Possible existence of quaternary structure in the high-affinity serotonin transport complex

During exercise, dynamic hyperinflation-induced intrinsic positive end-expiratory pressure (PEEPi) and decreased dynamic lung compliance (CL,dyn) of patients with chronic obstructive pulmonary disease (COPD) increase the elastic work of inspiration (Wi) more than would be predicted from the increase in tidal volume (VT). This contributes significantly to their exertional breathlessness. In 10 stable patients with COPD, the dynamic Wi was measured during incremental bicycle exercise to exhaustion. The total Wi was then partitioned into the portion required to overcome PEEPi (Wi,PEEPi) and nonPEEPi elastic load (Wi,nonPEEPi). The latter is used to overcome the increase in the total respiratory system elastance during inflation. From resting breathing to peak exercise, Wi more than doubled (p<0.001). This increase was largely due to Wi,PEEPi, which significantly rose from 1.7+/-0.3 to 5.3+/-0.8 L x cm H2O(-1) (p<0.001). In comparison, Wi,nonPEEPi increased from only 3.0+/-0.4 to 5.1+/-0.5 L x cm H2O(-1) (p<0.01). Consequently, Wi,PEEPi as a fraction of total Wi increased from 35.5+/-5.6 to 51.0+/-3.3% (p<0.02). In addition, the measured Wi,nonPEEPi at peak exercise, when expressed as a percentage of its value during resting breathing, was 25% more than that predicted from the increase in VT alone. Assuming a constant chest wall compliance, this can be attributed to the exercise-induced decrease in CL,dyn, which was 0.27+/-0.04 and 0.17+/-0.02 L x cm H2O(-1) (p<0.01), respectively, during resting breathing and peak exercise. In conclusion, the dynamic hyperinflation-induced intrinsic positive end-expiratory pressure is more important than the increase in tidal volume in raising the work of inspiration during exercise in patients with chronic obstructive pulmonary disease; the decrease in dynamic lung compliance plays a definite but less important role.     

Taxol induces concomitant hyperphosphorylation and reorganization of vimentin intermediate filaments in 9L rat brain tumor cells

Taxol, a microtubule stabilizing agent, has been extensively investigated for its antitumor activity. The cytotoxic effect of taxol is generally attributed to its antimicrotubule activity and is believed to be cell cycle dependent. Herein, we report that taxol induces hyperphosphorylation and reorganization of the vimentin intermediate filament in 9L rat brain tumor cells, in concentration- and time-dependent manner. Phosphorylation of vimentin was maximum at 10(-6) M of taxol treatment for 8 h and diminished at higher (10(-5) M) concentration. Enhanced phosphorylation of vimentin was detectable at 2 h treatment with 10(-6) M taxol and was maximum after 12 h of treatment. Taxol-induced phosphorylation of vimentin was largely abolished in cells pretreated with staurosporine and bisindolymaleimide but was unaffected by H-89, KT-5926, SB203580, genistein, and olomoucine. Thus, protein kinase C may be involved in this process. Hyperphosphorylation of vimentin was accompanied by rounding up of cells as revealed by scanning electron microscopy. Moreover, there was a concomitant reorganization of the vimentin intermediate filament in the taxol-treated cells, whereas the microtubules and the actin microfilaments were less affected. Taken together, our data demonstrate that taxol induces hyperphosphorylation of vimentin with concomitant reorganization of the vimentin intermediate filament and that this process may be mediated via a protein kinase C signaling pathway.     

Fidelity of T cell activation through multistep T cell receptor zeta phosphorylation

The T cell receptor (TCR) alphabeta heterodimer interacts with its ligands with high specificity, but surprisingly low affinity. The role of the zeta component of the murine TCR in contributing to the fidelity of antigen recognition was examined. With sequence-specific phosphotyrosine antibodies, it was found that zeta undergoes a series of ordered phosphorylation events upon TCR engagement. Completion of phosphorylation steps is dependent on the nature of the TCR ligand. Thus, the phosphorylation steps establish thresholds for T cell activation. This study documents the sophisticated molecular events that follow the engagement of a low-affinity receptor.     

Histogenesis of dermatofibrosarcoma protuberans]

In order to specify the histogenetic appurtenance of dermatofibrosarcoma protuberance, the ultrastructure of cells from three tumors was studied. The similarity between the ultrastructure of the tumor cells and normal fibroblasts suggests the fibroblastic origin of the tumor.