Search

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.

Summary Background The pathogenesis of aspirin-induced asthma (AIA) is presumed to involve the aspirin/non-steroidal anti-inflammatory drug (NSAID)-induced abnormal metabolism of arachidonic acid, resulting in an increase in 5-lipoxygenase (5-LO) metabolites, particularly leukotriene C4 (LTC4). However, the role of LTC4 in the development of AIA has yet to be conclusively demonstrated. Objective The aim of this study was to evaluate the contribution of the lipid product LTC4 secreted by the 5-LO pathway to the pathogenesis of AIA. Methods To evaluate antigen-induced airway inflammation, the concentrations of T-helper type 2 cytokine in bronchoalveolar lavage fluid (BALF) obtained from LTC4 synthase-transgenic (Tg) and wild-type (WT) mice after challenge with ovalbumin were measured. Subsequently, the ex vivo and in vivo effects of the NSAID sulpyrine were investigated in these Tg and WT mice by measuring the secretion of LTC4 from sulpyrine-treated BAL cells and the levels of LTC4 in BALF following challenge with sulpyrine. Finally, the sulpyrine-induced airway response by the administration of pranlukast, an antagonist of the cysteinyl (cs)-LT1 receptor, was analysed. Results The concentrations of IL-4, -5, and -13 in BALF from Tg mice were significantly higher than those in WT mice. In addition, sulpyrine augmented the secretion of LTC4 in BALF and by BAL cells in Tg mice, but not in WT mice. Additionally, the increased airway resistance induced by sulpyrine could be reduced by treatment with pranlukast. Furthermore, the secretion of LTC4 from mast cells, eosinophils, and macrophages was increased in the allergen-stimulated LTC4 synthase gene Tg mice, even in the absence of sulpyrine, as well as in BAL cells after sulpyrine. Conclusion and clinical relevance The over-expression of the LTC4 synthase in a mouse asthma model also replicates the key features of AIA. And our study supports that cys-LTs play a major role in the pathogenesis of AIA in patients with chronic asthma. Cite this as: H. Hirata, M. Arima, Y. Fukushima, K. Honda, K. Sugiyama, T. Tokuhisa and T. Fukuda, Clinical & Experimental Allergy, 2011 (41) 1133–1142.

To identify problems in early diagnosis of tuberculosis and to design countermeasures against the disease, we examined the status of active tuberculosis among patients admitted to a university hospital that did not have an isolation ward for tuberculosis. Between 2005 and 2007, we analyzed demographic characteristics, disease type, chest radiologic findings, and the process leading to diagnosis. Active tuberculosis was diagnosed after admission in 55 patients (34 males and 21 females): pulmonary tuberculosis, 26; tuberculous pleuritis, 13; tuberculous meningitis, 6; miliary tuberculosis, 4; tuberculous pericarditis, 3; lymph-node tuberculosis, 2; and tracheal and bronchial tuberculosis, 1. Although radiographic examinations provided abundant information, chest radiography showed normal findings in 7 patients (12.7%). Computed tomographic scanning was useful for detailed evaluation of abnormalities. Twenty patients (36.4%) were given diagnoses at departments other than ours (Department of Pulmonary Medicine). Numbers of days between hospital admission and diagnosis of tuberculosis (50th percentile/80th percentile) were 8.0/37.8 for miliary tuberculosis, 8.0/8.0 for tracheal and bronchial tuberculosis, 7.5/17.8 for tuberculous pleuritis, 7.0/8.8 for tuberculous pericarditis, 6.0/15.6 for pulmonary tuberculosis, 3.5/4.4 for lymph-node tuberculosis, and 1/1 for tuberculous meningitis. Early diagnosis of tuberculosis requires adherence to the following precautions. Tuberculosis should be suspected in any patient with respiratory symptoms. Sputum tests for acid-fast bacteria should be performed at least three times initially. If findings on chest X-ray films are equivocal, high-resolution computed tomography should be performed to confirm details of shadows and to detect minimal pulmonary shadows or cavitary lesions. Physicians from all specialties should be repeatedly informed about the risk of tuberculosis and should include tuberculosis in the differential diagnosis in patients suspected to have pulmonary diseases.

We report a rare case of sarcoidosis that developed during induction chemotherapy for primary lung cancer, mimicking progressive disease. A 63-year-old man had an abnormal shadow in the right upper lung, and a bronchoscopic examination revealed a squamous cell carcinoma. Swelling of a pretracheal lymph node was also noted. Thus, we gave induction chemotherapy consisting of paclitaxel (days 1, 8) + carboplatin (days 1, 8) for two cycles under clinical staging of T2N2M0. After induction chemotherapy, (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) showed positive accumulation of FDG in mediastinal and bilateral hilar lymph nodes that had been negative in a previous FDG-PET examination, which led us to suspect disease progression. Transbronchial lymph node biopsy results showed sarcoid granulomas in the specimens. Following complete resection of the lung cancer, sarcoid granulomas were revealed in both nonneoplastic lung tissue and lymph nodes, which resulted in a diagnosis of lung cancer accompanied with sarcoidosis.

