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)

A 47-year-old man was admitted to our hospital in June 1997 because of nasal bleeding. He presented with anemia in addition to physical characteristics of Werner's syndrome (WS). Peripheral blood examination disclosed pancytopenia with 4% blasts. Bone marrow aspiration was a dry tap; biopsy specimens revealed myelofibrosis. Chromosomal analysis of peripheral blood revealed hypodiploidy with complex abnormalities including -5 and del(7)(q21). Serum levels of PDGF, FGF, and TGF beta 1 were normal. A diagnosis of acute myelofibrosis was made. The patient's condition became quickly deteriorated and he died of pneumonia in October 1997. In the literature, we found 6 reported cases of myelofibrosis associated with WS. Considering that only approximately 1,100 cases of WS have been reported so far, the incidence of myelofibrosis in WS seems relatively high. This case suggested a link between WS and myelofibrosis, and the mechanism of myelofibrosis in WS was discussed.
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PMID:[Werner's syndrome associated with acute myelofibrosis]. 1072 41

Cytokine levels in bronchoalveolar lavage fluid from patients with eosinophilic pneumonia (n = 7), allergic alveolitis (n = 11), (cryptogenic) fibrosing alveolitis (n = 8), sarcoidosis (n = 10) were determined, as well as levels in control samples from healthy non-smoking volunteers (n = 11). Fibronectin levels were increased in all the patient categories, the highest absolute levels of fibronectin (100-fold increase) being found in eosinophilic pneumonia and allergic alveolitis. TGF-beta (transforming growth factor-beta) was significantly elevated in allergic alveolitis only. There was a significant difference between allergic alveolitis on the one hand and both sarcoidosis and fibrosing alveolitis on the other. Tumour necrosis factor-alpha (TNF-alpha) was significantly increased in eosinophilic pneumonia and allergic alveolitis; allergic alveolitis and fibrosing alveolitis differed significantly in this respect. Platelet-derived growth factor-BB (PDGF-BB) levels were significantly elevated in allergic alveolitis and fibrosing alveolitis. It was found that the level of PDGF-BB was significantly decreased in the case of sarcoidosis, with no overlapping with allergic alveolitis or fibrosing alveolitis. Interferon-gamma (IFN-gamma) was decreased in all patient categories. A significant difference in extent of the decrease was found between allergic alveolitis and sarcoidosis. The interstitial lung diseases thus differed in the pattern of cytokines expressed, indicating that these cytokines could well be a part of the pathogenic process, and also that the measurement of cytokine levels could be diagnostically useful.
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PMID:Studies of cytokine levels in bronchoalveolar fluid lavage from patients with interstitial lung diseases. 1272 67

Although pulmonary fibrosis is a frequent and serious consequence of radiotherapy for thoracic malignant diseases such as lung cancer, the pathogenesis of this radiation-induced lung disorder remains unclear. To clarify the mechanisms underlying radiation pneumonitis and pulmonary fibrosis, we investigated the expression of platelet-derived growth factor receptor (PDGFR) on fibroblasts obtained from irradiated rat lungs and on control fibroblasts. Whole lungs of male Wistar rats were irradiated with a single dose of 15 Gy, and lung fibroblasts were isolated at 4 weeks after the irradiation. The chemotactic response of irradiated lung fibroblasts to PDGF-BB was significantly higher than that of control lung fibroblasts, whereas there was no significant difference between irradiated lung fibroblasts and control lung fibroblasts in the response to PDGF-AA. Receptor binding assay showed more specific binding sites for PDGF-BB on irradiated lung fibroblasts than on control lung fibroblasts, and the displacement of (125)I-labeled PDGF binding to fibroblasts by unlabeled PDGF showed that (125)I-labeled PDGF-BB was displaced by PDGF-BB but not by PDGF-AA. These results suggest that the increased binding sites for PDGF-BB on irradiated lung fibroblasts correspond mainly to PDGFRB. Scatchard analysis of the saturation data demonstrated an approximately twofold increase both in the number of PDGF-BB binding sites and in the binding affinity in irradiated lung fibroblasts compared to that in control lung fibroblasts. Those results suggest that the increased chemotactic response of irradiated lung fibroblasts to PDGF-BB is related to the overexpression of PDGFRB, which may have an important role in the pathogenesis of radiation-induced pneumonitis and pulmonary fibrosis.
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PMID:Increased binding and chemotactic capacities of PDGF-BB on fibroblasts in radiation pneumonitis. 1275 64

