We have examined the role of heparinlike molecules in the regulation of coagulation by perfusing rat hindquarters with purified human thrombin and with its plasma inhibitor, antithrombin. Our data indicate that contact of the hemostatic components with the endothelium enhances the rate of thrombin-antithrombin complex formation by as much as 19-fold over the uncatalyzed rate of enzyme-inhibitor interaction. Heparinlike molecules are responsible for the antithrombin accelerating activity. The amount of thrombin-antithrombin complex generated within the hindlimb preparation after pretreatment of the vasculature with purified Flavobacterium heparinase or with addition of platelet Factor IV to the hemostatic components, was equal to the uncatalyzed levels. These heparinlike molecules appear to be tightly bound to the luminal surface of the endothelium, since they could not be detected within the physiologic buffer that was perfused through the animal. The above mucopolysaccharides function in a manner similar to commercial heparin, since modification of antithrombin at a site critical for heparin-dependent acceleration of the protease inhibitor resulted in a level of interaction product identical to the uncatalyzed amount. Finally, addition of diisofluorophosphate-thrombin to the enzyme perfusion stream reduced the amount of thrombin-antithrombin complex formed in the animal by 30-40%, which suggested that thrombin bound to the endothelium as well as enzyme free in solution are accessible to antithrombin that has interacted with heparinlike molecules present on the endothelium.
J A Marcum, J B McKenney, R D Rosenberg
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Protein Engineering for Therapeutics Part B | 2012 |
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Cardiovascular biomaterials: when the inflammatory response helps to efficiently restore tissue functionality?: Inflammatory response to cardiovascular biomaterials
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Principles of Regenerative Medicine | 2011 |
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The International Journal of Biochemistry & Cell Biology | 2005 |
Chemistry and Biology of Heparin and Heparan Sulfate
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Blood Coagulation & Fibrinolysis | 2003 |
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Platelet factor 4 neutralizes heparan sulfate-enhanced antithrombin inactivation of factor Xa by preventing interaction(s) of enzyme with polysaccharide
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Biochemical and Biophysical Research Communications | 2003 |
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Archives of Biochemistry and Biophysics | 2003 |
Brain Ischemia
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Glycoconjugate Journal | 2002 |
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The Journal of biological chemistry | 2002 |
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Archives of pathology & laboratory medicine | 2002 |
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Biological & Pharmaceutical Bulletin | 2001 |
Maintaining the Endothelium: Preventive Strategies for Vessel Integrity
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Preventive Cardiology | 2001 |
Metabolism of rabbit plasma-derived factor VII in relation to prothrombin in rabbits
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American journal of physiology. Endocrinology and metabolism | 2001 |
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Biomedecine & Pharmacotherapy | 2000 |
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The Journal of Heart and Lung Transplantation | 2000 |
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The British journal of surgery | 2000 |
Endothelial cell function and thrombosis
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Best Practice & Research Clinical Haematology | 1999 |
