Researchers Database

komine mayumi

    Dermatology Professor
Last Updated :2021/11/23

Researcher Information

URL

J-Global ID

Research Interests

  • ケモカイン   表皮細胞   樹状細胞   ケラチノサイト   TARC   転写因子   表皮角化細胞   炎症性皮膚疾患   尋常性乾癬   シグナル伝達   CTACK   機械的刺激   発現制御機構   MAPキナーゼ   NFκB   デコイ型核酸   VEGF   Groα   マクロライド   乾癬   STAT1   GM-CSF   IL-33   ランゲルハンス細胞   サイトカイン   活性化   メラニン代謝物質   アレルギー疾患   尋常性白斑   メラニン   

Research Areas

  • Life sciences / Dermatology
  • Life sciences / Pathobiochemistry

Academic & Professional Experience

  • 2018/08 - Today  Jichi Medical UniversityDermatologyProfessor
  • 2007/06 - 2018/07  Jichi Medical UniversitySchool of MedicineAssociate Professor

Published Papers

  • Mayumi Komine, Akimichi Morita
    Expert review of clinical immunology 17 (9) 1015 - 1027 2021/09 
    INTRODUCTION: Generalized pustular psoriasis (GPP) is a rare, inflammatory skin disease characterized by recurrent flares of pustulation accompanied by systemic symptoms that can be life-threatening. The clinical and humanistic burden of GPP in Japan is high, and it is a designated intractable disease. We reviewed clinical evidence and guidelines for GPP treatment in Japan to identify unmet needs and assess data supporting the development and use of new targeted therapies. AREAS COVERED: Using specific search terms in PubMed and Embase, with additional back-referencing, we retrieved literature related to GPP in Japan focusing on clinical and pathogenic characteristics, diagnosis, and treatment. EXPERT OPINION: Although there are approved systemic therapies for GPP in Japan, all present uncertainties in terms of safety and efficacy. Clinical evidence supporting their use comes mostly from studies in patients with mild or moderate disease, and their effectiveness in treating acute phase GPP is unknown. The interleukin-36 pathway appears to be central to GPP pathogenesis. New therapies targeting this pathway show promise in patients presenting with acute phase GPP. The rarity and intermittent course of GPP make it challenging to recruit sufficient patients for trials and robustly investigate the efficacy and safety of these agents to treat GPP.
  • Mari Kishibe, Yasuaki Saijo, Satomi Igawa, Ayano Maruyama, Risa Tamagawa-Mineoka, Emi Nishida, Yuko Higashi, Mayumi Komine, Yayoi Tada, Yumi Aoyama, Michihiro Hide, Akemi Ishida-Yamamoto
    Journal of dermatological science 102 (1) 2 - 6 2021/04 
    BACKGROUND: A wide gender gap exists in many fields in Japan, including the academic society of dermatology. Women are substantially underrepresented in the highest academic ranks. OBJECTIVE: We aimed to clarify the possible factors contributing to the current gender gap in the field of academic dermatology and to recommend necessary measures to decrease the gender gap. METHODS: We performed a cross-sectional study of faculty members' academic productivity at the dermatology departments of all the educational institutions in Japan in 2019. RESULTS: Women had significantly lower academic productivity than men. A significant gender difference in academic productivity was found in lecturers and assistant professors but not in associate professor and professor positions. This gender difference was still significant after normalizing the productivity for career length. CONCLUSION: Our findings suggest the need to encourage women lecturers and assistant professors to improve their academic achievement to decrease the gender gap in academic dermatology.
  • Hidehisa Saeki, Tadashi Terui, Akimichi Morita, Shigetoshi Sano, Shinichi Imafuku, Akihiko Asahina, Mayumi Komine, Takafumi Etoh, Atsuyuki Igarashi, Hideshi Torii, Masatoshi Abe, Hidemi Nakagawa, Akira Watanabe, Hiroshi Yotsuyanagi, Mamitaro Ohtsuki
    The Journal of dermatology 47 (3) 201 - 222 0385-2407 2020/03 [Refereed][Not invited]
     
    As the first biologics for psoriasis in Japan, infliximab and adalimumab, anti-tumor necrosis factor-α antibodies, became available in the field of dermatology in 2010, followed by ustekinumab, an anti-interleukin (IL)-12/IL-23p40 antibody, which was launched in Japan in 2011. Since 2015, three IL-17 inhibitors of secukinumab and ixekizumab, anti-IL-17A antibodies, and brodalumab, an anti-IL-17 receptor antibody, and two anti-IL-23p19 antibodies of guselkumab and risankizumab, have also been launched. It is important for physicians to select appropriate biologic therapy for each psoriatic patient after due consideration of disease factors, treatment factors and patient background factors, sharing such information with patients. The following can be listed as points to be considered for the selection of biologics: drug effects (e.g. strength of effectiveness, time to onset of effectiveness, effectiveness against arthritis, primary failure, secondary failure), safety (e.g. infections, administration-related reactions and relationships with other comorbidities), convenience for patients (e.g. hospital visit intervals, self-injection, maintenance therapy at clinics, feasibility of drug discontinuation/re-administration) and payment (medical costs) borne by patients. This guidance has been prepared with the aim of allowing dermatologists experienced in the treatment of psoriasis to use biologics appropriately according to the circumstances of individual patients after consideration of the above-mentioned factors.
  • Takuma Shibata, Masato Taoka, Shin-Ichiroh Saitoh, Yoshio Yamauchi, Yuji Motoi, Mayumi Komine, Etsuko Fujita, Ryota Sato, Hiroshi Sagara, Takeshi Ichinohe, Mimi Kawazoe, Chiharu Kato, Katsuhiro Furusho, Yusuke Murakami, Ryutaro Fukui, Mamitaro Ohtsuki, Umeharu Ohto, Toshiyuki Shimizu, Nobuaki Yoshida, Toshiaki Isobe, Kensuke Miyake
    2019/12 [Refereed][Not invited]
     
    AbstractA lysosomal transmembrane protein SLC29A3 transports nucleosides from lysosomes to the cytoplasm. Loss-of-function mutations of the SLC29A3 gene cause lysosomal nucleoside storage in monocyte/macrophages, leading to their accumulation called histiocytosis in humans and mice. Little is known, however, about a mechanism behind nucleoside-dependent histiocytosis. TLR7, an innate immune sensors for single stranded RNA, bind and respond to nucleosides. We here show that they drive nucleoside-mediated histiocytosis. Patrolling monocyte/macrophages accumulate in the spleen of Slc29a3−/− mice but not Slc29a3−/−Tlr7−/− mice. Accumulated patrolling monocyte/macrophages stored nucleosides derived from cell corpse. TLR7 was recruited to phagosomes and activated as evidenced by TLR7-dependent phagosomal maturation. TLR7 induced hyper-responsiveness to M-CSF in Slc29a3−/− monocyte/macrophages. These results suggest that TLR7 drives histiocytosis in SLC29A3 disorders. One Sentence SummarySLC29A3 disorders are caused by activation of TLR7 with accumulated nucleosides in lysosomes.
  • Maekawa T, Okada K, Okada H, Kado S, Kamiya K, Komine M, Murata S, Oka K, Ishibashi S, Ohtsuki M
    The Journal of dermatology 46 (12) e463 - e464 0385-2407 2019/12 [Refereed][Not invited]
  • Yoneyama S, Kamiya K, Kishimoto M, Komine M, Ohtsuki M
    The Journal of dermatology 46 (11) e442 - e443 0385-2407 2019/11 [Refereed][Not invited]
  • Hioki T, Kamiya K, Tsuda H, Maekawa T, Komine M, Murata S, Ohtsuki M
    The Journal of dermatology 46 (11) e443 - e444 0385-2407 2019/11 [Refereed][Not invited]
  • Kishimoto M, Komine M, Kamiya K, Sugai J, Mieno M, Ohtsuki M
    The Journal of dermatology 0385-2407 2019/11 [Refereed][Not invited]
  • Ando T, Kamiya K, Maekawa T, Komine M, Murata S, Ohtsuki M
    The Journal of dermatology 46 (10) e360 - e362 0385-2407 2019/10 [Refereed][Not invited]
  • Chiang B, Kamiya K, Sato A, Maekawa T, Komine M, Murata S, Ohtsuki M
    The Journal of dermatology 46 (10) e345 - e346 0385-2407 2019/10 [Refereed][Not invited]
  • Kamiya K, Kishimoto M, Sugai J, Komine M, Ohtsuki M
    International journal of molecular sciences 20 (18) 2019/09 [Refereed][Not invited]
  • Chiang B, Kamiya K, Sashikawa M, Maekawa T, Komine M, Murata S, Ohtsuki M
    The Journal of dermatology 0385-2407 2019/09 [Refereed][Not invited]
  • Kishimoto M, Komine M, Kamiya K, Sugai J, Ohtsuki M
    The Journal of dermatology 46 (7) 615 - 617 0385-2407 2019/07 [Refereed][Not invited]
  • 毛孔性紅色粃糠疹の2例
    日置 智之, 小宮根 真弓, 津田 英利, 大槻 マミ太郎
    角化症研究会記録集 角化症研究会事務局 33 108 - 112 2019/03 [Refereed][Not invited]
  • Kamiya K, Karakawa M, Komine M, Kishimoto M, Sugai J, Ohtsuki M
    The Journal of dermatology 46 (3) 199 - 205 0385-2407 2019/03 [Refereed][Not invited]
  • Waki Y, Kamiya K, Maekawa T, Komine M, Murata S, Ohtsuki M
    The Journal of dermatology 46 (1) e34 - e35 0385-2407 2019/01 [Refereed][Not invited]
  • Iwasaki M, Kamiya K, Murata S, Maekawa T, Komine M, Ohtsuki M
    The Journal of dermatology 46 (1) e42 - e43 0385-2407 2019/01 [Refereed][Not invited]
  • Akimasa Adachi, Mayumi Komine, Hidetoshi Tsuda, Saeko Nakajima, Kenji Kabashima, Mamitaro Ohtsuki
    The journal of allergy and clinical immunology. In practice 7 (1) 325 - 327 2213-2198 2019/01 [Refereed][Not invited]
  • Adachi A, Maekawa T, Komine M, Murata S, Ohtsuki M
    The Journal of dermatology 46 (1) e48 - e49 0385-2407 2019/01 [Refereed][Not invited]
  • ニボルマブ投与患者の口腔内に生じ扁平苔癬様病変の1例
    中村 知寿, 神部 芳則, 岩上 藍, 小宮根 真弓, 出光 俊郎, 森 良之
    日本口腔内科学会雑誌 (一社)日本口腔内科学会 24 (2) 83 - 83 2186-6147 2018/12
  • Noguchi E, Kamiya K, Maekawa T, Komine M, Murata S, Ohtsuki M
    The Australasian journal of dermatology 59 (4) e313 - e314 0004-8380 2018/11 [Refereed][Not invited]
  • Kishimoto M, Komine M, Hioki T, Kamiya K, Sugai J, Ohtsuki M
    The Journal of dermatology 45 (11) 1345 - 1348 0385-2407 2018/11 [Refereed][Not invited]
  • Hideki Fujita, Tadashi Terui, Koremasa Hayama, Masashi Akiyama, Shigaku Ikeda, Tomotaka Mabuchi, Akira Ozawa, Takuro Kanekura, Michiko Kurosawa, Mayumi Komine, Kimiko Nakajima, Shigetoshi Sano, Osamu Nemoto, Masahiko Muto, Yasutomo Imai, Kiyofumi Yamanishi, Yumi Aoyama, Keiji Iwatsuki
    The Journal of dermatology 45 (11) 1235 - 1270 0385-2407 2018/11 [Refereed][Not invited]
     
    Generalized pustular psoriasis (GPP) is a rare disease characterized by recurrent fever and systemic flushing accompanied by extensive sterile pustules. The committee of the guidelines was founded as a collaborative project between the Japanese Dermatological Association and the Study Group for Rare Intractable Skin Diseases under the Ministry of Health, Labour, and Welfare Research Project on Overcoming Intractable Diseases. The aim of the guidelines was to provide current information to aid in the treatment of patients with GPP in Japan. Its contents include the diagnostic and severity classification criteria for GPP, its pathogenesis, and recommendations for the treatment of GPP. Since there are few clinical trial data with high levels of evidence for this rare disease, recommendations by the committee are described in the present guidelines.
  • 脇 裕磨, 村田 哲, 野口 絵麻, 神谷 浩二, 前川 武雄, 小宮根 真弓, 大槻 マミ太郎
    臨床皮膚科 (株)医学書院 72 (11) 916 - 922 0021-4973 2018/10 
    <文献概要>2007年1月〜2016年12月の10年間に,自治医科大学皮膚科で生検し偽リンパ腫と診断した27例を対象として,臨床像,皮疹および浸潤する細胞の特徴,治療法とその効果を検討した.初診時の平均年齢は54歳で男女差はなかった.単発16例,多発11例で,26例が顔面に生じていた.皮疹の性状は,22例で結節を形成していた.浸潤する細胞は,B細胞優位17例,T細胞優位10例であった.治癒を確認した21例を検討したところ,切除8例,生検のみ6例,ステロイド外用5例,ステロイド内服および外用1例,ステロイド局注1例であった.偽リンパ腫は良性疾患であり,生検のみでも消退を望めるため,まずは確定診断を目的とした部分生検を考慮すべきと考えた.
  • Jin M, Komine M, Tsuda H, Oshio T, Ohtsuki M
    The Journal of dermatology 45 (7) 855 - 857 0385-2407 2018/07 [Refereed][Not invited]
  • Takayuki Fusumae, Koji Kamiya, Takeo Maekawa, Mayumi Komine, Satoru Murata, Satoru Inoda, Ryota Takahashi, Hidetoshi Kawashima, Mamitaro Ohtsuki
    The Journal of dermatology 45 (6) e159-e160 - e160 0385-2407 2018/06 [Refereed][Not invited]
  • Waki Y, Kamiya K, Komine M, Maekawa T, Murata S, Ishii N, Hashimoto T, Ohtsuki M
    European journal of dermatology : EJD 28 (3) 413 - 414 1167-1122 2018/06 [Refereed][Not invited]
  • 皮膚生検で診断に至った鼻孔部偽リンパ腫の2例
    脇 裕磨, 野口 絵麻, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎
    日本皮膚科学会雑誌 (公社)日本皮膚科学会 128 (4) 622 - 622 0021-499X 2018/04
  • 抗リウマチ薬による口腔粘膜びらんの1例
    中村 知寿, 神部 芳則, 岡田 成生, 柏崎 明子, 山本 亜紀, 森 良之, 小宮根 真弓
    栃木県歯科医学会誌 (一社)栃木県歯科医師会 70 7 - 11 2018/04 
    症例は72歳女性で、関節リウマチで通院中であったが、約7ヵ月前から左頬粘膜、下唇に水疱、びらんが出現した。扁平苔癬、自己免疫性水疱症などを疑い精査を行ったが確定診断には至らず、経過観察となった。その後、口腔内のびらんが拡大してきたため当科紹介となった。メトトレキサート(MTX)による口腔粘膜びらんを疑い、血液検査を施行した。その結果、白血球数、赤血球数、ヘマトクリット値の低値を認めた。汎血球減少を伴う口腔粘膜潰瘍の診断で、直ちに主治医に連絡しMTXの中止を依頼した。MTXは直ちに中止となり、汎血球減少に対し入院下に輸血が行われた。口腔粘膜はMTX中止後に改善し、3週間後にはほぼ上皮化した。
  • Jitlada Meephansan, Urairack Subpayasarn, Saranyoo Ponnikorn, Panlop Chakkavittumrong, Premjit Juntongjin, Mayumi Komine, Mamitaro Ohtsuki, Yong Poovorawan
    Journal of Dermatology 45 (3) 322 - 325 1346-8138 2018/03 [Refereed][Not invited]
     
    Interleukin (IL)-33 can function both as a conventional cytokine and as a nuclear factor regulating gene transcription. IL-33 expression is strongly upregulated in the nucleus of keratinocytes and serum of patients with psoriasis. However, the role of IL-33 in psoriasis is unclear, and IL-33 expression in the lesional psoriatic skin after conventional systemic treatments has not been investigated. In this study, we aimed to compare IL-33 mRNA in patients’ lesional skin samples and IL-33 protein expression in patients’ serum before and after treatment with methotrexate (MTX) and narrowband ultraviolet B (NB-UVB). IL-33 mRNA levels in lesional skin and IL-33 protein levels in serum were downregulated after treatment with MTX. Results revealed a significant decrease in IL-33 protein expression (P = 0.028). IL-33 expression increased after NB-UVB treatment. IL-33 production is associated with inflammatory skin in psoriasis, possibly through its cytokine function. However, high expression of IL-33 after NB-UVB treatment suggests the occurrence of unknown functions to alleviate psoriatic lesions without IL-33 involvement.
  • Yoshitaka Ueda, Mayumi Komine, Koji Kamiya, Hidetoshi Tsuda, Takeo Maekawa, Satoru Murata, Mamitaro Ohtsuki
    Journal of Dermatology 45 (3) 326 - 328 1346-8138 2018/03 [Refereed][Not invited]
     
    A 92-year-old man developed an erythematous eruption on the trunk and extremities with numerous pustules accompanied by fever. He had never experienced pustular eruption or been diagnosed with psoriasis previously. Skin biopsy revealed Kogoj's spongiform pustule, and he was diagnosed with generalized pustular psoriasis (GPP). Genomic DNA was extracted from his peripheral blood and the sequence of IL36RN gene was analyzed, which revealed a p.Arg10X homozygous mutation. Several cases of elderly-onset GPP have been reported, however, this is the oldest case of GPP. The existence of splice variants of IL36RN was suspected, but we could not detect any splice variants of IL36RN in this case or in a healthy control from peripheral blood samples.
  • Suda K, Kamiya K, Chiang B, Okada H, Mato N, Maekawa T, Komine M, Murata S, Ohtsuki M
    Allergology international : official journal of the Japanese Society of Allergology 67 (3) 425 - 426 1323-8930 2018/03 [Refereed][Not invited]
  • C型肝炎に併発した、分節型に分布する限局性強皮症の1例
    脇 裕磨, 神谷 浩二, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎
    日本皮膚科学会雑誌 (公社)日本皮膚科学会 128 (2) 252 - 253 0021-499X 2018/02
  • Nobuki Maki, Mayumi Komine, Hidetoshi Tsuda, Yurika Fujita, Etsuko Fujita, Satoru Murata, Toshio Demitsu, Atsushi Utani, Mamitaro Ohtsuki
    Journal of Dermatology 45 (2) 244 - 246 1346-8138 2018/02 [Refereed][Not invited]
  • Yuma Waki, Koji Kamiya, Takeo Maekawa, Mayumi Komine, Satoru Murata, Mamitaro Ohtsuki
    Journal of Dermatology 45 (1) e9 - e10 1346-8138 2018/01 [Refereed][Not invited]
  • Takayuki Fusumae, Koji Kamiya, Binluen Chiang, Hirofumi Okada, Naomi Nakano, Takeo Maekawa, Mayumi Komine, Satoru Murata, Mamitaro Ohtsuki
    Journal of Dermatology 45 (1) 87 - 90 1346-8138 2018/01 [Refereed][Not invited]
     
    Mucosal melanoma is a rare aggressive cancer with a very poor prognosis. Clinical and pathological characteristics of mucosal melanoma differ from those of cutaneous melanoma and there are no established management guidelines for mucosal melanoma. Complete surgical excision is one of the most effective treatments for localized lesions, while targeted therapies and immunotherapies, such as monoclonal antibodies that target cytotoxic T-lymphocyte-associated molecule-4, and the programmed death (PD)-1/PD-ligand 1 pathway inhibitors, are treatment options for unresectable or metastatic lesions. Here, we describe the case of a patient with oral mucosal melanoma with multiple metastases. In our case, local injection of interferon (IFN)-β with dacarbazine–nimustine–vincristine therapy provided antitumor effects on an invasive tumor on the upper gingiva. Nivolumab therapy produced complete remission of lymph node and bone metastases. In contrast, the remaining in situ portion of oral mucosal melanoma on the hard palate was refractory to IFN-β monotherapy and nivolumab therapy. However, after administration of nivolumab, peritumoral injection of IFN-β showed rapid therapeutic effects. Our case suggested that nivolumab upregulated the antitumor effects of IFN-β, which induced the recruitment of CD8+ T cells into the tumor microenvironment contributing to the deletion of tumor cells. Combination therapy of IFN-β and nivolumab may be a potential treatment option for patients with oral mucosal melanoma.
  • Takayuki Fusumae, Koji Kamiya, Takeo Maekawa, Mayumi Komine, Satoru Murata, Mamitaro Ohtsuki
    Journal of Dermatology 45 (1) 115 - 116 1346-8138 2018/01 [Refereed][Not invited]
  • 永島 和貴, 梅本 尚可, 津田 英利, 小宮根 真弓, 出光 俊郎, 川瀬 正昭
    皮膚病診療 (株)協和企画 39 (12) 1247 - 1250 0387-7531 2017/12 [Refereed][Not invited]
     
    <症例のポイント>乾癬性紅皮症の治療経過中にnarrow band ultraviolet B(以下、NB-UVB)照射療法を行い膿疱性乾癬が誘発された。IL36RN遺伝子変異検索ではp.Asn47Serのヘテロ変異を認めた。通常はキャリアと解釈されるヘテロ変異症例でもなんらかの複合要因のもとに炎症反応が強く働き、膿疱性乾癬の皮疹が発症する可能性があり、自験例は光線過敏症が要因と考えた。(著者抄録)
  • 一時的な核内のIL-33の消失は表皮角化細胞の細胞分裂を抑制する
    津田 英利, 小宮根 真弓, 大槻 マミ太郎
    生命科学系学会合同年次大会 生命科学系学会合同年次大会運営事務局 2017年度 [2P - 0360] 2017/12 [Refereed][Not invited]
  • Naomi Nakano, Takeo Nakaya, Koji Kamiya, Mayumi Komine, Satoru Murata, Hirotoshi Kawata, Shigeo Yokoyama, Akira Tanaka, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 44 (11) 1327 - 1328 0385-2407 2017/11 [Refereed][Not invited]
  • Mamitaro Ohtsuki, Yukari Okubo, Mayumi Komine, Shinichi Imafuku, Robert M. Day, Peng Chen, Rosemary Petric, Allan Maroli, Osamu Nemoto
    JOURNAL OF DERMATOLOGY 44 (8) 873 - 884 0385-2407 2017/08 [Refereed][Not invited]
     
    Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, works intracellularly within immune cells to regulate inflammatory mediators. This phase 2b randomized, placebo-controlled study evaluated efficacy and safety of apremilast among Japanese patients with moderate to severe plaque psoriasis. In total, 254 patients were randomized to placebo, apremilast 20 mg b.i.d. (apremilast 20) or apremilast 30 mg b.i.d. (apremilast 30) through week 16; thereafter, all placebo patients were re-randomized to apremilast 20 or 30 through week 68. Efficacy assessments included achievement of 75% or more reduction from baseline in Psoriasis Area and Severity Index score (PASI-75; primary) and achievement of static Physician Global Assessment (sPGA; secondary) score of 0 (clear) or 1 (minimal) at week 16. Safety was assessed through week 68. At week 16, PASI-75 response rates were 7.1% (placebo), 23.5% (apremilast 20; P = 0.0032 vs placebo) and 28.2% (apremilast 30; P = 0.0003 vs placebo); sPGA response rates (score of 0 or 1) were 8.8% (placebo), 23.9% (apremilast 20; P = 0.0165 vs placebo) and 29.6% (apremilast 30; P = 0.0020 vs placebo). Responses were maintained with apremilast through week 68. Most common adverse events (AEs) with placebo, apremilast 20 and apremilast 30 (0-16 weeks) were nasopharyngitis (8.3%, 11.8%, 11.8%), diarrhea (1.2%, 8.2%, 9.4%), and abdominal discomfort (1.2%, 1.2%, 7.1%), respectively. Exposure-adjusted incidence of these AEs did not increase with continued apremilast treatment (up to 68 weeks). Apremilast demonstrated efficacy and safety in Japanese patients with moderate to severe plaque psoriasis through 68 weeks that was generally consistent with prior studies.
  • Koji Kamiya, Mayumi Komine, Satoru Murata, Mamitaro Ohtsuki
    INTERNATIONAL JOURNAL OF DERMATOLOGY 56 (8) E173 - E175 0011-9059 2017/08 [Refereed][Not invited]
  • Yoshitaka Ueda, Koji Kamiya, Takeo Maekawa, Mayumi Komine, Satoru Murata, Mamitaro Ohtsuki
    EUROPEAN JOURNAL OF DERMATOLOGY 27 (4) 423 - 425 1167-1122 2017/07 [Refereed][Not invited]
  • 最近経験した慢性膿皮症の2例
    脇 裕磨, 前川 武雄, 神谷 浩二, 小宮根 真弓, 村田 哲, 大槻 マミ太郎
    日本皮膚外科学会誌 (NPO)日本皮膚外科学会 21 (2別冊) 245 - 245 1880-4470 2017/06
  • Akimasa Adachi, Mayumi Komine, Takeo Maekawa, Satoru Murata, Aiko Shiohama, Akiharu Kubo, Mamitaro Ohtsuki
    ACTA DERMATO-VENEREOLOGICA 97 (6) 756 - 758 0001-5555 2017/06 [Refereed][Not invited]
  • 多発と考えたMicrocystic adnexal carcinoma(MAC)の1例
    脇 裕磨, 神谷 浩二, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎
    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集 (一社)日本皮膚悪性腫瘍学会 33回 190 - 190 2017/05
  • 部分生検が有用であった鼻孔部偽リンパ腫の2例
    脇 裕磨, 野口 絵麻, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎
    日本皮膚科学会雑誌 (公社)日本皮膚科学会 127 (5) 1149 - 1149 0021-499X 2017/05
  • Akimasa Adachi, Takeo Maekawa, Mayumi Komine, Satoru Murata, Yukiko Ueda, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 44 (2) 222 - 223 0385-2407 2017/02 [Refereed][Not invited]
  • Ai Matsumoto, Mayumi Komine, Masaru Karakawa, Megumi Kishimoto, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 44 (2) 202 - 204 0385-2407 2017/02 [Refereed][Not invited]
     
    We report a case of a 70-year-old woman with generalized pustular psoriasis (GPP) who responded well to infliximab therapy and adalimumab therapy after secondary failure of infliximab therapy, but did not respond to ustekinumab therapy. We speculate that the pathogenic factor in this case favored anti-tumor necrosis factor (TNF)- therapy to anti-interleukin-12/23 therapy. Herein, we also briefly present three additional cases of treatment with adalimumab after secondary failure of infliximab. GPP is often difficult to treat, and no placebo-controlled trials have been conducted to guide the use of biologics against it because of a paucity of cases. Infliximab and adalimumab are anti-TNF- antibodies that specifically block the interaction of TNF- with its receptors. Infliximab has been reported to be effective, with a rapid clearance of symptoms, even in cases of severe GPP. Adalimumab could be a good biologic candidate that can be administrated after secondary failure of infliximab therapy.
  • Tomoyuki Oshio, Mayumi Komine, Hidetoshi Tsuda, Shin-ichi Tominaga, Hirohisa Saito, Susumu Nakae, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGICAL SCIENCE 85 (2) 106 - 114 0923-1811 2017/02 [Refereed][Not invited]
     
    Background: Skin is the outermost tissue of the human body, and works as a mechanical, chemical, and biological barrier. The epidermis is the uppermost layer of the skin, and keratinocytes constitute the majority of epidermal cells. Wounds are disruptions of skin integrity, and cause tremendous disadvantages to humans; accordingly, rapid wound healing is very important. Interleukin (IL)-33 is expressed in barrier tissue cells, such as epithelial and endothelial cells. Upon injury, IL-33 is released to stimulate immune cells, functioning as an "alarmin." ST2 is a receptor for IL-33; its soluble form (s)ST2 acts as a decoy receptor and competes for IL-33 binding. Objectives: We aimed to clarify the role of IL-33 in wound healing. Materials and methods: Wild-type (WT), IL-33 knockout (IL33 KO) mice, and sST2 transgenic (Tg) mice were wounded with a 4-mm punch, and the wound healing process was compared. Immunohistochemical analyses were performed to detect macrophages, neutrophils, and mast cells. Total RNA was extracted from the skin samples and real-time PCR was performed. An in vitro scratch wound assay was performed. Results: Wound healing was delayed in IL33 KO mice compared to WT mice, while wound healing in sST2 Tg mice was comparable to that of WT mice. A histological examination showed delayed elongation of the epidermal tongue in IL-33 KO mice. An immunohistochemical study revealed prolonged neutrophilic infiltration at a later stage in IL-33 KO mice. IL-6, IL-1 beta, and CXCL1 transcripts were more abundant in the wounds of IL-33 KO mice than WT mice. Intraperitoneal administration of an NF kappa B inhibitor to IL-33 KO mice normalized the delayed wound healing and the enhanced expression of IL-6 in IL-33 KO mice. Epidermal keratinocytes from IL-33 KO mice showed delayed wound closure compared to those from WT mice. Conclusion: Our results indicate that nuclear IL-33, but not IL-33 as a cytokine, has beneficial effects on wound healing in mice, probably by suppressing NF kappa B to inhibit excessive inflammation and by maintaining keratinocyte proliferation or migration for epithelialization. (C) 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
  • Hidetoshi Tsuda, Mayumi Komine, Shin-ichi Tominaga, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGICAL SCIENCE 85 (2) 137 - 140 0923-1811 2017/02 [Refereed][Not invited]
  • Akimasa Adachi, Mayumi Komine, Tomoko Hirano, Hidetoshi Tsuda, Masaru Karakawa, Satoru Murata, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 43 (12) 1439 - 1440 0385-2407 2016/12 [Refereed][Not invited]
  • Akimasa Adachi, Mayumi Komine, Satoru Murata, Takeo Maekawa, Shin-ichi Ansai, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 43 (11) 1364 - 1365 0385-2407 2016/11 [Refereed][Not invited]
  • Akimasa Adachi, Mayumi Komine, Satoru Murata, Hidetoshi Tsuda, Yuta Kawahara, Akira Morimoto, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 43 (11) 1377 - 1378 0385-2407 2016/11 [Refereed][Not invited]
  • Akimasa Adachi, Mayumi Komine, Masayuki Suzuki, Satoru Murata, Tomoko Hirano, Norito Ishii, Takashi Hashimoto, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 43 (11) 1389 - 1391 0385-2407 2016/11 [Refereed][Not invited]
  • Masaru Karakawa, Mayumi Komine, Megumi Kishimoto, Nobuki Maki, Ai Matsumoto, Junichi Sugai, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 43 (11) 1354 - 1357 0385-2407 2016/11 [Refereed][Not invited]
     
    Adalimumab is a biologic that is very effective for treatment of psoriasis. However, recalcitrant or recurrent lesions sometimes occur during treatment. Maxacalcitol is an active vitamin D3 ointment that is effective in treatment of psoriasis. Topical therapy may be beneficial in treatment of recalcitrant or recurrent lesions during treatment with systemic therapy, but there is little evidence on this topic. We investigated the effect of maxacalcitol on skin lesions during treatment with adalimumab in patients with psoriasis. Twelve patients with psoriasis were randomly assigned to two groups after informed consent - treatment with adalimumab only (n = 6), and treatment with adalimumab and maxacalcitol (n = 6) - and they were evaluated every 4 weeks for 44 weeks. Exacerbation was defined as an increase of the Psoriasis Area and Severity Index (PASI) score. The interval between adalimumab treatments was elongated to 3-4 weeks from 2 weeks according to the individual patient's condition. The PASI score was evaluated every 4 weeks, and the frequency of exacerbations was counted. The overall improvement in PASI score was not statistically different between the two groups, but the frequency of exacerbations was significantly less in the maxacalcitol combination group compared with the adalimumab monotherapy group (Mann-Whitney U-test, P < 0.05). The better control of skin lesions in patients who elongated the interval of adalimumab administration was achieved in the maxacalcitol combination group compared with the adalimumab monotherapy group. Topical maxacalcitol treatment is effective and useful in controlling skin lesions in patients with psoriasis when used in combination with adalimumab.
  • Shinichi Imafuku, Masaru Honma, Yukari Okubo, Mayumi Komine, Mamitaro Ohtsuki, Akimichi Morita, Noriko Seko, Naoko Kawashima, Saori Ito, Tomohiro Shima, Hidemi Nakagawa
    JOURNAL OF DERMATOLOGY 43 (9) 1011 - 1017 0385-2407 2016/09 [Refereed][Not invited]
     
    Generalized pustular psoriasis (GPP) is a severe inflammatory skin disease characterized by the presence of sterile pustules covering almost the entire body and systemic symptoms such as fever. Secukinumab, a fully human-recombinant anti-interleukin-17A monoclonal antibody was indicated for psoriasis vulgaris and psoriatic arthritis in Japan but is not yet investigated for GPP. In this phase III, open-label multicenter single arm study, the efficacy and safety of secukinumab as monotherapy or with co-medication was evaluated in 12 Japanese patients with GPP. All the patients received secukinumab 150 mg s.c. at baseline, week 1, 2, 3 and 4, and then every 4 weeks. Two non-responders were up-titrated to 300 mg. Change in GPP severity from baseline was evaluated by clinical global impression (CGI) categorized as "worsened", "no change", "minimally improved", "much improved" or "very much improved". Treatment success was achieved by 83.3% (n = 10) of patients at week 16 (primary end-point) with CGI evaluated as "very much improved" (n = 9) and " much improved" (n = 1). Moreover, the area of erythema with pustules improved as early as week 1 and resolved by week 16 in most of the patients. The improvements were sustained throughout 52 weeks. Over the 52-week treatment period, secukinumab was well tolerated with no unexpected safety signals. Nasopharyngitis, urticaria, diabetes mellitus and arthralgia were the frequent adverse events reported. The data from this study shows that secukinumab can become one of the potent treatment options for GPP.
  • Pavida Pittayapruek, Jitlada Meephansan, Ornicha Prapapan, Mayumi Komine, Mamitaro Ohtsuki
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 17 (6) 1422-0067 2016/06 [Refereed][Not invited]
     
    Matrix metalloproteinases (MMPs) are zinc-containing endopeptidases with an extensive range of substrate specificities. Collectively, these enzymes are able to degrade various components of extracellular matrix (ECM) proteins. Based on their structure and substrate specificity, they can be categorized into five main subgroups, namely (1) collagenases (MMP-1, MMP-8 and MMP-13); (2) gelatinases (MMP-2 and MMP-9); (3) stromelysins (MMP-3, MMP-10 and MMP-11); (4) matrilysins (MMP-7 and MMP-26); and (5) membrane-type (MT) MMPs (MMP-14, MMP-15, and MMP-16). The alterations made to the ECM by MMPs might contribute in skin wrinkling, a characteristic of premature skin aging. In photocarcinogenesis, degradation of ECM is the initial step towards tumor cell invasion, to invade both the basement membrane and the surrounding stroma that mainly comprises fibrillar collagens. Additionally, MMPs are involved in angiogenesis, which promotes cancer cell growth and migration. In this review, we focus on the present knowledge about premature skin aging and skin cancers such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma, with our main focus on members of the MMP family and their functions.
  • Satomi Hosoda, Akimasa Adachi, Masayuki Suzuki, Tomoko Yamada, Mayumi Komine, Satoru Murata, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 43 (2) 194 - 196 0385-2407 2016/02 [Refereed][Not invited]
     