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.

Objective To examine the relation between annual trends in the antimicrobial susceptibility of Pseudomonas aeruginosa and drug usage, we compared annual changes in the susceptibility rates of P. aeruginosa clinical isolates during a 4-year period and annual trends in the overall usage of antimicrobials during the same period. Methods We studied annual trends in MIC(90)/MIC(50), antimicrobial use density (AUD), and antimicrobial susceptibility rates based on clinical breakpoints for 150 strains of P. aeruginosa isolated from respiratory specimens at Dokkyo Medical University Hospital from 2005 through 2008. Results The MIC(90)/MIC(50) of antimicrobials effective against P. aeruginosa in years 2005, 2006, 2007, and 2008 were as follows: imipenem, 32/2, 32/1, 8/2, and 16/1 microg/mL; meropenem, 8/1, 8/1, 4/0.5, and 4/0.5 microg/mL; and biapenem, 16/1, 32/0.5, 4/0.5, and 8/0.5 microg/mL, indicating that susceptibility to carbapenems increased slightly. The MIC(90)/MIC(50) was 4/0.25, 2/0.125, 1/0.125, and 2/0.25 microg/mL for ciprofloxacin, 8/4, 8/4, 4/4, and 8/4 microg/mL for amikacin, 64/16, 64/16, 64/16, and 64/16 microg/mL for sulbactam/cefoperazone, 8/2, 16/2, 32/2, and 8/2 microg/mL for ceftazidime, indicating little change. The AUDs of fourth-generation cephalosporins increased from 2005 to 2008 (16.2, 18.4, 28.0, and 23.0), while the AUDs of carbapenems decreased (25.7, 23.7, 10.9, and 12.5). Conclusion The decrease in the AUDs of carbapenems was associated with increased susceptibility rates of P. aeruginosa to carbapenem derivatives. A continuous understanding of trends in the resistance of P. aeruginosa and various other pathogens is essential for designing countermeasures against nosocomial infections, including the proper and effective use of antimicrobials.

Background and objective: Leucocytes, especially lymphocytes and neutrophils, as well as alveolar macrophages, that infiltrate into the lung are involved in the development of pulmonary fibrosis. However, the role of T helper (Th)2-type inflammation, mediated by Th2 cells and eosinophils, in fibrosis remains unknown. Transgenic mice deficient in the transcriptional repressor, Bcl6, display an attenuation of Th2 cytokine production. We studied the effects of Th2-type pulmonary inflammation on bleomycin-induced pulmonary fibrosis using Bcl6 transgenic mice. Methods: Bleomycin was administered to ovalbumin (OVA)-sensitized Bcl6 transgenic and wild-type mice by intratracheal instillation during sequential OVA antigen challenge. Concentrations of transforming growth factor-β1 in the BAL fluid were measured 2 weeks after bleomycin administration. At the same time lung tissue was examined histopathologically, and homogenized to assess collagen levels and Th1/Th2 cytokine mRNA expression. Results: Although OVA-sensitized, bleomycin-treated Bcl6 transgenic mice had markedly lower numbers of eosinophils in both BAL and lung tissue compared with OVA-sensitized, bleomycin-treated wild-type mice, the development of pulmonary fibrosis in response to bleomycin was similar in Bcl6 transgenic mice and wild-type mice. Conclusion: These results suggest that Th2-dominant inflammation in the lung is not essential for the development of bleomycin-induced pulmonary fibrosis.

Background Increased prevalence of chronic interstitial pneumonia (CIP) is reported in dust-exposed subjects. We investigated the prevalence of CIP in silicosis and mixed-dust pneumoconiosis and sought morphologic differences of CIP between the pneumoconiosis and idiopathic pulmonary fibrosis (IPF). Methods We reviewed CT scans of 243 silicosis and mixed-dust pneumoconiosis patients to identify any cases of parenchymal lung lesions showing a CIP pattern, and compared the CT findings with those of 62 patients with IPF. Two observers independently scored CT images and classified the CT pattern as typical or not typical for IPF. Differences were sought between the groups using a nonparametric test, Fisher exact test, and a logistic regression analysis. A radiopathologic correlation was performed in 11 pneumoconiosis patients. Results Twenty-eight patients (11.5%) showed CIP on CT. Seven patients (25%) showed a pattern not typical of IPF, while the remaining patients showed a pattern typical of IPF, 11 of which were confirmed pathologically. The extent of fibrosis did not differ between the groups; however, patients with pneumoconiosis showed less traction bronchiectasis (odds ratio [OR], 0.19; 95% confidence interval [CI], 0.08 to 0.48; p Conclusions Prevalence of CIP in pneumoconiosis was approximately 12% on CT. One fourth of patients showed an atypical IPF pattern, and the others showed a typical IPF pattern.

