Thrombin: An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN.Receptors, Thrombin: A family of proteinase-activated receptors that are specific for THROMBIN. They are found primarily on PLATELETS and on ENDOTHELIAL CELLS. Activation of thrombin receptors occurs through the proteolytic action of THROMBIN, which cleaves the N-terminal peptide from the receptor to reveal a new N-terminal peptide that is a cryptic ligand for the receptor. The receptors signal through HETEROTRIMERIC GTP-BINDING PROTEINS. Small synthetic peptides that contain the unmasked N-terminal peptide sequence can also activate the receptor in the absence of proteolytic activity.Thrombin Time: Clotting time of PLASMA mixed with a THROMBIN solution. It is a measure of the conversion of FIBRINOGEN to FIBRIN, which is prolonged by AFIBRINOGENEMIA, abnormal fibrinogen, or the presence of inhibitory substances, e.g., fibrin-fibrinogen degradation products, or HEPARIN. BATROXOBIN, a thrombin-like enzyme unaffected by the presence of heparin, may be used in place of thrombin.Hirudins: Single-chain polypeptides of about 65 amino acids (7 kDa) from LEECHES that have a neutral hydrophobic N terminus, an acidic hydrophilic C terminus, and a compact, hydrophobic core region. Recombinant hirudins lack tyr-63 sulfation and are referred to as 'desulfato-hirudins'. They form a stable non-covalent complex with ALPHA-THROMBIN, thereby abolishing its ability to cleave FIBRINOGEN.Receptor, PAR-1: A thrombin receptor subtype that couples to HETEROTRIMERIC GTP-BINDING PROTEINS resulting in the activation of a variety of signaling mechanisms including decreased intracellular CYCLIC AMP, increased TYPE C PHOSPHOLIPASES and increased PHOSPHOLIPASE A2.Antithrombins: Endogenous factors and drugs that directly inhibit the action of THROMBIN, usually by blocking its enzymatic activity. They are distinguished from INDIRECT THROMBIN INHIBITORS, such as HEPARIN, which act by enhancing the inhibitory effects of antithrombins.Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.Blood Coagulation: The process of the interaction of BLOOD COAGULATION FACTORS that results in an insoluble FIBRIN clot.Antithrombin III: A plasma alpha 2 glycoprotein that accounts for the major antithrombin activity of normal plasma and also inhibits several other enzymes. It is a member of the serpin superfamily.Fibrinopeptide A: Two small peptide chains removed from the N-terminal segment of the alpha chains of fibrinogen by the action of thrombin during the blood coagulation process. Each peptide chain contains 18 amino acid residues. In vivo, fibrinopeptide A is used as a marker to determine the rate of conversion of fibrinogen to fibrin by thrombin.Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia.Hemostatics: Agents acting to arrest the flow of blood. Absorbable hemostatics arrest bleeding either by the formation of an artificial clot or by providing a mechanical matrix that facilitates clotting when applied directly to the bleeding surface. These agents function more at the capillary level and are not effective at stemming arterial or venous bleeding under any significant intravascular pressure.Platelet Activation: A series of progressive, overlapping events, triggered by exposure of the PLATELETS to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug.Heparin Cofactor II: A sulfated plasma protein with a MW of approximately 66kDa that resembles ANTITHROMBIN III. The protein is an inhibitor of thrombin in plasma and is activated by dermatan sulfate or heparin. It is a member of the serpin superfamily.Factor Xa: Activated form of factor X that participates in both the intrinsic and extrinsic pathways of blood coagulation. It catalyzes the conversion of prothrombin to thrombin in conjunction with other cofactors.Platelet Aggregation: The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.Fibrin: A protein derived from FIBRINOGEN in the presence of THROMBIN, which forms part of the blood clot.Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation.Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation.Pipecolic AcidsHeparin: A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.Fibrinopeptide B: Two small peptide chains removed from the N-terminal segment of the beta chains of fibrinogen by the action of thrombin. Each peptide chain contains 20 amino acid residues. The removal of fibrinopeptides B is not required for coagulation.Thromboplastin: Constituent composed of protein and phospholipid that is widely distributed in many tissues. It serves as a cofactor with factor VIIa to activate factor X in the extrinsic pathway of blood coagulation.Partial Thromboplastin Time: The time required for the appearance of FIBRIN strands following the mixing of PLASMA with phospholipid platelet substitute (e.g., crude cephalins, soybean phosphatides). It is a test of the intrinsic pathway (factors VIII, IX, XI, and XII) and the common pathway (fibrinogen, prothrombin, factors V and X) of BLOOD COAGULATION. It is used as a screening test and to monitor HEPARIN therapy.Blood Coagulation Tests: Laboratory tests for evaluating the individual's clotting mechanism.Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process.Kinetics: The rate dynamics in chemical or physical systems.Factor V: Heat- and storage-labile plasma glycoprotein which accelerates the conversion of prothrombin to thrombin in blood coagulation. Factor V accomplishes this by forming a complex with factor Xa, phospholipid, and calcium (prothrombinase complex). Deficiency of factor V leads to Owren's disease.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Coagulants: Agents that cause clotting.Anticoagulants: Agents that prevent clotting.Factor VIII: Blood-coagulation factor VIII. Antihemophilic factor that is part of the factor VIII/von Willebrand factor complex. Factor VIII is produced in the liver and acts in the intrinsic pathway of blood coagulation. It serves as a cofactor in factor X activation and this action is markedly enhanced by small amounts of thrombin.Hirudin Therapy: Use of HIRUDINS as an anticoagulant in the treatment of cardiological and hematological disorders.Hemostasis: The process which spontaneously arrests the flow of BLOOD from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements (eg. ERYTHROCYTE AGGREGATION), and the process of BLOOD COAGULATION.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Factor X: Storage-stable glycoprotein blood coagulation factor that can be activated to factor Xa by both the intrinsic and extrinsic pathways. A deficiency of factor X, sometimes called Stuart-Prower factor deficiency, may lead to a systemic coagulation disorder.Thrombosis: Formation and development of a thrombus or blood clot in the blood vessel.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Platelet Glycoprotein GPIb-IX Complex: Platelet membrane glycoprotein complex essential for normal platelet adhesion and clot formation at sites of vascular injury. It is composed of three polypeptides, GPIb alpha, GPIb beta, and GPIX. Glycoprotein Ib functions as a receptor for von Willebrand factor and for thrombin. Congenital deficiency of the GPIb-IX complex results in Bernard-Soulier syndrome. The platelet glycoprotein GPV associates with GPIb-IX and is also absent in Bernard-Soulier syndrome.Fibrinolysis: The natural enzymatic dissolution of FIBRIN.Receptors, Proteinase-Activated: A class of receptors that are activated by the action of PROTEINASES. The most notable examples are the THROMBIN RECEPTORS. The receptors contain cryptic ligands that are exposed upon the selective proteolysis of specific N-terminal cleavage sites.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Carboxypeptidase U: A metallocarboxypeptidase that removes C-terminal lysine and arginine from biologically active peptides and proteins thereby regulating their activity. It is a zinc enzyme with no preference shown for lysine over arginine. Pro-carboxypeptidase U in human plasma is activated by thrombin or plasmin during clotting to form the unstable carboxypeptidase U.Factor XI: Stable blood coagulation factor involved in the intrinsic pathway. The activated form XIa activates factor IX to IXa. Deficiency of factor XI is often called hemophilia C.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Fibrinolysin: A product of the lysis of plasminogen (profibrinolysin) by PLASMINOGEN activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins.Factor Va: Activated form of factor V. It is an essential cofactor for the activation of prothrombin catalyzed by factor Xa.Oligopeptides: Peptides composed of between two and twelve amino acids.Receptor, PAR-2: A G-protein-coupled, proteinase-activated receptor that is expressed in a variety of tissues including ENDOTHELIUM; LEUKOCYTES; and the GASTROINTESTINAL TRACT. The receptor is activated by TRYPSIN, which cleaves off the N-terminal peptide from the receptor. The new N-terminal peptide is a cryptic ligand for the receptor. The uncleaved receptor can also be activated by the N-terminal peptide present on the activated THROMBIN RECEPTOR and by small synthetic peptides that contain the unmasked N-terminal sequence.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Platelet Membrane Glycoproteins: Surface glycoproteins on platelets which have a key role in hemostasis and thrombosis such as platelet adhesion and aggregation. Many of these are receptors.Batroxobin: A proteolytic enzyme obtained from the venom of fer-de-lance (Bothrops atrox). It is used as a plasma clotting agent for fibrinogen and for the detection of fibrinogen degradation products. The presence of heparin does not interfere with the clotting test. Hemocoagulase is a mixture containing batroxobin and factor X activator. EC 3.4.21.-.Prothrombin Time: Clotting time of PLASMA recalcified in the presence of excess TISSUE THROMBOPLASTIN. Factors measured are FIBRINOGEN; PROTHROMBIN; FACTOR V; FACTOR VII; and FACTOR X. It is used for monitoring anticoagulant therapy with COUMARINS.Protease Nexins: Extracellular protease inhibitors that are secreted from FIBROBLASTS. They form a covalent complex with SERINE PROTEASES and can mediate their cellular internalization and degradation.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Serine Proteinase Inhibitors: Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Ancrod: An enzyme fraction from the venom of the Malayan pit viper, Agkistrodon rhodostoma. It catalyzes the hydrolysis of a number of amino acid esters and a limited proteolysis of fibrinogen. It is used clinically to produce controlled defibrination in patients requiring anticoagulant therapy. EC 3.4.21.-.Dermatan Sulfate: A naturally occurring glycosaminoglycan found mostly in the skin and in connective tissue. It differs from CHONDROITIN SULFATE A (see CHONDROITIN SULFATES) by containing IDURONIC ACID in place of glucuronic acid, its epimer, at carbon atom 5. (from Merck, 12th ed)Umbilical Veins: Venous vessels in the umbilical cord. They carry oxygenated, nutrient-rich blood from the mother to the FETUS via the PLACENTA. In humans, there is normally one umbilical vein.Fibrinogens, Abnormal: Fibrinogens which have a functional defect as the result of one or more amino acid substitutions in the amino acid sequence of normal fibrinogen. Abnormalities of the fibrinogen molecule may impair any of the major steps involved in the conversion of fibrinogen into stabilized fibrin, such as cleavage of the fibrinopeptides by thrombin, polymerization and cross-linking of fibrin. The resulting dysfibrinogenemias can be clinically silent or can be associated with bleeding, thrombosis or defective wound healing.Adenosine Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Amino Acid Chloromethyl Ketones: Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.Phosphatidylinositols: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.Factor XIII: A fibrin-stabilizing plasma enzyme (TRANSGLUTAMINASES) that is activated by THROMBIN and CALCIUM to form FACTOR XIIIA. It is important for stabilizing the formation of the fibrin polymer (clot) which culminates the coagulation cascade.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Aptamers, Nucleotide: Nucleotide sequences, generated by iterative rounds of SELEX APTAMER TECHNIQUE, that bind to a target molecule specifically and with high affinity.Platelet Adhesiveness: The process whereby PLATELETS adhere to something other than platelets, e.g., COLLAGEN; BASEMENT MEMBRANE; MICROFIBRILS; or other "foreign" surfaces.Platelet Aggregation Inhibitors: Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.Fibrin Fibrinogen Degradation Products: Soluble protein fragments formed by the proteolytic action of plasmin on fibrin or fibrinogen. FDP and their complexes profoundly impair the hemostatic process and are a major cause of hemorrhage in intravascular coagulation and fibrinolysis.Bleeding Time: Duration of blood flow after skin puncture. This test is used as a measure of capillary and platelet function.Isoflurophate: A di-isopropyl-fluorophosphate which is an irreversible cholinesterase inhibitor used to investigate the NERVOUS SYSTEM.Antithrombin Proteins: An endogenous family of proteins belonging to the serpin superfamily that neutralizes the action of thrombin. Six naturally occurring antithrombins have been identified and are designated by Roman numerals I to VI. Of these, Antithrombin I (see FIBRIN) and ANTITHROMBIN III appear to be of major importance.Blood Coagulation Disorders: Hemorrhagic and thrombotic disorders that occur as a consequence of abnormalities in blood coagulation due to a variety of factors such as COAGULATION PROTEIN DISORDERS; BLOOD PLATELET DISORDERS; BLOOD PROTEIN DISORDERS or nutritional conditions.Fibrinolytic Agents: Fibrinolysin or agents that convert plasminogen to FIBRINOLYSIN.Endothelium: A layer of epithelium that lines the heart, blood vessels (ENDOTHELIUM, VASCULAR), lymph vessels (ENDOTHELIUM, LYMPHATIC), and the serous cavities of the body.Factor VIIa: Activated form of factor VII. Factor VIIa activates factor X in the extrinsic pathway of blood coagulation.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Trypsin: A serine endopeptidase that is formed from TRYPSINOGEN in the pancreas. It is converted into its active form by ENTEROPEPTIDASE in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Dansyl Compounds: Compounds that contain a 1-dimethylaminonaphthalene-5-sulfonyl group.

