Updated on 2022/05/03

写真a

 
MORIZANE Shin
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Professor
Position
Professor
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Degree

  • 医学博士 ( 岡山大学 )

Research Interests

  • kallikrein-related peptidases

  • antimicrobial peptides

  • epidermal keratinocytes

  • Innate immunity in the skin

Research Areas

  • Life Science / Dermatology

Education

  • Okayama University   医学系研究科   病態制御科学

    - 2006

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    Country: Japan

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  • Okayama University   医学部   医学科

    - 2000

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    Country: Japan

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Research History

  • 岡山大学大学院医歯薬学総合研究科   教授

    2018.7

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  • Okayama University   Okayama University Hospital   Lecturer

    2018.1 - 2018.6

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  • Okayama University   Okayama University Hospital   Assistant Professor

    2009 - 2017

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  • 米国カリフォルニア大学サンディエゴ校医学部皮膚科学講座 ポストドクトラルフェロー

    2007 - 2009

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Professional Memberships

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Committee Memberships

  • 日本皮膚科学会   代議員  

    2019.4   

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  • 日本乾癬学会   評議員  

    2018.9   

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    Committee type:Academic society

    日本乾癬学会

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  • 日本皮膚免疫アレルギー学会   代議員  

    2015.4   

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    Committee type:Academic society

    日本皮膚アレルギー・接触皮膚炎学会

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  • 日本研究皮膚科学会   評議員  

    2013.4   

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    Committee type:Academic society

    日本研究皮膚科学会

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Papers

  • Obesity and Dyslipidemia Synergistically Exacerbate Psoriatic Skin Inflammation. International journal

    Kenta Ikeda, Shin Morizane, Takahiko Akagi, Sumie Hiramatsu-Asano, Kota Tachibana, Ayano Yahagi, Masanori Iseki, Hideaki Kaneto, Jun Wada, Katsuhiko Ishihara, Yoshitaka Morita, Tomoyuki Mukai

    International journal of molecular sciences   23 ( 8 )   2022.4

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    Patients with psoriasis are frequently complicated with metabolic syndrome; however, it is not fully understood how obesity and dyslipidemia contribute to the pathogenesis of psoriasis. To investigate the mechanisms by which obesity and dyslipidemia exacerbate psoriasis using murine models and neonatal human epidermal keratinocytes (NHEKs), we used wild-type and Apoe-deficient dyslipidemic mice, and administered a high-fat diet for 10 weeks to induce obesity. Imiquimod was applied to the ear for 5 days to induce psoriatic dermatitis. To examine the innate immune responses of NHEKs, we cultured and stimulated NHEKs using IL-17A, TNF-α, palmitic acid, and leptin. We found that obesity and dyslipidemia synergistically aggravated psoriatic dermatitis associated with increased gene expression of pro-inflammatory cytokines and chemokines. Treatment of NHEKs with palmitic acid and leptin amplified pro-inflammatory responses in combination with TNF-α and IL-17A. Additionally, pretreatment with palmitic acid and leptin enhanced IL-17A-mediated c-Jun N-terminal kinase phosphorylation. These results revealed that obesity and dyslipidemia synergistically exacerbate psoriatic skin inflammation, and that metabolic-disorder-associated inflammatory factors, palmitic acid, and leptin augment the activation of epidermal keratinocytes. Our results emphasize that management of concomitant metabolic disorders is essential for preventing disease exacerbation in patients with psoriasis.

    DOI: 10.3390/ijms23084312

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  • Impetigo herpetiformis successfully treated with brodalumab. International journal

    Yumi Nakai, Himino Ashida, Ai Kajita, Emi Yokoyama, Kazumitsu Sugiura, Shin Morizane

    The Journal of dermatology   2021.12

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  • Epithelioid cell granuloma formation in CARD14-associated papulosquamous eruptions. International journal

    Takuya Takeichi, Kenta Ikeda, Yoshinao Muro, Tomoo Ogi, Shin Morizane, Masashi Akiyama

    Journal of the European Academy of Dermatology and Venereology : JEADV   2021.12

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    DOI: 10.1111/jdv.17890

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  • Multifaceted Analysis of IL-23A- and/or EBI3-Including Cytokines Produced by Psoriatic Keratinocytes. International journal

    Kota Tachibana, Nina Tang, Hitoshi Urakami, Ai Kajita, Mina Kobashi, Hayato Nomura, Minori Sasakura, Satoru Sugihara, Fan Jiang, Nahoko Tomonobu, Masakiyo Sakaguchi, Mamoru Ouchida, Shin Morizane

    International journal of molecular sciences   22 ( 23 )   2021.11

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    Interleukin (IL) 23 (p19/p40) plays a critical role in the pathogenesis of psoriasis and is upregulated in psoriasis skin lesions. In clinical practice, anti-IL-23Ap19 antibodies are highly effective against psoriasis. IL-39 (p19/ Epstein-Barr virus-induced (EBI) 3), a newly discovered cytokine in 2015, shares the p19 subunit with IL-23. Anti-IL-23Ap19 antibodies may bind to IL-39; also, the cytokine may contribute to the pathogenesis of psoriasis. To investigate IL23Ap19- and/or EBI3-including cytokines in psoriatic keratinocytes, we analyzed IL-23Ap19 and EBI3 expressions in psoriasis skin lesions, using immunohistochemistry and normal human epidermal keratinocytes (NHEKs) stimulated with inflammatory cytokines, using quantitative real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and liquid chromatography-electrospray tandem mass spectrometry (LC-Ms/Ms). Immunohistochemical analysis showed that IL-23Ap19 and EBI3 expressions were upregulated in the psoriasis skin lesions. In vitro, these expressions were synergistically induced by the triple combination of tumor necrosis factor (TNF)-α, IL-17A, and interferon (IFN)-γ, and suppressed by dexamethasone, vitamin D3, and acitretin. In ELISA and LC-Ms/Ms analyses, keratinocyte-derived IL-23Ap19 and EBI3, but not heterodimeric forms, were detected with humanized anti-IL-23Ap19 monoclonal antibodies, tildrakizumab, and anti-EBI3 antibodies, respectively. Psoriatic keratinocytes may express IL-23Ap19 and EBI3 proteins in a monomer or homopolymer, such as homodimer or homotrimer.

    DOI: 10.3390/ijms222312659

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  • Case of inherited epidermolysis bullosa simplex with KLHL24 gene mutation in Japan. International journal

    Tomoko Miyake, Ken Natsuga, Takatsune Umayahara, Seiko Naito, Junko Yoshimoto, Akemi Senoo, Han-Tang Wang, Chao-Kai Hsu, Osamu Yamasaki, Shin Morizane

    The Journal of dermatology   2021.10

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  • Persistent local inflammation surrounding cement substance of a tick Amblyomma testudinarium after sufficient removal of its mouthpart. International journal

    Shiho Sato, Yoshio Kawakami, Yohei Yasutomi, Emi Yokoyama, Toshiko Yoshioka, Osamu Yamasaki, Shin Morizane

    The Journal of dermatology   2021.10

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  • Multifunctionality of CD8+ T cells and PD-L1 expression as a biomarker of anti-PD-1 antibody efficacy in advanced melanoma. International journal

    Keiko Manabe, Osamu Yamasaki, Yuki Nakagawa, Tomoko Miyake, Heiichiro Udono, Shin Morizane

    The Journal of dermatology   48 ( 8 )   1186 - 1192   2021.8

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    Anti-programmed cell death protein-1 (PD-1) antibodies have become a standard treatment for advanced melanoma. However, a predictive biomarker for assessing the efficacy of anti-PD-1 antibodies has not been identified. In cancer, CD8+ T cells specific for tumor antigens undergo repeated T-cell receptor stimulation due to the persistence of cancer cells and gradually lose their ability to secrete interleukin 2 (IL-2), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). We aimed to evaluate multi-cytokine production and immune exhaustion of peripheral CD8+ T cells in melanoma patients treated with anti-PD-1 antibodies. Twenty-four melanoma patients treated with nivolumab were included. Effector cytokine production (IL-2, TNF-α, and IFN-γ) and expression of an exhaustion marker (PD-1) in patients' CD8+ cells were analyzed with flow cytometry. The relationships between parameters such as the neutrophil-to-lymphocyte ratio (NLR) and clinical response to nivolumab were examined. Immunohistochemistry for programmed death-ligand 1 (PD-L1) expression in tumor cells and tumor-infiltrating lymphocytes (TILs) and analysis of their association with clinical response were performed. The clinical response rate to nivolumab was 29%. Regarding TILs, NLR, and several other parameters, no significant difference was found between responders and non-responders. The responder group showed an increase in the percentage of PD-1+ CD8+ /TNF-α+ IFN-γ+ or PD-1+ CD8+ /IFN-γ+ IL-2+ TNF-α+ T cells compared to non-responders. Positivity for PD-L1 expression was significantly higher in the responder group than the non-responder group. In advanced melanoma, the percentage of multifunctional CD8+ PD-1+ T cells and PD-L1 expression in the tumors may be a biomarker for a good response to anti-PD-1 antibody monotherapy.

    DOI: 10.1111/1346-8138.15904

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  • Analysis of clonality in cutaneous B-cell lymphoma and B-cell pseudolymphoma using skin flow cytometry: Comparison of immunophenotyping and gene rearrangement studies. International journal

    Yuki Nakagawa, Toshihisa Hamada, Takahide Takahashi, Tomoko Miyake, Yoji Hirai, Keiji Iwatsuki, Shin Morizane

    The Journal of dermatology   2021.7

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    To identify clonal neoplastic cells in skin affected by B-cell lymphoma using skin flow cytometry (FCM) techniques, we investigated light-chain restriction using skin FCM with clonality assessed by polymerase chain reaction and light-chain restriction by in situ hybridization (ISH). We retrospectively analyzed 16 cases of B-cell lymphoma with cutaneous involvement: primary cutaneous diffuse large B-cell lymphoma, leg type (pcDLBCL-LT) (n = 7), DLBCL-not otherwise specified (DLBCL-NOS) (n = 6), primary cutaneous follicle center lymphoma (pcFCL) (n = 1), and follicular lymphoma (n = 2), as well as cutaneous B-cell pseudolymphoma (n = 9). Results of skin FCM light-chain restriction analyses were compared with immunoglobulin H (IgH) gene rearrangement and κ/λ ISH findings. Skin FCM detected light-chain restriction in 11 of 14 B-cell lymphoma patients but none of the B-cell pseudolymphoma patients. The sensitivity of skin FCM for distinguishing B-cell lymphoma and B-cell pseudolymphoma was 79%, and the specificity was 100%. Eleven of 13 B-cell lymphoma patients exhibited gene rearrangement (sensitivity 85%), whereas six of seven pseudolymphoma patients were negative (specificity 86%). ISH was positive in three of 16 B-cell lymphoma cases (sensitivity 19%) but none of the B-cell pseudolymphoma cases (specificity 100%). ISH sensitivity was 29% for pcDLBCL-LT, 17% for DLBCL-NOS, and 0% for pcFCL and follicular lymphoma. Skin FCM therefore appears to be more sensitive than ISH in detecting light-chain restriction in DLBCL and follicular lymphoma, and as sensitive as IgH gene rearrangement analysis in detecting clonality. Skin FCM is thus a promising diagnostic tool for identifying monoclonal neoplastic B-cell populations.

    DOI: 10.1111/1346-8138.16057

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  • Granular C3 dermatosis: Report of a case resembling dermatophytid in association with tinea pedis. International journal

    Yoshio Kawakami, Yumi Aoyama, Kotaro Tada, Kazushi Anzawa, Akiko Nishibu, Takashi Mochizuki, Shin Morizane

    The Journal of dermatology   48 ( 7 )   e320-e321   2021.7

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  • Updated allele frequencies of SERPINB7 founder mutations in Asian patients with Nagashima-type palmoplantar keratosis/keratoderma. International journal

    Yasutoshi Ito, Takuya Takeichi, Kenta Ikeda, Kana Tanahashi, Takenori Yoshikawa, Yuya Murase, Yoshinao Muro, Yoshio Kawakami, Yasuo Nakamura, Kanako Matsuyama, Jun Muto, Naoki Oiso, Shin Morizane, Kazumitsu Sugiura, Yasushi Suga, Mariko Seishima, Akira Kawada, Tomoo Ogi, Masashi Akiyama

    Journal of dermatological science   2021.6

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  • Hypothalamic Mass Detected in Langerhans Cell Histiocytosis.

    Ryosuke Takase, Yasuhiro Nakano, Shin Morizane, Fumio Otsuka

    Internal medicine (Tokyo, Japan)   60 ( 11 )   1795 - 1795   2021.6

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    DOI: 10.2169/internalmedicine.5946-20

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  • Spitz母斑と黒子様色素細胞母斑の隣接発生例 免疫染色によるROS1過剰発現とBRAFV600E変異蛋白の証明

    山下 珠代, 山崎 修, 高田 実, 谷口 恒平, 後藤 啓介, 森実 真

    西日本皮膚科   83 ( 3 )   266 - 267   2021.6

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    Language:Japanese   Publisher:日本皮膚科学会-西部支部  

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  • 悪性黒色腫の術後補助療法の選択についての検討

    水田 康生, 山崎 修, 杉原 悟, 森実 真, 加持 達弥

    西日本皮膚科   83 ( 3 )   275 - 275   2021.6

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    Language:Japanese   Publisher:日本皮膚科学会-西部支部  

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  • Cutaneous adult T-cell leukemia/lymphoma with granulomatous reaction. International journal

    Yuki Nakagawa, Yoshio Kawakami, Tomoko Kawamoto, Tomoko Miyake, Yoji Hirai, Osamu Yamasaki, Shin Morizane

    The Journal of dermatology   48 ( 6 )   e273-e274   2021.6

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  • ハンセン病患者に生じた有棘細胞癌

    安富 陽平, 山崎 修, 立花 宏太, 杉本 佐江子, 森実 真

    Skin Cancer   36 ( 1 )   71 - 75   2021.6

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    Language:Japanese   Publisher:(一社)日本皮膚悪性腫瘍学会  

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  • Spitz母斑と黒子様色素細胞母斑の隣接発生例 免疫染色によるROS1過剰発現とBRAFV600E変異蛋白の証明

    山下 珠代, 山崎 修, 高田 実, 谷口 恒平, 後藤 啓介, 森実 真

    西日本皮膚科   83 ( 3 )   266 - 267   2021.6

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  • 乾癬の生物学的製剤治療に対する結核対策実態の多施設共同調査

    金子 栄, 鶴田 紀子, 伊藤 宏太郎, 山口 和記, 宮城 拓也, 高橋 健造, 東 裕子, 森実 真, 野村 隼人, 山口 道也, 日野 亮介, 澤田 雄宇, 中村 元信, 大山 文悟, 大畑 千佳, 米倉 健太郎, 林 宏明, 柳瀬 哲至, 松阪 由紀, 杉田 和成, 菊池 智子, 三苫 千景, 中原 剛士, 古江 増隆, 岡崎 布佐子, 小池 雄太, 今福 信一, 西日本炎症性皮膚疾患研究会

    日本皮膚科学会雑誌   131 ( 6 )   1525 - 1532   2021.5

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    乾癬治療における生物学的製剤使用時の結核スクリーニングの現状について西日本の18施設を調査した。事前の検査ではinterferon gamma release assay(IGRA)が全施設で行われ、画像検査はCTが15施設、胸部レントゲンが3施設であった。フォローアップでは検査の結果や画像所見により頻度が異なっていた。全患者1,117例のうち、IGRA陽性で抗結核薬を投与されていた例は64例、IGRA陰性で抗結核薬を投与されていた例は103例であり、副作用を認めた患者は23例15%であった。これらの適切な検査と治療により、結核の発生頻度が低く抑えられていると考えられた。(著者抄録)

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  • Staphylococcal enterotoxin B- and lipopolysaccharide-induced toxic shock syndrome in a burn patient. International journal

    Osamu Yamasaki, Satoru Sugihara, Ai Kajita, Emi Yokoyama, Tomoko Miyake, Yoji Hirai, Shin Morizane

    The Journal of dermatology   48 ( 4 )   547 - 550   2021.4

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    Toxic shock syndrome (TSS) is caused by toxic shock syndrome toxin 1 or enterotoxins secreted by Staphylococcus aureus. Lipopolysaccharide (LPS) has also been shown to play a major role in the development of sepsis. Staphylococcal superantigens and LPS operate synergistically in conditioning cytokine release and lethal shock in mice. An 80-year-old woman was admitted because of a 20% mixed-depth flame burn. Despite two excisions and grafts, necrotic ulcers with methicillin-resistant Staphylococcus aureus (MRSA) colonization remained. On the 7th day after the operation, she developed shock with an erythematous rash. Blood examination revealed evidence of disseminated intravascular coagulation, and liver and renal dysfunction. A blood culture revealed a staphylococcal enterotoxin B (SEB)-producing strain of MRSA and Klebsiella pneumoniae. The septic symptoms were prolonged, but the condition gradually improved with extensive treatment. T-cell receptor analysis demonstrated a marked accumulation of SEB-mediated Vβ T cells. Stimulation of peripheral blood mononuclear cells in the recovery phase with SEB and LPS induced additive effects on tumor necrosis factor-α, interferon-γ, and interleukin-6 production. Although the present case did not fulfill the clinical criteria for TSS, the additive effects of SEB and LPS might have caused the severe septic shock.

    DOI: 10.1111/1346-8138.15729

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  • Two cases of severe congenital hypotrichosis caused by compound heterozygous mutations in the LSS gene. International journal

    Mami Murata, Ryota Hayashi, Yoshio Kawakami, Shin Morizane, Yutaka Shimomura

    The Journal of dermatology   48 ( 3 )   392 - 396   2021.3

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    It has recently been shown that bi-allelic mutations in the lanosterol synthase (LSS) gene, which was originally reported as a causative gene for congenital cataracts, underlie a non-syndromic form of hypotrichosis. Furthermore, it has also been revealed that mutations in the LSS gene can cause syndromic forms of hypotrichosis. To date, however, clear genotype-phenotype correlations have not completely been characterized. In this study, we identified two Japanese patients who had severe congenital hypotrichosis without any other associated findings. Their scalp hairs were extremely short and thin, and were able to be plucked easily. Observation of the plucked hairs showed aberrantly-miniaturized anagen hair follicles. Genetic analysis demonstrated that both patients carried bi-allelic mutations in the LSS gene in a compound heterozygote state. Our findings further underscore the crucial roles of the LSS gene in hair follicle development and hair growth in humans.

    DOI: 10.1111/1346-8138.15679

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  • A case of allergic contact dermatitis due to 3-glyceryl ascorbate in a skin-lightening lotion. International journal

    Yoshio Kawakami, Takatsune Umayahara, Yoji Hirai, Shin Morizane

    Contact dermatitis   2021.2

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    DOI: 10.1111/cod.13820

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  • Monoclonal Gammopathy of Undetermined Significanceを基礎疾患とし,難治性下腿潰瘍を伴った皮膚白血球破砕性血管炎の1例

    藤田 周作, 川上 佳夫, 三宅 智子, 池田 賢太, 山崎 悠, 高橋 正幸, 山崎 修, 森実 真

    皮膚科の臨床   63 ( 2 )   211 - 215   2021.2

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    Language:Japanese   Publisher:金原出版(株)  

    <文献概要>82歳,女性。6年前に両側下腿に紫斑が出現した。病理組織学的所見では皮膚白血球破砕性血管炎で,血液検査ではIgA-κ型のM蛋白血症を認めた。多発性骨髄腫は否定的で,monoclonal gammopathy of undetermined significanceと診断した。紫斑は自然に軽快し,無治療で経過観察していた。4ヵ月前より両側下肢全体に点状紫斑が出現した。プレドニゾロン30mg/日の経口投与で一旦改善するも,漸減終了後に再燃し,さらに両側下腿に難治性の潰瘍を発症した。自験例ではM蛋白血症に重症な皮膚症状を伴っており,Lipskerの提唱するmonoclonal gammopathy of cutaneous significanceに該当するものと考える。

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  • Case of tufted angioma treated successfully with tranilast, topical steroids and tacrolimus ointment. International journal

    Yuki Nakagawa, Yoji Hirai, Masatoshi Jinnin, Shin Morizane

    The Journal of dermatology   48 ( 2 )   e84-e85   2021.2

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  • Tattoo skin reaction as a skin manifestation of systemic sarcoidosis. International journal

    Tomoyuki Mukai, Dan Fujiwara, Tomoko Miyake, Shunichi Fujita, Shin Morizane, Yoshitaka Morita

    Modern rheumatology case reports   5 ( 1 )   167 - 171   2021.1

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    A 41-year-old man presented with itching of the skin surrounding his tattoos, blurred vision, fever, general fatigue, and arthralgia. Physical examination revealed skin bulges confined to the tattoo ink lines. Histological analyses of the skin revealed non-caseating granulomas surrounding the tattoo inks. Together with other clinical manifestations including uveitis, lymph nodes swelling, and elevated serum angiotensin-converting enzyme and lysozyme, he was diagnosed with systemic sarcoidosis. The administration of prednisolone alleviated the sarcoidosis-related symptoms, including skin changes. This case illustrates that skin changes on tattoos can be a presenting manifestation of systemic sarcoidosis and that skin biopsy is useful in early diagnosis.

    DOI: 10.1080/24725625.2020.1816645

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  • Coexistence of Mycobacterium ulcerans ssp. shinshuense and Mycobacterium avium in a patient with Buruli ulcer-compatible lesions. Reviewed International journal

    Shusaku Fujita, Yoshio Kawakami, Haruka Yamasaki, Satoru Sugihara, Tomoko Miyake, Yuji Miyamoto, Yoshihiko Hoshino, Norihisa Ishii, Osamu Yamasaki, Shin Morizane

    The Journal of dermatology   47 ( 11 )   e400-e401   2020.11

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    DOI: 10.1111/1346-8138.15542

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  • Familial nasal dermoid sinus cysts skipping generations. Reviewed International journal

    Kimiko Nishigaki, Osamu Yamasaki, Yoshio Kawakami, Minori Sasakura, Tomoko Miyake, Aiji Ohtsuka, Junko Kousogabe, Shin Morizane

    The Journal of dermatology   47 ( 10 )   e373-e375 - e375   2020.10

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    DOI: 10.1111/1346-8138.15497

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  • Classical Vohwinkel syndrome with heterozygous p.Asp66His mutation in GJB2 gene: Second Asian case. International journal

    Kenta Ikeda, Takuya Takeichi, Yasutoshi Ito, Yoshio Kawakami, Yuki Nakagawa, Seiko Naito, Osamu Yamasaki, Masashi Akiyama, Shin Morizane

    The Journal of dermatology   47 ( 10 )   e352-e354 - e354   2020.10

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    DOI: 10.1111/1346-8138.15513

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  • iPhone charger-induced chemical burn from overnight contact with sweat: Two cases. Reviewed International journal

    Yuki Nakagawa, Takafumi Uchida, Shin Morizane

    The Journal of dermatology   47 ( 10 )   1187 - 1190   2020.10

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    Smartphones have become essential devices in modern society. The coverage rate of smartphones in 2017 in Japan was 75% according to the Ministry of Internal Affairs and Communications. The iPhone is one of the most well-known smartphone brands. According to the manufacturer of iPhones (Apple), more than 200 million iPhones had been sold worldwide by 2017. These devices are often charged at night-time, especially while being used in bed. There are only three reports of smartphone charger-induced skin damage. We present two new cases of skin ulcers induced by an iPhone charger. The iPhone's "lightning cable" has electrodes outside, and we found that this can present a higher risk of causing a skin injury compared with other types of phone chargers. We also investigated the mechanism of the skin ulcers caused by the iPhone charger. The results indicated that these ulcers were chemical burns rather than an electrical injury or heat-induced burn.

    DOI: 10.1111/1346-8138.15475

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  • Solitary fi brous tumor of inguinal region displaying heterogeneous echogenicity and its correlation with histopathologic findings Reviewed

    Our Dermatology Online   2020.8

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  • Surgical site infection caused by Aeromonas hydrophila presenting as necrotizing soft tissue infection after esophagectomy. Reviewed International journal

    Osamu Yamasaki, Eizo Takahashi, Kazuyo Noda, Nobuhiko Kanaya, Shunsuke Tanabe, Yasuhiro Shirakawa, Shin Morizane

    The Journal of dermatology   47 ( 6 )   673 - 676   2020.6

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    Several virulence factors of Aeromonas such as hemolysin, proteases and lipases have been characterized. The relationship between these virulence factors and disease remains unclear. A 71-year-old man underwent thoracoscopic esophagectomy, lymph node dissection and Roux-en-Y reconstruction for esophageal cancer. On postoperative day 1, redness around the wound on the thoracic abdominal wall gradually enlarged and necrosis became apparent with septic shock. Necrotizing soft tissue infection was suspected and emergency surgical debridement was performed. Blood and wound cultures were positive for Aeromonas hydrophila. The strain was found to have hemolytic activity, proteolytic activity and extremely high elastolytic activity. In addition, the strain actively produced elastolytic metalloprotease, which may contribute to extensive tissue necrosis.

