Quantitative Evaluation of Changes in Three-Dimensional CT Density Distributions in Pulmonary Alveolar Proteinosis after GM-CSF Inhalation.

BACKGROUND: A previous clinical trial for autoimmune pulmonary alveolar proteinosis (APAP) demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation reduced the mean density of the lung field on computed tomography (CT) across 18 axial slice planes at a two-dimensional level. In contrast, in this study, we challenged three-dimensional analysis for changes in CT density distribution using the same datasets. METHODS: As a sub-study of the trial, CT data of 31 and 27 patients who received GM-CSF and placebo, respectively, were analyzed. To overcome the difference between various shooting conditions, a newly developed automatic lung field segmentation algorithm was applied to CT data to extract the whole lung volume, and the accuracy of the segmentation was evaluated by five pulmonary physicians independently. For normalization, the percent pixel (PP) in a certain density range was calculated as a percentage of the total number of pixels from -1,000 to 0 HU. RESULTS: The automatically segmented images revealed that the lung field was accurately extracted except for 7 patients with minor deletion or addition. Using the change in PP from baseline to week 25 (ΔPP) as the vertical axis, we created a histogram with 143 HU bins set for each patient. The most significant difference in ΔPP between GM-CSF and placebo groups was observed in two ranges: from -1,000 to -857 and -143 to 0 HU. CONCLUSION: Whole lung extraction followed by density histogram analysis of ΔPP may be an appropriate evaluation method for assessing CT improvement in APAP.

Inhaled GM-CSF for Pulmonary Alveolar Proteinosis.

BACKGROUND: Pulmonary alveolar proteinosis is a disease characterized by abnormal accumulation of surfactant in the alveoli. Most cases are autoimmune and are associated with an autoantibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) that prevents clearing of pulmonary surfactant by alveolar macrophages. An open-label, phase 2 study showed some therapeutic efficacy of inhaled recombinant human GM-CSF in patients with severe pulmonary alveolar proteinosis; however, the efficacy in patients with mild-to-moderate disease remains unclear. METHODS: We conducted a double-blind, placebo-controlled trial of daily inhaled recombinant human GM-CSF (sargramostim), at a dose of 125 µg twice daily for 7 days, every other week for 24 weeks, or placebo in 64 patients with autoimmune pulmonary alveolar proteinosis who had a partial pressure of arterial oxygen (Pao2) while breathing ambient air of less than 70 mm Hg (or <75 mm Hg in symptomatic patients). Patients with severe pulmonary alveolar proteinosis (Pao2 <50 mm Hg) were excluded to avoid possible exacerbation of the disease in patients who were assigned to receive placebo. The primary end point was the change in the alveolar-arterial oxygen gradient between baseline and week 25. RESULTS: The change in the mean (±SD) alveolar-arterial oxygen gradient was significantly better in the GM-CSF group (33 patients) than in the placebo group (30 patients) (mean change from baseline, -4.50±9.03 mm Hg vs. 0.17±10.50 mm Hg; P = 0.02). The change between baseline and week 25 in the density of the lung field on computed tomography was also better in the GM-CSF group (between-group difference, -36.08 Hounsfield units; 95% confidence interval, -61.58 to -6.99, calculated with the use of the Mann-Whitney U test and the Hodges-Lehmann estimate of confidence intervals for pseudo-medians). Serious adverse events developed in 6 patients in the GM-CSF group and in 3 patients in the placebo group. CONCLUSIONS: In this randomized, controlled trial, inhaled recombinant human GM-CSF was associated with a modest salutary effect on the laboratory outcome of arterial oxygen tension, and no clinical benefits were noted. (Funded by the Japan Agency for Medical Research and Development and the Ministry of Health, Labor, and Welfare of Japan; PAGE ClinicalTrials.gov number, NCT02835742; Japan Medical Association Center for Clinical Trials number, JMA-IIA00205.).

Characteristics of pleural effusion with a high adenosine deaminase level: a case-control study.

