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To gain insight into the molecular pathogenesis of the myelodysplastic syndromes (MDS), we performed global gene expression profiling and pathway analysis on the hematopoietic stem cells (HSC) of 183 MDS patients as compared with the HSC of 17 healthy controls. The most significantly deregulated pathways in MDS include interferon signaling, thrombopoietin(More)
This review presents a concise update on the inhibitors of the neuroenzyme, acetylcholinesterase (AChE; EC 3.1.1.7). AChE is a serine protease, which hydrolyses the neurotransmitter, acetylcholine into acetate and choline thereby terminating neurotransmission. Molecular interactions (mode of binding to the target enzyme), clinical applications and(More)
Antimicrobial agents are commonly used after hematopoietic stem cell transplant (HSCT) to prevent bacterial, viral and fungal infections. A pharmacy practice survey was undertaken to evaluate prevailing practices. The 31 centers evaluated transplanted over 3400 patients in 2001. Over half used bacterial prophylaxis; all with fluoroquinolones. A(More)
Voriconazole, a new antifungal agent, is increasingly being used after HSCT. The hepatic cytochrome P450 isoenzyme 2C19 plays a significant role in voriconazole metabolism. As CYP2C19 exhibits significant genetic polymorphism, some patients metabolize voriconazole poorly resulting in increased plasma drug levels. The clinical significance of this is(More)
To establish the incidence of CMV viremia after allogeneic blood stem cell transplantation, we studied 51 consecutive allogeneic peripheral blood stem cell (PBSC) transplant recipients. A total of 12 recipients were at moderate risk for CMV disease and 39 were at high risk. Conditioning regimens varied, but GvHD prophylaxis consisted of tacrolimus and(More)
Myelodysplastic syndromes (MDSs) are a group of heterogeneous clonal hematologic malignancies that are characterized by defective bone marrow (BM) hematopoiesis and by the occurrence of intramedullary apoptosis. During the past decade, the identification of key genetic and epigenetic alterations in patients has improved our understanding of the(More)
6506 Background: Signaling through the RAS/RAF/MEK pathway is activated in many human cancers. GSK212 is a potent, selective allosteric inhibitor of MEK1/2 that inhibits proliferation of myeloid cell lines in vitro. A phase I/II study of a single, daily, oral dosing regimen was conducted to define the recommended phase II dose (RP2D) and evaluate(More)
Myelodysplastic syndromes (MDS) are common hematologic disorders that are characterized by decreased blood counts due to ineffective hematopoiesis. MDS is considered a 'preleukemic' disorder linked to a significantly elevated risk of developing an overt acute leukemia. Cytopenias can be observed in all three myeloid lineages suggesting the involvement of(More)