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1論文
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Allergology international : official journal of the Japanese Society of Allergology 72(1) 182-184 2023年1月
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Allergology international : official journal of the Japanese Society of Allergology 72(2) 279-285 2022年12月12日BACKGROUND: Immediate allergy caused by natto, a popular Japanese food prepared by fermenting soybeans with Bacillus subtilis var. natto, has been reported. Polygamma glutamic acid (PGA) in the sticky substance around natto beans has been reported to be a causative allergen of natto allergy. However, some of our patients with natto allergy were negative for PGA in the skin prick test (SPT). The sticky substance of natto beans contains a subtilisin family serine protease, nattokinase, along with PGA. In this study, we aimed to examine the antigenicity of nattokinase in natto allergy. METHODS: Eight patients, who developed symptoms after ingesting natto and positively reacted to natto (seven to the sticky substance in natto and one to the whole natto product) in their SPT, were enrolled in this study. To analyze IgE reactivity, we performed immunoblotting, ELISA, and SPT for natto (bean and sticky substance), and/or PGA, and/or nattokinase and/or cultured B. subtilis var. natto extract. RESULTS: In the SPT, four cases each were PGA-positive and PGA-negative. Immunoblotting of the sera from PGA-negative patients showed a protein band at 30 kDa, which was identified as nattokinase. Three PGA-negative cases, but not three PGA-positive cases, showed a positive reaction to nattokinase in the SPT and had a history of atopic dermatitis. The ELISA for nattokinase revealed a positive reaction of PGA-negative cases and negative reaction of PGA-positive cases in the SPT. CONCLUSIONS: We identified a subtilisin family serine protease, nattokinase, as a novel allergen in natto allergy patients unsensitized to PGA.
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皮膚科の臨床 64(6) 1041-1046 2022年5月<文献概要>16歳,女性。モモ,イチジク摂取後にアナフィラキシー症状を発症した。複数の果物類摂取後にアレルギー症状を繰り返したとの臨床経過からgibberellin-regulated protein(GRP)抗原の関与を疑い,諸検査を施行した。その結果,プリックテストではイチジク(4+),モモ自体・モモGRPともに(3+)陽性であり,モモGRPの特異的IgEも陽性で,かつこの抗原はイチジク粗抗原で阻害されたため,自験例をGRPアレルギーと診断した。GRPは熱安定性および消化酵素抵抗性を有しているため当初はクラス1アレルゲンであると考えられていたが,近年はヒノキ花粉やスギ花粉中のGRP抗原との交差反応性に注目されており,今後同様の症例の発現に留意する必要がある。
MISC
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Journal of Environmental Dermatology and Cutaneous Allergology 6(2) 67-84 2012年 査読有り
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Visual Dermatology 11(3) 302-303 2012年 査読有り
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皮膚の科学 11(3) 220-223 2012年 査読有り51歳,男性。初診の15日前に静岡県浜名湖付近でみかん狩りをした。初診の8日前に愛知県名古屋市の公園の池へ釣りに行き,5日後に発熱をきたし,頭痛が出現したため,当院を受診した。初診時 38°C の発熱と頭痛を認め,体幹と四肢に淡い紅斑,また左下腿に痂皮を伴う刺し口と思われる病変と両鼠径部のリンパ節腫脹を認めた。臨床所見よりツツガムシ病を疑って患者血液を用いた PCR 法を実施し,Kawasaki 型ツツガムシリケッチアによるツツガムシ病と確定した。初診時より塩酸ミノサイクリンを2週間投与し略治した。発疹を伴う発熱性疾患では常にツツガムシ病を念頭に置き, そのような患者に対しては迅速な検査と治療の開始が重要であると考えられた。(皮膚の科学,11: 220-223, 2012)
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Skin Cancer 27(2) 226-230 2012年 査読有り74歳,男性。初診6ヵ月前より下口唇にびらんを伴う扁平隆起性局面を認め,当院を受診した。扁平苔癬や日光口唇炎などとの鑑別のため2度にわたり部分生検を行ったが,明らかな悪性像は認められず,確定診断には至らなかったが,腫瘍は初診から約5ヵ月間で直径15 mmから45 mmにまで急激に増大していった。臨床像と病理組織所見から最終的に口唇部有棘細胞癌と診断し,皮膚側から粘膜側までの全層を含めて腫瘍を全摘しAbbe's flapを用いて再建した。全摘標本の病理組織所見では筋層への浸潤を認める高分化型の有棘細胞癌であった。口唇部有棘細胞癌は初期の段階や高分化型の組織型では細胞異型が軽度であり部分生検で確定診断がつきにくい場合があるので注意が必要と考えた。
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CONTACT DERMATITIS 66(1) 51-52 2012年1月 査読有り
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DERMATITIS 22(6) 348-349 2011年11月 査読有りAlthough there are many reported cases of immediate allergy after ingestion of foods containing cochineal, there are few reports of allergic contact dermatitis from carmine. We present a rare case of allergic contact dermatitis due to carmine. A 52-year-old female presented with an itchy erythema on her cheeks at the site where blush had been applied. Patch-tested with her cosmetics, she showed a positive reaction to the blush (30% in petrolatum) and to 0.2% (but not 0.1%) carmine in petrolatum. In this case, the optimum patch-test concentration of carmine was 0.2% in petrolatum.
