記述言語：英語   掲載種別：研究論文（学術雑誌）  

Tumor necrosis factor (TNF) inhibitors, including adalimumab, are widely used to treat refractory psoriatic arthritis (PsA). Although isoniazid chemoprophylaxis is generally effective in preventing reactivation of latent tuberculosis infection (LTBI), prophylactic measures do not fully protect against development of active tuberculosis. We report a rare case of active tuberculosis despite chemoprophylaxis for LTBI in a patient receiving adalimumab for PsA. A 60-year-old Japanese woman who had received a diagnosis of psoriasis at age 35 years presented with arthralgia of the right hand, which she first noticed 2 months previously. Physical examination showed scattered erythematous papules and plaques with scales on her trunk, extremities, and scalp. Her right metacarpophalangeal and proximal interphalangeal joints were swollen and painful, and her right wrist and elbow were painful. PsA was diagnosed and adalimumab was initiated. Because an interferon-γ release assay (IGRA) showed a borderline result at screening, isoniazid was administered as chemoprophylaxis for LTBI. At 22 months after initiation of adalimumab, IGRA was positive and chest CT disclosed centrilobular nodules in both lungs and swelling of multiple lymph nodes. Culture of sputum at 24 months demonstrated Mycobacterium tuberculosis. Active tuberculosis was diagnosed, and treatment with a combination of isoniazid, rifampicin, ethambutol hydrochloride, and pyrazinamide was started. To ensure timely diagnosis and treatment of active tuberculosis, a tuberculosis expert should be consulted at an early stage, with regular screening and monitoring.

DOI： 10.1272/jnms.JNMS.2023_90-610

PubMed

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This is an abridged edition of English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence-based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling, and advice about daily life. In the present revised guidelines, the description about three new drugs, namely, dupilumab, delgocitinib, and baricitinib, has been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.

DOI： 10.1016/j.alit.2022.06.009

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This is the English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence-based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling, and advice about daily life. In the present revised guidelines, descriptions of three new drugs, namely, dupilumab, delgocitinib, and baricitinib, have been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.

DOI： 10.1111/1346-8138.16527

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

This is the English version of guidelines for the management of asteatosis 2021 in Japan. Asteatosis is a synonym of xerosis found in a wide range of diseases that induce dry skin through impaired functions of either water retention of the stratum corneum or skin covering with acid mantle. Patients with asteatosis may be accompanied by pruritus. Moisturizers are the first-line treatment for asteatosis and their adequate use must be recommended. The main purpose of the present guidelines is to define skin symptoms requiring treatment with moisturizers for medical use in patients with asteatosis. If the deterioration of marked scaling or scratch marks is predicted, therapeutic intervention with moisturizers for medical use should be considered even in the absence of pruritus. Regarding six important points requiring decision-making in clinical practice (clinical questions), we evaluated the balance between the benefits and harm of medical interventions in reference to previous reports of clinical research, and presented the recommendation grades and evidence levels to optimize the patient outcome by medical interventions.

DOI： 10.1111/1346-8138.16293

PubMed

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/1346-8138.16293

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by hyperproliferation of epidermal keratinocytes. Biologics have been available for the treatment of patients with refractory psoriasis since 2010 in Japan, and as of December 2021, 10 biologics were available. The Biologics Review Committee of the Japanese Dermatological Association for Psoriasis recommends blood examination tests for antinuclear antibodies (ANA), Krebs von den Lugen (KL)-6, hepatitis B surface antigen (HBsAg), hepatitis B surface antibodies (HBsAb), hepatitis B core antibodies (HBcAb), hepatitis C virus (HCV) antibodies, HIV antibodies, human T-cell leukemia virus (HTLV)-1 antibodies, β-D-glucan, and the T-cell spot (T-SPOT) test before initiation of biologics at screening. In this study, we evaluated the use of biologics for 127 psoriasis patients and the blood examination screening data before initiation of biologics in the real-world setting. Tumor necrosis factor inhibitors, interleukin (IL)-17 inhibitors and IL-23 inhibitors were initiated for 54 (42.5%), 36 (28.3%), and 37 (29.1%) patients, respectively. The numbers of patients positive for ANA, HBsAg, HBsAb, HBcAb, HCV antibody, HIV antibody, HTLV-1 antibody, and T-SPOT were 27 (21.3%), 0 (0%), 22 (17.3%), 20 (15.7%), three (2.4%), zero (0%), one (0.8%), and 4 (3.1%), respectively. The numbers of patients whose KL-6 and β-D-glucan levels were higher than the reference values were seven (5.5%) and seven (5.5%), respectively. In the real-world setting, it is sometimes unavoidable to use biologics for those patients with abnormal data although careful monitoring is necessary.

DOI： 10.1111/1346-8138.16333

PubMed

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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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Three categories of biologics-tumor necrosis factor (TNF) inhibitors, interleukin (IL) -17 inhibitors, and IL-23 inhibitors-are available for treatment of refractory psoriasis. Recent studies have shown that laboratory biomarkers such as peripheral blood neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and serum C-reactive protein (CRP) levels are associated with psoriasis or its severity. This study evaluated associations of transition of NLR, PLR, MLR, and CRP with transition of disease activity in psoriasis patients treated with the three categories of biologics. METHODS: Data from 67 patients were analyzed. Associations of transition of psoriasis area and severity index (PASI) score with the abovementioned laboratory markers were evaluated by using a mixed effects model with PASI as the response variable, laboratory markers as fixed effects collectively, and patients as random effects. RESULTS: In an analysis of all the patients, serum CRP and NLR were associated with PASI score (P=0.006 and P=0.001, respectively). In patients treated with TNF inhibitors, CRP and NLR were associated with PASI score (P=0.043 and P=0.002, respectively). In patients treated with IL-17 inhibitors, NLR was associated with PASI score (P=0.001). CONCLUSIONS: NLR appears to be the most reliable biomarker of the effect of treatment with biologics, especially IL-17 inhibitors.

