Outpatient management of patients following pulmonary embolism.

Pulmonary embolus is a common reason for hospitalization and requires close follow-up and management in the office setting. The main issues facing the clinician include determination of the appropriate anticoagulation regimen, how long to anticoagulate, and whether an evaluation for hypercoagulable states is indicated. The decisions will depend on individual patient factors and assessment of the risks and benefits for that patient.

Adenosine promotion of cellular migration in bronchial epithelial cells is mediated by the activation of cyclic adenosine monophosphate-dependent protein kinase A.

Migration of neighboring cells into the injury is important for rapid repair of damaged airway epithelium. We previously reported that activation of the A(2A )receptors (A(2A)ARs) mediates adenosine-stimulated epithelial wound healing, suggesting a role for adenosine in migration. Because A(2A)AR increases cyclic adenosine monophosphate (cAMP) levels in many cells, we hypothesized that cAMP-dependent protein kinase A (PKA) is involved in adenosine-mediated cellular migration.

Adenosine A2A receptors promote adenosine-stimulated wound healing in bronchial epithelial cells.

Adenosine produces a wide variety of physiological effects through the activation of specific adenosine receptors (A(1), A(2A), A(2B), A(3)). Adenosine, acting particularly at the A(2A) adenosine receptor (A(2A)AR), is a potent endogenous anti-inflammatory agent and sensor of inflammatory tissue damage. The complete healing of wounds is the final step in a highly regulated response to injury.

TGF-beta1 and serum both stimulate contraction but differentially affect apoptosis in 3D collagen gels.

Apoptosis of fibroblasts may be key for the removal of cells following repair processes. Contraction of three-dimensional collagen gels is a model of wound healing and remodeling. Here two potent inducers of contraction, TGF-beta1 and fetal calf serum (FCS) were evaluated for their effect on fibroblast apoptosis in contracting collagen gels.

Malondialdehyde-acetaldehyde adducts decrease bronchial epithelial wound repair.

Most people who abuse alcohol are cigarette smokers. Previously, we have shown that malondialdehyde, an inflammation product of lipid peroxidation, and acetaldehyde, a component of both ethanol metabolism and cigarette smoke, form protein adducts that stimulate protein kinase C (PKC) activation in bronchial epithelial cells. We have also shown that PKC can regulate bronchial epithelial cell wound repair.

Alcohol intake is associated with altered pulmonary function.

Little is known about the effect of moderate alcohol intake on lung function in the general population. Because moderate alcohol intake appears to reduce cardiovascular disease risk, we hypothesized that moderate alcohol intake is associated with better pulmonary function. To test this hypothesis, we examined the association between alcohol intake and pulmonary function, measured by spirometry, in a representative sample of U.

Pathogenesis of COPD.

Chronic obstructive pulmonary disease (COPD) is characterized and defined by limitation of expiratory airflow. This can result from several types of anatomical lesions, including loss of lung elastic recoil and fibrosis and narrowing of small airways. Inflammation, edema, and secretions also contribute variably to airflow limitation.

Tumor necrosis factor-alpha hyper-responsiveness to endotoxin in whole blood is associated with chronic bronchitis in farmers.

Many farmers experience chronic bronchitis, airflow obstruction, and asthma. It is thought that these respiratory problems may be related to workplace inhalation of organic dust containing endotoxin. The purpose of this study was to determine whether whole blood cytokine responsiveness to endotoxin is associated with airflow disorders (i.

Ethanol treatment reduces bovine bronchial epithelial cell migration.

Background: Chronic ethanol abuse is associated with significant lung disease. Excessive alcohol intake increases risk for a variety of respiratory tract diseases, including pneumonia and bronchitis. Damage to airway epithelium is critical to the pathogenesis of airway disorders such as chronic bronchitis and chronic obstructive pulmonary disease.

Ethanol increases phosphodiesterase 4 activity in bovine bronchial epithelial cells.

Ethanol exposure in airway epithelium increases cyclic AMP (cAMP)-dependent protein kinase (PKA) activity. Activation of PKA and cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) has been shown to increase ciliary beat frequency (CBF) in bovine bronchial epithelial cells (BBECs). We have shown that biologically relevant concentrations of ethanol stimulate increases in CBF in a nitric oxide-dependent manner, mediated through elevated cAMP levels and subsequent PKA activation.

Gamma radiation inhibits fibroblast-mediated collagen gel retraction.

Radiation exposure is known to impair healing in irradiated areas. Fibroblasts play a major role in the production and modification of extracellular matrix in wound repair. Since one important aspect of wound repair is the contraction of the wound, this study investigated the effects of radiation on the ability of fibroblasts to mediate collagen gel contraction in an in vitro model of wound retraction.

Agricultural lung disease.

Agricultural work is associated with high rates of injury, disability, and illness. Agricultural workers are at increased risk for a variety of illnesses including respiratory disorders, dermatologic conditions, and cancer. The recognition of ODTS led to increased understanding of acute illness in farmers and grain workers.