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  • イピリムマブ投与後にACTH欠損症を発症した悪性黒色腫の1例

    篠倉 美理, 藤本 裕子, 神野 泰輔, 山崎 修, 森実 真

    皮膚科の臨床   62 ( 7 )   1109 - 1112   2020.6

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    <文献概要>82歳,男性。悪性黒色腫Stage IIIC(T4bN2bM0),BRAF遺伝子変異なし。イピリムマブ投与開始9週目頃から食思不振・全身倦怠感が出現し入院した。夏季の非特異的症状であり,熱中症との鑑別を要したが,副腎皮質刺激ホルモン(ACTH),コルチゾールが低値であり,ACTH欠損による二次性副腎不全と診断した。ヒドロコルチゾン内服で症状は改善したが,その後ACTH分泌能は回復していない。イピリムマブ誘発性下垂体炎/下垂体機能障害は,非特異的症状での発症も多く,ときに早期診断が困難である。ニボルマブとの併用療法の適応追加に伴い,今後イピリムマブの使用が増えることが予想され,注意が必要である。

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  • 在宅医と連携した進行期悪性黒色腫

    石井 芙美, 山崎 修, 加持 達弥, 川上 佳夫, 森実 真, 片山 英樹, 國末 充央, 武藤 純, 小森 栄作

    Skin Cancer   35 ( 1 )   1 - 5   2020.6

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    近年、免疫チェックポイント阻害剤やBRAF+MEK阻害剤などの進行期悪性黒色腫に対する新規治療が生存期間の延長に寄与している。さらに進行した場合でも緩和治療を行いながら、積極的な治療介入も可能である。しかし緩和ケア病棟など緩和ケアを専門に提供する病院では原病の新規治療が困難な場合がある。がん診療専門病院と在宅医が連携することにより悪性黒色腫の新規治療をしながら在宅療養することも1つの選択肢となる。当科で経験した新規治療中で、訪問診療専門クリニックと連携した4例について検討した。男性3名、女性1名、年齢は36〜84歳、全例病期IV、在宅医紹介時の治療は、BRAF+MEK阻害剤1例、ニボルマブ2例、イピリブマブ1例、在宅診療期間は24〜84日であった。1例は当院、3例は自宅での看取りとなった。在宅診療の介入パターンはさまざまであるが、患者の希望に沿う進行期の治療が提供できた。(著者抄録)

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  • The aim of the measurement of Epstein-Barr virus DNA in hydroa vacciniforme and hypersensitivity to mosquito bites. Reviewed International journal

    Tomoko Miyake, Keiji Iwatsuki, Yoji Hirai, Takenobu Yamamoto, Toshihisa Hamada, Kazuyasu Fujii, Hideaki Imamura, Shin Morizane

    Journal of medical virology   2020.4

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    Epstein-Barr virus (EBV) DNA load in the blood increases in posttransplant lymphoproliferative disorders and chronic active EBV infection. In this report, we analyzed the EBV DNA load in the peripheral blood mononuclear cells (PBMCs) and plasma of patients with hydroa vacciniforme (HV) and/or hypersensitivity to mosquito bites (HMB) to understand the clinical significance of EBV DNA load. All 30 patients showed high DNA loads in the PBMCs over the cut-off level. Of 16 plasma samples, extremely high in two samples obtained from patients with hemophagocytic lymphohistiocytosis (HLH). The amount of cell-free DNA in plasma was correlated to the serum levels of lactate dehydrogenase and inversely correlated to platelet counts. These results indicate that the EBV DNA load in PBMCs can provide one of the diagnostic indicators for HV and HMB and marked elevation of cell-free EBV DNA in plasma might be related to cytolysis such as that observed in HLH.

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  • Atezolizumab-induced lichen planus pemphigoides in a patient with metastatic non-small-cell lung cancer. Reviewed International journal

    Haruka Senoo, Yoshio Kawakami, Emi Yokoyama, Osamu Yamasaki, Shin Morizane

    The Journal of dermatology   47 ( 4 )   e121-e122 - e122   2020.4

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  • Mycobacterium tuberculosis infection in psoriatic patients treated with biologics: Real-world data from 18 Japanese facilities. Reviewed International journal

    Sakae Kaneko, Noriko Tsuruta, Kazuki Yamaguchi, Takuya Miyagi, Kenzo Takahashi, Yuko Higashi, Shin Morizane, Hayato Nomura, Michiya Yamaguchi, Ryosuke Hino, Yu Sawada, Motonobu Nakamura, Bungo Ohyama, Chika Ohata, Kentaro Yonekura, Hiroaki Hayashi, Tetsuji Yanase, Yuki Matsuzaka, Kazunari Sugita, Satoko Kikuchi, Chikage Mitoma, Takeshi Nakahara, Masutaka Furue, Fusako Okazaki, Yuta Koike, Shinichi Imafuku

    The Journal of dermatology   47 ( 2 )   128 - 132   2020.2

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    Although rare, tuberculosis has been reported with biologic treatment against psoriasis in Japan, a tuberculosis medium-burden country. Mycobacterial infection often develops after a long incubation period and might not have been adequately identified in clinical trials or post-marketing surveillance. To determine the real-world incidence of tuberculosis in psoriatic patients treated with biologics, we conducted a retrospective, multicenter, observational study in 18 facilities in Western Japan. Psoriatic patients who visited a participating facility between 2010 and March 2017 and received biologic reagents were enrolled. Information on sex, age at first biologic treatment, results of interferon-γ release assay (IGRA) for Mycobacterium tuberculosis, treatment history with isoniazid, and onset of active and/or latent tuberculosis was collected. A total of 1117 patients (830 men and 287 women) were enrolled. The mean duration of biologic treatment was 3.54 years. Sixty-five patients (5.8%) showed positive IGRA results at screening. Active tuberculosis developed in two patients after the administration of tumor necrosis factor inhibitors (both involved miliary tuberculosis). Latent tuberculosis was observed in two patients treated with anti-interleukin-12/23p40 antibody. The incidence rate of tuberculosis, including latent tuberculosis, in this survey was 0.36%. Although the incidence rate of tuberculosis was low considering the observation period of biologic treatment, active tuberculosis was found in both the screening-negative group and a screening-positive subject after isoniazid prophylaxis (both miliary tuberculosis), concluding that negative screening or isoniazid treatment does not always assure that an individual has no tuberculosis. Hence, dermatologists still need to pay careful attention to tuberculosis at every patient visit.

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  • Multifaceted Analyses of Epidermal Serine Protease Activity in Patients with Atopic Dermatitis. Reviewed International journal

    Hayato Nomura, Mutsumi Suganuma, Takuya Takeichi, Michihiro Kono, Yuki Isokane, Ko Sunagawa, Mina Kobashi, Satoru Sugihara, Ai Kajita, Tomoko Miyake, Yoji Hirai, Osamu Yamasaki, Masashi Akiyama, Shin Morizane

    International journal of molecular sciences   21 ( 3 )   2020.1

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    The serine proteases kallikrein-related peptidase (KLK) 5 and KLK7 cleave cell adhesion molecules in the epidermis. Aberrant epidermal serine protease activity is thought to play an important role in the pathogenesis of atopic dermatitis (AD). We collected the stratum corneum (SC) from healthy individuals (n = 46) and AD patients (n = 63) by tape stripping and then measuring the trypsin- and chymotrypsin-like serine protease activity. We also analyzed the p.D386N and p.E420K of SPINK5 variants and loss-of-function mutations of FLG in the AD patients. The serine protease activity in the SC was increased not only in AD lesions but also in non-lesions of AD patients. We found, generally, that there was a positive correlation between the serine protease activity in the SC and the total serum immunoglobulin E (IgE) levels, serum thymus and activation-regulated chemokine (TARC) levels, and peripheral blood eosinophil counts. Moreover, the p.D386N or p.E420K in SPINK5 and FLG mutations were not significantly associated with the SC's serine protease activity. Epidermal serine protease activity was increased even in non-lesions of AD patients. Such activity was found to correlate with a number of biomarkers of AD. Further investigations of serine proteases might provide new treatments and prophylaxis for AD.

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  • Simultaneous development of IgA vasculitis and eosinophilic granulomatosis with polyangiitis. International journal

    Yosuke Asano, Yoshinori Matsumoto, Tatsuhiko Miyazaki, Akihiro Ishizu, Shin Morizane, Keigo Hayashi, Yuriko Yamamura, Sumie Hiramatsu, Yoshia Miyawaki, Michiko Morishita, Keiji Ohashi, Haruki Watanabe, Katsue Sunahori Watanabe, Tomoko Kawabata, Ken-Ei Sada, Hirofumi Makino, Jun Wada

    Modern rheumatology case reports   4 ( 1 )   63 - 69   2020.1

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    Immunoglobulin A (IgA) vasculitis (IgAV) is a small vessel vasculitis presenting cutaneous purpura, arthralgias and/or arthritis, acute enteritis and glomerulonephritis caused by deposition of the IgA1-mediated immune complex. Eosinophilic granulomatosis with polyangiitis (EGPA) is an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) characterised by eosinophil-rich and granulomatous inflammation in small to medium-sized vessels. Both IgAV and EGPA are classified as autoimmune systemic vasculitis, but the pathogenesis of immune complex-mediated IgAV and that of pauci-immune EGPA are different. Here we report a rare case of simultaneous development of IgAV and EGPA presenting palpable purpura and numbness in a patient with a history of asthma. Histological examination revealed leukocytoclastic vasculitis with deposition of IgA, IgM and C3 in the upper dermis and necrotising vasculitis with eosinophilic infiltration and granulomatous formation in the lower dermis and subcutaneous fat, indicating the existence of IgAV and EGPA. Our case provides evidence of concurrent development of two different types of vasculitis, which may affect disease-associated complications, therapeutic strategy and prognosis.

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  • Serum 5-S-cysteinyl-dopa levels as a predictive marker for the efficacy of nivolumab in advanced malignant melanoma. Reviewed International journal

    Hiroshi Umemura, Tatsuya Kaji, Kota Tachibana, Shin Morizane, Osamu Yamasaki

    The International journal of biological markers   34 ( 4 )   414 - 420   2019.12

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    PURPOSE: With the recent developments in novel molecular targeted therapy such as immune-checkpoint blockades, serine/threonine-protein kinase B-Raf, and mitogen-activated protein kinase kinase inhibitors, the prognosis of advanced malignant melanoma has been improving. 5-S-cysteinyl-dopa (5-S-CD), a precursor of pheomelanin, has been previously revealed to be a useful biomarker for advanced-stage malignant melanoma, especially in patients with distant metastases. Here, we aimed to assess and compare the utility of serum 5-S-CD and lactate dehydrogenase levels as markers for predicting the effects of nivolumab in advanced malignant melanoma. METHODS: Baseline serum 5-S-CD and lactate dehydrogenase levels in patients with unresectable stage IIIC and IV malignant melanoma treated with nivolumab (n = 21) were analyzed to determine their utility as predictive markers for survival. We also analyzed the prognostic value of these markers among patients with only stage IV malignant melanoma (n = 17). RESULTS: Our analysis showed that patients with baseline serum 5-S-CD levels >25.0 nmol/L had significantly poor prognosis. In contrast, serum lactate dehydrogenase levels at the upper limit of the normal range did not exhibit such changes. CONCLUSIONS: Serum 5-S-CD levels have the potential to be an excellent predictive marker for the efficacy of nivolumab therapy in patients with advanced malignant melanoma.

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  • The expression of cell adhesion molecule 1 and its splicing variants in Sézary cells and cell lines from cutaneous T-cell lymphoma. Reviewed International journal

    Mari Yamaguchi, Shin Morizane, Toshihisa Hamada, Tomoko Miyake, Makoto Sugaya, Hiroaki Iwata, Kazuyasu Fujii, Rie Haramoto-Shiratsuki, Yuki Nakagawa, Mayumi Miura, Koichi Ohshima, Kazuhiro Morishita, Takahide Takahashi, Masahide Imada, Ken Okada, Jiro Uehara, Junko Sowa-Osako, Keiji Iwatsuki

    The Journal of dermatology   46 ( 11 )   967 - 977   2019.11

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    Cell adhesion molecule 1 (CADM1) is aberrantly expressed by T-cell neoplasms such as adult T-cell leukemia/lymphoma (ATLL) and mycosis fungoides (MF). We studied the expression of CADM1 and its splicing variants in Sézary syndrome (SS), MF, other cutaneous T-cell lymphoma (CTCL), and cell lines derived from T- and B-cell lymphomas. Soluble CADM1 was measured in the patients' sera. CADM1+ cells in the blood and skin lesions were examined by flow cytometry and immunostaining, respectively. Soluble CADM1 was measured by ELISA, and the splicing variants of CADM1 transcripts were determined by reverse transcriptase-polymerase chain reaction, followed by sequencing. As a result, circulating CADM1+ cells were significantly increased in seven out of 10 patients with SS, ranging from 7.9% to 74.5% of the CD3+CD4+ fractions (median 33.7%; cut-off value 6.5%). The percentages of CADM1+ cells were usually less than those of circulating Sézary cells. CADM1 was expressed, to various degrees, in six of nine T-cell lines derived from SS, MF, ATLL, and anaplastic large cell lymphoma (ALCL), but negative in B-cell lymphoma-derived cell lines. CADM1+ cells were present in the skin infiltrates of MF, SS, ATLL and ALCL. Serum levels of soluble CADM1 were not significantly elevated in SS/MF. Three major splicing variants of CADM1 expressed by neoplastic T-cells contained different combinations of the exons 7, 8, 9 and 11, including a putative oncogenic variant composed of exons 7-8-9-11. In conclusion, CADM1 is frequently expressed in Sézary cells and cell lines from CTCL.

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  • Single institutional experience of radiation therapy for angiosarcoma of the scalp without cervical lymph node metastases: Impact of concurrent chemoradiation with maintenance chemotherapy using taxanes on patient prognosis. Reviewed International journal

    Hiroki Ihara, Tatsuya Kaji, Kuniaki Katsui, Tomoko Miyake, Takahiro Waki, Norihisa Katayama, Hidenobu Matsuzaki, Osamu Yamasaki, Masahiro Kuroda, Shin Morizane, Susumu Kanazawa

    Molecular and clinical oncology   11 ( 5 )   498 - 504   2019.11

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    Cutaneous angiosarcoma is a rare aggressive malignant tumor. Concurrent chemoradiation (CCRT) with maintenance chemotherapy using taxanes is one of the primary treatments. The aim of the present study was to retrospectively analyze the efficacy of CCRT with maintenance chemotherapy using taxanes in localized angiosarcoma of the scalp without cervical lymph node metastases. A total of 19 patients treated with radiation therapy for localized angiosarcomas of the scalp without cervical lymph node metastases were enrolled. The overall survival (OS), progression-free survival (PFS), and local control (LC) rates were calculated using Kaplan-Meier analysis. Univariate analyses were performed for various potential prognostic factors for OS, PFS, and LC. The median radiation dose was 70 Gy (range, 60-70 Gy), and the fractional dose was 2 Gy. Radiation therapy alone, radiation therapy + interleukin-2, surgery + CCRT with maintenance chemotherapy, CCRT with maintenance chemotherapy, and CCRT without maintenance chemotherapy were administered to 2, 4, 2, 9 and 2 patients, respectively. The 1- and 3-year OS, PFS, and LC rates were 88 and 52%, 47 and 33%, and 74 and 56%, respectively. CCRT with maintenance chemotherapy and surgery were significant prognostic factors for PFS (P=0.036 and 0.025, respectively). Therefore, CCRT with maintenance chemotherapy using taxanes might be effective in treating localized angiosarcomas of the scalp without cervical lymph node metastases.

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  • Pediatric-onset annular pustular psoriasis in a patient with Down syndrome. Reviewed International journal

    Anri Morita, Yoshio Kawakami, Tatsuya Kaji, Yoji Hirai, Tomoko Miyake, Masayuki Takahashi, Osamu Yamasaki, Kazumitsu Sugiura, Shin Morizane

    The Journal of dermatology   46 ( 10 )   e367-e368   2019.10

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  • TNF-α and IL-17A induce the expression of lympho-epithelial Kazal-type inhibitor in epidermal keratinocytes. Reviewed International journal

    Satoru Sugihara, Saeko Sugimoto, Kota Tachibana, Mina Kobashi, Hayato Nomura, Tomoko Miyake, Yoji Hirai, Osamu Yamasaki, Shin Morizane

    Journal of dermatological science   96 ( 1 )   26 - 32   2019.10

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    BACKGROUND: Serine proteases have important roles in skin barrier function and desquamation, and the aberrant expression or the dysfunction of serine proteases is associated with the pathogenesis of skin diseases. Serine protease activities are tightly regulated by serine proteases such as kallikrein-related peptidases (KLKs) and serine protease inhibitors such as lympho-epithelial Kazal-type related inhibitor (LEKTI). For a better understating of diseases' pathogenesis, the regulation mechanism of serine proteases and the inhibitors' expression in epidermal keratinocytes must be clarified. OBJECTIVES: To investigate the effects of the cytokines on the expression of LEKTI in epidermal keratinocytes. METHODS: Normal human epidermal keratinocytes (NHEKs) were stimulated with panels of inflammatory cytokines. The expression of serine protease inhibitors was analyzed using quantitative real-time PCR and ELISA. LEKTI expression in normal human skin and lesions from psoriasis or atopic dermatitis (AD) were analyzed by immunohistochemically and tape-stripping. Trypsin- and chymotrypsin-like serine protease activities in culture supernatants were measured by using specific substrates. RESULTS: TNF-α and IL-17A significantly induced the expression of LEKTI in NHEKs. The immunohistochemical and tape-stripping analysis revealed that psoriatic skin lesions had higher LEKTI expression compared to normal skin and AD lesions. Trypsin- and chymotrypsin-like protease activities in the culture media were upregulated 3-5 days later but attenuated 6-7 days later period by these cytokines. CONCLUSIONS: In epidermal keratinocytes, the Th1&Th17 cytokines TNF-α and IL-17A induce the expression of serine protease inhibitor LEKTI, and it might occur to suppress the increase in the serine protease activities under inflammation.

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  • Clinical manifestations of skin, lung and muscle diseases in dermatomyositis positive for anti-aminoacyl tRNA synthetase antibodies. Reviewed International journal

    Hiroko Fukamatsu, Yoji Hirai, Tomoko Miyake, Tatsuya Kaji, Shin Morizane, Emi Yokoyama, Toshihisa Hamada, Takashi Oono, Yoshinobu Koyama, Seiichiro Norikane, Keiji Iwatsuki

    The Journal of dermatology   46 ( 10 )   886 - 897   2019.10

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    Patients with dermatomyositis positive for anti-aminoacyl tRNA synthetase (ARS) antibodies, also known as antisynthetase syndrome (ASS), frequently present with mechanic's hand and interstitial lung disease (ILD). We first screened the antibody profiles of 59 patients with dermatomyositis, and then examined the cutaneous, muscular and pulmonary manifestations characteristic for patients with ASS. The anti-ARS antibodies Jo-1, PL-7, PL-12, EJ and KS, along with antibodies to TIF1-γ, MDA5 and Mi-2, were examined. Among the 59 patients, 20, 21, 15 and three patients were classified into the ASS, non-ASS, myositis-specific antibody-negative and unknown groups, respectively. Five of 16 patients (31%) with ASS had six relatives with a history of collagen diseases, within the second degree of relationship, including two cases of dermatomyositis (vs the non-ASS group, P = 0.018). Patients with ASS more frequently presented with fever and arthralgia, and had elevated levels of C-reactive protein. Nine of the 11 finger lesions (82%) clinically diagnosed as mechanic's hands showed a psoriasiform tissue reaction. ILD was observed in 19 of 20 patients (95%) with ASS, and eight of 21 patients (38%) in the non-ASS group, in which six patients possessed anti-MDA5 antibody. Patients with ASS showed higher serum levels of muscle enzymes, and four of 12 patients (33%) had fasciitis-dominant myopathy, while only one of 11 patients (9%) in the non-ASS group had fasciitis-dominant myopathy. Patients with ASS often present with a psoriasiform tissue reaction in the hand lesions and fasciitis-dominant myopathy, and the relatives of those with ASS are at high risk for collagen diseases.

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  • Clinical manifestations of skin, lung and muscle diseases in dermatomyositis positive for anti-aminoacyl tRNA synthetase antibodies. Reviewed

    Fukamatsu H, Hirai Y, Miyake T, Kaji T, Morizane S, Yokoyama E, Hamada T, Oono T, Koyama Y, Norikane S, Iwatsuki K.

    The Journal of Dermatology   2019.8

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  • 有茎広背筋皮弁で再建した冠動脈ステント留置後の右肩甲部放射線性皮膚潰瘍

    森田 安理, 石井 芙美, 川上 佳夫, 加持 達弥, 竹原 彩, 大塚 正樹, 山崎 修, 森実 真

    皮膚科の臨床   61 ( 9 )   1387 - 1390   2019.8

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    <文献概要>75歳,男性。狭心症で冠動脈ステント留置後3ヵ月目頃より右肩甲部に痒みを伴う紅斑が出現し,1年後に潰瘍化した。デブリードマンと外用療法で約1年半加療されるも難治であったため,精査・加療目的に当科を紹介受診した。初診時,右肩甲部に3×3cm大の深い潰瘍があり周囲8×7cm大の範囲に板状硬結,暗褐色色素沈着と血管拡張を認めた。MRIでは筋層まで達していた。冠動脈造影による放射線性皮膚潰瘍と考え,潰瘍,硬結を切除,有茎広背筋皮弁術を施行した。術後は機能面,整容面ともに良好であった。右肩甲部皮膚潰瘍の患者に遭遇した場合,冠動脈造影の既往を問診することが重要である。また再建方法としては有茎広背筋皮弁術が治療選択肢となる。

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  • Two cases of metallic foreign bodies hidden in recalcitrant wounds unexpectedly detected using magnetic resonance imaging. Reviewed International journal

    Kota Tachibana, Hiroshi Umemura, Shin Morizane, Osamu Yamasaki

    The Journal of dermatology   46 ( 6 )   e195-e196 - e196   2019.6

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  • アトピー性皮膚炎と表皮角化細胞産生カリクレイン関連ペプチダーゼ

    森実 真

    岡山医学会雑誌   131 ( 1 )   17 - 21   2019.4

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    過剰なカリクレイン関連ペプチダーゼ(KLK)の発現は正常な表皮バリア機能を崩壊させ、アトピー性皮膚炎(AD)の抗原となりうる外来物質が表皮内に容易に侵入し、Th2サイトカインを主体とするアレルギー性皮膚炎を誘導すると考えられる。皮膚において、KLK5、KLK6、KLK7、KLK8、KLK10、KLK11、KLK13およびKLK14の蛋白質レベルでの発現が確認されており、これらの表皮角化細胞産生KLKとADとの関連性について概説した。

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  • Cross-sectional multicenter observational study of psoriatic arthritis in Japanese patients: Relationship between skin and joint symptoms and results of treatment with tumor necrosis factor-α inhibitors. Reviewed

    Tsuruta N, Narisawa Y, Imafuku S, Ito K, Yamaguchi K, Miyagi T, Takahashi K, Fukamatsu H, Morizane S, Koketsu H, Yamaguchi M, Hino R, Nakamura M, Ohyama B, Ohata C, Kuwashiro M, Sato T, Saito K, Kaneko S, Yonekura K, Hayashi H, Yanase T, Morimoto K, Sugita K, Yanagihara S, Kikuchi S, Mitoma C, Nakahara T, Furue M, Okazaki F.

    The Journal of Dermatology   2019.3

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  • An effective and promising treatment with adalimumab for impetigo herpetiformis with postpartum flare-up. Reviewed

    Yamashita T, Hamada T, Maruta Y, Kajita A, Hirai Y, Morizane S, Watanabe S, Sugiura K, Iwatsuki K.

    International Journal of Dermatology   58 ( 3 )   350 - 353   2019.3

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    DOI: 10.1111/ijd.14141.

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  • An effective and promising treatment with adalimumab for impetigo herpetiformis with postpartum flare-up. Reviewed International journal

    Tamayo Yamashita, Toshihisa Hamada, Yuka Maruta, Ai Kajita, Yoji Hirai, Shin Morizane, Soichiro Watanabe, Kazumitsu Sugiura, Keiji Iwatsuki

    International journal of dermatology   58 ( 3 )   350 - 353   2019.3

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  • 【DIHS】臨床例 DIHS発症後皮膚にGVHD様反応が長期に続いた例

    三宅 智子, 木村 摩耶, 花山 宜久, 青山 裕美, 岩月 啓氏, 森実 真

    皮膚病診療   41 ( 3 )   245 - 248   2019.3

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    <文献概要>症例のポイント ●drug-induced hypersensitivity syndrome(DIHS)発症後,長期にgraft versushost disease like erythroderma(GVHD)様の皮膚症状が続いた.●GVHD様の皮膚症状に対してプレドニゾロン(PSL)のみでは軽快しないため,他の免疫抑制薬を併用し皮膚症状は軽快した.●免疫抑制薬使用中に脳内にEBV陽性びまん性大細胞型B細胞リンパ腫を生じた.

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  • Cross-sectional multicenter observational study of psoriatic arthritis in Japanese patients: Relationship between skin and joint symptoms and results of treatment with tumor necrosis factor-α inhibitors. Reviewed International journal

    Noriko Tsuruta, Yutaka Narisawa, Shinichi Imafuku, Kotaro Ito, Kazuki Yamaguchi, Takuya Miyagi, Kenzo Takahashi, Hiroko Fukamatsu, Shin Morizane, Hideki Koketsu, Michiya Yamaguchi, Ryosuke Hino, Motonobu Nakamura, Bungo Ohyama, Chika Ohata, Maki Kuwashiro, Toshihiro Sato, Kanami Saito, Sakae Kaneko, Kentaro Yonekura, Hiroaki Hayashi, Tetsuji Yanase, Kenichi Morimoto, Kazunari Sugita, Shigeto Yanagihara, Satoko Kikuchi, Chikage Mitoma, Takeshi Nakahara, Masutaka Furue, Fusako Okazaki

    The Journal of dermatology   46 ( 3 )   193 - 198   2019.3

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    Psoriatic arthritis (PsA) is an inflammatory arthritis with as yet unclear pathophysiology. This retrospective, multicenter, cross-sectional study was conducted in 19 facilities in western Japan and aimed to identify patients' characteristics and factors that affect the results of treatment with biologic agents. Of 2116 patients with psoriasis, 285 (13.5%) had PsA. Skin manifestations preceded joint manifestations in 69.8%, the onset was simultaneous in 17.2%, whereas PsA preceded skin manifestations in 2.5%. Peripheral arthritis was most common, occurring in 73.7%, compared with axial disease in 21.8%, enthesitis in 23.5% and dactylitis in 35.4%. Patients with severe skin manifestations were significantly younger at onset (P = 0.02) and more frequently had axial disease (P < 0.01). Biologic agents were used in 206 patients (72.3%), anti-tumor necrosis factor (TNF)-α antibodies being prescribed first to 157 of them. Anti-TNF-α antibodies were continued by 105 participants and discontinued by 47, the remaining five patients being lost to follow up. Patients who discontinued anti-TNF-α antibodies were significantly older than those who continued (55 vs 51 years, P = 0.04) and significantly older at onset of joint manifestations (50 vs 44 years, P = 0.01). Multivariate analysis revealed that patients over 50 years significantly more frequently terminated anti-TNF-α antibodies (P < 0.01). In conclusion, patients with PsA and severe skin manifestations have earlier onset and axial disease, which seriously impacts on quality of life. Anti-TNF-α antibodies were generally effective enough to continue but less so in patients aged over 50 years. Further detailed research is needed.

