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)

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

Serum copper (Cu) concentration was evaluated as an index of lung injury in two rat models of pneumotoxicity: hemithoracic irradiation and monocrotaline ingestion. In both models there was a dose- and time-dependent increase in serum Cu concentration. This hypercupremia paralleled the development of pulmonary endothelial dysfunction (decreased lung plasminogen activator activity and increased prostacyclin production) and pulmonary fibrosis (hydroxyproline accumulation). In the radiation model, lung injury and hypercupremia persisted for at least 6 months, and were spared similarly when the total dose was delivered in multiple daily fractions as compared to single doses. In irradiated rats, the elevated serum Cu concentration was accompanied by increases in plasma ceruloplasmin, lung Cu concentration, and lung Cu/Zn superoxide dismutase (SOD) activity. In monocrotaline-treated rats, lung damage and hypercupremia also were accompanied by a reduction in liver Cu concentration, and by a direct correlation between the concentrations of Cu and SGOT in the serum. In both models, some but not all modifiers of lung damage (penicillamine, angiotensin converting enzyme inhibitors, pentoxifylline) also partially prevented the insult-induced hypercupremia. In contrast, serum iron concentration was largely independent of treatment in all experiments. These data suggest that elevated serum copper concentration is an accurate and minimally invasive index of lung injury in irradiated and monocrotaline-treated rats.
 ...
PMID:Serum copper concentration as an index of experimental lung injury. 251 9

Pathogenic yersiniae undergo an established low calcium response (LCR) at 37 degrees C in Ca2+-deficient media characterized by restricted growth with synthesis of Lcr plasmid-encoded virulence functions. The latter include outer membrane peptides (Yops) known to undergo Pst plasmid-mediated post-translational degradation in Yersinia pestis but not in enteropathogenic yersiniae lacking this plasmid. Salient Yops of Y. pestis are shown here to be either maintained in the steady state or to exist as a stable degradation product (p24 of Yop E). Processing of plague plasminogen activator (p36 to p33), responsible for hydrolysis of Yops, required 2 h. Avirulence of mutants with inserted Mu dl1 (Apr lac) in yopE was verified and shown to occur independently of introduced fusion-dependent peptides. However, avirulence of such yopE mutants but not that of isolates lacking the Lcr plasmid was phenotypically suppressed in mice injected with iron. Appearance of 20,500 and 40,500 Da heat-shock peptides preceded onset of the LCR. Lcr plasmid mediated V antigen (p38) and p20, Pst plasmid-encoded p36, and chromosomally promoted p56 and p70 were synthesized throughout the LCR. Classical antigen 5 was equated with p70 which was shared by Yersinia pseudotuberculosis but not Yersinia enterocolitica.
 ...
PMID:Expression of the low calcium response in Yersinia pestis. 273 60

The pyrrolizidine alkaloid monocrotaline produces pulmonary inflammation, hemorrhage, fibrosis, and hypertension. In rats, monocrotaline pneumotoxicity can be ameliorated by cotreatment with inhibitors of angiotensin converting enzyme (ACE), such as CL242817. In the present study, serum and urine copper (Cu) concentrations were evaluated as indices of cardiopulmonary injury in rats sacrificed after six weeks of continuous administration of monocrotaline (0 to 3.6 mg per kg per day, in the drinking water) or CL242817 (60 mg per kg per day, in the feed), or both. Monocrotaline-treated rats exhibited dose-dependent increases in (1) pulmonary histopathology, (2) pulmonary endothelial dysfunction (decreased lung plasminogen activator activity, and increased prostacyclin and thromboxane production), (3) pulmonary hydroxyproline (collagen) content, and (4) cardiac right ventricular hypertrophy (an anatomic correlate of pulmonary hypertension). The severity of cardiopulmonary damage was accompanied by a dose-dependent elevation in serum Cu concentration. Serum iron concentration, in contrast, did not change. Urinary Cu concentration correlated roughly with that of serum, but the variability within groups was high. Cotreatment with the ACE inhibitor CL242817 not only ameliorated monocrotaline-induced right heart enlargement and lung hydroxyproline accumulation but also reduced the hypercupremia in monocrotaline-treated rats. Thus, serum copper concentration appears to be an accurate and minimally invasive index of monocrotaline pneumotoxicity in this model of pulmonary hypertension.
 ...
PMID:Serum copper concentration as an index of cardiopulmonary injury in monocrotaline-treated rats. 314 70

