Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental studies suggest that plasma fibronectin may be involved in the cryoprecipitation of cryoglobulins in essential mixed cryoglobulinaemia; reduced plasma concentrations of the glycoprotein have been shown in the disease. The present work was undertaken in order to verify this latter finding and to detect a possible structural alteration of plasma fibronectin as result of enzymatic digestion of the molecule in vivo. This could, in turn, induce a decreased reactivity of the protein in immunometric assays and a reduced opsonic activity, which is normally due to the affinity of fibronectin to the C1q component of complement. Moreover, since a polymorphic variant of fibronectin has been described in plasma during experimental vascular injury and in patients with autoimmune vascular diseases, the aim of this study was also to verify the presence of a polymorphism of the glycoprotein in cryoglobulinaemic vasculitis. Twenty seven patients with essential mixed cryoglobulinaemia and 26 normal subjects were included in the study. Significantly reduced concentrations of plasma fibronectin, as assessed by ELISA, were found in patients when compared with controls (231.7 +/- 15.3 vs 316.1 +/- 16.6 mg/l, P less than 0.0002). In contrast, when affinity-purified plasma fibronectin from 10 patients with essential mixed cryoglobulinaemia and 8 healthy subjects were analysed by western blotting, employing a panel of five monoclonal antibodies to different regions of the molecule, no differences were observed between patients and controls, suggesting integrity of the glycoprotein in the disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Structural and functional characterization of plasma fibronectin in patients with essential mixed cryoglobulinaemia. 144 61

Immune-complex-mediated vasculitis is a frequent complication of rheumatoid arthritis and systemic lupus erythematosus. The mechanism of deposition of immune complexes within the vessel wall in these diseases remains unknown, but probably involves other proteins. Fibronectin is a likely candidate since it possesses the ability to bind to collagen, endothelial cells, and possibly immunoglobulins and immune complexes. In this study, the binding of fibronectin to IgG and IgM cryoglobulins, cold soluble IgM, IgG, IgG subclasses and IgG fragments was investigated in the solution phase. Static light scattering, fluorescence anisotropy, fluorescence intensity, and PEG precipitation studies were used to investigate binding under different conditions of temperature and ionic strength. These studies failed to demonstrate significant binding between fibronectin and IgM, IgG, IgG subclasses and IgG fragments under the conditions studied. These findings argue against solution phase binding of fibronectin and immunoglobulins contributing to immune complex vasculitis. The possibility of important surface interactions between these proteins has not been ruled out.
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PMID:Lack of binding between cryoimmunoglobulins, immunoglobulins and fibronectin: implications for immune complex vasculitis. 182 33

Rabbits and rats were infected intratracheally with extracellular enzyme of Streptomyces thermohygroscopicus (H9-4) by only one exposure, and lesions of the lung developed including mononuclear macrophage infiltration as well as bronchitis and vasculitis. The obvious damages in type I pneumocytes, endothelial cells of capillaries and arterioles in the lung were observed by electron microscopy. Immunofluorescent histochemistry examination revealed exudation of plasma fibronectin which might play an important role during the process of lesion repairing in lung. The experiment also confirmed that extracellular enzyme of Streptomyces thermohygroscopicus might directly damage the lung tissue. These experimental data may serve as valuable reference for studying the etiology and pathogenesis of farmer's lung disease.
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PMID:An experimental study of lung lesions caused by extracellular enzyme of Streptomyces thermohygroscopicus. 187 46

Autoantibodies directed against cytoplasmic components of neutrophil granulocytes and monocytes (c-ANCA) are a disease specific marker for Wegner's granulomatosis (WG). Autoantibodies against cardiolipin (aCl) are specific for a subgroup of autoimmune disorders, which can also be associated with systemic vasculitis. Fibronectin (Fn) and von Willebrand factor antigen (vWfAg) are produced by blood vessel endothelial cells in response to injury. We tested sera of 61 patients with various types of systemic vasculitides, sera of 13 patients with retinal vasculitis, and sera of 199 patients with rheumatic diseases for c-ANCA, aCl, Fn, and vWfAg. c-ANCA was positive in 14/17 patients with WG, and 2/4 with polyarteritis nodosa (PAN). No serum from healthy donors or patients with other vasculitic or rheumatic diseases was positive for c-ANCA. Moreover, we found aCl, Fn, and vWfAg significantly elevated in almost all patients with vasculitic syndromes. Therefore, we consider c-ANCA a marker, specific for the diagnosis of WG or PAN, whereas aCl, Fn, and vWfAg are nonspecific but sensitive markers of vascular damage.
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PMID:The role of antineutrophil cytoplasm antibodies, anticardiolipin antibodies, von Willebrand factor antigen, and fibronectin for the diagnosis of systemic vasculitis. 194 24