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  • The Role of Kallikrein-Related Peptidases in Atopic Dermatitis. Reviewed

    Shin Morizane

    Acta medica Okayama   73 ( 1 )   1 - 6   2019.2

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    Excessive protease activity is a characteristic abnormality that affects the epidermal barrier in patients with atopic dermatitis (AD). Kallikrein-related peptidases (KLKs) are excessively expressed in AD lesions, and it is suggested that the abnormal action of KLKs is involved in the skin barrier dysfunction in AD. In other words, overexpressed KLKs disrupt the normal barrier function, and due to that breakdown, external substances that can become antigens of AD easily invade the epidermis, resulting in dermatitis, coupled with the induction of Th2 cytokines. Further investigations are required to elucidate the role of KLKs in AD; this knowledge could contribute to the design of new therapeutic and prophylactic drugs for AD.

    DOI: 10.18926/AMO/56452

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  • Autophagy in malnutrition-associated dermatoses. Reviewed

    Hirai Y, Miyake T, Hamada T, Yamasaki O, Morizane S, Mori T, Iwatsuki K.

    The Journal of Dermatology   46 ( 1 )   43 - 47   2019.1

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    DOI: 10.1111/1346-8138.14694.

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  • Two cases of metallic foreign bodies hidden in recalcitrant wounds unexpectedly detected using magnetic resonance imaging. Reviewed

    Tachibana K, Umemura H, Morizane S, Yamasaki O

    The Journal of Dermatology   2019.1

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    DOI: 10.1111/1346-8138.14756.

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  • A case of malignant melanoma associated with polymyositis treated with immune checkpoint inhibitors Reviewed

    Nomura, H., Yamasaki, O., Kaji, T., Wakabayashi, H., Miyawaki, Y., Morizane, S.

    Nishinihon Journal of Dermatology   81 ( 5 )   396 - 400   2019.1

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    DOI: 10.2336/nishinihonhifu.81.396

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  • Autophagy in malnutrition-associated dermatoses. Reviewed International journal

    Yoji Hirai, Tomoko Miyake, Toshihisa Hamada, Osamu Yamasaki, Shin Morizane, Tatsuhiko Mori, Keiji Iwatsuki

    The Journal of dermatology   46 ( 1 )   43 - 47   2019.1

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    Malnutrition-associated dermatoses including necrolytic migratory erythema (NME) and pellagra share common clinicopathological features; in particular, necrolytic changes in the upper epidermis. Here, we report the involvement of autophagy in the development of necrolysis in three patients with malnutrition-associated dermatoses. First, we examined an autophagy-specific molecule, microtubule-associated protein light chain 3 (LC3), using a monoclonal antibody. LC3 was strongly expressed in the granular layers of the active border, and less intensely observed in the perilesional areas. Little LC3 staining or only background levels were observed in control skin diseases including atopic dermatitis (n = 4), psoriasis vulgaris (n = 3), basal cell carcinoma with amyloid deposits (n = 3) and squamous cell carcinoma (n = 3). Electron microscopic observations revealed the presence of autophagosome-like structures in the necrolytic areas. No apoptotic signals were observed in the necrolytic lesion using the terminal deoxynucleotidyl transferase dUTP nick end labeling method. Epidermal Langerhans cells determined by anti-CD1a antibody were markedly decreased in number. Our observations suggest the possibility that malnutrition-associated necrolysis, as exemplified by NME and pellagra, may be induced by autophagy.

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  • Papuloerythroderma-like cutaneous involvement of a CD62L- subclone of T-cell prolymphocytic leukemia. Reviewed International journal

    Yuki Nakagawa, Toshihisa Hamada, Mayuko Matsuda, Taisuke Kanno, Takumi Kondo, Takahide Takahashi, Toshiyuki Watanabe, Ken Okada, Toru Kawakami, Tomoko Miyake, Shin Morizane, Keiji Iwatsuki

    The Journal of dermatology   46 ( 1 )   65 - 69   2019.1

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    We report the case of an 88-year-old Japanese man with erythrodermic involvement of T-cell prolymphocytic leukemia (T-PLL). He had a history of pharyngeal diffuse large B-cell lymphoma successfully treated with polychemotherapy including cyclophosphamide and epirubicin, 6 years before the current illness. He presented with numerous reddish, coalescing, flat-topped papules on the trunk and extremities, sparing the skin folds of the abdomen, the features of which mimicked those of papuloerythroderma. Immunohistochemistry showed perivascular and epidermotropic infiltration of CD3+ CD4+ T cells in the cutaneous lesion. However, flow cytometric analysis revealed that the skin infiltrating T cells were negative for surface CD4, and that CD3+ CD4- CD8- cells made up 92% of the T-cell fraction of peripheral blood. The circulating atypical T cells had a round or oval nucleus and prominent nucleoli, and the deletion of chromosomes 6q, 13 and 17. These cytological profiles were consistent with those of T-PLL and distinct from those of Sézary cells. The same T-cell clone was detected in the cutaneous lesion and peripheral blood, but the expression of CD62L was absent in the skin infiltrates and present in the circulating cells. No specific mutation was detected in STAT3 or STAT5B. Although low-dose oral etoposide had a beneficial effect on the skin rash, a fatal crisis of marked leukocytosis (169 × 103 /μL) occurred 19 months after the illness onset. CD62L-leukemic cells of T-PLL may infiltrate the skin to form papuloerythroderma-like cutaneous lesions.

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  • Toll-like receptor signalling induces the expression of serum amyloid A in epidermal keratinocytes and dermal fibroblasts. International journal

    S Morizane, A Kajita, K Mizuno, T Takiguchi, K Iwatsuki

    Clinical and experimental dermatology   44 ( 1 )   40 - 46   2019.1

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    BACKGROUND: Toll-like receptors (TLRs) play critical roles in innate immune response by sensing pathogen- or damage-associated molecular patterns. Epidermal keratinocytes and dermal fibroblasts also produce proinflammatory cytokines and chemokines under stimulation with TLR ligands. Serum amyloid A (SAA) is an essential factor in the pathogenesis of secondary amyloidosis, and also has immunomodulatory functions. SAA are produced mainly by hepatocytes but also by a variety of cells, including immune cells, endothelial cells, synoviocytes, and epidermal keratinocytes. However, SAA expression in human dermal fibroblasts has not been shown to date. AIM: To investigate the effect of TLR ligands on SAA expression in epidermal keratinocytes and dermal fibroblasts. METHODS: We investigated whether TLR ligands induce the expression of SAA in normal human epidermal keratinocytes (NHEKs) and normal human dermal fibroblasts (NHDFs) by real-time quantitative PCR and ELISA. The effect of SAA on its own expression in NHDFs was also studied. RESULTS: SAA expression was induced via nuclear factor-κB by TLR1/2, 3, 5 and 2/6 ligands in NHEKs. In NHDFs, TLR1/2 and TLR2/6 ligands increased SAA expression. SAA further induced its own expression via TLR1/2 and NF-κB in NHDFs, as previously reported for NHEKs. CONCLUSIONS: Our results provide new evidence that the skin's innate immune response contributes to the production of SAA, which might lead to an increased risk of systemic complications such as secondary amyloidosis of recessive dystrophic epidermolysis bullosa.

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  • Toll-like receptor signaling induces the expression of lympho-epithelial Kazal-type inhibitor in epidermal keratinocytes. Invited Reviewed International journal

    Saeko Sugimoto, Shin Morizane, Hayato Nomura, Mina Kobashi, Satoru Sugihara, Keiji Iwatsuki

    Journal of dermatological science   92 ( 2 )   181 - 187   2018.11

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    BACKGROUND: Lympho-epithelial Kazal-type inhibitor (LEKTI) tightly controls the activities of serine proteases such as kallikrein-related peptidase (KLK) 5 and KLK7 in the epidermis. LEKTI is known to be an essential molecule for the epidermal skin barrier, as demonstrated by SPINK5 nonsense mutation, which results in Netherton syndrome. Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns or damage-associated molecular patterns and produce inflammatory cytokines, chemokines, and antimicrobial peptides. However, the effect of TLR signaling on the expression of LEKTI is not clear. OBJECTIVE: To investigate whether TLR signaling can affect expression of LEKTI in epidermal keratinocytes. METHODS: We stimulated a panel of TLR ligands and investigated the expression of LEKTI in normal human epidermal keratinocytes (NHEKs). We further measured trypsin or chymotrypsin-like serine protease activity in NHEK cultured media under stimulation with TLR3 ligand, poly (I:C). Immunostaining for LEKTI was performed using skin samples from skin infectious diseases. RESULTS: TLR1/2, 3, 5, and 2/6 ligands induced the expression of LEKTI in NHEKs. The trypsin or chymotrypsin-like serine protease activity in NHEKs was up-regulated with the stimulation of poly (I:C). The gene expressions of KLK6, KLK10, KLK11, and KLK13 were also increased by poly (I:C). An immunohistochemical analysis demonstrated that the expression of LEKTI was up-regulated in the lesions of varicella, pyoderma, and rosacea. CONCLUSIONS: TLR signaling induces the expression of LEKTI in epidermal keratinocytes, which might contribute to the control of aberrant serine protease activities in inflammatory skin diseases.

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  • Clinical and Laboratory Markers Associated With Relapse in Cutaneous Polyarteritis Nodosa. International journal

    Azusa Kato, Toshihisa Hamada, Tomoko Miyake, Shin Morizane, Yoji Hirai, Osamu Yamasaki, Keiji Iwatsuki

    JAMA dermatology   154 ( 8 )   922 - 926   2018.8

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    Importance: In cutaneous polyarteritis nodosa (CPAN), less aggressive treatments can be selected, because CPAN is not associated with life-threatening or progressive outcomes. Although patients with a recurrent clinical course may require additional immunosuppressive therapies, no pretreatment factors associated with a worse prognosis in CPAN have been reported. Objective: To identify clinical or laboratory markers associated with relapse of CPAN. Design, Setting, and Participants: This retrospective case series was performed at a dermatology clinic of a tertiary referral center in Okayama, Japan, from October 1, 2001, through April 30, 2017. Of 30 patients identified with CPAN, the 21 with histopathologic evidence of disease were eligible and enrolled in the study. Main Outcomes and Measures: The medical database was examined for sex, age at diagnosis, affected anatomical sites, type and extent of skin lesion, laboratory data, initial therapies, duration of follow-up, and current status. Relapse was defined as the first reoccurrence or new onset of cutaneous disease that required further escalation of treatment with prednisolone at a dosage of greater than 20 mg/d and/or add-on use of immunosuppressant therapy, more than 6 months after initial treatment. The pretreatment factors were statistically evaluated between the groups without and with relapse. Results: The 21 patients included 5 males and 16 females with a median age of 49 years (range, 11-74 years) at diagnosis. The median follow-up was 42 months (range, 8-374 months). Pretreatment cutaneous ulcer was significantly associated with relapse between the 2 groups (0 of 11 in the nonrelapse group vs 4 of 10 in the relapse group; χ21 = 4.67; P < .05). In the laboratory test results, significantly higher mean (SD) values were observed in the relapse group for C-reactive protein level (0.23 [2.00] vs 6.03 [3.10] mg/dL; standard error of the mean [SEM], 3.40 mg/dL; 95% CI, 0.01-10.8 mg/dL; P = .01), absolute neutrophil count (ANC) (3.4 × 103/μL [1.1 × 103/μL] vs 6.0 × 103/μL [3.2 × 103/μL]; SEM, 2.9 × 103/μL; 95% CI, 1.9 × 103/μL to 14.6 × 103/μL; P = .001), neutrophil-to-lymphocyte ratio (1.4 [0.8] vs 2.8 [0.9]; SEM, 1.2; 95% CI, 1.1-4.9; P = .002), and systemic immune-inflammation index (5.1 × 105 [3.9 × 105] vs 11.7 × 105 [7.7 × 105]; SEM, 7.3 × 105; 95% CI, 3.3 × 105 to 31.1 × 105; P = .007). The estimated 2-year cumulative relapse rate was significantly high in the patients with blood ANC of greater than 4.9 × 103/μL compared with 4.9 × 103/μL or less (9 of 10 [90%] vs 2 of 11 [18%]; 95% CI, 6%-72%). Conclusions and Relevance: Pretreatment status of cutaneous ulcer, the serum C-reactive protein level, the blood ANC, the neutrophil-to-lymphocyte ratio, and the systemic immune-inflammation index are associated with a worse prognosis in CPAN.

    DOI: 10.1001/jamadermatol.2018.1601

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  • The synergistic activities of the combination of tumour necrosis factor-α, interleukin-17A and interferon-γ in epidermal keratinocytes. International journal

    S Morizane, H Nomura, K Tachibana, Y Nakagawa, K Iwatsuki

    The British journal of dermatology   179 ( 2 )   496 - 498   2018.8

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    DOI: 10.1111/bjd.16443

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  • Speckled lentiginous naevus: understanding the process of development and regression. International journal

    K Iwatsuki, T Hamada, O Yamasaki, S Morizane, M Muto

    The British journal of dermatology   178 ( 6 )   1447 - 1448   2018.6

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    DOI: 10.1111/bjd.16319

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  • Analysis of All 34 Exons of the SPINK5 Gene in Japanese Atopic Dermatitis Patients.

    Shin Morizane, Mamoru Ouchida, Ko Sunagawa, Saeko Sugimoto, Mina Kobashi, Satoru Sugihara, Hayato Nomura, Kazuhide Tsuji, Atsushi Sato, Yoshihiro Miura, Hiroaki Hattori, Kotaro Tada, Wook-Kang Huh, Akemi Seno, Keiji Iwatsuki

    Acta medica Okayama   72 ( 3 )   275 - 282   2018.6

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    Lympho-epithelial Kazal-type-related inhibitor (LEKTI) is a large multidomain serine protease inhibitor that is expressed in epidermal keratinocytes. Nonsense mutations of the SPINK5 gene, which codes for LEKTI, cause Netherton syndrome, which is characterized by hair abnormality, ichthyosis, and atopy. A single nucleotide polymorphism (SNP) of SPINK5, p.K420E, is reported to be associated with the pathogenesis of atopic dermatitis (AD). We studied all 34 exons of the SPINK5 gene in Japanese 57 AD patients and 50 normal healthy controls. We detected nine nonsynonymous variants, including p.K420E; these variants had already been registered in the SNP database. Among them, p.R654H (n=1) was found as a heterozygous mutation in the AD patients, but not in the control. No new mutation was detected. We next compared the data of the AD patients with data from the Human Genetic Variation Database provided by Kyoto University; a significant difference was found in the frequency of the p.S368N genotype distribution. PolyPhen-2 and SIFT, two algorithms for predicting the functional effects of amino acid substitutions, showed significant scores for p.R654H. Therefore, R654H might be a risk factor for epidermal barrier dysfunction in some Japanese AD patients.

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  • Type D (CD8+) lymphomatoid papulosis in a patient with classic (CD4+) mycosis fungoides. International journal

    Junko Hori-Kosogabe, Toshihisa Hamada, Shin Morizane, Yoji Hirai, Tomoko Miyake, Tadashi Yoshino, Keiji Iwatsuki

    European journal of dermatology : EJD   28 ( 2 )   267 - 268   2018.4

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    DOI: 10.1684/ejd.2018.3234

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  • Epstein-Barr virus-positive mucocutaneous ulcer in a patient with polycythemia vera treated with oral hydroxyurea. International journal

    Toshihisa Hamada, Mariko Kawata, Yoshinobu Maeda, Tadashi Yoshino, Tomoko Miyake, Shin Morizane, Yoji Hirai, Keiji Iwatsuki

    The Journal of dermatology   45 ( 4 )   e82-e83   2018.4

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  • A Case of Psoriasis Complicated by Breast Cancer after Systemic Treatments Including Biologics.

    Shin Morizane, Saeko Sugimoto, Takayuki Motoki, Norihisa Katayama, Masako Omori, Keiji Iwatsuki

    Acta medica Okayama   72 ( 2 )   185 - 187   2018.4

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    Psoriasis is a common chronic inflammatory skin disorder that is characterized by scaly, erythematous, sharply demarcated plaques. The treatment for psoriasis has dramatically changed over the last 10 years with the introduction of biologics. However, the risk of cancer induced by biologics for psoriasis has not been fully analyzed, since these agents have such a short history of use. Here we report the case of a 74-year-old woman with psoriasis vulgaris and psoriatic arthritis complicated by breast cancer after systemic treatments including etretinate, cyclosporine, methotrexate, adalimumab, and ustekinumab.

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  • High calcium enhances the expression of double-stranded RNA sensors and antiviral activity in epidermal keratinocytes. International journal

    Yuriko Yamamura, Shin Morizane, Takenobu Yamamoto, Jun Wada, Keiji Iwatsuki

    Experimental dermatology   27 ( 2 )   129 - 134   2018.2

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    Double-stranded RNA (dsRNA) sensors including TLR3, MDA5 and RIG-I are expressed in epidermal keratinocytes and play an important immunological role by enhancing various innate and adaptive immune responses. Although the role of elevated extracellular calcium concentration in keratinocyte differentiation is well understood, the effect of high calcium on dsRNA sensors is not well studied. We investigated alterations in dsRNA sensor expression and antiviral activity induced by a high extracellular concentration of calcium in epidermal keratinocytes. Normal human epidermal keratinocytes (NHEKs) were stimulated with high calcium and/or synthetic dsRNA, poly (I:C). TLR3, IFIH1 (MDA5) and DDX58 (RIG-I) expression were measured via qPCR, and IFN-β and human beta-defensin 2 (HBD2) levels were measured using ELISA. TLR3 localization was evaluated with immunocytofluorescence. Antiviral activity was quantified with virus plaque assays using herpes simplex virus type 1 (HSV-1). High calcium significantly upregulated mRNA expression of TLR3, IFIH1 and DDX58 in NHEKs. In addition, high calcium significantly enhanced poly (I:C)-induced anti-HSV-1 activity in NHEKs. The antiviral molecule HBD2 but not IFN-β induction by poly (I:C) was enhanced by high calcium. Our findings indicate that high levels of extracellular calcium enhance the expression of dsRNA sensors and augment antiviral activity in epidermal keratinocytes.

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  • Clinical outcomes of primary cutaneous anaplastic large cell lymphoma: data from a single Japanese centre. International journal

    Yuka Maruta, Toshihisa Hamada, Hiroko Fukamatsu, Tatsuya Kaji, Shin Morizane, Yoji Hirai, Tomoko Miyake, Osamu Yamasaki, Tadashi Yoshino, Keiji Iwatsuki

    European journal of dermatology : EJD   27 ( 6 )   669 - 671   2017.12

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  • Two arginine residues in the COOH-terminal of human β-defensin-3 constitute an essential motif for antimicrobial activity and IL-6 production. Reviewed International journal

    Yoko Sakagami-Yasui, Yoshinori Shirafuji, Osamu Yamasaki, Shin Morizane, Toshihisa Hamada, Hiroshi Umemura, Keiji Iwatsuki

    Experimental dermatology   26 ( 11 )   1026 - 1032   2017.11

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    Human β-defensin-3 (HBD-3) possesses antimicrobial activities and the potential to induce proinflammatory cytokines. HBD-3 contains a unique motif of two arginine residues (Arg or R) in the COOH-terminal region. To understand the bioactive properties of the Arg residues of HBD-3, we examined antimicrobial activities against Staphylococcus aureus and Pseudomonas aeruginosa using synthetic HBD-2, HBD-3 and two variant peptides of HBD-3: the Arg-truncated variant designated desR HBD-3 and NRR HBD-3, in which both Arg residues were shifted to the N-terminal region. IL-6 production from keratinocytes was studied using the peptides. HBD-3 possessed approximately five-fold more potent antimicrobial activities, evaluated as the minimum inhibitory concentration (MIC), against S. aureus compared with desR and NRR HBD-3, while no significant activity was observed in HBD-2. The antimicrobial activity of HBD-3 against S. aureus was well preserved even at high sodium chloride concentrations, but was attenuated in desR and NRR HBD-3. All the peptides exhibited similar antimicrobial activities against P. aeruginosa, but HBD-2 and desR HBD-3 showed diminished antimicrobial activities against P. aeruginosa at high salt concentrations. IL-6 production was significantly induced in keratinocytes with HBD-3, but not remarkably with stimulation by other peptide. These Arg residues are essential for the antimicrobial and biological properties of HBD-3.

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  • Possible macrophage activation in melanoma patients receiving combined kinase inhibitor therapy following anti-PD-1 therapy: a cytokine profiling study of two cases. International journal

    H Umemura, O Yamasaki, S Morizane, K Iwatsuki

    Annals of oncology : official journal of the European Society for Medical Oncology   28 ( 10 )   2624 - 2625   2017.10

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  • The Involvement of Serum Amyloid A in Psoriatic Inflammation. International journal

    Shin Morizane, Kazuko Mizuno, Tetsuya Takiguchi, Saeko Sugimoto, Keiji Iwatsuki

    The Journal of investigative dermatology   137 ( 3 )   757 - 760   2017.3

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  • Persistent elevation of serum interleukin-6 and serum amyloid A levels in patients with recessive dystrophic epidermolysis bullosa. International journal

    Shin Morizane, Kazuko Mizuno, Tetsuya Takiguchi, Satoko Ogita, Yoshinobu Nishida, Yoshio Kawakami, Keiji Iwatsuki

    European journal of dermatology : EJD   27 ( 1 )   80 - 81   2017.2

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  • Comparative study on driver mutations in primary and metastatic melanomas at a single Japanese institute: A clue for intra- and inter-tumor heterogeneity. International journal

    Tatsuya Kaji, Osamu Yamasaki, Minoru Takata, Masaki Otsuka, Toshihisa Hamada, Shin Morizane, Kenji Asagoe, Hiroyuki Yanai, Yoji Hirai, Hiroshi Umemura, Keiji Iwatsuki

    Journal of dermatological science   85 ( 1 )   51 - 57   2017.1

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    BACKGROUND: Searching for driver mutations in melanoma is critical to understanding melanoma genesis, progression and response to therapy. OBJECTIVES: We aimed to investigate the frequency and pattern of driver mutations in Japanese primary and metastatic melanomas including cases of unknown primary origin, in relation to their clinicopathologic manifestations. METHODS: Seventy-seven samples from 60 patients with melanoma were screened for 70 driver mutations of 20 oncogenes by Sequenom MelaCarta MassARRAY, and the results for primary and metastatic melanomas were compared. RESULTS: Of 77 tissue samples, BRAF V600E was detected in 21 samples (27%), CDK4 R24C in 7, EPHB6 G404S in 6, BRAF V600K in 2, NEK10 E379K in 2, and CDK4 R24H, NRAS Q61K, NRAS Q61R, KRAS G12A, KIT L576P, KIT V559A, ERBB4 E452K, and PDGFRA E996K in one sample each. No driver mutations related to the MAPK cascade including RAS and BRAF were detected in the chronically sun-damaged (CSD) group of melanoma. Dual or triple driver mutations were found in four of 40 (10%) samples from the primary melanomas, and three of 37 (8%) of the metastatic melanomas. Fourteen of 26 (54%) samples of non-CSD melanoma, and 3 of 6 (50%) melanomas of unknown primary origin had the BRAF V600E mutation. Mutations in membrane-bound receptors including KIT, ERBB4 and EPHB6 were detected in 8 of 77 (10%) samples. Of 17 pairs of primary and metastatic melanomas from the same patient, the primary mutation pattern was changed to a novel one in three cases, and only one of the plural mutations in the primary melanoma was found in the metastatic lesions in two cases. CONCLUSIONS: BRAF V600E is a predominant mutation in non-CSD melanoma and melanomas of unknown primary origin. Mutational heterogeneity may exist in the primary melanoma (intra-tumor heterogeneity), and between the primary and metastatic lesions (inter-tumor heterogeneity).

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  • Identification of an S100A8 Receptor Neuroplastin-β and its Heterodimer Formation with EMMPRIN. International journal

    Masakiyo Sakaguchi, Mami Yamamoto, Masashi Miyai, Tatsuo Maeda, Junichiro Hiruma, Hitoshi Murata, Rie Kinoshita, I Made Winarsa Ruma, Endy Widya Putranto, Yusuke Inoue, Shin Morizane, Nam-Ho Huh, Ryoji Tsuboi, Toshihiko Hibino

    The Journal of investigative dermatology   136 ( 11 )   2240 - 2250   2016.11

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    We previously reported a positive feedback loop between S100A8/A9 and proinflammatory cytokines mediated by extracellular matrix metalloproteinase inducer, an S100A9 receptor. Here, we identify neuroplastin-β as an unreported S100A8 receptor. Neuroplastin-β and extracellular matrix metalloproteinase inducer form homodimers and a heterodimer, and they are co-localized on the surface of cultured normal human keratinocytes. Knockdown of both receptors suppressed cell proliferation and proinflammatory cytokine induction. Upon stimulation with S100A8, neuroplastin-β recruited GRB2 and activated extracellular signal-regulated kinase, resulting in keratinocyte proliferation. Keratinocyte proliferation in response to inflammatory stimuli was accelerated in involucrin promoter-driven S100A8 transgenic mice. Further, S100A8 and S100A9 were strongly up-regulated and co-localized in lesional skin of atopic dermatitis patients. Our results indicate that neuroplastin-β and extracellular matrix metalloproteinase inducer form a functional heterodimeric receptor for S100A8/A9 heterodimer, followed by recruitment of specific adaptor molecules GRB2 and TRAF2, and this signaling pathway is involved in activation of both keratinocyte proliferation and skin inflammation in atopic skin. Suppression of this pathway might have potential for treatment of skin diseases associated with chronic inflammation such as atopic dermatitis.

