W Scott Argraves

Publications (160) View all

• Article: Fibulin-1 is a marker for arterial extracellular matrix alterations in type 2 diabetes.

  Claudia Cangemi, Vibe Skov, Michael Kjaer Poulsen, Jonas Funder, Waleed O Twal, Mari-Anne Gall, Vibeke Hjortdal, Marie Louise Jespersen, Torben A Kruse, Jan Aagard, Hans-Henrik Parving, Steen Knudsen, Poul-Flemming Høilund-Carlsen, Peter Rossing, Jan Erik Henriksen, William Scott Argraves, Lars Melholt Rasmussen
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  ABSTRACT: Extracellular matrix alterations are important elements in the arterial changes seen in diabetes, being associated with increased vascular stiffness and the development of cardiovascular diseases. However, no biomarkers for diabetes-related arterial changes have been defined. Mammary artery specimens from 17 men with type 2 diabetes and 18 nondiabetic individuals were used for microarray expression profiling, quantitative real-time PCR, immunoassay, and immunohistochemical analyses. A derived candidate marker, fibulin-1, which is an elastin-associated matrix molecule, was measured immunochemically in plasma from (a) 70 patients scheduled for vascular surgery, (b) 305 patients with type 2 diabetes examined with carotid ultrasonography and echocardiography, and (c) 308 patients with type 2 diabetes, followed for 15 years. The most upregulated transcript in nonatherosclerotic arterial tissue from patients with type 2 diabetes encoded the extracellular matrix protein, fibulin-1. Higher concentrations of fibulin-1-protein were present in artery extracts from patients with diabetes than extracts from individuals without diabetes, and increased fibulin-1 immunostaining was apparent around the external elastic lamina of diabetic arteries. Patients with diabetes displayed increased plasma concentrations of fibulin-1 (P = 0.006). Plasma fibulin-1 concentrations correlated with hemoglobin A(1c) (P < 0.001), arterial stiffness indices including pulse pressure (P < 0.001), and carotid compliance (P = 0.004), as well as plasma N-terminal pro-B-type natriuretic peptide concentrations (P < 0.001) and were predictive of 15-year mortality (P = 0.013). Fibulin-1 accumulates in the arterial wall and in plasma of patients with type 2 diabetes, and appears to be a factor associated with arterial extracellular matrix changes in type 2 diabetes.
  Clinical Chemistry 09/2011; 57(11):1556-65. · 7.91 Impact Factor
• Article: Collective cell motion in endothelial monolayers.

  A Szabó, R Unnep, E Méhes, W O Twal, W S Argraves, Y Cao, A Czirók
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  ABSTRACT: Collective cell motility is an important aspect of several developmental and pathophysiological processes. Despite its importance, the mechanisms that allow cells to be both motile and adhere to one another are poorly understood. In this study we establish statistical properties of the random streaming behavior of endothelial monolayer cultures. To understand the reported empirical findings, we expand the widely used cellular Potts model to include active cell motility. For spontaneous directed motility we assume a positive feedback between cell displacements and cell polarity. The resulting model is studied with computer simulations and is shown to exhibit behavior compatible with experimental findings. In particular, in monolayer cultures both the speed and persistence of cell motion decreases, transient cell chains move together as groups and velocity correlations extend over several cell diameters. As active cell motility is ubiquitous both in vitro and in vivo, our model is expected to be a generally applicable representation of cellular behavior.
  Physical Biology 01/2010; 7(4):046007. · 2.60 Impact Factor
• Source

  Available from: Steingrimur Stefansson

  Patent: Use of the High Density Lipoprotein (HDL) Holoparticle Endocytosis Receptor and HDL-Receptor Antagonists.

  S. M. Hammad, S. Stefansson, W. O. Twal, C. J. Drake, P. Fleming, H. A. Remaley, H. B. Brewer, W. S. Argraves
  Ref. No: 6,846,636, Year: 01/2005
• Article: MYH9 spectrum of autosomal-dominant giant platelet syndromes: unexpected association with fibulin-1 variant-D inactivation.

  Amos Toren, Galit Rozenfeld-Granot, Karen E Heath, Ninette Amariglio, Bianca Rocca, John Crosson, Charles J Epstein, Ferdinando Laghi, Raffaele Landolfi, Lena E Carlsson, Scott Argraves, Nicola Bizzaro, Marva Moxey-Mims, Frida Brok-Simoni, John A Martignetti, Andreas Greinacher, Gideon Rechavi
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  ABSTRACT: The autosomal-dominant giant platelet syndromes (Fechtner, Epstein, and Sebastian platelet syndromes and May-Hegglin anomaly) represent a group of disorders characterized by variable degrees of macrothrombocytopenia with further combinations of neutrophil inclusion bodies and Alport-like syndrome manifestations, namely, deafness, renal disease, and eye abnormalities. The disease-causing gene of these giant platelet syndromes was previously mapped by us to chromosome 22. Following their successful mapping, these syndromes were shown to represent a broad phenotypic spectrum of disorders caused by different mutations in the nonmuscle myosin heavy chain 9 gene (MYH9). In this study, we examined the potential role of another gene, fibulin-1, encoding an extracellular matrix protein as a disease modifier. Eight unrelated families with autosomal-dominant giant platelet syndromes were studied for DNA sequence mutations and expression of the four fibulin-1 splice variants (A-D). A mutation in the splice acceptor site of fibulin-1 exon 19 was found in affected individuals of the Israeli Fechtner family, whereas no MYH9 mutations were identified. Unexpectedly, fibulin-1 variant D expression was absent in affected individuals from all eight families and coupled with expression of a putative antisense RNA. Transfection of the putative antisense RNA into H1299 cells abolished variant D expression. Based on the observation that only affected individuals lack variant D expression and demonstrate antisense RNA overexpression, we suggest that these autosomal-dominant giant platelet syndromes are associated, and may be modified, by aberrant antisense gene regulation of the fibulin-1 gene.
  American Journal of Hematology 01/2004; 74(4):254-62. · 4.67 Impact Factor
• Article: Informatics tools to improve clinical research

  S. Argraves, C. A. Brandt, R. Money, P. Nadkarni
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  ABSTRACT: During the conduct of complex clinical trials, there are numerous sources and types of data collection and project coordination problems. Methods and approaches to address the conduct of a trial vary in both the cost and time to perform and the potential benefit. Informatics tools can help trial coordinators and investigators ensure the collection of high quality research data during all phases of a clinical trial.
  AMIA ... Annual Symposium proceedings / AMIA Symposium. AMIA Symposium 02/2005;