Lung fibrosis is the end-point of numerous lung disorders induced by a pneumonia or by a variety of different noxes, one of which is the cytostatic drug bleomycin (BLM). Fibrosis is characterized by excessive extracellular matrix accumulation. Macrophage-fibroblast interactions are suggested to play an important role in the development of this disease. The present study was addressed to investigate one possible pathway of this interaction, the influence of soluble mediators produced by BLM-stimulated macrophages on lung fibroblast collagen synthesis and modification. Conditioned media (CM) of BLM-exposed macrophages of the cell line NR8383 submitted to rat lung fibroblast cultures increased the activity of prolyl 4-hydroxylase (P4H) in fibroblasts in a dose dependent manner. CM of stimulated macrophages increased the collagen concentration in fibroblast culture supernatant. The level of mRNAs specific for the alpha-subunit of P4H and that for alpha1(I) collagen were found to be increased by about two-fold, that for lysyloxidase (LO) by about 2.5-fold in fibroblasts cultured in CM of stimulated macrophages. Pre-incubation of CM of BLM-exposed macrophages with neutralizing antibodies against TGF-beta or against PDGF resulted in a partial reversal of the increasing effect of the CM on P4H- and LO-activities in fibroblasts. Both growth factors, TGF-beta and PDGF, added to fibroblast cultures led to significant increases of P4H activity in the treated cells. We conclude that TGF-beta and PDGF produced by stimulated macrophages are involved in the regulation of the expression of alpha1(I) collagen, of P4H-alpha-subunit and LO in lung fibroblasts. The results indicate that this is not a direct effect but involves the action of a so far unidentified mediator responsible for autocrine stimulation of collagen production.
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PMID:Evidence for the involvement of TGF-beta and PDGF in the regulation of prolyl 4-hydroxylase and lysyloxidase in cultured rat lung fibroblasts. 1470 71

We present a case of metastatic pulmonary calcification. Histologically, deposition of hematoxyphilic materials was seen along the alveolar and vessel walls. Fibrous tissues were also seen within the alveolar lumens, resulting in intra-alveolar fibrous pneumonia. Immunohistochemically, CD34-positive perivascular adventitial fibroblasts were seen in normal alveolar septa, whereas no myofibroblasts were observed. In contrast, perivascular adventitial fibroblasts were absent in the alveolar septa of the lesion of metastatic calcification, whereas many myofibroblasts were present in the fibrous tissue within alveolar lumens. No positive cells for TGF-(beta1) were observed in the lesion of metastatic calcification, but positive cells for PDGF-BB were focally seen in adveolar epithelial cells. Finally, many myofibroblasts appear in the alveolar lumens of metastatic pulmonary calcification, and we suggest that these myofibroblasts may be derived from CD34-positive perivascular adventitial fibroblasts and PDGF-BB may be involved in the pathogenesis of surrounding fibrosis.
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PMID:Myofibroblasts in the stroma of metastatic pulmonary calcification in a patient with chronic renal failure. 1699 27

The patient was a 64-year-old woman who had undergone partial enterectomy for a small intestinal tumor in August 2005, and gastrointestinal stromal tumor (GIST) was diagnosed. Administration of imanitib mesylate was initiated as postoperative chemotherapy in November 2005. In February 2006, a slight ground-glass opacity was noted in the right lower lobe on chest CT. In April, cough and dyspnea appeared, and non-segmental reticular ground-glass opacity was noted in bilateral lung fields. Drug-induced pneumonia associated with imatinib mesylate was suspected based on the clinical course, and administration of imatinib mesylate was discontinued. Oral administration of 30mg prednisolone was initiated, and the symptoms and shadows on X-ray films improved. The steroid dose was gradually reduced, and recovery of the patient was smooth. Imatinib mesylate is anticipated to be a good potential therapeutic drug for interstitial pneumonia because it blocks PDGF receptors. However, the risk of imatinib-induced interstitial pneumonia should be noticed.
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PMID:[Drug-induced pneumonia that may have been caused by imatinib mesylate administered for gastrointestinal stromal tumor]. 1768 71

The pathogenesis of pulmonary fibrosis remains unclear. The receptor for advanced glycation end-products (RAGE) is a multi-ligand receptor known to be involved in the process of fibrotic change in several organs, such as peritoneal fibrosis and kidney fibrosis. The aim of this study was to examine the contribution of RAGE during the acute inflammation and chronic fibrotic phases of lung injury induced by intratracheal instillation of bleomycin in mice. Bleomycin-induced lung fibrosis was evaluated in wild-type and RAGE-deficient (RAGE-/-) mice. Bleomycin administration to wild-type mice caused an initial pneumonitis that evolved into fibrosis. While RAGE-/- mice developed a similar early inflammatory response, the mice were largely protected from the late fibrotic effects of bleomycin. The protection afforded by RAGE deficiency was accompanied by reduced pulmonary levels of the potent RAGE-inducible profibrotic cytokines transforming growth factor (TGF)-beta and PDGF. In addition, bleomycin administration induced high mobility group box 1 (HMGB-1) production, one of the ligands of RAGE, from inflammatory cells that accumulated within the air space. Coculture with HMGB-1 induced epithelial-mesenchymal transition (EMT) in alveolar type II epithelial cells from wild-type mice. However, alveolar type II epithelial cells derived from RAGE-/- mice did not respond to HMGB-1 treatment, such that the RAGE/HMGB-1 axis may play an important role in EMT. Also, bleomycin administration induced profibrotic cytokines TGF-beta and PDGF only in wild-type mouse lungs. Our results suggested that RAGE contributes to bleomycin-induced lung fibrosis through EMT and profibrotic cytokine production. Thus, RAGE may be a new therapeutic target for pulmonary fibrosis.
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PMID:The role of the receptor for advanced glycation end-products in lung fibrosis. 1795 14