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JOURNAL OF DERMATOLOGICAL SCIENCE 62(2) 98-106 2011年5月 査読有りBackground: In recent years, it has been reported that stem cells exist in the mesenchymal tissues of the bone marrow and adipose. These stem cells are thought to express specific cell surface markers such as CD44, CD54, CD105, CD90, and CD271 and have been confirmed to be pluripotent. Furthermore, although it has been reported that stem cells are also present in the dermis, their cell surface markers and characteristics are not fully understood. Objective: To confirm the presence of stem cells in the dermis and their ability, employing the mesenchymal stem cell markers which have previously been reported as an indication. Methods: We analyzed the percentages of CD44 (+), CD54 (+), CD90 (+), CD105 (+), and CD271 (+) cells in the dermis of neonatal mice (HR-1 mouse) by performing immunostaining and FACS. Secondly, we isolated each type of marker-positive and -negative cells from dermal tissues and evaluated their proliferation potential and their ability to differentiate into adipocytes, osteoblasts, and chondrocytes. Results: According to the immunostaining and FACS results, we confirmed that stem cells that express CD44, CD54, CD90, CD105, and CD271 are present in the dermal tissues of neonatal mice. In addition, when we measured the proliferation and differentiation potentials of each type of marker-positive cells, it was revealed that cells expressing CD54 or CD271 have a high proliferation potential and are able to differentiate into adipocytes, osteoblasts, and chondrocytes. Conclusions: These results indicated that dermal tissues contain stem cells that express CD44, CD54, CD90, CD105, and CD271 which are stem cell markers. More precisely, it was suggested that both CD54 (+) and CD271 (+) stem cells have high proliferation and differentiation potentials. (C) 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
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Journal of Environmental Dermatology and Cutaneous Allergology 5(2) 115-123 2011年 査読有り
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日本ラテックスアレルギー研究会会誌 15(1) 40-45 2011年 査読有り
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Allergology International 60(1) 97-101 2011年 査読有りA 13-year-old girl who had had pollinosis since the age of eight began to experience itching of the ears and vomiting after eating fresh fruits such as peach, apple and watermelon. This occurred at 10 years of age. The girl displayed positive reactions to six kinds of pollens, eleven kinds of fruits, numerous vegetables and to recombinant: rBet v2 present in specific IgE antibodies. She also reacted positively to several pollens, fruits and rBet v2 in the skin prick test. In the component-resolved diagnosis (CRD) using microarray technology, she also tested positive for profilin, a pan-allergen among plants. It is reported that profilin cross-reacts between pollen, fruits, vegetables and latex. From these results, we concluded that the allergic reactions to multiple kinds of foodstuff and pollens observed in this subject were due to cross-reactivity induced by profilin. Our results demonstrate that CRD by microarray is a reliable test in the diagnosis of PFAS. © 2011 Japanese Society of Allergology.
