Symptom-related sputum microbiota in stable chronic obstructive pulmonary disease.

Background: The role of airway microbiota in COPD is highly debated. Symptomology assessment is vital for the management of clinically stable COPD patients; however, the link between symp toms and the airway microbiome is currently unknown.

Purpose: The present study aimed to evaluate the relationship among stable COPD patients.

Validation of the St. George's Respiratory Questionnaire in Nepal.

The St. George's Respiratory Questionnaire (SGRQ) is a standardized questionnaire for measuring impaired health and perceived well-being in chronic airway disease, but it is not available in the Nepali language. We translated the original SGRQ into Nepali and validated its use in 150 individuals aged 40 to 80 years with and without COPD.

Gender Disparities in Academic Practice.

Background: In academia, women remain underrepresented. The authors' sought to examine differences in faculty position and professional satisfaction among academic physicians by gender.

Methods: From 2008 to 2012, academic faculty members at a single institution were surveyed (2008, n = 737; 2010, n = 1151; and 2012, n = 971) regarding current position, choice of position, professional satisfaction, and desire for leaving.

[Preparation of metagenomic DNA from bronchoalveolar lavage fluids of patients with chronic obstructive pulmonary diseases].

Objective: To optimize the method of isolating a small amount of metagenomic DNA efficiently from bronchoalveolar lavage fluids (BALF) of patients with stable chronic obstructive pulmonary diseases (COPD) , which will facilitate subsequent PCR and DNA sequencing.

Methods: BALF (5mL) of stable COPD patients was spun down to collect the cells. To extract genomic DNA from Gram-positive bacteria more efficiently, QIAGEN's DNA extraction protocol was optimized as follows: Added Buffer ATL to the pellets and used bead tubes and tissue homogenizers to break cell walls; then added proteinase K and incubated; after adding Buffer AL and ethanol, pipetted the mixture into a DNeasy spin column then centrifuged; washed the column with Buffer AW1 and Buffer AW2, finally added 50 microL Buffer AE to elute DNA.

Use of direct gradient analysis to uncover biological hypotheses in 16s survey data and beyond.

This study investigated the use of direct gradient analysis of bacterial 16S pyrosequencing surveys to identify relevant bacterial community signals in the midst of a "noisy" background, and to facilitate hypothesis-testing both within and beyond the realm of ecological surveys. The results, utilizing 3 different real world data sets, demonstrate the utility of adding direct gradient analysis to any analysis that draws conclusions from indirect methods such as Principal Component Analysis (PCA) and Principal Coordinates Analysis (PCoA). Direct gradient analysis produces testable models, and can identify significant patterns in the midst of noisy data.

Regulation of alveolar epithelial cell apoptosis and pulmonary fibrosis by coordinate expression of components of the fibrinolytic system.

Alveolar type II (ATII) cell apoptosis and depressed fibrinolysis that promotes alveolar fibrin deposition are associated with acute lung injury (ALI) and the development of pulmonary fibrosis (PF). We therefore sought to determine whether p53-mediated inhibition of urokinase-type plasminogen activator (uPA) and induction of plasminogen activator inhibitor-1 (PAI-1) contribute to ATII cell apoptosis that precedes the development of PF. We also sought to determine whether caveolin-1 scaffolding domain peptide (CSP) reverses these changes to protect against ALI and PF.

Hepatocyte growth factor acts as a mitogen and chemoattractant for postnatal subventricular zone-olfactory bulb neurogenesis.

Neural progenitor cells persist throughout life in the forebrain subventricular zone (SVZ). They generate neuroblasts that migrate to the olfactory bulb and differentiate into interneurons, but mechanisms underlying these processes are poorly understood. Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic factor that influences cell motility, proliferation and morphogenesis in neural and non-neural tissues.

Activation of urokinase plasminogen activator and its receptor axis is essential for macrophage infiltration in a prostate cancer mouse model.

Macrophages within the tumor microenvironment promote angiogenesis, extracellular matrix breakdown, and tumor cell migration, invasion, and metastasis. Activation of the urokinase plasminogen activator (uPA) and its receptor (uPAR) axis promotes prostate cancer tumorigenicity, invasion, metastasis, and survival within the tumor microenvironment. The link between macrophage infiltration and the uPA/uPAR axis in prostate cancer development has not been established, although it has been reported that uPA plays a critical role inmonocyte and macrophage chemotaxis.

Predictors of job satisfaction among academic faculty members: do instructional and clinical staff differ?

Objectives: This study aimed to identify and compare predictors of job satisfaction between instructional and clinical faculty members.

Methods: A 61-item faculty job satisfaction survey was distributed to 1898 academic faculty members at the University of Michigan Medical School. The anonymous survey was web-based.

Induction of tissue factor by urokinase in lung epithelial cells and in the lungs.

Rationale: Urokinase-type plasminogen activator (uPA) regulates extracellular proteolysis in lung injury and repair. Although alveolar expression of uPA increases, procoagulant activity predominates.

Objectives: This study was designed to investigate whether uPA alters the expression of tissue factor (TF), the major initiator of the coagulation cascade, in lung epithelial cells (ECs).

