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Item does not contain fulltext A case of disseminated nontuberculous mycobacteria(l) (NTM) infection in a patient with positive neutralizing anti-interferon-gamma (IFN-gamma) autoantibodies involving bone, bronchus, systemic lymph nodes, and skin is reported. The causative NTMs were two different strains: Mycobacterium gordonae, which rarely causes true disease, and Mycobacterium mantenii, which is extremely rare. Anti-mycobacterial treatment successfully ameliorated all disseminated lesions. Although the concentration of anti-IFN-gamma autoantibodies increased during the pre-treatment period, it gradually decreased after anti-mycobacterial treatment was started.

Numerous in vitro and in vivo studies in both animals and patients with asthma have shown that interleukin (IL)-9 is an important inflammatory mediator in asthma. To examine the effects of IL-9 antagonism on airway inflammation, ovalbumin-sensitized BALB/c mice were intravenously given anti-IL-9 antibody or an isotype-matched control antibody 30 minutes before challenge with aerosolized ovalbumin. Airway response to methacholine was measured, and samples of bronchoalveolar lavage fluid (BALF) were obtained 24 hours after the last antigen challenge. Lung tissue was harvested and examined histopathologically. After ovalbumin challenge, there were significant increases in airway hyperreactivity, the numbers of inflammatory cells in lung, and IL-4, IL-5, and IL-13 production in BALF. Treatment with anti-IL-9 antibody significantly prevented airway hyperreactivity in response to methacholine inhalation. Blockade of IL-9 reduced the numbers of eosinophils (0.3 +/- 0.1 x 10(5) and 23.6 +/- 0.5 x 10(5)/ml, anti-IL-9 antibody/control immunoglobulin G) and lymphocytes (0.2 +/- 0.2 x 10(5) and 0.8 +/- 0.1 x 10(5)/ml) in BALF. Anti-IL-9 antibody treatment also reduced the concentrations of IL-4 (from 70.6 +/- 4.6 to 30.8 +/- 5.2 pg/ml), IL-5 (from 106.4 +/- 12 to 54.4 +/- 6.6 pg/ml), and IL-13 (from 44.2 +/- 7.6 to 30.1 +/- 5.5 pg/ml) in BALF. Macrophage-derived cytokine expression in the airways was also decreased by IL-9 blockade. Taken together, our findings emphasize the importance of IL-9 in the pathogenesis of asthma and suggest that blockade of IL-9 may be a new therapeutic strategy for bronchial asthma.

Sarcoidosis is a chronic granulomatous disease that can affect multiple organs. The lungs, eyes, and skin are known to be highly affected organs in sarcoidosis. There have been reports based on random muscle biopsy that 32-80% of systemic sarcoidosis comprises noncaseating granulomas; however, muscle involvement in sarcoidosis is generally asymptomatic and has an unknown frequency. We describe a case of acute to subacute sarcoid myositis of the skeletal and extraocular muscles. Typical ophthalmic involvement (manifested by infiltration of the ocular adnexa, intraocular inflammation, or infiltration of the retrobulbar visual pathways) and extraocular sarcoid myositis (as with the present case) is infrequently reported. It is important to keep in mind the rare yet perhaps underestimated entity of sarcoid myositis, and to utilize muscle biopsy and imaging tests for appropriate diagnosis and management of patients with sarcoidosis.