    We report a case involving a 62-year-old woman with invivo-bound immunoglobulin (Ig)G and IgA antibodies in both the intercellular space (ICS) and basement membrane zone (BMZ). Her clinical and histopathological features were identical with those of pemphigus vulgaris, while the immunopathological findings suggested IgG/IgA pemphigus. Direct immunofluorescence (IF) showed invivo-bound IgG and IgA antibodies in the ICS and BMZ, whereas indirect IF showed circulating IgG but not IgA antibodies in the ICS and BMZ. The anti-ICS IgG bound to desmoglein-3, while the anti-BMZ antibodies bound to the epidermal side of 1mol/L NaCl-split skin. To the best of our knowledge, only two similar cases have been reported so far. Furthermore, we also examined IgG subclass distribution of the invivo-bound and circulating anti-ICS and BMZ antibodies, and found that IgG1, IgG2 and IgG4 bound to ICS of the lesional skins, while IgG1 and IgG3 bound to the BMZ. The circulating anti-ICS antibodies belonged to IgG1 and IgG4, while the circulating anti-BMZ antibodies to IgG1, IgG2 and IgG4. We report a case involving a 62-year-old woman with invivo-bound immunoglobulin (Ig)G and IgA antibodies in both the intercellular space (ICS) and basement membrane zone (BMZ). Her clinical and histopathological features were identical with those of pemphigus vulgaris, while the immunopathological findings suggested IgG/IgA pemphigus. Direct immunofluorescence (IF) showed invivo-bound IgG and IgA antibodies in the ICS and BMZ, whereas indirect IF showed circulating IgG but not IgA antibodies in the ICS and BMZ. The anti-ICS IgG bound to desmoglein-3, while the anti-BMZ antibodies bound to the epidermal side of 1mol/L NaCl-split skin. To the best of our knowledge, only two similar cases have been reported so far. Furthermore, we also examined IgG subclass distribution of the invivo-bound and circulating anti-ICS and BMZ antibodies, and found that IgG1, IgG2 and IgG4 bound to ICS of the lesional skins, while IgG1 and IgG3 bound to the BMZ. The circulating anti-ICS antibodies belonged to IgG1 and IgG4, while the circulating anti-BMZ antibodies to IgG1, IgG2 and IgG4.
  • Etsuko Fujita, Mayumi Komine, Hidetoshi Tsuda, Akimasa Adachi, Satoru Murata, Yasuyuki Kamata, Seiji Minota, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 42 (12) 1169 - 1171 0385-2407 2015/12 [Refereed][Not invited]
     
    We describe a case of H syndrome with massive skin involvement, retroperitoneal fibrosis and Raynaud's phenomenon. A 48-year-old man with parents of a consanguineous marriage, first appeared with decreased urine output, skin sclerosis on his inner thighs and short stature (142 cm, 47 kg). The patient had suffered from hearing loss since the age of 1 year, and his secondary sexual characteristics had not developed. Computed tomography showed periaortic fibrosis, bilateral ureteral stenosis, hydronephrosis and sclerosis of the germinal cords. A biopsy from the retroperitoneal mass revealed remarkable fibrosis with chronic inflammatory cells. Biopsies from the skin lesion showed thick collagen bundles through the dermis and lymphohistiocytic infiltration with numerous plasma cells. Serum inflammatory markers, such as C-reactive protein, vascular endothelial factor, transforming growth factor-beta and soluble interleukin-2 receptor, were elevated. Prednisolone was effective in treating skin lesions and in lowering serum inflammatory markers. After a long period of follow up, genomic DNA of the patient was obtained, and we identified a homozygous mutation in exon 5, c.625G>A, which caused transition of glycine to arginine, p.Gly208Arg, in the patient, but not in DNA samples from another 50 healthy individuals. This is the first case of H syndrome with Raynaud's phenomenon and retroperitoneal fibrosis, and the first Japanese case of H syndrome reported in the English published work with a novel mutation in the SLC29A3 gene.
  • Rina Nakajima, Mayumi Komine, Yukiko Miyamoto, Takayuki Fusumae, Yurika Fujita, Takeo Maekawa, Satoru Murata, Noriyoshi Fukushima, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 42 (11) 1083 - 1086 0385-2407 2015/11 [Refereed][Not invited]
     
    We report a case of sarcomatoid carcinoma of the skin in a 63-year-old man who was treated with the carbon dioxide snow freezing method for a huge congenital pigmented nevus that extended from the right upper extremity to the right trunk during childhood. He had an exophytic red tumor on the nevus in the right upper extremity that grew slowly for 4years and rapidly recently. Histological and immunohistochemical studies revealed both epithelial and mesenchymal malignancy in the same tumor. The epithelial component was composed of basaloid cells forming multiple nests with peripheral palisading, positive for keratins and BerEP4, implying basal cell carcinoma. The mesenchymal component was composed of spindle-shaped cells negative for keratins and positive for vimentin, suggesting sarcoma. This is, to our knowledge, the first report of sarcomatoid carcinoma arising in the primary pigmented nevus that had been treated by the carbon dioxide snow freezing method.
  • E. Toyonaga, W. Nishie, M. Komine, S. Murata, S. Shinkuma, K. Natsuga, H. Nakamura, M. Ohtsuki, H. Shimizu
    British Journal of Dermatology 172 (4) 1141 - 1144 1365-2133 2015/04 [Refereed][Not invited]
     
    Toyonaga E, Nishie W, Komine M, Murata S, Shinkuma S, Natsuga K, Nakamura H, Ohtsuki M, Shimizu H, The British journal of dermatology, 2014
  • Chizuko Yano, Hidehisa Saeki, Mayumi Komine, Shinji Kagami, Yuichiro Tsunemi, Mamitaro Ohtsuki, Hidemi Nakagawa
    ANNALS OF DERMATOLOGY 27 (2) 152 - 156 1013-9087 2015/04 [Refereed][Not invited]
     
    CC chemokine ligand 17 (CCL17) and CCL22 are the functional ligands for CCR4. We previously reported that inhibitors of nuclear factor-kappa B and p38 mitogen-activated protein kinase (p38 MAPK), but not of extracellular signal-related kinase (ERK), inhibited tumor necrosis factor (TNF)- alpha - and interferon (IFN)- gamma -induced production of CCL17 by the human keratinocyte cell line, HaCaT. Further, an inhibitor of epidermal growth factor receptor (EGFR) enhanced the CCL17 production by these keratinocytes. Objective: To identify the mechanism underlying CCL22 production by HaCaT cells. Methods: We investigated the signal transduction pathways by which TNF- alpha and IFN- gamma stimulate HaCaT cells to produce CCL22 by adding various inhibitors. Results: TNF- alpha - and IN-gamma - induced CCL22 production was inhibited by PD98059, PD153035, Bay 11-7085, SB202190, c-Jun N-terminal kinase (INK) inhibitor II, and Janus kinase OAK) inhibitor 1. Conclusion: Our results indicate that CCL22 production in HaCaT cells is dependent on ERK, EGFR, p38 MAPK, JNK, and JAK and is mediated by different signal pathways from those regulating CCL17 production. Altogether, our previous and present results suggest that EGFR activation represses CCL17 but enhances CCL22 production by these cells.
  • Takeo Maekawa, Mayumi Komine, Satoru Murata, Noriyoshi Fukushima, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 42 (3) 318 - 321 0385-2407 2015/03 [Refereed][Not invited]
     
    Intravascular large B-cell lymphoma (IVLBCL) is classified as a rare type of non-Hodgkin's B-cell lymphoma by the World Health Organization. It is characterized by the presence of lymphoma cells in the lumens of the small vessels of several organs, most notably the skin. Diagnosis of IVLBCL is difficult because of the lack of lymphadenopathy and because lesions need to be histologically confirmed via a biopsy of the affected organs. Random skin biopsy (RSB) of normal-appearing skin is a useful and apparently safe means of evaluating IVLBCL. However, patients with IVLBCL often exhibit thrombocytopenia, and we describe a case in which a patient with thrombocytopenia experienced hemorrhagic shock and died shortly after RSB. For this reason, we reviewed cases of RSB performed at our hospital and found that the middle adipose tissue contained a higher percentage of atypical lymphoid cells than other layers of the skin. On the basis of our findings, we propose a strategy for the safer performance of RSB in IVLBCL patients with thrombocytopenia and coagulation abnormalities.
  • Shin-ichi Tominaga, Kenji Tago, Hidetoshi Tsuda, Mayumi Komine
    CYTOKINE 72 (1) 105 - 108 1043-4666 2015/03 [Refereed][Not invited]
     
    The interleukin-33 (IL-33)-ST2L signaling pathway has been shown to play important roles in the field of immunology, especially as a trigger for allergic reactions such as bronchial asthma. However, coming back to the original finding that the ST2 gene is induced during initiation of the cell cycle of fibroblastic cell lines, the possible functions of the ST2 gene products and their specific ligand, IL-33, in the field of cell growth regulation are still interesting problems to be solved. In this study, we used NIH-3T3 mouse cell line and added IL-33 before and after cell proliferation assay, which revealed the dual function of IL-33. When IL-33 was added to the confluent cells before the start of cell proliferation, it suppressed the cell growth concentration-dependently. On the other hand, if IL-33 was added after the start of cell proliferation, it enhanced the cell growth. The negative effect of IL-33 on cell proliferation is a novel finding and would provide an important clue to the roles of IL-33 and ST2/ST2L in growth regulation. (C) 2014 Elsevier Ltd. All rights reserved.
  • Akimasa Adachi, Mayumi Komine, Satoru Murata, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 42 (2) 224 - 225 0385-2407 2015/02 [Refereed][Not invited]
  • Masaru Karakawa, Mayumi Komine, Yasushi Hanakawa, Hidetoshi Tsuda, Koji Sayama, Kunihiko Tamaki, Mamitaro Ohtsuki
    JOURNAL OF CELLULAR PHYSIOLOGY 229 (12) 1935 - 1945 0021-9541 2014/12 [Refereed][Not invited]
     
    The cutaneous T cell-attracting chemokine (CTACK)/CCL27 is indispensable in skin inflammation. CTACK/CCL27 is exclusively produced by epidermal keratinocytes to attract CCR10-expressing T lymphocytes to the skin. We investigated the mechanism of CTACK/CCL27 production from normal human epidermal keratinocytes (NHEKs) by the proinflammatory cytokines TNF and IFN. CTACK/CCL27 production was induced by TNF via ERK, JNK, p38, and NFB. The induction of CTACK/CCL27 by TNF was suppressed by IFN via a pathway dependent on JAK, STAT1, and STAT3. Our results also demonstrated that IFN and TNF induced the phosphorylation of EGFR and the following phosphorylation of ERK, which is partly responsible for the suppressive effect of IFN on TNF-induced production of CTACK/CCL27. Peri-lesional skin of psoriasis demonstrates early inflammatory changes as we have previously reported. CTACK/CCL27 expression was diffuse in the peri-lesional epidermis, while it was restricted to basal layer in lesional epidermis, suggesting that CTACK/CCL27 expression was induced in the early stage of psoriatic plaque formation, and IFN could participate in the suppression of CTACK/CCL27 expression in the lesional epidermis, reflecting the later stage of psoriatic plaque formation. Our study suggests that CTACK/CCL27 may have a pivotal role in the early stage of psoriasis plaque formation, but should be downregulated in the later stage to induce inflammation characteristic for chronic psoriasis plaques. J. Cell. Physiol. 229: 1935-1945, 2014. (c) 2014 Wiley Periodicals, Inc.
  • Masayuki Suzuki, Satomi Hosoda, Tomoko Yamada, Mayumi Komine, Satoru Murata, Hideto Yokokura, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 41 (11) 1030 - 1031 0385-2407 2014/11 [Refereed][Not invited]
  • Takeo Maekawa, Mayumi Komine, Satoru Murata, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 41 (10) 944 - 946 0385-2407 2014/10 [Refereed][Not invited]
  • Yukiko Miyamoto, Mayumi Komine, Yuka Takatsuka, Takeo Maekawa, Satoru Murata, Kazue Nakanaga, Norihisa Ishii, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 41 (8) 771 - 772 0385-2407 2014/08 [Refereed][Not invited]
  • Takeo Maekawa, Mayumi Komine, Satoru Murata, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 40 (12) 1058 - 1059 0385-2407 2013/12 [Refereed][Not invited]
  • Satomi Hosoda, Masayuki Suzuki, Mayumi Komine, Etsuko Fujita, Tomoko Yamada, Satoru Murata, Hiroshi Koga, Takashi Hashimoto, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 40 (12) 1067 - 1068 0385-2407 2013/12 [Refereed][Not invited]
  • Chieh-Shan Wu, Mayumi Komine, Seiki Fujimoto, Hanako Ohmatsu, Kanako Kikuchi, Yayoi Tada, Hsin-Su Yu, Mamitaro Ohtsuki, Kunihiko Tamaki
    JOURNAL OF DERMATOLOGICAL SCIENCE 72 (1) 66 - 68 0923-1811 2013/10 [Refereed][Not invited]
  • Tadashi Nagai, Masaru Karakawa, Mayumi Komine, Kazuo Muroi, Mamitaro Ohtsuki, Keiya Ozawa
    EUROPEAN JOURNAL OF HAEMATOLOGY 91 (3) 270 - 272 0902-4441 2013/09 [Refereed][Not invited]
     
    The tyrosine kinase inhibitor (TKI) imatinib has been shown to promote psoriasis in some patients with chronic myelogenous leukaemia (CML), but it remained unclear whether second-generation TKIs such as nilotinib and dasatinib had a similar potential. Here, we present a patient in whom psoriatic erythema appeared at 26months after initiation of nilotinib treatment. Topical ointments of activated vitamin D-3 derivative and corticosteroid were applied; whereupon, the erythema gradually improved. During the clinical course, nilotinib administration continued without reduction in its dose. This is the first report of psoriasis that developed during nilotinib treatment. We also discuss the mechanisms of nilotinib-mediated progression of psoriasis.
  • Mamitaro Ohtsuki, Tadashi Terui, Akira Ozawa, Akimichi Morita, Shigetoshi Sano, Hidetoshi Takahashi, Mayumi Komine, Takafumi Etoh, Atsuyuki Igarashi, Hideshi Torii, Akihiko Asahina, Osamu Nemoto, Hidemi Nakagawa
    Journal of Dermatology 40 (9) 683 - 695 0385-2407 2013/09 [Refereed][Not invited]
     
    The clinical use of adalimumab and infliximab, human anti-tumor necrosis factor (TNF)-α monoclonal antibodies, for psoriasis began in January 2010. In January 2011, ustekinumab, a human anti-interleukin-12/23p40 (IL-12/23p40) monoclonal antibody, was newly approved as the third biologic with an indication for psoriasis. While all of these biologics are expected to exhibit excellent therapeutic effect for psoriasis and to contribute to the improvement of quality of life in patients, these drugs require careful safety measures to prevent adverse drug reactions, such as serious infections. The new guidance, an English version prepared by revising the Japanese Guidance/Safety Manual for Use of Biologics for Psoriasis 2011 (in Japanese), is intended to provide up-to-date, evidence-based recommendations and safety measures on the use of biologics, and describes the optimal use of the three biologics, medical requirements for facilities for using biologics, details of safety measures against reactivation of tuberculosis and hepatitis B virus infection, and recommendable combination therapies with biologics. © 2013 Japanese Dermatological Association.
  • Jitlada Meephansan, Mayumi Komine, Hidetoshi Tsuda, Masaru Karakawa, Shin-ichi Tominaga, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGICAL SCIENCE 71 (2) 107 - 114 0923-1811 2013/08 [Refereed][Not invited]
     
    Background: Interleukin (IL)-33 is a dual functional, IL-1 family member cytokine, whose exact roles in inflammatory skin diseases are still unknown. IL-17A is a key cytokine in the pathogenesis of psoriasis. Objectives: We investigated if IL-17A could induce IL-33 in epidermal keratinocytes, and the signaling mechanisms involved. Methods: IL-33 levels were evaluated by RT-PCR and western blot in human keratinocytes following IL-17A simulation. IL-33 immunohistochemical staining of psoriatic skin samples was also performed and compared with that of control tissues. The role of signaling pathways downstream of IL-17A was investigated using small molecule inhibitors of EGFR, ERK, p38, and JAK. Adenovirus vector expressing dominant negative STAT1 was also utilized. Results: IL-33 and its receptor, ST2L, were expressed in the psoriatic epidermis, and the associated infiltrating cells. IL-17A induced IL-33 expression at mRNA and protein levels in a time- and concentration-dependent manner. IL-17A caused phosphorylation of EGFR, ERK, p38, and STAT1. IL-17A-induced IL-33 expression was blocked by the addition of EGFR, ERK, p38, and JAK inhibitors, and dominant negative STAT1-expressing adenovirus vector. Conclusion: IL-17A induced IL-33 in NHEKs through EGFR, ERK, p38, and JAK/STAT1 pathways, which were necessary for the induction of IL-33. IL-33, induced by IL-17A in epidermal keratinocytes, may be involved in the pathophysiology of inflammatory skin diseases, including psoriasis. (C) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
  • Nobuki Maki, Mayumi Komine, Yuka Takatsuka, Takeo Maekawa, Satoru Murata, Mamitaro Ohtsuki
    Journal of Dermatology 40 (4) 299 - 300 0385-2407 2013/04 [Refereed][Not invited]
  • Satomi Hosoda, Tomoko Yamada, Masayuki Suzuki, Satoru Murata, Mayumi Komine, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 40 (3) 211 - 212 0385-2407 2013/03 [Refereed][Not invited]
  • Makiko Morita, Mayumi Komine, Yuka Takatsuka, Satomi Hosoda, Hiroshi Onda, Takeo Maekawa, Satoru Murata, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 40 (2) 132 - 134 0385-2407 2013/02 [Refereed][Not invited]
  • Jitlada Meephansan, Mayumi Komine, Satomi Hosoda, Hidetoshi Tsuda, Masaru Karakawa, Satoru Murata, Toshio Demitsu, Mamitaro Ohtsuki
    JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY 68 (1) 138 - 143 0190-9622 2013/01 [Refereed][Not invited]
     
    Background: Degos disease or malignant atrophic papulosis is a rare occlusive vasculopathic disease characterized by pathognomonic cutaneous lesions and frequently fatal systemic involvement. The etiology of malignant atrophic papulosis remains unclear, and there is currently no effective treatment for malignant atrophic papulosis. Several chemokines can potentiate and expand the platelet response to increase thrombus formation. Among these chemokines, this study examined the expression of stromal cell-derived factor (SDF)-1/CXCL12, which is secreted by bone-marrow stromal and endothelial cells, activates megakaryocyte precursors, and costimulates platelet activation. Objective: We sought to investigate and compare the expression of SDF-1/CXCL12 in tissue sections taken from 2 patients with Degos disease, 2 patients with other vaso-occlusive diseases, and 2 healthy control subjects. Methods: Immunohistochemical staining involving antibodies to SDF-1/CXCL12 was performed on 3 skin biopsy specimens taken from 2 patients with Degos disease, 1 from a patient with antiphospholipid syndrome, 1 from a patient with cryoglobulinemia, and 2 from healthy control subjects. Results: Strong SDF-1/CXCL12 staining was observed in the infiltrating inflammatory cells in the perivascular, intravascular, and perineural areas in tissue samples from patients with Degos disease. No staining was observed in samples from patients with antiphospholipid syndrome or cryoglobulinemia or from healthy control subjects. Limitations: The number of cases available for evaluation was small. The findings were based primarily on the immunohistochemical results and were not confirmed using other techniques. Conclusions: The intense staining of SDF-1/CXCL12 in lesions attributed to Degos disease, demonstrated for the first time to our knowledge in this study, suggests SDF-1/CXCL12 involvement in the pathogenesis of the disease. (J Am Acad Dermatol 2013;68:138-43.)
  • J. Meephansan, M. Komine, H. Tsuda, M. Ohtsuki
    Clinical and Experimental Dermatology 37 (8) 889 - 896 0307-6938 2012/12 [Refereed][Not invited]
     
    Background. Vitamin D3 is a potent regulator of cell growth, differentiation and death, tumour invasion, and angiogenesis. Production of matrix metalloproteinase (MMP)-9 and MMP-13 by tumour cells may promote tumour growth, invasion and metastasis. Aim. To investigate whether calcipotriol could suppress the expression of MMP-9 and MMP-13 in a human squamous cell carcinoma (SCC) cell line (DJM cells), and to examine the mechanism of modulation of MMP-9 and MMP-13 by calcipotriol in DJM cells treated with tumour necrosis factor (TNF)-α. Methods. Protein and mRNA levels of MMP-9 and MMP-13 were examined by ELISA and real-time PCR, respectively. Activation of signalling cascades was assessed using several inhibitors of signalling molecules and western blot analysis. Results. Production of MMP-9 and MMP-13 markedly increased when the cells were treated with TNF-α. Calcipotriol suppressed the production of MMP-9 and MMP-13 mRNA and proteins significantly, in a dose-dependent manner. Induction of MMP-9 by TNF-α was suppressed by an extracellular signal-regulated kinase (ERK) inhibitor but not by a p38 inhibitor, whereas induction of MMP-13 was inhibited by a p38 inhibitor but not by an ERK inhibitor. Calcipotriol inhibited the phosphorylation of both ERK and p38, as shown by western blotting. Conclusion. Calcipotriol reduces MMP-9 and MMP-13 production through inhibiting the phosphorylation of ERK and p38, respectively. © 2012 British Association of Dermatologists.
  • Jitlada Meephansan, Hidetoshi Tsuda, Mayumi Komine, Shin-ichi Tominaga, Mamitaro Ohtsuki
    JOURNAL OF INVESTIGATIVE DERMATOLOGY 11 132 (11) 2593 - 2600 0022-202X 2012/11 [Refereed][Not invited]
     
    IL-33, a member of the IL-1 family, is implicated in type 2 T helper cell immune reactions and acts as an "alarmin" to induce activation of dendritic cells in response to external stimuli. We investigated the effect of inflammatory cytokines on IL-33 expression in normal human epidermal keratinocytes. IFN-gamma dose- and time-dependently induced IL-33 expression in protein and mRNA; this was dependent on extracellular signal-regulated kinase, p38, EGFR, and JAK phosphorylation. Combined IFN-gamma and tumor necrosis factor (TNF)-alpha treatment induced expression of a 20-kDa band corresponding to mature IL-33, which was abolished by the addition of a calpain inhibitor. The addition of the inhibitor to IFN-gamma and TNF-alpha-stimulated cells also induced strong expression of a 25-kDa band. Small interference (si) RNA for IL-33 abolished expression of the smaller bands and the 30-kDa IL-33 band, suggesting that these IL-33 forms were IL-33 transcription products. Recombinant IL-33 added in the medium induced IL-8 production, and RNA knockdown by siRNA enhanced IL-8 expression, suggesting its dual role as a cytokine and a nuclear factor. These results indicate that IL-33 has a role in inflammatory skin diseases, in which IFN-gamma and TNF-alpha are present in high levels.
  • Hidetoshi Tsuda, Mayumi Komine, Masaru Karakawa, Takafumi Etoh, Shin-ichi Tominaga, Mamitaro Ohtsuki
    JOURNAL OF INVESTIGATIVE DERMATOLOGY 132 (11) 2661 - 2664 0022-202X 2012/11 [Refereed][Not invited]
  • Satomi Hosoda, Mayumi Komine, Masaru Karakawa, Hidetoshi Tsuda, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 39 (10) 855 - 857 0385-2407 2012/10 [Refereed][Not invited]
  • Yasushi Matsuyama, Hitoaki Okazaki, Motoaki Hoshino, Sachiko Onishi, Yasuyuki Kamata, Katsuya Nagatani, Takao Nagashima, Masahiro Iwamoto, Taku Yoshio, Hiromi Ohto-Ozaki, Hiroyuki Tamemoto, Mayumi Komine, Hitoshi Sekiya, Shin-ichi Tominaga, Seiji Minota
    RHEUMATOLOGY INTERNATIONAL 5 32 (5) 1397 - 1401 0172-8172 2012/05 [Refereed][Not invited]
     
    Although TNF inhibitors have dramatically improved the outcome of patients with rheumatoid arthritis, 30-40% of patients do not respond well to them and treatment needs to be changed. In an effort to discriminate good and poor responders, we focused on the change in serum and synovial fluid levels of interleukin (IL-) 33 before and after treatment with TNF inhibitors. They were also measured in synovial fluids from 17 TNF inhibitor-na < ve patients, and fibroblast-like synoviocytes (FLS) in-culture from 6 patients and correlated with various pro-inflammatory cytokines. Serum levels of IL-33 at 6 months after treatment decreased significantly in responders, while they did not change in non-responders. Synovial fluid levels of IL-33 in 6 patients under treatment with TNF inhibitors stayed high in 3 who were refractory and slightly elevated in 2 moderate responders, while they were undetectable in one patient under remission. Among inflammatory cytokines measured in 17 synovial fluids from TNF inhibitor-na < ve patients, levels of IL-33 showed a significant positive correlation only to those of IL-1 beta. IL-1 beta increased IL-33 expression markedly in FLS in vitro, compared to TNF-alpha. IL-1 beta might be inducing RA inflammation through producing pro-inflammatory IL-33 in TNF inhibitor-hypo-responders. Sustained elevation of serum and/or synovial levels of IL-33 may account for a poor response to TNF inhibitors, although how TNF inhibitors affect the level of IL-33 remains to be elucidated.
  • Yuka Takatsuka, Mayumi Komine, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 39 (5) 474 - 476 0385-2407 2012/05 [Refereed][Not invited]
  • Koji Wakatabi, Mayumi Komine, Jitlada Meephansan, Yasushi Matsuyama, Hidetoshi Tsuda, Shin-ichi Tominaga, Mamitaro Ohtsuki
    EUROPEAN JOURNAL OF DERMATOLOGY 22 (3) 333 - 336 1167-1122 2012/05 [Refereed][Not invited]
     
    Soluble ST2 (sST2) is a soluble form of the transmembrane receptor for interleukin (IL)-33, ST2L, and is a member of the IL-1 receptor family. sST2 antagonizes IL-33-ST2L signaling by competing with ST2L as a decoy receptor for IL-33. We investigated the sST2 and IL-33 levels in the sera and bullous fluid of bullous pemphigoid patients and compared these with the corresponding levels in normal healthy controls. As controls, we used the bullous fluid of burn patients and that from suction blisters induced in normal healthy volunteers. The serum sST2 concentrations of bullous pemphigoid patients were higher than those of healthy controls. Serum sST2 levels correlated with the area of skin involvement and serum lactate dehydrogenase levels, suggesting that serum sST2 levels reflect disease severity. The sST2 concentrations in bullous fluid from bullous pemphigoid patients were higher than those from controls. The concentration of IL-33 ligand was below the detectable limits in all enzyme-linked immunosorbent assay samples. Thus, our study suggested that the serum sST2 level may be a useful marker of disease severity and that sST2 functions as a negative regulator in the pathophysiology of bullous pemphigoid.
  • 急速に増数し免疫組織化学的に診断に苦慮した多発性骨髄腫皮膚転移の1例
    唐川 大, 池田 雄一, 村田 哲, 小宮根 真弓, 大槻 マミ太郎, 河田 浩敏, 山本 千鶴
    日本皮膚科学会雑誌 (公社)日本皮膚科学会 122 (2) 409 - 409 0021-499X 2012/02
  • Jitlada Meephansan, Mayumi Komine, Hidetoshi Tsuda, Shin-ichi Tominaga, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGICAL SCIENCE 65 (1) 72 - 74 0923-1811 2012/01 [Refereed][Not invited]
  • Satomi Hosoda, Masayuki Suzuki, Mayumi Komine, Satoru Murata, Takashi Hashimoto, Mamitaro Ohtsuki
    ACTA DERMATO-VENEREOLOGICA 92 (2) 164 - 166 0001-5555 2012 [Refereed][Not invited]
  • Onda H, Komine M, Murata S, Ohtsuki M
    Dermatology online journal 12 17 11  2011/12 [Refereed][Not invited]
  • Masaru Karakawa, Mayumi Komine, Tomonori Takekoshi, Naoki Sakurai, Yosaku Minatani, Yayoi Tada, Hidehisa Saeki, Kunihiko Tamaki
    JOURNAL OF DERMATOLOGY 38 (7) 655 - 660 0385-2407 2011/07 [Refereed][Not invited]
     
    The remission period of psoriasis vulgaris following narrowband ultraviolet B (NB-UVB) light therapy with topical vitamin D(3) application was evaluated retrospectively to investigate the therapeutic efficacy. Fifty-two patients (60 cases) were treated with a 5-day/week protocol of NB-UVB light irradiation plus topical vitamin D ointment application for 1 month and followed up for at least 12 months. We considered re-exacerbation as the time when the patients needed treatment other than topical therapy. The remission period was defined as the duration from the end of treatment until re-exacerbation. Twenty-seven cases (56%) of psoriasis showed a remission period longer than 12 months. The patients with a past history of systemic therapy or phototherapy had a significantly shorter remission period than those without such a history. No statistically significant differences were observed in sex, age, period before treatment, Psoriasis Area and Severity Index score and total irradiation dose. A previous history of systemic therapy or phototherapy may mean that the disease is severe and sufficiently active to form multiple new lesions requiring these treatments. Our results suggest that the 5-day/week NB-UVB light protocol for 4 weeks is an effective and safe treatment for psoriasis vulgaris and can induce long-term remission.
  • Aya Tatsuta, Mayumi Komine, Yoshiko Taguchi, Hideto Yokokura, Yumiko Koike, Satoru Murata, Noriyoshi Fukushima, Mamitaro Ohtsuki
    JOURNAL OF DERMATOLOGY 38 (7) 730 - 732 0385-2407 2011/07 [Refereed][Not invited]
  • Yukiko Kikuchi, Yoshifumi Kashii, Yuji Gunji, Akira Morimoto, Aki Masuzawa, Yuka Takatsuka, Etsuko Fujita, Mayumi Komine, Mamitaro Ohtsuki, Daisuke Matsubara, Chie Kobayashi, Ayako Sakurai, Kentaro Yanase, Keisuke Kato, Kazutoshi Koike, Masahiro Tsuchida, Mariko Y. Momoi
    PEDIATRICS INTERNATIONAL 53 (3) 393 - 396 1328-8067 2011/06 [Refereed][Not invited]
  • Seiko Aochi, Kazuhide Tsuji, Masakiyo Sakaguchi, Namho Huh, Tatsuya Tsuda, Kiyofumi Yamanishi, Mayumi Komine, Keiji Iwatsuki
    JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY 64 (5) 879 - 887 0190-9622 2011/05 [Refereed][Not invited]
     
    Background: Serum levels of S100A8/A9 may correlate with disease activity in psoriasis. Objective: We sought to elucidate the association of serum levels of S100A8/A9 heterodimers with the clinical subtypes of psoriasis and the major cell source. Methods: Serum samples were collected from patients with psoriasis vulgaris (n = 30), psoriatic arthritis (PA) (n = 16),. pustular psoriasis (n = 24), and atopic dermatitis (n = 14) and from healthy control subjects (n = 21). Serum concentrations of S100A8/A9 were measured, and the expression levels were examined in psoriatic lesions. The messenger RNA levels were quantified in circulating monocytes and neutrophils. Results: Serum levels of S100A8/A9 were significantly increased in all subtypes of psoriasis as compared with healthy controls and atopic dermatitis. Among the psoriatic subtypes, PA and pustular psoriasis showed remarkably high concentrations of S100A8/A9 heterodimers. The higher serum levels were associated with the presence of articular symptoms, but not significantly correlated with body surface areas of psoriatic lesions. S100A8 was expressed by both keratinocytes and infiltrating mononuclear cells, whereas S100A9 was predominantly expressed by neutrophils. The expression levels of S100A8 and S100A9 messenger RNA in monocytes were increased by approximately 2.25- and 1.91-fold in PA, respectively, whereas no significant increase was observed in psoriasis vulgaris and pustular psoriasis. Limitations: Difficulty in acquisition of clinical and laboratory samples in untreated patients, and of a sufficient number of subjects, were limitations. Conclusions: Although serum levels of S100A8/A9 were increased in all types of psoriasis examined, patients with PA had higher levels of S100A8/A9, probably because of an activated monocyte/macrophage system. (J Am Acad Dermatol 2011;64:879-87.)
  • Seiki Fujimoto, Mayumi Komine, Masaru Karakawa, Hideya Uratsuji, Shinji Kagami, Yayoi Tada, Hidehisa Saeki, Mamitaro Ohtsuki, Kunihiko Tamaki
    CYTOKINE 54 (2) 191 - 199 1043-4666 2011/05 [Refereed][Not invited]
     
    Histamine is a biological amine that plays an important role in allergic responses. However, the involvement of histamine signaling in late allergic responses in the skin is poorly understood. Therefore, we attempted to investigate the involvement of histamine signaling in late allergic responses, especially in keratinocytes (KCs). HaCaT KCs and normal human KCs (NHKs) predominantly expressed histamine H1 receptor (Hi R) and H2 receptor (H2R). Histamine suppressed tumor necrosis factor alpha (TNF-alpha)- and interferon-gamma (IFN-gamma)-induced production of CC chemokine ligand 17(CCL17), a type 2 T-helper (Th2) chemokine, by HaCaT KCs. It suppressed the phosphorylation of p38 mitogen-activated protein (MAP) kinase, but not that of extracellular signal-regulated kinases (ERKs), and TNF-alpha- and IFN-gamma-induced nuclear factor kappa B (NF kappa B) activity. In contrast, histamine enhanced the production of CXC chemokine ligand 10 (CXCL10), a Th1 chemokine, by TNF-alpha- and IFN-gamma-stimulated HaCaT KCs and NHKs. TNF-alpha- and IFN-gamma-induced CXCL10 production was upregulated by suppression of p38 MAP kinase or NF-kappa B activity, which could explain histamine involvement. We concluded that histamine suppresses CCL17 production by KCs by suppressing p38 MAP kinase and NF-kappa B activity through H1R and may act as a negative-feedback signal for existing Th2-dominant inflammation by suppressing CCL17 and enhancing CXCL10 production. (C) 2011 Elsevier Ltd. All rights reserved.
  • 腹腔内転移発見の契機となった胃癌による腫瘍塞栓の1例
    唐川 大, 小宮根 真弓, Meephansan Jitlada, 藤田 悦子, 村田 哲, 大槻 マミ太郎, 森澤 宏行, 金丸 理人
    日本皮膚科学会雑誌 (公社)日本皮膚科学会 121 (6) 1121 - 1121 0021-499X 2011/05
  • 特異な臨床像を示した汗孔角化症の1例
    唐川 大, 小宮根 真弓, 大槻 マミ太郎
    角化症研究会記録集 角化症研究会事務局 25 98 - 101 2011/03
  • CTACK/CCL27の表皮角化細胞からの産生に対するIFNγの作用と乾癬局面における分布に関する検討
    唐川 大, 小宮根 真弓, Meephansan Jitlada, 津田 英利, 大槻 マミ太郎
    日本皮膚科学会雑誌 (公社)日本皮膚科学会 121 (3) 565 - 565 0021-499X 2011/03
  • 急速に増数し免疫組織化学的に診断に苦慮した多発性骨髄腫皮膚転移の1例
    唐川 大, 池田 雄一, 村田 哲, 小宮根 真弓, 大槻 マミ太郎, 河田 浩敏, 山本 千鶴
    日本皮膚科学会雑誌 (公社)日本皮膚科学会 121 (4) 740 - 740 0021-499X 2011/03
  • Ken Natsuga, Wataru Nishie, Satoru Shinkuma, Hideki Nakamura, Yoichiro Matsushima, Aya Tatsuta, Mayumi Kornine, Hiroshi Shimizu
    JOURNAL OF DERMATOLOGICAL SCIENCE 61 (1) 38 - 44 0923-1811 2011/01 [Refereed][Not invited]
     
    Background: Kindler syndrome (KS) is a rare, inherited skin disease characterized by blister formation and generalized poikiloderma. Mutations in KIND1, which encodes kindlin-1, are responsible for KS. c.1089del/1089+1del is a recurrent splice-site deletion mutation in KS patients. Objective: To elucidate the effects of c.1089del/1089+1del at the mRNA and protein level. Methods: Two KS patients with c.1089del/1089+1del were included in this study. Immunofluorescence analysis of KS skin samples using antibodies against the dermo-epidermal junction proteins was performed. Exon-trapping experiments were performed to isolate the mRNA sequences transcribed from genomic DNA harbouring c.1089del/1089+1del. beta 1 integrin activation in HeLa cells transfected with truncated KIND1 cDNA was analyzed. Results: Immunofluorescence study showed positive expression of kindlin-1 in KS skin with c.1089del/1089+1del mutation. We identified the exon-8-skipped in-frame transcript as the main product among multiple splicing variants derived from that mutation. HeLa cells transfected with KIND1 cDNA without exon 8 showed impaired beta 1 integrin activation. Exon-8-coding amino acids are located in the FERM F2 domain, which is conserved among species, and the unstructured region between F2 and the pleckstrin homology domain. Conclusion: This study suggests that exon-8-skipped truncated kindlin-1 is functionally defective and does not compensate for the defects of KS, even though kindlin-1 expression in skin is positive. (c) 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
  • Masaru Karakawa, Mayumi Komine, Kunihiko Tamaki, Mamitaro Ohtsuki
    ARCHIVES OF DERMATOLOGICAL RESEARCH 10 302 (10) 763 - 767 0340-3696 2010/12 [Refereed][Not invited]
     