Background: Fatal asthma remains a serious problem, and patient self-management of asthma is important to prevent exacerbation. Aims: To reduce the asthma mortality rate, we analyzed the characteristics of patients who visited an emergency care unit with exacerbation of asthma. Methods: Subjects were 336 patients with exacerbation of asthma (148 men, 188 women; 48.3 years) who visited the emergency room at university hospitals in two prefectures in Japan. When categorized by severity based on treatment, 42.0% of patients were intermittent, 13.1% were mild, 16.1% were moderate, 28.2% were severe, and 0.6% were unknown. When categorized by primary care physician, 61.0% of patients had a primary care physician at a university hospital, 13.4% had one at another hospital, and 25.6% had no primary care physician. When categorized by recovery from exacerbation, control was achieved within 1 day in 63.1% of cases, after more than 1 day in 29.8% of cases, and required admission in 7.1% of cases. Results: The number of admissions was highest for cases with intermittent treatment (intermittent, 54.2%; mild, 20.8%; moderate, 8.3%; and severe, 16.7%;p 2 ) was lower in the admission group (92.4%) than in the non-admission group (95.2%, p Conclusion: Patients with intermittent treatment who visit an emergency unit with exacerbation of asthma may be needed regular treatment for asthma. When initial SpO 2 is less than 92%, we should consider hospitalization for treatment of asthma.

Study objectives: We described the features seen on serial high-resolution CT scans of nonspecific interstitial pneumonia (NSIP) that was associated with polymyositis (PM) and dermatomyositis (DM), and we correlated the changes in the CT scan findings with those of pulmonary function test results. Design, setting and patients: Serial CT scans of 14 patients with histologically proven NSIP and PM/DM from two university hospitals were evaluated retrospectively (follow-up period, 3 to 61 months; mean follow-up period, 27.6 months). Using initial and follow-up CT scan findings, the extent of each type of opacity and the total area of increased opacity were calculated and correlated with the results of pulmonary function tests. Measurements and results: The predominant findings on the initial CT scans were of reticular and/or ground-glass opacities with or without consolidation. Reticular and ground-glass opacities predominated in the lower zone of each lung, and consolidation predominated at the lung periphery. Thirteen patients showed significant improvement of the total area of increased opacity (p r = −0.650; p = 0.031). Ground-glass and reticular opacities also were improved significantly in 11 and 13 patients, respectively. The decrease in the extent of ground-glass opacity correlated inversely with the changes in FVC ( r = −0.758; p = 0.0119) and diffusion capacity for carbon monoxide ( r = −0.669; p = 0.0448). In one patient, ground-glass opacity progressed, and death occurred after 3 months. Traction bronchiectasis was seen in 12 patients, and it improved in four patients after treatment. Honeycomb lung was not noted in any patient during follow-up. Conclusions: With treatment, serial CT scans of PM/DM patients with NSIP showed significant improvement in the abnormal opacities, and radiographic progression of lung fibrosis was limited. The CT scan features and clinical course of NSIP in PM/DM patients were relatively uniform, and this constitutes a subset of NSIP.

Background: Ves v 5 and Pol d 5, which constitute antigen 5, are recognized as the major, most potent allergens of family Vespidae. Several studies have reported the diagnostic sensitivity of the novel recombinant (r)Ves v 5 and rPol d 5 allergens in routine clinical laboratory settings by analyzing a group of Vespula and Polistes venom-allergic patients. In this study, we analyzed the sensitivity to venom specific (s)IgE by spiking with rVes v 5 and rPol d 5 in Japanese patients suspected of Hymenoptera venom allergy. Methods: Subjects were 41 patients who had experienced systemic reactions to hornet and/or paper wasp stings. Levels of serum sIgE against hornet and paper wasp venom by spiking with rVes v 5 and rPold d 5, respectively, as improvement testing, compared with hornet and paper wasp venom, as conventional testing, were measured by ImmunoCAP. Results: Of the 41 patients, 33 (80.5%) were positive (≥0.35 UA/ml) for hornet and/or paper wasp venom in conventional sIgE testing. sIgE levels correlated significantly (P

