Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have developed a Silica Clotting Time (SCT) test suitable to screen patients with lupus anticoagulants (LA) and compatible with photo-optical instruments. The SCT results were considered to be positive for LA whenever the clotting times were longer than the upper normal limit at low phospholipid concentration and to be confirmed when the prolonged clotting times were corrected to normal by high phospholipid concentration. We studied plasmas from healthy subjects, patients with known diagnoses of LA, patients with acquired deficiencies of blood coagulation and hemophiliacs with anti-factor VIII antibodies. The test was positive for all LA patients, and negative for all non-LA patients except 7 hemophiliacs with anti-factor VIII antibodies. Our data indicate that the SCT is a sensitive test, suitable for screening patients suspected of having LA. Its compatibility with photo-optical instruments makes it a suitable candidate to replace the kaolin clotting time. The contemporaneous performance of SCT at low and high phospholipid concentrations provides screening and confirmation in a single procedure.
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PMID:Silica clotting time (SCT) as a screening and confirmatory test for detection of the lupus anticoagulants. 132 61

In recent years, with the aging of patients with pneumoconiosis, autoimmune diseases as a complication have been observed. One of the reasons for this may be that autoimmune diseases are prone to develop among the elderly. On the other hand, it has been reported that dust itself, such as silica for example, has adjuvant effect. A review of the recent literature published in Japan and abroad was made to clarify the relationship between pneumoconiosis and autoimmune diseases and the following results were obtained. 1) Disorders which accompany pneumoconiosis: Scleroderma, rheumatoid arthritis, systemic lupus erythematosus (SLE), and disorders of the kidney and liver have been reported. In Japan, about 30 cases of pneumoconiosis accompanied with autoimmune diseases have been reported. In many of the reports, patients with pneumoconiosis and scleroderma have a past history of exposure to silica. In both case studies and case control studies, patients with rheumatoid arthritis and history of silica exposure are prone to develop pneumoconiosis. 2) Immunological studies of patients with pneumoconiosis: As for humoral immunity, elevation of polyclonal gamma-globulin, especially IgG, has been often reported together with high positive rate of autoantibodies such as antinuclear antibodies. In cellular immunity, decreased delayed type skin reaction and decreased CD4/8 ratio have been reported. In human leukocyte antigen (HLA) typing the elevated frequency of DR4 has been reported. In the study of BAL increased production of superoxide anion O2- by alveolar macrophages has been observed. 3) EXPERIMENTAL STUDIES: Silica is well known for its toxicity to cells and also for its adjuvant effect. In the German Democratic Republic, patients with scleroderma and history of long term silica exposure are recognized as patients with occupational disease even though pneumoconiosis is not clearly demonstrated on X-ray film. It is difficult from this review to nrake a definite conclusion regarding the relation between silicosis and autoimmune diseases. There is a need to repeat this review of the literature on autoimmune diseases and pneumoconiosis in the near future.
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PMID:[Relationship between autoimmune diseases and pneumoconiosis]. 140 2

Next to oxygen silicium is the most common substance of our environment. It occurs mostly in form of quartz (SiO2). In the past silica was usually mentioned in connection with foreign body granulomas in dermatological papers. Recently relations between occupational silica exposure and several diseases were reported. Silica exposure was related to the development of scleroderma, lupus erythematodes and sarcoidosis. Pathogenetic connections may be due to a stimulating effect on fibroblasts and due to immunmodulating properties of silica.
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PMID:[Quartz--its relevance for dermatology]. 283 Oct 19

Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated small-vessel vasculitis (SVV) and systemic lupus erythematosus (SLE) are rare diseases with unknown causes. Silica dust exposure has been suggested to be an environmental factor that may increase the risk of developing these and other autoimmune disorders. This is a report of two case-control studies to determine whether silica dust exposure is independently associated with ANCA-SVV with glomerulonephritis and SLE nephritis. Patients were screened through a collaborative network of 225 private practice and university nephrologists (the Glomerular Disease Collaborative Network). Patients with ANCA-SVV or SLE, all with biopsy-proven renal involvement, were included. Control subjects were patients without ANCA-SVV or SLE who had been referred to the same renal clinics and were matched for gender, race, and age (within 5 yr). Exposures to silica, exposures to other environmental agents, and smoking histories were evaluated using a self-administered questionnaire. Enrollment consisted of 65 patients with ANCA-SVV and 51 patients with SLE nephritis. Silica dust exposure was reported by 46% of patients with ANCA-SVV, compared with 20% of control subjects (P = 0.001). The odds ratio of silica dust exposure was 4.4 times greater for patients with ANCA-SVV, compared with control subjects (95% confidence interval, 1.36 to 13.4; P = 0.013). The odds ratios for silica dust exposure were similar for patients with ANCA-SVV with lung or sinus vasculitis (odds ratio, 4.5; 95% confidence interval, 0.99 to 20.83; P = 0.054) and those without lung or sinus vasculitis (odds ratio, 4.7; 95% confidence interval, 1.34 to 16.24; P = 0.016). Silica dust exposure was reported by 12% of patients with SLE nephritis, compared with 25% of control subjects (P = 0.047). The odds ratio for exposure to silica dust was not statistically different for patients with SLE nephritis, compared with control subjects (odds ratio, 0.001; 95% confidence interval, <0.01 to >100; P = 0.993). Activities and environments known to cause high levels of exposure to silica dust were associated with ANCA-SVV but not with SLE nephritis.
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PMID:Silica exposure in anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and lupus nephritis. 1113 59

The dilute Russell's viper venom time (dRVVT) and the kaolin clotting time (KCT) are two among the most commonly used coagulation tests for the detection of lupus anticoagulants. The dRVVT seems superior to the KCT in identifying LA-positive patients at risk of thrombosis. However, this relationship is greatly influenced by both the source of reagents and the instrumentation employed to carry out the assays. Therefore, 4 dRVVTs ("home-made" dRVVT, DVV test, Bioclot LA, LA Screen), and one KCT (Kaoclot) were performed in two centers and compared for their retrospective correlation with the thrombotic complications of 72 patients with a previously established diagnosis of lupus anticoagulants. Two other assays ("home-made" KCT, and Colloidal Silica Clotting Time, CSCT) were performed in one of the two centers, and compared with Kaoclot for their clinical correlations in the same population of patients, 44 of whom (61%) had suffered from arterial and/or venous thrombosis. A rather good degree of inter-laboratory and inter-assay correlations of the different tests was found. However, a statistically significant association with thrombosis was found only with the coagulation profile generated using the "home-made" dRVVT. When the commercially available dRVVTs were used, none of the coagulation profiles remained associated with thrombosis. When the assays were analyzed separately, the association with thrombosis was statistically significant for LA screen (p = 0.0019), DVV test (p = 0.0043), and Bioclot (p = 0.0255), and of borderline significance for the "home-made" dRVVT (p = 0.0503) in one center. This last assay was also significantly associated with thrombosis in the other center (p = 0.0139). When venous and arterial thrombosis were considered separately, DVV test was statistically associated with venous thrombosis in both centers (p = 0.0076 and p = 0.0187, respectively), and LA screen in one center (p = 0.0303). No dRVVT was found to correlate with arterial thrombosis. Kaoclot, Colloidal Silica Clotting Time, and the "home-made" KCT did not correlate with thrombosis. The prevalence of IgG and/or IgM antibodies to cardiolipin, beta2-glycoprotein I and prothrombin were 74%, 86% and 85%, respectively. Increased titers of IgG anticardiolipin antibodies were associated with arterial thrombosis (p = 0.0375), whereas IgM anti-beta2-glycoprotein I antibodies were associated with venous thrombosis (p = 0.0433). In conclusion, these retrospective data support the notion that the dRVVT, rather than other coagulation or ELISA tests, are able to identify lupus anticoagulant-positive patients at risk of thrombosis. This property appears common to several commercially available dRVVT kits, making this type of assay the ideal target of future efforts of laboratory standardization.
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PMID:Lupus anticoagulants and thrombosis: clinical association of different coagulation and immunologic tests. 1115 7

