Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the normal stomach of male rats marked differences in plasminogen activator activity (PAA) and plasmin inhibition (PI), but not in plasminogen activator inhibition (PAI), were noted among cardiac area, body and pyloric region. Chronic ethanol consumption (for 15 or 30 days) at the concentration of 6% or 12% in the drinking water induced an increase in PAA in the pyloric region and the body of the stomach (the higher concentration after 15 days and both concentrations after 30 days). The response was time- and dose-dependent. At the cardiac area no change of PAA was noted. Ethanol at both concentrations induced after 30 days a decreased PAI in the pyloric region and the body of the stomach, which was expressed against u-PA, but not against t-PA. A decreased PI was noted at both concentrations of ethanol after 30 days only in the pyloric region. Therefore, changes in PAA, PAI and PI after chronic ethanol consumption were dependent on the concentration, the period of the consumption and the area along the gastric wall.
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PMID:Enhancement of plasminogen activator activity in the gastric wall after chronic ethanol consumption. 182 83

The effects of tranexamic acid, an inhibitor of plasminogen activator, were evaluated in a rabbit model of osteoarthritis induced by section of the knee joint anterior cruciate ligament. Prophylactic treatment administered intramuscularly thrice weekly for 12 or 24 weeks significantly reduced cartilage destructive lesions, increased cartilage hypertrophy but did not prevent changes in cartilage water and proteoglycan content. A suppression of synovial membrane stromelysin and collagenase activity was found while phospholipase A2 activity was unaffected.
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PMID:Study of an inhibitor of plasminogen activator (tranexamic acid) in the treatment of experimental osteoarthritis. 185 Dec 28

In the critically ill, accurate measurements of left ventricular (LV) filling pressure using pulmonary artery occlusion pressure (Ppao) are important for diagnostic and therapeutic purposes. In patients receiving positive end-expiratory pressure (PEEP), Ppao may not reflect LV filling pressure because of elevated pericardial pressure (Ppc). It has been proposed that in humans, Ppc and right atrial pressure (PRA) are equal, so that referencing Ppao to PRA may improve the assessment of LV filling pressure when Ppc is elevated. Similarly, it has also been shown in the dog that nadir Ppao immediately after airway disconnection from PEEP (nadir Ppao), accurately reflects LV filling pressure when LV filling pressure is greater than or equal to 10 mm Hg. We examined methods of estimating LV filling pressure using Ppao measurements under conditions in which increases in Ppc were the primary determinants of differences in the two measurements. Using left atrial pressure (PLA) relative to Ppc, called transmural PLA (PLAtm), as LV filling pressure, we compared the accuracy of Ppao, nadir Ppao, and Ppao relative to PRA to reflect PLAtm in 15 postoperative cardiac surgery patients in whom an air-filled pericardial balloon catheter and a left atrial catheter were inserted during surgery. PEEP was sequentially increased from zero to 15 cm H2O. We found that PRA always exceeded Ppc (p less than 0.01) and increased less with PEEP than did Ppc (p less than 0.05). At less than or equal to 5 cm H2O PEEP, both Ppao and nadir Ppao were similar to each other and to PLAtm.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Estimating left ventricular filling pressure during positive end-expiratory pressure in humans. 192 77

The Escherichia coli outer-membrane phospholipase A (OM PLA) is a membrane-bound acyl hydrolase with a broad substrate specificity. In order to obtain more insight into the mechanism of action of this enzyme, we designed an active-site-directed inhibitor for OM PLA on the basis of the known substrate specificity as a first step in the elucidation of the catalytic mechanism of this enzyme. The inhibitor, hexadecanesulfonyl fluoride, consists of a long hydrocarbon chain for high-affinity binding by the enzyme and a sulfonyl fluoride moiety as a reactive group. The kinetics of the inactivation of OM PLA by hexadecanesulfonyl fluoride were studied in Triton X-100 micelles. Inactivation is very fast, specific and shows the same characteristics with respect to acyl specificity, pH profile and metal ion requirement as the activity of OM PLA on substrates. Incubation of OM PLA with a stoichiometric amount of hexadecanesulfonyl fluoride leads to a total and irreversible loss of enzyme activity, resulting from the sulfonylation of Ser144. This Ser144, which we suggest to be the active-site serine of OM PLA, is part of the sequence HDSNG, whereas in the water-soluble serine proteases and lipases the structural motif GXSXG is normally encountered. On the basis of the kinetics of inactivation of OM PLA by hexadecanesulfonyl fluoride, we discuss a possible catalytic mechanism of the enzyme.
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PMID:Inactivation of Escherichia coli outer-membrane phospholipase A by the affinity label hexadecanesulfonyl fluoride. Evidence for an active-site serine. 204 Feb 86