Role of thrombin receptor in breast cancer invasiveness. (1/5662)

Invasion, the ability of an epithelial cancer cell to detach from and move through a basement membrane, is a central process in tumour metastasis. Two components of invasion are proteolysis of extracellular matrix and cellular movement through it. A potential promoter of these two processes is thrombin, the serine proteinase derived from the ubiquitous plasma protein prothrombin. Thrombin promotes the invasion of MDA-MB231 breast tumour cells (a highly aggressive cell line) in an in vitro assay. Invasion by MDA-MB436 and MCF-7 cells, less aggressive cell lines, is not promoted by thrombin. Thrombin, added to the cells, is a stimulator of cellular movement; fibroblast-conditioned medium is the chemotaxin. Thrombin-promoted invasion is inhibited by hirudin. Stimulation of invasion is a receptor-mediated process that is mimicked by a thrombin receptor-activating peptide. Thrombin has no effect on chemotaxis in vitro. Thrombin receptor is detectable on the surface of MDA-MB231 cells, but not on the other two cell lines. Introduction of oestrogen receptors into MDA-MB231 cells by transfection with pHEO had no effect on thrombin receptor expression, in the presence or absence of oestradiol. This paper demonstrates that thrombin increases invasion by the aggressive breast cancer cell line MDA-MB231 by a thrombin receptor-dependent mechanism.  (+info)

Activation of stimulus-specific serine esterases (proteases) in the initiation of platelet secretion. I. Demonstration with organophosphorus inhibitors. (2/5662)

The effect of organophosphorus inhibitors of serine esterases (proteases) on secretion from washed rabbit platelets was examined. Five noncytotoxic stimuli were employed: collagen, thrombin, heterologous anti-platelet antibody (in the absence of complement), rabbit C3 bound to zymosan, and platelet activating factor derived from antigen-stimulated, IgE-sensitized rabbit basophils. Diisoprophyl phosphofluoridate, three series of p-nitrophenyl ethyl phosphonates, and a series of cyclohexyl phenylalkylphosphonofluridates were all found to be inhibitory to the platelet secretion. These are irreversible inhibitors of serine proteases but in this system were only inhibitory if added to the platelets concurrently with the stimuli. Pretreatment of either the platelets or the stimuli with the inhibitors followed by washing, was without effect on the subsequent reaction. This suggested the involvement of stimulus-activatable serine proteases in the secretory process. The concept was supported by finding that nonphosphorylating phosphonates or hydrolyzed phosphonates or phosphonofluoridates were without inhibitory action. The effect of a series of phosphonates or phosphonoflouridates in inhibiting each stimulus exhibited a unique activity-structure profile. The demonstration of such unique profiles with four series of inhibitors for each of the five stimuli was interpreted as demonstrating that a specific activatable serine protease was involved in the platelet secretory response to each stimulus.  (+info)

Exosites 1 and 2 are essential for protection of fibrin-bound thrombin from heparin-catalyzed inhibition by antithrombin and heparin cofactor II. (3/5662)

Assembly of ternary thrombin-heparin-fibrin complexes, formed when fibrin binds to exosite 1 on thrombin and fibrin-bound heparin binds to exosite 2, produces a 58- and 247-fold reduction in the heparin-catalyzed rate of thrombin inhibition by antithrombin and heparin cofactor II, respectively. The greater reduction for heparin cofactor II reflects its requirement for access to exosite 1 during the inhibitory process. Protection from inhibition by antithrombin and heparin cofactor II requires ligation of both exosites 1 and 2 because minimal protection is seen when exosite 1 variants (gamma-thrombin and thrombin Quick 1) or an exosite 2 variant (Arg93 --> Ala, Arg97 --> Ala, and Arg101 --> Ala thrombin) is substituted for thrombin. Likewise, the rate of thrombin inhibition by the heparin-independent inhibitor, alpha1-antitrypsin Met358 --> Arg, is decreased less than 2-fold in the presence of soluble fibrin and heparin. In contrast, thrombin is protected from inhibition by a covalent antithrombin-heparin complex, suggesting that access of heparin to exosite 2 of thrombin is hampered when ternary complex formation occurs. These results reveal the importance of exosites 1 and 2 of thrombin in assembly of the ternary complex and the subsequent protection of thrombin from inhibition by heparin-catalyzed inhibitors.  (+info)

Activation of G12/G13 results in shape change and Rho/Rho-kinase-mediated myosin light chain phosphorylation in mouse platelets. (4/5662)

Platelets respond to various stimuli with rapid changes in shape followed by aggregation and secretion of their granule contents. Platelets lacking the alpha-subunit of the heterotrimeric G protein Gq do not aggregate and degranulate but still undergo shape change after activation through thromboxane-A2 (TXA2) or thrombin receptors. In contrast to thrombin, the TXA2 mimetic U46619 led to the selective activation of G12 and G13 in Galphaq-deficient platelets indicating that these G proteins mediate TXA2 receptor-induced shape change. TXA2 receptor-mediated activation of G12/G13 resulted in tyrosine phosphorylation of pp72(syk) and stimulation of pp60(c-src) as well as in phosphorylation of myosin light chain (MLC) in Galphaq-deficient platelets. Both MLC phosphorylation and shape change induced through G12/G13 in the absence of Galphaq were inhibited by the C3 exoenzyme from Clostridium botulinum, by the Rho-kinase inhibitor Y-27632 and by cAMP-analogue Sp-5,6-DCl-cBIMPS. These data indicate that G12/G13 couple receptors to tyrosine kinases as well as to the Rho/Rho-kinase-mediated regulation of MLC phosphorylation. We provide evidence that G12/G13-mediated Rho/Rho-kinase-dependent regulation of MLC phosphorylation participates in receptor-induced platelet shape change.  (+info)

Regulation of the activities of thrombin and plasmin by cholesterol sulfate as a physiological inhibitor in human plasma. (5/5662)

Thrombin and plasmin, both of which are serine proteases in the plasma of vertebrates, play essential roles in blood clotting and fibrinolysis, respectively, and regulation of their activities is important to suppress the excessive reactions within the vascular network and to prevent tissue injury. Along with the peptidic inhibitors belonging to the serpin family, we found that cholesterol sulfate (CS), which is present at the concentration of 2.0+/-1.2 nmol/ml in human plasma, was a potent inhibitor of both plasma thrombin and plasmin. Thrombin, as determined both using a chromogenic substrate and the natural substrate, fibrinogen, was inactivated upon reaction with CS in a dose-dependent manner, but not in the presence of the structurally related steroid sulfates, I3SO3-GalCer and II3NAalpha-LacCer, suggesting that both the sulfate group and the hydrophobic side chain of CS are necessary for the inhibitory activity of CS. Preincubation of thrombin with CS at 37 degrees C for 10 min was required to achieve maximum inhibition, and virtually complete inhibition was achieved at a molar ratio of CS to thrombin of 18:1. CS-treated thrombin had the same Km and a lower Vmax than the original enzyme, and a higher molecular weight. The molecular weight and activity of the original enzyme were not observed on the attempted separation of the CS-treated enzyme by gel permeation chromatography and native PAGE, indicating that the inactivation of thrombin by CS is irreversible. In contrast, CS was readily liberated from the enzyme by SDS-PAGE, suggesting that hydrophobic interactions are involved in the CS-mediated inactivation of thrombin. When acidic lipids were reacted with thrombin after dissolving them in DMSO, I3SO3-GalCer, steroid sulfates and II3NAalpha-LacCer, as well as CS, but not SDS and sodium taurocholate, exhibited inhibitory activity, probably due to micellar formation facilitating interaction between thrombin and negatively charged lipids. On the other hand, plasmin, as determined using a chromogenic substrate, was more susceptible to acidic lipids than thrombin. CS, I3SO3-GalCer and II3NAalpha-LacCer, all of which are present in serum, inhibited the activity of plasmin in aqueous media, as well as in DMSO-mediated lipid solutions. Thus, acidic lipids in plasma were demonstrated to possess regulatory activity as endogenous detergents toward both enzymes for blood clotting and fibrinolysis.  (+info)

Unexpected crucial role of residue 225 in serine proteases. (6/5662)

Residue 225 in serine proteases of the chymotrypsin family is Pro or Tyr in more than 95% of nearly 300 available sequences. Proteases with Y225 (like some blood coagulation and complement factors) are almost exclusively found in vertebrates, whereas proteases with P225 (like degradative enzymes) are present from bacteria to human. Saturation mutagenesis of Y225 in thrombin shows that residue 225 affects ligand recognition up to 60,000-fold. With the exception of Tyr and Phe, all residues are associated with comparable or greatly reduced catalytic activity relative to Pro. The crystal structures of three mutants that differ widely in catalytic activity (Y225F, Y225P, and Y225I) show that although residue 225 makes no contact with substrate, it drastically influences the shape of the water channel around the primary specificity site. The activity profiles obtained for thrombin also suggest that the conversion of Pro to Tyr or Phe documented in the vertebrates occurred through Ser and was driven by a significant gain (up to 50-fold) in catalytic activity. In fact, Ser and Phe are documented in 4% of serine proteases, which together with Pro and Tyr account for almost the entire distribution of residues at position 225. The unexpected crucial role of residue 225 in serine proteases explains the evolutionary selection of residues at this position and shows that the structural determinants of protease activity and specificity are more complex than currently believed. These findings have broad implications in the rational design of enzymes with enhanced catalytic properties.  (+info)

