Research Topics
Species | Kenneth G MannSummaryAffiliation: University of Vermont Country: USA Publications
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Publications
Thrombin formationKenneth G Mann
Department of Biochemistry, University of Vermont College of Medicine, Burlington, VT 05405, USA
Chest 124:4S-10S. 2003..This review provides a brief summary of the evolution of knowledge with respect to present-day concepts of thrombin generation via the tissue factor pathway and its regulation...
Membrane binding events in the initiation and propagation phases of tissue factor-initiated zymogen activation under flowLaura M Haynes
Department of Biochemistry, University of Vermont College of Medicine, Colchester, Vermont 05446, USA
J Biol Chem 287:5225-34. 2012....
Posttranslational modifications and activity of natural and recombinant tissue factorSaulius Butenas
Department of Biochemistry, University of Vermont, 208 South Park Drive, Burlington, VT 05446, USA
Thromb Res 125:S26-8. 2010..Thus the use of recombinant tissue factor proteins for the quantitation of natural tissue factor is misleading...
The impact of uncertainty in a blood coagulation modelChristopher M Danforth
Department of Mathematics and Statistics, Center for Complex Systems, Vermont Advanced Computing Center, University of Vermont, Burlington, VT 05401, USA
Math Med Biol 26:323-36. 2009....
Modeling of human factor Va inactivation by activated protein CMARIA CRISTINA BRAVO
Cell and Molecular Biology Program, University of Vermont, 89 Beaumont Ave, Burlington, VT 05405, USA
BMC Syst Biol 6:45. 2012..An empirically validated mathematical model of this process would be useful in advancing the predictive capacity of comprehensive models of coagulation...
Tissue factor in thrombosis and hemorrhageSaulius Butenas
Department of Biochemistry, University of Vermont, Colchester, VT 05446, USA
Surgery 142:S2-14. 2007....
Influence of bivalirudin on tissue factor-triggered coagulationSaulius Butenas
Department of Biochemistry, University of Vermont, College of Medicine, Burlington, Vermont, USA
Blood Coagul Fibrinolysis 18:407-14. 2007..In conclusion, bivalirudin at pharmacologic concentrations is an efficient inhibitor of thrombin generation, platelet activation and clot formation, which acts not as a modulator but as an 'on-off' switch of blood coagulation...
Active tissue factor and activated factor XI in patients with acute ischemic cerebrovascular eventsAnetta Undas
Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland
Eur J Clin Invest 42:123-9. 2012..We sought to investigate whether circulating activated FXI (FXIa) and TF on admission can predict clinical outcomes in patients with acute cerebrovascular events...
Carbohydrates and activity of natural and recombinant tissue factorJolanta Krudysz-Amblo
Department of Biochemistry, University of Vermont, Burlington, Vermont 05405, USA
J Biol Chem 285:3371-82. 2010..The carbohydrates of rTF(1-263) contain high mannose, hybrid, and fucosylated glycans. Natural pTF contains no high mannose glycans but is modified with hybrid, highly fucosylated, and sialylated sugars...
Differences in the fractional abundances of carbohydrates of natural and recombinant human tissue factorJolanta Krudysz-Amblo
Department of Biochemistry, University of Vermont, Burlington, VT 05405, USA
Biochim Biophys Acta 1810:398-405. 2011..Previously we have shown that the activity of the natural placental TF (pTF) and the recombinant TF (rTF) from Sf9 insect cells is different (Krudysz-Amblo, J. et al (2010) J. Biol. Chem. 285, 3371-3382)...
The nature of the stable blood clot procoagulant activitiesThomas Orfeo
Department of Biochemistry, University of Vermont, Colchester, VT 05446, USA
J Biol Chem 283:9776-86. 2008..e. hemophilias A and B, result in an impaired capacity to mount a resupply response; and 3) in normal hemostasis the intrinsic factor Xase function contributes to the durability of the resupply response...
Prothrombin activation in blood coagulation: the erythrocyte contribution to thrombin generationMatthew F Whelihan
Department of Biochemistry, University of Vermont, Burlington, VT, USA
Blood 120:3837-45. 2012..These data indicate that RBCs participate in thrombin generation in Tf-activated blood, producing a membrane that supports prothrombin activation through the meizothrombin pathway...
Tissue factor in coagulation: Which? Where? When?Saulius Butenas
Department of Biochemistry, University of Vermont, 208 South Park Drive, Suite 2, Room 235A, Colchester, VT 05446, USA
Arterioscler Thromb Vasc Biol 29:1989-96. 2009..We also highlight controversies concerning the expression/presence of TF on various cells and in blood in normal and pathological states...
