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Background and objective:The calcium-binding protein S100A4 belongs to the S100 family and is involved in fibrotic and inflammatory processes, in which tissue remodeling, cell motility, and epithelialmesenchymal transition play major roles. Cytoplasmic S100A4 is a marker of lung fibroblasts in pulmonary fibrosis;however, the effects of exogenous S100A4 on fibrotic and inflammatory processes in pulmonary fibrosis are unclear. This study examined the effects of exogenous S100A4 protein in mice with bleomycin-induced pulmonary fibrosis.Methods:Bleomycin was administered to mice by intratracheal instillation on day 1. Intratracheal S100A4 protein was administered 4 times after bleomycin treatment. Bronchoalveolar lavage fluid was obtained and lung histological examinations were performed on day 14 after bleomycin administration. Lung tissue was homogenized on the same day to assess the mRNA expression of cytokines, fibroblast growth factors, and S100A4.Results:Unexpectedly, we observed that the administration of exogenous S100A4 protein apparently reduced lung fibrosis in bleomycin-treated mice. In addition, the levels of lymphocyte accumulation and insulin-like growth factor-1 mRNA were significantly reduced in bleomycin-treated lung by S100A4 administration.Conclusions:Exogenous S100A4 protein attenuates bleomycin-induced pulmonary fibrosis in mice by reducing lymphocyte function and the levels of fibroblast growth factors.

局所麻酔下胸腔鏡が施行され,胸膜生検検体にて乾酪性肉芽腫を認め,結核性胸膜炎と診断された症例の臨床的検討を行った.対象は,1999 年12 月から2011 年1 月までに局所麻酔下胸腔鏡により病理学的に診断された結核性胸膜炎32例.男性25例,女性7例.平均年齢62.8歳( 24〜89歳).右側胸水が14例,左側胸水が16 例,両側胸水が2 例.胸水リンパ球比率の平均は90.9%,胸水ADA の平均は69.1 IU/l であった.胸水のTb-PCR( tuberculosis-polymerase chain reaction) は全例で陰性,胸水抗酸菌培養は1例のみ陽性で,陽性率は極めて低値であった.胸腔鏡所見では,壁側胸膜のびまん性の白色小結節病変が最も多く19例( 59.4%)で認められ,胸膜肥厚や癒着,血管増生などの非特異的な所見も高率に認めた.胸膜生検検体の結核菌培養陽性率は約40%であった.結節病変を認めた例では,結節病変を認めなかった例と比較してより年齢が若く,発症から検査までの日数が有意に短かった.結核性胸膜炎の診断は,胸水穿刺だけでは診断効率が低く,局所麻酔下胸腔鏡を行うことにより診断効率は大きく向上し,内科医が施行できる安全性の高い極めて有用性の高い検査法といえる., We reviewed our patients with tuberculous pleurisy underwentmedical thoracoscopy. From December 1999 toJanuary 2011, 32 patients were diagnosed as having tuberculouspleurisy by pleural biopsy pathologically. The typicalthoracoscopic findings of tuberculous pleurisy such as diffusesmall white nodules on the parietal pleura were seen in23 cases (71.9 %). Non-specific pleural findings such asthickness on the pleura or adhesion were seen in 9 cases(22.2 %). In all these patients, pathological diagnoses of tuberculouspleurisy were made by pleural biopsies. Sincemedical thoracoscopy is useful for the diagnosis of tuberculouspleurisy, it is recommended as a diagnostic procedurefor cases with pleural effusion.

