Biomedical subjects

William C Aird

Publications and source records attributed to William C Aird.

39 records · Page 3Linked to original sources

PubMed2002

Endothelial cell dynamics and complexity theory.

OBJECTIVE: To apply complexity theory to understanding endothelial cell function in health and disease. DATA SOURCES AND STUDY SELECTION: Published research and review articles in the English language related to complexity theory and endothelial cell biology. DATA EXTRACTION AND SYNTHESIS: The results of published studies have been used to generate a hypothesis of nonlinear dynamics in endothelial cell biology. CONCLUSIONS: The endothelium displays nonlinear complexity. I propose a model in which healthy endothelium retains a broad range of responses and is therefore highly active, whereas dysfunctional endothelium becomes locked into a narrow range of responses, approaching a single steady state and eventual quiescence. These concepts lay a foundation for understanding the pathophysiology of endothelial cell dysfunction in the multiple organ dysfunction syndrome.

Blood Coagulation↗

PubMedDate not supplied

Endothelial biomedicine: its status as an interdisciplinary field, its progress as a basic science, and its translational bench-to-bedside gap.

The endothelium, a layer of endothelial cells lining the luminal surface of all blood vessels, functions as a highly metabolically active organ spatially distributed throughout the body. Despite enormous advances in our understanding of endothelial cell biology, little awareness of this organ reaches clinical practice. The present study aims to document the extent and scope of the bench-to-bedside gap in endothelial biomedicine, and to offer hypotheses to explain the gaping chasm. A PubMed search using keywords "endothelial cells" and "endothelium" yielded over 90,000 publications, increasing exponentially over the past decade. A Scirus search without date restriction returned journal results for the endothelium not greatly fewer than for the epithelium. A survey of representative vascular biology meetings revealed a high percentage of talks related to the endothelium. The number of grants awarded by the National Institutes of Health for studies in endothelial cell biology continues to steadily increase. At the bedside, however, few clinicians give consideration to the health of the endothelium. A survey of the major medical textbooks revealed a paucity of index entries for "endothelial cells" or "endothelium." The endothelium does not offer itself for inspection, palpation, percussion, and/or auscultation. No convenient blood tests measure endothelial function. The authors propose to explain the bench-to-bedside gap in endothelial biomedicine as a function of (1) historical constraints, (2) the unseen and diffuse nature of the cell layer, (3) the complexity of the system, and (4) its adaptability. Until the bench-to-bedside gap closes, the enormous potential of the endothelium as a diagnostic, preventive, and therapeutic target will remain largely untapped.

Animals↗

PubMedDate not supplied

Cloning and characterization of the human lung endothelial-cell-specific molecule-1 promoter.

Endothelial-cell-specific molecule-1 (ESM-1) is a cysteine-rich protein that is expressed primarily in endothelial cells of the lung, kidney and gut. In the present study, we have cloned and sequenced 3,888 bp of the 5' flanking region of the human ESM-1 gene. The full-length promoter directed high-level expression of the luciferase reporter gene in bovine lung microvascular endothelial cells and bovine aortic endothelial cells, but not in nonendothelial cell types. In 5' deletion analyses, a region spanning -81 to +58 was shown to contain information for endothelial-cell-specific expression. Mutational analysis in transient transfection assays uncovered an important role for an Ets-binding motif located between -77 and -74 and a cAMP-response-element (CRE)-like motif located between -68 and -62 in mediating high-level expression in endothelial cells. A second Ets site (-63 to -60) as well as a novel 6-bp palindromic sequence (-58 to -53) were found to inhibit expression. In DNase footprint analyses, both the Ets-binding motifs were protected specifically in endothelial cells, while the CRE-like element and palindrome were protected in endothelial and nonendothelial cells alike. Taken together, these results provide an important foundation for studying endothelial-cell-subtype-specific gene regulation.

Animals↗