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

Fibrin structure contributes to the regulation of the fibrinolytic rate. As the fibrin fiber size is decreased, the fibrinolytic rate also decreases. Fibrin structure was altered by either changing the ratio of thrombin to fibrinogen, i.e. altering the assembly rate or by adding a fibrin assembly inhibitor, iopamidol. Changes in the fibrinolytic rate were followed by measuring the time dependence of the decrease in the fiber mass/length ratio during fibrinolysis. A measure of the overall fibrinolytic rate was determined from the decrease in the mass/length ratio versus time. An 8-fold reduction in the fibrinolytic rate was seen on decreasing the mass/length ratio from 2.7 x 10(12) daltons/cm to 0.5 x 10(12) daltons/cm. It is shown that thin fibrin fibers have a decreased rate of conversion of plasminogen to plasmin by tissue plasminogen activator and that thin fibrin fibers are lysed more slowly than thick fibrin fibers.
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PMID:The effect of fibrin structure on fibrinolysis. 144 76

Previously, we have reported that some guanidino-substituted alpha- and beta-aryl enol lactones I and II behaved as selective, mechanism-based inhibitors of some trypsin-like proteases (Rai, R.; Katzenellenbogen, J.A. J. Med. Chem., submitted). In this study, we describe the synthesis and kinetic evaluation of some related, guanidino-substituted enol lactones having greater conformational mobility and affording additional hydrogen-bonding sites at the active site. The alpha-aryl-substituted lactones 1 and 2, which have greater conformational mobility in the guanidinoaryl linkage than I, selectively inhibited the trypsin-like enzymes, and they were relatively poor inactivators of alpha-chymotrypsin and human neutrophil elastase (HNE). The iodo enol lactone 2 permanently inactivated trypsin, urokinase, tissue plasminogen activator, and plasmin, showing exceptionally high specificity in its interaction with trypsin and urokinase. The selectivity pattern exhibited by the closely related, conformationally less mobile alpha-aryl-substituted iodo lactone Ib, which was previously shown to be a selective suicide substrate of urokinase and plasmin, provides an interesting comparison. The alpha-benzamido-substituted lactones 3 and 4, which afford an additional site for active-site hydrogen bonding, were found to be very potent alternate substrate inhibitors of trypsin and urokinase. In addition, the iodo lactone 4 permanently inactivated alpha-chymotrypsin. The importance of secondary interactions in increasing the specificities in the case of alpha-chymotrypsin is discussed.
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PMID:Effect of conformational mobility and hydrogen-bonding interactions on the selectivity of some guanidinoaryl-substituted mechanism-based inhibitors of trypsin-like serine proteases. 144 34

A 37-year-old man was admitted with facial edema and right arm swelling. Venography, computed tomography and magnetic resonance imaging showed massive organizing thrombi in the superior vena cava and bilateral internal jugular as well as subclavian veins, and showed no mass lesions occluding the veins in the mediastinum. Angioscopy demonstrated a white thrombus at the entrance of the right subclavian vein. All results of blood coagulation tests were normal. The patient was diagnosed as having superior vena cava syndrome caused by idiopathic venous thrombosis. Anti-coagulant therapy with intravenous tissue plasminogen activator injection and continuous urokinase and heparin infusion into the thrombi through a catheter were not effective in lysing the thrombi. Collateral circulation gradually developed and his symptoms decreased. We decided to follow this patient on warfarin medication because of the difficulty in removing the thrombi surgically.
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PMID:[A case of superior vena cava syndrome due to extensive venous thrombosis of an idiopathic nature]. 144 55

The fibrinolytic system was investigated in 38 patients (21 males and 17 females) affected by type 1 diabetes mellitus (18 free from complications, 10 with retinopathy, and 10 with autonomic neuropathy) and in 8 healthy controls. Two separate fibrinolysis-stimulating tests were done: standardized venous occlusion and 1-desamino-8-D-arginine vasopressin infusion. Plasma tissue plasminogen activator antigen and activity and plasma plasminogen activator inhibitor activity were measured. All the patients were in good metabolic control (mean HbA1c 7.4%, range 6.1-8.0%). No significant differences were observed either between the diabetic patients and the control subjects, nor among the subgroups of diabetic patients. The fibrinolytic system is probably not involved in type 1 diabetes mellitus.
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PMID:Normal tissue plasminogen activator and plasminogen activator inhibitor activity in plasma from patients with type 1 diabetes mellitus. 145 17

