA vaccination prevented the occurrence of the AD skin phenotype. Furthermore, administration of MIF-DNA vaccine to mice that had already developed AD produced a rapid improvement in AD skin manifestation. There were reduced histologic signs of inflammation and lower serum IgE levels in treated mice compared with those seen in control animals. Finally, passive transfer of IgG from MIF-DNA vaccinated mice to AD mice also produced a significant therapeutic effect. These results demonstrate that MIF-DNA vaccination not only prevents the development of AD but also improves the symptoms of pre-existing AD. CONCLUSION: Taken together, the induction of an anti-MIF autoantibody response using MIF-DNA vaccination appears to be a useful approach in the treatment of AD.

    DOI: 10.1016/j.jaci.2009.04.025

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  • A novel OSMR mutation in familial primary localized cutaneous amyloidosis in a Japanese family. 査読 国際誌

    Ken Arita, Riichiro Abe, Keiko Baba, John A McGrath, Masashi Akiyama, Hiroshi Shimizu

    Journal of dermatological science   55 ( 1 )   64 - 5   2009年7月

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    記述言語:英語   出版者・発行元:1  

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  • Immunological reconstitution after autologous hematopoietic stem cell transplantation in patients with systemic sclerosis: relationship between clinical benefits and intensity of immunosuppression. 査読 国際誌

    Toshiyuki Bohgaki, Tatsuya Atsumi, Miyuki Bohgaki, Akira Furusaki, Makoto Kondo, Kazuko C Sato-Matsumura, Riichiro Abe, Hiroshi Kataoka, Tetsuya Horita, Shinsuke Yasuda, Yoshiharu Amasaki, Mitsufumi Nishio, Ken-Ichi Sawada, Hiroshi Shimizu, Takao Koike

    The Journal of rheumatology   36 ( 6 )   1240 - 8   2009年6月

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    記述言語:英語   出版者・発行元:6  

    OBJECTIVE: To analyze the relationship between clinical benefits and immunological changes in patients with systemic sclerosis (SSc) treated with autologous hematopoietic stem cell transplantation (HSCT). METHODS: Ten patients with SSc were treated with high-dose cyclophosphamide followed by highly purified CD34+ cells (n=5) or unpurified grafts (n=5). Two groups of patients were retrospectively constituted based on their clinical response (good responders, n=7; and poor responders, n=3). As well as clinical findings, immunological reconstitution through autologous HSCT was assessed by fluorescence-activated cell sorter analysis, quantification of signal joint T cell receptor rearrangement excision circles (sjTREC), reflecting the thymic function, and foxp3, a key gene of regulatory T cells, mRNA levels. RESULTS: Patients' clinical and immunological findings were similar between good and poor responders, or CD34-purified and unpurified groups at inclusion. The sjTREC values were significantly suppressed at 3 months after autologous HSCT in good responders compared with poor responders (p=0.0152). Reconstitution of CD4+CD45RO- naive T cells was delayed in good responders compared with poor responders. The phenotype of other lymphocytes, cytokine production in T cells, and foxp3 gene expression levels after autologous HSCT did not correlate with clinical response in good or poor responders. Clinical and immunological findings after autologous HSCT were similar between CD34-purified and unpurified groups. CONCLUSION: Our results suggest that immunosuppression intensity, sufficient to induce transient suppression of thymic function, is attributable to the feasible clinical response in patients with SSc treated with autologous HSCT. Appropriate monitoring of sjTREC values may predict clinical benefits in transplanted SSc patients after autologous HSCT.

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  • Bone marrow-derived cells are not the origin of the cancer stem cells in ultraviolet-induced skin cancer. 査読 国際誌

    Satomi Ando, Riichiro Abe, Mikako Sasaki, Junko Murata, Daisuke Inokuma, Hiroshi Shimizu

    The American journal of pathology   174 ( 2 )   595 - 601   2009年2月

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    記述言語:英語   出版者・発行元:2  

    Several lines of evidence have demonstrated that various cancers are derived from cancer stem cells (CSCs), which are thought to originate from either tissue stem or progenitor cells. However, recent studies have suggested that the origin of CSCs could be bone marrow-derived cells (BMDCs); for example, gastric cancer, which follows persistent gastric inflammation, appears to originate from BMDCs. Although our previous research showed the capability of BMDCs to differentiate into epidermal keratinocytes, it has yet to be determined whether skin CSCs originate from BMDCs. To assess the possibility that BMDCs could be the origin of CSCs in skin squamous cell carcinoma (SCC), we used a mouse model of UVB-induced skin SCC. We detected a low percentage of BMDCs in the lesions of epidermal dysplasia (0.59%), SCC in situ (0.15%), and SCC (0.03%). Furthermore, we could not find any evidence of clonal BMDC expansion. In SCC lesions, we also found that most of the BMDCs were tumor-infiltrating hematopoietic cells. In addition, BMDCs in the SCC lesions lacked characteristics of epidermal stem cells, including expression of stem cell markers (CD34, high alpha6 integrin) and the potential retention of BrdU label. These results indicate that BMDCs are not a major source of malignant keratinocytes in UVB-induced SCC. Therefore, we conclude that BMDCs are not the origin of CSCs in UVB-induced SCC.

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  • Autoantibodies against type XVII collagen C-terminal domain in a patient with bullous pemphigoid associated with psoriasis vulgaris 査読

    D. Inokuma, K. Kodama, K. Natsuga, M. Kasai, M. Abe, W. Nishie, R. Abe, T. Hashimoto, H. Shimizu

    BRITISH JOURNAL OF DERMATOLOGY   160 ( 2 )   451 - 454   2009年2月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    DOI: 10.1111/j.1365-2133.2008.08961.x

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  • Type XVII collagen is a key player in tooth enamel formation. 査読 国際誌

    Takuya Asaka, Masashi Akiyama, Takanori Domon, Wataru Nishie, Ken Natsuga, Yasuyuki Fujita, Riichiro Abe, Yoshimasa Kitagawa, Hiroshi Shimizu

    The American journal of pathology   174 ( 1 )   91 - 100   2009年1月

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    記述言語:英語   出版者・発行元:1  

    Inherited tooth enamel hypoplasia occurs due to mutations in genes that encode major enamel components. Enamel hypoplasia also has been reported in junctional epidermolysis bullosa, caused by mutations in the genes that encode type XVII collagen (COL17), a component of the epithelial-mesenchymal junction. To elucidate the pathological mechanisms of the enamel hypoplasia that arise from the deficiency of epithelial-mesenchymal junction molecules, such as COL17, we investigated tooth formation in our recently established Col17(-/-) and Col17 rescued mice. Compared with wild-type mice, the incisors of the Col17(-/-) mice exhibited reduced yellow pigmentation, diminished iron deposition, delayed calcification, and markedly irregular enamel prisms, indicating the presence of enamel hypoplasia. The molars of the Col17(-/-) mice demonstrated advanced occlusal wear. These abnormalities were corrected in the Col17 rescued humanized mice. Thus, the Col17(-/-) mice clearly reproduced the enamel hypoplasia in human patients with junctional epidermolysis bullosa. We were able to investigate tooth formation in the Col17(-/-) mice because the Col17(-/-) genotype is not lethal. Col17(-/-) mouse incisors had poorly differentiated ameloblasts that lacked enamel protein-secreting Tomes' processes and reduced mRNA expression of amelogenin, ameloblastin, and of other enamel genes. These findings indicated that COL17 regulates ameloblast differentiation and is essential for normal formation of Tomes' processes. In conclusion, COL17 deficiency disrupts the epithelial-mesenchymal interactions, leading to both defective ameloblast differentiation and enamel malformation.

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  • A novel DNA vaccine-targeting macrophage migration inhibitory factor improves the survival of mice with sepsis 査読

    S. Tohyama, S. Onodera, H. Tohyama, K. Yasuda, J. Nishihira, Y. Mizue, A. Hamasaka, R. Abe, Y. Koyama

    GENE THERAPY   15 ( 23 )   1513 - 1522   2008年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Sepsis is a common and frequently fatal condition and there is an urgent need for new therapies that will further reduce sepsis-induced mortality. Macrophage migration inhibitory (MIF) factor is important in the regulation of innate and adaptive immunity and is believed to play a key regulatory role in sepsis and autoimmune disease. As MIF deficiency or immunoneutralization protects mice or rats from fatal endotoxic shock or other inflammatory diseases, we examined whether DNA vaccination against this molecule would also be protective. DNA vaccines can stimulate both humoral and cellular immunity simultaneously and have been shown to be effective against a variety of pathogens or cytokine-driven pathologies. Mice were immunized with a MIF/tetanus toxin (TTX) DNA vaccine and sepsis was then induced by lipopolysaccharide or cecal ligation and puncture. The MIF/TTX DNA-vaccinated mice were protected from the lethal effect of sepsis compared with control-vaccinated mice in both models. Compared with the control-vaccinated mice, the MIF/TTX DNA-vaccinated mice also showed significantly lower serum tumor necrosis factor (TNF)-alpha a protein levels and reduced mRNA expression of TNF-alpha, interleukin (IL)-1 beta, IL-6, macrophage inflammatory protein-2 and Toll-like receptor-4 in the lungs. Thus, the MIF/TTX DNA vaccine may be useful for the prophylaxis of septic shock.

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  • Toxic epidermal necrolysis and Stevens-Johnson syndrome: soluble Fas ligand involvement in the pathomechanisms of these diseases. 査読 国際誌

    Riichiro Abe

    Journal of dermatological science   52 ( 3 )   151 - 9   2008年12月

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    記述言語:英語   出版者・発行元:3  

    Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are considered part of a spectrum of adverse cutaneous drug reactions showing severe and extensive skin detachment. TEN and SJS are morphologically characterized by active apoptotic keratinocyte cell death that results in the separation of the epidermis from the dermis. TEN is a life-threatening disease with a high mortality rate (20-30%). Although several therapies have been tried, there is no specific outstanding of generally accepted treatment for TEN at present. The pathogeneses of TEN and SJS have not yet been fully elucidated. We have demonstrated that high concentrations of soluble FasL (sFasL) are detected in TEN/SJS patients' serum samples and sFasL secreted by peripheral blood mononuclear cells interacts with the Fas expressed on diseased keratinocytes in TEN/SJS. Our data suggested sFasL is a prime candidate for therapeutic intervention, whereas a few recent papers have reported sFasL levels were not elevated in some TEN patients. An urgent review of the pathophysiology in TEN/SJS is needed to resolve this issue and to determine more effective treatment regimes.

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  • Depressed area on the abdomen: lipodystrophia centrifugalisabdominalis infantilis (LCAI). 査読 国際誌

    Satoru Shinkuma, Riichiro Abe, Nao Torii-Saito, Hiroshi Shimizu

    Archives of dermatology   144 ( 12 )   1651 - 1651   2008年12月

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    記述言語:英語   出版者・発行元:12  

    DOI: 10.1001/archderm.144.12.1651-c

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  • Increased soluble Fas ligand levels in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis preceding skin detachment. 査読 国際誌

    Junko Murata, Riichiro Abe, Hiroshi Shimizu

    The Journal of allergy and clinical immunology   122 ( 5 )   992 - 1000   2008年11月

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    記述言語:英語   出版者・発行元:5  

    BACKGROUND: It is difficult to distinguish the early phase of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) from other ordinary types of drug-induced skin reactions (ODSRs). Levels of several serum soluble factors, including soluble Fas ligand (sFasL), have been reported to be increased in patients with SJS/TEN; however, the marker to predict the onset of SJS/TEN before the development of skin detachment or mucosal lesions has not been identified. OBJECTIVE: We sought to determine whether sFasL might be a useful marker in the early stages of SJS/TEN. METHODS: Sera of 19 patients with SJS and 16 patients with TEN at 1 or multiple time points were obtained from Japanese multiple hospitals. The disease onset (day 1) was defined when erosion/ulceration of the mucocutaneous or ocular lesion first developed. For the investigation of soluble factors, including sFasL, TNF-alpha, IFN-gamma, IL-6, and sCD40 ligand, we used ELISAs and Cytometric Bead Arrays. RESULTS: Before disease onset (day -4 to approximately -2), 7 samples were available, and we detected the highest concentrations of sFasL in 5 (71.4%) of 7 patients. Increased sFasL levels decreased rapidly within 5 days of disease onset. In all 32 patients with ODSRs and 33 healthy control subjects, no increase of sFasL levels was detected. Other soluble factor concentrations did not show significant difference with those seen in patients with SJS/TEN before disease onset and ODSRs. CONCLUSION: The sFasL levels of sera in patients with SJS/TEN are significantly increased before development of skin detachment, mucosal lesions, or both.