    Cutaneous T cell-attracting chemokine (CTACK)/CCL27 and macrophage inflammatory protein (MIP)-3 alpha/CCL20 are the major inflammatory chemokines involved in skin inflammation. The present study showed that roxithromycin (RXM) suppressed the TNF alpha-induced production of CCL27 and CCL20 in HaCaT keratinocytes and normal human keratinocytes (NHKs) in a dose-dependent manner. The production of CCL20 induced by TNF alpha was suppressed by the addition of inhibitors of nuclear factor kappa B (NF kappa B). RXM suppressed NF kappa B activity induced by TNF alpha, RXM, by regulating CCL27 and CCL20, may contribute to the modulation of inflammation.
  • 陰茎縫線嚢腫の1例
    西山 有希子, 小宮根 真弓, 土肥 凌, 金子 健彦
    皮膚科の臨床 金原出版(株) 52 (12) 1930 - 1931 0018-1404 2010/11 [Refereed][Not invited]
     
    31歳男。陰茎腹側の縫線上に径5mmの表面平滑、白色調で弾性軟の結節を認めた。病理組織学的所見で真皮内に単房性嚢腫を認め、その壁は1〜数層、主として立方ないし円柱上皮で構成されていた。免疫組織化学的所見でCarcinoembryonic antigenは嚢腫壁の内腔側に顆粒状の陽性像を示し、S-100、アクチンはともに陰性で、種々の抗サイトケラチン抗体を用いた免疫染色ではK8、18は嚢腫壁の最内側に陽性、K7、19は壁の全層にわたって陽性像を示した。局所麻酔下に切除縫縮し、術後20ヵ月の現在、再発はない。
  • Tomonori Takekoshi, Yayoi Tada, Takahiro Watanabe, Makoto Sugaya, Toshihiko Hoashi, Mayumi Komine, Tomohiko Kawashima, Teruo Shimizu, Carren Sy Hau, Akihiko Asahina, Takehiko Yokomizo, Shinichi Sato, Kunihiko Tamaki
    JOURNAL OF BIOLOGICAL CHEMISTRY 285 (41) 31876 - 31884 0021-9258 2010/10 [Refereed][Not invited]
     
    Dendritic cells (DCs) are a group of professional antigen-presenting cells, and many genes are known to be associated with their maturation. We compared the transcriptional profiles of immature and mature mouse Langerhans cells using the suppressive, subtractive hybridization method and identified a novel gene of unknown function, termed herein transmembrane protein 123 (Tmem123), of which mRNA expression was enhanced in mature but not in immature Langerhans cells. Its expression was also enhanced in other mature DCs such as bone marrow-derived DCs (BMDCs) and splenic DCs. Interestingly, CD40 expression was up-regulated on mature BMDCs cultured with colchicine concurrently with the enhanced expression of Tmem123 compared with that of fresh BMDCs. Furthermore, the expression of CD40 was enhanced on Tmem123-transfected DC2.4 cells, a mouse BMDC-derived cell line, compared with that on mock-transfected DC2.4 cells. This enhancement of CD40 expression did not occur after deletion of lysosome/endosome targeting YXX phi motifs (where X is any amino acid and phi is a bulky hydrophobic amino acid) in the Tmem123 cytoplasmic tail. By stimulation with anti-CD40 monoclonal antibody, these transfectants secreted an increased amount of IL-12/23 p40 compared with mock-transfected DC2.4 cells. Thus, our study demonstrates that Tmem123 may be used as a new maturation marker in DCs and that this molecule may be closely associated with the cell surface expression of CD40.
  • Akiko Nakajima, Taizo Matsuki, Mayumi Komine, Akihiko Asahina, Reiko Horai, Susumu Nakae, Harumichi Ishigame, Shigeru Kakuta, Shinobu Saijo, Yoichiro Iwakura
    JOURNAL OF IMMUNOLOGY 185 (3) 1887 - 1893 0022-1767 2010/08 [Refereed][Not invited]
     
    IL-1 is a proinflammatory cytokine consisting of two molecular species, IL-1 alpha and IL-1 beta, and IL-1R antagonist ( gene: Il1rn) is the endogenous suppressor. Il1rn(-/-) mice spontaneously develop autoimmune diseases, such as arthritis and aortitis, and a dermatitis that histologically resembles human psoriasis. The pathogenic mechanisms underlying this dermatitis, however, remain to be elucidated. In this study, we demonstrated that the production of inflammatory cytokines and chemokines was enhanced at the site of inflammation. The development of dermatitis was completely suppressed in Tnfsf1a(-/-) but not in Il6(-/-) mice, similar to that observed in arthritis and aortitis. However, IL-17 deficiency did not affect the development of dermatitis at all, in clear contrast to that of arthritis and aortitis. Different from arthritis and aortitis, adoptive transfer of Il1rn(-/-) T cells did not induce dermatitis in the recipient SCID mice and skin lesions developed in Il1rn(-/-) SCID mice, indicating that T cells are not involved in the development of skin lesions. In support for this, bone marrow cell transplantation experiments showed that TNF produced by skin residential cells, but not bone marrow cell-derived cells, was important for the development of dermatitis. Furthermore, we showed that IL-1 directly enhanced TNF and chemokine expression in keratinocytes. These observations suggest that excess IL-1 signaling directly activates keratinocytes to produce TNF and chemokines, resulting in the development of psoriasis-like skin lesions without the involvement of autoimmunity in Il1rn(-/-) mice. The Journal of Immunology, 2010, 185: 1887-1893.
  • 西山 有希子, 水嶋 淳一, 永井 國雄, 小宮根 真弓, 金子 健彦
    臨床皮膚科 (株)医学書院 64 (2) 141 - 144 0021-4973 2010/02 [Refereed][Not invited]
     
    72歳,女性.15年前から徐々に増大する前頭部の皮下結節を主訴に当科を受診した.初診時,35×35×20mmの皮表はやや紅色調で外方に突出した弾性硬の腫瘤を認めた.病理組織学的には,外毛根鞘性角化を呈し,線維性被膜に囲まれた多房性の嚢腫様構造を認め,増殖性外毛根鞘性腫瘍と診断した.PCNAおよびKi-67染色では,両者とも腫瘍胞巣の最も外側で陽性細胞を認めた.抗サイトケラチン抗体染色でK8,K19はともに腫瘍壁に陰性であったが,K16,K17は外毛根鞘性角化を呈する部分に陽性であった.これらより腫瘍の増殖活性と角化傾向の特徴を示唆する所見と考えた.(著者抄録)
  • Sayaka Shibata, Hidehisa Saeki, Yayoi Tada, Masaru Karakawa, Mayumi Komine, Kunihiko Tamaki
    JOURNAL OF DERMATOLOGICAL SCIENCE 55 (1) 62 - 63 0923-1811 2009/07 [Refereed][Not invited]
  • Mayumi Komine
    JOURNAL OF PHARMACOLOGICAL SCIENCES 110 (3) 260 - 264 1347-8613 2009/07 [Refereed][Not invited]
     
    Atopic dermatitis frequently accompanies bronchial asthma, allergic rhinitis, and allergic conjunctivitis, the pathogenesis of which has frequently focused on the immunological aspects; however, skin eruption in atopic dermatitis occurs mainly in the epidermis, whose barrier function and cytokine expression have been revealed to be abnormal. In addition, the epidermis contains Langerhans cells, antigen-presenting cells, which could be considered the sentinel of the immune system. Some atopic dermatitis patients have been revealed to have mutations or SNPs (single-nucleotide polymorphisms) in the filaggrin gene, which affect the epidermal barrier function. Proteinases in the epidermis are of importance in maintaining the epidermal barrier, abnormalities of which have been reported in atopic dermatitis. Abnormalities of various cytokines and chemokines produced by keratinocytes have also been reported. Thymic stromal lymphopoietin (TSLP) produced by keratinocytes has recently been a focus in atopic dermatitis. Adrenergic/cholinergic responses in the epidermis could also influence the pathogenesis of atopic dermatitis. Considering epidermal keratinocytes as a trigger of immune abnormalities, not only as a peripheral effector, would be important to further disclose the pathogenesis of this enigmatic disorder.
  • Ken Futaki, Mayumi Komine, Satomi Hosoda, Miho Hirashima, Hideto Yokokura, Tomoko Yamada, Satoru Murata, Yasushi Matsuyama, Takao Nagashima, Hiroyuki Nara, Seiji Minota, Mamitaro Ohtsuki
    EUROPEAN JOURNAL OF DERMATOLOGY 19 (3) 266 - 267 1167-1122 2009/05 [Refereed][Not invited]
  • Yuka Takatsuka, Mayumi Komine, Etsuko Fujita, Yumiko Koike, Tomoko Yamada, Satoru Murata, Mamitaro Ohtsuki
    INTERNATIONAL JOURNAL OF DERMATOLOGY 48 (3) 324 - 326 0011-9059 2009/03 [Refereed][Not invited]
  • Sayaka Shibata, Yayoi Tada, Mayumi Komine, Naoko Hattori, Satsuki Osame, Naoko Kanda, Shinichi Watanabe, Hidehisa Saeki, Kunihiko Tamaki
    JOURNAL OF DERMATOLOGICAL SCIENCE 53 (1) 34 - 39 0923-1811 2009/01 [Refereed][Not invited]
     
    Background: Anti-cyclic citrullinated peptide antibodies (anti-CCP) are reported to be found in 5-13% of patients with psoriatic arthritis (PsA). However, whether anti-CCP-positive PsA patients and rheumatoid arthritis (RA) patients have a similar pathophysiological background still remains uncertain. Objective: To determine the prevalence of anti-CCP antibodies in patients with PsA and characterize these anti-CCP-positive patients of PsA. Methods: We measured the serum levels of the anti-CCP antibodies in patients with PsA (n = 16), psoriasis (n = 15), RA (n = 9) and healthy controls (n = 11). Serum levels of rheumatoid factor (RF), matrix metalloproteinase-3 (MMP-3), cartilage oligomeric matrix protein (COMP), interleukin (IL)-23p19 and IL-12p40 were also measured in all the samples. Results: Two of the 16 PsA patients (13%) were positive for anti-CCP antibodies with high titers of RF. However, the serum IL-23p19 levels were two orders of magnitude higher in the anti-CCP-positive PsA patients as compared with those in the RA patients and anti-CCP-negative PsA patients. No significant elevation of the serum levels of MMP-3, COMP and IL-12p40 was found in these patients. Conclusion: Thirteen percent of the PsA patients were positive for anti-CCP. These patients do not fulfill the American College of Rheumatology (ACR) classification criteria for RA so far. Furthermore, they showed the typical clinical features of PsA rather than those of RA. Although anti-CCP-positive PsA patients may possibly be have a risk of developing RA, we propose that these patients be classified, for the moment, into a independent subtype of PsA, as a different entity from RA. (c) 2008 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
  • K. Kikuchi, K. Wakamatsu, Y. Tada, M. Komine, S. Ito, K. Tamaki
    Clinical and Experimental Dermatology 33 (6) 750 - 753 0307-6938 2008/11 [Refereed][Not invited]
     
    Background. Ultraviolet (UV) B radiation from sunlight can result in tanning or burning of the skin. Narrowband UVB (NB-UVB), a relatively new light source that is not yet widely available, is effective for treating generalized psoriasis without the use of psoralens. Aims. The melanin-related metabolite 5-S-cysteinyldopa (5-S-CD), which reflects pheomelanin production, has been used as a biological marker of melanoma progression, but there are no studies available on therapeutic UVB effects on serum 5-S-CD of human subjects. In the present study, we measured the time course of changes in serum levels of 5-S-CD in patients with psoriasis undergoing NB-UVB phototherapy. Methods. In total, 11 Japanese patients with generalized psoriasis vulgaris received NB-UVB treatment five times per week, at an initial dose of 0.1 J/cm2. The dose was increased by 10-20% per treatment for > 20 treatments. Serum samples were taken before and 3, 7, 10, 14 and 28 days after phototherapy. Results. After 4 weeks of NB-UVB treatment, 9 of 11 patients were in remission, confirming the effectiveness of NB-UVB for treating Japanese patients with psoriasis. Two patients withdrew before day 28 because of other complications. Mean level of 5-S-CD in serum was significantly increased on day 7, 10 14 and 28 compared with the level before phototherapy and it peaked on day 10. Conclusions. Serum 5-S-CD levels were significantly increased by therapeutic UVB exposure. Sustained levels of 5-S-CD in serum appear to reflect the degree of skin injury during NB-UVB phototherapy. © 2008 The Author(s).
  • Yuri Masui, Mayumi Komine, Takafumi Kadono, Nobuko Ishiura, Takeo Maekawa, Hironobu Ihn, Kanako Kikuchi, Kunihiko Tamaki
    Journal of cutaneous pathology 35 Suppl 1 55 - 8 0303-6987 2008/10 [Refereed][Not invited]
     
    A 46-year-old man had a cystic mass on the right side of his scalp. Histological examination revealed a cystic dermal nodule composed of relatively circumscribed lobules of proliferating squamous epithelium, with atypical mitoses and dyskeratotic cells of invasive structure, which was diagnosed as proliferating tricholemmal cystic carcinoma (PTCC). Most of the cyst was composed of thick layers of highly proliferating, atypical, dedifferentiated epithelium (dedifferentiated part), which was attached to a highly proliferative but mildly differentiated part. A completely differentiated, tricholemmal cyst (TC)-like part was also attached to the main cyst, which supports the idea of PTCC beginning in a pre-existing TC. The dedifferentiated and mildly differentiated parts exhibited a high frequency of proliferating cell nuclear antigen (PCNA)-positive cells both in the basal and the suprabasal layers, while PCNA staining was almost negative in the TC-like part. Expression of cytokeratin (CK)10 and CK16 suggested disturbed epidermal differentiation in dedifferentiated part, while TC-like part showed well-differentiated trichilemmal epithelium and the mildly differentiated part was in the middle of these two.
  • Seiki Fujimoto, Hideya Uratsuji, Hidehisa Saeki, Shinji Kagami, Yuichiro Tsunemi, Mayumi Komine, Kunihiko Tamaki
    CYTOKINE 44 (1) 172 - 178 1043-4666 2008/10 [Refereed][Not invited]
     
    CC chemokine ligand (CCL)17 and CCL27 produced by epidermal keratinocytes (KCs) recruit CC chemokine receptor (CCR)4 and CCR10 expressing T cells into the skin, respectively, resulting in enhanced skin inflammation. However, CCR4/CCL17 and CCR10/CCL27 interactions in epidermal KCs have not been investigated. The purpose of this study was to evaluate the role of the CCR4/CCL17 and CCR10/CCL27 loops in cutaneous immune reaction. Normal human KCs (NHKS) and HaCaT KCs expressed both CCR4 and CCR10 at mRNA and Protein levels. CCR4 ligand CCL17 but not CCR10 ligand CCL27 induced production of IL-12 p40, granulocyte/monocyte colony-stimulating factor (GM-CSF) and nerve growth factor (NGF) by KCs. Both CCL17 and CCL27 induced migration of KCs in Boyden chamber assay and wound scratch assay. This study revealed that CCR4 and CCR10 are expressed on epidermal KCs and that both are functional in terms of skin cytokine production and/or migration to their ligand CCL17 and CCL27, respectively. Thus this study provided new insight into chemokine/chemokine receptors of KCs. (C) 2008 Elsevier Ltd. All rights reserved
  • Hidehisa Saeki, Aya Watanabe, Yayoi Tada, Takashi Kakinuma, Mayumi Komine, Hironobu Ihn, Akihiko Asahina, Takafumi Etoh, Sachiko Kitanaka, Utako Sato, Hirotsugu Kano, Takashi Igarashi, Kunihiko Tamaki
    The Journal of dermatology 35 (9) 601 - 3 0385-2407 2008/09 [Refereed][Not invited]
  • Taisuke Kondo, Tamio Suzuki, Yoshihiko Mitsuhashi, Shiro Ito, Michihiro Kono, Mayumi Komine, Hirotaka Akita, Yasushi Tomita
    JOURNAL OF DERMATOLOGY 35 (7) 395 - 406 0385-2407 2008/07 [Refereed][Not invited]
     
    Dyschromatosis symmetrica hereditaria (DSH), is a pigmentary genodermatosis of autosomal dominant inheritance. Since we clarified that the disease is caused by a mutation of the adenosine deaminase acting on the RNA 1 gene (ADAR1) in 2003, the molecular pathogenesis of a peculiar clinical feature of the disease has been expected to be clarified. We examined five familial cases and one sporadic case of Japanese families with DSH. The mutation analyses were done with single-strand conformation polymorphism/heteroduplex (SSCP/HD) analysis and direct sequencing of ADAR1. The DNA analysis of each patient revealed one missense mutation (p.F1091S), two nonsense mutations (p.C893X, p.S581X) and three frame-shift mutations (p.E498fsX517, p.F1091fsX1092, p.L855fsX856). Visual and electron microscopic findings showed abundant melanin pigment deposited all over the basal layer, and enlarged melanocytes with long dendrites located in the pigmented lesions with small or immature melanosomes scattered sparsely in the cytoplasm, but in the adjacent keratinocytes many small melanosomes were singly dispersed or aggregated. The hypopigmented areas showed little melanin deposition and reduced numbers of melanocytes in which much degenerative cytoplasmic vacuole formation could be observed by electron microscopy. Herein, we report six cases of DSH with six novel mutations. The variety of their clinical phenotypes even in the pedigree may suggest the presence of factors other than the ADAR1 gene influencing the extent of the clinical skin lesion. Microscopic findings suggest that the clinical appearance must have developed directly by melanocyte variations mainly induced by the ADAR1 gene mutations.
  • Shinji Kagami, Hidehisa Saeki, Yuichiro Tsunemi, Koichiro Nakamura, Yoshihiro Kuwano, Mayumi Komine, Takashi Nakayama, Osamu Yoshie, Kunihiko Tamaki
    EUROPEAN JOURNAL OF IMMUNOLOGY 38 (3) 647 - 657 0014-2980 2008/03 [Refereed][Not invited]
     
    CCL27 is one of the CC chemokines produced by epidermal keratinocytes and is suggested to be involved in the pathogenesis of inflammatory skin diseases. To clarify the contribution of CCL27 in skin inflammation, we created transgenic C57BL/6 mice that constitutively produce CCL27 in epidermal keratinocytes. These mice had high serum CCL27 levels and did not show any phenotypical change. Thus we stimulated these mice with various reagents by single and repeated application. Interestingly, only contact hypersensitivity to repeated application with fluorescein isothiocyanate was significantly enhanced in transgenic mice compared to non-transgenic mice. Under this condition, the numbers of inflammatory cells, CCR10-positive cells, CCR4-positive cells and cutaneous lymphocyte-associated antigen-positive cells were increased, and IL-4 mRNA expression was higher in the lesional skin of transgenic mice. Increased number of mast cells and higher serum IgE levels, which were similar to atopic dermatitis, were also observed. These results indicated that CCL27 modified inflammation by attracting CCR10-positive and CCR4-positive cells into the lesional skin, and may participate in the pathogenesis of Th2-shifted skin diseases such as atopic dermatitis.
  • Yoshihiro Kuwano, Manabu Fujimoto, Rei Watanabe, Nobuko Ishiura, Hiroko Nakashima, Mayumi Komine, Tatsuo S. Hamazaki, Kunihiko Tamaki, Hitoshi Okochi
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 361 (1) 224 - 229 0006-291X 2007/09 [Refereed][Not invited]
     
    The control of the stem cell compartment in epidermis is closely linked to the regulation of keratinocyte proliferation and differentiation. beta 1 integrins are expressed 2-fold higher by stem cells than transit-amplifying cells. Signaling from these beta 1 integrins is critical for the regulation of the epidermal stem cell compartment. To clarify the functional relevance of this differential expression of beta 1 integrins, we established HaCaT cells with high beta 1integrin expression by repeated flow cytometric sorting of this population from the parental cell line. In these obtained cells expressing beta 1 integrins by 5-fold, MAPK activation was markedly increased. Regarding the upstream of MAPK, Gab I phosphorylation was also higher with high beta 1 integrin expression, while She phosphorylation was not altered. In addition, enhanced phosphatidylinositol 3-kinase activation was also observed. These observations suggest that Gab1 and phosphatidylinositol 3-kinase play pivotal roles in the beta 1 integrin-mediated regulation of the epidermal stem cell compartment. (C) 2007 Elsevier Inc. All rights reserved.
  • Mayumi Komine, Masaru Karakawa, Tomonori Takekoshi, Naoki Sakurai, Yosaku Minatani, Hiroshi Mitsui, Yayoi Tada, Hidehisa Saeki, Akihiko Asahina, Kunihiko Tamaki
    JOURNAL OF INVESTIGATIVE DERMATOLOGY 127 (8) 1915 - 1922 0022-202X 2007/08 [Refereed][Not invited]
     
    Early inflammatory changes in psoriatic plaques were investigated immunohistochemically by studying the normal-appearing skin adjacent to the plaques (perilesional skin), lesional skin, and distant uninvolved skin from psoriasis patients. Perilesional epidermis contained numerous CD1a-positive Langerhans cells, some of which expressed HLA-DR, CD83, CD80, and CD86, at the same time expressing Langerin. There were also numerous CD83-positive, CD11c-positive, Langerin-negative clendritic cells (DCs) in the epidermal-dermal junction of perilesional skin. CD3-positive T lymphocytes were sparse in the perilesional skin. Perilesional epidermis expressed keratin K6 and K16, inflammatory keratins, and C/EBP beta, a transcription factor related to inflammatory cytokines. Our results demonstrated the abundant distribution of activated DCs in the perilesional skin of psoriatic plaques, where early inflammatory changes occur in the epidermal keratinocytes, which suggests their involvement in the provocation of epidermal inflammation in the perilesional epidermis and further pathogenic roles in the formation of psoriatic plaques.
  • Hideki Fujita, Akihiko Asahina, Mayumi Komine, Kunihiko Tamaki
    JOURNAL OF DERMATOLOGY 34 (6) 403 - 406 0385-2407 2007/06 [Refereed][Not invited]
  • Hidehisa Saeki, Shusaku Hosono, Yuichiro Tsunemi, Kiyo Sasaki, Takafumi Kadono, Hironobu Ihn, Mayumi Komine, Akihiko Asahina, Kanako Kikuchi, Kunihiko Tamaki
    The Journal of dermatology 34 (5) 356 - 9 0385-2407 2007/05 [Refereed][Not invited]
  • Hideki Fujita, Akihiko Asahina, Mayumi Komine, Kunihiko Tamaki
    CELLULAR IMMUNOLOGY 245 (2) 70 - 79 0008-8749 2007/02 [Refereed][Not invited]
     
    The action of vitamin D-3 on Langerhans cells (LCs) is not well understood. Using highly purified murine LCs (> 95%), we investigated the direct action of 1 alpha,25-dihydroxyvitamin D-3 (1,25(OH)(3)D-3) on their functions. 1,25(OH)(2)D-3 inhibited the expression of cell surface molecules including I-A(d), CD40, CD80, and CD86, leading to impaired ability of LCs to stimulate allogenic T cells in the mixed leukocyte reaction. Furthermore, this reagent inhibited chemotaxis of LCs to CCL21 and their survival. Interestingly, 1,25(OH)(2)D-3 reduced the IL-10 production by LCs, whereas the production of IL-6 and IL-12p40 upon activation by CD40 ligation was enhanced. With regard to inflammatory cytokines and chemokines, 1,25(OH)(2)D-3 upregulated the production of IL-1 beta, CCL3, CCL4, and CCL5. The production of Th2-type chemokines, represented by CL17 and CCL22, was inhibited, whereas IFN-gamma-triggered production of Th1-type chemokines, represented by CXCL9, CXCL10, and CXCL11, was augmented. These data indicate that the mode of regulation of cytokine and chemokine production in association with 1,25(OH)(2)D-3 treatment seems to be another characteristic discriminating LCs from classical myeloid dendritic cells. (c) 2007 Elsevier Inc. All rights reserved.
  • Yoshihiro Kuwano, Rei Watanabe, Manabu Fujimoto, Mayumi Komine, Akihiko Asahina, Norihisa Tsukada, Kunihiko Tamaki
    INTERNATIONAL JOURNAL OF DERMATOLOGY 45 (10) 1265 - 1267 0011-9059 2006/10 [Refereed][Not invited]
  • Hidehisa Saeki, Kensuke Nakamura, Yuichiro Tsunemi, Mayumi Komine, Kunihiko Tamaki
    JOURNAL OF DERMATOLOGY 10 33 (10) 692 - 695 0385-2407 2006/10 [Refereed][Not invited]
     
    We describe a 19-year-old Japanese male with Kobner-type epidermolysis bullosa simplex (EBS-KB) with a novel keratin gene mutation. The patient developed blisters on the feet, palms, elbows and knees soon after birth. His father is similarly affected with blistering, but his mother and younger brother are not affected. Histological examination revealed that the primary separation in the blister occurred within the basal cell layer. Sequence analysis demonstrated an A-to-T transition at the second position of codon 158 in the keratin 5 (K5) gene. The amino acid at codon 158 was deduced to have changed from asparagine to valine. We identified a novel mutation (Asp158Val) in the H1 domain of the K5 gene in this Japanese patient with EBS-KB. This is the first gene mutation report of EBS-KB in the H1 domain of the K5 gene.
  • Kiyo Shimazu, Yuichiro Tsunemi, Naoko Hattori, Hidehisa Saeki, Mayumi Komine, Makoto Adachi, Kunihiko Tamaki
    INTERNATIONAL JOURNAL OF DERMATOLOGY 45 (9) 1128 - 1130 0011-9059 2006/09 [Refereed][Not invited]
  • Yuichiro Tsunemi, Hidehisa Saeki, Koichiro Nakamura, Daisuke Nagakubo, Takashi Nakayama, Osamu Yoshie, Shinji Kagami, Kiyo Shimazu, Takafumi Kadono, Makoto Sugaya, Mayumi Komine, Koji Matsushima, Kunihiko Tamaki
    EUROPEAN JOURNAL OF IMMUNOLOGY 36 (8) 2116 - 2127 0014-2980 2006/08 [Refereed][Not invited]
     
    CC chemokine ligand (CCL)17 is implicated in the pathogenesis of atopic dermatitis (AD). To study the effect of CCL17 produced by keratinocytes (KC) during inflammation, we created transgenic (Tg) mice in which CCL17 is overexpressed in KC. Th2-type contact hypersensitivity (CHS) was enhanced and Th1-type CHS was suppressed in these mice. Increased numbers of CC chemokine receptor (CCR)4(+) cells and mast cells infiltrated in Tg mice. Levels of IL-4 mRNA were higher and those of IFN-gamma mRNA were lower in both acute and chronic CHS. Higher levels of serum IgE were observed after CHS. Numbers of CCR4(+) cells among PBMC were increased in Tg mice challenged acutely on the trunk. Chronic irritation with croton oil induced dermatitis and an elevation of serum IgE levels. Tg mice showed enhanced ear swelling after tape stripping. CCL17 was thought to modify the inflammation caused by sensitizing reagents as well as irritant reagents by attracting CCR4(+) cells into the lesional skin and creating a Th2-dominant condition. AD-like conditions such as increased number of mast cells and elevated levels of serum IgE were observed. Thus, CCL17 may participate in the pathogenesis of skin diseases such as AD by regulating both allergic and irritant inflammation.
  • Hiroko Nakashima, Mayumi Komine, Kiyo Sasaki, Hiroshi Mitsui, Manabu Fujimoto, Hironobu Ihn, Akihiko Asahina, Kanako Kikuchi, Kunihiko Tamaki
    The Journal of dermatology 33 (8) 557 - 62 0385-2407 2006/08 [Refereed][Not invited]
     
    Necrolytic migratory erythema (NME) is an uncommon inflammatory dermatosis with a distinctive clinical and histological appearance. It shows irregular erythema, bullae, erosion, crusts and pigmentation. While it is typically associated with glucagonoma, some cases of NME without glucagonoma have been reported. Herein, we report a case of necrolytic migratory erythema associated with malabsorption 30 years after ileocolectomy. She presented erosive erythema with scale or partly flaccid bullae on her intergluteal cleft, buttock and extremities. Her laboratory data revealed essential amino acid deficiency and a slightly decreased serum zinc level, while her plasma glucagon level was low. With diagnosis of non-glucagonoma-associated NME with malabsorption due to short-bowel syndrome, she was treated and improved by i.v. amino acid supplement. Histological findings of NME include necrotic changes of keratinocytes in the upper epidermis, proliferation of those in the lower epidermis and inflammatory cell infiltration of upper dermis. We also examined the expression pattern of epidermal keratins (K6, K10) and Ki-67, one of the markers of proliferative activity, to assess the proliferation and differentiation of keratinocytes in a NME lesion by immunostaining. The findings with these immunostainings support the characteristics of HE-staining, and suggest hyponutrition may induce changing differentiation/proliferation of keratinocytes.
  • Y. Tada, A. Asahina, T. Takekoshi, E. Kishimoto, H. Mitsui, H. Saeki, M. Komine, K. Tamaki
    British Journal of Dermatology 154 (6) 1180 - 1183 0007-0963 2006/06 [Refereed][Not invited]
     
    Background: Psoriasis is a T-helper (Th)1 cytokine-mediated chronic skin disease and interleukin (IL)-12 has been shown to play a major role in the development of Th1 responses. Objectives: To elucidate the role of IL-12 in the pathogenesis of psoriasis and to study the effect of ciclosporin A (CsA) on Th1 deviation of this disease. Patients/Methods: We investigated IL-12 production by stimulated monocytes from patients with psoriasis who were treated with or without CsA. Monocytes were stimulated with interferon-γ plus lipopolysaccharide (LPS) or Staphylococcus aureus Cowan strain I (SAC). The amount of IL-12 p70 produced by stimulated monocytes was evaluated by enzyme-linked immunosorbent assay. Results: Compared with those from normal controls, LPS- but not SAC-stimulated monocytes from patients with psoriasis produced significantly higher amounts of IL-12. Interestingly, LPS-stimulated monocytes from patients with psoriasis treated with CsA produced significantly decreased amounts of IL-12 compared with those patients not treated with CsA. Conclusions: Our results suggest that IL-12 production by monocytes may have a critical role in the pathogenesis of psoriasis, and that the therapeutic effect of CsA on psoriasis may be achieved by correcting the deviation of the Th1/Th2 balance. © 2006 British Association of Dermatologists.
  • S Yano, M Komine, M Fujimoto, H Okochi, K Tamaki
    EXPERIMENTAL DERMATOLOGY 15 (5) 356 - 361 0906-6705 2006/05 [Refereed][Not invited]
     
    Mechanical stretching represents an important part of the signaling in skin. We have previously demonstrated that mechanical stretching induced proliferative phenotypes in human keratinocytes, as shown in increased 5-bromo-2'-deoxyuridine (BrdU) incorporation, ERK1/2 activation, and keratin K6 induction. Here we have further investigated the antiapoptotic signals in human keratinocytes provoked by mechanical stretching in vitro. Keratinocytes were plated on flexible silicone supports to transmit mechanical stretching to keratinocytes, involving continuous stretching by +20%. Stretching of these cells for 15-30 min caused the phosphorylation and activation of Akt. Inhibition of mitogen and extracellular signal-regulated kinase (MEK1/2) with U0126 and phosphoinositide 3-OH kinase (PI 3-K) with Wortmannin attenuated Akt activation. The epidermal growth factor (EGF) receptor kinase inhibitor, AG1478, and calcium channel inhibitor, gadolinium (Gd3+), also inhibited Akt activation. In summary, our results demonstrate the activation of the Akt signaling pathway by mechanical stretching, generating not only proliferative but also antiapoptotic signals in human keratinocytes.
  • S Kagami, H Saeki, M Komine, T Kakinuma, K Nakamura, Y Tsunemi, K Sasaki, A Asahina, K Tamaki
    EXPERIMENTAL DERMATOLOGY 15 (2) 95 - 100 0906-6705 2006/02 [Refereed][Not invited]
     
    Both CCL27 and CCL28 are ligands for CCR10 and attract CCR10(+) lymphocytes. We previously demonstrated that CCL27 and CCL28 were strongly expressed in sera and lesional keratinocytes of patients with atopic dermatitis and psoriasis vulgaris. However, the regulation of CCL27 and CCL28 production in keratinocytes has not been well documented. In this study, we showed that CCL27 and CCL28 expression and production by a human keratinocyte cell line, HaCaT cells, were strongly induced by inflammatory cytokines tumor necrosis factor-alpha and interleukin-1 beta. CCL27 production was downregulated by inhibitors of p38 mitogen-activated protein kinase and nuclear factor-kappa B (NF-kappa B). By contrast, CCL28 production was downregulated by inhibitors of extracellular signal-regulated kinase and NF-kappa B. Our study results suggest that CCL28 produced by keratinocytes is mediated by different signal pathways from CCL27 and that both CCL27 and CCL28 are involved in the pathogenesis of inflammatory skin diseases.
  • Tomonori Takekoshi, Akihiko Asahina, Mayumi Komine, Kunihiko Tamaki
    ACTA DERMATO-VENEREOLOGICA 86 (4) 375 - 376 0001-5555 2006 [Refereed][Not invited]
  • K Shimazu, Y Tsunemi, N Hattori, M Adachi, S Imakado, H Saeki, M Komine, K Tamaki
    JOURNAL OF DERMATOLOGY 32 (10) 859 - 861 0385-2407 2005/10 [Refereed][Not invited]
  • M Komine, T Kakinuma, S Kagami, Y Hanakawa, K Hashimoto, K Tamaki
    JOURNAL OF INVESTIGATIVE DERMATOLOGY 125 (3) 491 - 498 0022-202X 2005/09 [Refereed][Not invited]
     
    Stimulation with tumor necrosis factor (TNF)alpha and interferon (IFN)gamma synergistically induced thymus- and activation-regulated chemokine (TARC)/CCL17 production from HaCaT keratinocytes (KC). Inhibitors for nuclear factor kappa B (NF kappa B), parthenolide, and Bay 11-7085, and an inhibitor of p38, SB202190, inhibited TNF alpha- and IFN gamma-induced production of CCL17 by HaCaT KC. Surprisingly, an inhibitor of epidermal growth factor receptor tyrosine kinase, PD153035, enhanced the production of CCL17 in HaCaT KC. Roxithromycin (RXM), a 14-membered ring macrolide, suppressed CCL17 production by HaCaT KC induced by IFN gamma and TNF alpha. RXM partially suppressed p38 phosphorylation and NF kappa B-driven luciferase activity induced by TNF alpha and IFN gamma. Degradation of inhibitor of nuclear factor kappa B (I kappa B) alpha upon stimulation with IFN gamma and TNF alpha was not affected by the addition of RXM. Through elucidating the mechanism of CCL17 production, our study indicates that RXM suppresses the production through the inhibition of p38 and NF kappa B, independent of the inhibition of I kappa B degradation.
  • Shinji Kagami, H. Saeki, M. Komine, T. Kakinuma, Y. Tsunemi, K. Nakamura, K. Sasaki, A. Asahina, K. Tamaki
    Clinical and Experimental Immunology 141 (3) 459 - 466 0009-9104 2005/09 [Refereed][Not invited]
     
