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)

Activation of the vascular endothelium is thought to be an important facet of inflammation, thrombosis, and vasculitis. Activated endothelial cells express a number of immunologically relevant surface markers not expressed by normal endothelial cells. Many of these surface antigens are thought to augment adhesion reactions and migration. Our results show that endothelial activation may play a central role in the pathogenesis of multiple sclerosis (MS). Normal human central nervous system microvessels isolated from autopsy material do not express endothelial cell activation markers, including the adhesion proteins vascular cell adhesion molecule-1 (VCAM-1) and endothelial cell leukocyte adhesion molecule-1 (E-selectin/ELAM-1). They exhibit little to no constitutive expression of immunoreactive intercellular adhesion molecule-1 (ICAM-1) or the urokinase plasminogen activator receptor. Control microvessels exhibit no major histocompatibility complex (MHC) class II antigen. MS microvessels express significant levels of MHC class II antigens, ICAM-1, VCAM-1, and urokinase plasminogen activator receptor. E-selectin was expressed by 3 of 5 MS brains tested. Histologically unaffected areas of MS brain expressed less VCAM-1, ICAM-1, and E-selectin than did microvessels from periplaque zones. However, MHC class II antigens and urokinase plasminogen activator receptor were increased in areas exhibiting little to no evidence of leukocyte infiltration. When microvessels were examined for dual expression of activation markers, we found that in periplaque areas, 50% of microvessels coexpressed HLA-DR and VCAM-1, 28% of microvessels coexpressed HLA-DR and urokinase plasminogen activator receptor, and 43% of microvessels coexpressed HLA-DR and ICAM-1.
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PMID:Expression of immunologically relevant endothelial cell activation antigens on isolated central nervous system microvessels from patients with multiple sclerosis. 750 77

Extensive damage is thought to occur to endothelial cells in renal vasculitis and other glomerulopathies. The state of inflammation of these endothelial cells was investigated through the use of a panel of monoclonal antibodies (MAb) directed against thrombospondin (TSP), von Willebrand factor (vWF), integrins (alpha IIb beta 3, alpha v beta 3), CD36, and classical markers of inflammation (P-selectin, E-selectin, ICAM-1, VCAM). Results show that the anti-TSP MAb (LYP10) stains large areas of interstitium in focal sclerosis, vasculitis, membranous glomerulonephritis (GN), and diabetic GN but does not in normal kidney. In contrast, very limited areas are stained by LYP10 in minimal change nephropathy and Berger's disease. On paraffin-embedded specimens these areas stained by LYP10 appear edematous and early fibrous. Up-regulation of vWF and ICAM-1 is matched by an increased binding of LYP10 to the interstitium. In addition, fibrous crescents in injured glomeruli are stained by LYP10. This study reports for the first time an increased TSP secretion in glomerulopathies. Such TSP secretion may be part of physiological adaptive changes associated with inflammation and early fibrosis.
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PMID:Thrombospondin in human glomerulopathies. A marker of inflammation and early fibrosis. 751 60

The plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1), E-selectin (sE-selectin), and vascular cell adhesion molecule-1 (sVCAM-1), might reflect endothelial activation and injury and would therefore be useful markers of disease activity in vasculitis. To investigate this we measured the levels of sICAM-1, sE-selectin, and sVCAM-1 by two-site ELISAs in the plasma of patients with (a) active vasculitis (n = 16), (b) vasculitis in remission (n = 15), (c) chronic renal failure (CRF) (n = 10), and (d) normal healthy controls (n = 10). Plasma sICAM-1 levels were significantly higher in patients with active vasculitis, 323 ng/ml (193-607) compared with patients with inactive vasculitis, 199 ng/ml (131-297); P = 0.0006 and healthy controls, 188 ng/ml (138-259); P = 0.0002. Plasma sE-selectin levels were also significantly higher in the patients with active vasculitis, 45 ng/ml (15-65) compared with patients with inactive vasculitis, 25 ng/ml (15-55); P = 0.027 but not when compared with healthy controls, 35 ng/ml (20-55); P = 0.16. There was no difference in plasma sVCAM-1 levels between patients with active vasculitis, OD 0.56 (0.45-0.85) and inactive disease, OD 0.58 (0.47-0.79) (P = 0.12) or with healthy controls OD 0.49 (0.42-0.68) (P = 0.48). There were no significant differences between the plasma levels of any of the soluble adhesion molecules between patients with active vasculitis and patients with chronic failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Circulating soluble adhesion molecules in systemic vasculitis. 752 74

