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

Human adenovirus can cause persistent infections in man. Implicated in this phenomenon is the early transcription unit 3 (E3) of the virus which encodes proteins that are primarily devoted to counteract the lytic attack by the host immune system: Several E3 proteins (14.7K, 10.4K and 14.5K) protect infected cells from the lytic activity of tumor necrosis factor alpha (TNF) while the most abundant E3 protein, E3/19K, inhibits lysis by cytotoxic T cells. E3/19K interacts with class I histocompatibility (MHC) antigens in the rough endoplasmic reticulum, thereby preventing transport of MHC molecules to the cell surface and, consequently, MHC-restricted T cell recognition. In addition, the 10.4K and 14.5K proteins downregulate cell surface expression of the epidermal growth factor receptor. Interestingly, adenovirus-mediated pneumonia in mice is accompanied by induction of TNF, a cytokine known to enhance MHC expression. We previously showed that TNF is unable to restore MHC class I expression in E3/19K transfected cells but rather leads to a further reduction of MHC antigens. This effect correlated with an increased production of E3/19K mRNA and protein. We now find in addition an upregulation of other E3 proteins in transfected as well as in infected cells. This coordinated upregulation of E3 proteins indicates that TNF stimulates the E3 promoter, probably by activating the transcription factor NF-kappa B. Thus, a novel interaction between the immune system and adenovirus is described in which the virus takes advantage of an immune mediator to promote expression of several immunosubversive proteins supporting its escape from immunosurveillance.
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PMID:Tumor necrosis factor alpha increases expression of adenovirus E3 proteins. 853 Jan 42

Legionella pneumophila is an intracellular parasite of protozoa and human phagocytes. To examine adaptation of this bacterium to parasitize protozoa, the sequence of events of the intracellular infection of the amoeba Hartmannella vermiformis was examined. The previously described uptake phenomenon of coiling phagocytosis by human monocytes was not detected. A 1 h postinfection with wild-type strain AA100, mitochondria were observed within the vicinity of the phagosome. At 2.5 h postinfection, numerous vesicles surrounded the phagosomes and mitochondria were in close proximity to the phagosome. At 5 h postinfection, the bacterium was surrounded by a ribosome-studded multilayer membrane. Bacterial multiplication was evident by 8 h postinfection, and the phagosome was surrounded by a ribosome-studded multilayer membrane until 15 h postinfection. The recruitment of organelles and formation of the ribosome-studded phagosome was defective in an isogenic attenuated mutant of L. pneumophila (strain AA101A) that failed to replicate within amoebae. At 20 h postinfection with wild-type strain AA100, numerous bacteria were present in the phagosome and ribosome were not detected around the phagosome. These data showed that, at the ultrastructural level, the intracellular infection of protozoa by L. pneumophila is highly similar to that of infection of macrophages. Immunocytochemical studies provided evidence that at 5 h postinfection the phagosome containing L. pneumophila acquired an abundant amount of the endoplasmic reticulum-specific protein (BiP). Similar to phagosomes containing heat-killed wild-type L. pneumophila, the BiP protein was not detectable in phagosomes containing the mutant strain AA101A. In addition to the absence of ribosomes and mitochondria, the BiP protein was not detected in the phagosomes at 20 h postinfection with wild-type L. pneumophila. The data indicated that the ability of L. pneumophila to establish the intracellular infection of amoebae is dependent on its capacity to reside and multiply within a phagosome surrounded by the rough endoplasmic reticulum. This compartment may constitute a rich source of nutrients for the bacteria and is probably recognized as cellular compartment. The remarkable similarity of the intracellular infections of macrophages and protozoa by L. pneumophila strongly supports the hypothesis that adaptation of the bacterium to the intracellular environment of protozoa may be the mechanism for its ability to adapt to the intracellular environment of human alveolar macrophages and causes pneumonia.
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PMID:The phagosome containing Legionella pneumophila within the protozoan Hartmannella vermiformis is surrounded by the rough endoplasmic reticulum. 878