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  • Acquired perforating dermatosis appearing as elastosis perforans serpiginosa and perforating folliculitis 査読

    R. Abe, S. Murase, Y. Nomura, K. Natsuga, Y. Tateishi, Y. Tomita, Y. Tsuji-Abe, T. Matsumura, H. Shimizu

    CLINICAL AND EXPERIMENTAL DERMATOLOGY   33 ( 5 )   653 - 654   2008年9月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    DOI: 10.1111/j.1365-2230.2008.02770.x

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  • Precursor B-cell lymphoblastic lymphoma presented with intraocular involvement and unusual skin manifestations. 査読 国際誌

    Satoru Shinkuma, Ken Natsuga, Masashi Akiyama, Akari Saito, Wataru Saito, Shuichi Ota, Takeshi Kondo, Riichiro Abe, Kazuo Kodama, Hiroshi Shimizu

    Annals of hematology   87 ( 8 )   677 - 9   2008年8月

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    記述言語:英語   出版者・発行元:8  

    DOI: 10.1007/s00277-008-0472-1

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  • Disseminated subcutaneous nodules alone as manifestations of Churg-Strauss syndrome. 査読 国際誌

    Riichiro Abe, Tsuyoshi Hirayama, Hiroshi Shimizu

    International journal of dermatology   47 ( 5 )   532 - 3   2008年5月

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    記述言語:英語   出版者・発行元:5  

    DOI: 10.1111/j.1365-4632.2008.03420.x

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  • 免疫グロブリン大量静注療法が著効した水疱性類天疱瘡の1例

    新熊 悟, 阿部 由紀子, 冨田 幸希, 夏賀 健, 氏家 英之, 阿部 理一郎, 秋山 真志, 清水 宏

    日本皮膚科学会雑誌   118 ( 5 )   933 - 937   2008年4月

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    記述言語:日本語   出版者・発行元:(公社)日本皮膚科学会  

    83歳女性。略全身の浮腫性紅斑と水疱、びらんを主訴に来院した。臨床、病理組織、免疫組織学的所見およびBP180ELISA値から水疱性類天疱瘡と診断した。ステロイドの全身投与(prednisolone,0.75mg/kg/日)を開始したが、内服開始後4週間の時点でも紅斑、水疱の新生を認めた。肺癌を併発しており全身状態が不良であることから、免疫抑制剤の併用や血漿交換療法はリスクが高いと考え、免疫グロブリン大量静注療法(400mg/kg/日、5日間)を施行した。投与直後より皮疹の著明な改善とBP180ELISA値の著明な低下を認め、その後ステロイドの減量を行うも皮疹の再燃は認めなかった。(著者抄録)

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  • Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type. 査読 国際誌

    Mikako Sasaki, Riichiro Abe, Yasuyuki Fujita, Satomi Ando, Daisuke Inokuma, Hiroshi Shimizu

    Journal of immunology (Baltimore, Md. : 1950)   180 ( 4 )   2581 - 7   2008年2月

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    記述言語:英語  

    Mesenchymal stem cells (MSCs) can differentiate not only into mesenchymal lineage cells but also into various other cell lineages. As MSCs can easily be isolated from bone marrow, they can be used in various tissue engineering strategies. In this study, we assessed whether MSCs can differentiate into multiple skin cell types including keratinocytes and contribute to wound repair. First, we found keratin 14-positive cells, presumed to be keratinocytes that transdifferentiated from MSCs in vitro. Next, we assessed whether MSCs can transdifferentiate into multiple skin cell types in vivo. At sites of mouse wounds that had been i.v. injected with MSCs derived from GFP transgenic mice, we detected GFP-positive cells associated with specific markers for keratinocytes, endothelial cells, and pericytes. Because MSCs are predominantly located in bone marrow, we investigated the main MSC recruitment mechanism. MSCs expressed several chemokine receptors; especially CCR7, which is a receptor of SLC/CCL21, that enhanced MSC migration. Finally, MSC-injected mice underwent rapid wound repaired. Furthermore, intradermal injection of SLC/CCL21 increased the migration of MSCs, which resulted in an even greater acceleration of wound repair. Taken together, we have demonstrated that MSCs contribute to wound repair via processes involving MSCs differentiation various cell components of the skin.

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  • Macrophage migration inhibitory factor (MIF) in bullous pemphigoid. 査読 国際誌

    Yukie Asano, Teruhiko Makino, Osamu Norisugi, Hirokazu Watanabe, Riichiro Abe, Hiroshi Shimizu, Tadamichi Shimizu

    Journal of dermatological science   49 ( 1 )   95 - 7   2008年1月

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    記述言語:英語   出版者・発行元:1  

    DOI: 10.1016/j.jdermsci.2007.09.011

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  • Interleukin-1beta and macrophage migration inhibitory factor (MIF) in dermal fibroblasts mediate UVA-induced matrix metalloproteinase-1 expression. 査読 国際誌

    Ayumi Honda, Riichiro Abe, Teruhiko Makino, Osamu Norisugi, Yasuyuki Fujita, Hirokazu Watanabe, Jun Nishihira, Yoichiro Iwakura, Sho-ichi Yamagishi, Hiroshi Shimizu, Tadamichi Shimizu

    Journal of dermatological science   49 ( 1 )   63 - 72   2008年1月

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    記述言語:英語   出版者・発行元:1  

    BACKGROUND: Exposure to solar UV radiation is the main environmental factor that causes premature aging of the skin. Matrix metalloproteinases (MMP)-1 is a member of the MMP family and degrades types I and III collagens, which are the major structural components of the dermis. OBJECTIVE: We evaluated the involvement IL-1beta and macrophage migration inhibitory factor (MIF) in MMP-1 expression under ultraviolet A (UVA) irradiation. METHODS: IL-1beta and MIF in MMP-1 expression in cultured human dermal fibroblasts and the UVA effects on MMPs production using IL-1alpha/beta-deficient mice were analyzed. Furthermore, fibroblasts derived from MIF-deficient mice were used to analyze the effect of IL-1beta-induced MMPs production. RESULTS: IL-1beta-enhanced MIF expression and induced MMP-1 in cultured human dermal fibroblasts. IL-1beta-induced MMP-1 expression is inhibited by neutralizing anti-MIF antibody. Dermal fibroblasts of IL-1alpha/beta-deficient mice produced significantly decreased levels of MMPs compared to wild-type mice after UVA irradiation. Furthermore, fibroblasts of MIF-deficient mice were much less sensitive to IL-1beta-induced MMPs production. On the contrary, IL-1beta produced significantly decreased levels of MMPs in MIF-deficient mice fibroblasts. The up-regulation of MMP-1 mRNA by IL-1beta stimulation was found to be inhibited by a p38 inhibitor and a JNK inhibitor. In contrast, the MEK inhibitor and inhibitor were found to have little effect on expression of MMP-1 mRNA. CONCLUSIONS: IL-1beta is involved in the up-regulation of UVA-induced MMP-1 in dermal fibroblasts, and IL-1beta and MIF cytokine network induce MMP-1 and contribute to the loss of interstitial collagen in skin photoaging.

    DOI: 10.1016/j.jdermsci.2007.09.007

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  • Pigment epithelium-derived factor prevents melanoma growth via angiogenesis inhibition. 査読 国際誌

    Riichiro Abe, Yasuyuki Fujita, Sho-ichi Yamagishi, Hiroshi Shimizu

    Current pharmaceutical design   14 ( 36 )   3802 - 9   2008年

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    記述言語:英語   出版者・発行元:36  

    Pigment epithelium-derived factor (PEDF) has recently been shown to be the most potent inhibitor of angiogenesis in the mammalian eye, and is involved in the pathogenesis of angiogenic eye disease such as proliferative diabetic retinopathy. However, a functional role for PEDF in tumor growth and angiogenesis remains to be determined. Melanoma is one of the most highly invasive and metastatic tumors. Malignant Melanoma is an increasingly common malignancy and also one the most invasive and metastatic tumors, and its mortality rates have been rapidly increasing above those of any other cancer in recent years. Surgical resection and systemic chemotherapy are the main therapeutic strategies for the treatment of malignant melanoma. However, these approaches are insufficiently effective and may be associated with significant adverse effects. Angiogenesis, a process by which new vascular networks are formed from pre-existing capillaries, is required for tumors to grow, invade and metastasize. Tumor vessels are genetically stable, and less likely to accumulate mutations that allow them to develop drug resistance in a rapid manner. Therefore, targeting vasculatures that support tumor growth, rather than cancer cells, is currently considered the most promising approach to malignant melanoma therapy. Now, novel anti-angiogenic agents with tolerable side effects are actually desired for the treatment of patients with malignant melanoma. In this paper, we review the current understanding of anti-angiogenic therapy for malignant melanoma, especially focusing on PEDF, which was recently identified as the most potent endogenous inhibitor of angiogenesis in the mammalian eye.

    DOI: 10.2174/138161208786898626

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  • AGE-RAGE system and carcinogenesis. 査読 国際誌

    Riichiro Abe, Sho-ichi Yamagishi

    Current pharmaceutical design   14 ( 10 )   940 - 5   2008年

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    記述言語:英語   出版者・発行元:10  

    Recent clinical studies have reported an increased risk for various types of cancers in patients with diabetes. Diabetes is characterized by increased oxidative stress conditions. Hyperglycemia induces oxidative stress generation in a variety of cells via various metabolic pathways, thus causing oxidative DNA damage, an initial step of carcinogenesis. There is accumulating evidence that advanced glycation end products (AGE), senescent macroprotein derivatives formed at an accelerated rate under normal aging process and diabetes, are involved in the development and progression of cancers. AGE stimulate oxidative stress generation through the interaction with a receptor for AGE (RAGE), while oxidative stress generation promotes the formation of AGE and increases the expression of RAGE. These findings suggest that the crosstalk between the AGE-RAGE system and oxidative stress generation may form a positive feedback loop, thus further increasing the risk for cancers in patients with diabetes. This paper reviews current knowledge about the role of AGE-RAGE system in the development of various types of cancers.

    DOI: 10.2174/138161208784139765

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  • Angiogenesis in tumor growth and metastasis. 査読 国際誌

    Riichiro Abe

    Current pharmaceutical design   14 ( 36 )   3779 - 3779   2008年

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    記述言語:英語   出版者・発行元:36  

    DOI: 10.2174/138161208786898671

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  • Clinical approaches toward tumor angiogenesis: past, present and future. 査読 国際誌

    Yasuyuki Fujita, Riichiro Abe, Hiroshi Shimizu

    Current pharmaceutical design   14 ( 36 )   3820 - 34   2008年

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    記述言語:英語   出版者・発行元:36  

    Angiogenesis is a complex process which is critical for the growth, invasion, and metastasis of tumors. In the past ten years numerous new agents have been developed as angiogenesis inhibitors. Angiogenesis inhibitors can be classified by their targeted area of the angiogenic process; (1) VEGF and its receptors VEGFR (e.g. Bevacizumab); (2) tyrosine kinases within endothelial cells (Sunitinib); (3) proliferation of endothelial cells (Endostatin); (4) MMPs (Marimastat); (5) intercellular interactions via integrins (Cilengitide) and (6) combinations of the above mechanisms (Thalidomide). Some showed anti-tumor effects with objective responses and stable disease, and some disappeared from clinical use due to unexpected side effects or insufficient efficacies. Further investigations of combined therapies including angiogenesis inhibitors will shed light on the treatment of advanced and metastasized malignancies.

    DOI: 10.2174/138161208786898680

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  • Pigment epithelium-derived factor inhibits vascular endothelial growth factor-induced vascular hyperpermeability both in vitro and in vivo 査読

    S. Yamagishi, R. Abe, Y. Jinnouchi, T. Matsui, T. Imaizumi, H. Inoue

    JOURNAL OF INTERNATIONAL MEDICAL RESEARCH   35 ( 6 )   896 - 899   2007年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:FIELD HOUSE PUBLISHING LLP  

    Administration of pigment epithelium-derived factor (PEDF) inhibits advanced glycation end products-elicited retinal vascular hyperpermeability, as well as cold injury-induced brain oedema in rats. However, the underlying molecular mechanism by which PEDF blocks the hyperpermeability in vivo is not fully understood. This study investigated whether PEDF could inhibit vascular endothelial growth factor (VEGF)-induced vascular hyperpermeability both in vitro and in vivo. The Miles assay revealed that, after intradermal injection of VEGF in nude mice, simultaneous administration of PEDF inhibited vascular hyperpermeability in a dose-dependent manner. The in vitro permeability assay also showed that PEDF blocked the VEGF-induced barrier dysfunction in endothelial cells. These results demonstrated that PEDF could inhibit the VEGF-induced vascular hyperpermeability both in vitro and in vivo, and suggest that PEGF may be suitable to be considered as a novel therapeutic agent for various vasopermeable disorders in which VEGF is involved.