BACKGROUND: Increased pleural fluid adenosine deaminase (ADA) is useful for diagnosing tuberculous pleurisy (TB), but high ADA levels are associated with other diseases. In this study, we compare various disease characteristics in patients with high-ADA pleural effusion. METHODS: We retrospectively collected data for 456 patients with pleural fluid ADA levels of ≥ 40 U/L from January 2012 to October 2021. Cases were classified as TB (n = 203), pleural infection (n = 112), malignant pleural effusion (n = 63), nontuberculous mycobacteria (n = 22), malignant lymphoma (ML) (n = 18), autoimmune diseases (n = 11), and other diseases (n = 27), and data were compared among those diseases. Predictive factors were identified by comparing data for a target disease to those for all other diseases. A diagnostic flowchart for TB was developed based on those factors. RESULTS: The most frequent disease was TB, though 60.0% of patients were diagnosed with other diseases. Median ADA levels in patients with TB were 83.1 U/L (interquartile range [IQR] 67.2-104.1), higher than those of patients with pleural infection (median 60.9 [IQR 45.3-108.0], p = 0.004), malignant pleural effusion (median 54.1 [IQR 44.8-66.7], p < 0.001), or autoimmune diseases (median 48.5 [IQR 45.9-58.2], p = 0.008), with no significant difference from NTM (p = 1.000) or ML (p = 1.000). Pleural fluid lactate dehydrogenase (LDH) levels of < 825 IU/L were beneficial for the diagnosis of TB. Neutrophil predominance or cell degeneration, white blood cell count of ≥ 9200/µL or C-reactive protein levels of ≥ 12 mg/dL helped in diagnosing pleural infection. Pleural fluid amylase levels of ≥ 75 U/L and a pleural fluid ADA/total protein (TP) ratio of < 14 helped in diagnosing malignant pleural effusion. High serum LDH and high serum/pleural fluid eosinophils helped in diagnosing ML and autoimmune diseases, respectively. The flowchart was comprised of the following three factors: pleural fluid LDH < 825 IU/L, pleural fluid ADA/TP of < 14, and neutrophil predominance or cell degeneration, which were decided by a decision tree. The diagnostic accuracy rate, sensitivity, and specificity for the diagnosis of TB were 80.9%, 78.8%, and 82.6%, respectively. CONCLUSION: Cases involving high pleural fluid ADA levels should be investigated using several factors to distinguish TB from other diseases.

Rapidly progressive respiratory failure with multiple halo signs on computed tomography in a patient with primary cardiac angiosarcoma derived from the right atrium: a case report.

BACKGROUND: Primary cardiac neoplasms are extremely rare, with an autopsy incidence of 0.0001-0.003%. Primary cardiac sarcoma is usually derived from the right atrium and it manifests as chest pain, arrhythmia, hemoptysis, dyspnea, and fatigue. The most common target organ for metastasis of primary angiosarcoma is the lungs, but the radiological-pathological correlation has been rarely reported. CASE PRESENTATION: A 38-year-old healthy Japanese man was admitted to our hospital with persistent hemoptysis, exaggerated dyspnea, and two episodes of loss of consciousness in the past 3 months. Non-enhanced thoracic computed tomography (CT) revealed multiple scattered nodules with halo signs. Contrast-enhanced thoracic CT revealed a filling defect in the right atrium, which corresponded to the inhomogeneously enhancing tumor in the right atrium on enhanced electrocardiogram-gated cardiac CT. On day 2, acute respiratory failure occurred, and the patient was placed on mechanical ventilation. The patient was diagnosed with primary cardiac angiosarcoma based on the urgent transcatheter biopsied specimen of the right atrium mass and was treated with intravenous administration of doxorubicin. However, his respiratory status rapidly deteriorated, and he died on day 20. Postmortem biopsy showed that the multiple lung nodules with the halo signs corresponded to the intratumoral hemorrhagic necrosis and peripheral parenchymal hemorrhage in their background, suggesting the fragility of the lung tissue where the tumor had invaded, which caused hemoptysis. Furthermore, two episodes of loss of consciousness occurred probably due to a decreased cardiac output because of a massive tumor occupying the right atrium, recognized as an inhomogeneous centripetal enhancement on enhanced electrocardiogram-gated cardiac CT. CONCLUSIONS: This case clearly demonstrated that primary cardiac angiosarcoma could expand in the right atrial cavity, which led to a decreased cardiac output resulting in repeated syncope, together with the fragility of lung tissue by tumor invasion, thereby generating a halo sign on thoracic CT.

