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)

There is a severe defect in the surfactant system in adult respiratory distress syndrome (ARDS). According to animal studies oxidant injury acutely alters the synthesis and secretion of surfactant. Plasma-derived surfactant inhibitors cause an early decrease in surface activity in high permeability lung oedema. Alveolar inflammation severely disturbs the surfactant system as a result of enzymatic breakdown of its components and inhibition of surfactant function. Analysis of bronchoalveolar lavage fluid obtained following unilateral irradiation of the lung revealed a striking increase in inhibitory serum proteins and a decrease in surfactant components (SP 35 apoprotein, phosphatidylglycerol, saturated phosphatidylcholine), before appearance of irradiation pneumonitis. In lysinuric protein intolerance (LPI), an autosomal recessive disorder in renal-intestinal-hepatic diamino acid transport, there is an increased risk of ARDS. In asymptomatic LPI the concentration of diamino acids in alveolar epithelial lining was strikingly increased, suggesting that the basolateral epithelial transport defect additionally involves alveolar epithelium and predisposes to ARDS.
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PMID:Composition and function of pulmonary surfactant in adult respiratory distress syndrome. 266 93

Detection of a biochemical marker indicating radiation lung injury prior to the onset of clinical pathologic events could prove valuable in patient management. An increased level of alveolar surfactant is one of the earliest detectable changes following lung irradiation, starting within hours of irradiation and persisting a maximum of 2-6 weeks. However, because broncho-alveolar lavage is impracticable and endothelial cell damage due to radiation results in changes in permeability of vessel wall with leakage of alveolar proteins into serum, identification of serum markers was sought. A series of experiments in rabbits are described that clearly demonstrate serum surfactant apoprotein is an accurate marker and predictor for later lethal radiation pneumonitis. At 3-7 days after graded single doses to lung, surfactant was found in the serum paralleling the dose response for lethality. Control studies with a physiologic agent such as terbutaline release alveolar surfactant, but no serum surfactant was detected. Monitoring serum surfactant could direct preventive intervention prior to clinicopathologic manifestation of pulmonary radiation syndromes.
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PMID:Serum markers for prediction of pulmonary radiation syndromes. Part I: Surfactant apoprotein. 277 46

Pneumocystis carinii (PC) pneumonia remains one of the most important opportunistic pulmonary infections. The alveolar macrophage (AM) is likely the primary cell for recognition and removal of PC. The histopathology of PC pneumonia is characterized by a surfactant-like alveolar exudate. We hypothesize that surfactant protein A(SP-A), the major apoprotein of surfactant, mediates attachment of PC to rat AMs by acting as a ligand between the organism and the AM. In this study, attachment of PC was determined using (51)Cr-labeled PC incubated at 4 degrees C with normal rat AM monolayers in the presence or absence of human SP-A. SP-A significantly enhanced attachment of PC from 14.2 +/- 1.2% to 42.0 +/- 3.8% (P<0.05). This enhanced attachment was visualized and quantified morphologically with confocal microscopy. PC attachment by SP-A was calcium- and mannose-dependent as SP-A-mediated attachment was significantly reduced in the presence of EGTA and mannose to 13.1 +/- 1.6% and 19.3 +/- 2.6%, respectively (P<0.05). Addition of type V collagen and antibodies to SP-A also significantly reduced SP-A-mediated attachment to 4.9 +/- 1.2% and 10.1 +/- 1.2%, respectively (P<0.05). We conclude that SP-A can function as a ligand between PC and the AM and may represent an important detection and clearance mechanism of PC from the alveolar spaces.
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PMID:Human surfactant protein A enhances attachment of Pneumocystis carinii to rat alveolar macrophages. 884 73

We have found that Legionella dumoffii strain Tex-KL (ATCC 33343) invades into and proliferates in the human lung alveolar epithelial-cell line A549 in vitro. The organism associated with the A549 cells at a 10-fold greater magnitude than L. pneumophila Philadelphia-1 during in vitro coculture for 1 h. Thereafter, L. dumoffii Tex-KL invaded the cells at a significantly higher rate (100- to 1,000-fold) than did L. pneumophila Philadelphia-1. After internalization, however, both bacteria proliferated at the same rate. This in vitro finding led us to examine the bacterial localization in lungs in a fatal case of L. dumoffii pneumonia. Double immunostaining revealed the bacteria in surfactant apoprotein A-positive cells (i.e., type II alveolar epithelial cells). Next, we infected guinea pigs intratracheally with L. dumoffii Tex-KL. The animals became sick with a fever from 24 h to 48 h after infection with 10(4) to 10(9) cfu of L. dumoffii Tex-KL. The lung tissues were examined through electron microscopy at definite intervals. Many bacteria were found not only inside phagocytic cells in the alveolar space, but also in type I and type II alveolar epithelial cells. These findings strongly suggest that L. dumoffii has an ability to invade into and proliferate in human alveolar epithelial cells, which may explain the rapid and fulminant progress of pneumonia caused by L. dumoffii.
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PMID:Entry and intracellular growth of Legionella dumoffii in alveolar epithelial cells. 962 Sep 34