Lipoproteins and the haemostatic system in atherothrombotic disorders
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The Journal of biological chemistry | 1997 |
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The Journal of biological chemistry | 1992 |
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Annals of the New York Academy of Sciences | 1991 |
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Acta Anaesthesiologica Scandinavica | 1991 |
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Thrombosis Research | 1991 |
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Analytical Biochemistry | 1991 |
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Cardiology Clinics | 1991 |
Biologically Active Heparin Coating in Medical Devices
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The International Journal of Artificial Organs | 1991 |
Infrared characterization of complex sandwich structures: Heparin immobilized on polyethylene surfaces
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Molecular Engineering | 1991 |
Recombinant Technology in Hemostasis and Thrombosis
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1991 | |
A kinetic model for the alpha-thrombin-catalyzed conversion of plasma levels of fibrinogen to fibrin in the presence of antithrombin III
MC Naski, JA Shafer |
The Journal of biological chemistry | 1991 |
Clinical and biochemical characterization of antithrombin III Franconville, a variant with Pro 41 Leu mutation
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British Journal of Haematology | 1990 |
The vascular endothelial cell as a vehicle for gene therapy
AD Callow |
Journal of Vascular Surgery | 1990 |
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The Journal of Cell Biology | 1990 |
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Proceedings of the National Academy of Sciences | 1990 |
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AA Horner |
Biochemical Journal | 1990 |
Platelet factor 4 blocks the binding of basic fibroblast growth factor to the receptor and inhibits the spontaneous migration of vascular endothelial cells
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Biochemical and Biophysical Research Communications | 1990 |
Heparin-like glycosaminoglycan is a receptor for Antithrombin III-dependent but not for thrombin-dependent prostacyclin production in human endothelial cells
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Thrombosis Research | 1990 |
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JJ Zwaginga, JJ Sixma, PG de Groot |
Arteriosclerosis (Dallas, Tex.) | 1990 |
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G Landbeck, R Marx, I Scharrer, W Schramm |
1990 | |
Encyclopedic Reference of Vascular Biology & Pathology
A Bikfalvi |
1990 | |
New Trends in Haemostasis
J Harenberg, DL Heene, G Stehle, G Schettler |
1990 | |
Monocyte-derived neutrophil chemotactic factor (MDNCF/IL-8) resides in a gene cluster along with several other members of the platelet factor 4 gene superfamily
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Human Genetics | 1990 |
Vitronectin (S protein) is associated with platelets
CJ Parker, OL Stone, VF White, NJ Bernshaw |
British Journal of Haematology | 1989 |
Role of Endothelial Cell Surface Heparin-like Polysaccharides
JA Marcum, RD Rosenberg |
Annals of the New York Academy of Sciences | 1989 |
The role of vitronectin as multifunctional regulator in the hemostatic and immune systems
KT Preissner |
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Journal of Vascular Surgery | 1989 |
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Thrombosis Research | 1989 |
Improved method for purification of human platelet factor 4 by affinity and ion-exchange chromatography
I Medici, AD Martino, G Cella, L Callegaro, M Prosdocimi |
Thrombosis Research | 1989 |
Effect of rabbit thrombomodulin on thrombin inhibition by antithrombin in the presence of heparin