    DOI: 10.1177/147323000703500619

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  • Non-Hodgkin lymphoma preceded by recalcitrant eczema. 査読 国際誌

    Ken Natsuga, Riichiro Abe, Hideyuki Ujiie, Akihiko Shibaki, Daisuke Sawamura, Mitsufumi Nishio, Katsuya Fujimoto, Takao Koike, Hiroshi Shimizu

    European journal of haematology   79 ( 4 )   369 - 70   2007年10月

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    記述言語:英語   出版者・発行元:4  

    DOI: 10.1111/j.1600-0609.2007.00897.x

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  • Unilateral periorbital oedema due to sarcoid infiltration of the eyelid: an unusual presentation of sarcoidosis with facial nerve palsy and parotid gland enlargement 査読

    M. Yaosaka, R. Abe, H. Ujiie, Y. Abe, H. Shimizu

    BRITISH JOURNAL OF DERMATOLOGY   157 ( 1 )   200 - 202   2007年7月

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    記述言語:英語   出版者・発行元:BLACKWELL PUBLISHING  

    DOI: 10.1111/j.1365-2133.2007.07939.x

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  • Angiogenesis and metastasis inhibitors for the treatment of malignant melanoma. 査読 国際誌

    Riichiro Abe, Yasuyuki Fujita, Sho-ichi Yamagishi

    Mini reviews in medicinal chemistry   7 ( 6 )   649 - 61   2007年6月

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    記述言語:英語   出版者・発行元:6  

    Malignant melanoma is one of the most highly invasive and metastatic tumors. Melanoma is an increasingly common malignancy as well, and its mortality rates have been rapidly increasing above those of any other cancer in recent years. Surgical resection and systemic chemotherapy are the main therapeutic strategies for the treatment of malignant melanoma. However, these approaches are insufficiently effective and may be associated with significant adverse effects. Angiogenesis, a process by which new vascular networks are formed from pre-existing capillaries, is required for tumors to grow, invade and metastasize. Tumor vessels are genetically stable, and less likely to accumulate mutations that allow them to develop drug resistance in a rapid manner. Therefore, targeting vasculatures that support tumor growth, rather than cancer cells, is considered the most promising approach to malignant melanoma therapy. Now, novel anti-angiogenic agents with tolerable side effects is actually desired for the treatment of patients with malignant melanoma. In this paper, we review the current understanding of anti-angiogenic therapy for malignant melanoma, especially focusing on pigment epithelium-derived factor (PEDF), which was recently identified as the most potent endogenous inhibitor of angiogenesis in the mammalian eye. We also discuss here the involvement of a receptor for advanced glycation end products (RAGE) in angiogenesis, melanoma growth and metastasis, and the therapeutic implications of the blockers of RAGE in this devastating disorder.

    DOI: 10.2174/138955707780859440

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  • Granulomatous arteritis in cutaneous lesions of Churg-Strauss syndrome. 査読 国際誌

    Ko-Ron Chen, Michiie Sakamoto, Kumiko Ikemoto, Riichiro Abe, Hiroshi Shimizu

    Journal of cutaneous pathology   34 ( 4 )   330 - 7   2007年4月

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    記述言語:英語   出版者・発行元:4  

    BACKGROUND: Although granulomatous arteritis is usually found in extracutaneous Churg-Strauss syndrome (CSS) lesions, the vasculitis in CSS cutaneous lesions typically shows small vessel vasculitis (leukocytoclastic vasculitis) without demonstrating the feature of granulomatous arteritis confirming the proper classification of CSS in the category of granulomatous vasculitis. METHODS: Four deep excisional biopsies were obtained from three untreated CSS patients who presented with livedo reticularis and subcutaneous nodules. Tissue blocks were recut and submitted for hematoxylin and eosin and elastic tissue staining to evaluate the histological features of the affected vessels. Immunostaining for histiocytes, lymphocytes, and neutrophils were performed on serial sections to confirm the cellular infiltration. RESULTS: In all specimens, subcutaneous granulomatous arteritis was observed. The unique histological feature distinct from other vasculitic disorders is characterized by marked infiltration of histiocytes and multinucleated giant cells in and around the disrupted subcutaneous arterial walls mixed with an eosinophilic infiltrate. In two specimens, granulomatous arteritis was found in the subsequent serial sections, not in the initial sections. The initial section may show extravascular granulomatous inflammation without evidence of vasculitis. CONCLUSIONS: Granulomatous arteritis as identified in the extracutaneous lesions can also be found in subcutaneous CSS lesions presenting with livedo reticularis and/or subcutaneous nodules.

    DOI: 10.1111/j.1600-0560.2006.00614.x

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  • Soluble Fas ligand: is it a critical mediator of toxic epidermal necrolysis and Stevens-Johnson syndrome? 査読 国際誌

    Junko Murata, Riichiro Abe

    The Journal of investigative dermatology   127 ( 4 )   744 - 5   2007年4月

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    記述言語:英語   出版者・発行元:4  

    Although soluble Fas ligand (sFasL) is an important candidate in toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), Stur and colleagues report that elevated sFasL has been detected in maculopapular rashes. In addition to sFasL, other factors, including predisposing genetic factors, should also be investigated to determine their precise pathogenesis in TEN and SJS.

    DOI: 10.1038/sj.jid.5700693

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  • Small-diameter porous poly (epsilon-caprolactone) films enhance adhesion and growth of human cultured epidermal keratinocyte and dermal fibroblast cells. 査読 国際誌

    James R McMillan, Masashi Akiyama, Masaru Tanaka, Sadaki Yamamoto, Maki Goto, Riichiro Abe, Daisuke Sawamura, Masatsugu Shimomura, Hiroshi Shimizu

    Tissue engineering   13 ( 4 )   789 - 98   2007年4月

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    記述言語:英語  

    Autologous keratinocyte grafts provide clinical benefit by rapidly covering wounded areas, but they are fragile. We therefore developed biocompatible hexagonal-packed porous films with uniform, circular pore sizes to support human keratinocytes and fibroblasts. Cells were cultured on these porous poly (epsilon-calprolactone) films with pore sizes ranging from novel ultra-small 3 microm to 20 microm. These were compared with flat (pore-less) films. Cell growth rates, adhesion, migration, and ultrastructural morphology were examined. Human keratinocytes and fibroblasts attached to all films. Furthermore, small-pore (3-5 microm) films showed the highest levels of cell adhesion and survival and prevented migration into the pores and opposing film surface. Keratinocyte migration over small-pore film surface was inhibited. Keratinocytes optimally attached to 3-microm-pore films due to a combination of greater pore numbers (porosity), a greater circumference of the pore edge per unit surface area, and greater frequency of flat surface areas for attachment, allowing better cell-substrate and cell-cell attachment and growth. The 3-microm pore size allowed cell-cell communication, together with diffusion of soluble nutrients and factors from the culture medium or wound substrate. These characteristics are considered important in developing grafts for use in the treatment of human skin wounds.

    DOI: 10.1089/ten.2006.0321

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  • CTACK/CCL27 accelerates skin regeneration via accumulation of bone marrow-derived keratinocytes. 査読 国際誌

    Daisuke Inokuma, Riichiro Abe, Yasuyuki Fujita, Mikako Sasaki, Akihiko Shibaki, Hideki Nakamura, James R McMillan, Tadamichi Shimizu, Hiroshi Shimizu

    Stem cells (Dayton, Ohio)   24 ( 12 )   2810 - 6   2006年12月

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    記述言語:英語   出版者・発行元:12  

    Recent studies have suggested that bone marrow (BM) cells transdifferentiate to regenerate a variety of cellular lineages. Due to the relatively small population of BM-derived cells in each organ, it is still controversial whether these BM-derived cells are really present in sufficient numbers for effective function. Conversely, it is speculated that chemokine/chemokine receptor interactions mediate this migration of the tissue-specific precursor cells from BM into the target tissue. Here, we show that cutaneous T-cell attracting chemokine (CTACK)/CCL27 is the major regulator involved in the migration of keratinocyte precursor cells from BM into skin. By screening various chemokine expression patterns, we demonstrated that CTACK is constitutively expressed in normal skin and upregulated in wounds and that approximately 20% of CD34(+) BM cells expressed CCR10, the ligand for CTACK. Intradermal injection of CTACK/CCL27 into the periphery of skin wounds significantly enhanced BM-derived keratinocyte (BMDK) migration, and CTACK/CCL27 neutralizing antibody inhibited this BMDK migration. Furthermore, increased BMDK migration caused by CTACK/CCL27 significantly accelerated the wound-healing process without any influence over either angiogenesis or keratinocyte proliferation. These results provide direct evidence that recruitment of BM keratinocyte precursor cells to the skin is regulated by specific chemokine/chemokine receptor interactions, making possible the development of new regenerative therapeutic strategies.

    DOI: 10.1634/stemcells.2006-0264

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  • Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes. 査読 国際誌

    An Chi, Julio C Valencia, Zhang-Zhi Hu, Hidenori Watabe, Hiroshi Yamaguchi, Nancy J Mangini, Hongzhan Huang, Victor A Canfield, Keith C Cheng, Feng Yang, Riichiro Abe, Shoichi Yamagishi, Jeffrey Shabanowitz, Vincent J Hearing, Cathy Wu, Ettore Appella, Donald F Hunt

    Journal of proteome research   5 ( 11 )   3135 - 44   2006年11月

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    記述言語:英語   出版者・発行元:11  

    Melanin, which is responsible for virtually all visible skin, hair, and eye pigmentation in humans, is synthesized, deposited, and distributed in subcellular organelles termed melanosomes. A comprehensive determination of the protein composition of this organelle has been obstructed by the melanin present. Here, we report a novel method of removing melanin that includes in-solution digestion and immobilized metal affinity chromatography (IMAC). Together with in-gel digestion, this method has allowed us to characterize melanosome proteomes at various developmental stages by tandem mass spectrometry. Comparative profiling and functional characterization of the melanosome proteomes identified approximately 1500 proteins in melanosomes of all stages, with approximately 600 in any given stage. These proteins include 16 homologous to mouse coat color genes and many associated with human pigmentary diseases. Approximately 100 proteins shared by melanosomes from pigmented and nonpigmented melanocytes define the essential melanosome proteome. Proteins validated by confirming their intracellular localization include PEDF (pigment-epithelium derived factor) and SLC24A5 (sodium/potassium/calcium exchanger 5, NCKX5). The sharing of proteins between melanosomes and other lysosome-related organelles suggests a common evolutionary origin. This work represents a model for the study of the biogenesis of lysosome-related organelles.

    DOI: 10.1021/pr060363j

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  • Chain saw blade granuloma: reaction to a deeply embedded metal fragment. 査読 国際誌

    Rinko Osawa, Riichiro Abe, Daisuke Inokuma, Koichi Yokota, Hiroko Ito, Motoyuki Nabeshima, Hiroshi Shimizu

    Archives of dermatology   142 ( 8 )   1079 - 80   2006年8月

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    記述言語:英語   出版者・発行元:8  

    DOI: 10.1001/archderm.142.8.1079

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  • Increase in macrophage migration inhibitory factor levels in lacrimal fluid of patients with severe atopic dermatitis. 査読 国際誌

    Nobuyoshi Kitaichi, Tadamichi Shimizu, Ayumi Honda, Riichiro Abe, Kazuhiro Ohgami, Kenji Shiratori, Hiroshi Shimizu, Shigeaki Ohno

    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie   244 ( 7 )   825 - 8   2006年7月

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    記述言語:英語   出版者・発行元:7  

    BACKGROUND AND AIMS OF THE STUDY: Atopic dermatitis is a chronic inflammatory skin disorder that often involves some ophthalmic features. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is associated with the generation of cell-mediated immune responses. Although serum MIF levels may be elevated in severe atopic dermatitis, the quantity of MIF in regional ocular fluid remains unknown. We measured MIF levels in tears (lacrimal fluid) of patients with atopic dermatitis. PATIENTS AND METHODS: Tear samples were collected from 16 patients with atopic dermatitis, 10 patients with allergic conjunctivitis, and 15 healthy control subjects. The clinical severity of atopic dermatitis was evaluated according to the Scoring Atopic Dermatitis (SCORAD) index. The index was calculated by summing the following scores: extent criteria, intensity criteria, and subjective symptoms. Macrophage migration inhibitory factor levels were determined by a human MIF enzyme-linked immunosorbent assay. All comparisons were two-tailed, and P values <0.01 were considered as statistically significant. RESULTS: The mean MIF concentration in lacrimal fluid collected from healthy control subjects was 0.69+/-0.2 ng/ml. The mean tear MIF levels were 17.87+/-6.3 ng/ml in moderate-to-severe atopic dermatitis (SCORAD> or =15, P=0.002), 0.93+/-0.08 ng/ml in mild atopic dermatitis (SCORAD<15), and 2.76+/-0.86 ng/ml in allergic conjunctivitis (P=0.008). CONCLUSIONS: A proinflammatory cytokine MIF level was elevated in tears as well as serum in cases of severe atopic dermatitis. These results suggest that MIF may play an important role in the induction or enhancement of ophthalmic features related to severe atopic dermatitis.