DOI： 10.1272/jnms.JNMS.2022_89-613

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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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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01174&link_issn=&doc_id=20211223220001&doc_link_id=10.14924%2Fdermatol.131.2691&url=https%3A%2F%2Fdoi.org%2F10.14924%2Fdermatol.131.2691&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

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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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00009&link_issn=&doc_id=20211209410001&doc_link_id=%2Fcw4aller%2F2021%2F007010%2F001%2F1257-1342%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw4aller%2F2021%2F007010%2F001%2F1257-1342%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：金原出版(株)  

＜文献概要＞基底細胞癌は本邦でもっとも多い皮膚悪性腫瘍であり,その治療の原則は手術治療である。被髪頭部は可動性に乏しく,有毛部であるという特性をもつため,整容的な問題が生じないように再建術式を選択する必要がある。症例は79歳,男性。左頭部に生じた腫瘍径約30mm大の基底細胞癌に対して3mmマージンで切除し,約40mm大の欠損部に対してピンホイール皮弁を用いて再建した。術後3ヵ月のフォローでも皮弁の壊死は認めず,整容的にも良好な結果が得られた。脱毛斑を残さない被髪頭部の再建法としてピンホイール皮弁は有用であると考えた。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J01266&link_issn=&doc_id=20211122060041&doc_link_id=10.18888%2Fhi.0000002961&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fhi.0000002961&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

出版者・発行元：金原出版  

DOI： 10.18888/hi.0000002969

CiNii Books

CiNii Research

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その他リンク： https://search.jamas.or.jp/link/ui/2022045474

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Dupilumab, a fully human monoclonal antibody that blocks signalling pathways of interleukin (IL)-4 and IL-13, is effective in treating patients with atopic dermatitis (AD). We previously showed that transitions of serum thymus and activation-regulated chemokine (TARC) levels and eosinophil numbers were strongly associated with that of AD activity and that the transitions of serum lactate dehydrogenase (LDH) and immunoglobulin E (IgE) levels were weakly and not associated with that of AD activity, respectively, in patients treated without dupilumab. OBJECTIVES: The purpose of this study was to elucidate whether the association of the transition of laboratory marker levels and transition of disease activity in dupilumab-treated AD patients (present study) was different from that in patients who are not treated with dupilumab (previous study). METHODS: Sixty AD outpatients treated with dupilumab were included in this study. Associations between the transition of the eczema area and severity index (EASI) score and those of above-mentioned laboratory marker levels were evaluated using a mixed effects model of EASI as the response variable, laboratory markers as fixed effects and patients as random effects. RESULTS: The transitions of serum TARC and LDH levels were associated strongly with that of AD activity, but the transitions of serum IgE level and eosinophil numbers were associated with that of AD activity intermediately and weakly, respectively. CONCLUSIONS: Laboratory markers are useful for evaluating the effects of treatments for AD, but the meaning of each laboratory marker depends on the drugs used for treatment.

DOI： 10.1111/ajd.13719

PubMed

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/1346-8138.16023

PubMed

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/1346-8138.16023

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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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01174&link_issn=&doc_id=20210927470001&doc_link_id=10.14924%2Fdermatol.131.2255&url=https%3A%2F%2Fdoi.org%2F10.14924%2Fdermatol.131.2255&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/1346-8138.15974

PubMed

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/1346-8138.15974

担当区分：最終著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Korean Dermatological Association and The Korean Society for Investigative Dermatology  

DOI： 10.5021/ad.2021.33.6.593

PubMed

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その他リンク： https://anndermatol.org/DOIx.php?id=10.5021/ad.2021.33.6.593

記述言語：英語  

DOI： 10.1111/1346-8138.15691

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Atopic dermatitis (AD) is a common eczematous skin disorder that profoundly reduces the quality of life due to intractable pruritus. Excellent therapeutic success of the anti-interleukin 4 receptor-α antibody dupilumab in clinical trials and a real-world clinical context indicates the crucial roles of interleukin (IL)-4 and IL-13 in the pathogenesis of AD. Along with the clinical improvement in skin scores and pruritus, dupilumab significantly and progressively reduces and normalizes the upregulated expression of T helper type 2 signatures such as Chemokine (C-C motif) ligand (CCL)17, CCL18, CCL22, and CCL26 in the lesional skin of AD. However, no blood/serum biomarkers are known to predict good or poor outcome in patients with AD treated with dupilumab. METHODS: Patients are at least 18 years of age and have moderate-to-severe AD with Eczema Area and Severity Index (EASI) ≥16, Investigator's Global Assessment ≥3, and body surface area ≥10%. We are going to enroll more than 130 subjects from 18 medical facilities. Clinical objective findings will be evaluated by EASI. Subjective symptoms will be assessed by Patient-Oriented Eczema Measure, Numerical Rating Scale for Pruritus (Pruritus-NRS), Skin Comfort-NRS, and Treatment Satisfaction-NRS. We will measure 18 blood/serum biomarkers including % eosinophils in blood cell count, lactate dehydrogenase, total IgE, soluble interleukin 2 receptor, CCL17, CCL18, CCL22, CCL26, CCL27, IL-13, IL-22, IL-24, IL-25, IL-31, IL-33, thymic stromal lymphopoietin, periostin, and squamous cell carcinoma antigen-2. The clinical evaluation and biomarker sampling will be performed at 0, 2, 4, 8, and 16 weeks of dupilumab treatment. We will also perform proteomic analysis (of roughly 300 proteins) of the patients' sera obtained at 0 and 2 weeks of treatment. The primary endpoint is the association between "baseline levels of 18 biomarkers" and "% change from baseline of EASI at 16 weeks of dupilumab treatment." DISCUSSION: This is the first clinical trial to explore the biomarkers, including potential proteomic markers, most strongly associated with improvement in EASI in patients with moderate-to-severe AD treated with dupilumab for 16 weeks (B-PAD study). A limitation is that we will only enroll Japanese patients.

