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)

Plasminogen activator inhibitor-1 (PAI-1) is a serpin that suppresses fibrinolysis by inhibiting the activity of plasminogen activator (PA). Together with PA, PAI-1 is expressed in the central nervous system and may play a role in the regulation of PA activity. Our present study has demonstrated that, in cultures of PC-12 neurons, depletion of PAI-1 from the culture medium induces disappearance of the cell's neurites and the cell death. Aprotinin and antipain, the inhibitors of PA, were not counterparts of PAI-1 in the protection of neurite disappearance. We also found that PAI-1 had the abilities to promote release of the survival factors of neurons, IL-6 and VEGF and activation of a survival serine/threonine kinase Akt. These results suggest that PAI-1 has physiological functions other than its role as PA inhibitor for the survival of neurons.
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PMID:[A novel function of anti-fibrinolytic factor, PAI-1, in the central nervous system: a possible role as the neurotrophic factor]. 1249 82

We measured the plasma level of fibrinogen in 560 patients with disseminated intravascular coagulation (DIC) and evaluated its relationship with outcome and with other hemostatic markers. Forty-seven percent of patients had >200 mg/dL of plasma fibrinogen and 24% had <100 mg/dl of plasma fibrinogen, suggesting that plasma fibrinogen level is not a sensitive marker for DIC. In our analysis of outcome and plasma fibrinogen levels, the rate of death was high in leukemia/lymphoma patients with high fibrinogen concentration, but no significant difference in outcome was observed in relation to plasma fibrinogen concentration in non-leukemia/lymphoma patients with DIC. Among patients with leukemia/lymphoma, the frequency of organ failure was markedly high in patients with high plasma levels of fibrinogen. Among patients without leukemia/lymphoma, the frequency of organ failure increased concomitantly with the increase in plasma fibrinogen levels. The international normalized ratio was significantly increased in leukemia/lymphoma patients with low fibrinogen. FDP levels were slightly increased in patients with low fibrinogen. Platelet count was significantly low in patients without leukemia/lymphoma with high fibrinogen. DIC score increased concomitantly with the reduction in plasma fibrinogen levels. Plasma levels of thrombomodulin and tissue factor were significantly high in patients with high fibrinogen levels. Plasma levels of antiplasmin and plasminogen were significantly decreased in patients with low fibrinogen. Plasma levels of plasmin plasmin-inhibitor complex and tissue type plasminogen activator/plasminogen activator inhibitor-1 complex (PAI-I) were significantly higher in patients with low fibrinogen than in those with high fibrinogen. Plasma levels of PAI-I and IL-6 were significantly higher in patients with high fibrinogen than in those with low fibrinogen. Patients with high fibrinogen levels showed less activation of secondary fibrinolysis, which might explain the occurrence of organ failure and poor outcome.
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PMID:High plasma fibrinogen level is associated with poor clinical outcome in DIC patients. 1250 60

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has been identified as a coronary heart disease (CHD) risk predictor. Both its anti-inflammatory role by hydrolysing platelet activating factor, and pro-inflammatory generation of atherogenic mediators may influence CHD risk. We investigated the association of the activity-reducing A379V variant with risk of myocardial infarction (MI) in a large European case-control study, which compared 527 post-MI men with 566 age-matched controls from north and south Europe. Overall, the frequency of the V379 allele was 0.24 (95%CI 0.21-0.26), with no evidence for differences between centres. Homozygosity for the V379 allele was associated with lower risk of MI, (Odds Ratio (OR) 0.56, 95%CI 0.32-0.98), maintained after adjustment for lifestyle factors and levels of inflammatory risk factors (C-reactive protein, fibrinogen, IL-6) (OR 0.46, 0.22-0.93). There was no evidence of heterogeneity of effect between the centres in the north and south of Europe (P-value for interaction=0.80). Since homozygosity for V379 occurs in only 5-6% of subjects, this genotype is not a major determinant of population genetic risk of CHD, but the association of this genotype with low levels of Lp-PLA(2), strongly support the pro-inflammatory causative, and not consequential, role of Lp-PLA(2) in CHD.
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PMID:Association between the Ala379Val variant of the lipoprotein associated phospholipase A2 and risk of myocardial infarction in the north and south of Europe. 1280 11