Injury-induced gelatinase and thrombin-like activities in regenerating and nonregenerating nervous systems. (7/5662)

It is now widely accepted that injured nerves, like any other injured tissue, need assistance from their extracellular milieu in order to heal. We compared the postinjury activities of thrombin and gelatinases, two types of proteolytic activities known to be critically involved in tissue healing, in nonregenerative (rat optic nerve) and regenerative (fish optic nerve and rat sciatic nerve) neural tissue. Unlike gelatinases, whose induction pattern was comparable in all three nerves, thrombin-like activity differed clearly between regenerating and nonregenerating nervous systems. Postinjury levels of this latter activity seem to dictate whether it will display beneficial or detrimental effects on the capacity of the tissue for repair. The results of this study further highlight the fact that tissue repair and nerve regeneration are closely linked and that substances that are not unique to the nervous system, but participate in wound healing in general, are also crucial for regeneration or its failure in the nervous system.  (+info)

Platelet aggregation and incident ischaemic heart disease in the Caerphilly cohort. (8/5662)

BACKGROUND: Platelets are involved in myocardial infarction but evidence of prediction of infarction by measures of platelet function are sparce. METHODS: Platelet aggregation to thrombin and to ADP in platelet rich plasma was recorded for 2176 men aged 49-65 years in the Caerphilly cohort study. RESULTS: Results from 364 men were excluded, 80 of whom had not fasted before venepuncture; most of the others were excluded because antiplatelet medication had been taken shortly before the platelet tests. During the five years following the platelet tests 113 ischaemic heart disease (IHD) events which fulfilled the World Health Organisation criteria were identified--42 fatal and 71 non-fatal. No measure of platelet aggregation was found to be significantly predictive of incident IHD. The possibility that platelet function is predictive for only a limited time after it is characterised, and that prediction falls off with time, was tested. When IHD events are grouped by their time of occurrence after aggregation had been measured, the test results show a gradient suggestive of prediction of early IHD events. Thus, 24% of the men who had an event within 500 days of the test had had a high secondary response to ADP while only 12% of those whose IHD event had been 1000 or more days after the test had shown a high platelet response at baseline. The trend in these proportions is not significant. CONCLUSIONS: Platelet aggregation to thrombin and ADP in platelet rich plasma was recorded in the Caerphilly cohort study. No measure of aggregation was found to be predictive of IHD.  (+info)