DOI： 10.1097/MD.0000000000022043

PubMed

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記述言語：日本語   出版者・発行元：金原出版(株)  

＜文献概要＞66歳,女性。腰部脊柱管狭窄症にリドカイン(1%キシロカイン),トリアムシノロンアセトニド(ケナコルト-A )を用いて仙骨硬膜外ブロック注射を施行したところ,1〜2分後に呼吸困難感,胸痛を自覚し,その後意識消失した。アナフィラキシーショックと診断され,前医で加療後,原因精査のため紹介受診した。被疑薬剤のトリアムシノロンアセトニド注射液中の成分を用いた皮内テストで,添加物として含まれているカルボキシメチルセルロースが陽性となった。カルボキシメチルセルロースはセルロースを原料とする高分子で,人体に対して不活性とされているため,増粘剤として医薬品やさまざまな食品,日用品に使用されている。本剤によるアナフィラキシーの本邦報告例は7例のみと比較的まれであるが,他の物質によるアレルギーと誤認識されている症例が少なからずあるものと推測する。

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記述言語：日本語   出版者・発行元：金原出版(株)  

66歳女性。左上肢の疼痛と紅色丘疹小水疱を主訴に、帯状疱疹と診断のもとバラシクロビル内服を開始したが、症状の改善が乏しく精査加療目的で入院となった。入院時よりアシクロビルの点滴静注を開始したが、入院4日目に左C5-C6の運動麻痺が出現した。本症例は皮疹のデルマトームと同じ髄節レベルの運動麻痺であったことより、帯状疱疹後の運動麻痺と考えられた。そこで、入院5日目よりステロイドパルス(メチルプレドニゾロン)療法を開始したところ、徐々に外転可動領域の改善が認められた。以後、入院10日目からはプレドニゾロンに変更し、入院14日目には外転可動領域は180°と入院前と同様レベルまで改善し、入院20日目に退院となった。

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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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記述言語：日本語   出版者・発行元：(公社)日本薬学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01316&link_issn=&doc_id=20200417270001&doc_link_id=10.14894%2Ffaruawpsj.56.4_301&url=https%3A%2F%2Fdoi.org%2F10.14894%2Ffaruawpsj.56.4_301&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

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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記述言語：日本語   出版者・発行元：東亜医学協会  

症例は68歳女性で、40歳頃からまれに両季肋部を締め付けられるような感覚、だるさ、重苦しさを自覚するようになったが、その都度自然軽快していた。X年10月頃から同症状および全身倦怠感が出現し、改善しないため前医受診した。甲状腺機能低下症、副腎不全、慢性貧血などに対してスクリーニング検査を施行されたが異常所見なしであった。気分障害の可能性が疑われ、同院精神科で抗不安薬(ジアゼパム)を処方され頓用していた。本人より当研究所受診の希望あり、X年12月、紹介初診となった。初診時、胸肋部の圧迫感、左頸肩腕部痛、下腹部の圧痛(両臍傍部、左右腸骨窩部、両鼠径部)、左背部の凝りを目標に疎肝湯を処方した。3週間後には症状の改善傾向が見られ、7週間後には季肋部の重だるさ、痺れ、臍傍部圧痛はいずれも消失し、よく眠れるようになった。初診時にはなかった軽度便秘の訴えが出現したが、疎肝湯の内服間隔をあけて漸減終了した。疎肝湯終了後も状態はおおむねよかったが、1年1ヵ月後に両季肋部のだるい感じと全身疲労感が再燃し、疎肝湯1ヵ月間分再開した。2年後にも症状の再発があり再診、疎肝湯再開し、飲み切り終了とした。その後も「疎肝湯を内服するといつのまにか症状が消えている」との患者談で疎肝湯を必要時投与し、便通関連の訴えはなくなっていた。

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記述言語：日本語   出版者・発行元：(株)南江堂  

＜文献概要＞▼乾癬皮疹部では,最終的にIL-17とIL-22から誘導される表皮角化細胞の過増殖が生じている.▼生物学的製剤による治療では,標的となるサイトカインの作用が抑制された結果,細胞レベルで機能変化が起こって効果が発揮される.