Lupus anticoagulants (LAs) are antiphospholipid antibodies capable of interfering with the coagulation system and modifying in vitro the phospholipid-dependent clotting tests. Colloidal silica was used as activator to perform an activated partial thromboplastin time (aPTT) in 73 plasma samples with pathologically elevated kaolin clotting time (KCT) values using a photooptical automated coagulometer. Samples were incubated for 5 min with micronized silica, and after recalcification, the clotting times were measured. Pathologically prolonged results were confirmed by a confirmation and a neutralization test adding platelet-poor normal plasma (PPNP) and natural phospholipids, respectively. Silica clotting time (SCT) was abnormally elevated in 72/73 (98.6%) (mean ratio 1.71 +/- 0.28) KCT positive samples and normalized (mean ratio 1.03 +/- 0.16) after adding natural phospholipids to test plasma. The values expressed as SCT and KCT ratios were significantly correlated (r = .92; P < .001). SCT was normal in 40 healthy subjects utilised as controls (mean ratio 0.99 +/- 12). Sensitivity, specificity and diagnostic accuracy of SCT were 98.6%, 100% and 97.6%, respectively. Our data suggest that SCT is a sensitive test for detecting LA with a prolonged KCT in automated photooptical coagulometers. This peculiarity makes it particularly useful, in combination with diluted Russel viper venom time (dRVVT), for large-scale screening tests on LA.
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PMID:As compared to kaolin clotting time, silica clotting time is a specific and sensitive automated method for detecting lupus anticoagulant. 1134 5

Residual platelets in plasma are considered detrimental after freezing-thawing, as phospholipids released from ruptured platelets may quench lupus anticoagulants (LA). We aimed at assessing the effect of residual platelets after freezing-thawing plasmas tested with two procedures for LA. Blood from 52 patients suspected of having LA were centrifuged at 2,500 g. Plasmas were subdivided into 2 aliquots. One was filtered to remove residual platelets and both were frozen and stored at -70 degrees C. Silica clotting time (SCT) at low and high phospholipid concentrations and Staclot LA with and without Hexagonal phospholipids were performed on thawed plasmas. Plasmas were considered LA-positive when both SCT and Staclot LA performed on filtered plasmas were diagnostic for LA. Forty-two of 52 plasmas fulfilled the diagnostic criteria and were retained for subsequent analysis. SCT on non-filtered plasmas was diagnostic for LA in 42 of 42 plasmas. Though the median (range) percentage correction recorded after phospholipids addition for filtered plasmas, i.e., 67% (36%-83%) was reduced to 54% (25%-81%) for non-filtered plasmas (p <0.001), it was still above the cut-off (i.e., 20.9%). Staclot LA on non-filtered plasmas was diagnostic for LA in 42 of 42 plasmas. Though the median (range) clotting time difference recorded after phospholipid addition for filtered plasmas, i.e., 40.8 (10-103.5) s was reduced to 31.7 (2.8-88.8) s for non-filtered plasmas (p <0.001), it was still above the cut-off (i. e., 1.7 s). In conclusion, residual platelets do not affect the diagnostic efficacy of SCT and Staclot LA. However, the fact that the percentage correction for SCT and the clotting time difference for Staclot LA are reduced by residual platelets, suggests that weak LA may be lost upon freezing-thawing non-filtered plasmas.
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PMID:Laboratory diagnosis of lupus anticoagulants--effect of residual platelets in plasma, assessed by Staclot LA and silica clotting time. 1203 89