Thrombolytic therapy not always improves clinical outcome in ischemic stroke patients. This could cause lymphomonocyte accumulation in the infarcted brain area. These produce an excessive amount of proinflammatory cytokines, such as IL-1 beta, IL-6 and TNF-alfa. The aim of our study was to determine ILs levels in fibrinolytic therapy treated patients, compared with healthy controls and to evaluate if the varying levels can predictors of neurological outcome. Eighteen patients underwent thrombolytic treatment with t-PA within 3 h. Plasma levels of IL-1 beta, IL-6, TNF-alfa and IL-10 were determined by ELISA method before and within 24 h after t-PA infusion and compared with controls. Significantly higher levels of IL-1 beta and Il-6 emerged in stroke patients before treatment compared with the control group (P < 0.05 and 0.04, respectively). Slightly higher plasma levels of TNF-alfa and lower plasma levels of IL-10 were also found at base line in stroke patients. After thrombolytic treatment no significant variations were observed in the levels of TNF-alfa and IL-6, whereas a trend toward lower values for IL-1 beta and higher levels for IL-10 was observed. Positive correlations among the values of IL-6, TNF-alfa and National Institute of Health Stroke Scale (NIHSS) at discharges were observed. A similar correlation with modified Rankin scale score at 3 month was found. Pre-treatment cytokine status seems to influence pre-and long-term clinical outcome. Therefore an investigation into the possible predictor of cytokines seem worthy.
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PMID:Different cytokine levels in thrombolysis patients as predictors for clinical outcome. 1517 33

C-reactive protein remains the single standard biochemical marker for predicting the severity of AP. Because the combination of clinical-physiological scores and CRP provide good information at 48 hours, research has focused on the predictive ability of various markers when applied in the initial 24 hours after admission to the hospital. After detailed review of the literature, the authors conclude that there is no single tool that serves as the optimal predictor of severity. There are, however, data that support the use of certain tests to improve upon the clinician's early predictive ability on the subsequent course of AP. These include an APACHE II score greater than 7 and IL-6 at the time of admission, and urine TAP, urine trypsinogen-2, and serum PMN elastase at 24 hours (Table 4). These markers only will be able to help the clinician's predictive ability if they can be performed locally and if the results can be available ina timely manner. Future research should focus on promising markers such as procalcitonin, IL-8, IL-I ra, sTNFR, CAPAP, PLA-2, novel markers, and the combined use of more than one marker. The conventional research approach in predicting severity used in the last 15 years has limitations and appears to have reached its maximal potential. Novel conceptions and approaches, such as identification of genetic polymorphisms that predispose to severe course and complications of AP or other approaches are needed for a quantum step forward.
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PMID:Predictors of severity and necrosis in acute pancreatitis. 1552 23

Poly(lactide-co-glycolide) (PLGA), a biocompatible and biodegradable polyester co-polymer of PLA and PGA, has been recognized for its ability to deliver genes. However, gene delivery by PLGA nanoparticles is limited by their negative charge and their poor transport through mucosal barriers. In this study, PLGA nanoparticles were surface modified with cationic chitosan in an effort to improve their gene delivery capability. PLGA nanoparticles were synthesized by emulsion-diffusion-evaporation technique using PVA-chitosan (PLGA1) or PVA-chitosan-PEG (PLGA2) blend as stabilizers. This method is reproducible and produces nanoparticles with hydrodynamic diameter <200 nm. The nanoparticles were characterized by zetasizer, photon correlation spectroscopy and atomic force microscopy. A549 epithelial cells were transfected in vitro with PLGA particles complexed with a reporter plasmid encoding green fluorescent protein. PLGA particles transferred EGFP gene, but were less efficient than the lipofectamine control. The nanoparticles were also tested for their ability to transport across the nasal mucosa in vivo in mice. The results show that both PLGA1 and PLGA2 facilitate gene delivery and expression in vivo with increased efficiency and without causing inflammation, as measured by IL-6. Together, these results indicate that chitosan-modified PLGA nanoparticles have greater potential as gene carriers.
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PMID:Cationic poly(lactide-co-glycolide) nanoparticles as efficient in vivo gene transfection agents. 1565 92

To date, CRP remains the single standard biochemical marker for predicting the severity of AP. Because the combination of clinico-physiological scores and CRP provides good information at 48 hours, research has focused on the predictive ability of various markers when applied in the initial 24 hours after admission to the hospital. After detailed review of the literature, the authors conclude that there is no single tool that serves as the optimal predictor of severity. There are, however, data supporting the use of certain tests to improve upon the clinician's early predictive ability on the subsequent course of AP. These include an APACHE II score greater than seven, IL-6 at the time of admission, and urine TAP, urine trypsinogen-2,and serum PMN-elastase at 24 hours (Box 1). These markers will only be able to help the clinician's predictive ability if they can be performed locally and if the results can be available in a timely manner. Future research should focus on markers such as procalcitonin, IL-8, IL-I ra, sTNFR,CAPAP, PLA-2, novel markers, and the combined use of more than one marker. The conventional research approach in predicting severity used in the last15 years has limitations and appears to have reached its maximal potential. Novel conceptions and approaches, such as identification of genetic polymorphisms that predispose to severe course and complications of AP, are needed for a quantum step forward.
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PMID:Inflammatory markers of disease severity in acute pancreatitis. 1574 30

