Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.4.21.5 (thrombin)
33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

All agree on altered platelet function in vitro (and increasingly in vivo) in diabetics of substantial duration and/or with clinical evidence of angiopathy. However, a platelet abnormality earlier in the disease remains uncertain. Three sets of data from Oxford will be reviewed: (1) Observations of Honour on platelet aggregation at sites of minimal injury within blood vessels of anesthetized rabbits, with greater sensitivity to superfused ADP when hyperglycemia has followed alloxan only days previously. This increased aggregatability (not hyperglycemia determined) is reversed by a few days of insulin treatment or by dipyrimadole (alone or with synergistic acetyl salicylic acid): (2) Beta-thromboglobulin is released from platelets and is increased in venesected blood from diabetics after a standardized procedure (no prostaglandin E1 in anticoagulant) with final radioimmunoassay. Results in diabetics after surgery, etc., will also be presented, and (3) in a prospective study of newly-diagnosed, mostly maturity-onset type diabetics, an increase in plasma fibrinogen (thrombin coagulation of plasma, controlled against normals) was observed during the first 3 yr, largely due to males treated with sulfonylureas; decreases in platelet count and in prothrombin concentration were also statistically significant.
...
PMID:Direct animal and indirect human evidence of altered platelet function in diabetics. 16 73

The effects on hemostasis of two high-flux membranes in hollow-fiber configuration, polyamide (PAM) and polyacrylonitrile (AN69), were analyzed in a cross-over study involving ten chronic hemodialyzed patients. Blood samples were obtained at arterial and venous sites of the extracorporeal circuit before dialysis and at 15, 30 and 180 min. Primary hemostasis: PAM induced an early significant drop in platelet counts, but at 180 min there was no longer any difference between membranes. Beta-thromboglobulin release by PAM was significantly higher at all time points. Coagulation: thrombin-antithrombin III complexes (TAT) and fibrinopeptide A increased significantly, the highest values being found with AN69. With both membranes the arterio-venous differences in TAT levels were negative throughout the sessions. Fibrinolysis: no significant differences were observed. In conclusion, both membranes induced hemostatic changes. Although these two hollow-fiber dialyzers look relatively similar, the changes observed were different, polyamide acting mainly on primary hemostasis and polyacrylonitrile on coagulation.
...
PMID:Hemostatic disturbances induced by two hollow-fiber hemodialysis membranes. 160 10

Chronic malignant pleural effusions are usually treated with an intrapleurally administered irritant that creates an inflammatory reaction. The induced inflammation results in fibrin deposition and termination of fluid exudation. In the present study several factors in the coagulation system in the pleural fluid were followed during treatment with tube drainage and quinacrine instillation into the pleural space. In the chronic exudative phase before treatment, both thrombin activity and fibrinopeptide A (FPA), were present at low levels. During treatment the levels increased markedly. Beta-thromboglobulin, a platelet marker, showed a similar pattern. Prothrombin, antithrombin III, prekallikrein and kallikrein inhibiting activity showed no such variations in activity. The high thrombin activity and FPA level induced by treatment reflect an active process of fibrin formation which seems to play an important role in arresting chronic pleural exudation.
...
PMID:Increased coagulation activity of the pleura after tube drainage and quinacrine instillation in malignant pleural effusion. 183 67

The aim of this research was to evaluate in vitro interactions between platelets and polymorphonuclear leukocytes. The effects of supernatant from thrombin-activated platelets and two platelet release products (adenosine triphosphate and beta-thromboglobulin) were tested on the following features of polymorphonuclear leukocytes activation: opsonized zymosan and phorbol myristate acetate stimulated chemiluminescence, release of membrane bound calcium, NADPH-oxidase activity, and membrane fluidity (fluorescent polarization). The results showed that the addition of platelet supernatant to polymorphonuclear leukocytes induces a significant activation of cells. On the other hand, after three hours of preincubation of polymorphonuclear leukocytes with platelet supernatant, a decreased response of polymorphonuclear leukocytes to stimulation with phorbol myristate acetate, a significant decrease in NADPH-oxidase activity, and a lowered membrane fluidity were observed. Adenosine triphosphate modulated only opsonized zymosan stimulated chemiluminescence, with and without preincubation with polymorphonuclear leukocytes. Beta-thromboglobulin caused a decrease of the chemiluminescent response of polymorphonuclear leukocytes, using both agonists, with and without preincubation with polymorphonuclear leukocytes. Moreover beta-thromboglobulin only caused a decrease of the polymorphonuclear leukocytes membrane fluidity without preincubation with the cells. These results support the thesis that platelets have a "time-related" modulating activity on polymorphonuclear leukocytes.
...
PMID:Platelet release products modulate some aspects of polymorphonuclear leukocyte activation. 183 44