B Marie-Claude |
Thrombosis Research | 1989 |
Serpin receptor 1: A hepatic receptor that mediates the clearance of antithrombin III-proteinase complexes
SV Pizzo |
The American Journal of Medicine | 1989 |
Biochemistry of heparin antithrombin interactions, and the physiologic role of this natural anticoagulant mechanism
RD Rosenberg |
The American Journal of Medicine | 1989 |
Congenital antithrombin III deficiency: insights into the pathogenesis of the hypercoagulable state and its management using markers of hemostatic system activation
KA Bauer, RD Rosenberg |
The American Journal of Medicine | 1989 |
9 Antithrombin: Structure, genomic organization, function and inherited deficiency
DA Lane, R Caso |
Baillière's Clinical Haematology | 1989 |
The mechanism of precartilage mesenchymal condensation: A major role for interaction of the cell surface with the amino-terminal heparin-binding domain of fibronectin
DA Frenz, NS Jaikaria, SA Newman |
Developmental Biology | 1989 |
Human platelet factor 4 monomer-dimer-tetramer equilibria investigated by proton NMR spectroscopy
KH Mayo, MJ Chen |
Biochemistry | 1989 |
Synthesis and expression of C1 inhibitor by human umbilical vein endothelial cells
AH Schmaier, SC Murray, GD Heda, A Farber, A Kuo, K McCrae, DB Cines |
The Journal of biological chemistry | 1989 |
Thrombin and Histamine Stimulate the Phosphorylation of Elongation Factor 2 in Human Umbilical Vein Endothelial Cells
KP Mackie, AC Nairn, G Hampel, G Lam, EA Jaffe |
The Journal of biological chemistry | 1989 |
Albuminuria reflects widespread vascular damage: The Steno hypothesis
T Deckert, B Feldt-Rasmussen, K Borch-Johnsen, T Jensen, A Kofoed-Enevoldsen |
Diabetologia | 1989 |
The role of vitronectin as multifunctional regulator in the hemostatic and immune systems
KT Preissner |
Blut Zeitschrift für die Gesamte Blutforschung | 1989 |
Proposed heparin binding site in antithrombin based on arginine 47. A new variant Rouen-II, 47 Arg to Ser
JY Borg, MC Owen, C Soria, J Soria, J Caen, RW Carrell |
Journal of Clinical Investigation | 1988 |
Influence of blood flow and the effect of protamine on the thromboresistant properties of a covalently bonded heparin surface
C Arnander, P Olsson, O Larm |
Journal of Biomedical Materials Research | 1988 |
Inherited factors in thrombosis
PM Mannucci, A Tripodi |
Blood Reviews | 1988 |
Effects of fibroblasts and endothelial cells on inactivation of target proteases by protease nexin-1, heparin cofactor II, and C1-inhibitor
SA Hiramoto, DD Cunningham |
Journal of Cellular Biochemistry | 1988 |
Isolation of heparan sulfates with antithrombin III affinity and anticoagulant potency from 3T3, B16.F10 melanoma, and cutaneous fibrosarcoma cell lines
M Piepkorn, P Hovingh, WM Hentschel |
Biochemical and Biophysical Research Communications | 1988 |
Binding, internalization and degradation of heparin and heparin fragments by cultured endothelial cells
S Vannucchi, F Pasquali, F Porciatti, V Chiarugi, L Magnelli, P Bianchini |
Thrombosis Research | 1988 |
Neutralization of thrombin by antithrombin III in the presence of cultured human fibroblasts
JT Brandt, RE Stephens, GH Hinkle |
Thrombosis Research | 1988 |
Preparation and characterization of monolconal antibodies against the human thrombin-antithrombin III complex
S Asakura, N Yoshida, M Matsuda, H Murayama, G Soe |
Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology | 1988 |
International Review of Experimental Pathology
P Hoedemaeker |
International Review of Experimental Pathology | 1988 |
The Molecular and Cellular Biology of Wound Repair
RA Clark, PM Henson |
1988 | |
Endothelial Cell Biology in Health and Disease
N Simionescu, M Simionescu |
1988 | |
Sulfated N-linked oligosaccharides in mammalian cells. II. Identification of glycosaminoglycan-like chains attached to complex-type glycans
G Sundblad, S Holojda, L Roux, A Varki, HH Freeze |
The Journal of biological chemistry | 1988 |
