Distribution of Fodrin in the Keratinocyte In Vivo and In Vitro

Distribution of fodrin in the keratinocyte, both in vivo and in vitro, was examined by immunofluorescence microscopy. In the rat epidermis in vivo, fodrin was localized in the cell periphery of the spinous layer of all the skins studied. In only the basal layer of the thick skin, however, fodrin was seen intensely in the cytoplasm. As in vitro keratinocytes, a mouse cell line (Pam 212) cultured in low (0.06 mM) as well as standard (1.87 mM) Ca2+ was examined. In low Ca2+, fodrin was observed throughout the cytoplasm without marked accumulation irrespective of the cell density. The cytoplasmic labeling in low Ca2+ looked filamentous and became aggregated when cells were treated with cytochalasin B; at least some of the aggregates coexisted with those of F-actin. In contrast, fodrin distribution was not affected with colchicine. On the other hand, in standard Ca2+, the protein became concentrated along the cell periphery and less conspicuous in the cytoplasm as the cells reached confluency. When cells were transferred from low to standard Ca2+, the distribution of fodrin changed accordingly within 180min. The present results indicate that fodrin in the keratinocyte is likely to be associated with actin filaments and that it takes two different ways of distribution both in vivo and in vitro. The peripheral and the cytoplasmic labeling of in vivo and in vitro cells are likely to correspond. It may be that fodrin changes its localization according to the cell's proliferative activity

Further Evidence for the ~ 9 s Pulsation in LS 5039 from NuSTAR and ASCA

The present study aims to reinforce the evidence for the ~9 s pulsation in the gamma-ray binary LS 5039, derived with a Suzaku observation in 2007 and that with NuSTAR in 2016 (Yoneda et al 2000). Through a reanalysis of the NuSTAR data incorporating the orbital Doppler correction, the 9.0538 s pulsation was confirmed successfully even in the 3--10 keV range, where it was undetectable previously. This was attained by perceiving an energy-dependent drift in the pulse phase below 10 keV, and correcting the pulse timing of individual photons for that effect. Similarly, an archival 0.7--12 keV data set of LS 5039, taken with the ASCA GIS in 1999 October, was analyzed. The data showed possible periodicity at about 8.882 s, but again the energy-dependent phase drift was noticed below 10 keV. By correcting for this effect, and for the orbital Doppler delays in the LS 5039 system, the 2.8--12 keV periodicity became statistically significant at 8.891+- 0.001 s. The periods measured with ASCA, Suzaku, and NuSTAR approximately follow an average period derivative of dP/dt = 3.0 e-10 s/s. These results provide further evidence for the pulsation in this object, and strengthen the scenario by (Yoneda et al 2000), that the compact object in LS 5039 is a strongly magnetized neutron star.Comment: 20 pages, 16 figures, accepted for publication in The Astrophysical Journa

Effect of human airway trypsin-like protease on intracellular free Ca2+ concentration in human bronchial epithelial cells

It has been shown that human airway trypsin-like protease (HAT) is localized in human bronchial epithelial cells (HBEC), and trypsin activates protease-activated receptor-2(PAR-2). Activation of PAR-2 activates G-protein followed by an increase of intracellular free Ca2+, [Ca2+]in. This study was undertaken to clarify whether HAT can activate PAR-2in HBEC or not. RT-PCR showed that HAT mRNA is expressed in HBEC, and PAR-2 mRNA is the most strongly expressed of the known PARs in HBEC. Both PAR-2 agonist peptide (PAR-2 AP) and HAT increased [Ca2+]in in HBEC in a biphasic fashion a prompt, sharp increase (peak I) and a sustained low plateau (peak II). PAR-2 AP over 100-200 μM and HAT over 200-300 mU/ml (0.08-0.12 μM) induced both peak I and II, and PAR-2 AP below100 μM and HAT below 200 mU/ml induced only peak II. Both PAR-2 AP-induced and　HAT-induced peak I were induced by Ca2+ mobilization from intracellular stores, because　they appeared even in Ca2+-free medium. Both PAR-2 AP-induced and HAT-induced peak II were induced by an influx of extracellular Ca2+, because they were abolished in Ca2+-free medium. The Ca2+ response to HAT was desensitized by exposure of HBEC to PAR-2 AP. These results indicate that HBEC have a functional PAR-2, and HAT regulates cellular functions of HBEC via activation of PAR-2