    DOI: 10.1007/s00417-005-0168-3

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  • Mycosis fungoides bullosa. 査読 国際誌

    Ken Natsuga, Tadamichi Shimizu, Riichiro Abe, Kazuo Kodama, Hiroshi Shimizu

    Archives of dermatology   142 ( 6 )   793 - 5   2006年6月

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    記述言語:英語   出版者・発行元:6  

    DOI: 10.1001/archderm.142.6.793

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  • Presence of circulating CCR10+ T cells and elevated serum CTACK/CCL27 in the early stage of mycosis fungoides. 査読 国際誌

    Yasuyuki Fujita, Riichiro Abe, Mikako Sasaki, Ayumi Honda, Megumi Furuichi, Yukie Asano, Osamu Norisugi, Tadamichi Shimizu, Hiroshi Shimizu

    Clinical cancer research : an official journal of the American Association for Cancer Research   12 ( 9 )   2670 - 5   2006年5月

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    記述言語:英語   出版者・発行元:9  

    PURPOSE: Mycosis fungoides (MF), a common type of cutaneous T cell lymphoma with an indolent clinical course, has the characteristic that malignant T cell clones are recruited into the skin from the early disease stages. The mechanisms of recruitment have been suggested from our knowledge of various chemokine-chemokine receptor interactions. Recently, CCR10 and CTACK/CCL27 were proposed to play a role in the recruitment of other types of cutaneous T cell lymphoma. We examined the expression of CCR10 in peripheral blood and serum CTACK/CCL27 levels in patients with MF. EXPERIMENTAL DESIGN: Eighteen patients with MF, six patients with atopic dermatitis, and nine healthy volunteers were enrolled in our investigation. We investigated the differences in CCR10+ CD4+ expression in peripheral blood mononuclear cells by flow cytometry. Serum CTACK/CCL27 levels were determined using a CTACK/CCL27 ELISA assay kit. RESULTS: The number of circulating CCR10+ CD4+ cells was significantly higher in MF peripheral blood than in controls, even during the early stages. In lesional MF skin, infiltrating tumor cells also showed extensive expression of CCR10. The serum level of CTACK/CCL27 was higher in patients with MF than normal controls, but no statistical difference was found compared with atopic dermatitis patients. CONCLUSIONS: CCR10-CTACK/CCL27 interactions between circulating T cells and keratinocytes would seem to play an important role in the pathophysiology of MF from the early disease stages.

    DOI: 10.1158/1078-0432.CCR-05-1513

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  • Peginterferon alfa-2b for mycosis fungoides. 査読 国際誌

    Teruki Yanagi, Tadamichi Shimizu, Hideyuki Ujiie, Miki Ito, Riichiro Abe, Yukiko Tsuji-Abe, Shuhei Hige, Hiroshi Shimizu

    Archives of dermatology   142 ( 5 )   649 - 51   2006年5月

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    記述言語:英語   出版者・発行元:5  

    DOI: 10.1001/archderm.142.5.649

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  • Coexistence of a systemic lupus erythematosus and porphyria cutanea tarda: case successfully improved by avoidance of sun exposure. 査読 国際誌

    Junko Murata, Tadamichi Shimizu, Yasuyuki Tateishi, Riichiro Abe, Hiroshi Shimizu

    International journal of dermatology   45 ( 4 )   435 - 7   2006年4月

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    記述言語:英語   出版者・発行元:4  

    DOI: 10.1111/j.1365-4632.2006.02461.x

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  • Two cases of folliculosebaceous cystic hamartoma 査読

    S Tanimura, K Arita, F Iwao, M Kasai, Y Fujita, H Kawasaki, R Abe, D Sawamura, T Kimura, H Shimizu

    CLINICAL AND EXPERIMENTAL DERMATOLOGY   31 ( 1 )   68 - 70   2006年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING  

    Folliculosebaceous cystic hamartoma (FSCH) is a rare cutaneous hamartoma composed of dilated folliculosebaceous units associated with mesenchymal elements. Two cases of FSCH with typical histopathological features are reported. Patient 1 was a 60-year-old man presented with a normal skin-coloured asymptomatic nodule on his scalp. Patient 2 was a 70-year-old man with an asymptomatic nodule on his right auricle that had persisted for the previous 15 years. In all, 34 cases of FSCH have been reported in the English literature. Clinically, the lesions are asymptomatic, usually rubbery to firm in consistency, and usually occur on or above the neck (&gt; 90%). Most lesions do not exceed 25 mm in diameter (&gt; 90%). Histopathologically, FSCH shares several similar features to sebaceous trichofolliculoma, but it is usually possible to differentiate these two tumours.

    DOI: 10.1111/j.1365-2230.2005.01974.x

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  • Tissue regeneration using macrophage migration inhibitory factor-impregnated gelatin microbeads in cutaneous wounds. 査読 国際誌

    Yunan Zhao, Tadamichi Shimizu, Jun Nishihira, Yoshikazu Koyama, Toshihiro Kushibiki, Ayumi Honda, Hirokazu Watanabe, Riichiro Abe, Yasuhiko Tabata, Hiroshi Shimizu

    The American journal of pathology   167 ( 6 )   1519 - 29   2005年12月

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    記述言語:英語   出版者・発行元:6  

    Migration inhibitory factor (MIF) responds to tissue damage and regulates inflammatory and immunological processes. To elucidate the function of MIF in cutaneous wound healing, we analyzed MIF knockout (KO) mice. After the excision of wounds from the dorsal skin of MIF KO and wild-type (WT) mice, healing was significantly delayed in MIF KO mice compared to WT mice. Lipopolysaccharide treatment significantly increased [(3)H]thymidine uptake in WT mouse fibroblasts compared to MIF KO mouse fibroblasts. Furthermore, there was a significant reduction in fibroblast and keratinocyte migration observed in MIF KO mice after 1-oleoyl-2-lysophosphatidic acid treatment. We subsequently examined whether MIF-impregnated gelatin slow-release microbeads could accelerate skin wound healing. Injection of more than 1.5 microg/500 microl of MIF-impregnated gelatin microbeads around a wound edge accelerated wound healing compared to a single MIF injection without the use of microbeads. MIF-impregnated gelatin microbeads also accelerated skin wound healing in C57BL/6 mice and diabetic db/db mice. Furthermore, incorporating MIF-impregnated gelatin microbeads into an artificial dermis implanted into MIF KO mice accelerated procollagen production and capillary formation. These findings suggest that MIF is crucial in accelerating cutaneous wound healing and that MIF-impregnated gelatin microbeads represent a promising treatment to facilitate skin wound healing.

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  • Expression of macrophage migration inhibitory factor in rat skin during embryonic development. 査読 国際誌

    Tadamichi Shimizu, Akihiko Ogata, Ayumi Honda, Jun Nishihira, Hirokazu Watanabe, Riichiro Abe, Yunan Zhao, Hiroshi Shimizu

    Experimental dermatology   14 ( 11 )   819 - 23   2005年11月

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    記述言語:英語   出版者・発行元:11  

    We have previously shown that human epidermal keratinocytes express macrophage migration inhibitory factor (MIF) mRNA, and immunohistochemical studies showed that MIF is expressed in human epidermis. To explore the possible pathophysiological roles of MIF in skin during rat fetal development, we examined the expression patterns of MIF during rat epidermal development using Northern blot analysis and in situ hybridization. Expression of MIF mRNA was first detected by in situ hybridization in the developing epidermis and hair germ cells from embryonic day (ED) 16. From ED 19, moderate levels of MIF expression were detected in the epidermis and epithelial sheath cells of growing hair follicles. In postnatal rat skin, higher MIF expression was detected in the epidermis and hair follicles on postnatal day 3. These observations were also confirmed by Northern blot analysis. Immunohistochemical analysis with an anti-MIF antibody showed a similar distribution to that of the mRNA. Our results suggest that MIF is associated with epidermal and hair follicle development.

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  • Clinical images: Drumstick-like fingers indicating psoriatic onycho-pachydermo periostitis. 査読 国際誌

    Akiko Tsubota, Riichiro Abe, Akihiko Shibaki

    Arthritis and rheumatism   52 ( 9 )   2954 - 2954   2005年9月

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    記述言語:英語   出版者・発行元:9  

    DOI: 10.1002/art.21370

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  • Multicentric reticulohistiocytosis associated with rheumatoid arthritis. 査読 国際誌

    Daichi Hoshina, Tadamichi Shimizu, Riichiro Abe, Junko Murata, Koichi Tanaka, Hiroshi Shimizu

    Rheumatology international   25 ( 7 )   553 - 4   2005年9月

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    記述言語:英語   出版者・発行元:7  

    Due to the fact that both multicentric reticulohistiocytosis (MRH) and rheumatoid arthritis (RA) are destructive arthritic and skin disorders, it is often difficult to differentiate one from the other. Here, we report the case of a 67-year-old Japanese woman who had been diagnosed as suffering from RA 20 years ago, and who developed MRH. MRH may be misdiagnosed as RA, but evaluation of the time course of specific symptoms can greatly help in the correct diagnosis.

    DOI: 10.1007/s00296-004-0559-5

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  • Zinc dental fillings and palmoplantar pustulosis 査読

    T Yanagi, T Shimizu, R Abe, H Shimizu

    LANCET   366 ( 9490 )   1050 - 1050   2005年9月

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    記述言語:英語   出版者・発行元:LANCET LTD  

    DOI: 10.1016/S0140-6736(05)67384-9

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  • Lupus erythematosus panniculitis (lupus profundus): clinical, histopathological, and molecular analysis of nine cases. 査読 国際誌

    Cesare Massone, Kazuo Kodama, Wolfgang Salmhofer, Riichiro Abe, Hiroshi Shimizu, Aurora Parodi, Helmut Kerl, Lorenzo Cerroni

    Journal of cutaneous pathology   32 ( 6 )   396 - 404   2005年7月

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    記述言語:英語   出版者・発行元:6  

    BACKGROUND: The diagnosis of lupus erythematosus panniculitis (LEP) may be very difficult in cases in which involvement of the subcutaneous fat is the only manifestation of the disease. The main differential diagnosis is subcutaneous panniculitis-like T-cell lymphoma (SPTCL). METHODS: We performed a retrospective study reviewing the histopathologic features of 11 biopsy specimens from nine patients with LEP (M : F = 2 : 7; median age: 48 years; range: 20-71 years). RESULTS: Histopathologically, all biopsies revealed a lobular panniculitis, with concomitant septal involvement in 82% of them. Dermal changes included the presence of superficial and deep infiltrates (82%) and mucin deposition (73%). The majority of cases (73%) presented also some form of epidermal involvement. The subcutaneous infiltrate was composed of lymphocytes in all cases, admixed with plasma cells in 91% of cases. Lymphoid follicles with reactive germinal centers were detected in 45% of cases. Immunohistochemistry showed a predominance of alpha/beta-T-helper and cytotoxic lymphocytes in 80% of cases admixed with B lymphocytes. The polymerase chain reaction analysis of the T-cell receptor (TCR)-gamma gene showed a polyclonal smear in all cases. CONCLUSIONS: Our study shows that the most useful histopathologic criteria for distinguishing LEP from SPTCL are the presence of involvement of the epidermis, lymphoid follicles with reactive germinal centers, mixed cell infiltrate with prominent plasma cells, clusters of B lymphocytes, and polyclonal TCR-gamma gene rearrangement.