Surfactant proteins (SP)-A and SP-D are collagen-like glycoproteins belonging to the "collectin" class of C-type lectins, which are primarily synthesized in type II cells. Recent studies reported the possibility of local production of SP-A and SP-D in the airways, but the amounts of surfactant proteins in patients with bronchial asthma have not been studied. The composition of surfactant proteins in mild, stable asthmatics in the first lavage as bronchial lavage (BL) and the second and third lavages consecutively as alveolar lavages (AL) were therefore, analysed separately. The co-relationships in the BL between the amounts of surfactant proteins and those of fucose, which is one of the markers of submucosal secretion were also analysed. Increased amounts of SP-A in BL and AL of in asthmatics were found as compared with those in controls. A high concentration of SP-D in the AL asthma patients was also found. The levels of SP-A correlated with those of fucose in patients with bronchial asthma (r=0.849, p

Familial Mediterranean fever (FMF) is characterized by repeated episodes of fever, peritonitis, pleuritis, and synovitis. We describe here 3 Japanese patients (a mother and 2 children) in whom FMF was diagnosed on analysis of MEFV. A 40-year-old woman presented with fever and abdominal pain. The patient had had these symptoms on and off since childhood and consulted many hospitals. A 38-year-old man had abdominal pain and fever since the age of 30 years. A 59-year-old woman had had episodes of fever, abdominal pain, and chest pain for more than 20 years. MEFV gene analysis showed compound heterozygosity for L110P, E148Q, and M694I in all three patients. In Japanese patients with FMF, this mode of autosomal true dominant inheritance has not yet been reported. FMF is difficult to diagnose unless it is included in the differential diagnosis by physicians. We hope that our valuable experience will promote increased awareness and understanding of FMF.

We encountered two Japanese siblings who had Hermansky-Pudlak syndrome (HPS) and major mental disorders (schizophrenia and major depression) as well. As it is known that HPS is caused by a local mutation in one of the human genes, named HPS1 to HPS8 and PLDN (HPS9), encoding subunit proteins involved in endosomal trafficking pathways, here, we report the mutation causing the siblings disease and a case-control association study of schizophrenia using polymorphisms of a gene to be screened in the mutation analysis.We analyzed three HPS-causing genes, HPS1, HPS4, and HPS7, to identify a genetic mutation involved in the siblings. A case-control association study of nine tagging single-nucleotide polymorphisms of the entire genetic region of the HPS4 gene resulting from the screening in the siblings was carried out for schizophrenic patients (n=422) and controls (n=578).The two patients with HPS were homozygous for nonsense mutation (T/T) for the c.541CT (rs119471022) in the HPS4 gene, which is mapped to human chromosome 22q12.1. The same nonsense mutation existed in the heterozygous state (C/T) in their mother and in two other siblings. The genotypic distribution of rs9608491 (C/T) in intron 4 showed a trend toward an association with schizophrenia as indicated by a corrected P-value of 0.053 controlling for multiple testing. Haplotype analyses showed that two of two-locus haplotypes, and all of three-locus, four-locus, and five-locus haplotypes, as they share rs9608491, yielded significant evidence for association with schizophrenia as shown by the following omnibus P-values. When rs4822724, rs61276843, rs9608491, rs713998, and rs2014410, five haplotype tagging single-nucleotide polymorphisms, are assigned serial numerals (1, 2, 3, 4, and 5), the omnibus P-values for the resulting haplotypes were P=0.0039 for 2-3, P=0.0142 for 3-4, P=0.0083 for 1-2-3, P=0.0187 for 2-3-4, P=0.0191 for 3-4-5, P=0.0270 for 1-2-3-4, P=0.0246 for 2-3-4-5, and 0.0261 for 1-2-3-4-5.These results suggest that the HPS4 gene confers a susceptibility to schizophrenia.

Although anti-IgE antibody (Ab) therapy was recently shown to be effective in patients with bronchial asthma, no study has reported the effect of IgE therapy in the prevention of wasp venom anaphylaxis. In this study, we used a mouse model of wasp venom allergy to investigate the effect of anti-IgE Ab on wasp venom anaphylaxis.We developed a mouse model of wasp venom allergy by intraperitoneally (i.p.) injecting wasp venom into BALB/c mice twice on experimental day (day) 0 and 7. On day 20, a group of mice received an i.p. injection of mouse anti-IgE Ab as a pretreatment, and another group received rat anti-IgG1 Ab. On day 21, the animals were challenged by i.p. injection of wasp venom, and 30 min later, body temperature was measured and serum levels of leukotriene (LT) B4 and LTC4 were determined using enzyme immunoassay.The body temperature of mice treated with anti-IgE Ab and controls before and after wasp venom challenge was 37.8±0.2 vs 37.7± 0.3°C before challenge and 37.8±0.2 vs 37.1± 0.3°C after challenge, respectively, showing that anti-IgE Ab treatment significantly prevented body temperature from falling (p0.05). Furthermore, anti-IgE Ab treatment reduced total serum IgE levels in the treated mice (42.2±15.9 pg/ml), compared with controls (105.9±23.1 pg/ml, p0.05), and inhibited the secretion of LTC4 in the treated mice (32.0±18.8 pg/ml), but not in the controls (162.4±12.4 pg/ml, p0.05), following challenge with wasp venom.The results of the present study indicate that anti-IgE Ab treatment is an effective preventive measure against wasp venom-induced anaphylaxis.

