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PubMed2000

Detection of alternatively spliced variant messages of Fas gene and mutational screening of Fas and Fas ligand coding regions in peripheral blood mononuclear cells derived from silicosis patients.

Silicosis is clinically characterized not only by respiratory disorders but by immunological abnormalities such as the appearance of autoantibodies and complications of autoimmune diseases. Dysregulation of apoptosis, particularly in the Fas/Fas ligand (FasL) pathway, has been considered to play a role in the pathogenesis of autoimmune diseases. It has been found that serum soluble Fas (sFas) levels are elevated in silicosis patients (SIL) and the sFas message is dominantly expressed in peripheral blood mononuclear cells (PBMC) derived from these individuals. In the present study, one tried to detect alternatively spliced variant messages including typical sFas message and found four that were highly and frequently expressed, and which possess a signal peptide domain, but not transmembrane and signal transducing domains, in PBMC derived from SIL. Functional mutations were not detected in Fas and FasL genes in silicosis PBMC. Still, alternative spliced variants of the Fas gene including typical sFas message appear to play an important role in the immunological dysregulation in SIL.

Aged↗
PubMedDate not supplied

The role of bronchoalveolar lavage in quantifying inhaled particles in silicosis.

Silicosis is a disease caused by inhalation and deposition of crystalline silica that produces a fibrous tissue reaction. Bronchoalveolar lavage is a noninvasive technique that allows identifying particles, thus characterizing exposure to mineral dust. The aim of this work was to study bronchoalveolar lavage as a mean of estimating the amount of alveolar particles in different forms of silicosis. Bronchoalveolar lavage was carried out in 27 silicotic patients with simple (n = 12), complicated (n = 13), and acute (n = 2) forms of the disease and 7 healthy individuals as a control group. Macrophages were scored enumerating the percentage of cells with particles by polarizing light microscopy. Silicotic patients showed a marked increase in BAL cell particles compared to control population, however, relating simple to complicated silicosis, no significant difference was observed. In acute silicotic patients with massive silica dust exposure, more than 70% of BAL alveolar macrophages contained dust particles. When duration of exposure and retirement from work were evaluated, an inverse correlation between duration of exposure and the amount of alveolar dust, and a tendency to a smaller involvement on macrophages with the greater period of retirement from work were observed. These results suggest that particle analysis in BAL may be important in order to establish the nature and intensity of exposure.

Adult↗
PubMedDate not supplied

[Comparative study of high resolution computer-assisted tomography with chest radiograph in silicosis].

The diagnosis of silicosis is based on the history of exposure to silica dust associated with the radiological alterations compatible with the disease. With the main objective of comparing the alterations found in the chest radiography to those of high resolution computed tomography 49 patients with silicosis were selected. These imaging methods were evaluated separately by three readers and the results summarized through the median of the readings. The following alterations were analysed: nodules, coalescences, large opacities, lynfadenopathy. The patients were male, at an average age of 47.1 years, the majority being sandblasters, with an average exposure time to dust of 15.3 years. When the chest radiography was compared to high resolution computed tomography the following alterations were observed: i) the high resolution computed tomography showed greater profusion of nodules in 19 cases; ii) the high resolution computed tomography detected isolated coalescence and large opacities in 28 cases, seven of them who were classified initially as having simple silicosis were later changed to the complicated form; iii) the high resolution computed tomography was superior in the evaluation of lynfadenopathy in 16 cases. So, from the 49 analysed patients the high resolution computed tomography was more sensitive than the chest radiography in the evaluation of the alterations studied in 38 (77,5%) cases. Other alterations such as cavities, pleural thickening and emphysema were also observed only by this method in 5 cases. In the last 6 (12,2%) cases the high resolution computed tomography did not add any data when compared to chest radiography, four of these showed the initial form of the disease.

Adult↗
PubMed2006

Mode of action of poly(vinylpyridine-N-oxide) in preventing silicosis: effective scavenging of carbonate anion radical.

