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写真a

タカムラ ナオコ
高村 直子
Naoko Takamura
所属
医学研究科 医科学専攻 皮膚科学 助教
医学部 医学科
職名
助教
プロフィール

皮膚免疫・アレルギーに関して、基礎・臨床研究を行っている。横浜市立大学大学院では、乾癬、重症薬疹の病態解明と新規治療ターゲットに関して、サウスカロライナ医科大学にて強皮症の皮膚線維化病態と新規治療ターゲットについての研究を行った。

外部リンク

学位

  • 博士(医学) ( 2019年3月   横浜市立大学 )

研究キーワード

  • 乾癬

  • 薬疹

  • 強皮症

研究分野

  • ライフサイエンス / 皮膚科学

論文

  • 特発性後天性全身性無汗症(AIGA)の臨床的特徴についての検討

    井上 舞, 高村 直子, 渡邉 裕子, 杉浦 暖人, 森本 悠里江, 今井 紗綾, 田中 理子, 山口 由衣

    日本皮膚免疫アレルギー学会総会学術大会プログラム・抄録集   54回   230 - 230   2024年12月

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    記述言語:日本語   出版者・発行元:(一社)日本皮膚免疫アレルギー学会  

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  • A water-soluble caveolin-1 peptide inhibits psoriasis-like skin inflammation by suppressing cytokine production and angiogenesis. 国際誌

    Chika Asai, Naoko Takamura, Tomoya Watanabe, Miho Asami, Noriko Ikeda, Charles F Reese, Stanley Hoffman, Yukie Yamaguchi

    Scientific reports   14 ( 1 )   20553 - 20553   2024年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The plasma membrane protein caveolin-1 (CAV-1) regulates signaling by inhibiting a wide range of kinases and other enzymes. Our previous study demonstrated that the downregulation of CAV-1 in psoriatic epidermal cells contributes to inflammation by enhancing JAK/STAT signaling, cell proliferation, and chemokine production. Administration of the CAV-1 scaffolding domain (CSD) peptide suppressed imiquimod (IMQ)-induced psoriasis-like dermatitis. To identify an optimal therapeutic peptide derived from CAV-1, we have compared the efficacy of CSD and subregions of CSD that have been modified to make them water soluble. We refer to these modified peptides as sCSD, sA, sB, and sC. In IMQ-induced psoriasis-like dermatitis, while all four peptides showed major beneficial effects, sB caused the most significant improvements of skin phenotype and number of infiltrating cells, comparable or superior to the effects of sCSD. Phosphorylation of STAT3 was also inhibited by sB. Furthermore, sB suppressed angiogenesis both in vivo in the dermis of IMQ-induced psoriasis mice and in vitro by blocking the ability of conditioned media derived from CAV-1-silenced keratinocytes to inhibit tube formation by HUVEC. In conclusion, sB had similar or greater beneficial effects than sCSD not only by cytokine suppression but by angiogenesis inhibition adding to its ability to target psoriatic inflammation.

    DOI: 10.1038/s41598-024-71350-1

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  • Retrospective study of the clinical significance of the neutrophil-to-lymphocyte ratio in 79 patients with palmoplantar pustulosis. 国際誌

    Tomoya Watanabe, Yuko Watanabe, Chika Asai, Miho Asami, Naoko Takamura, Yukie Yamaguchi