Tuberculous (TB) pleurisy and parapneumonic effusion (PPE) are common causes of pleural fibrosis. The mechanisms underlying fibrin deposition may be different since involved inflammatory cells are distinct. In this study, we measured various cytokines and fibrinolytic enzymes and compared the differences between the two effusions. PPE was further divided into noncomplicated PPE and complicated PPE/empyema subgroups. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-8, macrophage inflammatory protein (MIP)-1beta, monocyte chemoattractant protein (MCP)-1, plasminogen activator inhibitor type 1 (PAI-1) and tissue type plasminogen activator (tPA) were measured using enzyme-linked immunosorbent assays. Significantly higher values of PAI-1, PAI-1/tPA ratio, IL-1beta, IL-8 and MIP-1beta and significantly lower values of TNF-alpha, IL-6 and MCP-1 were observed in PPE/empyema than in TB effusions. Compared to noncomplicated PPE, complicated PPE/empyema had significantly higher levels of TNF-alpha, IL-1beta, IL-8 and MIP-1beta. TB pleurisy patients who had higher effusion levels of TNF-alpha, IL-1beta and IL-8 were predisposing to residual pleural thickening. The underlying mechanisms of fibrin formation and deposition between the two effusions studied (PPE/empyema and TB pleurisy) could not be fully explained by the results of the present study. More studies are needed to explore this further.
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PMID:Cytokines and fibrinolytic enzymes in tuberculous and parapneumonic effusions. 1589 10

Phospholipid-derived mediators, inflammatory cytokines and extracellular matrix remodelling enzymes are all involved in the initiation of human labour and delivery. We have previously demonstrated that natural and synthetic PPAR-gamma ligands regulate LPS-stimulated pro-inflammatory cytokine release from human gestational tissues, however, the effect of these ligands on the basal and/or LPS-induced expression of prostaglandins and proteases is not known. Therefore, the aim of this study was to determine the effects of 15d-PGJ(2) and troglitazone on the expression of basal and LPS-stimulated inflammatory mediators in human gestational tissues. Human placenta, amnion and choriodecidua (n=5) were incubated in the presence or absence of 15 microM 15d-PGJ(2) and 30 microM troglitazone under basal and LPS-stimulated (10 microg/ml) conditions. Treatment of placenta, amnion and choriodecidua with both 15d-PGJ(2) and troglitazone decreased basal and LPS-stimulated IL-1beta, IL-6, IL-10 and TNF-alpha release. Basal type II PLA(2) release from placental tissues was also significantly decreased by 15d-PGJ(2) and troglitazone. There was no effects of 15d-PGJ(2) and troglitazone on cPLA(2) protein expression. Both 15d-PGJ(2) and troglitazone significantly decreased basal and LPS-stimulated PGE(2) and PGF(2alpha) release from placenta and amnion. However, in choriodecidua, although 15d-PGJ(2) decreased basal and/or LPS-stimulated PGE(2) and PGF(2alpha) release, there was an increase in PGE(2) and PGF(2alpha) release in the presence of troglitazone. 15d-PGJ(2) and troglitazone inhibited MMP-9 release from human amnion. NF-kappaB DNA binding activity and NF-kappaB p65 protein expression was inhibited by treatment with 15d-PGJ(2) in human amnion. There was no effect of 15d-PGJ(2) or troglitazone on PPAR-gamma protein, and GW9662 failed to alleviate 15d-PGJ(2) and troglitazone inhibition of IL-6 and TNF-alpha release in placenta, amnion and choriodecidua. The data demonstrated in this study suggest that the 15d-PGJ(2) and troglitazone exhibit anti-inflammatory properties in human gestational tissues via PPAR-gamma independent actions.
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PMID:15-Deoxy-Delta(12,14)-prostaglandin J(2) and troglitazone regulation of the release of phospholipid metabolites, inflammatory cytokines and proteases from human gestational tissues. 1643 95

Group IIA phospholipase A(2) (PLA(2)) are major components in Viperidae/Crotalidae venom. In the present study, a novel PLA(2) named promutoxin with Arg at the site 49 has been purified from the venom of Protobothrops mucrosquamatus by chromatography. It consists of 122 amino acid residues with a molecular mass of 13,656 Da assessed by MALDI-TOF. It has the structural features of snake venom group IIA PLA(2)s, but has no PLA(2) enzymatic activity. Promutoxin shows higher amino acid sequence identity to the K49 PLA(2)s (72-95%) than to D49 PLA(2)s (52-58%). Promutoxin exhibits potent myotoxicity in the animal model with as little as 1 microg of promutoxin causing myonecrosis and myoedema in the gastrocnemius muscle of mice. Promutoxin is also able to stimulate the release of IL-12, TNFalpha, IL-6 and IL-1beta from human monocytes, and induce IL-2, TNFalpha and IL-6 release from T cells, indicating that this snake venom group IIA PLA(2) is actively involved in the inflammatory process in man caused by snake venom poisoning.
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PMID:Purification, characterization and cytokine release function of a novel Arg-49 phospholipase A(2) from the venom of Protobothrops mucrosquamatus. 1679 92


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