Thrombolytic therapy using recombinant-tissue plasminogen activator, urokinase and streptokinase for acute myocardial infarction was instituted in the coronary care unit of the Prince of Wales Hospital in Hong Kong in 1988. To evaluate its impact on hospital mortality of acute myocardial infarction, the database of 465 patients (mean age 65.2 +/- 12.6 yr) admitted into the coronary care unit in the period between 1985-1990 was collected prospectively and their clinical course reviewed. Three hundred and thirty-five patients were males and 130 were females. Patients in the prethrombolytic era (1985-87) and the thrombolytic era (1988-90) were matched for age, proportion of females and clinical severity. One hundred and two patients (39.5%) received thrombolytic therapy. The overall hospital mortality (18.6%) in the thrombolytic era and that for each sex (18.2% in the males; 19.5% in the females) were significantly lower than those of prethrombolytic era (27.1%, 23.4% and 37.7%, respectively). No death was due to bleeding complication. The benefit of thrombolytic therapies in the Chinese was confirmed. More effort is needed to popularize this concept in the Chinese communities, to shorten the prehospital delay of patients and to extend its utilisation to the elderly patients.
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PMID:The impact of thrombolytic therapy on hospital mortality from acute myocardial infarction in the Chinese in Hong Kong. 145 73

Although a considerable number of publications on tissue plasminogen activator (t-PA) in human milk have appeared, most investigators have determined t-PA activity using an assay on fibrin plates [1, 2, 3, 4]. We measured t-PA activity by a bioimmunoassay and t-PA antigen by ELISA using a monoclonal antibody (SP-322) [6], and estimated t-PA index ((t-PA activity, ng/ml)/(t-PA antigen, ng/ml) x 100) in human colostrum and milk to evaluate the fluctuations of post-delivery t-PA. The concentrations of t-PA activity decreased slowly related to the duration of lactation varying between days one and two hundred and ten and showed significant negative correlation with the duration (P less than 0.001). The t-PA antigen made a slow descent, followed by a reciprocal ascent of the t-PA index to the fifty eighth post-delivery day and showed significant correlations with the duration (P less than 0.001, P less than 0.05, respectively). This information suggests that a high concentration of t-PA may be released into the narrow channels of the glands functioning to maintain duct patency under the regulation of an inhibitor such as plasminogen activator inhibitor (PAI).
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PMID:Determination of t-PA activity and t-PA antigen in human milk. 145 94

Tyrosylprolylarginyl chloromethyl ketone (YPRck) is a radioiodinatable inhibitor that irreversibly binds the active site of tissue plasminogen activator (tPA). A two-step reaction is employed where (1) the YPRck reagent is iodinated and (2) the 125I-YPRck is reacted with the tPA sample; therefore the oxidative effects of conventional protein iodination are avoided. Using fibrin binding as a probe of native tPA binding function, YPRck labeling was shown to be superior to other types of surface iodination. 125I-YPRck was prepared at a high specific radioactivity; i.e., one 125I per 3.5 molecules of peptidyl chloromethyl ketone. Labeled YPRck formed a one to one covalent, sodium dodecyl sulfate stable, complex with tPA resulting in a preparation of 10 mCi per milligram protein, which corresponded to an incorporation ratio of 1:3.5 (125I-YPRck:tPA). Both one-chain and two-chain forms of tPA reacted with YPRck. Radiolabeling tPA with 125I-YPRck occurred in a time-dependent manner with half-maximal incorporation at approximately 30 min under the conditions employed in these studies. The pH optimum for the reaction of tPA with 125I-YPRck was 7.4. Solutions of tPA at less than 1 microgram/ml were efficiently labeled with 125I-YPRck, thus allowing the quantitation of functional protease by incorporation of radiolabel. Significantly, 125I-YPRck specifically labeled tPA in cell culture supernatants after transient transfection of cells with plasmid DNA containing the gene for tPA. Other serine proteases were tested for their relative reactivity with 125I-YPRck. Thrombin and Factor Xa incorporated 125I-YPRck to higher levels than two-chain tPA; whereas plasmin, urokinase, and other plasma proteases were not as efficiently radiolabeled. The use of 125I-YPRck allows rapid and specific radiolabeling of a large number of tPA samples in a nondenaturing environment with a known localization of the radiolabeling reagent.
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PMID:Radioiodination of the active site of tissue plasminogen activator: a method for radiolabeling serine proteases with tyrosylprolylarginyl chloromethyl ketone. 145 45

