Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tissue plasminogen activator (t-PA), tissue plasminogen activator inhibitor, (PAI), and von Willebrand factor (vWF) were measured in 30 diabetics and 17 control subjects. These studies were performed to clarify the role of obesity in causing abnormalities of the fibrinolytic system in diabetics. The t-PA antigen response measured after the infusion of desmopressin acetate (DDAVP) was similar in all groups. Peak responses to DDAVP for controls, type I diabetics, and type II diabetics were 21.2 +/- 9.5 ng/mL, 27.5 +/- 9.0 ng/mL, and 28.8 +/- 11.0 ng/mL (NS), respectively. These responses did not correlate with the body mass index (BMI) or any other of the indices examined. A significant decrease of t-PA activity as contrasted with t-PA antigen following DDAVP occurred in type II diabetics only. The decrease of t-PA activity strongly correlated with greater basal levels of plasminogen activator inhibitor in these same subjects. The plasma level of plasminogen activator inhibitor correlated with BMI but with no other index examined. In contrast to t-PA activity and PAI, vWF responses to DDAVP inversely correlated to basal vWF concentration in all groups. Basal concentrations of vWF were increased in both type I and II diabetics and showed no relationship to degree of obesity. In summary, these results suggest that type II diabetic subjects have decreased t-PA activity, which is best explained by increased levels of PAI. The increased PAI appears related to obesity and not diabetes per se.
 ...
PMID:Fibrinolytic capacity following stimulation with desmopressin acetate in patients with diabetes mellitus. 250 17

The genes encoding the two plasminogen activators, tissue plasminogen activator and urokinase, were mapped to mouse chromosomes using probes derived from the respective mouse cDNAs. DNA from mouse-Chinese hamster and mouse-rat somatic cell hybrids was digested with BamHI and EcoRI, respectively, and analyzed by Southern blot hybridization for the segregation of the two genes. Tissue plasminogen activator and urokinase cosegregated with mouse chromosomes 8 and 14, respectively. The plasminogen activator genes thus fall into two syntenic groups that are conserved in human and mouse.
 ...
PMID:Chromosomal assignments of genes for tissue plasminogen activator and urokinase in mouse. 282 34

We have constructed a high-efficiency vector for expression of genes of interest in myeloma cells. This vector is comprised of regulatory sequences from immunoglobulin (Ig) genes, including the heavy-chain enhancer, a kappa light-chain promoter and splice site, and the polyadenylation signal downstream from the kappa constant region. The expression capacity of this vector was assayed in J558L myeloma cells using human tissue plasminogen activator as a reporter gene. Stable transfectants were analyzed for protein, RNA, DNA copy number and transcription rate. Expression was compared to that of intact, transfected Ig genes and to endogenous Ig. Tissue plasminogen activator cloned into this vector was found to be expressed as efficiently as intact, transfected Ig genes, producing 1-2% of total cellular mRNA from a single copy of the gene. RNA levels and transcription rates relative to those of endogenous Ig genes were found to be about 25% and 38%, respectively. Because of its high efficiency, potential for gene amplification, and various scale-up advantages of myeloma cells, this vector-host system may yield levels of desired proteins than currently available systems.
 ...
PMID:A high-efficiency vector for expression of foreign genes in myeloma cells. 284 Mar 48

The interaction of tissue plasminogen activator derived from a melanoma cell line with a specific plasminogen activator inhibitor from placental tissue, which inhibits urokinase and tissue plasminogen activator but not plasmin, was studied. Tissue plasminogen activator exists in two forms, a one chain and a two chain molecule. It was found that the two enzyme species each form 1:1 complexes with the inhibitor and that the two chain enzyme binds the inhibitor very strongly, Ki = 3 X 10(-10) mol/l, whereas the one chain enzyme forms a much weaker complex, Ki is approximately 10(-7) to 10(-8) mol/l. Substrate hydrolysis is much more efficiently catalysed by the two chain plasminogen activator than by the one chain activator.
 ...
PMID:Different inhibition of one and two chain tissue plasminogen activator by a placental inhibitor studied with two tripeptide-p-nitroanilide substrates. 293 Aug 96

Recent studies in patients with transmural acute myocardial infarction have demonstrated that intravenous thrombolytic therapy with streptokinase or tissue plasminogen activator improves left ventricular function and reduces mortality. To accomplish this, these agents must be infused early, ie, within 3 to 4 hours of the onset of chest pain; later administration of the agents exerts no significant beneficial effect. Tissue plasminogen activator appears to be the most effective and safest of the available thrombolytic agents: its intravenous administration is followed by coronary reperfusion in about 70% of patients, and its use is not associated with allergic reactions, a systemic fibrinolytic state, or a prolonged fibrinolytic effect. Once reperfusion has been established with an intravenous thrombolytic agent, intravenous heparin is given for several days, followed by oral aspirin to prevent reocclusion. Since many of these patients have a residual high-grade coronary artery stenosis in the infarct-related artery, mechanical alleviation of the residual stenosis with angioplasty or bypass surgery is an attractive therapy 2 to 4 days after reperfusion, and preliminary data indicate that elective coronary angioplasty 3 days after thrombolytic therapy is beneficial. However, further studies are needed to assess more definitively the use of such an aggressive therapeutic strategy.
 ...
PMID:Evolving concepts in the treatment of acute myocardial infarction. 304 33