Relaxin stimulates bronchial epithelial cell PKA activation, migration, and ciliary beating.

Relaxin is an insulin-like serum protein secreted during pregnancy and found in many tissues, including the lung. Relaxin is reported to stimulate epithelial cell proliferation, but the effects of relaxin on airway epithelium are unknown. We tested the hypothesis that relaxin would stimulate the increased migration of bronchial epithelial cells (BEC) in response to wounding.

Effect of cigarette smoke on fibroblast-mediated gel contraction is dependent on cell density.

Cigarette smoke exposure has been associated with a variety of diseases, including emphysema. The current study evaluated the interaction of cell density and cigarette smoke extract (CSE) on fibroblast contraction of collagen gels. Protein levels of transforming growth factor (TGF)-beta1, fibronectin, PGE(2), and TGF-beta1 mRNA were quantified.

Activation of protein kinase A accelerates bovine bronchial epithelial cell migration.

Bronchial epithelial cell migration is required for the repair of damaged airway epithelium. We hypothesized that bronchial epithelial cell migration during wound repair is influenced by cAMP and the activity of its cyclic nucleotide-dependent protein kinase, protein kinase A (PKA). We found that, when confluent monolayers of bronchial epithelial cells are wounded, an increase in PKA activity occurs.

Interleukin-4- and interleukin-13-enhanced transforming growth factor-beta2 production in cultured human bronchial epithelial cells is attenuated by interferon-gamma.

Cytokines derived from lymphocytes are believed to play key roles in a variety of diseases, including airway diseases such as asthma. The current study was designed to evaluate the hypothesis that cytokines derived from Th2 cells, interleukin (IL)-4 and IL-13, might contribute to tissue remodeling by modulating the production of transforming growth factor (TGF)-beta. In addition, the ability of interferon (IFN)-gamma, a cytokine derived from Th1 cells that can antagonize many effects of IL-4 and IL-13, was also assessed for its effects on TGF-beta production.

Cigarette smoke inhibits human bronchial epithelial cell repair processes.

By interfering with the ability of airway epithelial cells to support repair processes, cigarette smoke could contribute to alterations of airway structures and functions that characterize chronic obstructive pulmonary disease (COPD). The current study assessed the ability of cigarette smoke extract (CSE) to alter human airway epithelial cell chemotaxis, proliferation, and contraction of three-dimensional collagen gels, a model of extracellular matrix remodeling. The volatile components contained in cigarette smoke, acetaldehyde and acrolein, were able to inhibit all three processes.

Retinoic acid attenuates cytokine-driven fibroblast degradation of extracellular matrix in three-dimensional culture.

Proteolytic degradation of extracellular matrix is thought to play an important role both in emphysema and in tissue development and repair. Retinoic acid has been suggested to modify tissue injury, and in an animal model of emphysema may induce alveolar repair. Since cytokines can induce matrix metalloproteinase (MMP) production in fibroblasts and neutrophil elastase (NE) can activate MMPs, we hypothesized that retinoic acid could attenuate collagen degradation by modifying MMP production and activation.

Prostaglandin E(2) inhibits fibroblast chemotaxis.

Fibroblasts are the major source of extracellular connective tissue matrix, and the recruitment, accumulation, and stimulation of these cells are thought to play important roles in both normal healing and the development of fibrosis. Prostaglandin E(2) (PGE(2)) can inhibit this process by blocking fibroblast proliferation and collagen production. The aim of this study was to investigate the inhibitory effect of PGE(2) on human plasma fibronectin (hFN)- and bovine bronchial epithelial cell-conditioned medium (BBEC-CM)-induced chemotaxis of human fetal lung fibroblasts (HFL1).

Synergistic neutrophil elastase-cytokine interaction degrades collagen in three-dimensional culture.

Proteolytic degradation of extracellular matrix is thought to play an important role in many lung disorders. In the current study, human lung fibroblasts were cast into type I collagen gels and floated in medium containing elastase, cytomix (combination of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma), or both. After 5 days, gel collagen content was determined by measuring hydroxyproline.

Cytokine inhibition of fibroblast-induced gel contraction is mediated by PGE(2) and NO acting through separate parallel pathways.

Contraction of three-dimensional collagen gels is a model of the contraction that characterizes normal healing and remodeling after injury. In the current study, we evaluated the hypothesis that a number of inflammatory factors, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and interferon (IFN)-gamma, modulate this process by induction of prostaglandin (PG) E(2) and nitric oxide (NO) production and that these secondary mediators function in an autocrine or paracrine manner to modulate contraction. Human fetal lung fibroblasts (HFL) were cultured in type I collagen gels and floated in medium containing TNF-alpha, IL-1 beta, or IFN-gamma alone or in combination (cytomix).