CD26, the T cell activation molecule dipeptidyl peptidase IV (DPPIV), associates with a 43-kilodalton protein. Amino acid sequence analysis and immunoprecipitation studies demonstrated that this 43-kilodalton protein was adenosine deaminase (ADA). ADA was coexpressed with CD26 on the Jurkat T cell lines, and an in vitro binding assay showed that the binding was through the extracellular domain of CD26. ADA deficiency causes severe combined immunodeficiency disease (SCID) in humans. Thus, ADA and CD26 (DPPIV) interact on the T cell surface, and this interaction may provide a clue to the pathophysiology of SCID caused by ADA deficiency.

Conclusion. These data suggest that IL-22, produced by synovial fibroblasts and macrophages, promotes inflammatory responses in RA synovial tissues by inducing the proliferation and chemokine production of synovial fibroblasts.

Abstract. A reduction in ankle-brachial BP index (ABPI) is associated with generalized atherosclerotic diseases and predicts cardiovascular mortality and morbidity in several patient populations. However, a large-scale analysis of ABPI is lacking for hemodialysis (HD) patients, and its use in this population is not fully validated. A cohort of 1010 Japanese patients undergoing chronic hemodialysis was studied between November 1999 and May 2002. Mean age at entry was 60.6 Ϯ 12.5 yr, and duration of follow-up was 22.3 Ϯ 5.6 mo. Patients were stratified into five groups (Ͻ 0.9, Ն 0.9 to Ͻ 1.0, Ն 1.0 to Ͻ 1.1, Ն 1.1 to Ͻ 1.3, and Ն 1.3) by ABPI measured at entry by an oscillometric method. The frequency distribution of ABPI was 16.5% of patients Ͻ 0.9, 8.6% of patients Ն 0.9 to Ͻ 1.0, 16.9% of patients 1.0 Ն to Ͻ 1.1, and 47.0% of patients Ն 1.1 to Ͻ 1.3, whereas 10.9% of patients had an abnormally high ABPI (Ն 1.3). The relative risk of a history of diabetes mellitus (DM), cardiovascular, and cerebrovascular disease was significantly higher in patients with lower ABPI than those with ABPI Ն 1.1 to Ͻ1.3. During the study period, 77 cardiovascular and 41 noncardiovascular fatal events occurred. On the basis of Cox proportional hazards regression analysis, ABPI emerged as a strong independent predictor of all-cause and cardiovascular mortality. After adjustment for confounding variables, the hazard ratio (HR) for ABPI Ͻ 0.9 was 4.04 (95% confidence interval, 2.38 to 6.95) for all-cause mortality and 5.90 (2.83 to 12.29) for cardiovascular mortality. Even those with modest reductions in the ABPI (Ն 0.9 to Ͻ1

CUB domain-containing protein 1 (CDCP1) is a membrane protein that is highly expressed in several solid cancers. We reported previously that CDCP1 regulates anoikis resistance as well as cancer cell migration and invasion, although the underlying mechanisms have not been elucidated. In this study, we found that expression of CDCP1 in pancreatic cancer tissue was significantly correlated with overall survival and that CDCP1 expression in pancreatic cancer cell lines was relatively high among solid tumor cell lines. Reduction of CDCP1 expression in these cells suppressed extracellular matrix (ECM) degradation by inhibiting matrix metalloproteinase-9 secretion. Using the Y734F mutant of CDCP1, which lacks the tyrosine phosphorylation site, we showed that CDCP1 regulates cell migration, invasion, and ECM degradation in a tyrosine phosphorylation-dependent manner and that these CDCP1-associated characteristics were inhibited by blocking the association of CDCP1 and protein kinase Cdelta (PKCdelta). CDCP1 modulates the enzymatic activity of PKCdelta through the tyrosine phosphorylation of PKCdelta by recruiting PKCdelta to Src family kinases. Cortactin, which was detected as a CDCP1-dependent binding partner of PKCdelta, played a significant role in migration and invasion but not in ECM degradation of pancreatic cells. These results suggest that CDCP1 expression might play a crucial role in poor outcome of pancreatic cancer through promotion of invasion and metastasis and that molecules blocking the expression, phosphorylation, or the PKCdelta-binding site of CDCP1 are potential therapeutic candidates.