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  • Epstein-Barr virus reactivation is induced, but abortive, in cutaneous lesions of systemic hydroa vacciniforme and hypersensitivity to mosquito bites. International journal

    Takenobu Yamamoto, Yoji Hirai, Tomoko Miyake, Toshihisa Hamada, Osamu Yamasaki, Shin Morizane, Wataru Fujimoto, Keiji Iwatsuki

    Journal of dermatological science   82 ( 3 )   153 - 9   2016.6

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    BACKGROUND: Epstein-Barr virus (EBV)-associated T/natural killer (NK)-lymphoproliferative disorders (LPDs) include hydroa vacciniforme (HV) and hypersensitivity to mosquito bites (HMB). The pathomechanisms of these diseases are still unclear. OBJECTIVE: To understand the inflammatory process, we examined EBV reactivation markers, BZLF1 and BDRF1 mRNA in the tissue and blood from patients with EBV-associated T/NK-LPDs. METHODS: Sixty-four patients with EBV-associated LPDs and epithelial neoplasms, and EBV+ cell line cells were studied. DNase-treated and resistant EBV DNA load in blood and cell culture supernatants were calculated. An EBV reactivation signal was analyzed in the tissue, blood and cell line cells. RESULTS: In the tissue, BZLF1 mRNA was detected in 5 of 6 (83%) samples of EBV+ epithelial neoplasms, 16 of 21 (76%) of EBV+ lymphomas, and 5 of 15 (33%) of systemic HV and/or HMB, but negative in all 15 patients with classical HV. In the blood, BZLF1 mRNA was detected in only one of 19 (5.3%) samples of EBV-associated T/NK-LPDs. A down-stream reactivation signal, BDRF1 mRNA was expressed in all 6 samples of EBV+ epithelial neoplasms, but it was positive in only one of 15 (6.7%) samples from systemic HV and HMB in the tissue. EBV+ T/NK-cell line cells treated with phorbol 12-myristate 13-acetate produced BZLF1 and BDRF1 mRNA, and encapsidated EBV DNA was detected in the culture supernatants of cell line cells. CONCLUSION: Stimulation-induced EBV reactivation occurred both in vivo and in vitro, but it was almost abortive in vivo. Reactivation-related EBV antigens might be responsible for induction of systemic HV and HMB.

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  • Dexamethasone but not tacrolimus suppresses TNF-α-induced thymic stromal lymphopoietin expression in lesional keratinocytes of atopic dermatitis model. International journal

    Kazuko Mizuno, Shin Morizane, Tetsuya Takiguchi, Keiji Iwatsuki

    Journal of dermatological science   80 ( 1 )   45 - 53   2015.10

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    BACKGROUND: Thymic stromal lymphopoietin (TSLP) initiates the Th2-type allergic inflammation, and is thought to play an important role in the pathogenesis of atopic dermatitis (AD). TNF-α is a key cytokine which is involved in the pathophysiology of various inflammatory diseases, and the expression level is elevated in the sera and skin of patients with AD. In addition, TNF-α has been reported to induce TSLP expression in epidermal keratinocytes. Topical glucocorticoids and calcineurin inhibitors are safe and effective agents for AD, but the effects of these agents on TNF-α-induced TSLP expression are not fully understood. OBJECTIVE: To investigate whether the glucocorticosteroid dexamethasone and the calcineurin inhibitor tacrolimus could affect TSLP expression induced by TNF-α in lesional keratinocytes of AD. METHODS: The effects of topical dexamethasone and tacrolimus on TSLP expression were evaluated in an AD mouse model induced by repeated 2,4,6-trinitro-1-chlorobenzene application. Co-immunostaining for TSLP and TNF-α was performed using skin samples from AD patients and the mouse model. Normal human epidermal keratinocytes (NHEKs) were cultured with dexamethasone or tacrolimus in the presence of TNF-α to analyze TSLP expression. RESULTS: Topical application of dexamethasone but not tacrolimus repressed TSLP expression in the mouse model. TSLP and TNF-α showed similar distribution pattern in epidermal keratinocytes of AD lesions and the mouse model. TSLP expression was induced by TNF-α via NF-κB in a dose-dependent and an autocrine and/or paracrine manner in NHEKs, which was significantly suppressed by dexamethasone but not by tacrolimus. Similarly to TSLP expression, IL-6, TNF-α, IL-8, and IL-36γ expression induced by TNF-α were significantly suppressed by dexamethasone but not by tacrolimus in NHEKs. CONCLUSION: Dexamethasone but not tacrolimus suppresses the TSLP expression induced by TNF-α in lesional keratinocytes of AD model. Our observations uncover the unreported functional difference between topical glucocorticosteroids and calcineurin inhibitors in cutaneous inflammatory diseases.

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  • Interferon-Gamma Enhances TLR3 Expression and Anti-Viral Activity in Keratinocytes. Reviewed International journal

    A I Kajita, Shin Morizane, Tetsuya Takiguchi, Takenobu Yamamoto, Masao Yamada, Keiji Iwatsuki

    The Journal of investigative dermatology   135 ( 8 )   2005 - 2011   2015.8

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    Toll-like receptors (TLRs) recognize specific microbial products in the innate immune response. TLR3, a double-stranded RNA sensor, is thought to have an important role in viral infections, but the regulation of TLR3 expression and its function in keratinocytes are not fully understood. Here we show the Th1 cytokine IFN-γ increased the TLR3 expression via STAT1 in cultured normal human epidermal keratinocytes (NHEKs). Co-stimulation with IFN-γ and the TLR3 ligand poly (I:C) synergistically increased the expression of IFN-β, IL-6, IL-8, and human β-defensin-2 in NHEKs compared with poly (I:C) or IFN-γ alone. These synergistic inductions were significantly inhibited by an endosomal acidification inhibitor, chloroquine, and by TLR3 siRNA. Co-stimulation with IFN-γ and poly (I:C) also significantly enhanced the anti-viral activity against herpes simplex virus type-1 in NHEKs compared with poly (I:C) or IFN-γ alone. In addition to the in vitro findings, an immunohistochemical analysis revealed IFN-γ-positive cells surrounding herpetic vesicles. These findings indicate that IFN-γ might contribute to the innate immune response to cutaneous viral infections by enhancing TLR3 expression and function in keratinocytes.

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  • Immune escape phenomenon in molluscum contagiosum and the induction of apoptosis. International journal

    Akiko Yamauchi-Yamada, Takenobu Yamamoto, Yumi Nakayama, Kazuko Ikeda, Tomoko Miyake, Mari Yamaguchi, Yoji Hirai, Yoshinori Shirafuji, Shin Morizane, Yumi Aoyama, Keiji Iwatsuki

    The Journal of dermatology   41 ( 12 )   1058 - 64   2014.12

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    Molluscum contagiosum (MC) may persist for many weeks, evading host immunity. We studied the mechanism of immune escape phenomenon in MC, and the possible inducer of apoptosis. Using tissue samples of MC, we examined the numbers of epidermal Langerhans cells (LC), the expression levels of macrophage inflammatory protein-3α (MIP-3α) and thymic stromal lymphopoietin (TSLP), and the apoptotic signals. After molluscum contagiosum virus (MCV) genotyping, we studied the expression of MCV-encoded MC148 mRNA and MC159 mRNA which correspond to viral antagonist for CCR8 and viral Fas-linked interleukin (IL)-1β converting enzyme (FLICE)-like inhibitor protein (vFLIP), respectively. The nutlin-3-induced apoptosis in MC was observed ex vivo. The numbers of CD1a(+) or Langerin(+) epidermal LC and the expression levels of MIP-3α were markedly decreased in MC. The expression of TSLP was enhanced in the lesional epidermis of atopic dermatitis and human papillomavirus-induced warts, whereas the expression was observed locally in MC. All 14 MC samples examined harbored MCV type 1. The MC148 mRNA was detected in all 14 samples and the MC159 mRNA was detected in 13 samples. Apoptotic cells were absent or at a background level in the living layers of MC, but their numbers were increased in the molluscum bodies by overnight incubation with 5 μmol/L nutlin-3 in culture medium. In conclusion, molluscum bodies are protected from host immune responses and apoptotic signals by being surrounded by LC-depleted epidermal walls and viral immunosuppressive molecules, but could be eradicated by reagents inducing p53-dependent apoptosis.

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  • Cathelicidin antimicrobial peptide LL-37 augments interferon-beta expression and antiviral activity induced by double-stranded RNA in keratinocytes

    Takiguchi T, Morizane S, Yamamoto T, Kajita A, Ikeda K, Iwatsuki K

    British Journal of Dermatology   171 ( 3 )   492 - 498   2014.9

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  • A higher correlation of the antibody activities against the calcium-dependent epitopes of desmoglein 3 quantified by ethylenediaminetetraacetic acid-treated enzyme-linked immunosorbent assay with clinical disease activities of pemphigus vulgaris. International journal

    Koji Kamiya, Yumi Aoyama, Yoshinori Shirafuji, Toshihisa Hamada, Shin Morizane, Kazuyasu Fujii, Keiji Iwatsuki

    Journal of dermatological science   70 ( 3 )   190 - 5   2013.6

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    BACKGROUND: Nonpathogenic anti-desmoglein (Dsg) 3 antibodies can be found in pemphigus vulgaris (PV) patients' sera. Previously, ethylenediaminetetraacetic acid (EDTA)-treated enzyme-linked immunosorbent assay (ELISA) was found to detect only nonpathogenic anti-Dsg3 antibodies against the non-calcium (Ca(2+))-dependent epitopes. OBJECTIVE: We examined whether the calculated anti-Dsg3 antibody titer for Ca(2+)-dependent epitopes, using the conventional and EDTA-treated ELISAs, correlated better with the disease activity of PV. METHODS: We analyzed 123 serum samples from 19 PV patients. Of these samples, there were 52 samples from 15 PV patients obtained in asymptomatic phases. The difference between conventional Dsg3 ELISA index and EDTA-treated Dsg3 ELISA index was calculated as the anti-Dsg3 antibody activity for Ca(2+)-dependent conformational epitopes (conformational Dsg3 ELISA index). We analyzed the correlation between Dsg3 ELISA index values and the pemphigus disease area index (PDAI). Moreover, we examined whether the conformational Dsg3 ELISA index fluctuated in parallel with the disease activity during clinical courses of 6 PV patients. We evaluated the pathogenicity of anti-Dsg3 antibodies detected in remission phases using a dissociation assay. RESULTS: The conventional Dsg3 ELISA index showed a high positive rate in the asymptomatic phase of PV. By contrast, the conformational Dsg3 ELISA index showed a much closer correlation to the disease activity when monitored in individual cases. Nonpathogenic anti-Dsg3 antibodies were detected in these cases. CONCLUSION: The conformational Dsg3 ELISA index reflected the pathogenicity of anti-Dsg3 antibodies more accurately than the conventional Dsg3 ELISA index. Using both conventional and EDTA-treated ELISAs would be useful in monitoring the disease activity of PV.

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  • Immunological and structural remodeling in human papillomavirus-induced warts and Bowen disease. International journal

    Keiji Iwatsuki, Yumi Nakayama, Toshihisa Hamada, Gen Nakanishi, Yoshinori Shirafuji, Shin Morizane

    European journal of dermatology : EJD   2013.4

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    Human papillomavirus-associated warts (HPV-warts) are persistent, evading host immune surveillance. However, these warts sometimes disappear spontaneously, following inflammation. Non-inflamed HPV-warts demonstrated decreased numbers of epidermal Langerhans cells (LCs), low expression levels of MIP3α and E-cadherin, and no apoptotic cells. In the inflamed HPV-warts, on the other hand, various dendritic cell (DC) subsets and many CD8+ cytotoxic T lymphocytes (CTLs) were recruited in association with epidermal MIP3α expression. Many apoptotic keratinocytes were observed in the dermo-epidermal junction. Cellular events were different in HPV-induced Bowen disease (HPV-Bowen): a few LCs were retained in the lesional epidermis, and considerable numbers of B-cells and plasma cells were also observed in the infiltrates, with little or no infiltration of plasmacytoid DCs or dermal/mature DCs. Multiple HPV16-Bowen diseases in the same individuals showed the presence of different sizes of E6/E7-containing cellular transcripts, which indicated that HPV genomes were integrated into the different sites of chromosomes. Toll-like receptor (TLR) 3 was expressed by the lesional keratinocytes even in the non-inflamed HPV-warts, and type 1 interferons (IFNs) were produced in cultured keratinocytes by TLR3 stimulation. HPV-warts are protected from host immune responses and apoptotic signals because they are surrounded by LC-depleted epidermal walls, and viral anti-apoptotic molecules. The up-regulation of epidermal TLR3 signaling might inhibit further HPV spreading.

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  • Eccrine poromatosis associated with polychemotherapy. International journal

    Kazuyasu Fujii, Seiko Aochi, Chinatsu Takeshima, Masaki Ohtsuka, Toshihisa Hamada, Kenji Asagoe, Yumi Aoyama, Shin Morizane, Keiji Iwatsuki

    Acta dermato-venereologica   92 ( 6 )   687 - 90   2012.11

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    Eccrine poroma frequently occurs as a solitary tumour, and only a few reports have described the occurrence of multiple lesions. Multiple eccrine poromas, or eccrine poromatosis, may occur in patients who have undergone radiotherapy and/or polychemotherapy. We report here four cases of multiple eccrine poromas in patients who were either undergoing, or had undergone, intensive chemotherapy (from 6 months to 16 years prior to onset). Three patients had non-Hodgkin's lymphoma and one had malignant fibrous histiocytosis. The number of lesions varied from 3 to > 20 in each patient, and all the lesions occurred on non-irradiated skin. The histopathological features were consistent with those of eccrine poroma, Pinkus type. In addition to radiation therapy, intensive chemotherapy may play a role in the pathogenesis of multiple eccrine poromas even many years after treatment.

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  • The antimicrobial protein REG3A regulates keratinocyte proliferation and differentiation after skin injury. International journal

    Yuping Lai, Dongqing Li, Changwei Li, Beda Muehleisen, Katherine A Radek, Hyun Jeong Park, Ziwei Jiang, Zhiheng Li, Hu Lei, Yanchun Quan, Tian Zhang, Yelin Wu, Paul Kotol, Shin Morizane, Tissa R Hata, Keiji Iwatsuki, Ce Tang, Richard L Gallo

    Immunity   37 ( 1 )   74 - 84   2012.7

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    Epithelial keratinocyte proliferation is an essential element of wound repair, and abnormal epithelial proliferation is an intrinsic element in the skin disorder psoriasis. The factors that trigger epithelial proliferation in these inflammatory processes are incompletely understood. Here we have shown that regenerating islet-derived protein 3-alpha (REG3A) is highly expressed in keratinocytes during psoriasis and wound repair and in imiquimod-induced psoriatic skin lesions. The expression of REG3A by keratinocytes is induced by interleukin-17 (IL-17) via activation of keratinocyte-encoded IL-17 receptor A (IL-17RA) and feeds back on keratinocytes to inhibit terminal differentiation and increase cell proliferation by binding to exostosin-like 3 (EXTL3) followed by activation of phosphatidylinositol 3 kinase (PI3K) and the kinase AKT. These findings reveal that REG3A, a secreted intestinal antimicrobial protein, can promote skin keratinocyte proliferation and can be induced by IL-17. This observation suggests that REG3A may mediate the epidermal hyperproliferation observed in normal wound repair and in psoriasis.

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  • TH2 cytokines increase kallikrein 7 expression and function in patients with atopic dermatitis. International journal

    Shin Morizane, Kenshi Yamasaki, Ai Kajita, Kazuko Ikeda, Maosheng Zhan, Yumi Aoyama, Richard L Gallo, Keiji Iwatsuki

    The Journal of allergy and clinical immunology   130 ( 1 )   259 - 61   2012.7

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  • Hydroa vacciniforme is associated with increased numbers of Epstein-Barr virus-infected γδT cells. International journal

    Yoji Hirai, Takenobu Yamamoto, Hiroshi Kimura, Yoshinori Ito, Kazuhide Tsuji, Tomoko Miyake, Shin Morizane, Daisuke Suzuki, Kazuyasu Fujii, Keiji Iwatsuki

    The Journal of investigative dermatology   132 ( 5 )   1401 - 8   2012.5

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    Hydroa vacciniforme (HV) is a rare photosensitivity disorder of childhood associated with Epstein-Barr virus (EBV)(+) T-cell infiltration. We have summarized clinical manifestations of HV, and analyzed EBV(+) T-cell subsets as well as EBV DNA load in lymphocyte fractions, in comparison with hypersensitivity to mosquito bites (HMB), an EBV-associated T/natural killer (NK) lymphoproliferative disorder. We found that 31 of 33 (93.9%) HV lesions were composed of EBV(+) T cells and reactive EBV(-) cytotoxic T cells, without significant CD56(+) cell infiltration, whereas many CD56(+) cells were present in 8 of 9 (88.9%) HMB lesions. Of 13 (20.6%) HMB patients with or without HV, 12 (92.3%) showed increased percentages (>32%) of NK cells in the peripheral blood, whereas in the 16 patients with HV alone, 14 (87.5%) showed no increase. Of the 11 HV patients, 10 (90.9%) had increased percentages (>5%) of circulating γδT cells, with a mean value of 15.7 ± 2.9%, and the γδT-cell fractions contained larger amounts of EBV DNA than non-γδT-cell fractions. A triple-labeling method revealed that all three HV patients examined had increased percentages of EBER(+), T-cell receptor (TCR)γδ(+), and TCRαβ(-) cells. Our observations indicate that HV is associated with increased numbers of EBV(+) γδT cells, whereas HMB is associated with EBV(+) NK cells.

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  • Antimicrobial peptides in the pathogenesis of psoriasis. International journal

    Shin Morizane, Richard L Gallo

    The Journal of dermatology   39 ( 3 )   225 - 30   2012.3

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    One characteristic abnormality of lesional skin in psoriasis is the excessive production of antimicrobial peptides and proteins (AMPs). AMPs typically are small (12-50 amino acids), have positive charge and amphipathic structure, and are found in all living organisms including mammals, insects, plants and invertebrates. These peptides are best known for their integral role in killing pathogenic microorganisms; however, in vertebrates, they are also capable of modifying host inflammatory responses by a variety of mechanisms. In psoriatic lesions, many AMPs are highly expressed, and especially the associations between psoriasis and cathelicidin, β-defensins or S100 proteins have been well studied. Among them, a cathelicidin peptide, LL-37, has been highlighted as a modulator of psoriasis development in recent years. AMPs had been thought to worsen psoriatic lesions but recent evidence has also suggested the possibility that the induction of AMPs expression might improve aspects of the disease. Further investigations are needed to uncover a previously underappreciated role for AMPs in modulating the immune response in psoriasis, and to improve disease without the risks of systemic immunosuppressive approaches.

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  • Cathelicidin antimicrobial peptide LL-37 in psoriasis enables keratinocyte reactivity against TLR9 ligands. International journal

    Shin Morizane, Kenshi Yamasaki, Beda Mühleisen, Paul F Kotol, Masamoto Murakami, Yumi Aoyama, Keiji Iwatsuki, Tissa Hata, Richard L Gallo

    The Journal of investigative dermatology   132 ( 1 )   135 - 43   2012.1

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    Here we show that keratinocytes in psoriatic lesional skin express increased Toll-like receptor (TLR) 9 that similarly localizes with elevated expression of the cathelicidin antimicrobial peptide LL-37. In culture, normal human keratinocytes exposed to LL-37 increased TLR9 expression. Furthermore, when keratinocytes were exposed to LL-37 and subsequently treated with TLR9 ligands, such as CpG or genomic DNA, they greatly increased production of type I IFNs. This response mimicked observations in the epidermis of psoriatic lesional skin as keratinocytes in psoriatic lesions produce greater amounts of IFN-β than normal skin lacking LL-37. The mechanism for induction of type I IFNs in keratinocytes was dependent on TLR9 expression but not on a DNA-LL-37 complex. These findings suggest that keratinocytes recognize and respond to DNA and can actively participate in contributing to the immunological environment that characterizes psoriasis.

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  • Dendritic cell subsets and immunological milieu in inflammatory human papilloma virus-related skin lesions. International journal

    Yumi Nakayama, Kenji Asagoe, Akiko Yamauchi, Takenobu Yamamoto, Yoshinori Shirafuji, Shin Morizane, Gen Nakanishi, Keiji Iwatsuki

    Journal of dermatological science   63 ( 3 )   173 - 83   2011.9

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    BACKGROUND: Human papilloma virus (HPV)-related warts persist, evading host immune surveillance, but sometimes disappear with inflammation. OBJECTIVES: To elucidate the immune evasion mechanisms of HPV, we have examined the density, dynamics, and subsets of dendritic cell (DC) types in non-inflammatory or inflammatory HPV-related skin lesions such as warts and Bowen's disease (HPV-Bowen), and compared the epidermal expression levels of macrophage inflammatory protein (MIP)-3α and E-cadherin. METHODS: The expression of various DC markers, MIP-3α, and E-cadherin in the tissue samples obtained from patients with warts, HPV-Bowen and HPV-unrelated skin diseases was evaluated by immunohistochemistry. MIP-3α gene expression levels were examined in warts and HPV-Bowen by in situ hybridization (ISH) and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The numbers of Langerhans cells (LCs) and the expression levels of MIP-3α and E-cadherin were decreased in non-inflammatory warts and HPV-Bowen, as compared with normal skin. Both epidermal LCs and MIP-3α expression reappeared in inflammatory warts, associated with dermal infiltrates composed of many cytotoxic T cells and various subsets of DCs, while cellular infiltrates in HPV-Bowen contained many B cells and plasma cells with sparse infiltration of DCs. The upregulation of MIP-3α gene expression was confirmed in the inflammatory warts and HPV-Bowen by ISH and RT-qPCR. CONCLUSIONS: The depletion of LCs in the non-inflammatory warts and HPV-Bowen is associated with a down-regulation of expression levels of MIP-3α and E-cadherin in the lesional keratinocytes. MIP-3α expression is upregulated in lesional keratinocytes of inflammatory warts, with the subsequent recruitment of various DC subsets and cytotoxic T cells, whereas plasma cell-rich infiltration was induced in HPV-Bowen.

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  • TLR2 expression is increased in rosacea and stimulates enhanced serine protease production by keratinocytes. International journal

    Kenshi Yamasaki, Kimberly Kanada, Daniel T Macleod, Andrew W Borkowski, Shin Morizane, Teruaki Nakatsuji, Anna L Cogen, Richard L Gallo

    The Journal of investigative dermatology   131 ( 3 )   688 - 97   2011.3

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    A diverse environment challenges skin to maintain temperature, hydration, and electrolyte balance while also maintaining normal immunological function. Rosacea is a common skin disease that manifests unique inflammatory responses to normal environmental stimuli. We hypothesized that abnormal function of innate immune pattern recognition could explain the enhanced sensitivity of patients with rosacea, and observed that the epidermis of patients with rosacea expressed higher amounts of Toll-like receptor 2 (TLR2) than normal patients. Increased expression of TLR2 was not seen in other inflammatory skin disorders such as atopic dermatitis or psoriasis. Overexpression of TLR2 on keratinocytes, treatment with TLR2 ligands, and analysis of TLR2-deficient mice resulted in a calcium-dependent release of kallikrein 5 from keratinocytes, a critical protease involved in the pathogenesis of rosacea. These observations show that abnormal TLR2 function may explain enhanced inflammatory responses to environmental stimuli and can act as a critical element in the pathogenesis of rosacea.

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  • Bilateral conjunctival lesions in blastic plasmacytoid dendritic cell neoplasm.

    Toshihiko Matsuo, Kouichi Ichimura, Takehiro Tanaka, Shin Morizane, Keiji Iwatsuki, Motoharu Eguchi, Tadashi Yoshino

    Journal of clinical and experimental hematopathology : JCEH   51 ( 1 )   49 - 55   2011

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    The purpose of this study is to report on a patient who developed conjunctival lesions of blastic plasmacytoid dendritic cell neoplasm (BPDCN) after radiation to skin lesions of the same pathological type. A 79-year-old man developed salmon-pink lesions in the lower fornix of the conjunctiva of both eyes and biopsy revealed BPDCN. One and a half years previously, he noticed an erythematous plaque with a 30-mm diameter, which later became multiple, on the left chest, and the biopsy revealed BPDCN. The bone marrow was negative for CD56-positive cells, but fluorescence-activated cell sorting analysis of peripheral blood cells revealed a group of cells positive for CD4 and CD56, or CD4 and CD123. The monocyte fraction, in an increased percentage of white blood cell counts, did contain atypical cells positive for the three markers. Whole-body 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography demonstrated no abnormal uptake lesions. He received 30 Gy of radiation to the chest lesions, and later, the same dose of radiation to novel skin lesions on the back, waist, and chest, and also to pharyngeal lesions. In conclusion, the conjunctiva could be involved with BPDCN and pathological differential diagnosis by biopsy is mandatory to establish the correct diagnosis.

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  • Kallikrein expression and cathelicidin processing are independently controlled in keratinocytes by calcium, vitamin D(3), and retinoic acid. International journal

    Shin Morizane, Kenshi Yamasaki, Filamer D Kabigting, Richard L Gallo

    The Journal of investigative dermatology   130 ( 5 )   1297 - 306   2010.5

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    Cathelicidin has dual functions in the skin, acting as an innate antibiotic and as an immunomodulator in diseases such as rosacea and psoriasis. The serine proteases kallikrein 5 (KLK5) and kallikrein 7 (KLK7) control enzymatic processing of cathelicidin precursor in the skin and regulate the eventual function of the final forms of these peptides. We analyzed factors that control expression of KLK5 and KLK7 in normal human epidermal keratinocytes to better understand how these may influence cathelicidin processing and function. Increased extracellular calcium-induced KLK5 and KLK7 mRNA expression and protein release in a time-dependent manner that is similar to induction of differentiation markers such as keratin 10 and involucrin. However, 1,25(OH)(2) vitamin D(3), 9-cis retinoic acid (RA), and 13-cis RA also induced the KLKs, but the timing and pattern of KLK induction for each were different and distinct from changes in differentiation markers. Increased protease activity and differential processing of cathelicidin accompanied increased KLK expression. These findings show that the expression and activity of KLK are under fine control and can be distinctly influenced by variables such as differentiation, calcium, vitamin D, and RA. Thus, these variables may further control the functions of antimicrobial peptides in the skin.

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  • The host defense peptide cathelicidin is required for NK cell-mediated suppression of tumor growth. International journal

    Amanda S Büchau, Shin Morizane, Janet Trowbridge, Jürgen Schauber, Paul Kotol, Jack D Bui, Richard L Gallo

    Journal of immunology (Baltimore, Md. : 1950)   184 ( 1 )   369 - 78   2010.1

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    Tumor surveillance requires the interaction of multiple molecules and cells that participate in innate and the adaptive immunity. Cathelicidin was initially identified as an antimicrobial peptide, although it is now clear that it fulfills a variety of immune functions beyond microbial killing. Recent data have suggested contrasting roles for cathelicidin in tumor development. Because its role in tumor surveillance is not well understood, we investigated the requirement of cathelicidin in controlling transplantable tumors in mice. Cathelicidin was observed to be abundant in tumor-infiltrating NK1.1(+) cells in mice. The importance of this finding was demonstrated by the fact that cathelicidin knockout mice (Camp(-/-)) permitted faster tumor growth than wild type controls in two different xenograft tumor mouse models (B16.F10 and RMA-S). Functional in vitro analyses found that NK cells derived from Camp(-/-) versus wild type mice showed impaired cytotoxic activity toward tumor targets. These findings could not be solely attributed to an observed perforin deficiency in freshly isolated Camp(-/-) NK cells, because this deficiency could be partially restored by IL-2 treatment, whereas cytotoxic activity was still defective in IL-2-activated Camp(-/-) NK cells. Thus, we demonstrate a previously unrecognized role of cathelicidin in NK cell antitumor function.

