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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pneumocystis carinii causes life-threatening pneumonia in immunocompromised patients. The inability to culture P. carinii has hampered basic investigations of the organism's life cycle, limiting the development of new therapies directed against it. Recent investigations indicate that P. carinii is a fungus phylogenetically related to other ascomycetes such as Schizosaccharomyces pombe. The cell cycles of S. pombe and homologous fungi are carefully regulated by cell-division-cycle molecules (cdc), particularly cell-division-cycle 2 (Cdc2), a serine-threonine kinase with essential activity at the G1 restriction point and for entry into mitosis. Antibodies to the proline-serine-threonine-alanine-isoleucine-arginine (PSTAIR) amino-acid sequence conserved in Cdc2 proteins specifically precipitated, from P. carinii extracts, a molecule with kinase activity consistent with a Cdc2-like protein. Cdc2 molecules exhibit differential activity throughout the life cycle of the organisms in which they occur. In accord with this, the P. carinii Cdc2 showed greater specific activity in P. carinii trophic forms (trophozoites) than in spore-case forms (cysts). In addition, complete genomic and complementary DNA (cDNA) sequences of P. carinii Cdc2 were cloned and found to be most closely homologus to the corresponding sequences of other pathogenic fungi. The function of P. carinii cdc2 cDNA was further documented through its ability to complement the DNA of mutant strains of S. pombe with temperature-sensitive deficiencies in Cdc2 activity. The P. carinii cdc2 cDNA restored normal Cdc2 function in these mutant strains of S. pombe, and promoted fungal proliferation. These studies represent the first molecular analysis of the cell-cycle-regulatory machinery in P. carinii. Further understanding of P. carinii's life cycle promises novel insights for preventing and treating the intractable infection it causes in immunocompromised patients.
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PMID:Pneumocystis carinii contains a functional cell-division-cycle Cdc2 homologue. 949 Jun 47

Pneumocystis jiroveci is an important cause of pneumonia in immunocompromised individuals. This organism cannot be cultured, and therefore, diagnosis relies on microscopic identification of the organism using stains or antibodies. Although simple, these tests are insensitive and require expertise for accurate interpretation. We developed a real-time polymerase chain reaction (PCR) assay that provides sensitive and objective detection of Pneumocystis from bronchoalveolar lavage fluid. Primers and fluorescence resonance energy transfer probes were developed that target the cdc2 gene of P. jiroveci. Assay sensitivity is 6 copies of target per microliter of sample. No cross-reactivity occurs with other pathogens, and the PCR assay has a 21% increase in clinical sensitivity as compared with Calcofluor white staining. The real-time PCR assay provides a sensitive, rapid, and objective method for the detection of Pneumocystis from bronchoalveolar lavage fluid.
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PMID:A real-time polymerase chain reaction assay for detection of Pneumocystis from bronchoalveolar lavage fluid. 1642 88

Pneumocystis jirovecii pneumonia is a significant cause of morbidity and mortality in AIDS patients as well as those with non-HIV immunosuppressive diseases. To aid diagnosis, the commercial MycAssay Pneumocystis real-time PCR assay (Myconostica, Ltd., Manchester, United Kingdom) targeting the mitochondrial ribosomal large subunit (mtLSU) has been developed to detect P. jirovecii in bronchoalveolar lavage (BAL) specimens. Here, we validated this assay against a laboratory standard of direct immunofluorescence microscopy, a cdc2 real-time PCR assay, or conventional PCR and sequencing of mtLSU. While more sensitive than any of these three assays analyzed individually, the MycAssay Pneumocystis assay demonstrated 100% sensitivity, 100% specificity, a 100% negative predictive value, and a 100% positive predictive value for detecting the presence of P. jirovecii in BAL specimens compared to the laboratory standard. Of note, two samples with positive cycle threshold (C(T)) values according to the MycAssay Pneumocystis assay lacked exponential amplification curves and thus were deemed negative. Also negative according to the laboratory standard, these samples highlight the importance of examining the amplification curves, in addition to noting the C(T) values, when interpreting positive results. Comparison of the MycAssay Pneumocystis assay to a laboratory standard establishes this assay to be a highly sensitive and specific method for the detection of P. jirovecii in bronchoalveolar lavage specimens. The approach may also be useful for the clinical laboratory validation of other sensitive real-time PCR assays.
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PMID:Validation of the MycAssay Pneumocystis kit for detection of Pneumocystis jirovecii in bronchoalveolar lavage specimens by comparison to a laboratory standard of direct immunofluorescence microscopy, real-time PCR, or conventional PCR. 2242 55

Internalization of Staphylococcus aureus by nonprofessional phagocytic cells is a major suspected cause of persistent and difficult-to-treat infections, including pneumonia. In this study, we established an infection model with 16HBE14o- human bronchial epithelial cells and demonstrated internalization, escape from phagosomal clearance, and intracellular replication of S. aureus HG001 within the first 4 h postinfection. We used quantitative phosphoproteomics to identify characteristic signaling networks in the host at different infection stages. Although we found only minor changes in protein abundance, the infection was accompanied by highly dynamic alterations in phosphorylation events primarily in proteins that are associated with pathways of cytoskeleton dynamics, cell-cell and cell-matrix contacts, vesicle trafficking, autophagy, and GTPase signaling. Analyses of host protein kinases by kinase-substrate mapping, active regulatory site immunoblotting, and prediction algorithms highlighted known and novel host kinases with putative critical roles in S. aureus infection-accompanied signaling including FAK, PKA, PKC, and CDK. Targeted pharmacological inhibition of these kinases resulted in a significant reduction of intracellular S. aureus cells. The current study constitutes a valuable resource for better understanding the infection-relevant molecular pathomechanisms of airway cells and for developing novel host-centric anti-infective strategies for treating S. aureus infections.
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PMID:Quantitative Proteomics Reveals the Dynamics of Protein Phosphorylation in Human Bronchial Epithelial Cells during Internalization, Phagosomal Escape, and Intracellular Replication of Staphylococcus aureus. 2776 62