Endotoxin enhances tissue factor and suppresses thrombomodulin expression of human vascular endothelium in vitro
KL Moore, SP Andreoli, NL Esmon, CT Esmon, NU Bang |
Journal of Clinical Investigation | 1987 |
Aging-associated changes in indices of thrombin generation and protein C activation in humans. Normative Aging Study
KA Bauer, LM Weiss, D Sparrow, PS Vokonas, RD Rosenberg |
Journal of Clinical Investigation | 1987 |
Suppression of hemostatic system activation by oral anticoagulants in the blood of patients with thrombotic diatheses
EM Conway, KA Bauer, S Barzegar, RD Rosenberg |
Journal of Clinical Investigation | 1987 |
Glomerular deposition of cross–linked fibrin in human kidney diseases
T Takemura, K Yoshioka, N Akano, H Miyamoto, K Matsumoto, S Maki |
Kidney International | 1987 |
Current views on the pathophysiology and investigations of thrombotic disorders
HH Salem, CA Mitchell, BG Firkin |
American Journal of Hematology | 1987 |
Localization of the binding sites of porcine tissue-type plasminogen activator and plasminogen to heparin
S Soeda, M Kakiki, H Shimeno, A Nagamatsu |
Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology | 1987 |
An abnormal antithrombin III (AT III) with low heparin affinity: AT III Clichy
M Aiach, D Franclois, P Priollet, L Capron, M Roncato, M Alhenc-Gelas, JN Fiessinger |
British Journal of Haematology | 1987 |
Presidential address: The microcosm of the arterial wall—A plea for research
AD Callow |
Journal of Vascular Surgery | 1987 |
The active roles of cells of the blood vessel wall in health and disease
P Libby |
Molecular Aspects of Medicine | 1987 |
Comparative effect of heparin and heparan sulphate on two abnormal antithrombin III type 3 variants
AM Fischer, S Beguin, C Sternberg, MD Dautzenberg |
British Journal of Haematology | 1987 |
Antithrombin III Northwick Park: demonstration of an inactive high MW complex with increased affinity for heparin
DA Lane, A Flynn, H Ireland, H Erdjument, D Samson, D Howarth, E Thompson |
British Journal of Haematology | 1987 |
Human platelet factor 4 and protamine sulphate interaction with glycosaminoglycans in the rabbit
G Cella, CJ Myers, M Prosdocimi, AA Sasahara |
European Journal of Clinical Investigation | 1987 |
Matrix-driven translocation: dependence on interaction of amino-terminal domain of fibronectin with heparin-like surface components of cells or particles
SA Newman, DA Frenz, E Hasegawa, SK Akiyama |
Proceedings of the National Academy of Sciences | 1987 |
Formation and regulation of platelet and fibrin hemostatic plug
J Hawiger |
Human Pathology | 1987 |
Cell biology of endothelial cells
EA Jaffe |
Human Pathology | 1987 |
Thrombosis in inherited deficiencies of antithrombin, protein C, and protein S
RD Rosenberg, KA Bauer |
Human Pathology | 1987 |
interaction of antithrombin III and thrombinantithrombin III complex with cultured aortic endothelial cells
K Bartha, T Kovacs, I Lerant, B Papp, E Csonka, K Kolev, R MacHovich |
Thrombosis Research | 1987 |
Uptake and inactivation of thrombin on the subendothelium: Comparisons with endothelium
S Frebelius, J Swedenborg |
Thrombosis Research | 1987 |
Biology of Proteoglycans
EJ Thonar, KE Kuettner |
Biology of Proteoglycans | 1987 |
Immune Endothelial-Cell Injury in Heparin-Associated Thrombocytopenia
DB Cines, A Tomaski, S Tannenbaum |
New England Journal of Medicine | 1987 |
Endothélium et thrombose
P Molho-Sabatier |
La Revue de Médecine Interne | 1987 |
Conditions for radioiodination of antithrombin III retaining its biological properties
J Caix, AP Minnot, A Beziade, L Vuillemin, F Belloc, C Baquey, D Ducassou |
International Journal of Radiation Applications and Instrumentation. Part A. Applied Radiation and Isotopes | 1987 |
The Pulmonary Circulation in Health and Disease
J Hughes |
The Pulmonary Circulation in Health and Disease | 1987 |
Binding of thrombin to thrombomodulin accelerates inhibition of the enzyme by antithrombin III. Evidence for a heparin-independent mechanism
