Background: Prognosis in chronic obstructive pulmonary disease (COPD) is poorly predicted by indices of air flow obstruction, because other factors that reflect the systemic nature of the disease also influence prognosis. Objective: To test the hypothesis that a reduction in quadriceps maximal voluntary contraction force (QMVC) is a useful predictor of mortality in patients with COPD. Methods: A mortality questionnaire was sent to the primary care physician of 184 patients with COPD who had undergone quadriceps strength measurement over the past 5 years. QMVC was expressed as a percentage of the patient's body mass index. The end point measured was death or lung transplantation, and median (range) follow-up was 38 (1-54) months. Results: Data were obtained for 162 patients (108 men and 54 women) with a mean (SD) percentage of forced expiratory volume in 1 s (FEV 1 ) predicted of 35.6 (16.2), giving a response rate of 88%. Transplantfree survival of the cohort was 93.5% at 1 year and 87.1% at 2 years. Cox regression models showed that the mortality risk increased with increasing age and with reducing QMVC. Only age (HR 1.72 (95% CI 1.14 to 2.6); p = 0.01) and QMVC (HR 0.91 (95% CI 0.83 to 0.99); p = 0.036) continued to be significant predictors of mortality when controlled for other variables in the multivariate analysis. Conclusion: QMVC is simple and provides more powerful prognostic information on COPD than that provided by age, body mass index and forced expiratory volume in 1 s. C hronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the world, 1 but prognosis is only poorly predicted by indices of air flow obstruction. Given this limitation, a new severity classification, the Body Mass Index, Airflow Obstruction, Dyspnoea and Exercise Capacity (BODE) Index, 2 has been proposed that takes into account the multicomponent nature of COPD with considerable emphasis being placed on the body mass index (BMI) as an indicator of poor prognosis.3-6 However, many investigators consider that it is, more specifically, the loss of skeletal muscle mass which confers a poorer prognosis in patients with COPD. 7-10Muscle mass depletion is associated with reduced exercise performance, 11 12 increased dyspnoea 13 and worse health-related quality of life.14 Similarly, skeletal muscle weakness is a common finding in COPD and is associated with reduced exercise capacity. [15][16][17] As exercise capacity is thought to be an important factor in determining mortality in COPD, 18 it perhaps follows that muscle weakness should also predict mortality.In a recent paper by Marquis et al, 7 CT scanning was used to measure the mid-thigh cross-sectional area (MTCSA CT ) in patients with COPD. This radiological measure of quadriceps bulk was shown to predict mortality better than BMI, and this was particularly so in patients with more severe COPD (forced expiratory volume in 1 s, (FEV 1 ) ,50%). This measure is attractive as a single reproducible predictor of mortality from COPD, but some obvious drawbacks limi...

A close chromatin conformation precludes gene expression in eukaryotic cells. Genes activated by external cues have to overcome this repressive state by locally changing chromatin structure to a more open state. Although much is known about hormonal gene activation, how basal repression of regulated genes is targeted to the correct sites throughout the genome is not well understood. Here we report that in breast cancer cells, the unliganded progesterone receptor (PR) binds genomic sites and targets a repressive complex containing HP1g (heterochromatin protein 1g), LSD1 (lysine-specific demethylase 1), HDAC1/2, CoREST (corepressor for REST [RE1 {neuronal repressor element 1} silencing transcription factor]), KDM5B, and the RNA SRA (steroid receptor RNA activator) to 20% of hormone-inducible genes, keeping these genes silenced prior to hormone treatment. The complex is anchored via binding of HP1g to H3K9me3 (histone H3 tails trimethylated on Lys 9). SRA interacts with PR, HP1g, and LSD1, and its depletion compromises the loading of the repressive complex to target chromatinpromoting aberrant gene derepression. Upon hormonal treatment, the HP1g-LSD1 complex is displaced from these constitutively poorly expressed genes as a result of rapid phosphorylation of histone H3 at Ser 10 mediated by MSK1, which is recruited to the target sites by the activated PR. Displacement of the repressive complex enables the loading of coactivators needed for chromatin remodeling and activation of this set of genes, including genes involved in apoptosis and cell proliferation. These results highlight the importance of the unliganded PR in hormonal regulation of breast cancer cells.

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A novel inhibitor of interactions between signaling proteins in T cells demonstrates promising preventive and therapeutic effects in several models of autoimmune disease.