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)

In order to characterize BAL (bronchoalveolar lavage) in CEP (chronic eosinophilic pneumonia) and to investigate the possible role of mast cells and tryptase in the pathogenesis of this interstitial disease, cells and tryptase levels were determined in BAL of patients with CEP and in a group of healthy controls. The results show that a statistically significant increase in tryptase concentration was found in patients with CEP compared with the healthy controls. This is the first report that shows an increase in tryptase levels in CEP and could reflect higher mast cell activation as well as larger mast cell populations in the lungs of these patients. These results strongly support the involvement of mast cells and eosinophils in the immunopathogenesis of CEP.
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PMID:Tryptase concentrations in bronchoalveolar lavage from patients with chronic eosinophilic pneumonia. 1553 94

We examined the roles of Th1-Th2 cytokine cross talk in Legionella pneumophila-infected bone marrow-derived (BM) macrophages in the presence of costimulation with interleukin-12 (IL-12) and IL-18. Treatment with gamma interferon (IFN-gamma) alone or treatment with IL-12 in combination with IL-18 resulted in a 3- or 2-log reduction in bacterial numbers, respectively, in BM macrophages, whereas treatment with IL-12 or IL-18 alone had no effect. Significant amounts of IFN-gamma were detected in the culture supernatants of infected macrophages stimulated with IL-12 and IL-18 in combination but not independently. Neutralization of IFN-gamma by antibody completely abolished the growth inhibitory effects of IL-12 and IL-18. Interestingly, higher infectivity ratios of L. pneumophila or the addition of increasing concentrations of heat-killed bacteria (HKB) suppressed the production of IFN-gamma, which resulted in the increased intracellular growth of bacteria. Significant amounts of IL-10 were detected in culture supernatants when Legionella-infected macrophages were cocultured with HKB. Furthermore, neutralization of IL-10 by antibody resulted in an increase in IFN-gamma production by infected BM macrophages when cocultured with HKB. Treatment of HKB with trypsin but not polymyxin B attenuated the growth-promoting effects of HKB, suggesting the involvement of a protein component(s) in regulation of the growth of L. pneumophila. These findings demonstrate a crucial role of Th1-Th2 cross talk in L. pneumophila-infected BM macrophages. Our results also suggest that L. pneumophila modulates the cytokine balance from IFN-gamma-driven Th1 to more Th2 responses, likely through the induction of IL-10 by a bacterial protein component(s). These data provide new insights not only into the cellular mechanisms of Th1-Th2 cross talk in Legionella-infected macrophages but also into the pathogenesis of L. pneumophila pneumonia in humans.
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PMID:Legionella pneumophila evades gamma interferon-mediated growth suppression through interleukin-10 induction in bone marrow-derived macrophages. 1584 73

Human metapneumovirus (hMPV), a recently described paramyxovirus, is a major etiological agent for lower respiratory tract disease in young children that can manifest with severe cough, bronchiolitis, and pneumonia. The hMPV fusion glycoprotein (F) shares conserved functional domains with other paramyxovirus F proteins that are important for virus entry and spread. For other paramyxovirus F proteins, cleavage of a precursor protein (F0) into F1 and F2 exposes a fusion peptide at the N terminus of the F1 fragment, a likely prerequisite for fusion activity. Many hMPV strains have been reported to require trypsin for growth in tissue culture. The majority of these strains contain RQSR at the putative cleavage site. However, strains hMPV/NL/1/00 and hMPV/NL/1/99 expanded in our laboratory contain the sequence RQPR and do not require trypsin for growth in Vero cells. The contribution of this single amino acid change was verified directly by generating recombinant virus (rhMPV/NL/1/00) with either proline or serine at position 101 in F. These results suggested that cleavage of F protein in Vero cells could be achieved by trypsin or S101P amino acid substitution in the putative cleavage site motif. Moreover, trypsin-independent cleavage of hMPV F containing 101P was enhanced by the amino acid substitution E93K. In hamsters, rhMPV/93K/101S and rhMPV/93K/101P grew to equivalent titers in the respiratory tract and replication was restricted to respiratory tissues. The ability of these hMPV strains to replicate efficiently in the absence of trypsin should greatly facilitate the generation, preclinical testing, and manufacturing of attenuated hMPV vaccine candidates.
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PMID:An S101P substitution in the putative cleavage motif of the human metapneumovirus fusion protein is a major determinant for trypsin-independent growth in vero cells and does not alter tissue tropism in hamsters. 1605 60

