Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0037116 (silicosis)
 1,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

58 miners affected by VWF were studied by some immunological tests: electrophoresis, quantitantive immunoglobulin determination, latex test. C3c, C3PA and C4, cryoglobulin, ANA and ati-DNA antibody, L.E. cell. Slight hyperimmunoglobulinaemia G was observed in 31% of cases; this abnormality was significantly more frequent in patients also suffering for pulmonary silicosis. Authors indicate pneumoconiosis as an important confounding variable, which importance for epidemiological studies has not yet satisfactorily assessed.
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PMID:[Immunological changes in disease caused by vibrating instruments. Preliminary tests]. 718 41

The carcinogenic effects of crystalline silica in rat lungs were extensively demonstrated by many experimental long-term studies, showing a marked predominance for adenocarcinomas originating from alveolar type II cells and associated with areas of pulmonary fibrosis (silicosis). In contrast with its effects in rats, silica did not induce alveolar type II hyperplasia and lung tumors in mice and hamsters, pointing to a critical role for host factors. Using these animal models, we are investigating the role of cytokines and other cellular mediators on the proliferation of alveolar type II cells. Immunohistochemical localization of TGF-beta 1 precursor in alveolar type II cells adjacent to silicotic granulomas was shown to occur in rats, but not in mice, and hamsters, suggesting a pathogenetic role for this regulatory growth factor. Recent investigations in our laboratory on the biologic mechanisms of crystalline silica included determination of anionic sites on crystalline silica surfaces by binding of the cationic dye Janus Green B; binding of crystalline silica to DNA, demonstrated by infrared spectrometry; production of oxygen radicals by crystalline silica in aqueous media; induction of DNA strand breakage and base oxidation in vitro and its potentiation by superoxide dismutase and by hydrogen peroxide; and induction by crystalline silica of neoplastic transformation and chromosomal damage in cells in culture. On the basis of these in vitro studies, we propose that DNA binding to crystalline silica surfaces may be important in silica carcinogenesis by anchoring DNA close to sites of oxygen radical production on the silica surface, so that the oxygen radicals are produced within a few A from their target DNA nucleotides.
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PMID:Mechanisms of carcinogenesis by crystalline silica in relation to oxygen radicals. 770 91

A 60-year-old stonemason, suffering for many years from joint pains and exertional dyspnoea, developed a high fever with weight loss. Physical examination revealed reddening of light-exposed skin areas, fine rales and overly warm and reddened hand and knee joints. Abnormal laboratory findings were increased erythrocyte sedimentation rate of 66 mm/h, C-reactive protein concentration of 1 mg/dl, haemoglobin of 9.4 g/dl and white cell count of 3300/microliters. Urine contained albumin (100 mg/dl) and cylinders. Titres of both antinuclear and anti-ds-DNA antibodies were elevated (1:2560 and > 97 U/ml, respectively). The chest radiography showed enlarged hili, as well as reticular and nodular shadows which histologically showed silicosis. Systemic lupus erythematodes was diagnosed and the patient was treated with prednisone (2 mg/kg daily), the dosage being reduced to 12 mg daily within 3 months. When the joint pains recurred, azathioprine (50 mg daily) was added for 24 months. At present he is receiving prednisone (12 mg daily) and there has been no recurrence for 4 years.
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PMID:[Systemic lupus erythematosus and silicosis]. 785 45

Tetrandrine, an herbal drug, has been employed in China to treat pulmonary fibrosis. To date, the mechanisms governing the antifibrotic action of tetrandrine are unknown. The present study employs a fibroblast mitogenic assay to determine whether tetrandrine directly inhibits the ability of fibroblasts to respond to stimulation by growth factors. The data indicate that tetrandrine blocks proliferation and the incorporation of tritiated thymidine into DNA by fibroblasts stimulated with human serum, PDGF plus plasma, FGF plus plasma, or TNF plus plasma. Since tetrandrine inhibits the response to a variety of growth factors, its action does not appear to involve the blockade of a specific stimulatory receptor. Tetrandrine is effective in inhibiting thymidine incorporation when added up to 6 hr after stimulation of quiescent cells, suggesting either that tetrandrine does not block the attainment of competence by fibroblasts or that its activity is not limited to blocking the attainment of competence by these cells. Growth factor-induced mitogenesis is also inhibited by nitrendipine, a calcium channel blocker, and by cytochalasin B, a microfilament blocker. However, tetrandrine treatment of fibroblasts neither results in the changes of morphology seen with cytochalasin B nor is limited to the early events of stimulus-response coupling. Therefore, the mechanism of action for tetrandrine is not identical to that for either cytochalasin B or nitrendipine. In summary, these results suggest that the antifibrotic action of tetrandrine may be mediated in part by direct inhibition of fibroblast proliferation normally associated with the development and progression of silicosis.
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PMID:Inhibition of proliferative activity of pulmonary fibroblasts by tetrandrine. 810 60

