The human exosome: an autoantigenic complex of exoribonucleases in myositis and scleroderma

The anti-PM/Scl autoantibodies are known to characterize a subset of autoimmune patients with myositis, scleroderma (Scl), and the PM/Scl overlap syndrome. The major autoantigens that are recognized by anti-PM/Scl autoantibodies are designated PM/Scl-100 and PM/Scl-75. These autoantigens have been reported to associate into a large complex consisting of 11 to 16 proteins and to play a role in ribosome synthesis. Recently, it was discovered that the PM/Scl complex is the human counterpart of the yeast (Saccharomyces cerevisiae) exosome, which is an RNA-processing complex consisting of 11 3' → 5' exoribonucleases. To date, 10 human exosome components have been identified, although only some of these were studied in more detail. In this review, we discuss some recent advances in the characterization of the PM/Scl complex.     

Inspiratory pressure generation: comparison of subjects with COPD and age-matched normals

We continuously monitored esophageal (Pes) and gastric (Pga) pressures and used these measurements in a three-component model to estimate instantaneous diaphragmatic (DIA), inspiratory accessory muscle (IAM), and postexpiratory recoil (PER) pressures at various times during inspiration. We validated our model both by volume-pressure relationships of the respiratory system (Vrc-Pga and Vab-Pga, where Vrc and Vab are the rib cage and abdominal volumes, respectively) as well as electromyography of the respiratory muscles. Measurements were carried out at rest and during graded treadmill exercise in 11 subjects with chronic obstructive pulmonary disease (COPDs) and 8 age-matched normal subjects (AMNs). AMNs were 59 +/- 2 (SE) yr and had a forced expiratory volume at 1 s (FEV1.0) of 3.6 +/- 0.2 liters; COPDs were 66 +/- 2 yr and had a FEV1.0 of 1.0 +/- 0.1 liters. We noted the following. At rest, both AMNs and COPDs exhibited an increasing DIA pressure (PDIA) across inspiratory time (TI) at rest. As expired minute ventilation increased with exercise intensity, AMNs continued to maintain this PDIA ramp across inspiration; in contrast, COPDs exhibited higher values of PDIA during the first half of TI than during the second half. At all intensities of exercise, COPDs exhibited higher IAM and PER pressures than the AMNs.