    Eotaxin-2/CCL24 and eotaxin-3/CCL26 are CC chemokines and their receptor, CC chemokine receptor 3 is preferentially expressed on eosinophils. It was reported that vascular endothelial cells and dermal fibroblasts produced CCL26. However, the regulation of CCL24 and CCL26 production in keratinocytes has not been well documented. We investigated the expression and production of CCL24 and CCL26 in the human keratinocyte cell line, HaCaT cells. Reverse transcription and polymerase chain reaction was performed using these cells and Enzyme-linked immunosorbent assay was carried out using supernatant of these cells. The production of CCL24 in HaCaT cells was slightly enhanced by IL-4 and that of CCL26 was strongly enhanced by IL-4 and IL-13. Furthermore, TNF-α generated a synergistic effect on IL-4 enhanced CCL26 production. Dexamethasone, IFN-γ and the p38 mitogen-activated protein kinase inhibitor SB202190 inhibited IL-4 enhanced CCL26 production. IL-4 enhanced production of CCL26 was inhibited by leflunomide and JAK inhibitor 1, but not by JAK3 inhibitor, which indicates that it is mediated by JAK1-STAT6-dependent pathway. This result also strongly suggests the involvement of the type 2 IL-4 receptor in IL-4 enhanced production of CCL26. These results suggest that keratinocytes are involved in the migration of CC chemokine receptor 3 positive cells such as eosinophils in a Th2-dominant situation like atopic dermatitis. © 2005 British Society for Immunology.
  • Y Iizuka, T Yokomizo, K Terawaki, M Komine, K Tamaki, T Shimizu
    JOURNAL OF BIOLOGICAL CHEMISTRY 280 (26) 24816 - 24823 0021-9258 2005/07 [Refereed][Not invited]
     
    Leukotriene B4 (LTB4) is a potent chemoattractant and activator for granulocytes and macrophages and is considered to be an inflammatory mediator. Two G-protein-coupled receptors for LTB4, BLT1 and BLT2, have been cloned from human and shown to be high and low affinity LTB4 receptors, respectively. To reveal the biological roles of BLT2 using mouse disease models, we cloned and characterized mouse BLT2. Chinese hamster ovary cells stably expressing mouse BLT2 exhibited specific binding to LTB4, LTB4-induced calcium mobilization, inhibition of adenylyl cyclase, and phosphorylation of extracellular signal-regulated kinase. We found that Compound A (4'-{[pentanoyl (phenyl) amino] methyl}1, 1'-biphenyl-2-carboxylic acid) was a BLT2-selective agonist and induced Ca2+ mobilization and phosphorylation of extracellular signal-regulated kinase through BLT2, whereas it had no effect on BLT1. 12-epi LTB4 exhibited a partial agonistic activity against mBLT1 and mBLT2, whereas 6-trans-12-epi LTB4 did not. Northern blot analysis showed that mouse BLT2 is expressed highly in small intestine and skin in contrast to the ubiquitous expression of human BLT2. By in situ hybridization and the reverse transcriptase polymerase chain reaction, we demonstrated that mouse BLT2 is expressed in follicular and interfollicular keratinocytes. Compound A, LTB4, and 12-epi LTB4 all induced phosphorylation of extracellular signal-regulated kinase in primary mouse keratinocytes. Furthermore, Compound A and LTB4 induced chemotaxis in primary mouse keratinocytes. These data suggest the presence of functional BLT2 in primary keratinocytes.
  • 乾癬患者における血清IgE及び血清中炎症性分子についての検討
    ニンデル・マーギット, 唐川 大, 桜井 直樹, 竹腰 知紀, 岸本 恵美, 三井 浩, 佐伯 秀久, 小宮根 真弓, 朝比奈 昭彦, 玉置 邦彦
    日本皮膚科学会雑誌 (公社)日本皮膚科学会 115 (7) 1063 - 1063 0021-499X 2005/06
  • S Kagami, T Kakinuma, H Saeki, Y Tsunemi, H Fujita, K Sasaki, K Nakamura, T Takekoshi, M Kishimoto, H Mitsui, M Komine, A Asahina, K Tamaki
    JOURNAL OF INVESTIGATIVE DERMATOLOGY 124 (5) 1088 - 1090 0022-202X 2005/05 [Refereed][Not invited]
  • H Mitsui, T Watanabe, M Komine, H Nakamura, H Shimizu, K Tamaki
    JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY 52 (2) 371 - 373 0190-9622 2005/02 [Refereed][Not invited]
  • M Komine, K Tamaki
    ACTA DERMATO-VENEREOLOGICA 85 (4) 360 - 362 0001-5555 2005 [Refereed][Not invited]
  • Y Tsunemi, M Komine, T Sekiya, H Saeki, K Nakamura, K Hirai, T Kakinuma, S Kagami, H Fujita, N Asano, Y Tanida, M Wakugawa, H Torii, K Tamaki
    EXPERIMENTAL DERMATOLOGY 13 (11) 715 - 719 0906-6705 2004/11 [Refereed][Not invited]
     
    Background: Thymus and activation-regulated chemokine (TARC) plays an important role in the pathogenesis of atopic dermatitis (AD). We recently detected the single nucleotide polymorphism (SNP) (-431C>T) in the 5'-flanking region of TARC gene. Objectives: To examine whether the -431C>T SNP of the TARC gene is associated with susceptibility to AD and whether it affects the promoter activity of the TARC gene. Methods: We investigated the genotype and allele frequencies of the SNP in 193 AD patients and 158 healthy controls by polymerase chain reaction-restriction fragment length polymorphism method. We compared the promoter activities between TARC promoter carrying 431C and that carrying -431T by transient-transfection assay in DJM-1 cell line. Results: There were no significant differences in genotype or allele frequencies between AD patients and controls (genotype: P = 0.38, allele: P = 0.22). Luciferase activity was higher in -431T constructs than in -431C constructs (2.3-fold, P = 9.5 x 10(-6)). Conclusion: These results suggest that the -431C>T SNP of the TARC gene enhances the promoter activity of TARC gene but is not associated with susceptibility to AD in Japanese population.
  • S Yano, M Komine, M Fujimoto, H Okochi, K Tamaki
    JOURNAL OF INVESTIGATIVE DERMATOLOGY 122 (3) 783 - 790 0022-202X 2004/03 [Refereed][Not invited]
     
    Epidermal keratinocytes are continuously exposed to mechanical forces. The human skin surface can be thickened and enlarged by various stresses such as tissue expander or abrasive pressure. To investigate the mechanism of epidermal hyperproliferation by mechanical stress, keratinocytes were plated on flexible silicone dishes, which were continuously stretched by + 20%. Stretching of cells for 24 h caused upregulation of 5-bromo-2'-deoxyuridine (BrdU)-positive cells to 200%-220% and activation of extracellular signal-regulated kinases (ERK)1/2. Inhibition of mitogen and ERK with U0126 and phosphoinositide 3-OH kinase attenuated BrdU incorporation and ERK1/2 activation. The EGF receptor kinase inhibitor and the calcium channel inhibitor also inhibited BrdU incorporation and the activation of ERK1/2. Twenty-four hours of stretching stimulated reporter activity driven by activator protein 1(AP-1), induction of K6, and suppression of K10, which were inhibited by U0126. Our results indicate that mechanical stretching induces proliferative signals on human keratinocytes via induction of calcium influx, phosphorylation of epidermal growth factor receptor (EGFR), and ERK1/2. These mechanisms may contribute to the hyperproliferative nature of the epidermis, which is mechanically stretched by various stimuli.
  • Y Tsunemi, H Saeki, M Kishimoto, H Mitsui, Y Tada, H Torii, M Komine, A Asahina, K Tamaki, T Sekiya
    JOURNAL OF DERMATOLOGICAL SCIENCE 32 (2) 163 - 165 0923-1811 2003/08 [Refereed][Not invited]
  • T Xiao, S Kagami, H Saeki, M Sugaya, T Kakinuma, H Fujita, S Yano, H Mitsui, H Torii, M Komine, A Asahina, K Nakamura, K Tamaki
    JOURNAL OF DERMATOLOGICAL SCIENCE 31 (2) 111 - 117 0923-1811 2003/04 [Refereed][Not invited]
     
    Background: Macrophage-derived chemokine (MDC) is a Th2 type chemokine and its receptor CC chemokine receptor 4 (CCR4) is preferentially expressed on Th2 cells. Recent reports demonstrated that MDC is expressed not only by macrophages,, dendritic cells and lymphocytes, but also by cultured human keratinocytes (KCs). However, the regulation of MDC production in KCs by various cytokines has not been well documented. Objective: In this study, we investigated how Th1/Th2 cytokines regulate MDC production in a human KC cell line, HaCaT cells. Methods: HaCaT cells were cultured with or without various cytokines for 24 h and RT-PCR was performed using these cells to evaluate MDC mRNA levels. ELISA was carried out using supernatant of HaCaT cells to calculate secreted MDC protein levels. Results: MDC mRNA was weakly expressed in HaCaT cells, and upon stimulation with TNF-alpha or IFN-gamma, MDC expression was strongly upregulated. The supernatant MDC levels when stimulated with TNF-alpha or IFN-gamma were significantly higher than those without stimulation, and were synergistically increased when stimulated with a combination of TNF-alpha and IFN-gamma. Both interteukin-4 (IL-4) and IL-13 inhibited TNF-alpha and IFN-gamma enhanced MDC production in HaCaT cells in a dose-dependent manner. Conclusion: Th2-type cytokines IL-4 and IL-13 downregulate the production of MDC, a Th2 type chemokine, by KCs. This may partially contribute to maintaining Th1/Th2 balance inflammatory skin diseases like atopic dermatitis. (C) 2002 Japanese Society for Investigative Dermatology Elsevier Science Ireland Ltd. All rights reserved.
  • Komine M, Kakinuma H, Tamaoki K
    The Japanese journal of antibiotics 56 Suppl A 109 - 112 0368-2781 2003/04 [Refereed][Not invited]
  • T Kakinuma, H Saeki, Y Tsunemi, H Fujita, N Asano, H Mitsui, Y Tada, M Wakugawa, T Watanabe, H Torii, M Komine, A Asahina, K Nakamura, K Tamaki
    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 111 (3) 592 - 597 0091-6749 2003/03 [Refereed][Not invited]
     
    Both atopic dermatitis (AD) and psoriasis vulgaris (PsV) are characterized as chronic and relapsing inflammatory skin diseases associated with various immunologic abnormalities. Cutaneous T cell-attracting chemokine (CTACK; CCL27) is a member of the CC chemokine family and a functional ligand for CC chemokine receptor 10. It is selectively expressed in skin and attracts CC chemokine receptor 10-expressing skin-homing memory T cells. The epidermal keratinocyte is a main source of CTACK, suggesting the involvement of various inflammatory skin diseases. Objective: The purpose of this investigation was to clarify whether CTACK produced by keratinocytes is detected in the sera of patients with AD and PsV and to examine the correlation between the serum CTACK levels and disease activity of patients with AD and PsV. Methods: We measured the serum CTACK levels in 50 patients with AD, 30 patients with PsV, and 22 healthy control subjects. We also divided 50 patients with AD into 3 groups (ie, those with mild, moderate, and severe disease) and compared them among 3 categories. Moreover, we compared the serum CTACK levels of patients with AD and PsV with clinical or laboratory data. Immunohistochemical staining of CTACK and IFN-induced protein of 10 kd (IP-10; CXCL10) was performed on the lesional skin of patients with AD and PsV. Results: The serum CTACK levels in,patients with AD and PsV were significantly higher than those in healthy control subjects. The serum CTACK levels in patients with AD significantly correlated with scoring atopic dermatitis (SCORAD) scores, serum soluble IL-2 receptor levels, serum soluble E-selectin levels, serum thymus and activation-regulated chemokine levels, and serum macrophage-derived chemokine levels. Serum CTACK levels in patients with PsV significantly correlated with the serum IP-10 levels but not with the Psoriasis Area and Severity Index score. Immunohistochemical staining showed CTACK was strongly expressed in lesional keratinocytes of patients with AD and PsV, whereas IP-10 was strongly expressed in lesional keratinocytes of patients with PsV and focally in those with AD. Conclusion: These results suggest that CTACK might be one of the important chemokines for the pathogenesis of AD and PsV.
  • S Yano, M Komine, M Fujimoto, H Okochi, K Tamaki
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 301 (4) 841 - 847 0006-291X 2003/02 [Refereed][Not invited]
     
    Interleukin 15 (IL-15) is a potent stimulator of proliferation and an inhibitor of apoptosis in lymphocytes. We attempted to elucidate the mechanism of IL-15 function in HaCaT keratinocytes. We found that 5-bromo-2'-deoxyuridine incorporation increased in a dose-dependent manner with IL-15. This was blocked by MEK inhibitor U0126 or PI 3-K inhibitor LY294002. ERK1/2 and Akt phosphorylation by IL-15 were detected in a dose- and time-dependent manner. U0126 and LY294002 abolished ERK1/2 and Akt phosphorylation, respectively. DNA fragmentation and Annexin V binding accompanied by UVB-induced apoptosis were reduced by 30-50% with IL-15. Taken together, IL-15 induced cellular proliferation and had an anti-apoptotic effect on keratinocytes, in which ERK1/2 and Akt phosphorylation played crucial roles. The signal transduction pathways of IL-15 in keratinocytes were partially elucidated; they share a substantial part with growth signals induced by EGF. These results suggest a therapeutic approach to inflammatory skin diseases by controlling these signals. (C) 2003 Elsevier Science (USA). All rights reserved.
  • H Mitsui, M Komine, A Shirai, N Kanda, A Asahina, H Okochi, S Hitomi, S Kimura, K Tamaki
    ACTA DERMATO-VENEREOLOGICA 83 (1) 31 - 35 0001-5555 2003 [Refereed][Not invited]
     
    A 60-year-old man presented with recurrent genital and oral ulcers, necrotic papules on his face and scalp, spiking fever and indurated skin erythema on the trunk. A diagnosis of chronic active Epstein-Barr virus infection and IgG3 subclass deficiency was made, and he was supplemented by intravenous gammaglobulin injection. The spiking fever was resistant to treatment, but the addition of systemic interferon-alpha therapy was partially effective in treating his clinical symptoms, although the patient eventually died from pulmonary effusions and cardiac insufficiency.
  • Y Tsunemi, A Nishibu, H Saeki, N Oyama, K Nakamura, M Kishimoto, H Mitsui, Y Tada, H Torii, M Komine, A Asahina, F Kaneko, K Tamaki
    DERMATOLOGY 207 (4) 371 - 374 1018-8665 2003 [Refereed][Not invited]
     
    Background: Psoriasis features an increased level and activity of tumor necrosis factor alpha (TNF-alpha). The TNF-alpha gene has single nucleotide polymorphisms (SNPs) at positions -308 (-308G>A) and -238 (-238G>A) in the promoter region, and the -238G>A SNP has been reported to be associated with psoriasis vulgaris (PV) and psoriatic arthritis in Caucasians. Objective: To examine whether these SNPs are associated with susceptibility to PV in Japanese patients, we investigated the genotype and allele frequencies at each SNP in Japanese PV patients and in controls. Methods: We examined 163 PV patients and 96 healthy individuals. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. Results: No significant association between the genotypes or alleles of these SNPs and susceptibility to PV was observed. Conclusion: These SNPs themselves are not associated with susceptibility to PV in the Japanese. Copyright (C) 2003 S. Karger AG, Basel.
  • Significant elevation of serum levels of eotaxin-3 (CCL26), but not of eotaxin-2 (CCL24), in patients with atopic dermatitis: Serum eotaxin-3 levels reflect the disease activity of atopic dermatitis.
    Kagami S, Kakinuma T, Saeki H, Tsunemi Y, Fujita H, Takekoshi T, Kishimoto M, Mitsui H, Torii H, Komine M, Asahina A, Tamaki K
    Clin Exp Immunol 134 134 - 313 2003 [Refereed][Not invited]
  • Y Tsunemi, N Hattori, H Saeki, M Adachi, M Komine, H Nakagawa, K Tamaki
    JOURNAL OF DERMATOLOGY 29 (12) 768 - 772 0385-2407 2002/12 [Refereed][Not invited]
     
    We described a 5-year-old Japanese girl with epidermolytic palmoplantar keratoderma I and examined her for a keratin 9 gene mutation. Physical examination disclosed diffuse yellowish hyperkeratosis with an erythematous border limited strictly to the palms and soles. Histological examination revealed hyperkeratosis with vacuolar degeneration in the spinous and granular layers of the epidermis. Sequence analysis demonstrated an A to G transition at the middle position of codon 160 in the 1A domain of the keratin 9 gene. The amino acid at codon 160 was deduced to have changed from asparagine (Asn) to serine (Ser). This is the first case with an Asn160Ser mutation in a japanese. The substitution of Ser for Asn at codon 160 of the keratin 9 gene is assumed to be fatal for keratin filament assembly regardless of race or ethnicity.
  • Y Tsunemi, H Saeki, K Nakamura, T Sekiya, K Hirai, H Fujita, N Asano, M Kishimoto, Y Tanida, T Kakinuma, H Mitsui, Y Tada, M Wakugawa, H Torii, M Komine, A Asahina, K Tamaki
    JOURNAL OF DERMATOLOGICAL SCIENCE 30 (2) 161 - 166 0923-1811 2002/11 [Refereed][Not invited]
     
    Interleukin-12 (IL-12) is believed to play an important role in inducing Th1-type cytokine profiles. Atopic dermatitis (AD) and psoriasis vulgaris (PsV) are considered to be Th2 and Th1 type disease, respectively. The IL-12 p40 subunit gene (IL12B) is located at chromosome 5q31-33 and linkage findings of AD on 5q31 were reported. Recently single nucleotide polymorphism (SNP) (1188A/C) of IL12B has been reported. In function, it has been reported that this SNP is associated with IL12B mRNA expression levels. To learn whether this SNP is associated with susceptibility to AD or PsV, we investigated the genotype and allele frequencies of the SNP in AD patients, in PsV patients and in controls, examining 164 AD patients, 143 PsV patients and 100 healthy individuals in Japanese population. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. The A allele was decreased in AD patients (40.9%, p = 0.031) and increased in PsV patients (60.1%, p = 0.035) compared with controls (50.5%). This suggests that IL12B SNP is associated with susceptibility to AD and PsV, presumably by affecting the Th1/Th2 balance. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
  • H Saeki, N Asano, Y Tsunemi, T Takekoshi, M Kishimoto, H Mitsui, Y Tada, H Torii, M Komine, A Asahina, K Tamaki
    JOURNAL OF DERMATOLOGICAL SCIENCE 30 (2) 167 - 171 0923-1811 2002/11 [Refereed][Not invited]
     
    We examined polymorphisms of vitamin D receptor (VDR) gene in Japanese patients with psoriasis vulgaris (PsV). We also studied the association between VDR gene polymorphisms and the response to vitamin D (VD) topical treatment in psoriatic patients. FokI, BsmI, ApaI and TaqI genotypes were determined by restriction fragment patterns in patients (n = 115) and controls (n = 69). In addition, 54 psoriatic patients were divided into two groups in terms of their response to VD (tacalcitol) topical treatment: non-responsive (n = 30) and responsive (n = 24) patients. The frequencies of B allele and t allele were lower in patients than in controls (9 vs. 19%: p < 0.01, 7 vs. 14%: p < 0.05, respectively). In regard to response to VD treatment, F allele was lower in non-responsive patients than in controls (47 vs. 64%, p < 0.05). We show that polymorphisms of VDR gene are associated with Japanese patients with PsV., Allelic variance in the VDR gene or other genes in linkage disequilibrium with this gene might predispose to the development of PsV. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
  • T Kakinuma, K Nakamura, M Wakugawa, S Yano, H Saeki, H Torii, M Komine, A Asahina, K Tamaki
    CYTOKINE 20 (1) 1 - 6 1043-4666 2002/10 [Refereed][Not invited]
     
    It is known that both interleukin-4 (IL-4) and IL-13 are produced by Th2-type cells and share similar biological. functions with each other. However, recently accumulated evidences have revealed that IL-4 may be involved in the Th1-type response. Both thymus and activationregulated chemokine (TARC/CCL17), a ligand for CC chemokine receptor 4 that is mainly expressed on Th2-type cells, and interferon-induced protein of 10kDa (IP-10/CXCL10), a ligand for CXC chemokine receptor 3 that is mainly expressed on Th1-type cells, are produced by keratinocytes after the stimulation with the primary cytokines such as tumor necrotic factor-alpha (TNF-alpha) and/or interferon-gamma (IFN-gamma). In this study, we investigated the regulation of TARC or IP-10 production from HaCaT cells, an immortalized human keratinocyte cell line, after stimulation with TNF-alpha, IFN-gamma, IL-4 and/or IL-13. Without stimulation, HaCaT cells did not produce TARC. When both TNF-alpha and IFN-gamma were added, they increased synergistically (P<0.003). In addition, when HaCaT cells were stimulated with IL-4, but not IL-13, in combination with TNF-alpha and IFN-gamma, the supernatant TARC levels significantly decreased compared to those with both TNF-alpha and IFN-gamma (P<0.009). This inhibition was completely abolished with the addition of neutralizing anti-IL-4 antibody. The supernatant IP-10 levels also increased synergistically by stimulation with TNF-alpha and IFN-gamma for 24 h (P<0.001). When IL-4, but not IL-13, was added to the medium and the cells were co-cultured with these cytokines, the IP-10 levels significantly increased compared to those with both TNF-alpha and IFN-gamma (P<0.04). Furthermore, the effects of IL-4 on TARC and IP-10 production in these cells were detected in a dose-dependent manner. These data strongly suggest that IL-4 may act not only as a mediator of Thl-type response but also as a down-regulator of Th2-type response in terms of the regulation of chemokine production by HaCaT cells. (C) 2002 Elsevier Science Ltd. All rights reserved.
  • N Hattori, M Komine, S Yano, T Kaneko, Y Hanakawa, K Hashimoto, K Tamaki
    JOURNAL OF INVESTIGATIVE DERMATOLOGY 119 (2) 403 - 410 0022-202X 2002/08 [Refereed][Not invited]
     
    Keratin K6 is known as an inflammatory and hyperproliferative keratin, and is induced by an inflammatory and hyperproliferative agent. In this study, we demonstrated that interferon-gamma, an antiproliferative agent, also induces keratin K6. We used normal human ex vivo skin, normal human cultured keratinocytes, HaCaT keratinocytes, and DJM cells to examine the induction of K6 by interferon-gamma, by immunohistochemical staining, Western blot analysis, promoter chloramphenicol acetyl transferase assay, and reverse transcriptase polymerase chain reaction of mRNA. We succeeded in demonstrating the induction of keratin K6 by interferon-gamma in ex vivo human skin and HaCaT keratinocytes at the protein and message level, and in cultured normal human keratinocytes at the promoter level. The inhibition of the signal transducing activator of transcription 1 pathway by a dominant-negative transfer gene caused the inhibition of K6 induction by interferon-gamma, and the blocking of nuclear factor kappaB using antisense oligonucleotides also inhibited the K6 induction. We also blocked the released interleukin-1alpha from keratinocytes after stimulation with interferon-gamma by neutralizing antibodies, which showed a decrease in the K6 induction. Our results suggest that a small amount of interleukin-1alpha, which cannot induce K6 by itself, is secreted upon stimulation by interferon-gamma, and that the induction of K6 occurs through the synergistic effect of the interferon-gamma/signal transducing activator of transcription 1 and interleukin-1alpha/nuclear factor kappaB pathways. This is the first report to describe K6 induction in epidermal keratinocytes by interferon-gamma and indicate a probable signal transduction pathway, and demonstrates that K6 is a possible partner of K17 in the inflammatory process.
  • H Mitsui, M Komine, T Watanabe, K Kikuchi, H Okochi, K Tamaki
    BRITISH JOURNAL OF DERMATOLOGY 146 (5) 908 - 911 0007-0963 2002/05 [Refereed][Not invited]
     
    We report a Japanese patient with Hermansky-Pudlak syndrome (HPS) who developed systemic lupus erythematosus (SLE). This is the second case report of HPS complicated with SLE. A 1-bp duplication of adenine at codon 441 was found in the HPS gene, namely HPS1, which caused a frameshift. This case serves as evidence indicating that a patient with HPS can be predisposed to SLE.
  • H Ogasawara, S Ishii, T Yokomizo, T Kakinuma, M Komine, K Tamaki, T Shimizu, T Izumi
    JOURNAL OF BIOLOGICAL CHEMISTRY 277 (21) 18763 - 18768 0021-9258 2002/05 [Refereed][Not invited]
     
    Cysteinyl leukotrienes (LTs) are important proinflammatory mediators. Their precise roles in mice need to be elucidated to interpret mouse models of inflammatory diseases. For this purpose, we cloned and characterized mouse receptors for cysteinyl LTs, mCysLT(1) and mCysLT(2). mCysLT(1) and mCysLT(2) were composed of 339 amino acids with 87.3% identity and 309 amino acids with 73.4% identity to human orthologues, respectively. A pharmacological difference was noted between mouse and human CysLT(2). Pranlukast, a specific inhibitor for human CysLT(1), antagonized mCysLT(2) responses as determined by Ca2+ elevation and receptor-induced promoter activation. The mRNA expressions of both mCysLTs were higher in C57BL/6 mice than in 129 mice. mCysLT(1) mRNA was expressed mainly in skin, lung, and small intestine. mCysLT(2) was seen more ubiquitously with high expressions in spleen, lung, and small intestine. By in situ hybridization we demonstrated for the first time that mCysLT(1) and mCysLT(2) were expressed in subcutaneous fibroblasts. The different pharmacological characteristics of CysLT(2) between human and mouse and the different distributions of CysLTs between mouse strains suggest that careful choice and interpretation are necessary for a study of CysLTs using animal models.
  • 金子 健彦, 浅野 善英, 服部 尚子, 小宮根 真弓, 川端 康浩, 相馬 良直, 薦田 房子
    臨床皮膚科 (株)医学書院 56 (4) 291 - 294 0021-4973 2002/04 [Refereed][Not invited]
     
    11歳女児.背部の環状紅斑を主訴とした.長野県軽井沢町で刺症し,20日後に拡大傾向を示す紅斑を生じた.抗Borrelia burgdorfei IgM抗体は経過とともに陰性から陽性に転じ,IgG抗体はより多数の陽性バンドを認めるようになった.虫刺痕部分の組織学的検索で虫体口器の残存を認め,標記と診断した.ドキシサイクリンハイドロクロタライド投与により皮疹は初診7日後に消失し,以後4週間の投薬を続けた.国内の報告は40〜60歳代が半数を超え,刺症部位は上肢が最も多かった.皮膚症状のみは32%で,関節痛,リンパ節腫脹などを43%に,何らかの神経症状を21%に認めた.脳神経炎では顔面神経麻痺を6例に認め,皮膚科臨床医にとって注目すべき症状と考えた
  • M Komine, M Hino, M Shiina, Kanazawa, I, Y Soma, K Tamaki
    BRITISH JOURNAL OF DERMATOLOGY 146 (3) 500 - 502 0007-0963 2002/03 [Refereed][Not invited]
     
    We describe a 20-year-old woman with trisomy 18 mosaicism, who presented with skeletal anomalies, epilepsy, mental retardation, and linear and whorled naevoid hypermelanosis.
  • 拇指多指症の1例
    藤田 英樹, 金子 健彦, 服部 尚子, 小宮根 真弓, 川端 康浩, 菊池 かな子, 相馬 良直
    皮膚科の臨床 金原出版(株) 44 (3) 313 - 315 0018-1404 2002/03 [Refereed][Not invited]
     
    生後0日女児.出生時に右拇指基部橈側の小腫瘤を指摘された.生後3ヵ月半で,局所麻酔下に単純切除縫縮術を行った.組織学的に,腫瘤中央部に軟骨組織を認めたが,関節形成や骨分枝を認めず,中川らの分類によるfloating typeの拇指多指症と考えられた.術後1年2ヵ月が経過し,再発はない
  • T Kakinuma, K Nakamura, M Wakugawa, H Mitsui, Y Tada, H Saeki, H Torii, M Komine, A Asahina, K Tamaki
    CLINICAL AND EXPERIMENTAL IMMUNOLOGY 127 (2) 270 - 273 0009-9104 2002/02 [Refereed][Not invited]
     
    Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by the predominant infiltration of T cells, eosinophils and macrophages in lesional skin. Recently, macrophage-derived chemokine (MDC)/CCL22, a CC chemokine, was identified as a selective chemoattractant for CC chemokine receptor 4 (CCR4)-expressing cells, in addition to thymus and activation-regulated chemokine (TARC). We have previously reported that serum TARC levels correlate with the severity of AD. In this report, we investigated the participation of MDC in AD. First, we measured serum MDC levels in 45 patients with AD, 25 patients with psoriasis vulgaris and 25 healthy controls. Serum MDC levels in AD patients were significantly higher than those in healthy controls and psoriasis patients. Furthermore, the increases in serum MDC levels in AD patients were greater in the severely affected group than in the moderate or mild groups. We compared serum MDC levels in 11 AD patients, before and after treatment, and observed a significant decrease after treatment. Moreover, the serum MDC levels significantly correlated with the Scoring AD (SCORAD) index, serum soluble (s) E-selectin levels, serum soluble interleukin-2 receptor (sIL-2R) levels, serum TARC levels and eosinophil numbers in peripheral blood. Our study strongly suggests that serum MDC levels have a notable correlation with disease activity and that MDC, as well as the CC chemokine TARC, may be involved in the pathogenesis of AD.
  • M Komine, M Okinaga, F Takeda, K Nashiro, K Kikuchi, T Murakami, Y Soma, K Tamaki
    BRITISH JOURNAL OF DERMATOLOGY 145 (2) 223 - 228 0007-0963 2001/08 [Refereed][Not invited]
     
    Background Bowen's disease is a well-established in situ malignancy of the epidermis. The keratin expression in Bowen's disease has been studied in many reports. However, the patterns of keratin (K) 14 expression in each case have not been closely examined. Objectives To investigate if the pattern of expression of K14 has a relationship with tumour progression, we analysed the expression patterns of K14 in relation to the nature of tumour cells, comparing tumour cells in direct contact with the dermis, tumour cells separated from the dermis, and tumour cells invading into the dermis. Methods Twenty-seven tissue sections from 22 patients were stained with anti-K14 antibody, as well as with antilaminin and periodic acid-Schiff (PAS) staining to evaluate the conditions of the basement membrane. Staining patterns of K10 and integrin betal, and their relationships with proliferating cell nuclear antigen (PCNA) and Ki-67 staining patterns. were also examined. Results Tumour cells with no, or with obscured, basement membranes always showed positive staining for K14, while those with continuous (intact) basement membranes usually did not. Of 10 sections showing dermal involvement of Bowen's disease, five were K14 positive and five were K14 negative. All of these K14-positive sections with dermal involvement showed negative or obscured laminin and PAS staining. Most of the sections having K14-negative tumour cells with dermal involvement showed K14-positive lining cells with continuous staining with laminin and PAS-positive basement membranes. K10 was reciprocally expressed with K14 in most of the sections. Integrin beta1 was expressed in the basal layers of non-tumour epidermal cells, but not in tumour cells. Ki-67 and PCNA were expressed at high frequencies in tumour cells, clearly demarcating tumour cells from non-tumour cells. Conclusions Tumour cells separated from the dermis by lining cells were K14 negative with PAS- and laminin-positive basement membranes around them; tumour cells without lining cells were K14 positive with or without continuous basement membranes. K14 expression may be a marker of tumour progression in Bowen's disease.
  • IM Freedberg, M Tomic-Canic, M Komine, M Blumenberg
    JOURNAL OF INVESTIGATIVE DERMATOLOGY 116 (5) 633 - 640 0022-202X 2001/05 [Refereed][Not invited]
     
    In wound healing and many pathologic conditions, keratinocytes become activated: they turn into migratory, hyperproliferative cells that produce and secrete extracellular matrix components and signaling polypeptides. At the same time, their cytoskeleton is also altered by the production of specific keratin proteins. These changes are orchestrated by growth factors, chemokines, and cytokines produced by keratinocytes and other cutaneous cell types. The responding intracellular signaling pathways activate transcription factors that regulate expression of keratin genes. Analysis of these processes led us to propose the existence of a keratinocyte activation cycle, in which the cells first become activated by the release of IL-1. Subsequently, they maintain the activated state by autocrine production of proinflammatory and proliferative signals. Keratins K6 and K16 are markers of the active state. Signals from the lymphocytes, in the form of Interferon-gamma, induce the expression of K17 and make keratinocytes contractile. This enables the keratinocytes to shrink the provisional fibronectin-rich basement membrane. Signals from the fibroblasts, in the form of TGF-beta, induce the expression of K5 and K14, revert the keratinocytes to the healthy basal phenotype, and thus complete the activation cycle.
  • 病理組織型と耐糖能障害の関連を示唆した脂肪類壊死の2例
    浅野 善英, 藤田 悦子, 服部 尚子, 湧川 基史, 金子 健彦, 鳥居 秀嗣, 小宮根 真弓, 朝比奈 昭彦, 川端 康浩, 相馬 良直
    皮膚科の臨床 金原出版(株) 43 (4) 562 - 563 0018-1404 2001/04 [Refereed][Not invited]
     
    症例1:79歳男.糖尿病はなく,10ヵ月前に両下腿に紅褐色斑が出現し,徐々に増数,拡大した.境界型耐糖能障害があり,necrobiotic typeの脂肪類壊死と診断した.フランカルボン酸モメタゾンの外用で浸潤と紅斑は消失し,淡褐色調の局面となっている.症例2:74歳女.糖尿病はなく,1ヵ月前より両下腿に褐色斑が出現し,徐々に増数,拡大した.耐糖能異常は見られず,granulomatous typeの脂肪類壊死と診断した.フランカルボン酸モメタゾンを外用しているが,特に変化は見られない
  • M Komine, LS Rao, IM Freedberg, M Simon, Milisavljevic, V, M Blumenberg
    JOURNAL OF INVESTIGATIVE DERMATOLOGY 116 (2) 330 - 338 0022-202X 2001/02 [Refereed][Not invited]
     
    Keratinocytes respond to injury by releasing the proinflammatory cytokine interleukin-1, which serves as the initial "alarm signal" to surrounding cells. Among the consequences of interleukin-1 release is the production of additional cytokines and their receptors by keratinocytes and other cells in the skin. Here we describe an additional effect of interleukin-1 on keratinocytes, namely the alteration in the keratinocyte cytoskeleton in the form of the induction of keratin 6 expression. Keratin 6 is a marker of hyperproliferative, activated keratinocytes, found in wound healing, psoriasis, and other inflammatory disorders. Skin biopsies in organ culture treated with interleukin-1 express keratin 6 in all suprabasal layers of the epidermis, throughout the tissue. In cultured epidermal keratinocytes, the induction of keratin 6 is time and concentration dependent. Importantly,1, subconfluent cultures do not. In the cells starved of growth factors, epidermal growth factor or tumor necrosis factor-alpha, if added simultaneously with interleukin-1, they synergistically augment the effects of interleukin-1. Using DNA-mediated cell transfection, we analyzed the molecular mechanisms regulating the keratin 6 induction by interleukin-1, and found that the induction occurs at the transcriptional level. We used a series of deletions and point mutations to identify the interleukin-1 responsive DNA element in the keratin 6 promoter, and determined that it contains a complex of C/EBP binding sites. The transcription factor C/EBP beta binds this element in vitro, and the binding is augmented by pretreatment of the cells with interleukin-1. The interleukin-1 responsive element is clearly distinct from the epidermal growth factor responsive one, which means that the proinflammatory and proliferative signals independently regulate the expression of keratin 6. Thus, interleukin-1 initiates keratinocyte activation not only by triggering additional signaling events, but also by inducing directly the synthesis of keratin 6 in epidermal keratinocytes, and thus changing the composition of their cytoskeleton.
  • M Komine, LMS Rao, T Kaneko, M Tomic-Canic, K Tamaki, IM Freedberg, M Blumenberg
    JOURNAL OF BIOLOGICAL CHEMISTRY 275 (41) 32077 - 32088 0021-9258 2000/10 [Refereed][Not invited]
     