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  • Promoter region polymorphism of macrophage migration inhibitory factor is strong risk factor for young onset of extensive alopecia areata 査読

    T Shimizu, N Hizawa, A Honda, Y Zhao, R Abe, H Watanabe, J Nishihira, M Nishimura, H Shimizu

    GENES AND IMMUNITY   6 ( 4 )   285 - 289   2005年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    We have demonstrated that serum macrophage migration inhibitory factor (MIF) was significantly elevated in patients with extensive alopecia areata ( AA). Recently, functional polymorphisms have been identified in the MIF promoter region. To address the functional and prognostic relevance of the - 173G/C and - 794[CATT](5-8) repeat polymorphisms in MIF genes in patients with extensive AA, 113 patients with extensive AA and 194 healthy controls were genotyped. We found that MIF - 173* C was a risk factor for early onset (&lt;20 years) of extensive AA ( odds ratio for GC heterozygotes with - 173G/C was 4.88 (95% CI, 2.04 - 11.8), P = 0.00038; odds ratio for CC homozygotes with - 173G/C was 10.42 ( 95% CI, 2.56 - 43.5), P = 0.0011). We found no statistically significant differences in the genotype frequencies of the - 794[ CATT] 5 - 8 repeat polymorphism and extensive AA. These results suggest that polymorphisms within the MIF - 173* C allele confer an increased risk of susceptibility to the extensive forms of AA, especially with an early onset of disease. MIF is therefore suggested to be closely implicated in the pathogenesis of the more extensive forms of AA.

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  • Direct injection of plasmid DNA into the skin induces dermatitis by activation of monocytes through toll-like receptor 9 査読

    D Sawamura, R Abe, M Goto, M Akiyama, H Hemmi, S Akira, H Shimizu

    JOURNAL OF GENE MEDICINE   7 ( 5 )   664 - 671   2005年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOHN WILEY & SONS LTD  

    Background Direct injection of naked DNA into skin can be efficiently used to transfer genes into keratinocytes in vivo. However, bacterial DNA is known to be a potent stimulus for vertebrate immune cells and immune systems. Towards the clinical use of this method, this study examined whether the application of plasmid DNA by direct injection induces any adverse skin effects.
    Methods Several plasmid preparations were prepared and directly injected into rat and human skin. Migration, IL-6 production, and reactive oxygen production assays were performed to determine the type of the primary cells responsible for the reaction. Involvement of toll-like receptor (TLR) 9 was examined by experiments using TLR9-knockout mice.
    Results Injection of several plasmid preparations into rat and human skin resulted in an inflammatory reaction at the treated site. Contamination by endotoxin in the plasmid preparation was shown to worsen this skin inflammation reaction. Immunohistochemical analysis showed that the infiltrating cells in the skin lesions were predominantly monocytes and neutrophils. Further experiments examining migration, IL-6 production, and reactive oxygen production indicated that the primary responsible cells were monocytes rather than neutrophils. Since it was recently shown that cytosine-guanosine dinucleotide (CpG) motif is critical for immune reaction induction in bacterial DNA and cellular responses were mediated by TLR9, we injected plasmids into the ear skin of TLR9-knockout mice. A decrease in ear swelling was noted in the knockout mice, compared to controls, suggesting that plasmid-DNA-induced dermatitis was mediated mostly by TLR9.
    Conclusions This study demonstrates that injection of plasmid DNA induces skin inflammation initiated by monocyte activation via TRL9. We should therefore attempt to counteract this dermatitis during the clinical use of the naked DNA injection method in skin. Copyright (c) 2005 John Wiley & Sons, Ltd.

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  • MIF浸透ゼラチンビーズを用いた皮膚創傷の治療への応用

    趙 宇楠, 清水 忠道, 西平 順, 本田 歩, 渡辺 宏数, 阿部 理一郎, 田畑 泰彦, 櫛引 俊宏, 清水 宏

    日本研究皮膚科学会年次学術大会・総会プログラム   30回   90 - 90   2005年4月

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    記述言語:日本語   出版者・発行元:(一社)日本研究皮膚科学会  

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  • Plasma exchange; a promising treatment for toxic epidermal necrolysis with AIDS. 査読 国際誌

    Toshifumi Nomura, Riichiro Abe, Katsuya Fujimoto, Tomoyuki Endo, Hiroshi Shimizu, Takao Koike

    AIDS (London, England)   18 ( 18 )   2446 - 8   2004年12月

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    記述言語:英語  

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  • Minodronate, a newly developed nitrogen-containing bisphosphonate, suppresses melanoma growth and improves survival in nude mice by blocking vascular endothelial growth factor signaling. 査読 国際誌

    Sho-ichi Yamagishi, Riichiro Abe, Yosuke Inagaki, Kazuo Nakamura, Hiroshi Sugawara, Daisuke Inokuma, Hideki Nakamura, Tadamichi Shimizu, Masayoshi Takeuchi, Akihiko Yoshimura, Richard Bucala, Hiroshi Shimizu, Tsutomu Imaizumi

    The American journal of pathology   165 ( 6 )   1865 - 74   2004年12月

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    記述言語:英語  

    Angiogenesis, a process by which new vascular networks are formed from pre-existing capillaries, is required for tumors to grow, invade, and metastasize. Vascular endothelial growth factor (VEGF), a specific mitogen to endothelial cells, is a crucial factor for tumor angiogenesis. In this study, we investigated whether minodronate, a newly developed nitrogen-containing bisphosphonate, could inhibit melanoma growth and improve survival in nude mice by suppressing the VEGF signaling. We found here that minodronate inhibited melanoma growth and improved survival in nude mice by suppressing the tumor-associated angiogenesis and macrophage infiltration. Minodronate completely inhibited the VEGF-induced increase in DNA synthesis and tube formation in endothelial cells by suppressing NADPH oxidase-mediated reactive oxygen species generation and Ras activation. Furthermore, minodronate inhibited the VEGF-induced expression of intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 in endothelial cells. Minodronate decreased DNA synthesis and increased apoptotic cell death of cultured melanoma cells as well. Our present study suggests that minodronate might suppress melanoma growth and improve survival in nude mice by two independent mechanisms; one is by blocking the VEGF signaling in endothelial cells, and the other is by inducing apoptotic cell death of melanoma. The present study provides a novel potential therapeutic strategy for the treatment of melanoma.

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  • Impregnated gelatin beads containing MIF accelerates cutaneous wound healing. 査読

    Zhao, Y, Shimizu, T, Nishihira, J, Honda, A, Watanabe, H, Abe, R, Tabata, Y, Kushibiki, T, Nakayama, T, Taniguchi, M, Shimizu, H

    8th China-Japan Joint Meeting of Dermatology(2004.11.11-12. Beijing)   2004年11月

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  • Pigment epithelium-derived factor inhibits TNF-alpha-induced interleukin-6 expression in endothelial cells by suppressing NADPH oxidase-mediated reactive oxygen species generation. 査読 国際誌

    Sho-Ichi Yamagishi, Yosuke Inagaki, Kazuo Nakamura, Riichiro Abe, Tadamichi Shimizu, Akihiko Yoshimura, Tsutomu Imaizumi

    Journal of molecular and cellular cardiology   37 ( 2 )   497 - 506   2004年8月

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    記述言語:英語   出版者・発行元:2  

    Pigment epithelium-derived factor (PEDF) has recently been shown to be involved in the pathogenesis of proliferative diabetic retinopathy. Atherosclerosis is an inflammatory-fibroproliferative disease as well. Oxidative stress plays a major role in retinopathy and atherosclerosis. Accordingly, we investigated effects of PEDF on reactive oxygen species (ROS) generation, NF-kappaB activation and interleukin (IL)-6 expression in TNF-alpha-exposed HUVEC. TNF-alpha significantly increased intracellular ROS generation, which was completely blocked by PEDF or diphenylene iodonium, an inhibitor of NADPH oxidase. Further, PEDF completely prevented the TNF-alpha-induced increase in NADPH oxidase activity. PEDF or an antioxidant, N-acetylcysteine, significantly inhibited the TNF-alpha-induced NF-kappaB activation. PEDF inhibited TNF-alpha-induced expression of IL-6 at both mRNA and protein levels. Moreover, TNF-alpha downregulated PEDF mRNA levels. Ligand blot analysis revealed that HUVEC possessed a membrane protein with binding affinity for PEDF. The results demonstrated that PEDF inhibited TNF-alpha-induced NF-kappaB activation and subsequent IL-6 overexpression in HUVEC by suppressing NADPH oxidase-mediated ROS generation. Our present study suggests that PEDF may play an important role in the development and progression of atherosclerosis.

    DOI: 10.1016/j.yjmcc.2004.04.007

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  • Induction of macrophage migration inhibitory factor precedes the onset of acute tonsillitis. 査読 国際誌

    Tadamichi Shimizu, Hironori Niizeki, Osamu Takeuchi, Yuichiro Yamasaki, Nobuko Inamoto, Yukihiro Kusunoki, Kunihiko Kobayashi, Riichiro Abe, Hiroshi Shimizu, Takeji Nishikawa, Kazuhiro Hashiguchi, Jun Nishihira

    Mediators of inflammation   13 ( 4 )   293 - 5   2004年8月

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    記述言語:英語   出版者・発行元:4  

    We investigated the serum macrophage migration inhibitory factor (MIF) levels of palmoplantar pustulosis patients, before and after the tonsillar provocation test. Higher serum MIF levels of palmoplantar pustulosis patients were decreased after the tonsillar provocation test (n=29). To confirm these phenomena, two patients with acute tonsillitis had their changes in body temperature, C-reactive protein (CRP) and serum MIF levels examined during the course of their illness. Surprisingly, increased MIF preceded fever and CRP elevation, and MIF subsequently decreased at the onset of fever and CRP elevation. Since MIF is an initiator of other proinflammatory cytokines, we suggest that the induction of MIF may precede other inflammatory conditions.

    DOI: 10.1080/09629350400003175

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  • Macrophage migration inhibitory factor is induced by thrombin and factor Xa in endothelial cells. 査読 国際誌

    Tadamichi Shimizu, Jun Nishihira, Hirokazu Watanabe, Riichiro Abe, Ayumi Honda, Teruo Ishibashi, Hiroshi Shimizu

    The Journal of biological chemistry   279 ( 14 )   13729 - 37   2004年4月

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    記述言語:英語   出版者・発行元:14  

    Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, has been shown to play a role in wound-healing processes. In this study, we investigated whether protease-activated receptor (PAR)-1 and PAR-2 mediated MIF expression in human endothelial cells. Thrombin, factor Xa (FXa), and trypsin induced MIF expression in human dermal microvascular endothelial cells and human umbilical vein endothelial cells, but other proteases, including kallikrein and urokinase, failed to do so. Thrombin-induced MIF mRNA expression was significantly reduced by the thrombin-specific inhibitor hirudin. Thrombin receptor activation peptide-6, a synthetic PAR-1 peptide, induced MIF mRNA expression, suggesting that PAR-1 mediates MIF expression in response to thrombin. The effects of FXa were blocked by antithrombin III, but not by hirudin, indicating that FXa might enhance MIF production directly rather than via thrombin stimulation. The synthetic PAR-2 peptide SLIGRL-NH(2) induced MIF mRNA expression, showing that PAR-2 mediated MIF expression in response to FXa. Concerning the signal transduction, a mitogen-activated protein kinase kinase inhibitor (PD98089) and a nuclear factor (NF)-kappaB inhibitor (SN50) suppressed the up-regulation of MIF mRNA in response to thrombin, FXa, and PAR-2 agonist stimulation, whereas a p38 inhibitor (SB203580) had little effect. These facts indicate that up-regulation of MIF by thrombin or FXa is regulated by p44/p42 mitogen-activated protein kinase-dependent pathways and NF-kappaB-dependent pathways. Moreover, we found that PAR-1 and PAR-2 mRNA expression in endothelial cells was enhanced by MIF. Furthermore, we examined the inflammatory response induced by PAR-1 and PAR-2 agonists injected into the mouse footpad. As shown by footpad thickness, an indicator of inflammation, MIF-deficient mice (C57BL/6) were much less sensitive to either PAR-1 or PAR-2 agonists than wild-type mice. Taken together, these results suggest that MIF contributes to the inflammatory phase of the wound healing process in concert with thrombin and FXa via PAR-1 and PAR-2.