    The Journal of dermatology   51 ( 9 )   1208 - 1215   2024年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Palmoplantar pustulosis (PPP) is a chronic relapsing inflammatory skin disease characterized by multiple vesicles, pustules, and erythematous plaques on the palms and soles. The exacerbation of PPP is strongly associated with focal infections, such as tonsillitis, dental infections, and sinusitis, in Japan. Recently, the neutrophil-to-lymphocyte ratio (NLR) has been widely used as a convenient and useful marker for clinical conditions and various diseases; however, an association between PPP and NLR has not yet been established. We retrospectively analyzed 79 patients with PPP from our hospital to evaluate the clinical significance of the NLR. The average NLR value in patients with PPP was significantly higher than that in healthy controls (2.30 ± 1.02 vs 1.69 ± 0.45, P < 0.001). A comparative analysis of patients with PPP with and without infectious complications showed that there was a statistical difference in the NLR between patients with PPP with and without focal infections, whereas no significant difference was found for metal allergy, smoking, and pustulotic arthro-osteitis. Multivariate analysis indicated that the NLR was significantly associated with focal infections (odds ratio = 18.38, 95% confidence interval 3.86-87.35, P < 0.001). The NLR was also significantly correlated with C-reactive protein levels (P = 0.013, r = 0.2857). Interestingly, after symptom improvement, the NLR significantly decreased from the baseline levels. Furthermore, statistical analysis using the Youden's index revealed that an NLR of 2.28 or higher was associated with the risk of any focal infections in patients with PPP. These results suggest that the NLR has potential applications as a biomarker of the presence of focal infections in patients with PPP.

    DOI: 10.1111/1346-8138.17272

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  • 薬疹・遅延型薬物アレルギー 複数の感染性DIHS関連合併症を併発し,死亡したアロプリノールによる薬剤性過敏症症候群の1例

    頼母木 まゆ美, 渡邉 裕子, 乙竹 泰, 高村 直子, 山口 由衣

    アレルギー   73 ( 6-7 )   827 - 827   2024年8月

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    記述言語:日本語   出版者・発行元:(一社)日本アレルギー学会  

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  • アトピー性皮膚炎・接触皮膚炎・遺伝性血管性浮腫 美容液に含まれる3-グリセリルアスコルビン酸によるアレルギー性接触皮膚炎の1例

    荒川 遥, 高村 直子, 永山 貴紗子, 渡邉 裕子, 廣門 未知子, 山口 由衣

    アレルギー   73 ( 6-7 )   856 - 856   2024年8月

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    記述言語:日本語   出版者・発行元:(一社)日本アレルギー学会  

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  • デュピルマブ投与中に結膜炎を生じたアトピー性皮膚炎患者の臨床的解析

    頼母木 まゆ美, 渡邉 裕子, 浅見 美穂, 永山 貴紗子, 高村 直子, 山口 由衣

    西日本皮膚科   86 ( 3 )   330 - 330   2024年6月

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    記述言語:日本語   出版者・発行元:日本皮膚科学会-西部支部  

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  • JAK阻害薬投与後にIgE,TARC値が著増し,二次無効となったアトピー性皮膚炎の3例

    村田 智孝, 浅井 知佳, 渡邉 裕子, 荒川 遥, 頼母木 まゆ美, 永山 貴紗子, 高村 直子, 山口 由衣

    日本皮膚科学会雑誌   134 ( 5 )   1485 - 1485   2024年5月

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    記述言語:日本語   出版者・発行元:(公社)日本皮膚科学会  

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  • アトピー性皮膚炎患者におけるデュピルマブ関連結膜炎の臨床的解析

    永山 貴紗子, 渡邉 裕子, 頼母木 まゆ美, 浅見 美穂, 高村 直子, 山口 由衣

    日本皮膚免疫アレルギー学会総会学術大会プログラム・抄録集   53回   204 - 204   2023年12月

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    記述言語:日本語   出版者・発行元:(一社)日本皮膚免疫アレルギー学会  

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  • 遅延型薬疹患者における炎症性バイオマーカーの推移についての検討

    荒川 遥, 渡邉 裕子, 頼母木 まゆ美, 久保 玲子, 永山 貴紗子, 浅見 美穂, 高村 直子, 山口 由衣

    日本皮膚免疫アレルギー学会総会学術大会プログラム・抄録集   53回   226 - 226   2023年12月

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    記述言語:日本語   出版者・発行元:(一社)日本皮膚免疫アレルギー学会  