胸腔鏡下肺生検にて病理組織学的に非特異性間質性肺炎 (nonspecific interstitial pneumonia:NSIP) と診断された18例( 特発性NSIP:7例,膠原病に伴うNSIP:11例) を,ステロイド治療の反応性によって2 群に分け,臨床上改善が得られた群をresponder,得られなかった群をnon-responder とし,2 群間の病理組織所見,呼吸機能,血液ガス,バイオマーカー,bronchoalveolar lavage fluid( BALF),胸部high-resolutionCT( HRCT) 所見の比較検討を行った.responder群は10例,non-responder群は8例であり,両群共に女性に多い傾向はあったが,平均年齢,PaO2 に有意差は認められなかった.病理組織所見では,non-responder群において組織学的により線維化が強い傾向があり,画像上reticulation 優位のパターンが8 例中4 例に認められた.また,non-responder 群における診断時のKL-6,SP-D は,responder 群と比較して高値を示していた.胸部CT においてconsolidation を示す部位はステロイドによる初期治療に反応する場合が多く,画像所見は治療反応規定因子として重要であると思われた., Eighteen patients of nonspecific interstitial pneumonia(NSIP) were evaluated retrospectively to know the predictivefactors for response to corticosteroid therapy. The diagnosiswas established based on lung biopsy performed byvideo-assisted thoracoscopic surgery. Early phase response(after 1 month) to therapy was determined by pretreatmentand post-treatment clinical (dyspnea), radiographic(chest HRCT), and physiologic (pulmonary function andblood gas analysis) scores (CRP). Ten (55.6 %) patientswere responders, 8( 44.4%) were non-responders. Patientswith cellular pattern ware more likely to respond comparedto patients with fibrosing pattern after treatment withprednisolone. The presence of advanced fibrosis was themost important factor influencing responsiveness to steroid.Consolidation pattern on HRCT indicated better response tosteroid whereas reticular pattern indicated poor response.

症例は16 歳女性,咳嗽,発熱,左前胸部痛を主訴に来院.胸部CT にて内部不均一な径7 cm の前縦隔腫瘍及び左舌区・下葉の完全無気肺を確認,また,MRI にて前縦隔腫瘍内に脂肪組織と同一の吸収域を認め,成熟型奇形腫穿破による膿胸と診断.膿胸に対し胸腔内繊維素溶解療法,ドレナージ及び抗生剤にて加療,膿胸改善を確認した上で,前縦隔腫瘍摘出術施行,病理にて嚢胞性成熟型奇形腫と診断した.病理組織にて膵類似の腺組織を確認,穿破の原因として,腫瘍内膵酵素の存在が考えられた.成熟型縦隔奇形腫は穿破により重篤な合併症発生の危険性があり,また経過中悪性転化する可能性もあることから,早期の外科治療が重要と考えられた., A 16-year-old female visited our hospital, complaining ofcough, fever, and left precordial pain. Chest computed tomographyshowed a heterogeneous anterior mediastinal tumormeasuring 7 cm in diameter and complete atelectasis inthe lingula and lower lobe of the left lung. Magnetic resonanceimaging also showed an area of intensity identical tothat of adipose tissue in the anterior mediastinal tumor.Thus, empyema due to rupture of a mature teratoma wasdiagnosed. The empyema was treated with intra-pleural fibrinolytictherapy, drainage, and antibiotics. After confirmingresolution of the empyema, we resected the anteriormediastinal tumor and pathologically diagnosed it as cysticmature teratoma. Histopathological examination showedglandular tissue resembling the pancreas, suggesting thatthe rupture had been caused by pancreatic enzymes in thetumor. Mediastinal mature teratoma carries a risk of seriouscomplications developing due to rupture and the possibilityof malignant transformation during the diseasecourse. Thus, early surgical treatment is important.

74 歳男性.顔面,四肢,体幹の紅斑に続き,構音障害および嚥下障害,四肢筋肉痛並び脱力が出現し,起立困難となり入院となった.CK, ALD, AST, LDH 等筋原性酵素の著明上昇及び臨床所見により皮膚筋炎と診断された.高用量ステロイド療法その後シクロスポリンの追加にて治療開始し,検査所見に続き,臨床所見も改善傾向にあった.同時にproGRP 高値並びに全身CT 画像上縦隔リンパ節腫大認め,気管支鏡下気管支粘膜生検にて小細胞肺癌の病理診断が得られ,CBDCA+CPT-11 にて化学療法を施行,腫瘍の縮小効果を見た.皮膚筋炎が腫瘍随伴症候として,小細胞癌とほぼ同時期に発病したことを示唆した症例であった, A 74-year-old man was admitted because of erythemaon face, extremities and trunk, followed by dysarthria, dysphagia,extremity myalgia accompanied with weakness, andthen difficulty in upstanding. Dermatomyositis (DM) wasdiagnosed on the basis of a marked increase in serum levelof myogenic enzymes, such as creatinin kinase, aldolase, aspartateaminotransferase and lactate dehydrogenase, andthe clinical manifestations. Introduction of high-dose glucocorticoidtherapy, subsequently concurrent administrationof cyclosporin, made laboratory data gradually return tonormal and produced slight symptom improvement. Inscreening for malignancies, high level of proGRP detectedin peripheral blood, computed tomography scan showed mediastinallymphadenopathy, and histopathologial testing ofthe transbronchial biopsy specimens revealed small celllung cancer (SCLC). Chemotherapy (CBDCA+CPT-11)started, resulting in tumor reduction. The current case maysuggest that DM coincided with SCLC around at the sametime, as a mean of paraneoplastic syndrome.