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  • Bcl-3 acts as an innate immune modulator by controlling antimicrobial responses in keratinocytes. International journal

    Amanda S Büchau, Daniel T MacLeod, Shin Morizane, Paul F Kotol, Tissa Hata, Richard L Gallo

    The Journal of investigative dermatology   129 ( 9 )   2148 - 55   2009.9

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    Innate immune responses involve the production of antimicrobial peptides (AMPs), chemokines, and cytokines. We report here the identification of B-cell leukemia (Bcl)-3 as a modulator of innate immune signaling in keratinocytes. In this study, it is shown that Bcl-3 is inducible by the Th2 cytokines IL-4 and IL-13 and is overexpressed in lesional skin of atopic dermatitis (AD) patients. Bcl-3 was shown to be important to cutaneous innate immune responses as silencing of Bcl-3 by small-interfering RNA (siRNA) reversed the downregulatory effect of IL-4 on the HBD3 expression. Bcl-3 silencing enhanced vitamin D3 (1,25D3)-induced gene expression of cathelicidin AMP in keratinocytes, suggesting a negative regulatory function on cathelicidin transcription. Furthermore, 1,25D3 suppressed Bcl-3 expression in vitro and in vivo. This study identified Bcl-3 as an important modulator of cutaneous innate immune responses and its possible therapeutic role in AD.

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  • IL-17A enhances vitamin D3-induced expression of cathelicidin antimicrobial peptide in human keratinocytes. International journal

    Mark Peric, Sarah Koglin, Song-Min Kim, Shin Morizane, Robert Besch, Jörg C Prinz, Thomas Ruzicka, Richard L Gallo, Jürgen Schauber

    Journal of immunology (Baltimore, Md. : 1950)   181 ( 12 )   8504 - 12   2008.12

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    Cathelicidin is strongly expressed in lesional skin in psoriasis and may play an important role as both an antimicrobial peptide and as an autoinflammatory mediator in this chronic skin disease. The mechanism of increased cathelicidin in psoriatic keratinocytes is not known, but recent observations have found that psoriasis has abundant Th17 cells that produce IL-17A and IL-22. We found that human keratinocytes stimulated with supernatants from T cells isolated from lesional psoriatic skin increased expression of cathelicidin when stimulated in the presence of 1,25-dihydroxyvitamin D(3) (1,25D(3)). This increase was signaled through the IL-17RA. In vitro, IL-17A, but not IL-22, enhanced cathelicidin mRNA and peptide expression in keratinocytes dependent on the presence of 1,25D(3). At the same time, coincubation with 1,25D(3) blocked induction of human beta-defensin 2 (HBD2), IL-6, and IL-8, which are other target genes of IL-17A. Act1, an adaptor associated with IL-17RA and essential for IL-17A signaling, mediated cathelicidin induction, as its suppression by small interfering RNA inhibited HBD2 and cathelicidin. Both, 1,25D(3) and IL-17A signaled cathelicidin induction through MEK-ERK. These results suggest that increased IL-17A in psoriatic skin increases cathelicidin through a vitamin D(3)-, Act1-, and MEK-ERK-dependent mechanism. Therapy targeting this cathelicidin-regulating system might be beneficial in patients suffering from psoriasis.

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  • Karyotypic analysis of bone marrow cells in pyodermic lesions associated with myelodysplastic syndrome. International journal

    Toshihisa Hamada, Hironori Matsuura, Takashi Oono, Shin Morizane, Osamu Yamasaki, Kenji Asagoe, Takenobu Yamamoto, Kazuhide Tsuji, Keiji Iwatsuki

    Archives of dermatology   144 ( 5 )   643 - 8   2008.5

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    BACKGROUND: Recalcitrant pyodermic lesions and neutrophilic dermatoses are often associated with subclinical myelodysplastic syndrome (MDS). In this case series, we assessed the diagnostic importance of karyotypic analysis of bone marrow cells in 4 patients with MDS-associated pyodermic eruptions treated at our university hospital. Karyotypic analysis was performed in bone marrow cells and peripheral blood lymphocytes obtained. Serum levels of granulocyte colony-stimulating factor were measured. OBSERVATIONS: Four patients with pyodermic eruptions or neutrophilic dermatosis had chromosomal abnormalities in bone marrow cells, including del(20)(q11;q13.3) in 2 patients, trisomy 8 in 1 patient, and t(11;22)(q23;q11) in 1 patient. Three patients without morphologic findings suggestive of MDS were diagnosed as having refractory anemia. One female patient had refractory anemia with ringed sideroblasts associated with del(20). Two patients with refractory anemia had a normal karyotype in peripheral blood lymphocytes. Two patients with elevated serum levels of granulocyte colony-stimulating factor had more active or widespread cutaneous diseases. CONCLUSIONS: Karyotypic analysis of bone marrow cells, but not of peripheral blood lymphocytes, is essential in proving a diagnosis of MDS-associated pyodermic lesions. The overexpression of granulocyte colony-stimulating factor, which may compensate for impaired hematopoiesis in patients with MDS, seems to be a key cytokine leading to neutrophilic infiltration.

    DOI: 10.1001/archderm.144.5.643

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  • Panton-Valentine leukocidin produced by Staphylococcus aureus induces an intense inflammation in the skin Invited Reviewed

    S. Morizane, O. Yamasaki, F. Kato, J. Kaneko, K. Iwatsuki

    JOURNAL OF INVESTIGATIVE DERMATOLOGY   127   S131 - S131   2007.4

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  • A novel, noninvasive diagnostic probe for hydroa vacciniforme and related disorders: detection of latency-associated Epstein-Barr virus transcripts in the crusts. International journal

    Takenobu Yamamoto, Kazuhide Tsuji, Daisuke Suzuki, Shin Morizane, Keiji Iwatsuki

    Journal of microbiological methods   68 ( 2 )   403 - 7   2007.2

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    OBJECTIVE: To establish a new diagnostic method for Epstein-Barr virus (EBV)-associated cutaneous disorders. DESIGN: Skin biopsy is usually required to confirm the latent EBV infections in cutaneous lesions of EBV-associated NK/T-cell lymphoproliferative disorders, including hydroa vacciniforme (HV) and hypersensitivity to mosquito bites (HMB). We have devised a novel, noninvasive method to detect EBV-encoded small RNA (EBER), BamHI A rightward transcripts (BARTs) in the skin crusts and scales of such patients. PATIENTS: Six patients with EBV-associated cutaneous lesions were enrolled in the present study, including three patients with HV, one with HV-like eruptions and chronic active EBV infection, and two with EBV-associated cutaneous lymphoma. MAIN OUTCOME MEASURES: RNA was extracted from the crusts obtained from the cutaneous lesions by forceps, converted to cDNA, and processed for polymerase chain reaction (PCR) amplification with a specific set of primers. The PCR products were assayed by a DNA sequencer. RESULTS: Intact RNAs were successfully extracted from the crusts as well as control materials. EBER1 and BARTs RNAs were detected in all 7 crusts, and in 6 of 7 crusts of EBV-associated cutaneous diseases, respectively. One of 23 crusts from non EBV-associated diseases was positive for EBER1 RNA. The sensitivity and specificity of our assay for latent EBV infection were 100% and 95.8% for EBER1 RNA, and 85.7% and 100% for BARTs mRNA, respectively. The correct DNA sequence for EBER1 and BARTs was confirmed in the PCR products by a direct sequencing method. CONCLUSIONS: Our procedure may be of use as a biomarker for EBV-associated cutaneous lesions, including HV, HMB, and NK/T-cell lymphomas.

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  • Staphylococcal cutaneous infections: invasion, evasion and aggression. International journal

    Keiji Iwatsuki, Osamu Yamasaki, Shin Morizane, Takashi Oono

    Journal of dermatological science   42 ( 3 )   203 - 14   2006.6

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    Staphylococcal infections cause a variety of cutaneous and systemic infections, including impetigo, furuncle, subcutaneous abscess, staphylococcal scalded skin syndrome (SSSS), toxic shock syndrome (TSS) and neonatal toxic shock syndrome-like exanthematous disease (NTED), in association with microbial virulence factors. The virulence factors produced by Staphylococcus aureus have a wide array of biological properties, including disruption of the epithelial barrier, inhibition of opsonization by antibody and complement, interference with neutrophil chemotaxis, cytolysis of neutrophils, and inactivation of antimicrobial peptides. Exfoliative toxins (ETs) induce the 'acantholytic' infection of S. aureus due to the disruption of cell-to-cell cohesion, which allows the pathogenic organisms to spread within the epithelium. Furthermore, S. aureus expresses exotoxins with biological properties of superantigens that induce T-cell activation with subsequent anergy and immunosuppression. Of the S. aureus leukotoxins, Panton-Valentine leukocidin (PVL) is involved in the development of multiple furuncles with more intense erythema, particularly in healthy young adults. TSS is an acute life-threatening illness caused by TSS toxin-1 (TSST-1) and is usually classified into two categories; menstrual TSS, originally described in association with tampon use, and nonmenstrual TSS with a variety of clinical settings. NTED is a neonatal disease induced by TSST-1 although clinical symptoms are much milder than those of TSS. In TSS and NTED, the expansion of TSST-1-reactive Vbeta2-positive T cells is observed. The production of pathogenic S. aureus exotoxins and biofilm formation is regulated by the accessory gene regulator (agr) locus in the quorum-sensing signaling pathway. There is no doubt that targeting the quorum-sensing signaling pathway or anti-toxin therapy is a promising therapeutic approach supportive of primary antibiotic therapy.

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  • Pathogenic link between hydroa vacciniforme and Epstein-Barr virus-associated hematologic disorders. International journal

    Keiji Iwatsuki, Masataka Satoh, Takenobu Yamamoto, Takashi Oono, Shin Morizane, Mikio Ohtsuka, Zi-Gang Xu, Daisuke Suzuki, Kazuhide Tsuji

    Archives of dermatology   142 ( 5 )   587 - 95   2006.5

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    OBJECTIVES: To determine the pathogenic association of latent Epstein-Barr virus (EBV) infections with both typical hydroa vacciniforme (HV) and severe HV-like eruptions, and to survey the complications and outcomes of patients. DESIGN: Case series. PATIENTS: Twenty-nine patients with HV or severe HV-like eruptions. INTERVENTIONS: In situ hybridization and immunostaining of biopsy specimens; extraction of DNA samples from cutaneous lesions and/or peripheral blood mononuclear cells for EBV DNA assay. MAIN OUTCOME MEASURES: Clinicopathologic manifestations, hematologic findings, complications, and outcomes; presence of latent EBV infection. RESULTS: T cells positive for EBV-encoded small nuclear RNA (EBER) were detected, to various degrees, in cutaneous infiltrates in 28 (97%) of 29 patients, including all 6 patients with definite HV with a positive phototest reaction, 11 of 12 patients with probable HV without evidence of photosensitivity, and all 11 patients with severe HV associated with systemic symptoms. In addition to EBER-positive T cells, many cytotoxic T lymphocytes expressing T-cell intracellular antigen 1 and granzyme B were present in the cutaneous lesions. Natural killer (NK) cells were absent or at a background level. The UV-induced cutaneous lesions showed histopathologic findings consistent with those of HV, containing many EBER-positive cells. Although no hematologic abnormalities were found in the definite and probable HV groups, the amounts of EBV DNA were increased in the peripheral blood mononuclear cells. By contrast, the severe HV group had markedly increased levels of EBV DNA associated with NK-cell lymphocytosis, and complications including chronic active EBV infection, hypersensitivity to mosquito bites, and hemophagocytic syndrome. Five patients with severe disease died of EBV-associated NK/T-cell lymphomas or hemophagocytic syndrome 2 to 14 years after onset. CONCLUSION: Both typical and severe HV are included within the spectrum of cutaneous disorders mediated by EBV-infected T cells, and the severe HV group may have overt EBV-associated NK/T-cell lymphoproliferative disorders with a frequently fatal outcome.

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  • Tendon destruction induced by Panton-Valentine leukocidin-positive Staphylococcus aureus in a patient with Sézary syndrome. Reviewed International journal

    O Yamasaki, S Morizane, H Akiyama, K Iwatsuki, J Kaneko, Y Kamio

    The British journal of dermatology   152 ( 3 )   586 - 7   2005.3

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    DOI: 10.1111/j.1365-2133.2005.06470.x

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  • The association between Staphylococcus aureus strains carrying panton-valentine leukocidin genes and the development of deep-seated follicular infection. Invited Reviewed International journal

    Osamu Yamasaki, Jun Kaneko, Shin Morizane, Hisanori Akiyama, Jirô Arata, Sachiko Narita, Jun-ichi Chiba, Yoshiyuki Kamio, Keiji Iwatsuki

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America   40 ( 3 )   381 - 5   2005.2

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    BACKGROUND: Panton-Valentine leukocidin (PVL) is mainly associated with necrotic suppurative lesions, such as furuncles and abscesses in the skin and subcutaneous tissue, but it has also been isolated from patients with community-acquired, severe, necrotizing pneumonia. However, the clinical manifestations of furuncles caused by PVL-producing Staphylococcus aureus and the role of patients' background are not fully understood. METHODS: We used polymerase chain reaction amplification to test for the PVL gene in 161 strains of S. aureus isolated from suppurative skin lesions. For all PVL gene-positive strains isolated from furuncles, we analyzed cutaneous manifestations, patient background characteristics, and bacteriological markers, including coagulase types, presence of the mecA gene, and toxin profiles, and we compared these results with those for PVL gene-negative strains. RESULTS: PVL genes were detected in 16 (40%) of the 40 S. aureus strains isolated from furuncles, 2 (28%) of the 7 strains isolated from carbuncles, 1 (14%) of the 7 strains isolated from abscesses, and 1 (5%) of the 20 strains isolated from folliculitis. PVL gene-positive S. aureus usually causes multiple (rather than single) furuncles, and such furuncles are usually associated with more-intense erythema around the lesions. PVL gene-positive strains were isolated from young adults without underlying diseases, whereas PVL gene-negative strains were isolated from patients with various systemic complications, including diabetes, leukemia, and autoimmune diseases. CONCLUSIONS: PVL gene-positive S. aureus strains are involved in the development of multiple furuncles with more-intense erythema, particularly in healthy young adults. An understanding of the characteristics of furuncles due to PVL gene-positive strains might be useful for preventing the development of the severe systemic infections.

    DOI: 10.1086/427290

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  • The association of Staphylococcus aureus strains carrying Panton-Valentine leukocidin genes with the development of deep-seated follicular infections. Invited Reviewed

    O. Yamasaki, S. Morizane, J. Kaneko, Y. Kamio, J. Arata, K. Iwatuki

    J. investgative Dermatology   124 ( 4 )   A124 - 431   2005

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  • Involvement of granulysin-producing T cells in the development of superficial microbial folliculitis. Reviewed International journal

    T Oono, S Morizane, O Yamasaki, Y Shirafuji, W-K Huh, H Akiyama, K Iwatsuki

    The British journal of dermatology   150 ( 5 )   904 - 9   2004.5

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    BACKGROUND: Granulysin is a recently identified antimicrobial protein expressed on cytotoxic T cells, natural killer (NK) cells and NKT cells. It has been shown that granulysin contributes to the defence mechanisms against mycobacterial infection. Superficial microbial folliculitis is a common skin disease. In a previous report, we showed that, as a first line of defence, alpha-defensin, a human neutrophil peptide, and beta-defensin (human beta-defensin-2) were expressed in infiltrating neutrophils and in lesional epidermal keratinocytes, respectively, in superficial folliculitis. As we also observed many infiltrating lymphocytes in lesional dermis, we hypothesized that infiltrating lymphocytes may possess antimicrobial substances, such as granulysin, and play a role in the defence mechanism as a second line of defence. OBJECTIVES: Seven specimens of superficial microbial folliculitis diagnosed clinically and histologically were examined by means of immunohistochemistry. To identify the phenotype of cells expressing granulysin, confocal laser microscopic examination was performed. RESULTS: A dense lymphoid cell infiltrate was observed in pustules, in the perivascular regions. A large number of these lymphoid cells were positive for granulysin. Phenotypically, cells consisted of CD3+ T cells, CD8+ T cells and UCHL-1+ T cells. CD20+ cells and CD56+ cells were not observed. Microscopic examination with a confocal laser showed that the lymphocytes producing granulysin were CD3+ and CD4+ T cells but not CD8+ T cells. CONCLUSIONS: We showed that many granulysin-bearing T cells infiltrated affected follicles and perilesional dermis in superficial microbial folliculitis. However, few granulysin-positive lymphoid cells were observed in sterile pustular lesions. Our observations indicated that adaptive immunity such as granulysin, a lymphocyte-produced antimicrobial protein, may play an important role in the cutaneous defence mechanism.

    DOI: 10.1111/j.0007-0963.2004.05925.x

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  • Assessment of Streptococcus pyogenes microcolony formation in infected skin by confocal laser scanning microscopy. Reviewed International journal

    Hisanori Akiyama, Shin Morizane, Osamu Yamasaki, Takashi Oono, Keiji Iwatsuki

    Journal of dermatological science   32 ( 3 )   193 - 9   2003.9

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    BACKGROUND: Streptococcus pyogenes and Staphylococcus aureus are often simultaneously detected from many cases of non-bullous impetigo with atopic dermatitis. OBJECTIVES: Using confocal laser scanning microscopy (CLSM), to investigate formation of S. pyogenes microcolonies in skin lesions. METHODS: The S. pyogenes cells in the stationary growth phase alone were strongly stained with fluorescein isothiocyanate-concanavalin A (FITC-ConA), and this staining was reduced by pretreatment with amylase. Although the components of sugars in glycocalyx produced by S. pyogenes cells are unknown, we suggested that the materials stained by FITC-ConA were consistent with the presence of ConA-reactive sugars in glycocalyx produced by S. pyogenes cells. RESULTS: S. pyogenes cells associated with streptococcal impetigo skin and croton-oil inflamed mouse skin formed microcolonies encircled by materials (glycocalyx) that stained strongly with FITC-ConA, and these findings were consistent with those in biofilms. In croton-oil inflamed mouse skin, polymorphonuclear leukocytes (PMNs) infiltrated to just below the epidermis in the cefdinir-treated group but only to the middle dermis in the cefdinir-non-treated group. In this case S. pyogenes and S. aureus cells formed separate microcolonies and existed independently in the outer walls of pustule lesions of streptococcal impetigo. CONCLUSION: In skin infections, S. pyogenes and S. aureus formed aggregates of microcolonies (similar to that in biofilms) encircled by glycocalyx, which can make the infection hard to eradicate using an antimicrobial agent alone. The effect of conventional antimicrobial agents against biofilm is mainly due to the increase of the invasion of PMNs into the biofilm.

    DOI: 10.1016/S0923-1811(03)00096-3

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Books

  • Evolution of Atopic Dermatitis in the 21st Century

    Springer  2017 

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  • EBM皮膚疾患の治療up-to-date

    中外医学社  2015 

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  • 今日の処方改訂第5版「(共著)」

    南江堂  2013 

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  • 今日の治療と看護 改訂第3版

    南江堂  2013 

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  • 皮膚のリンパ腫 最新分類に基づく診療ガイド「(共著)」

    中山書店  2012 

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  • 皮膚疾患最新の治療2011-2012(共著)

    南江堂  2011 

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  • フィッツパトリック皮膚科学アトラス

    丸善株式会社  2008 

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MISC

  • カルシウム製剤の血管外漏出による医原性石灰沈着症の2例

    臼井 真菜, 山崎 修, 赤松 由規, 森田 安理, 杉原 悟, 三宅 智子, 横山 恵美, 森実 真

    日本皮膚科学会雑誌   131 ( 11 )   2453 - 2453   2021.10

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  • 染毛剤の重合体が原因と考えられたアナフィラキシーの1例

    徳田 真優, 三宅 智子, 赤松 由規, 前 琴絵, 芦田 日美野, 山崎 修, 森実 真, 松浦 浩徳

    日本皮膚科学会雑誌   131 ( 11 )   2453 - 2453   2021.10

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  • 緩徐に進行するBRAF遺伝子変異陽性悪性黒色腫の1例

    竹崎 大輝, 立花 宏太, 杉原 悟, 山崎 修, 森実 真

    日本皮膚科学会雑誌   131 ( 11 )   2455 - 2455   2021.10

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  • 濾胞性リンパ腫(FL)に腫瘍随伴性天疱瘡(PNP)と閉塞性細気管支炎(BO)を合併した1例

    赤松 由規, 藤井 江利子, 川本 友子, 三宅 智子, 山崎 修, 森実 真, 鳥越 利加子, 大山 矩史, 藤原 英晃, 石井 文人

    日本皮膚科学会雑誌   131 ( 11 )   2451 - 2452   2021.10

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  • 乾癬の経過中に発症した落葉状天疱瘡の1例

    芦田 日美野, 前 琴絵, 赤松 由規, 徳田 真優, 三宅 智子, 梶田 藍, 山崎 修, 森実 真

    日本皮膚科学会雑誌   131 ( 11 )   2451 - 2451   2021.10

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  • センチネルリンパ節生検を施行した類上皮肉腫の1例

    徳田 真優, 杉原 悟, 赤松 由規, 前 琴絵, 芦田 日美野, 山崎 修, 森実 真, 谷口 恒平

    日本皮膚科学会雑誌   131 ( 11 )   2451 - 2451   2021.10

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  • 膿疱化・紅皮症化をきたし急性呼吸窮迫症候群を併発した尋常性乾癬の1例

    芦田 日美野, 前 琴絵, 横山 恵美, 梶田 藍, 浦上 仁志, 森実 真, 谷口 暁彦, 大野 貴司

    日本皮膚科学会雑誌   131 ( 11 )   2445 - 2445   2021.10

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  • トラベクテジン血管外漏出による皮膚壊死2例の治療経験

    杉原 悟, 池田 賢太, 山崎 修, 森実 真, 下江 敬生, 中村 圭一郎

    西日本皮膚科   83 ( 5 )   417 - 422   2021.10

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  • 長期生存を得た肝転移乳房外Paget病の1例

    内藤 聖子, 神野 泰輔, 山崎 修, 森実 真, 野村 隼人, 河田 真理子, 吉富 惠美, 荒川 謙三

    西日本皮膚科   83 ( 5 )   431 - 435   2021.10

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  • 無症候性急性期脳梗塞を合併した日本紅斑熱の1例

    山崎 江利子, 山崎 修, 赤松 由規, 川本 友子, 三宅 智子, 森実 真, 田所 功, 高谷 陽一

    日本皮膚科学会雑誌   131 ( 11 )   2448 - 2448   2021.10

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  • Trichophyton interdigitaleによる足白癬を合併し、汗疱様皮疹を示したGranular C3 dermatosisの1例

    川上 佳夫, 青山 裕美, 多田 光太郎, 安澤 数史, 西部 明子, 望月 隆, 森実 真

    日本皮膚科学会雑誌   131 ( 11 )   2450 - 2450   2021.10

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  • 手掌に生じたacquired smooth muscle hamartomaの1例

    中井 友美, 野村 隼人, 山崎 修, 森実 真, 谷口 恒平

    日本皮膚科学会雑誌   131 ( 11 )   2447 - 2447   2021.10

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  • 臀部〜陰嚢基部に生じた増殖性外毛根鞘性嚢腫(PTC)の1例

    赤松 由規, 山崎 修, 山崎 江利子, 川本 友子, 森実 真, 深松 紘子

    日本皮膚科学会雑誌   131 ( 11 )   2447 - 2448   2021.10

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  • NB-UVBによって消退したpatch granuloma annulareの1例

    池田 賢太, 山崎 修, 森実 真, 水野 佳寿子

    日本皮膚科学会雑誌   131 ( 11 )   2450 - 2450   2021.10

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  • 遺伝性毛髪疾患の情報のアップデート

    下村 裕, 村田 真美, 林 良太, 川上 佳夫, 森実 真

    西日本皮膚科   83 ( 5 )   475 - 475   2021.10

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  • 皮膚T細胞性リンパ腫における皮膚FCMの有用性の検討

    中川 裕貴, 三宅 智子, 平井 陽至, 山崎 修, 岩月 啓氏, 森実 真, 高橋 孝英, 濱田 利久

    日本皮膚科学会雑誌   131 ( 11 )   2446 - 2446   2021.10

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  • 濾胞性樹状細胞肉腫に合併した腫瘍随伴性天疱瘡の1例

    前 琴絵, 芦田 日美野, 三宅 智子, 森実 真, 西 達也, 田端 雅弘, 石井 文人

    日本皮膚科学会雑誌   131 ( 11 )   2446 - 2446   2021.10

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  • 肥満・高脂血症が乾癬病変を悪化させる機序の検討

    池田 賢太, 向井 知之, 赤木 貴彦, 浅野 澄恵, 守田 吉孝, 森実 真

    日本臨床免疫学会総会プログラム・抄録集   49回   109 - 109   2021.10

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  • 臨床講義 乾癬の病態理解の進歩と最新の治療

    森実 真

    皮膚科の臨床   63 ( 9 )   1365 - 1371   2021.8

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    Language:Japanese   Publisher:金原出版(株)  

    <文献概要>乾癬に関する研究は世界中で精力的に行われており,病態の理解も飛躍的に進歩している。その目覚ましい研究の成果が臨床応用され,乾癬に対する新しい薬剤や治療法が毎年のように登場している。本稿では乾癬の病態理解の進歩と最新の治療について詳説する。

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  • 【診察室での患者さんの質問に答えます】扁平苔癬 原因はなんですか 口腔粘膜

    森実 真

    皮膚科の臨床   63 ( 6 )   876 - 877   2021.6

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  • 【好酸球が関与する皮膚病】好酸球浸潤が著明であったPanton-Valentine leukocidin陽性MRSAによるせつ腫症

    小橋 美那, 橋本 倫子, 三宅 智子, 山崎 修, 森実 真

    皮膚病診療   43 ( 6 )   524 - 527   2021.6

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    <文献概要>症例のポイント ・健常人のPanton-Valentine leukocidin(PVL)産生の市中型MRSA(methicillin-resistant Staphylococcus aureus)感染によるせつ腫症であり,再発を繰り返し治療に難渋した.・せつ,せつ腫症の典型の病理組織像では毛包周囲の壊死,好中球の浸潤を認めるが,著明な好酸球の浸潤を認めた.