Exposure to silica dust can result in lung inflammation that may progress to fibrosis, for which there is no effective clinical treatment. The mechanisms involved in the development of pulmonary silicosis have not been well defined; however, most current evidence implicates a central role for alveolar macrophages (AM) in this process. We propose that the fibrotic potential of a particulate depends upon its ability to cause apoptosis in AM. In this study, human AM were treated with fibrogenic, poorly fibrogenic, and nonfibrogenic model particulates, such as silica (133 micrograms/ml), amorphous silica (80 micrograms/ml), and titanium dioxide (60 micrograms/ml), respectively. Cell were treated with these particulates in vitro for 6 and 24 hr and examined for apoptosis by morphological analysis, DNA fragmentation, and levels of cytosolic histone-bound DNA fragments (cell death ELISA assays). Treatment with silica resulted in morphological changes typical of apoptotic cells, enhanced DNA fragmentation (a characteristic feature of programmed cell death), and significant alveolar macrophage apoptosis as observed by cell death ELISA assays. In contrast, amorphous silica and titanium dioxide demonstrated no significant apoptotic potential. To elucidate the possible mechanism by which silica causes apoptosis, we investigated the role of the scavenger receptor (SR) in silica-induced apoptosis. Cells were pretreated with and without SR ligand binding inhibitor, polyinosinic acid (poly(I), 500 micrograms/ml), for 10 min prior to silica treatment. Pretreatment with poly(I) resulted in complete inhibition of silica-induced apoptosis as measured by cell death ELISA. Further, we examined the involvement of interleukin-converting enzyme (ICE) in silica-mediated apoptosis using an ICE inhibitor, Z-Val-Ala-Asp-fluoromethyl ketone. Z-Val-Ala-Asp-fluoromethyl ketone inhibited silica-induced apoptosis and IL-1 beta release. These results suggest that fibrogenic particulates, such as silica, caused apoptosis of alveolar macrophages and that this apoptotic potential of fibrogenic particulates may be a critical factor in initiating an inflammatory response resulting in fibrosis. Additionally, silica-induced apoptosis of alveolar macrophages may be due to the interaction of silica particulates with the SR, initiating one or a number of signaling pathways involving ICE, ultimately leading to apoptosis.
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PMID:Silica-induced apoptosis mediated via scavenger receptor in human alveolar macrophages. 891 79

Iron oxides are present in many occupational atmospheres mainly in iron ore mines and in steel industry. Among these workers, epidemiological studies indicated an excess of lung cancer deaths. In mines, it was difficult to involve iron oxides exposure because there are other possible causes as radon, polycyclic aromatic hydrocarbon (PAH) present in diesel exhausts, silicosis or siderosis. The contradictory results of these studies are due to the differences of exposure levels or to the presence or not of these cofactors or of a sufficient prevention. But generally the results agree with an interaction of iron oxide dusts and smoking habits. It is unclear if this interaction supports an additive or multiplicative risk of lung cancer. Experimental studies with Fe2O3 showed that these particles are able to induce lung cancers only in the presence of PAH when administered to animals. In vitro studies permitted to observe an interaction in the metabolism of benzo(a)pyrene (BaP) leading to a higher level of precursors of the ultimate carcinogen. As this metabolism of BaP is known to be enhanced during lipoperoxidation, it is possible to involve this mechanism with Fe2O3. After phagocytosis and dissolution with production of ferric ions, Fe2O3 can enhance the production of reactive oxygen species responsible of damaging both lipidic constituents and DNA. Fe3O4 and mainly FeO may be more toxic, introducing directly ferrous ions in the cells after dissolution, but the cancerogenicity of the these compounds is unknown, making necessary to develop research.
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PMID:Interactive effects of polycyclic aromatic hydrocarbons and iron oxides particles. Epidemiological and fundamental aspects. 916 58

Silicosis is characterized by mononuclear cell inflammation with macrophage activation, accumulation of lymphocytes, and fibrosis. Interferon-gamma (IFN-gamma) is a lymphocyte cytokine with broad effects, particularly macrophage activation. Mice exposed to an aerosol of cristobalite silica (70 mg/m3, 12 d, 5 h/d) developed diffuse pulmonary pathologic changes with macrophage, lymphocyte, and neutrophil recruitment, and increased lung collagen. IFN-gamma messenger RNA (mRNA) was more abundant by semiquantitative reverse transcription-polymerase chain reaction in the lungs of silica-exposed mice than in control animals. IFN-gamma mRNA transcripts were detected by in situ hybridization with digoxigenin-labeled complementary DNA probes in normal mouse lung tissue within bronchial-associated lymphoid tissues (BALT). In silica- exposed mice, mononuclear cells with IFN-gamma mRNA were more numerous in the silicotic lesions and enlarged BALT structures. Lung-cell suspensions were prepared by enzyme digestion, stained with fluorescent-labeled antibodies against intracellular cytokines, and enumerated by flow cytometry. The percentage of cells producing IFN-gamma was increased in silicotic mice (19% versus 11%). Interleukin (IL)-4 mRNA transcripts were less abundant in the lung tissue from silica-exposed mice than in control mice. Cells staining for IL-4 mRNA were found rarely in either the air-sham or the silica-exposed mouse lungs, and almost all appeared to be within BALT structures. Approximately 3% of cells stained for IL-4 in the digested lungs from both groups. Similar cytokine patterns were observed in mediastinal lymph node/thymus and spleen tissues. The augmented IFN-gamma response, with IL-4 unchanged or decreased, in the lung lesions and lymphoid tissue of mice with silicosis suggests a Th-1-like lymphocyte-mediated immune-inflammatory response.
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PMID:Expansion of interferon-gamma-producing lung lymphocytes in mouse silicosis. 1010 Oct 15