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

Objectives Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are particularly effective in non-small cell lung cancer (NSCLC) patients harboring active EGFR mutations. However, some studies have reported survival benefits in NSCLC patients with wild-type EGFR upon erlotinib treatment. This trial was conducted to evaluate the efficacy of erlotinib monotherapy and investigate the predictive values of several biomarkers. Patients and methods Patients with previously treated NSCLC but without EGFR gene mutations that had never or light smoked were eligible for this study. Gene status screening was performed using the PNA-LNA PCR clamp method. Erlotinib was administered until disease progression or unacceptable toxicities occurred. EGFR gene status was re-evaluated using the fragment method to detect exon 19 deletions and the Cycleave-PCR method to detect point mutations. Expression of hepatocyte growth factor (HGF), Met, and thymidylate synthase (TS) were evaluated using immunohistochemistry. Results Forty-seven patients were enrolled in the study between March 2010 and November 2011. Objective response rate (ORR) and disease control rate (DCR) were 15.2% and 41.3%. Re-evaluations for EGFR gene were performed in 32 tumor samples. EGFR gene mutations were found in eight samples (5:exon 19 deletion, 2:G719X, 1:L858R). Six patients had PR and two had SD among these eight patients. A total of 24 patients were confirmed as wild-type EGFR using different methods. ORR and DCR were 4.2% and 41.7%. The median progression free survival (PFS) and median survival times were 2.0 and 6.0 months, respectively. Patients with tumors expressing HGF showed shorter PFS but not MET or TS. Conclusions Re-examination of EGFR gene status using different detecting method or different sample should be considered to grasp a chance of erlotinib treatment after first line treatment. In confirmed EGFR wild NSCLC, negative HGF staining could be a biomarker for longer PFS by erlotonib treatment.

International audience; The thermal conductivities of molten alkali fluorides (LiF, NaF, and KF) and their mixtures (LiF-NaF, LiF-KF, and NaF-KF binaries and LiF-NaF-KF ternary) are predicted using molecular dynamics simulation with the Green-Kubo method. A polarizable ion model is used to describe the interionic interactions. All the systems except LiF-KF and LiF-NaF-KF mixtures follow a scaling law: it is proportionnal to mA-1/2(N/V)2/3, where mA is the arithmetic average of the ionic species masses in a given melt and N is the total number of ions included in the system volume V. In LiF-KF and LiF-NaF-KF mixtures a significant departure from the scaling law is observed. By examining separately the effects of the cation mass and size asymmetry in LiF-KF mixtures, we show that both of them account for half of the deviation. Finally, we observe that the temperature dependence of the thermal conductivity is very small in these molten fluorides.

The melanophores in the dermis on scales in the bitterling, Acheilognathus lanceolatus were studies to obtain information about the control mechanism of aggregation and dispersion using intact, membrane-permeabilized and cultured cells. The cultured melanophores showed supersensitivity, namely, they responded to norepinephrine with much higher sensitivity than intact cells. The cultured melanophores failed to respond to high KCl. Melatonin aggregated and adenosine dispersed melanosomes within a cell. Digitonin permeabilized cells showed aggregation with Ca ions and dispersion by cyclic adenosine 3',5'-monophosphate (cAMP) in the presence of ATP. Movement of melanosomes was observed under the high magnification of light microscope and the tracks of each pigment granule were followed. The granules moved fast and linearly during aggregation, whereas they showed to-and-fro movement during dispersion.

Reactive oxygen species (ROS) play an important role in the pathogenesis of pulmonary fibrosis. We previously demonstrated that N-acetylcysteine (NAC), an antioxidant, inhibited adhesion molecule expression and cytokine production in lung cells. When NAC is inhaled into the alveolar space, it is expected to directly interact with inflammatory cells and to elevate glutathione levels in the epithelial lining fluids. We therefore examined whether inhaled NAC inhibits lung fibrosis induced by bleomycin (BLM). Male ICR mice were given a single intravenous injection of BLM (150 mg/ kg). Thirty milliliters of NAC (70 mg/ml) or saline were inhaled twice a day for 28 d using an ultrasonic nebulizer. In the inflammatory phase (Day 7), NAC administration attenuated the cellular infiltration in both bronchoalveolar lavage fluid (BALF) and alveolar tissues. At Day 28, the fibrotic changes estimated by Aschroft's criteria and hydroxyproline content in the NAC inhalation group were significantly decreased compared with the BLM-only group (p < 0.05). CXC chemokines, macrophage inflammatory protein-2 (MIP-2), cytokine-induced neutrophil chemoattractant (KC), and CC chemokines, macrophage inflammatory protein-1alpha (MIP-1alpha), in BALF were mostly elevated on Day 7 in the BLM-only group; however, these elevations were significantly repressed by NAC inhalation (p < 0.05). Lipid hydroperoxide (LPO) was also quantified in BALF. LPO was markedly increased on Day 3 in the BLM-only group, and this increase was significantly decreased by NAC inhalation (p < 0.05). These results revealed that aerosolized NAC ameliorated acute pulmonary inflammation induced by BLM injection via the repression of chemokines and LPO production, resulting in the attenuation of subsequent lung fibrosis. These findings are limited to the BLM-induced lung fibrosis animal model. However, NAC inhalation will be expected to be a potential therapy for patients with other interstitial pneumonias because ROS are involved in the pathogenesis of lung injury in most interstitial pneumonia.

