Lysophosphatidic Acid Induces Allergic Inflammation

Background: Lysophosphatidic acid (LPA), a prototypic member of a large family of lysophospholipids, has been recently shown to play a role in immune responses to respiratory diseases. The involvement of LPA in allergic airway inflammation has been reported, but the mechanism remains unclear. Object: We analyzed the biological activity of LPA in vitro and in vivo and investigated its role in allergic inflammation in mice using an LPA receptor 2 (LPA2) antagonist. Methods: We used a murine model with acute allergic inflammation, in which mice are sensitized and challenged with house dust mite, and analyzed airway hyperresponsiveness (AHR), pathological findings, Th2 cytokines, and IL-33 in bronchoalveolar lavage fluid (BALF) and lung homogenates. The effect of LPA on Th2 differentiation and cytokine production was examined in vitro using naive CD4+ T cells isolated from splenocytes. We also investigated in vivo the effects of LPA on intranasal administration in mice. Results: The LPA2 antagonist suppressed the increase of AHR, the number of total cells, and eosinophils in BALF and lung tissue. It also decreased the production of IL-13 in BALF and IL-33 and CCL2 in the lung. LPA promoted Th2 cell differentiation and IL-13 production by Th2 cells in vitro. Nasal administration of LPA significantly increased the number of total cells and IL-13 in BALF via regulating the production of IL-33 and CCL-2-derived infiltrating macrophages. Conclusion: These findings suggest that LPA plays an important role in allergic airway inflammation and that the blockade of LPA2 might have therapeutic potential for bronchial asthma

A novel atrial volume reduction technique to enhance the Cox maze procedure: Initial results

ObjectiveLarge left atrial diameter is reported to be a predictor for recurrent atrial fibrillation after the Cox maze procedure, and left atrial diameter by itself influences the chance of sinus rhythm recovery, as well as maintenance of sinus rhythm. However, additional cut-and-sew procedures to decrease left atrial diameter extend operative time and can cause bleeding. Thus we developed a no-bleeding, faster, and therefore less invasive left atrial volume reduction technique to enhance the Cox maze procedure.MethodsThe modified Cox maze III procedure with cryoablation or the left atrial maze procedure in association with mitral valve surgery was performed in 80 patients with atrial fibrillation and enlarged left atria (≥60 mm). Among them, 44 patients had the concomitant volume reduction technique (VR group); continuous horizontal mattress sutures for left atrial plication were placed on the left atrial wall along the pulmonary vein isolation line. Cryoablation was applied to the suture line so that the plicated left atrium is anatomically and electrically isolated. Another 36 patients did not have the volume reduction technique (control group).ResultsThe VR group had preoperative left atrial diameters similar to those of the control group (67.1 ± 7.8 vs 64.5 ± 6.7 mm) and a longer preoperative duration of atrial fibrillation (14.1 ± 5.4 vs 9.5 ± 5.1 years, P < .05) but had smaller postoperative left atrial diameters (47.6 ± 6.3 vs 62.1 ± 7.9 mm, P < .01). There were no differences in mean crossclamp/bypass time and chest tube drainage for 12 hours between the groups. Twelve months after surgical intervention, the sinus rhythm recovery rate of the VR group was better than that of the control group (90% vs 69%, P < .05).ConclusionsEven in patients with long-standing atrial fibrillation and an enlarged left atrium, maze procedures concomitant with the novel left atrial volume reduction technique improved the sinus rhythm recovery rate without increasing complications. Although further study with a larger number of patients and a longer follow-up period is needed, this safe and thus far potent technique that catheter-based ablation cannot copy might extend indication of the Cox maze procedure for patients with tough atrial fibrillation

Singlet oxygen -derived nerve growth factor exacerbates airway hyperresponsiveness in a mouse model of asthma with mixed inflammation

