A previous study reported that intercellular adhesion molecule-1 (ICAM-1) expression by human vascular endothelial cells (HUVEC) is augmented by intracellular signal transmission mainly through the protein kinase C (PKC) system stimulated by TXA2 receptors. In the present study, we show that a TXA2 receptor agonist, U46619, augments the expression of not only ICAM-1, but also vascular cell adhesion molecule-1 (VCAM-1) or endothelial leucocyte adhesion molecule-1 (ELAM-1) in HUVEC both at protein and mRNA levels. Pretreatment with SQ29,548 (a TXA2 receptor antagonist) or PKC inhibitors greatly diminished the extent of U46619-induced mRNA accumulation and surface expression of the adhesion molecules. An inhibitor of nuclear factor kappaB (NF-kappaB) activation, PDTC, diminishes U46619-induced VCAM-1 mRNA accumulation. NAC, which inhibits NF-kappaB and activation protein 1 (AP-1) binding activity, inhibits the expression of ICAM-1 or ELAM-1 at protein and mRNA levels. These findings suggest that ICAM-1 or ELAM-1 expression of HUVEC stimulated via TXA2 receptors is augmented by induction of NF-kappaB and AP-1 binding activity through the PKC system, and that VCAM-1 expression is augmented by induction of NF-kappaB binding activity.

A Randomized, Double-Blind, Placebo-Controlled Trial TOSHIHIKO HIDAKA, KIMIHIRO SUZUKI, YASUNORI MATSUKI, MITSUYO TAKAMIZAWA-MATSUMOTO, KOUJI KATAHARADA, TOSHIAKI ISHIZUKA, MAKOTO KAWAKAMI, and HARUO NAKAMURA Objective. To determine the efficacy and safety of filtration leukocytapheresis (LCP) for the treatment of rheumatoid arthritis (RA). Methods. Twenty-five patients with drug-resistant RA were randomly assigned to undergo filtration LCP and 7 to undergo sham apheresis (control group) in a randomized, double-blind, placebo-controlled study. Three apheresis procedures were performed, with 1-week intervals between procedures. The efficacy of filtration LCP was evaluated according to the American College of Rheumatology definition of improvement in RA. Medications for each patient were unchanged for at least 6 months prior to enrollment and throughout the study. Results. Tender joint counts, swollen joint counts, patient assessment of pain and global severity, physician assessment of global severity, and Health Assessment Questionnaire Disability Index were significantly improved in the LCP group compared with the control group (P < 0.05 for patient assessment of pain; P < 0.01 for all others). Seventy-nine percent of the patients in the LCP group exhibited significant overall improvement , while none of the patients in the control group were improved (P < 0.001). Conclusion. The results indicate that filtration LCP is an effective and well-tolerated treatment for patients with drug-resistant RA.

The purpose of this study is to determine the changes in CD4+ T lymphocyte subsets in the circulating blood and synovial fluid following filtration leukocytapheresis (LCP) therapy for patients with rheumatoid arthritis (RA). A Cellsorba column packed with polyester fibers was used for the removal of circulating leukocytes. For patients with RA, filtration LCP or sham procedures were performed 3 times with 1 week intervals between procedures. T lymphocyte surface markers in the peripheral blood and synovial fluid were measured by flow cytometry. The proportions of activated CD4+ T cells

No abstract