Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in the alveolar hemostatic balance in severe pneumonia were compared with those in the acute respiratory distress syndrome (ARDS). Analysis was performed in bronchoalveolar lavage fluids (BALF) of patients with ARDS triggered by nonpulmonary underlying events in the absence of lung infection (ARDS; n = 25), pneumonia demanding mechanical ventilation (PNEU-vent; n = 114), spontaneously breathing patients with pneumonia (PNEU-spon; n = 40), and ARDS in combination with lung infection (ARDS+PNEU; n = 43); comparison with healthy control subjects (n = 35) was performed. In all groups of patients, BALF total procoagulant activity was increased by nearly two orders of magnitude, being largely attributable to the tissue factor pathway of coagulation. Concomitantly, markedly reduced overall fibrinolytic capacity (fibrin plate assay) was noted in the lavage fluids of all patients. BALF levels of urokinase-type plasminogen activator were significantly reduced throughout, whereas the lavage concentrations of tissue-type plasminogen activator did not differ from those in control subjects. In addition, markedly enhanced levels of plasminogen activator- inhibitor I and alpha(2)-antiplasmin were noted in ARDS, ARDS+PNEU, and PNEU-vent, but not in PNEU-spon. In all groups of patients, the changes in the lavage enzymatic activities were paralleled by manifold increased BALF concentrations of fibrinopeptide A and D-dimer, reflecting in vivo coagulation processes. Within the overall number of patients with pneumonia, changes in the alveolar hemostatic balance were more prominent in alveolar and interstitial pneumonia than in bronchopneumonia. Acute inflammatory lung injury, whether triggered by nonpulmonary systemic events or primary lung infection, is thus consistently characterized by both enhanced procoagulant and depressed fibrinolytic activities in the alveolar lining layer, with the appearance of fibrin formation in this compartment. Profile and extent of changes in severe pneumonia demanding respirator therapy are virtually identical to those in ARDS, whereas somewhat less prominent alterations of the alveolar hemostatic balance are noted in spontaneously breathing patients with pneumonia.
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PMID:Alveolar fibrin formation caused by enhanced procoagulant and depressed fibrinolytic capacities in severe pneumonia. Comparison with the acute respiratory distress syndrome. 1067 85

Leukocytes express both urokinase-type plasminogen activator (uPA) and the urokinase receptor (uPAR, CD87). Evidence in vitro has implicated uPAR as a modulator of beta2 integrin function, particularly CR3 (CD11b/CD18, Mac-1). Pseudomonas aeruginosa infection has been demonstrated to recruit neutrophils to the pulmonary parenchyma by a beta2 integrin-dependent mechanism. We demonstrate that mice deficient in uPAR (uPAR-/-) have profoundly diminished neutrophil recruitment in response to P. aeruginosa pneumonia compared with wild-type (WT) mice. The requirement for uPAR in neutrophil recruitment is independent of the serine protease uPA, as neutrophil recruitment in uPA-/- mice is indistinguishable from recruitment in WT mice. uPAR-/- mice have impaired clearance of P. aeruginosa compared with WT mice, as demonstrated by CFU and comparative histology. WT mice have diminished neutrophil recruitment to the lung when an anti-CD11b mAb is given before inoculation with the pathogen, while recruitment of uPAR-/- neutrophils is unaffected. We conclude that uPAR is required for the recruitment of neutrophils to the lung in response to P. aeruginosa pneumonia and that this requirement is independent of uPA. Further, we show that uPAR and CR3 act by a common mechanism during neutrophil recruitment to the lung in response to P. aeruginosa. This is the first report of a requirement for uPAR during cellular recruitment in vivo against a clinically relevant pathogen.
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PMID:Urokinase receptor-deficient mice have impaired neutrophil recruitment in response to pulmonary Pseudomonas aeruginosa infection. 1090 58

Several studies have indicated that the serine protease urokinase-plasminogen-activator (uPA) is an important factor in host defense against pulmonary pathogens. To gain a better insight into the role of uPA in Pneumocystis carinii (P. carinii) pneumonia (PCP), we evaluated PA production in alveolar macrophages (AMs) obtained from rats with steroid-induced PCP. Treatment with cortisone acetate favored PCP in 91% of rats. In the bronchoalveolar lavage (BAL) samples of immunosuppressed rats both with and without PCP, we observed a decrease in uPA activity as well as a decrease in cell number. Urokinase-PA production by AMs was reduced in rats treated with cortisone alone. However, an increase in cell-associated uPA was observed in rats with PCP. This increase appears to be produced in response to P carinii infection. In fact, when AMs obtained from untreated healthy or immunosuppressed uninfected rats were challenged with P carinii, a significant increase in PA activity in cell lysates was observed, though a lower response was obtained in cortisone-treated animals. Our results suggest that healthy AMs respond to the presence of P carinii with an increase in uPA production and that this response in immunodepressed rat-AMs is partially impaired.
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PMID:Plasminogen activator production in a rat model of Pneumocystis carinii pneumonia. 1159 34

