Evaluation of filtration leucocytapheresis for use in the treatment of patients with rheumatoid arthritis.

OBJECTIVES: To evaluate the efficacy of filtration leucocytapheresis (LCP) for rheumatoid arthritis (RA). METHODS: LCP was carried out three times, with 1 week separating each session, in 25 drug-resistant RA patients. RESULTS: During each session, 96, 98, 61, 84 and 8% of the granulocytes, monocytes, lymphocytes, platelets and erythrocytes, respectively, that entered the LCP filter were removed. The number of granulocytes, monocytes and lymphocytes in the peripheral blood significantly decreased during each session of LCP. However, there was no significant decrease in the number of circulating blood cells during the study period. On average, 110 x 10(8) granulocytes, 5.23 x 10(8) monocytes, and 20.5 x 10(8) lymphocytes were removed during LCP therapy. Assessment of RA before and after LCP showed a substantial and rapid improvement in the tender joints counts, swollen joint counts, and patient's and physician's assessments. No adverse reactions or complications were noted. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels decreased following LCP, although the change in the latter parameter was statistically insignificant. The concentrations of serum albumin, gamma-globulin, IgG, IgM, CH50 and rheumatoid factor titres did not change during or after LCP. Careful analysis indicated that 16 of 25 patients with RA showed > or =20% improvement following LCP therapy. CONCLUSIONS: Our results suggest that filtration LCP to remove leucocytes from the peripheral blood exerts an immunomodulatory effect in patients with RA.

Mg2+ inhibits formation of 4Ca(2+)-calmodulin-enzyme complex at lower Ca2+ concentration. 1H and 113Cd NMR studies.

Our previous 1H NMR studies indicated that when mastoparan (MP) is added to Ca(2+)-half-saturated calmodulin (2Ca(2+)-CaM) in the absence of Mg2+ ions, Ca2+ ions transfer from the C-terminal-half domain of CaM not interacting with MP to the N-terminal-half domain of CaM interacting with MP at lower MP concentrations (Ohki, S., Yazawa, M., Yagi, K., and Hikichi, K. (1991b) J. Biochem. (Tokyo) 110, 737-742). As a consequence, the active form of 4Ca(2+)-CaM.MP complex is formed. In the present study, we studied the effect of Mg2+ ions on Ca2+ transfer. In the presence of Mg2+ ions, such Ca2+ transfer does not occur. The effects of Mg2+ ions are also studied by observing 113Cd NMR in the presence of M13, the 26-residue peptide of the CaM-binding region of myosin light chain kinase. The 113Cd NMR results show that Mg2+ ions prevent to form the active complex. Mg2+ plays an important role as an inactivating factor to CaM.