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

Several hormones and inducers of intracellular messengers, known to affect plasminogen-activator (PA) production in other systems, were investigated for putative effects on bovine embryos. Day 8 embryos were cultured for 5 days in a humidified atmosphere of 5% CO2 in air at 37 degrees C in media containing different concentrations of progesterone, oestradiol, dexamethasone, retinoic acid, dibutyryl cyclic AMP (dbcAMP) and phorbol myristate acetate (PMA). At intervals of 24 h, the medium was recovered for PA analysis and overall embryonic diameter was measured. While none of the hormones and agents tested affected PA production (P > 0.05), dimethyl sulfoxide, which was used to dissolve PMA, inhibited PA production during the first 72 h of culture (P < 0.05). PA production was affected by duration of culture (P < 0.05). Concentrations of plasminogen activator in the media were low during the first 48 h, had increased after 72 and 96 h in culture, and either remained high or decreased slightly toward the end of the culture period. With the exceptions of dbcAMP and PMA, the hormones tested in this study did not affect embryonic size. Dibutyryl cAMP caused a progressive decrease in embryonic diameter. PMA resulted in embryo death at high concentrations but at lower concentrations it enhanced overall embryonic diameter throughout the time of culture (P < 0.05). These results suggest that cultured bovine embryos produce PA in a fixed, time-dependent manner, independent of exogenous hormonal regulation.
 ...
PMID:Lack of effect of hormones and inducers of intracellular messengers on plasminogen activator production by bovine embryos in vitro. 133 38

Polyhydroxy acids [poly(L-lactic acid) (L-PLA), poly(D,L-lactic acid) (DL-PLA), and poly-(glycolic acid) (PGA)], biocompatible and bioerodible polymers that are being investigated for controlled delivery of pharmaceuticals and are approved by the Food and Drug Administration for in vivo sutures and bone repair implants, have been dissolved in supercritical CO2 and precipitated by rapid expansion of the resulting supercritical solutions (RESS). The formation of these microparticles and microspheres is a first step toward the goal of producing, in a single processing step, drug-loaded polymeric microspheres for use in controlled release applications. Nucleation of poly(L-lactic acid) from CO2 and CO2-acetone mixtures produced microparticles and microspheres ranging from 4 to 25 microns. Microspheres (2-20 microns) were also obtained with chlorotrifluoromethane as solvent. Commercial L-PLA precipitated after extraction of low molecular weight oligomers showed degradation kinetics similar to that of the starting material. The precipitation of DL-PLA from CO2 produced irregular-sized particles (10-20 microns). PGA, a polymer insoluble in most organic solvents, was found to be soluble in supercritical CO2. Nucleation of PGA from CO2 produced both regular-sized particles and needles of 10-40-microns length. The total solubility of commercial L-PLA in supercritical CO2 at 250 bar and 55 degrees C decreased from 0.14 wt % to less than 0.05 wt % and then leveled off as the cumulative flow of CO2 per unit mass of L-PLA loaded in the extractor increased beyond 20 standard L of CO2/g of L-PLA. Use of acetone (1 wt %) as a cosolvent increased L-PLA solubility by approximately 500%.
 ...
PMID:Formation of bioerodible polymeric microspheres and microparticles by rapid expansion of supercritical solutions. 136 63

Mechanical forces due to fluid flow and cyclical strain can alter endothelial cell morphology and function, including the release of vasoactive materials endothelin, prostacyclin (PGI2), and tissue plasminogen activator (t-PA). In this study, effects of cyclical strain were modeled by culturing bovine aortic endothelial cells on fibronectin-coated elastic membranes of silicone rubber (Silastic) or poly-etherurethane urea (Mitrathane). After growing to confluence under static conditions of 37 degrees C in humidified air with 5% CO2, cells were strained cyclically at membrane elongations of 5% or 10% for 24 hours at 1 Hz. Controls were maintained under static conditions or were exposed to fluid motions similar to the strained cells but without stretching. Secretion rates were constant throughout experiments in the strain chamber with no initial burst in metabolism associated with the initiation of strain. Secretion rates were not altered by choice of elastic membrane. At a physiological level of 10% cyclical strain, prostacyclin and endothelian secretion rates were increased by 2.5-fold and 1.7-fold, respectively, above stationary controls. Endothelin production demonstrated a dose-dependent response with cyclical strain, while PGI2 appeared to require a threshold strain before an increase in secretion occurred. No significant differences in t-PA levels were seen in cyclically strained cells compared with controls. These results indicate that endothelial cells respond metabolically to cyclical strain and suggest that mechanical strain may modulate secretion of selective vasoactive materials by vascular endothelial cells.
 ...
PMID:Cyclical strain effects on production of vasoactive materials in cultured endothelial cells. 156 46