Cell recruitment is a multistep process regulated by cytokines, chemokines, and growth factors. Previous work has indicated that the urokinase plasminogen activator receptor (uPAR) may also play a role in this mechanism, presumably by an interaction with the beta(2) integrin CD11b/CD18. Indeed, an essential role of uPAR in neutrophil recruitment during pulmonary infection has been demonstrated for beta(2) integrin-dependent respiratory pathogens. We investigated the role of uPAR and urokinase plasminogen activator (uPA) during pneumonia caused by a beta(2) integrin-independent respiratory pathogen, Streptococcus pneumoniae. uPAR-deficient (uPAR(-/-)), uPA-deficient (uPA(-/-)), and wild-type (Wt) mice were intranasally inoculated with 10(5) CFU S. pneumoniae. uPAR(-/-) mice showed reduced granulocyte accumulation in alveoli and lungs when compared with Wt mice, which was associated with more S. pneumoniae CFU in lungs, enhanced dissemination of the infection, and a reduced survival. In contrast, uPA(-/-) mice showed enhanced host defense, with more neutrophil influx and less pneumococci in the lungs compared with Wt mice. These data suggest that uPAR is necessary for adequate recruitment of neutrophils into the alveoli and lungs during pneumonia caused by S. pneumoniae, a pathogen eliciting a beta(2) integrin-independent inflammatory response. This function is even more pronounced when uPAR is unoccupied by uPA.
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PMID:Urokinase receptor is necessary for adequate host defense against pneumococcal pneumonia. 1190 12

Pseudomonas aeruginosa is widely prevalent in the hospital environment, especially in intensive care units. Selective IgA deficiency is characterized by a serum IgA level less than 5 mg/dl with no deficiency of other immunoglobulins. The occurrence of community-acquired P. aeruginosa pneumonia with empyema is rare in pediatric patients. We present a 10-month-old male infant who was referred due to persistent fever and progressive respiratory distress for 1 week. A chest radiograph revealed a right lobar pneumonia with pleural effusion. P. aeruginosa that was subsequently isolated from both blood and pleural effusion cultures. The patient received treatment with ceftazidime and intrapleural instillation of urokinase to promote drainage of empyema. Subsequent immunological screening revealed a very low serum IgA level (<5 mg/dl). We present our experience in successfully treating a loculated empyema with intrapleural instillation of urokinase in an infant. It is also important for pediatricians to be aware that they should be alert for the patient who present with respiratory infections due to unusual organisms. An advanced immunological study to investigate the underlying disorders in these patients is mandatory.
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PMID:Community-acquired Pseudomonas aeruginosa pneumonia complicated with loculated empyema in an infant with selective IgA deficiency. 1214 67

AIMS: This study evaluated the treatment of early coronary stent thrombosis with intracoronary urokinase or the platelet glycoprotein IIb/IIIa receptor inhibitor ReoPro (abciximab). METHODS AND RESULTS: Seventy-four patients (126 stents) were treated immediately after identification of early (0-30 days) coronary stent thrombosis. Twenty-nine patients were treated with intracoronary urokinase (UK) (UK alone in 19; UK and additional balloon angioplasty in 10) and another 45 patients were given ReoPro((R)) (abciximab) (0.25 mg/kg as a bolus alone in 26, abciximab with additional balloon angioplasty in 19) within 30 days of stent implantation. TIMI grade 3 flow was obtained in 23 patients (79%) in the UK group and in 38 (84%) in the abciximab group (nonsignificant). Three patients (10%) in the UK group and one (2%) in the abciximab group underwent repeat percutaneous transluminal coronary angioplasty (PTCA) (nonsignificant). Five patients (17%) in the UK group and three (7%) in the abciximab group were referred for urgent coronary artery bypass graft surgery (CABG) because of residual thrombus and refractory ischemia (nonsignificant). Repeat revascularization was necessary in eight patients (28%) in the UK group versus four (9%) in the abciximab group (p < 0.05). Five patients (17%) in the UK group and eight (18%) in the abciximab group developed myocardial infarction (nonsignificant). Five patients (17%) in the UK group (cardiogenic shock (three), cerebral hemorrhage (one) and pneumonia (one)) and three (6.6%) in the abciximab group (cardiogenic shock (two), heart failure (one)) died within 30 days (nonsignificant). Overall, noncardiac complications (bleeding including surgical repair of groin) were observed in 11 patients (38%) in the UK group and three (7%) in the abciximab group (p < 0.001). CONCLUSION: Compared to urokinase, abciximab reduced the need for repeat revascularization procedures and the risk of noncardiac events, including bleeding complications in patients with early coronary stent thrombosis.
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PMID:Comparison of ReoPro((R)) (abciximab) versus intracoronary thrombolysis for early coronary stent thrombosis. 1247 Mar 68