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J00974&link_issn=&doc_id=20200310080023&doc_link_id=issn%3D0022-1961%26volume%3D125%26issue%3D3%26spage%3D443&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0022-1961%26volume%3D125%26issue%3D3%26spage%3D443&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

記述言語：日本語   出版者・発行元：金原出版(株)  

＜文献概要＞81歳,女性。初診の4ヵ月前より四肢・躯幹に浮腫性紅斑,水疱が出現した。皮膚生検の結果,類天疱瘡の診断となった。ステロイド投与を開始したが,投与17日目に胸部CTで右肺塞栓があり,ヘパリン投与を開始した。その後貧血進行,巨大下腿血腫を認めたため,抗凝固療法は中止した。血漿交換療法と免疫グロブリン大量静注療法を行い,皮疹は軽快した。海外のコホート研究によると,類天疱瘡患者はコントロール群と比較し肺塞栓症を3.12倍,肺炎を2.94倍発症しやすい。類天疱瘡患者に肺塞栓症が生じた本邦報告例は,2000〜2018年には3例であり類天疱瘡と肺塞栓症の合併は非常にまれと思われるが,肺塞栓症は致死的になりうるので注意すべきである。

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01266&link_issn=&doc_id=20200214130008&doc_link_id=10.18888%2Fhi.0000001788&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fhi.0000001788&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

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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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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記述言語：日本語   出版者・発行元：金原出版(株)  

＜文献概要＞40歳,女性。左手から手首にかけて全周性に発赤・腫脹があった。全指の色調は蒼白で冷感があり知覚鈍麻も認めたため,コンパートメント症候群と診断し,緊急入院のうえ減張切開術を施行した。画像上は有意な所見はなかったが,臨床所見と経過より壊死性筋膜炎からコンパートメント症候群を生じたと考えて早期に減張切開に踏み切り,良好な経過を示した。コンパートメント症候群は外傷によって生じることが多いが,皮膚感染症に合併することもある。このことを念頭に置き,画像所見に頼らず,臨床経過によっては早期に外科的処置を検討する必要がある。

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01266&link_issn=&doc_id=20191122180043&doc_link_id=10.18888%2Fhi.0000001693&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fhi.0000001693&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：金原出版(株)  

＜文献概要＞79歳,男性。2017年1月に当科を受診。臨床的にはパンツ型紅斑を呈していた。組織学的に癌性リンパ管症を伴う外陰部乳房外Paget病と診断した。多発骨転移,多発リンパ節転移があったためStage IVと診断した。放射線療法とドセタキセル投与にて紅斑局面はほぼ消失した。統合失調症の既往があり,外来での放射線療法,化学療法の施行が困難だったため,上記治療は基本的に入院で施行した。当初は一般病棟入院としたが,徘徊・不眠症状が強く入院継続困難となり,精神科病棟に転棟し精神科管理の下で,幻聴などの陽性症状なく安定した精神状態を維持できた。統合失調症の合併症のある癌患者では,癌治療のための入院中にせん妄の問題を生じることが多い。しかし細かな精神科回診などを行えば,ほとんどの例で入院継続が可能である。

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：金原出版(株)  

＜文献概要＞79歳,男性。数年前より左前腕に圧痛のある結節を自覚し,当科を初診した。左前腕に12×8mm大の下床との可動性良好な弾性硬の皮下結節を認めた。造影CTではリング状に造影された。全摘除術を行い,病理組織では,血管周皮細胞様パターンがあり,一部に血管を同心円状に細胞が取り巻く像を認めた。αSMA陽性,S100とCD34は陰性であった。これらより,周皮細胞/血管周囲腫瘍である筋周皮腫,グロムス腫瘍,筋線維腫,血管平滑筋腫のうち,組織学的に筋周皮腫と診断した。自験例では,造影CTでリング状に造影されたことが特徴的であった。リング状に造影される疾患は脳内病変を除くとまれであり,本疾患の特徴であるかもしれない。

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01266&link_issn=&doc_id=20190722170015&doc_link_id=10.18888%2Fhi.0000001485&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fhi.0000001485&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.14766

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.14728

PubMed

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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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記述言語：日本語   出版者・発行元：(一社)日本皮膚悪性腫瘍学会  

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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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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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/ajd.12868

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1346-8138.14474

PubMed

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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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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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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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記述言語：英語  

DOI： 10.1111/1346-8138.14129

PubMed

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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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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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記述言語：英語   出版者・発行元：WILEY  

DOI： 10.1111/1346-8138.13939

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記述言語：英語  

DOI： 10.1111/1346-8138.13939

PubMed

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記述言語：英語  

DOI： 10.1111/1346-8138.13625

PubMed

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記述言語：英語   出版者・発行元：WILEY  

DOI： 10.1111/1346-8138.13625

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MEDICAL ASSOC NIPPON MEDICAL SCH  

An external dental fistula is a skin manifestation caused by an underlying dental problem. We report a rare case of external dental fistula associated with a fixed cantilever denture. A 77-year-old Japanese woman presented with an enlarging reddish granulomatous lesion on her right cheek that was diagnosed as an external dental fistula. A fixed cantilever denture had initially been attached to her upper jaw with her seven bona fide teeth. However, six teeth were completely lost and the denture was attached to only one tooth, which showed apical periodontitis. Subsequently, the external dental fistula developed. We should keep in mind that a patient with a fixed cantilever denture can suffer from apical periodontitis and a subsequent external dental fistula due to a failure to maintain appropriate oral hygiene.