Recent in vitro studies have suggested that interleukin-4 (IL-4) may be involved in the preferential migration of eosinophils into the airways in allergic asthma through its capacity to selectively increase vascular cell adhesion molecule-1 (VCAM-1) expression on vessels. To test this hypothesis, we studied the expression of VCAM-1, E-selectin, and intercellular adhesion molecule-1 (ICAM-1) on vascular endothelium in bronchial mucosal biopsies from 20 allergic asthmatics using an immunohistochemistry technique and related the observations to IL-4 levels in bronchoalveolar lavage (BAL) fluid simultaneously obtained and to eosinophil infiltration in the bronchial mucosa. IL-4 was detectable in BAL fluid from nine subjects (range, 15.1 to 110 pg/ml in 20-fold concentrated BAL fluid) (IL-4-positive asthmatics) but unmeasurable in the remaining 11 subjects (IL-4-negative asthmatics). The IL-4-positive asthmatics showed a significantly increased expression of VCAM-1 but not E-selectin and ICAM-1 on vessels as compared with both IL-4-negative asthmatics (P < 0.001) and diseased control subjects (P < 0.001). In asthmatics, VCAM-1 expression was positively correlated with BAL IL-4 levels (rs = 0.89; P < 0.0001). Moreover, there was a significant correlation between the endothelial expression of VCAM-1 and the number of eosinophils, but not neutrophils, in the bronchial submucosa (r2 = 0.76; P < 0.001). A significant correlation was also found between BAL IL-4 levels and the number of eosinophils. These results suggest that IL-4 is a VCAM-1-selective activator also in human airways and the VCAM-1-dependent pathways play a role in selective migration of eosinophils into the airways in allergic asthma, and support the hypothesis described above.

When stimulated with mite antigens, peripheral blood mononuclear cells obtained from patients with mite allergy release eosinophil chemotactic factor, a type of protein. Complementary DNA libraries were formulated from both peripheral blood mononuclear cells stimulated with mite antigens and those not stimulated with mite antigens and underwent subtraction and differential screening. The authors obtained 13 genes for which expression had increased because of mite antigens. Of these, nine were mitochondrial genes; two, h-satellite DNA III; one, factor XIII; and one, ferritin heavy subunit. As a result of polymerase chain reaction on both cDNA libraries, IL-5 genes were amplified only from the cDNA library that had been stimulated with mite antigens. (J ALLERGY CLIN IMMUNOL 1995;96:1076-82.)

Background Asthma is characterized by a chronic inflammatory process involving high numbers of inflammatory cells and mediators which have multiple inflammatory effects on the airway. Interferon (IFN)-alpha, which is used widely for treating chronic hepatitis C, is reported to have an effect on patients with Churg-Strauss syndrome. Therefore, it may also be suitable for patients with severe asthma. Objective We studied the effect of IFN-alpha on airway eosinophilia in a guinea pig model of asthma and the expression of adhesion molecules on human eosinophils and vascular endothelial cells. Methods After antigen challenge, airway hyperresponsiveness and airway eosinophilia were measured in a guinea pig asthma model with or without airway IFN-alpha administration. Expression of adhesion molecules on eosinophils and cultured human umbilical vein endothelial cells (HUVECs) was also evaluated with or without IFN-alpha. Results IFN-alpha inhibited eosinophil recruitment into the tracheal wall and improved airway hyperresponsiveness in sensitized guinea pigs. IFN-alpha also significantly suppressed IL-1 beta-induced intercellular adhesion molecule-1 (ICAM-1) expression on HUVECs. However, IFN-alpha did not suppress platelet-activating factor-induced macrophage antigen-1 expression on human eosinophils. IFN-alpha significantly inhibited eosinophil adhesion to IL-1 beta-induced HUVECs and migration through IL-1 beta induced HUVECs. Conclusion The findings suggest that the modulation of ICAM-1 in lung with pre-existing inflammation following treatment with IFN-alpha may be a novel and selective treatment for control of chronic airway inflammation and hyperresponsiveness associated with asthma.