Animal models are used extensively in the ongoing investigation of a possible causal link between Chlamydia pneumoniae infection and conditions such as asthma and cardiovascular disease. Respiratory infections have been studied in monkeys, while mouse and rabbit models have been used to study both respiratory and cardiovascular infections. The degree of disease induced in mice depends on the strain used, the virulence of the C. pneumoniae strain used, and the dose administered. A characteristic mononuclear pneumonitis occurs, although the infection is systemic and the agent is found outside the lungs, in the circulation, spleen and liver. The infective dose used in the model tends to produce persistent infection, with inflammation continuing after the agent can no longer be cultured from the lungs. In reinfected animals the titre of infective chlamydia in lungs is much diminished, but the inflammation can be quite marked. The continuous persistence of the agent can be demonstrated by polymerase chain reaction (PCR), or, in chronically infected animals, after immunosuppression with cortisone. New Zealand White (NZW) rabbits provide an experimental model, not only for lung infections, but also for C. pneumoniae-induced atherosclerosis. Three laboratories have now reported that after inoculation, plaques develop in the arterial walls of experimental animals on a normal diet. In addition, one laboratory has reported from their studies on atherosclerosis in apoE-deficient and normal mice, that the persistence of the agent in aortic walls could be seen. Further studies are needed to evaluate the effect of the strain of chlamydia and dosage used, the importance of reinfection, the effect of diet and the effect of antibiotic treatment in these models.
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PMID:Animal models for Chlamydia pneumoniae infection. 985 20

Lipoprotein lipid and apoprotein concentrations are known to be altered during the acute-phase response. We have previously shown that the serum activity of lecithin:cholesterol acyltransferase (LCAT) and concentration of cholesteryl esters, both constituents of the high-density lipoprotein (HDL) fraction, are reduced in calves inoculated with Pasteurella haemolytica and bovine herpes virus-1, the two major pathogens for calf pneumonia. The concentration of apolipoprotein C-III (apoC-III), a low molecular mass protein component distributed mainly in the HDL fraction, was therefore examined in bacteria- and virus-inoculated calves. An enzyme-linked immunosorbent assay demonstrated that it was decreased by inoculations of Pasteurella haemolytica and bovine herpes virus-1. The decrease was detected as early as 1 day after inoculation in both groups. A decreased serum apoC-III concentration was also observed by immunoblot analysis. It was detected in the HDL fractions from the bacteria- and virus-inoculated calves, and HDL apoC-III concentrations in the inoculated calves were decreased compared with controls. These results, coupled with the previous findings on LCAT activity and the cholesteryl ester concentration, indicate that a decreased HDL concentration is one of the early events occurring during the acute-phase response evoked by infections with Pasteurella haemolytica and bovine herpes virus-1.
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PMID:Decreased apolipoprotein C-III concentration in the high-density lipoprotein fraction from calves inoculated with Pasteurella haemolytica and bovine herpes virus-1. 1067 89

A 47-year-old male had symptoms of coughing and with fever and was admitted to our hospital where tests revealed he had anemia and thrombocytopenia. Following the results obtained from a bone marrow aspiration, he was diagnosed as having acute myeloid leukemia (AML). A chest radiograph and a CT scan demonstrated nodular shadows and pleural exudate in both lungs. We suspected atypical pneumonia, or fungal pneumonia, and he was subsequently given antibiotics and antifungal agents, which were, however, ineffective. On the third day after admission, he was put on mechanical ventilation, and a bronchoalveolar lavage examination revealed no germs. His respiration, however, progressively worsened and he died on the twelfth day after admission. Although the autopsy findings revealed no infectious lesions in his lungs, a PAS-positive intra-alveolar eosinophilic material, which was positive for surfactant apoprotein A staining, was present. As a result of the autopsy findings, a diagnosis of secondary pulmonary alveolar proteinosis (PAP) associated with AML was made. Among the reported cases of PAP in hematological malignancy, there has not been one case detected at the time AML was diagnosed. If there is evidence of an unknown cause of lung infiltration when AML is diagnosed, attention should be paid to the possibility of the presence of PAP.
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PMID:[Acute myeloid leukemia complicated with pulmonary alveolar proteinosis at presentation]. 1644 Jul 46

Streptococcus pneumoniae (Sp) strain TIGR4 is a virulent, encapsulated serotype that causes bacteremia, otitis media, meningitis and pneumonia. Increased bacterial resistance and limited efficacy of the available vaccine to some serotypes complicate the treatment of diseases associated to this microorganism. Flavodoxins are bacterial proteins involved in several important metabolic pathways. The Sp flavodoxin (Spfld) gene was recently reported to be essential for the establishment of meningitis in a rat model, which makes SpFld a potential drug target. To facilitate future pharmacological studies, we have cloned and expressed SpFld in E. coli and we have performed an extensive structural and biochemical characterization of both the apo form and its active complex with the FMN cofactor. SpFld is a short-chain flavodoxin containing 146 residues. Unlike the well-characterized long-chain apoflavodoxins, the Sp apoprotein displays a simple two-state thermal unfolding equilibrium and binds FMN with moderate affinity. The X-ray structures of the apo and holo forms of SpFld differ at the FMN binding site, where substantial rearrangement of residues at the 91-100 loop occurs to permit cofactor binding. This work will set up the basis for future studies aiming at discovering new potential drugs to treat S. pneumoniae diseases through the inhibition of SpFld.
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PMID:Streptococcus pneumoniae TIGR4 Flavodoxin: Structural and Biophysical Characterization of a Novel Drug Target. 2764 88