Small particles of crystalline silicon dioxide (crystallites) are exceptionally toxic. Inhalation of quartz crystallites causes silicosis, a devastating lung disease afflicting miners, particularly coal and stone workers. Poly(vinylpyridine-N-oxide)s (PVPNOs) have been applied in the prevention and treatment of silicosis, but their mode of action has been obscure. Recently, the sites of inducible *NO synthase activation and of nitrotyrosine formation were associated anatomically with the pathological quartz particle-caused lesions in the lungs. It has been suggested that the *NO formed combines rapidly with O2*- to yield ONOO-, a potential mediator of lung injury following silica exposure. Here, we show that PVPNOs do not react with peroxynitrite but scavenge exceptionally rapidly CO3*- radicals, which are produced in the decomposition of ONOO- in bicarbonate solutions. The rate constant for the reaction of CO3*- with PVPNO was found to be independent of the type and size of PVPNO, i.e., k = (1.9 +/- 0.2) x 10(5) M(-1) s(-1) per monomer. In contrast, the rate constant for the reaction of CO3*- with the small molecule 4-methylpyridine N-oxide did not exceed 1 x 10(4) M(-1) s(-1). The underlying reason for the difference is that, in the dissolved polymeric PVPNOs, the electrostatic repulsion between the N-oxide zwitterions destabilizes them, increasing dramatically their pKa. The protonated N-oxides at physiological pH have abstractable hydrogen atoms and are expected to react rapidly with CO3*-, just as cyclic hydroxylamines do. It is also shown that PVPNO inhibits tyrosine nitration by peroxynitrite at pH 7.6 in the presence of excess of CO2 in a concentration-dependent manner. Hence, binding of PVPNO to the quartz particles and eliminating CO3*- could prevent the killing of macrophages, the associated release of macrophage-recruiting cytokines, and the amplification of the local concentration of *NO by the recruited macrophages. The latter causes necrosis of the macrophage-infiltrated lung tissue and, upon repair of the necrotic lesion, results in the growth of the dysfunctional fibrotic tissue, which is the hallmark of silicosis.

Bicarbonates↗
PubMed1998

Soluble Fas mRNA is dominantly expressed in cases with silicosis.

Although it is well known that cases with silicosis exhibit various immunological abnormalities, the mechanisms involved in the occurrence of immuno-dysfunction or dysregulation induced by silica compounds have not yet been determined. Fas is a well-known cell surface molecule that is involved in the apoptosis pathway that belongs to the tumour necrosis factor-receptor family. Soluble Fas (sFas) is produced as an alternatively spliced product of the Fas gene and protects cells from apoptosis due to antagonization of the binding between membrane form of the Fas gene (mFas) and the Fas ligand. To determine the role of the Fas/Fas ligand system in silica-induced immunological abnormalities, we investigated Fas and Fas-ligand message expression levels using the multiplex reverse transcription-polymerase chain reaction (RT-PCR) method with peripheral blood mononuclear cells from silicosis cases with no clinical symptoms of autoimmune diseases. Although the relative expression levels of the Fas or Fas-ligand genes were not remarkably altered in these cases, we observed the sFas message was dominantly expressed compared with mFas expression. These results suggest that self-recognizing clones in cases with silicosis survive for decades, escaping the exclusion mechanisms induced by apoptosis. Then they cause the appearance of autoantibodies and the acquisition of autoimmune diseases sequentially.

Adult↗
PubMed2003

Arthritis and interstitial granulomatous dermatitis (Ackerman syndrome) with pulmonary silicosis.

OBJECTIVE: To describe the case of a patient suffering from pulmonary silicosis associated with a rheumatoid factor negative, antinuclear antibody positive, symmetrical, nonerosive synovitis, and interstitial granulomatous dermatitis (IGD) and compare it with similar cases reported in the literature. METHODS: Literature search to identify published cases of IGD with arthritis and cases associated with silicosis. RESULTS: Thiry-eight cases of IGD with arthritis were found. These cases were associated with various conditions such as drug reactions, autoimmune diseases, chronic infections, or paraneoplastic syndromes for which no specific underlying cause was identified. The patient had skin lesions corresponding to the rope sign, as noted in other reports. Histology showed a histiocytic, granulomatous dermatitis, which, in association with arthritis, was first described by Ackerman et al. Circulating immune complexes or altered apoptosis have been discussed as mechanisms, although there is no experimental evidence to support either hypothesis. As in other cases, treatment had limited success. Most relief was achieved with hydroxychloroquine, dapsone, and corticosteroids. CONCLUSIONS: Arthritis and IGD associated with silicosis is a rare clinical entity that can be differentiated from other conditions. This condition should be considered when patients present with typical dermatologic features, such as the rope sign, and arthritis.

Adult↗
PubMed2002

Respirable concrete dust--silicosis hazard in the construction industry.

