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)

In order to verify the value of the determination of serum angiotensin converting enzyme (ACEs) in the assessment of silicosis and silicotuberculosis, we studied 105 subjects: 61 suffering from silicosis, 12 from silicotuberculosis, 19 from tuberculosis and 13 from chronic obstructive pulmonary disease (COPD). The patients with silicosis and silicotuberculosis were classified into two categories on the basis of the radiological pattern of pneumoconiosis according to the ILO 1980 CLASSIFICATION: mild silicosis (from 1/1 to 2/1) and severe silicosis (from 2/2 to 3+ and/or conglomerate masses). ACEs values were higher in the subjects suffering from silicotuberculosis and silicosis; in the latter, however, we did not find any significant relation between ACEs values and the radiological pattern. The lowest values of ACEs were found in the COPD group. Our data showed a statistically significant difference between silicotic or silicotuberculotic patients and the COPD group (p less than 0.05). It can be supposed that COPD, which was also found in all subjects suffering from silicosis or silicotuberculosis, might have caused an underestimation of the observed ACEs values which, however, were higher than normal. This increase might have been caused by a numerical or functional enhancement of the macrophages, which produce ACE and play an important role in the pathogenesis of such diseases.
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PMID:[The evaluation of serum angiotensin-converting enzyme in silicosis and silicotuberculosis]. 196 97

The purposes of this study were (1) to investigate the chronology of events in cellular and biochemical changes thought to be important in the development of silicosis, (2) to relate these to changes in lung function and radiograph, and (3) to evaluate the relation of quartz exposure and retention to individual response leading to early silicosis. Thirty-six sheep were exposed by repeated intratracheal infusion at 10-day intervals to 100 mg Minusil-5 in 100 ml saline (Si group), and 10 sheep were exposed at the same intervals to 100 ml saline (control). All sheep were investigated at 3-month intervals by chest radiograph, lung function, and lung lavage. At month 9, chest radiograph score of parenchymal opacities was significantly increased at 2.8 +/- 0.6 versus 0.4 +/- 0.4 in the Si group (p less than .05), establishing early radiologic silicosis. Lung function was significantly altered with reduction in lung compliance, vital capacity, and diffusion capacity (p less than .05). Lung lavage cellularity revealed significant increase in total cells (X 2.5), macrophages (X3), and neutrophils (X3). Albumin in BAL remained at the control level. Fibronectin production was significantly increased, as was the fibroblast growth activity, without significant change in procollagen 3 at this early stage of disease. Total phospholipids were significantly elevated in the Si-exposed sheep, and the profile demonstrated an increase in all the phospholipid components. Spontaneous release of hydrogen peroxide by alveolar cells was not increased, but in the presence of phorbol myristate acetate (PMA) higher levels of peroxide were found in the quartz-exposed sheep (p less than .05). The cellular and biochemical alterations of lung lavage preceded other changes. At month 12, there were good correlations (r greater than .49, p less than .001) between parameters evaluating related phenomena but poor correlations between measurements evaluating different aspects of the disorder. To investigate the heterogeneity in the individual response of sheep to the same exposure (susceptibility), individual quartz retention levels at month 12 were measured and found to correlate well with individual parameters of disease activity. We concluded that in early silicosis of sheep, cellular and biochemical changes in lung lavage preceded derangements of pulmonary function and radiographic abnormalities. Thereafter, parameters of lung lavage, lung function, and radiograph were significantly interrelated, but for a given exposure the degree of quartz retention appeared to determine the intensity of the silicotic process.
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PMID:Quartz exposure, retention, and early silicosis in sheep. 254 36

Tetrandrine is a plant alkaloid useful in the treatment of silicosis. Its mode of action is unknown, but results of the present study show dose-dependent inhibition of human neutrophil and monocyte adherence at concentrations (0.1-10 micrograms/ml) easily achieved in plasma during drug therapy. Monocytes were shown to be more sensitive to tetrandrine than neutrophils. Dye-exclusion experiments indicate that tetrandrine is non-toxic to these cells at 10 micrograms/ml concentrations. Suppression of adherence was reversible by washing, suggesting that the drug does not bind tightly to membrane components. Enhancement of adherence by the tumour promoter, phorbol myristate acetate, was abolished by tetrandrine. The uptake of deoxyglucose by neutrophils and monocytes was suppressed by tetrandrine. These results indicate that tetrandrine may act by interfering with the recruitment of these cells into silicotic lesions.
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PMID:Inhibitory effects of tetrandrine on human neutrophil and monocyte adherence. 375 46