Benign metastasizing leiomyoma (BML) is a very rare disease, and although it was reported as early as1939 to result from metastasis of benign uterine myoma to the lungs and lymph nodes, its pathology remainsobscure. Here, we describe a case of pulmonary BML occurring after uterine myomectomy in a42-year-old woman. She presented with a 2-week history of dry cough on exertion. Chest radiography andcomputed tomography( CT) revealed bilateral multiple nodular lesions. The patient had a history of uterinemyoma and previously underwent myomectomy. For definitive diagnosis, lung biopsy was performed byvideo associated thoracoscopic surgery. Histopathologic examination of biopsy specimens revealed pulmonaryBML occurring after uterine myomectomy. For treatment of the pulmonary BML, gonadotropin-releasinghormone was initially administered, and 1 month later the patient underwent complete hysterectomyand bilateral salpingo-oophorectomy. Chest CT 6 months after surgery showed that the size and number oflung multiple nodular lesions did not increase compared with those before surgery. In future studies, we aimto investigate a larger number of pulmonary BML cases, as well as establish specific treatments and investigatethe prognosis of the disease.Abbreviations:BML:benign metastasizing leiomyomaSS:Sjögren's syndromeCT:computed tomographyH&E:hematoxylin and eosinVATS:video associated thoracoscopic surgeryCA:carbohydrate antigenIg:immunoguloblina SMA:a smooth muscle actin

獨協医科大学病院呼吸器・アレルギー内科を受診したHIV感染者を解析し,わが国および栃木県のHIV 感染者との比較検討を行った.対象は,2002年7月より2009年6月までの間,当科に受診歴のある34名(男27名,女7名,日本人29名,外国人5名),平均年齢は44.2歳(29歳〜67歳).男性の感染理由は,異性間(風俗,不特定)40.7%,同性間37.0%,女性はパートナーからの感染が57.1 %であった.64.7%がAIDS 発症によりHIV感染が判明し,HIV感染判明時の精査では79.4%がAIDSを発症しており,全症例の55.9%にニューモシスチス肺炎の合併を認めた.治療開始が推奨されているCD4陽性細胞低値(350/m l以下)は,97.1%の症例に認めた.以上の結果より,感染理由や年齢層については,全国の平均と同様な傾向を認めた.全国的には,HIV感染判明者の約7割がAIDS 発病前のキャリアの状態でHIV 感染が判明し,栃木県でも同様の傾向である.しかし,当科では大多数がAIDS 発症後およびAIDS 発症直前の低免疫状態でHIV 感染が判明しており,早期発見および早期介入が課題と考えられた., To be clear the clinical characteristics in Tochigi, we analyzedpatients with HIV infection in our department. Patientswith HIV infection between July 2002 and June 2009were 34 subjects (Man:Woman=27:7, Japanese:Foreigner=29:5), and mean age was 44.2 years old. In reasonof HIV infection for men, men who were infected by sexualintercourse with indefinite women were 40.7 % and menwho were infected by sexual intercourse with men were37.0 %. Women who were infected by their partners were57.1 %. 64.7 % of patients were recognized HIV infection byshowing AIDS. 79.4% of patients already had complicationsindicating AIDS, when they came to our hospital, and 55.9% of patients had pneumocystis jiroveci pneumonia. In 97.1% of patients, the number of CD4 positive cells were under350/m l. In conclusion, around 70 % of patients were recognizedHIV infection before they become AIDS in Japan. But,a large majority of patients in our department were withbecoming AIDS or just before AIDS. We need to developthe system of early intervention for HIV infection.