Concrete is an extremely important part of the infrastructure of modern life and must be replaced as it ages. Many of the methods of removing, repairing, or altering existing concrete structures have the potential for producing vast quantities of respirable dust. Since crystalline silica in the form of quartz is a major component of concrete, airborne respirable quartz dust may be produced during construction work involving the disturbance of concrete, thereby producing a silicosis hazard for exposed workers. Silicosis is a debilitating and sometimes fatal lung disease resulting from breathing microscopic particles of crystalline silica. Between 1992 and 1998, the National Institute for Occupational Safety and Health (NIOSH) made visits to construction projects where concrete was being mechanically disturbed in order to obtain data concerning respirable crystalline silica dust exposures. The construction activities studied included: abrasive blasting, concrete pavement sawing and drilling, and asphalt/concrete milling. Air samples of respirable dust were obtained using 10-mm nylon cyclone pre-separators, 37-mm polyvinyl chloride (PVC) filters, and constant-flow pumps calibrated at 1.7 L/min. In addition, high-volume respirable dust samples were obtained on 37-mm PVC filters using 1/2" metal cyclones (Sensidyne model 18) and constant-flow pumps calibrated at 9.0 L/min. Air sample analysis included total weight gain by gravimetric analysis according to NIOSH Analytical Method 600 and respirable crystalline silica (quartz and cristobalite) using x-ray diffraction, as per NIOSH Analytical Method 7500. For abrasive blasting of concrete structures, the respirable crystalline silica (quartz) concentration ranged up to 14.0 mg/m3 for a 96-minute sample resulting in an eight-hour time-weighted average (TWA) of 2.8 mg/m3. For drilling concrete highway pavement the respirable quartz concentrations ranged up to 4.4 mg/m3 for a 358-minute sample, resulting in an eight-hour TWA of 3.3 mg/m3. For concrete wall grinding during new building construction the respirable quartz measurements ranged up to 0.66 mg/m3 for a 191-minute sample, resulting in an eight-hour TWA of 0.26 mg/m3. The air sampling results for concrete sawing ranged up to 14.0 mg/m3 for a 350-minute sample resulting in an eight-hour TWA of 10.0 mg/m3. During the milling of asphalt from concrete highway pavement, the sampling indicated a respirable quartz concentration ranging up to 0.34 mg/m3 for a 504-minute sample, resulting in an eight-hour TWA of 0.36 mg/m3. The results of this work indicate the potential for respirable quartz concentrations involving disturbance of concrete to range up to 280 times the NIOSH Recommended Exposure Limit (REL) of 0.05 mg/m3 assuming exposure for an eight- to ten-hour workday. Considering the aging of the concrete infrastructure in the United States, these results pose a challenge to all who have an interest in preventing silica exposures and the associated disease silicosis.

Environmental Monitoring↗
PubMed1986

Serum angiotensin-converting enzyme levels in patients with silicosis.

In a group of control subjects, the mean serum angiotensin-converting enzyme (ACE) level was 38.1 +/- 10.6 nmol/min X ml (n = 30), and in a group of silicosis patients the mean serum ACE level was 45.2 +/- 16.0 (n = 26). Thirteen of these patients were classified as having nodular silicosis, and their mean serum ACE level was 44.2; 10 of these patients were classified as having progressive massive fibrosis, and their mean serum ACE level was 39.4. Three of these patients had confirmed silicotuberculosis, and their serum ACE levels were 63, 67, and 77 (mean = 69); these serum ACE levels are somewhat higher than those having been reported for patients with acute sarcoidosis. Thus, when serum ACE levels are being used to assist in distinguishing between silicosis and sarcoidosis, the possibility of silicotuberculosis must be also considered when high serum ACE levels are encountered.

Adult↗
PubMed1981

Silicosis in the 1980's.

At the request of the Mine Safety and Health Administration (MSHA), the National Institute for Occupational Safety and Health (NIOSH) recently investigated the health of workers at two silica flour mills. Both mills have a long history of failure to maintain workplace concentrations of dust containing free silica below the MSHA exposure standard. Thirty-seven percent of sixty-one workers and ex-workers with one or more years of silica dust exposure had chest radiographic evidence of silicosis. Because of the high prevalence of silicosis in workers at these two silica flour producers, MSHA silica dust measurements were reviewed for twenty-five other active U.S. silica flour producers. Eighty-nine percent of the work force in these 27 silica flour producers are employed at workplaces where more than twenty-five percent of the dust samples reviewed were above the exposure standard. Fifty-three percent of all samples were above the MSHA standard. No significant decline in silica dust levels occurred during the period (1974-1979) covered by the data supplied by MSHA. Based on the NIOSH study and MSHA data, it is apparent that the risk of silicosis is very high among workers in this industry. Prevention of this disease will require a concerted effort of government enforcement agencies, workers and management.

Dust↗
PubMed2006

Silicosis in Turkish denim sandblasters.