Tissue plasminogen activator and urokinase were evaluated in a model of prosthetic graft thrombosis. In addition, the effects of thrombus age on lysability and the effect of thrombolytic agents on endothelium were examined. Polytef (polytetrafluoroethylene [PTFE]) grafts (3 mm X 3.5 cm) were placed in femoral arteries of dogs and graft thrombosis was induced. Grafts were treated with a local infusion of either urokinase or tissue plasminogen activator (4000 units/min) and the times for initial flow, complete thrombolysis, and anastomotic bleeding were noted. The luminal surfaces of the grafts and the proximal arterial segments were assayed for the production of thromboxane A2 and prostacyclin and examined with scanning electron microscopy. No difference in the ease of graft lysis was observed, but 50% of tissue plasminogen activator-treated vs 0% of urokinase treated grafts had extravasation of blood through the wall. Grafts treated with tissue plasminogen activator produced less thromboxane A2 and had less thrombus than those treated with urokinase. No differences between arteries exposed to either agent and control arteries were seen. Grafts treated 1,3,5, and 7 days after thrombosis were progressively more difficult to lyse. We conclude that tissue plasminogen activator is an effective thrombolytic agent, but has a potential for local bleeding complications. Grafts of PTFE are thrombogenic after lysis, but may be less so with tissue plasminogen activator than with urokinase. No effect on arterial endothelium was seen, and our studies confirm the clinical impression that older thrombi are more difficult to lyse.
 ...
PMID:Efficacy of tissue plasminogen activator and urokinase in a canine model of prosthetic graft thrombosis. 308 27

Tissue plasminogen activator is one of the two plasminogen activators, both serine proteases, that catalyze the conversion of inactive plasminogen to plasmin, which then degrades the fibrin network of blood clots. By combining somatic cell genetics, in situ hybridization, and Southern blot hybridization, we localized the human tissue plasminogen activator gene to the pericentromeric region of chromosome 8.
 ...
PMID:Tissue-type plasminogen activator gene is on chromosome 8. 308 7

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, contraindications, and dosage and administration of tissue plasminogen activator are reviewed. Tissue plasminogen activator (t-PA) is a serine protease that binds to fibrin-plasminogen complex, catalyzing the conversion of plasminogen to plasmin. Unlike streptokinase or urokinase, t-PA binds slowly, if at all, to free circulating plasminogen. This clot specificity suggests t-PA will not produce a systemic lytic effect; however, clot specificity appears to be dose-related, and concentrations similar to those achieved in recent clinical trials have been associated with hemostatic defects. Most clinical trials have used a recombinant DNA product (rt-PA). In the treatment of acute myocardial infarction, intravenous infusions of rt-PA appear to be more effective than intravenous streptokinase. Similar rates of hemorrhage, reperfusion arrhythmias, and reocculsion have been reported. Contraindications to rt-PA use are similar to those for other thrombolytic agents. Preliminary studies of rt-PA in various thromboembolic disorders are encouraging. Marketing approval of a t-PA product (rt-PA, Activase, Genentech, Inc.) is expected in the United States by mid-1987. Clinical trials suggest that rt-PA is more effective and as safe as intravenous streptokinase in lysing occlusive coronary-artery thrombi; however, safety and efficacy appear to be dose-related, and further study is needed to determine the optimal dose.
 ...
PMID:Tissue plasminogen activator: a new thrombolytic agent. 311 81

Tissue plasminogen activator-inhibitor complexes were purified from the conditioned medium of human umbilical vein endothelial cells by affinity chromatography followed by gel filtration. It was found that a single complex was isolated which can exist in two distinct interconvertible conformations. These may be separated by electrophoresis into a form with a 105,000 apparent molecular weight and a form with an 88,000 apparent molecular weight. The particular conformation which predominates may be altered by changing the pH at which preparations are incubated or by including dithiothreitol in incubation buffers. Plasminogen activator enzymatic activity may be partially recovered from purified complexes by incubation in the presence of fibrin. Incubation in 1.5 M NH4OH results in the dissociation of the complex into two major polypeptides of 67 and 40 kilodaltons (kDa). The 40-kDa protein was isolated by gel filtration high-pressure liquid chromatography. N-Terminal amino acid analysis of this protein revealed three distinct sequences. Two of these were nearly identical and matched the N-terminal sequence recently reported for the native plasminogen activator inhibitor from endothelial cells. The third sequence exactly matched an internal portion of the same protein. The results suggest that the internal sequence is located at the site where the inhibitor is cleaved by tissue plasminogen activator.
 ...
PMID:Purification and characterization of a tissue plasminogen activator-inhibitor complex from human umbilical vein endothelial cell conditioned medium. 312 30

We evaluated the efficacy of intravenously administered recombinant tissue plasminogen activator to lyse laser-induced arterial thrombi in the stroke-prone, spontaneously hypertensive rat model. The arterial thrombi were confirmed histologically, and assessed by color photographs and fluorescein angiography before and after intravenous tissue plasminogen activator or saline therapy. Experimental animals received tissue plasminogen activator (1 mg/kg of body weight) given intravenously over one hour, and control animals received similar volumes of normal saline. Tissue plasminogen activator was effective in lysing experimental retinal arterial thrombi.
 ...
PMID:Recombinant tissue plasminogen activator to lyse experimentally induced retinal arterial thrombi. 312 46


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>