Essential mixed cryoglobulinemia (EMC) is a rheumatic disorder characterized by widespread vasculitis. To better define the nature of the vasculitic process and to possibly outline assessment methods reliable for using in a clinical context, we studied plasma levels of three endothelial related peptides: fibronectin (FN), von Willebrand factor (vWF) and tissue plasminogen activator (t-PA), and those of thrombin-antithrombin III complexes (TAT) as markers of activation of the coagulation in 21 patients and in 16 controls. In EMC we found a picture consisting of reduced FN and increased vWF, t-PA, and TAT levels, suggesting a condition of endothelial cell damage with thrombin formation in vivo. Since we previously demonstrated the presence of chronic disseminated intravascular coagulation in these patients, we may assume that endothelial cells stressed by cryoprecipitation or stimulated by soluble mediators may be actively involved in the vasculitic process and possibly express procoagulant properties. This is a good example of the complex interplay existing between autoimmunity and coagulation mechanisms. We also suggest that FN, vWF, t-PA and TAT should be considered as additional clinical parameters when evaluating patients with EMC.
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PMID:Clinical significance of endothelial damage markers in essential mixed cryoglobulinemia. 195 Mar 76

Fibronectin is a known component of plasma cryoprecipitates. It is seen in cryoglobulins from patients with monoclonal gammopathies and also from rheumatoid arthritis, and patients with systemic lupus erythematosus and other connective tissue diseases. We evaluated the clinical relevance of measures of cryoprecipitable fibronectin from the sera of 88 patients with rheumatic diseases and 27 healthy controls. There were 28 patients with rheumatoid arthritis, 19 with systemic vasculitis, 5 with cutaneous vasculitis, and 36 with a systemic connective tissue disorder. We measured total and cryoprecipitable fibronectin and for comparison immunoglobulins G, A, and M and complement C3 and C4. Cryoprecipitable fibronectin was detected in 33% control sera and 42% patient sera. The mean levels were higher in the sera of patients in all diagnostic groups. The highest levels were seen in rheumatoid patients with systemic disease, systemic vasculitis, and connective tissue diseases. The presence of cryoprecipitable fibronectin was related to the clinical activity of systemic vasculitis; none of the 6 patients with clinically inactive vasculitis had detectable fibronectin in their cryoprecipitates; but it was seen in 7 to 13 cases with active vasculitis. There were only weak relationships between cryoprecipitable fibronectin and immunoglobulin and complement levels in cryoprecipitates. We conclude that routinely measuring fibronectin levels in cryoprecipitates is generally of doubtful diagnostic value. However, it appears to be a useful marker of the clinical activity of systemic vasculitis and we recommend its use in the laboratory assessment of vasculitis.
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PMID:Diagnostic relevance of fibronectin in cryoprecipitates. 234 38

In patients with systemic lupus erythematosus (SLE) both a haemorrhagic diathesis and a tendency to thrombosis of the venous and arterial vessels can be observed. In the course of the disease, thrombosis of the leg or pelvic veins developed in 20 per cent of 188 patients. The levels of alpha 2-plasmin inhibitor, plasminogen, fibronectin and of factor VIII complex were increased in patients with SLE compared with a control group. Fifty per cent of the patients showed no increase in fibrinolytic activity after venous occlusion measured with the fibrin plate method. This suggests a reduced fibrinolytic capacity in SLE probably caused by alteration of the endothelial cells through immune complex vasculitis. In addition, the lupus anticoagulant and an acquired antithrombin III deficiency in nephrotic syndrome in SLE are to be considered thrombophilic mechanisms. In the individual case there is an overlapping of hyper- and hypocoagulability.
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PMID:[Status of fibrinolysis in systemic lupus erythematosus]. 242