BACKGROUND: Sandblasting of jeans in small Turkish workshops has recently been recognized as a cause of silicosis. CASE SERIES: Between August 2004 and March 2006, we admitted 16 young men with a history of working in small workplaces producing sandblasted jeans. Of these, 14 presented with respiratory symptoms and the remaining two through awareness of their work colleagues. In the first two cases, open-lung biopsy was required to confirm the diagnosis of silicosis. Later cases were diagnosed through a combination of their work history and the clinical and radiological findings. The mean age at presentation was 23 years with mean duration of employment as a sandblaster being 3 years. The first two cases died and the remainder, except two, are still receiving treatment. CONCLUSION: The production of sandblasted jeans in small uncontrolled workplaces may entail significant exposure to silica and the development of rapidly fatal silicosis. Urgent action is required to prevent further cases and mortality.

Adolescent↗
PubMed1995

Silicosis and workers' compensation in New Jersey.

The employer is expected to maintain responsibility for health care expenses and lost income that result from occupational injury and illness through the workers' compensation insurance system. However, financial support for individuals with occupational illnesses, especially those with long latency, is often from sources other than workers' compensation. Silicosis, a well defined, chronic, occupational lung disease, can be viewed as a sentinel for the inadequacy of the public policy to compensate workers for chronic occupational lung disease. Three hundred twenty-nine patients with confirmed silicosis were identified by the silicosis surveillance program in the New Jersey Department of Health using source data from 1979 through 1992. One hundred seventy-seven of these individuals provided information on the status of any compensation claims against their employer. Only 31% of these patients stated that a claim had been filed; 84% of those whose claims were settled were awarded payments. Severity of radiologic findings was not associated with the likelihood of filing a claim or with being awarded a payment; whereas, smoking was associated with these outcomes. The implications of these findings for the health care system are discussed.

Aged↗
PubMed1990

Type III collagen aminopropeptide and laminin P1 levels in serum of patients with silicosis-associated and idiopathic systemic scleroderma.

A group of 191 patients with systemic scleroderma and 12 patients with silicosis-associated scleroderma were investigated for connective tissue turnover. The serum levels of type III collagen aminopropeptide (P-III-P), the laminin PI (Lam PI) fragment and the acid lysosomal beta-galactosidase (beta-Gal) were determined by specific radioimmunoassays and spectrofluorometry, respectively. Increased levels of type III collagen aminopropeptide strongly correlated with enhanced activity of beta-galactosidase. Both parameters correlated with the clinical course in idiopathic systemic scleroderma and in silicosis-associated scleroderma. Serum levels of Lam PI were also found to be elevated in both groups, although there was no correlation with the severity of the disease. Autoantibodies directed against the DNA topoisomerase Scl-70 and against centromeric proteins were found in a similar range in patients with idiopathic systemic and silicosis-associated scleroderma. These results suggest that P-III-P, Lam PI and beta-Gal are useful serological markers of fibrotic activity and demonstrate similarities between idiopathic systemic scleroderma and scleroderma associated with silica-dust exposure.

Aged↗
PubMed2005

Detection, epitope-mapping and function of anti-Fas autoantibody in patients with silicosis.

Dysregulation of apoptosis through the Fas-Fas ligand pathway is associated with the onset of autoimmune disease. Since autoantibodies directed against unknown antigens are present in the sera of these patients, sera samples were examined for the presence of autoantibodies directed against the Fas molecule. Using Western blotting and a ProteinChip analysis, autoantibodies against Fas were detected in patients with silicosis, systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), and weakly detected in healthy individuals. Using epitope mapping employing 12-amino-acid polypeptides with the SPOTs system, a minimum of four epitopes and a maximum of 10 epitopes were found. Several amino acid residues involved in binding FasL, such as C66, R87, L90, E93 and H126, were presented within the epitopes. Serum containing a large amount of anti-Fas autoantibody from silicosis patients inhibited the growth of a Fas-expressing human cell line, but did not inhibit the growth of a low Fas-expresser nor a Fas-expresser in which the Fas gene had been silenced by small interference RNA. All epitopes in the intracellular region of Fas were located in the death domain. The possible roles of anti-Fas autoantibody detected in healthy volunteers and patients with silicosis or autoimmune diseases are discussed here.

Aged↗
PubMed1980

Role of family susceptibility, occupational and family histories and individuals' blood groups in the development of silicosis.

A previous investigation has shown that family susceptibility and occupational and family histories have a decisive role in the development of byssinosis among workers exposed to flax dust. Results of investigation of silicosis in 814 male workers exposed to silica-bearing dust showed that family susceptibility has an important role in the development of silicosis among examined workers, and workers whose fathers had an occupational history of exposure to silica-bearing dust were more resistant to the development of the disease than those with non-exposed fathers. The degree of consanguinity of parents and individuals' blood groups, also, have a role. Workers with cousin parents were relatively highly susceptible to the development of silicosis as well as workers with blood groups "O" or "AB". It has been concluded that the investigated factors might have a role in the development of other occupational diseases and further investigations are indicated.