Fifty-nine children with acute Kawasaki disease (KD), a childhood vasculitis, were compared with 35 children with fever due to infection and 48 healthy children. Levels of soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) in the healthy children were double those found in adults. All three soluble cell adhesion molecules and von Willebrand factor (vWF) were higher in the children with KD than in the healthy children, but only sE-selectin, a marker for activated endothelial cells, and sICAM-1 were higher than in the febrile children. The high levels of vWF in KD appear to reflect the prominent acute-phase reaction. This information can help us to understand further the complex interactions between cytokines, circulating inflammatory cells and the vascular endothelium, and may lead to new therapeutic avenues in KD and other inflammatory diseases and vasculitides.
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PMID:Soluble cell adhesion molecules and von Willebrand factor in children with Kawasaki disease. 754 71

Endothelial cell activation is achieved by the rapid, protein synthesis-independent induction of a characteristic set of genes. Because of the abundance of binding sites for the transcription factor NF-kappa B in the regulatory region of the aforementioned genes, we hypothesized that this factor might play a key role. Reactive oxygen intermediates act as second messengers in the activation of NF-kappa B. We have used the antioxidant pyrrolidine dithiocarbamate to analyze the effect of NF-kappa B inhibition on TNF alpha-induced EC activation in vitro. We show that pyrrolidine dithiocarbamate strongly reduces the TNF alpha-mediated induction of E-selectin, VCAM-1, ICAM-1, PAI-1, tissue factor, IL-8 and I kappa B-alpha. We present evidence identifying NF-kappa B as a central of EC activation. Therefore, this factor may represent a prime target for therapeutic intervention in pathologic conditions associated with EC activation such as allo- and xenograft rejection, atherosclerosis, ischemic reperfusion injury and vasculitis.
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PMID:Inhibition of NF-kappa B by pyrrolidine dithiocarbamate blocks endothelial cell activation. 754 93

We compared the levels of soluble adhesion molecules E-selectin (sE-selectin), intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) alongside von Willebrand factor (vWf), CRP and rheumatoid factor in 40 patients in serum by ELISA, rheumatoid factor by sheep red blood cell agglutination and CRP by immunonephelometry. Compared to controls, increased sE-selectin was found in patients with RA (P = 0.0015), vasculitis (P < 0.0003) and SSc (P = 0.0126), whilst raised sICAM-1 was found in RA (P < 0.0003), vasculitis (P < 0.0003) and SSc (P < 0.0378). sVCAM was lower in RA than in controls (P = 0.0102), but was unchanged in vasculitis or in SSc. vWF was raised in RA (P = 0.0102), vasculitis (P < 0.0003) and SSc (P < 0.0003). In a Spearman's rank analysis of all the data, vWf correlated with sVCAM-1 and sICAM-1 (both P < 0.001), sE-selectin with sICAM-1 (P < 0.001) and sVCAM with sICAM-1 (P < 0.005). Levels of rheumatoid factor correlated with those of sE-selectin (P = 0.003) and sVCAM-1 (P = 0.012), but there were no correlations between any index and CRP. The strongest correlations within the RA group were between sICAM and sVCAM (P = 0.001), in vasculitis it was between sE-selectin and sICAM (P < 0.001), and in SSc it was between sE-selectin and sVCAM (P = 0.019). These data suggest that the differing levels of vWf, sE-selectin and sICAM-1 in the inflammatory vasculitides may be useful in establishing a role for leucocyte/endothelial adhesion in these diseases.
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PMID:Altered levels of soluble adhesion molecules in rheumatoid arthritis, vasculitis and systemic sclerosis. 758 19

