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

The thrombospondins are a family of extracellular calcium-binding proteins that modulate cellular phenotype. Thrombospondin-1 (TSP-1) reportedly regulates cellular attachment, proliferation, migration, and differentiation in vitro. To explore its function in vivo, we have disrupted the TSP-1 gene by homologous recombination in the mouse genome. Platelets from these mice are completely deficient in TSP-1 protein; however, thrombin-induced platelet aggregation is not diminished. TSP-1-deficient mice display a mild and variable lordotic curvature of the spine that is apparent from birth. These mice also display an increase in the number of circulating white blood cells, with monocytes and eosinophils having the largest percent increases. The brain, heart, kidney, spleen, stomach, intestines, aorta, and liver of TSP-1-deficient mice showed no major abnormalities. However, consistent with high levels of expression of TSP-1 in lung, we observe abnormalities in the lungs of mice that lack the protein. Although normal at birth, histopathological analysis of lungs from 4-wk-old TSP-1-deficient mice reveals extensive acute and organizing pneumonia, with neutrophils and macrophages. The macrophages stain for hemosiderin, indicating that diffuse alveolar hemorrhage is occurring. At later times, the number of neutrophils decreases and a striking increase in the number of hemosiderin-containing macrophages is observed associated with multiple-lineage epithelial hyperplasia and the deposition of collagen and elastin. A thickening and ruffling of the epithelium of the airways results from increasing cell proliferation in TSP-1-deficient mice. These results indicate that TSP-1 is involved in normal lung homeostasis.
 ...
PMID:Thrombospondin-1 is required for normal murine pulmonary homeostasis and its absence causes pneumonia. 948 68

The diagnosis of ventilator-associated pneumonia (VAP) is difficult for several reasons. Firstly, clinical markers show a large percentage of false-positive and false-negative results. Secondly, microbiological diagnosis based on quantitative cultures of protected specimen brush (PSB), bronchoalveolar lavage (BAL), and endotracheal aspirates also present false-positive and false-negative results. Furthermore, definite results are delayed for 48-72 hours. For all these reasons it would be an advantage to have a biological marker of ventilator-associated pneumonia in clinical practice. Since clinical features of pneumonia in mechanically ventilated patients are neither specific nor sensitive, rapid markers of pneumonia might be of great assistance to the clinician in deciding whether to start an empiric antibiotic regimen. A marker of ventilator-associated pneumonia could be a rapid alternative diagnostic method which permits the definite diagnosis of pneumonia. Accordingly, specific markers of VAP, namely the presence of intracellular microorganisms, the detection of elastin fibres, the antibody-coated bacteria test, the level of endotoxin in bronchoalveolar lavage fluid, the local production of interleukin-8, the levels of lactate dehydrogenase, and decreased surfactant protein A, may be important as they can provide a rapid diagnosis of VAP. Among the markers alluded to above, the search for intracellular bacteria in polymorphonuclear leukocytes or macrophages is the most widely validated technique with an excellent specificity, provided that prior antibiotics are not given. However, this technique has its own limitations; it requires a considerable time effort for the microbiologist, and also compels the performance of BAL, a technique not always harmless to the patient.
 ...
PMID:Markers of ventilator-associated pneumonia. 1015 May 59

Human neutrophil elastase (HNE), an enzyme secreted by activated neutrophils, can bind to and degrade extracellular matrix including human lung elastin. This protease is believed to play an important role in several destructive processes including pulmonary emphysema. In this study, we hypothesized that an alveolar macrophage (AM) product or products may interact with neutrophil elastase (NE) and modulate its binding to elastin. Elastase binding to elastase was evaluated by a modified elastase functional assay using a synthetic substrate. Supernatants from cultured AM inhibited elastase binding to elastin at a dose-dependent manner without inhibiting functional elastase activity. The AM products had a heterogeneous molecular weight ranging from 440,000 to 54,000. The activity was heat-stable, but was lost after ultracentrifugation. After lipid fractionation, neither the aqueous nor the lipid fractions contained activity, suggesting that the factor may be a lipid complex. Culture supernatants from smokers' AM released significantly higher amounts of the factor than nonsmokers. In addition, high-molecular-weight elastase was present in bronchoalveolar lavage fluid (BALF) obtained from patients with pneumonia. Most of the in vivo high-molecular-weight elastase was lost after lipid extraction. In conclusion, macrophages release a factor or factors, probably lipid, which can interact with NE and inhibit its binding to human lung elastin without inhibiting elastase activity. This macrophage-derived factor may play a role in protecting the lung from NE by partitioning elastase into the airspace and thus protecting the interstitial connective tissue matrix from elastase degradation.
 ...
PMID:Modulation of elastase binding to elastin by human alveolar macrophage-derived lipids. 1047