キカンシ ゼンソク ゾウカ ノ ヨウイン ト サイキン ノ チリョウ ノ トピックス

Increasing asthma prevalence is a major problem in Western countries. Various factors, such as allergic sensitization to indoor allergens, change in incidence in infectious diseases, and increase of air pollutants, are considered to be possible factors for increasing prevalence. Inhaled corticosteroids play an important role in asthma treatment, and its impact on asthma morbidity and mortality has already been established. In addition, recent attention has been focused on molecular targeted therapy in the treatment of bronchial asthma. Promising results of anti-IgE antibody are reported in several clinical trials and anti-CD23 antibody is now introduced in clinical trials

Imatinib ameliorates bronchiolitis obliterans via inhibition of fibrocyte migration and differentiation

Background: Imatinib, a tyrosine kinase inhibitor, has been proposed as a potential anti-fibrotic agent for fibroproliferative diseases, including bronchiolitis obliterans (BO). However, the underlying anti-fibrotic mechanisms of the agent remain unclear. We evaluated whether bone (BM)-derived progenitor cells, fibrocytes, might be a target of imatinib in the attenuation of BO. Methods: We used a murine BO model induced by heterotopic tracheal transplantation and assessed the origin of fibroblasts by using green fluorescent protein-BM chimeric mice. We also evaluated the effects of imatinib on luminal obstruction and fibrocyte accumulation. The effects of imatinib on fibrocyte migration and differentiation were assessed by culturing fibrocytes in vitro. Results: In the murine BO model, tracheal allografts showed epithelial injury and developed complete luminal occlusion 28 days after transplantation. Most of the mesenchymal cells that had accumulated in the tracheal allograft were derived from BM cells. Imatinib treatment ameliorated the airway luminal occlusion and significantly reduced the number of fibrocytes in the allografts. In vitro studies showed that imatinib inhibited migration of cultured blood fibrocytes via the platelet-derived growth factor/platelet-derived growth factor receptor axis. Imatinib also inhibited differentiation of fibrocytes via suppression of c-Abl activity that was essential for the differentiation of monocytes to fibrocytes. Conclusions: Imatinib prevents airway luminal obstruction by inhibiting the migration and differentiation of fibrocytes. Fibrocytes may be a novel target in the prevention and treatment of BO. © 2016 International Society for Heart and Lung Transplantation.Embargo Period 12 month

Inhaled steroid therapy and hospitalization for bronchial asthma : trend in Tokushima University Hospital

With the recognition that airway inflammation is present even in patients with mild bronchial asthma, therapy with inhaled corticosteroids is now indicated in various stages of patients. In the present article, we retrospectively examined the prescriptions for inhaled corticosteroids and other drugs for the treatment of outpatients with bronchial asthma at Tokushima University Hospital. We also analyzed asthma control in these patients, in terms of the incidence of emergency consultations and hospitalizations due to asthma exacerbations. To analyze the recent trend, the patients observed from 1998 to 2000 (recent years) were included, and for control purpose, those in 1990 and 1991 (earlier years) were also included. The percentage of patients treated with inhaled corticosteroids remarkably increased in recent years (mean 81.3%) compared to earlier years (mean 23.5%). In contrast, the usage of oral corticosteroids, oral xanthine derivatives, β2-adrenergic receptor agonists and anti-allergic agents tended to decrease in the 10 years period. After the introduction in 1995, considerable patients up to 25% have been treated with anti-leukotrienes. Emergency consultations decreased in recent years (mean 0.18/patient/year) compared to earlier years (mean 0.79/patient/year). Emergency hospitalizations also decreased in recent years (mean 0.043/patient/year) compared to earlier years (mean 0.23/patient/year).In the present study, spread of inhaled corticosteroid therapy and decline in incidence of emergency consultation and hospitalization were simultaneously observed at Tokushima University Hospital, and the former has, at least in part, a contribution to the latter