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Chorioamnionitis is frequently associated with preterm deliveries before 30 weeks gestation. Chorioamnionitis correlates both with an increased risk of bronchopulmonary dysplasia and with a decreased risk of r...
Chronic obstructive pulmonary disease (COPD) is a significant cause of global morbidity and mortality. Previous studies have shown that COPD aggregates in families, suggesting a genetic predisposition to airfl...
The morbidity and mortality from asthma have markedly increased since the late 1970s. The hospitalization rate, an important marker of asthma severity, remains substantial.
Despite much information on their catalytic properties and gene regulation, we actually know very little of what matrix metalloproteinases (MMPs) do in tissues. The catalytic activity of these enzymes has been...
Respirable antisense oligonucleotides (RASONs), which attenuate specific disease-associated mRNAs, represent a new class of respiratory therapeutics with considerable potential. RASONs overcome previous obstac...
Glucocorticoids (GCs) are routinely used as anti-inflammatory drugs in the treatment of asthma. They act through binding to glucocorticoid receptor α (GRα), which represses numerous genes encoding pro-inflamma...
The human lysosomal cysteine proteases are a family of 11 proteases whose members include cathepsins B, C, H, L, and S. The biology of these proteases was largely ignored for decades because of their lysosomal...
Although bronchogenic carcinomas progress through a very well defined sequence of metaplasia, dysplasia and carcinoma in situ, very little is known about the early progression of glandular neoplasms of the lung. ...
The increase in numbers of adults with cystic fibrosis (CF) has allowed us to identify previously unrecognized chronic complications of CF, as well as appreciate unique presentations of cystic fibrosis-related...
The transcription factors nuclear factor interleukin-6 (NF-IL6), early growth response-1 (EGR-1) and hypoxia-inducible factor-1 (HIF-1) have important roles in the molecular pathophysiology of hypoxia-associat...
Since their discovery 15 years ago, the role of γδ T cells has remained somewhat elusive. Responses of γδ T cells have been found in numerous infectious and non-infectious diseases. New evidence points to γδ T...
Deficient microbial stimulation of the immune system, caused by hygiene, may underly the atopy and allergic asthma epidemic we are currently experiencing. Consistent with this 'hygiene hypothesis', research on...
One component of host defense at mucosal surfaces seems to be epithelium-derived antimicrobial peptides. Antimicrobial peptides are classified on the basis of their structure and amino acid motifs. Peptides of...
Many pulmonary diseases preferentially affect the large airways or the alveoli. Although the mechanisms are often particular to each disease process, site-specific differences in leukocyte trafficking and the ...
Regeneration and restoration of the airway epithelium after mechanical, viral or bacterial injury have a determinant role in the evolution of numerous respiratory diseases such as chronic bronchitis, asthma an...
The identification of the cystic fibrosis (CF) gene opened the way for gene therapy. In the ten years since then, proof of principle in vitro and then in animal models in vivo has been followed by numerous clinic...
The lung is the product of a set of complex developmental interactions between two distinct tissues, the endodermally derived epithelium and the mesoderm. Each tissue contributes to lung development by fine-tu...
The acute respiratory distress syndrome (ARDS) is an inflammatory disease of the lungs characterized clinically by bilateral pulmonary infiltrates, decreased pulmonary compliance and hypoxemia. Although suppor...
Surfactant protein-D (SP-D) participates in the innate response to inhaled microorganisms and organic antigens, and contributes to immune and inflammatory regulation within the lung. SP-D is synthesized and se...
Secretory leukocyte proteinase inhibitor and elafin are two low-molecular-mass elastase inhibitors that are mainly synthesized locally at mucosal sites. It is thought that their physicochemical properties allo...
Inflammatory diseases of the respiratory tract are commonly associated with elevated production of nitric oxide (NO•) and increased indices of NO• -dependent oxidative stress. Although NO• is known to have ant...
Over the past decade there has been a significant shift to the use of murine models for investigations into the molecular basis of respiratory diseases, including asthma and chronic obstructive pulmonary disea...
Asthma is a complex inflammatory disorder controlled by both genetic and environmental influences. Multiple genetic analyses have identified the T helper type 2 (Th2) cytokine gene cluster on chromosome 5q as ...
Airway hyper-reactivity is a characteristic feature of many inflammatory lung diseases and is defined as an exaggerated degree of airway narrowing. Chemokines and their receptors are involved in several pathol...
Recombinant adeno-associated virus (rAAV) vectors mediate long-term gene transfer without any known toxicity. The primary limitation of rAAV has been the small size of the virion (20 nm), which only permits th...
The cellular and molecular mechanisms that are involved in airway hyper-responsiveness are unclear. Current studies suggest that tumor necrosis factor (TNF)-α, a cytokine that is produced in considerable quant...
Activity of voltage-gated potassium (Kv) channels controls membrane potential, which subsequently regulates cytoplasmic free calcium concentration ([Ca2+]cyt) in pulmonary artery smooth muscle cells (PASMCs). Acu...
PM10 (the mass of particles present in the air having a 50% cutoff for particles with an aerodynamic diameter of 10 μm) is the standard measure of particulate air pollution used worldwide. Epidemiological studies...
The medical research community is experiencing a marked increase in the amount of information available on genomic sequences and genes expressed by humans and other organisms. This information offers great opp...
The limitations of currently available treatment for severe respiratory infection are demonstrated by the relatively fixed mortality associated with these infections despite advances in nutrition, vaccines, an...
The interleukin-4 (IL-4) signalling cascade has been identified as a pathway potentially important in the development of asthma. Genetic variants within this signalling pathway might contribute to the risk of ...
The hedgehog signalling pathway has been implicated in many different processes in fly and vertebrate development. It is now known that the hedgehog cascade is crucial for the patterning of the early respirato...
Idiopathic pulmonary fibrosis (IPF) is a condition that has a poor prognosis, with a median survival of 4-5 years irrespective of treatment. Ziescheet al (N Engl J Med 1999,341: 1264-1269) describe an open random...
Phosphoinositide 3-kinases (PI-3Ks) are enzymes that generate lipid second messenger molecules, resulting in the activation of multiple intracellular signalling cascades. These events regulate a broad array of...
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