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CONTACT DERMATITIS 64(5) 301-302 2011年 査読有り
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JOURNAL OF IMMUNOLOGY 185(10) 5743-5750 2010年11月 査読有りIL-33 is a member of the IL-1 family and mediates its biological effects via the ST2 receptor, which is selectively expressed on Th2 cells and mast cells. Although polymorphic variation in ST2 is strongly associated with asthma, it is currently unclear whether IL-33 acts directly on lung tissue cells at sites of airway remodeling. Therefore, we aimed to identify the IL-33-responsive cells among primary human lung tissue cells. ST2 mRNA was expressed in both endothelial and epithelial cells but not in fibroblasts or smooth muscle cells. Correspondingly, IL-33 promoted IL-8 production by both endothelial and epithelial cells but not by fibroblasts or smooth muscle cells. Transfection of ST2 small interference RNA into both endothelial and epithelial cells significantly reduced the IL-33-dependent upregulation of IL-8, suggesting that IL-33-mediated responses in these cells occur via the ST2 receptor. Importantly, Th2 cytokines, such as IL-4, further enhanced ST2 expression and function in both endothelial and epithelial cells. The IL-33-mediated production of IL-8 by epithelial cells was almost completely suppressed by corticosteroid treatment. In contrast, the effect of corticosteroid treatment on the IL-33-mediated responses of endothelial cells was only partial. IL-33 induced activation of both ERK and p38 MAPK in endothelial cells but only ERK in epithelial cells. p38 MAPK was required for the IL-33-mediated responses of endothelial cells, whereas ERK was required for IL-33-mediated IL-8 production by epithelial cells. Taken together, these findings suggest that IL-33-mediated inflammatory responses of lung tissue cells may be involved in the chronic allergic inflammation of the asthmatic airway. The Journal of Immunology, 2010, 185: 5743-5750.
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日本皮膚科学会雑誌 120(9) 1893-1900 2010年 査読有り粉製品に含まれたダニの経口摂取によるアナフィラキシー2症例を経験したので報告する.症例1は50歳女性で,開封後に常温保存したお好み焼き粉を,自宅にて調理摂取した約30分後に全身浮腫性紅斑や動悸,嘔気が出現した.患者が摂取したお好み焼き粉は,賞味期限より2年が経過していた.患者血清ダニ抗原特異IgE値はヤケヒョウヒダニ23.4 IU/ml,コナヒョウヒダニ33.7 IU/mlで,コムギ関連特異IgE値はコムギ<0.35 IU/ml,グルテン<0.35 IU/mlと陰性であった.持参した同一銘柄の未開封お好み焼き粉と冷凍保存された薄力粉でのスクラッチテストは陰性であったが,ダニ抗原(鳥居薬品)のプリックテストはscore 3+の陽性を示した.症例2は28歳女性で,開封後に数カ月間常温保存したお好み焼き粉(以下事故粉)を自宅において調理中に喘息症状が出現し,摂取中に呼吸困難感や嘔吐,腹痛が出現し,アナフィラキシーショックとなった.患者血清ダニ抗原特異IgE値はヤケヒョウヒダニ51.6 IU/ml,コナヒョウヒダニ55.6 IU/mlで,コムギ関連特異IgEはコムギ<0.35 IU/ml,グルテン<0.35 IU/mlと陰性であった.プリックテストは事故粉でscore 3+の陽性,ダニ抗原(鳥居薬品)でscore 4+の陽性であった.また冷凍保存された薄力粉は陰性であった.事故粉にはコナヒョウヒダニが50匹/g検出され,ELISA法で測定したところ,ダニ主要抗原であるDer f 1が64.1 μg/gと多量に検出された.事故粉と患者血清(症例2)を用いたImmunoblot法ではダニ抗原と思われる25 kDa部位にバンドが検出された.さらに血清とダニ粗抽出液を用いたInhibition immunoblot法ではダニ粗抽出物と共通分子量付近に認められた複数のバンドは事故粉より消失した.この結果から事故粉に認められたバンドは粉中のダニ抗原に反応したバンドと考えられた.上記の検討を踏まえ,お好み焼き粉におけるダニ繁殖の実態を調査するため,我々は,お好み焼き用ミックス粉3銘柄と薄力粉におけるダニ数及びダニ抗原の増殖性の違いについて検討した.各粉にコナヒョウヒダニを添加培養し,3週間後と6週間後に評価した.培養6週間後にミックス粉のダニ数とダニ抗原は,薄力粉に比較して3銘柄ともに増加傾向を認め,1銘柄は有意に増加していた.粉類でダニの増殖を防ぐには冷蔵保存が良いとされる.市販のミックス粉の注意書きには冷蔵保存と明記する必要があり,また我々皮膚科医は小麦アレルギーと誤診しないよう注意が必要である.