Synthesis of cysteinyl leukotrienes (cys-LT) is thought to cause inflammatory disorders such as bronchial asthma and allergic rhinitis. Recent reports have suggested that leukotriene C4 (LTC4 ) is an important regulator of pulmonary fibrosis. This study examined the effect of LTC4 in LTC4 synthase-overexpressed transgenic mice with bleomycin-induced pulmonary fibrosis. The function of lung-derived fibroblasts from transgenic mice was also investigated.Bleomycin was administrated to transgenic mice and wild-type (WT) mice by intratracheal instillation. Concentrations of interleukin (IL)-4 and -13, interferon-γ, and transforming growth factor (TGF)-β1 in bronchoalveolar lavage fluid were measured 1, 3, 7 and 14 days after the administration of bleomycin. Lung tissue was examined histopathologically on day 14. In addition, lung-derived fibroblasts from transgenic and WT mice were cultured for 7 days. Expression of TGF-β1 mRNA was measured by real-time polymerase chain reaction.Both the pathological scores for pulmonary fibrosis (3.8 ± 0.4 vs 2.0 ± 0.1, P 0.05) and the levels of IL-4 (12.1 ± 2.3 vs7.8 pg/mL, P 0.05), IL-13 (26.5 ± 5.2 vs7.8 pg/mL, P 0.01) and TGF-β1 (211.1 ± 30.2 vs 21.3 ± 1.2 pg/mL, P 0.01) on day 14 were significantly greater in transgenic than in WT mice. Furthermore, the reduction of LTC4 by pranlukast hydrate, a cys-LT1 receptor antagonist, in fibroblasts from transgenic significantly (P 0.05) decreased the expression of TGF-β1 mRNA (by ∼50%) compared with those from WT mice.Overexpression of LTC4 , amplifies bleomycin-induced pulmonary fibrosis in mice. Our findings suggest a role for LTC4 in lung fibrosis.

Recently direct evidence for the role of interleukin-5 (IL-5) in eosinophilic inflammation in the airways of persons with asthma has been provided by an in situ hybridization study that used radioisotope-labeled IL-5 complementary RNA probes. Radioisotope-labeled probes, although sensitive, require autoradiographic detection, which is time-consuming. In the most recent study we attempted to detect IL-5 messenger RNA in the bronchial biopsy specimens from patients with asthma using nonradioactive in situ hybridization, which gives rapid results. Bronchial biopsy specimens were obtained from eight patients with asthma and seven diseased control subjects. IL-5 complementary DNA probes were labeled with digoxigenin-deoxyuridine triphosphate and hybridized to permeabilized sections. Hybridization signals were visualized by an immunohistochemistry technique. Positive hybridization signals were observed in six of the eight biopsy specimens from patients with asthma. Pretreatment with ribonuclease or hybridization with an unrelated probe produced negative results. Immunohistochemical staining of serial sections with a monoclonal antibody to IL-5 revealed that a few cells within the mucosa positively stained, suggesting active synthesis of IL-5. Biopsy results from the seven diseased control subjects did not show any hybridization signal. These results confirm and extend previous observations of IL-5 messenger RNA expression in the airways of patients with asthma, and suggest that digoxigenin-labeled IL-5 complementary DNA probes would be a powerful research tool. (J ALLERGY CLIN IMMUNOL 1994;94:584-93.)

We report a rare case of anaphylaxis due to caffeine intake. A 27-year-old woman suffered her first episode of anaphylaxis and a positive skin prick test suggested that the anaphylaxis was due to an IgE-mediated hypersensitivity reaction to caffeine. She was diagnosed with caffeine allergy and has not had an allergic reaction after avoiding foods and drinks containing caffeine. Although caffeine is known to have antiallergic effects, this case shows that caffeine can be an allergen and cause anaphylaxis.

Eosinophilic lung disease shows diverse pathological characteristics and chest imaging findings. It can be caused by various factors, including parasitic and fungal infections, allergies, drugs, radiation, hazardous materials, smoking, vasculitis, or be idiopathic. Among potential causes, allergic bronchopulmonary mycosis and allergic granulomatous vasculitis/Churg-Strauss syndrome are also associated with bronchial asthma. In 2001, chronic eosinophilic bronchiolitis was proposed as an atypical eosinophilic lung disease (Takayanagi et al., 2001). Subsequently, similar cases have been accompanied by asthma-like symptoms and dyspnea, suggesting an association with bronchial asthma (Nakagome et al., 2003; Nagata et al., 2004; Tsuburai et al., 2006; Morimoto et al., 2006). We describe a case of bronchial asthma that showed diffuse centrilobular granular shadows and airway thickening on computed tomography (CT) of the chest and was diagnosed as eosinophilic bronchitis/bronchiolitis on histopathological examination.

