Clinical Significance of Propionibacterium acnes in the Formation of Noncaseating Epithelioid-Cell Granulomas of the Mediastinal Lymph Nodes and Lung in Patients with Lung Cancer:Differential Diagnosis Between Sarcoid Reactions and Sarcoidosis

Objectives:Sarcoidosis is a systemic noncaseating epithelioid-cell granulomatous disease of unknown origin.Granulomas occurring around malignant tumors and regional lymph nodes can be caused by sarcoid reactions.The mechanisms underlying sarcoidosis and sarcoid reactions remain unclear. Whether increaseduptake of fluorodeoxyglucose( FDG) in lymph nodes on positron emission tomography( PET) is caused bytumor metastasis, the concurrent presence of sarcoidosis, or sarcoid reactions must be determined to ensureproper disease staging and selection of treatment policy. We studied patients who underwent surgery forlung cancer and had no histopathological evidence of lymph-node metastasis in whom concurrent sarcoidosisor sarcoid reactions were diagnosed.Methods:In six patients who underwent surgery for primary lung cancer, granulomatous lesions werehistopathologically studied in dissected lymph nodes and lung. Tissue sections were stained with monoclonalantibodies against Propionibacterium acnes( PAB antibodies).Results:The six patients had noncaseating epithelioid-cell granulomas in mediastinal lymph nodes andlung. Clinically, concurrent sarcoidosis was suspected, but the results of staining the tissue specimens withPAB antibodies( in granulomas, alveolar macrophages, Hamazaki-Wesenberg bodies, and lymphatic sinuses)suggested sarcoid reactions in 5 patients. In one patient in whom granulomas stained positive with PAB antibodies,concurrent sarcoidosis was diagnosed.Conclusions:In patients with lung cancer who have no distinct systemic evidence of sarcoidosis, thepresence of noncaseating epithelioid-cell granulomas in the lung hilum or mediastinum is usually caused bysarcoid reactions

A Case of Inflammatory Lung Disease and Retroperitoneal Fibrosis Attributed to Systemic IgG4-related Disease

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

Clinical Characteristics of Acute Exacerbations of Idiopathic Pulmonary Fibrosis and Involvement of Viral, Mycoplasma pneumoniae, and Chlamydophila pneumoniae Infections

Background and Objective:To clarify the clinical characteristics of acute exacerbation of idiopathic pulmonaryfibrosis (IPF) and the involvement of infections with pathogenic microorganisms and viruses inacute exacerbation.Methods:During the 12 years from 2000 through 2011, we studied 50 patients who were admitted andreceived treatment for acute exacerbation of IPF in our department. Demographic characteristics, imagingfindings, laboratory findings, changes in antibody titers against bacteria, Mycoplasma pneumoniae, Chlamydophilapneumoniae, and known viruses, and outcomes were studied.Results:Among the 50 patients with acute exacerbation of IPF( 41 men and 9 women) 29 patients died(mortality rate, 58.0%). Computed tomography showed subpleural peripheral ground-glass opacities( GGO)in 5 patients, multiple patchy GGO in 19, and diffuse GGO in 26. Only the PaO2/FiO2 ratio was significantlylower in the non-survivors compared with survivors. Three patients had high titers of IgM antibodiesagainst C. pneumoniae, but acute infection was ruled out by the changes in IgA and IgG antibodies in pairedserum samples. Antibody titers against known viruses significantly increased in 2 patients( respiratory syncytialvirus in 1 and adenovirus 11 in 1). In acute-phase serum samples, 7 patients had increased antibodytiters against parainfluenza virus 3, resulted in no significant change in paired serum samples.Conclusions:Our results suggest that known pathogens do not play a role in acute exacerbation of IPF.The outcomes of IPF remain poor, and the elucidation of the causes and pathological features of acute exacerbationof IPF, including the identification of unknown pathogens, is awaited

A Case of Pulmonary Benign Metastasizing Leiomyoma Occurring after Uterine Myomectomy

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\u27s syndromeCT:computed tomographyH&E:hematoxylin and eosinVATS:video associated thoracoscopic surgeryCA:carbohydrate antigenIg:immunoguloblina SMA:a smooth muscle acti

Prostaglandin D_2 Augments Low-dose Antigen-induced Th2 Type Airway Inflammation in Mice

