PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells

PADGEM protein (PADGEM), also known as GMP140, is a platelet alpha- granule membrane protein that is translocated to the external membrane after platelet activation. Although the biosynthesis of this protein was originally thought to be confined to megakaryocytes, the synthesis of PADGEM in endothelial cells was recently demonstrated (McEver et al: Blood 70:1974a, 1987). We now describe the subcellular localization of this protein in endothelial cells. Immunofluorescence staining of permeabilized human umbilical vein endothelial cells with KC4, a well characterized monoclonal antibody to PADGEM, showed positively stained elongated structures similar in distribution and shape to Weibel-Palade bodies. Their identity as Weibel-Palade bodies was confirmed by double label immunofluorescence using KC4 and a polyclonal antiserum to von Willebrand factor (vWf), a protein known to be specifically stored in these organelles. All Weibel-Palade bodies were found to contain PADGEM. In contrast to strong perinuclear staining produced with anti- vWf antibodies, no significant perinuclear staining was obtained with KC4, indicating that relatively little PADGEM is present in the endoplasmic reticulum and in the Golgi apparatus. In endothelial cells treated with secretagogues that stimulate vWf release the elongated structures positive for PADGEM disappeared, further identifying these structures as Weibel-Palade bodies. This observation extends the parallels between Weibel-Palade bodies and alpha-granules and suggests a possible functional association between vWf and PADGEM.     

BUILDING THE FOUNDATION OF EXCELLENCE IN HEART FAILURE NURSING

This column contains the presidential address presented during the Third Annual Meeting of the American Association of Heart Failure Nurses on June 28, 2007, in San Diego, California, titled "Building the Foundation of Excellence in Heart Failure Nursing."     

Building bridges between neural models and complex decision making behaviour.

Diffusion processes, and their discrete time counterparts, random walk models, have demonstrated an ability to account for a wide range of findings from behavioural decision making for which the purely algebraic and deterministic models often used in economics and psychology cannot account. Recent studies that record neural activations in non-human primates during perceptual decision making tasks have revealed that neural firing rates closely mimic the accumulation of preference theorized by behaviourally-derived diffusion models of decision making. This article bridges the expanse between the neurophysiological and behavioural decision making literatures specifically, decision field theory [Busemeyer, J. R. & Townsend, J. T. (1993). Decision field theory: A dynamic-cognitive approach to decision making in an uncertain environment. Psychological Review, 100, 432-459], a dynamic and stochastic random walk theory of decision making, is presented as a model positioned between lower-level neural activation patterns and more complex notions of decision making found in psychology and economics. Potential neural correlates of this model are proposed, and relevant competing models are also addressed.