Although sarcoidosis and lung cancer are both frequently encountered conditions, their simultaneous occurrence in the same patient is unusual. In this report, we describe 4 cases of their concurrence and discuss the possible pathogenic mechanisms of their concurrent appearance. In particular, in 2 of the cases, both diseases had coexisted for a long period (more than 6 and 4 years, respectively), showing a surprisingly slow growth of cancers. Although the chest computed tomography showed hilar and mediastinal lymphadenopathy, the histopathological findings of the excised lymph nodes of both cases revealed no metastasis. The causal relationship between sarcoidosis and lung cancer remains uncertain, but cases such as these may be helpful in elucidating its precise nature.

New quinolone (NQ) antimicrobials have strong bactericidal effects and a broad spectrum of antimicrobial activities. In this study, we investigated the in vitro effects of grepafloxacin (GPFX), a newly developed fluoroquinolone, on neutrophil functions. Superoxide production by neutrophils was measured using the ferricytochrome reduction assay. Enhancement of Superoxide production was observed in the presence of more than 10μg/ml of GPFX when stimulated with formyl-methionyl-leucyl-phenylalanine (FMLP) and more than 3μg/ml when stimulated with phorbol myristate acetate (PMA) . Neutrophils pretreated with more than 30μg/ml of GPFX also showed enhancement of superoxide production in response to both of the two stimuli. On the other hand, GPFX had no effect on FMLP-induced neutrophil chemotaxis at any of the concentrations (1 to 100μg/ml) . These results suggest that GPFX facilitates the improvement of bacterial infections with the combination of its bactericidal effect and the activation of neutrophils in vivo.

To clarify the bronchoscopic findings in metastatic spread to the bronchi, we analyzed the records of 65 cases of metastatic pulmonary disease in which fiberoptic bronchoscopy had been done. Forty-five patients (69.2%) had abnormal bronchoscopic findings. These patients could be divided into three groups, according to bronchoscopic findings and route of metastatic spread to the bronchi: endobronchial metastasis (n=15), bronchial involvement (that is, direct extension to the bronchi from adjacent metastatic foci, n=15), and lymphangitis carcinomatosa (n=15). Breast cancer and colon cancer were common in cases of endobronchial metastasis, and the bronchial tumor often presented as a polypoid or nodular lesion covered with necrotic material. Submucosal swelling with an irregular margin and narrowing of the bronchial lumen were seen in cases of bronchial involvement. In conclusion, each type of primary extrapulmonary tumor is associated with characteristic endobronchial findings of pulmonary metastases such as endobronchial metastasis and bronchial involvement, which should be discriminated if possible, because of their different metastatic process.

Recent studies suggest that nitric oxide (NO) may play an important role in the pathophysiology of pulmonary hypertension. Nitroglycerin is metabolized to NO, which is a potent vascular smooth muscle relaxant. The aim of the present study was to compare the effects of inhaled and infused nitroglycerin on pulmonary hemodynamics and gas exchange in anesthetized, artificially ventilated dogs. Nitroglycerin was administrated either by inhalation or by infusion. Systemic blood pressure (SBP), pulmonary arterial pressure (PAP), and pulmonary capillary wedge pressure (PCWP) were measured, and cardiac output was estimated by an electromagnetic flowmeter. Blood gas measurements were performed during hypoxic gas exposure (FiO2; 0.1) with a continuous inhalation or infusion of nitroglycerin (1, 2.5 µg/kg/min). Inhaled (n = 4) and infused (n = 4) nitroglycerin (1 µg/kg/min) did not produce any detectable effects on the hemodynamics. Inhaled nitroglycerin (2.5 µg/kg/min) reduced SBP, PAP and calculated pulmonary vascular resistance (PVR) in all dogs. Cardiac output did not change. In addition, inhaled nitroglycerin increased PaO2. In contrast, the continuous infusion of nitroglycerin (2.5 µg/kg/min) did not change in PAP, whereas infused nitroglycerin decreased the mean SBP. Infused nitroglycerin did not alter cardiac output and calculated PVR. A decreased PaO2 was noted in 2 dogs on nitroglycerin infusion. These findings indicate that inhaled nitroglycerin effects the pulmonary circulation relatively more than infused nitroglycerin, which tends to have more of a general effect on the systemic circulation. The effects of inhaled nitroglycerin may thus be comparable to the effects of NO inhalation.