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  • 【診察室での患者さんの質問に答えます】扁平苔癬 原因はなんですか 口腔粘膜

    森実 真

    皮膚科の臨床   63 ( 6 )   876 - 877   2021.6

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  • ハンセン病患者に生じた有棘細胞癌

    安富 陽平, 山崎 修, 立花 宏太, 杉本 佐江子, 森実 真

    Skin Cancer   36 ( 1 )   71 - 75   2021.6

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    Language:Japanese   Publisher:(一社)日本皮膚悪性腫瘍学会  

    91歳,男性。既往にハンセン病,尿管癌がある。ADLが悪く,ほぼ寝たきり状態。2年前に顔面神経麻痺のある左頬にびらんと痂皮が散在し,日光角化症として液体窒素などで加療されていたが,腫瘤になり徐々に増大し,生検で有棘細胞癌と診断された。他院では手術や放射線治療が検討されたが保存的治療の方針となっていた。創部を触る動作が増えたためアセトアミノフェン内服,潰瘍面より出血がありモーズ療法を行っていた。その後さらに腫瘤は増大し,当科を紹介受診した。左頬に中央に潰瘍を伴う12×10cmの淡紅褐色,広基性の腫瘤があった。CTではリンパ節,遠隔転移は認めなかった。超高齢でADLが悪く,低アルブミン血症,胸水があり,腫瘤が大きく輸血が必要でハイリスク症例であった。局所制御目的で全身麻酔下に切除,植皮を行った。しかし術後5ヵ月後に肺炎で永眠された。(著者抄録)

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  • 【好酸球が関与する皮膚病】好酸球浸潤が著明であったPanton-Valentine leukocidin陽性MRSAによるせつ腫症

    小橋 美那, 橋本 倫子, 三宅 智子, 山崎 修, 森実 真

    皮膚病診療   43 ( 6 )   524 - 527   2021.6

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    <文献概要>症例のポイント ・健常人のPanton-Valentine leukocidin(PVL)産生の市中型MRSA(methicillin-resistant Staphylococcus aureus)感染によるせつ腫症であり,再発を繰り返し治療に難渋した.・せつ,せつ腫症の典型の病理組織像では毛包周囲の壊死,好中球の浸潤を認めるが,著明な好酸球の浸潤を認めた.

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  • 乾癬の生物学的製剤治療に対する結核対策実態の多施設共同調査

    金子 栄, 鶴田 紀子, 伊藤 宏太郎, 山口 和記, 宮城 拓也, 高橋 健造, 東 裕子, 森実 真, 野村 隼人, 山口 道也, 日野 亮介, 澤田 雄宇, 中村 元信, 大山 文悟, 大畑 千佳, 米倉 健太郎, 林 宏明, 柳瀬 哲至, 松阪 由紀, 杉田 和成, 菊池 智子, 三苫 千景, 中原 剛士, 古江 増隆, 岡崎 布佐子, 小池 雄太, 今福 信一, 西日本炎症性皮膚疾患研究会

    日本皮膚科学会雑誌   131 ( 6 )   1525 - 1532   2021.5

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    乾癬治療における生物学的製剤使用時の結核スクリーニングの現状について西日本の18施設を調査した。事前の検査ではinterferon gamma release assay(IGRA)が全施設で行われ、画像検査はCTが15施設、胸部レントゲンが3施設であった。フォローアップでは検査の結果や画像所見により頻度が異なっていた。全患者1,117例のうち、IGRA陽性で抗結核薬を投与されていた例は64例、IGRA陰性で抗結核薬を投与されていた例は103例であり、副作用を認めた患者は23例15%であった。これらの適切な検査と治療により、結核の発生頻度が低く抑えられていると考えられた。(著者抄録)

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  • CVポート部より漏出したトラベクテジンによる広範囲壊死の2例

    杉原 悟, 池田 賢太, 山崎 修, 森実 真, 下江 敬生, 中村 圭一郎

    日本皮膚外科学会誌   25   54 - 55   2021.5

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  • 口腔扁平苔癬から発症し、歯科金属除去後に毛孔性扁平苔癬を合併した1例

    横山 恵美, 木村 摩耶, 山崎 修, 森実 真, 山内 晶子, 濱田 利久, 佐々木 朗

    西日本皮膚科   83 ( 2 )   120 - 124   2021.4

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    68歳,女性。半年前に舌痛および口腔内違和感が生じ,口腔外科にて口腔扁平苔癬と診断され,その後下腿に暗紅色の紅斑が出現した。金属パッチテストで,亜鉛陽性となり,該当歯科金属を除去したところ,数日後より頭皮にそう痒を伴う脱毛が多発した。初診時,頭部に淡紅色の紅斑を伴う脱毛斑が9ヶ所みられ,病理組織学的に毛包漏斗部および峡部上皮のリンパ球浸潤と周囲間質の線維化および正常毛球の残存を認めた。下腿紅斑は表皮真皮境界部の空胞変性と真皮の帯状リンパ球浸潤の像であった。脱毛斑に対しステロイド局注を開始し,約2ヵ月後にそう痒と紅斑は改善し,約8ヵ月後に,小型の脱毛斑2ヶ所は治癒した。その後脱毛瘢痕部にエキシマライトを約1.5年間照射し脱毛斑はさらに3ヶ所治癒した。口腔粘膜部のびらんや下腿紅斑は出没を繰り返し,初診より1.5年後,腟周囲にびらんおよび白色局面が出現し,いずれもステロイド外用を継続中である。自験例は歯科金属除去後に扁平苔癬の一部として毛包性扁平苔癬が生じ,既存の口腔や下腿病変の増悪と腟周囲にも病変が生じた経過が特徴的であった。当院で過去2年間のうち金属パッチテスト陽性の扁平苔癬は15例あり,年齢は39歳から84歳までの男性4名,女性11名で,粘膜型13例,皮膚型1例,皮膚粘膜毛孔性扁平苔癬型1例(自験例)であった。該当金属を除去したのは4例で,経過不明の2例をのぞき,自験例を含めいずれも症状は改善しなかった。(著者抄録)

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  • らい性結節性紅斑が慢性化したLL型ハンセン病

    篠倉 美理, 尾崎 元昭, 川上 佳夫, 梅川 康弘, 吉原 由樹, 石井 則久, 山崎 修, 森実 真

    日本皮膚科学会雑誌   131 ( 2 )   329 - 335   2021.2

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    20歳代の在日外国人男性。右手疼痛を主訴に整形外科を受診した際に皮疹を指摘され、当科を受診した。顔面・四肢末梢・腰腹部に光沢のある境界明瞭な結節を多数認め、臨床症状、皮膚スメア検査、組織所見、らい菌特異的PCR陽性よりLL型ハンセン病と診断した。ハンセン病およびらい反応は、治療が遅れると後遺症を残しうるため早期診断・早期治療が重要である。自験例は多剤併用療法開始後に皮膚症状の悪化や神経・眼症状、発熱、関節痛など多彩ならい性結節性紅斑の症状が出現し、その後慢性化したが、ほとんど後遺症なく経過している。(著者抄録)

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  • 臭化カリウム減量により症状が軽快した臭素疹の1例

    安富 陽平, 川上 佳夫, 篠倉 美理, 平井 陽至, 山崎 修, 森実 真

    西日本皮膚科   83 ( 1 )   18 - 21   2021.2

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    1歳,女児。乳児早期発症てんかんで治療中であったが,けいれん発作のコントロールが不良で臭化カリウムの内服を開始した。内服開始2ヵ月半後に四肢に紅色丘疹が出現し,膿疱を伴う紅色局面に進展した。病理組織では表皮内に好中球の浸潤,真皮では全層にわたって膠原線維束に分け入るような好中球の浸潤があり,とくに毛包周囲や毛包上皮への好中球の浸潤が顕著であった。血中臭化物濃度は91.8mg/dlと高値であり,臭素疹と診断した。臭化カリウムを減量してステロイド軟膏の外用で皮疹は軽快した。内服減量により皮疹が軽快したことから,臭素疹の機序はアレルギー性ではなく,用量依存性に発症する機序が推測される。(著者抄録)

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  • Spitz母斑と黒子様色素細胞母斑の隣接発生例 免疫染色によるROS1過剰発現とBRAF V600E変異蛋白の証明

    山下 珠代, 山崎 修, 高田 実, 松浦 能子, 谷口 恒平, 後藤 啓介, 森実 真

    西日本皮膚科   83 ( 1 )   30 - 33   2021.2

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    25歳,女性。初診の約6ヵ月前より右上腕に紅色結節が出現し,急速に増大した。肉眼所見では5×10mmの境界明瞭な紅色扁平結節が存在しそれと隣接して2mmの黒褐色の小色素斑が認められた。病理組織学的に結節部はSpitz母斑,小色素斑は黒子様色素細胞母斑であった。さらに,免疫組織化学的に結節部にはROS1蛋白の過剰発現が,色素斑にはBRAF V600E変異蛋白が検出され,両者は発生機序の異なる病変であることが示された。(著者抄録)

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  • 瀬戸内海に生息するナルトビエイによる外傷後に生じたMycobacterium marinum感染症の1例

    谷本 尚吾, 川上 佳夫, 安富 陽平, 山崎 修, 森実 真

    西日本皮膚科   82 ( 6 )   460 - 463   2020.12

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    71歳,男性。2018年8月上旬に,瀬戸内海での漁で網にかかったナルトビエイ(Aetobatus narutobiei)を外していた時に,尻尾の棘が左小指の基部に刺さった。直後に海水で洗浄し,しばらく自宅で様子をみていたが,同部位が次第に腫脹してきたため,1ヵ月半後に当科を受診した。初診時,左小指MP関節の背側に中心がクレーター状に陥凹し,潰瘍化している15×14mmの紅色結節を認めた。組織片を2%小川培地に接種し,30℃と35℃の条件下で培養を行ったところ,いずれの条件下でも28日目に灰白色のコロニー形成を認め,MALDI-TOF MSのマススペクトルのパターンからMycobacterium marinumと診断した。皮膚病変はミノサイクリン塩酸塩(200mg/日内服を3ヵ月間)を投与して完治した。エイ刺傷は,その鋭利な尾棘による損傷と刺毒による炎症を特徴とし,創部感染のリスクもある。近年ナルトビエイの瀬戸内海での生息域の拡大が問題視されている。そのため,エイ刺傷への対応を知ることは大切である。(著者抄録)

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  • 【抗菌ペプチドとマイクロバイオーム】オーバービュー 抗菌ペプチドとマイクロバイオーム

    森実 真

    皮膚アレルギーフロンティア   18 ( 3 )   127 - 130   2020.11

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    微生物の侵入から身体を守る皮膚のバリア機構においては、「抗菌ペプチド」が重要な役割を果たしている。抗菌ペプチドは広域の抗菌活性をもつのみならず、炎症誘導、創傷治癒促進、血管新生促進など、さまざまな機能を有していることも報告され、アラーミン(alarmin)の一種とも考えられている。一方、皮膚のバリア形成には、その場に存在する常在菌も重要な役割を果たしていることがわかってきた。常在菌叢を構成する個々の細菌種のゲノムの集合体を「マイクロバイオーム」と呼ぶ。近年のシークエンス技術の発展によって、正常皮膚および皮膚疾患病変部のマイクロバイオームに関しても、さまざまな新知見が得られている。(著者抄録)

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  • カセリサイディンLL-37の真の役割は?

    森実 真, 山崎 研志

    皮膚アレルギーフロンティア   18 ( 3 )   154 - 161   2020.11

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  • ボリコナゾール長期内服中に発症した有棘細胞癌と多発日光角化症の1例

    篠倉 美理, 光井 聖子, 山崎 修, 森実 真

    臨床皮膚科   74 ( 11 )   887 - 891   2020.10

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    <文献概要>73歳,男性.4年前に肺アスペルギルス症の治療のためボリコナゾールを内服開始した.2年前から頭部,顔面,両手背に角化性の丘疹,紅斑が多発した.病理組織所見は,顔面は有棘細胞癌,頭部・手背は日光角化症であった.ボリコナゾール内服中止とイミキモド外用により皮疹は改善した.ボリコナゾールは,その代謝物が紫外線を吸収して活性酸素を産生し,表皮のDNA損傷を惹起する.さらにボリコナゾールそのものがCOX-2の転写活性を誘導することで発癌を促進させる可能性が示されており,長期内服中に光線過敏症状を経て日光角化症,有棘細胞癌を生じうる.ボリコナゾールの光線関連皮膚障害は本邦ではまだ報告が少ないものの,十分な遮光指導を受けていない肺アスペルギルス症の患者に多い.ボリコナゾール内服患者には具体的な遮光指導と慎重な皮膚症状の経過観察を行うことで,光線関連皮膚障害を最小限に抑えることが期待できる.

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  • 【乾癬は奥深い】日光角化症に対するイミキモドクリームで誘発された乾癬

    妹尾 春佳, 山崎 修, 森実 真, 辻 和英

    皮膚病診療   42 ( 9 )   758 - 761   2020.9

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    <文献概要>症例のポイント ・イミキモドは単球および形質細胞様樹状細胞を主体としたTLR7に作用し,その結果IL-17/IL-23の産生を促し,乾癬のマウスモデルとして使用されている.・日光角化症の患者に対するイミキモドクリーム外用により,外用部位以外にも角化性紅斑が出現し,乾癬が誘発された.・患者は乾癬の既往はなかったが,イミキモドクリームにより強い紅斑反応を示していた.

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  • セツキシマブ・パクリタキセル併用療法中に生じたLeukocytoclastic Vasculitisの1例

    安富 陽平, 川上 佳夫, 篠倉 美理, 神野 泰輔, 藤本 裕子, 三宅 智子, 山崎 修, 森実 真

    西日本皮膚科   82 ( 4 )   271 - 275   2020.8

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    58歳,男性。右外耳道有棘細胞癌に対してepidermal growth factor receptor(EGFR)阻害剤のセツキシマブとパクリタキセルの併用療法を6ヵ月間,合計14回施行した。最終投与日から13日後に四肢に一部血疱や浸潤を伴う点状紫斑が多発し,腎機能障害も認めた。皮膚病理所見では真皮全層の血管周囲に好中球や好酸球の浸潤と核塵を認め,真皮浅層から中層の毛細血管に血管壁のフィブリノイド変性があり,leukocytoclastic vasculitis(LCV)に矛盾しない所見であった。蛍光抗体直接法では真皮上層の血管周囲にC3の沈着が認められたが,IgAの沈着は認めなかった。セツキシマブ・パクリタキセルを休薬し,プレドニゾロン(PSL)20mg/日内服と細胞外液の補液を開始したところ,皮疹,腎機能ともに速やかに改善した。しかし,蛋白尿と尿潜血が持続して検出されたため,PSL8.0mg/日を維持量として継続した。その後外耳道癌が再び増大し,4ヵ月後にセツキシマブ・パクリタキセルを再投与したが皮疹の再燃は認めなかった。EGFR阻害剤投与中に,血管周囲にC3の沈着を伴うLCVの報告が本症例以外にも3例ある。そのうち1例では潰瘍化や壊死を伴う臨床像を呈し,1例では下血を合併していた。本症例ではEGFR阻害剤がLCV発症の直接の誘因になったかどうかは不明だが,EGFR阻害剤によりLCVが重症化した可能性が考えられる。(著者抄録)

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  • 私の診療経験から 当科におけるアトピー性皮膚炎診療・研究 表皮セリンプロテアーゼ活性について

    森実 真

    臨牀と研究   97 ( 8 )   1042 - 1046   2020.8

  • アトピー性皮膚炎と表皮セリンプロテアーゼ活性

    森実 真

    西日本皮膚科   82 ( 3 )   213 - 214   2020.6

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  • 臨床研究 患者への情報提供を目的とした頭部血管肉腫に対する化学放射線療法の有害事象の検討

    黒田 桂子, 山崎 修, 三宅 智子, 加持 達弥, 岩月 啓氏, 森実 真

    皮膚科の臨床   62 ( 4 )   445 - 448   2020.4

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    <文献概要>頭部血管肉腫に対して,放射線療法とタキサン系抗癌剤による化学放射線療法が主流となっており,有害事象や合併症により入院が長期化することがある。しかしながら,高齢の患者が治療について十分に理解できていないことも多く,治療のコンプライアンス低下につながる。そこで患者への正確な情報提供を目的として,頭部血管肉腫の入院中の有害事象について検討した。入院期間は中央値57日,化学放射線療法による有害事象は放射線皮膚炎94%,皮膚びらんからの感染41%,脱毛53%,血球減少53%であり,発現時期と期間を明確にできた。事前に主なスケジュールと有害事象について十分説明することが重要である。

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  • 【アレルギー疾患の最新の治療】最新のアレルギー疾患治療 薬疹

    森実 真

    臨牀と研究   97 ( 3 )   309 - 314   2020.3

  • 皮疹を契機に発見され視床下部障害を呈した成人発症LCHの1例

    高瀬了輔, 中野靖浩, 佐住洋祐, 水田有紀, 榮浩行, 長谷川功, 三好智子, 小川弘子, 森実真, 大塚文男

    日本内分泌学会雑誌   96 ( 2 )   2020

  • 西日本豪雨災害における皮膚科診療支援と岡山県下皮膚科の災害医療対策について

    辻 和英, 神崎 寛子, 服部 浩明, 森実 真, 青山 裕美, 林 宏明, 佐藤 淳

    日本臨床皮膚科医会雑誌   36 ( 6 )   724 - 730   2019.11

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  • 免疫チェックポイント阻害薬を投与した多発性筋炎合併悪性黒色腫の1例

    野村 隼人, 山崎 修, 加持 達弥, 若林 宏, 宮脇 義亜, 森実 真

    西日本皮膚科   81 ( 5 )   396 - 400   2019.10

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    61歳,男性。2013年5月に多発性筋炎と診断され,プレドニゾロン(PSL)で治療が開始された。治療開始前のCTで左頸部と左腋窩リンパ節腫脹を認め経過観察されていたが,リンパ節は増大傾向を呈し,リンパ節生検で悪性黒色腫と診断された。精査では原発巣は認められなかった。DTIC療法とDAC-Tam-Feron療法を受けたが効果に乏しく,2015年3月からベムラフェニブを開始し転移巣は速やかに縮小したが,転移巣が増大してきたため,2015年11月にニボルマブ2mg/kgを3週間間隔で投与開始した。ニボルマブ2回目投与後から筋原性酵素の上昇や疲労感を認め,多発性筋炎の増悪と考えた。ニボルマブを継続しつつ,PSLを5mgから20mgに増量したところ,筋症状は改善した。しかし転移巣は増大傾向にあったため,ニボルマブは5回で中止した。イピリムマブも効果がなく,2016年6月からダブラフェニブとトラメチニブの併用療法を開始した。転移巣は速やかに縮小したが,次第に耐性を示すようになった。2017年7月に多発転移により全身状態が悪化し,永眠した。免疫チェックポイント阻害薬により既存の自己免疫疾患が悪化したが,自己免疫疾患悪化時も適切な対応を行うことにより免疫チェックポイント阻害薬は継続可能であった。(著者抄録)

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  • 【肉芽腫症】皮疹から診断された全身リンパ節腫脹をきたしたサルコイドーシスの1例

    森田 安理, 川上 佳夫, 三宅 智子, 平井 陽至, 加持 達弥, 山崎 修, 森実 真

    皮膚科の臨床   61 ( 11 )   1611 - 1614   2019.10

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    <文献概要>65歳,女性。4年前より左耳前部に紅斑が出現した。近医皮膚科でステロイド外用を開始されるも難治であった。生検で真皮内に類上皮細胞肉芽腫を認め,サルコイドーシスの疑いで精査・加療目的に当科を紹介受診した。初診時,左耳前部に鱗屑を付す4×5cm大の円板状紅斑,耳介部に潰瘍形成,頭頂部に15×20mm大の瘢痕様紅斑を認めた。単純CTで両側縦隔リンパ節に加え,両鼠径リンパ節など全身のリンパ節腫脹を認めた。皮膚生検,鼠径リンパ節生検,気管支鏡検査でいずれも非乾酪性肉芽腫を認めたため,サルコイドーシスと確定診断した。自験例は感染症との鑑別を要する非典型的臨床像であったが,鼠径リンパ節生検により診断を裏づけることができた。また,Th2優位に移行した成熟期のサルコイドーシスであったと推測する。

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  • アトピー性皮膚炎とカリクレイン関連ペプチダーゼ

    森実 真

    西日本皮膚科   81 ( 5 )   367 - 371   2019.10

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    表皮のバリア形成に重要な役割を果たす表皮角化細胞産生カリクレイン関連ペプチダーゼとアトピー性皮膚炎(AD)との関連性について述べた。多くのカリクレイン(KLKs)はAD病変部において発現が増強されており、表皮バリア機能を低下させることによって病態形成と関連している可能性がある。表皮角化細胞はKLKsの阻害因子であるリンパ上皮Kazal型関連阻害因子(LEKTI)、さらにSLPI、PI3、SPINK6、SPINK9なども発現するため、AD病変部の過剰なプロテアーゼ活性については酵素のみならず、阻害因子の発現量および機能、さらにはpHの変化も含めて総合的に酵素活性増強機構を検討する必要がある。

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  • 【帯状疱疹の新時代-診療の基本と最新情報-】(Part2)気になる帯状疱疹のサイン ヘルペス型水疱における中心臍窩形成のメカニズム

    森実 真

    Visual Dermatology   18 ( 9 )   906 - 906   2019.8

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  • 有茎広背筋皮弁で再建した冠動脈ステント留置後の右肩甲部放射線性皮膚潰瘍

    森田 安理, 石井 芙美, 川上 佳夫, 加持 達弥, 竹原 彩, 大塚 正樹, 山崎 修, 森実 真

    皮膚科の臨床   61 ( 9 )   1387 - 1390   2019.8

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    <文献概要>75歳,男性。狭心症で冠動脈ステント留置後3ヵ月目頃より右肩甲部に痒みを伴う紅斑が出現し,1年後に潰瘍化した。デブリードマンと外用療法で約1年半加療されるも難治であったため,精査・加療目的に当科を紹介受診した。初診時,右肩甲部に3×3cm大の深い潰瘍があり周囲8×7cm大の範囲に板状硬結,暗褐色色素沈着と血管拡張を認めた。MRIでは筋層まで達していた。冠動脈造影による放射線性皮膚潰瘍と考え,潰瘍,硬結を切除,有茎広背筋皮弁術を施行した。術後は機能面,整容面ともに良好であった。右肩甲部皮膚潰瘍の患者に遭遇した場合,冠動脈造影の既往を問診することが重要である。また再建方法としては有茎広背筋皮弁術が治療選択肢となる。

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  • 各診療科の協力で切除し得た宗教的輸血拒否患者のびまん性神経線維腫

    立花 宏太, 山崎 修, 光井 聖子, 山下 珠代, 岩月 啓氏, 森実 真, 西森 久和, 生口 俊浩, 坂野 彩, 谷口 新, 小林 求, 森田 幸子, 橋本 倫子

    皮膚科の臨床   61 ( 8 )   1303 - 1306   2019.7

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    <文献概要>69歳,女性。神経線維腫1型に伴うびまん性神経線維腫と特発性血小板減少性紫斑病(ITP)を合併。宗教的輸血拒否患者。25年前より右下腹部の腫瘤が徐々に増大してきていた。2016年当科を初診し,手術を計画したが,宗教上の輸血療法不能を理由に中止となった。2017年腫瘤の増大と表面の紫斑が出現した。腫瘤表面に拳大の紫斑と内部に硬結を触知,貧血の進行を認め,腫瘤内出血が疑われ緊急入院した。医療安全上の対応と周術期の対策を各科・各部署の協力で検討した。ITPに対してプレドニゾロン内服,術前に動脈塞栓術を施行後,術中の閉鎖回路による希釈式自己血灌流のうえ,術中出血は200mlで腫瘍を切除できた。院内の医療連携システムの充実が重要である。

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  • 【間葉系腫瘍】下口唇に生じたSolitary Fibrous Tumorの1例

    香曽我部, 純子, 川上 佳夫, 光井 聖子, 三宅 智子, 山崎 修, 岩月 啓氏, 小田 和歌子, 森実 真

    皮膚科の臨床   61 ( 8 )   1195 - 1198   2019.7

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    <文献概要>52歳,男性。2年前より下口唇の口腔粘膜部に自覚症状のない粘膜下結節が出現した。超音波検査では,境界明瞭な10mm大の粘膜下結節を認め,内部不均一な低エコー像を示した。カラードプラ像では豊富な血流信号を認めた。結節を全摘出したところ,病理組織では異型に乏しい長紡錘形細胞が特定の配列をとることなく増殖し,間質に不規則に分枝した鹿角様血管を認めた。免疫染色ではCD34とbcl-2がびまん性に陽性で,CD31とfactorVIIIは陰性であった。また,抗STAT6抗体による免疫染色では,核に陽性であった。以上の所見からsolitary fibrous tumor(SFT)と診断した。臨床所見ではmucous cystとの鑑別を要したが,超音波検査で血流を確認することがSFTの診断の一助となると考えた。

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  • ニボルマブが奏効した食道悪性黒色腫の2例

    加持 達弥, 山崎 修, 森実 真, 岩月 啓氏, 前田 直見, 白川 靖博

    Skin Cancer   34 ( 1 )   35 - 40   2019.6

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    症例1:60歳、男性。2015年、食道悪性黒色腫と診断された。BRAF変異陰性。後腹膜、腸間膜に多発転移あり。ニボルマブ投与を開始し、腹膜播種病変は画像上消失した。原発巣と近傍のリンパ節転移は残存したため、食道亜全摘+所属リンパ節郭清術を施行した。術後、ニボルマブ投与を再開したが、脳転移が出現。イピリムマブ投与に変更し、全脳照射を施行したが、永眠された。症例2:72歳、女性。2015年、食道悪性黒色腫と診断された。BRAF変異陰性。PET/CTにてL2椎体に転移あり。ニボルマブ投与により転移巣は画像上消失し、原発巣は色素沈着のみとなった。ニボルマブ投与継続していたが、食道原発巣の再発を認め、食道亜全摘+所属リンパ節郭清術を施行した。術後、無治療で経過観察中であるが、現在のところ再発、転移はない。進行期の食道悪性黒色腫にニボルマブが奏効した2例を経験したので、報告した。(著者抄録)

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  • Neuroplastinβとextracellular matrix metalloprotease inducerはS100A8/A9に対する機能的な受容体であり,ケラチノサイトの増殖とアトピーの皮膚炎症の増強に関与している. Critical role of novel receptors to S100A8/A9, EMMPRIN and NPTNβ, on keratinocyte growth and inflammation in atopic dermatitis.