Plasma factor and inhibitor composition contributes to thrombin generation dynamics in patients with acute or previous cerebrovascular eventsMatthew Gissel
Department of Biochemistry, University of Vermont, Colchester, VT, USA
Thromb Res 126:262-9. 2010..We evaluated whether plasma factor composition and thrombin generation dynamics might be a contributor to the thrombotic phenotype of ischemic cerebrovascular events...
Thrombin functions during tissue factor-induced blood coagulationKathleen E Brummel
Department of Biochemistry, University of Vermont, College of Medicine, Burlington, VT 05405, USA
Blood 100:148-52. 2002..6 +/- 0.6 minutes). These results illustrate that the initial activation of thrombin substrates occurs during the initiation phase at less than 2 nM thrombin (0.2%). Most thrombin (96%) is formed well after clotting occurs...
The "normal" factor VIII concentration in plasmaSaulius Butenas
Department of Biochemistry, College of Medicine, University of Vermont, Burlington, VT 05446, USA
Thromb Res 126:119-23. 2010..The quantitation of factor (F)VIII by activity-based assays is influenced by the method, procedure, the quality and properties of reagents used and concentrations of other plasma proteins, including von Willebrand factor (VWF)...
Dilutional control of prothrombin activation at physiologically relevant shear ratesLaura M Haynes
Department of Biochemistry, University of Vermont, College of Medicine, Colchester, Vermont, USA
Biophys J 100:765-73. 2011....
Models of blood coagulationKenneth G Mann
Department of Biochemistry, 208 South Park Drive, Suite 2, University of Vermont, College of Medicine, Colchester, VT 05446, USA
Blood Cells Mol Dis 36:108-17. 2006..Ideally, our results will provide descriptions which predict the behavior of the biological blood coagulation system under normal and pathologic conditions...
Quantitation of anti-factor VIII antibodies in human plasmaJolanta Krudysz-Amblo
Department of Biochemistry, College of Medicine, University of Vermont, Burlington, VT, USA
Blood 113:2587-94. 2009..6 to 6.2 nM, whereas 13 (33%) of the 39 inhibitor-free hemophilia A subjects were positive for anti-fVIIIAb in the range of 0.5 to 20 nM. The method may be useful for therapeutic management of hemophilia A patients...
Mechanism of factor VIIa-dependent coagulation in hemophilia bloodSaulius Butenas
College of Medicine, University of Vermont, 89 Beaumont Ave, Burlington, VT 05405-0068, USA
Blood 99:923-30. 2002..Thus, pharmacologic concentrations of factor VIIa cannot restore normal thrombin generation in hemophilia A and hemophilia B blood in vitro. The efficacy of factor VIIa (10-50 nM) in hemophilia blood is dependent on TF...
The factor V activation paradoxThomas Orfeo
Department of Biochemistry, University of Vermont, 89 Beaumont Avenue, Burlington, VT 05405 0068, USA
J Biol Chem 279:19580-91. 2004..Direct activation of factor V by factor Xa at physiologically relevant concentrations does not appear to be a significant contributor to factor Va formation...
Tissue factor controversiesKenneth G Mann
University of Vermont, Department of Biochemistry, Burlington, VT, corrected USA
Thromb Res 129:S5-7. 2012..This presentation will review data on the architecture and functions of the tissue factor-factor VIIa complex and discuss the elements of the controversies associated with tissue factor presentation in both normal and pathologic milieu...
Cellular regulation of blood coagulation: a model for venous stasisJames E Campbell
Department of Biochemistry, University of Vermont, Colchester, VT 05446, USA
Blood 116:6082-91. 2010....
Factor XIa and tissue factor activity in patients with coronary artery diseaseSaulius Butenas
University of Vermont, Department of Biochemistry, Burlington, Vermont, USA
Thromb Haemost 99:142-9. 2008..59 and 0.39, respectively) and between FXIa and TAT (R(2) = 0.64 and 0.63, respectively). In conclusion, the majority of ACS and CAD-MI patients have circulating FXIa that correlates with markers of coagulation and inflammation...
Tissue factor activity and function in blood coagulationSaulius Butenas
Department of Biochemistry, University of Vermont, Burlington, VT, USA
Thromb Res 122:S42-6. 2008....
