National Jewish Health

About: National Jewish Health is a healthcare organization based out in Denver, Colorado, United States. It is known for research contribution in the topics: T cell & Asthma. The organization has 883 authors who have published 833 publications receiving 79201 citations. The organization is also known as: National Jewish Medical and Research Center.

Platelet-activating factor triggers the phosphorylation and activation of MAP-2 kinase and S6 peptide kinase activity in human B cell lines.

Abstract: Platelet activating factor (PAF), a phospholipid mediator produced by a variety of cell types, has potent biological activities in many cellular systems. We report that stimulation of B cell lines with PAF induced tyrosine phosphorylation of a protein, approximately 42 kDa in size. The PAF receptor antagonist WEB 2086 as well as the structural analogue PAF antagonist CV3988 inhibited the response, demonstrating that the tyrosine phosphorylation was attributable to PAF binding to a specific receptor. Immunoblot analysis, using an antibody to microtubule-associated protein-2 kinase, demonstrated the presence of a single protein species in unstimulated cells. PAF treatment induced the appearance of an additional species with a slightly reduced mobility in the gel. This PAF-inducible band had the same mobility on SDS-PAGE gels as the protein that was tyrosine-phosphorylated after PAF stimulation. Tyrosine phosphorylation of the 42-kDa protein was rapid, detectable within 30 s, and evident over a wide range of PAF concentrations (10(-7) to 10(-10) M). Treatment of cells with phorbol myristate acetate induced tyrosine phosphorylation of a protein with the same mobility in SDS-PAGE gels as the protein induced after PAF stimulation. Lysates from PAF-stimulated lymphoblastoid cells exhibited more than twice the ability to phosphorylate myelin basic protein than lysates from untreated cells. In addition, the ribosomal S6 peptide kinase activity (S6PK) was increased after PAF stimulation of the B cells. Taken together, the results suggest that PAF stimulation of B cells induces the tyrosine phosphorylation and activation of microtubule-associated protein-2 kinase.

MUC5B variant is associated with visually and quantitatively detected preclinical pulmonary fibrosis

Abstract: Background Relatives of patients with familial interstitial pneumonia (FIP) are at increased risk for pulmonary fibrosis. We assessed the prevalence and risk factors for preclinical pulmonary fibrosis (PrePF) in first-degree relatives of patients with FIP and determined the utility of deep learning in detecting PrePF on CT. Methods First-degree relatives of patients with FIP over 40 years of age who believed themselves to be unaffected by pulmonary fibrosis underwent CT scans of the chest. Images were visually reviewed, and a deep learning algorithm was used to quantify lung fibrosis. Genotyping for common idiopathic pulmonary fibrosis risk variants in MUC5B and TERT was performed. Findings In 494 relatives of patients with FIP from 263 families of patients with FIP, the prevalence of PrePF on visual CT evaluation was 15.6% (95% CI 12.6 to 19.0). Compared with visual CT evaluation, deep learning quantitative CT analysis had 84% sensitivity (95% CI 0.72 to 0.89) and 86% sensitivity (95% CI 0.83 to 0.89) for discriminating subjects with visual PrePF diagnosis. Subjects with PrePF were older (65.9, SD 10.1 years) than subjects without fibrosis (55.8 SD 8.7 years), more likely to be male (49% vs 37%), more likely to have smoked (44% vs 27%) and more likely to have the MUC5B promoter variant rs35705950 (minor allele frequency 0.29 vs 0.21). MUC5B variant carriers had higher quantitative CT fibrosis scores (mean difference of 0.36%), a difference that remains significant when controlling for age and sex. Interpretation PrePF is common in relatives of patients with FIP. Its prevalence increases with age and the presence of a common MUC5B promoter variant. Quantitative CT analysis can detect these imaging abnormalities.

Air–Liquid Interface Culture of Human and Mouse Airway Epithelial Cells

Abstract: Air-liquid interface culture enables airway epithelial cells to differentiate into a pseudostratified cell layer, consisting of ciliated cells, goblet/secretory cells, and basal cells (Ghio et al., Part Fibre Toxicol 10:25, 2013). This technique is critically important for in vitro studies of lung diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis, since differentiated airway epithelial cells are more representative of the in vivo lung environment than non-differentiated cells (Derichs et al., FASEB J 25:2325-2332, 2011; Hackett et al., Am J Respir Cell Mol Biol 45:1090-1100, 2011;Schneider et al., Am J Respir Crit Care Med 182: 332-340, 2010). Here we describe the process of isolating and expanding human and mouse airway epithelial cells, as well as differentiation of airway epithelial cells by air-liquid interface culture.