Increasing evidence has linked the anaerobic bacteria forming periodontopathic biofilms with aspiration pneumonia in elderly persons. In experiments designed to eliminate the potent respiratory pathogens forming biofilms in the oral cavity, we have shown that the mechanical and chemical oral cleansing using povidone-iodine effectively reduced the detection rates and numbers of methicillin-sensitive Staphylococcus species, Streptococcus pneumoniae, and Haemophilus influenzae in patients scheduled to undergo oral surgery requiring endotracheal intubation. We confirmed the pathogenicity of periodontopathic anaerobic bacteria for aspiration pneumonia in an experimental mouse model. Based upon the finding of the coexistence of Porphyromonas gingivalis with Treponema denticola in chronic periodontitis lesions, we innoculated a mixed culture of P. gingivalis and T. denticola into the mouse trachea; the resulting infection induced inflammatory cytokine production and caused pneumonia. In another series of investigations, professional oral health care (POHC), mainly cleansing administered by dental hygienists once a week for 24 months to elderly persons requiring daily care, resulted in the reduction of the number of total anaerobes, Candida albicans, and Staphylococcus species and in the number of cases of fatal aspiration pneumonia. We also found that the POHC treatment of elderly persons for 6 months in the winter season reduced the salivary levels of protease, trypsin-like activity, and neuraminidase and also decreased the frequency of influenza cases.
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PMID:Involvement of periodontopathic anaerobes in aspiration pneumonia. 1627 88

Severe pneumonia is found in simultaneous influenza pneumonia and bacterial infection, and suggests a relationship with immunological mechanisms. Here, we performed two-dimensional gel electrophoresis to detect immunological molecules related to the fulminant pneumonia caused by influenza virus and Streptococcus pneumoniae co-infection in mice. We found two spots that were expressed strongly in co-infected mouse lungs, compared with S. pneumoniae or influenza virus singly infected mouse lungs. The spots were analysed by mass spectrometry, and identified as alpha-1 anti-trypsin (A1AT), known as an anti-protease for neutrophil-derived proteolytic enzymes, and creatine kinase, which reflects a greater degree of lung damage and cell death. A1AT expression was increased significantly, and proteolytic enzymes from neutrophils, such as neutrophil elastase, myeloperoxidase and lysozyme, were also secreted abundantly in influenza virus and S. pneumoniae co-infected lungs compared with S. pneumoniae or influenza virus singly infected lungs. These data suggest that A1AT may play a central role as a molecule with broad anti-inflammatory properties, and regulation of the neutrophil-mediated severe lung inflammation is important in the pathogenesis of co-infection with influenza virus and bacteria.
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PMID:Two-dimensional gel electrophoresis analysis in simultaneous influenza pneumonia and bacterial infection in mice. 1834 13

Nasogastric enteral feeding is not tolerated in patients with gastric atony and in many critically-ill patients in whom gastric emptying may be delayed and in whom gastro-oesophageal regurgitation may lead to pulmonary aspiration of enteral feed and the development of pneumonia. Initial attempts to overcome these problems led to the development of post pyloric enteral feeding techniques with the infusion port of the tubes positioned in the duodenum. In many centres this technique is still the most practised post-pyloric enteral feeding technique. Nasoduodenal feeding tubes often retroperistalse into the stomach. The technique of choice, therefore, in these difficult patients is to position the infusion port of the feeding tube well distal to the ligament of trietz (post ligament of trietz nasojejunal enteral tube feeding). While nasogastric and nasoduodenal enteral feeding techniques have been shown to elicit a stimulatory exocrine pancreatic response, distal jejunal enteral feeding does not. During this mode of feeding the ileal brake is activated and pancreatic exocrine pancreatic secretion inhibited by the action of the released peptide YY and glucagon-like peptide-1 hormones, in turn the inhibition of pancreatic secretion being the result of inhibition of trypsin secretion. In the light of the findings showing the absence of a stimulatory pancreatic exocrine response to nasojejunal enteral feeding these patients should receive a predigested rather than a polymeric enteral diet.
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PMID:Formulation of enteral diets for use in jejunal enteral feeding. 1849 70