Background: Refractory asthma, which is caused by several factors including neutrophil infiltration is a serious complication of bronchial asthma. We previously reported that nerve growth factor (NGF) is involved in AHR. NGF-derived induction of hyperalgesia is dependent on neutrophils; however, this relationship remains unclear in respiratory disease. In this study, we examined the roles of neutrophils and NGF in refractory asthma. Methods: Using intranasal house dust mite sensitization, we established a mouse model of asthma with mixed inflammation (Mix-in). AHR, NGF production and hyperinnervation of the lungs were examined with or without different inhibitory treatments. The levels of the singlet oxygen markers, 10- and 12-(Z,E)-hydroxyoctadecadienoic acids (HODE) in the lungs, were measured by liquid chromatography-tandem mass spectrometry. An in vitro experiment was also performed to evaluate the direct effect of singlet oxygen on NGF production. Results: NGF production and hyperinnervation were higher in Mix-in mice than in conventional eosinophilic-asthmatic mice and were positively correlated with AHR. Asthmatic parameters were inhibited by NGF neutralizing Abs and myeloperoxidase (MPO) inhibition. The 10- and 12-(Z,E)-HODEs levels were increased in the lungs and were positively correlated with MPO activity and NGF production. NGF was produced by bronchial epithelial cells in vitro upon stimulation with singlet oxygen. Conclusions: Our findings suggest that neutrophil MPO-derived singlet oxygen induces increased NGF production, leading to AHR and 10- and 12-(Z,E)-HODEs production. These findings may help to develop new therapies targeting this mechanism and to establish a new biomarker for non-type 2 and refractory asthma

COPD・肺がんの予防

Chronic obstructive pulmonary disease (COPD) is a long-standing, crippling disease characterized by the accelerated decline of lung function, commonly brought by aging and long-time inhalation of toxic chemicals such as tobacco smoking. Consequently, most COPD patients suffer from chronic cough, sputum and dyspnea on exertion. Moreover, in addition to the decline of lung function due to the destruction of the alveolar structure, COPD is closely related to other diseases such as osteoporosis, cardiovascular diseases, diabetes, muscle dysfuncion, and lung cancer. Therefore, COPD is currently recognized as a systemic disease that the comprehensive management and care are necessary. Although COPD represents an increasing burden throughout the world and is one of the major causes of death word-wide, the issue has been arisen that the recognition of COPD in the general society is still low, especially in Japan. On the other hand, lung cancer is a life-threatening disease with the leading cause of malignancy-related death world-wide, the etiology of which is also closely related to tobacco smoking. Because the pathogenesis and the mortality of COPD and lung cancer are closely related each other, the action to prevent these diseases could be made simultaneously, primarily by the smoking cessation and the detection survey. In this article, we describe the present situation of COPD and lung cancer, the importance of smoking cessation, and the effort of Tokushima City Medical Association to manage COPD in Tokushima

Interleukin (IL)-12 gene transduction and its functional expression into human bronchial epithelial cells (BEAS-2B) by adenovirus vector

Interleukin (IL)-12 is known as a cytokine that augments the Th1 type response. Especially in allergic diseases such as a bronchial asthma, IL-12 induced restoration of the balance of the Th1/Th2 type immune response is an attractive strategy. In this study, the functional properties of the human bronchial epithelial cell line (BEAS-2B) transduced by an adenoviral vector encoding the human IL-12 gene were examined. Adenovirus vectors, AxCAegfp and Ax1CIhp40ip35 were transduced into BEAS -2B cells. Wild and gene-transduced BEAS -2B cells were incubated and the concentrations of IL-12and IFN-γ produced by co-cultured lymphocytes in the supernatant were measured using ELISA. The expressions of surface adhesion molecules, such as CD54 and CD106 were analyzed using flow cytometry. The efficiency of transgene expression of BEAS-2B cells was in a multiplicity of infection(MOI)-dependent manner and at an MOI of 30, the efficiency was approximately 80%. The gene-modified BEAS-2B cells produced biologically active IL-12 in dose - and time-dependent manners. IL-12 gene transduction did not significantly affect the expression of adhesion molecules (CD 54, CD106 and HLA-A,B,C) by BEAS-2B cells. These results suggest that the IL-12 gene may be successfully transduced into human bronchial epithelial cells by adenoviral vector to express IL-12 activity in vivo

Loss of histone H4K20 trimethylation predicts poor prognosis in breast cancer and is associated with invasive activity