    DOI: 10.1074/jbc.M400150200

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  • Overexpression of pigment epithelium-derived factor decreases angiogenesis and inhibits the growth of human malignant melanoma cells in vivo. 査読 国際誌

    Riichiro Abe, Tadamichi Shimizu, Sho-Ichi Yamagishi, Akihiko Shibaki, Shinjiro Amano, Yosuke Inagaki, Hirokazu Watanabe, Hiroshi Sugawara, Hideki Nakamura, Masayoshi Takeuchi, Tsutomu Imaizumi, Hiroshi Shimizu

    The American journal of pathology   164 ( 4 )   1225 - 32   2004年4月

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    記述言語:英語  

    Pigment epithelium-derived factor (PEDF) has recently been shown to be the most potent inhibitor of angiogenesis in the mammalian eye, and is involved in the pathogenesis of angiogenic eye disease such as proliferative diabetic retinopathy. However, a functional role for PEDF in tumor growth and angiogenesis remains to be determined. In this study, we have investigated both the in vitro and in vivo growth characteristics of human malignant melanoma G361 cell lines, stably transfected to overexpress human PEDF. Expression levels of PEDF proteins in melanoma cell lines G361 and A375 were comparable with that of human cultured melanocytes, whereas vascular endothelial growth factor levels in two tumor cell lines were much stronger than that in normal melanocytes. Overexpression of PEDF was found to significantly inhibit tumor growth and vessel formation in G361 nude mice xenografts. Furthermore, in vitro proliferation rates of G361 cells were decreased in PEDF-transfected cells. PEDF proteins showed dose-dependent induced growth retardation and apoptotic cell death in nontransfected G361 cells, which were completely prevented by treatment with antibodies against the Fas ligand. Our present study highlights two beneficial effects of PEDF treatment on melanoma growth and expansion; one is the suppression of tumor angiogenesis, and the other is induction of Fas ligand-dependent apoptosis in tumor cells. PEDF therefore might be a promising novel therapeutic agent for treatment of patients with melanoma.

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  • Expression of c-maf and mafB genes in the skin during rat embryonic development. 査読 国際誌

    Akihiko Ogata, Tadamichi Shimizu, Riichiro Abe, Hiroshi Shimizu, Masaharu Sakai

    Acta histochemica   106 ( 1 )   65 - 7   2004年2月

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    記述言語:英語   出版者・発行元:1  

    The maf oncogene (v-maf) was initially identified in an avian oncogenic retrovirus, AS42, which induces musculoaponeurotic fibrosarcoma in vivo and transforms chicken embryo fibroblasts in vitro. Genes of the maf family have important roles in embryonic development and cellular differentiation. Both genes are expressed in a wide variety of tissues including spleen, kidney, lens and liver. The present study was performed to analyze expression of c-maf-1 and mafB genes in skin of embryonic stages from 15 days onwards using in situ hybridization. Expression of c-maf mRNA was first detected on embryonic day (ED) 16 in the nuclei of cells in the basal layer in developing epidermis. On ED 19, high expression was detected in the nucleus of basal keratinocytes and developing hair germs. On postnatal day (PD) 3, expression of c-maf had disappeared in epidermis and hair follicles. MafB showed similar expression patterns as c-maf. Our findings indicate that c-maf and mafB are involved in embryonic development of epidermis and hair follicles.

    DOI: 10.1016/j.acthis.2003.10.001

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  • Regulation of human melanoma growth and metastasis by AGE-AGE receptor interactions. 査読 国際誌

    Riichiro Abe, Tadamichi Shimizu, Hiroshi Sugawara, Hirokazu Watanabe, Hideki Nakamura, Hiroshi Choei, Nobuyuki Sasaki, Sho-ichi Yamagishi, Masayoshi Takeuchi, Hiroshi Shimizu

    The Journal of investigative dermatology   122 ( 2 )   461 - 7   2004年2月

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    記述言語:英語   出版者・発行元:2  

    Advanced glycation end products (AGE), nonenzymatically glycated protein derivatives, have been implicated in the development and progression of diabetic angiopathies, including skin dermopathy. Nevertheless, the involvement of AGE in the development and progression of melanoma has not been fully elucidated. In this study we investigated the expression levels of their receptor for AGE (RAGE) in human melanoma and subsequently studied the effects of AGE on melanoma growth and migration. First, RAGE was detected in the cytoplasm of human melanoma cells (G361 and A375). Among the different types of AGE, glyceraldehyde- and glycolaldehyde-derived AGE significantly stimulated the growth and migration of human melanoma cells. Furthermore, tumor formation of melanoma cell xenografts in athymic mice was prevented by treatment with anti-RAGE neutralizing antibodies. In tumor-bearing mice, survival rates were prolonged, and spontaneous pulmonary metastases were inhibited by treatment using anti-RAGE neutralizing antibodies. In addition, all AGE were present in beds of human melanoma tumor, whereas they were barely detected in normal skin. These results suggest that AGE might be involved in the growth and invasion of melanoma through interactions with RAGE and represent promising candidates for assessing the future therapeutic potential of this therapy in treating patients with melanoma.

    DOI: 10.1046/j.0022-202X.2004.22218.x

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  • Ultraviolet A-induced production of matrix metalloproteinase-1 is mediated by macrophage migration inhibitory factor (MIF) in human dermal fibroblasts. 査読 国際誌

    Hirokazu Watanabe, Tadamichi Shimizu, Jun Nishihira, Riichiro Abe, Toshinori Nakayama, Masaru Taniguchi, Hisataka Sabe, Teruo Ishibashi, Hiroshi Shimizu

    The Journal of biological chemistry   279 ( 3 )   1676 - 83   2004年1月

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    記述言語:英語   出版者・発行元:3  

    Matrix metalloproteinases (MMPs) are thought to be responsible for dermal photoaging in human skin. In the present study, we evaluated the involvement of macrophage migration inhibitory factor (MIF) in MMP-1 expression under ultraviolet A (UVA) irradiation in cultured human dermal fibroblasts. UVA (20 J/cm(2)) up-regulates MIF production, and UVA-induced MMP-1 mRNA production is inhibited by an anti-MIF antibody. MIF (100 ng/ml) was shown to induce MMP-1 in cultured human dermal fibroblasts. We found that MIF (100 ng/ml) enhanced MMP-1 activity in cultured fibroblasts assessed by zymography. Moreover, we observed that fibroblasts obtained from MIF-deficient mice were much less sensitive to UVA regarding MMP-13 expression than those from wild-type BALB/c mice. Furthermore, after UVA irradiation (10 J/cm(2)), dermal fibroblasts of MIF-deficient mice produced significantly decreased levels of MMP-13 compared with fibroblasts of wild-type mice. Next we investigated the signal transduction pathway of MIF. The up-regulation of MMP-1 mRNA by MIF stimulation was found to be inhibited by a PKC inhibitor (GF109203X), a Src-family tyrosine kinase inhibitor (herbimycin A), a tyrosine kinase inhibitor (genistein), a PKA inhibitor (H89), a MEK inhibitor (PD98089), and a JNK inhibitor (SP600125). In contrast, the p38 inhibitor (SB203580) was found to have little effect on expression of MMP-1 mRNA. We found that PKC-pan, PKC alpha/beta II, PKC delta (Thr505), PKC delta (Ser(643)), Raf, and MAPK were phosphorylated by MIF. Moreover, we demonstrated that phosphorylation of PKC alpha/beta II and MAPK in response to MIF was suppressed by genistein, and herbimycin A as well as by transfection of the plasmid of C-terminal Src kinase. The DNA binding activity of AP-1 was significantly up-regulated 2 h after MIF stimulation. Taken together, these results suggest that MIF is involved in the up-regulation of UVA-induced MMP-1 in dermal fibroblasts through PKC-, PKA-, Src family tyrosine kinase-, MAPK-, c-Jun-, and AP-1-dependent pathways.

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  • Cetirizine, an H1-receptor antagonist, suppresses the expression of macrophage migration inhibitory factor: its potential anti-inflammatory action 査読

    T Shimizu, J Nishihira, H Watanabe, R Abe, T Ishibashi, H Shimizu

    CLINICAL AND EXPERIMENTAL ALLERGY   34 ( 1 )   103 - 109   2004年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING LTD  

    Background H1-receptor antagonists are often effective in the treatment of allergic disorders such as atopic dermatitis. Cetirizine, a putative H1-receptor antagonist, has recently been shown to have anti-inflammatory properties through the inhibition of leucocyte recruitment and activation, and by the reduction of ICAM-1 expression on keratinocytes.
    Objective To further elucidate the anti-inflammatory properties of cetirizine, we first examined its effects on antigen-induced eosinophilia and neutrophila in vivo. We then examined the anti-inflammatory effects of cetirizine on a human keratinocyte A431cell line.
    Methods Mice were sensitized subcutaneously with ragweed pollen and were challenged intraperitoneally with the allergen. Cetirizine diluted in sterile water (0-20 mg/kg) or only sterile water was administered orally. Peritoneal cells were obtained at 8 and 24 h after challenge. The eosinophilia and neutrophilia induced by ragweed pollen extract were quantitated. Macrophage migration inhibitory factor (MIF), macrophage inflammatory protein 2 (MIP-2) and eotaxin contents of peritoneal fluid were also measured by mouse ELISA. The effects of cetirizine on MIF-induced IL-8 production in A431 cells were examined by ELISA. The effects of cetirizine on MIF expression and production in A431 cells were examined by human MIF ELISA and Northern blot analysis.
    Results Eosinophilia and neutrophilia induced by ragweed pollen extract were found to be significantly reduced in cetirizine-treated mice (20 mg/kg). MIF, a pleuripotent cytokine, was significantly decreased at 8 and 24 h in the peritoneal fluid by cetirizine treatment. MIP-2 and eotaxin were also decreased 8 and 24 h, respectively, after challenge in the peritoneal fluid with cetirizine treatment. MIF stimulates IL-8 production in A431 cells. We found that MIF production in A431 cells was inhibited by 10 muM cetirizine. Consistent with this, cetirizine significantly inhibited MIF-induced IL-8 production.
    Conclusion These results suggest that cetirizine exerts its anti-inflammatory effects by inhibiting MIF as well as IL-8 production, such as those involved in inflammatory allergic skin disease, suggesting a broad spectrum of action beyond its mere H1-receptor-antagonistic function.

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  • Tissue regeneration by incorporation of macrophage migration inhibitory factor \n(MIF)-impregnated gelatin beads into cutaneous wound. 査読

    Shimizu, T, Zhao, Y, Nishihira, J, Honda, A, Watanabe, H, Abe, R, Tabata, Y, Kushibiki, T, Nakayama, T, Taniguchi, M, Shimizu, H

    79th Societa Italiana di Dermatologica, Joint Meeting of the JSID and GIRSDE(Italian Group of Experimental Research in Dermatology)(2004.5.26-29. Nova Yardinia)   2004年

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  • The use of ELISA to detect desmoglein antibodies in a pregnant woman and fetus. 査読 国際誌

    Satomi Okubo, Kazuko C Sato-Matsumura, Riichiro Abe, Satoru Aoyagi, Masashi Akiyama, Koichi Yokota, Hiroshi Shimizu

    Archives of dermatology   139 ( 9 )   1217 - 8   2003年9月

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    記述言語:英語   出版者・発行元:9  

    DOI: 10.1001/archderm.139.9.1217

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  • Impaired contact hypersensitivity in macrophage migration inhibitory factor-deficient mice. 査読 国際誌

    Tadamichi Shimizu, Riichiro Abe, Jun Nishihira, Akihiko Shibaki, Hirokazu Watanabe, Toshinori Nakayama, Masaru Taniguchi, Teruo Ishibashi, Hiroshi Shimizu

    European journal of immunology   33 ( 6 )   1478 - 87   2003年6月

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    記述言語:英語   出版者・発行元:6  

    To determine whether macrophage migration inhibitory factor (MIF) is required for contact hypersensitivity (CHS) response, MIF-deficient (MIF KO) and wild-type (WT) mice were sensitized with trinitrochlorobenzene (TNCB) or oxazolone on their abdominal skin and challenged on the dorsum skin of one ear 5 days later. Significant ear swelling was observed in the WT mice, but this response was inhibited in the MIF KO mice (p<0.01 for MIF KO vs. WT mice in 24 h). In addition, lymph node cells from hapten-sensitized MIF KO mice showed a decreased capacity for transferring the CHS response. A topical application of TNCB (200 microg) caused a significant decline in epidermal Langerhans cell (LC) density (20.3%; p<0.01 compared with vehicle) 4 h after application in WT mice, but it failed to provoke a significant epidermal LC migration in MIF KO mice (7.4%). By mixed lymphocyte reaction, the T cell proliferative response to alloantigen was significantly decreased in the MIF KO mice compared with WT mice (p<0.005). Taken together, these results indicate that MIF is pivotal in the regulation of cutaneous immune responses and plays a central role in LC migration and T cell proliferation for the CHS response.