A plasminogen activator of human origin, urokinase, was endowed with magnetic property. The magnetic urokinase was composed of magnetite, polyethylene glycol derivative and urokinase, and dispersed in saline. Its particle size of magnetite was approximately 30-60 nm. It was selectively delivered to fibrin clot by magnetic force in continuously circulating plasma and exerted fibrinolytic activity without degrading fibrinogen.
 ...
PMID:Magnetic urokinase: targeting of urokinase to fibrin clot. 336 51

Mammalian conceptuses must provide a chemical signal to the maternal system to insure maintenance of corpus luteum (CL) function and of progesterone production and continuation of uterine endometrial secretory activity. These events insure that the developing conceptus is provided with appropriate nutrients, regulatory enzymes and endocrine state to allow successful establishment and maintenance of pregnancy. Pig blastocysts begin to produce estrogens by Day 11 of pregnancy, which prevents secretion of the uterine luteolytic factor (PGF2 alpha) in an endocrine direction, but allows secretion in an exocrine direction, i.e., into the uterine lumen. Therefore, CL are "protected." Blastocyst estrogens also trigger secretion of a group of proteins, including uteroferrin, an iron transport protein, and a family of protease inhibitors whose biosynthesis within the uterine glandular epithelium is under the control of progesterone. Estrogen also appears to promote accumulation of glucose and fructose within the uterine lumen. A complex in vivo "culture medium" is thereby established to promote conceptus development. Pig blastocysts do not undergo invasive implantation within the uterine lumen although they produce the protease, plasminogen activator. Invasion may be prevented by endometrial secretion of progesterone-induced protease inhibitors which are produced in large amounts. In addition to estrogens of conceptus origin, calcium and prostaglandins PGF2 alpha and E2 may affect the uterine vasculature, water and electrolyte transport, capillary permeability, conceptus steroid production, and related events during pregnancy. The blastocysts of the large domestic animals also secrete proteins which include a large glycoprotein (Mr approximately 600,000) and a small acidic protein (Mr approximately 17,000). The latter has been purified from sheep and named ovine trophoblast protein I. These proteins may play unique roles in early pregnancy with respect to establishment and maintenance of pregnancy in the ewe, sow, mare, and cow.
 ...
PMID:Biochemical aspects of conceptus--endometrial interactions. 636 10

High energy beta-emitting radioisotopes like Yttrium-90 have a radiotoxic range of about one centimeter. For cancer treatment they must be brought near the tumor cells and kept there for as long as they are radioactive. We developed as carriers for the ionic form of 90Y a matrix-type polymeric drug delivery system, poly(lactic acid) (PLA) microspheres. This radiopharmaceutical could be selectively delivered to the target site after incorporating 10% Fe3O4 (magnetite) which made the magnetic microspheres (MMS) responsive to an external magnetic field. Furthermore, MMS are biodegradable and slowly hydrolyze into physiologic lactic acid after the radioactivity is completely decayed. Previously prepared 10-40 microns MMS were radiochemically loaded to high specific activity with 90Y at a pH of 5.7. Stability studies showed that approximately 95% of added 90Y is retained within the PLA matrix after 28 days (> 10 half-lives) at 37 degrees C in serum, and electron microscopy showed that the microspheres retained their characteristic morphologic appearance for the same time period. Cytotoxicity studies with SK-N-SH neuroblastoma cells growing in monolayer showed that the radiocytotoxicity of the microspheres could be directed magnetically to either kill or spare specific cell populations, thus making them of great interest for targeted intracavitary tumor therapy. We are currently optimizing this system for use in the treatment of neoplastic meningitis.
 ...
PMID:Magnetically directed poly(lactic acid) 90Y-microspheres: novel agents for targeted intracavitary radiotherapy. 798 88