Background Exacerbation of asthma has a negative impact on quality of life and increases the risk of fatal asthma. One of the known risk factors for patients with a history of near-fatal asthma is reduced sensitivity to dyspnea. Objective We aimed to identify patients with such risk before they experienced severe exacerbation of asthma. Methods We analyzed asthma symptoms and peak expiratory flow rate (PEFR) values of 53 patients recorded daily in a diary over a mean period of 274 days. Patients matched their symptoms to one of eight categories ranging in severity from 'absent' to 'severe attack'. We then analyzed the relationship between PEFR and asthma symptoms by dividing the PEFR value by the values of clinical parameters, including asthma symptom level. Results Average PEFR was 75.2% (50.5-100%) in the 'absent' symptom category, 64.5% (36.6-92.6%) in 'wheeze', 57.3% (25.0-94.7%) in 'mild attack' and 43.6% (20.4-83.1%) in 'moderate attack', with the personal best reading taken as 100%. Thus, differences in PEFR in patients in the same symptom category varied widely. PEFR in wheeze, mild attack and moderate attack did not correlate significantly with duration of asthma, forced expiratory volume in one second or proportion of personal best to standard predicted PEFR values. These PEFRs showed no significant difference in groups divided by type of regular treatment, but showed a significant negative correlation with the coefficient of variation (CV) of PEFR when asthma symptoms were absent. CV for absent symptoms should be between +4.0 and -4.0% when using regression analysis to measure PEFR if the decreased PEFR is in agreement with guidelines. Conclusion To determine which patients have reduced sensitivity to dyspnea, CV of PEFR should be considered when asthma symptoms are reported as absent. When patients present with more than 8% fluctuation in PEFR, we should intervene in their treatment, even when they claim to be stable.

Concurrent combination therapy with chemotherapy(cisplatin(CDDP)and vinorelbine(VNR))and thoracic radiotherapy was administered to patients with unresectable locally advanced non-small cell lung cancer. The subjects were 19 patients with stage III non-small cell lung cancer, PS 0-1. They were able to undergo thoracic radiotherapy, had not received previous therapy, and had maintained main organ functions. CDDP(40mg/m / 2)and VNR(20mg/m2)were administered on days 1, 8, 22, and 29, and thoracic radiotherapy was performed every day except for those on which chemotherapy was conducted, 5 days a week at 2 Gy/day(total: 60 Gy). Four subjects were stage III A, 15 were stage III B, and their ages ranged from 42 to 75 years(median age: 65 years). The subjects were 18 males and 1 female, and concerning their histological types, 12, 5, and 2 were diagnosed squamous cell, adeno- and adenosquamous carcinoma, respectively. Regarding the therapeutic efficacy, 0, 14, and 5 subjects were clinically CR, cPR, and cSD, respectively, and their response rate was 73. 7%. The median survival time was 27. 2 months, and the one-year survival rate was 71. 2%. Concerning≥grade 3 adverse effects, 14 and 12 cases had leukocytopenia and neutropenia, respectively. However, no esophagitis was observed, and only one case experienced≥grade 3 nausea and vomiting. Radiation pneumonitis(≥grade 3)was observed in one case, but there was no severe liver or renal dysfunction, and no treatment-related death. It was suggested that this treatment reduces the occurrence of renal toxicity and digestive symptoms, and that a marked antitumor effect can be expected from its administration.

Considerable progress has been made in the management of asthma with the increasing use of inhaled corticosteroids. However, asthma exacerbation remains a problem. To analyze the characteristics of patients with exacerbation of asthma who visited our hospital in order to better understand the risk factors for fatal asthma.We studied 100 patients who presented at Dokkyo Medical University Hospital (DMUH) with asthma exacerbation.Entry sheets were completed by physicians and questionnaires by patients.Before the exacerbation, the severity was assessed as Step 1 in 46% of patients, Step 2 in 15%, Step 3 in 11%, and Step 4 in 18%. With regard to primary care physicians, 45% were treated at DMUH and 36% had no primary care physicians. Among the DMUH group, the largest proportion was aged 60-69 years and was in Step 4 category. According to asthma control test (ACT) scores, disease was poorly controlled in 83%. Patients with no primary care physician were most often aged 20-39 years (p0.01), and severity was assessed as Step 1 in 86% (p0.01). However, 44% were poorly controlled according to ACT (p0.05).Patients could be classified into two groups: older patients with severe intractable asthma, treated by a specialist and younger patients considered to have mild asthma, half of whom had poorly controlled asthma and no primary care physician. Systems are needed that allow the emergency physicians to evaluate the need for regular treatment in patients with exacerbation because such patients often visit the hospital at night or on a non-working day.