The tissue factor requirement in blood coagulationThomas Orfeo
Department of Biochemistry, University of Vermont, Burlington, Vermont 05405, USA
J Biol Chem 280:42887-96. 2005..These observations support the hypothesis that the transient, localized expression of TF is sufficient to sustain a TF-independent procoagulant response as long as flow persists...
Taking the thrombin "fork"Kenneth G Mann
University of Vermont, College of Medicine, 208 South Park Drive, Colchester, VT 05446, USA
Arterioscler Thromb Vasc Biol 30:1293-9. 2010..take it." My career is a consequence of chance interactions with great mentors and talented students and the opportunities provided by a succession of ground-breaking improvements in technology...
Tissue factor activity in whole bloodSaulius Butenas
University of Vermont, Department of Biochemistry, Given Building, 89 Beaumont Ave, Burlington, VT 05405 0068, USA
Blood 105:2764-70. 2005..Our data indicate that the concentration of physiologically active TF in non-cytokine-stimulated blood from healthy individuals cannot exceed and is probably lower than 20 fM...
Influence of factor VIIa and phospholipids on coagulation in "acquired" hemophiliaSaulius Butenas
University of Vermont, College of Medicine, Burlington, VT 05405-0068, USA
Arterioscler Thromb Vasc Biol 23:123-9. 2003..CONCLUSIONS: The influence of rFVIIa is dependent on TF, and phospholipids substantially increase the hemostatic (or thrombotic) potential of rFVIIa/TF...
Thrombin: can't live without it; probably die from itKenneth G Mann
Department of Biochemistry, University of Vermont College of Medicine, Burlington, VT 05405, USA
Chest 124:1S-3S. 2003
The dynamics of thrombin formationKenneth G Mann
Department of Biochemistry, University of Vermont, College of Medicine, Burlington, VT 05405, USA
Arterioscler Thromb Vasc Biol 23:17-25. 2003....
Factor V: a combination of Dr Jekyll and Mr HydeKenneth G Mann
Department of Biochemistry, University of Vermont, College of Medicine, Burlington 05405, USA
Blood 101:20-30. 2003
The prothrombotic phenotypes in familial protein C deficiency are differentiated by computational modeling of thrombin generationKathleen E Brummel-Ziedins
Department of Biochemistry, University of Vermont, College of Medicine, Burlington, Vermont, United States of America
PLoS ONE 7:e44378. 2012..In addition, variations within the plasma composition of each individual can further segregate out increased procoagulant phenotypes, with gender-associated plasma compositional differences playing a large role...
Posttranslational modifications of tissue factorSaulius Butenas
Department of Biochemistry, College of Medicine, University of Vermont, Burlington, VT 05446, USA
Front Biosci (Elite Ed) 4:381-91. 2012..Overall, it is clear that some modifications of TF have an effect on TF procoagulant activity, signaling functions and trafficking. The influences of other modifications are debatable...
The resuscitative fluid you choose may potentiate bleedingKathleen Brummel-Ziedins
Department of Biochemistry, School of Medicine, University of Vermont, Burlington, Vermont 05405, USA
J Trauma 61:1350-8. 2006..Little is known about how various resuscitative paradigms affect the coagulation cascade, which is essential to controlling hemorrhagic shock...
Rivaroxaban delivery and reversal at a venous flow rateLaura M Haynes
Department of Biochemistry, University of Vermont College of Medicine, Colchester, VT 05446, USA
Arterioscler Thromb Vasc Biol 32:2877-83. 2012....
A model for the stoichiometric regulation of blood coagulationMatthew F Hockin
Department of Biochemistry, College of Medicine, University of Vermont, Burlington, Vermont 05405, USA
J Biol Chem 277:18322-33. 2002..A comparison of the model with empirical laboratory data illustrates that most experimentally observable parameters are captured, and the pathology that results in enhanced or deficient thrombin generation is accurately described...
Prothrombin activation by platelet-associated prothrombinase proceeds through the prethrombin-2 pathway via a concerted mechanismLaura M Haynes
Department of Biochemistry, University of Vermont College of Medicine, Burlington, Vermont 05405, USA
J Biol Chem 287:38647-55. 2012..Collectively, these findings suggest that platelet-associated prothrombinase activates prothrombin via an efficient concerted mechanism in which neither intermediate is released...