We report a case of Pneumocystis carinii pneumonia (PCP) in which acute lung tissue destruction progressed within a few days to form multiple bullae in a patient with no HIV-1 infection. A 59-year-old man with mild pulmonary emphysema had been followed for two years. He had smoked 40 cigarettes per day for forty years. Six months before, bronchogenic carcinoma had been diagnosed in the lower right lung. After chemotherapy and radiotherapy, he had a sudden onset of high fever with respiratory failure. PCP was diagnosed by examination of the bronchoalveolar lavage fluid (BALF), and the patient was treated with intravenously administered trimethoprim-sulphamethoxazole (TMP-SMX) and methylprednisolone. His chest radiograph was not typical for PCP, and showed no diffuse ground-grass or fine granular opacities. A high-resolution CT of the chest revealed a low attenuation area consistent with severe emphysematous alterations and progressively enlarging bullae. A few cases have been reported of progressive pulmonary cystic disease associated with PCP pneumonia in patients with AIDS, in which the cause of bulla formation was thought to be lung parenchyma destruction induced by HIV itself, or increased elastase release from HIV-infected macrophages. The present case demonstrated that HIV infection was not an essential factor in the development of bullous changes. In a patient with a long history of smoking and emphysema, PCP may trigger-macrophage activation and an excessive release of leukocyte elastase, leading to elastin destruction in the alveoli.
 ...
PMID:[A case of acute progressive pulmonary cystic disease associated with Pneumocystis carinii pneumonia in a non-HIV-infected patient]. 1157 32

124 sera of children with chronic bronchitis, chronic pneumonia, bronchial asthma, exogenic allergic alveolitis, congenital developmental defects of the lungs and the syndrome of the situs inversus of organs were examined with a view to study the state of humoral immunity to tissues. The study was carried out by means of the enzyme-linked immunosorbent assay with the use of collagen, elastin, DNA (native and denaturated), membrane antigens of the lung, the liver, the small intestine and the large intestine. Among all groups of patients autoimmune disturbances, manifested by a rise in the level of autoantibodies of different specificity, were registered. The degree of manifestation of autoimmune disturbances depended on the kind of pathology. After treatment a decrease in the level of autoantibodies was registered in the examinees.
 ...
PMID:[Autoantibodies in children with chronic inflammatory lung diseases]. 1188 97

Respiratory colonization of preterm infants with Ureaplasma urealyticum is a significant risk factor for bronchopulmonary dysplasia, a chronic lung disease characterized by arrest of alveolar development, variable interstitial fibrosis, and disordered elastic fibers in the distal airspaces. As indicated in previous studies, moderate to severe fibrosis is a hallmark of pathology in the Ureaplasma-infected preterm lung. To further characterize the preterm lung's response to Ureaplasma, lung specimens from 4 gestational controls (GC), 12 other pneumonia and 5 Ureaplasma-infected infants were analyzed by immunohistochemistry for alpha-smooth muscle actin (alphaSMA) and transforming growth factor beta1 (TGFbeta1), Hart's elastin staining, and in situ hybridization for tropoelastin (TE) expression. Cells positive for alphaSMA were observed in thickened, extensive bundles surrounding terminal airspaces in Ureaplasma and other pneumonia cases compared to individual myofibroblasts in GC. The myofibroblast pattern correlated with the severity of fibrosis, but not duration of ventilation. Transforming growth factor beta1 immunostaining was primarily localized to alveolar macrophages and was increased in Ureaplasma more than in other pneumonia cases. Elastic fibers and TE-expressing cells were spatially limited to emerging septal tips in GC. In pneumonia cases, increased deposition of elastic fibers was observed surrounding terminal airspaces, but TE expression was similar to GC. In Ureaplasma specimens, accumulation of elastic fibers correlated with duration of ventilation, and TE expression was extensive throughout the walls of terminal airspaces. These findings suggest that Ureaplasma is associated with alveolar macrophage TGFbeta1 immunostaining and myofibroblast proliferation contributing to abnormal septation, interstitial fibrosis, and a prolonged and strong elastogenic response in the preterm lung.
 ...
PMID:Disordered pulmonary myofibroblast distribution and elastin expression in preterm infants with Ureaplasma urealyticum pneumonitis. 1682 87

Elastin fibres in sputum have been described as a more sensitive marker of pulmonary necrosis than plain chest X-rays. This study aimed to determine the prevalence of elastin fibres using non-directed non-protected mini-bronchoalveolar lavage (BM-BAL) in mechanically ventilated patients in the intensive care unit. Patients admitted to the general intensive care unit of a tertiary referral hospital requiring more than 48 hours of mechanical ventilation had surveillance BM-BAL performed on admission and were then examined weekly using potassium hydroxide wet preparations for the presence of elastin fibres. All positive and a random selection of 16 negative preparations from patients with acute respiratory distress syndrome or pneumonia were fixed and examined using Weigert's staining method for elastin. Of 412 patients enrolled, 130 (32%) had pneumonia on admission, 50 (12%) developed 58 episodes of ventilator-associated pneumonia and acute respiratory distress syndrome was diagnosed in 86 patients (21%). No chest X-ray showed cavitating infiltrates. Of 985 specimens examined, only seven had elastin fibres. Elastin fibres are uncommonly found using BM-BAL in general screening, acute respiratory distress syndrome or pneumonia in the intensive care unit, the incidence too low to be a useful indicator of pulmonary necrosis.
 ...
PMID:Use of elastin fibres detected in non-directed low volume bronchial lavage in ventilated ICU patients. 1744 6