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  • 【psoriatic disease~全身疾患へのアプローチ~】乾癬の生物学的製剤投与後に発症したIgA腎症

    高村 直子, 渡邉 裕子, 山口 由衣

    皮膚病診療   45 ( 10 )   891 - 895   2023年10月

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    記述言語:日本語   出版者・発行元:(株)協和企画  

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  • 蕁麻疹・血管性浮腫・その他の皮膚アレルギー 遅延型薬疹患者における薬疹発症前後の炎症性バイオマーカーの推移

    永山 貴紗子, 渡邉 裕子, 荒川 遥, 高村 直子, 山口 由衣

    アレルギー   72 ( 6-7 )   907 - 907   2023年8月

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    記述言語:日本語   出版者・発行元:(一社)日本アレルギー学会  

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  • アトピー性皮膚炎の治療と管理1 デュピルマブ投与中に結膜炎を生じたアトピー性皮膚炎患者における臨床的解析

    頼母木 まゆ美, 浅見 美穂, 永山 貴紗子, 高村 直子, 渡邉 裕子, 山口 由衣

    アレルギー   72 ( 6-7 )   876 - 876   2023年8月

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    記述言語:日本語   出版者・発行元:(一社)日本アレルギー学会  

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  • 薬疹におけるDLSTの陽性率に関与する因子 単一施設後方視的研究

    川村 飛翔, 渡邉 裕子, 高村 直子, 今井 紗綾, 鈴木 華織, 渡邊 友也, 田村 惇, 三枝 祐輔, 山口 由衣

    日本皮膚科学会雑誌   133 ( 5 )   1351 - 1351   2023年5月

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    記述言語:日本語   出版者・発行元:(公社)日本皮膚科学会  

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  • 手指の難治性潰瘍を契機に診断された硬性下疳の1例

    頼母木 まゆ美, 高村 直子, 渡辺 雪彦, 渡邉 裕子, 高橋 ユエ, 山口 由衣

    日本皮膚科学会雑誌   133 ( 4 )   735 - 735   2023年4月

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    記述言語:日本語   出版者・発行元:(公社)日本皮膚科学会  

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  • 免疫チェックポイント阻害薬によるStevens-Johnson症候群・中毒性表皮壊死症における炎症性バイオマーカーの推移

    渡邉 裕子, 高村 直子, 石川 秀幸, 渡邊 友也, 金岡 美和, 山口 由衣

    日本皮膚科学会雑誌   133 ( 2 )   265 - 265   2023年2月

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    記述言語:日本語   出版者・発行元:(公社)日本皮膚科学会  

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  • 全身性ステロイド減量により再燃を繰り返した薬剤性過敏症症候群の小児例

    今井 紗綾, 渡邉 裕子, 石川 秀幸, 高村 直子, 渡邊 友也, 山口 由衣

    日本皮膚科学会雑誌   133 ( 1 )   70 - 70   2023年1月

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    記述言語:日本語   出版者・発行元:(公社)日本皮膚科学会  

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  • Abnormal inflammatory traits and downregulated caveolin-1 expression in monocytes of psoriasis patients may be associated with psoriatic inflammation and atherosclerosis. 国際誌

    Miho Asami, Yasushi Ototake, Naoko Takamura, Yuko Watanabe, Michiko Aihara, Yukie Yamaguchi