Using polymerase chain reaction single strand conformation polymorphism analysis (PCR-SSCP), the authors mutations in exon 5, 7 and 8 of the p53 gene in lung cancer tissue from 15 of 36 silicotic patients. Mutations existed in exon 5, exon 7 and exon 8, but occured more frequently in exon 8. The authors also found that p53 gene mutation rate in lung adenocarcinomas of silicotic patients was higher than that of those without silicosis. A single base substitution was found by DNA sequencing analysis in sample C8. As a result, No. 144 codon was mutated from CAG to AAG, so Gln was substituted by Lys. The authors' data suggest that p53 mutation may play an important role in the pathogenesis of lung cancer of silicotic patients.
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PMID:[The research on p53 gene mutation in lung cancer tissue of silicotic patients by PCR-SSCR]. 1032 39

Silica exposure results in an initially acute inflammatory response followed by chronic fibrotic change. The mechanism for the maintenance of silica-induced inflammation has not been understood yet. In silica-induced acute inflammation and chronic fibrosis, various mediators such as reactive oxygen species, cytokines and growth factors are released. And these substances are suggested to have the regulatory role for the inflammation and fibrosis by possessing the potential to influence apoptosis. To demonstrate the apoptosis as an underlying mechanism for the development of silicosis, in vitro and in vivo models were designed. In in vitro study, we evaluated that apoptotic cell fraction in silica (10, 50 microg/cm2)-treated A549 cells was significantly increased in comparison with control by FACS (fluorescein activated cell sorter). Also genomic DNA from silica (10, 50 microg/cm2)-treated A549 showed DNA ladder formation while control and 1 microg/cm2 groups didn't. In in vivo study, total cell numbers and apoptotic cell numbers of BAL (bronchoalveolar lavage) fluid from silica (10, 20, 40 mg/kg)-instilled rats were significantly higher than control group from 1 week. From these results, we concluded acute and chronic presence of apoptosis may contributes to silica-induced acute inflammation and chronic fibrosis.
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PMID:Silica-induced apoptosis in vitro and in vivo. 1051 Dec 80

Nuclear factor-kappaB (NF-kappaB) is a multiprotein complex that may regulate a variety of inflammatory cytokines involved in the initiation and progression of silicosis. The present study documents the ability of in vitro silica exposure to induce DNA-binding activity of NF-kappaB in a mouse peritoneal macrophage cell line (RAW264.7 cells) and investigates the role of reactive oxygen species (ROS) and/or protein tyrosine kinase in this activation. In vitro exposure of mouse macrophages to silica (100 microg/ml) resulted in a twofold increase in ROS production, measured as the generation of chemiluminescence (CL), and caused activation of NF-kappaB. Silica-induced CL was inhibited 100% by superoxide dismutase (SOD) and 75% by catalase, while NF-kappaB activation was inhibited by a variety of antioxidants (catalase, superoxide dismutase, alpha-tocopherol, pyrrolidine dithiocarbamate, or N-acetylcysteine). Further evidence for the involvement of ROS in NF-kappaB activation is that 1 mM H2O2 enhanced NF-kappaB/DNA binding and that this activation was inhibited by catalase. Specific inhibitors of protein tyrosine kinase, such as herbimycin A, genistein, and AG-494, prevented NF-kappaB activation in silica-treated cells. Genistein and AG-494 also reduced NF-kappaB activation in H2O2-treated cells. Results confirm that tyrosine phosphorylation of several cellular proteins (approximate molecular mass of 39, 58-70, and 103 kD) was increased in silica-exposed macrophages and that genistein inhibited this silica-induced phosphorylation. In contrast, inhibitors of protein kinase A or C, such as H89, staurosporin, calphostin C, and H7, had no marked inhibitory effect on silica-induced NF-kappaB activation. The results suggest that ROS may play a role in silica-induced NF-kappaB activation in macrophages and that phosphorylation events mediated by tyrosine kinase may be involved in this activation.
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PMID:Silica-induced nuclear factor-kappaB activation: involvement of reactive oxygen species and protein tyrosine kinase activation. 1083 16


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