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)

The comparison of activator activity of blood, urine and pleural fluid in 55 patients suffering from chronic circulatory insufficiency, tuberculosis, pneumonia and lung cancer helped to determine pathognomonic signs for each of the exudates examined. Cardiac decompensation is associated with high activity of plasminogen activator in the transudate against low activator activity of the blood and urine. In tuberculous pleuritis there is low activator activity of the exudate in normal blood and urine parameters. Reduced activator activity of the blood, urine and pleural fluid is characteristic of parapneumonic pleuritis, while high activity of plasminogen activator in the blood and pleural exudate in its normal activity in the urine is seen in cancer pleuritis. The findings obtained can be used in clinical medicine for verification of pleural fluid nature.
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PMID:[Assessment of the activity of plasminogen activators in the differential diagnosis of pleural effusion]. 178 78

This study was designed to evaluate major fibrinolytic parameters in relation to parameters of inflammation associated with different kinds of pleural effusion. Sixty patients with pleural effusion were studied. The underlying aetiology was empyema in 10 cases, tuberculosis in 9, cancer in 31, cardiac failure in 7, and undetermined in 3. Plasminogen, plasminogen activator inhibitor 1 (PAI-1) and 2 (PAI-2), tissue type plasminogen activator (t-PA), urokinase (u-PA) and D-dimers (D-D) were quantified in plasma samples and pleural effusion specimens. These data were then correlated with inflammatory or infectious parameters, i.e. fibrinogen, von Willebrand factor (vWF), erythrocyte sedimentation rate (ESR), protein concentration, and white blood cell count. D-D levels were higher in pleural fluid than in plasma. D-D levels were not correlated with either plasminogen activator or plasminogen activator inhibitor levels, suggesting the presence of other fibrinolytic pathways. PAI levels (PAI activity, PAI-1 antigenicity, PAI-2 antigenicity) and vWF levels were significantly higher in patients with tuberculosis and empyema than in patients with cancer or cardiac failure. Regression analysis between inflammatory and fibrinolytic parameters showed that pleural PAI levels were significantly correlated with pleural neutrophil count, vWF levels, and plasma fibrinogen levels. D-D levels were correlated with blood ESR. No significant difference in pleural t-PA, u-PA and D-D levels was observed between aetiologies. The highest pleural t-PA and u-PA values were noted in patients with cancer, especially lymphoma. Plasma t-PA levels were higher inpatients with pleural effusion secondary to congestive heart failure, but this difference did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fibrinolytic and inflammatory processes in pleural effusions. 748 3

Functional interrelations between immune and fibrinolytic systems were studied in 107 patients with disseminated tuberculosis patients. The findings showed a depression in plasminogen activator activity associated with high yield of fibrin degradation products. Lymphocyte blast transformation with PHA decreased, whereas that with PPD increased. Concentrations of IgA and IgG rose in a small drop of IgM in peripheral blood. The above changes were more pronounced in marked clinical symptoms. The results may give rise to further developments in pathogenetic mechanisms of pulmonary tuberculosis and new approaches to its treatment.
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PMID:[Immune reactivity and fibrinolysis in patients with disseminated pulmonary tuberculosis]. 832 38

Microspheres prepared from synthetic, biodegradable poly (L-lactide) [PLA] and copolymers of lactide and glycolide such as poly (DL lactide co-glycolide) [PLG] have been widely investigated for controlled delivery of encapsulated vaccine antigens. In this study we describe novel lamellar microparticles produced from PLA to which protein antigens can be adsorbed. These particles when administered to mice, induced strong Th1-type T cell responses to the adsorbed 38 kDa protein antigen from M. tuberculosis characterised by high levels of Interferon-gamma. In addition to proteins, we were also able to adsorb synthetic peptides resulting in specific T cell proliferation. Induction of strong cellular immunity together with the versatility of antigen adsorption to these particles should make such lamellae a useful tool to deliver protective antigens from intracellular pathogens.
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PMID:Induction of cellular immunity to a mycobacterial antigen adsorbed on lamellar particles of lactide polymers. 1021 78

ESAT-6 from Mycobacterium tuberculosis is an important T-cell antigen for cell-mediated immunity in the early phase of tuberculosis infection. Since the lung is the organ in which infection is initiated, immune responses in the lung play a significant role in restricting the initial infection with M. tuberculosis. The aim of the present study was to assess whether efficient cell-mediated immune responses in the lung and draining mediastinal lymph nodes could be stimulated by pulmonary administration of ESAT-6 encapsulated in poly(lactide) (PLA) microspheres. BALB/c mice were immunised intranasally on days 1, 28 and 56 with 2 microg microencapsulated ESAT-6. Cellular responses in the lungs, spleen and mediastinal lymph nodes (MLN) were characterised using ELISPOT and proliferation assays. Fluorescence activated cell sorting (FACS) was used to assess the expression of CD44 on CD4+ and CD8+ cells derived from the MLN of immunised animals. For comparison, groups of mice were immunised intranasally with soluble 'free' ESAT-6 or intramuscularly with ESAT-6 in Alhydrogel. Intranasal instillation of microencapsulated ESAT-6 induced greatest numbers of ESAT-6 specific IFN-gamma and IL-4 secreting cells in the lung and MLN (P<0.05). Similarly, ESAT-6 specific recall responses were strongest following intranasal immunisation of mice with microsphere encapsulated antigen (P<0.05). FACS demonstrated a higher proportion of T cells expressing CD44 in the MLN from mice immunised intranasally with microencapsulated ESAT-6. These data support the notion that the immune system is compartmentalised and responses are often strongest in compartments proximal to the site of vaccine application. Furthermore, our data indicate that, for efficient activation of cell-mediated responses, antigens must be presented to the immune system in an appropriate formulation.
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PMID:Mucosal delivery of microparticle encapsulated ESAT-6 induces robust cell-mediated responses in the lung milieu. 1586 35