Recently, immunoglobulin (Ig) G4-related diseases such as autoimmune pancreatitis (AIP), sclerosingsialadenitis, retroperitoneal fibrosis, and sclerosing cholangitis have been reported. IgG4-related diseases arecharacterized by high serum IgG4 concentrations, sclerosing inflammation with numerous IgG4-positiveplasma cells, and steroid sensitivity, irrespective of their organ of origin. We describe a case of inflammatorylung disease and retroperitoneal fibrosis, suggested to involve IgG4. The patient was a 76-year-old man. Acomputed tomographic scan of the chest showed nodular air-space consolidation in the left upper lobe. Theserum IgG4 concentration was abnormally elevated, but there was no evidence of AIP. Bilateral hydronephrosisassociated with thickened soft tissue around the abdominal aorta had been diagnosed previously. Hehad undergone surgery, and retroperitoneal fibrosis was diagnosed histologically (hematoxylin and eosinstain). Histological examination of bronchoscopic specimens taken from the left S3 region showed mononuclear-cell infiltration of the fibrotic bronchial wall, including many IgG4-positive plasma cells. Specimens ofthe region affected by retroperitoneal fibrosis were retrospectively reanalyzed, and the cells were positivefor IgG4 on immunostaining, similar to the lung tissue. The patient responded to treatment with corticosteroids.In conclusion, the present case shared many clinical and clinicopathological similarities with systemicIgG4-related autoimmune disease. To our knowledge, however, this is the first reported case of inflammatorylung disease with retroperitoneal fibrosis in a patient with systemic IgG4-related autoimmune disease.

35歳男性.入院約6週前より喀痰,咳嗽出現.数日前に左上肺空洞影指摘,喀痰中抗酸菌(3+)検出され入院.INH,RFP,PZA 及びEB による標準化学療法が開始された.咳嗽,呼吸困難,両肺野狭窄音聴取及び多量排菌持続し,気管支鏡所見上気管〜両側主気管支に隆起性潰瘍病変を認め,気管支結核を確定.高度の呼吸器症状遷延のため中等量のステロイド点滴投与を開始し,症状ならびに気道粘膜病変は改善した.高率に気管・気管支瘢痕収縮へ移行しうる気道粘膜像であったが,中等量の全身ステロイド療法により回避された.気道瘢痕狭窄回避のため,気管支結核活動性病変には中等量以上の全身ステロイド療法を考慮すべきと考えられた., A 35-year-old man admitted to the hospital because of acavitary lesion in the lung and acid-fast bacilli (AFB) (3+) in a sputum specimen, a polymerase-chain-reaction ofwhich revealed positive for M. tuberculosis. He had beenwell until approximately 6 weeks before admission, whenproductive cough developed. He also had temperature of upto 38 ℃, hoarseness, and shortness of breath couple of daysbefore. Intractable cough, dyspnea, wheeze in both lungfields, and numerous AFB in a sputum sustained, despiteprompt introduction of conventional chemotherapy containingINH, rifampicin, pyrazinamide, and ethambutol. Diagnosisof EBTB was confirmed by fibroptic bronchoscopy,which revealed granulomatous ulceration in the mucosa oftrachea and both main bronchi. Accordingly, intravenousmedium-dose methylprednisolone was administered, resultingrelief from serious respiratory manifestation and avoidanceof cicatricial stenosis of trachea and bronchi. This outcomesuggested that the current early intervention withglucocorticoid should be considered in serious active lesionof tracheal and bronchial mucosa in patients with EBTB.

Airway remodeling has an important role in the pathogenesis of bronchial asthma and is associated with severe, intractable disease. A lot of mediators, especially cysteinyl leukotrienes (CysLTs) and transforming growth factor (TGF)-β that influence pathophysiology of bronchial asthma are involved in the formation of airway remodeling. We hypothesized that responsiveness of fibroblasts to CysLTs is not the same as that of activated myofibroblasts induced by TGF-β. We examined the effects of leukotriene C_4 (LTC_4) on collagen production from fibroblasts and myofibroblasts transformed by TGF-β. Furthermore, we investigated mRNA expression of CysLTl receptor and a-smooth muscle actin (α-SMA) as a marker of myofibroblast. TGF-β_1 stimulated collagen production from human fetal lung fibroblasts (HFL-1), but LTC_4 alone did not. Meanwhile, LTC_4 in combination with TGF-β_1 enhanced collagen production as compared with TGF-β alone. Real time PCR revealed that stimulation with TGF-β significantly upregulated CysLTIR and α-SMA mRNA expression in HFL-1. LTC_4 increased the collagen production through upregulation of CysLTIR induced by TGF-β. In the TGF-β-rich milieu such as asthma, activated myofibroblasts expressing CysLTIR can respond to CysLTs and produce abundant extracellular matrix thereby forming airway remodeling. These data suggest that leukotriene receptor antagonists may be an effective therapeutics for preventing airway remodeling in asthmatics.