We describe a patient with common acute lymphoblastic leukemia associated with blood and cerebrospinal fluid (CSF) eosinophilia. Serum obtained at onset and conditioned medium prepared from T cells obtained at remission stimulated with interleukin-2 contained eosinophil colony stimulating activity (Eo-CSA), which was confirmed to be predominantly GM-CSF. Leukemic cell conditioned medium and serum obtained at remission contained no Eo-CSA. The CSF contained increased eosinophil chemotactic activity, however, this factor was not identified.

The pathogenesis of aspirin-induced asthma (AIA) is presumed to involve the aspirin /non-steroidal anti-inflammatory drug (NSAID)-induced abnormal metabolism of arachidonic acid, resulting in an increase in 5-lopoxygenase (5-LO) metabolites, particularly leukotriene C4 (LTC4)&x3000;which is a highly potent bronchial constrictor. However, the role of LTC4 in the development of AIA has yet to be conclusively demonstrated. To elucidate the effect of LTC4 on the development of AIA, we generated LTC4 synthase (Ltc4s) gene transgenic (LTC4S-Tg) mice. In contrast to wild-type (WT) mice, LTC4S-Tg mice displayed NSAID-induced airway obstruction that was associated with increases of LTC4 and Th2 cytokines in lung tissue. This is the first study to demonstrate clearly that a balance shift towards the 5-LO pathway contributes to the pathogenesis of AIA in the presence of elevated levels of LTC4S.

A 73-year-old woman who had been followed in our department of gynecology because of ovarian cancer since 2002, was admitted with liver dysfunction and complaining of back pain and light precordial chest pain. The chest radiograph on admission revealed a tumor in her left upper lung field, and chest CT revealed a tumor adjacent to the chest wall and mediastinum. FDG-positron emission tomography (PET) showed abnormal uptake in the tumor and Th6/7, and the subaortic lymph nodes. On the basis of these findings, primary lung cancer with bone metastasis was suspected. She had a high grade fever on admission, and blood cultures were positive for group G streptococcus. The treatment with intravenous penicillin was started. Percutaneous biopsy of the tumor in her left chest showed an abscess wall in the chest wall, but no evidence of malignancy. Transbronchial lung biopsy and CT-guided biopsy also showed no malignant cells. Since the tumor decreased in size and back pain improved gradually by only antibiotic treatment, a diagnosis of sepsis of group G streptococcus, chest wall abscess, and vertebral osteomyelitis was made. She was treated with intravenous penicillin for 4 weeks and oral amoxicillin for another 4 weeks. After 60 days of antibiotic treatment, the tumor vanished.

We described the features seen on serial high-resolution CT scans of nonspecific interstitial pneumonia (NSIP) that was associated with polymyositis (PM) and dermatomyositis (DM), and we correlated the changes in the CT scan findings with those of pulmonary function test results.Serial CT scans of 14 patients with histologically proven NSIP and PM/DM from two university hospitals were evaluated retrospectively (follow-up period, 3 to 61 months; mean follow-up period, 27.6 months). Using initial and follow-up CT scan findings, the extent of each type of opacity and the total area of increased opacity were calculated and correlated with the results of pulmonary function tests.The predominant findings on the initial CT scans were of reticular and/or ground-glass opacities with or without consolidation. Reticular and ground-glass opacities predominated in the lower zone of each lung, and consolidation predominated at the lung periphery. Thirteen patients showed significant improvement of the total area of increased opacity (p0.05), and this decrease in extent inversely correlated with changes in FVC (r = -0.650; p = 0.031). Ground-glass and reticular opacities also were improved significantly in 11 and 13 patients, respectively. The decrease in the extent of ground-glass opacity correlated inversely with the changes in FVC (r = -0.758; p = 0.0119) and diffusion capacity for carbon monoxide (r = -0.669; p = 0.0448). In one patient, ground-glass opacity progressed, and death occurred after 3 months. Traction bronchiectasis was seen in 12 patients, and it improved in four patients after treatment. Honeycomb lung was not noted in any patient during follow-up.With treatment, serial CT scans of PM/DM patients with NSIP showed significant improvement in the abnormal opacities, and radiographic progression of lung fibrosis was limited. The CT scan features and clinical course of NSIP in PM/DM patients were relatively uniform, and this constitutes a subset of NSIP.