The effects of several chelators, including hinokitiol, on embryonal carcinoma F9 cell differentiation were assessed by assaying the production of plasminogen activator (PA) as a differentiation marker protein. Hinokitiol and tropolone which were potent differentiation inducers lost their activity following preincubation with Fe2+ and Fe3+ ions. Other metal ions had no or little effect on the hinokitiol-induced differentiation. Of several chelators examined, dithizone induced differentiation as effectively as did hinokitiol and tropolone. Dithizone-induced differentiation was also inhibited by preincubation with Fe3+ ions. It was concluded that some potent iron chelators could trigger the teratocarcinoma F9 cells to differentiate through the chelation with intracellular iron ions.
 ...
PMID:Induction of differentiation of embryonal carcinoma F9 cells by iron chelators. 874 90

The authors report on a 33-year old woman with massive, life-threatening pulmonary embolism at the third trimester of pregnancy. The diagnosis was rapidly accomplished in the Emergency Department by two dimensional-Doppler echocardiography that showed signs of pulmonary hypertension as well as a large, floating thromboembolus in the right atrium. As the hemodynamic deterioration persisted after treatment with iv heparin, the patient received alteplase 50 mg as a bolus over 5 minutes. About 30 minutes later, a further 50 mg infusion of alteplase was given over 60 minutes because clinical conditions were progressively worsening. After an alteplase dose of 75 mg, the woman showed a definite improvement in clinical-hemodynamic status and echocardiography documented a reduction of right ventricular overload and atrial clot disappearance. Two hours later the patient was submitted to cesarean section, because of the onset of uterine contractions, and delivered a vital baby. The occurrence of uterine bleeding was antagonized by the infusion of fresh-frozen plasma and a moderate anemia was subsequently treated with iron preparations. The mother and her baby were discharged on 16th day in fairly good general conditions. The authors emphasize the leading role of early echocardiography in the clinical decision making and the lifesaving potential of full dose thrombolytic therapy without serious adverse effects.
 ...
PMID:[Massive pulmonary embolism during the third trimester of pregnancy: effectiveness of thrombolytic treatment with alteplase]. 924 13

Hypoxia underlies a number of biologic processes in which cellular migration and invasion occur. Because earlier studies have shown that the receptor for urokinase-type plasminogen activator (uPAR) may facilitate such events, we studied the effect of hypoxia on the expression of uPAR by first trimester human trophoblasts (HTR-8/SVneo) and human umbilical vein endothelial cells (HUVEC). Compared with control cells cultured under standard conditions (20% O2), HTR-8/SVneo cells and HUVEC cultured in 1% O2 expressed more uPAR, as determined by flow cytometric and [125I]-prourokinase ligand binding analyses. Increased uPAR expression paralleled increases in uPAR mRNA. The involvement of a heme protein in the hypoxia-induced expression of uPAR was suggested by the observations that culture of cells with cobalt chloride, or sodium 4, 5-dihydroxybenzene-1,3-disulfonate (Tiron), an iron-chelating agent, also stimulated uPAR expression, and that the hypoxia-induced uPAR expression was inhibited by adding carbon monoxide to the hypoxic atmosphere. Culture of HTR-8/SVneo cells with vascular endothelial growth factor (VEGF) did not increase uPAR mRNA levels, suggesting that the hypoxia-mediated effect on uPAR expression by these cells did not occur through a VEGF-dependent mechanism. The functional importance of these findings is suggested by the fact that HTR-8/SVneo cells cultured under hypoxia displayed higher levels of cell surface plasminogen activator activity and greater invasion through a reconstituted basement membrane. These results suggest that hypoxia may promote cellular invasion by stimulating the expression of uPAR through a heme protein-dependent pathway.
 ...
PMID:Hypoxia stimulates urokinase receptor expression through a heme protein-dependent pathway. 955 86


1 2 3 4 5 6 7 8 9 Next >>