Author
Timothy Moore
Other affiliations: University of Michigan, National Institutes of Health, University of South Alabama
Bio: Timothy Moore is an academic researcher from Auburn University. The author has contributed to research in topics: Medicine & Endothelial stem cell. The author has an hindex of 27, co-authored 80 publications receiving 2172 citations. Previous affiliations of Timothy Moore include University of Michigan & National Institutes of Health.
Papers published on a yearly basis
Papers
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TL;DR: A role for endogenously expressed Trp1 in regulating a Ca2-selective current activated upon Ca2+ store depletion is supported.
Abstract: SPECIFIC AIMTo determine whether host selenium (Se) deficiency can induce changes in the genome of a replicating influenza virus such that a normally mild virus converts into a more virulent strain and to characterize such genomic changes.PRINCIPAL FINDINGS1. Replication of a mild strain of influenza virus in Se-deficient mice results in a novel virulent strain that causes severe lung pathology even when passed into Se-adequate miceSe-deficient mice developed much more severe lung pathology postinfection with influenza virus than Se-adequate infected mice. To determine whether host factors or viral factors were responsible for the increased pathogenicity of influenza virus that had replicated in Se-deficient mice, a passage experiment was performed. We infected groups of Se-adequate and Se-deficient mice with influenza A/Bangkok/1/79 (H3N2). At 5 days postinfection, the mice were killed and virus was recovered from the lungs. Five separate isolates from each group of mice were used to inoculate five indiv...
262 citations
TL;DR: Increased permeability in RPAECs is not sufficient in RPMVECs, which show an apparent uncoupling of [Ca2+]isignaling pathways or dominant Ca2+-independent mechanisms from controlling cellular gap formation and permeability.
Abstract: Cytosolic Ca2+ concentration ([Ca2+]i) plays an important role in control of pulmonary vascular endothelial cell (ECs) barrier function. In this study, we investigated whether thapsigargin- and ion...
161 citations
TL;DR: The roles of [Ca2+]iand cAMP in mediating site-specific alterations in endothelial permeability are considered, which indicate that endothelial cells derived from different vascular sites within the pulmonary circulation exhibit distinct sensitivities to permeability-inducing stimuli.
Abstract: Pulmonary endothelium forms a semiselective barrier that regulates fluid balance and leukocyte trafficking. During the course of lung inflammation, neurohumoral mediators and oxidants act on endoth...
151 citations
TL;DR: This study indicates that Ca2+ entry in pulmonary endothelial cells through SOCs produces cell shape change that is dependent on site-specific rearrangement of the microfilamentous cytoskeleton and Trp1 may be a component of pulmonary arterial endothelial SOCs.
Abstract: Activation of Ca2+ entry is known to produce endothelial cell shape change, leading to increased permeability, leukocyte migration, and initiation of angiogenesis in conduit-vessel endothelial cell...
132 citations
TL;DR: Leukocyte adherence in the pulmonary, microvasculature and subsequent permeability increase after I/R is dependent on the integrin CD18, its endothelial cell ligand intercellular adhesion molecule 1, and the endothelialcell rolling factor P-selectin but not the leukocyte rolling factor L- selectin.
Abstract: Leukocyte adherence to the endothelium after ischemia and reperfusion contributes to microvascular injury in most organs. The purpose of this study was to evaluate the leukocyte and endothelial cel...
102 citations
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TL;DR: The key electrophysiological features of I(CRAC) and other store-operated Ca(2+) currents and how they are regulated are described, and recent advances that have shed insight into the molecular mechanisms involved in this ubiquitous and vital Ca( 2+) entry pathway are considered.
Abstract: In electrically nonexcitable cells, Ca2+ influx is essential for regulating a host of kinetically distinct processes involving exocytosis, enzyme control, gene regulation, cell growth and prolifera...
2,248 citations
TL;DR: This review summarizes and analyzes the recent data from genetic, physiological, cellular, and morphological studies that have addressed the signaling mechanisms involved in the regulation of both the paracellular and transcellular transport pathways.
