Prevention of coronary restenosis by stenting

Balloon angioplasty fails to provide acceptable long-term results for a significant proportion of patients. An intravascular mechanical support, developed with the aim of preventing restenosis and acute closure of diseased arteries after transluminal angioplasty, was implanted in 44 patients (39 male and five female), aged from 35 to 70 years (mean 56 years) with documented restenosis of native coronary artery (41 stents) and bypass grafts (12 stents). In the group of bypass graft patients there was no local restenosis and no major complication. In patients in whom stents were placed in native coronary arteries, the complication rate was higher (two patients died after coronary bypass surgery). One patient died suddenly at home. Except for one patient, in whom a new lesion developed proximally with extension into the stent, no case of restenosis could be observed. Despite the still relatively high complication rate, we feel that stenting may present a rational approach to the unresolved problem of restenosis after coronary angioplast

Prevention of coronary restenosis by stenting

Balloon angioplasty fails to provide acceptable long-term results for a significant proportion of patients. An intravascular mechanical support, developed with the aim of preventing restenosis and acute closure of diseased arteries after transluminal angioplasty, was implanted in 44 patients (39 male and five female), aged from 35 to 70 years (mean 56 years) with documented restenosis of native coronary artery (41 stents) and bypass grafts (12 stents). In the group of bypass graft patients there was no local restenosis and no major complication. In patients in whom stents were placed in native coronary arteries, the complication rate was higher (two patients died after coronary bypass surgery). One patient died suddenly at home. Except for one patient, in whom a new lesion developed proximally with extension into the stent, no case of restenosis could be observed. Despite the still relatively high complication rate, we feel that stenting may present a rational approach to the unresolved problem of restenosis after coronary angioplasty

Mapping of the nuclear matrix-bound chromatin hubs by a new M3C experimental procedure

We have developed an experimental procedure to analyze the spatial proximity of nuclear matrix-bound DNA fragments. This protocol, referred to as Matrix 3C (M3C), includes a high salt extraction of nuclei, the removal of distal parts of unfolded DNA loops using restriction enzyme treatment, ligation of the nuclear matrix-bound DNA fragments and a subsequent analysis of ligation frequencies. Using the M3C procedure, we have demonstrated that CpG islands of at least three housekeeping genes that surround the chicken α-globin gene domain are assembled into a complex (presumably, a transcription factory) that is stabilized by the nuclear matrix in both erythroid and non-erythroid cells. In erythroid cells, the regulatory elements of the α-globin genes are attracted to this complex to form a new assembly: an active chromatin hub that is linked to the pre-existing transcription factory. The erythroid-specific part of the assembly is removed by high salt extraction. Based on these observations, we propose that mixed transcription factories that mediate the transcription of both housekeeping and tissue-specific genes are composed of a permanent compartment containing integrated into the nuclear matrix promoters of housekeeping genes and a ‘guest’ compartment where promoters and regulatory elements of tissue-specific genes can be temporarily recruited

Genome-wide profiling of forum domains in Drosophila melanogaster

Forum domains are stretches of chromosomal DNA that are excised from eukaryotic chromosomes during their spontaneous non-random fragmentation. Most forum domains are 50–200 kb in length. We mapped forum domain termini using FISH on polytene chromosomes and we performed genome-wide mapping using a Drosophila melanogaster genomic tiling microarray consisting of overlapping 3 kb fragments. We found that forum termini very often correspond to regions of intercalary heterochromatin and regions of late replication in polytene chromosomes. We found that forum domains contain clusters of several or many genes. The largest forum domains correspond to the main clusters of homeotic genes inside BX-C and ANTP-C, cluster of histone genes and clusters of piRNAs. PRE/TRE and transcription factor binding sites often reside inside domains and do not overlap with forum domain termini. We also found that about 20% of forum domain termini correspond to small chromosomal regions where Ago1, Ago2, small RNAs and repressive chromatin structures are detected. Our results indicate that forum domains correspond to big multi-gene chromosomal units, some of which could be coordinately expressed. The data on the global mapping of forum domains revealed a strong correlation between fragmentation sites in chromosomes, particular sets of mobile elements and regions of intercalary heterochromatin

Nuclear Scaffold Attachment Sites within ENCODE Regions Associate with Actively Transcribed Genes

The human genome must be packaged and organized in a functional manner for the regulation of DNA replication and transcription. The nuclear scaffold/matrix, consisting of structural and functional nuclear proteins, remains after extraction of nuclei and anchors loops of DNA. In the search for cis-elements functioning as chromatin domain boundaries, we identified 453 nuclear scaffold attachment sites purified by lithium-3,5-iodosalicylate extraction of HeLa nuclei across 30 Mb of the human genome studied by the ENCODE pilot project. The scaffold attachment sites mapped predominately near expressed genes and localized near transcription start sites and the ends of genes but not to boundary elements. In addition, these regions were enriched for RNA polymerase II and transcription factor binding sites and were located in early replicating regions of the genome. We believe these sites correspond to genome-interactions mediated by transcription factors and transcriptional machinery immobilized on a nuclear substructure