DOI： 10.1272/jnms.84.198

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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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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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記述言語：日本語   出版者・発行元：金原出版(株)  

症例は41歳女性で、13年前より両下腿の隆起性局面を自覚しており、以降、右下腿蜂窩織炎で2度当科入院歴があった。入院前日より発熱と下痢を認め、翌日より右下腿が発赤・腫脹し、蜂窩織炎の診断で緊急入院となった。スルバクタム/アンピシリンとクリンダマイシンの投与を開始し、右下肢挙上とクーリングを行った。臨床所見上、軽度悪化傾向がみられたため、第7病日よりレボフロキサシンに変更し、第10病日まで投与した。また、脛骨前粘液水腫の治療として第7病日よりジフルプレドナート軟膏外用、第9病日よりプレドニゾロン内服を開始し漸増した。右下腿の発赤は軽快、腫脹は左下腿と同程度まで軽快し、第16病日に退院した。退院後、上記外用・内服継続と弾性包帯着用を開始した。右下腿の腫脹に著変はなかったが、蜂窩織炎は再燃せず経過している。

DOI： 10.18888/hi.0000000170

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J01266&link_issn=&doc_id=20170814150023&doc_link_id=10.18888%2Fhi.0000000170&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fhi.0000000170&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

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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記述言語：日本語   出版者・発行元：金原出版(株)  

症例は80歳男性で、4ヵ月程前より右耳甲介に皮疹が出現した。近医にて外用治療を継続するも増大傾向であり、当科を紹介受診した。病理組織学的所見では、腫瘍は表皮と連続する隆起性の病変で、真皮に核が濃染し胞体の少ない毛芽細胞様細胞が結節状あるいは索状に増加していた。臨床および皮膚生検による病理組織学的所見より、小結節型基底細胞癌と診断した。初診より1週間後に、全身麻酔下で切除術および分層植皮術による再建を施行した。水平方向は腫瘍辺縁から5mm離して、垂直方向は耳介軟骨を含めて切除した。その際に対輪下脚の一部を切除したが、耳輪は完全に温存した。右大腿部より採皮し、皮膚・軟骨欠損部へ植皮した。その後の経過は良好であり、術後3ヵ月の時点で植皮部の拘縮はみられず、耳介の形態は保たれていて整容的に満足のいくものであった。

DOI： 10.18888/hi.0000000156

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J01266&link_issn=&doc_id=20170814150012&doc_link_id=10.18888%2Fhi.0000000156&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fhi.0000000156&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：英語  

DOI： 10.1016/j.alit.2016.12.006

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記述言語：英語   出版者・発行元：JAPANESE SOCIETY ALLERGOLOGY  

DOI： 10.1016/j.alit.2016.12.006

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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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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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記述言語：日本語   出版者・発行元：金原出版(株)  

81歳男性。当院にて慢性色素性紫斑に対する治療中に、20歳頃より自覚していた足背の皮疹についても診察を希望された。受診時、足背に5〜7mm大の茶褐色の鱗屑を付着する丘疹が散在してみられ、病理組織学的所見より固定性扁豆状角化症と診断された。診断後はマキサカルシトール軟膏の外用を開始し、3ヵ月後に皮疹は軽快した。本症例は息子にも同症を認め、家族内発症であることが判明した。

DOI： 10.18888/J01266.2017233466

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J01266&link_issn=&doc_id=20170410250006&doc_link_id=10.18888%2FJ01266.2017233466&url=https%3A%2F%2Fdoi.org%2F10.18888%2FJ01266.2017233466&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：英語  

DOI： 10.1111/1346-8138.13614

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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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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記述言語：英語  

DOI： 10.1111/1346-8138.13467

PubMed

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記述言語：英語   出版者・発行元：WILEY  

DOI： 10.1111/1346-8138.13467

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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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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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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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記述言語：日本語   出版者・発行元：(一社)日本皮膚アレルギー・接触皮膚炎学会  

症例は21歳男性。3年前、サケのホイル焼きを摂食後、全身にそう痒を伴う発疹が出現し、呼吸苦をきたした。その後もハモで顔面腫脹・発疹・呼吸苦、タラで顔面腫脹・発疹、ウナギおよびサンマで口腔内違和感、アミノコラーゲン入り栄養ドリンクで膨疹が出現した。Prick to prick testではウナギ(加熱)、アナゴ(加熱)、サンマ(生)が陽性だったが、サンマ以外の生魚は陰性であった。ELISA法によるアレルゲンの検索を行い、魚類コラーゲンが原因抗原であると診断した。魚類コラーゲンアレルギー患者では、生魚を用いたprick to prick testでは偽陰性になることがあり注意を要する。また、コラーゲンは加熱によっても抗原性が低減化しない。さらに近年では、魚類コラーゲンが栄養ドリンクや化粧品にも用いられている。ウナギ目の魚類による即時型アレルギーの報告は少なく、検査方法および生活指導に注意を要する。(著者抄録)

DOI： 10.18934/jedca.11.1_50

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J04984&link_issn=&doc_id=20170210410008&doc_link_id=%2Fdl4jedca%2F2017%2F001101%2F008%2F0050-0054%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdl4jedca%2F2017%2F001101%2F008%2F0050-0054%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

An external dental fistula is a skin manifestation caused by an underlying dental problem. We report a rare case of external dental fistula associated with a fixed cantilever denture. A 77-year-old Japanese woman presented with an enlarging reddish granulomatous lesion on her right cheek that was diagnosed as an external dental fistula. A fixed cantilever denture had initially been attached to her upper jaw with her seven bona fide teeth. However, six teeth were completely lost and the denture was attached to only one tooth, which showed apical periodontitis. Subsequently, the external dental fistula developed. We should keep in mind that a patient with a fixed cantilever denture can suffer from apical periodontitis and a subsequent external dental fistula due to a failure to maintain appropriate oral hygiene.