The challenge of regulating anticoagulant drugs: focus on warfarinKenneth G Mann
Vermont College of Medicine, Department of Biochemistry, University of Vermont, Burlington, VT 05405, USA
Am Heart J 149:S36-42. 2005
The significance of circulating factor IXa in bloodSaulius Butenas
Department of Biochemistry, University of Vermont, Burlington, Vermont 05405 0068, USA
J Biol Chem 279:22875-82. 2004....
The crystal structure of activated protein C-inactivated bovine factor Va: Implications for cofactor functionTy E Adams
Department of Biochemistry, College of Medicine, University of Vermont, 89 Beaumont Avenue, Burlington, VT 05405, USA
Proc Natl Acad Sci U S A 101:8918-23. 2004..This structure represents the largest physiologically relevant fragment of factor Va solved to date and provides a new scaffold for the future generation of models of coagulation cofactors...
Statins and blood coagulationAnetta Undas
Department of Medicine, Jagiellonian University School of Medicine, Krakow, Poland
Arterioscler Thromb Vasc Biol 25:287-94. 2005..Treatment with statins can lead to a significant downregulation of the blood coagulation cascade, most probably as a result of decreased tissue factor expression, which leads to reduced thrombin generation...
Intracellular and surface distribution of monocyte tissue factor: application to intersubject variabilityElena M Egorina
Department of Biochemistry, Institute of Medical Biology, University of Tromsø, Tromsø, Norway
Arterioscler Thromb Vasc Biol 25:1493-8. 2005..We characterized patterns of intracellular accumulation, externalization, and shedding of TF in response to LPS in mononuclear cells (MNCs) from high responders (HRs) and low responders (LRs)...
Structural requirements for expression of factor Va activityMichael Kalafatis
Department of Chemistry, Cleveland State University, and The Lerner Research Institute, The Cleveland Clinic Foundation, Ohio, USA
J Biol Chem 278:33550-61. 2003....
Simvastatin given for 3 days can inhibit thrombin generation and activation of factor V and enhance factor Va inactivation in hypercholesterolemic patientsAnetta Undas
Arterioscler Thromb Vasc Biol 25:1524-5. 2005
Blood coagulation at the site of microvascular injury in healthy and coumadin-treated subjects heterogenous for factor V Leiden mutationAnetta Undas
Department of Medicine, Jagiellonian University School of Medicine, Crakow, Poland
Thromb Haemost 98:1024-30. 2007..Inactivation of FVa by the APC mechanism is attenuated significantly in carriers of FV Leiden but the magnitude of this effect is smaller than that observed in most purified systems...
Antithrombotic properties of aspirin and resistance to aspirin: beyond strictly antiplatelet actionsAnetta Undas
Institute of Cardiology, Jagiellonian University School of Medicine, Krakow, Poland
Blood 109:2285-92. 2007..Elucidation of the actual impacts of aspirin other than antiaggregation effects could be important in view of the widespread use of this drug in the prevention of thrombotic manifestations of atherosclerosis...
Identification of an inactivating cleavage site for alpha-thrombin on the heavy chain of factor VaEvrim Erdogan
Department of Chemistry, Cleveland State University, 2351 Euclid Avenue, Science and Research Center SR 370, Cleveland, Ohio 44115, USA
Thromb Haemost 98:998-1006. 2007..Our data demonstrate that cleavage of FVa at Arg(643) by alpha-thrombin results in a partially inactive cofactor molecule and provides for an activated protein C (APC)-independent anticoagulant effect of alpha-thrombin...
Aspirin alters the cardioprotective effects of the factor XIII Val34Leu polymorphismAnetta Undas
Department of Medicine, Jagiellonian University School of Medicine, Cracow, Poland
Circulation 107:17-20. 2003....
Factor VII-activating protease: coagulation, fibrinolysis, and atherothrombosis?Kenneth G Mann
Circulation 107:654-5. 2003
A critical review of the methods for cleavage of fusion proteins with thrombin and factor XaRichard J Jenny
Haematologic Technologies, Inc, Essex Junction, VT, USA
Protein Expr Purif 31:1-11. 2003..Examples are presented which describe the proteolysis of the protein of interest by either factor Xa or thrombin...
A review of the therapeutic uses of thrombinRoger L Lundblad
Department of Pathology, University of North Carolina at Chapel Hill, USA
Thromb Haemost 91:851-60. 2004..However, the availability of a safe human thrombin preparation will be critical for the continued use of thrombin as a therapeutic...
Active tissue factor in blood?Saulius Butenas
Nat Med 10:1155-6; author reply 1156. 2004