Neutrophil-activating peptide 2 (NAP-2) is generated by cleavage of two inactive precursors, connective-tissue-activating peptide III (CTAP-III) and platelet basic protein (PBP), which are stored in the alpha-granules of blood platelets. Using highly purified CTAP-III as the substrate we studied the generation of NAP-2 by several neutral tissue proteinases. CTAP-III was rapidly cleaved by chymotrypsin, cathepsin G and trypsin, yielding products with neutrophil-stimulating activity. This activity remained unchanged for 24 h in the presence of chymotrypsin, decreased only slowly in the presence of cathepsin G, but was rapidly destroyed by trypsin. CTAP-III was also degraded by human neutrophil elastase and porcine pancreatic elastase, but no active fragments were obtained. By contrast, no degradation of CTAP-III was observed with thrombin, plasmin or 'granzymes' from cytolytic T-lymphocyte granules. Two active fragments of CTAP-III, generated by chymotrypsin or cathepsin G, were purified and partially sequenced, and were found to have the same N-terminal sequence as NAP-2. These results indicate that both proteinases cleave preferentially the bond between amino acids 15 (Tyr) and 16 (Ala) of CTAP-III. We conclude that chymotrypsin-like proteolytic activity in the vicinity of activated platelets may generate NAP-2 intravascularly. Due to its presence in the primary granules of neutrophils and monocytes cathepsin G is likely to be involved in this process.
...
PMID:Formation of neutrophil-activating peptide 2 from platelet-derived connective-tissue-activating peptide III by different tissue proteinases. 203 37

Platelet basic protein (PBP) was purified from the supernatant of thrombin-stimulated, washed human platelets by ion-exchange, affinity, molecular sieve, and high-performance liquid chromatography (HPLC). The NH2-terminal amino acid sequence was determined by automated Edman degradation, revealing 9 unique residues followed by 10 residues of the established low-affinity platelet factor 4/beta-thromboglobulin (LA-PF4/beta TG) sequence. Among the nine were three basic residues, accounting for the high isoelectric point of PBP. Additional evidence for precursor status includes the immunological cross-reactivity of all three species and the ability of plasmin and trypsin to produce from PBP a species resembling beta TG in charge, hydrophobicity, and size. Tryptic peptide maps of PBP and LA-PF4 obtained by reverse-phase HPLC were very similar, and from each protein, a peptide was isolated which showed the amino acid composition predicted for the COOH-terminal tryptic peptide of beta TG. Normal platelets contained predominantly LA-PF4, with PBP ranging from 10% to 30% of total beta TG antigen. This was true even when fresh platelets were lysed with trichloroacetic acid in order to provide the most complete and rapid inhibition of proteolytic activity. beta TG itself was never detected in this situation or in the release supernatant of stimulated platelets, and only rarely in unprotected lysates. In agreement with earlier results, crude preparations of PBP were mitogenic for 3T3 cells, but highly purified preparations of PBP and LA-PF4 were free of this activity.
...
PMID:Characterization of human platelet basic protein, a precursor form of low-affinity platelet factor 4 and beta-thromboglobulin. 242 19

