Outstanding issues regarding these drugs include identification of the optimal dosing strategy, their role (if any)
in the treatment of polycythemia vera or essential thrombocythemia, and the potential for combining them LXH254 solubility dmso with other therapeutic agents. Leukemia (2011) 25, 218-225; doi:10.1038/leu.2010.269; published online 16 November 2010″
“Introduction: Technetium-99m-sestamibi (MIBI) is the most frequently used myocardial perfusion tracer in patients with ischemic heart disease. In patients with acute ST-elevation myocardial infarction, we previously found that the defect in myocardial MUM uptake was the same in patients injected with MIBI before primary angioplasty and in patients injected immediately after successful treatment. Thus, reperfusion may not be followed by increased uptake of MIBI. Instead, the MIBI defect after reperfusion may reflect the area at risk (AAR) defined by MIBI injected before treatment. We intended to investigate whether myocardial imaging with MIBI administered after reperfusion reflects myocardial perfusion or rather the ischemic AAR.
Methods: In 12 pigs, left anterior descending coronary artery was totally occluded for 45 min with an angioplasty balloon. After a 2-h reperfusion, MIBI was injected intravenously, and BGJ398 (153)Gd-microspheres
were injected in left atrium. AAR and infarct size (IS) were determined by histochemical staining. MTBI and microsphere distribution were evaluated by counting the sliced left ventricle on a gamma camera. Defects were defined as uptake less than 45% of maximum uptake.
Results: The mean +/- S.D. defect size as a fraction of left ventricle was for MIBI 21%+/- 5.5%, AAR 25%+/- 6.3%, IS 13%+/- 3.9% and microspheres defect size 7.3% 5.5%. MIBI defect size overestimated IS (P=.0005) and microspheres defect size (P=.0001), but it was not significantly different from AAR (P=.30).
Conclusion: In a porcine model of click here myocardial infarction after 45 min of ischemia, MIBI administered 120 min after reperfusion delineates AAR. (C) 2011 Elsevier Inc. All rights reserved.”
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number of cancers possess constitutive activity of the dsRNA-dependent kinase, PKR. Inhibition of PKR in these cancers leads to tumor cell death. We recently reported the increased presence of PKR phosphorylated on Thr451 (p-T451 PKR) in clinical samples from myelodysplastic syndrome (MDS) patients and acute leukemia cell lines. Whereas p-T451 PKR in low-risk patient samples or PTEN-positive acute leukemia cell lines was mostly cytoplasmic, in high-risk patient samples and acute leukemia cell lines deficient in PTEN, p-T451 PKR was mainly nuclear. As nuclear activity of PKR has not been previously characterized, we examined the status of nuclear PKR in acute leukemia cell lines. Using antibodies to N-terminus, C-terminus and the kinase domain in conjunction with a proteomics approach, we found that PKR exists in diverse molecular weight forms in the nucleus.