Objective. Cellular adhesion and differentiation molecules (CAMs) may play a role in the recruitment and retention of inflammatory cells into rheumatoid arthritis synovial tissue (RA ST). In order to determine if certain CAMs are up‐regulated in RA ST compared with normal ST, we studied the distribution of intercellular adhesion molecules (ICAMs) 1, 2, and 3 in ST. We also studied the MS‐1 antigen since it is preferentially expressed on discontinuous endothelia, such as those found in RA ST; MS‐1 is also expressed differentially upon cytokine activation of cells in vitro or in pathologic conditions in situ. Thus, we postulated a possible similarity between MS‐1 and ICAM‐1 expression in inflamed ST. Methods. Immunohistochemical analysis was used to determine the distribution of ICAMs and MS‐1 in ST from 10 patients with RA, 10 with osteoarthritis (OA), and 4 normal individuals. Results. ICAM‐1 expression was found on significantly more RA ST endothelial cells compared with normal cells, as well as on RA ST macrophages and lining cells. ICAM‐2, also found on endothelial cells, showed no differential staining pattern. ICAM‐3 was present on RA ST macrophages and lining cells as well as on some RA and OA endothelial cells. The MS‐1 antigen was present on most RA and OA ST endothelia, lining cells, and macrophages. ICAM‐1 expression and MS‐1 expression in the lining layer were positively correlated in both RA and OA. Conclusion. ICAM‐1, while found mainly on endothelial cells, is up‐regulated on RA ST macrophages and lining cells, suggesting a role for these cells in the infiltration and tissue damage seen in the RA ST. ICAM‐3, which is present mainly on normal resting leukocytes but not on normal endothelium, is expressed by some diseased ST leukocytes and endothelial cells. MS‐1 is also found on the RA ST specialized, fenestrated endothelium, on macrophages, and in the lining layer. These results suggest that the differential expression of ICAMs and MS‐1 in RA ST compared with normal ST might play a special role in the pathogenesis of RA.

BackgroundIncreasing evidence suggests seizures cause blood–brain barrier (BBB) dysfunction including decreased seizure threshold and higher onset potential of future seizures. However, the mechanisms underlying BBB damage in seizures remains poorly understood. Evidence in human and animal models shows BBB disruption is associated with activation of matrix metalloproteinase-9 (MMP-9) after cerebral ischemia and inflammation. The objective of this study was to determine whether MMP-9 concentrations in cerebral spinal fluid (CSF) are associated with BBB disruption in patients after epileptic seizures.MethodsThirty-one patients with generalized tonic-clonic (GTC) seizures were included in the study: 20 had recurrent GTC seizures (RS), and 11 had a single GTC seizure (SS) episode. Twenty-five adult non-seizure patients were used as controls. CSF samples were collected by lumbar puncture within 24 h after seizure cessation (range: 3–15 h, mean 6.2 h). CSF MMP-9 levels were determined by an enzyme-linked immunosorbent assay (ELISA). MMP enzyme activity was measured by gelatin zymography. The CSF/serum albumin ratio (albumin quotient, QAlb) was used as a measure of blood–brain barrier permeability.ResultsWe found significantly higher CSF MMP-9 concentrations in seizure patients compared with controls (P < 0.001). CSF MMP-9 levels and QAlb values were higher in RS patients compared with SS and controls. Moreover, CSF MMP-9 concentration showed strong correlation between QAlb values (r = 0.76, P < 0.0001) and between CSF leukocyte counts (r = 0.77, P < 0.0001) in patients after seizures. Gelatin zymography showed MMP-9 proteolytic activity only in GTC seizure patients.ConclusionsOur results suggest MMP-9 plays a role in BBB dysfunction, characterized by invasion of leukocytes into the CSF during seizures.

Our data suggested a trend of association between VEGF gene polymorphisms and RA, and patients who carried the haplotype GA of rs2010963 and rs833070 were more susceptible to RA. Our study was performed in a small population, and further studies in other populations are needed to confirm these results.