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Uptake of penicillin-G has been studied in rabbit intestinal brush-border membrane vesicles (BBMV). Penicillin-G was transported into the lumen of BBMV via an H+-dependent, Na+-independent uptake system. This was a saturable carrier-mediated process, which adhered to Michaelis-Menten kinetics, having a pH optimum of 4.5 and resulting in a net-negative(More)
Spinal muscular atrophy (SMA) is caused by low survival motor neuron (SMN) levels and patients represent a clinical spectrum due primarily to varying copies of the survival motor neuron-2 (SMN2) gene. Patient and animals studies show that disease severity is abrogated as SMN levels increase. Since therapies currently being pursued target the induction of(More)
Antisense oligonucleotides (AOs) are currently the most promising therapeutic intervention for Duchenne muscular dystrophy (DMD). AOs modulate dystrophin pre-mRNA splicing, thereby specifically restoring the dystrophin reading frame and generating a truncated but semifunctional dystrophin protein. Challenges in the development of this approach are the(More)
Induced splice modulation of pre-mRNAs shows promise to correct aberrant disease transcripts and restore functional protein and thus has therapeutic potential. Duchenne muscular dystrophy (DMD) results from mutations that disrupt the DMD gene open reading frame causing an absence of dystrophin protein. Antisense oligonucleotide (AO)-mediated exon skipping(More)
Proximal spinal muscular atrophy (SMA) results from loss of the survival motor neuron 1 (SMN1) gene, with retention of its nearly identical homolog, SMN2. There is a direct correlation between disease severity and SMN2 copy number. Mice do not have a Smn2 gene, and thus cannot naturally replicate the disorder. However, two murine models of SMA have been(More)
Average tissue compositions have been derived for seven groups of soft tissues found in "Reference Man". The analyses took into account some 40 soft tissues comprising the adult human. Different groups of soft tissues were selected to provide average tissue compositions of practical value in radiation dosimetry. In addition, as more reliable skeletal tissue(More)
The hydrophobic plasma membrane constitutes an indispensable barrier for cells, allowing influx of essential molecules while preventing access to other macromolecules. Although pivotal for the maintenance of cells, the inability to cross the plasma membrane is one of the major obstacles toward current drug development. Oligonucleotides (ONs) are a group of(More)
RNA mis-splicing diseases account for up to 15% of all inherited diseases, ranging from neurological to myogenic and metabolic disorders. With greatly increased genomic sequencing being performed for individual patients, the number of known mutations affecting splicing has risen to 50-60% of all disease-causing mutations. During the past 10years, genetic(More)
Ectopic expression of LMO2 occurs in approximately 45% of T-lineage acute lymphoblastic leukemias (T-ALL), sometimes in association with chromosomal translocations. Recently, a lymphoproliferative disorder developed in two participants in a gene therapy trial due to LMO2 activation via integration of the retroviral vector. To investigate these regulatory(More)