Ellipsoidal Artificial Melanin Particles as Building Blocks for Biomimetic Structural Coloration.

Inspired by the structural coloration of anisotropic materials in nature, we demonstrate the preparation of structural color materials by the assembly of anisotropic particles. Spherical artificial melanin particles consisting of a polystyrene core and polydopamine shell were stretched asymmetrically to form uniform-sized ellipsoidal particles with different aspect ratios. The aspect ratio and assembly method of the ellipsoidal particles influence the structural coloration, indicating that the particle shape is one of the important parameters for controlling the structural coloration. The discovery of a method to control the structural color using ellipsoidal particles is useful in basic research on structural colors in nature and provides flexibility in material design and extends the application range of structural color materials.

Pilot study for risk assessment of aspiration pneumonia based on oral bacteria levels and serum biomarkers.

BACKGROUND: Aspiration pneumonia is a serious problem among elderly patients; it is caused by many risk factors including dysphagia, poor oral hygiene, malnutrition, and sedative medications. The aim of this study was to define a convenient procedure to objectively evaluate the risk of aspiration pneumonia in the clinical setting. METHODS: This prospective study included an aspiration pneumonia (AP) group, a community-acquired pneumonia (CAP) group, and a control (Con) group (patients hospitalized for lung cancer chemotherapy). We used the Oral Health Assessment Tool (OHAT), which assesses oral hygiene, and evaluated performance status, body mass index, serum albumin levels, substance P values in plasma, and oral bacterial counts. RESULTS: The oral health as assessed by the OHAT of the aspiration pneumonia group was significantly impaired compared with that of the CAP group and the control (5.13 ± 0.18, 4.40 ± 0.26, 3.90 ± 0.22, respectively; p < 0.05). The oral bacterial count in the aspiration pneumonia group (7.20 ± 0.11) was significantly higher than that in the CAP group (6.89 ± 0.12), consistent with the OHAT scores. Oral bacterial count was significantly reduced by oral care. CONCLUSIONS: OHAT and oral bacterial counts can be a tool to assess the requirement of taking oral care and other preventive procedures in patients at high risk of aspiration pneumonia.

Pseudomonas aeruginosa-derived flagellin stimulates IL-6 and IL-8 production in human bronchial epithelial cells: A potential mechanism for progression and exacerbation of COPD.

Background and purpose of the study:Pseudomonas aeruginosa commonly colonizes the airway of patients with chronic obstructive pulmonary disease (COPD) and exacerbates their symptoms. P. aeruginosa carries flagellin that stimulates toll-like receptor (TLR)-5; however, the role of flagellin in the pathogenesis of COPD remains unclear. The aim of the study was to evaluate the mechanisms of the flagellin-induced innate immune response in bronchial epithelial cells, and to assess the effects of anti-inflammatory agents for treatment. Materials and methods: We stimulated BEAS-2B cells with P. aeruginosa-derived flagellin, and assessed mRNA expression and protein secretion of interleukin (IL)-6 and IL-8. We also used mitogen-activated protein kinases (MAPK) inhibitors to assess the signaling pathways involved in flagellin stimulation, and investigated the effect of clinically available anti-inflammatory agents against flagellin-induced inflammation. Results: Flagellin promoted protein and mRNA expression of IL-6 and IL-8 in BEAS-2B cells and induced phosphorylation of p38, ERK, and JNK; p38 phosphorylation-induced IL-6 production, while IL-8 production resulted from p38 and ERK phosphorylation. Fluticasone propionate (FP) and dexamethasone (DEX) suppressed IL-6 and IL-8 production in BEAS-2B cells, but clarithromycin (CAM) failed to do so. Conclusions:P. aeruginosa-derived flagellin-induced IL-6 and IL-8 production in bronchial epithelial cells, which partially explains the mechanisms of progression and exacerbation of COPD. Corticosteroids are the most effective treatment for the suppression of flagellin-induced IL-6 and IL-8 production in the bronchial epithelial cells.

Serum sST2 levels predict severe exacerbation of asthma.