A simple method for the quantitative assay of vascular plasminogen activator is described. From 24 chronic renal failure patients who were undergoing surgery for A/V fistular or shunt construction, small pieces of artery (mean 7.8 mg, range 3.0-18.5 mg) and vein (mean 4.5 mg, range 3.0-8.8 mg) were used. The fibrinolytic activity was assayed on a well-controlled fibrin plate by only distilled water immersion and incubation at 37 degrees C. Basal fibrinolytic activity was correlated with venous fibrinolytic activity (r = 0.773, p less than 0.0001) and with arterial fibrinolytic activity (r = 0.55, 0.005 less than p less than 0.01). The increment of fibrinolytic activity by venous occlusion was correlated to venous fibrinolytic activity (r = 0.849, p less than 0.0001) but not to arterial fibrinolytic activity (r = 0.34, 0.1 less than p less than 0.25).
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PMID:A simple quantitative assay of vascular plasminogen activator--not only stimulated fibrinolytic activity but also basal fibrinolytic activity are correlated with venous fibrinolytic activity. 209 97

Mechanical ventilation with high peak airway pressures (Paw) has been shown to induce pulmonary edema in animal experiments, but the relative contributions of transvascular filtration pressure and microvascular permeability are unclear. Therefore, we examined the effects of positive-pressure ventilation on two groups of open-chest dogs ventilated for 30 min with a peak Paw of 21.8 +/- 2.3 cm H2O (Low Paw) or 64.3 +/- 3.5 cm H2O (High Paw). No hemodynamic changes were observed in the Low Paw group during ventilation, but mean pulmonary artery pressure (Ppa) increased by 9.9 cm H2O, peak inspiratory Ppa by 24.6 cm H2O, and estimated mean microvascular pressure by 12.5 cm H2O during High Paw ventilation. During the same period, lung lymph flow increased by 435% in the High Paw and 35% in the Low Paw groups, and the terminal extravascular lung water/blood-free dry weight ratios were 5.65 +/- 0.27 and 4.43 +/- 0.13 g/g, respectively, for the two groups. Lung lymph protein clearances and minimal lymph/plasma ratios of total protein were significantly higher (p less than 0.05) after 2 h of increased left atrial pressure (PLA) in the High Paw group versus the Low Paw group, which indicates a significant increase in microvascular permeability. Lymph prostacyclin concentration in pulmonary lymph, measured as the stable metabolite 6-0-PGF1 alpha, was increased significantly by 70 to 150% from baseline (p less than 0.05) in both groups during the periods of increased Paw and increased PLA, but it was not significantly different between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lung edema caused by high peak inspiratory pressures in dogs. Role of increased microvascular filtration pressure and permeability. 211 48

Poly-L-lactic acid (MW 6000) microspheres (PLA-MS) containing 5-fluoro-2'-deoxyuridine (FUdR) or four ester prodrugs of FUdR were prepared and examined with regard to the in vitro release kinetics. The incorporation efficiency of the lipophilic prodrugs into the PLA-MS was higher than that of FUdR or the hydrophilic prodrugs. The release of the lipophilic FUdR prodrugs from PLA-MS was sustained as compared with that of FUdR from PLA-MS. The release kinetics of the FUdR prodrugs appears to fit the Higuchi, Baker, and Lonsdale model in the early stage of the release process. The slope of the Baker and Lonsdale plots of the release of divaleryl-FUdR from PLA-MS decreased as the initial drug loading was decreased. The order of the release rates of FUdR prodrugs from PLA-MS with the same prodrug content was similar to that of the water solubilities of the prodrugs. These results suggest that the ester prodrugs could be released from PLA-MS by diffusion through water-filled capillaries or a series of pores rather than by diffusion through the PLA matrix.
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PMID:Controlled release of 3',5'-diester prodrugs of 5-fluoro-2'-deoxyuridine from poly-L-lactic acid microspheres. 214 64

