Objective. The transcription factor–κB (NF‐κB) has been implicated in the inflammatory response and is known to be activated by a process involving reactive oxygen intermediates. The purpose of the present study was to demonstrate the presence and distribution of activated NF‐κB in synovium samples from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and from autopsy subjects with no known history of arthritis. Methods. Immunohistochemical staining was performed using both polyclonal and monoclonal “activity‐specific” antibodies to the Rel‐A (p65) subunit of NF‐κB (anti‐Rel‐A nuclear location sequences). Histologic features of inflammation were also scored. Results. Both antibodies demonstrated positive staining of synovial tissue, with a cellular distribution that was nuclear. The staining was associated with specific cell types within the tissue, in particular, type A synoviocytes and vascular endothelium. Notably, lymphoid aggregates were unstained. Using the monoclonal antibody, a further study was carried out to investigate the distribution of staining in tissues from patients with different disease activities and clinical diagnoses, as well as in normal control tissue obtained at autopsy. Patients with acute RA more commonly showed vessel staining (P = 0.05) and, conversely, showed less frequent staining of the synovial lining (P < 0.005) compared with OA patients. Synovial tissue from controls exhibited either no staining or only weak staining in the synovial lining. Conclusion. The activation of NF‐κB in vascular endothelium and type A synovial lining cells is a feature of synovial tissue from both RA and OA patients. The distribution of this staining appears to be related to the clinical diagnosis.
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Objective. To develop a method for quantifying acute synovial inflammation in rheumatoid arthritis (RA), utilizing magnetic resonance imaging (MRI).Methods. Gadolinium4iethylenetriamine pentaacetic acid-enhanced MRI was performed in 21 patients with knee synovitis. Changes in synovial membrane signal intensity were identified and quantified by line profile analysis. Multiple synovial biopsies were obtained by a blind biopsy technique, and standard clinical and laboratory measurements of disease activity were recorded.Results. The rate of synovial membrane enhancement correlated with histologic features of acute inflammation (r = 0.63, P < 0.01), but not with clinical or laboratory assessments.Conclusion. Dynamic MRI is a valuable technique for assessing acute synovial inflammation in RA.Magnetic resonance imaging (MRI) allows direct visualization of rheumatoid synovium following intravenous administration of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and has been proposed as a potentially valuable tool for evaluating synovitis (14). Synovial membrane uptake of Gd-DTPA (enhancement) is dependent on tissue perfusion and microvascular permeability, and manifests as increased signal intensity (brightness) on T1-weighted images. Therefore, since both increased tissue perfusion and microvascular permeability are cardinal features of all acute inflammatory processes, quantification of the rate of synovial membrane enhancement Supported by the Arthritis and Rheumatism Council (UK).
Objective-To examine the relation between rate of synovial membrane enhancement, intra-articular pressure (IAP), and histologically determined synovial vascularity in rheumatoid arthritis, using gadolinium-DTPA enhanced magnetic resonance imaging (MRI). Methods-Dynamicgadolinium-DTPA enhanced MRI was performed in 31 patients with knee synovitis (10 patients IAP study, 21 patients vascular morphometry study). Rate of synovial membrane enhancement was quantified by line profile analysis using the image processing package ANALYZE. IAP was measured using an intra-compartmental pressure monitor system. Multiple synovial biopsy specimens were obtained by a blind biopsy technique. Blood vessels were identified immunohistochemically using the endothelial cell marker QBend30 and quantified (blood vessel numerical density and fractional area). Results-Median Conclusions-Gadolinium-DTPAenhanced MRI may prove to be a valuable technique for evaluating drugs that influence angiogenesis.
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