BACKGROUND: Neutrophilic inflammation is associated with poorly controlled asthma. Serum levels of sST2, a soluble IL-33 receptor, increase in neutrophilic lung diseases. We hypothesized that high serum sST2 levels in stable asthmatics are a predictor for exacerbation within a short duration. METHODS: This prospective observational study evaluated the serum sST2 levels of 104 asthmatic patients who were treated by a lung disease specialist with follow-ups for 3 months. RESULTS: High serum sST2 levels (> 18 ng/ml) predicted severe asthma exacerbation within 3 months. Serum sST2 levels correlated positively with asthma severity (treatment step), airway H2O2 levels, and serum IL-8 levels. High serum sST2 levels and blood neutrophilia (> 6000 /µl) were independent predictors of exacerbation. We defined a post-hoc exacerbation-risk score combining high serum sST2 level and blood neutrophilia, which stratified patients into four groups. The score predicted exacerbation-risk with an area under curve of 0.91 in the receiver operating characteristic curve analysis. Patients with the highest scores had the most severe phenotype, with 85.7% showing exacerbation, airflow limitation, and corticosteroid-insensitivity. CONCLUSIONS: High serum sST2 levels predicted exacerbation within the general asthmatic population and, when combined with blood neutrophil levels, provided an exacerbation-risk score that was an accurate predictor of exacerbation occurring within 3 months.

Bronchial epithelial cells produce CXCL1 in response to LPS and TNFα: A potential role in the pathogenesis of COPD.

RATIONALE: Neutrophilic airway inflammation plays a central role in chronic obstructive pulmonary disease (COPD). CXC chemokine ligand (CXCL)1 is a neutrophil chemokine involved in the pathogenesis of COPD. However, its clinical significance in COPD patients is poorly understood. AIM OF THE STUDY: To assess the production of CXCL1 by bronchial epithelial cells in response to lipopolysaccharide (LPS) and tumor necrosis factor (TNF)α. MATERIALS AND METHODS: We measured sputum CXCL1 and CXCL8 levels in patients with COPD, asthma, and asthma-COPD overlap (ACO), and compared them to those of patients with interstitial pneumonia (IP). Using primary human bronchial epithelial cells and BEAS-2B cells, CXCL1 protein release and mRNA expression were measured after LPS or TNFα stimulation. We evaluated signal transduction mechanisms for CXCL1 production using nuclear factor-κ B (NF-kB) and mitogen-activated protein kinase (MAPK) inhibitors, and examined the effects of anti-inflammatory agents on CXCL1 production in BEAS-2B cells. RESULTS: Sputum CXCL1 levels in COPD and ACO patients were higher than in IP patients, whereas sputum CXCL8 levels were not. Sputum CXCL1 levels were not affected by inhaled corticosteroid usage, whereas sputum CXCL8 levels tended to be affected. LPS and TNFα stimulated CXCL1 production and mRNA expression in bronchial epithelial cells. NF-kB and MAPK p38 were involved in LPS-induced CXCL1 production. Therapeutic anti-inflammatory agents minimally attenuated CXCL1 production and considerably inhibited CXCL8 production in BEAS-2B cells. CONCLUSIONS: Sputum CXCL1 levels is a potentially better diagnostic marker for COPD than sputum CXCL8 levels, which is explained by that CXCL1 production in bronchial epithelial cells is less affected by therapeutic anti-inflammatory agents than CXCL8 production.

Diagnostic Value of Vascular Endothelial Growth Factor, Transforming Growth Factor-ß, Interleukin-8, and the Ratio of Lactate Dehydrogenase to Adenosine Deaminase in Pleural Effusion.

PURPOSE: We studied the diagnostic value of cytokines, including vascular endothelial growth factor (VEGF), transforming growth factor-ß (TGF-ß), and interleukin-8 (IL-8), and the ratio of lactate dehydrogenase (LDH) to adenosine deaminase (ADA) in pleural fluid. METHODS: Prospective analysis of 44 inpatients or outpatients with pleural fluid, from December 2016 to March 2017 was conducted. RESULTS: We enrolled patients with malignant pleural effusion (MPE, N = 15), empyema (N = 11), parapneumonic effusion (PPE, N = 7), chronic renal failure (CRF)/chronic heart failure (CHF) (N = 7), and tuberculous pleural effusion (TBPE, N = 4). The pleural fluid values of IL-8 and VEGF were significantly higher in empyema patients than in CRF/CHF or PPE patients. In all patients, the pleural fluid VEGF and IL-8 values were significantly positively correlated (r = 0.405, p = 0.006; r = 0.474, p = 0.047, respectively). TGF-ß was elevated in patients with empyema, PPE, TBPE, and MPE. The pleural LDH-to-ADA ratio in patients with MPE or empyema/PPE was significantly higher than in patients with CRF/CHF or TBPE. LDH and ADA levels correlated significantly only in patients with MPE (r = 0.648, p = 0.009) and empyema/PPE (r = 0.978, p < 0.001). CONCLUSIONS: VEGF and IL-8 production in the pleural cavity appear to accelerate the progression of PPE to empyema, by enhancing vascular permeability associated with inflammation. Sequential sampling would be needed to confirm this. The pleural LDH/ADA ratio may be a useful diagnostic tool for discriminating between various pleural effusion etiologies.