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皮膚の科学 9(2) 141-146 2010年 査読有り患者1:55歳,男性。患者2:76歳,男性。患者3:91歳,男性。それぞれ近医にて抗ヒスタミン薬,ステロイド外用薬,ステロイド内服薬などを処方されていたが難治の皮疹を主訴に来院した。3例とも湿潤しない充実性丘疹と大きな皺に一致した皮疹の欠如を示しており,丘疹-紅皮症と診断した。悪性腫瘍の合併は否定的であった。これら3例に対しナローバンド UVB 療法を施行し,計4~7回の照射で皮疹や自覚症状の軽減を得ることができ,約10回で皮疹はほぼ消失した。その後,軽度の増悪を認めたものの,3例とも照射終了から現在に至るまで皮疹の再燃は認めていない。その他の治療と比べ,その簡便さ,副作用の少なさから丘疹-紅皮症に対しナローバンド UVB 療法は有用な治療法であると考えた。
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Allergology International 59(3) 277-284 2010年 査読有りBackground: Amphiregulin (AR) is expressed in Th2 cells, rather than Th1 cells, and plays an important role in Th2 cell/cytokine-mediated host defense against nematodes. We also found earlier that AR mRNA expression was strongly upregulated in inflamed tissue during Th2 cell/cytokine-mediated fluorescein isothiocyanate (FITC)-induced contact hypersensitivity (CHS), suggesting a contribution of AR to the induction of those responses. Methods: To elucidate the role of AR in the induction of FITC- or dinitrofluorobenzene (DNFB)-induced CHS, AR-deficient mice were sensitized and/or challenged with FITC or DNFB epicutaneously. The levels of FITCmediated skin dendritic cell (DC) migration and FITC-specific lymph node cell proliferation and cytokine production were assessed by flow cytometry, [3H]-thymidine incorporation and ELISA, respectively, after FITC sensitization. The degree of ear swelling, the activities of myeloperoxidase (MPO) and eosinophil peroxidase (EPO) in inflammatory sites and the levels of FITC-specific immunoglobulin (Ig) in sera were determined by histological analysis, colorimetric assay and ELISA, respectively, after FITC challenge. Results: DC migration and FITC-specific lymph node cell proliferation and cytokine production were normal in the AR-deficient mice. Ear swelling, tissue MPO and EPO activities and FITC-specific serum Ig levels were also similar in AR-deficient and -sufficient mice. Conclusions: Amphiregulin is not essential for the induction of FITC- or DNFB-induced CHS responses in mice. © 2010 Japanese Society of Allergology.
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JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 124(3) 612-U328 2009年9月 査読有り
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Arerugi 58(5) 481-490 2009年5月 査読有り
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JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 123(2) S38-S38 2009年2月
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Journal of Environmental Dermatology and Cutaneous Allergology 3(1) 32-41 2009年 査読有り
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Journal of Environmental Dermatology and Cutaneous Allergology 3(2) 94-100 2009年 査読有り
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Journal of Environmental Dermatology and Cutaneous Allergology 3(2) 105-110 2009年 査読有り
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皮膚の科学 8(2) 158-163 2009年 査読有り当科で経験したStevens-Johnson syndrome(SJS)の2例について,HLAの遺伝子マーカーの検討を行ったので報告する。症例1は53歳,女性。内服誘発試験の結果,アロプリノール,クラリスロマイシン,ロキソプロフェンナトリウムの3剤同時服用によるSJSと診断した。遺伝子解析の結果,HLA-B∗5801が検出された。症例2は54歳,男性。カルバマゼピンに対する薬剤誘発リンパ球幼弱化試験が陽性であり,カルバマゼピンによるSJSと診断した。遺伝子解析ではHLA-B∗1502は検出されなかった。
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日本ラテックスアレルギー研究会会誌 13(1) 32-35 2009年 査読有り花粉飛散時期に、もやしによるアナフィラキシーを来した11歳男児症例について検討した。5月に外食での摂取後にアナフィラキシーを認めた。皮膚検査や血清学的検査ではシラカンバ>100、ハンノキ>100、生のもやしが強陽性で、感染特異的タンパク質(PR)-10関連抗原による交差反応性を示すpollen-food allergy sydromeと考えられた。この症例は、もやし摂取によりアナフィラキシーを来した時期とシラカンバ飛散時期が一致していること、花粉の飛散時期を過ぎると症状が消失していたなどの特徴が認められた。
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JOURNAL OF DERMATOLOGY 36(1) 45-49 2009年1月 査読有りWe report a 22-year-old woman with urticaria, dyspnea and bronchial asthma-like attacks after eating curried rice. We found the symptoms to be due to an immediate-type allergy caused by spice antigens contained in curry spices by detailed questioning, skin test and measurement of specific immunoglobulin (Ig)E antibodies. This case was complicated with pollen-food allergy syndrome (PFAS) from melon and latex allergy (LA) to natural rubber latex (NRL) antigen and she had also had atopic dermatitis, allergic rhinitis and pollinosis. Serum specific IgE antibodies to birch profilin (Bet v 2), latex profilin (Hev b 8), and timothy profilin (Phl p 12) were detected. She also showed positive reactions to several Apiaceae families, fruits and latex antigens in skin prick test. Based on these findings, we considered her symptoms to be involved with spice allergy, PFAS and latex-fruit syndrome.
