Faculty Profiles - HIRAI Youji

Papers - HIRAI Youji

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色素性乾皮症に生じた頭頂部悪性黒色腫

梶田藍, 河野淳子, 難波裕子, 平井陽至, 加持達弥, 山崎修, 岩月啓氏

日本皮膚科学会雑誌 126 ( 8 ) 1482 - 1482 2016.7

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

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

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

Language：English Publishing type：Research paper (scientific journal)

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

DOI： 10.1016/j.jdermsci.2016.03.001

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

三宅智子, 平井陽至, 濱田利久, 岩月啓氏, 山本剛伸

日本皮膚科学会雑誌 126 ( 7 ) 1305 - 1305 2016.6

病院現況および患者視点からみた進行期悪性黒色腫に対する新規治療

山崎修, 加持達弥, 平井陽至, 梅村啓史, 森実真, 濱田利久, 岩月啓氏, 勝井邦彰, 合地明

日本皮膚科学会雑誌 126 ( 5 ) 935 - 935 2016.5

帯状疱疹ウイルス・単純疱疹ウイルスの重複再活性化例の臨床及び遺伝子産物解析

三宅智子, 平井陽至, 山本剛伸, 片山治子, 森実真, 岩月啓氏

日本皮膚科学会雑誌 126 ( 5 ) 994 - 994 2016.5

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

岩月啓氏, 平井陽至, 山崎修, 濱田利久, 森実真, 三宅智子, 加持達弥, 梅村啓史, 武藤正彦

日本皮膚科学会雑誌 126 ( 6 ) 1152 - 1152 2016.5

非バイアス次世代TCRレパトア解析によるEBV関連リンパ増殖性疾患への応用

平井陽至, 三宅智子, 森実真, 濱田利久, 北浦一孝, 松谷隆治, 岩月啓氏

日本皮膚悪性腫瘍学会学術大会プログラム・抄録集 32回 144 - 144 2016.5

Detection of herpesvirus-encoded gene products in herpetiform vesicles and crusts

70 ( 5 ) 75 - 78 2016.4

大腿に発生したintraepithelial sebaceous carcinoma

梶田藍, 河野淳子, 難波裕子, 平井陽至, 加持達弥, 山崎修, 岩月啓氏, 谷口恒平, 柳井広之

日本皮膚科学会雑誌 126 ( 3 ) 322 - 323 2016.3

痂皮と水疱蓋を用いた種痘様水疱症と蚊刺過敏症の低侵襲診断的検査の鋭敏度と特異度に関する研究

三宅智子, 平井陽至, 山本剛伸, 岩月啓氏

日本皮膚科学会雑誌 125 ( 4 ) 947 - 947 2015.4

種痘様水疱症分子生物学的に検証した記載皮膚科学の確かさ

岩月啓氏, 平井陽至, 三宅智子, 濱田利久, 大熊登, 山本剛伸

皮膚の科学 14 ( 1 ) 37 - 37 2015.2

Survival rates and prognostic factors of Epstein-Barr virus-associated hydroa vacciniforme and hypersensitivity to mosquito bites. International journal

T Miyake, T Yamamoto, Y Hirai, M Otsuka, T Hamada, K Tsuji, S Morizane, D Suzuki, Y Aoyama, K Iwatsuki

The British journal of dermatology 172 ( 1 ) 56 - 63 2015.1

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Epstein-Barr virus (EBV)-associated T/natural-killer lymphoproliferative disorders form a group of diseases that includes classical and systemic hydroa vacciniforme (HV) and hypersensitivity to mosquito bites (HMB). Patients with systemic HV (sHV) and HMB often have a poor prognosis, although little is known about the prognostic factors. OBJECTIVES: To elucidate the prognostic factors of HV and HMB. METHODS: We studied clinicopathological manifestations, routine laboratory findings, anti-EBV titres, EBV DNA load and EBV-encoded gene expression, including expression of BZLF1, in 50 patients with classical HV (cHV), sHV, HMB only and HMB with HV (HMB + HV), and further analysed 30 patients who were available for follow-up. RESULTS: The median age of disease onset was 5 years (range 1-74). A follow-up study indicated that fatal outcomes were observed in three of eight patients with sHV, two of six patients with HMB only, and two of five patients with HMB + HV. The main causes of death were complications from haematopoietic stem-cell transplantation and multiorgan failure. There were no fatalities among the 11 patients with cHV. Univariate analysis revealed two poor prognostic indicators: (i) onset age > 9 years and (ii) the expression of an EBV-encoded immediate-early gene transcript, BZLF1 mRNA, in the skin lesions (P < 0·001 and P = 0·003, respectively). CONCLUSIONS: No prognostic correlation was observed in EBV-infected lymphocyte subsets, anti-EBV antibody titres or EBV DNA load. Late onset and EBV reactivation are both related to more severe phenotypes of the disease, and thus may predict a poor prognosis.