To elucidate the role of major chemotactic factors, cytokine-induced neutrophil chemoattractant (CINC), leukotriene B4 (LTB4) and C5a in lipopolysaccharide (LPS)-induced acute lung injury in rat, we employed three reagents: anti-CINC-1 antibody, an LTB4 receptor antagonist (ONO-4057) and an anti-complementary agent (K-76COONa). Rats were divided into five groups: (1)control group; (2) LPS group, which received intratracheal instillation of LPS (100 microg/kg); (3) Anti-CINC group, which received intratracheal coinstillation of LPS with anti-CINC-1 antibody (1 mg/kg); (4) LTB4-Ra group, which received intravenous ONO-4057 (10 mg/kg) prior to intratracheal LPS; (5) Anti-C5a group, which received intravenous K-76COONa (100 mg/kg) prior to intratracheal LPS. The number of neutrophils in bronchoalveolar lavage (BAL) fluids 6 h after LPS instillation was significantly reduced in the Anti-CINC group, however, no reduction was found in either the LTB4-Ra group or Anti-C5a group. The levels of CINC-1, CINC-2alpha and CINC-3 in BAL fluids were significantly higher in the LPS group than in the saline-instilled control group. In vitro, the production of CINC-1 and CINC-3 from LPS-stimulated macrophages was significantly elevated compared to unstimulated macrophages 6 h later. The increase in CINC-2alpha production was markedly less than that of CINC-1 or CINC-3. These results indicate that CINCs, especially CINC-1 and CINC-3 play an important role in the recruitment of neutrophils to the lung in LPS-induced acute lung injury.

The origin of both weak temperature dependence and packing fraction dependence of $T^{1/4}\eta^{3/2}$ in the thermal conductivity of the simple Lennard-Jones (LJ) liquid is explored. In order to discuss the relative contributions from attractive or repulsive part of the interaction potential separately, the thermal conductivity of a series of Weeks-Chandler-Anderson (WCA) fluids is calculated by molecular dynamics simulations. The results show that the repulsive part plays the main role in the heat conduction, while the attractive part has no direct effect on the thermal conductivity for a given packing fraction. By investigating WCA fluids with potentials of varying softness, we explain the difference observed between the LJ liquids such as argon and Coulombic liquids such as NaCl., Comment: 4 pages, 4 figures

Since lung is a directly affected organ by cigarette smoking, various respiratory diseases including lung cancer, chronic obstructive pulmonary disease, interstitial lung diseases, bronchial asthma, are caused and worsen by cigarette smoking not only in case of active smoking but also in case of passive smoking. A lot of carcinogen in cigarette smoke causes lung cancer through the DNA damage. Oxidants in cigarette smoke induce airway inflammation and tissue injury. Various kinds of protease including neutrophil elastase and matrix metalloproteinase cause emphysema. Meanwhile, inflammation also induces lung fibrosis. Cigarette smoking is a risk factor for the development of asthmas and is associated with decreased asthma control and increased risk of mortality and exacerbations.

