OBJECTIVE To study the short-term effects of physical therapy (ice massage or wax packs, thermal baths, and faradic hand baths) and exercise therapy on the rheumatoid hand. METHODS The effect of individual physical therapy and exercise therapy programs was evaluated in 50 randomly selected rheumatoid arthritis inpatients (38 women and 12 men). Mean patient age (+/- SD) was 47.94 +/- 11.22 years, and mean disease duration was 5.04 +/- 4.80 years. The control group consisted of 50 randomly selected rheumatoid arthritis outpatients (37 women and 13 men; mean age 48.46 +/- 10.65 years, mean duration of disease 5.23 +/- 4.89 years) who at the time of the investigation were not receiving any physical or exercise therapy. The clinical indices used for evaluation of inflammation included erythrocyte sedimentation rate (ESR), pain intensity, proximal interphalangeal (PIP) joint size, and Ritchie articular index. Hand grip strength, palmar tip-to-tip and key pinch finger strength, finger range of motion, and activities of daily living (ADL) were the parameters used to assess the functional hand status. The study was single-blinded and of 3 weeks duration. RESULTS In the physical therapy treated group, there was an improvement for most of the observed indices from baseline parameters that achieved statistical significance (P < 0.01 and P < 0.005) after the 3-week study period. ESR and PIP joint size improved clinically but failed to reach statistical significance. Patients had a more significant improvement in hand pain, joint tenderness, and ADL score (P < 0.005) than in range of motion (P < 0.01). All parameters in the control group slightly deteriorated over the study period. CONCLUSION At least in the short term, physical and, particularly, exercise therapy produce a favorable improvement in the functional status of the rheumatoid hand.

The dynamics of pigment-pigment and pigment-protein interactions in light-harvesting complexes is studied with an approach that combines molecular dynamics simulations with quantum chemistry calculations and a polaron model analysis. The molecular dynamics simulation of light-harvesting (LH) complexes was performed on an 87 055 atom system comprised of a LH-II complex of Rhodospirillum molischianum embedded in a lipid bilayer and surrounded with appropriate water layers. For each of the 16 B850 bacteriochlorophylls (BChls), we performed 400 ab initio quantum chemistry calculations on geometries that emerged from the molecular dynamical simulations, determining the fluctuations of pigment excitation energies as a function of time. From the results of these calculations we construct a time-dependent Hamiltonian of the B850 exciton system from which we determine within linear response theory the absorption spectrum. Finally, a polaron model is introduced to describe both the excitonic and coupled phonon degrees of freedom by quantum mechanics. The exciton-phonon coupling that enters into the polaron model, and the corresponding phonon spectral function, are derived from the molecular dynamics and quantum chemistry simulations. The model predicts that excitons in the B850 BChl ring are delocalized over five pigments at room temperature. Also, the polaron model permits the calculation of the absorption and circular dichroism spectra of the B850 excitons from the sole knowledge of the autocorrelation function of the excitation energies of individual BChls, which is readily available from the combined molecular dynamics and quantum chemistry simulations. The obtained results are found to be in good agreement with the experimentally measured absorption and circular dichroism spectra.

The signaling mechanisms downstream of growth factor-stimulated proliferation in myeloid leukemia cells have not yet been fully elucidated. Recent evidence suggests that alternate pathways to the mitogen-activated protein kinase cascade are required. We have previously shown that Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) activates cytosolic phospholipase A2 (cPLA2), which is involved in the proliferation of vascular smooth muscle cells. In the present study, the contribution of this pathway was investigated in the proliferation of U-937 myeloid leukemia cells. In U-937 cells, fetal bovine serum (FBS)-induced proliferation was attenuated by CaM kinase II inhibitor KN-93 but not by its inactive analog KN-92. Inhibitors of cPLA2 (methyl arachidonyl fluorophosphonate and arachidonyl trifluoromethyl ketone) also reduced proliferation of U-937 cells. FBS-induced proliferation was also attenuated by cotransfection with cPLA2 antisense oligonucleotides. These results suggest a role for CaM kinase II and cPLA2 in the proliferation of U-937 cells. FBS stimulated CaM kinase II and cPLA2 activities in a time-dependent manner. Moreover, FBS-stimulated phosphorylation and activation of cPLA2 activation was inhibited by KN-93. FBS-stimulated phosphorylation of CaM kinase II was blocked by KN-93 but not by cPLA2 inhibitors, suggesting that CaM kinase II activates cPLA2. The products of phospholipid hydrolysis produced by cPLA2, lysophosphatidylcholine but not arachidonic acid, increased [3H]thymidine incorporation in U-937 cells. These data suggest that exposure of U-937 cells to FBS promotes phosphorylation and activation of CaM kinase II, leading to stimulation of cPLA2 and generation of lysophosphatidylcholine and resultant proliferation of these cells.