    Journal of dermatological science   107 ( 2 )   65 - 74   2022年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Monocytes and macrophages are implicated in inflammation and atherosclerosis, whereas monocytes are involved in psoriasis lesion formation. We previously reported a psoriatic inflammation-associated significant decrease in the membrane protein caveolin-1 (CAV-1) in psoriasis patient monocytes. However, the phenotype of circulating monocytes and their macrophage differentiation in psoriasis patients remain unclear. OBJECTIVE: We sought to clarify circulating monocyte and monocyte-derived macrophage (MDM) phenotypes in psoriasis patients with and without comorbidities. METHODS: Thirty-one patients with psoriasis vulgaris and 28 control subjects were included. Surface macrophage markers and inflammatory status were examined in circulating monocytes and MDMs from both groups. Expression of CD36, which mediates macrophage uptake of oxidized low-density lipoprotein (oxLDL), was evaluated in these cells. CAV-1-silenced monocytes were differentiated into macrophages to investigate the effects of CAV-1 downregulation on psoriatic inflammation and atherosclerosis. RESULTS: Macrophage surface markers were detectable in circulating monocytes. A significant M1 shift was detected in monocytes and MDMs in psoriasis patients, including those without cardiovascular disease risk factors, as compared to controls. MDMs of psoriasis patients had more CD36-expressing cells, which are associated with atherosclerosis risk. Additionally, CAV-1-silencing in monocytes increased the likelihood of M1-biased macrophage differentiation and increased pro-inflammatory cytokine production. CONCLUSIONS: Monocytes from psoriasis patients were more likely to differentiate into M1-dominant macrophages, correlating with inflammatory status and CAV-1 expression. These aberrant inflammatory monocytes not only contribute to psoriatic inflammation by producing psoriatic cytokines, but also have a phenotype that could increase atherosclerosis risk by uptake of oxLDL and formation of foam cells.

    DOI: 10.1016/j.jdermsci.2022.07.003

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  • A pediatric case of Stevens-Johnson syndrome with acute liver failure, resulting in liver transplantation. 国際誌

    Michiru Totsuka, Tomoya Watanabe, Naoko Takamura, Yuko Watanabe, Takafumi Kumamoto, Yasushi Honda, Masato Yoneda, Satoru Saito, Shoji Yamanaka, Michiko Aihara

    The Journal of dermatology   48 ( 9 )   1423 - 1427   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are fatal adverse skin reactions characterized by high fever, epidermal detachment, and mucositis. It is well known that SJS/TEN occasionally affects various organs, leading to permanent damage and death in some patients. Although acute liver dysfunction is a relatively common complication of SJS/TEN, severe acute liver dysfunction requiring liver transplantation is rare. We present the case of a 14-year-old girl with SJS complicated by severe and rapidly progressive liver dysfunction, specifically, acute liver failure (ALF) requiring liver transplantation. A lymphocyte transformation test showed positive results for acetaminophen and cefdinir. Furthermore, human leukocyte antigen (HLA) genotyping revealed the presence of the HLA-A*02:06 genotype, which is reported to be strongly associated with acetaminophen-related SJS/TEN with severe ocular complications. These results suggested that our patient may have presented with acetaminophen-induced SJS complicated by ALF, but no ocular complications. This is the first report of a pediatric patient with SJS who required liver transplantation. In rare instances, severe liver dysfunction requiring liver transplantation should be considered as a possible complication of SJS/TEN.

    DOI: 10.1111/1346-8138.15963

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  • Mortality and risk factors on admission in toxic epidermal necrolysis: A cohort study of 59 patients. 国際誌

    Tomoya Watanabe, Hirofumi Go, Yusuke Saigusa, Naoko Takamura, Yuko Watanabe, Yumiko Yamane, Michiru Totsuka, Hideyuki Ishikawa, Kazuko Nakamura, Setsuko Matsukura, Takeshi Kambara, Shunsuke Takaki, Yukie Yamaguchi, Michiko Aihara