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  • Toxic epidermal necrolysis and Stevens-Johnson syndrome are induced by soluble Fas ligand. 査読 国際誌

    Riichiro Abe, Tadamichi Shimizu, Akihiko Shibaki, Hideki Nakamura, Hirokazu Watanabe, Hiroshi Shimizu

    The American journal of pathology   162 ( 5 )   1515 - 20   2003年5月

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    記述言語:英語   出版者・発行元:5  

    The pathogeneses of toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), both severe blistering diseases usually associated with drug intake, are not fully elucidated. Histologically, both TEN and SJS are characterized by extensive keratinocyte apoptosis. Previous studies have shown that keratinocyte apoptosis in TEN and SJS was induced by a suicidal interaction between Fas and Fas ligand (FasL), which are both expressed by keratinocytes. However, our preliminary examinations demonstrated that FasL is hardly detected on keratinocytes. We hypothesized that soluble FasL (sFasL) is secreted by peripheral blood mononuclear cells (PBMCs), and this interacts with the Fas expressed on keratinocytes in TEN and SJS. To justify this hypothesis, we investigated whether sFasL secreted by PBMCs could induce the keratinocyte apoptosis in TEN and SJS. Enzyme-linked immunosorbent assay analysis demonstrated that there was no significant sFasL increase in any samples of healthy controls (<40 pg/ml, n = 14) and patients with an ordinary erythema multiforme-type drug eruption (41.5 +/- 3.1 pg/ml, n = 14), whereas high concentrations are detected in all samples of TEN and SJS patients (TEN: 131.5 +/- 57.4 pg/ml, n = 8; SJS: 119.1 +/- 41.0 pg/ml, n = 14) (P < 0.0001). In vitro analysis using cultured keratinocytes revealed that the sera of TEN and SJS patients induced abundant keratinocyte apoptosis compared to erythema multiforme-type drug eruption sera. Furthermore, on stimulation with the causal drug, PBMCs obtained from TEN and SJS patients secreted high levels of sFasL. Taken together, these results indicate that sFasL secreted by PBMCs, not keratinocytes, plays a crucial role in the apoptosis and pathomechanism of TEN and SJS, and that the serum sFasL level may be a good indicator for the early diagnosis of TEN and SJS.

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  • A novel polymorphic CAAT/enhancer-binding protein beta element in the FasL gene promoter alters Fas ligand expression: a candidate background gene in African American systemic lupus erythematosus patients. 査読 国際誌

    Jianming Wu, Christine Metz, Xiulong Xu, Riichiro Abe, Andrew W Gibson, Jeffrey C Edberg, Jennifer Cooke, Fenglong Xie, Glinda S Cooper, Robert P Kimberly

    Journal of immunology (Baltimore, Md. : 1950)   170 ( 1 )   132 - 8   2003年1月

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    記述言語:英語   出版者・発行元:1  

    A single-nucleotide polymorphism (SNP), identified at nucleotide position -844 in the 5' promoter of the FasL gene, lies within a putative binding motif for CAAT/enhancer-binding protein beta (C/EBPbeta). Electrophoretic mobility shift and supershift assays confirmed that this element binds specifically to C/EBPbeta and demonstrated that the two alleles of this element have different affinities for C/EBPbeta. In luciferase reporter assays, the -844C genotype had twice the basal activity of the -844T construct, and basal expression of Fas ligand (FasL) on peripheral blood fibrocytes was also significantly higher in -844C than in -844T homozygous donors. FasL is located on human chromosome 1q23, a region that shows linkage to the systemic lupus autoimmune phenotype. Analysis of 211 African American systemic lupus erythematosus patients revealed enrichment of the -844C homozygous genotype in these systemic lupus erythematosus patients compared with 150 ethnically matched normal controls (p = 0.024). The -844C homozygous genotype may lead to the increased expression of FasL, to altered FasL-mediated signaling in lymphocytes, and to enhanced risk for autoimmunity. This functionally significant SNP demonstrates the potential importance of SNPs in regulatory regions and suggests that differences in the regulation of FasL expression may contribute to the development of the autoimmune phenotype.

    DOI: 10.4049/jimmunol.170.1.132

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  • Nifedipine inhibits apoptotic cell death of cultured endothelial cells induced by tumor necrosis factor-alpha 査読

    S Yamagishi, Y Inagaki, R Abe, S Kikuchi, N Sasaki, M Takeuchi

    DRUGS UNDER EXPERIMENTAL AND CLINICAL RESEARCH   29 ( 4 )   141 - 145   2003年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOSCIENCE EDIPRINT INC  

    Impaired endothelial cell (EC) growth and function have been suggested to be an initial event that leads to the development of atherosclerosis. We have very recently found that nifedipine, one of the most popularly used dihydropyridine-based calcium antagonists, prevented EC monocyte chemoattractant protein-1 production elicited by tumor necrosis factor-alpha (TNF-alpha) through its antioxidative properties. However, the effects of nifedipine on EC growth and apoptosis are not fully understood. In this study, we investigated whether nifedipine could inhibit tumor necrosis factor (TNF)-alpha-induced growth retardation and apoptotic cell death in human umbilical vein ECs (HUVECs). TNF-alpha inhibited EC proliferation, which was significantly blocked by nifedipine or antioxidant N-acetylcysteine (NAC). Nifedipine or NAC was also found to significantly inhibit apoptotic cell death of TNF-alpha-exposed HUVECs. Our present study suggests that nifedipine may play a protective role against the development and progression of atherosclerosis by promoting EC repair through its antioxidative properties.

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  • 高齢者に生じた陰茎悪性黒色腫の1例 査読

    青柳哲, 松村和子, 秦洋郎, 谷村心太郎, 阿部理一郎, 清水忠道, 澤村大輔, 清水宏

    Skin Cancer   18 ( 3 )   308 - 311   2003年

  • Severe refractory chronic actinic dermatitis successfully treated with tacrolimus ointment. 査読

    Abe R, Shimizu T, Tsuji A, Matsumura T, Shimizu H

    Br J Dermatol   147 ( 6 )   1273 - 1275   2002年12月

  • Angiogenesis induced by advanced glycation end products and its prevention by cerivastatin. 査読 国際誌

    Tamami Okamoto, Sho-ichi Yamagishi, Yosuke Inagaki, Shinjiro Amano, Kohachiro Koga, Riichiro Abe, Masayoshi Takeuchi, Shigeaki Ohno, Akihiko Yoshimura, Zenji Makita

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology   16 ( 14 )   1928 - 30   2002年12月

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    記述言語:英語   出版者・発行元:14  

    We previously have found that advanced glycation end products (AGE), senescent macroproteins formed at an accelerated rate in diabetes, arise in vivo not only from glucose but also from reducing sugars. Furthermore, we recently have shown that glyceraldehyde- and glycolaldehyde-derived AGE (glycer- and glycol-AGE) are mainly involved in loss of pericytes, the earliest histopathological hallmark of diabetic retinopathy. However, the effects of these AGE proteins on angiogenesis, another vascular derangement in diabetic retinopathy, remain to be elucidated. In this study, we investigated whether these AGE proteins elicit changes in cultured endothelial cells that are associated with angiogenesis. When human skin microvascular endothelial cells (EC) were cultured with glycer-AGE or glycol-AGE, growth and tube formation of EC, the key steps of angiogenesis, were significantly stimulated. The AGE-induced growth stimulation was significantly enhanced in AGE receptor (RAGE)-overexpressed EC. Furthermore, AGE increased transcriptional activity of nuclear factor-kB (NF-kB) and activator protein-1 (AP-1) and then up-regulated mRNA levels of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) in EC. Cerivastatin, a hydroxymethylglutaryl CoA reductase inhibitor; pyrrolidinedithiocarbamate; or curcumin was found to completely prevent the AGE-induced increase in NF-kB and AP-1 activity, VEGF mRNA up-regulation, and the resultant increase in DNA synthesis in microvascular EC. These results suggest that the AGE-RAGE interaction elicited angiogenesis through the transcriptional activation of the VEGF gene via NF-kB and AP-1 factors. By blocking AGE-RAGE signaling pathways, cerivastatin might be a promising remedy for treating patients with proliferative diabetic retinopathy.

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  • Histochemical analysis of macrophage migration inhibitory factor in psoriasis vulgaris. 査読 国際誌

    Tadamichi Shimizu, Jun Nishihira, Yuka Mizue, Hideki Nakamura, Riichiro Abe, Hirokazu Watanabe, Teruo Ishibashi, Hiroshi Shimizu

    Histochemistry and cell biology   118 ( 3 )   251 - 7   2002年9月

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    記述言語:英語   出版者・発行元:3  

    Psoriasis is a persistent cutaneous disease characterized by skin inflammation and infiltration of immunocytes such as lymphocytes and monocytes/macrophages, concomitant with abnormal epidermal hyperproliferation. We previously showed that the serum level of macrophage migration inhibitory factor (MIF) and its production by peripheral blood mononuclear cells of patients with psoriasis were closely correlated with the severity of clinical symptoms; however, the precise role of MIF in psoriatic epidermis remains to be clarified. The current study was carried out to elucidate the possible involvement of MIF in psoriasis, using immunohistochemistry and in situ hybridization. In contrast to elevated serum MIF in psoriasis, MIF-positive staining in the lesional psoriatic epidermis was significantly decreased, as demonstrated by immunohistochemical analysis using an anti-MIF antibody. Consistent with this finding, we found, by in situ hybridization, that MIF mRNA concomitantly decreased in the psoriatic lesions. Although the reason for the different MIF levels in the psoriatic epidermis and in the circulation remains unknown, it is hypothesized that MIF, a potential growth factor, might be decreased in psoriatic lesions to counterregulate the abnormal epidermal proliferation caused by dysregulation of cytokines and growth factors.

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  • Increased macrophage migration inhibitory factor (MIF) in the sera of patients with extensive alopecia areata. 査読 国際誌

    Tadamichi Shimizu, Yuka Mizue, Riichiro Abe, Hirokazu Watanabe, Hiroshi Shimizu

    The Journal of investigative dermatology   118 ( 3 )   555 - 7   2002年3月

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    記述言語:英語   出版者・発行元:3  

    DOI: 10.1046/j.0022-202x.2001.01669.x

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  • Fibrocytes induce an angiogenic phenotype in cultured endothelial cells and promote angiogenesis in vivo. 査読

    Hartlapp I, Abe R, Saeed RW, Peng T, Voelter W, Bucala R, Metz CN

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology   15 ( 12 )   2215 - 2224   2001年10月

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    出版者・発行元:12  

    DOI: 10.1096/fj.01-0049com

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  • High macrophage migration inhibitory factor (MIF) serum levels associated with extended psoriasis 査読

    T Shimizu, J Nishihira, Y Mizue, H Nakamura, R Abe, H Watanabe, A Ohkawara, H Shimizu

    JOURNAL OF INVESTIGATIVE DERMATOLOGY   116 ( 6 )   989 - 990   2001年6月

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    記述言語:英語   出版者・発行元:BLACKWELL SCIENCE INC  

    DOI: 10.1046/j.0022-202x.2001.01366.x

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  • Peripheral blood fibrocytes: differentiation pathway and migration to wound sites. 査読

    Abe R, Donnelly SC, Peng T, Bucala R, Metz CN

    Journal of immunology (Baltimore, Md. : 1950)   166 ( 12 )   7556 - 7562   2001年6月

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  • A new case of α-N-acetylgalactosaminidase deficiency with angiokeratoma corporis diffusum, with Meniere's symdrome and without mental retardation. 査読

    Kodama K, Kobayashi H, Abe R, Ohkawara A, Yoshii N, Yotsumoto S, Fukushige T, Nagatsuka Y, Hirabayashi Y, Kanzaki T

    Br J Dermatol   144 ( 2 )   363 - 368   2001年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1046/j.1365-2133.2001.04028.x

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  • Regulation of the CTL response by macrophage migration inhibitory factor. 査読

    Abe R, Peng T, Sailors J, Bucala R, Metz CN

    Journal of immunology (Baltimore, Md. : 1950)   166 ( 2 )   747 - 753   2001年1月

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  • Enhancement of macrophage migration inhibitory factor (MIF) expression in injured epidermis and cultured fibroblasts 査読

    R Abe, T Shimizu, AA Ohkawara, J Nishihira

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE   1500 ( 1 )   1 - 9   2000年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    After the cDNA of human macrophage migration inhibitory factor (MIF) was cloned in 1989, this protein has been reevaluated as a pro-inflammatory cytokine, pituitary hormone and glucocorticoid-induced immunoregulatory protein. We previously reported the expression of MIF in the basal cell layers of the epidermis, but its pathophysiological function in the skin has not been well understood. In this study, we examined the expression of MIF during the wound healing of rat skin injured by excision. Reverse transcription-polymerase chain reaction in combination with Southern blot analysis revealed that the increase of MIF mRNA expression was biphasic. The maximum peaks were observed at 3 and 24 h after the injury. Similarly, maximal increases of the serum MIF level were observed at 3 and 24 h after the injury. Immunohistochemical analysis at 12 h after injury demonstrated enhanced expression of MIF protein in the whole epidermal lesion of the wound tissue. By the Boyden chamber assay, we demonstrated that MIF had a chemotactic effect on freshly prepared keratinocytes from rat skin. Additionally, cultured fibroblasts from the skill wound lesion secreted a higher amount of MIF in response to lipopolysaccharide compared to those of the normal skin. Furthermore, administration of anti-MIF antibodies induced a delay of wound healing in vivo. Taken together, these results suggest that MIF contributes to the wound healing process of skin tissue. (C) 2000 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0925-4439(99)00080-0

