Randall O Dull

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We investigated the nonlinear dynamics of the pressure vs. hydraulic conductivity (L(p)) relationship in lung microvascular endothelial cells and demonstrate that heparan sulfates, an important component of the endothelial glycocalyx, participate in pressure-sensitive mechanotransduction that results in barrier dysfunction. The pressure vs. L(p)(More)
The mechanical properties of endothelial glycocalyx were studied using atomic force microscopy with a silica bead (diameter ∼18 μm) serving as an indenter. Even at indentations of several hundred nanometers, the bead exerted very low compressive pressures on the bovine lung microvascular endothelial cell (BLMVEC) glycocalyx and allowed for an averaging of(More)
The endothelial glycocalyx is believed to play a major role in microvascular permeability. We tested the hypothesis that specific components of the glycocalyx, via cytoskeletal-mediated signaling, actively participate in barrier regulation. With the use of polymers of arginine and lysine as a model of neutrophil-derived inflammatory cationic proteins, we(More)
BACKGROUND Acute lung injury (ALI) is associated with high mortality due to the lack of effective therapeutic strategies. Mechanical ventilation itself can cause ventilator-induced lung injury. Pulmonary vascular barrier function, regulated in part by Src kinase-dependent phosphorylation of caveolin-1 and intercellular adhesion molecule-1 (ICAM-1), plays a(More)
INTRODUCTION Severe sepsis is associated with approximately 50% mortality and accounts for tremendous healthcare costs. Most patients require ventilatory support and propofol is commonly used to sedate mechanically ventilated patients. Volatile anesthetics have been shown to attenuate inflammation in a variety of different settings. We therefore(More)
Angiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell(More)
BACKGROUND Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, as well as in reproductive functions, is expressed as a type-1 membrane glycoprotein on the surface of endothelial and epithelial cells. ACE also presents as a soluble form in biological fluids, among(More)
Simvastatin, an HMG-CoA reductase inhibitor, has lung vascular-protective effects that are associated with decreased agonist-induced integrin β4 (ITGB4) tyrosine phosphorylation. Accordingly, we hypothesized that endothelial cell (EC) protection by simvastatin is dependent on these effects and sought to further characterize the functional role of ITGB4 as a(More)
BACKGROUND Matrix-metalloproteinases (MMP) and cancer cell invasion are crucial for solid tumour metastasis. Important signalling events triggered by inflammatory cytokines, such as tumour necrosis factor α (TNFα), include Src-kinase-dependent activation of Akt and focal adhesion kinase (FAK) and phosphorylation of caveolin-1. Based on previous studies(More)
Inhalational anesthetics have been shown to influence T cell functions both in vitro and in vivo, in many cases inducing T cell death, suggesting that exposure to these drugs could modify the course of an autoimmune disease. We tested the hypothesis that in mice immunized to develop experimental autoimmune encephalomyelitis (EAE), a well established model(More)
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