DOI： 10.1272/jnms.84.198

PubMed

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚アレルギー・接触皮膚炎学会  

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記述言語：日本語   出版者・発行元：(一社)日本美容皮膚科学会  

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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  

J-GLOBAL

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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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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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記述言語：日本語   出版者・発行元：(一社)日本皮膚悪性腫瘍学会  

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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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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

BackgroundAcanthosis nigricans (AN) can occur as a cutaneous manifestation of genetic diseases, one of which is associated with activating mutations of the fibroblast growth factor receptor 3 gene (FGFR3).
ObjectiveWe explored familial AN patients with FGFR3 mutations and examined the effectiveness of glycolic acid (GA) peeling in improving their skin manifestations.
MethodsSanger sequencing was performed for the genomic DNA extracted from leucocytes of the family members involving familial AN. GA peeling was carried out for the two patients of familial AN once every 2 weeks.
ResultsHeterozygous c.1949A>C (p.K650T) mutation in FGFR3 was identified for the affected family members examined, whereas the wild-type sequence was found for two unaffected individuals. Hyperpigmentation and coarseness of the skin were improved by GA peeling at regular intervals with few adverse effects.
ConclusionWe diagnosed our cases as familial generalized AN caused by heterozygous c.1949A>C (p.K650T) mutation of FGFR3. We propose that GA peeling is a useful and safe therapeutic option to treat familial AN.

DOI： 10.1111/jdv.13580

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(株)医学書院  

症例1:38歳,女性.頭頂部に6mm大の皮膚常色ドーム状結節性病変があった.症例2:52歳,女性.上背部に10mm大の淡紅色隆起性結節があった.いずれも色素性母斑の臨床診断で切除した.病理組織所見は2症例ともに境界明瞭な結節で,細胞成分に乏しく,真皮内に硝子化した膠原線維のタマネギ状の増生を認めた.2症例ともにCowden症候群の身体徴候を欠いており,sclerotic fibroma of the skinと診断した.症例1の結節辺縁には膠原線維と線維芽細胞の軽度増加を伴う皮膚線維腫様の病理所見があり,本症が皮膚線維腫からの移行病変である可能性が考えられた.(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J01559&link_issn=&doc_id=20160108020012&doc_link_id=10.11477%2Fmf.1412204640&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1412204640&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

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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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

We expressed the fusion proteins of the muscarinic acetylcholine receptor M2 subtype (M2 receptor) with a maltose-binding protein (MBP) and various G protein α subunits (Gα(i1-i3/o)) at its N- and C-terminals, respectively (MBP-M2-Gα(i/o)), in Escherichia coli, and examined the effect of G protein βγ subunits (Gβγ) on the receptor-Gα interaction as assessed by agonist- and GDP-dependent [(35)S]GTPγS binding of the fusion proteins. We found that (i) Gβγ promoted both the agonist-dependent and -independent [(35)S]GTPγS binding with little effect on the guanine nucleotide-sensitive high-affinity agonist binding, (ii) the specific [(35)S]GTPγS binding activity was much greater for MBP-M2-Gα(oA) than for MBP-M2-Gα(i1-i3) in the absence of Gβγ, whereas Gβγ preferentially promoted the agonist-dependent decrease in the affinity for GDP of MBP-M2-Gα(i1-i3) rather than of MBP-M2-Gα(oA), and (iii) the proportion of agonist-dependent [(35)S]GTPγS binding was roughly 50% irrespective of species of Gα and the presence or absence of Gβγ. These results demonstrate that receptor-Gα fusion proteins expressed in E. coli could be useful for studies of receptor-G interaction.

DOI： 10.1093/jb/mvu036

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DL-2-Haloacid dehalogenase from Methylobacterium sp. CPA1 (DL-DEX Mb) is a unique enzyme that catalyzes the dehalogenation reaction without the formation of an ester intermediate. A recombinant form of DL-DEX Mb has been expressed in Escherichia coli, purified and crystallized using the hanging-drop vapour-diffusion method. The crystal belongs to the hexagonal space group P6(3), with unit-cell parameters a = b = 186.2, c = 114.4 A. The crystals are likely to contain between four and eight monomers in the asymmetric unit, with a V(M) value of 4.20-2.10 A3 Da(-1). A self-rotation function revealed peaks on the chi = 180 degrees section. X-ray data have been collected to 1.75 A resolution.

DOI： 10.1107/S1744309107027273

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INT UNION CRYSTALLOGRAPHY  

DL-2-Haloacid dehalogenase from Methylobacterium sp. CPA1 (DL-DEX Mb) is a unique enzyme that catalyzes the dehalogenation reaction without the formation of an ester intermediate. A recombinant form of DL-DEX Mb has been expressed in Escherichia coli, purified and crystallized using the hanging-drop vapour-diffusion method. The crystal belongs to the hexagonal space group P6(3), with unit-cell parameters a = b = 186.2, c = 114.4 angstrom. The crystals are likely to contain between four and eight monomers in the asymmetric unit, with a V-M value of 4.20-2.10 angstrom(3) Da(-1). A self-rotation function revealed peaks on the chi = 180 degrees section. X-ray data have been collected to 1.75 angstrom resolution.

DOI： 10.1107/S1744309107027273

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

Signal transduction mediated by heterotrimeric G proteins regulates a wide variety of physiological functions. We are interested in the manipulation of G-protein-mediating signal transduction using G-protein-coupled receptors, which are derived from evolutionarily distant organisms and recognize unique ligands. As a model, we tested the functionally coupling GOA-1, G alpha(i/o) ortholog in the nematode Caenorhabditis elegans, with the human muscarinic acetylcholine receptor M2 subtype (M2), which is one of the mammalian G alpha(i/o)-coupled receptors. GOA-1 and M2 were prepared as a fusion protein using a baculovirus expression system. The affinity of the fusion protein for GDP was decreased by addition of a muscarinic agonist, carbamylcholine and the guanosine 5'-[3-O-thio]triphosphate ([35S]GTPgammaS) binding was increased with an increase in the carbamylcholine concentrations in a dose-dependent manner. These effects evoked by carbamylcholine were completely abolished by a full antagonist, atropine. In addition, the affinity for carbamylcholine decreased under the presence of GTP as reported for M2-G alpha(i/o) coupling. These results indicate that the M2 activates GOA-1 as well as G alpha(i/o).