KT Preissner, U Delvos, G Mueller-Berghaus |
Biochemistry | 1987 |
Human placental anticoagulant protein: isolation and characterization
T Funakoshi, RL Heimark, LE Hendrickson, BA McMullen, K Fujikawa |
Biochemistry | 1987 |
Modulation of glycosaminoglycan production and antithrombin III binding by cultured aortic endothelial cells treated with 4-methylumbelliferyl-beta-D-xyloside
K Shimada, T Ozawa |
Arteriosclerosis (Dallas, Tex.) | 1987 |
In vitro stimulation of megakaryocyte maturation by megakaryocyte stimulatory factor
SM Greenberg, DJ Kuter, RD Rosenberg |
The Journal of biological chemistry | 1987 |
Correlation between thrombin-induced prostacyclin production and inositol trisphosphate and cytosolic free calcium levels in cultured human endothelial cells
EA Jaffe, J Grulich, BB Weksler, G Hampel, K Watanabe |
The Journal of biological chemistry | 1987 |
Activation of heparin cofactor II by fibroblasts and vascular smooth muscle cells
EA McGuire, DM Tollefsen |
The Journal of biological chemistry | 1987 |
Identification of a factor IX/IXa binding protein on the endothelial cell surface
S Rimon, R Melamed, N Savion, T Scott, PP Nawroth, DM Stern |
The Journal of biological chemistry | 1987 |
Structural requirements for the neutralization of heparin-like saccharides by complement S protein/vitronectin
DA Lane, AM Flynn, G Pejler, U Lindahl, J Choay, K Preissner |
The Journal of biological chemistry | 1987 |
Endothelial cell function in diabetic microangiopathy
M Porta, ML Selva, P Molinatti, GM Molinatti |
Diabetologia | 1987 |
Disseminated intravascular coagulation
S Fruchtman, LM Aledort |
Journal of the American College of Cardiology | 1986 |
A pathway of coagulation on bovine capillary endothelial cells
PP Nawroth, DM Stern, W Kisiel, M Dietrich |
British Journal of Haematology | 1986 |
Clearance of thrombin in vivo: significance of alternative pathways
TH Carlson |
Molecular and Cellular Biochemistry | 1986 |
Thrombin-Cellular Interactions
MA Shuman |
Annals of the New York Academy of Sciences | 1986 |
Thrombin
JW Fenton |
Annals of the New York Academy of Sciences | 1986 |
Anticoagulantly active heparin-like molecules from cultured fibroblasts
JA Marcum, EM Conway, H Youssoufian, RD Rosenberg |
Experimental Cell Research | 1986 |
Heparin fractions and analogues: a new therapeutic possibility for thrombosis
D Prost |
Trends in Pharmacological Sciences | 1986 |
Choices among the Possible Reaction Routes Catalyzed by Thrombin
R Machovich |
Annals of the New York Academy of Sciences | 1986 |
Endothelial binding sites for heparin. Specificity and role in heparin neutralization
T Bârzu, JL van Rijn, M Petitou, P Molho, G Tobelem, JP Caen |
Biochemical Journal | 1986 |
Structure and function of heparan sulphate proteoglycans
JT Gallagher, M Lyon, WP Steward |
Biochemical Journal | 1986 |
Functional domains of rabbit thrombomodulin
MC Bourin, MC Boffa, I Björk, U Lindahl |
Proceedings of the National Academy of Sciences | 1986 |
Higher susceptibility of mast-cell-deficient W/WV mutant mice to brain thromboembolism and mortality caused by intravenous injection of India ink
Y Kitamura, T Taguchi, M Yokoyama, M Inoue, A Yamatodani, H Asano, T Koyama, A Kanamaru, K Hatanaka, BK Wershil |
The American Journal of Pathology | 1986 |
A unique heparan sulfate in the nuclei of hepatocytes: structural changes with the growth state of the cells
NS Fedarko, HE Conrad |
The Journal of Cell Biology | 1986 |
Specific association of thrombin-antithrombin complexes with a human hepatoma cell line
DS Fair, EF Plow |
Thrombosis Research | 1986 |
Anticoagulantly active heparin from clam (Mercenaria mercenaria)
RE Jordan, JA Marcum |
Archives of Biochemistry and Biophysics | 1986 |
Measurement of the kinetics of inhibition of activated coagulation factor X in human plasma: The effect of plasma and inhibitor concentration
J Jesty |
Analytical Biochemistry | 1986 |
Heparin: Do We Understand Its Antithrombotic Actions?
