IL-4–producing basophils promote the trapping of N. brasiliensis in the skin during secondary infection, a process critical for limiting the spread of infection to the lungs.
Developmental processes of hematopoietic cells are orchestrated by transcriptional networks. GATA-1, the founding member of the GATA family of transcription factors, has been demonstrated to play crucial roles in the differentiation of erythroid cells, magakaryocytes, eosinophils, and mast cells. However, the role of GATA-1 in basophils remains elusive. Here we show that basophils abundantly express Gata1 mRNAs, and that siRNA-mediated knockdown of Gata1 resulted in impaired production of IL-4 by basophils in response to the stimulation with IgE plus antigens. ΔdblGATA mice that carry the mutated Gata1 promoter and are widely used for functional analysis of eosinophils owing to their selective loss of eosinophils showed a decreased number of basophils with reduced expression of Gata1 mRNAs. The number of basophil progenitors in bone marrow was reduced in these mice, and the generation of basophils from their bone marrow cells in culture with IL-3 or thymic stromal lymphopoietin was impaired. ΔdblGATA basophils responded poorly ex vivo to stimulation with IgE plus antigens compared with wild-type basophils as assessed by degranulation and production of IL-4 and IL-6. Moreover, ΔdblGATA mice showed impaired responses in basophil-mediated protective immunity against intestinal helminth infection. Thus, ΔdblGATA mice showed numerical and functional aberrancy in basophils in addition to the known deficiency of eosinophils. Our findings demonstrate that GATA-1 plays a key role in the generation and function of basophils and underscore the need for careful distinction of the cell lineage responsible for each phenotype observed in ΔdblGATA mice.
Background: Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonias (IIPs) of unknown etiology that often affects male, elderly smokers. However, it is sometimes observed in never smokers. This study aimed to clarify the clinical characteristics of IPF in never-smoking patients compared with those in smoking patients.
Methods:We retrospectively reviewed medical records, pulmonary function tests, and chest highresolution computed tomography (HRCT) scan of never-smoking and smoking IPF patients from July 1, 2008 to June 30, 2013 at our hospital.Results: We identified 32 never-smoking IPF patients and 66 smoking IPF patients. Never-smoking IPF patients developed more acute exacerbation (AE) than smoking IPF patients (50% vs. 18.2%, P<0.0001).
Conclusions:In conclusion, never-smoking IPF patients developed AE more often and showed poor prognosis compared with smoking IPF patients. The 1-year mMRC breathlessness scale was an important predictor of mortality at our hospital.
Aims and Scope Eurasian Journal of Medicine (Eurasian J Med) is an international, scientific, open access periodical published by independent, unbiased, and tripleblinded peer-review principles. The journal is the official publication of
Nontuberculous mycobacteria (NTM) lung disease is increasing globally. Although the etiological epidemiology of NTM is different across regions, Mycobacterium avium complex (MAC) is the leading cause of NTM lung disease in most countries, including mainland Japan. Okinawa is located in the southernmost region of Japan and is the only prefecture categorized as a subtropical region in Japan, it is therefore likely the etiological epidemiology of NTM lung disease is different from mainland Japan. From 2009 to 2015, the medical records of patients, with respiratory specimens positive for NTMs, visiting or admitted to two Okinawan hospitals, were retrospectively analyzed. NTM lung disease cases were defined according to the American Thoracic Society criteria and patient epidemiology and clinical information were evaluated. Results indicate four hundred sixteen patients had bacterial cultures positive for NTM. The most common NTM was M. abscessus complex (MABC) (n = 127; 30.5%), followed by M. intracellulare (n = 85; 20.4%). NTM lung disease was diagnosed in 114 patients. Of these cases, MABC was most common (n = 41; 36.0%), followed by M. intracellulare (n = 31; 27.2%). Chronic obstructive pulmonary disease (COPD) and tracheostomy patients were more likely to develop MABC than MAC lung disease. Multivariate analysis showed a probable association between COPD and MABC lung disease. Chest computed tomography (CT) evaluation revealed bronchiectasis, nodules, and consolidation were less frequently observed in MABC patients compared with MAC patients. Our data suggests Okinawa may be one of the few places where MABC is the predominant pathogen causing NTM lung disease and our results add new insight to MABC lung disease, which is not yet well understood.
Background : Dermatomyositis (DM) and polymyositis (PM) often have association with interstitial lung disease (ILD) which have disease specific autoantibody. Methodology : We reviewed medical records of DM/PM associated ILD from January 2000 to December 2017 according to the autoantibody. Result : We identified 52 patients, of whom 30 were antibody negative, 18 had anti aminoacyl-tRNA synthetases (ARS) antibodies and 4 had anti melanoma differentiation-associated gene (MDA)-5 antibody. In high resolution computed tomography (HRCT) of the chest, area of ground glass opacity (GGO), consolidation, and lung tip consolidation were more extensive in anti MDA-5 antibody positive patients (p=0.051, p=0.026, and p=0.027, respectively). Among laboratory findings, GOT had strong correlations with CPK (r=0.889, p 0.001), and LDH (r=0.910, p 0.001). Among roentgenographic findings, there were moderate correlations between GGO and consolidation (r=0.668, p 0.001), and between reticular shadow and traction bronchiectasis (p=0.633, p 0.001). ILD patients with anti MDA-5 antibodies had decreased survival (1.00 vs 84.3, 22.9 months, p 0.001). Conclusion : ILD patients with anti ARS antibody had intense inflammation, but reversible fibrosis and good prognosis. On the other hand, anti MDA-5 antibody positive ILD patients had shorter survival. Extent of parenchymal shadow and serum GOT were useful indicator of disease activity of PM/DM associated ILD patients in our cohort.
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