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JOURNAL OF DERMATOLOGY 36(1) 50-55 2009年1月 査読有りOral allergy syndrome to soy milk is classified as a phenotype of pollen-food allergy syndrome (PFAS). As causative antigens, Gly m 4 (Bet v 1 homolog, 17 kD) and oleosin (23 kD), have been reported. In this study, we report two cases of PFAS to soy milk. Both cases showed positive reactions to soy milk in skin prick tests (SPT) and to Gly m 4 in specific serum immunoglobulin (Ig)E antibody. When we measured specific serum IgE antibody of soy-related proteins using a new laboratory testing method, microarray analysis, both cases showed a positive reaction for Bet v 1. One case was weakly positive for a soybean protein, beta-conglycinin. Other results for reactivity to soy, peanut, cross-reactive carbohydrate determinants and profilin were negative. Based on these results, we diagnosed the two cases as PFAS to Gly m 4. We also performed protein microarray analysis and found it useful as a screening test for immediate allergy, such as PFAS.
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CONTACT DERMATITIS 60(3) 183-184 2009年 査読有り
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Allergology International 58(3) 347-355 2009年 査読有りBackground: Natural rubber latex (NRL) allergy is a common occupational disease in health care workers (HCW). However, few reports have compared the major allergen of HCWs to those in gloves that are routinely used in the hospital. The aim of this study was to evaluate the major NRL allergens in gloves used by HCWs. Methods: We studied 20 HCWs who were suspected to have latex allergy (LA). We performed a skin prick test (SPT) using NRL allergens. Serological testing was performed using the ImmunoCAP™. The total amount of protein and the antigenic protein concentrations extracted from NRL gloves were measured. Four different types of FITkit™ were used to measure the concentrations of Hev b 1, 3, 5, and 6.02 in the gloves. Results: A SPT using NRL extract identified 14 cases with positive reactions. The sensitivity and specificity of the SPT scores to the NRL glove extract were 100%. The sensitivity of latex specific IgE was 100% but the specificity was 14.2%. The sensitivity and specificity of rHev b 6.02 specific IgE were 100% in the LA group. The total amounts of protein from the medical gloves for surgery and examination were 265 μg/g and 95 μg/g, respectively. The antigenic protein concentrations in the gloves were 24.9 μg/g and 1.0 μg/g, respectively. The total amounts of the specific four allergens in the NRL gloves were 2.18 μg/g and 0.45 μg/g, respectively. Conclusions: We concluded that the main allergen of HCWs who have been sensitized occupationally by NRL gloves was Hev b 6.02. ©2009 Japanese Society of Allergology.
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JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 121(2) S29-S29 2008年2月
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日本皮膚科学会雑誌 = THE JAPANESE JOURNAL OF DERMATOLOGY 115(13) 2228-2231 2005年12月
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Journal of environmental dermatology : the official journal of the Japanese Society for Contact Dermatitis 12(4) 192-195 2005年10月1日
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日本皮膚科学会雑誌 = THE JAPANESE JOURNAL OF DERMATOLOGY 114(14) 2319-2326 2004年12月20日
書籍等出版物
42講演・口頭発表等
195共同研究・競争的資金等の研究課題
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日本学術振興会 科学研究費助成事業 2021年4月 - 2024年3月
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日本学術振興会 科学研究費助成事業 2017年4月 - 2020年3月
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日本学術振興会 科学研究費助成事業 2012年4月 - 2015年3月
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日本学術振興会 科学研究費助成事業 2010年 - 2012年
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日本学術振興会 科学研究費助成事業 2004年 - 2005年
教育内容・方法の工夫(授業評価等を含む)
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件名皮膚・形成系講義担当(M4)開始年月日2009
教育方法・教育実践に関する発表、講演等
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件名アレルギー大学:アトピー性皮膚炎の治療について開始年月日2009
その他教育活動上特記すべき事項
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件名医学部M5担当開始年月日2011
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件名広報委員会委員開始年月日2011
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件名疫学・臨床研究倫理審査委員会 委員開始年月日2011終了年月日2013
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件名藤田保健衛生大学ヒトゲノム・遺伝子解析研究倫理審査委員会 委員開始年月日2011