The serum activity of angiotensin-converting enzyme (ACE, EC 3.4.15.1) in 135 male silicosis patients was analyzed. Twenty-eight of the patients had referents matched for silica dust exposure and age but without roentgenographic signs of silicosis. A reference group not exposed to silica dust comprised 34 lumberjacks. The serum mean activity of ACE was higher in silicosis patients (46.6 +/- 12.1 units/L) than in the referents exposed to silica (38.5 +/- 8.1 units/L) or in the lumberjacks (36.6 +/- 9.7 units/L). There was an association between the serum ACE level and the roentgenographic severity of fibrosis. A retrospective side-by-side assessment of roentgenographic progression was made in 49 silicosis patients. The ACE was higher in the 18 patients with progression (50.5 +/- 16.4 units/L) than in those with no progression (41.5 +/- 9.5 units/L). According to the multivariate regression analysis, progression of fibrosis explained the elevation of ACE better than profusion. The results confirm that the serum ACE activity is elevated in silicosis and suggest that the elevation is associated with progression of the disease.
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PMID:Increased activity of serum angiotensin-converting enzyme in progressive silicosis. 608 42

Serum angiotensin conversion enzyme (serum ACE) is a dipeptidylcarboxypeptidase which activates angiotensin I to angiotensin II and inactivates bradykinine. It is a glycoprotein with an MW of 126,000 to 480,000. It is produced by all endothelial cells, and is located on the cell membrane. It is inhibited by EDTA (chelator of Zn-- cofactor), teprotide (snake venom nonapeptide) and captopril. Estimation of ACE has greatly benefitted from the use of synthetic tripeptides. An example is the method of Cushman and Cheung using hippuryl histidyl leucine. A raised serum ACE level in sarcoidosis has been demonstrated by Liebermann in 1975. The diagnostic value is limited by the existence of high levels in other pulmonary diseases (asbestosis, silicosis). Serum ACE levels in sarcoidosis are all higher when the disease is diffuse from a pulmonary and extrapulmonary standpoint. They decrease when the disease regresses spontaneously and rise if it worsens. Radiological improvement in pulmonary sarcoid lesions under the influence of corticosteroid therapy is accompanied by a fall in serum ACE levels. Persistence of this normalization as the dose is decreased is a favourable sign, whilst the reappearance of a high serum level may either reflect simple and isolated biological "rebound" or may accompany a recurrence of signs of the disease. Serum ACE measurement is thus an important factor in the surveillance of cases of treated sarcoidosis when the dose of corticosteroids is to be reduced.
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PMID:[Characteristics, assay and semeiologic value of angiotensin converting enzyme (ACE)]. 618 19

Exposure to mineral dusts such as silica has been associated with progressive pulmonary inflammation and fibrosis. There is evidence that the release of reactive oxygen intermediates (ROI) and cytokines by alveolar macrophages (AM) is involved in lung injury associated with silica exposure. However, the chronology and relationship between these two mediators are poorly understood. In this study, an animal model of silicosis has been used, allowing simultaneous follow-up of lung histopathologic state, AM TNF-alpha production at the protein (biologic assay) and mRNA (reverse transcriptase-PCR) levels, and the release of ROI (luminol-dependent chemiluminescence), after bronchoalveolar lavages. In particular, it has been shown that intratracheal instillation of silica (50 mg/kg) in rats led to fibrosis characterized by cellular interstitial infiltrates with granulomas, and in AM, it led to 1) an early and continuous increase in 12-O-tetradecanoylphorbol-13-acetate- or zymosan-triggered ROI production (days 1, 3, 14, and 28 post-treatment), and 2) a rise of TNF-alpha mRNA expression and protein secretion on days 3 and 14. A free radical scavenger pretreatment (N-ter-butyl-alpha-phenylnitrone) reversed lung histopathologic changes and decreased AM ROI production and TNF-alpha expression at the level of mRNA. These findings suggest that ROI production is an important primary event determining the silica-induced inflammatory process. ROI may act in an autocrine or paracrine manner and regulate TNF-alpha production by a mechanism promoting gene expression. The critical role of this cytokine in the pathogenesis of silicosis was confirmed by anti-TNF-alpha Ab treatment.
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PMID:Reactive oxygen intermediates as regulators of TNF-alpha production in rat lung inflammation induced by silica. 856 58

Nuclear transcription factor kappa B (NF-kappa B) is a multiprotein complex that regulates a variety of genes important for immunity and inflammation. The present study investigates the silica-induced activation of this transcription factor in mouse macrophage cell line RAW 264.7 cells, the role of free radical reactions in the mechanism of the activation, and its possible inhibition. Tetrandrine, a benzylisoquinoline alkaloid, which has been used as an antifibrotic drug to treat the lesions of silicosis and has been characterized as a hydroxyl radical (.OH) scavenger, inhibited the NF-kappa B activation induced by silica, lipopolysaccharide (LPS), and phorbol 12-myristate 13-acetate (PMA). Catalase, metal chelator, deferoxamine, and the silanol group (SiOH) blocker, poly(2-vinylpyridine-N-oxide) (PVPNO), also inhibited silica-induced NF-kappa B activation. Electron spin resonance (ESR) spin trapping measurements show that both deferoxamine and PVPNO decreased silica-mediated .OH radical generation from H2O2. It is shown that Fe(II) and not Fe(III) is able to cause NF-kappa B activation. The antioxidant, ascorbate, attenuated the NF-kappa B activation induced by silica but not by LPS. The .OH radical scavenger, sodium formate, inhibited NF-kappa B activation induced by silica but had only a minor effect on NF-kappa B activation induced by LPS. The results indicate that silica-mediated free radical generation via the Fenton or Fenton-like reaction (M(n)+ + H2O2-->M(n + 1)+ + OH- + .OH) and silanol groups on the silica surface play an important role in silica-induced NF-kappa B activation.
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PMID:Role of hydroxyl radical in silica-induced NF-kappa B activation in macrophages. 951 78