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  • High expression of macrophage migration inhibitory factor in human melanoma cells and its role in tumor cell growth and angiogenesis 査読

    T Shimizu, R Abe, H Nakamura, A Ohkawara, M Suzuki, J Nishihira

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   264 ( 3 )   751 - 758   1999年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC  

    Macrophage migration inhibitory factor (MIF) is known to function as a cytokine, hormone, and glucocorticoid-induced immunoregulator. In this study, we reported for the first time that human melanocytes and melanoma cells express MIF mRNA and produce MIF protein. Immunohistochemical analysis demonstrated that MIF was mostly localized in the cytoplasm of melanocytes and G361 cells, a widely available human melanoma cell line. In particular, strong positive staining was observed at the dendrites of these cells. Expression of MIF mRNA and production of MIF protein were much higher in human melanoma cells such as G361, A375, and L32 than in normal cultured melanocytes. To assess the role of MIF overexpression in melanoma cells, G361 cells were transfected with an antisense human MIF plasmid. The results demonstrated that the cell growth rate of the transfected cells was markedly suppressed, suggesting that MIF participates in the mechanism of proliferation of melanoma cells. To further evaluate the function of MIF, we employed the Boyden chamber method to examine the effect on tumor cell migration and found that MIF enhanced the migration of G361 cells in a dose-dependent manner. Furthermore, we administered anti-MIF antibody into tumor (G361 cells in a Millipore chamber)-bearing mice to assess the effect on tumor-associated angiogenesis. The anti-MIF antibody significantly suppressed tumor-induced angiogenesis. Taken together, these results indicated that it is likely that MIF may function as a novel growth factor that stimulates incessant growth and invasion of melanoma concomitant with neovascularization. (C) 1999 Academic Press.

    DOI: 10.1006/bbrc.1999.1584

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  • Increased production of macrophage migration inhibitory factor by PBMCs of atopic dermatitis 査読

    T Shimizu, R Abe, A Ohkawara, J Nishihira

    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY   104 ( 3 )   659 - 664   1999年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MOSBY-YEAR BOOK INC  

    Background: Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disorder. The underlying cause of AD is multifactorial, and several cytokines are considered to be involved in this severe inflammatory skin disease. Macrophage migration inhibitory factor (MIF) is an immunoregulatory cytokine essential for T-cell activation and delayed-type hypersensitivity. Recently we demonstrated that serum MIF content was significantly elevated in patients with AD, Consistent with this, expression of MLF messenger RNA in keratinocytes of the eczematous skin lesion was up-regulated.
    Objective and Method: Although keratinocytes are considered to be a potential source of increased serum MIF content in AD, precise evaluation has not been carried out in other tissues. NIP is ubiquitously expressed in various cells, including T cells and macrophages. In this study we examined MIF production and its messenger RNA level of PBMCs from patients with AD to investigate the contribution of these cells to elevated serum MIF content and to its pathologic characteristics.
    Results: Consistent with our previous findings, the serum MIF content of patients with AD was significantly elevated compared with nonatopic healthy control subjects and patients with chronic urticaria without eczema. As for the MIF productivity of unstimulated PBMCs, the MIF content in the culture medium of PBMCs obtained from patients with AD (40.4 +/- 8.4 ng/mL) (mean +/- SEM) was significantly increased compared with that from healthy control subjects (6.6 +/- 1.1 ng/mL) and patients with chronic urticaria (8.5 +/- 1.4 ng/ml) (P &lt; .0001). When PBMCs were stimulated by concanavalin A, MIF production by PBMCs of patients with AD was more enhanced than in control subjects or patients with chronic urticaria, The increased ratio of MIF production by PBMCs in response to concanavalin A was significantly correlated with the severity of clinical features of AD. Supporting these results, the level of MIF mRNA in PMBCs of patients with AD was significantly higher than in nonatopic healthy control subjects.
    Conclusions: The current results showed that PBMCs should be an important source of increased serum MIF in AD. Because MIF has the potential to induce local and systemic inflammatory and immune responses, it is conceivable that MIF produced by PBMCs may affect Local and systemic pathologic features in AD.

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  • Ultraviolet B radiation upregulates the production of macrophage migration inhibitory factor (MIF) in human epidermal keratinocytes 査読

    T Shimizu, R Abe, A Ohkawara, J Nishihira

    JOURNAL OF INVESTIGATIVE DERMATOLOGY   112 ( 2 )   210 - 215   1999年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL SCIENCE INC  

    Human epidermal cells are capable of secreting various cytokines with immunologic, inflammatory, and proliferative properties. In a previous study, by reverse transcription-polymerase chain reaction and immunohistochemical analysis, we have shown that human epidermal keratinocytes express macrophage migration inhibitory factor and identified its presence in the cytoplasm, In this study, we detected an increased serum macrophage migration inhibitory factor level by enzyme-linked immunosorbent assay after a single total-body ultraviolet B exposure in vivo, indicating that human keratinocytes respond and release this cytokine in response to ultraviolet B irradiation. Moreover, we evaluated the effect of ultraviolet B on migration inhibitory factor production in cultured human epidermal keratinocytes and epidermal sheets. The results of enzyme-linked immunosorbent assay and northern blot analyses showed that migration inhibitory factor production of cultured keratinocytes was increased by ultraviolet B exposure. During the past few years, migration inhibitory factor was found to have a variety of biologic functions, such as being essential for T cell activation and induction of inflammatory cytokines, In this context, these results should encourage further investigation on the pathophysiologic role of migration inhibitory factor in cutaneous inflammatory reactions and immune responses.

    DOI: 10.1046/j.1523-1747.1999.00486.x

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  • Cis-urocanic acid down-regulates histamine-mediated activation of adenylate cyclase in the pig epidermis 査読

    T Shimizu, H Koizumi, H Nishino, R Abe, A Ohkawara

    ACTA DERMATO-VENEREOLOGICA   78 ( 5 )   348 - 350   1998年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SCANDINAVIAN UNIVERSITY PRESS  

    Urocanic acid (UCA), one of the skin's major components for absorbing UV radiation, is present naturally in the stratum corneum as a trans-isomer. On absorption of UVB radiation either in vitro or in the skin, UCA undergoes trans- to cis-isomerization in a dose-dependent manner. Although the mechanism by which cis-UCA suppresses immunity remains unelucidated, recent studies have indicated that cis-UCA appears to inhibit the induction of cyclic AMP in fibroblasts, which suggests that this molecule plays an active role in modifications to the skin, Here, we report that although neither trans-UCA nor cis-UCA increases cyclic AMP in the pig epidermis, cis-UCA actively down-regulates the increase of cyclic AMP induced by histamine, The effects of cis-UCA on the pig epidermis are revealed through the modulation of the effects caused by histamine, These findings suggest that in the pig epidermis, the initial biochemical and cellular event for UVB-induced immune suppression - that is, the step immediately following the isomerization of trans-UCA to cis-UCA is down-regulation of cyclic AMP brought about by the activity of cis-UCA.

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  • Macrophage migration inhibitory factor is an essential immunoregulatory cytokine in atopic dermatitis 査読

    T Shimizu, R Abe, A Ohkawara, Y Mizue, J Nishihira

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   240 ( 1 )   173 - 178   1997年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS  

    Macrophage migration inhibitory factor (MIF) is one of the immunoregulatory cytokines involved in T-cell activation and delayed-type hypersensitivity. To elucidate involvement of this cytokine in the pathogenesis of atopic dermatitis (AD), we examined serum MIF concentrations of patients with AD and non-atopic normal healthy individuals. The mean serum MIF concentration of the AD patients (n = 36) was 36.4 +/- 3.7 ng/ml (mean +/- SEM), whereas that of the non-atopic dermatitis patients (n = 17) or healthy individuals (n = 61) were 13.1 +/- 1.8 or 6.5 +/- 0.45 ng/ml, respectively, Accordingly, immunohistochemistry of the inflammatory skin lesion of an AD patient demonstrated that MIF protein was diffusely expressed throughout the whole epidermal layer. After 4-week steroid ointment treatment, the MIF concentration decreased as clinical symptoms improved. The serum level of TNF-alpha was also decreased in parallel with that of MIF. Considering the T-cell dysfunction and disordered cytokine-network reported in AD, it was strongly suggested that MIF was a critical protein for immunoregulation in the pathophysiological mechanism of AD. In this context, MIF may become a useful laboratory parameter to comprehend the clinical course of the disease. (C) 1997 Academic Press.

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  • Effective high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation in a patient with the aggressive form of cytophagic histiocytic panniculitis 査読

    K Koizumi, K Sawada, M Nishio, E Katagiri, J Fukae, Y Fukada, T Tarumi, A Notoya, T Shimizu, R Abe, H Kobayashi, T Koike

    BONE MARROW TRANSPLANTATION   20 ( 2 )   171 - 173   1997年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:STOCKTON PRESS  

    A 20-year-old Japanese man developed generalized, subcutaneous, painless nodules, fever, abnormal liver function, serosal effusions, hepatosplenomegaly, lymphadenopathy and anemia, Skin biopsies revealed lobular panniculitis with a morphologically benign histiocytic infiltration and prominent phagocytosis. Atypical T lymphocytes were also present in the skin and liver, The diagnosis given was aggressive cytophagic histiocytic panniculitis (CHP) or aggressive subcutaneous panniculitic T cell lymphoma (SPTCL), He received cyclophosphamide, doxorubicin, and vincristine on day 1, prednisolone on days 1-5, and etoposide on days 1, 3 and 5 (CHOP-E), with the support of granulocyte colony-stimulating factor, This regimen was repeated every 2 weeks and complete clinical remission (CCR) was attained after three cycles of CHOP-E. As the clinical course of aggressive CHP is recurrent and often fatal, he was given high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (APBSCT), after five cycles of CHOP-E, He has remained in CCR for 12 months after APBSCT, High-dose chemotherapy followed by APBSCT is considered to be one of the most beneficial therapies for patients with aggressive CHP and aggressive phase SPTCL.

    DOI: 10.1038/sj.bmt.1700858

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▶ 全件表示

書籍等出版物

  • 皮膚疾患最新の治療2017-2018

    南江堂  2017年 

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  • 今日の治療指針2014年版

    医学書院  2014年 

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  • 1冊でわかる皮膚アレルギー

    文光堂  2012年 

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  • 今日の治療指針2011年版(ポケット判)

    医学書院  2011年 

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  • ナースが悩むQ&A

    メディカルレビュー社  2010年 

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  • Progress in Skin Cancer Research

    Nova Science Publishers  2007年 

     詳細を見る

  • 片山一朗 and 古川福実: 目で見るアレルギー性皮膚疾患.

    南山堂  2007年 

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  • 皮膚疾患の最新医療

    先端医療技術研究所  2006年 

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  • 最新皮膚科学体系19巻

    中山書店  2004年 

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  • AGEs研究の最前線

    メディカルレビュー社  2004年 

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  • 最新皮膚科学体系11巻

    中山書店  2002年 

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▶ 全件表示

MISC

産業財産権

  • 骨髄幹細胞移植治療用医薬

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    出願番号:2004-369272 

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  • 色素上皮由来因子の新規治療用途(193839)

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    出願番号:2004-080387 

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  • .

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    出願番号:2004-369272 

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  • .

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    出願番号:2004-080387 

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受賞

  • POLA PHARMA RISING STAR AWARD 2018

    2018年  

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  • 日本研究皮膚科学会 Fellowship SHISEIDO Award

    2007年  

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    受賞国:日本国

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  • Poster Award: Society of Investigative Dermatology

    2002年  

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  • Travel Fellowship: Japanese Society of Investigative Dermatology

    2002年  

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共同研究・競争的資金等の研究

  • 重症薬疹の発症機序解明

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    資金種別:競争的資金

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担当経験のある授業科目

  • 医学序説 II

    2021年
    -
    現在
    機関名:新潟大学

  • 臨床医学講義(集中)

    2020年
    -
    現在
    機関名:新潟大学

  • 臓器別講義・演習Ⅱ

    2020年
    -
    現在
    機関名:新潟大学

  • 医学序説 I

    2020年
    -
    現在
    機関名:新潟大学

  • 皮膚・形成系

    2017年
    機関名:新潟大学