INTRODUCTION: Loss of histone H4 lysine 20 trimethylation (H4K20me3) is associated with multiple cancers, but its role in breast tumors is unclear. In addition, the pathological effects of global reduction in H4K20me3 remain mostly unknown. Therefore, a major goal of this study was to elucidate the global H4K20me3 level in breast cancer tissue and investigate its pathological functions. METHODS: Levels of H4K20me3 and an associated histone modification, H3 lysine 9 trimethylation (H3K9me3), were evaluated by immunohistochemistry in a series of breast cancer tissues. Univariate and multivariate clinicopathological and survival analyses were performed. We also examined the effect of overexpression or knockdown of the histone H4K20 methyltransferases, SUV420H1 and SUV420H2, on cancer-cell invasion activity in vitro. RESULTS: H4K20me3, but not H3K9me3, was clearly reduced in breast cancer tissue. A reduced level of H4K20me3 was correlated with several aspects of clinicopathological status, including luminal subtypes, but not with HER2 expression. Multivariate analysis showed that reduced levels of H4K20me3 independently associated with lower disease-free survival. Moreover, ectopic expression of SUV420H1 and SUV420H2 in breast cancer cells suppressed cell invasiveness, whereas knockdown of SUV420H2 activated normal mammary epithelial-cell invasion in vitro. CONCLUSIONS: H4K20me3 was reduced in cancerous regions of breast-tumor tissue, as in other types of tumor. Reduced H4K20me3 level can be used as an independent marker of poor prognosis in breast cancer patients. Most importantly, this study suggests that a reduced level of H4K20me3 increases the invasiveness of breast cancer cells in a HER2-independent manner

Super-responder to pirfenidone therapy in IPF

Background : Pirfenidone (PFD), an anti-fibrosis drug for idiopathic pulmonary fibrosis (IPF), suppresses disease progression and delays decline of forced vital capacity. However, this drug rarely makes marked improvement of pulmonary function, chest high-resolution computed tomography (HRCT) findings and hypoxia. Case presentation : A 59 year-old-man, who was a former smoker and had a history of alcoholic liver cirrhosis, developed exertional dyspnea and was referred to our hospital. HRCT showed honeycomb changes with surrounding ground-glass opacity (GGO) in a predominantly basal and subpleural distribution. He was diagnosed with IPF and the treatment with PFD was started. At 16 months after the start of treatment, the predicted forced vital capacity value markedly improved from 82.9% to 98.6%. His resting-state partial pressure of arterial oxygen while breathing room air increased from a minimum of 54.7 mmHg (at 2 months treatment) to 72.5 mmHg. The GGO observed at diagnosis disappeared in HRCT. But after 32 months of treatment, his general condition got worse gradually, and he died from chronic progression of IPF after 48 months of treatment. Conclusion : Our case suggests that a complication of chronic liver disease and the existence of GGO may be characteristics of super-responder to PFD treatment for IPF patients

Pressure effect on magnetic hysteresis parameters of single-domain magnetite contained in natural plagioclase crystal

金沢大学理工研究域地球社会基盤学系This study investigates pressure effects on the magnetic properties of non-interacting singledomain (SD) magnetite. Using a high-pressure cell specially designed for a Magnetic Property Measurement System, magnetic hysteresis measurements were conducted under high pressures of up to 1 GPa on natural plagioclase crystals containing much acicular SD magnetite. Coercivity and saturation magnetization were nearly constant with pressure, while saturation remanent magnetization and coercivity of remanence decreased with pressure at moderate rates of -8 per cent GPa-1 and -18 per cent GPa-1, respectively. These results suggest that temperature effects govern the magnetic behaviour of acicular SD magnetite grains in the middle and lower crusts. © The Authors 2015

New bleeding model of additives in a polypropylene film under atmospheric pressure

Many additives are commercially used to add more favorable qualities to films. The bleeding process by which the additive in a film comes to the surface is considered. A new bleeding model of additives in a polypropylene film under atmospheric pressure was investigated. Solubility and diffusion are found to be important for explaining this bleeding process. The solubilities and diffusion coefficients of higher fatty acid amides such as erucamide (13-cis-docosenamide) and behenamide (docosanamide) were determined between 40 and 70°C and the difference between the solubilities and the diffusion coefficients was discussed. The experimental results are explained more precisely by assuming two transport processes between the crystalline regions and the amorphous ones. © 2007 Wiley Periodicals, Inc