Leukocytes express both urokinase-type plasminogen activator (uPA) and the urokinase receptor (uPAR, CD87). We have shown that neutrophil recruitment to the lung during P. aeruginosa pneumonia is impaired in uPAR-deficient (uPAR-/-) mice but is normal in uPA-/- mice. However, both uPA-/- mice and uPAR-/- mice have impaired lung clearance of P. aeruginosa compared with wild-type (WT) mice. To determine the role of uPA and uPAR in antibacterial host defense, we compared neutrophil bacterial-phagocytosis, respiratory burst, and degranulation among uPA-/-, uPAR-/-, and WT mice. Neutrophil phagocytosis was significantly diminished comparing uPA-/- and uPAR-/- mice with WT mice at all time points. The generation of superoxide by both uPA-/- and uPAR-/- neutrophils was about half of that seen in WT neutrophils. Degranulation of azurophilic granules was significantly diminished in uPA-/- neutrophils compared with either uPAR-/- or WT neutrophils. By contrast, agonist-stimulated release of specific granules was not diminished in either uPA-/- or uPAR-/- mice compared with WT. We conclude that the uPA/uPAR system modulates several of the crucial steps in neutrophil activation that result in bacterial killing and effective innate host defense.
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PMID:Urokinase-deficient and urokinase receptor-deficient mice have impaired neutrophil antimicrobial activation in vitro. 1524 Jul 45

Infections caused by Streptococcus suis, a major swine pathogen, include meningitis, arthritis, pneumonia and septicaemia. In this study, we investigated interactions that may occur between human brain microvascular endothelial cells (HBMEC), the main constituent of the blood-brain barrier, and S. suis. We show that S. suis acquires plasmin activity in a time-dependent manner when in contact with cultured HBMEC. Cell-associated plasmin activity reached a plateau following a 48h co-incubation period. Zymography analysis revealed that HBMEC produce urokinase, which is probably involved in activation of plasminogen bound to S. suis. We also show that a S. suis culture supernatant which possesses both phospholipase C and haemolysin (suilysin) activities was able to induce the release of arachidonic acid from the membrane of HBMEC. Evidence suggests that the action of suilysin on HBMEC may be a prerequisite for the action of additional molecules such as phospholipase C. These new biological effects associated with S. suis may play an important role in the migration of S. suis through the blood-brain barrier and in the modulation of local inflammation.
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PMID:Acquisition of plasmin activity and induction of arachidonic acid release by Streptococcus suis in contact with human brain microvascular endothelial cells. 1618 70

Otherwise unexplained clinical signs of infection in patients with tunneled or totally implanted central venous access devices (CVAD) are highly suspicious of an underlying CVAD-associated infection. Diagnostic methods include catheter swabs, blood cultures and cultures of the catheter tip or port reservoir. In case of a suspected CVAD-related blood stream infection in pediatric cancer patients in situ treatment without prompt removal of the device can be tried. The removal of the CVAD should be considered, if bacteremia persists or relapses 72 hours or longer after the initiation of an (in vitro effective) antibacterial therapy administered through the line. The CVAD should be removed even earlier, if the patient suffers from hypotension or other signs of severe organ dysfunction related to the infection. If S. aureus, Pseudomonas aeruginosa, multiresistant Acinetobacter baumannii or Candida spp.are isolated from blood cultures taken through a CVAD, patients are at a high risk for severe complications and immediate device removal is also recommended. Duration of therapy depends on the immunological recovery of the patient (neutrophils counts), the pathogen isolated and on the presence of related complications like thrombosis, pneumonia, endocarditis, osteomyelitis. Antibiotic-lock techniques in addition to systemic treatment are beneficial in Gram-positive infections. Although prospectively controlled studies are missing, the concomitant use of urokinase- or taurolidine seems to favour catheter salvage.
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PMID:[Diagnostics and management of central venous line infections in pediatric cancer patients]. 1628 55

Macrophages play a pivotal role in a host's defence against pulmonary infections. Macrophage functions are impaired in immunosuppressed (IS) patients, regardless of whether they are HIV-positive (HIV+) or -negative (HIV-). Several studies have indicated that urokinase plasminogen activator (uPA) and transforming growth factor beta (TGF-beta) are important factors in a host's defence against pulmonary pathogens. We measured uPA and TGF-beta activity in unstimulated peripheral blood monocytes (PBM) of both HIV-infected and non-infected IS patients with or without Pneumocystis jiroveci (formerly carinii) pneumonia (PCP). As previously found in alveolar macrophages (AMs), the majority of uPA activity was found in cell lysates. The highest values of uPA activity were found in control subjects. All the patients displayed a decreased production of uPA, irrespective of HIV infection. Similarly, active TGF-beta was higher in control subjects than in HIV+ and IS patients. The presence of P. jiroveci infection further lowered uPA and TGF-beta activity. Decreased TGF-beta activation might be a consequence of lower uPA production, which may, in turn, influence virus replication, since it has been demonstrated that TGF-beta can suppress human HIV expression in monocytes/macrophages. Further studies are warranted to elucidate whether the decrease in uPA and TGF-beta activity impairs a host's defence against P. jiroveci infection.
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PMID:Urokinase plasminogen activator and TGF-beta production in immunosuppressed patients with and without P. Jiroveci infection. 1670 17


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