Tetrandrine, a purified traditional Chinese medicinal herb that acts as an immunosuppressant and a Ca2+ channel blocker, has been clinically used to treat patients with arthritis, silicosis and hypertension. Since T cells play a critical role as autoreactive and pathogenic population in autoimmune diseases, in this study, we examined the immunosuppressive effect of tetrandrine on human peripheral blood T cells. We showed that tetrandrine inhibited phorbol 12-myristate 13-acetate (PMA) + ionomycin-induced T cell proliferation, interleukin-2 secretion and the expression of the T cell activation antigen, CD71. Further investigation of the molecular mechanism demonstrated that tetrandrine inhibited the expression of the protein kinase C-dependent interleukin-2 receptor alpha chain and CD69 but not the expression of the Ca2+-dependent CD40 ligand and CD69. Interestingly, when tetrandrine and cyclosporin A were added together, significant synergism in the suppression of T cell activation was observed. Moreover, of the several tetrandrine analogues studied, hernandezine was the most potent inhibitor of protein kinase C signaling events. These results also suggest that the protein kinase C-inhibitory capacity of tetrandrine and its analogues may not be associated with their function as Ca2+ channel blockers. Lastly, we showed that, within therapeutic concentrations, tetrandrine and its analogues could induce cellular apoptosis, which is defective in autoimmune diseases. In conclusion, our findings provide novel information about the molecular mechanism of the immunosuppressive effect of tetrandrine and its analogues in human peripheral blood T cells.
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PMID:Plant alkaloid tetrandrine downregulates protein kinase C-dependent signaling pathway in T cells. 1007 15

39 years old man with granulomatous lesions in both lungs caused by occupational contact with glass fibers was described. He has been working as an bricklayer-plasterer for 18 years and was in contact with lime, cement, plaster, asbestos, dust of coal and wood and with glass fibers. For the last two years before admission in 1993 he has had frequent bronchial infections. On admission he was in good general condition, his spirometric examination and blood gases were within normal limits. On chest x-ray disseminated lesions were found. Those lesions were of the round shapes on chest CT. Many sputum cultures for tubercle bacilli were negative. ANA and ANCA were not found in the serum. ACE was within normal limits. No precipitins to environmental antigens were found. Cancer metastases were suspected and lung biopsy during videothoracoscopy was done. Many foreign body type granulomas were found throughout the specimen. The character of the lesions was not typical for tuberculosis, sarcoidosis, extrinsic allergic alveolitis, silicosis or asbestosis. There are some reports concerning the possibility of development of such lesions after the exposition to glass fibers. We suspect that case is an example of such pathology. His occupational exposition was stopped in 1993 and he was observed without treatment. During the 5 years of observation (up till 1998) he was in good health with stable chest x-ray picture and results of respiratory system function.
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PMID:[Granulomatous lung lesions after occupational exposure to glass fibers]. 1100 67

The objective of this study was to investigate potential role of taurine and niacin supplementation, and their combination, in an in vitro model of silica-induced, macrophage-mediated pulmonary fibroblast proliferation. Human monocytic cell line (THP-1 cell) was primed to differentiation into macrophages by phorbol myristate acetate (PMA). PMA-primed THP-1 cells were subjected to silicon dioxide exposure. Other PMA-primed THP-1 cells incubated with taurine and niacin concentration gradients, respectively, and then were treated with silicon dioxide for 6 hours. Collected THP-1 supernatants preconditioned with taurine and niacin gradients were added to human pulmonary WI-38 cells to evaluate proliferative activity. Transforming growth factor (TGF)-beta1 mRNA in macrophages and protein level in supernatant were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Taurine- and niacin-preconditioned macrophages were more resistant to silica-induced TGF-beta1 up-regulation than macrophages without precondition. Furthermore, medium conditioned with supernatant from silica-exposed macrophages following taurine and niacin pretreatment could facilitate inhibition of pulmonary fibroblast proliferation. Moreover, the above effects could be accentuated by the combination of taurine and niacin. Down-regulation of TGF-beta 1 expression in macrophages by taurine and niacin could attenuate silica-induced pulmonary fibroblasts proliferation in vitro, which may be of therapeutic potential for early stage silicosis.
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PMID:Attenuation of silica-induced pulmonary fibroblasts proliferation by taurine and niacin in vitro. 1933 3


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