Abstract: The microvascular endothelial cell monolayer localized at the critical interface between the blood and vessel wall has the vital functions of regulating tissue fluid balance and supplying the essential nutrients needed for the survival of the organism. The endothelial cell is an exquisite "sensor" that responds to diverse signals generated in the blood, subendothelium, and interacting cells. The endothelial cell is able to dynamically regulate its paracellular and transcellular pathways for transport of plasma proteins, solutes, and liquid. The semipermeable characteristic of the endothelium (which distinguishes it from the epithelium) is crucial for establishing the transendothelial protein gradient (the colloid osmotic gradient) required for tissue fluid homeostasis. Interendothelial junctions comprise a complex array of proteins in series with the extracellular matrix constituents and serve to limit the transport of albumin and other plasma proteins by the paracellular pathway. This pathway is highly regulated by the activation of specific extrinsic and intrinsic signaling pathways. Recent evidence has also highlighted the importance of the heretofore enigmatic transcellular pathway in mediating albumin transport via transcytosis. Caveolae, the vesicular carriers filled with receptor-bound and unbound free solutes, have been shown to shuttle between the vascular and extravascular spaces depositing their contents outside the cell. This review summarizes and analyzes the recent data from genetic, physiological, cellular, and morphological studies that have addressed the signaling mechanisms involved in the regulation of both the paracellular and transcellular transport pathways.
1,575 citations
TL;DR: The goal of this review is to summarize the strengths and weaknesses of existing models of lung injury and help guide investigators in the design and interpretation of animal studies of acute lung injury.
Abstract: Acute lung injury in humans is characterized histopathologically by neutrophilic alveolitis, injury of the alveolar epithelium and endothelium, hyaline membrane formation, and microvascular thrombi. Different animal models of experimental lung injury have been used to investigate mechanisms of lung injury. Most are based on reproducing in animals known risk factors for ARDS, such as sepsis, lipid embolism secondary to bone fracture, acid aspiration, ischemia-reperfusion of pulmonary or distal vascular beds, and other clinical risks. However, none of these models fully reproduces the features of human lung injury. The goal of this review is to summarize the strengths and weaknesses of existing models of lung injury. We review the specific features of human ARDS that should be modeled in experimental lung injury and then discuss specific characteristics of animal species that may affect the pulmonary host response to noxious stimuli. We emphasize those models of lung injury that are based on reproducing risk factors for human ARDS in animals and discuss the advantages and disadvantages of each model and the extent to which each model reproduces human ARDS. The present review will help guide investigators in the design and interpretation of animal studies of acute lung injury.
1,453 citations
TL;DR: An historical perspective of the understanding of endothelial heterogeneity is provided, the scope of phenotypic diversity across the vascular tree is discussed, and the proximate and evolutionary mechanisms of endothelium heterogeneity are addressed.
Abstract: Endothelial cells, which form the inner cellular lining of blood vessels and lymphatics, display remarkable heterogeneity in structure and function. This is the first of a 2-part review focused on phenotypic heterogeneity of blood vessel endothelium. This review provides an historical perspective of our understanding of endothelial heterogeneity, discusses the scope of phenotypic diversity across the vascular tree, and addresses proximate and evolutionary mechanisms of endothelial cell heterogeneity. The overall goal is to underscore the importance of phenotypic heterogeneity as a core property of the endothelium.
1,430 citations
TL;DR: The goal is to underscore the importance of site-specific properties of the endothelium in mediating homeostasis and focal vascular pathology, while at the same time emphasizing the value of approaching the endot Helium as an integrated system.
Abstract: Endothelial cells, which form the inner cellular lining of blood vessels and lymphatics, display remarkable heterogeneity in structure and function. This is the second of a 2-part review on the phenotypic heterogeneity of blood vessel endothelial cells. The first part discusses the scope, the underlying mechanisms, and the diagnostic and therapeutic implications of phenotypic heterogeneity. Here, these principles are applied to an understanding of organ-specific phenotypes in representative vascular beds including arteries and veins, heart, lung, liver, and kidney. The goal is to underscore the importance of site-specific properties of the endothelium in mediating homeostasis and focal vascular pathology, while at the same time emphasizing the value of approaching the endothelium as an integrated system.
1,200 citations