    阪口政清, 山本真実, 宮井雅史, 松元 有羽子, 木下理恵, 村田 等, 山本健一, 森実 真, 岩月啓氏, 許 南浩, 坪井良治, 日比野 利彦

    臨床免疫   49 ( 6 )   594 - 598   2017

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  • 【アトピー性皮膚炎の病態研究】 Neuroplastin βとextracellular matrix metallo-protease inducerはS100A8/A9に対する機能的な受容体であり、ケラチノサイトの増殖とアトピーの皮膚炎症の増強に関与している

    阪口 政清, 山本, 真実, 宮井 雅史, 木下 理恵, 村田 等, 山本 健一, 森実 真, 岩月 啓氏, 許 南浩, 坪井 良治, 日比野 利彦

    臨床免疫・アレルギー科   67 ( 6 )   594 - 598   2017

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  • 【皮膚疾患ペディア】角化症 Gibertばら色粃糠疹

    日本医師会雑誌   145 ( S2 )   S213-S213   2016

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  • レンサ球菌感染症のすべて

    山崎修, 森実真

    Monthly Book Derma   242   71 - 76   2016

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  • 病院現況および患者視点からみた進行期悪性黒色腫に対する新規治療

    山崎 修, 加持 達弥, 梅村 啓史, 平井 陽至, 森実 真, 濱田 利久, 高田 実, 岩月 啓氏, 勝井 邦彰, 合地 明

    日本皮膚科学会雑誌   126 ( 9 )   1709 - 1716   2016

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    DOI: 10.14924/dermatol.126.1709

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  • 【皮膚疾患ペディア】角化症 乾癬

    日本医師会雑誌   145 ( S2 )   S208-S209   2016

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  • 【皮膚疾患ペディア】角化症 扁平苔癬

    日本医師会雑誌   145 ( S2 )   S211-S212   2016

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  • 処置室の感染対策はどうしていますか?

    Visual Dermatology   13 ( 6 )   706 - 708   2014

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  • 乾癬の治療(生物学的製剤を除く) 乾癬の内服療法 国内外の知見から(解説)

    森実真

    日本皮膚科学会雑誌   123 ( 13 )   2549 - 2551   2013

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  • 皮膚の炎症と表皮バリア機能

    アレルギーの臨床   33 ( 2 )   48 - 52   2013

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  • Th2サイトカインはアトピー性皮膚炎患者におけるカリクレイン7の発現と機能を増強する

    森実真, 山崎研志, 梶田藍, 池田佳寿子, Maosheng Zhan, 青山裕美, Richard L.Gallo, 岩月啓氏

    岡山医学会雑誌   125 ( 3 )   217 - 220   2013

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    Authorship:Lead author   Language:Japanese  

    DOI: 10.4044/joma.125.217

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  • Hematological complications of epidermolysis bullosa

    66 ( 5 )   50 - 53   2012.4

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  • Epstein-Barrウイルス感染症と種痘様水疱症(共著)

    平井陽至, 山本剛伸, 三宅智子, 山内晶子, 藤井一恭, 森実真, 岩月啓氏

    Monthly Book Derma   191   48 - 53   2012

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  • 後天性魚鱗癬との鑑別を要した魚鱗癬様菌状息肉症

    森実 真

    Visual Dermatology   11 ( 9 )   920 - 921   2012

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  • 角化細胞カリクレイン発現および皮膚バリア

    森実真

    皮膚の科学   10 ( 16 )   29 - 33   2011

  • 細菌アレルギーとベーチェット病(共著)

    森実真, 山崎修

    皮膚アレルギーフロンティア   9 ( 2 )   109 - 113   2011

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  • Crohn病に伴った結節性紅斑

    竹島千夏, 白藤宜紀, 森実真, 岩月啓氏, 鈴木英之

    皮膚科の臨床   53 ( 6 )   817 - 819   2011

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  • 特集 知っておきたい皮膚科の知識 専門医の診方・治し方 乾癬

    森実真

    耳鼻咽喉j科・頭頸部外科   83 ( 12 )   923 - 925   2011

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  • カポジ水痘様発疹症の複数回罹患

    森実 真

    日本医事新報   ( 4495 )   80 - 81   2010

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  • 皮膚細菌感染症におけるPanton-Valentine型ロイコシジンの発現制御機構

    山崎 修, 森実 真, 岩月 啓氏, 加藤 文紀, 金子 淳

    日本皮膚科学会雑誌   117 ( 4 )   721 - 721   2007.3

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  • Panton-Valentine型ロイコシジン(PVL)と皮膚感染症

    山崎 修, 森実 真, 岩月 啓氏, 荒田 次郎, 武藤 正彦

    西日本皮膚科   68 ( 6 )   721 - 721   2006.12

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  • 皮膚における抗菌ペプチドの発現部位と発現細胞の検討

    大野 貴司, 白藤 宜紀, 森 実真, 許 郁江, 山崎 修, 岩月 啓氏

    山口医学   55 ( 5 )   188 - 188   2006.10

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  • 偽性腸閉塞を伴ったoverlap症候群と全身性強皮症.

    樫野かおり, 松浦浩徳, 中西 元, 辻 和英, 野村知代, 森實 真, 岩月啓氏, 岡田裕之, 松下貴史

    臨床皮膚科   2006

  • 木村病.

    鈴木大介, 辻 和英, 森実 真, 浅越健治, 岩月啓氏

    皮膚病診療   2006

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  • Panton-Valentine型ロイコシジン(PVL)産生黄色ブドウ球菌によるせつの臨床的検討

    山崎 修, 森実 真, 岩月 啓氏, 金子 淳, 神尾 好是, 荒田 次郎

    日本小児皮膚科学会雑誌   24 ( 2 )   192 - 192   2005.11

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  • 血管腫を疑ったaneurysmal fibrous histiocytomaの2例.

    森實 真, 山崎 修, 辻 和英, 浅越健治, 岩月啓氏

    日本皮膚外科学会誌   2005

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  • ステロイド内服療法が奏効した後頭部懸垂性苺状血管腫の1例.

    濱田利久, 浅越健治, 郷原亜以子, 森實 真, 岩月啓氏, 高村志保, 片山治子

    皮膚科の臨床   2005

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  • Aneurysmal fibrous histiocytoma?皮膚超音波所見と病理組織所見の比較検討.

    森實 真, 浅越健治, 松浦浩徳, 大野貴司, 岩月啓氏

    皮膚科の臨床   2005

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  • 低pH環境下における黄色ブドウ球菌定着について

    秋山 尚範, 森実 真, 山崎 修, 大野 貴司, 岩月 啓氏

    西日本皮膚科   66 ( 5 )   528 - 528   2004.10

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  • 下顎部病変治療後に両鼠径部巨大腫瘤を認めた木村病

    鈴木 大介, 辻 和英, 森実 真, 山崎 修, 牧野 英一, 浅越 健治, 岩月 啓氏

    西日本皮膚科   66 ( 3 )   302 - 302   2004.6

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  • 共焦点レーザー顕微鏡を用いたレンサ球菌性膿痂疹の研究

    秋山 尚範, 森実 真, 山崎 修, 大野 貴司, 岩月 啓氏

    西日本皮膚科   66 ( 3 )   313 - 313   2004.6

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  • 魚鱗癬様菌状息肉症の3例

    森實 真, 内藤 洋子, 山崎 修, 辻 和英, 浅越 健治, 岩月 啓氏

    西日本皮膚科   66 ( 3 )   301 - 301   2004.6

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  • マウス皮膚炎部黄色ブドウ球菌感染症に対する低pH外用薬の効果

    秋山 尚範, 森実 真, 山崎 修, 大野 貴司, 岩月 啓氏, 市川 秀之

    日本皮膚科学会雑誌   114 ( 3 )   619 - 619   2004.3

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  • 皮膚細菌感染症病変におけるリンパ球産生抗菌蛋白質granulysinの局在

    大野 貴司, 許 郁江, 山崎 修, 森実 真, 秋山 尚範, 岩月 啓氏

    日本皮膚科学会雑誌   113 ( 5 )   762 - 762   2003.4

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  • Panton-Valentine型ロイコシジン産生黄色ブドウ球菌の臨床的・細菌学的検討

    山崎 修, 森実 真, 秋山 尚範, 岩月 啓氏, 金子 淳, 神尾 好是, 荒田 次郎

    日本皮膚科学会雑誌   113 ( 5 )   786 - 786   2003.4

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  • 平滑筋母斑の1例.

    森實 真, 山田 潤, 山本剛伸, 大野貴司, 岩月啓氏

    皮膚科の臨床   2003

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  • 塩酸ミノサイクリンによる即時型アレルギーの2例 反応閾値についての検討

    中安 慎二, 森実 真, 井上 雅子, 山崎 修, 荒田 次郎

    皮膚科の臨床   44 ( 6 )   639 - 641   2002.6

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    49歳女(症例1).4年前に感冒症状で塩酸ミノサイクリン点滴を受けたところ,開始直後に呼吸困難,意識レベル低下を来たした.薬剤アレルギーの精査で,濃度1mg/mlのスクラッチテストを左前腕内側に施行した.15分後に同部位に15×27mmの紅斑が出現し,30分後には6×7mmの膨疹となった.更に45分後,腰仙部に手掌大の膨疹が出現した.膨疹は数時間で消失し,呼吸困難,意識レベル消失はなかった.61歳男(症例2).ミノマイシン内服で30〜40分後,全身に紅斑が出現し,数時間後に消失した.塩酸ミノサイクリン1mg/mlの皮内テストを施行したところ,15分後に同部位に15×10mmの膨疹を伴う35×40mmの紅斑が出現し,30分後には30×35mmに縮小した.濃度0.05mg/mlでは15分後に8×7mmの膨疹を伴う15×20mmの紅斑が出現した

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  • 塩酸ミノサイクリンによる即時型アレルギーの2例

    中安 慎二, 森実 真, 筒井 雅子, 山崎 修, 荒田 次郎

    日本皮膚科学会雑誌   111 ( 11 )   1603 - 1603   2001.10

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Presentations

  • LL型ハンセン病新規発症例の治療経過

    篠倉 美理, 尾崎 元昭, 川上 佳夫, 梅川 康弘, 吉原 由樹, 山崎 修, 森 実真

    日本ハンセン病学会雑誌  2021.5  日本ハンセン病学会

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    Event date: 2021.5

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  • 好中球関連皮膚疾患 Up to date 好中球関連皮膚疾患の共通のメカニズムは?

    森実 真

    日本皮膚科学会雑誌  2021.5  (公社)日本皮膚科学会

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    Event date: 2021.5

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  • ここまでわかったアトピー性皮膚炎における表皮バリア機能異常

    森実 真

    日本皮膚科学会雑誌  2021.5  (公社)日本皮膚科学会

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    Event date: 2021.5

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  • 免疫チェックポイント阻害薬でCRとなり,中止した悪性黒色腫6例

    杉原 悟, 山崎 修, 森実 真, 加持 達弥, 南 満芳

    日本皮膚科学会雑誌  2021.5  (公社)日本皮膚科学会

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    Event date: 2021.5

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  • Lanosterol synthase(LSS)遺伝子の複合ヘテロ接合型変異によって生じた先天性乏毛症の2例

    村田 真美, 林 良太, 川上 佳夫, 森実 真, 下村 裕

    日本皮膚科学会雑誌  2021.5  (公社)日本皮膚科学会

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    Event date: 2021.5

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  • DFSPとの鑑別と整容面への配慮を要した顔面のdeep penetrating dermatofibroma(DPDF)の3例

    谷本 尚吾, 三宅 智子, 杉原 悟, 山崎 修, 森実 真, 加持 達弥, 谷口 恒平

    日本皮膚科学会雑誌  2021.5  (公社)日本皮膚科学会

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    Event date: 2021.5

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  • モガムリズマブ投与後に移植片対宿主病が重症化した成人T細胞白血病の3例

    横山 恵美, 赤松 由規, 山崎 修, 山本 晃, 大山 矩史, 神原 由依, 淺田 騰, 谷口 恒平, 吉野 正, 森実 真

    日本皮膚科学会雑誌  2021.5  (公社)日本皮膚科学会

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    Event date: 2021.5

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  • 無疹部の皮膚生検により診断された遺伝性ATTR型アミロイドーシス

    小橋 美那, 平井 陽至, 篠倉 美理, 横山 恵美, 加持 達弥, 山崎 修, 森実 真, 中村 一文, 山下 徹, 山下 太郎

    日本皮膚科学会雑誌  2021.2  (公社)日本皮膚科学会

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    Event date: 2021.2

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  • 二次感染を契機に増悪し、モガムリズマブが奏効したセザリー症候群の1例

    赤松 由規, 平井 陽至, 渡部 桃子, 中川 裕貴, 小橋 美那, 内藤 聖子, 三宅 智子, 山崎 修, 森実 真, 山本 晃, 淺田 騰

    日本皮膚科学会雑誌  2021.2  (公社)日本皮膚科学会

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    Event date: 2021.2

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  • GJB2遺伝子のヘテロ接合性変異を同定したVohwinkel症候群の1例

    池田 賢太, 中川 裕貴, 内藤 聖子, 川上 佳夫, 山崎 修, 森実 真, 伊藤 靖敏, 武市 拓也, 秋山 真志

    日本皮膚科学会雑誌  2021.2  (公社)日本皮膚科学会

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    Event date: 2021.2

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  • 1次治療としてタキサン系化学療法を施行した進行期乳房外パジェット病の8例

    山崎 江利子, 山崎 修, 杉原 悟, 三宅 智子, 森実 真, 加持 達弥

    日本皮膚科学会雑誌  2021.2  (公社)日本皮膚科学会

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  • 岡山大学における乾癬診療・研究 Invited

    森実 真

    日本皮膚科学会愛媛地方会第69回学術大会 

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    Event date: 2019.3.30

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

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  • 乾癬診療と基礎研究 Invited

    森実 真

    第3回中国五県乾癬治療を語る会 

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    Event date: 2019.3.23

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

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  • 種痘様水疱症と蚊刺過敏症における血球・血漿EBV DNA定量の臨床的意義

    三宅智子、山本剛伸、平井陽至、岩月啓氏、森実 真

    第28回EBウイルス感染症研究会 

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    Event date: 2019.3.17

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • 当科における乾癬診療・研究?外用剤から生物学的製剤まで? Invited

    森実 真

    日本皮膚科学会第226回熊本地方会 

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    Event date: 2019.3.10

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

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  • 皮膚科が関わる指定難病

    森実 真

    第2回岡山県難病診療連携拠点病院研修会 

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    Event date: 2019.2.25

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  • 経皮感作とスキンケア Invited

    森実 真

    岡山県医師会学術奨励賞受賞講演並びに日本医師会生涯教育講座 

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    Event date: 2019.2.9

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

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  • 当科における乾癬診療・研究 Invited

    森実 真

    第21回岐阜臨床皮膚科懇話会 

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    Event date: 2019.1.26

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

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  • Exfoliative cheilitis

    濱田利久,芦田日美野,細川洋一郎,池田政身,森実 真

    第276回 日本皮膚科学会岡山地方会 

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    Event date: 2019.1.19

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  • 親族に同症のあるnasal dermoid sinus cystの1例

    西垣貴美子,山? 修,篠倉美理,川上佳夫,三宅智子,森実 真,香曽我部純子

    第276回 日本皮膚科学会岡山地方会 

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    Event date: 2019.1.19

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  • 臭化カリウム減量により症状が軽快した臭素疹の1例

    安富陽平,川上佳夫,平井陽至,山? 修,森実 真

    第276回 日本皮膚科学会岡山地方会 

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    Event date: 2019.1.19

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  • イピリムマブ投与後にACTH単独欠損症を発症した悪性黒色腫の1例

    篠倉美理,藤本裕子,神野泰輔,山? 修,森実 真

    第276回 日本皮膚科学会岡山地方会 

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    Event date: 2019.1.19

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  • 抗PD-1抗体投与後に発症した類天疱瘡の2例

    横山恵美,森田安理,山? 修,森実 真,久保寿男,高本 篤

    第276回 日本皮膚科学会岡山地方会 

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    Event date: 2019.1.19

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • 結節性硬化症の皮膚病変に対しシロリムス局所外用療法を導入した4例

    小橋美那,平井陽至,三宅智子,加持達弥,川上佳夫,山? 修,森実 真

    第276回 日本皮膚科学会岡山地方会 

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    Event date: 2019.1.19

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • 岡山大学における乾癬診療・研究 Invited

    森実 真

    鳥取県臨床皮膚科医会学術講演会 

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    Event date: 2019.1.17

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

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  • 乾癬病変部角化細胞におけるTNF-α/IL-17A/IFN-γの相乗作用 Invited

    森実 真

    乾癬治療?エキスパートから学ぶ基礎研究? 

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    Event date: 2019.1.9

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

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  • ハンセン病LL型新規発症の1例

    篠倉美理、杉本佐江子、川上佳夫、山? 修、吉原由樹、多田讓治、尾崎元昭、石井則久、森実 真

    第82回日本皮膚科学会東京支部学術大会 

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    Event date: 2018.12.1 - 2018.12.2

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • 当科におけるIL-17Aを標的とした乾癬診療・研究 Invited

    森実 真

    ふじのくに乾癬Expert Meeting 

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    Event date: 2018.11.29

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

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  • IL-17Aを標的とした乾癬治療・研究 Invited

    森実 真

    第2回西讃地区トルツ学術講演会 

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    Event date: 2018.11.27

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

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  • 当科における皮膚炎診療 Invited

    森実 真

    和気医師会学術講演会 

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    Event date: 2018.11.22

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

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  • 円盤状エリテマトーデスに対するヒドロキシクロロキンの使用経験

    安富陽平、三宅智子、橋本倫子、山? 修、森実 真

    第45回岡山膠原病研究会 

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    Event date: 2018.11.20

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • メシル酸ガレノキサシン水和物の(ジェニナック)による固定薬疹の一例。

    石井芙美、川上佳夫、三宅智子、森実 真

    第48回日本皮膚免疫アレルギー学会総会学術大会 

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    Event date: 2018.11.16 - 2018.11.18

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • IL-17Aを標的とした乾癬診療・研究 Invited

    森実 真

    日常診療における乾癬治療を考える会 

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    Event date: 2018.11.14

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

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  • 乾癬病変部角化細胞におけるTNF-α/IL-17A/IFN-γの相乗作用 Invited

    森実 真

    第70回日本皮膚科学会西部支部学術大会 

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    Event date: 2018.11.10 - 2018.11.11

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

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  • 岡山大学病院皮膚科において2013年度から2017年度に実施された金属パッチテスト301省令のまとめ

    高橋正幸、横山恵美、安原千夏、橋本倫子、加持達弥、三宅智子、川上佳夫、平井陽至、山? 修、森実 真

    第70回日本皮膚科学会西部支部学術大会 

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    Event date: 2018.11.10 - 2018.11.11

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • 抗BP180NC16a抗体陰性で、経過中に全長BP180ELISA法にて診断し得た水疱性類天疱瘡の1例

    石井芙美、三宅智子、川上佳夫、森田安理、山? 修、泉 健太郎、西江 渉、森実 真

    第70回日本皮膚科学会西部支部学術大会 

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    Event date: 2018.11.10 - 2018.11.11

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • 有茎広背筋皮弁加療した冠動脈ステント留置後の右肩甲部放射性皮膚潰瘍の1例

    森田安理、山? 修、石井芙美、川上佳夫、加持達弥、竹原 彩、大塚正樹、森実 真

    第70回日本皮膚科学会西部支部学術大会 

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    Event date: 2018.11.10 - 2018.11.11

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • ニボルマブが著効した悪性黒色腫in-transit転移における腫瘍浸潤リンパ球の解析

    神野泰輔、山?修、眞部恵子、三宅智子、中川裕貴、森実 真、岩月啓氏

    第70回日本皮膚科学会西部支部学術大会 

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    Event date: 2018.11.10 - 2018.11.11

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • ソメイヨシノによるアレルギーと抗原蛋白質の解析

    光井聖子、白築理恵、神谷浩二、千貫祐子、森田栄伸、森実 真

    第70回日本皮膚科学会西部支部学術大会 

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    Event date: 2018.11.10 - 2018.11.11

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • 乾癬と糖尿病 Invited

    森実 真

    Dermatology Diabetes Forum 

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    Event date: 2018.11.8

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

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  • アトピー性皮膚炎患者における遺伝子多型および角層中セリンプロテアーゼ活性について

    野村隼人、森実 真

    第14回中国研究皮膚科セミナー 

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    Event date: 2018.11.3

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • Cetuximab投与中に生じたleukocytoclastic vasculitis

    安富陽平、篠倉美理、神野泰輔、藤本裕子、川上佳夫、山? 修、森実 真

    第82回日本皮膚科学会東部支部学術大会 

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    Event date: 2018.10.6 - 2018.10.7

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • Hydroa vacciniforme and hydroa vaccinifotme-like lymphoproliferative disorder: Disease spectrum, responsible T-cell subsets and prognosis International conference

    Iwatsuki K, Miyake T, Hirai Y, Morizane S

    EORTC-CLTF 2018 meeting on cutaneous lymphoma: biology, treatment, and patient view 

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    Event date: 2018.9.27 - 2018.9.29

    Language:English   Presentation type:Oral presentation (general)  

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  • Indolent hematodermic CD4+ T-cell lymphoma lacking surface CD3 expression: Structural and functional deficiency of T-cell receptor/CD3 complex International conference

    Iwatsuki K, Nakagawa Y, Hamada T, Uchida T, Morizane S, Takahashi T, Watanabe T, Miyake T, Manabe K, Asagoe K

    EORTC-CLTF 2018 meeting on cutaneous lymphoma: biology, treatment, and patient view 

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    Event date: 2018.9.27 - 2018.9.29

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  • 長期残存した、草刈り機の破片による左下腿の皮下金属異物

    立花宏太、山? 修、篠倉美理、神野泰輔、藤本裕子、森実 真、梅村啓史

    第275回日本皮膚科学会岡山地方会 森実 真 教授就任記念地方会 

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    Event date: 2018.9.9

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  • ステロイド内服が奏効した関節運動障害合併皮下型サルコイドーシスの1例

    篠倉美理、三宅智子、加持達弥、山? 修、森実 真、安井陽子

    第275回日本皮膚科学会岡山地方会 森実 真 教授就任記念地方会 

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    Event date: 2018.9.9

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  • Dabrafenib/Trametinib 併用療法を施行した進行期悪性黒色腫の10例

    藤本裕子、加持達弥、山? 修、森実 真、松三友子

    第275回日本皮膚科学会岡山地方会 森実 真 教授就任記念地方会 

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    Event date: 2018.9.9

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  • 当科における炎症性皮膚疾患診療?乾癬を中心に? Invited

    森実 真

    佐世保皮膚科医会学術講演会 長崎県医師会生涯教育認定講座 

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    Event date: 2018.6.13

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

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  • 口腔粘膜部に生じたsolitary fibrous tumorの1例

    保利純子、光井聖子、川上佳夫、三宅智子、森実 真、岩月啓氏、小田和歌子

    第274回日本皮膚科学会岡山地方会 

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    Event date: 2018.5.12

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  • 乾癬とサイトカインに関する最近の話題

    森実 真

    IL-17A WEB Seminar 

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    Event date: 2018.4.25

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • 2018207640 隆起性皮膚線維肉腫が疑われ、COL1A1-PDGFB融合遺伝子解析を行った5例

    日本皮膚科学会岡山地方会第273回例会  2018 

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  • 皮膚症状が長期に遷延するも免疫抑制剤の併用により軽快したDIHSの1例

    第47回日本皮膚アレルギー・接触皮膚炎学会総会学術大会  2017 

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  • 当科における皮膚動脈炎の予後不良因子の検討

    日本皮膚科学会第68回中部支部学術大会  2017 

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  • 表皮角化細胞産生セリンプロテアーゼ阻害因子の発現制御機構

    第22回日本病態プロテアーゼ学会学術集会  2017 

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  • アトピー性皮膚炎患者におけるSPINK5遺伝子変異解析

    第116回日本皮膚科学会総会  2017 

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  • 副腎皮質ホルモンおよび免疫抑制剤内服中に発症した皮膚非結核性抗酸菌症の2例

    第271回日本皮膚科学会岡山地方会  2017 

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  • 前脛骨型栄養障害型表皮水疱症と痒疹型栄養障害型表皮水疱症の位置づけ:genotype-phenotype解析の結果から

    第271回日本皮膚科学会岡山地方会  2017 

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  • New nonsynonymous variants of SPINK5 gene in Japanese atopic dermatitis patients

    76th Annual Meeting of Society of Investigative Dermatology  2017 

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  • 乾癬性関節炎の頻度と病型別最適治療の発見のための多施設共同観察調査(中間報告)

    日本皮膚科学会第79回沖縄地方会  2017 

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  • Double-stranded RNA enhances serine protease activities in epidermal keratinocytes

    The 42nd Annual Meeting of the Japanese Society for Investigative Dermatology  2017 

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  • 抗セントロメア抗体陽性全身性強皮症患者に生じたサルコイドーシス HLA-DR解析と全身性ステロイド療法について

    日本皮膚科学会山口地方会第169回例会  2016 

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  • 抗PD-1抗体治療後BRAF阻害療法中の進行期メラノーマ患者に生じた原田病 抗PD-1投与前後の免疫応答を含めて

    日本皮膚科学会第98回大分地方会  2016 

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  • 進行性Sezary症候群の腫瘍細胞が発現する新規バイオマーカーCADM1の臨床的解析

    日本皮膚科学会第76回沖縄地方会  2016 

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  • アトピー性皮膚炎におけるセリンプロテアーゼインヒビターの発現および機能解析

    第46回日本皮膚アレルギー・接触皮膚炎学会総会学術大会  2016 

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  • Th2環境が表皮角化細胞産生カリクレインの発現および皮膚バリアに与える影響

    第46回日本皮膚アレルギー・接触皮膚炎学会総会学術大会  2016 

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  • 乾癬の診断と治療2016

    岡山PsA超音波実技講習会2016  2016 

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  • アトピー性皮膚炎におけるカリクレイン5および7の関与

    第21回日本病態プロテアーゼ学会学術集会  2016 

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  • 皮膚科医からみたPsA

    GRAPPA in 中四国 Internet Live Seminar  2016 

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  • 病院現況および患者視点からみた進行期悪性黒色腫に対する新規治療

    第115回日本皮膚科学会総会  2016 

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  • 帯状疱疹ウイルス・単純疱疹ウイルスの重複再活性化例の臨床及び遺伝子産物解析

    第115回日本皮膚科学会総会  2016 

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  • 非バイアス次世代TCRレパトア解析によるEBV関連リンパ増殖性疾患への応用

    第32回日本皮膚悪性腫瘍学会学術大会  2016 

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  • Pseudoxanthoma elasticum-like papillary dermal elastolysisの1例

    第32回日本臨床皮膚科医会総会・臨床学術大会  2016 

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  • 乾癬病変部角化細胞が産生するKey molecules

    阪神皮膚科カンファレンス  2016 

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  • The expression of serine protease inhibitors in epidermal keratinocytes is increased by calcium, but not 1,25(OH)2 vitamin D3 or retinoic acid

    The 41st Annual Meeting of the Japanese Society for Investigative Dermatology  2016 

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  • The expression of serine protease inhibitors are induced by TNF-α and IL-17A in skin inflammatory diseases

    The 41st Annual Meeting of the Japanese Society for Investigative Dermatology  2016 

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  • TLR signaling regulates the expression of the expression of serine protease inhibitors in epidermal keratinocytes

    The 41st Annual Meeting of the Japanese Society for Investigative Dermatology  2016 

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  • 乾癬病変部角化細胞で産生される血清アミロイドA蛋白に関する研究

    第30回日本乾癬学会学術大会  2015 

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  • 複数の全身療法施行後に乳癌を発症した関節症性乾癬の1例

    第30回日本乾癬学会学術大会  2015 

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  • 岡山大学病院におけるセクキヌマブ使用症例

    Psoriasis&IL-17Aフォーラムin広島  2015 

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  • 経過中にリウマチ因子が陽転化し,抗TNF-a抗体,抗IL-12/IL-23p40抗体に治療抵抗性を示した関節症性乾癬の1例

    日本皮膚科学会第373回福岡地方会  2015 

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  • Inflammatory cytokines and antimicrobial peptides highly expressed in psoriatic lesions induce serum amyloid A expression in epidermal keratinocytes.