Two cases of autoimmune and secondary pulmonary alveolar proteinosis during immunosuppressive therapy in dermatomyositis with interstitial lung disease.

Interstitial lung disease (ILD) with dermatomyositis often requires intensive immunosuppressive therapy. Here, we report two cases of pulmonary alveolar proteinosis (PAP) in dermatomyositis with ILD. One case was secondary PAP, and the other was autoimmune PAP positive for the anti-granulocyte macrophage-colony-stimulating factor antibody. PAP arose during immunosuppressive therapy and symptoms ceased by attenuating immunosuppression. Exacerbation of pulmonary lesions during intensive immunosuppressive therapy may distinguish PAP from worsening ILD and attenuating immunosuppression should be considered.

Yolk/Shell Colloidal Crystals Incorporating Movable Cores with Their Motion Controlled by an External Electric Field.

Yolk/shell particles composed of a submicrometer-sized movable core and a silica shell are promising building blocks for novel optical colloidal crystals, because the locations of cores in the shell compartment can be reversibly changed by using external stimuli. Two dimensional arrays of yolk/shell particles incorporating movable cores were prepared by a self-assembly method. The movable cores of colloidal crystals in water could be observed with an optical microscope under application of external electric field. The motions of inner silica cores depended on the electric field strength and frequency and were categorized into three cases: (1) Random Brownian motion, (2) anisotropic motion of cores moving in a direction orthogonal to a field, and (3) suppressed motion fixed in the center of shell compartment. Random Brownian motion of cores was scarcely affected by field strength when a high frequency (in the MHz range) electric field was applied. On the other hand, an increase in field strength at low-frequency fields (kHz) transiently changed the core motion from (1) to (2) and a further increase in field strength changed it from (2) to (3). When the silica core was incorporated in a large void a stronger electric field was needed to suppress its motion than when it was in a small void. The high responsivity to electric fields in a low-frequency range indicated the importance of electric double layer (EDL) interaction between core and inner shell in controlling the core location in yolk/shell colloidal crystals. It was also shown that movable titania cores in yolk/shell particles required a low-frequency field with a high strength to change from the random to anisotropic motion. The result suggested that the electrostatic interaction between EDLs of the silica core and the inner silica wall could be stronger than that between EDLs of the titania core and the silica shell.

Imprinting Dimples on Narrowly Dispersed Polymeric Spheres by Heterocoagulation between Hard Polymer Particles and Soft Oil Droplets.

Golf ball-like particles having a number of dimples on their spherical surfaces were prepared by a combined method of heterocoagulation between hard polymer particles and soft silicone oil droplets, polymerization of the oil droplets, and dissolution of the polymer particles with tetrahydrofuran. In the heterocoagulation, polystyrene (PSt) particles of three different sizes were employed as hard particles. Distribution of dimples formed with small-sized PSt particles was less homogeneous than that with middle-sized PSt particles (MPS). Narrowly dispersed golf ball-like particles with homogeneously distributed dimples were successfully prepared with a high number ratio of MPS to oil droplets. The employment of large-sized PSt particles in the heterocoagulation decreased the number of PSt particles required for the stabilization of the oil droplets, which created polyhedron-like particles having dimples on their surface. Additional experiments in which polymer particles with different surface affinities to the oil droplets were heterocoagulated with the droplets revealed that a high surface affinity of particles to the droplets could deeply embed the polymer particles into the droplets and form dimples with a low contact angle.

IL-17A synergistically stimulates TNF-α-induced IL-8 production in human airway epithelial cells: A potential role in amplifying airway inflammation.