A mouse model of pulmonary tuberculosis induced by the intratracheal instillation of live and virulent mycobacteria strain H37-Rv was used to examine the relationship of the histopathological findings with the local kinetics production and cellular distribution of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) and transforming growth factor-beta (TGF-beta). The histopathological and immunological studies showed two phases of the disease: acute or early and chronic or advanced. The acute phase was characterized by inflammatory infiltrate in the alveolar-capillary interstitium, blood vessels and bronchial wall with formation of granulomas. During this acute phase, which lasted from 1 to 28 days, high percentages of TNF-alpha and IL-1 alpha immunostained activated macrophages were observed principally in the interstium-intralveolar inflammatory infiltrate and in granulomas. Electron microscopy studies of these cells, showed extensive rough endoplasmic reticulum, numerous lysosomes and occasional mycobacteria. Double labelling with colloid gold showed that TNF-alpha and IL-1 alpha were present in the same cells, but were confined to separate vacuoles near the Golgi area, and mixed in larger vacuoles near to cell membrane. The concentration of TNF-alpha and IL-1 alpha as well as their respective mRNAs were elevated in the early phase, particularly at day 3 when the bacillary count decreased. A second peak was seen at days 14 and 21-28 when granulomas appeared and evolved to full maturation. In contrast, TGF-beta production and numbers of immunoreactive cells were low in comparison with the advanced phase of the disease. The chronic phase was characterized by histopathological changes indicative of more severity (i.e. pneumonia, focal necrosis and extensive interstitial fibrosis) with a decrease in the TNF-alpha and IL-1 alpha production that coincided with the highest level of TGF-beta. The bacillary counts were highest as the macrophages became large, vacuolated foamy cells, and containing numerous bacilli with immunoreactivity to mycobacterial lipids and lipoarabinomannan (LAM). These macrophages displayed poor and scarce TNF-alpha and IL-1 alpha immunostaining but still strong immunoreactivity to TGF-beta. These cytokine production kinetics and the spatial relationship between immunostained cells and lung lesions corroborate the important role of TNF-alpha and IL-1 alpha in the constitution of granulomas and immune protection during the early phase of the infection, and also suggest an important if not primary role for TGF-beta in the immunopathogenesis of the advanced forms of pulmonary tuberculosis.
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PMID:Analysis of the local kinetics and localization of interleukin-1 alpha, tumour necrosis factor-alpha and transforming growth factor-beta, during the course of experimental pulmonary tuberculosis. 917 16

Legionella pneumophila is the cause of Legionnaires' pneumonia. After Internalization by macrophages, it bypasses the normal endocytic pathway and occupies a replicative phagosome bound by endoplasmic reticulum. Here, we show that lysis of macrophages and red blood cells by L. pneumophila was dependent on dotA and other loci known to be required for proper targeting of the phagosome and replication within the host cell. Cytotoxicity occurred rapidly during a high-multiplicity infection, required close association of the bacteria with the eukaryotic cell and was a form of necrotic cell death accompanied by osmotic lysis. The differential cytoprotective ability of high-molecular-weight polyethylene glycols suggested that osmotic lysis resulted from insertion of a pore less than 3 nm in diameter into the plasma membrane. Results concerning the uptake of membrane-impermeant fluorescent compounds of various sizes are consistent with the osmoprotection analysis. Therefore, kinetic and genetic evidence suggested that the apparent ability of L. pneumophila to insert a pore into eukaryotic membranes on initial contact may play a role in altering endocytic trafficking events within the host cell and in the establishment of a replicative vacuole.
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PMID:Evidence for pore-forming ability by Legionella pneumophila. 948 88

Legionella pneumophila first commanded attention in 1976, when investigators from the Centers for Disease Control and Prevention identified it as the culprit in a massive outbreak of pneumonia that struck individuals attending an American Legion convention (). It is now clear that this gram-negative bacterium flourishes naturally in fresh water as a parasite of amoebae, but it can also replicate within alveolar macrophages. L. pneumophila pathogenesis is discussed using the following model as a framework. When ingested by phagocytes, stationary-phase L. pneumophila bacteria establish phagosomes which are completely isolated from the endosomal pathway but are surrounded by endoplasmic reticulum. Within this protected vacuole, L. pneumophila converts to a replicative form that is acid tolerant but no longer expresses several virulence traits, including factors that block membrane fusion. As a consequence, the pathogen vacuoles merge with lysosomes, which provide a nutrient-rich replication niche. Once the amino acid supply is depleted, progeny accumulate the second messenger guanosine 3',5'-bispyrophosphate (ppGpp), which coordinates entry into the stationary phase with expression of traits that promote transmission to a new phagocyte. A number of factors contribute to L. pneumophila virulence, including type II and type IV secretion systems, a pore-forming toxin, type IV pili, flagella, and numerous other factors currently under investigation. Because of its resemblance to certain aspects of Mycobacterium, Toxoplasma, Leishmania, and Coxiella pathogenesis, a detailed description of the mechanism used by L. pneumophila to manipulate and exploit phagocyte membrane traffic may suggest novel strategies for treating a variety of infectious diseases. Knowledge of L. pneumophila ecology may also inform efforts to combat the emergence of new opportunistic macrophage pathogens.
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PMID:Legionella pneumophila pathogesesis: a fateful journey from amoebae to macrophages. 1101 38