Beta-thromboglobulin (beta TG), serotonin (5HT) and fibrinopeptide A (FPA) were assessed in twenty-two normal donors before, during, and at the end of leukapheresis. Seven procedures were carried out adding heparin to the circuit, and seven adding acetyl salicylic acid (ASA). The remaining eight procedures were carried out using only citrate and served as controls. Plasma beta TG increased both during and after the apheresis, together with a significant decrease of the intra-platelet content. Platelet 5HT did not show significant changes whereas FPA increased significantly. Using heparin, we obtained a complete prevention of FPA cleavage during the entire procedure, while beta TG increased at the middle of the procedure. No significant effects were observed using ASA both on beta TG and FPA levels. These features clearly indicate the activation of platelets and the thrombin generation in the apheresis circuit. Nevertheless, the activation of the clotting system seems to be predominant, as supported by the improved effect of heparin on beta TG and FPA amounts.
...
PMID:Effect of heparin and aspirin on platelet and clotting activation during leukapheresis. 293 Dec 80

Blood platelets of patients with essential hypertension display signs of both increased sensitivity in vitro to aggregating stimuli believed to contribute to thrombosis and of activation in vivo possibly expressing the release of vasoactive products. The mean features of the modified platelet profile in hypertension include an increased alpha 2-adrenergic receptor density, an enhanced rate of adhesion/aggregation in particular in response to ADP and arachidonic acid, a greater sensitivity for thrombin and adrenaline to stimulate increases in cytoplasmic-free Ca2+, increased resting levels of cytoplasmatic-free Ca2+, a reduced content of serotonin often combined with a defective uptake mechanism, a facilitated efflux rate of noradrenaline, an exaggerated release reaction in vivo as indicated by the increased plasma levels of Beta-thromboglobulin and a shortened platelet life span. These changes occur to various extents in some, but not all, hypertensive patients and are not always strictly related to the degree of blood pressure increase. On the contrary, platelet cyclooxygenase and thromboxane synthetase activity are in the normal range.
...
PMID:Blood platelets in human essential hypertension. 353 21

Low-affinity platelet factor 4 and beta-thromboglobulin are low molecular weight platelet secretory proteins that have common antigenic determinants. Four amino acids (Asn-Leu-Ala-Lys) at the amino terminus of beta-thromboglobulin are deleted, but the remaining sequences of the two peptides appear to be identical. Low-affinity platelet factor 4 and beta-thromboglobulin have respective isoelectric points at pH 8.0 and at pH 7.0. Identification, quantitation, and separation of both proteins was achieved by a method combining preparative isoelectric focusing and specific radioimmunoassay with anti-low-affinity platelet factor 4 antibody. It has been determined that the supernate processes immediately after platelet aggregation induced by ionophore A23187 or thrombin contains approximately 80% low-affinity platelet factor 4, 8% beta-thromboglobulin, and 12% highly cationic immunoreactive material (platelet basic protein). Experimental evidence suggests that low-affinity platelet factor 4 is originally secreted by platelets and then converted to beta-thromboglobulin by a platelet-derived, heat-labile protease that is inhibited by phenylmethylsulfonyl fluoride.
...
PMID:Identification and separation of secreted platelet proteins by isoelectric focusing. Evidence that low-affinity platelet factor 4 is converted to beta-thromboglobulin by limited proteolysis. 615 37

Human beta-thromboglobulin, low affinity platelet factor 4 and platelet basic protein have been purified to homogeneity from the material released by thrombin-stimulated platelets. Purification steps included isoelectric focusing and heparin-agarose chromatography. Antibodies against each of these proteins have been raised in rabbits. Antigenic identity of the proteins has been demonstrated in radioimmunoassay using 125I-labelled platelet basic protein or 125I-labelled low affinity platelet factor 4 and a variety of antibodies. The molecular weight of platelet basic protein estimated by gel filtration in 6 M guanidine hydrochloride using Sepharose 6B corresponded to approx. 10 000 daltons, slightly higher than that of beta-thromboglobulin (8851 daltons) and low affinity platelet factor 4 (9278 daltons). These findings raise the possibility that the formation of low affinity platelet factor 4 beta-thromboglobulin may be a consequence of the action of proteolytic enzymes on platelet basic protein.
...
PMID:Human platelet basic protein. Its relation to low affinity platelet factor 4 and beta-thromboglobulin. 617 75


1 2 3 Next >>

---