    Epidermal keratinocytes respond to injury by becoming activated, i.e. hyperproliferative, migratory, and proinflammatory. These processes are regulated by growth factors and cytokines. One of the markers of activated keratinocytes is keratin K6. We used a novel organ culture system to show that tumor necrosis factor alpha (TNF alpha) induces the expression of K6 protein and mRNA in human skin. Multiple isoforms of K6 are encoded by distinct genes and have distinct patterns of expression. By having shown previously that proliferative signals, such as epidermal growth factor (EGF), induce expression of the cytoskeletal protein keratin K6b, we here demonstrate that the same isoform, K6b, is also induced by TNF alpha, a proinflammatory cytokine. Specifically, TNF alpha induces the transcription of the K6b gene promoter. By using co-transfection, specific inhibitors, and antisense oligonucleotides, we have identified NF kappa B and C/EBP beta as the transcription factors that convey the TNFa! signal. Both transcription factors are necessary for the induction of K6b by TNFa and act as a complex, although only C/EBP beta binds the K6b promoter DNA. By using transfection, site-directed mutagenesis, and footprinting, we have mapped the site that responds to TNF alpha, NF kappa B, and C/EBP beta. This site is separate from the one responsive to EGF and AP1. Our results show that the proinflammatory (TNF alpha) and the proliferative (EGF) signals in epidermis separately and independently regulate the expression of the same K6b keratin isoform. Thus, the cytoskeletal responses in epidermal cells can be precisely tuned by separate proliferative and inflammatory signals to fit the nature of the injuries that caused them.
  • N Radoja, M Komine, SH Jho, M Blumenberg, M Tomic-Canic
    MOLECULAR AND CELLULAR BIOLOGY 20 (12) 4328 - 4339 0270-7306 2000/06 [Refereed][Not invited]
     
    Glucocorticoids (GCs), important regulators of epidermal growth, differentiation, and homeostasis, are used extensively in the treatment of skin diseases. Using keratin gene expression as a paradigm of epidermal physiology and pathology we have developed a model system to study the molecular mechanism of GCs action in skin. Here we describe a novel mechanism of suppression of transcription by the glucocorticoid receptor (GR) that represents an example of customizing a device for transcriptional regulation to target a specific group of genes within the target tissue, in our case, epidermis. We have shown that GCs repress the expression of the basal-cell-specific keratins K5 and K14 and disease-associated keratins K6, K16, and K17 but not the differentiation-specific keratins K3 and K10 or the simple epithelium-specific keratins K8, K18, and K19. We have identified the negative recognition elements (nGREs) in all five regulated keratin gene promoters. Detailed footprinting revealed that the function of nGREs is to instruct the GR to bind as four monomers. Furthermore, using cotransfection and antisense technology we have found that, unlike SRC-1 and GRIP-1, which are not involved in the GR complex: that suppresses keratin genes, histone acetyltransferase and CBP are. In addition, we have found that GR, independently from GREs, blocks the induction of keratin gene expression by AP1. We conclude that GR suppresses keratin gene expression through two independent mechanisms: directly, through interactions of keratin nGREs with four GR monomers, as well as indirectly, by blocking the AP1 induction of keratin gene expression.
  • Y Tada, M Komine, S Suzuki, K Kikuchi, M Sasaki, N Kaneko, K Tamaki
    ACTA DERMATO-VENEREOLOGICA 80 (3) 233 - 235 0001-5555 2000/05 [Refereed][Not invited]
  • M Komine, N Hattori, K Tamaki
    AMERICAN JOURNAL OF DERMATOPATHOLOGY 22 (2) 171 - 175 0193-1091 2000/04 [Refereed][Not invited]
     
    Eccrine syringofibroadenoma is an uncommon benign eccrine tumor, which was first described by Mascaro in 1963. It usually develops on the extremities of elderly persons. We report on a 74-year-old man who presented with a 2-year history of a slowly growing lesion on his face. A detailed histologic and immunohistochemical study was performed on the biopsy material. The tumor consisted of epidermal-derived anastomosing thin epithelial cords embedded in a fibrovascular stroma. The epithelial cords contained ductal and cystic structures lined by luminal cells, which were decorated by antibodies against carcinoembryonic antigen, keratin K19, K8, and K18. Antibody to keratin K6 decorated the luminal walls of the acrosyringia. Antibodies to filaggrin decorated the superficial luminal structures. These results suggest dual acrosyringial and dermal duct differentiation in syringofibroadenoma.
  • M. Komine, K. Tamaki
    Journal of Dermatology 27 (8) 508 - 512 0385-2407 2000 [Refereed][Not invited]
     
    Seventeen patients were included in a clinical open trial of macrolides for treatment of psoriasis vulgaris. PASI scores, itch and ointment scores were used to evaluate their effectiveness. PASI scores dropped from 22.8 to 13.7 this was statistically significant. Itch reduced in 11 out of 13 patients, and the extent of itch reduced significantly by 54% on average. Ointment scores reduced from 44.9 to 34.4, which was also statistically significant. Macrolides are known not only as potent anti-biotics, but also as immunomodulatory agents. These data suggest that macrolides could be used as one of the adjunctive therapies of psoriasis vulgaris, and this study is a first step toward the future evaluation of macrolides in a double blind trial.
  • M Komine, Y Watabe, S Shimaoka, F Sato, K Kake, H Nishina, M Ohtsuki, H Nakagawa, K Tamaki
    ARCHIVES OF DERMATOLOGICAL RESEARCH 291 (9) 500 - 506 0340-3696 1999/09 [Refereed][Not invited]
     
    Topical vitamin D-3 has relatively recently been introduced for the treatment of psoriasis. Synthetic vitamin D-3 analogues with a high potential for inducing differentiation of cells, but with a low hypercalcemic effect have recently been developed. One such synthetic analogue of 1,25-dihydroxyvitamin D-3 (calcitriol), 22-oxacalcitriol (OCT), is a novel agent for the topical treatment of psoriasis, The activity of OCT in vitro was investigated and compared with that of a series of vitamin D-3 analogues as to their ability to inhibit murine T lymphocyte proliferation stimulated by con-A, to suppress IL-6 and IL-8 production by keratinocytes stimulated with IL-1 alpha and TNF alpha, and to inhibit AP-1- and NF kappa B-dependent reporter gene expression. OCT inhibited, the proliferation of lymphocytes and suppressed IL-8 and IL-6 production by keratinocytes to the same extent as the other vitamin D-3 analogues. It also inhibited AP-1- and NF kappa B-controlled luciferase activity to the same extent as the other vitamin D-3 analogues, which demonstrates its mechanism of action in the suppression of inflammatory processes.
  • M Tomic-Canic, M Komine, IM Freedberg, M Blumenberg
    JOURNAL OF DERMATOLOGICAL SCIENCE 17 (3) 167 - 181 0923-1811 1998/07 [Refereed][Not invited]
     
    In the area of biology, many laboratories around the world are dissecting and characterizing signal transduction mechanisms and transcription factors responsive to various growth factors and cytokines, in various cell types. However, because of the differences in systems used, it is not clear whether these systems coexist, whether they interact meaningfully, and what their relative roles are. Epidermal keratinocytes are the perfect cell type in which to integrate this knowledge, because in these cells these mechanisms are known to be relevant. Keratinocytes both produce and respond to growth factors and cytokines, especially in pathological conditions and during wound healing, when the physiology of keratinocytes is altered in a way specified by the presence of a subset growth factors and cytokines. In fact, growth factors and cytokines cause the major changes in gene expression and keratinocyte behavior in various cutaneous diseases. In some cases, such as in wound healing, these responses are highly beneficial; in others, such as in psoriasis, they are pathological. It is not clear at present which are operating in which conditions, which are important for the healing process and which are harmful. Growth factors and cytokines affect keratinocytes sometimes simultaneously, at other times individually. In this manuscript we describe the signal transduction pathways responsible for the effects of interferons, the EGF/TGF alpha family and the TNF alpha/IL-1 family of signaling molecules. We also describe the important transcription factors known to be functional in epidermis, with particular emphasis on those factors that are activated by growth factors and cytokines. Finally, we describe what is known about transcriptional regulation of keratin genes, especially those specifically expressed in pathological processes in the epidermis. We expect that the enhanced understanding of the pathways regulating gene expression in keratinocytes will identify the pharmacological targets, the signal transducing proteins and the corresponding transcription factors, used by growth factors and cytokines. This research will lead to development of compounds precisely aimed at those targets, allowing us to isolate and inhibit the harmful side effects of growth factors and cytokines. Such compounds should lead to highly specific and therefore more effective treatments of the cutaneous disorders in which these pathways play significant roles. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.
  • M Komine, IM Freedberg, M Blumenberg
    JOURNAL OF INVESTIGATIVE DERMATOLOGY 107 (4) 569 - 575 0022-202X 1996/10 [Refereed][Not invited]
     
    Keratin K17, the myoepithelial keratin, is expressed in psoriasis but is not present in healthy skin. Psoriasis is associated with production of gamma interferon (IFN gamma), which induces the expression of keratin K17 by activating transcription factor STAT1. Our hypothesis states that the induction of K17 is specific for the inflammatory reactions associated with high levels of IFN gamma and activation of STAT1. One of the corollaries of the hypothesis is that the STAT1-activating cytokines should induce the expression of keratin K17, whereas those cytokines that work through other mechanisms should not. Furthermore, because the STAT activation pathway is dependent upon protein phosphorylation events, phosphorylation inhibitors should attenuate the induction of keratin K17, whereas protein phosphatase inhibitors should augment it. To test this hypothesis, we analyzed lesional samples of inflammatory diseases using immunofluorescence, transfected keratinocytes with K17 gene promoter DNAs in the presence of various cytokines, and followed nuclear translocation of STAT1 in keratinocytes using specific antibodies. Confirming the hypothesis, we found that K17 is induced in psoriasis and dermatitis caused by delayed type hypersensitivity, which are associated with high levels of IFN gamma, but not in samples of atopic dermatitis, which is not. Two cytokines, interleukin-6 and leukemia inhibitory factor, which can induce phosphorylation of STAT1, can also induce K17 expression, whereas interleukin-3, interleukin-4, interleukin-10, and granulocyte macrophage colony stimulating factor have no effect on K17 expression. As expected, staurosporine and genistein inhibited, whereas okadaic acid augmented, the induction of K17 by IFN gamma. Our data indicate that in inflammatory skin diseases, lymphocytes, through the cytokines they produce, differently regulate not only each other, but also keratin gene expression in epidermis, one of their target tissues.
  • Iwao Ando, Mayumi Komine, Fujio Otsuka, Atsushi Kukita
    Journal of Dermatology 23 (4) 225 - 229 0385-2407 1996 [Refereed][Not invited]
     
    In lesions of malignant melanoma, melanoma cells are exposed to various cytokines produced by inflammatory reactions. As a result, transformation of melanoma cells is expected to occur. We studied alterations in human melanoma cell line ganglioside composition after exposing melanoma cell lines to interferon (IFN)-γ, interleukin (IL)-2, and IL-4 by biochemical methods. IFN-γ increases the ratio of a-series gangliosides and the ratio of GM3/GD3. This suggests an alteration of immunoreactivity, a decrease in ganglioside sialyltransferase II activity, and an decrease in the malignant character of these cells. The alteration of the ganglioside profile varied among cytokines and cell lines. The progression of malignant melanoma may be influenced by reciprocal interactions between the melanoma cells and the host immune system.
  • H Saeki, N Hayashi, M Komine, Y Soma, S Shimada, K Watanabe, T Hashimoto
    BRITISH JOURNAL OF DERMATOLOGY 134 (1) 152 - 155 0007-0963 1996/01 [Refereed][Not invited]
     
    We describe a 31-year-old Japanese woman with generalized pustular psoriasis treated with PUVA who subsequently developed a bullous disease. Throughout the disease course, there was no phase of psoriasis vulgaris. Although several reports describe coexistence of psoriasis vulgaris and bullous disease such as bullous periphigoid, coexistence of generalized pustular psoriasis without any phase of psoriasis vulgaris and bullous disease is rare. As for the bullous disease, direct immunofluorescence study showed IgG and C3 deposition along the basement membrane zone. Indirect immunofluorescence disclosed IgG antibasement membrane zone antibodies. Indirect immunofluorescence on 1 mol/l sodium chloride-split skin demonstrated linear IgG staining almost exclusively on the dermal side of the split. Western immunoblot analysis revealed that the antibody was directed to neither epidermolysis bullosa acquisita antigen nor bullous pemphigoid antigens. Considering the unusual clinical course, we suspect the possibility of a novel autoimmune blistering disease.
  • M KOMINE, IM FREEDBERG, M BLUMENBERG
    JOURNAL OF INVESTIGATIVE DERMATOLOGY 103 (4) 580 - 582 0022-202X 1994/10 [Refereed][Not invited]
     
    Keratinocytes are known to produce, store, and release IL-1 alpha and therefore we suspected that the DNA-mediated cell transfection procedure may release the stored IL-1 alpha from keratinocytes into the medium. Using enzyme-linked immunosorbent assay, we determined the IL-1 alpha concentration in culture supernatants during keratinocyte transfection. The following transfection methods were compared: lipofection with lipofectACE and lipofectAMINE (GIBCO), Ca-3(PO4)(2) co-precipitation, and polybrene-dimethylsulfoxide (DMSO). The supernatants were collected immediately prior to transfection, after 5-h incubation with lipofectin or Ca-3(PO4)(2), and 24 and 48 h after transfection. In the polybrene-DMSO method, the supernatant was also collected immediately before and after DMSO shock. LipofectAMINE caused the highest release of IL-1 alpha, whereas the lipofectACE and polybrene-DMSO mediated transfection with confluent cells released the least. The other two methods released intermediate levels of IL-1 alpha. Our data indicate that a substantial amount of IL-1 alpha is released during the keratinocyte transfection procedure, which can affect the results of transfection in studies of gene expression.
  • M KOMINE, K NASHIRO, A ASAHINA, T MATSUYAMA, M FURUE, T TSUCHIDA, Y ISHIBASHI
    INTERNATIONAL JOURNAL OF DERMATOLOGY 31 (12) 868 - 870 0011-9059 1992/12 [Refereed][Not invited]
     
    A 33-year-old Japanese woman was first seen in April 1987 complaining of small, itchy, erosive lesions and vesicles, which at first were restricted to her face, scalp, and oral mucosa for 1 year and gradually appeared on her legs and trunk. She developed these lesions during her third pregnancy in 1985. There were no abnormal findings in her baby and no correlation between the menstrual cycle and the appearance of the eruptions. Her past and family history was not contributory. Physical examination showed pruritic butterfly rash-like faint erythema with a few erosions and vesicles up to 8 mm in size on her face (Fig. 1). Similar small, itchy, crusted lesions and vesicles without an erythematous base were also scattered on the face, chest, upper back, and lower legs (Fig. 2). The edematous and erythematous plaques usually seen in vesicular pemphigoid (VP) were not found. She also noted gingival involvement with repeated vesicle formation (Fig. 3). Although the majority of the lesions healed without scar formation, some left milia and hypertrophic scars on which vesicles tended to recur repeatedly. Laboratory examination, including complete blood cell count, blood chemistry, urinalysis, chest x-ray, and upper GI tract studies, were all normal. Histologic examination demonstrated subepidermal blistering with moderate cellular infiltrates of lymphocytes and marked eosinophils in the upper dermis. Direct immunofluorescence study revealed the deposition of IgG and C3 at the basement membrane zone. Neither IgM nor IgA deposits were seen. Indirect immunofluorescence showed positive antibasement membrane zone IgG antibody at a titer of 1:20; however, complement-fixing antibasement membrane zone IgG antibody (herpes gestationis factor) was not detected. Indirect immunofluorescence using NaCl-separated skin as a substrate disclosed IgG deposition along the base of the epidermal roof, and there was no IgG deposition on the dermal side (Fig. 4). The ultrastructural localization of IgG deposition was observed in lamina lucida by direct immunoelectron microscopic study (Fig. 5). The patient was treated with oral antihistamines and topical steroid application with moderate improvement; however, a small number of vesicles (up to 5 mm in diameter) continued to appear occasionally. Neither large bulla nor swollen erythema were noted during her clinical course.
  • M KOMINE, T MATSUYAMA, Y NOJIMA, S MINODA, M FURUE, T TSUCHIDA, S SAKAI, Y ISHIBASHI
    INTERNATIONAL JOURNAL OF DERMATOLOGY 31 (9) 653 - 656 0011-9059 1992/09 [Refereed][Not invited]

MISC

  • 日本皮膚科学会マニュアル 乾癬における生物学的製剤の使用ガイダンス(2019年版)
    大槻 マミ太郎, 佐伯 秀久, 照井 正, 森田 明理, 佐野 栄紀, 今福 信一, 朝比奈 昭彦, 小宮根 真弓, 江藤 隆史, 鳥居 秀嗣, 安部 正敏, 五十嵐 敦之, 中川 秀己, 渡辺 彰, 四柳 宏, 日本皮膚科学会乾癬生物学的製剤検討委員会  日本皮膚科学会雑誌  129-  (9)  1845  -1864  2019/08  [Not refereed][Not invited]
  • 日本皮膚科学会マニュアル 乾癬における生物学的製剤の使用ガイダンス(2019年版)
    大槻 マミ太郎, 佐伯 秀久, 照井 正, 森田 明理, 佐野 栄紀, 今福 信一, 朝比奈 昭彦, 小宮根 真弓, 江藤 隆史, 鳥居 秀嗣, 安部 正敏, 中川 秀己, 渡辺 彰, 四柳 宏, 日本皮膚科学会乾癬生物学的製剤検討委員会  日本皮膚科学会雑誌  129-  (9)  1845  -1907  2019/08  [Not refereed][Not invited]
  • Japanese Dermatological Association Guidelines Development Committee for the Guidelines for the Management and Treatment of Generalized Pustular Psoriasis
    Fujita H, Terui T, Hayama K, Akiyama M, Ikeda S, Mabuchi T, Ozawa A, Kanekura T, Kurosawa M, Komine M, Nakajima K, Sano S, Nemoto O, Muto M, Imai Y, Yamanishi K, Aoyama Y, Iwatsuki K  J Dermatol  45-  (11)  1235  -1270  2018/11  [Refereed][Not invited]
  • 【原因が明らかな皮膚病】 <臨床例> Muir-Torre症候群
    加藤 めぐみ, 北島 麻耶子, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  皮膚病診療  40-  (2)  161  -164  2018/02  [Not refereed][Not invited]
     
    <症例のポイント>Muir-Torre症候群(MTS)は、DNAミスマッチ修復遺伝子変異が原因の、主に大腸癌をはじめとする遺伝性多発癌疾患であるLynch症候群のうち、脂腺腫瘍やケラトアカントーマを合併する一亜型である。胸部脂腺腫の切除治療を契機に、過去切除された皮膚腫瘍と大腸癌、家族歴、既往歴などの再検討から、MTSと診断した1例を報告した。大腸癌組織を用いたマイクロサテライト不安定性検査が陽性であること、脂腺腫の免疫染色でDNAミスマッチ修復遺伝子の1つであるMLH1蛋白の発現がみられないことを確認し、さらに遺伝子検査でMLH1遺伝子のExon4-19に及ぶ欠損を同定した。(著者抄録)
  • 【乾癬-病態・臨床の最新知見-】 乾癬の治療 治療総論
    小宮根 真弓, 大槻 マミ太郎  日本臨床  76-  (1)  86  -90  2018/01  [Not refereed][Not invited]
  • 乾癬の病態理論と治療の変遷
    小宮根 真弓  皮膚病診療  39-  (12)  1236  -1241  2017/12  [Not refereed][Not invited]
  • 【乾癬-2017】 <臨床例>photosensitive psoriasis
    永島 和貴, 梅本 尚可, 津田 英利, 小宮根 真弓, 出光 俊郎, 川瀬 正昭  皮膚病診療  39-  (12)  1247  -1250  2017/12  [Not refereed][Not invited]
     
    <症例のポイント>乾癬性紅皮症の治療経過中にnarrow band ultraviolet B(以下、NB-UVB)照射療法を行い膿疱性乾癬が誘発された。IL36RN遺伝子変異検索ではp.Asn47Serのヘテロ変異を認めた。通常はキャリアと解釈されるヘテロ変異症例でもなんらかの複合要因のもとに炎症反応が強く働き、膿疱性乾癬の皮疹が発症する可能性があり、自験例は光線過敏症が要因と考えた。(著者抄録)
  • H. Tsuda, M. Komine, M. Ohtsuki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  137-  (10)  S261  -S261  2017/10  [Not refereed][Not invited]
  • T. Demitsu, Y. Jinbu, M. Komine, N. Umemoto, M. Kakurai, K. Yoneda, A. Yamamoto, H. Tsuda, M. Ohtsuki, Y. Mori  JOURNAL OF INVESTIGATIVE DERMATOLOGY  137-  (10)  S217  -S217  2017/10  [Not refereed][Not invited]
  • H. Okada, M. Komine, H. Tsuda, K. Kamiya, M. Ohtsuki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  137-  (10)  S295  -S295  2017/10  [Not refereed][Not invited]
  • 【痒み十人十色-がんこな痒みの仕組みと対処法】 (Part1)痒い疾患の対処法ア・ラ・カルト(case 11) 乾癬の痒み
    小宮根 真弓, 大槻 マミ太郎  Visual Dermatology  16-  (11)  1076  -1077  2017/10  [Not refereed][Not invited]
  • 鈴木 正之, 細田 里美, 山田 朋子, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  127-  (10)  2313  -2319  2017/09  [Not refereed][Not invited]
     
    77歳、男の水疱性類天疱瘡(BP)で、プレドニゾロン(PSL)内服とDFPP、ミノサイクリン、ニコチン酸アミドなどの併用をしたが、難治の症例であった。経過中に膀胱がんの再発や肺結核の疑いが生じたため、皮疹再発時に免疫抑制をきたす治療法を選択することが困難な状況であった。このため大量免疫グロブリン(IVIG)療法の併用を選択し、皮疹の再燃を抑制した。その後PSLの減量を進めながらBPの再発を防ぐ目的でIVIG療法の併用を継続した。計16クール施行し、その間再燃なくPSL漸減が可能であった。(著者抄録)
  • 小川 智広, 中野 尚美, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎, 福留 潤  皮膚科の臨床  59-  (9)  1391  -1394  2017/08  [Not refereed][Not invited]
     
    症例は71歳男性で、3年前より右耳介後部に黒色結節を自覚しており、時々掻破による出血があった。精査加療目的で当科を紹介受診した。頭頸部造影MRIでは右耳介後部にT1強調画像で低信号領域、T2強調画像で高信号領域を認め、筋層との境界は一部不明瞭で筋への浸潤が疑われた。皮膚生検で基底細胞癌(BCC)と診断後、局所麻酔下で局面より5mm離し、僧帽筋膜直上まで人工真皮植皮術を施行した。切除標本から、神経周囲浸潤、筋層浸潤およびリンパ節への直接浸潤を認めた浸潤型BCCと最終診断した。切除断端陰性であることを確認し、待機的に全層植皮術を行った。高リスク型のBCCとして、放射線療法を施行(50Gy、25Fr、週5日)した。術後8ヵ月(放射線治療終了4ヵ月後)のフォローで再発転移なく、現在経過観察中である。
  • 小川 智広, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  臨床皮膚科  71-  (8)  635  -639  2017/07  [Not refereed][Not invited]
     
    36歳,女性.4年前から肛門周囲に潰瘍が出現した.近医皮膚科や肛門科で抗菌薬外用等するも改善せず,生検病理組織像でLCHを疑われ当院を紹介受診した.外陰部から会陰,肛門周囲に多発潰瘍,額に黄色丘疹,点状痂皮,体幹に褐色斑の多発を認めた.再生検でCD1a陽性細胞の表皮内浸潤,真皮の結節状浸潤あり,LCHと確定診断した.ステロイド外用にて陰部潰瘍は縮小傾向を認め,一定の効果を示したが,全身精査で腟壁,尿道,甲状腺浸潤がみられ,多臓器型として今後化学療法を施行予定である.また,LCHではBRAF V600変異がみられる例があり分子標的薬の有効性が指摘されているが,自験例では変異はみられなかった.(著者抄録)
  • M. Jin, M. Komine, H. Tsuda, S. Tominaga, M. Ohtsuki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  137-  (5)  S74  -S74  2017/05  [Not refereed][Not invited]
  • 右耳介後部皮膚の気管支原性上皮迷入の1例
    中野 尚美, 小宮根 真弓, 村田 哲, 大槻 マミ太郎, 仲矢 丈雄, 河田 浩敏, 田中 亨, 和田 聖哉, 河野 由美, 矢田 ゆかり  日本皮膚科学会雑誌  127-  (4)  636  -637  2017/04  [Not refereed][Not invited]
  • 【最近のトピックス2017 Clinical Dermatology 2017】皮膚科医のための臨床トピックス ジェネリックからバイオシミラーへ
    小宮根 真弓  臨床皮膚科  71-  (5)  183  -185  2017/04  [Not refereed][Not invited]
     
    ジェネリックとは,低分子医薬品の後発医薬品を指すが,バイオシミラーはバイオ医薬品の後続品を指す.低分子医薬品の開発は頭打ちであり,今後はバイオ医薬品の開発の伸びが期待されており,バイオシミラーの開発が進むことが予想される.低分子医薬品と比較して,バイオ医薬品の製造工程は複雑であり,環境に依存する微生物の細胞内で産生され,培養,精製など多数の工程を踏む必要がある.バイオシミラーでは他社が製造した先行品の詳細な情報を得ることが難しいため,宿主・ベクター系,培養・精製の工程を独自に確立する必要があり,アミノ酸配列は同一であっても,糖鎖修飾や不純物プロファイルが異なるために,免疫原性や有効性が異なる可能性がある.そのため,バイオシミラーは,先行品と同等・同質の品質,安全性,有効性を示すことが厚生労働省から求められており,最終的には臨床試験による同等性,同質性の証明が必要である.(著者抄録)
  • 【鼻の皮膚病】 臨床例 鼻翼に生じた有茎性粉瘤
    平野 智子, 村田 哲, 伏間江 貴之, 前川 武雄, 小宮根 真弓, 大槻 マミ太郎  皮膚病診療  39-  (3)  279  -282  2017/03  [Not refereed][Not invited]
     
    <症例のポイント>左鼻翼に生じた多彩な毛細血管拡張を伴う有茎性表皮嚢腫の1例を経験した。有茎性となった理由として、下床・皮膚・嚢腫の硬さのバランスがあげられる。切除組織標本の一部に毛包様構造を認めており、背景にfolliculosebaceous cystic hamartoma(FSCH)が存在していた可能性がある。(著者抄録)
  • 小川 智広, 藤田 有理香, 佐藤 篤子, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  臨床皮膚科  71-  (3)  221  -224  2017/03  [Not refereed][Not invited]
     
    82歳,女性.13年前胃癌全摘,2年前よりアルツハイマー型認知症あり.介護度は全介助で,おむつを着用していた.1ヵ月前より臀部,大陰唇に弾性硬,紫紅色の扁平隆起性結節が左右対称性に多発,部分的に融合し敷石状を呈していた.発症前後で下痢,軟便があった.生検病理組織像にて表皮突起の延長,真皮浅層血管周囲に形質細胞,好酸球,好中球を含む単核球浸潤を認め,diaper area granuloma of the agedと診断した.清潔指導およびベタメタゾン酪酸エステルプロピオン酸エステルの外用を行い,2週間後には軽快した.過去30年の文献検索で自験例を含めた22症例を集積検討した結果,20例が女性と明らかに性差があることを見出し,その原因について考察した.(著者抄録)
  • エポキシ樹脂による職業性全身型接触皮膚炎の1例
    福田 浩孝, 伏間江 貴之, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  Journal of Environmental Dermatology and Cutaneous Allergology  10-  (4)  440  -440  2016/10  [Not refereed][Not invited]
  • 【皮膚疾患ペディア】 膿疱性乾癬(汎発型)診療ガイドライン
    小宮根 真弓  日本医師会雑誌  145-  (特別2)  S210  -S210  2016/10  [Not refereed][Not invited]
  • ニボルマブが遠隔転移に早期から奏効した口腔粘膜悪性黒色腫の1例
    伏間江 貴之, 前川 武雄, 小宮根 真弓, 村田 哲, 中野 崇史, 土屋 欣之, 大槻 マミ太郎  西日本皮膚科  78-  (5)  544  -544  2016/10  [Not refereed][Not invited]
  • 瓢箪型結節を形成し片側のみメラニン色素のみられたBednar腫瘍(pigmented dermatofibrosarcoma protuberans)の1例
    福田 浩孝, 伏間江 貴之, 前川 武雄, 小宮根 真弓, 村田 哲, 大山 正彦, 大槻 マミ太郎  西日本皮膚科  78-  (5)  544  -544  2016/10  [Not refereed][Not invited]
  • M. Jin, M. Komine, H. Tsuda, S. Tominaga, M. Ohtsuki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  136-  (9)  S218  -S218  2016/09  [Not refereed][Not invited]
  • H. Tsuda, M. Komine, M. Jin, S. Tominaga, M. Ohtsuki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  136-  (9)  S176  -S176  2016/09  [Not refereed][Not invited]
  • 【脊椎関節炎の病態と治療】 乾癬性関節炎に対する生物学的製剤治療
    岸本 恵美, 小宮根 真弓, 大槻 マミ太郎  炎症と免疫  24-  (5)  421  -425  2016/08  [Not refereed][Not invited]
     
    乾癬性関節炎は、関節リウマチ同様、初期の治療介入が重要であることが示されている。現在わが国で乾癬性関節炎に保険適応のある生物学的製剤はインフリキシマブ、アダリムマブ、ウステキヌマブ、セクキヌマブの4剤にかぎられており、いずれの薬剤をどの時期に使うかについては、国内外のガイドラインを準拠するとともに、個々の症例の特性、合併症などに照らし合わせて決定するべきである。現時点では、乾癬性関節炎に生物学的製剤を導入する際、多くの場合でTNF阻害薬が第一選択と考えられている。一方、ウステキヌマブやセクキヌマブも関節炎に一定の効果を示す報告がなされ、TNF阻害薬が使えない症例や効果不十分例ではそれらの薬剤も考慮できるようになり、治療の選択肢が広がっている。(著者抄録)
  • 広範に広がるボーエン様丘疹症の1例
    前川 武雄, 足立 晃正, 伏間江 貴之, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚外科学会誌  20-  (2)  152  -153  2016/08  [Not refereed][Not invited]
  • 外科的切除を行った径2cm大の左側頭部血管肉腫の1例
    伏間江 貴之, 前川 武雄, 中野 尚美, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚外科学会誌  20-  (2別冊)  220  -220  2016/08  [Not refereed][Not invited]
  • Hideshi Torii, Tadashi Terui, Miyuki Matsukawa, Kazumi Takesaki, Mamitaro Ohtsuki, Hidemi Nakagawa, Osamu Nemoto, Hidetoshi Takahashi, Mayumi Komine, Takafumi Etoh, Atsuyuki Igarashi, Akihiko Asahina, Akira Ozawa, Akimichi Morita, Shigetoshi Sano  Journal of Dermatology  43-  (7)  767  -778  2016/07  [Refereed][Not invited]
     
    © 2015 Japanese Dermatological Association A large-scale prospective post-marketing surveillance was conducted to evaluate the safety and efficacy of infliximab in Japanese patients with plaque psoriasis, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma. This study was conducted in all psoriasis patients treated with infliximab after its Japanese regulatory approval. Infliximab was administrated at 5 mg/kg at weeks 0, 2 and 6, and every 8 weeks thereafter. Patients were serially enrolled and observed for 6 months to evaluate the safety and efficacy. The safety and efficacy were evaluated in 764 and 746 patients, respectively. Incidences of any and serious adverse drug reactions were 22.51% and 6.94%, respectively, and those of any and serious infusion reactions were 6.15% and 1.31%, respectively, which were comparable with the results in the post-marketing surveillance with 5000 rheumatoid arthritis patients in Japan. Major adverse drug reactions during the follow-up period were infections (5.10%) including pneumonia, cellulitis and herpes zoster, however, no tuberculosis was observed. The safety profiles were equivalent, regardless of the psoriasis types. No new safety problems were identified. The response rates on global improvement and median improvement rate of Psoriasis Area and Severity Index in all patients were 88.0% and 85.0%, respectively. Of note, the efficacy was equivalent for each psoriasis type as well as for each body region. Infliximab was also effective in pustular psoriasis symptoms, joint symptoms and nail psoriasis, as well as improvement of quality of life. Infliximab was confirmed to be highly effective and well tolerated in treating refractory psoriasis, including pustular psoriasis and psoriatic erythroderma.
  • 泌尿器科との合同手術で腫瘍完全切除をし得た外陰部Bowen病の1例
    伏間江 貴之, 前川 武雄, 藤田 有理香, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚外科学会誌  20-  (1)  80  -81  2016/07  [Not refereed][Not invited]
  • Muir-Torre症候群の1例
    加藤 めぐみ, 北島 麻耶子, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  126-  (7)  1311  -1311  2016/06  [Not refereed][Not invited]
  • ニフェジピン内服にて繰り返し汎発性膿疱化が誘発された膿疱性乾癬の1例
    松本 藍, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  126-  (7)  1315  -1315  2016/06  [Not refereed][Not invited]
  • photosensitive psoriasisの1例
    永島 和貴, 中村 哲史, 梅本 尚可, 山田 朋子, 高澤 摩耶, 塚原 理恵子, 出光 俊郎, 五野 貴久, 寺井 千尋, 津田 英利, 小宮根 真弓, 大槻 マミ太郎  日本皮膚科学会雑誌  126-  (7)  1316  -1316  2016/06  [Not refereed][Not invited]
  • 若年者に発症した尋常性天疱瘡の1例
    北島 麻耶子, 加藤 めぐみ, 伏間江 貴之, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎, 作山 葵, 神部 芳則, 橋本 隆  日本皮膚科学会雑誌  126-  (7)  1320  -1320  2016/06  [Not refereed][Not invited]
  • 径5mm大の若年者足底悪性黒色腫と診断した1例
    伏間江 貴之, 足立 晃正, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  126-  (7)  1326  -1326  2016/06  [Not refereed][Not invited]
  • 塚原 理恵子, 若旅 功二, 山田 朋子, 小宮根 真弓, 村田 哲, 出光 俊郎, 大槻 マミ太郎  皮膚科の臨床  58-  (7)  1198  -1199  2016/06  [Not refereed][Not invited]
     
