Loss of GD1-positive Lactobacillus correlates with inflammation in human lungs with COPD.

Objectives: The present study assesses the relationship between contents of GD1 (glycerol dehydratase)-positive Lactobacillus, presence of Lactobacillus and the inflammatory response measured in host lung tissue in mild to moderate chronic obstructive pulmonary disease (COPD). We hypothesise that there will be a loss of GD1 producing Lactobacillus with increasing severity of COPD and that GD1 has anti-inflammatory properties.

Setting: Secondary care, 1 participating centre in Vancouver, British Columbia, Canada.

Respiratory viral detection and small airway inflammation in lung tissue of patients with stable, mild COPD.

Background: Viral respiratory tract infections are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). In lung tissue specimens from patients with stable, mild COPD and from control smokers without airflow obstruction, we determined the prevalence and load of nucleic acid from common respiratory viruses and concomitant inflammation of small airways measuring less than 2-mm in diameter.

Methods: Frozen lung tissue obtained from patients with stable, mild COPD (n = 20) and control subjects (n = 20) underwent real-time quantitative PCR (qPCR) for 13 respiratory viruses, and quantitative histology for inflammation of small airways.

Proteomic identification of dysferlin-interacting protein complexes in human vascular endothelium.

Dysferlin is a membrane-anchored protein known to facilitate membrane repair in skeletal muscles following mechanical injury. Mutations of dysferlin gene impair sarcolemma integrity, a hallmark of certain forms of muscular dystrophy in patients. Dysferlin contains seven calcium-dependent C2 binding domains, which are required to promote fusion of intracellular membrane vesicles.

Myoferlin gene silencing decreases Tie-2 expression in vitro and angiogenesis in vivo.

Angiogenesis consists in the growth of new blood vessels from pre-existing ones. Although anti-angiogenesis interventions have been shown to have therapeutic properties in human diseases such as cancer, their effect is only partial and the identification of novel modulators of angiogenesis is warranted. Recently, we reported the unexpected proteomic identification in endothelial cells (EC) of Myoferlin, a member of the Ferlin family of transmembrane proteins.

The relationship between respiratory viral loads and diagnosis in children presenting to a pediatric hospital emergency department.

Background: respiratory viral infections account for a considerable proportion of pediatric emergency room visits. Illnesses range in severity from mild upper respiratory tract infections to serious lower respiratory tract infections (LRTI). The relationship between viral load and specific viruses to clinical diagnosis made by physicians in this setting is poorly understood.

A new role for the muscle repair protein dysferlin in endothelial cell adhesion and angiogenesis.

Objective: Ferlins are known to regulate plasma membrane repair in muscle cells and are linked to muscular dystrophy and cardiomyopathy. Recently, using proteomic analysis of caveolae/lipid rafts, we reported that endothelial cells (EC) express myoferlin and that it regulates membrane expression of vascular endothelial growth factor receptor 2 (VEGFR-2). The goal of this study was to document the presence of other ferlins in EC.

Toll-like receptor 4-mediated activation of p38 mitogen-activated protein kinase is a determinant of respiratory virus entry and tropism.

Respiratory viruses exert a heavy toll of morbidity and mortality worldwide. Despite this burden there are few specific treatments available for respiratory virus infections. Since many viruses utilize host cell enzymatic machinery such as protein kinases for replication, we determined whether pharmacological inhibition of kinases could, in principle, be used as a broad antiviral strategy for common human respiratory virus infections.

The nature of small-airway obstruction in chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is a major public health problem associated with long-term exposure to toxic gases and particles. We examined the evolution of the pathological effects of airway obstruction in patients with COPD.

Methods: The small airways were assessed in surgically resected lung tissue from 159 patients--39 with stage 0 (at risk), 39 with stage 1, 22 with stage 2, 16 with stage 3, and 43 with stage 4 (very severe) COPD, according to the classification of the Global Initiative for Chronic Obstructive Lung Disease (GOLD).