Severe acute respiratory syndrome coronavirus (SARS-CoV), a newly identified group 2 coronavirus, is the causative agent of severe acute respiratory syndrome, a life-threatening form of pneumonia in humans. Coronavirus replication and transcription are highly specialized processes of cytoplasmic RNA synthesis that localize to virus-induced membrane structures and were recently proposed to involve a complex enzymatic machinery that, besides RNA-dependent RNA polymerase, helicase, and protease activities, also involves a series of RNA-processing enzymes that are not found in most other RNA virus families. Here, we characterized the enzymatic activities of a recombinant form of the SARS-CoV helicase (nonstructural protein [nsp] 13), a superfamily 1 helicase with an N-terminal zinc-binding domain. We report that nsp13 has both RNA and DNA duplex-unwinding activities. SARS-CoV nsp13 unwinds its substrates in a 5'-to-3' direction and features a remarkable processivity, allowing efficient strand separation of extended regions of double-stranded RNA and DNA. Characterization of the nsp13-associated (deoxy)nucleoside triphosphatase ([dNTPase) activities revealed that all natural nucleotides and deoxynucleotides are substrates of nsp13, with ATP, dATP, and GTP being hydrolyzed slightly more efficiently than other nucleotides. Furthermore, we established an RNA 5'-triphosphatase activity for the SARS-CoV nsp13 helicase which may be involved in the formation of the 5' cap structure of viral RNAs. The data suggest that the (d)NTPase and RNA 5'-triphosphatase activities of nsp13 have a common active site. Finally, we established that, in SARS-CoV-infected Vero E6 cells, nsp13 localizes to membranes that appear to be derived from the endoplasmic reticulum and are the likely site of SARS-CoV RNA synthesis.
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PMID:Multiple enzymatic activities associated with severe acute respiratory syndrome coronavirus helicase. 1514 Sep 59

This paper reports the histopathological findings in the eyes of a 26-year-old female patient diagnosed with systemic lupus erythematosus (SLE) with peripheral neuropathy. The patient had no significant ocular problems. She died of pneumonia after two years of suffering. The eyeballs were procured at autopsy and the retina, choroid and optic nerve processed for light and electron microscopy, and immunohistochemistry for immunoglobulin G (IgG), glial fibrillary acidic protein (GFAP), calbindin and parvalbumin. Histologically, there was haemorrhaging in the retinal nerve fibre layer. Ultrastructurally, the axons of this layer were swollen, and contained an unusual accumulation of microtubules and smooth endoplasmic reticulum. There were degenerative changes in the pericytes and smooth muscle cells of blood vessels. The capillary lumen was partially obliterated, and contained IgG, which was also detected throughout the choroid and wall of choroidal arterioles. The latter and Bruch's membrane showed fibrin deposits. The optic nerve showed infiltrated mononuclear cells near the degenerated axons, these axons lacked immunoreactivity to calbindin and parvalbumin. Compared to the control, the connective tissue sheaths of the central retinal vessels possessed a vast number of proliferated fibroblast cells, and trichrome staining showed transmural vessel scarring. Dense GFAP immunoreactivity was observed surrounding the vessel wall. These pathological changes are due to impaired blood circulation caused by haemorrhaging and vasculitis, and vessel occlusion by fibrin. The nature of the changes observed tends to indicate that a regular, thorough ophthalmic examination should be conducted even in the absence of significant ocular symptoms in SLE.
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PMID:Histopathological changes in the eyes in systemic lupus erythematosus: an electron microscope and immunohistochemical study. 1573 40

A case of inherited homozygous complement C3 deficiency (C3D) in a patient with systemic lupus erythematosus (SLE) and the molecular basis for this deficiency are reported. A 22-year-old Japanese male was diagnosed as having SLE and his medical history revealed recurrent tonsillitis and pneumonia. He was diagnosed as having C3D because of undetectable serum C3 level. His parents were consanguineous. Sequence analysis of C3D cDNA revealed a homozygous deletion of exon 39 (84bp). A single base substitution (AG to GG) in the 3'-splice acceptor site of intron 38 was identified by sequencing the genomic DNA. Expression of C3Delta(ex39) cDNA, the C3cDNA lacking exon 39, in COS-7 cells revealed that C3Delta(ex39) was retained in endoplasmic reticulum-Golgi intermediate compartment because of defective secretion. These data indicate that a novel AG-->GG 3'-splice acceptor site mutation in intron 38 caused aberrant splicing of exon 39, resulting in defective secretion of C3.
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PMID:Molecular analysis of a novel hereditary C3 deficiency with systemic lupus erythematosus. 1578 Dec 64