Severe Plasmodium falciparum malaria is characterized by multiple organ involvement due to sequestration of infected erythrocytes in small vessels. Endothelial cell adhesion molecules play an important role in this interaction. During the course of a severe cerebral P. falciparum malaria infection we found very markedly elevated levels of the soluble adhesion molecules intercellular adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1, with a maximum increase of nine, seven, and eight times, respectively. These very high levels of soluble adhesion molecules point to an endothelial cell injury as an additional cause to physiological release or shedding due to receptor interactions. Soluble thrombomodulin (sTM) levels showed an extremely marked elevation up to 332 ng/ml (up to 13 times the normal value) as well. Malaria patients without severe organ involvement/cerebral manifestation showed only a mild elevation of sTM levels. TM is a parameter independent of the immunological system. It is regarded as a marker of vasculitis and endothelial cell destruction. Therefore, markedly elevated sTM levels document a substantial endothelial cell injury in severe malarial infection and may be of diagnostic and prognostic importance.
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PMID:Serum levels of adhesion molecules and thrombomodulin as indicators of vascular injury in severe Plasmodium falciparum malaria. 781 16

VCAM-1 was first identified as an adhesion molecule induced on human endothelial cells (HEC) by inflammatory cytokines such as IL-1, tumour necrosis factor (TNF), and lipopolysaccharide (LPS). The molecule binds to a variety of leucocytes, including B cells, T cells, basophils, eosinophils and monocytes. Vascular expression of VCAM-1 has been associated with a number of disease states, including rheumatoid arthritis and vasculitis. The detection of anti-neutrophil cytoplasmic antibodies (ANCA), especially to proteinase 3 (PR3), has become important in the diagnosis of Wegener's granulomatosis (WG) and related vasculitides. Recently we were able to demonstrate a direct effect of anti-PR3 antibodies on neutrophil-endothelial interactions (Blood 1993; 82:1221). Binding of anti-PR3 antibodies to their antigen translocated into the membrane of HEC leads to an enhanced adhesion of neutrophils via induction of E-selectin (Clin Exp Immunol 1993; 94:440). The aim of this study was to investigate the effect of anti-PR3 antibodies on the expression of VCAM-1. HEC were isolated from umbilical vein and cultured on microtitre plates. After preincubation with purified anti-PR3 antibody, purified control antibodies (SS-A, SS-B, RNP) (IgG and F(ab')2 fragments) or different cytokines (controls), VCAM-1 was detected on the surface of unfixed HEC by cyto-ELISA and polymerase chain reaction analysis. Incubation of HEC with anti-PR3 antibodies led to a marked increase of endothelial VCAM-1 expression with a peak after 8 h. Incubation with TNF-alpha also led to maximal VCAM-1 expression after 4-6 h (control). Increased adhesion of T lymphocytes to HEC after binding of anti-PR3 antibodies to their antigen could be confirmed by performing adherence assays. This effect could be inhibited by antibodies to VLA-4. In conclusion, we have been able to show that cytokine-like effects of anti-PR3 antibodies on HEC are not limited to induction of neutrophil adhesion. Anti-PR3 antibodies may thus contribute to the regulation of T lymphocyte migration from the blood by HEC in ANCA-related vasculitides.
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PMID:Antibodies to proteinase 3 mediate expression of vascular cell adhesion molecule-1 (VCAM-1). 856 9