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

We describe mycobacterial phospholipase A activity (MPLA) and, using reverse genetics, have associated this activity with putative mycobacterial cutinase. PLAs, which hydrolyze fatty acids on phospholipids, play a significant role in human inflammatory states and disease pathogenesis. In prokaryotes, the recognition of their role in virulence is more recent. Cutinases are serine esterases whose primary substrate is cutin, the waxy exterior layer of plants. Mycobacterium tuberculosis has maintained seven putative cutinases, though it should not encounter cutin; we demonstrate that known cutinases and MPLA cleave phospholipids in a PLA-type manner and also hydrolyze Tween. We analyzed cutinase motifs in mycobacteria and found the motif very prevalent. All mycobacteria tested had MPLA activity. These studies suggest an alternative use for putative cutinases by the M. tuberculosis group that is likely related to MPLA activity and lipid metabolism.
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PMID:Purification and characterization of mycobacterial phospholipase A: an activity associated with mycobacterial cutinase. 1741 58

Microparticles containing large payloads of two anti-tuberculosis (TB) drugs were prepared and evaluated for suitability as a dry powder inhalation targeting alveolar macrophages. A solution containing one part each of isoniazid and rifabutin, plus two parts poly(lactic acid) (L-PLA) was spray-dried. Drug content and in vitro release were assayed by HPLC, and DSC was used to elucidate release behaviour. Particle size was measured by laser scattering and aerosol characteristics by cascade impaction using a Lovelace impactor. Microparticles were administered to mice using an in-house inhalation apparatus or by intra-tracheal instillation. Drugs in solution were administered orally and by intra-cardiac injection. Flow cytometry and HPLC were used to investigate the specificity and magnitude of targeting macrophages. Microparticles having drug content approximately 50% (w/w), particle size approximately 5 microm and satisfactory aerosol characteristics (median mass aerodynamic diameter, MMAD=3.57 microm; geometric standard deviation, GSD=1.41 microm; fine particle fraction, FPF(<4.6 microm)=78.91+/-8.4%) were obtained in yields of >60%. About 70% of the payload was released in vitro in 10 days. Microparticles targeted macrophages and not epithelial cells on inhalation. Drug concentrations in macrophages were approximately 20 times higher when microparticles were inhaled rather than drug solutions administered. Microparticles were thus deemed suitable for enhanced targeted drug delivery to lung macrophages.
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PMID:Inhalable microparticles containing large payload of anti-tuberculosis drugs. 1768 58

The title compounds have been synthesized and tested for structure activity relationship for Phospholipase A2 (PLA2) [E.C. 3.1.1.4] enzyme inhibition. The in vitro anti-tubercular, PLA(2) enzyme inhibitory activities of azetidin-2-one derivatives and in vivo anti-inflammatory studies using mice are highlighted. The analogues of azetidin-2-one were prepared based on the initial activity against Mycobacterium tuberculosis (Mtb). Certain azetidin-2-one analogues described herein showed moderate to good anti-tubercular activity. In particular, two compounds (4f) and (4g) exhibited MIC values of 1.56 and 0.78 microg/mL respectively against the Mtb H(37)Rv strain. Chloro substitution on aryloxy acid apparently enhanced the antimycobacterial activity and also PLA2 inhibition in the azetidin-2-one series described herein. The ability of azetidin-2-one analogues as anti-inflammatory agents has also been determined. The results show some correlation between anti-inflammatory, anti-tubercular activity and expression of PLA2 enzyme.
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PMID:Anti-tubercular and anti-inflammatory activities of azetidin-2-one derivatives and their effects on the activity of Phospholipase A2. 1833 38

In previous studies, we have shown that reactive oxygen species (ROS)-mediated inflammatory signaling is essential for microglial proinflammatory responses to Mycobacterium tuberculosis (Mtb). To further investigate the molecular mechanisms governing these processes, we sought to describe the role of phospholipase A(2) (PLA(2)) in Mtb-induced ROS generation and inflammatory mediator release by microglia. Inhibition of secretory PLA(2) (sPLA(2)), but not cytosolic PLA(2) (cPLA(2)), profoundly abrogated Mtb-mediated ROS release, the generation of various inflammatory mediators (tumor necrosis factor, interleukin-6, cyclooxygenase-2, inducible nitric oxide synthase, and matrix metalloproteinase-2 and -9), and the activation of nuclear factor (NF)-kappaB and MAPKs (ERK1/2, p38, and JNK/SAPK) by murine microglial BV-2 cells or primary mixed glial cells. Interruption of the Ras/Raf-1/MEK1/ERK1/2 pathway abolished Mtb-induced sPLA(2) activity, whereas the blockage of JNK/SAPK or p38 activity had no effect. Specific inhibition of sPLA(2), but not cPLA(2), suppressed the upregulation of ERK1/2 phosphorylation by Mtb stimulation, suggesting the existence of a mutual dependency between the ERK1/2 and sPLA(2) pathways. Moreover, examination of the protein kinase C (PKC) family revealed that classical PKCs are involved in Mtb-induced sPLA(2) activation by microglia. Taken together, our results demonstrate for the first time that sPLA(2), either through pathways comprising Ras/Raf-1/MEK1/ERK1/2 or the classical PKC family, plays an essential role in Mtb-mediated ROS generation and inflammatory mediator release by microglial cells.
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PMID:Secretory phospholipase A2 plays an essential role in microglial inflammatory responses to Mycobacterium tuberculosis. 1911 85


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