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OBJECTIVE: A hallmark of rheumatoid arthritis (RA) is invasion of the synovial pannus into cartilage, and this process requires degradation of the collagen matrix. The aim of this study was to explore the role of one of the collagen-degrading matrix metalloproteinases (MMPs), membrane type 1 MMP (MT1-MMP), in synovial pannus invasiveness. METHODS: The expression and localization of MT1-MMP in human RA pannus were investigated by Western blot analysis of primary synovial cells and immunohistochemical analysis of RA joint specimens. The functional role of MT1-MMP was analyzed by 3-dimensional (3-D) collagen invasion assays and a cartilage invasion assay in the presence or absence of tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2, or GM6001. The effect of adenoviral expression of a dominant-negative MT1-MMP construct lacking a catalytic domain was also examined. RESULTS: MT1-MMP was highly expressed at the pannus-cartilage junction in RA joints. Freshly isolated rheumatoid synovial tissue and isolated RA synovial fibroblasts invaded into a 3-D collagen matrix in an MT1-MMP-dependent manner. Invasion was blocked by TIMP-2 and GM6001 but not by TIMP-1. Invasion was also inhibited by the overexpression of a dominant-negative MT1-MMP, which inhibits collagenolytic activity and proMMP-2 activation by MT1-MMP on the cell surface. Synovial fibroblasts also invaded into cartilage in an MT1-MMP-dependent manner. This process was further enhanced by removing aggrecan from the cartilage matrix. CONCLUSION: MT1-MMP serves as an essential collagen-degrading proteinase during pannus invasion in human RA. Specific inhibition of MT1-MMP-dependent invasion may represent a novel therapeutic strategy for RA. [ABSTRACT FROM AUTHOR]

BACKGROUND: Total ankle arthroplasty (TAA) is becoming an effective treatment for end-stage ankle arthritis. It is unknown if TAA alters the patient's ability to sense ankle joint position. MATERIALS AND METHODS: Thirteen unilateral TAA patients with a minimum of 2-years followup completed proprioceptive testing of the TAA and the contralateral side. The task was to reproduce a given ankle angle using a joystick-driven device while the lower limb was obscured from view. Nine angles were tested, including two angles in dorsiflexion, three in plantarflexion, two in inversion, and two in eversion. A repeated-measures ANOVA was used to evaluate the results. RESULTS: No statistically significant differences between the TAA ankle and the contralateral side were found. CONCLUSION: TAA does not cause a change in proprioceptive abilities in arthritis patients when compared to the contralateral, unaffected side in a small sample of unilateral patients. Surgeons and rehabilitation professionals may use this information when designing rehabilitation plans following the insertion of a TAA. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We sought to assess the ability of human epididymis protein 4 (HE4) and CA-125 to distinguish among benign, borderline, and malignant pelvic masses in premenopausal women. STUDY DESIGN: We conducted a subset analysis of data from a prospective clinical trial that enrolled women undergoing surgery for an adnexal mass. Diagnostic performance of CA-125 and HE4 for epithelial ovarian cancer (EOC) detection in premenopausal women was determined. RESULTS: Of 229 premenopausal patients, 195 (85%) had benign masses, 18 (8%) had EOC, and 16 (7%) had borderline ovarian tumor. The sensitivity of CA-125 and HE4 for EOC detection was 83.3% and 88.9%, respectively. The specificity of CA-125 and HE4 was 59.5% and 91.8%, respectively. A normal HE4 level ruled out invasive cancer in 98% of women with an elevated CA-125. CONCLUSION: HE4 offers superior specificity compared to CA-125 for the differentiation of benign and malignant adnexal masses in premenopausal women. [ABSTRACT FROM AUTHOR]