DB Cines |
Chest | 1986 |
New Insights into Hypercoagulable States
RD Rosenberg, KA Bauer |
Hospital Practice | 1986 |
The mechanism of fibrin-induced disorganization of cultured human endothelial cell monolayers
B Weimar, U Delvos |
Arteriosclerosis (Dallas, Tex.) | 1986 |
Hemostatic regulation and Whitehead's philosophy of organism
JA Marcum, GM Verschuuren |
Acta Biotheoretica | 1986 |
The anticoagulant properties of thrombomodulin
H Salem, I Maruyama, H Ishii, CE Bell, CA Mitchell, EA Thompson, PW Majerus |
The Medical Journal of Australia | 1986 |
2 The Multiple Levels of Endothelial Cell-Coagulation Factor Interactions
PP Nawroth, D Handley, DM Stern |
Clinics in Haematology | 1986 |
5 The Natural Anticoagulants
HH Salem |
Clinics in Haematology | 1986 |
Cloned bovine aortic endothelial cells synthesize anticoagulantly active heparan sulfate proteoglycan
JA Marcum, DH Atha, LM Fritze, P Nawroth, D Stern, RD Rosenberg |
The Journal of biological chemistry | 1986 |
Cultured bovine aortic endothelial cells promote activated protein C-protein S-mediated inactivation of factor Va
DM Stern, PP Nawroth, K Harris, CT Esmon |
The Journal of biological chemistry | 1986 |
Neutralization of heparin-related saccharides by histidine-rich glycoprotein and platelet factor 4
DA Lane, G Pejler, AM Flynn, EA Thompson, U Lindahl |
The Journal of biological chemistry | 1986 |
The kinetics of inhibition of alpha-thrombin in human plasma
J Jesty |
The Journal of biological chemistry | 1986 |
Current Issues in Thrombosis Prevention with Antiplatelet Drugs:
G de Gaetano, C Cerletti, E Dejana, J Vermylen |
Drugs | 1986 |
Interaction of antithrombin III with bovine aortic segments. Role of heparin in binding and enhanced anticoagulant activity
D Stern, P Nawroth, J Marcum, D Handley, W Kisiel, R Rosenberg, K Stern |
Journal of Clinical Investigation | 1985 |
Evidence that cell surface heparan sulfate is involved in the high affinity thrombin binding to cultured porcine aortic endothelial cells
K Shimada, T Ozawa |
Journal of Clinical Investigation | 1985 |
Elevated factor Xa activity in the blood of asymptomatic patients with congenital antithrombin deficiency
KA Bauer, TL Goodman, BL Kass, RD Rosenberg |
Journal of Clinical Investigation | 1985 |
Die Bedeutung des Endothels der Gefäßwand für die Aufrechterhaltung der Hämostase
U Delvos, G Müller-Berghaus |
Klinische Wochenschrift | 1985 |
A pathway of coagulation on endothelial cells
PP Nawroth, DM Stern |
Journal of Cellular Biochemistry | 1985 |
Self-regulation of procoagulant events on the endothelial cell surface
DM Stern, I Bank, PP Nawroth, J Cassimeris, W Kisiel, JW 2nd, C Dinarello, L Chess, EA Jaffe |
Journal of Experimental Medicine | 1985 |
An endothelial cell-dependent pathway of coagulation
D Stern, P Nawroth, D Handley, W Kisiel |
Proceedings of the National Academy of Sciences | 1985 |
Comparison of the behaviour in vivo of two molecular forms of antithrombin III
TH Carlson, AC Atencio, TL Simon |
Biochemical Journal | 1985 |
An antiproliferative heparan sulfate species produced by postconfluent smooth muscle cells
LM Fritze, CF Reilly, RD Rosenberg |
The Journal of Cell Biology | 1985 |
Heparinlike molecules with anticoagulant activity are synthesized by cultured endothelial cells
JA Marcum, RD Rosenberg |
Biochemical and Biophysical Research Communications | 1985 |
Interaction of complement S-protein with thrombin-antithrombin complexes: A role for the S-protein in haemostasis
D Jenne, F Hugo, S Bhakdi |
Thrombosis Research | 1985 |
Mechanisms of Stimulus—Response Coupling in Platelets
J Westwick, MF Scully, DE MacIntyre, VV Kakkar |
1985 | |
Formation of the Fibrin Clot: the Balance of Procoagulant and Inhibitory Factors
B Lämmle, JH Griffin |
Clinics in Haematology | 1985 |
The Role of Endothelium in the Homeostatic Balance of Haemostasis
P Nawroth, W Kisiel, D Stern |
Clinics in Haematology | 1985 |
Verhandlungen der Deutschen Gesellschaft für Innere Medizin
B Schlegel |
1962 |