Sulphated N-linked carbohydrate chains isolated from recombinant human tissue plasminogen activator expressed in mouse epithelial (C127) cells were analysed as oligosaccharide alditols by methylation analysis, liquid secondary ion mass spectrometry, and one- and two-dimensional 1H-NMR spectroscopy. The results demonstrate that the major component has the following novel structure: NeuAc-alpha 2-6Gal beta 1-4GlcNAc beta 1-2[NeuAc alpha 2-3Gal beta 1- 4GlcNAc beta 1-4]-Man alpha 1-3[NeuAc alpha 2-3(SO4-6)Gal beta 1- 4-GlcNAc beta 1-2Man alpha 1-6]-Man beta 1-4GlcNAc beta 1- 4[Fuc alpha 1-6]GlcNAc-o1.
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PMID:Structure elucidation of sulphated oligosaccharides from recombinant human tissue plasminogen activator expressed in mouse epithelial cells. 145 70

Forty-five patients who had been subjected to jejuno-ileal bypass (JIB) surgery for morbid obesity and 10 obese nonsurgery subjects were studied. The former group was examined 14 to 20 years after surgery, and was found to have lower mean plasminogen activator inhibitor type 1 (PAI-1) activity (8.4 v 32 U/mL, P < .001), tissue plasminogen activator (tPA) antigen concentrations (7.2 v 12 micrograms/L, P < .01), body mass index (BMI), and fasting plasma insulin, triglyceride, and cholesterol levels. The PAI-1 levels were correlated with BMI, waist to hip ratio, and insulin, triglyceride, and cholesterol levels. Thus, previously obese subjects have normal PAI levels 14 to 20 years after treatment with JIB surgery, in contrast to the high PAI-1 levels in nonsurgery obese subjects.
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PMID:Normal plasminogen activator inhibitor levels at long-term follow-up after jejuno-ileal bypass surgery in morbidly obese individuals. 146 Nov 44

In our previous study (Adv. Exp. Med & Biol., 247B. 569. 1989, 198B. 41. 1986, blood & vessel, 17: 51. 1986), we reported on the mechanism of coagulation-fibrinolysis system and kallikrein-kinin system in the utero-placental circulation during normal pregnancy, labor and puerperium. The samples were collected from the uterine artery (UA), uterine vein (UV) and peripheral vein (PV). In this study, we tried to elucidate the mechanism of coagulation-fibrinolysis with relation to kks by measuring of Thrombin/Antithrombin III complex (TAT), tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI) complex (tPA.PAI.C), active plasminogen activator inhibitor 1 (active PAI), alpha 2-plasmin inhibitor/plasmin complex (PIC). In 20 normal pregnant women, the levels of TAT, tPA.PAI.C and active PAI significantly increased the first trimester (TAT 4.31 +/- 2.05 ng/ml, tPA.PAI.C 39.52 +/- 17.34 ng/ml, active PAI 39.58 +/- 15.29 ng/ml, n = 20 M +/- SD P < 0.001) to the third trimester (TAT 6.39 +/- 1.93 ng/ml, tPA.PAI.C 57.94 +/- 30.80 ng/ml, active PAI 304.24 +/- 148.64 ng/ml, n = 20 M +/- SD P < 0.001) as compared with those of non-pregnant women (TAT 1.60 +/- 0.89 ng/mg, tPA.PAI.C 11.72 +/- 4.59 ng/ml, active PAI 11.53 +/- 7.48 ng/ml, n = 16 M +/- SD). In utero-placental circulation, the levels of TAT significantly increased (TAT 22.12 +/- 20.03 ng/ml n = 20 M +/- SD P < 0.001) in UV, and tPA.PAI.C and PIC. markedly increased (tPA.PAI.C 93.38 +/- 56.05 ng/ml, PIC 1.03 +/- 0.94 micrograms/ml n = 20 M +/- SD P < 0.02) in UV, but active PAI markedly decreased (active PAI 244.18 +/- 87.55 ng/ml n = 20 M +/- SD P < 0.02) as compared with those in PV (TAT 6.1 +/- 2.09 ng/ml, tPA.PAI.C 59.34 +/- 18.99 ng/ml, PIC 0.49 +/- 0.24 micrograms/ml, active PAI 349.14 +/- 157.34 ng/ml, n = 20 M +/- SD). These findings suggest that the significant increase in those complexes in UA has produced a deposition of fibrin clots in the area in contact with utero-placental blood vessel, although the marked increase in tPA.PAI.C and PIC incompletely inhibited the fibrinolytic activity of tPA by the active PAI. The kks shows a consumption of prekallikrein, LMW-kininogen and HMW-kininogen, and an overproduction of kinin in UV.
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PMID:Studies on blood coagulation-fibrinolysis system regarding kallikrein-kinin system in the utero-placental circulation during normal pregnancy, labor and puerperium. 146 39


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