To the best of our knowledge, this is the first study investigating TG-related parameters following PCC administration in acute trauma patients. PCC therapy resulted in significantly higher ETP than in patients who received fibrinogen concentrate only or no coagulation therapy at all and, importantly, this was sustained over the first 3 to 4 days following PCC administration. AT was significantly lower in the FC-PCC group from ER admission until 3 to 4 days later, reaching a nadir on day 2. Hemostasis relies on a delicate balance between pro- and anticoagulant factors, and between thrombin potential and thrombin inhibition potential. This balance may have been impaired in the FC-PCC group, during a period when fibrinogen levels were increased above the normal range; similar findings have been reported in previous studies [34, 35]. The overall picture is increased thrombin potential (day 1 to day 4), increased substrate for coagulation (that is, fibrinogen reaching a plateau on day 4) and ...
The aim of this thesis is to evaluate thrombin generation in patients with thrombophilia (Paper I), in patients with venous thromboembolism (Paper II), in healthy women during the menstrual cycle (Paper III), in patients with liver disease (Paper IV) and in patients with mild deficiency of factor VII (Paper V).. For this purpose, thrombin generation was measured in platelet poor plasma by the calibrated automated thrombogram (CAT®) assay. Thrombin generation expresses the overall haemostatic potential, in contrast to the more traditional coagulation tests, which concentrate on individual factors or coagulation pathways. The thrombin generation markers that were measured and studied were: lagtime (clotting time), endogenous thrombin potential (ETP, total thrombin concentration), peak (maximum thrombin concentration) and time to peak (ttpeak).. The cohorts for Papers I and II are part of a larger cohort (The LInköping Study on Thrombosis, LIST), which included 516 consecutive patients who ...
The aim of this thesis is to evaluate thrombin generation in patients with thrombophilia (Paper I), in patients with venous thromboembolism (Paper II), in healthy women during the menstrual cycle (Paper III), in patients with liver disease (Paper IV) and in patients with mild deficiency of factor VII (Paper V).. For this purpose, thrombin generation was measured in platelet poor plasma by the calibrated automated thrombogram (CAT®) assay. Thrombin generation expresses the overall haemostatic potential, in contrast to the more traditional coagulation tests, which concentrate on individual factors or coagulation pathways. The thrombin generation markers that were measured and studied were: lagtime (clotting time), endogenous thrombin potential (ETP, total thrombin concentration), peak (maximum thrombin concentration) and time to peak (ttpeak).. The cohorts for Papers I and II are part of a larger cohort (The LInköping Study on Thrombosis, LIST), which included 516 consecutive patients who ...
The present study demonstrates that thrombin, the central protease of the coagulation cascade, can be functionally imaged in vivo by using a novel NIR thrombin-activatable reporter. In vitro experiments first confirmed that the probe was specifically activated by endogenous thrombin within blood. In experimental murine thrombosis models, thrombin activation of the probe resulted in focal NIRF signal enhancement in occlusive and nonocclusive thrombi. Thrombin activity was detected within acute and subacute thrombi with the use of probe injections at clinically relevant time points, did not require preinjection of the probe, and could be rapidly detected in vivo by fluorescence reflectance imaging systems.. Although in vitro thrombin activity has been detected for many years with the use of chromogenic or fluorogenic substrates,18,19⇓ current experimental results now show that thrombin activity can be imaged in vivo by using the NIRF-activatable probe scheme previously developed in our ...
In this Cochrane meta-analysis, researchers analyzed the overall efficacy and safety of direct thrombin inhibitors, compared to warfarin or LMWH, in preventing VTE after orthopedic surgeries (hip and knee arthroplasty). In14 studies involving over 20,000 participants, they found no difference in efficacy between direct thrombin inhibitors, warfarin, or LMWH, but did find higher mortality and bleeding in the thrombin group compared to LMWH (but no difference between the thrombin group and warfarin) (abstract). The timing of the thrombin inhibitors also matters, as pre-operative dosing results in fewer VTEs but likely higher bleeding. Dabigatran is the oral direct thrombin inhibitor that is currently approved in Canada and throughout Europe, but US FDA approval is pending.. ...
Thrombin demonstrates a high level of allosteric regulation.[2] Allosterism in thrombin is regulated by the exosites 1 and 2 and the sodium binding site. A recent patent review has shown that the general consensus among researchers is that allosteric inhibitors may provide a more regulatable anticoagulant.[3] Some of the allosteric inhibitors discovered include DNA aptamers,[3] benzofuran dimers,[4] benzofuran trimers,[5] as well as polymeric lignins.[6] A new sulfated β-O4 lignin (SbO4L) has been discovered which has shown a dual mechanism of action for anti-thrombosis. This SbO4L shows allosteric inhibition of thrombin for fibrinogen, while providing a competitive inhibition of thrombin interaction with platelet glycoprotein Ibα (GPIbα), thereby preventing thrombin mediated platelet aggregation.[7] However, despite the growing interest and the advances in allosterism, no allosteric thrombin inhibitor has yet reached the stage of clinical trials.. ...
Direct thrombin inhibitors (DTIs) are a class of anticoagulant drugs that can be used to prevent and treat embolisms and blood clots caused by various diseases. They inhibit thrombin, a serine protease which affects the coagulation cascade in many ways. DTIs have undergone rapid development since the 90s. With technological advances in genetic engineering the production of recombinant hirudin was made possible which opened the door to this new group of drugs. Before the use of DTIs the therapy and prophylaxis for anticoagulation had stayed the same for over 50 years with the use of heparin derivatives and warfarin which have some well known disadvantages. DTIs are still under development, but the research focus has shifted towards factor Xa inhibitors, or even dual thrombin and fXa inhibitors that have a broader mechanism of action by both inhibiting factor IIa (thrombin) and Xa. A recent review of patents and literature on thrombin inhibitors has demonstrated that the development of allosteric ...
Background Venous thromboembolism (VTE) is a common complication in patients with cancer receiving chemotherapy. Currently no anticoagulant is approved for VTE prophylaxis in this setting. Semuloparin is an ultra-LMWH generated through a highly selective depolymerization of heparin which protects the antithrombin (AT) binding site in order to improve the benefit/risk ratio compared to existing anitcoagulants.. Aims We studied in vitro the mechanism of action of semuloparin on the inhibition of thrombin generation (TG) of human platelet poor plasma (PPP) triggered by human pancreatic cancer cells BXPC3. We compared the antithrombotic efficiency of semuloparin to that of enoxaparin and the specific AT-dependent factor Xa inhibitor fondaparinux.. Materials and methods BXPC3 cells were suspended in PPP spiked with clinically relevant concentrations of semuloparin, enoxaparin and fondaparinux. The endogenous thrombin potential (ETP) and the mean rate index (MRI) of the propagation phase of TG were ...
Purpose: The purpose was to investigate the presence of hypercoagulability in the very early phase of the host response to an infection in the clinical course of sepsis and septic shock. Material and Methods: Twenty-four patients with chemotherapy-associated febrile neutropenia were evaluated at baseline, at the time of fever onset, and 48 hours thereafter using the thrombin generation test, a more physiological and global assay of hemostasis. Results: The rate of thrombin generation was decreased and no signals of systemic hypercoagulability could be observed during the first 48 hours of sepsis. Moreover, patients that evolved to septic shock presented a more significant impairment in thrombin generation than those with noncomplicated sepsis. Conclusions: Patients with sepsis and febrile neutropenia present an impairment in thrombin generation from very early stages of their disease course. These results suggest that the procoagulant in vitro alterations described during sepsis do not ...
TY - JOUR. T1 - Thrombin induces proliferation of osteoblast-like cells through phosphatidylcholine hydrolysis. AU - Suzuki, Atsushi. AU - Kozawa, Osamu. AU - Shinoda, Junji. AU - Watanabe, Yasuko. AU - Saito, Hidehiko. AU - Oiso, Yutaka. PY - 1996/7/1. Y1 - 1996/7/1. N2 - We examined the effect of thrombin on phosphatidylcholine-hydrolyzing phospholipase D activity in osteoblast-like MC3T3-E1 cells. Thrombin stimulated the formation of choline dose dependently in the range between 0.01 and 1 U/ml, but not the phosphocholine formation. Diisopropylfluorophosphate (DFP)-inactivated thrombin had little effect on the choline formation. The combined effects of thrombin and 12-O-tetradecanoylphorbol-13-acetate, a protein kinase C-activating phorbol ester, on the choline formation were additive. Staurosporine, an inhibitor of protein kinases, had little effect on the thrombin-induced formation of choline. Combined addition of thrombin and NaF, an activator of heterotrimeric GTP-binding protein, did not ...
We have developed an aptamer-based microarray for human thrombin detection exploiting two non-overlapping DNA thrombin aptamers recognizing different exosites of the target protein. The 15-mer aptamer (TBA1) binds the fibrinogen-binding site, whereas the 29-mer aptamer (TBA2) binds the heparin binding domain. Extensive analysis on the complex formation between human thrombin and modified aptamers was performed by Electrophoresis Mobility Shift Assay (EMSA), in order to verify in solution whether the chemical modifications introduced would affect aptamers/protein recognition. The validated system was then applied to the aptamer microarray, using the solid phase system devised by the solution studies. Finally, the best procedure for Sandwich Aptamer Microarray (SAM) and the specificity of the sandwich formation for the developed aptasensor for human thrombin were optimized.
Thrombin (EC 3.4.21.5, fibrinogenase, thrombase, thrombofort, topical, thrombin-C, tropostasin, activated blood-coagulation factor II, blood-coagulation factor IIa, factor IIa, E thrombin, beta-thrombin, gamma-thrombin) is a serine protease, an enzyme that, in humans, is encoded by the F2 gene. Prothrombin (coagulation factor II) is proteolytically cleaved to form thrombin in the clotting process. Thrombin in turn acts as a serine protease that converts soluble fibrinogen into insoluble strands of fibrin, as well as catalyzing many other coagulation-related reactions. After the description of fibrinogen and fibrin, Alexander Schmidt hypothesised the existence of an enzyme that converts fibrinogen into fibrin in 1872. Thrombin is produced by the enzymatic cleavage of two sites on prothrombin by activated Factor X (Xa). The activity of factor Xa is greatly enhanced by binding to activated Factor V (Va), termed the prothrombinase complex. Prothrombin is produced in the liver and is ...
Thrombin is a serine protease that in humans is encoded by the F2 gene. Thrombin is an intriguing coagulation protease demonstrating an array of effects on endothelial cells, vascular smooth muscle cells (VSMC), monocytes, and platelets, all of which are involved in the pathophysiology of atherosclerosis. There is mounting evidence that thrombin acts as a powerful modulator of many processes like regulation of vascular tone, permeability, migration and proliferation of VSMC, recruitment of monocytes into the atherosclerotic lesions, induction of diverse pro-inflammatory markers, and all of these are related to the progression of cardiovascular disease. Recent studies in transgenic mice models indicate that the deletion of the natural thrombin inhibitor heparin cofactor II promotes an accelerated atherogenic state. The combined evidence points to thrombin as a pivotal contributor to vascular pathophysiology. Considering the clinical development of selective anticoagulants including direct ...
Background: Pregnant women are at increased risk of venous thrombosis compared to non-pregnant women. Epidemiological and laboratory data suggest that hypercoagulability begins in the first trimester but it is unknown exactly how early in pregnancy this develops. The mechanisms that result in a prothrombotic state may involve oestrogens and progestogens. Methods: Plasma samples were taken prior to conception and five times in early pregnancy, up to Day 59 gestation, from 22 women undergoing natural cycle in vitro fertilization, who subsequently gave birth at term following a normal pregnancy. Thrombin generation, free Protein S, Ddimer, Fibrinogen, factor VIII, estradiol and progesterone were measured. To counter inter-individual variability, the change in laboratory measurements between the pre-pregnant and pregnant state were measured over time. Results: Peak thrombin, Endogenous Thrombin Potential, Velocity Index and fibrinogen significantly increased, and free Protein S significantly ...
