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William I Smith

Publications and source records attributed to William I Smith.

2 recordsLinked to original sources

Carotid artery atherosclerosis: in vivo morphologic characterization with gadolinium-enhanced double-oblique MR imaging initial results.

In nine subjects with carotid atherosclerosis, double-oblique, contrast material-enhanced, double inversion-recovery, fast spin-echo magnetic resonance (MR) images were acquired through atheroma in the proximal internal carotid artery. Fibrocellular tissue within atheroma selectively enhanced 29% after administration of gadolinium-based contrast agent. Contrast enhancement helped discriminate fibrous cap from lipid core with a contrast-to-noise ratio as good as or better than that with T2-weighted MR images but with approximately twice the signal-to-noise ratio (postcontrast images, 36.6 +/- 3.6; T2-weighted images, 17.5 +/- 2.1; P <.001).

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Fibronectin-based masking molecule blocks platelet adhesion.

Vessel wall extracellular matrix, which underlies the endothelium, is a potent stimulator of platelet adhesion and activation. Exposure of this matrix can result from damage incurred by vascular interventions, such as saphenous vein bypass grafting and angioplasty. Fibrillar collagens are an important component of the thrombogenic extracellular matrix. Herein we describe a means of targeting poly(ethylene glycol) (PEG)-mediated blockade directly to platelet-binding ECM molecules, such as type I collagen, thereby selectively blocking platelet adhesion to vascular matrix. Purified fibronectin (FN), a matrix protein that interacts with fibrillar collagens and platelets, was selectively pegylated to generate a targeted molecular shielding reagent that masked ECM ligands from platelet recognition and adhesion. This approach protects the functions of other vascular proteins, including surface proteins on intact endothelium. To mask the platelet-binding site of FN, PEG-propyl moieties (5000 Da) were covalently appended to lysine residues on the surface of FN, generating FNPEG-5K. To preserve the collagen-binding function of FN, it was pegylated while bound to a gelatin agarose matrix. We demonstrate that FNPEG-5K blocks platelet adhesion to purified type I collagen. Moreover, the same preparation blocks platelet adhesion to vascular wall components, including collagens.

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