    56歳男。受診の約3年前、左腋窩に母指頭大の結節が出現し、1年前には手挙大まで増大した。約3ヵ月前に結節の一部が潰瘍化し、軽度の出血を認めるようになった。初診時、結節は8.0×6.5cm大でドーム状に隆起しており、結節の胸側は深く大きく潰瘍化し、黒色の小結節からなる周堤を形成していた。結節の背側は硬く充実性で、表面に大小さまざまな小結節が多発融合し、顆粒状ないし桑実状を呈していた。これらの病変は4つの部分に大別することができ、内訳は、1)胸腹側黒色小結節からなる周堤部、2)背側淡紅色透明な小結節が融合する部分、3)中央部の白色調部分、4)胸側潰瘍部であり、各々の組織像は、1)が充実型の基底細胞癌(BCC)、2)が嚢腫型のBCC、3)がモルフェア型のBCC、4)が腺様型のBCCであった。治療は、腫瘍の辺縁から1〜2cmのマージンをとり大胸筋の深さまでの腫瘍切除術を行い、術後3年の現在まで再発・転移は認めていない。
  • 薬疹治療中に一過性に出現した線状IgA水疱症の1例
    中野 尚美, 足立 晃正, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  西日本皮膚科  78-  (3)  304  -304  2016/06  [Not refereed][Not invited]
  • 4歳児に発症した弾性線維性仮性黄色腫(PXE)
    牧 伸樹, 藤田 有理香, 藤田 悦子, 小宮根 真弓, 村田 哲, 大槻 マミ太郎, 出光 俊郎, 大久保 佑美, 宇谷 厚志  西日本皮膚科  78-  (3)  310  -310  2016/06  [Not refereed][Not invited]
  • 乾癬治療における生物学的製剤の位置づけの再考 生物学的製剤はファーストラインになりうるか?
    小宮根 真弓  日本皮膚科学会雑誌  126-  (5)  844  -844  2016/05  [Not refereed][Not invited]
  • 汎発型Hailey-Hailey病の1例
    北島 麻耶子, 小宮根 真弓, 村田 哲, 大槻 マミ太郎, 岡田 嘉右衛門  日本皮膚科学会雑誌  126-  (5)  945  -945  2016/05  [Not refereed][Not invited]
  • 乳房下縁の紅色硬結を主訴に当科紹介された乳癌の1例
    加藤 めぐみ, 佐藤 篤子, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  126-  (5)  954  -954  2016/05  [Not refereed][Not invited]
  • 瓢箪型結節を形成し片側のみメラニン色素のみられたBednar腫瘍の1例
    福田 浩孝, 伏間江 貴之, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎, 大山 正彦  日本皮膚科学会雑誌  126-  (5)  958  -958  2016/05  [Not refereed][Not invited]
  • 右耳介後部皮膚の気管支原性上皮迷入の1例
    中野 尚美, 小宮根 真弓, 村田 哲, 大槻 マミ太郎, 仲矢 丈雄, 河田 浩敏, 田中 亨, 和田 聖哉, 河野 由美, 矢田 ゆかり  日本皮膚科学会雑誌  126-  (5)  963  -963  2016/05  [Not refereed][Not invited]
  • Hepatitis B virus-associated vasculitis(Chapel Hill分類2012)の1例
    平野 智子, 佐藤 篤子, 小宮根 真弓, 村田 哲, 大槻 マミ太郎, 橋壁 道雄  日本皮膚科学会雑誌  126-  (5)  964  -964  2016/05  [Not refereed][Not invited]
  • シクロスポリンが著効した毛孔性紅色粃糠疹の1例
    伏間江 貴之, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  126-  (5)  980  -980  2016/05  [Not refereed][Not invited]
  • 認知症でおむつ常用患者にみられたdiaper area granuloma of the agedの1例
    小川 智広, 藤田 有理香, 佐藤 篤子, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  126-  (5)  1000  -1000  2016/05  [Not refereed][Not invited]
  • 当科における新規薬剤による悪性黒色腫治療の現状
    前川 武雄, 伏間江 貴之, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  126-  (6)  1124  -1124  2016/05  [Not refereed][Not invited]
  • CEA陽性表皮増生を伴ったpapillary tubular adenomaの1例
    村田 哲, 宮本 有希子, 小宮根 真弓, 大槻 マミ太郎  日本皮膚科学会雑誌  126-  (6)  1137  -1137  2016/05  [Not refereed][Not invited]
  • 原発性皮膚CD4陽性小・中細胞型T細胞リンパ腫を疑った一例
    北島 麻耶子, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚悪性腫瘍学会学術大会プログラム・抄録集  32回-  130  -130  2016/05  [Not refereed][Not invited]
  • ベムラフェニブ投与中にVogt-小柳-原田病を合併した1例
    伏間江 貴之, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚悪性腫瘍学会学術大会プログラム・抄録集  32回-  151  -151  2016/05  [Not refereed][Not invited]
  • CBDCA+VP-16による化学療法を施行したメルケル細胞癌の2例
    前川 武雄, 北島 麻耶子, 伏間江 貴之, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚悪性腫瘍学会学術大会プログラム・抄録集  32回-  172  -172  2016/05  [Not refereed][Not invited]
  • 診断に苦慮した鼻背発症の汗腺系附属器癌の1例
    中野 尚美, 小川 智広, 小宮根 真弓, 村田 哲, 大槻 マミ太郎, 山根 康弘  日本皮膚科学会雑誌  126-  (4)  438  -438  2016/04  [Not refereed][Not invited]
  • 薬疹治療中に一過性に出現した線状IgA水疱症の1例
    中野 尚美, 足立 晃正, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  126-  (3)  306  -306  2016/03  [Not refereed][Not invited]
  • 両足背潰瘍、浮腫、疼痛を主訴とした両側重症下肢虚血の1例
    北島 麻耶子, 足立 晃正, 平野 智子, 伏間江 貴之, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎, 佐藤 弘隆, 堀内 早苗  日本皮膚科学会雑誌  126-  (3)  306  -306  2016/03  [Not refereed][Not invited]
  • イレッサ内服に関連したerosive pustular dermatosis of the scalp様皮疹の1例
    加藤 めぐみ, 北島 麻耶子, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  126-  (3)  306  -306  2016/03  [Not refereed][Not invited]
  • ヨウ化カリウム内服に温熱療法を併用し短期間で改善を得たスポロトリコーシスの小児例
    伏間江 貴之, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  126-  (3)  307  -307  2016/03  [Not refereed][Not invited]
  • 特発性後天性全身性無汗症の1例
    岡田 寛文, 伏間江 貴之, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  126-  (3)  307  -307  2016/03  [Not refereed][Not invited]
  • 両側眼瞼腫脹を契機に診断されたMikulicz病の1例
    伏間江 貴之, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  126-  (3)  307  -307  2016/03  [Not refereed][Not invited]
  • 左手首屈側に帯状に集簇する汗管腫の1例
    中野 尚美, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  126-  (3)  308  -308  2016/03  [Not refereed][Not invited]
  • Muir-Torre症候群の1例
    加藤 めぐみ, 北島 麻耶子, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  126-  (3)  308  -308  2016/03  [Not refereed][Not invited]
  • 尋常性乾癬に合併した自己免疫性水疱症の1例
    中野 尚美, 加藤 めぐみ, 小宮根 真弓, 村田 哲, 大槻 マミ太郎, 鈴木 宏  日本皮膚科学会雑誌  126-  (3)  308  -308  2016/03  [Not refereed][Not invited]
  • diaper area granuloma of the agedの1例
    小川 智広, 藤田 有理香, 佐藤 篤子, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  126-  (3)  308  -308  2016/03  [Not refereed][Not invited]
  • 乳房下縁紅色結節を主訴に当科紹介された乳癌の1例
    加藤 めぐみ, 佐藤 篤子, 小宮根 真弓, 村田 哲, 大槻 マミ太郎, 塚田 篤子  日本皮膚科学会雑誌  126-  (3)  309  -309  2016/03  [Not refereed][Not invited]
  • 中年鼻背に急速増大した石灰化上皮腫の1例
    福田 浩孝, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎, 藤平 正利  日本皮膚科学会雑誌  126-  (3)  309  -309  2016/03  [Not refereed][Not invited]
  • ニフェジピン内服にて繰り返し汎発性膿疱化が誘発された膿疱性乾癬の1例
    松本 藍, 小宮根 真弓, 大槻 マミ太郎  角化症研究会記録集  30-  108  -111  2016/03  [Not refereed][Not invited]
  • 遺伝性・非遺伝性白色海綿状母斑の免疫組織化学的および電顕的検討
    出光 俊郎, 梅本 尚可, 神部 芳則, 山本 亜紀, 森 良之, 米田 耕造, 津田 英利, 大槻 マミ太郎, 小宮根 真弓  角化症研究会記録集  30-  122  -126  2016/03  [Not refereed][Not invited]
  • 神経周囲浸潤、筋層浸潤およびリンパ節への直接浸潤を認めた右耳介後部の浸潤型基底細胞癌の一例
    小川 智広, 中野 尚美, 加藤 めぐみ, 北島 麻耶子, 藤田 悦子, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  Skin Surgery  25-  (1)  61  -61  2016/02  [Not refereed][Not invited]
  • 当科における耳介からの複合組織移植(composite graft)による鼻翼再建を行った症例の検討
    伏間江 貴之, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  Skin Surgery  25-  (1)  66  -66  2016/02  [Not refereed][Not invited]
  • 【免疫疾患Update】 皮膚関連疾患 皮膚科における関節症性乾癬(PsA)診療のコツ
    小宮根 真弓  クリニシアン  63-  (2)  235  -239  2016/02  [Not refereed][Not invited]
  • イレッサ内服に関連したerosive pustular dermatosis of the scalp様皮疹の1例
    加藤 めぐみ, 北島 麻耶子, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  126-  (1)  29  -29  2016/01  [Not refereed][Not invited]
  • 【臨床医として皮膚病変をこう診る】 乾癬
    小宮根 真弓  成人病と生活習慣病  46-  (1)  81  -90  2016/01  [Not refereed][Not invited]
     
    乾癬は、寛解・増悪を繰り返す、難治性の慢性炎症性皮膚疾患である。尋常性乾癬、滴状乾癬、関節症性乾癬、膿疱性乾癬、乾癬性紅皮症の5型があるが、90%は尋常性乾癬が占める。遺伝的背景に環境要因が加わって発症すると考えられているが、その原因は不明である。近年、生物学的製剤の発展から病態が急速に解明されつつあり、Th17細胞、形質細胞様樹状細胞、骨髄由来樹状細胞の重要性と、膿疱性乾癬では表皮細胞に発現する分子の遺伝子異常が報告されている。メタボリックシンドロームとの病態の共通性、関連性が重視され、乾癬は皮膚のみならず全身の炎症性疾患であるととらえられている。治療は、外用を中心とした局所治療と、内服、光線、生物学的製剤などの全身治療がある。外用剤にはステロイド外用剤、活性型ビタミンD3外用剤、およびその合剤がある。内服薬としてはシクロスポリン、エトレチナート、乾癬に対する適応はないがメトトレキサートがしばしば使用されている。光線療法ではPUVA療法、PUVA-bath療法、ナローバンドUVB療法が行われている。生物学的製剤では、現在アダリムマブ、インフリキシマブ、ウステキヌマブ、セクキヌマブが使用可能である。(著者抄録)
  • 左手関節部の橈骨動脈瘤に合併した多発類上皮血管腫の1例
    平野 智子, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  西日本皮膚科  77-  (6)  609  -609  2015/12  [Not refereed][Not invited]
  • IL-33は表皮角化細胞核内で細胞分裂に関与している
    津田 英利, 小宮根 真弓, 富永 眞一, 大槻 マミ太郎  日本生化学会大会・日本分子生物学会年会合同大会講演要旨集  88回・38回-  [1P0122]  -[1P0122]  2015/12  [Not refereed][Not invited]
  • 【整形外科診療に役立つ皮膚科の知識】 掌蹠膿疱症 掌蹠膿疱症性骨関節炎、SAPHO症候群
    小宮根 真弓  整形・災害外科  58-  (12)  1561  -1566  2015/11  [Not refereed][Not invited]
  • 複数の市販鎮痛薬で固定薬疹を生じた1例
    伏間江 貴之, 村田 哲, 小宮根 真弓, 大槻 マミ太郎  Journal of Environmental Dermatology and Cutaneous Allergology  9-  (5)  451  -451  2015/11  [Not refereed][Not invited]
  • 照井 正, 秋山 真志, 池田 志斈, 小澤 明, 金蔵 拓郎, 黒澤 美智子, 小宮根 真弓, 佐野 栄紀, 根本 治, 武藤 正彦, 山西 清文, 岩月 啓氏, 青山 裕美, 今井 康友, 中島 喜美子, 馬渕 智生, 藤田 英樹, 葉山 惟大, 日本皮膚科学会膿疱性乾癬, 汎発型, 診療ガイドライン作成委員会  日本皮膚科学会雑誌  125-  (12)  2211  -2257  2015/11  [Not refereed][Not invited]
  • メトトレキサート関連リンパ増殖性疾患の1例
    上田 有希子, 小宮根 真弓, 村田 哲, 丸山 暁人, 畑野 かおる, 大槻 マミ太郎  皮膚科の臨床  57-  (11)  1755  -1758  2015/10  [Not refereed][Not invited]
     
    75歳女。四肢や臀部に多発する皮下結節を主訴とした。メトトレキサート(MTX)、アダリムマブにて加療中の関節リウマチ患者であり、4ヵ月前より主訴が出現した。両前腕、左大腿、臀部に皮下の結節病変を認めたが、発熱や体重減少などの全身症状はなかった。結節病変の生検の病理組織学的所見では真皮内から脂肪織に中型〜大型で歪な核を有する好塩基性細胞が巣状に浸潤し、皮膚組織のEBV-DNA PCRは陽性、免疫染色はCD20、CD30陽性、CD79a、CD3、EBER陰性であり、diffuse large B-cell lymphomaに類似した組織像であった。検査所見や治療経過などからEBV再活性化を伴うMTX関連リンパ増殖性疾患と診断し、MTXのみ中止としたところ、皮膚病変はすべて消退した。
  • T. Oshio, M. Komine, H. Tsuda, S. Tominaga, H. Saito, S. Nakae, M. Ohtsuki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  135-  S29  -S29  2015/09  [Not refereed][Not invited]
  • H. Tsuda, M. Komine, S. Tominaga, M. Ohtsuki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  135-  S74  -S74  2015/09  [Not refereed][Not invited]
  • 広範に広がるボーエン様丘疹症の1例
    前川 武雄, 足立 晃正, 伏間江 貴之, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚外科学会誌  19-  (2別冊)  205  -205  2015/09  [Not refereed][Not invited]
  • 泌尿器科との合同手術で腫瘍完全切除をし得た外陰部Bowen病の1例
    伏間江 貴之, 前川 武雄, 藤田 有理香, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚外科学会誌  19-  (2別冊)  206  -206  2015/09  [Not refereed][Not invited]
  • 当科におけるニボルマブの使用経験
    伏間江 貴之, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚悪性腫瘍学会学術大会プログラム・抄録集  31回-  145  -145  2015/07  [Not refereed][Not invited]
  • 鼡径リンパ節転移をきたした大腿部基底細胞癌の1例
    前川 武雄, 藤田 有理香, 佐藤 篤子, 伏間江 貴之, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚悪性腫瘍学会学術大会プログラム・抄録集  31回-  181  -181  2015/07  [Not refereed][Not invited]
  • 当科での非挿管下局所麻酔手術におけるデクスメデトミジンの使用経験
    伏間江 貴之, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚外科学会誌  19-  (1)  40  -41  2015/07  [Not refereed][Not invited]
  • 当科における下肢静脈瘤血管内レーザー焼灼術の治療経験
    前川 武雄, レパヴー・アンドレ, 伏間江 貴之, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚外科学会誌  19-  (1)  60  -61  2015/07  [Not refereed][Not invited]
  • 生物学的製剤時代における乾癬治療
    尹 浩信, 小宮根 真弓  西日本皮膚科  77-  (3)  288  -288  2015/06  [Not refereed][Not invited]
  • 皮膚筋炎との鑑別を要した抗セントロメア抗体陽性の限局型全身性強皮症の1例
    伏間江 貴之, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  125-  (7)  1449  -1449  2015/06  [Not refereed][Not invited]
  • 踵部の石灰化を伴う血管平滑筋腫(angiomyoma with severe calcification)
    平野 智子, 伏間江 貴之, 藤田 有理香, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  125-  (7)  1449  -1449  2015/06  [Not refereed][Not invited]
  • 線維肉腫様変化を伴う隆起性皮膚線維肉腫(fibrosarcomatous variant of dermatofibrosarcoma portuberans)の1例
    松本 藍, 足立 晃正, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  125-  (7)  1449  -1449  2015/06  [Not refereed][Not invited]
  • 上口唇の基底細胞癌切除後、オープン法で治療した1例
    中山 一, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  125-  (7)  1450  -1450  2015/06  [Not refereed][Not invited]
  • 鼻背インプラント除去5年後に再発したパラフィノーマの1例
    松本 藍, 足立 晃正, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  125-  (7)  1450  -1450  2015/06  [Not refereed][Not invited]
  • 鼻翼に発生した有茎性表皮嚢腫の1例
    近藤 泰之, 伏間江 貴之, 平野 智子, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎, 高山 五郎  日本皮膚科学会雑誌  125-  (7)  1450  -1450  2015/06  [Not refereed][Not invited]
  • 踵部に生じた角化型悪性黒色腫の1例
    中川 志保, 松本 藍, 足立 晃正, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  125-  (7)  1451  -1451  2015/06  [Not refereed][Not invited]
  • 踵部に生じたclear cell sarcoma
    平野 智子, 伏間江 貴之, 藤田 有理香, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  125-  (7)  1451  -1451  2015/06  [Not refereed][Not invited]
  • 栄養障害に伴う皮膚粘膜障害の1例 ペラグラ、壊死性遊走性紅斑、亜鉛欠乏性皮膚炎の異同について
    松本 藍, 足立 正晃, 藤田 有理香, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  125-  (7)  1451  -1451  2015/06  [Not refereed][Not invited]
  • 高齢者陰嚢の疣状黄色腫(Verruciform xanthoma)の1例
    中村 明生, 足立 晃正, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  125-  (7)  1452  -1452  2015/06  [Not refereed][Not invited]
  • 臨床的に足底表皮嚢腫が疑われたporoid cell neoplasmの1例
    村上 琢哉, 足立 晃正, 藤田 有理香, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎, 澤田 実  日本皮膚科学会雑誌  125-  (7)  1452  -1452  2015/06  [Not refereed][Not invited]
  • 赤色、白色衛星病変を伴い術前診断に苦慮した踵部悪性黒色腫の1例
    近藤 泰之, 伏間江 貴之, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  125-  (7)  1452  -1452  2015/06  [Not refereed][Not invited]
  • 前額と頸部に限局して夏期に皮疹を反復するダリエー(Darier)病の1例
    松本 藍, 小宮根 真弓, 村田 哲, 大槻 マミ太郎, 平賀 教子  日本皮膚科学会雑誌  125-  (7)  1453  -1453  2015/06  [Not refereed][Not invited]
  • 苔癬様型皮膚サルコイドの1例
    岸 由利子, 松本 藍, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  125-  (7)  1453  -1453  2015/06  [Not refereed][Not invited]
  • MRIで脂肪肉腫が疑われたspindle cell lipomaの1例
    中野 尚美, 伏間江 貴之, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  125-  (7)  1453  -1453  2015/06  [Not refereed][Not invited]
  • 未治療糖尿病ありコルヒチン単独内服で治療した後天性表皮水疱症の1例
    平野 智子, 足立 晃正, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  125-  (7)  1453  -1453  2015/06  [Not refereed][Not invited]
  • H. Tsuda, M. Komine, S. Tominaga, M. Ohtsuki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  135-  S64  -S64  2015/05  [Not refereed][Not invited]
  • 前川 武雄, 伏間江 貴之, 足立 晃正, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  125-  (6)  1237  -1243  2015/05  [Not refereed][Not invited]
     
    当科では、2013年8月から下肢静脈瘤に対するELVeSレーザーを用いた血管内焼灼術を開始し、2014年9月までに58例(65肢)に対して施行した。重篤な合併症はみられず、治療効果については良好な結果を示した一方で、約7割の症例で術後の一過性の疼痛や紫斑が出現した。本邦における下肢静脈瘤血管内焼灼術は、主に血管外科を中心に報告されており、皮膚科からの報告は未だない。今後、皮膚科での治療も発展する分野と考え、当科での治療経験についてその有用性と合併症について報告し、今後の血管内焼灼術の展望についても考察する。(著者抄録)
  • 鼻翼溝部に発生した有茎性表皮嚢腫の1例
    平野 智子, 伏間江 貴之, 藤田 有理香, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  125-  (6)  1277  -1277  2015/05  [Not refereed][Not invited]
  • 踵部に生じたclear cell sarcomaの1例
    伏間江 貴之, 前川 武雄, 平野 智子, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  125-  (6)  1279  -1279  2015/05  [Not refereed][Not invited]
  • 【小児を診る!皮膚科医の心得】(第I部)(2章)小児皮膚アトラス 乾癬
    小宮根 真弓  皮膚科の臨床  57-  (6)  920  -924  2015/05  [Not refereed][Not invited]
  • 患者の全身炎症を意識した乾癬治療
    小宮根 真弓  日本皮膚科学会雑誌  125-  (4)  798  -798  2015/04  [Not refereed][Not invited]
  • 生物学的製剤時代の乾癬治療における外用剤の役割
    小宮根 真弓  日本皮膚科学会雑誌  125-  (4)  826  -826  2015/04  [Not refereed][Not invited]
  • 前額と頸部に限局して夏期に皮疹を反復するダリエー(Darier)病の1例
    松本 藍, 小宮根 真弓, 村田 哲, 平賀 教子, 大槻 マミ太郎  日本皮膚科学会雑誌  125-  (4)  909  -909  2015/04  [Not refereed][Not invited]
  • 体幹の点状・網状紫斑から診断確定した全身性アミロイドーシスの一例
    平野 智子, 藤田 有理香, 小宮根 真弓, 村田 哲, 大槻 マミ太郎, 山中 祐子  日本皮膚科学会雑誌  125-  (4)  917  -917  2015/04  [Not refereed][Not invited]
  • 赤色、白色衛星病変を伴い術前診断に苦慮した踵部悪性黒色腫の1例
    伏間江 貴之, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  125-  (4)  941  -941  2015/04  [Not refereed][Not invited]
  • Pseudoxanthoma elasticum-like papillary dermal elastolysisの1例
    足立 晃正, 宮本 有希子, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  125-  (4)  955  -955  2015/04  [Not refereed][Not invited]
  • 伴性劣性魚鱗癬の1例
    小宮根 真弓, 中山 一, 足立 晃正  角化症研究会記録集  29-  96  -99  2015/03  [Not refereed][Not invited]
  • 体幹、臀部、下肢に広範囲に生じた慢性膿皮症の1例
    伏間江 貴之, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  125-  (2)  278  -278  2015/02  [Not refereed][Not invited]
  • 脊髄損傷患者の感覚残存部位のみに皮疹がみられた慢性多形痒疹の1例
    足立 晃正, 小宮根 真弓, 細田 里美, 村田 哲, 大槻 マミ太郎  皮膚の科学  14-  (1)  44  -44  2015/02  [Not refereed][Not invited]
  • 【外用製品による皮膚病】 臨床例 2%フシジン酸ナトリウム軟膏外用により治癒した形質細胞性口唇炎
    上田 有希子, 小宮根 真弓, 村田 哲, 大槻 マミ太郎, 林 宏美  皮膚病診療  37-  (1)  55  -58  2015/01  [Not refereed][Not invited]
     
    <症例のポイント>2%フシジン酸ナトリウム軟膏の外用により軽快した形質細胞性口唇炎(plasma cell cheilitis)の症例を経験した。形質細胞性口唇炎を含む開口部形質細胞症は比較的まれな疾患であり、良性であるが難治例が多い。これまで副腎皮質ステロイドの外用や局注、外科的切除、グリセオフルビン内服等の治療報告があるが、無効例も多い。2%フシジン酸ナトリウム軟膏は作用機序が不明な部分もあるが、有効例においては比較的速やかに効果がみられることが多く、形質細胞性口唇炎に対して積極的に試してよい治療の選択肢である。(著者抄録)
  • 【皮膚型と全身型-その移行はあるか?】 (Part1.)炎症性疾患(case 06) 限局性膿疱性乾癬(掌蹠膿疱症)と汎発性膿疱性乾癬
    小宮根 真弓, 大槻 マミ太郎  Visual Dermatology  14-  (2)  156  -159  2015/01  [Not refereed][Not invited]
  • 免疫アレルギー集中講義 今日的視点から見たCoombs&Gelのアレルギー分類
    小宮根 真弓  日本皮膚科学会雑誌  124-  (13)  2662  -2664  2014/12  [Not refereed][Not invited]
  • 乾癬治療生物学的製剤の光と陰 乾癬治療における生物学的製剤の副作用
    小宮根 真弓  日本皮膚科学会雑誌  124-  (13)  2768  -2771  2014/12  [Not refereed][Not invited]
  • 胃癌切除後、皮疹が一時軽快した菌状息肉症の1例
    宮本 有希子, 平嶋 海帆, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  西日本皮膚科  76-  (6)  633  -633  2014/12  [Not refereed][Not invited]
  • 線維肉腫様変化を伴う隆起性皮膚線維肉腫(fibrosarcomatous variant of dermatofibrosarcoma protuberans)の1例
    松本 藍, 足立 晃正, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  124-  (14)  3177  -3177  2014/12  [Not refereed][Not invited]
  • 神経線維腫症1型に生じた多発悪性末梢神経鞘腫瘍(MPNST)の1例
    足立 晃正, 松本 藍, 藤田 有理香, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  124-  (14)  3177  -3177  2014/12  [Not refereed][Not invited]
  • 踵部の石灰化を伴う血管平滑筋腫(angiomyoma with severe calcification)
    平野 智子, 伏間江 貴之, 藤田 有理香, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  124-  (14)  3188  -3188  2014/12  [Not refereed][Not invited]
  • 紅皮症型薬疹の改善後に丘疹紅皮症型薬疹を呈した1例
    松本 藍, 足立 晃正, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  Journal of Environmental Dermatology and Cutaneous Allergology  8-  (5)  466  -466  2014/11  [Not refereed][Not invited]
  • ハンドクリームによる接触皮膚炎に接触蕁麻疹症候群の合併を疑った1例
    平野 智子, 村田 哲, 小宮根 真弓, 大槻 マミ太郎  Journal of Environmental Dermatology and Cutaneous Allergology  8-  (5)  512  -512  2014/11  [Not refereed][Not invited]
  • 藤田 有理香, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎, 添野 文雄  Skin Cancer  29-  (2)  176  -180  2014/11  [Not refereed][Not invited]
     
    22歳、女性。約10年前から後頭部に小豆大の結節を自覚していたが、緩徐に増大し、拇指頭大になったため、2013年1月に近医で切除後、悪性腫瘍の疑いで紹介受診となった。初診時、左後頭部に3cm大の手術痕があった。前医からの借用標本の病理組織所見では、弱拡大では中央に膠原線維の変性を伴う単結節で、強拡大像では膨化した膠原線維の介在を伴って類円形の上皮様細胞と紡錘形細胞の2種類の腫瘍細胞が増生していた。免疫染色では、AE1/AE3、EMA、CD34陽性、α-SMA、desmin、S-100蛋白陰性、INI1蛋白陰性、MIB-1 indexは10%であった。以上からepithelioid sarcomaと診断した。前回の手術痕から2cmのマージンをとり頭蓋骨外板を含めて切除し、人工真皮を貼付した。追加切除検体の病理組織所見は前回と同様であり、断端陰性を確認した後、二期的に左大腿後面からの分層植皮で再建した。(著者抄録)
  • 新・皮膚科セミナリウム 分子標的薬の現状と展望 分子標的治療薬 これからの展望
    小宮根 真弓  日本皮膚科学会雑誌  124-  (12)  2281  -2290  2014/11  [Not refereed][Not invited]
     
    分子標的薬とは、高分子の生物学的製剤およびキナーゼ阻害剤などの低分子化合物を含む概念である。皮膚科領域では炎症性皮膚疾患である乾癬に対し抗体製剤が使用可能となっている。また低分子化合物であるJAK阻害剤を含め、多くの分子標的薬が今後使用可能となる可能性がある。悪性腫瘍に対しては、増殖の抑制を目的とした分子標的薬と、腫瘍が形成する免疫抑制状態を解除する目的を持つ分子標的薬がある。前者ではメラノーマに対するベムラフェニブ、後者では同じくメラノーマに対するニボルマブやイピリムマブがある。(著者抄録)
  • Akimasa Adachi, Mayumi Komine, Satoru Murata, Satoru Morimoto, Mamitaro Ohtsuki  JOURNAL OF DERMATOLOGY  41-  62  -62  2014/10  [Not refereed][Not invited]
  • H. Tsuda, M. Komine, T. Ohshio, S. Tominaga, M. Ohtsuki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  134-  S61  -S61  2014/09  [Not refereed][Not invited]
  • T. Oshio, M. Komine, H. Tsuda, S. Tominaga, H. Saito, S. Nakae, M. Ohtsuki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  134-  S101  -S101  2014/09  [Not refereed][Not invited]
  • 紅皮症を呈した白血球、好酸球増多を伴う慢性活動性EBV関連T細胞リンパ増殖性疾患の1例
    足立 晃正, 小宮根 真弓, 村田 哲, 大槻 マミ太郎, 畑野 かおる, 翁 家国  日本皮膚科学会雑誌  124-  (10)  1943  -1943  2014/09  [Not refereed][Not invited]
  • インフリキシマブが著効した妊婦の膿疱性乾癬
    中島 理奈, 藤田 有理香, 前川 武雄, 村田 哲, 小宮根 真弓, 大槻 マミ太郎  日本皮膚科学会雑誌  124-  (9)  1766  -1766  2014/08  [Not refereed][Not invited]
  • 膿疱性乾癬(汎発型)診療ガイドライン改訂版(平25)の概要
    葉山 惟大, 照井 正, 小宮根 真弓, 池田 志斈, 黒沢 美智子, 馬渕 智生, 小澤 明, 秋山 真志, 山西 清文, 青山 裕美, 岩月 啓氏, 佐野 栄記, 武藤 正彦, 金蔵 拓郎  日本皮膚科学会雑誌  124-  (9)  1767  -1767  2014/08  [Not refereed][Not invited]
  • Metastatic cutaneous Crohn's diseaseの1例
    足立 晃正, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚科学会雑誌  124-  (9)  1781  -1781  2014/08  [Not refereed][Not invited]
  • 2%フシジン酸ナトリウム軟膏外用により治癒した形質細胞性口唇炎の1例
    宮本 有希子, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎, 林 宏美, 神部 芳則  日本皮膚科学会雑誌  124-  (9)  1785  -1785  2014/08  [Not refereed][Not invited]
  • 当科における下肢静脈瘤血管内レーザー焼灼術の治療経験
    前川 武雄, レパヴー・アンドレ, 伏間江 貴之, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚外科学会誌  18-  (2別冊)  202  -202  2014/08  [Not refereed][Not invited]
  • 当科での非挿管下局所麻酔手術におけるデクスメデトミジンの使用経験
    伏間江 貴之, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚外科学会誌  18-  (2別冊)  217  -217  2014/08  [Not refereed][Not invited]
  • 若年男性の陰茎に2個隣接して生じた淡紅色小結節
    足立 晃正, 前川 武雄, 宮本 有希子, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚悪性腫瘍学会学術大会プログラム・抄録集  30回-  117  -117  2014/07  [Not refereed][Not invited]
  • 末節骨のbone splitを試みた爪部悪性黒色腫の1例
    前川 武雄, 藤田 有理香, 中島 理奈, 足立 晃正, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚悪性腫瘍学会学術大会プログラム・抄録集  30回-  133  -133  2014/07  [Not refereed][Not invited]
  • 良性・悪性の鑑別に苦慮したhidradenomaの1例
    藤田 有理香, 前川 武雄, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚悪性腫瘍学会学術大会プログラム・抄録集  30回-  139  -139  2014/07  [Not refereed][Not invited]
  • 先天性色素性母斑に生じたsarcomatoid carcinomaの1例
    伏間江 貴之, 前川 武雄, 中島 理奈, 藤田 有理香, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚悪性腫瘍学会学術大会プログラム・抄録集  30回-  142  -142  2014/07  [Not refereed][Not invited]
  • 内腹斜筋内に生じた腹壁デスモイドの1例
    前川 武雄, レパヴー・アンドレ, 藤田 有理香, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚外科学会誌  18-  (1)  64  -65  2014/07  [Not refereed][Not invited]
  • 轡田志穂, 岡部杏慈, 林隆洋, 高塚由佳, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎, 後藤千秋  日本皮膚科学会雑誌  124-  (6)  1159  2014/05  [Not refereed][Not invited]
  • 細田里美, 藤田悦子, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  124-  (6)  1156  2014/05  [Not refereed][Not invited]
  • 宮本有希子, 小宮根真弓, 村田哲, 大槻マミ太郎, 丸山暁人, 畑野かおる  日本皮膚科学会雑誌  124-  (6)  1160  2014/05  [Not refereed][Not invited]
  • 牧伸樹, 高塚由佳, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  124-  (6)  1155  2014/05  [Not refereed][Not invited]
  • 宮本有希子, 牧伸樹, 高塚由佳, 遠田博, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  124-  (6)  1155  -1156  2014/05  [Not refereed][Not invited]
  • 瀬川春奈, 宮本有希子, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  124-  (6)  1157  2014/05  [Not refereed][Not invited]
  • 牧伸樹, 藤田悦子, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  124-  (6)  1154  2014/05  [Not refereed][Not invited]
  • 足立晃正, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  124-  (6)  0060  -1161  2014/05  [Not refereed][Not invited]
  • 高塚由佳, 牧伸樹, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎, 野崎恵美, 石井則久, 中永和枝  日本皮膚科学会雑誌  124-  (6)  1155  2014/05  [Not refereed][Not invited]
  • 森田真紀子, 三宅温, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  124-  (6)  1155  2014/05  [Not refereed][Not invited]
  • 渡邊伸貴, 宮本有希子, 足立晃正, 高塚由佳, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  124-  (6)  1158  2014/05  [Not refereed][Not invited]
  • 遠田博, 小宮根真弓, 村田哲, 大槻マミ太郎, 西江渉, 清水宏  日本皮膚科学会雑誌  124-  (6)  1154  2014/05  [Not refereed][Not invited]
  • 宮本有希子, 佐藤篤子, 高塚由佳, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  124-  (6)  1154  2014/05  [Not refereed][Not invited]
  • 中島理奈, 宮本有希子, 藤田有理香, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  124-  (6)  1161  2014/05  [Not refereed][Not invited]
  • 礒田雅代, 足立晃正, 藤田有理香, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  124-  (6)  1159  2014/05  [Not refereed][Not invited]
  • 足立晃正, 宮本有希子, 遠田博, 前川武雄, 小宮根真弓, 大槻マミ太郎, 神永時雄  日本皮膚科学会雑誌  124-  (6)  1158  2014/05  [Not refereed][Not invited]
  • 坂口優, 宮本有希子, 佐藤篤子, 藤田有理香, 小宮根真弓, 村田哲, 大槻マミ太郎, 佐藤一也, 大嶺謙, 小澤敬也  日本皮膚科学会雑誌  124-  (6)  1161  2014/05  [Not refereed][Not invited]
  • 宮本有希子, 小宮根真弓, 村田哲, 大槻マミ太郎, 森本哲, 新井聖一  日本皮膚科学会雑誌  124-  (6)  1157  2014/05  [Not refereed][Not invited]
  • 中島理奈, 藤田有理香, 小宮根真弓, 村田哲, 大槻マミ太郎, 高山五郎  日本皮膚科学会雑誌  124-  (6)  1157  2014/05  [Not refereed][Not invited]
  • 渡邊伸貴, 足立晃正, 宮本有希子, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  124-  (6)  1160  2014/05  [Not refereed][Not invited]
  • 林隆洋, 宮本有希子, 高塚由佳, 藤田有理香, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  124-  (6)  1159  2014/05  [Not refereed][Not invited]
  • 牧伸樹, 藤田有理香, 藤田悦子, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  124-  (6)  1156  2014/05  [Not refereed][Not invited]
  • 林隆洋, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  124-  (6)  1157  2014/05  [Not refereed][Not invited]
  • 齋藤寿大, 足立晃正, 林隆洋, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  124-  (6)  1158  2014/05  [Not refereed][Not invited]
  • 足立晃正, 高塚由佳, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎, 原典明  日本皮膚科学会雑誌  124-  (6)  1159  -1160  2014/05  [Not refereed][Not invited]
  • 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎, 小西宏明  日本皮膚科学会雑誌  124-  (6)  1161  2014/05  [Not refereed][Not invited]
  • 藤田有理香, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  124-  (6)  1156  2014/05  [Not refereed][Not invited]
  • H. Tsuda, M. Komine, T. Ohshio, S. Tominaga, M. Ohtsuki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  134-  S76  -S76  2014/05  [Not refereed][Not invited]
  • 足立晃正, 細田里美, 高塚由佳, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  124-  (5)  971  2014/04  [Not refereed][Not invited]
  • 中島理奈, 藤田有理香, 前川武雄, 村田哲, 小宮根真弓, 大槻マミ太郎  日本皮膚科学会雑誌  124-  (5)  968  2014/04  [Not refereed][Not invited]
  • 小宮根真弓  日本皮膚科学会雑誌  124-  (4)  607  2014/04  [Not refereed][Not invited]
  • 宮本有希子, 平嶋海帆, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  124-  (4)  824  -824  2014/04  [Not refereed][Not invited]
  • 岸本恵美, 中島里奈, 中島里奈, 小宮根真弓, 唐川大, 大槻マミ太郎  日本皮膚科学会雑誌  124-  (4)  794  2014/04  [Not refereed][Not invited]
  • 足立晃正, 細田里美, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  124-  (4)  785  2014/04  [Not refereed][Not invited]
  • 小宮根真弓  日本皮膚科学会雑誌  124-  (4)  627  2014/04  [Not refereed][Not invited]
  • 足立晃正, 遠田博, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎  角化症研究会記録集  28th-  46  -48  2014/03  [Not refereed][Not invited]
  • 宮本有希子, 小宮根真弓, 大槻マミ太郎  Vis Dermatol  13-  (3)  245  -247  2014/02  [Not refereed][Not invited]
  • 唐川大, 小宮根真弓, 菅井順一, 大槻マミ太郎  Vis Dermatol  13-  (3)  264  -266  2014/02  [Not refereed][Not invited]
  • 宮本有希子, 遠田博, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎, 池田雄一  日本皮膚科学会雑誌  124-  (2)  196  2014/02  [Not refereed][Not invited]
  • 足立晃正, 牧伸樹, 遠田博, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎, 釜田康行, 簑田清次  日本皮膚科学会雑誌  124-  (2)  206  2014/02  [Not refereed][Not invited]
  • 小宮根真弓, 馬渕智生, 小澤明, 青山裕美, 岩月啓氏, 秋山真志, 池田志斈, 黒沢美智子, 金蔵拓郎, 佐野栄紀, 武藤正彦, 山西清文, 照井正  日本皮膚科学会雑誌  124-  (2)  201  2014/02  [Not refereed][Not invited]
  • 小宮根真弓  日本皮膚科学会雑誌  124-  (2)  190  -191  2014/02  [Not refereed][Not invited]
  • 小宮根真弓, 唐川大, 大槻マミ太郎  Vis Dermatol  13-  (2)  184  -185  2014/01  [Not refereed][Not invited]
  • 小宮根真弓, 唐川大, 牧伸樹, 津田英利, 大塩智之, 大槻マミ太郎  稀少難治性皮膚疾患に関する調査研究 平成25年度 総括・分担研究報告書  75  -77  2014  [Not refereed][Not invited]
  • 黒沢美智子, 池田志斈, 照井正, 青山裕美, 岩月啓氏, 秋山真志, 小宮根真弓, 谷川瑛子, 玉井克人  稀少難治性皮膚疾患に関する調査研究 平成25年度 総括・分担研究報告書  23  -28  2014  [Not refereed][Not invited]
  • 佐藤篤子, 小宮根真弓, 村田哲, 大槻マミ太郎  皮膚脈管膠原病研究会抄録集  37th-  54  2014  [Not refereed][Not invited]
  • 宮本有希子, 唐川大, 小宮根真弓, 村田哲, 大槻マミ太郎  皮膚科の臨床  56-  (1)  95  -98  2014/01  [Not refereed][Not invited]
  • 足立晃正, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎  J Environ Dermatol Cutan Allergol  7-  (5)  458  2013/11  [Not refereed][Not invited]
  • 多田弥生, 小宮根真弓, 大槻マミ太郎  Vis Dermatol  12-  (10)  1054  -1055  2013/09  [Not refereed][Not invited]
  • 牧伸樹, 小宮根真弓, 村田哲, 大槻マミ太郎, 大津晃  日本皮膚科学会雑誌  123-  (10)  1965  2013/09  [Not refereed][Not invited]
  • Nikolaos Panagiotopoulos, Sandra Gelvez-Zapata, Doris Rassl, Aman Coonar, Marco Scarci  ANNALS OF THORACIC SURGERY  96-  (3)  E79  -E79  2013/09  [Not refereed][Not invited]
  • 村田哲, 前川武雄, 藤田有理香, 小宮根真弓, 大槻マミ太郎  日本皮膚科学会雑誌  123-  (8)  1555  2013/07  [Not refereed][Not invited]
  • 足立晃正, 前川武雄, 村田哲, 小宮根真弓, 大槻マミ太郎  西日本皮膚科  75-  (3)  267  2013/06  [Not refereed][Not invited]
  • 宮本有希子, 牧伸樹, 高塚由佳, 遠田博, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  123-  (6)  1089  2013/05  [Not refereed][Not invited]
  • H. Tsuda, M. Komine, T. Ohshio, S. Tominaga, M. Ohtsuki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  133-  S115  -S115  2013/05  [Not refereed][Not invited]
  • E. Toyonaga, W. Nishie, H. Onda, M. Komine, S. Murata, S. Shinkuma, H. Nakamura, M. Ohtsuki, H. Shimizu  JOURNAL OF INVESTIGATIVE DERMATOLOGY  133-  S135  -S135  2013/05  [Not refereed][Not invited]
  • 牧伸樹, 唐川大, 小宮根真弓, 大槻マミ太郎  日本皮膚科学会雑誌  123-  (5)  957  2013/04  [Not refereed][Not invited]
  • 藤田有理香, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  123-  (5)  973  2013/04  [Not refereed][Not invited]
  • 宮本有希子, 藤田有理香, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  123-  (5)  950  2013/04  [Not refereed][Not invited]
  • 小宮根真弓  日本皮膚科学会雑誌  123-  (4)  444  2013/04  [Not refereed][Not invited]
  • 牧伸樹, 高塚由佳, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  123-  (4)  457  2013/04  [Not refereed][Not invited]
  • 森田真紀子, 三宅温, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  123-  (4)  491  2013/04  [Not refereed][Not invited]
  • 開陽子, 中山雅之, 間藤尚子, 中屋孝清, 細野達也, 山沢英明, 坂東政司, 杉山幸比古, 小宮根真弓, 大槻マミ太郎  日本呼吸器学会誌  2-  189  2013/03  [Not refereed][Not invited]
  • 小宮根真弓  JIM  23-  (2)  122  -125  2013/02  [Not refereed][Not invited]
  • 藤田有理香, 前川武雄, 塚原理恵子, 小宮根真弓, 村田哲, 大槻マミ太郎  臨床皮膚科  67-  (2)  159  -162  2013/02  [Not refereed][Not invited]
  • 小宮根真弓  Mon Book Derma  (200)  51  -56  2013/01  [Not refereed][Not invited]
  • 藤田悦子, 小宮根真弓, 村田哲, 大槻マミ太郎  皮膚脈管膠原病研究会抄録集  36th-  31  2013  [Not refereed][Not invited]
  • 宮本有希子, 高塚由佳, 小宮根真弓, 村田哲, 大槻マミ太郎, 中永和枝, 石井則久  日本小児皮膚科学会学術大会プログラム・抄録集  37th-  106  2013  [Not refereed][Not invited]
  • 前川武雄, 村田哲, 藤田有理香, 小宮根真弓, 大槻マミ太郎  日本皮膚悪性腫瘍学会学術大会プログラム・抄録集  29th-  103  2013  [Not refereed][Not invited]
  • 小宮根真弓  日本口腔診断学会総会プログラム・抄録集  26th-  36  -37  2013  [Not refereed][Not invited]
  • 小宮根真弓  日本皮膚悪性腫瘍学会学術大会プログラム・抄録集  29th-  91  2013  [Not refereed][Not invited]
  • 小宮根真弓, 津田英利, 大塩智之, 唐川大, MEEPHANSAN Jitlada, 花川靖, 佐山浩二, 富永眞一, 大槻マミ太郎  稀少難治性皮膚疾患に関する調査研究 平成24年度 総括・分担研究報告書  197  -200  2013  [Not refereed][Not invited]
  • 秋山真志, 青山裕美, 黒沢美智子, 池田志斈, 小宮根真弓, 玉井克人  稀少難治性皮膚疾患に関する調査研究 平成24年度 総括・分担研究報告書  39  -41  2013  [Not refereed][Not invited]
  • 黒沢美智子, 池田志斈, 上原里程, 中村好一, 岩月啓氏, 大野貴司, 清水宏, 山本明美, 山西清文, 小宮根真弓, 青山裕美, 永井正規, 太田晶子, 稲葉裕  稀少難治性皮膚疾患に関する調査研究 平成24年度 総括・分担研究報告書  27  -37  2013  [Not refereed][Not invited]
  • 照井正, 小澤明, 馬淵智生, 武藤正彦, 岩月啓氏, 青山裕美, 山西清文, 今井友康, 池田志斈, 黒沢美智子, 金蔵拓郎, 佐野栄紀, 中島喜美子, 秋山真志, 小宮根真弓, 稲冨徹, 葉山惟大  稀少難治性皮膚疾患に関する調査研究 平成24年度 総括・分担研究報告書  141  -146  2013  [Not refereed][Not invited]
  • 足立晃正, 宮本有希子, 遠田博, 前川武雄, 小宮根真弓, 大槻マミ太郎, 神永時雄  日本皮膚悪性腫瘍学会学術大会プログラム・抄録集  29th-  124  2013  [Not refereed][Not invited]
  • 津田英利, 小宮根真弓, 大塩智之, 富永眞一, 大槻マミ太郎  日本分子生物学会年会プログラム・要旨集(Web)  36th-  WEB ONLY 3P-0192  2013  [Not refereed][Not invited]
  • 森田真紀子, 唐川大, 小宮根真弓, 村田哲, 大槻マミ太郎  皮膚病診療  35-  (1)  71  -74  2013/01  [Not refereed][Not invited]
  • MAEKAWA Takeo, FUJITA Yurika, MORITA Makiko, TSUKAHARA Rieko, WAKATABI Kouji, KOMINE Mayumi, MURATA Satoru, OHTSUKI Mamitaro, KAWADA Hirotoshi, YAMAGUCHI Takehiko  Skin Cancer  27-  (3)  355  -360  2013  [Not refereed][Not invited]
     