In vivo, thrombin serves as both the primary stimulus for thrombosis and subsequent thrombus growth on a template of activated platelets or platelet-derived procoagulant microparticles (15-17). Our group has shown that patients with clinically stable coronary artery disease (CAD) have evidence of increased thrombin activity and generation (18)as do those with unstable angina (19,20)and acute MI (21)in whom the abnormality persists for weeks to months after the presenting event (22). Consistent with prior observations (23), patients in this study exhibited increased thrombin generation despite treatment with UFH (10,18,24,25). The limitations associated with UFH administration may, at least in part, be the result of its relative inaccessibility to clot-bound thrombin and an inability to effectively neutralize factor Xa-mediated procoagulant activity (26).. The thrombogenicity of atheromatous plaques and dysfunctional endothelial cells is strongly influenced by tissue factor which is considered ...
TY - JOUR. T1 - Hyperglycemia-induced thrombin formation in diabetes. T2 - The possible role of oxidative stress. AU - Ceriello, A.. AU - Giacomello, R.. AU - Stel, G.. AU - Motz, E.. AU - Taboga, C.. AU - Tonutti, L.. AU - Pirisi, M.. AU - Falleti, E.. AU - Bartoli, E.. PY - 1995. Y1 - 1995. N2 - Diabetes is characterized by the existence of a thrombosis-prone condition, possibly related to hyperglycemia. However, the mechanism linking hyperglycemia to the activation of the coagulation cascade is still unclear. It has been recently suggested that diabetes is accompanied by increased oxidative stress. In this work, the possibility that oxidative stress may be involved in the hyperglycemia-induced coagulation activation has been evaluated. Prothrombin fragment 1 + 2 (F1+2), which represents a reliable marker of the amount of thrombin released in the circulation, has been chosen for studying thrombin formation in vivo. In nine type II diabetic patients and in seven healthy control subjects, ...
The major finding of the present study is that GIT1 is a novel mediator for thrombin signal transduction in ECs modulating thrombin-induced changes in cell shape and EC barrier function. Specifically, we show that GIT1 is recruited to FAs in a RhoA-dependent manner. GIT1 is phosphorylated on tyrosine residues in an agonist-dependent manner that requires Rho kinase, Src, and FAK activation. Finally, an important role for GIT1 in EC rounding and endothelial barrier recovery was demonstrated by GIT1 depletion. Based on these findings, we propose a model for thrombin-induced changes in EC function mediated by GIT1 (Figure 8). Specifically, binding of thrombin to its receptor initiates a F-actin-dependent EC contraction involving activation of RhoA and Rho kinase. GIT1 then translocates to FAs, where in concert with FAK and Src, it modulates FA (dis)assembly contributing to changes in cell shape. An intact F-actin cytoskeleton is necessary for GIT1 recruitment to FAs, as disruption of the F-actin ...
Abstract. Abstract 41Background. Therapy with by-passing agents (BPA) in patients with hemophilia and inhibitors still lacks a laboratory test able to assess
In an effort to reduce the risks of a possible iatrogenic transmission of bovine spongiform encephalitis (BSE) through the use of bovine-derived medicinal products, we patented in the USA in 1999 a polysaccharide from brown algae, endowed with interesting pharmacological activities: (a) concentration-dependent inhibition of thromboplastin or cephalin-kaolin-induced thrombin generation from platelets, (b) concentration-dependent inhibition of thrombin-induced platelet aggregation, (c) thrombin has hypotensive effect, which was blunted and zeroed by our fucansulfate in a dose-dependent way, (d) when aortae are stimulated with thrombin, they become stickier for polymorphonucleated leukocytes (PMNs); our fucansulfate decreased concentration-dependently, PMNs sticking to autologous rabbit aortae, (e) dose-dependent inhibition of thrombin-induced thrombosis. All the above data suggest that our fucansulfate could be a heparin substitute endowed with antithrombotic and anti-inflammatory activities, devoid or
1000 G indicates 1000 Genome; CAD/MI, coronary artery disease/myocardial infarction; CI, confidence interval; ETP, endogenous thrombin potential; FVIII, factor VIII; IVW, inverse variance weighting; OR, odds ratio; NA, not available; PAI, plasminogen activator inhibitor; SNP, single-nucleotide polymorphism; tPA, tissue-type plasminogen activator; vWF, von Willebrand factor; WGLM, weighted generalized linear regression model; and WM, weighted median method. ...
The binding of thrombin to fibrin is thought to be an important mechanism by which thrombi exhibit procoagulant activity; however, the extent to which other procoagulants are associated with thrombi has not been previously defined. This study was designed to determine whether clotting factors other than thrombin are bound to whole-blood clots and can thereby contribute to significant procoagulant activity. Clots formed in vitro from human blood exhibited minimal thrombin activity when incubated in plasma depleted of vitamin K-dependent factors by barium-citrate adsorption, as indicated by increases in the concentration of fibrinopeptide A (FPA), a marker of fibrin formation, to 72 nM after 30 min. Incubation of clots in barium-absorbed plasma repleted with 0.9 microM human prothrombin under the same conditions resulted in marked increases in the concentration of FPA (, 1,000 nM) and clotting by 30 min. The increases in FPA were attributable to activation of the added prothrombin by ...
The present study shows that PAR1 acts as a cofactor for thrombin activation of PAR4 on human platelets and other cells and provides a mechanistic basis to understand PAR1-PAR4 synergy. By selectively ablating the PAR1 signal with a potent inhibitor of the PAR1 tethered ligand,23 we determined that PAR4 is activated at surprisingly low concentrations of thrombin on human platelets. By inhibiting the ability of thrombin to associate with PAR1, we show that PAR1 plays a critical helper function in assisting PAR4 activation by thrombin. A cleavage-sensitive PAR4-Ab was used to demonstrate that PAR1 and PAR4 exist as a complex on human platelets. Stable hetero-oligomerization between PAR1 and PAR4 was also observed in recombinant systems and did not require prior cleavage by thrombin.. The present work supports earlier observations with PAR1 and PAR4 pepducin antagonists7 and blocking antibodies8,10,31 that targeting only PAR1 and not PAR4 may have a partial therapeutic effect. Thus, a combination ...
... ,Determination of the Thrombin Time by STA Analyzers. Freeze-dried human thrombin (1.5NIH units/mL) with calcium.,medicine,medical supply,medical supplies,medical product
Thrombin is a serine protease that in humans is encoded by the F2 gene. Prothrombin (coagulation factor II) is proteolytically cleaved to form thrombin in the coagulation
Thrombin can be used outside the body exploiting its serine cleaving properties. As a biochemical tool, it is used to fuse proteins.. It can also be used in the food industry to bind different types of meat together. The coagulating properties enable meat manufacturers to blend different types of meat like fish and beef to form a new meat mixture.. In the medical field, it can be used during surgery where there is blood loss and if it is not handled carefully it can lead to hemorrhage. Its been useful in many other important functions in the field of science.. Topical administration of aqueous thrombin helps in hemostasis. Therefore, it is also essential in maintaining normal balance and flow of nutrients and oxygen in the body.. ...
TY - JOUR. T1 - Thrombin-induced gap formation in confluent endothelial cell monolayers in vitro. AU - Laposata, Michael. AU - Dovnarsky, D. K.. AU - Shin, H.. PY - 1983. Y1 - 1983. N2 - When thrombin is incubated with confluent monolayers of human umbilical vein endothelial cells in vitro, there is a change in the shape of the endothelial cells that results in gaps in the monolayer disrupting the integrity of the endothelium and exposing the subendothelium. Using a grid assay to measure this phenomenon, we observed that up to 80% of the surface area once covered by cells was uncovered after a 15-min incubation with 10-2 U/ml (10-10 M) thrombin. The effect was apparent within 2 min and did not remove cells from the surface of the culture dish. The gaps in the monolayer completely disappeared within 2 hr after exposure to thrombin. The effect of thrombin was inhibited by preincubation of thrombin with hirudin or antithrombin III plush heparin or by preincubation of the monolayers with dibutyryl ...
Thrombin removel His tag protein digestion - posted in Protein and Proteomics: After thrombin cutting of his - tagged protein , Iam unable to purify the protein from by using size exclusion chromatography .always showing the contamination of thrombin residuals as per sds page .i am using PBS buffer for throbin cutting . could you please give any suggestion to remove throbin removal ?
Abstract. Pediatric patients with acute lymphoblastic leukemia (ALL) are at an increased risk of thromboembolic events. Potential responsible mechanisms includ
A prothrombotic state is one of the hallmarks of advanced cancer, and thromboembolic disease contributes significantly to the mortality of cancer patients (reviewed in1). Tissue factor (TF), the cellular activator of the coagulation cascade, is central to the hypercoagulable state of cancer patients and responsible for local thrombin generation and fibrin deposition in the tumor stroma. TF also triggers remote thrombotic complications involving procoagulant TF+ microparticles2 with potential contribution from other cancer procoagulants (reviewed in3). TF-dependent coagulation generates thrombin and induces pleiotrophic cellular effects of thrombin on platelets through G protein-coupled protease-activated receptors (PARs)4 as well as thrombin-initiated vascular-protective signaling of the endogenous activated protein C-EPCR-PAR1 pathway.5 Direct signaling by TF-associated proteases are mediated by the binary TF-VIIa enzyme complex that activates PAR2 or the ternary TF-VIIa-Xa coagulation ...
Intestinal epithelium produces active thrombin, which plays an unsuspected shield role against gut microbial community living on mucosal surface.
Piperazinyl-amide derivatives of N-alpha-(3-trifluoromethyl-benzenesulfonyl)-L-arginine (1) were synthesized as graftable thrombin inhibitors. The possible disturbance of biological activity due to a variable spacer-arm fixed on the N-4 piperazinyl position was evaluated in vitro, against human alpha-thrombin, and in blood coagulation assay. Molecular modelling (in silico analysis) and X-ray diffraction studies of thrombin-inhibitor complexes were also performed. The fixation of bioactive molecules on poly(butylene terephthalate) (PBT) and poly(ethylene terephthalate) (PET) membranes was performed by wet chemistry treatment and evaluated by XPS analysis. Surface grafting of inhibitor 1d improved the membrane hemocompatibility by reducing blood clot formation on the modified surface. ...
Dang, Q. D., and Di Cera, E. (1997) Nat. Biotechnol. 15, 891-895; and Le Bonniec, B. F., MacGillivray, R. T., and Esmon, C. T. (1991) J. Biol. Chem. 266, 13796-13803). Optimal binding interactions witin thrombin occur only if these tripeptide substrates contain an amino acid residue in the (D)-configuration, such as (d)Phe at P3 (Blomback, B., Blomback, M., Olsson, P., Svendsen, L., and Aberg, G. (1969) Scand. J. Clin. Lab Invest SuppI 107, 59-61), which mimics the natural Pg"residue in FpA (Ni, F., Meinwald, Y. C, Vasquez, M., and Scheraga, H. A. (1989) Biochemistry 28, 3094-3105; Stubbs, M. T., Oschkinat, H., Mayr, I., Huber, R., Angliker, H., Stone, S. R., and Bode, W. (1992) Eur. J. Biochem. 206, 187-195; and Martin, P. D., Robertson, W., Turk, D., Huber, R., Bode, W., and Edwards, B. F. (1992) J. Biol. Chem. 267, 7911-7920). However, these minimalistic peptide substrates probe only the active site apparatus of thrombin and related binding events, which were found to be mildly sensitive to ...
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Unless specified otherwise, MP Biomedicals products are for laboratory research use only, not for human or clinical use. For more information, please contact our customer service department ...
A purified therapeutic grade thrombin is described which is essentially free of lipid envelope viruses, has a specific activity of about 2200 NIH units per milligram of protein to about 3200 NIH units per milligram of protein, is essentially homogeneous and may be produced on a commercial-scale. The thrombin is acceptable from human administration.
Thrombin antibody LS-C392770 is an unconjugated rabbit polyclonal antibody to human Thrombin (F2 / Prothrombin ). Validated for Peptide-ELISA and WB.