Plasma concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin) and intercellular adhesion molecule-1 (sICAM-1) were measured by enzyme-linked immunosorbent assay in four groups of children. Group 1 consisted of 20 patients with acute diarrhoea-associated haemolytic uraemic syndrome (D+HUS), the aetiology of HUS being verocytotoxin-producing Escherichia coli infection in each case. Controls consisted of 11 patients who had previously had D+HUS (group 2), 12 with chronic renal failure (group 3) and 8 healthy controls (group 4). When compared with healthy controls, the acute D+HUS group had higher sVCAM-1 (median 1,875 ng/ml, range 1,200-6,450 ng/ml vs. 1,200 ng/ml, range 975-2,125 ng/ml), von Willebrand factor antigen, (1.9 U/ml, range 0.85-5.1 U/ml vs. 0.55 U/ml, range 0.3-1.57 U/ml), white cell count (WBC, 14.5 x 10(9)/l, range 7.8-43.1 10(9)/l vs. 8.9 10(9)/l, range 5.7-10.8 10(9)/l) and neutrophil count (PMN, 10.1 x 10(9)/l, range 4.3-26.5 10(9)/l vs. 4.3 10(9)/l, range 3.7-6.6 10(9)/l), all P < 0.005, and sICAM-1 was reduced (230 ng/ml, range 130-340 ng/ml vs. 400 ng/ml, range 260-690 ng/ml), P < 0.05. Within the acute D+HUS group there was a significant correlation between sICAM-1 and PMN (r = 0.56, P < 0.01). There was no correlation between any adhesion molecule and plasma creatinine or von Willebrand factor. Comparing the acute HUS group with children with chronic renal failure, WBC (P < 0.001), PMN (P < 0.01) and sVCAM-1 (P < 0.01) were significantly elevated, but there was no difference between the von Willebrand factor (P = 0.08) or the sICAM-1 (P > 0.1). sVCAM-1 is elevated and sICAM-1 decreased in acute D+HUS. This pattern of altered adhesion molecule concentration is unlike that in adults with vasculitis and suggests that different endothelial regulatory factors are at play.
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PMID:Soluble circulating cell adhesion molecules in haemolytic uraemic syndrome. 858 13

Cell surface adhesion molecules (CAM) are important promotors of the immunoinflammatory cascade. The circulating levels of soluble intercellular adhesion molecule 1 (ICAM-1) have previously been shown to correlate with disease activity in inflammatory bowel disease. The primary aim of this study was consequently to investigate if this also applies to mucosal levels of soluble ICAM-1. We measured soluble ICAM-1 levels in intestinal biopsy specimens and the endoscopic activity of 69 patients with ulcerative colitis (UC) and 14 controls and found that the median concentration of soluble ICAM-1 was significantly higher in patients with moderately or very active UC (15.0 ng/ml) as compared to slightly active (9.8 ng/ml) and inactive UC (9.5 ng/ml) as well as controls (6.5 ng/ml) (P < 0.005). To further elucidate the interactions, two other CAM [E-selectin and vascular cellular adhesion molecule 1 (VCAM-1)], together with interleukin-8 (IL-8), IL-2 receptor (IL-2R) alpha and beta chains, were also measured. A significant trend towards higher soluble E-selectin levels in biopsies with active UC (1.8 pg/ml) as compared to inactive UC (1.3 pg/ml) and to controls (< 1.0 pg/ml) (P < 0.01) was also found. In contrast, soluble VCAM-1 was barely detectable in biopsies from two UC patients. A significant correlation was found between soluble ICAM-1 and IL-8 concentrations (r = 0.46; P < 0.0001), and between sICAM-1 and sIL-2R alpha concentrations (r = 0.69; P < 0.0001), while sIL-2R beta was not detected. This study shows that intestinal ICAM-1 and E-selectin correlate with endoscopic activity of UC and with IL-8 and IL-2R alpha levels. These mediators may be useful in monitoring mucosal inflammation in studies exploring the therapeutical potential of targeting CAM. The lack of detectable VCAM-1, which is induced only in venous endothelium is interesting. It may suggest that intestinal inflammation mainly affects arterial endothelial cells and support the theory that intestinal vasculitis is involved in the pathogenesis of inflammatory bowel disease.
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PMID:Increased mucosal concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), sE-selectin, and interleukin-8 in active ulcerative colitis. 879 94


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