    An 87-year-old man noticed a nodule on his abdomen a month ago, which had been increasing in size. Computed tomography (CT) demonstrated a tumor within the subcutaneous adipose tissue which showed iso-density to the muscle, and which was 22 mm in size. When magnetic resonance imaging (MRI) was performed two months later, the tumor showed rapid growth to 34 mm in size, and infiltration to the muscle. Histopathological examination of an incisional biopsy suggested spindle cell sarcoma. Immunohistochemical examination showed the tumor cells were negative for CD34, smooth muscle actin and pan-cytokeratin. Based on these findings, synovial sarcoma was suspected, and we proceeded with molecular diagnostic analysis by FISH (fluorescence in situ hybridization) using a dual-color, break-apart SS18 probe. As a result, translocation involving the SS18 gene was detected by the split signal, and a diagnosis of synovial sarcoma was confirmed.[Skin Cancer (Japan) 2012 ; 27 : 355-360]
  • 小宮根真弓  日本皮膚科学会雑誌  122-  (13)  3082  -3085  2012/12  [Not refereed][Not invited]
  • 塚原理恵子, 若旅功二, 池田雄一, 小宮根真弓, 村田哲, 大槻マミ太郎  皮膚科の臨床  54-  (13)  1889  -1892  2012/12  [Not refereed][Not invited]
  • 高塚由佳, 細田里美, 遠田博, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎  皮膚科の臨床  54-  (12)  1679  -1682  2012/11  [Not refereed][Not invited]
  • 佐藤篤子, 細田里美, 小宮根真弓, 村田哲, 大槻マミ太郎, 内海雅雄  日本皮膚科学会雑誌  122-  (11)  2680  2012/10  [Not refereed][Not invited]
  • 藤田有理香, 前川武雄, 森田真紀子, 塚原理恵子, 若旅功二, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  122-  (11)  2682  2012/10  [Not refereed][Not invited]
  • 森田真紀子, 唐川大, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  122-  (11)  2681  2012/10  [Not refereed][Not invited]
  • 平嶋海帆, 村田哲, 小宮根真弓, 大槻マミ太郎, 塚田篤子  日本皮膚科学会雑誌  122-  (11)  2681  -2682  2012/10  [Not refereed][Not invited]
  • 遠田博, 三宅温, 反田茉莉, 高塚由佳, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  122-  (11)  2680  2012/10  [Not refereed][Not invited]
  • 三宅温, 池田雄一, 森田真紀子, 藤田有理香, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎, 野崎重之, 大塚勤  日本皮膚科学会雑誌  122-  (11)  2679  2012/10  [Not refereed][Not invited]
  • 平嶋海帆, 小宮根真弓, 村田哲, 大槻マミ太郎, 阿久津礼子  日本皮膚科学会雑誌  122-  (11)  2679  2012/10  [Not refereed][Not invited]
  • 三宅温, 池田雄一, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  122-  (11)  2681  2012/10  [Not refereed][Not invited]
  • 高塚由佳, 遠田博, 前川武雄, 村田哲, 小宮根真弓, 大槻マミ太郎, 石井則久  日本皮膚科学会雑誌  122-  (11)  2679  -2680  2012/10  [Not refereed][Not invited]
  • 高塚由佳, 佐藤篤子, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  122-  (11)  2682  2012/10  [Not refereed][Not invited]
  • 藤田有理香, 前川武雄, 塚原理恵子, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  122-  (11)  2681  2012/10  [Not refereed][Not invited]
  • 牧伸樹, 高塚由佳, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  122-  (11)  2682  2012/10  [Not refereed][Not invited]
  • 藤田有理香, 塚原理恵子, 遠田博, 佐藤篤子, 前川武雄, 小宮根真弓, 村田哲, 須藤智幸, 遠藤俊輔, 大槻マミ太郎  皮膚科の臨床  54-  (10)  1387  -1390  2012/10  [Not refereed][Not invited]
  • 藤田悦子, 小宮根真弓, 村田哲, 大槻マミ太郎, 釜田康行, 簑田清次  日本皮膚科学会雑誌  122-  (10)  2526  2012/09  [Not refereed][Not invited]
  • MEEPHANSAN Jitlada, 小宮根真弓, 津田英利, 富永眞一, 大槻マミ太郎  医薬の門  52-  (4)  304  -306  2012/09  [Not refereed][Not invited]
  • J. Meephansan, H. Tsuda, M. Komine, M. Karakawa, S. Tominaga, M. Ohtsuki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  132-  S20  -S20  2012/09  [Not refereed][Not invited]
  • 立田彩, 田口佳代子, 横倉英人, 小宮根真弓, 村田哲, 大槻マミ太郎  皮膚科の臨床  54-  (9)  1306  -1307  2012/09  [Not refereed][Not invited]
  • 唐川大, 遠田博, 小宮根真弓, 村田哲, 大槻マミ太郎, 室井一男  日本皮膚科学会雑誌  122-  (9)  2346  2012/08  [Not refereed][Not invited]
  • 唐川大, 小宮根真弓, 平嶋海帆, 藤田悦子, 村田哲, 大槻マミ太郎  J Environ Dermatol Cutan Allergol  6-  (3)  266  2012/07  [Not refereed][Not invited]
  • 唐川大, 小宮根真弓, 大槻マミ太郎  日本皮膚科学会雑誌  122-  (7)  1806  2012/06  [Not refereed][Not invited]
  • Makiko Morita, Mayumi Komine, Yuka Takatsuka, Satomi Hosoda, Hiroshi Onda, Takeo Maekawa, Satoru Murata, Mamitaro Ohtsuki  JOURNAL OF DERMATOLOGY  39-  37  -38  2012/06  [Not refereed][Not invited]
  • Satomi Hosoda, Etsuko Fujita, Mayumi Komine, Satoru Murata, Mamitaro Ohtsuki  JOURNAL OF DERMATOLOGY  39-  277  -277  2012/06  [Not refereed][Not invited]
  • 腹部に生じた滑膜肉腫の1例
    藤田 有理香, 前川 武雄, 森田 真紀子, 塚原 理恵子, 若旅 功二, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚悪性腫瘍学会学術大会プログラム・抄録集  28回-  135  -135  2012/06  [Not refereed][Not invited]
  • 転移・寛解を繰り返す悪性黒色腫の1例
    前川 武雄, 藤田 有理香, 若旅 功二, 横倉 英人, 小宮根 真弓, 村田 哲, 大槻 マミ太郎  日本皮膚悪性腫瘍学会学術大会プログラム・抄録集  28回-  153  -153  2012/06  [Not refereed][Not invited]
  • 唐川大, 小宮根真弓, 平嶋海帆, 菅井順一, 大槻マミ太郎  西日本皮膚科  74-  (3)  346  2012/06  [Not refereed][Not invited]
  • 遠田博, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  122-  (6)  1599  2012/05  [Not refereed][Not invited]
  • 高塚由佳, 細田里美, 遠田博, 山田朋子, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  122-  (6)  1604  2012/05  [Not refereed][Not invited]
  • J. Meephansan, H. Tsuda, M. Komine, M. Karakawa, S. Tominaga, M. Ohtsuki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  132-  S5  -S5  2012/05  [Not refereed][Not invited]
  • M. Karakawa, M. Komine, S. Hosoda, J. Meephansan, H. Tsuda, J. Sugai, M. Ohtsuki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  132-  S10  -S10  2012/05  [Not refereed][Not invited]
  • 遠田博, 小宮根真弓, 村田哲, 大槻マミ太郎  皮膚科の臨床  54-  (5)  761  -765  2012/05  [Not refereed][Not invited]
  • 森田真紀子, 唐川大, 塚原理恵子, 高塚由佳, 藤田有理香, 細田里美, 池田雄一, 菅井順一, 小宮根真弓, 大槻マミ太郎  皮膚科の臨床  54-  (5)  725  -728  2012/05  [Not refereed][Not invited]
  • 遠田 博, 小宮根 真弓, 村田 哲  皮膚科の臨床  54-  (5)  761  -765  2012/05  [Not refereed][Not invited]
  • 森田真紀子, 村田哲, 小宮根真弓, 大槻マミ太郎, 矢野智則  日本皮膚科学会雑誌  122-  (4)  1218  2012/04  [Not refereed][Not invited]
  • 小宮根真弓  日本皮膚科学会雑誌  122-  (4)  1009  2012/04  [Not refereed][Not invited]
  • 三宅温, 池田雄一, 森田真紀子, 藤田有理香, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎, 野崎重之, 大塚勤  日本皮膚科学会雑誌  122-  (4)  1207  2012/04  [Not refereed][Not invited]
  • 細田里美, 遠田博, 佐藤篤子, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  122-  (4)  1215  2012/04  [Not refereed][Not invited]
  • 高塚由佳, 横倉英人, 小宮根真弓, 村田哲, 大槻マミ太郎, 大津晃  皮膚科の臨床  54-  (4)  541  -544  2012/04  [Not refereed][Not invited]
  • 小宮根真弓, 大槻マミ太郎, 三井浩, 玉置邦彦  西日本皮膚科  74-  (2)  208  2012/04  [Not refereed][Not invited]
  • 藤田有理香, 塚原理恵子, 遠田博, 佐藤篤子, 前川武雄, 小宮根真弓, 村田哲, 大槻マミ太郎, 須藤智幸, 岩下ちひろ, 光田清佳, 山本真一, 遠藤俊輔  日本皮膚科学会雑誌  122-  (3)  654  2012/03  [Not refereed][Not invited]
  • 平嶋海帆, 小宮根真弓, 村田哲, 大槻マミ太郎  日本皮膚科学会雑誌  122-  (3)  654  2012/03  [Not refereed][Not invited]
  • KOIKE YUMIKO, YAMADA TOMOKO, KOMINE MAYUMI, MURATA SATORU, OTSUKI MAMITARO, KATO HIDEYUKI, HASHIMOTO TAKASHI, SASANUMA HIDEKI  日本皮膚科学会雑誌  122-  (1)  96  -97  2012/01  [Not refereed][Not invited]
  • 照井正, 黒沢美智子, 岩月啓氏, 小澤明, 武藤正彦, 池田志斈, 小宮根真弓, 山西清文, 佐野栄紀, 金蔵拓郎, 馬淵智生  稀少難治性皮膚疾患に関する調査研究 平成23年度 総括・分担研究報告書  39  -44  2012  [Not refereed][Not invited]
  • FUJITA Yurika, MAEKAWA Takeo, KOMINE Mayumi, MURATA Satoru, OHTSUKI Mamitaro  Skin Cancer  27-  (2)  179  -185  2012  [Not refereed][Not invited]
     
    The cases of 82 patients with extrmammary Paget's disease treated at the Department of Dermatology at Jichi Medical University Hospital between 1999 and 2010 were statistically studied. The average age was 71.4 years old, and the male/female ratio was 1.8 : 1. Seventy patients had lesions on the genital area. Six patients had lesions on the axilla, and two patients each had lesions on the abdomen or perianal area. 8.5% of the patients studied had lymph node metastases. All of them had invasive primary lesions. 4.1% of the patients showed local recurrence, and the primary lesions of all of the patients were in situ. The five-year survival rate of the patients was 100%, 65% and 0% with no, unilateral or bilateral lymph node metastases, respectively. The five-year survival rate of stages 1, 2, 3 and 4 was 100%, 100%, 75% and 0%, respectively. Both of the survival curves were very similar. Therefore, it seems that the prognosis of extramammary Paget's disease is strongly related with the existence of lymph node metastasis.[Skin Cancer (Japan) 2012 ; 27 : 179-185]
  • 全身に結節型皮膚サルコイドが多発したサルコイドーシスの1例
    宮垣 朝光, 佐伯 秀久, 柴田 彩, 大野 祐樹, 常深 祐一郎, 浅野 善英, 小宮根 真弓, 菊池 かな子, 玉置 邦彦  日本皮膚科学会雑誌  121-  (14)  3425  -3425  2011/12  [Not refereed][Not invited]
  • 小宮根 真弓, 大槻 マミ太郎  医学のあゆみ  238-  (6)  707  -711  2011/08  [Not refereed][Not invited]
  • M. Karakawa, M. Komine, H. Tsuda, K. Tamaki, S. Sato, M. Ohtsuki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  131-  S46  -S46  2011/04  [Not refereed][Not invited]
  • I. Meephansan, M. Komine, H. Tsuda, S. Yano, S. Tominaga, M. Ohtsuki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  131-  S2  -S2  2011/04  [Not refereed][Not invited]
  • 唐川 大, 小宮根 真弓, 大槻 マミ太郎  臨床皮膚科  65-  (5)  10  -14  2011/04  [Not refereed][Not invited]
  • Ohtsuki Mamitaro, Terui Tadashi, Ozawa Akira, Morita Akimichi, Sano Shigetoshi, Takahashi Hidetoshi, Komine Mayumi, Etoh Takafumi, Torii Hideshi, Asahina Akihiko, Nemoto Osamu, Nakagawa Hidemi  The Japanese Journal of Dermatology  121-  (8)  1561  -1572  2011  [Not refereed][Not invited]
     
    Clinical use of TNFα (tumor necrosis factor α) inhibitors, adalimumab and infliximab, for psoriasis began in January 2010 when an additional indication for this disease was approved. In January 2011, an interleukin-12/23 p40 (IL-12/23 p40) inhibitor, ustekinumab, was newly approved as the third biologic agent with an indication for psoriasis. All of these biologic agents are expected to exhibit excellent efficacy against not only psoriasis but also psoriatic arthritis, and to contribute to the improvement of quality of life (QOL) of psoriatic patients. At the same time, however, they require safety measures to prevent adverse drug reactions such as serious infections. We therefore decided to prepare this Guideline/Safety Manual for the Use of Biologic Agents in Psoriasis (The 2011 Version) by revising that for the use of TNFα Inhibitors prepared by the Biologics Review Committee of the Japanese Dermatological Association in February 2010. In this new unified version for all three biologic agents including ustekinumab, requirements for clinical facilities for the use of biologic agents, contents of safety measures against reactivation of tuberculosis and hepatitis B, and recommendable combination therapies with biologic agents, have been renewed and added. This guideline/safety manual has been prepared to assist dermatology specialists experienced in clinical practice of psoriasis to use biologic agents safely and properly.
  • 黒沢美智子, 池田志斈, 上原里程, 中村好一, 岩月啓氏, 大野貴司, 清水宏, 山本明美, 山西清文, 小宮根真弓, 青山裕美, 永井正規, 太田晶子, 稲葉裕  稀少難治性皮膚疾患に関する調査研究 平成22年度 総括・分担研究報告書  33  -37  2011  [Not refereed][Not invited]
  • 黒沢美智子, 池田志斈, 上原里程, 中村好一, 岩月啓氏, 大野貴司, 清水宏, 山本明美, 山西清文, 小宮根真弓, 青山裕美, 川村孝, 永井正規, 太田晶子, 稲葉裕  特定疾患の疫学に関する研究 平成22年度 総括・分担研究報告書  186  -197  2011  [Not refereed][Not invited]
  • 小宮根 真弓, 大槻 マミ太郎  アレルギ-・免疫  18-  (1)  73  -81  2011/01  [Not refereed][Not invited]
  • Masaru Karakawa, Mayumi Komine, Yasushi Hanakawa, Koji Hashimoto, Shinichi Sato, Kunihiko Tamaki, Mamitaro Ohtsuki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  130-  S85  -S85  2010/09  [Not refereed][Not invited]
  • Jitlada Meephansan, Satomi Hosoda, Mayumi Komine, Satoru Murata, Mamitaro Ohtsuki  JOURNAL OF DERMATOLOGY  37-  141  -141  2010/09  [Not refereed][Not invited]
  • Jitlada Meephansan, Mayumi Komine, Mamitaro Ohtsuki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  130-  S52  -S52  2010/09  [Not refereed][Not invited]
  • J. Meephansan, M. Komine, K. Wakatabi, S. Tominaga, M. Ohtsuki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  130-  S73  -S73  2010/04  [Not refereed][Not invited]
  • 岩月 啓氏, 照井 正, 小澤 明, 小宮根 真弓, 梅澤 慶紀, 鳥居 秀嗣, 中西 元, 原 弘之, 馬渕 智生, 青山 裕美, 北島 康雄  日本皮膚科学会雑誌  120-  (4)  815  -839  2010/03  [Not refereed][Not invited]
  • 青地聖子, 辻和英, 阪口政清, 許南浩, 津田達也, 山西清文, 小宮根真弓, 岩月啓氏  日本皮膚科学会雑誌  120-  (3)  691  2010/03  [Not refereed][Not invited]
  • Satoru Murata, Hideto Yokokura, Tomokazu Masuda, Etsuko Fujita, Yuichi Ikeda, Yumiko Koike, Yoshiko Taguchi, Koji Wakatabi, Hiroshi Onda, Satomi Hosoda, Yuka Takatsuka, Aya Tatsuta, Atsuko Sato, Masahiko Oyama, Mitsuo Fujimoto, Tomoharu Kiyosawa, Tomoko Yamada, Mayumi Komine, Hidemi Nakagawa, Mamitaro Ohtsuki  Jichi Medical University journal  32-  43  -49  2010/03  [Not refereed][Not invited]
     
    A total of 121 patients (54 males and 67 females) with melanoma were treated and their records reviewed in the Department of Dermatology at Jichi Medical University Hospital between 1998 and 2008. Patients' age distribution ranged from 70 to 79 for females and from 60 to 69 years for males. The number of early-stage cases of melanoma in this study increased in comparison to a study previously reported by Umemoto et al. at Jichi Medical University Hospital between 1977 and 1992. Acral lentiginous melanoma accounted for 44.6% of cases, lentigo maligna melanoma for 10.7%, superficial spreading melanoma for 20.7%, and nodular melanoma for 19.8%. The five-year survival rates for stage-I, II and III cases were 93.3%, 82.6% and 39.4%, respectively. The survival rate for stage-IV cases was 14.8% at 30 months.
  • Ohtsuki Mamitaro, Terui Tadashi, Ozawa Akira, Morita Akimichi, Sano Shigetoshi, Takahashi Hidetoshi, Komine Mayumi, Etoh Takafumi, Torii Hideshi, Asahina Akihiko, Nemoto Osamu, Nakagawa Hidemi  The Japanese Journal of Dermatology  120-  (2)  163  -171  2010/02  [Not refereed][Not invited]
     
    Anti-TNFα (tumor necrosis factor-α) agents, adalimumab and infliximab, are the first biologics approved for the treatment of psoriasis in Japan. Although these agents are expected to have remarkable effects on psoriasis and/or psoriatic arthritis, and to improve QOL (quality of life) of patients with psoriasis, there is growing concern regarding the potential serious adverse reactions such as infections including tuberculosis as well as bacterial and Pneumocystis pneumonia. The guideline and safety manual have been developed to ensure that anti-TNFα agents are properly used by board-certified dermatologists experienced in practice of psoriasis. Requirements for physicians and medical institutions, eligible patients for treatment with anti-TNFα agents, dosage and administration of each anti-TNFα agents, general considerations for administration, contraindications, safety precautions for high-risk patients for adverse reactions, and recommendable combination therapies with anti-TNFα agents are referred.
  • 池田志斈, 高木敦, 黒沢美智子, 山本明美, 小宮根真弓, 橋本隆, 清水宏, 山西清文, 武藤正彦  稀少難治性皮膚疾患克服のための生体試料の収集に関する研究 平成21年度 総括・分担研究報告書  23  -27  2010  [Not refereed][Not invited]
  • Akimichi Morita, Akira Maeda, Takuya Furuhashi, Kana Kawashima, Toshihiro Ito, Osamu Fukuchi, Hidemi Nakagawa, Kouki Endoh, Daisuke Watabe, Toshihide Akasaka, Junichi Sugai, Mayumi Komine, Miho Hirashima, Mamitaro Ohtsuki  Nishinihon Journal of Dermatology  72-  (4)  397  -404  2010  [Not refereed][Not invited]
     
    Forty-five patients with psoriasis vulgaris of the scalp who had used topical tacalcitol lotions (high or low concentration) or topical steroid lotions for the treatment of skin eruptions were enrolled in this study. The patients had previously used high-concentration tacalcitol lotion (19 patients), low-concentration tacalcitol lotion (1 patient), and/or steroid lotions (very potent: 23 patients; mildly or moderately potent: 8 patients). The efficacy, safety, and usefulness of topical maxacalcitol lotion (Oxarol® Lotion 25 μg/g) were evaluated. Efficacy, scores for erythema infiltration/thickening, scale formation, and the total of these three scores were significantly decreased at weeks 4 and 8 (Wilcoxon signed-rank test p<0.001). Safety: local side effects were observed in 2 patients, but no systemic side effects were observed. Usefulnes: 87.2% of the patients rated it as "very effective" or "effective". In conclusion, topical maxacalcitol lotion was highly effective without any adverse effects when used as a replacement for other topical lotions, including high- and low-concentration tacalcitol lotion and steroid lotions. Maxacalcitol lotion is a highly effective treatment for psoriasis vulgaris on the scalp.
  • 小宮根 真弓  日本皮膚科学会雑誌  119-  (11)  2151  -2156  2009/10  [Not refereed][Not invited]
  • M. Karakawa, M. Komine, K. Tamaki, M. Ohtsuki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  129-  S14  -S14  2009/09  [Not refereed][Not invited]
  • 小宮根 真弓  日本皮膚科学会雑誌  119-  (5)  863  -871  2009/04  [Not refereed][Not invited]
  • M. Komine, Y. Hanakawa, K. Wakatabi, H. Yokokura, K. Hashimoto, K. Tamaki, M. Ohtsuki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  129-  S86  -S86  2009/04  [Not refereed][Not invited]
  • T. Takekoshi, Y. Tada, T. Watanabe, M. Sugaya, M. Komine, T. Shimizu, A. Asahina, T. Yokomizo, K. Tamaki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  129-  S107  -S107  2009/04  [Not refereed][Not invited]
  • KOIKE YUMIKO, YAMADA TOMOKO, KOMINE MAYUMI, MURATA SATORU, OTSUKI MAMITARO, KATO HIDEYUKI, HASHIMOTO TAKASHI, SASANUMA HIDEKI  日本皮膚科学会雑誌  119-  (4)  741  -741  2009/03  [Not refereed][Not invited]
  • MINATANI Yosaku, KOMINE Mayumi, SAKURAI Naoki, TAKEKOSHI Tomonori, MITSUI Hiroshi, TADA Yayoi, SAEKI Hidehisa, TAMAKI Kunihiko  Japanese journal of dermatology  119-  (1)  39  -47  2009/01  [Not refereed][Not invited]
  • 池田志斈, 黒沢美智子, 山本明美, 小宮根真弓, 橋本隆, 清水宏, 山西清文  稀少難治性皮膚疾患に関する調査研究 平成20年度 総括・分担研究報告書  100  -102  2009  [Not refereed][Not invited]
  • Murata Satoru, Yokokura Hideto, Masuda Tomokazu, Taguchi Yoshiko, Fujita Etsuko, Koike Yumiko, Wakatabi Koji, Onda Hiroshi, Hosoda Satomi, Takatsuka Yuka, Sato Atsuko, Oyama Masahiko, Fujimoto Mitsuo, Kiyosawa Tomoharu, Yamada Tomoko, Komine Mayumi, Nakagawa Hidemi, Ohtsuki Mamitaro  Jichi Medical University journal  31-  23  -29  2008/12  [Not refereed][Not invited]
     
    The cases of 16 patients with angiosarcoma treated in the Department of Dermatology at Jichi Medical University Hospital between 1992 and 2007 were reviewed. Median age was 77 years (range, 58-96 years). Ten patients displayed lesions on the scalp. Five female patients had lesions on the lower extremity with chronic lymphedema following treatment of cancer of the uterus. Only 1 patient with a lesion on the back has been cured, while 2 patients remain under treatment and 13 patients died within 3-35 months (mean, 13 months) after the first visit.
  • NAGAO Mayuko, KADONO Takafumi, KOMINE Mayumi, KIKUCHI Kanako, TAMAKI Kunihiko, MAEKAWA Takeo, SIKADA Junichiro, IHN Hironobu  Japanese journal of dermatology  118-  (6)  1079  -1083  2008/05  [Not refereed][Not invited]
  • 和泉 里江子, 小宮根 真弓, 中島 広子  皮膚科の臨床  50-  (5)  641  -644  2008/05  [Not refereed][Not invited]
  • M. Komine, M. Otsuki, K. Tamaki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  128-  S72  -S72  2008/04  [Not refereed][Not invited]
  • 遺伝子解析で診断した伴性遺伝性魚鱗癬の1例
    常深 祐一郎, 渡邊 孝宏, 宮垣 朝光, 土肥 凌, 佐伯 秀久, 菊池 かな子, 玉置 邦彦, 小宮根 真弓, 服部 尚子  角化症研究会記録集  22-  122  -125  2008/03  [Not refereed][Not invited]
  • Mayumi Komine  JOURNAL OF PHARMACOLOGICAL SCIENCES  106-  41P  -41P  2008  [Not refereed][Not invited]
  • N. Ishiura, M. Komine, T. Kadono, K. Kikuchi, K. Tamaki  BRITISH JOURNAL OF DERMATOLOGY  157-  (6)  1287  -1289  2007/12  [Not refereed][Not invited]
  • FUKUCHI Osamu, OHTA Arihito, ISHIJI Takaoki, HONDA Mariko, KAMIDE Ryoichi, NAKAGAWA Hidemi, KOMINE Mayumi, HASEGAWA Tomonori  Japanese journal of dermatology  117-  (12)  1969  -1976  2007/11  [Not refereed][Not invited]
  • 成人Still病の3例
    冨田 学, 玉城 善史郎, 永尾 麻由子, 増井 友里, 渡邉 彩, 蘆田 龍一, 佐々木 苗胤, 浅野 善英, 白井 明, 三井 浩, 山根 謙一, 菅谷 誠, 矢澤 徳仁, 門野 岳史, 佐伯 秀久, 渡邊 孝宏, 小宮根 真弓, 菊池 かな子, 玉置 邦彦, 前川 武雄, 久保 正英, 尹 浩信  西日本皮膚科  69-  (3)  334  -335  2007/06  [Not refereed][Not invited]
  • S. Kagami, H. Saeki, Y. Tsunemi, K. Nakamura, T. Nakayama, O. Yoshie, M. Komine, K. Tamaki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  127-  S113  -S113  2007/04  [Not refereed][Not invited]
  • M. Komine, M. Karakawa, T. Takekoshi, N. Sakurai, Y. Minatani, H. Mitsui, Y. Tada, H. Saeki, A. Asahina, K. Tamaki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  127-  S42  -S42  2007/04  [Not refereed][Not invited]
  • K. Kikuchi, M. Komine, T. Takekoshi, K. Tamaki  CLINICAL AND EXPERIMENTAL DERMATOLOGY  32-  (1)  107  -108  2007/01  [Not refereed][Not invited]
  • Y. Masui, M. Sugaya, S. Kagami, H. Fujita, S. Yano, M. Nagao, M. Komine, H. Saeki, H. Ihn, K. Kikuchi, K. Tamaki  Clinical and Experimental Dermatology  32-  (1)  57  -59  2007/01  [Not refereed][Not invited]
     