Sodium dodecyl sulphate-polyacrylamide gel electrophoresis and zymography were used to determine the tissue source and to characterize the types of plasminogen activator (PA) produced by bovine blastocysts. Day 12-14 blastocysts were collected at slaughter from oestrus-synchronized, superovulated and artificially inseminated Holstein cows. In Expt 1, blastocysts were cultured for 24 h in Ham's F-12 in a humidified atmosphere of 5% CO2 in air at 37 degrees C. After culture, blastocysts and medium were recovered and stored separately at -20 degrees C. In Expt 2, embryonic discs were separated from trophoblast by microdissection. Intact blastocysts, embryonic discs and trophoblast were then cultured for 24 h and recovered as in Expt 1. In both experiments, embryonic tissues and media were electrophoresed with PA and molecular mass standards. Polyacrylamide gels were laid onto casein-agar gel plates (zymograms) and incubated at room temperature for 24-48 h. Caseinolytic zones in zymograms containing plasminogen were evidence of PA. In Expt 1, bovine blastocysts contained and secreted light and heavy forms of PA (47.0 +/- 1.0 and 86.1 +/- 0.7 kDa, respectively). In Expt 2, intact blastocysts and trophoblast produced both forms of PA (41.5 +/- 1.5 and 92.2 +/- 2.7 kDa) but PAs were not detected in embryonic discs. The results suggest that Day 12-14 bovine blastocysts produce urokinase-type PA (41.5-47.0 kDa) and a form of high molecular mass (86.1-92.2 kDa) that is either a novel tissue-type PA or a PA inhibitor which complexes with the lighter form.
 ...
PMID:Electrophoretic characterization of the plasminogen activator produced by bovine blastocysts. 178 69

We report a series of seven patients (age: 43-77 years, preoperative American Society of Anesthesiologists (ASA) physical status II-III) with perioperative, life-threatening pulmonary embolism and severe cardiogenic shock treated with recombinant tissue type plasminogen activator (rt-PA). Diagnosis was established by ECG (n = 7), arterial blood gas analysis (n = 7), massive elevation of mean pulmonary arterial pressure (MPAP: 40 +/- 6 mmHg SD, n = 7), echocardiography (n = 3), increased arterial/end-tidal CO2 difference (30 +/- 16 mmHg, n = 3), and pulmonary angiography (n = 4). All patients had to be ventilated, six with an FIO2 of 1.0. To achieve a mean arterial pressure of above 60 mmHg all patients received norepinephrine 0.4 +/- 0.2 microgram.kg-1.min-1 in combination with dopamine 11 +/- 5 micrograms.kg-1.min-1 (n = 6), epinephrine 0.13 +/- 0.04 microgram.kg-1.min-1 (n = 5) or dobutamine 14 +/- 6 micrograms.kg-1.min-1 (n = 3). In addition, six of seven patients had to be resuscitated by external chest compression (duration of resuscitation: 5 to 40 min) prior to or during the thrombolytic therapy. The dosages of rt-PA ranged from 10 to 150 mg, and the duration of administration up to 31 h. Six patients survived neurologically intact. In these six patients MPAP had decreased from 41 +/- 6 mmHg to 33 +/- 6 mmHg (P less than 0.05, Wilcoxon rank test) 2 h after the start of thrombolytic therapy, with concomitant reduction of vasopressor and inotropic support.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Recombinant tissue-type plasminogen activator for the emergency treatment of perioperative life-threatening pulmonary embolism (stage IV). Results in 7 patients]. 190 1