    Allergology international : official journal of the Japanese Society of Allergology   70 ( 2 )   229 - 234   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening disorders characterized by widespread epidermal necrosis of the skin and mucosa. The severity-of-illness scoring system for TEN (SCORTEN) was widely used since 2000 as a standard prognostic tool consisting of seven clinical values. METHODS: To evaluate the prognosis using current treatments and risk factors for mortality, we retrospectively analyzed 59 cases of TEN, including SJS/TEN overlap treated in two university hospitals from January 2000 to March 2020. RESULTS: The mortality rate of TEN was 13.6% (8/59). All patients treated with high-dose steroid administration in combination with plasma exchange and/or immunoglobulin therapy recovered. Logistic regression analysis showed nine clinical composite scores, namely: heart rate (≧120 bpm), malignancy present, percentage of body surface area with epidermal detachment (>10%), blood urea nitrogen (>28 mg/dL), serum bicarbonate level (<20 mEq/L), serum glucose level (>252 mg/dL), age (≧71 years), the interval between disease onset and treatment initiation at the specialty hospital (≧8 days), and respiratory disorder within 48 h after admission. The receiver operating characteristic curves confirmed a high potential for predicting the prognosis of TEN. CONCLUSIONS: Recent developments in treatment strategies have contributed to the improved prognosis of TEN patients. A modified severity scoring model composed of nine scores may be helpful in the prediction of TEN prognosis in recent patients. Further large-scale studies are needed to confirm mortality findings to improve prognostication in patients with TEN.

    DOI: 10.1016/j.alit.2020.11.004

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  • 急性肺障害を合併した中毒性表皮壊死症の3例

    鹿毛 勇太, 渡邉 裕子, 佐川 展子, 石川 秀幸, 渡邊 友也, 高村 直子, 金岡 美和, 池田 信昭, 山口 由衣, 相原 道子

    日本皮膚科学会雑誌   131 ( 1 )   100 - 100   2021年1月

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    記述言語:日本語   出版者・発行元:(公社)日本皮膚科学会  

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  • HIV-associated psoriasis with fasciitis and arthritis successfully treated using antiretroviral therapy. 国際誌

    Yukihiko Watanabe, Yukie Yamaguchi, Yuko Watanabe, Miho Asami, Naoko Takamura, Tomoya Watanabe, Hideaki Kato, Michiko Aihara

    The Journal of dermatology   47 ( 11 )   e386-e387   2020年11月

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  • Increased level of high mobility group box 1 in the serum and skin in patients with generalized pustular psoriasis. 国際誌

    Tomoya Watanabe, Yukie Yamaguchi, Yuko Watanabe, Naoko Takamura, Michiko Aihara

    The Journal of dermatology   47 ( 9 )   1033 - 1036   2020年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    High-mobility group box 1 (HMGB-1) is a highly abundant pro-inflammatory protein associated with the pathogenesis of inflammatory and autoimmune diseases. HMGB-1 expression level increases in patients with psoriasis vulgaris (PV). However, HMGB-1 expression in patients with generalized pustular psoriasis (GPP) is unknown. In this study, we investigated HMGB-1 expression in GPP. HMGB-1 expression levels were examined in the skin and serum of patients with GPP, PV, atopic dermatitis (AD) and healthy controls (HC) using enzyme-linked immunosorbent assay and immunohistochemistry. The elevation in HMGB-1 expression was significantly higher in GPP patients than in PV, AD and HC patients. In addition, patients with GPP had elevated serum HMGB-1 levels compared with those with AD and HC. Furthermore, serum HMGB-1 levels were significantly decreased after systemic treatment. In the correlation analysis, a significant positive correlation was detected between serum HMGB-1 levels and the Japanese severity score for GPP. HMGB-1 may be involved in the pathogenesis of GPP and can be useful to evaluate disease severity and the effectiveness of GPP treatment.

    DOI: 10.1111/1346-8138.15467

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  • 横浜市立大学附属2病院におけるStevens-Johnson症候群および中毒性表皮壊死症132例の検討 査読

    渡邊 友也, 高村 直子, 渡邉 裕子, 山根 裕美子, 戸塚 みちる, 石川 秀幸, 中村 和子, 松倉 節子, 蒲原 毅, 山口 由衣, 相原 道子

    日本皮膚科学会雑誌   130 ( 9 )   2059 - 2067   2020年8月

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    記述言語:日本語   出版者・発行元:(公社)日本皮膚科学会  

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  • Toxic epidermal necrolysis accompanied by several immune-related adverse events developed after discontinuation of nivolumab. 国際誌