DOI： 10.1111/bjd.13411

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

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

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

Language：English Publishing type：Research paper (scientific journal)

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

DOI： 10.1111/1346-8138.12695

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Cathelicidin peptide LL-37 increases UVB-triggered inflammasome activation: possible implications for rosacea. International journal

Suzanna Salzer, Sonja Kresse, Yoji Hirai, Sarah Koglin, Markus Reinholz, Thomas Ruzicka, Jürgen Schauber

Journal of dermatological science 76 ( 3 ) 173 - 9 2014.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: In patients with rosacea, environmental stressors, especially UVB radiation, trigger disease flares that are characterized by inflammation and vascular hyperactivity. An altered innate immune detection and response system, modulated to a large extent by the aberrant production and processing of human cathelicidin LL-37, is thought to play a central role in disease pathogenesis. OBJECTIVE: To investigate whether the proinflammatory and proangiogenic effects of UV radiation are enhanced in the presence of cathelicidin LL-37. METHODS: Human skin ex vivo and epidermal keratinocytes in vitro were exposed to UVB irradiation. The proinflammatory effects of UVB exposure in the presence and absence of LL-37 were characterized using immunoblot, transfection, qPCR, and a cell-based second messenger assay. ELISA was used to assess cytokine release and the angiogenic potential of endothelial cells was evaluated using an in vitro angiogenesis assay. RESULTS: UVB irradiation triggered the inflammasome-mediated processing and release of IL-1β. LL-37 augmented this UV-induced IL-1β secretion by acting on the P2X7 receptor on keratinocytes. P2X7 receptor activation by UVB and LL-37 resulted in an increase in intracellular calcium concentrations, which enhances inflammasome activation and subsequent IL-1β release. Furthermore, IL-1β and LL-37 worked synergistically to increase the angiogenic potential of endothelial cells. CONCLUSION: Cathelicidin LL-37 modulates the proinflammatory and proangiogenic effects of UV radiation and thereby contributes to enhanced sensitivity to sun exposure in rosacea.

DOI： 10.1016/j.jdermsci.2014.09.002

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種痘様水疱症様皮疹を生じるadult-onset例 early-onsetおよびelderly-onset例との比較

平井陽至, 三宅智子, 岩月啓氏, 山本剛伸

Skin Cancer 28 ( 2 ) 234 - 234 2013.11

【EBウイルス感染症-その多様な病態】EBウイルスと皮膚疾患

平井陽至, 山本剛伸, 三宅智子, 岩月啓氏

成人病と生活習慣病 43 ( 9 ) 1086 - 1093 2013.9

Language：Japanese Publisher：(株)東京医学社

EBウイルスが関与している皮膚疾患として、(A)皮膚病変部にEBウイルス感染細胞が検出されるもの(EBウイルス特異疹)と、(B)反応性変化により皮疹形成するもの(非特異疹)とに大別される。EBウイルスリンパ球増殖症におけるEBウイルス特異疹として、T細胞性のものとNK細胞性のものに大別される。T細胞性リンパ球増殖症(多くはγδT細胞)として小児のまれな光線過敏症にHVがあげられるが、予後良好で多くは自然寛解の経過をとる古典型HVと予後不良で発熱・肝機能障害などの全身症状を伴う全身型HVの2タイプに分けられる。NK細胞性リンパ球増殖症としてHMBがあり全身型HV同様にCAEBVを合併していることが多い。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J03723&link_issn=&doc_id=20131003110010&doc_link_id=%2Faq9seijd%2F2013%2F004309%2F010%2F1086-1095%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faq9seijd%2F2013%2F004309%2F010%2F1086-1095%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

種痘様水疱症様皮疹を生じるadult-onset例 early-onsetおよびelderly-onset例との比較

平井陽至, 山本剛伸, 三宅智子, 岩月啓氏

日本皮膚悪性腫瘍学会学術大会プログラム・抄録集 29回 134 - 134 2013.8

ヘルペスウイルス感染に伴うウイルス側・宿主側からみた免疫回避・誘導のメカニズム

山本剛伸, Cohen Jeffrey I., 三宅智子, 平井陽至, 藤本亘, 岩月啓氏

山口医学 62 ( 3 ) 181 - 181 2013.8

Chronic active Epstein-Barr virus infection with progression to large granular lymphocytic leukemia. International journal

Satoshi Komori, Jun Asai, Hideya Takenaka, Junya Kuroda, Yoji Hirai, Keiji Iwatsuki, Norito Katoh

The Journal of dermatology 40 ( 6 ) 487 - 8 2013.6

最近、当院で経験した術後深部静脈血栓症/肺塞栓症の4例

加持達弥, 杉生真帆, 瀧口徹也, 梅村啓史, 牧野麻貴, 鈴木規弘, 大塚正樹, 濱田利久, 山崎修, 岩月啓氏, 野田和代, 平井陽至

日本皮膚科学会雑誌 123 ( 7 ) 1261 - 1261 2013.6

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