    We describe a patient with Sézary syndrome (SS) who was successfully treated with topical steroid and narrowband UVB. Sézary cells in peripheral blood correlated with severity of skin lesions. In addition, serum levels of CCL17 and CCL27 decreased as disease activity improved. These chemokines may be important for the pathogenesis of SS. © 2007 The Author(s).
  • N. Hattori, M. Komine, T. Kaneko, K. Shimazu, Y. Tsunemi, M. Koizumi, J. Goto, T. Hashimoto  BRITISH JOURNAL OF DERMATOLOGY  155-  (5)  1062  -1063  2006/11  [Not refereed][Not invited]
  • FUKUCHI Osamu, FINLAY Andrew Y, OHTA Arihito, ISHIJI Takaoki, HONDA Mariko, KAMIDE Ryoichi, NAKAGAWA Hidemi, KOMINE Mayumi, HASEGAWA Tomonori  日本皮膚科学会雑誌 = THE JAPANESE JOURNAL OF DERMATOLOGY  116-  (11)  1583  -1591  2006/10  [Not refereed][Not invited]
  • Malignant proliferating trichilemmal cystの1例
    増井 友里, 浅島 信子, 前川 武雄, 門野 岳史, 小宮根 真弓, 尹 浩信, 菊池 かな子, 玉置 邦彦  日本皮膚科学会雑誌  116-  (9)  1348  -1348  2006/08  [Not refereed][Not invited]
  • ケラチン1遺伝子の2B領域に点突然変異を認め,掌蹠角化症類似の臨床像を示した軽症水疱型先天性魚鱗癬様紅皮症の1例
    嶋津 苗胤, 常深 祐一郎, 服部 尚子, 佐伯 秀久, 尹 浩信, 小宮根 真弓, 菊池 かな子, 玉置 邦彦, 石橋 康正  西日本皮膚科  68-  (3)  335  -335  2006/06  [Not refereed][Not invited]
  • Y. Tada, A. Asahina, T. Takekoshi, M. Kishimoto, H. Mitsui, H. Saeki, M. Komine, K. Tamaki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  126-  37  -37  2006/04  [Not refereed][Not invited]
  • K. Kikuchi, T. Hoashi, M. Komine, K. Tamaki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  126-  144  -144  2006/04  [Not refereed][Not invited]
  • M. Komine, S. Yano, H. Okochi, M. Blumenberg, K. Tamaki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  126-  33  -33  2006/04  [Not refereed][Not invited]
  • Y. Tsunemi, H. Saeki, K. Nakamura, D. Nagakubo, T. Nakayama, O. Yoshie, S. Kagami, K. Shimazu, T. Kadono, M. Sugaya, M. Komine, K. Matsushima, K. Tamaki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  126-  109  -109  2006/04  [Not refereed][Not invited]
  • 小宮根 真弓  アレルギ-科  21-  (4)  347  -354  2006/04  [Not refereed][Not invited]
  • Y Iizuka, T Yokomizo, K Terawaki, M Komine, K Tamaki, T Shimizu  PROSTAGLANDINS & OTHER LIPID MEDIATORS  79-  (1-2)  163  -164  2006/03  [Not refereed][Not invited]
  • TSUNEMI Yuichiro, SHIMAZU Kiyo, HATTORI Naoko, SHIRAI Akira, TOYAMA Keiko, SAEKI Hidehisa, KOMINE Mayumi, TAMAKI Kunihiko  日本皮膚科学会雑誌 = THE JAPANESE JOURNAL OF DERMATOLOGY  116-  (2)  193  -200  2006/02  [Not refereed][Not invited]
  • 尋常性乾癬の経過中に発症した上大静脈症候群の1例
    細野 周作, 佐々木 苗胤, 門野 岳史, 尹 浩信, 小宮根 真弓, 朝比奈 昭彦, 菊池 かな子, 玉置 邦彦  日本皮膚科学会雑誌  115-  (10)  1509  -1509  2005/09  [Not refereed][Not invited]
  • 飯塚 佳子, 横溝 岳彦, 小宮根 真弓, 玉置 邦彦, 清水 孝雄  脂質生化学研究  47-  212  -214  2005/06  [Not refereed][Not invited]
  • 血清中CCL17,CCL27濃度が病勢と一致したセザリー症候群の一例
    菅谷 誠, 鑑 慎司, 増井 友里, 藤田 英樹, 小宮根 真弓, 佐伯 秀久, 玉置 邦彦  日本リンパ網内系学会会誌  45-  94  -94  2005/06  [Not refereed][Not invited]
  • KOMINE Mayumi, YANO Shoichiro, OKOCHI Hitoshi, TAMAKI Kunihiko, BLUMENBERG Miroslav  Ensho Saisei  25-  (3)  186  -191  2005/05  [Not refereed][Not invited]
     
    Mechanical stress has profound influences on human body. Muscle training strengthens the muscles, and high blood pressure thickens the vessel walls. Intense studies have been made by various investigators on how mechanical stress influences the human tissues. Epidermal keratinocytes are continuously exposed to mechanical forces. The human skin surface can be thickened and enlarged by various stress such as tissue expander or abrasive pressure. Keratinocytes were plated on flexible silicone dishes, and they were continuously stretched. Stretching of keratinocytes caused up-regulation of 5-bromo-2'-deoxyuridine (BrdU)-positive cells and activation of extracellular signal-regulated kinases (ERK) 1/2. EGF receptor, calcium channel, and ERK were involved in stretch-induced BrdU incorporation. Stretching also induced keratin K6, which is expressed in activated and proliferating keratinocytes, and suppressed keratin K10, which is expressed in differentiated keratinocytes, and their regulation was inhibited by MEK1/2 inhibitor. EGF receptor as well as adhesion molecules have been reported to be involved in transducing mechanical stresses. Several diseases involving heart and palmoplantar skin are caused by the mutation in desmosomal proteins, indicating that adhesion molecules play an important part in sustaining normal structure of skin under the mechanical stress.
  • M Komine, S Yano, H Okochi, M Blumenberg, K Tamaki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  124-  (4)  A63  -A63  2005/04  [Not refereed][Not invited]
  • S Kagami, T Kakinuma, H Saeki, Y Tsunemi, H Fujita, K Sasaki, K Nakamura, T Takekoshi, M Kishimoto, H Mitsui, M Komine, A Asahina, K Tamaki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  124-  (4)  A110  -A110  2005/04  [Not refereed][Not invited]
  • 【物理化学的皮膚障害】 Interventional Radiologyに伴う放射線皮膚障害の4例
    竹腰 知紀, 鹿田 純一郎, レパヴー・アンドレ, 出月 健夫, 藤本 学, 尹 浩信, 小宮根 真弓, 川端 康浩, 朝比奈 昭彦, 玉置 邦彦, 多久嶋 亮彦  皮膚科の臨床  47-  (4)  521  -524  2005/04  [Not refereed][Not invited]
     
    症例1:68歳男.冠動脈造影(CAG)1回,経皮的冠動脈形成術(PTCA)2回施行され,4ヵ月後に右背部の照射部位に一致して境界明瞭な紅斑を認め,中央にびらんを伴った.再度CAGを行ったところ,中央が黒色調を呈する壊疽組織を付着する潰瘍を認め,現在保存治療を行っている.症例2:65歳男.CAG 3回,PTCA 4回施行され,5ヵ月後に右背部に手拳大の暗紅色紅斑が出現し潰瘍化した.保存的治療で出現・消退を繰り返している.症例3:52歳男.CAG 4回,PTCD 3回施行後,2ヵ月後より右側胸部に皮膚萎縮を伴う紅褐色局面と中央に黄白色壊死を付着する拇指頭大の潰瘍を認めた.病理組織像で潰瘍面は壊死組織で覆われ真皮膠原線維は硝子化を伴い著しく膨化・増生していた.デブリードマン,広背筋弁,分層植皮術を行ったが,術後30ヵ月の現在,潰瘍の再発はないが疼痛がある.症例4:39歳男.カテーテルアブレーション施行後,右上腕のマンシェット装着部位の発赤,水疱,潰瘍形成を認めた.現在,皮膚硬化に対し軟膏外用で加療中であるが,改善していない
  • 掌蹠に著明な角質増生を呈した尋常性乾癬の1例
    大江 隆之, 前川 武雄, 白井 明, ニンデル・マーギット, 佐伯 秀久, 尹 浩信, 小宮根 真弓, 朝比奈 昭彦, 菊池 かな子, 玉置 邦彦  日本皮膚科学会雑誌  114-  (10)  1671  -1671  2004/09  [Not refereed][Not invited]
  • Interventional radiology(IVR)に伴う放射線皮膚障害の4例
    竹腰 知紀, 鹿田 純一郎, レパヴー・アンドレ, 出月 健夫, 藤本 学, 尹 浩信, 小宮根 真弓, 川端 康浩, 朝比奈 昭彦, 玉置 邦彦  西日本皮膚科  66-  (3)  305  -305  2004/06  [Not refereed][Not invited]
  • K Kikuchi, E Kato, M Komine, K Tamaki, T Hoashi, VJ Hearing  JOURNAL OF INVESTIGATIVE DERMATOLOGY  122-  (3)  A150  -A150  2004/03  [Not refereed][Not invited]
  • M Komine, E Kato, K Kikuchi, H Okochi, K Tamaki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  122-  (3)  A156  -A156  2004/03  [Not refereed][Not invited]
  • S Kagami, T Kakinuma, H Saeki, Y Tsunemi, K Nakamura, M Komine, A Asahina, K Tamaki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  122-  (3)  A115  -A115  2004/03  [Not refereed][Not invited]
  • 血清P-III-P値が病勢を反映した好酸球性筋膜炎の1例
    加藤 悦子, 鹿田 純一郎, 尹 浩信, 小宮根 真弓, 菊池 かな子, 玉置 邦彦  日本皮膚科学会雑誌  114-  (2)  199  -200  2004/02  [Not refereed][Not invited]
  • 潰瘍性大腸炎に合併した水疱性壊疽性膿皮症の1例
    加藤 悦子, 山根 謙一, 鹿田 純一郎, 尹 浩信, 小宮根 真弓, 菊池 かな子, 玉置 邦彦  日本皮膚科学会雑誌  114-  (2)  209  -209  2004/02  [Not refereed][Not invited]
  • TNF-αとIFN-γで相乗的に増強したヒト角化細胞(HaCaT細胞)のMDC産生はIL-4やIL-13により阻害された
    肖 汀, 佐伯 秀久, 柿沼 誉, 中村 晃一郎, 菅谷 誠, 三井 浩, 鳥居 秀嗣, 小宮根 真弓, 朝比奈 昭彦, 玉置 邦彦  日本研究皮膚科学会年次学術大会・総会プログラム  27回-  116  -116  2002/08  [Not refereed][Not invited]
  • T Kakinuma, K Nakamura, M Wakugawa, S Yano, H Saeki, H Torii, M Komine, A Asahina, K Tamaki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  119-  (1)  304  -304  2002/07  [Not refereed][Not invited]
  • M Komine, T Kakinuma, S Yano, K Tamaki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  119-  (1)  345  -345  2002/07  [Not refereed][Not invited]
  • Y Tsunemi, H Saeki, K Nakamura, T Kakinuma, H Fujita, N Asano, M Kishimoto, Y Tanida, H Mitsui, Y Tada, M Wakugawa, H Torii, M Komine, A Asahima, K Tamaki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  119-  (1)  262  -262  2002/07  [Not refereed][Not invited]
  • S Yano, M Komine, H Okochi, K Tamaki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  119-  (1)  274  -274  2002/07  [Not refereed][Not invited]
  • 【乾癬 その多様な臨床】 治療による皮膚の変化 narrowband UVB照射/カルシポトリオール軟膏外用の併用療法を行った尋常性乾癬
    竹腰 知紀, 小宮根 真弓, 朝比奈 昭彦  Visual Dermatology  1-  (5)  508  -509  2002/07  [Not refereed][Not invited]
  • alvoelar soft sarcomaの皮下転移と思われる1例
    藤田 英樹, 鳥居 秀嗣, 小宮根 真弓, 菊池 かな子, 水口 英彦, 元井 紀子  日本皮膚科学会雑誌  112-  (3)  276  -276  2002/03  [Not refereed][Not invited]
  • 柿沼 誉, 中村 晃一郎, 湧川 基史, 三井 浩, 多田 弥生, 佐伯 秀久, 鳥居 秀嗣, 小宮根 真弓, 朝比奈 昭彦, 玉置 邦彦  アレルギー  51-  (2)  2002/03  [Not refereed][Not invited]
  • N Hattori, M Komine, T Kaneko, K Kikuchi, Y Nakabayashi, K Tamaki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  117-  (2)  412  -412  2001/08  [Not refereed][Not invited]
  • H Saeki, N Furuya, H Mitsui, Y Tada, H Torii, M Komine, A Asahina, K Tamaki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  117-  (2)  514  -514  2001/08  [Not refereed][Not invited]
  • K Nakamura, M Komine, K Tamaki  JOURNAL OF INVESTIGATIVE DERMATOLOGY  117-  (2)  457  -457  2001/08  [Not refereed][Not invited]
  • CTCLに生じたKi-1 lymphomaの1例
    古屋 典子, 菅谷 誠, 林 伸和, 小宮根 真弓, 大河内 仁志, 菊池 かな子, 玉置 邦彦, 佐々木 学  西日本皮膚科  63-  (4)  472  -472  2001/07  [Not refereed][Not invited]
  • FUJITA Etsuko, KOMINE Mayumi, WAKUGAWA Motoshi, ASAHINA Akihiko, KAWABATA Yasuhiro, SOMA Yoshinao, SATO Hiroyuki, MOTOKURA Toru, TAMAKI Kunihiko  日本皮膚科学会雑誌  111-  (7)  1083  -1090  2001/06  [Not refereed][Not invited]
  • 【膠原病】 肺癌を合併した非定型強皮症の1例
    古屋 典子, 久保 正英, 小宮根 真弓, 尹 浩信, 菊池 かな子, 玉置 邦彦  皮膚科の臨床  43-  (5)  599  -602  2001/05  [Not refereed][Not invited]
     
    83歳女.体幹に掻痒,腹部に色素沈着及び皮膚硬化局面が出現した.急速に躯幹,四肢に拡大した為,当科受診.初診時,皮膚硬化は顔面や手足,乳頭部,乳房下部,肘・膝関節部を除いてほぼ左右対称性に存在していた.Raynaud現象はなく,抗核抗体・特異抗体共に陰性であった.全身検査にて食道蠕動低下及び肺に高分化型腺癌を認めた.なお肺線維症はなかった.肺癌治療後,皮膚硬化は自然軽快した
  • 肺癌を合併した非定型強皮症の1例
    古屋 典子, 小宮根 真弓, 尹 浩信, 菊池 かな子, 玉置 邦彦  日本皮膚科学会雑誌  110-  (2)  216  -216  2000/02  [Not refereed][Not invited]
  • M Komine, N Hattori, K Tamaki, M Blumenberg, IM Freedberg  JOURNAL OF INVESTIGATIVE DERMATOLOGY  112-  (4)  588  -588  1999/04  [Not refereed][Not invited]
  • T Kaneko, M Komine, K Tamaki, A Gazel, G Pintucci, IM Freedberg, M Blumenberg  JOURNAL OF INVESTIGATIVE DERMATOLOGY  112-  (4)  563  -563  1999/04  [Not refereed][Not invited]
  • 鈴木 さやか, 林 伸和, 小宮根 真弓, 中村 晃一郎, 菊池 かな子, 玉置 邦彦, 土屋 尚之, 徳永 勝士, 米本 広明, 井上 奈津彦, 南光 弘子, 南光 進一郎  アレルギー  48-  (2)  1999/03  [Not refereed][Not invited]
  • 原田 昭太郎, 五十嵐 敦之, 北原 比呂人, 中川 秀己, 大槻 マミ太郎, 朝比奈 昭彦, 佐伯 秀久, 小宮根 真弓, 玉置 邦彦, 小澤 明, 菅井 順一, 大城戸 宗男  西日本皮膚科 = The Nishinihon journal of dermatology  60-  (6)  832  -841  1998/12  [Not refereed][Not invited]
  • 原田 昭太郎, 五十嵐 敦之, 北原 比呂人, 中川 秀己, 大槻 マミ太郎, 朝比奈 昭彦, 佐伯 秀久, 小宮根 真弓, 玉置 邦彦, 小澤 明, 菅井 順一, 大城戸 宗男  西日本皮膚科 = The Nishinihon journal of dermatology  60-  (6)  842  -848  1998/12  [Not refereed][Not invited]
  • 小宮根 真弓, 玉置 邦彦, FREEDBERG I. M, BLUMENBERG M  日本皮膚科学会雑誌  108-  (12)  1562  -1563  1998/10  [Not refereed][Not invited]
  • M Blumenberg, M Komine, LM Rao, SH Ma, IM Freedberg  JOURNAL OF INVESTIGATIVE DERMATOLOGY  110-  (4)  494  -494  1998/04  [Not refereed][Not invited]
  • IM Freedberg, N Radoja, M TomicCanic, M Komine, M Blumenberg  JOURNAL OF INVESTIGATIVE DERMATOLOGY  108-  (4)  76  -76  1997/04  [Not refereed][Not invited]
  • M Komine, A Semat, IM Freedberg, M Blumenberg  JOURNAL OF INVESTIGATIVE DERMATOLOGY  106-  (4)  585  -585  1996/04  [Not refereed][Not invited]
  • M Komine, IM Freedberg, M Blumenberg  JOURNAL OF INVESTIGATIVE DERMATOLOGY  106-  (4)  202  -202  1996/04  [Not refereed][Not invited]
  • ARATA Jiro, AKIYAMA Hisanori, TORIGOE Rikako, MATSUURA Noriko, ISHIBASHI Yasumasa, TAKEHARA Kazuhiko, OHKOUCHI Hitoshi, KIKUCHI Kanako, YAMADA Nobuo, KOMINE Mayumi, KANEKO Takehiko, WAKUGAWA Motofumi, NIIMURA Michihito, KAMIDE Ryoichi, HONDA Mariko, INOUE Natsuhiko, YOKOI Kiyoshi, HASHIMOTO Toru, ITAMI Satomi, TANAKA Hiroyasu, ISHIJI Takaoki, SAWADA Shunichi, TAKAHASHI Hisashi, WATANABE Shinichi, OHSUMI Masayoshi, OHNISHI Takamitsu, TOMIZAWA Takanori, YAMADA Koji, WATABE Yoshihiro, ASADA Yasuo, AKAMATSU Hirohiko, AKAMATSU Maki, NISHIJIMA Setsuko, HORI Yoshiaki, KOGA Tetsuya, MATSUDA Tetsuo, TAKEUCHI Minoru, SATO Emiko, HARA Sachiko, URABE Atsumichi  日本化学療法学会雜誌 = Japanese journal of chemotherapy  43-  392  -405  1995/11  [Not refereed][Not invited]
  • M KOMINE, IM FREEDBERG, A SEMAT, M BLUMENBERG  JOURNAL OF INVESTIGATIVE DERMATOLOGY  104-  (4)  586  -586  1995/04  [Not refereed][Not invited]
  • M TOMICCANIC, M KOMINE, C SANTIAGO, D DIAZ, IM FREEDBERG, M BLUMENBERG  JOURNAL OF INVESTIGATIVE DERMATOLOGY  104-  (4)  593  -593  1995/04  [Not refereed][Not invited]
  • M BLUMENBERG, M KOMINE, S GORELICK, IM FREEDBERG  JOURNAL OF INVESTIGATIVE DERMATOLOGY  104-  (4)  591  -591  1995/04  [Not refereed][Not invited]
  • ARATA Jiro, SHIMOE Keisei, AKIYAMA Naonori, KANZAKI Hiroko, MATSUURA Yoshiko, YAMADA Taku, TORIGOE Rikako, OHGAWARA Akira, KOIZUMI Youko, NISHIKAWA Takeji, FUKUDA Tomoo, TAKAHASHI Hisashi, WATANABE Shini-ichi, MOGI Syoko, OKADA Hiroyuki, OHNISHI Yoshimitsu, TAMAKI Kunihiko, ISHIBASHI Yasumasa, TSUCHIDA Tetsuya, NAKAMURA Koichiro, MINAMI Haruo, IMAKADO Sumihisa, URA Hironobu, ASAHINA Akihiko, IOZUMI Ken, KANEKO Takehiko, OHKOCHI Hitoshi, ETO Takafumi, OHTSUKI Mamitaro, HARADA Shotaro, NAKANISHI Hiroshi, ABE Masanori, KAWABATA Yasuhiro, KOMINE Mayumi, TORII Hidenori, KANEKO Takehiko, SAITO Ryuzo, URUSHIBATA Osamu, MAKINO Sagae, NAKAJIMA Hiroshi, ISHII Norihisa, TOMIZAWA Takanori, YAMADA Koji, WATABE Yoshihiro, YASUNO Yoichi, OKUDA Ryoji, KONISHI Keisuke, ASADA Yasuo, FUTAMURA Shozo, IBA Hitoki, MASUDA Rie, KUROKAWA Ichiro, AKAI Yoko, UOI Miyuki, UMEMURA Shigeo, NAGAO Hiroshi, MASUDA Toshiki, NISHIHARA Osami, KATAYAMA Haruko, HIRANO Noriko, MIYOSHI Kaoru, YOKOO Masako, MORI Ken-ichi, AKAGI Osamu, NAKAKITA Takashi, YAMAMOTO Shoso, NAKAMURA Koji, HORI Yoshiyuki, KIRYU Hiromaro, KOGA Tetsuya, YASUMOTO Shin-ichiro, URABE Atsumichi, SATO Emiko, YSAUDA Masaru, WADA Kyoko, YAHATA Takashi, YOSHIDA Hikotaro, TANAKA Keiichi, DOI Takashi  Japanese Journal of Chemotherapy  43-  401  -414  1995/01  [Not refereed][Not invited]
     
    A multicenter clinical trial was conducted to evaluate the clinical efficacy, safety and usefulness of ritipenem acoxil (RIPM-AC), a new oral penem antibiotic, in the field of dermatology. Patients, aged more than 16 years, were enrolled in the trial after informed consent had been obtained. Two hundred eighty-four patients were enrolled. Clinical evaluation was done in 258 patients. The main dosage was 200 mg t. i. d. The duration of treatment was 7 days except for infected atheroma and miscellaneous subcutaneous abscesses, which were treated for 10 days. The overall efficacy rate was 88.8%. The bacteriological response rate was 90.5% (190/210). Adverse reactions were seen in 7.9% (22/278), but were all minor and mostly of gastrointestinal origin. Abnormal laboratory findings were seen in 7.9% (18/227). All were minor.
    The minimum inhibitory concentration (MIC) of ritipenem (RIPM) against Staphylococcus aureus stock strains (isolated in 1990-1991 at Okayama University Hospital, Department of Dermatology, 89 strains) ranged from 0.06-32μg/ml with the MIC inhibiting 90% of the strains (MIC90) at 1μg/ml, The MICs of RIPM against 88 isolates of S. aureus in this trial ranged from ≤0.05-> 100μg/ml with the MI90 at 0.20μg/ml. The concentrations of RIPM in the skin and plasma after a single oral administration of 150mg, 200mg or 400mg were determined in skin surgery patients after informed consent had been obtained. The samples were obtained 30-420 min after drug administration. The concentrations were undetectable in many samples. The reason for this was unknown. On the basis of the data obtained from the samples in which the concentrations both in skin and plasma could be detected, skin and plasma concentration ratios varied from 4.1 to 96.4%. Rates around 10% were most frequent.
  • Jiro Arata, Yoshiko Matsuura, Hisanori Akiyama, Akira Ogawara, Hiroko Koizumi, Yasumasa Ishibashi, Ken Iozumi, Takeshi Tamaki, Koichiro Nakamura, Kazuhiko Takehara, Hisashi Takahashi, Shin-ichi Watanabe, Takamitsu Ohnishi, Michihito Niimura, Ryoichi Kamide, Taketoshi Yaginuma, Shunichi Sawada, Kiyoshi Yokoi, Nakao Nomura, Osamu Urushibata, Sagae Makino, Ryuzo Saito, Shotaro Harada, Hiroshi Nakanishi, Mayumi Komine, Masanori Abe, Takanori Tomizawa, Kouji Yamada, Yoshihiro Watabe, Shunji Mori, Tadashi Nanba, Yuji Horiguchi, Takao Tachibana, Toshihiro Tanaka, Fukumi Furukawa, Kiichiro Danno, Koichi Ikai, Sadao Imamura, Yasuo Asada, Takeshi Horio, Setsuko Nishijima, Taiki Isei, Ichiro Kurokawa, Miyuki Uoi, Yoshio Urano, Shiro Sasaki, Yoshiyuki Kanno, Seiji Arase, Hajime Kodama, Masami Ikeda, Yoshiaki Hori, Juichiro Nakayama, Shinichiro Yasumoto, Shonosuke Nagae, Masaaki Tashiro, Mitsuru Setoyama, Tetsu Hamada, Tamotsu Kanzaki  Japanese Journal of Chemotherapy  43-  468  -480  1995  [Not refereed][Not invited]
     
    In a multicenter clinical trial, grepafloxacin (GPFX), a new fluoroquinolone, was examined in terms of its skin penetration and its clinical efficacy in the treatment of skin and skin structure infections. Patients were enrolled in the trial, after informed consent was obtained. Skin samples were obtained from the normal portions of excised materials in 22 skin surgery patients who received a single oral dose of 200mg of GPFX. The excision was done 51 to 266 min after drug administration in 20 patients and 24 h after drug administration in two patients. The blood samples were drawn about the same time as the skin excisions. The skin and blood levels were 0.12 to 2.35.μg/g and 0.06 to 1.07.μg/ml, respectively, where levels lower than the detectable limits (3 cases for skin and one for serum) were omitted. The skin concentration and serum concentration ratios varied from 14.6% to 343.3%. The skin and serum levels in two patients after 24 h were (0.72, 0.72.μg/g) and (0.10, 0.18.μg/ml), respectively. The skin concentration and serum concentration ratios were 720% and 400%. Minimum inhibitory concentrations (MICs) of GPFX against 63 clinical isolates of Staphylococcus aureus ranged from 0.024 to 12.5.μg/ml, with MIC inhibiting 50% of the strains at 0.05.μg/ml and MIC inhibiting 90% of the strains at 0.2.μg/ml. GPFX was administered to 179 patients. Clinical efficacy was evaluated in 169 patients. The daily dosages were 100 mg once a day in 43 patients, 200mg once a day in 39 patients, and 100mg twice a day in 87 patients. Clinical evaluation was done in less than 9 days except for infected atheroma and miscellaneous abscesses in which evaluation was done in less than 12 days. The overall clinical efficacy rate was 89.3%(151/169). The rates were 83.7%(36/43) in the group given 100mg once a day, 92.3%(36/39) in the group given 200mg once a day, and 90.8%(79/87) in the group given 100mg twice a day. The bacteriologic response rate was 81.1%(82.1% for S.aureus). Adverse reactions were seen in 4 out of 175 patients. Skin eruption was seen in 2 patients, but phototoxicity was not observed. Minor abnormalities of laboratory findings were seen in 7 out of 146 patients. We concluded that GPFX is worthy of further investigation in the dermatological field and that the dose of 200mg once a day will be useful in terms of compliance. Phototoxicity should be carefully monitored. © 1995, Japanese Society of Chemotherapy. All rights reserved.
  • JAM LATKOWSKI, M KOMINE, IM FREEDBERG, M BLUMENBERG  JOURNAL OF INVESTIGATIVE DERMATOLOGY  102-  (4)  640  -640  1994/04  [Not refereed][Not invited]
  • M KOMINE, DJ LUCAS, IM FREEDBERG, M BLUMENBERG  JOURNAL OF INVESTIGATIVE DERMATOLOGY  102-  (4)  640  -640  1994/04  [Not refereed][Not invited]
  • M KOMINE, IM FREEDBERG, M BLUMENBERG  JOURNAL OF INVESTIGATIVE DERMATOLOGY  102-  (4)  640  -640  1994/04  [Not refereed][Not invited]
  • ARATA JIRO, IHN HIRONOBU, ABE MASAMIZU, KOMINE MAYUMI, KUKITA ATSUSHI, HIRUMA MASATARO, MATSUI RYOSUKE, KANESHIGE YOSHIAKI, HARADA SHOTARO, MINAMI HARUO, TAMAKI TAKESHI, AKIYAMA HISANORI, ANZAI TAKASHI, JITSUKAWA KUMIKO, SAITO RYUZO, URUSHIBATA OSAMU, ASASHIMA HIROO, YASUNO YOICHI, KISHIMOTO SABURO, KONISHI KEISUKE, TAKENAKA HIDEYA, OKA FUMIKO, KANZAKI HIROKO, UEDA FUJIO, ASADA YASUO, YAMAWAKI MITSUO, ISEI TAIKI, IMAMURA SADAO, TACHIBANA TAKAO, OOTANI NORIO, AKIOKA NARIMI, DOI AKIRA, MASUDA RIE, TAKAHASHI HISASHI, AKAI YOKO, HAYAKAWA MINORU, HAYASHI MIZUYO, TANABE HIROSHI, UEKI HIROAKI, INAGAKI YASUNORI, MIYOSHI KAORU, NAKATSUKASA AKIHIRO, UMEMURA SHIGEO, SUWAKI MASAO, TANAKA YUI, AKAGI OSAMU, NAKAKITA TAKASHI, KODAMA HAJIME, YAMAMOTO YASUO, IKEDA MASAMI, HORI YOSHIAKI, NAGAE SHONOSUKE, TAKAHAMA HIDETO, FUJIMURA MAMI, KUSHIBUCHI SAYAKA, ISHIBASHI YASUMASA  The Japanese Journal of Antibiotics  45-  (2)  197  -207  1992  [Not refereed][Not invited]
     
    Panipenem/betamipron (PAPM/BP), a new carbapenem, was studied in dermatology.
    PAPM/BP was used clinically in the treatment of skin and skin structure infections in a multicenter trial. Fifty three patients were enrolled in the trial. Clinical evaluations were made in 50 patients. Most patients received intravenous infusion of PAPM/BP in a dose of 500 mg twice daily. Other dosages were used in some patients.
    The overall clinical efficacy rate was 78%. When 15 cases of secondary infections were excluded, the rate was 85.7%. Adverse responses were nausea and/or vomiting in 3 patients, redness with itching in 1 patient, headache or head heaviness in 2 patients and diarrhea in I patient. The patient with redness and itching had also nausea and vomiting. This occurred 1 hour after the start of the first infusion of this drug. After the discontinuation of the treatment the symptoms went away on the next day.
    Abnormalities in laboratory test results were observed in 7 out of 53 patients. One patient with liver cirrhosis and hepatocellular carcinoma developed anemia (RBC 372×104/mm3→275×104/mm3, Hb 11.9g/dl→8.8g/dl, 35.1%→26.0%). Other abnormalities were all mild.
    Penetration of the drug into skin tissues after intravenous infusion of 500mg of this drug in skin surgery patients was studied. Skin/serum concentration ratios ranged from 0.20 to 0.97. Skin concentrations were higher than the concentration of PAPM inhibiting 80% of clinical isolates over a period of 6 hours. In rats, skin concentrations were much lower than serum concentrations probably due to the difference in in vivo metabolism of PAPM.
    A few resistant strains of Staphylococcus aureus against PAPM and imipenem (IPM) were isolated. However, PAPM and IPM showed good antibacterial activities compared to other drugs tested.
    In conclusion, PAPM/BP is considered to be a useful drug in the treatment of skin and skin structure infections.

Research Grants & Projects

  • 文部科学省:科学研究費補助金(基盤研究(C))
    Date (from‐to) : 2011 -2013 
    Author : 小宮根 真弓
     
    今年度は主に培養表皮角化細胞からのIL-33産生機序と、マウスにおける接触過敏反応における可溶性ST2の役割について検討した。UVB照射により、表皮細胞においてIL-33の産生が誘導され、この誘導はEGF受容体、ERK、p38依存的であった。また、表皮細胞をIFNγで刺激することによりIL-33産生が誘導され、これはEGF受容体、ERK、p38、JAK依存的であったが、NFκBには依存していなかった。表皮細胞をIFNγと同時にTNFαで刺激することにより、IL-33のプロセッシングが促進され、これはCaspaseではなくCalpainに依存的であった。表皮細胞をmature IL-33で刺激することによりIL-8産生が誘導されたが、表皮細胞のIL-33をノックダウンすることにより、TNFによるIL-8産生は抑制された。以上より、表皮細胞におけるIL-33産生はUVB照射、IFNγ刺激により誘導され、TNF添加によりCalpain依存的なプロセッシングが促進されることが明らかとなった。またIL-33はサイトカインとしては炎症促進的に働くが、細胞内では炎症抑制的に作用することが示唆された。 また、表皮細胞をはじめとする各種細胞においてIL-33のSplice variantが少なくとも7種発現していることを示し、細胞種により各Variantの発現パターンが異なることを示した。
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(基盤研究(C))
    Date (from‐to) : 2006 -2009 
    Author : Mayumi KOMINE
     
    表皮細胞に発現するCTACK/CCL27、TARC/CCL17などのケモカインについて、トランスジェニックマウスを使用したin vivoの実験と、培養表皮細胞を用いたin vitroの実験から、炎症性皮膚疾患におけるケモカインの役割について検討した結果、CTACK/CCL27およびTARC/CCL17はアトピー性皮膚炎などの炎症性皮膚疾患において、接触アレルギー反応のなかでも特にTh2へ傾いた反応を増強する役割を持つことがわかった。また、表皮細胞から産生されるこれらのケモカインは治療薬である活性型ビタミンD3(カルシポトリオール、マキサカルシトール、天然型ビタミンD3)やステロイド剤(プロピオン酸クロベタゾール)により発現が制御されること、また活性型ビタミンD3の表皮ランゲルハンス細胞に対する作用を明らかにした。これらのことから乾癬やアトピー性皮膚炎に対するこれらの薬剤の効果の機序の一端が明らかとなった。また乾癬患者皮膚を用いた免疫組織学的検討により、乾癬局面周囲の、未だ明らかな皮膚病変を来たしていない部分においてもすでに早期の炎症性変化が生じており、この変化がリンパ球よりもむしろ樹状細胞により惹起されている可能性が示唆され、早期の炎症性変化をターゲットとした新たな治療の可能性が示唆された。
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(基盤研究(C))
    Date (from‐to) : 2002 -2004 
    Author : Mayumi KOMINE, Takashi KAKINUMA
     
    Thymus and activation-regulated chemokine (TARC/CCL17) is a potent chemokine, deeply associated with the pathogenesis of several inflammatory skin diseases, such as atopic dermatitis and bullous pemphigoid. Production of TARC from HaCaT keraitnocytes was synergistically induced by the stimulated with TNFα and IFNγ. NFkB and p38 are indispensable, EGF receptor was negatively involved, and STAT1 was not involved in this induction. PLA2 inhibitor, MAFP, and leukotrien B4 receptor inhibitor, LY, was also effective in suppressing TARC production. IMD, which was produced to suppress NFkB activation was effective in suppressing TARC production from HaCaT keratinocytes. Mechanical stress, are IL-15 are known to induce new lesions in psoriasis. They induced MAP kinase activation, proliferation, and attenuates apoptosis. Mechanical stress induced EGFR phosphorylation, ERK, and AP-1 activation. IL-15 induced ERK and PI3K activation. Suppression of these signaling molecules could be effective in treating inflammatory skin diseases such as psoriasis. We are planning to utilize these possibilities in vivo experiments.


Copyright © MEDIA FUSION Co.,Ltd. All rights reserved.