    Yuko Watanabe, Yukie Yamaguchi, Naoko Takamura, Yukitoshi Takahashi, Michiko Aihara

    European journal of cancer (Oxford, England : 1990)   131   1 - 4   2020年5月

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  • Prominence of IL6, IGF, TLR, and Bioenergetics Pathway Perturbation in Lung Tissues of Scleroderma Patients With Pulmonary Fibrosis. 国際誌

    Ludivine Renaud, Willian A da Silveira, Naoko Takamura, Gary Hardiman, Carol Feghali-Bostwick

    Frontiers in immunology   11   383 - 383   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Scleroderma-associated pulmonary fibrosis (SSc-PF) and idiopathic pulmonary fibrosis (IPF) are two of many chronic fibroproliferative diseases that are responsible for nearly 45% of all deaths in developed countries. While sharing several pathobiological characteristics, they also have very distinct features. Currently no effective anti-fibrotic treatments exist that can halt the progression of PF or reverse it. Our goal is to uncover potential gene targets for the development of anti-fibrotic therapies efficacious in both diseases, and those specific to SSc-PF, by identifying universal pathways and molecules driving fibrosis in SSc-PF and IPF tissues as well as those unique to SSc-PF. Using DNA microarray data, a meta-analysis of the differentially expressed (DE) genes in SSc-PF and IPF lung tissues (diseased vs. normal) was performed followed by a full systems level analysis of the common and unique transcriptomic signatures obtained. Protein-protein interaction networks were generated to identify hub proteins and explore the data using the centrality principle. Our results suggest that therapeutic strategies targeting IL6 trans-signaling, IGFBP2, IGFL2, and the coagulation cascade may be efficacious in both SSc-PF and IPF. Further, our data suggest that the expression of matrikine-producing collagens is also perturbed in PF. Lastly, an overall perturbation of bioenergetics, specifically between glycolysis and fatty acid metabolism, was uncovered in SSc-PF. Our findings provide insights into potential targets for the development of anti-fibrotic therapies that could be effective in both IPF and SSc-PF.

    DOI: 10.3389/fimmu.2020.00383

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  • A case of toxic epidermal necrolysis with refactory acute respiratory distress syndrome 査読

    Ishikawa H, Watanabe Y, Takamura N, Watanabe T, Yamaguchi Y, Aihara M

    J Cutan Immunol Allergy   3 ( 2 )   43 - 44   2020年

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  • Case of severe bullous erythema including intertrigo-like eruptions with angioedema induced by pegylated liposomal doxorubicin. 国際誌

    Michiru Totsuka, Yuko Watanabe, Chika Asai, Saki Takahashi, Hideyuki Ishikawa, Naoko Takamura, Mayumi Hagiwara, Michiko Aihara

    The Journal of dermatology   46 ( 6 )   535 - 539   2019年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Pegylated liposomal doxorubicin (PLD) is an anthracycline anticancer agent used in ovarian cancer and a form of doxorubicin enclosed in pegylated liposomes. There are only a few reports on intertrigo-like eruptions caused by PLD. We describe the first case of severe bullous erythema, including intertrigo-like eruptions with angioedema, induced by PLD in Japan. We present the case of a 53-year-old woman who was diagnosed with stage IIIC ovarian cancer. After receiving three cycles of PLD, the patient developed swelling of the upper lip and painful erythema with blisters and erosions on the axilla, upper back, flank and wrists. The patient was diagnosed with angioedema and severe skin lesions, including intertrigo-like eruptions induced by PLD. Although treatment with oral prednisolone and topical steroids was effective against these eruptions, the administration of PLD was discontinued because of its ineffectiveness against the primary disease. Several risk factors, such as obesity, perspiration and racial differences, may contribute toward a severe manifestation such as that seen in our patient. Moreover, our case was the first accompanied by angioedema. The mechanism of coexistence of intertrigo-like eruptions and angioedema is not clear; further studies are required to clarify the pathological mechanism of intertrigo-like eruptions.