DOI： 10.1111/j.1742-4658.2006.05542.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Fireflies communicate with each other by emitting yellow-green to yellow-orange brilliant light. The bioluminescence reaction, which uses luciferin, Mg-ATP and molecular oxygen to yield an electronically excited oxyluciferin species, is carried out by the enzyme luciferase. Visible light is emitted during relaxation of excited oxyluciferin to its ground state. The high quantum yield of the luciferin/luciferase reaction and the change in bioluminescence colour caused by subtle structural differences in luciferase have attracted much research interest. In fact, a single amino acid substitution in luciferase changes the emission colour from yellow-green to red. Although the crystal structure of luciferase from the North American firefly (Photinus pyralis) has been described, the detailed mechanism for the bioluminescence colour change is still unclear. Here we report the crystal structures of wild-type and red mutant (S286N) luciferases from the Japanese Genji-botaru (Luciola cruciata) in complex with a high-energy intermediate analogue, 5'-O-[N-(dehydroluciferyl)-sulfamoyl]adenosine (DLSA). Comparing these structures to those of the wild-type luciferase complexed with AMP plus oxyluciferin (products) reveals a significant conformational change in the wild-type enzyme but not in the red mutant. This conformational change involves movement of the hydrophobic side chain of Ile 288 towards the benzothiazole ring of DLSA. Our results indicate that the degree of molecular rigidity of the excited state of oxyluciferin, which is controlled by a transient movement of Ile 288, determines the colour of bioluminescence during the emission reaction.

DOI： 10.1038/nature04542

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その他リンク： http://www.nature.com/articles/nature04542

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

We have examined whether the long third intracellular loop (i3) of the muscarinic acetylcholine receptor M2 subtype has a rigid structure. Circular dichroism (CD) and nuclear magnetic resonance spectra of M2i3 expressed in and purified from Escherichia coli indicated that M2i3 consists mostly of random coil. In addition, the differential CD spectrum between the M2 and M2deltai3 receptors, the latter of which lacks most of i3 except N- and C-terminal ends, gave no indication of secondary structure. These results suggest that the central part of i3 of the M2 receptor has a flexible structure.

DOI： 10.1016/j.febslet.2005.11.042

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Fluoroacetate dehalogenase from Moraxella sp. B (FAc-DEX) catalyzes cleavage of the carbon-fluorine bond of fluoroacetate, whose dissociation energy is among the highest found in natural products. Asp105 functions as the catalytic nucleophile that attacks the alpha-carbon atom of the substrate to displace the fluorine atom. In spite of the essential role of Asp105, we found that site-directed mutagenesis to replace Asp105 by Asn does not result in total inactivation of the enzyme. The activity of the mutant enzyme increased in a time- and temperature-dependent manner. We analyzed the enzyme by ion-spray mass spectrometry and found that the reactivation was caused by the hydrolytic deamidation of Asn105 to generate the wild-type enzyme. Unlike Asn10 of the l-2-haloacid dehalogenase (L-DEX YL) D10N mutant, Asn105 of the fluoroacetate dehalogenase D105N mutant did not function as a nucleophile to catalyze the dehalogenation.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Fluoroacetate dehalogenase from Moraxella sp. B (FAc-DEX) catalyzes cleavage of the carbon-fluorine bond of fluoroacetate, whose dissociation energy is among the highest found in natural products. Asp105 functions as the catalytic nucleophile that attacks the a-carbon atom of the substrate to displace the fluorine atom. In spite of the essential role of Asp 105, we found that site-directed mutagenesis to replace Asp105 by Asn does not result in total inactivation of the enzyme. The activity of the mutant enzyme increased in a time- and temperature-dependent manner. We analyzed the enzyme by ion-spray mass spectrometry and found that the reactivation was caused by the hydrolytic deamidation of Asn105 to generate the wild-type enzyme. Unlike Asn10 of the L-2-haloacid dehalogenase (L-DEX YL) D10N mutant, Asn105 of the fluoroacetate dehalogenase D105N mutant did not function as a nucleophile to catalyze the dehalogenation. (C) 2003 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.bbapap.2003.10.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Fluoroacetate dehalogenase catalyzes the hydrolytic defluorination of fluoroacetate to produce glycolate. The enzyme is unique in that it catalyzes the cleavage of the highly stable carbon-fluorine bond in an aliphatic compound. The bacterial isolate FA1, which was identified as Burkholderia, grew on fluoroacetate as the sole carbon source to produce fluoroacetate dehalogenase (FAc-DEX FA1). The enzyme was purified to homogeneity and characterized. The molecular weights were estimated to be 79,000 and 34,000 by gel filtration and SDS-polyacrylamide gel electrophoresis (PAGE), respectively, suggesting that the enzyme is a dimer. The purified enzyme was specific to haloacetates, and fluoroacetate was the best substrate. The activities toward chloroacetate and bromoacetate were less than 5% of the activity toward fluoroacetate. The K-m and V-max values for the hydrolysis of fluoroacetate were 5.1 mM and 11 mumol per minute milligram, respectively. The gene coding for the enzyme was isolated, and the nucleotide sequence was determined. The open reading frame consisted of 912 nucleotides, corresponding to 304 amino acid residues. Although FAc-DEX FA1 showed high sequence similarity to fluoroacetate dehalogenase from Moraxella sp. B (FAc-DEX H1) (61% identity), the substrate specificity of FAc-DEX FA1 was significantly different from that of FAc-DEX H1: FAc-DEX FA1 was more specific to fluoroacetate than FAc-DEX H1. (C) 2003 Elsevier B.V. All rights reserved.

