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We employed gene targeting to study H2AX, a histone variant phosphorylated in chromatin surrounding DNA double-strand breaks. Mice deficient for both H2AX and p53 (H(delta/delta)P(-/-)) rapidly developed immature T and B lymphomas and solid tumors. Moreover, H2AX haploinsufficiency caused genomic instability in normal cells and, on a p53-deficient(More)
Antibody class switching in activated B cells uses class switch recombination (CSR), which joins activation-induced cytidine deaminase (AID)-dependent double-strand breaks (DSBs) within two large immunoglobulin heavy chain (IgH) locus switch (S) regions that lie up to 200 kilobases apart. To test postulated roles of S regions and AID in CSR, we generated(More)
The relations between membrane cholesterol content, basal (unstimulated) transmembrane 45Ca2+ movements, cytosolic calcium levels, and membrane fluidity were investigated in cultured rabbit aortic smooth muscle cells (SMCs) and isolated SMC plasma membrane microsomes. SMCs were enriched with unesterified (free) cholesterol (FC) for 18-24 hours with medium(More)
This study was designed to determine whether neuroleptic drugs have calcium channel blocking activity in isolated rings of rabbit thoracic aorta. The results confirm previous findings that pimozide and penfluridol are calcium channel blockers. However, the data do not support the conclusion that these agents are selective for the voltage-sensitive calcium(More)
This study was designed to determine whether the endothelium-derived relaxing factor induced by acetylcholine (1 microM) in rabbit thoracic aorta inhibits agonist-induced calcium mobilization, specifically calcium influx. Force generated in rings of rabbit thoracic aorta by norepinephrine (1 microM) was measured under isometric conditions. At the(More)
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