Objective. To examine the association of the Arg200Trp and Arg324Gly variants of FRZB with the risk and phenotype of radiographic osteoarthritis (OA) of the hip and serum levels of Frizzled-related protein (FRP) in a prospective cohort of elderly Caucasian women.Methods. Radiographic hip OA status of patients was defined by the presence of severe joint space narrowing (JSN) (feature grade >3), a summary grade >3, or definite osteophytes (grade >2) and JSN (grade >2) in the same hip. Genotypes were obtained in 569 patients with radiographic OA of the hip and in 1,317 and 4,136 controls for the Arg200Trp and Arg324Gly variants, respectively. Serum FRP levels were measured by enzyme-linked immunosorbent assay. Multivariate logistic regression was performed.Results. The minor allele frequency for the Arg200Trp polymorphism was 0.12 in the control group compared with 0.14 in the group with radiographic OA of the hip (P ‫؍‬ 0.12), and the minor allele frequency for the Arg324Gly variant was 0.083 in the control group compared with 0.088 in the group with radiographic OA of the hip (P ‫؍‬ 0.63). The multilocus genotypes available in 1,886 subjects suggested that inheritance of both minor alleles was a risk factor for developing OA characterized by JSN (P < 0.01). Patients with radiographic OA of the hip who were homozygous for the Arg200Trp minor allele had higher serum FRP levels than controls who were homozygous for the major allele.Conclusion. Our data confirm findings of another study, that a rare haplotype with both Arg200Trp and Arg324Gly FRZB variants contributes to the genetic susceptibility to hip OA among Caucasian women, and that these polymorphisms may contribute to increased serum levels of proteins as biomarkers of OA.

CD8 ؉ and CD8 ؊ T cell lines expressing the same antigen-specific receptor [the 2C T cell receptor (TCR)] were compared for ability to bind soluble peptide-MHC and to lyse target cells. The 2C TCR on CD8 ؊ cells bound a syngeneic MHC (K b؉ )-peptide complex 10 -100 times less well than the same TCR on CD8 ؉ cells, and the CD8 ؊ 2C cells lysed target cells presenting this complex very poorly. Surprisingly, however, the CD8 ؊ cells differed little from CD8 ؉ cells in ability to bind an allogeneic MHC (L d؉ )-peptide complex and to lyse target cells presenting this complex. The CD8 ؉ ͞CD8 ؊ difference provided an opportunity to estimate how long TCR engagements with peptide-MHC have to persist to initiate the cytolytic T cell response.

Chronic GC treatment in postmenopausal women resulted in significantly decreased BMD of the hip, measured by QCT, with loss of both trabecular and cortical bone. In addition, GC treatment decreased bone strength as determined by FEM. The reduced cortical and trabecular bone mass in the hip may contribute to the disproportionately high hip fracture rates observed in GC-treated subjects.