Thrombin antibody LS-C658904 is an unconjugated rabbit polyclonal antibody to human Thrombin (F2 / Prothrombin ). Validated for WB.
The mechanism of PAR1 activation is strikingly irreversible. Cleavage of PAR1 by thrombin is irrevocable, and the tethered ligand generated cannot diffuse away from the receptor. In the absence of the reversible ligation that characterizes most receptor systems, how is PAR1 shut off? The β2-adrenergic receptor has served as a prototype for dissecting the molecular events responsible for G protein-coupled receptor desensitization and resensitization (10-13). Upon activation, β2-adrenergic receptor is rapidly phosphorylated. It then binds arrestin, preventing further interaction with G proteins. Arrestin also mediates internalization of β2-adrenergic receptors via clathrin-coated pits (14, 15). Within an endosomal compartment, receptors dissociate from ligand, are dephosphorylated, and recycle back to the cell surface competent to signal again. Thus trafficking serves to remove activated β2-adrenergic receptors from the cell surface and to return the receptors to the surface in an off state, ...
Mono- and Stereopictres of 5.0 Angstrom coordination sphere of Sodium atom in PDB 3qx5: Thrombin Inhibition By Pyridin Derivatives
Mono- and Stereopictres of 5.0 Angstrom coordination sphere of Sodium atom in PDB 3qtv: Thrombin Inhibition By Pyridin Derivatives
JOURNAL «ANGIOLOGY AND VASCULAR SURGERY» №4 2016, VOLUME 22: Puncture treatment of pseudoaneurysms of femoral arteries with the use of human thrombin
Purified human Thrombin mainly in the α form. Prepared by activation of highly purified Prothrombin, in the presence of factor Xa, V and calcium.
Two drugs that are direct inhibitors of thrombin but that do not involve antithrombin III or vitamin K in their mechanism of action have been approved to
Thrombin - how to use it in the best way? - posted in Protein and Proteomics: Hello everybody! I have read a lot of topics about GST, Thrombin,...but I would like to be sure to do the experiment well, so I am here to ask you again some questions. I am doing a GST-pulldown using GST-protX (26Da) and a mouse brain lysate, I want see 2 proteins that we will call A and B with molecular weight 55kDa and 24KDa, respectively. So, the problem is that I cant see the protein B because the...
[117 Pages Report] Check for Discount on Global Thrombin Sales Market Report 2017 report by QYResearch Group. In this report, the global Thrombin market is valued at...
Thrombin Sawai is a medicine available in a number of countries worldwide. A list of US medications equivalent to Thrombin Sawai is available on the Drugs.com website.
Differentiated osteoclasts were generated and then cultured for 48 h in serum-free medium supplemented with 20 ng/ml M-CSF and 2 ng/ml RANKL. Conditioned medium was harvested, centrifuged. to remove cells and debris, and 600 μl/well was added to 24-well plates. Serum-free medium and medium containing 10% FBS, were supplemented with M-CSF and RANKL, and used as negative and positive controls, respectively. Wortmannin order Prior to the chemotaxis assay, γδ T cells were activated for 12 h with 100 U/ml rhIL-2. γδ T cells were then re-suspended in serum-free medium at 106 cells/ml and 80 μl of cell suspension was added into Transwell inserts (8 μm pore size). γδ T cells were incubated for 4 h at 37 °C to allow migration through the http://www.selleckchem.com/products/Staurosporine.html Transwell membrane. Cells that had migrated into the bottom chamber were harvested and quantified using flow cytometric analysis on an LSRII flow cytometer (BD Biosciences) by counting an equivalent volume ...
The highest DNA binding by 3-NBA in ES cells was observed at 10 μM after 24 h with 863 ± 74 adducts per 108 nucleotides (Fig. 3C). Interestingly, and in contrast to BaP, adduct levels for 3-NBA in MEFs were only 1.5-fold higher. (1266 ± 188 adduct per 108 nucleotides) under the same experimental conditions (Fig. 3D). DNA binding LDK378 in vivo was highest in MEFs at 10 μM after 48 h with 2478 ± 455 adducts per 108 nucleotides. Previously, in primary HUFs previously treated with 10 μM 3-NBA for 48 h, adduct levels were 680 ± 147 adducts per 108 nucleotides (Kucab et al., 2012). As 3-NBA is predominantly activated by NQO1 (Arlt et al., 2005), the expression of Nqo1 was studied in ES cells and MEFs by RT-PCR and revealed that Nqo1 mRNA expression increased in both cell types up to ∼60-fold; the induction was higher in MEFs than in ES cells ( Fig. 6C and D). This is in line with a previous study showing that Nqo1 protein levels were inducible in primary and immortal HUFs upon treatment with ...
1MKW: The co-crystal structure of unliganded bovine alpha-thrombin and prethrombin-2: movement of the Tyr-Pro-Pro-Trp segment and active site residues upon ligand binding.
Hi folks Does anyone know of any bead technology that exists that allows efficient removal of thrombin protease after cleavage of a fusion protein? thanks in advance Stephen Goodwin Stephen F Goodwin Brandeis University Biology Department (Jeff Hall Lab) 415 South Street, Waltham, MA e-mail: goodwin at binah.cc.brandeis.edu Phone: (617) 736 3168 Fax: (617) 736 3107 ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ you light a fire, Ill show you something good: A huge snowball Basho 1644-1694 ...
Each molecule of Factor Xa can generate 1000 molecules of thrombin. This large burst of thrombin is responsible for fibrin ... amplification of the procoagulant signal by thrombin generated on the TF-bearing cell and 3) propagation of thrombin generation ... It acts by cleaving prothrombin in two places (an arg-thr and then an arg-ile bond), which yields the active thrombin. This ... In stage 3, thrombin generation, Factor XIa activates free Factor IX on the surface of activated platelets. The activated ...
Luo C, Thielens NM, Gagnon J, Gal P, Sarvari M, Tseng Y, Tosi M, Zavodszky P, Arlaud GJ, Schumaker VN (May 1992). "Recombinant human complement subcomponent C1s lacking beta-hydroxyasparagine, sialic acid, and one of its two carbohydrate chains still reassembles with C1q and C1r to form a functional C1 complex". Biochemistry. 31 (17): 4254-62. doi:10.1021/bi00132a015. PMID 1533159 ...
Protein HtrA2, also known as Omi, is a mitochondrially-located serine protease. The human protein Serine protease HTRA2, mitochondrial is 49kDa in size and composed of 458 amino acids. The peptide fragment of 1-31 amino acid is the mitochondrial transition sequence, fragment 32-133 amino acid is propertied, and 134-458 is the mature protein Serine protease HTRA2, mitochondrial, and its theoretical pI of this protein is 6.12.[10] HtrA2 shows similarities with DegS, a bacterial protease present in the periplasm of gram-negative bacteria. Structurally, HtrA2 is a trimeric molecule with central protease domains and a carboxy-terminal PDZ domain, which is characteristic of the HtrA family. The PDZ domain preferentially binds C-terminus of the protein substrate and modulate the proteolytic activity of the trypsin-like protease domain.[11] ...
Seol JH, Woo SK, Jung EM, Yoo SJ, Lee CS, Kim KJ, Tanaka K, Ichihara A, Ha DB, Chung CH (April 1991). "Protease Do is essential for survival of Escherichia coli at high temperatures: its identity with the htrA gene product". Biochemical and Biophysical Research Communications. 176 (2): 730-6. doi:10.1016/s0006-291x(05)80245-1. PMID 2025286 ...
A trypsin inhibitor (TI) is a protein and a type of serine protease inhibitor (serpin) that reduces the biological activity of trypsin by controlling the activation and catalytic reactions of proteins.[1] Trypsin is an enzyme involved in the breakdown of many different proteins, primarily as part of digestion in humans and other animals such as monogastrics and young ruminants. When trypsin inhibitor is consumed it acts as an irreversible and competitive substrate.[2] It competes with proteins to bind to trypsin and therefore renders it unavailable to bind with proteins for the digestion process.[1] As a result, protease inhibitors that interfere with digestion activity have an antinutritional effect. Therefore, trypsin inhibitor is considered an anti-nutritional factor or ANF.[3] Additionally, trypsin inhibitor partially interferes with chymotrypsin function. Trypsinogen is an inactive form of trypsin, its inactive form ensures protein aspects of the body, such as the pancreas and muscles, are ...
Cholecystokinin (CCK) is a unique peptide released by the duodenal "I cells" in response to chyme containing high fat or protein content. Unlike secretin, which is an endocrine hormone, CCK actually works via stimulation of a neuronal circuit, the end-result of which is stimulation of the acinar cells to release their content.[5] CCK also increases gallbladder contraction, causing release of pre-stored bile into the cystic duct, and eventually into the common bile duct and via the ampulla of Vater into the second anatomic position of the duodenum. CCK also decreases the tone of the sphincter of Oddi, which is the sphincter that regulates flow through the ampulla of Vater. CCK also decreases gastric activity and decreases gastric emptying, thereby giving more time to the pancreatic juices to neutralize the acidity of the gastric chyme ...
"Crystallographic structures of thrombin complexed with thrombin receptor peptides: existence of expected and novel binding ... Tellez C, Bar-Eli M (May 2003). "Role and regulation of the thrombin receptor (PAR-1) in human melanoma". Oncogene. 22 (20): ... Ogino Y, Tanaka K, Shimizu N (Nov 1996). "Direct evidence for two distinct G proteins coupling with thrombin receptors in human ... Vu TK, Hung DT, Wheaton VI, Coughlin SR (Mar 1991). "Molecular cloning of a functional thrombin receptor reveals a novel ...
Direct thrombin inhibitorsEdit. Main article: direct thrombin inhibitor. Another type of anticoagulant is the direct thrombin ... It works by activating antithrombin III, which blocks thrombin from clotting blood. Heparin can be used in vivo (by injection ... An oral direct thrombin inhibitor, ximelagatran (Exanta) was denied approval by the Food and Drug Administration (FDA) in ... thrombin) inhibitor, and the factor Xa inhibitors rivaroxaban and apixaban. Clinical trials have shown them therapeutically ...
Treatment is with oral anticoagulants (not heparin as heparin acts via anti-thrombin 3 which is lost in the proteinuria so it ... Antithrombin III counteracts the action of thrombin. Thrombosis usually occurs in the renal veins although it can also occur in ...
Thrombin Sistem Koagulasi Cleaves the soluble plasma protein fibrinogen to produce insoluble fibrin, which aggregates to form a ... Thrombin can also bind to cells via the PAR1receptor to trigger several other inflammatory responses, such as production of ...
Hirose, Ruby (1934). "The Second Phase of Thrombin Action: Fibrin Resolution". American Journal of Physiology.. ... She did research on blood clotting and Thrombin, allergies, and researched cancer using antimetabolites. ... "Nature of Thrombin and Its Manner of Action".[11] A paper based on this thesis was later published in the American Journal of ... Physiology in 1934 with the title "The Second Phase of Thrombin Action: Fibrin Resolution".[12] ...
"Thrombin-Jmi". thrombin-jmi.com. Retrieved 2014-12-14. "Levoxyl® (levothyroxine sodium tablets, USP) , Safety Info". levoxyl. ... The primary therapeutic compounds marketed by the company include Thrombin-JMI and Levoxyl On May 30, 2000 the company became a ...
Direct thrombin inhibitors provides an excellent example of negative allosteric modulation. Allosteric inhibitors of thrombin ... "Allosteric networks in thrombin distinguish procoagulant vs. anticoagulant activities". Proceedings of the National Academy of ...
Orange or grey/yellow "tiger" Top: thrombin, a rapid clot activator, for stat serum testing ...
Steven FS, Griffin MM (1982). "Inhibition of thrombin cleavage of fibrinogen by polyestradiol phosphate; interaction with the ...
Li, J. J.; Huang, Y. Q.; Basch, R.; Karpatkin, S. (February 2001). "Thrombin induces the release of angiopoietin-1 from ... "Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and ...
An oral direct thrombin inhibitor, ximelagatran (Exanta) was denied approval by the Food and Drug Administration (FDA) in ... It works by activating antithrombin III, which blocks thrombin from clotting blood. Heparin can be used in vivo (by injection ... thrombin) inhibitor, and the factor Xa inhibitors rivaroxaban and apixaban. Clinical trials have shown them therapeutically ... "Direct thrombin inhibitors". N. Engl. J. Med. 353 (10): 1028-40. doi:10.1056/NEJMra044440. PMID 16148288. Costantinides, Fulvia ...
Thrombin levels increase. Protein S, an anticoagulant, decreases. However, the other major anticoagulants, protein C and ... September/October 2002 Volume 8, Issue 5 de Boer K, ten Cate JW, Sturk A, Borm JJ, Treffers PE (1989). "Enhanced thrombin ...
Lundblad, R.L., Kingdon, H.S. and Mann, K.G. (1976). „Thrombin". Methods Enzymol. 45: 156-176. PMID 1011989.. CS1 одржавање: ... Baughman, D.J. (1970). „Thrombin assay". Methods Enzymol. 19: 145-157.. *↑ Magnusson, S. (1970). „Bovine prothrombin and ...