The effect of anoxia and reoxygenation on the synthesis and secretion of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) was studied in primary cultures of human umbilical vein endothelial cells. Sublethal anoxia, determined by trypan blue dye exclusion and lactate dehydrogenase release, was produced by cell culture under a 95% N2, 5% CO2 atmosphere for 2-24 h and was followed by reoxygenation with 95% air, 5% CO2 for 24 or 48 h. Anoxia did not alter the levels of mRNA for t-PA or PAI-1 in the cells or the secretion of t-PA or PAI-1 into the medium. At 24 h, t-PA secreted into conditioned medium was 7.0 +/- 1.4 ng/2 x 10(6) cells (n = 9) and PAI-1 was 300 +/- 13 IU/2 x 10(6) cells (n = 9), whereas the content of t-PA mRNA was 2.2 pg/micrograms of RNA and PAI-1 mRNA was 180 pg/micrograms of RNA. During reoxygenation, however, t-PA antigen and PAI-1 activity as well as mRNA for PAI-1 decreased proportionally to the duration of anoxia, to reach 27 +/- 1.0, 49 +/- 2.0, and 47 +/- 14% of control values, respectively, within 24 h of anoxia. t-PA mRNA also decreased significantly during reoxygenation following anoxia, but the extent could not be accurately quantitated. Addition, during anoxia, of a 200 micrograms/ml concentration of the superoxide anion radical scavenger superoxide dismutase or of a 5 mM concentration of the iron chelator deferoxamine mesylate prevented the subsequent decrease of t-PA antigen during reoxygenation; addition of these compounds during reoxygenation had no effect. Superoxide dismutase, but not deferoxamine mesylate, when added during anoxia prevented the subsequent decrease in PAI-1 activity. These studies suggest that the marked alteration of endothelial cell fibrinolysis during anoxia followed by reoxygenation is most likely mediated by a mechanism dependent on oxygen radicals. Impaired endothelial cell fibrinolysis may contribute to the pathophysiology of ischemia/reperfusion injury.
 ...
PMID:Oxygen radicals generated during anoxia followed by reoxygenation reduce the synthesis of tissue-type plasminogen activator and plasminogen activator inhibitor-1 in human endothelial cell culture. 212 75

Activation of the plasma zymogen plasminogen to the enzyme plasmin by the early bovine embryo was evaluated. Sixteen-cell embryos to early morulae were collected at death from handmated synchronized and superovulated crossbred beef cows. Embryos were cultured in Ham's F-12 medium supplemented with 15 mg/ml bovine serum albumin containing 0, 15, 30, 60 or 120 micrograms/ml plasminogen in a humidified atmosphere of 5% CO2 in air at 37 degrees C. Cultures were observed every day, and stage of development was recorded. Medium was collected at 24-h intervals, starting at initiation and continuing through 288 h of culture. Plasminogen activator and plasmin levels in the culture media were determined, using a caseinolytic assay. The percentages of embryos developing to the initiating hatching blastocyst, hatched blastocyst, attached blastocyst, and attached blastocyst with trophoblastic outgrowth stages were not significantly different between the five levels of plasminogen. Initiation and completion of hatching, however, accelerated as plasminogen concentration increased in the culture media. Plasminogen activator production, expressed as milliunits X ml-1 X h-1 X viable embryo-1, was low for the first 48 h of culture, increased between 48-120 h, and tended to plateau thereafter. Plasminogen activation, measured indirectly as the plasmin concentration in a microdrop of medium and expressed as microgram plasmin X ml-1 X h-1 X viable embryo-1, followed plasminogen activator production, and was consistently low for the first 48-72 h of culture. Embryonic activation of plasminogen increased sharply thereafter, and also plateaued after 120 h.
 ...
PMID:Activation of plasminogen by the early bovine embryo. 295 97

