Publications by authors named "Loscalzo J"

von Willebrand protein was found to promote the incorporation of platelets into evolving fibrin thrombi. Using formalin-treated or fresh platelets, both the initial rate and extent of platelet incorporation into polymerizing fibrin were dependent on von Willebrand protein. von Willebrand protein was incorporated into evolving fibrin thrombi in parallel with platelets.

View Article and Find Full Text PDF

The interaction of the lanthanide Tb3+ with washed, human platelets was examined. When bound to the platelet surface, the fluorescence of this Ca2+ analog was increased approximately 200-fold, most likely by a Förster mechanism involving platelet surface protein aromatic residues. The binding of Tb3+ to the unactivated platelet was specific and saturable with an apparent approximate Kd of 195 microM.

View Article and Find Full Text PDF

Thirty cases of paradoxical embolism are reviewed to consolidate clinical presentations and common predisposing factors. The presence of patent foramen ovale in the great majority of these patients in association with maneuvers that transiently elevate right atrial pressure is emphasized in relation to the pathophysiology of the disorder. Contrast echocardiography with provocative maneuvers such as Valsalva and cough are discussed and treatment options highlighted.

View Article and Find Full Text PDF

A glutathione-S-transferase was isolated and purified to homogeneity from human platelets. With a combination of ammonium sulfate fractionation and chromatographic methods, 0.2 mg of pure enzyme was obtained from 9 X 10(11) platelets with a 12% recovery.

View Article and Find Full Text PDF

To test the hypothesis that structural abnormalities exist in the cell membrane in persons with essential hypertension and that these abnormalities affect membrane-related cellular functions, we examined several membrane-dependent phenomena and membrane lipid composition in the blood cells of subjects with essential hypertension. We analyzed platelet aggregability, membrane fluidity, membrane fatty acid composition, and erythrocyte deformability in four normolipidemic subjects with untreated essential hypertension and in five age-matched normotensive controls. As compared with the controls, the subjects with essential hypertension had platelets that aggregated at lower concentrations of adenosine 5'-diphosphate, platelet membranes that were less fluid, and erythrocytes that were more deformable.

View Article and Find Full Text PDF

The binding of von Willebrand factor (vWF) to platelet membrane glycoprotein Ib (GpIb) facilitates platelet adhesion to vascular subendothelium. In this study, we provide evidence that the vWF binding site is on glycocalicin (GC), a proteolytic fragment of GpIb, and we examine the role of the carbohydrate portion of GC on that binding. The binding to platelets of 6D1, a monoclonal antibody that recognizes an epitope on GpIb and blocks ristocetin-induced vWF binding to platelets, was inhibited by purified GC.

View Article and Find Full Text PDF

Platelet aggregation is currently felt to play an important role in the pathogenesis of ischemic vascular disorders. The smooth muscle relaxant, nitroglycerin, has been shown to inhibit platelet aggregation in vitro, but at concentrations that were felt to be unattainable in vivo. Because the in vivo action of nitroglycerin on smooth muscle cells has been shown to depend on the presence of reduced cytosolic sulfhydryl groups, the inhibitory effect of nitroglycerin on platelet aggregation was examined in the presence of the reduced thiol, N-acetylcysteine.

View Article and Find Full Text PDF

The reversible association of protomers of von Willebrand protein (vWF) was studied in order to analyze the forces and mechanism of vWF polymer assembly. At concentrations of vWF found in plasma (approximately 16 micrograms/mL), disulfide bond reduction with 50 mM 2-mercaptoethanol (2-ME) markedly reduced both vWF activity, as measured by ristocetin-dependent platelet agglutination, and average polymer size (Rh, the mean hydrodynamic radius) in solution, as determined by quasi-elastic light scattering (QLS) and by gel filtration chromatography. With increasing vWF concentration, activity and Rh increased despite reduction of interprotomer disulfide bonds.

View Article and Find Full Text PDF

von Willebrand factor (vWF) was analyzed by electron microscopic and quasi-elastic light scattering techniques in order to evaluate the size and shape of this heterogeneous polymeric plasma glycoprotein. Electron micrographs demonstrated that native vWF molecules are flexible, linear polymers, ranging in contour length from 100 to 1300 nm. In their typical configuration, the polymers were coiled upon themselves with maximal diameters ranging from 60 to 200 nm.

View Article and Find Full Text PDF

The interaction of platelet factor four (PF-4) with glycosaminoglycans (GAG) was evaluated using fluorescence spectroscopy, a radioligand binding assay, and a functional assay utilizing antithrombin III and factor Xa. In these studies, we have (i) characterized the binding parameters for PF-4 to several forms of heparin and to dextran sulfate; (ii) examined the structural features of these glycosaminoglycans which support PF-4 binding; and (iii) examined the effects of selective digestion of the carboxy terminus of PF-4 on binding. The binding of PF-4 to unfractionated porcine intestinal mucosal heparin ([Mr] = 11,000) was specific and saturable, with a molar stoichiometry of PF-4 to heparin of approximately 4:1 and an apparent estimated Kd of 3 X 10(-8) M.

View Article and Find Full Text PDF

We have studied the effect of streptokinase on platelets in platelet-rich plasma (PRP) and of plasmin on washed platelets. By three and one-half minutes after the addition of 50,000 IU/mL streptokinase to PRP, the maximum rate of ristocetin-induced platelet agglutination declined 40%, and by 60 minutes, it declined 70%. During the same time interval, the thrombin time increased from 20 seconds to over 120 seconds.

View Article and Find Full Text PDF

The conformational states of human von Willebrand protein (vWF) were studied by using ultraviolet (UV) difference, circular dichroism, and fluorescence spectrophotometric techniques in order to gain insight into the forces that maintain its asymmetric, flexible shape. vWF has 24% alpha-helix and 18% beta-pleated sheet structure in the native state. Disulfide bond reduction and carboxamidation reduced the beta-pleated sheet content by 50% without affecting the content of alpha-helix.

View Article and Find Full Text PDF

Candida has become the most prevalent cerebral mycosis at autopsy, indicating a significant incidence coupled with inadequate eradication. Of 29 patients with systemic candidiasis, 48 percent (14 of 29) also had central nervous system involvement. Of these patients, however, only 21 percent (three of 14) had antemortem diagnosis, and only one of these three patients remains alive; the two patients with antemortem diagnosis who died had a meningeal form that, although easier to document on the basis of cerebrospinal fluid examination, is now distinctly rarer than other forms of the disease in adults.

View Article and Find Full Text PDF

The decrease in amplitude of the electron spin resonance spectrum of the cysteine-bound spin-label, 3-(maleimidomethyl)-2,2,5,5-tetramethyl-1-pyrrolidinoxyl, brought about by the magnetic interaction with tightly bound manganous ion, was used as a probe of conformational change in actin on binding myosin. The magnitude of this "spin--spin" interaction first decreased then increased on increasing saturation of the actin filament with heavy meromyosin subfragment-1. That the "spin--spin" interaction occurred between spins of adjacent monomers was demonstrated by the observation that the change in magnitude of the "spin--spin" interaction was maintained on binding of heavy meromyosin subfragment-1 to copolymers in which actin monomers containing both manganous ion and spin label were diluted 7-fold with native actin monomers.

View Article and Find Full Text PDF