Prostaglandin D_2 (PGD_2), a mast cell-derived lipid mediator is detected in lage amounts in airways of asthmatics, but its role of largely unkown. To clarify the role of PGD_2 in Th2-type airway inflammation which characterizes asthma, we studied the effects of aerosolized PGD_2 on the inflammatory response to a low-dose antien challenge in airways of mice. Mice sensitized with ovalbumin (OVA) were challenged with a conventional-dose (1%) or a low dose (0.1%) aerosolized OVA. Mice received low - dose OVA challenge were pretreated with aerosolized PGD_2 (10^M) (PGD_2 plus low-dose OVA mice) or saline (low-dose OVA alone mice) 24 hrs before the OVA challenge. Some mice were pretreated with PGD_2 but challenged with saline (PGD_2 alone mice). Airway inflammation was evaluated by the numbers of eosinophils, lymphocytes and macrophages in bronchoalveolar lavage fluid. The degree of airway inflammation in the PGD_2 alone mice and the low-dose OVA alone mice were only marginal. However, the PGD_2 plus low-dose OVA mice displayed a similar degree of airway inflammation with mice received conventional-dose OVA challenge. Levels of interleukin (IL)-4 and IL-5 were significantly increased in the PGD_2 plus low-dose OVA mice than the low-dose OVA alone mice. PGD_2 (10^-10^ M) did not affect the Th2-type cytokine production by OVA specific T cells in response to OVA stimulation in vitro. Immunohistochemical analysis of lung tissue revealed that airway epithelium of the PGD_2 plus low-dose OVA alone mice were strongly stained with monoclonal antibody against macrophage-derived chemokine (MDC), a Th2 cell-specific chemokine. These results suggest that PGD_2 augments Th2 cell -type airway inflammation via epithelial experssion of MDC

Nonspecific Interstitial Pneumonia( NSIP) ニオケル ステロイド チリョウ ハンノウセイ キテイ インシ ノ ケントウ

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

ドッキョウ イカ ダイガク ビョウイン コキュウキ・アレルギー ナイカ ニオケル HIVカンセン カンジャ ノ カイセキ : トクニ ニューモシスチス ハイエン ノ ガッペイ レイ ニ ツイテ

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

ケッカクセイ キョウマクエン ノ シンダン ニオケル キョクショ マスイカ キョウコウキョウ ノ ユウヨウセイ ニ カンスル ケントウ

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

バイヨウ キドウ ジョウヒ サイボウ オヨビ ヘイカツキン サイボウ ニオケル キドウ リモデリング カンレン サイトカイン イデンシ ハツゲン ニ オヨボス シンケイ ペプチド ノ エイキョウ

気管支喘息の基本的病態は慢性の気道炎症として認識され,その機序が徐々に解明されてきている.特に重症・難治化には気道リモデリングがその要因として注目されている.今回,我々は神経原性炎症に深く関与している神経ペプチド(サブスタンスP,ニューロキニンA)が気道リモデリング,特に線維化サイトカインTGF-βのシグナル伝達機構に関与するTIEG, smad 7遺伝子発現に与える影響について検討した.これら神経ペプチドは線維化サイトカインTGF-βの発現を誘導し,さらにTGF-βの抑制型シグナル伝達分子smad 7の遺伝子発現を低下させた.これらの結果より神経ペプチドはTGF-βのシグナル伝達分子smad 7発現を抑制することによりリモデリング形成に関与している可能性が示唆された.持続するTh2型気道炎症はTGF-β産生増加へ傾きTIEG発現を誘導し,その結果smad 7の発現を抑制する事が知られている.我々は,気道平滑筋におけるサブスタンスP刺激によりTIEG遺伝子発現が誘導される事を見出した.また, TGF-β前処置後サブスタンスPで刺激することによりその効果は増強される事も確認した.これらの結果より,アレルギー性炎症により惹起された神経原性炎症はTIEG発現を誘導し,結果としてsmad 7発現が抑制され気道の線維化・リモデリング形成を促進している可能性が示唆された.Airway remodeling is a typical issue of asthma. Transforming growth factor (TGF)-β plays an important role for the regulation of airway inflammation and remodeling in asthma. The expression of TGF-β in the asthmatic airways was predominantly detected in eosinophils and fibroblasts and it was significantly correlated with the severity of the disease, basement membrane thickness, and submucosal fibroblast number, thus suggesting that TGF-β is involved in airway remodeling in adult asthma. TGF-β-inducible early gene (TIEG) is a Kruppel-like transcription factor that is rapidly induced upon TGF-β treatment TIEG promotes TGF-β/smad signaling by down-regulating negative feedback through the inhibitory smad 7. Among numerous peptide mediators such as tachykinin, calcitonin gene-related peptide, substance P or neurokinin A is one of the most abundant molecules found in the respiratory tract. Neurogenic inflammation might contribute to selective upregulation of TIEG through unknown mechanisms. We therefore examine whether neuropeptides modulate TGF-β and TIEG expression. In this study, we found that TIEG was significantly increased in the cultured smooth muscle cells stimulating with substance P. Furthermore, we found the synergistic effect on TIEG expression in cultured smooth muscle cells stimulating with substance P and pretreatment of TGF-β. These results suggest that increased TIEG expression in airway epithelial and smooth muscle cells might result in increased substance P, TGF-β activity and contribute to the development of airway inflammation seen in chronic asthma