Thrombin is a potent platelet activator, acting through Gq and G12. These are G protein coupled receptors and they turn on ... They aggregate in response to thrombin, but not to ADP, serotonin, nor adrenaline, as platelets do.[65][66] ... Tissue factor also binds to factor VII in the blood, which initiates the intrinsic coagulation cascade to increase thrombin ... Thrombin also promotes secondary fibrin-reinforcement of the platelet plug. Platelet activation in turn degranulates and ...
These platelets have thrombin receptors on their surfaces that bind serum thrombin molecules[1] which in turn convert soluble ... It is formed by the action of the protease thrombin on fibrinogen which causes it to polymerize. The polymerized fibrin ... From Fibrinogen to Fibrin with the help of Thrombin and Factor VIII. ...
Brass, Lawrence (September 2003). "Thrombin and Platelet activation". Chest: Journal of the College of Chest Physicians. USA. ...
Brass LF (September 2003). "Thrombin and platelet activation". Chest. 124 (3 Suppl): 18S-25S. doi:10.1378/chest.124.3_suppl.18S ...
It acts solely by inhibiting the actions of thrombin. It is taken orally twice daily, and rapidly absorbed by the small ... Ho SJ, Brighton TA (2006). "Ximelagatran: direct thrombin inhibitor". Vasc Health Risk Manag. 2 (1): 49-58. doi:10.2147/vhrm. ... a direct thrombin inhibitor, was the first member of this class that can be taken orally. ... dose-guiding study of the oral direct thrombin inhibitor ximelagatran compared with standard therapy for the treatment of acute ...
... s have ability to inhibit protein C, thrombin and other enzymes that are stimulated by heparin. The heparin ... Protein C inhibitor is activated by heparin against thrombin. Protein C inhibitor (PCI) is serine protease inhibitor of serpin ... "Thrombin inhibition by the serpins". Journal of Thrombosis and Haemostasis. 11 Suppl 1: 254-64. doi:10.1111/jth.12252. PMID ... inhibiting several blood coagulation enzymes counting thrombin and factor Xa. In the beginning, protein C inhibitor(PCI) was ...
It consists of a number of linked enzymatic reactions resulting in thrombin generation. Thrombin converts soluble fibrinogen ... It consists of a number of linked enzymatic reactions resulting in thrombin generation. Thrombin converts soluble fibrinogen ... Thrombin-Activatable Fibrinolysis Inhibitor. Author(s): Pauline F. Marx. Dept. Vascular Medicine, G1-114, Academic Medical ... Thrombin-activatable fibrinolysis inhibitor (TAFI), which is identical to the previously identified proteins ...
Thrombin activatable fibrinolysis inhibitor. -. dc.title. Structure of Activated Thrombin-Activatable Fibrinolysis Inhibitor, a ... Thrombin-activatable fibrinolysis inhibitor (TAFI) is a metallocarboxypeptidase (MCP) that links blood coagulation and ... TAFI is transformed through removal of its prodomain by thrombin-thrombomodulin into TAFIa, which is intrinsically unstable and ...
Thrombin Receptor Agonist Peptide; TRAP; Proteinase-activated receptor 1; PAR-1; Thrombin receptor; Coagulation factor II ... respectively corresponding to aa42-47 and aa42-55 of the human thrombin receptor were found to be as effective as thrombin for ... Thrombin signaling of platelets is mediated by a G protein-coupled protease-activated receptor (PAR). The PAR is activated ... Synthetic thrombin receptor agonist peptides (TRAP) of 6 residues (SFLLRN) and 14 residues (SFLLRNPNDKYEPF), ...
The coagulating activity of thrombin was increased by 120% and the esterase activity--by 100% after incubation of thrombin with ... The data obtained suggest that factor XIII or its fragment are effectors of enzymatic activity of thrombin in vitro and in vivo ... Umarova B.A. et al., Factor XIII as a stimulator of thrombin activity. Voprosy meditsinskoi khimii 22.4 (1976): 562-566. ... Umarova, B. A., Strukova, S. M., Kudriashov, B. A. (1976). Factor XIII as a stimulator of thrombin activity. Voprosy ...
... bovine TAFI was a substrate for transglutaminases and could be proteolytically cleaved by trypsin or thrombin/solulin complex, ... authentic full lenght bovine plasma thrombin-activatable fibrinolysis inhibitor (TAFI), and recombinant human TAFI have ... In a proximate set of wells, 1 μl of tPA (0.002 μg/μl) and 2 μl of thrombin (20 U/ml) were combined in a final volume of 50 μl ... SDS-PAGE of bovine or human TAFI (1 μg), which was cleaved using either 0.05 μg of trypsin, or thrombin/solulin complex in a ...
... accelerated thrombin inactivation by HCII but not AT by 2000-fold. SOS bound to two sites on thrombin, with dissociation ... accelerated thrombin inactivation by HCII but not AT by 2000-fold. SOS bound to two sites on thrombin, with dissociation ... accelerated thrombin inactivation by HCII but not AT by 2000-fold. SOS bound to two sites on thrombin, with dissociation ... accelerated thrombin inactivation by HCII but not AT by 2000-fold. SOS bound to two sites on thrombin, with dissociation ...
Keywords: Ischemic stroke, P-selectin, thrombin-activatable fibrinolysis inhibitor, carotid intima-media thickness. Dilek Y ... The Relation Between Serum P-selectin, Thrombin-activatable Fibrinolysis Inhibitor Levels, and Carotid Artery Intima-media ... The Relation Between Serum P-selectin, Thrombin-activatable Fibrinolysis Inhibitor Levels, and Carotid Artery Intima-media ... Thrombin-activatable fibrinolysis inhibitor (TAFI) is a procarboxypeptidase molecule that can be another marker of AIS, which ...
Factor II - Prothrombin; common pathway; converted to thrombin that converts fibrinogen to fibrin. ...
Ongoing hypoperfusion, this hypothesis goes, leads to excess activation of protein C, which inhibits thrombin generation, ...
E thrombin, beta-thrombin, gamma-thrombin) is a serine protease, an enzyme that, in humans, is encoded by the F2 gene. ... Thrombin is sold under the brand name Fibrimex for use as a binding agent for meat. The thrombin in Fibrimex derives from ... Thrombin interacts with thrombomodulin. As part of its activity in the coagulation cascade, thrombin also promotes platelet ... Due to its high proteolytic specificity, thrombin is a valuable biochemical tool. The thrombin cleavage site (Leu-Val-Pro-Arg- ...
Simulations of the effect of hirudin indicate that factor V is predominantly activated by thrombin and not by factor Xa. The ... A simulation model for the production of thrombin in plasma is presented. Values of the reaction rate constants as determined ... The dependence of this threshold value on different negative feedback reactions, e.g. the inactivation of thrombin and factor ... SBML L2V4 representation of Willems1991 - Simulating thrombin generation. 55.36 KB. Preview , Download. ...
A list of US medications equivalent to Thrombin Sawai is available on the Drugs.com website. ... Thrombin Sawai is a medicine available in a number of countries worldwide. ... Thrombin Sawai may be available in the countries listed below.. Ingredient matches for Thrombin Sawai. Thrombin. Thrombin is ...
Thrombin also has two exosites (1 and 2). Thrombin is a little different from other serine proteases as exosite 1 is anion- ... Thrombin is in the serine protease family. It has 3 binding domains in which thrombin-inhibition drugs bind to. Those proteases ... But heparin can also form a bridge between thrombin and fibrin which binds to exosite 1 which protects the thrombin from ... DTIs arent dependent to cofactors like antithrombin to inhibit thrombin so they can both inhibit free/soluble thrombin as well ...
... stephen goodwin goodwin at BINAH.CC.BRANDEIS.EDU Thu Oct 10 06:42:16 EST 1996 *Previous message: Looking for ... Hi folks Does anyone know of any bead technology that exists that allows efficient removal of thrombin protease after cleavage ...
Home : For health professionals : Refer a patient : Laboratory Services : Test Table : THROMBIN TIME ... Heparin, Direct Thrombin Inhibitors (Lepirudin, Argatroban, Dabigatran, etc.), Fibrin/fibrinogen degradation products may cause ... prolongation of the Thrombin Time. Other interferences include: Hemoglobin (,500 mg/dL), Triglycerides (1,000 mg/dL), Bilirubin ...
... Ding Ming ming at mbcrr.harvard.edu Fri Mar 24 12:35:13 EST 1995 *Previous message: MW of IgG? ... I would appreciate if you can tell me who produce the thrombin antibodies and what their telephone numbers. Thanks in advance. ...
THROMBIN HEAVY CHAINTHROMBIN LIGHT CHAINTHROMBIN PEPTIDEAcetate IonEthyl [(2z)-2-(Carbamimidoylimino)-6-Hydroxy-1,3- ...
Determination of the Thrombin Time by STA Analyzers. Freeze-dried human thrombin (1.5NIH units/mL) with calcium.,medicine, ... Determination of the Thrombin Time by STA Analyzers. Freeze-dried human thrombin (1.5NIH units/mL) with calcium. ...
A "high-affinity" thrombin receptor (PAR1 in human, PAR3 in mouse) is necessary for responses to low concentrations of thrombin ... LDPR/S binds thrombins active center, and the "hirudin-like" sequence DKYEPF binds thrombins fibrinogen-binding exosite (4, ... Human PAR1, PAR3, and PAR4 can be activated by thrombin, and sensing thrombin is likely, at least in part, their role in vivo ( ... 2). PAR1, PAR3, and PAR4 are thrombin receptors (2, 3, 31-33). PAR1 and human PAR3 respond to thrombin at subnanomolar ...
HIRUDINTHROMBIN HEAVY CHAINTHROMBIN LIGHT CHAIN(2s)-1-[cyclohexylamino)acetyl-n-{4-[amino(imino)methyl]benzyl}pyrrolidine-2-carboxamide(S)-N-(4-Carbamimidoylbenzyl)-1-(2-(Cyclohexylamino)ethanoyl)pyrrolidine-2-Carboxamide
Thrombin (Topical)). Includes indications, proper use, special instructions, precautions, and possible side effects. ... Thrombin-JMI Epistaxis Kit, Thrombin-JMI Pump Spray Kit, Thrombin-JMI Syringe Spray Kit ... Generic Name: Thrombin (Topical) (THROM bin, TOP i kal). Brand Name: Evithrom, Recothrom, Recothrom Spray Kit, Thrombi-Gel, ... If you have an allergy to thrombin or any other part of Recothrom (thrombin (topical)). ...
... , Topical Thrombin, Topical Thrombin in Gelatin, Floseal. ... Thrombin Hemostatic. Aka: Thrombin Hemostatic, Topical Thrombin, Topical Thrombin in Gelatin, Floseal ...
Kinetic analyses of thrombin activities are routinely used to monitor changes in thrombin reactivity. Computer modeling of ... THROMBIN RESEARCH PROJECT. My main interest of research, which has been funded by Research Corporation and the NIH, involves ... and the production of rabbit antibody fragments recognizing thrombin. ... determining structural features of the bovine clotting enzyme thrombin which control its reactivity with other clotting factors ...
Asp-189 of thrombin and d-Tyr of 8-5 are shown as stick models. Water 38 is represented as a blue ball. The thrombin surface is ... With the exception of the 149-loop (chymotrypsinogen numbering of thrombin), the main chain of the thrombin molecule was fully ... values measured with human thrombin. Like many of the known small-molecule thrombin inhibitors directed against the active site ... Thrombin inhibitors identified by computer-assisted multiparameter design. Daniel Riester, Frank Wirsching, Gabriela Salinas, ...
Exploring thrombin S3 pocket. Brandt, T., Baum, B., Hangauer, D., Heine, A., Klebe, G.. To be published. ...
  • The three-dimensional crystal structures of authentic mature bovine TAFI (TAFIa) in complex with tick carboxypeptidase inhibitor, authentic full lenght bovine plasma thrombin-activatable fibrinolysis inhibitor (TAFI), and recombinant human TAFI have recently been solved. (biomedcentral.com)
  • Ongoing hypoperfusion, this hypothesis goes, leads to excess activation of protein C, which inhibits thrombin generation, impairs clot formation, and degrades any clots that have formed. (aacc.org)
  • Equivalent to human TAFI, bovine TAFI was a substrate for transglutaminases and could be proteolytically cleaved by trypsin or thrombin/solulin complex, although small differences in the fragmentation patterns were observed. (biomedcentral.com)
  • This endothelial activation could lead to a secretion of many proinflammatory cytokines and growth factors, such as thrombin. (biomedsearch.com)
  • Thrombin and the atrial natriuretic peptide (ANP) possess a number of functionally antagonistic properties in vascular endothelial cells. (ahajournals.org)
  • Quantitative phosphoproteomics unveils temporal dynamics of thrombin signaling in human endothelial cells. (sigmaaldrich.com)
  • Because of its complexity, thrombin-induced signaling in endothelial cells has remained incompletely understood. (sigmaaldrich.com)
  • Here, we have combined stable isotope amino acids in cell culture, affinity-based phosphopeptide enrichment, and high-resolution mass spectrometry and performed a time-resolved analysis of the thrombin-induced signaling in human primary endothelial cells. (sigmaaldrich.com)
  • Our study provides a unique resource of phosphoproteins and phosphorylation sites that may generate novel insights into an intimate understanding of thrombin-mediated PAR signaling and the development of improved PAR1 antagonists that affect platelet but not endothelial cell function. (sigmaaldrich.com)
  • Thrombin mediates changes in endothelial barrier function and increases endothelial permeability. (ahajournals.org)
  • A feature of thrombin-enhanced endothelial hyperpermeability is contraction of endothelial cells (ECs), accompanied by formation of focal adhesions (FAs). (ahajournals.org)
