br ANTITHROMBOTIC TREATMENTS br VOLUME OUTCOME
VOLUME-OUTCOME RELATIONSHIP FOR REVASCULARIZATION PROCEDURES The guidelines also maintain the recommendations for training in PCI, both for ACS (≥ 75 procedures per operator in centers with at least 400 PCI procedures per year and a 24-hour on-call service) and for stable CAD (≥ 75 procedures per operator in centers with at least 200 PCI procedures per year). For the first time, the guidelines recommend that PCI treatment of LMCA disease be carried out by experienced operators (IIa C), defined in the article cited by the guidelines as those who treat at least 15 patients per year. An especially notable modification has been introduced into the recommendation regarding the treatment of elective PCI patients considered complex. The guidelines maintain the requirement for PCI in these patients to be performed by experienced operators, with access to circulatory support and intensive care treatment; however, the requirement in the previous guidelines for an on-site surgical team has been eliminated.
MEDICAL THERAPY, SECONDARY PREVENTION, AND FOLLOW-UP STRATEGIES
CONFLICTS OF INTEREST
Introduction The Drosophila Polycomb Group (PcG) proteins are required for heritable silencing of the homeotic KPT-330 and many others. PcG proteins form a number of distinct complexes. The ESC/E(Z) complex, also known as Polycomb Repressive Complex 2 (PRC2), methylates histone H3 on lysine 27 (H3K27) and contains the histone methyltransferase E(Z), the histone H3 binding protein ESC (Tie et al., 2007) and SU(Z)12. The PRC1 complex contains the PcG proteins PC, PH, PSC and RING, an E3 ubiquitin ligase that mono-ubiquitinates lysine 119 of histone H2A (Wang et al., 2004). Its PC subunit binds the trimethylated H3K27 (3mH3K27) sites created by E(Z). PcG complexes and their associated enzymatic activities are required continuously to maintain silencing. ESC originally appeared to be unique among PcG proteins in being required predominantly during early embryogenesis. Temperature shift experiments with a temperature-sensitive esc allele suggested that esc is required only during early embryogenesis (Struhl and Brower, 1982) and similar experiments with a heat-inducible hsp70-esc transgene also suggested that early esc expression is sufficient to promote normal development (Simon et al., 1995). This early requirement for esc is reflected in its temporal expression profile: esc mRNA is most abundant in early embryos, peaking at 8 h (Gutjahr et al., 1995, Sathe and Harte, 1995) and subsequently declines to almost undetectable levels by the end of embryogenesis. Similarly, the ESC protein is present at high levels during the first half of embryogenesis, peaking at mid-embryogenesis and declining to barely detectable levels by first instar (Simon et al., 1995). In contrast, the sole mammalian ESC ortholog, EED, appears to be expressed and required continuously (Schumacher et al., 1996). The temporal profile of esc expression suggested that ESC might be specifically required only for the establishment but not the subsequent maintenance of Polycomb silencing. E(Z), however, is required continuously throughout development (Beuchle et al., 2001), and recent biochemical studies demonstrate that ESC is required for E(Z) HMTase activity both in vitro (Czermin et al., 2002, Nekrasov et al., 2005) and in vivo, at least during embryogenesis (Ketel et al., 2005). This suggested that this essential function of ESC may be carried out by another protein after ESC levels drop. One obvious possibility was that such a protein would be similar to ESC itself. When the complete sequence of the Drosophila melanogaster genome became available, we conducted a BLASTP search using the ESC protein sequence as a query and identified a single predicted protein with a high degree of sequence similarity to ESC. This protein is encoded by the CG5202 gene, which we have renamed extra sex combs-like (escl). While this work was in progress, Wang et al. (2006) demonstrated that recombinant ESCL can substitute for ESC in reconstituted PRC2 complexes in an in vitro histone H3K27 methylation assay, indicating that their biochemical functions are similar if not identical.