Metastasis to the skin from lung cancer is less common than metastasis to other organs. We clinically reviewed 16 cases of skin metastasis. The incidence of skin metastasis was 2.8% among all 579 cases of lung cancer. Large cell carcinoma showed the greatest tendency to spread to the skin and epidermoid carcinoma showed the least tendency. The most common sites for skin lesions were the back. Almost all lesions ranged from 1 to 5 cm in diameter. Clinical manifestation of skin metastasis was nodular type in all cases. At the development of skin metastasis, all cases were accompanied by metastasis to other organs. There was only a slight response to combination chemotherapy carried out 5 cases for lung cancer, and most lesions were progressive. Median survival after skin involvement was approximately 4 months.

We report 2 cases of Legionnaires' disease that occurred in the same town in Japan at the end of October, 1994. Patient 1 was a 66-year-old male with well-controlled diabetes mellitus, while patient 2 was a previously healthy 46-year-old male. Both patients developed fever and general fatigue on admission, accompanied by disturbances of consciousness in patient 2. The clinical course in both patients showed progressive hypoxemia, expansion of pulmonary infiltration on chest x-ray, severe inflammatory reactions including reduced peripheral lymphocytes, and elevation of transaminases, LDH, and CPK. Both patients recovered completely following the administration of clarithromycin and rifampicin. Although no organism of anyLegionella species was isolated from clinical specimens,Legionella rDNAs were detected by polymerase chain reaction amplification using LEG primers in bronchial secretions from patient 1 and a pleural effusion from patient 2, andLegionella pneumophila serogroup 1 antigen was detected in the urine and pleural effusion of patient 2. The microagglutination test for the detection of serum anti-Legionella antibodies confirmed that the causative organism in patient 1 wasL. pneumophila serogroup 4 orLegionella dumoffii, and in patient 2,L. pneumophila serogroup 1A, suggesting that the 2 cases did not represent an outbreak, but were isolated cases.

悪性中皮腫と悪性黒色腫との重複癌で, 剖検胸膜中皮腫組織にてCDKN2遺伝子の異常を認めたと考えられる1例を経験した.症例は86歳, 男性.約10ヵ月前より胸水貯留による呼吸困難が出現し, 精査を行うも原因不明のため当科紹介となった.同時期に右第5足趾の黒子を指摘され, 悪性黒色腫と診断され, 第5趾切断術を施行した.胸水に関しては, 胸腔鏡下胸膜生検にて悪性中皮腫と診断された.その後中皮腫の進展に伴う呼吸不全により死亡した.原因不明の胸水症例では, 画像検査にて悪性が疑われる場合には, 積極的に胸腔鏡を施行すべきであると考えられた.また重複癌であった本症例の発症機序の1つの遺伝的要因として, CDKN2遺伝子にコードされたCDK抑制因子であるp16の関与が考えられた.今後, 重複癌においてはその発症機序解明に, 遺伝子異常の解析が重要であるものと思われた.

Background Dendritic cells (DCs) are professional antigen-presenting cells that play a crucial role in the initiation and modulation of immune responses. Human circulating blood DCs are divided into two major subsets: myeloid DCs (mDCs); and plasmacytoid DCs (pDCs). Furthermore, mDCs are subdivided into two subsets: Th1-promoting mDCs (mDC1s); and Th2-promoting mDCs (mDC2s). Although CD1a, CD1c, and CD141 are generally used for classifying mDC subsets, their adequacy as a specific marker remains unclear. We performed this study to compare circulating mDC, pDC, mDC1, and mDC2 subsets between Th1- and Th2-mediated diseases using CD1a and CD141, and to analyze the adequacy of CD1a and CD141 as a marker for mDC1s and mDC2s, respectively. Methods Thirty patients with sarcoidosis, 23 patients with atopic diseases, such as atopic bronchial asthma, and 23 healthy subjects as controls were enrolled in this study. Peripheral blood DC subsets were analyzed with flow cytometry according to expressions of CD11c, CD123, CD1a, and CD141. For functional analysis, we measured interleukin (IL) 12p40 levels produced by the sorted mDC subsets. Results The sarcoidosis group showed decreased total DC (P +mDC count (P -mDC count (P +mDC count in the atopy group was higher than controls (P +mDCs produced higher levels of IL-12p40 than CD1a-mDCs (P = 0.025) and CD141+mDCs (P = 0.018). Conclusions We conclude that decreased count of CD1a+mDC and increased count of CD141+mDC may reflect the Th2-skewed immunity in atopic diseases. The results of IL-12 levels produced by the sorted mDC subsets suggested the adequacy of CD1a and CD141 as a marker for mDC1 and mDC2, respectively, in vivo.