Feed amended with autoclaved culture material (CM) of Fusarium proliferatum containing fumonisin B1 (FB1) (61-546 ppm), fumonisin B2 (FB2) (14-98 ppm) and moniliformin (66-367 ppm) was given to 228 male chicks in three separate feeding trials. In a fourth feeding trial, purified FB1 (125 and 274 ppm) and moniliformin (27 and 154 ppm) were given separately and in combination (137 and 77 ppm, respectively). Chicks that died during the trial periods, survivors and controls were subjected to postmortem examination. Specimens (liver, kidney, pancreas, lung, brain, intestine, testis, bursa of Fabricius, heart and skeletal muscle) were examined grossly and preserved for subsequent histopathologic and ultrastructural examination. Prominent gross lesions in affected birds fed diets amended with CM or purified FB1 and moniliformin included ascites, hydropericardium, hepatopathy, nephropathy, cardiomyopathy, pneumonitis, gizzard ulceration, and enlarged bursa of Fabricius filled with caseous material. The various concentrations of FB1 and moniliformin in the amended rations produced well-defined dose-response lesions in all groups in all four trials. Histopathologic changes included hemorrhage, leucocytic infiltration, fatty change or infiltration, individual cell necrosis and fibrosis in liver, kidneys, lungs, heart, intestines, gizzard, bursa of Fabricius and pancreas. Edema and hemorrhage were prominent in brains of treated birds. Ultrastructural changes included cytoplasmic and nuclear enlargement of cells in affected liver, lungs, kidneys, heart and pancreas. There were thickened membranes of the smooth endoplasmic reticulum, dilation of the rough endoplasmic reticulum with loss of ribosomes and vacuolated or deformed mitochondria.
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PMID:Comparative pathologic changes in broiler chicks on feed amended with Fusarium proliferatum culture material or purified fumonisin B1 and moniliformin. 1598 42

The ability of Legionella pneumophila to cause pneumonia is dependent on intracellular replication within alveolar macrophages. The Icm/Dot secretion apparatus is essential for the ability of L. pneumophila to evade endocytic fusion, to remodel the phagosome by the endoplasmic reticulum (ER), and to replicate intracellularly. Protozoan and macrophage infectivity (pmi) mutants of L. pneumophila, which include 11 dot/icm mutants, exhibit defects in intracellular growth and replication within both protozoa and macrophages. In this study we characterized one of the pmi loci, pmiA. In contrast to the parental strain, the pmiA mutant is defective in cytopathogenicity for protozoa and macrophages. This is a novel mutant that exhibits a partial defect in survival within U937 human macrophage-like cells but exhibits a severe growth defect within Acanthamoeba polyphaga, which results in elimination from this host. The intracellular defects of this mutant are complemented by the wild-type pmiA gene on a plasmid. In contrast to phagosomes harboring the wild-type strain, which exclude endosomal-lysosomal markers, the pmiA mutant-containing phagosomes acquire the late endosomal-lysosomal markers LAMP-1 and LAMP-2. In contrast to the parental strain-containing phagosomes that are remodeled by the ER, there was a decrease in the number of ER-remodeled phagosomes harboring the pmiA mutant. Among several Legionella species examined, the pmiA gene is specific for L. pneumophila. The predicted amino acid sequence of the PmiA protein suggests that it is a transmembrane protein with three membrane-spanning regions. PmiA is similar to several hypothetical proteins produced by bacteria with a type IV secretion apparatus. Importantly, the defect in pmiA abolishes the pore-forming activity, which has been attributed to the Icm/Dot type IV secretion system. However, the mutant is sensitive to NaCl, and this sensitivity is abrogated in the icm/dot mutants. These results suggest that PmiA is a novel virulence factor that is involved in intracellular survival and replication of L. pneumophila in macrophages and protozoan cells.
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PMID:Characterization of Legionella pneumophila pmiA, a gene essential for infectivity of protozoa and macrophages. 1617 98


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