ABO Blood-Group System↗
PubMed1985

Silicosis in jade workers.

The recent finding of cases of silicosis among jade workers in Hong Kong points to this disease being an occupational hazard. The source was found to be the silica flour that was added in a polishing process. Five cases are described together with the results of environmental investigation in a workplace. In three cases the disease was of early onset, rapidly progressive, and presented the features of galloping silicosis noted in other occupational exposures to silica flour. One patient had massive fibrosis and severe glomerulonephropathy, an association that has also been previously noted. One case showed evidence of active tubercular infection in addition to silicosis and two had healed lesions. Silica concentrations in the workplace during the suepect process were well above accepted threshold limit values.

Adult↗
PubMed1998

Quartz exposures and severe silicosis: a role for the hilar nodes.

BACKGROUND: Two stonemasons working together in an environment with high concentrations of quartz pursued very different clinical courses; one died of rapidly progressive silicosis and the other developed hilar adenopathy and, later, early massive fibrosis. The exposures to quartz of these two men were investigated to allow comment on the pathogenesis of severe silicosis relative to concentrations of dust. METHODS: Estimates of exposure were based on previously taken personal dust samples, detailed lifetime occupational histories, and semiquantitative exposure modelling. RESULTS: One of the men who died had a 30 year exposure estimated to have averaged < 0.1 mg/m3, leading to hilar node fibrosis and calcification, followed by a five year exposure to about 2 mg/m3 which proved fatal. Estimates of exposure tallied with postmortem measurement of lung burden, suggesting retention of all dust deposited in the lungs over his final period of work. The younger man, working from the start of his apprenticeship alongside the older one, had a six year exposure to about 1.5 mg/m3, which caused hilar node enlargement and subsequent calcification but minimal lung involvement. CONCLUSIONS: Exposures to relatively low concentrations of quartz may be capable of causing hilar node fibrosis, impairing the clearance of any quartz inhaled subsequently. The findings support the concept that destruction of the hilar nodes by silicotic fibrosis, impairing lung clearance, has an important pathogenic role in the development of massive fibrosis, and in men subsequently exposed to very high concentrations of respirable quartz, rapidly progressive silicosis.

Adult↗
PubMed2003

Quantitative relations between exposure to respirable quartz and risk of silicosis.

AIMS: To reanalyse exposure-response data from a Scottish colliery to gain a more detailed knowledge of the relations between exposure to quartz and risks of silicosis in coal miners, and hence inform the debate on an appropriate occupational standard for respirable quartz. METHODS: Detailed data on working times at different quartz concentrations were combined to produce exposure profiles for miners who had provided a full chest radiograph at a follow up survey. Logistic regression methods were used to model profusion of radiographic abnormalities category 2/1+, and a general exposure index was used to compare different quartz exposure measures in these models. RESULTS: Results in 371 men aged 50-74 indicated that cumulative quartz exposure at higher concentrations resulted in proportionally greater risks of abnormalities. One g x h x m(-3) of cumulative exposure at quartz concentrations greater than 2 mg x m(-3) was estimated to have equivalent risks to 3 g x h x m(-3) at lower concentrations. The timing of exposure relative to follow up appeared less important, although the study had limited power to compare different lag periods between exposure and effect. CONCLUSIONS: Quantification of the risks of silicosis should take account of variations in quartz exposure intensity, particularly for exposure to concentrations of greater than 1 or 2 mg.m(-3), even if exposure is for relatively short periods. The risks of silicosis over a working lifetime can rise dramatically with even brief exposure to such high quartz concentrations. Risk estimates are given, to inform choice of control limits.

Aged↗
PubMed1986

Silicosis in barium miners.

Four men who mined barytes in Scotland and who developed pneumoconiosis are described. Three developed progressive massive fibrosis, from which two died; and one developed a nodular simple pneumoconiosis after leaving the industry. The radiological and pathological features of the men's lungs were those of silicosis and high proportions of quartz were found in two of them post mortem. The quartz was inhaled from rocks associated with the barytes in the mines. The features of silicosis in barium miners are contrasted with the benign pneumoconiosis, baritosis, that occurs in workers exposed to crushed and ground insoluble barium salts. Diagnostic difficulties arise when silicosis develops in workers mining minerals known to cause a separate and benign pneumoconiosis. These difficulties are compounded when, as not infrequently happens, the silicotic lesions develop or progress after exposure to quartz has ceased.

Aged↗