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.

The combination of carboplatin/paclitaxel is commonly used as chemotherapy for advanced non-small cell lung cancer. However, the relatively high incidence of neurotoxicity remains a problem. This study was undertaken to determine whether the fractionated administration regimen can reduce the neurotoxicity. Patients with stage III or IV non-small cell lung cancer were randomized to the nonfractionated (NF) dose group, which received paclitaxel (200 mg/m(2)) and carboplatin (area under the concentration-time curve=6) on day 1, or the fractionated dose (F) group, which received paclitaxel (100 mg/m(2)) and carboplatin (area under the concentration-time curve=3) on days 1 and 8. The cycle was repeated every 3 weeks. Peripheral neuropathy was objectively evaluated by measuring the current perception threshold (CPT) in the median nerve using a neurometer. Fourteen and 13 patients were assigned to the NF and F groups, respectively. The incidence of subjective numbness was significantly lower in the F group (15.4%) than in the NF group (57.1%). The CPT value determined at 2000 Hz showed significant increases in the NF group compared with the pretreatment baseline, but no significant changes were observed in the F group. The response rate was comparable in both groups. The fractionated administration of carboplatin/paclitaxel combination therapy showed a significant reduction in neurotoxicity. Measurement of CPT by a neurometer is a useful tool to evaluate the neurotoxicity of anticancer drugs objectively.

We investigated the mechanical properties of the flexor carpi radialis muscle (FCR), a forelimb muscle used mainly for amplexus in the breeding season (February to March), of the male Japanese brown frog, Rana japonica. In the present experiment, the changes in force and stiffness of the FCR before, during, and after contraction were measured at 4 degrees C. The total time from the end of stimulation to the end of relaxation was about 30 min. The time course of this prolonged relaxation was fitted by two exponential decay processes. Stiffness decreased during prolonged relaxation, but stayed higher than force, when normalized to peak values. These mechanical properties of the FCR were different from those of the glutaeus magnus muscle (GM) in the hindlimb, used for jumping. When a quick release was applied to the FCR during relaxation, the force recovered gradually after a sudden decrease. The time course of this force recovery was fitted by a single exponential term, and the rate constant decreased as the prolonged relaxation proceeded. The possible involvement of active process(es) in the prolonged relaxation is discussed.

Since adhesion of neutrophils (PMN) to endothelial cells may influence PMN activation responses, we examined whether adhesion of PMN to TNF alpha-activated human umbilical vein endothelial cells (HUVEC) stimulates leukotriene B4 (LTB4) production. Endothelial adhesivity towards PMN increased after HUVEC pretreatment with TNF alpha for 4 h. LTB4 production increased markedly in response to stimulation with arachidonic acid (20 microM) when PMN were added to the hyperadhesive HUVEC. In contrast, stimulation of PMN in suspension did not potentiate LTB4 production. LTB4 production persisted when PMN were applied to TNF alpha-pretreated HUVEC fixed with 1% paraformaldehyde excluding the possibility that metabolic activity of endothelium participates in this response. PMN adhesion to plastic and gelatin also enhanced LTB4 indicating that adhesion was a critical event in inducing LTB4 production. We used monoclonal antibodies (mAb) to adhesion molecules on endothelial cells (i.e., endothelial leukocyte adhesion molecule-1 (ELAM-1) and intercellular adhesion molecule-1 (ICAM-1)) or on PMN (CD18) to assess the role of PMN adhesion to the activated endothelium on LTB4 potentiation. Both anti-ELAM-1 mAb and anti-ICAM-1 mAb inhibited PMN adhesion (by 55 and 41%, respectively) as well as LTB4 production (by 65 and 50%, respectively). Anti-CD18 mAb also reduced the adhesion (65%) and the LTB4 production (66%). Furthermore, combination of anti-ELAM-1 mAb (H18/7) and anti-ICAM-1 mAb (RR1/1) or of anti-ELAM-1 mAb (H18/7) and anti-CD18 mAb (IB4) had an additive effect in inhibiting both PMN adhesion as well as LTB4 production. PMN adherence to immobilized recombinant soluble rELAM-1 or rICAM-1 also increased LTB4 production, which was prevented with relevant mAbs. However, neither rELAM-1 nor rICAM-1 stimulated LTB4 production of PMN in suspension. We conclude that PMN adhesion to TNF alpha-stimulated endothelial cells enhances LTB4 production by PMN, a response activated by binding of PMN to expressed endothelial cell surface adhesion molecules.