    DOI: 10.1111/1346-8138.14895

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  • Case of toxic epidermal necrolysis occurring after bone marrow transplantation accompanied by engraftment failure. 国際誌

    Chika Asai, Yuko Watanabe, Junko Mukaijo, Naoko Takamura, Tomoko Okawa, Yukie Yamaguchi, Ayako Matsumura, Kenji Matsumoto, Michiko Aihara

    The Journal of dermatology   46 ( 6 )   540 - 543   2019年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Toxic epidermal necrolysis (TEN) is a rare condition, causing life-threatening adverse cutaneous reactions. TEN occurrence after bone marrow transplantation (BMT) is a well-known phenomenon; however, to date, only a few cases have been reported in the published work. Here, we describe the case of a 53-year-old woman who experienced TEN after undergoing allogenic BMT for malignant lymphoma. Skin erosion spread across a maximum of 70% of the body surface area and severe mucosal lesions developed. Steroid pulse therapy, plasma apheresis and immunoglobulin therapy were administrated, which resulted in the complete resolution of TEN. However, she developed hemophagocytic lymphohistiocytosis and died 38 days after BMT, owing to rupture of the lower digestive tract complicated by multi-organ failure. In our case, engraftment failure occurred, and the peripheral white blood cell count was less than 100/μL during the TEN course, suggesting that the presence of only a few immune cells could cause TEN. Our findings showed that high mortality rates and widespread skin erosion could be regarded as the most important characteristics of TEN occurring after BMT.

    DOI: 10.1111/1346-8138.14913

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  • Downregulated Caveolin-1 expression in circulating monocytes may contribute to the pathogenesis of psoriasis. 国際誌

    Naoko Takamura, Yukie Yamaguchi, Yuko Watanabe, Miho Asami, Noriko Komitsu, Michiko Aihara

    Scientific reports   9 ( 1 )   125 - 125   2019年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Caveolin-1 (CAV-1) is the principal component of caveolae that regulates a variety of signaling molecules and receptors. Our previous study revealed CAV-1 reduction in the epidermis of patients with psoriasis, which leads to enhanced Janus kinase/signal transducer and activator of transcription activation and cytokine production, suggesting that aberrant CAV-1 expression may contribute to psoriatic inflammation. This study aimed to investigate whether abnormal modulation of CAV-1 on immune cells is involved in the pathogenesis of psoriasis. We observed that CAV-1 level in psoriasis patients was apparently reduced in peripheral blood mononuclear cells (PBMCs) and it was prominent in CD14+ monocytes. CAV-1 silencing in monocytes represented elevated levels of interleukin (IL)-1β and IL-6, and those had enhanced chemotaxis activity. In a murine model of psoriasis-like inflammation induced by imiquimod, we observed a significant CAV-1 reduction in PBMCs. Systemic administration of CAV-1 scaffolding domain peptide significantly improved the skin phenotype with less macrophage infiltration. Taken together, aberrant CAV-1 expression in monocytes may be involved in the pathogenesis of psoriasis.

    DOI: 10.1038/s41598-018-36767-5

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  • [Analysis of 76 patients with urticaria and angioedema induced by non-steroidal anti-inflammatory drugs (NSAIDs) in Japan].

    Maki Moriya, Michiko Aihara, Rie Hirota, Yuko Hirata, Naoko Ikinaga, Naoko Takamura, Yuko Kunimi, Takahisa Uchida, Zenro Ikezawa