The role of urokinase in idiopathic pulmonary fibrosis and implication for therapy.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and frequently fatal form of interstitial lung disease for which there are no proven drug therapies. The pathogenesis of IPF is complex and the urokinase-type plasminogen activator (uPA)/plasminogen system participates in the repair process. The balance between the activating enzyme uPA, and its inhibitor PAI-1, is a critical determinant of the amount of scar development that follows.

Current and emerging drugs for idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis is a chronic, progressive and often fatal form of interstitial lung disease. It is characterized by injury with loss of lung epithelial cells and abnormal tissue repair, resulting in abnormal accumulation of fibroblasts and myofibroblasts, deposition of extracellular matrix and distortion of lung architecture, leading to respiratory failure. This lethal lung disorder continues to pose major clinical challenges as an effective therapeutic regimen has yet to be developed.

New insights into the pathogenesis and treatment of idiopathic pulmonary fibrosis: a potential role for stem cells in the lung parenchyma and implications for therapy.

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and often fatal form of interstitial lung disease. It is characterized by injury with loss of lung epithelial cells and abnormal tissue repair, resulting in replacement of normal functional tissue, abnormal accumulation of fibroblasts and myofibroblasts, deposition of extracellular matrix, and distortion of lung architecture which results in respiratory failure. Despite improvements in the diagnostic approach to IPF and active research in recent years, the molecular mechanisms of the disease remain poorly understood.

Mactinin treatment promotes wound-healing-associated inflammation in urokinase knockout mice.

Mactinin, a 31 kDa fragment from the amino-terminal end of alpha-actinin, is chemotactic for monocytes and can promote monocyte/macrophage maturation. Macrophages are essential for wound healing, in which they play key roles in debridement, angiogenesis, fibroblast proliferation, and collagen metabolism. We have previously determined that urokinase is necessary to form mactinin from extracellular alpha-actinin, which may be present at sites of inflammation as a result of cell movement.

Induction of p53 by urokinase in lung epithelial cells.

Urokinase plasminogen activator (uPA) is a serine protease that catalyzes the conversion of plasminogen to plasmin. The plasminogen/plasmin system includes the uPA, its receptor, and its inhibitor (plasminogen activator inhibitor-1). Interactions between these molecules regulate cellular proteolysis as well as adhesion, cellular proliferation, and migration, processes germane to the pathogenesis of lung injury and neoplasia.

Urokinase-deficient and urokinase receptor-deficient mice have impaired neutrophil antimicrobial activation in vitro.

Leukocytes express both urokinase-type plasminogen activator (uPA) and the urokinase receptor (uPAR, CD87). We have shown that neutrophil recruitment to the lung during P. aeruginosa pneumonia is impaired in uPAR-deficient (uPAR-/-) mice but is normal in uPA-/- mice.

Pericellular proteolysis by leukocytes and tumor cells on substrates: focal activation and the role of urokinase-type plasminogen activator.

Previous studies have shown that the urokinase-type plasminogen activator receptor (uPAR) is localized to the adherence sites of leukocytes and tumor cells suggesting that pericellular proteolysis may accompany focal activation of adherence. To assess for focused pericellular proteolytic activity, we prepared two-dimensional substrates coated with FITC-casein or Bodipy FL-BSA. These molecules are poorly fluorescent, but become highly fluorescent after proteolytic degradation.

Urokinase-deficient mice fail to generate a type 2 immune response following schistosomal antigen challenge.

Activated lymphocytes express urokinase-type plasminogen activator (uPA). Previous work suggests that uPA modulates T-lymphocyte responses. Mice deficient in uPA (uPA(-/-)) fail to generate type 1 (T1) immune responses during infection with Cryptococcus neoformans.

Urokinase-type plasminogen activator potentiates lipopolysaccharide-induced neutrophil activation.

Urokinase plasminogen activator (uPA) is a serine protease that catalyzes the conversion of plasminogen to plasmin. Although increased circulating levels of uPA are present in endotoxemia and sepsis, conditions in which activated neutrophils contribute to the development of acute organ dysfunction, the ability of uPA to participate directly in LPS-induced neutrophil activation has not been examined. In the present experiments, we show that uPA can enhance activation of neutrophils exposed to submaximal stimulatory doses of LPS.

Urokinase is required for the formation of mactinin, an alpha-actinin fragment that promotes monocyte/macrophage maturation.

We have previously shown that lysates from HL-60 myeloid leukemia cells or from peripheral blood monocytes are able to degrade alpha-actinin to form a 31-kDa amino-terminal fragment with monocyte/macrophage maturation promoting activity. In contrast, intact alpha-actinin, which is a 100-kDa actin-binding protein, has no differentiating activity. The aim of this study was to investigate the enzyme responsible for the degradation of alpha-actinin to form this fragment, named mactinin.

Urokinase-type plasminogen activator is required for the generation of a type 1 immune response to pulmonary Cryptococcus neoformans infection.

Urokinase-type plasminogen activator (uPA)(-/-) mice cannot mount protective host defenses during infection with the opportunistic yeast Cryptococcus neoformans (52D). Because effective host defense against C. neoformans requires specific immune responses and the generation of type 1 (T1) cytokines, we determined how the absence of uPA impacts these processes.