DOI： 10.1016/S1381-1177(03)00098-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

L-2-Haloacid dehalogenase catalyzes the hydrolytic dehalogenation Of L-2-haloalkanoic acids to produce the corresponding D-2-hydroxyalkanoic acids. Asp10 Of L-2-haloacid dehalogenase from Pseudomonas sp. YL nucleophilically attacks the alpha-carbon atom of the substrate to form an ester intermediate, which is subsequently hydrolyzed by an activated water molecule. We previously showed that the replacement of Thr14, Arg41, Ser118, Lys151, Tyr157, Ser175, Asn177, and Asp 180 causes significant loss in the enzyme activity, indicating the involvement of these residues in catalysis. In the present study, we tried to determine which process these residues are involved in by monitoring the formation of the ester intermediate by measuring the molecular masses of the mutant enzymes using ionspray mass spectrometry. When the wild-type enzyme and the T14A, S118D, K151R, Y157F, S175A, and N177D mutant enzymes were mixed with the substrate, the ester intermediate was immediately produced. In contrast, the R41K, D180N, and D180A mutants formed the intermediate much more slowly than the wild-type enzyme, indicating that Arg41 and Asp180 participate in the formation of the ester intermediate. This study presents a new method to analyze the roles of amino acid residues in catalysis. (C) 2003 Elsevier B.V. All rights reserved.

DOI： 10.1016/S1381-1177(03)00097-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPANESE BIOCHEMICAL SOC  

Fluoroacetate dehalogenase from Moraxella sp. B (FAc-DEX) catalyzes the hydrolytic dehalogenation of fluoroacetate and other haloacetates. Asp(105) of the enzyme acts as a nucleophile to attack the alpha-carbon of haloacetate to form an ester intermediate, which is subsequently hydrolyzed by a water molecule activated by His(272) [Liu, J.Q., Kurihara, T., Ichiyama, S., Miyagi, M., Tsunasawa, S., Kawasaki, H., Soda, K., and Esaki, N. (1998) J. Biol. Chem. 273, 30897-30902]. In this study, we found that FAc-DEX is inactivated concomitantly with defluorination of fluoroacetate by incubation with ammonia. Mass spectrometric analyses revealed that the inactivation of FAc-DEX is caused by nucleophilic attack of ammonia on the ester intermediate to convert the catalytic residue, Asp(105), into an asparagine residue. The results indicate that ammonia reaches the active site of FAc-DEX without losing its nucleophilicity. Analysis of the three-dimensional structure of the enzyme by homology modeling showed that the active site of the enzyme is mainly composed of hydrophobic and basic residues, which are considered to be essential for an ammonia molecule to retain its nucleophilicity. In a normal enzyme reaction, the hydrophobic environment is supposed to prevent hydration of the highly electronegative fluorine atom of the substrate and contribute to fluorine recognition by the enzyme. Basic residues probably play a role in counterbalancing the electronegativity of the substrate. These results demonstrate that catalysis-linked inactivation is useful for characterizing the active-site environment as well as for identifying the catalytic residue.

DOI： 10.1093/oxfordjournals.jbchem.a003150

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER CHEMICAL SOC  

DOI： 10.1021/ja0160400

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掲載種別：研究論文（学術雑誌）   出版者・発行元：American Society for Biochemistry & Molecular Biology (ASBMB)  

DOI： 10.1074/jbc.m008065200

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Fluoroacetate dehalogenase (EC 3.8.1.3) catalyzes the dehalogenation of fluoroacetate and other haloacetates, The amino acid sequence of fluoroacetate dehalogenase from Moraxella sp, B is similar to that of haloalkane dehalogenase (EC 3.8.1.5) from Xanthobacter autotrophicus GJ10 in the regions around Asp-105 and His-272, which correspond to the active site nucleophile Asp-124 and the base catalyst His-289 of the haloalkane dehalogenase, respectively (Krooshof, G, H,, Kwant, E. M,, Damborsky, J,, Koca, J,, and Janssen, D, B, (1997) Biochemistry 36, 9571-9580), After multiple turnovers of the fluoroacetate dehalogenase reaction in (H2O)-O-18, the enzyme was digested with trypsin, and the molecular masses of the peptide fragments formed were measured by ion-spray mass spectrometry, Two O-18 atoms were shown to be incorporated into the octapeptide, Phe-99-Arg-106, Tandem mass spectrometric analysis of this peptide revealed that Asp-105 was labeled with two O-18 atoms. These results indicate that Asp-105 acts as a nucleophile to attack the alpha-carbon of the substrate, leading to the formation of an eater intermediate, which is subsequently hydrolyzed by the nucleophilic attack of a water molecule on the carbonyl carbon atom. A His-272 --> Asn mutant (H272N) showed no activity with either fluoroacetate or chloroacetate. However, ion-spray mass spectrometry revealed that the H272N mutant enzyme was covalently alkylated with the substrate. The reaction of the H272N mutant enzyme with [C-14]chloroacetate also showed the incorporation of radioactivity into the enzyme. These results suggest that His-272 probably acts as a base catalyst for the hydrolysis of the covalent eater intermediate.

DOI： 10.1074/jbc.273.47.30897

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記述言語：日本語   出版者・発行元：社団法人日本農芸化学会  

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記述言語：英語   会議種別：口頭発表（一般）  

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記述言語：英語   会議種別：ポスター発表  

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