Poly(DL-lactic acid) (DL-PLA, molecular weight 20,500) microcapsules containing phenobarbitone (PB) as a reference core were prepared using a water/oil (W/O) emulsion system. Surface morphology, particle size and 'encapsulation efficiency' of the microcapsules prepared using different preparative variables have been investigated. Buffer pH 9 was used as a dissolution medium to determine the affect of preparative variables on the release rate from these microcapsules. With an increase in temperature of evaporation the microcapsule surface became increasingly irregular and porous, due to deposition of phenobarbitone crystals near the vicinity of the microcapsule surface leading to rapid release of the core. The normalized release rate was found to increase exponentially with an increase in the temperature of evaporation. Microcapsule morphology was also severely affected due to differences in polymer concentration in the disperse phase solvent. With the increase in polymer concentration, the microcapsule surface was found to be increasingly irregular and non-continuous, due to rapid precipitation of the polymer. Increased polymer concentrations also increased mean microcapsule diameter. The release rate increased with the increase in polymer concentration due to surface defects and did not exhibit a straight line correlation. When core loading was very high (e.g. C:P, 2:1 and 1:1), crystals of phenobarbitone appeared at the surface and these caused a very rapid burst effect. However, microcapsules containing a lower phenobarbitone content were found to follow t1/2 dependent release. The encapsulation efficiency was not seriously affected due to variations in temperature of preparation and polymer concentration. However, with the decrease in initial core loading the encapsulation efficiency of microcapsules was found to be reduced.
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PMID:Microencapsulation using poly(DL-lactic acid). I: Effect of preparative variables on the microcapsule characteristics and release kinetics. 232 48

The kinetic behavior of fibrin clot lysis as induced by tissue-type plasminogen activator (t-PA) was studied using proton magnetic resonance (PMR) and a release assay of fibrin labeled with technetium-99m isotope (99mTc). The lysis pattern of the preformed clot was examined as a function of gradual changes in the amounts of added t-PA and deactivated t-PA. The behavior of fibrinolysis was found to depend strongly on the amount of t-PA in the assay, which markedly affects the lysis rate of fibrin. The changes induced by the lysis were reflected in pronounced prolongation of the transverse relaxation time. The PMR and the radioisotope release measurements point to the possibility that at least two steps are involved in the mechanism of lysis. The PMR seems to be associated with structural features of the clot and reflects the liberation of compartmentalized water from the clot, while the 99mTc analysis reflects the further fragmentation of fibrin.
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PMID:Structural changes in fibrin clot associated with the proteolytic activity induced by tissue type plasminogen activator. An NMR study. 249 19

The clot uptake of labeled active and inhibited t-PA was compared. The most efficient inhibition was obtained with diisopropyl fluorophosphate (DFP) after 4 h incubation at room temperature. Enzyme activity was followed by fibrin-plate assay, radioactivity-release technique and proton magnetic resonance (PMR). The novel PMR method developed by us is sensitive to the effect of as low as nanogram amounts of t-PA on the interaction between the fibrin and the compartmentalized water trapped in the clot. Binding of labeled enzyme to fibrin-coated plates showed that the deactivation by DFP did not impair the affinity of t-PA for fibrin. A rapid binding of 125I-labeled t-PA to the clot occurred, which reached a maximum in 30 min and declined with time. This pattern was explained by consecutive clot binding and lysis. The binding of DFP-t-PA to the clot differed markedly from that of the active protein; 2 h post-incubation the uptake of DFP-t-PA was more than double that of the untreated t-PA. Parallel measurements in clots prepared from human blood showed a qualitatively similar trend. The biodistribution of radiolabeled t-PA in mice was similar for the active and inhibited forms. Blood activity reached 10% of the injected dose within 10 min. DFP-t-PA may prove to be a useful reagent for in-vivo localization of thrombi.
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PMID:Clot uptake of labeled active and inhibited tissue plasminogen activator. 249 63


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