    Arerugi = [Allergy]   60 ( 6 )   699 - 707   2011年6月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The pathogenesis of urticaria and angioedema induced by non-steroidal anti-inflammatory drugs (NSAIDs) is still obscure. We analyzed the clinical characteristics of patients with NSAIDs-induced urticaria and angioedema without asthma in Japan. METHODS: We retrospectively collected the cases of NSAIDs-induced urticaria and angioedema from Japanese medical journals in 2000-2009. RESULTS: Seventy-six patients were analyzed. The male/female ratio was 1:2.5 and the mean age was 38.1 years. Urticaria was most frequent clinical manifestation in 3 groups; urticaria alone, urticaria and angioedema, and angioedema alone. Time interval from drug administration to onset was 5 minutes to 48 hours by aspirin at a dose of 25-1000 mg. Skin prick test was performed with aspirin in 33 patients, and the results were negative in all patients. Meloxicam, a selective cyclooxygenase-2 (COX-2) inhibitor, and celecoxib, a new selective COX-2 inhibitor, were administered safely in 4 of 6 patients and in 2 of 3 patients with NSAIDs-induced urticaria, respectively. These drugs were administered safely in all administered patients with NSAIDs-induced angioedema. Tiaramidehydrochroride (a basic COX-1 inhibitor) was safely used in 23 administered patients with NSAIDs-induced angioedema. Leukotriene receptor antagonists were effective in 2 of 5 patients administered, but aggravated symptoms in the others. CONCLUSION: Diversity of NSAIDs-induced urticaria and angioedema was shown in this study. Pathogenesis of NSAIDs-induced urticaria and angioedema without asthma seems to be different from that of NSAIDs-induced asthma.

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  • O55-4 横浜市立大学附属市民総合医療センターにおける分子標的薬による薬疹症例の検討(O55 薬物アレルギー2,口演,第61回日本アレルギー学会秋季学術大会)

    松倉 節子, 池澤 優子, 高村 直子, 三津山 信治, 渡邊 裕子, 守田 亜希子, 磯田 祐士, 相原 道子, 蒲原 毅

    アレルギー   60 ( 9 )   1447 - 1447   2011年

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    記述言語:日本語   出版者・発行元:一般社団法人 日本アレルギー学会  

    DOI: 10.15036/arerugi.60.1447_1

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共同研究・競争的資金等の研究課題

  • NF-kB活性化と直鎖状ポリユビキチン分解系の乾癬病態への関与の検討

    研究課題/領域番号:23K15272  2023年4月 - 2028年3月

    日本学術振興会  科学研究費助成事業  若手研究

    高村 直子

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    本研究はNF-kBシグナルの制御に関与する脱ユビキチン化酵素の一つであるOTULINに着目した。OTULINはNF-kBの活性を調整することで細胞増殖や免疫調整に関与する可能性が報告されているが、皮膚組織における役割は不明な点も多い。乾癬患者の皮膚におけるOTULINの発現を評価し、病態形成においての機能を明らかにし、OTULINによるNF-kBシグナルの調整が乾癬の治療標的となりうるか、疾患モデルマウスを用いて検討することを目的としている。
    本年度は感染患者皮膚検体におけるOTULINの発現量について免疫染色やPCR、ウェスタンブロットを用いてOTULINの遺伝子発現量、タンパク発現量の解析を行った。検体の収集に時間がかかり、当初予定していた目標数に達していないため引き続き検討を行うが、現時点では乾癬患者表皮ではOTULINの発現量が上昇する傾向が認められている。OTULINは本来脱ユビキチン化を行いNF-kBの活性を抑制する働きを持つため炎症抑制に働くが、乾癬患者で上昇しているOTULINは脱ユビキチン化酵素として機能していない可能性を考えた。これについては乾癬患者表皮のポリユビキチンをウェスタンブロットで検出し脱ユビキチン化が起こっているのかを確認する。
    また、乾癬患者表皮におけるOTULINの発現異常が乾癬病態形成における主軸のサイトカイン(TNF-α、IL-17、IL-23など)によって引き起こされている可能性を検討するため、ケラチノサイトをこれらサイトカインで刺激しOTULINの発現量に影響を与えるか、PCR法や免疫ブロット法を用い検討した。現在のところTNF-α、IL-17については影響を与えないという結果が出ている。他のサイトカインについても今後検討を進めていく。

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