BACKGROUND: Recent reports have suggested an involvement of neutrophilic inflammation driven by interleukin (IL)-17 from Th17 cells, especially in severe, refractory asthma. It remains unknown about the possible interactions of this cytokine and other proinflammatory cytokines to direct neutrophilic airway inflammation. MATERIALS AND METHODS: We evaluated the effects of IL-17A, IL-17E, and IL-17F in combination with other stimuli such as tumor necrosis factor (TNF) -α on the production and expression of IL-8 in human bronchial epithelial cells. We also studied their effects on other cytokine production. The possible role of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways was evaluated by specific inhibitors. We examined the effects of anti-asthma drugs, such as steroids or salmeterol. RESULTS: IL-17A alone induced only a minimal effect on IL-8 expression. IL-17A, but not IL-17E or IL-17F, in combination with TNF-α showed a synergistic effect on IL-8 expression. Similar findings were found when combination with IL-1ß and IL-17A were used, but such was not the case with lipopolysaccharide (LPS). In addition, we further found such synergy on GM-CSF production. The synergy with TNF-α and IL-17A was significantly inhibited by MAPKs inhibitors. Corticosteroids such as fluticasone propionate and dexamethasone, but not salmeterol, partially suppressed the IL-17A and TNF-α-induced IL-8 production. CONCLUSIONS: IL-17A in the combination with TNF-α or IL-1ß showed a synergistic augmenting effect on IL-8 and GM-CSF production in human airway epithelial cells.

Membrane surface-enhanced Raman spectroscopy for sensitive detection of molecular behavior of lipid assemblies.

The dynamic properties of phospholipid (PL) membranes (phase state and phase transition) play crucial roles in biological systems. However, highly sensitive, direct analytical methods that shed light on the nature of lipids and their assemblies have not been developed to date. Here, we describe the analysis of PL-modified Au nanoparticles (Au@PL) using membrane surface-enhanced Raman spectroscopy (MSERS) and report the properties of the self-assembled PL membranes on the Au nanoparticle. The Raman intensity per PL concentration increased by 50-170 times with Au@PL, as compared to large unilamellar vesicles (LUVs) at the same PL concentration. The phase state and phase transition temperature of the PL membrane of Au@PL were investigated by analyzing the Raman peak ratio (R = I2882/I2930). The enhancement at 714 cm(-1) (EF(714)) varied with the hydrocarbon chain length of the PLs and the assembled degree of Au@PLs. In calculation, the EF(714),assembled was estimated to be 111-142 when the distance between AuNPs was 7.0-7.5 nm, which was correlated to the speculative enhancement factor, suggesting that the assembly of the Au@PLs contributed to the MSERS.

Rattle-type colloidal crystals composed of spherical hollow particles containing an anisotropic, movable core.

Controls over the position and orientation of anisotropic particles in their assemblies are intriguing issues for functional colloidal crystals that are switchable with external fields such as electric and magnetic fields. We propose a novel approach for the fabrication of rattle-type colloidal crystals containing an anisotropic, movable core surrounded by a void space that allows rearrangement of the anisotropic core in the assembly. In the fabrication, multilayered core-shell particles composed of a titania core, polystyrene shell, and silica shell were prepared and then heated at 500 °C for 4 h to selectively remove the middle layer of polystyrene. The heating treatment induced deformation of spherical titania cores in the compartment of silica shells, while the void space required for the orientation and relocation of anisotropic core was generated. The rattle particles fabricated were self-assembled by a simple dip-coating to form an arrangement of the spherical yolk/shell particles incorporating an anisotropic core. Brownian motion of the anisotropic cores observed with an optical microscope showed that the assembly of rattle-type particles had the potential to control location and orientation of the anisotropic cores in the shell compartment by application of external fields.

Magnetic field aligned assembly of nonmagnetic composite dumbbells in nanoparticle-based aqueous ferrofluid.