Asbestosis has long been defined as a diffuse interstitial "fibrotic" process, in similarity to other chronic interstitial pulmonary diseases. To address the hypothesis (which was based on morphological nuances) that the interstitial connective tissue response in asbestosis may be fibroelastotic rather than fibrotic, a comparative characterization of the connective response in cases of asbestosis and other forms of interstitial lung disease was performed. Archival open lung biopsies or autopsy specimens of pulmonary diseases featuring interstitial connective tissue abnormalities (15 of asbestosis, 21 of organizing pneumonia, 15 usual interstitial pneumonitis/idiopathic pulmonary fibrosis [IPF], 9 organizing diffuse alveolar damage, 9 "nonspecific" interstitial pneumonitis, 4 sarcoidosis, 3 each of desquamative interstitial pneumonia and chronic amiodarone toxicity, 2 cryptogenic organizing pneumonias, and 1 each of chronic hypersensitivity pneumonitis and chronic eosinophilic pneumonitis [85 total]) were stained histochemically with hematoxylin and eosin, Perl's method, Gomori's trichrome procedure, and the Verhoeff-van Gieson technique. Representative subsets of the cases (n = 20) were also studied immunohistologically using an antibody to elastin. Fibroelastosis in each of the samples was assessed for the degree of response and its location using a 3-tiered scale. The degree of fibroelastosis in the 15 cases of asbestosis was variable, with the pattern being peribronchial and perivascular in all instances; at least 2 asbestos bodies were identified in fibroelastotic foci in each of the 15 cases as highlighted with Perl's stain. Forty-seven cases of nonasbestotic lung disease (71%) showed interstitial fibrosis with a variable (usually modest) amount of admixed elastic tissue; when present, elastic fibers were distributed in a diffuse interstitial pattern, with or without perivascular accentuation. All cases of IPF also showed areas of fibroelastosis, but those foci were confined to regions of overt "honeycomb" change. No asbestos bodies were seen in any disease except asbestosis, and a predominantly peribronchial pattern of fibroelastosis was not identified in any nonasbestotic interstitial lung disease in this study. The authors conclude that the types and patterns of pulmonary connective tissue response in interstitial lung diseases may provide additional diagnostic clues to the presence of asbestosis.
 ...
PMID:Asbestosis: demonstration of distinctive interstitial fibroelastosis: a pilot study. 1975 5

Solitary pulmonary nodules (SPN) have become increasingly prevalent and diagnostic management remains challenging. We demonstrate a novel technique in which probe-based confocal endomicroscopy (pCLE) could be performed to microimage SPN in vivo and in real-time. Two confocal wavelengths (488 and 660 nm with methylene blue (MB)) were used for elastin network and cellular imaging, respectively using pCLE in conjunction with r-EBUS and virtual navigation. In the first case, the 1-mm Alveoflex was used to image a metastatic melanoma in a subcentimetric nodule in the right middle lobe. In the next case, a malignant 2-cm nodule in the posterior segment of the upper lobe was imaged using the smaller 0.6-mm Cholangioflex. Lastly, we present a benign case revealing confocal characteristics of a nodular lipid pneumonitis. This reports for the first time the feasibility and utility of pCLE in vivo microimaging of SPN using either the Alveoflex or Cholangioflex miniprobes in addition to 660 nm/MB imaging.
 ...
PMID:A Novel Method for In Vivo Imaging of Solitary Lung Nodules Using Navigational Bronchoscopy and Confocal Laser Microendoscopy. 2621 23

Repeated cycles of infections, caused mainly by Pseudomonas aeruginosa, combined with a robust host immune response and tissue injury, determine the course and outcome of cystic fibrosis (CF) lung disease. As the disease progresses, P. aeruginosa adapts to the host modifying dramatically its phenotype; however, it remains unclear whether and how bacterial adaptive variants and their persistence influence the pathogenesis and disease development. Using in vitro and murine models of infection, we showed that P. aeruginosa CF-adaptive variants shaped the innate immune response favoring their persistence. Next, we refined a murine model of chronic pneumonia extending P. aeruginosa infection up to three months. In this model, including CFTR-deficient mice, we unveil that the P. aeruginosa persistence lead to CF hallmarks of airway remodelling and fibrosis, including epithelial hyperplasia and structure degeneration, goblet cell metaplasia, collagen deposition, elastin degradation and several additional markers of tissue damage. This murine model of P. aeruginosa chronic infection, reproducing CF lung pathology, will be instrumental to identify novel molecular targets and test newly tailored molecules inhibiting chronic inflammation and tissue damage processes in pre-clinical studies.
...
PMID:Tracking the immunopathological response to Pseudomonas aeruginosa during respiratory infections. 2688 59


<< Previous 1 2 3 Next >>