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Robert W. Colman

Bio: Robert W. Colman is an academic researcher from University of Pennsylvania. The author has contributed to research in topics: Platelet & Disseminated intravascular coagulation. The author has an hindex of 35, co-authored 100 publications receiving 4339 citations. Previous affiliations of Robert W. Colman include Harvard University & University of California, Los Angeles.


Papers
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Journal ArticleDOI
TL;DR: It is demonstrated that the cholesterol content of platelets is dependent on the lipid composition of the milier, and cholesterol acquired by platelets may exert its effect on platelet function by a modification of the platelet membrane.
Abstract: Platelets from individuals with familial hypercholesterolemia show increased sensitivity to the aggregating atents, epinephrine and ADP. Since the mechanism of this abnormal sensitivity is unknown, we examined, in vitro, the influence of the plasma lipid environment on the function of platelets. The composition of plasma lipids was altered by the addition of sonicated cholesterol-dipalmitoyl lecithin liposomes which were "cholesterol normal" (cholesterol-phospholipid mole ratio [C/P] equals 1.0, "cholesterol rich" (C/P eauals 2.2), or "cholesterol poor" (C/P equals 0). Cholesterol-normal liposomes had no influence on platelet lipids or platelet function. In contrast, after incubation for 5 h at 37 degrees C with cholesterol-rich liposomes, normal platelets acquired 39.2% excess cholesterol with no change in phospholipids or protein. The percent increase in platelet membrane cholesterol was three-fold that of the granule fraction. The acquisition of cholesterol by platelets was associated with a 35-fold increase in sensitivity to epinephrine-induced aggregation (P less than 0.001) and 15-fold increase to ADP aggregation (P less than 0.001), as determined both by aggregometry and by [13C]serotonin release. Response to thrombin or collagen was unchanged. Platelets incubated with cholesterol-poor liposomes underwent a selective loss of 21.4% cholesterol and this was associated with an 18-fold reduction in their sensitivity to epinephrine. These studies demonstrate that the cholesterol content of platelets is dependent on the lipid composition of the milier. Cholesterol acquired by platelets may exert its effect on platelet function by a modification of the platelet membrane.

457 citations

Journal ArticleDOI
TL;DR: Analysis of a large series of patients finds the presence of three abnormal screening tests to be diagnostic (prothrombin time, fibrinogen and platelets) and a test for fibrinolysis should be abnormal in order to establish the diagnosis of DIC.

262 citations

Journal ArticleDOI
TL;DR: Aprotinin in high doses completely inhibited kallikrein-CĪ-inhibitor complex activation of neutrophils and partially inhibited complement-induced activation, thus attenuating the "whole body inflammatory response" associated with cardiopulmonary bypass.

209 citations

Journal ArticleDOI
TL;DR: Hageman factor activation of fibrinolysis appears to be mediated by kallikrein-catalyzed formation of plasmin from plasmineogen, suggesting the formation of a stoichiometric equimolar complex of plAsmin and kallkrein in the course of the activation of pl asminogen by k allikreIn.

204 citations

Journal ArticleDOI
TL;DR: The location and severity of fibrin thrombi, the types of vessels affected, skin biopsy as a diagnostic procedure, unusual syndromes of disseminated intravascular coagulation, consequences of major vessel thromboses, and complications intrinsic to the disorder or those induced inadvertently by therapy are presented.

160 citations


Cited by
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Book ChapterDOI
TL;DR: This chapter describes two types of plasminogen activators—namely, the urokinase-type plasMinogen activator (u-PA) and the tissue- type plasmineg activator(t-PA), which are essentially different gene products.
Abstract: Publisher Summary This chapter discusses the role of plasminogen activators in various biological processes. In specific, it describes two types of plasminogen activators—namely, the urokinase-type plasminogen activator (u-PA) and the tissue-type plasminogen activator (t-PA), which are essentially different gene products. The amino acid sequences of these activators and nucleotide sequences of the corresponding cDNAs have largely been determined, and the cDNAs have been cloned using recombinant techniques. A variety of enzymatic as well as immunological assay and detection methods have also been developed that allows a precise quantification of the activators, a distinction between u-PA and t-PA, determination of whether an activator is present in its active or zymogen form, analysis of the kinetics of different steps of the cascade reaction, and immunocytochemical identification of u-PA and t-PA in tissue sections. Much of the studies on plasminogen activators and cancer has been guided by the hypothesis that proteolysis of the components of extracellular matrix, initiated by the release of plasminogen activator from the cancer cells, plays a decisive role for the degradation of normal tissue, and thereby for invasive growth and metastases.

2,545 citations

Journal ArticleDOI
TL;DR: Bleeding may be the presenting symptom in a patient with disseminated intravascular coagulation, a factor that can complicate decisions about treatment, and the use and subsequent depletion of platelets and coagulating proteins resulting from the ongoing coagulations may induce severe bleeding.
Abstract: Disseminated intravascular coagulation is characterized by the widespread activation of coagulation, which results in the intravascular formation of fibrin and ultimately thrombotic occlusion of small and midsize vessels.1–3 Intravascular coagulation can also compromise the blood supply to organs and, in conjunction with hemodynamic and metabolic derangements, may contribute to the failure of multiple organs. At the same time, the use and subsequent depletion of platelets and coagulation proteins resulting from the ongoing coagulation may induce severe bleeding (Figure 1). Bleeding may be the presenting symptom in a patient with disseminated intravascular coagulation, a factor that can complicate decisions about . . .

1,830 citations

Journal ArticleDOI
TL;DR: Membrane fatty acid composition, phospholipid composition, and cholesterol content can be modified in many different kinds of intact mammalian cells, and many of the functional responses probably are caused directly by the membrane lipid structural changes, which affect either bulk lipid fluidity or specific lipid domains.

1,437 citations

Journal ArticleDOI
20 May 1988-Cell
TL;DR: This work focuses on the molecular basis of blood coagulation with particular attention to the biochemistry and regulation of this pathway as it relates to humans in health and disease.

1,298 citations

Journal ArticleDOI
TL;DR: Current research in this area is directed toward the identification and structural characterization of nucleotide or P2-purinergic receptors that are activated when ATP or other nucleotides are bound.
Abstract: Extracellular ATP, at micromolar concentrations, induces significant functional changes in a wide variety of cells and tissues. ATP can be released from the cytosol of damaged cells or from exocytotic vesicles and/or granules contained in many types of secretory cells. There are also efficient extracellular mechanisms for the rapid metabolism of released nucleotides by ecto-ATPases and 5'-nucleotidases. The diverse biological responses to ATP are mediated by a variety of cell surface receptors that are activated when ATP or other nucleotides are bound. The functionally identified nucleotide or P2-purinergic receptors include 1) ATP receptors that stimulate G protein-coupled effector enzymes and signaling cascades, including inositol phospholipid hydrolysis and the mobilization of intracellular Ca2+ stores; 2) ATP receptors that directly activate ligand-gated cation channels in the plasma membranes of many excitable cell types; 3) ATP receptors that, via the rapid induction of surface membrane channels and/or pores permeable to ions and endogenous metabolites, produce cytotoxic or activation responses in macrophages and other immune effector cells; and 4) ADP receptors that trigger rapid ion fluxes and aggregation responses in platelets. Current research in this area is directed toward the identification and structural characterization of these receptors by biochemical and molecular biological approaches.

1,271 citations