    2015 Australasian Society for Dermatology Research Conference  2015 

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  • Interferon-gamma enhances TLR3 expression and anti-viral activity in keratinocytes

    The 74th Annual Meeting of Society of Investigative Dermatology  2015 

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  • 乾癬の診断と治療~皮膚科医の立場から~

    第1回皮膚科膠原病内科合同グループワーク  2015 

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  • Distinct lymphocyte subsets responsible for classical and systemic hydroa vacciniforme

    The 40th Annual Meeting of the Japanese Society for Investigative Dermatology  2015 

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  • Cathelicidin peptide LL-37 induces UVB-triggered inflammasome activation and angiogenesis: Possible implications for rosacea

    The 40th Annual Meeting of the Japanese Society for Investigative Dermatology  2015 

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  • TNF-alpha, IL-17A, a Toll-like receptor 3 ligand, and high calcium enhances the expression of SPINK6 in epidermal keratinocytes

    The 40th Annual Meeting of the Japanese Society for Investigative Dermatology  2015 

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  • TNF-alpha and IL-17A increase SPINK5 expression in epidermal keratinocytes

    The 40th Annual Meeting of the Japanese Society for Investigative Dermatology  2015 

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  • Calcium but not 1,25(OH)2 vitamin D3 or retinoic acid increases SPINK5 expression in epidermal keratinocytes

    The 40th Annual Meeting of the Japanese Society for Investigative Dermatology  2015 

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  • Terminal Differentiation of Keratinocytes EnhancesTLR3 Expression and Anti-Viral Activity

    The 40th Annual Meeting of the Japanese Society for Investigative Dermatology  2015 

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  • 乾癬の診断と治療

    日本脊椎関節炎学会第25回学術大会  2015 

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  • 躯幹に多発する暗紅色斑

    第65回日本皮膚科学会中部支部学術大会  2014 

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  • リュープロレリン酢酸塩皮下注射により生じた肉芽腫の2例

    第65回日本皮膚科学会中部支部学術大会  2014 

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  • 慢性炎症性皮膚疾患におけるセリンプロテアーゼ阻害因子の発現とその制御機構

    第113回日本皮膚科学会総会  2014 

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  • 当院におけるイミキモドクリームの適応拡大後の日光角化症治療について

    第261回日本皮膚科学会岡山地方会  2014 

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  • Chronic skin inflammation via Toll-like receptors increases a risk of secondary amyloidosis

    The 73rd Annual Meeting of the Society for Investigative Dermatology  2014 

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  • アトピー性皮膚炎の治療を考える~TSLPの発現に与える影響~

    第10回小児皮膚・疾患フォーラム  2013 

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  • 乾癬の内服療法~国内外の知見から~

    第112回日本皮膚科学会総会  2013 

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  • 血液学的異常を伴ったfolliculotropic mycosis fungoidesについて

    第112回日本皮膚科学会総会  2013 

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  • Th2サイトカインはアトピー性皮膚炎患者における組織カリクレイン7の発現および機能を増強する

    第112回岡山医学会総会  2013 

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  • Eradication of cutaneous herpesvirus infections by nucleic acid sensors and cytotoxic T lymphocyte-mediated apoptotic processes

    2013 International Investigative Dermatology Meeting  2013 

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  • Pathogenic cell types, molecular mechanisms and prognostic factors in EB virus-associated cutaneous T/NK lymphoproliferative disorders

    2013 International Investigative Dermatology Meeting  2013 

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  • Toll-like receptor signaling induces serum amyloid A and IL-6 expression in patients with recessive dystrophic epidermolysis bullosa

    2013 International Investigative Dermatology Meeting  2013 

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  • 血液学的異常をともなった毛包向性菌状息肉症

    第29回日本皮膚悪性腫瘍学会学術大会  2013 

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  • 岡山大学病院におけるウステキヌマブの使用症例の検討

    Psoriasis Meeting in Kagawa  2013 

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  • Cathelicidin(LL-37)は表皮角化細胞において2本鎖RNAによる抗ウィルス作用を増強する

    第9回中国研究皮膚科セミナー  2013 

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  • Inflammatory Cytokines Regulates Expression of Lympho-Epithelial Kazal-type-related Inhibitor in Epidermal Keratinocytes

    5th International Symposium on Kallikreins and Kallikrein-Related Peptidases  2013 

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  • Cahtelicidin antimicrobial peptide LL-37 enhances double-stranded RNA-induced IFN-beta expression and anti-viral activity in skin viral infection

    The 12th Awaji International Forum on Infection and Immunity  2013 

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  • 乾癬の理解と制御に向けた開発研究2013

    第28回日本乾癬学会学術大会  2013 

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  • 日本乾癬学会”乾癬遺伝子プロジェクト班(第2期)”の発足

    第27回日本乾癬学会学術大会  2012 

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  • 乾癬と抗菌ペプチド

    第27回日本乾癬学会学術大会  2012 

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  • 非天疱瘡患者に検出される抗デスモグレイン前駆体抗体の特徴とEDTA処理ELISA法を用いた検討

    第111回日本皮膚科学会総会  2012 

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  • 上皮成長因子受容体阻害剤薬による遅発性皮膚障害

    第111回日本皮膚科学会総会  2012 

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  • Thymic stromal lymphopoietin expression in keratinocytes are suppressed by clinical treatments in atopic dermatitis

    The 72nd Annual Meeting of the Society for Investigative Dermatology  2012 

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  • Clues for Epstein-Barr virus reactivation with the subsequent outbreak of immune responses in skin lesions of hypersensitivity to mosquito bites.

    The 72nd Annual Meeting of the Society for Investigative Dermatology  2012 

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  • Widespread chronic skin ulcers in epidermolysis bullosa patients trigger Castleman's disease-like condition through Toll-like receptors

    The 72nd Annual Meeting of the Society for Investigative Dermatology  2012 

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  • Cathelicidin antimicrobial peptide LL-37 augments anti-viral activity induced by double-stranded RNA in keratinocytes

    The 37th Annual Meeting of the Japanese Society for Investigative Dermatology  2012 

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  • Interferon gamma enhances anti-viral activity induced by double-stranded RNA in keratinocytes

    The 37th Annual Meeting of the Japanese Society for Investigative Dermatology  2012 

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  • Clinical treatments for atopic dermatitis modulate thymic stromal lympopoietin expression in keratinocytes

    The 37th Annual Meeting of the Japanese Society for Investigative Dermatology  2012 

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  • 疣贅と伝染性軟属腫における免疫回避機序について

    第362回日本皮膚科学会福岡地方会  2012 

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  • Interferon gamma enhances anti-viral activity induced by double-stranded RNA in keratinocytes surrounding herpetic vesicles

    The 11th Awaji International Forum on Infection and Immunity  2012 

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  • Castleman's disease-like condition in dystrophic epidermolysis bullosa

    22nd World Congress of Dermatology  2011 

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  • 尋常性天疱瘡の疾患活動性とEDTA処理ELISA法で検出される病因性抗体値の比較検討

    第253回日本皮膚科学会岡山地方会  2011 

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  • Increased REG3A/RegIIIγ by Th17 cytokines promotes keratinocyte proliferation after skin injury.

    第71回米国皮膚科学会  2011 

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  • Differences in epitopes of non-pathogenic autoantibodies todesmoglein1 in pemphigus foliaceus in comparison with thosein pemphigus vulgaris and rheumatoid arthritis.

    第71回米国研究皮膚科学会  2011 

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  • Interferon gamma enhances innate immune response of epidermis

    第71回米国研究皮膚科学会  2011 

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  • EDTAおよび表皮剥脱毒素(ET)処理ELISA法による天疱瘡自己抗体のエピトープ解析

    第110回日本皮膚科学会総会  2011 

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  • 表皮水疱症における血液学的異常とキャッスルマン様病態

    第110回日本皮膚科学会総会  2011 

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  • 角化細胞カリクレイン発現および皮膚バリア

    アトピー性皮膚炎治療研究会第16回シンポジウム  2011 

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  • 多剤併用化学療法は長期間の潜伏を経て多発性エクリン汗孔腫を発症させる

    日本皮膚科学会第134回徳島地方会  2011 

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  • Hydroa vacciniforme is pathogenically associated with circulating Epstein-Barr virus-infected gammadelta T-cells

    The 36th Annal Meeting of the Japanese Society for Investigative Dermatology  2011 

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  • 尋常性天疱瘡患者の治療反応性に関する多様性は抗体産生細胞の反応性の違いに起因する

    第62回日本皮膚科学会中部支部学術大会  2011 

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  • アトピー性皮膚炎の表皮角化細胞における組織カリクレイン7の発現

    日本皮膚科学会愛媛地方会第54回学術大会  2011 

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  • Kallikrein expression in keratinocytes in atopic dermatitis

    Conférence du Service d’Immunologie Clinique et d’Allergologie  2011 

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  • Antimicrobial peptide LL37 in skin

    Jean Thivolet Seminar  2011 

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  • Interferon gamma enhances TLR3 expression and function in keratinocytes surrounding herpetic vesicles

    41st Annnual ESDR meeting  2011 

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  • 表皮水疱症に伴う血液学的合併症

    稀少難治性皮膚疾患に関する調査研究班平成23年度第1回総会  2011 

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  • Eccrine poromatosis associated with polychemotheraphy

    22nd World Congress of Dermatology  2011 

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  • An elderly case of crohn's disease with erythema nodosum

    22nd World Congress of Dermatology  2011 

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  • Granulysin-producing cytotoxic T cells in the mucocutaneous lesions of Behcet's disease: a distinct inflammatory response from erythema nodosum

    22nd World Congress of Dermatology  2011 

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  • Improved enzyme-linked immunosolvent assay to monitor pathogenic pemphigus antibodies directed against calcium-dependent epitopes of desmoglein 3.

    22nd World Congress of Dermatology  2011 

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  • Interferon gamma enhances TLR3 expression and function in keratinocytes in viral skin infection

    The 36th Annal Meeting of the Japanese Society for Investigative Dermatology  2011 

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  • Two Arg in C-terminal of human beta-defensin-3 are essential for the stimulation of proinflammatory cytokine secretion in keratinocytes

    The 36th Annal Meeting of the Japanese Society for Investigative Dermatology  2011 

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  • The epitopes and IgG subclasses of anti-desmoglein antibodies detected in individuals without pemphigus

    The 36th Annal Meeting of the Japanese Society for Investigative Dermatology  2011 

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  • 歯科金属除去が奏効した金属アレルギーによる異汗性湿疹

    第252回日本皮膚科学会岡山地方会  2011 

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  • Th2 cytokines enhance tissue kallikrein 7 expression and the serine protease activity of keratinocytes in atopic dermatitis

    第40回欧州研究皮膚科学会  2010 

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  • 乾癬病変部における抗菌ペプチドLL-37の発現と機能

    第25回日本乾癬学会学術大会  2010 

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  • 先天性表皮水疱症に伴う血液学的異常

    第34回日本小児皮膚科学会学術大会  2010 

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  • 四肢関節のみに分布する結節性紅斑から診断に至った高齢者Crohn病

    第250回日本皮膚科学会岡山地方会  2010 

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  • Th2 cytokines enhance tissue kallikreins and serine protease activity of keratinocytes in atopic dermatitis

    第70回米国研究皮膚科学会学術大会  2010 

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  • 抗菌タンパクCathelicidinのプロセッシング酵素カリクレインの発現制御機構

    第109回日本皮膚科学会総会  2010 

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  • ヘルペス性水疱の治癒に関わる細胞・分子メカニズム

    第109回日本皮膚科学会総会  2010 

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  • Hematological abnormalities associated with epidermolysis bullosa

    The First Eastern Asia Dermatology Congress  2010 

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  • Th2 cytokines enhance tissue kallikreins and serine protease activity of keratinocytes in atopic dermatitis

    The 70th annual meeting of Society for Investigative Dermatology  2010 

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  • アトピー性皮膚炎における角化細胞産生カリクレイン7の発現制御機構

    第40回日本皮膚アレルギー・接触皮膚炎学会総会学術大会  2010 

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  • 歯科金属除去が奏功した金属アレルギーによる異汗性湿疹の1例

    第40回日本皮膚アレルギー・接触皮膚炎学会総会学術大会  2010 

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  • Toll-like receptor signaling increases kallikrein in rosacea and affect skin barrier function

    日本研究皮膚科学会 第35回年次学術大会・総会  2010 

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  • A simple method to detect pathogenic pemphigus antibodies directed against calcium-dependent epitopes of desmoglein 3

    日本研究皮膚科学会 第35回年次学術大会・総会  2010 

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  • Tissue kallikrein 7 expression and the protease activity in keratinocytes are enhanced by Th2 cytokines in atopic dermatitis

    日本研究皮膚科学会 第35回年次学術大会・総会  2010 

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  • 先天性表皮水疱症における血液学的異常

    第32回水疱症研究会  2010 

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  • 天疱瘡患者の病原性抗体をより高感度に検出するEDTA処理ELISA法の検討

    第32回水疱症研究会  2010 

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  • Hematological abnormalities associated with epidermolysis bullosa

    The First Eastern Asia Dermatology Congress  2010 

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  • The antimicrobial peptide LL37 in psoriasis enhances TLR9 responsiveness and increases IL-23 expression in keratinocytes

    日本研究皮膚科学会第34回年次学術大会・総会  2009 

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  • 抗菌ペプチドLL-37は乾癬でTLR9の機能を増強し、IL-23の産生を誘導する

    第5回中国研究皮膚科セミナー  2009 

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  • 皮膚における抗菌ペプチドLL-37の免疫修飾機能とそのプロセッシング酵素カリクレインの発現調節機構

    第22回岡山研究皮膚科フォーラム  2009 

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  • LL37 enhances TLR9 expression and activation in keratinocytes and is coordinately overexpressed in psoriasis

    第69回米国研究皮膚科学会学術大会  2009 

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  • LL37 enhances TLR9 expression and activation in keratinocytes and is coordinately overexpressed in psoriasis

    Gordon Research Conference on Antimicrobial Peptides  2009 

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  • The antimicrobial peptide LL37 in psoriasis enhances TLR9 responsiveness and increases IL-23 expression in keratinocytes

    2009 

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  • LL37 enhances TLR9 expression and activation in keratinocytes and is coordinately overexpressed in psoriasis

    The 69th annual meeting of the society for investigative dermatology  2009 

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  • 皮膚抗菌バリアと自然免疫応答・アレルギー

    第3回病態制御科学専攻系シンポジウム  2009 

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  • ヘルペス性水疱におけるアポトーシス誘導因子(免疫不全状態との比較)

    第243回日本皮膚科学会岡山地方会  2008 

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  • Panton-Valentine leukocidin produced by Staphylococcus aureus induces an intense inflammation in the skin

    第68回米国研究皮膚科学会学術大会  2007 

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  • Cytotoxic T lymphocyte(CTL)-mediated vasculopathy

    第144回日本皮膚科学会山口地方会  2007 

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Awards

  • 第4回高木賞

    2020.3  

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  • 2018年度公募課題研究助成金(リディアオリリー記念ピアス皮膚科学振興財団)

    2018.4  

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  • 公益財団法人岡山医学振興会第16回教育・研究助成

    2016.11  

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  • ASDR/JSID Exchange Program

    2015  

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    Country:Japan

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  • JD Award “Most cited paper in 2014 Impact Factor period”

    2015  

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    Country:Japan

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  • 第4回2014年日本乾癬学会「鳥居・帝國乾癬研究奨励賞」

    2014.9  

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  • JD Award “Most downloaded paper in 2013”

    2014  

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    Country:Japan

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  • JD Award “Most cited paper in 2013 Impact Factor period”

    2014  

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    Country:Japan

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  • 平成25年度日本皮膚科学会基礎医学研究費(資生堂寄附)

    2013.4  

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  • 平成24年度岡山医学会賞(結城賞)

    2013  

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    Country:Japan

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  • 2011年度財団法人日本リディアオリリー協会研究助成金

    2011.5  

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  • EADC Award

    2010  

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  • 第109回日本皮膚科学会総会ポスター賞

    2010  

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Research Projects

  • 乾癬病変部表皮角化細胞産生EBI3含有サイトカインに関する研究

    Grant number:20K08672  2020.04 - 2023.03

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

    森実 真

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    Grant amount:\4290000 ( Direct expense: \3300000 、 Indirect expense:\990000 )

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  • the elucidation of complication mechanism in patients with recessive dystrophic epidermolysis bullosa (RDEB)

    Grant number:16K19724  2016.04 - 2018.03

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

    Tenta Ai, MORIZANE Shin

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

    We found that patients with recessive dystrophic epidermolysis bullosa (RDEB) have persistently higher levels of serum amyloid A (SAA) and IL-6 in the serum. Furthermore, we demonstrated that Toll-like receptor (TLR) ligands induce SAA expression via NF-kB in epidermal keratinocytes and dermal fibroblasts, and that SAA induces its own expression via TLR1/2 in these cells. Our results provide new evidence that the skin’s innate immune response contributes to the production of SAA, which might lead to an increased risk of systemic complications such as secondary amyloidosis of recessive dystrophic epidermolysis bullosa.

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  • The analysis of regulation of serine protease inhibitors expression in epidermal keratinocytes

    Grant number:26461658  2014.04 - 2017.03

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

    Morizane Shin

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

    High calucium, TNF-alpha, IL-17A, and Toll-like receptor ligands significantly inudced the expression of LEKTI, SLPI, and elafin in normal human epidermal keratinocytes. In addition, high calcium up- and down-regulated trypsin- and chymotrypsin-like serine protease activities in epidermal keratinocytes, respectively.
    Immunohistochemical analysis revealed that the expression of LEKTI, SLPI, and elafin were increased in the lesion of psoriasis, rosacea, acne, chronic pyoderma, and herpes zoster.

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  • Studies on host immune responses induced by reactivation of EB virus-infected lymphocytes and resultant skin lesions

    Grant number:24591653  2012.04 - 2015.03

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

    IWATSUKI Keiji, YAMAMOTO Takenobu, MORIZANE Shin

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    Grant amount:\5330000 ( Direct expense: \4100000 、 Indirect expense:\1230000 )

    We performed diagnostic examinations on more than 50 cases of EB virus-associated T/NK lymphoproliferative disorders including hydroa vacciniforme (HV), hypersensitivity to mosquito bites (HMB), chronic active EB virus infections(CAEBV) and so on, and studied the pathogenesis. EB virus was found to be infected mainly in gdT cells in classical HV, abT cells in systemic HV, and NK cells in HMB. These results indicate that EB virus-infected lymphocyte subsets are closely related to the clinical phenotypes.
    We found prognostic factors in our series of patients: clinical phenotypes, age of the disease onset, and the expression of EB virus reactivation marker, BZLF1. The results suggest that host immune responses against the EBV antigens expressed in the skin lesions induce the severe clinical symptoms. Furthermore, we found elderly patients with atypical HV, and reported their cytological characteristics and EB virus gene expression patterns.

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  • The effect of aberrant expression of kallikrein 7 induced by Th2 cytokines on epidermal barrier

    Grant number:24791157  2012.04 - 2014.03

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

    MORIZANE Shin

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

    TNF-alpha and IL-17A significantly up-regulated the expression of LEKTI, SLPI, and elafin in cultured normal human epidermal keratinocytes. Immunohistochemical analysis confirmed LEKTI expression in atopic dermatitis lesions was almost same as in normal skin, but it was significantly higher in psoriasis lesions than in atopic dermatitis lesions.
    Topical application of serine protease inhibitors such as benzamidine did not significantly improve the skin lesions in a mouse model of Th2-dependent dermatitis.

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  • Investigation of expression regulation and pathological mechanism of Panton-valentine leukocidine in skin

    Grant number:23591646  2011 - 2013

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

    YAMASAKI Osamu, MORIZANE Shin, KANEKO Jun

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    Grant amount:\5200000 ( Direct expense: \4000000 、 Indirect expense:\1200000 )

    Panton-Valentine leukocidin (PVL) is a cytotoxin produced by Staphylococcus aureus, PVL exhibits very highly specific lytic activity against polymorphonuclear cells of human and rabbits. PVL gene-positive S. aureus is strongly associated with furunculosis and community-acquired necrotic pneumonia. We demonstrated PVL gene-positive S. aureus strains are involved in the development of multiple furuncles with more intense erythema, particularly in healthy young adults. However, the role of PVL in the development of furunculosis has not been fully elucidated. We analyzed regulatory factors of PVL toxin production and of the influence of PVL on keratinocytes, fibroblasts and endothelial cells. In addition, we investigated about PVL-carrying phage type in furunculosis.

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  • Preferable biological milieu for the growth of viral epithelial neoplasms and its regulation

    Grant number:22659205  2010 - 2011

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research  Grant-in-Aid for Challenging Exploratory Research

    IWATSUKI Keiji, AOYAMA Yumi, SHIRAFUJI Yoshinori, FUJII Kazuyasu, MORIZANA Shin

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    Grant amount:\3230000 ( Direct expense: \2900000 、 Indirect expense:\330000 )

    Dendritic cell(DC) subsets and regulatory mechanisms of host immune responses were studied in human papilloma virus(HPV)-and molluscum contagiosum virus(MCV)-associated warty lesions, Bowen disease, and various epithelial neoplasms. The depletion of Langerin+ DCs(LCs) was obvious in the non-inflammatory HPV-warts, MC, and HPV-Bowen. The lesional epidermis revealed diminished MIP-3αexpression and irregular distribution of E-cadherin. TSLP(thymic stromal lymphopoietin) was highly expressed in HPV-warts and solar keratosis, while a few MCV+ cells were positive for TSLP in MC. MCV-encoded immunoregulatory molecules such as MCV148 and MCV159 were expressed in MC. MIP-3αexpression is up-regulated in inflammatory warts, with the subsequent recruitment of various DC subsets and CD8+ cells. TSLP expression might be associated with immune suppression and Th2 type inflammation in HPV-warts, while MCV-encoded molecules possess a pivotal role in the persistence of MC.

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  • An effect of Th2 environment on kallikrein expression in keratinocytes and skin barrier

    Grant number:22791074  2010 - 2011

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

    MORIZANE Shin

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    Grant amount:\4030000 ( Direct expense: \3100000 、 Indirect expense:\930000 )

    We found that Th2 cytokines, IL-4 and IL-13, increase kallikrein 7 expression and function in keratinocytes. Further, KLK7 protein level in the sera of atopic dermatitis patients significantly correlated with IL-4 amounts in the sera. Our finding describes a link between the Th2 environment and epidermal barrier dysfunction in atopic dermatitis.

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Class subject in charge

  • Research Presentation in Pathophysiology (2021academic year) special  - その他

  • Dermatology (Core Clinical Practice) (2021academic year) special  - その他

  • Research Projects and Practicals: Dermatology I (2021academic year) special  - その他

  • Lecture and Research Projects: Dermatology I (2021academic year) special  - その他

  • Research Projects and Practicals: Dermatology II (2021academic year) special  - その他

  • Lecture and Research Projects: Dermatology II (2021academic year) special  - その他

  • Dermatology (2021academic year) special  - その他

  • Introduction to Clinical Medicine and Dentistry (2021academic year) Concentration  - その他

  • Elective Clinical Practice (Dermatology) (2021academic year) special  - その他

  • Elective Clinical Practice (Dermatology) (2021academic year) special  - その他

  • Research Presentation in Pathophysiology (2020academic year) Year-round  - その他

  • Pathophysiology (2020academic year) Year-round  - その他

  • Dermatology (Core Clinical Practice) (2020academic year) special  - その他

  • Research Projects and Practicals: Dermatology I (2020academic year) special  - その他

  • Lecture and Research Projects: Dermatology I (2020academic year) special  - その他

  • Research Projects and Practicals: Dermatology II (2020academic year) special  - その他

  • Lecture and Research Projects: Dermatology II (2020academic year) special  - その他

  • Dermatology (2020academic year) special  - その他

  • Introduction to Clinical Medicine and Dentistry (2020academic year) Concentration  - その他

  • Elective Clinical Practice (Dermatology) (2020academic year) special  - その他

  • Elective Clinical Practice (Dermatology) (2020academic year) special  - その他

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