  • Depletion of GIT1 with antisense GIT1 oligonucleotides had no effect on basal cell morphology, but increased cell rounding and contraction of HUVECs, increased FA formation, and increased FAK tyrosine phosphorylation in response to thrombin, concomitant with increased endothelial hyperpermeability. (ahajournals.org)
  • 2,3 Thrombin contraction is accompanied by formation of small gaps between cells and disturbed barrier function of the endothelial monolayer, 4,5 the major cause of vascular leakage under inflammatory conditions. (ahajournals.org)
  • Because the permeability-enhancing effects of thrombin are reversible and GIT1 regulates assembly of FAs, we hypothesized that GIT1 mediates recovery from thrombin-induced endothelial barrier injury. (ahajournals.org)
  • These compounds concentration-dependently inhibited the activities of thrombin and FXa and inhibited the generation of thrombin and FXa in human endothelial cells. (mdpi.com)
  • My main interest of research, which has been funded by Research Corporation and the NIH, involves determining structural features of the bovine clotting enzyme thrombin which control its reactivity with other clotting factors in the blood. (csbsju.edu)
  • This work involves purification and characterization of many proteins from bovine blood and lungs, synthesis of peptides (by manual solid state techniques) and characterization (by chemical and chromatographic techniques), and the production of rabbit antibody fragments recognizing thrombin. (csbsju.edu)
  • Bovine thrombin however, is capable of causing fatal severe bleeding or thrombosis Label . (drugbank.ca)
  • This thrombosis may result from the development of antibodies against bovine thrombin Label . (drugbank.ca)
  • Patients who are know or suspected to have antibodies to bovine thrombin and/or bovine factor V should not be re-exposed to the product Label . (drugbank.ca)
  • Patients who are administered bovine thrombin should be monitored for abnormal coagulation laboratory values, bleeding, or indeed, thrombosis Label . (drugbank.ca)
  • thrombin alfa) products are available as alternatives to using bovine thrombin. (drugbank.ca)
  • Bovine thrombin is a topical thrombin indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (like suture, ligature, or cautery) is ineffective or impractical Label . (drugbank.ca)
  • Additionally, topical bovine thrombin can also be used in combination with an absorbable gelatin sponge, USP Label . (drugbank.ca)
  • Little has been reported about the systemic pharmacodynamics and pharmacokinetics of bovine thrombin preparations 2 , but it is expected that bovine thrombin elicits similar activities as endogenous thrombin. (drugbank.ca)
  • Read the side effects of Thrombin Topical Bovine Origin as described in the medical literature. (medindia.net)
  • Omrix's Thrombin stand-alone, which is derived from human plasma, is designed to provide effective hemostasis (control of bleeding) without the risk of adverse reactions associated with the use of bovine-sourced hemostats. (fdanews.com)
  • Assay principle HEMOCLOT T.T. is an clotting assay developed for the determination of the Thrombin Time induced by bovine thrombin (Thrombin Time, T.T.), in presence of calcium, on human citrated plasma, and exploration of the anti-thrombin activities. (webwire.com)
  • This is a Phase 3 multiple site, randomized, double-blind, controlled trial designed to evaluate the comparative efficacy and safety of rhThrombin and bovine thrombin in patients undergoing spinal surgery, hepatic resection, peripheral arterial bypass surgery, or arteriovenous graft formation for hemodialysis access. (knowcancer.com)
  • After establishing eligibility, subjects will be randomized in a 1:1 ratio to receive rhThrombin (1000 U/mL) or bovine thrombin (1000 U/mL). (knowcancer.com)
  • During a surgical procedure, study participants will be treated with blinded study drug (rhThrombin or bovine thrombin) in combination with an absorbable gelatin sponge at appropriate bleeding evaluation site(s) and time to hemostasis (TTH) will be assessed for up to 10 minutes. (knowcancer.com)
  • Lee Biosolutions produces and supplies high purity bovine Thrombin for medical research of proteolytic enzymes and manufacturing of defibrinating human plasma and serum free media component. (leebio.com)
  • Lee Biosolutions High Specific Activity Bovine Thrombin product is used to cleave r-fusion proteins containing a thrombin site for removal of affinity tags as well as certain diagnostic pharmaceutical applications. (leebio.com)
  • Bovine Thrombin used as a reagent, which has proven useful in the laboratory evaluation of many fibrinogens. (leebio.com)
  • Bovine Thrombin is a multi-functional proteolytic enzyme which acts both specifically and non-specifically with several proteins, cells, surfaces, and other molecules. (leebio.com)
  • In line with a role of BGN in balancing thrombin activity, ApoE-/-/Bgn-/0 mice exhibited higher activity of circulating thrombin and greater platelet activation than did ApoE-/- mice. (ahajournals.org)
  • The present results indicate that BGN plays a previously unappreciated protective role during progression of atherosclerosis by inhibiting thrombin activity and platelet activation, and ultimately macrophage-mediated plaque inflammation. (ahajournals.org)
  • However, whether thrombin contributes to the pathologies of these diseases is unknown, although thrombin is a potent inflammatory mediator in other organ systems. (wiley.com)
  • The investigative therapy essentially works "like a thrombin sponge" that is exponentially more potent than current agents used to inhibit clotting, Dr. Wickline explained. (medicalxpress.com)
  • Thrombin promotes chemotaxis in monocytes, neurite retraction in neuron Thrombin serves as a potent mitogenic agent in fibroblast growth and functions as a serum-free media component for several cell lines. (leebio.com)
  • The primary efficacy objective is to demonstrate that the device time-to-hemostasis for the study group treated with the sealing device manufactured with Thrombin VSI is non-inferior to the study group treated with the sealing device manufactured with Thrombin JMI. (clinicaltrials.gov)
  • Thrombin is a pleiotropic enzyme best known for its contribution to fibrin formation and platelet aggregation during vascular hemostasis. (nih.gov)
  • Thrombin topical is used to help control minor bleeding and oozing during surgery. (mayoclinic.org)
  • Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of thrombin topical in children. (mayoclinic.org)
  • During the past 4 months I have conducted several double-blind studies to investigate the efficacy of topical thrombin in the control of bleeding from the puncture sites in dialysis patients. (annals.org)
  • Recombinant topical thrombin at a concentration of 1,000 IU/1 ml. was incrementally injected in small aliquots of 100 IU into the PSA under gray-scale and intermittent Doppler imaging until the PSA appeared thrombosed as determined by elimination of Doppler signal in the PSA sac. (appliedradiology.com)
  • PAR activation and the inflammation actions of thrombin 2.6. (powells.com)
  • Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. (inova.org)
  • These actions of thrombin on cells have been implicated in tissue repair processes and in the pathogenesis of inflammatory and fibroproliferative disorders such as pulmonary fibrosis and atherosclerosis. (nih.gov)
  • Thrombin (200-2000 U kg −1 intranasally), induced the recruitment of a small, but significant, number of neutrophils into the airways as assessed by differential counts of cells retrieved by bronchoalveolar lavage (BAL). (wiley.com)
  • Finally, the concentration of thrombin could be accurately determined by means of measuring the phosphorescence intensity change value (Δ P ). The limit of detection (LOD) was obtained as low as 15.26 pM with wide linear ranges both from 60 to 2000 pM and from 2 to 900 nM. (rsc.org)
  • For this reason, the authors retrospectively reviewed all cases of arterial PSAs that occurred at non-groin sites treated with percutaneous ultrasound-guided thrombin injection between January 2000 and October 2016 at Mayo Clinic in Rochester, MN to determine the safety and effectiveness of the procedure. (appliedradiology.com)
  • PAR1, PAR3, and PAR4 can all be activated by thrombin. (pnas.org)
  • Those sites were localized on proteins that are novel to thrombin signaling, but also on well-known players such as PAR1, Rho-associated kinase 2, phospholipase C, and proteins related to actin cytoskeleton, cell-cell junctions, and Weibel-Palade body release. (sigmaaldrich.com)
  • Contrary to crystal structures of active thrombin, hydrogen-deuterium exchange mass spectrometry studies indicate that this N-terminal Ile-NH3 does not become inserted into the β-barrel in the apo form of thrombin. (wikipedia.org)
  • One of the early orally active thrombin inhibitors, ximelagatran, demonstrated promising safety and efficacy compared with enoxaparin for thromboprophylaxis in major orthopaedic surgery but was subsequently abandoned after it was found to cause liver dysfunction in some patients. (mja.com.au)
  • Active thrombin is found in the airways of patients with a variety of inflammatory lung diseases. (wiley.com)
  • Biologically Active Thrombin-Containing Hydrogels Based on Poly(2-hydroxyethyl methacrylate) for Endovascular Occlusion", Polymers in Medicine, 1991, vol. (patentgenius.com)
  • There are three types of DTIs, dependent on their interaction with the thrombin molecule. (wikipedia.org)
  • The team found that inhibiting the inflammatory and blood -clotting molecule thrombin with targeted nanotherapy can protect against NEC-like injury in newborn mice. (medicalxpress.com)
  • Our data identified the inflammatory molecule thrombin, which plays a critical role in platelet-activated blood clotting, as a potential new therapeutic target for NEC," said coauthor Samuel Wickline, MD, professor of cardiovascular sciences at Morsani College of Medicine and director of the USF Health Heart Institute. (medicalxpress.com)
  • These results demonstrate that co-treatment with dabigatran etexilate significantly augments the anti-tumor activity of cisplatin in ovarian tumor progression by alleviating the immunosuppressive microenvironment, suggesting that thrombin may be a potential therapeutic target for treatment of ovarian cancer. (sigmaaldrich.com)
  • A variety of human thrombin and recombinant thrombin (ie. (drugbank.ca)
  • In the presence of an excess of a fully-glycosylated soluble recombinant human TM mutant (high-M(r) rec-TM), 0.11 nM thrombin inactivated 50% of 4.4nM scu-PA in 45min at 37°C. In the presence of a soluble recombinant TM mutant lacking the glycosaminoglycans (low-M(r) rec-TM), 1.9nM thrombin was needed to inactivate 50% scu-PA, as compared with 4.7nM thrombin in the absence of TM. (tudelft.nl)
  • Healthy infants up to age 6 months may have a slightly prolonged thrombin time by 2-3 seconds. (medscape.com)
  • A prolonged thrombin time indicates a fibrinogen abnormality, impairment of fibrin formation, and/or a thrombin inhibitory effect. (medscape.com)
  • The thrombin generation markers that were measured and studied were: lagtime (clotting time), endogenous thrombin potential (ETP, total thrombin concentration), peak (maximum thrombin concentration) and time to peak (ttpeak). (diva-portal.org)
  • Antiplatelet agents impairing platelet functions have proved effective in arterial thrombosis, in which high-flow conditions prevail, whereas anticoagulants act essentially by decreasing circulating thrombin concentrations, which are involved in many thrombotic events and particularly in venous thrombosis, in which stasis occurs. (ahajournals.org)
  • New drugs with these actions should add to our current repertoire of thrombin inhibitors used to treat thrombotic diseases. (nih.gov)
  • For pregnant women with preeclampsia, hypertension compared with women with normal pregnancies could lead to increased thrombin generation due to the synergistic effect of thrombotic risk factors. (prolekare.cz)
  • The identified lead compounds exhibited thrombin inhibitory constants in the lower nanomolar range. (pnas.org)
  • As a consequence of the inhibitory effect on calcium elevation and PS-expression, CLA significantly downregulated thrombin generation in PRP. (hindawi.com)
  • Lee SH, Lee W, Nguyen T, Um IS, Bae J-S, Ma E. Synthesis and Thrombin, Factor Xa and U46619 Inhibitory Effects of Non-Amidino and Amidino N 2 -Thiophenecarbonyl- and N 2 -Tosylanthranilamides. (mdpi.com)
  • The sensitivity reported in this first trial study is 0.04 nm/μM for thrombin detection in the concentration range from 0.25 to 1 μM and the limit of detection (LOD) is 0.19 μM. (mdpi.com)
  • The investigation has demonstrated that such a GMR aptasensor has the required sensitivity for the real time, label-free, in situ detection of thrombin and provides kinetic information related to the binding. (mdpi.com)
  • While investigating role of platelet depletion in NEC-related thrombocytopenia, the USF-Johns Hopkins researchers were surprised to find that thrombin mediates platelet-activated blood clotting early in the pathology of NEC-like injury-before bacteria leaks from inside the gut to circulating blood or other organs. (medicalxpress.com)