The strain designated Chlamydia trachomatis serovar L2 that was used for experiments in this paper is Chlamydia muridarum, a species closely related to C. trachomatis (and formerly termed the Mouse Pneumonitis strain of C. trachomatis). This conclusion was verified by deep sequencing and by PCR using species-specific primers. All data presented in the results section that refer to C. trachomatis should be interpreted as referring to C. muridarum. Since C. muridarum TARP lacks the consensus tyrosine repeats present in C. trachomatis TARP, we cannot make any conclusions about the role of TARP phosphorylation and C. muridarum entry. However, the conclusion that C. trachomatis L2 TARP is a target of Abl kinase is still valid as these experiments were performed with C. trachomatis L2 TARP [corrected]. To elucidate the mechanisms involved in early events in Chlamydia trachomatis infection, we conducted a large scale unbiased RNA interference screen in Drosophila melanogaster S2 cells. This allowed identification of candidate host factors in a simple non-redundant, genetically tractable system. From a library of 7,216 double stranded RNAs (dsRNA), we identified approximately 226 host genes, including two tyrosine kinases, Abelson (Abl) kinase and PDGF- and VEGF-receptor related (Pvr), a homolog of the Platelet-derived growth factor receptor (PDGFR). We further examined the role of these two kinases in C. trachomatis binding and internalization into mammalian cells. Both kinases are phosphorylated upon infection and recruited to the site of bacterial attachment, but their roles in the infectious process are distinct. We provide evidence that PDGFRbeta may function as a receptor, as inhibition of PDGFRbeta by RNA interference or by PDGFRbeta neutralizing antibodies significantly reduces bacterial binding, whereas depletion of Abl kinase has no effect on binding. Bacterial internalization can occur through activation of PDGFRbeta or through independent activation of Abl kinase, culminating in phosphorylation of the Rac guanine nucleotide exchange factor (GEF), Vav2, and two actin nucleators, WAVE2 and Cortactin. Finally, we show that TARP, a bacterial type III secreted actin nucleator implicated in entry, is a target of Abl kinase. Together, our results demonstrate that PDGFRbeta and Abl kinases function redundantly to promote efficient uptake of this obligate intracellular parasite.
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PMID:RNA interference screen identifies Abl kinase and PDGFR signaling in Chlamydia trachomatis entry. 1836 71

The aim of the investigation was to study the specific features of morphological manifestations and the molecular bases of lung tissue remodeling in progressive idiopathic pulmonary fibrosis (IPF). The investigation used open and transbronchial biopsy specimens from 110 patients with IPE/idiopathic pneumonia syndrome in 1997 to 2008. Immunohistochemical analysis was carried out on serial paraffin-embedded lung tissue slices from 20 patients with IPF and 20 control patients. Immunohistochemical staining for the detection of antigens in the paraffin-embedded slices was made using the antibodies to MMP-1, MMP-2, MMP-7, TIMP-4, Apo-CAS, PCNA, PDGF, EGFR, CD34, and SMA. Nonparametric statistical methods were employed. Our findings have indicated that in early-stage IPF, there are proliferating myofibroblasts in the myofibroblastic foci, mainly in the bronchioloalveolar transitional zone (BATZ), which express PCNA and PDGF. Both in early- and late-stage IPF, there were signs of increased readiness of the alveolar and bronchiolar epithelium of BATZ for apoptosis, as judged from Apo-CAS expression. At the same time no Apo-CAS expression was recorded in the myofibroblasts. In the early stage of the disease, the expression of MMP-1, MMP-2, MMP-7, and TIMP-4 in the epitheliocytes, macrophages, fibroblasts, and myofibroblasts was higher than that in the late stage of IPF. At the same time, late-stage IPF was characterized by the higher expression in all lung tissue cells than was early-stage IPF. There was also a significant increase in vessel density in both early and late stages of IPF as compared with intact lung tissue particularly in the BATZ in the control group. Thus, lung tissue remodeling in the progression of IPF from the early to late stage of the disease comprises interrelated processes that are largely localized in the BATZ, such as immune inflammation with pathological reparation, neoangiogenesis, apoptosis, and proliferation of epitheliocytes and myofibroblasts, which lead to the development of interstitial fibrosis and adenomatosis of the lung.
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PMID:[The mechanism of lung tissue remodeling in the progression of idiopathic pulmonary fibrosis]. 2108 35