The paper treats the results of the 5-year use of plasma protein heparin cryoprecipitation (selective plasmapheresis) (SPA) in patients with immune complex pathology. The method consists in the removal of fibronectin and bound complement components, cryoglobulins, cryofibrinogen, circulating immune complexes (CIC), and other gross-dispersed proteins in the presence of heparin in the cold. The SPA was applied to 122 patients with immune complex diseases and syndromes. Altogether 1279 procedures were carried out. The method turned out effective in 80% of patients with hemorrhagic vasculitis, systemic lupus erythematosus, rheumatoid arthritis, and other types of vasculitis. The changes in the blood serum concentration of immune complexes correlated with the time-course of changes in the clinical and laboratory parameters. The SPA efficacy was in agreement with the reduction in the level of immune complexes. Provided 2-3 procedures were carried out a week, the lowering of the level of immune complexes and other laboratory parameters marking the degree of inflammation could be seen by procedures 4-6. Therefore, to attain a stable clinical effect, its is necessary to perform not less than 6 SPA procedures. It has been demonstrated that SPA can be used an unlimited number of times, for the use of the method does not entail the development of plasma protein deficiency. This circumstance is of paramount importance for the treatment of chronic relapsing immune complex diseases.
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PMID:[The results of 5 years' use of a method for heparin cryoprecipitation of plasma proteins (selective plasmapheresis) in patients with an immune-complex pathology]. 253 73

Herpes simplex virus (HSV) infection may be involved in various endothelial-injury syndromes, including vasculitis and atherosclerosis. In a previous study, it was reported that HSV-infected human umbilical endothelial cells are more vulnerable to detachment mediated by granulocyte-secreted proteases. To elucidate the molecular basis of this observation, the authors examined the interaction of infected endothelial cells with the purified basement membrane proteins, fibronectin, laminin, and type IV collagen. HSV-infected endothelial cells exhibited defects in their ability to adhere, spread, and migrate on all three matrix components. This defective adhesion could be partially overcome by increasing concentrations of fibronectin; in contrast, no abrogation of deficient binding occurs with increased levels of laminin or collagen type IV. This suggests that endothelial cells may use different surface constituents for binding to the three proteins and use multiple "receptors" for adhesion to the fibronectin molecule--"receptors" that are variably affected by HSV infection. The authors investigated this supposition by assaying adhesion of normal and infected endothelial cells to two non-overlapping cell-adhesion promoting fragments of fibronectin: 1) a 75 kd motility-promoting fragment which contains the arginyl-glycyl-aspartylserine (RGDS) adhesion sequence, and 2) a 33 kd carboxyl-terminal heparin binding fragment, which promotes cell adhesion by an RGDS-independent mechanism. Normal endothelial cells adhered and spread on both purified fragments. In contrast, while infected endothelial cells could adhere, albeit rather poorly, to high coating concentrations of the 75 kd fragment, these cells did not bind to the 33 kd heparin binding fragment of fibronectin at all. These results support the concept that endothelial cells adhere to multiple domains of fibronectin, and that HSV infection preferentially abrogates binding to the heparin-binding domain, while leaving relatively intact receptors for the RGDS-containing domain. In support, soluble RGDS significantly blocked fibronectin adhesion of infected, but not control, endothelial cells. It is concluded that HSV infection inhibits the interaction of endothelial cells with basement membrane proteins and weakens their tethering to substratum. This tethering is inadequate for proper cell spreading or movement to occur and may result in both excessive endothelial lift-off and impaired vascular repair in HSV infections.
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PMID:Herpes simplex virus inhibits endothelial cell attachment and migration to extracellular matrix proteins. 253 23

Rabbits and rats were infected intratracheally with extracellular enzyme of streptomyces thermohygroscopicus (H9-4) for only one exposure and lesions of lung developed which included mononuclear macrophage infiltration as well as bronchitis and vasculitis. The obvious damages in type I pneumocytes, endothelial cells of capillaries and arterioles in the lung were observed by electron microscopy. Immunofluorecent histochemistry examination revealed exudation of plasma fibronectin which might be important to play certein role during the process of wound repairing in lung. The experiment also confirmed that extracellular enzyme of streptomyces thermohygroscopicus might directly damage the lung tissue, and these experimental data may serve valuable reference for studying the etiology and pathogenesis of farmer's lung diseases.
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PMID:[Study of experimental lung lesions caused by extracellular enzyme of Streptomyces thermohygroscopicus]. 258 45


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