Monodisperse, nonmagnetic, asymmetrical composite dumbbells in a suspension of magnetic nanoparticles (ferrofluid) were aligned by application of an external magnetic field to the ferrofluid. The asymmetrical composite dumbbells were prepared by two-step soap-free emulsion polymerization consisting of the first polymerization to coat spherical silica cores with cross-linked poly(methyl methacrylate) (PMMA) shell and the second polymerization to protrude a polystyrene (PSt) lobe from the core-shell particles. A chain structure of nonmagnetic dumbbells oriented to the applied magnetic field was observed at nanoparticle content of 2.0 vol % and field strengths higher than 1.0 mT. A similar chain structure of the dumbbells was observed under application of alternating electric field at strengths higher than 50 V/mm. Parallel and orthogonally combined applications of the electric and magnetic fields were also conducted to examine independence of the electric and magnetic applications as operational factors in the dumbbell assembling. Dumbbell chains stiffer than those in a single application of external field were formed in the parallel combined application of electric and magnetic fields. The orthogonal combination of the different applied fields could form a magnetically aligned chain structure of the nonmagnetic dumbbells oriented to the electric field. The present work experimentally indicated that the employment of inverse magnetorheological effect for nonmagnetic, anisotropic particles can be a useful method for the simultaneous controls over the orientation and the positon of anisotropic particles in their assembling.

Clarithromycin ameliorates pulmonary inflammation induced by short term cigarette smoke exposure in mice.

BACKGROUND: Cigarette smoking is considered to be one of major causes of acute worsening of asthma as well as chronic obstructive pulmonary disease (COPD). Macrolide antibiotics have been reported to reduce the risk of exacerbations of COPD, and possibly neutrophilic asthma. However, the effect of clarithromycin (CAM) on pulmonary inflammation caused by short term exposure to cigarette smoke still remains to be investigated. METHODS: C57BL/6J female mice were daily exposed to tobacco smoke using a tobacco smoke exposure system, or clean air for 8 days, while simultaneously treated with either oral CAM or vehicles. Twenty four hours after the last exposure, mice were anaesthetized and sacrificed, and bronchoalveolar lavage (BAL) fluids were collected. Cellular responses in BAL fluids were evaluated. Levels of cytokine mRNA in the lung tissues were measured by quantitative RT-PCR. Paraffin-embedded lung tissues were evaluated to quantitate degree of neutrophil infiltration. RESULTS: The numbers of total cells, macrophages and neutrophils in the BAL fluid of smoke-exposed mice were significantly increased as compared to clean air group. These changes were significantly ameliorated in CAM-treated mice. The lung morphological analysis confirmed decrease of neutrophils by CAM treatment. Studies by quantitative PCR demonstrated CAM treatment significantly reduced lung expression levels of IL-17A, keratinocyte-derived chemokine (KC), granulocyte-macrophage colony stimulating factor (GM-CSF) and MMP-9 induced by cigarette smoke. CONCLUSION: We demonstrate that CAM administration resolves enhanced pulmonary inflammation induced by short term cigarette smoke exposure in mice.

Outcome of corticosteroid administration in autoimmune pulmonary alveolar proteinosis: a retrospective cohort study.

BACKGROUND: Although no report has demonstrated the efficacy of corticosteroid therapy for autoimmune pulmonary alveolar proteinosis (aPAP), we sometimes encounter patients who have received this therapy for various reasons. However, as corticosteroids can suppress alveolar macrophage function, corticosteroid therapy might worsen disease severity and increase the risk of infections. METHODS: For this retrospective cohort study, we sent a screening form to 165 institutions asking for information on aPAP patients treated with corticosteroids. Of the resulting 45 patients screened, 31 were enrolled in this study. We collected demographic data and information about corticosteroid treatment period, dose, disease severity score (DSS) over the treatment period, and complications. RESULTS: DSS deteriorated during corticosteroid therapy in 23 cases (74.1 %) and the estimated overall cumulative worsening rate was 80.8 % for the total observation period. The worsening rate was significantly higher in patients treated with high-dose prednisolone (>18.9 mg/day, n = 16) than treated with low-dose prednisolone (≤18.9 mg/day, n = 15) divided by median daily dose (p < 0.02). Of patients with worsening, one died of disseminated aspergillosis and another of respiratory failure. Infections newly emerged in 6 cases during corticosteroid therapy (p < 0.05). Median serum granulocyte/macrophage colony-stimulating factor (GM-CSF) autoantibody levels were similar to previously reported data in a large cohort study. CONCLUSION: The results demonstrate that corticosteroid therapy may worsen DSS of aPAP, increasing the risk for infections.