Silica and silicate may disturb immune function such as autoimmunity and tumour immunity. The main objective of this study was to examine the relation between sodium silicate and induction of autoimmunity in genetically susceptible rats. In this study, thirty Brown Norway rats were randomised into four treatment groups, the first and second group receiving 3 mg of sodium silicate (NaSiO(4)) (equivalent to 2 mg silica) in 0.2 mL of normal saline either per oral or subcutaneously, and the third and fourth group (control) receiving 0.2 mL of normal saline (0.9%) through the same corresponding route. A significant number of rats (80%) (P < 0.05) which received sodium silicate by the subcutaneous route showed a high level of serum ANA compared with controls. In the oral, sodium silicate group showed high serum ANA in an insignificant number of rats. Other autoantibodies in both groups (anti-dsDNA, anti-Smith, anti-SSA, anti-SSB) showed gradual increased post exposure, but the numbers of rats with positive titres post exposure was statistically not significant. Silica exposure in rats appears to induce the development of autoimmunity. A longer duration post exposure to silicate seems to be associated with greater risks.
Lupus 2009 Apr
PMID:Induction of autoimmunity in Brown Norway rats by oral and parenteral administration of sodium silicate. 1931 93

Occupational exposure to heavy metals, organic solvents and silica is associated with a variety of renal manifestations. Improved understanding of occupational renal disease provides insight into environmental renal disease, improving knowledge of disease pathogenesis. Silica (SiO2) is an abundant mineral found in sand, rock, and soil. Workers exposed to silica include sandblasters, miners, quarry workers, masons, ceramic workers and glass manufacturers. New cases of silicosis per year have been estimated in the US to be 3600-7300. Exposure to silica has been associated with tubulointerstitial disease, immune-mediated multisystem disease, chronic kidney disease and end-stage renal disease. A rare syndrome of painful, nodular skin lesions has been described in dialysis patients with excessive levels of silicon. Balkan endemic nephropathy is postulated to be due to chronic intoxication with drinking water polluted by silicates released during soil erosion. The mechanism of silica nephrotoxicity is thought to be through direct nephrotoxicity, as well as silica-induced autoimmune diseases such as scleroderma and systemic lupus erythematosus. The renal histopathology varies from focal to crescentic and necrotizing glomerulonephritis with aneurysm formation suggestive of polyarteritis nodosa. The treatment for silica nephrotoxicity is non-specific and depends on the mechanism and stage of the disease. It is quite clear that further research is needed, particularly to elucidate the pathogenesis of silica nephropathy. Considering the importance of diagnosing exposure-related renal disease at early stages, it is imperative to obtain a thorough occupational history in all patients with renal disease, with particular emphasis on exposure to silica, heavy metals, and solvents.
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PMID:Silica nephropathy. 2302 96

Inhalation of dust containing crystalline silica is associated with a number of acute and chronic diseases including systemic autoimmune diseases. Evidence for the link with autoimmune disease comes from epidemiological studies linking occupational exposure to crystalline silica dust with the systemic autoimmune diseases systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Although little is known regarding the mechanism by which silica exposure leads to systemic autoimmune disease, there is a voluminous literature on silica exposure and silicosis that may help identify immune processes that precede development of autoimmunity. The pathophysiology of silicosis consists of deposition of silica particles in the alveoli of the lung. Ingestion of these particles by macrophages initiates an inflammatory response, which stimulates fibroblasts to proliferate and produce collagen. Silica particles are encased by collagen leading to fibrosis and the nodular lesions characteristic of the disease. The steps in the development of silicosis, including acute and chronic inflammation and fibrosis, have different molecular and cellular requirements, suggesting that silica-induced inflammation and fibrosis may be mechanistically separate. Significantly, it is unclear whether silica-induced inflammation and fibrosis contribute similarly to the development of autoimmunity. Nonetheless, the findings from human and animal model studies are consistent with an autoimmune pathogenesis that begins with activation of the innate immune system leading to proinflammatory cytokine production, pulmonary inflammation leading to activation of adaptive immunity, breaking of tolerance, and autoantibodies and tissue damage. The variable frequency of these immunological features following silica exposure suggests substantial genetic involvement and gene/environment interaction in silica-induced autoimmunity. However, numerous questions remain unanswered.
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PMID:Silica, Silicosis, and Autoimmunity. 2701 76


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