In Pseudomonas aeruginosa, cyclic AMP (cAMP) signaling regulates the transcription of hundreds of genes encoding diverse virulence factors, including the type II secretion system (T2SS) and type III secretion system (T3SS) and their associated toxins, type IV pili (TFP), and flagella. Vfr, a cAMP-dependent transcriptional regulator that is homologous to the Escherichia coli catabolite repressor protein, is thought to be the major cAMP-binding protein that regulates these important virulence determinants. Using a bioinformatic approach, we have identified a gene (PA4704) encoding an additional putative cAMP-binding protein in P. aeruginosa PAO1, which we herein refer to as CbpA, for cAMP-binding protein A. Structural modeling predicts that CbpA is composed of a C-terminal cAMP-binding (CAP) domain and an N-terminal degenerate CAP domain and is structurally similar to eukaryotic protein kinase A regulatory subunits. We show that CbpA binds to cAMP-conjugated agarose via its C-terminal CAP domain. Using in vitro trypsin protection assays, we demonstrate that CbpA undergoes a conformational change upon cAMP binding. Reporter gene assays and electrophoresis mobility shift assays defined the cbpA promoter and a Vfr-binding site that are necessary for Vfr-dependent transcription. Although CbpA is highly regulated by Vfr, deletion of cbpA did not affect known Vfr-dependent functions, including the T2SS, the T3SS, flagellum- or TFP-dependent motility, virulence in a mouse model of acute pneumonia, or protein expression profiles. Unexpectedly, CbpA-green fluorescent protein was found to be localized to the flagellated old cell pole in a cAMP-dependent manner. These results suggest that polar localization of CbpA may be important for its function.
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PMID:CbpA: a polarly localized novel cyclic AMP-binding protein in Pseudomonas aeruginosa. 1980 9

1. Caseous matter obtained from lymph glands which have not become secondarily infected contains substances which inhibit enzyme activity. These substances consist chiefly of soaps of the unsaturated fatty acids. 2. The inhibiting substances are present in relatively smaller amounts when the caseous matter has become secondarily infected. This is probably due to the dilution and washing out of the soaps. 3. Ferments are either entirely absent or present in very small amounts, unless the caseous matter has become secondarily infected. 4. Caseous material from the lungs contains smaller amounts of the inhibiting substances. This may be due to the acuteness of the process, which does not permit an accumulation of the soaps, or to the binding of the soaps with the ferments. 5. Ferments are present in caseous pneumonia. In the whole emulsion the ferments are less active in an alkaline than in an acid reaction; but removal of the soaps shows that those active in an alkaline reaction are also present in considerable amounts. 6. The previous treatment with iodin of caseous matter from both lymph glands and lungs increases the action of the trypsin.
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PMID:A STUDY OF THE FERMENTS AND FERMENT-INHIBITING SUBSTANCES IN TUBERCULOUS CASEOUS MATERIAL : STUDIES ON FERMENT ACTION. XII. 1986 78

Mycoplasma ovipneumoniae is associated with chronic non-progressive pneumonia of sheep and goats. As with many other mycoplasmas involved in animal diseases, protective immune responses have not been achieved with vaccines, even though antibody responses can be obtained. This study focuses on characterizing the interaction of M. ovipneumoniae with ovine PBMC using carboxy-fluorescein-succinimidyl-ester (CFSE) loading and flow cytometry to measure lymphoid cell division. M. ovipneumoniae induced a strong in vitro polyclonal suppression of CD4(+), CD8(+), and B blood lymphocyte subsets. The suppressive activity could be destroyed by heating to 60 degrees C, and partially impaired by formalin and binary ethyleneimine treatment that abolished its viability. The activity resided on the surface-exposed membrane protein fraction of the mycoplasma, since mild trypsin treatment not affecting viability was shown to reduce suppressive activity. Trypsin-treated mycoplasma regained suppressive activity once the mycoplasma was allowed to re-synthesize its surface proteins. Implications for the design of vaccines against M. ovipneumoniae are discussed.
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PMID:Global suppression of mitogen-activated ovine peripheral blood mononuclear cells by surface protein activity from Mycoplasma ovipneumoniae. 2018 58

The goal of these studies was to characterize the infiltrating inflammatory cells during pneumonitis caused by moderate doses of radiation. Two groups of male rats (WAG/RijCmcr, 8 weeks old) were treated with single 10- or 15-Gy doses of thoracic X radiation; a third group of age-matched animals served as controls. Only 25% rats survived the 15-Gy dose. Bronchoalveolar lavage fluid and whole lung mounts were subjected to cytological and histological evaluation after 8 weeks for distribution of resident macrophages, neutrophils, lymphocytes and mast cells. There was a modest increase in airway and airspace-associated neutrophils in lungs from rats receiving 15 Gy. Mast cells (detected by immunohistochemistry for tryptase) increased over 70% with 10 Gy and over 13-fold after 15 Gy, with considerable leakage of tryptase into blood vessels and airways. Circulating levels of eight inflammatory cytokines were not altered after 10 Gy but appeared to decrease after 15 Gy. In summary, there were only modest increases in cellular inflammatory infiltrate during pneumonitis after a non-lethal dose of 10 Gy, but there was a dramatic rise in mast cell infiltration after 15 Gy, suggesting that circulating levels of mast cell products may be useful markers of severe pneumonitis.
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PMID:Cellular inflammatory infiltrate in pneumonitis induced by a single moderate dose of thoracic x radiation in rats. 2033 27


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