Renal cyst enlargement is associated with the activation of both the circulating and intrarenal renin-angiotensin systems. Angiotensinogen (AGT) is the substrate for renin. The aim of the present study was to determine the effect of AGT inhibition on renal cyst enlargement. An AGT antisense oligonucleotide (ASO) that selectively inhibits AGT mRNA was injected once weekly in PKD2WS25 mice [an or...

In this issue of Clinical Cancer Research, Hong, et al (1) report on the safety and tolerability of LY2275796, a second generation antisense oligonucleotide (ASO) targeted to the eukaryotic translational initiation factor eIF-4E mRNA, a gene that has been reported to play a role in tumor initiation. In the study, ASO MTD and biologic effective dose was set at 1000 mg, due to a DLT of grade 3 fa...

OBJECTIVE The upregulated expression of heparin binding EGF-like growth factor (HB-EGF) in the vessel and circulation is associated with risk of cardiovascular disease. In this study, we tested the effects of HB-EGF targeting using HB-EGF-specific antisense oligonucleotide (ASO) on the development of aortic aneurysm in a mouse aneurysm model. APPROACH AND RESULTS Low-density lipoprotein recep...

AIM We sought to investigate the safety and efficacy of Cardio-O-Fix septal occluder (CSO) in percutaneous closure of atrial septal defects (ASD) as compared to the Amplatzer septal occluder (ASO). METHODS A consecutive of 351 patients received transcatheter ASD closure with CSO or ASO from July 2004 to October 2010 were studied. The ASDs were divided into simple- (isolated defects <26 mm) or...

The dependence of the reaction entropies, ASo,, for simple M(III/II) redox couples (M = Ru, Fe, Os, Cr) upon the nature of the ligands and the solvent is examined with a view toward correlating ASo, with simple physical parameters. For couples containing ammine, ethylenediamine, polypyridine, cyclopentadiene, or pseudohalide ligands, ASo, in a given solvent is found to correlate well with (Zo: ...

The aim of this study was to enhance the antileukemic efficacy of the alkylphosphocholine erucylphospho-N,N,N-trimethylpropylammonium (ErPC3) in chronic myeloid leukemia (CML)-derived cell lines by a bcr-directed antisense oligonucleotide (ASO-bcr). The mechanism was substantiated by Western blotting of the BCR-ABL expression level of CML cells, and the efficacy was substantiated by inhibition ...

A successful outcome of an arterial switch operation (ASO) for dextro-transposition of the great arteries (D-TGA) depends in large part on the transfer of the coronary arteries to the neoaorta without distortion or narrowing. However, the origins and distribution of the coronary arteries are quite variable in D-TGA; therefore, the entire experience with ASO at the Children's Hospital in Boston ...

The European Medicines Agency has expressed concern regarding (1) the potential for antisense oligonucleotide (ASO) therapeutics to induce sequence-specific mutation at genomic DNA and (2) the capability of ASO degradation products (nucleotide analogues) to incorporate into newly synthesized genomic DNA via DNA polymerase and cause mutation if base pairing occurs with reduced fidelity. Treating...

Adaptive stochastic optimization (ASO) optimizes an objective function adaptively under uncertainty. It plays a crucial role in planning and learning under uncertainty, but is, unfortunately, computationally intractable in general. This paper introduces two conditions on the objective function, the marginal likelihood rate bound and the marginal likelihood bound, which, together with pointwise ...

Andrew Taylor Still, MD, DO, founded the first school of osteopathy, the American School of Osteopathy (ASO), in 1892. Two graduates from the second class of the ASO, Elmer and Helen Barber, opened the "second school of osteopathy," the National School of Osteopathy (NSO), in 1895. The guiding principles of the NSO were vastly different than those of the ASO, and Still saw the Barbers as a thre...