Pulmonary endothelial cells and the renin-angiotensin-aldosterone (RAA) system respond to different types of injury (direct or indirect) with variations in their functions. These variations influence the regulatory mechanisms of pulmonary and systemic blood pressure, electrolyte balance and fibrinolysis. Concentration changes of some components of the RAA system and lung plasminogen activator were observed following NdYag laser application to the brain surface in rats. These changes were similar to those observed in cutaneous burn and haemorrhagic hypotension. CO2 laser application did not cause the same changes.
 ...
PMID:Brain surface exposure to CO2 and NdYag laser application: effect on pulmonary endothelium response in the rat. 303 May 14

The method and technique of organ culture of human chorionic villi was elaborated in our laboratory. In this report, placental specimens obtained at 15 to 18 weeks of gestation were studied in organ culture for 7 days in terms of the maintenance of morphological integrity and the preservation of functions. The morphological aspect of the viability of the various villous elements with special emphasis on the trophoblast cells was described histologically and ultrastructurally. The functional aspect of the viability was discussed by analysis of the suppressive effect of the cultivated villi on plasminogen activator (PA) secretion by OK-432 elicited mouse peritoneal macrophages, by analyses of the activity of delta 5-3 beta-hydroxysteroid dehydrogenase coupled with delta 5-delta 4-isomerase (HSD) and of the radioactivity of [125I]-Iododeoxyuridine ( [125I]-IUdR) retained in the DNA of the trophoblast cells. Specimens of normal placenta were obtained at the time of induced abortion. The gestational ages were 15, 16 and 18 weeks. Specimens for organ culture were prepared under sterile conditions within one hour after expulsion of the placenta. Through gross dissection, the villi were isolated and minced into fragments of approximately 1 to 2 mm3. Incubation was carried out at 37 degrees C in a conventional static chamber with a gas mixture of 95% air, 5% CO2. The culture dishes and culture media were renewed every day. Data are the mean values of the duplicate incubations. In the first series of organ culture, placental fragments were removed at the end of each day of incubation, washed thoroughly and transferred to the new dishes with a culture medium freed from fetal bovine serum, where further incubation was performed for 24 hours. After this, placental fragments were fixed in 4% neutral buffered formalin, processed through paraffin embedding, serially sectioned at 5 micron and stained by periodic-acid Schiff (PAS) procedure. Culture medium obtained in this series at each end of incubation was put into a "macrophage plate" with the addition of plasminogen in the concentration of 2 IU/m1, in which OK-432 elicited mouse peritoneal macrophages with the capacity to secrete PA were cultured. Reaction was terminated at 24 hours unless otherwise indicated. Ten microliters of the medium in the "macrophage plate" was applied to the fibrin plate, and reaction was performed for 18 hours. PA activity was expressed by plasmin activity converted from plasminogen measured by the single radial immuno-diffusion method.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Viability of human chorionic villi in organ culture]. 666 42

We investigated effects of tissue-type plasminogen activator (tPA) on regional pulmonary arterial hemodynamics in pulmonary thromboembolism (PTE) in a canine model of unilobar PTE. Ten beagle dogs were divided into two groups-tPA (n = 5) and control group (n = 5). In each dog an artificial blood circuit (ABC) consisting of a silicone tube and a cannulation-type electromagnetic blood flowmeter probe was placed at the left lower pulmonary artery. A unilobar PTE was induced by placing autologous clots into a metallic coil inside the ABC. The CO2 sampling tubes were positioned at the orifice of the left lower bronchus and the trachea, and the end-expiratory CO2 partial pressure (PET(CO2)) was measured. In the tPA group, blood flow at the left lower pulmonary artery (LL-flow) was improved to near baseline within approximately 30 min of receiving tPA, and PET(CO2) at the left lower bronchus (LL-PET(CO2)) increased in direct correlation with LL-flow. The hemodynamic improvement after tPA therapy correlated with the partial pressure of the regional pulmonary expiratory CO2. Moreover, it was suggested that changes in physiologic conditions in PTE were not determined by clot quantity alone.
 ...
PMID:Effect of tPA on regional lung perfusion in unilobar canine pulmonary thromboembolism. 937 64


1 2 3 Next >>