Reactive oxygen species play an important role in the pathogenesis of acute lung injury and pulmonary fibrosis. The present authors hypothesise that edaravone, a free-radical scavenger, is able to attenuate bleomycin (BLM)-induced lung injury in mice by decreasing oxidative stress. Lung injury was induced in female ICR mice by intratracheal instillation of 5 mg x kg(-1) of BLM. Edaravone (300 mg x kg(-1)) was administered by intraperitoneal administration 1 h before BLM challenge. Edaravone significantly improved the survival rate of mice treated with BLM from 25 to 90%, reduced the number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF) on day 7, and attenuated the concentrations of lipid hydroperoxide in BALF and serum on day 2. The fibrotic change in the lung on day 28 was ameliorated by edaravone, as evaluated by histological examination and measurement of hydroxyproline contents. In addition, edaravone significantly increased the prostaglandin E(2) concentration in BALF on day 2. In summary, edaravone was shown to inhibit lung injury and fibrosis via the repression of lipid hydroperoxide production and the elevation of prostaglandin E(2) production in the present experimental murine system.

Vascular endothelial cells produce or metabolize vasoactive substances, which regulate or modulate vascular tone. A potent vasodilator, prostaglandin I2 (PGI2) is known to be released from vascular endothelium in increased quantities in response to not only various chemical stimuli but also mechanical stimuli such as a increased blood flow. We performed this study to know whether pulmonary hemodynamic forces would affect lung PGI2 production and PGI2 acts on pulmonary vessels to maintain a low resistance in the pulmonary circulation. We measured plasma 6-keto-PGF1α, the metabolite of PGI2, during pulmonary blood flow alterations in rabbits.The alterations were made by unilateral complete pneumothorax or pulmonary artery occulusion, which decreased pulmonary vascular bed and increased blood flow in the redisual pulmonary vessels. Plasma 6-keto-PGF1α level increased during such procedures but the rise of pulmonary arterial pressure was small and transient. Cyclooxygenase inhibition did not affect the change of pulmonary arterial pressure during pulmonary artery occulusion.These data suggest that PGI2 is produced by pulmonary vessels in response to the increased blood flow but it may not participate in modulation of pulmonary hemodynamics.

Thoracoscopy has been recently established as an indispensable technique for diagnosis and treatment of respiratory diseases. Although, thoracoscopy is usually applied under general anesthesia by a surgeon, it can also be applied by a chest physician under local anesthesia if the target is limited to pleural diseases. The main objective of medical thoracoscopy under local anesthesia is to establish a diagnosis of pleural effusions by means of observation and biopsy in the thoracic cavity. Our main target diseases are the pleuritis carcinomatosa, malignant mesothelioma and tuberculous pleuritis. These 3 diseases are the diseases with which medical thoracoscopy is most useful because they can be reliably diagnosed by biopsies and because early diagnosis and early treatment are essential. In case of the pneumothorax, treatment with bulla looping or cauterization may be possible, but we do not treat pneumothorax with medical thoracoscopy because it is impossible to approach and find air leaks of lesions located in or near blind spots such as the apex or mediastinal part In case of acute emphysema, it is important to release adhesions and perform effective drainage using thoracoscopy as soon as possible since deposition of fibrin tends to form quickly compartments that make drainage difficult. Scince medical thoracoscopy under local anesthesia is rapid, easy, safe, and well-tolerated procedure with an excellent diagnostic yield, it is recommended as a diagnostic procedure for cases with pleural diseases.