Non-immunogenic utrophin gene therapy for the treatment of muscular dystrophy animal models.

The essential product of the Duchenne muscular dystrophy (DMD) gene is dystrophin, a rod-like protein that protects striated myocytes from contraction-induced injury. Dystrophin-related protein (or utrophin) retains most of the structural and protein binding elements of dystrophin. Importantly, normal thymic expression in DMD patients should protect utrophin by central immunologic tolerance.

Lower extremity angioplasty for claudication: a population-level analysis of 30-day outcomes.

Objective: With the increased availability of lower extremity percutaneous transluminal angioplasty (PTA), the conventional, non-interventional management of claudication may be evolving. This study evaluated changes in the use and short-term outcomes of PTA among patients with claudication and other manifestations of peripheral arterial disease (PAD).

Methods: A retrospective cohort study was conducted using the linked Washington State hospital discharge database (CHARS).

Efficient myocyte gene delivery with complete cardiac surgical isolation in situ.

Background: Previously, we used cardiopulmonary bypass with incomplete cardiac isolation and antegrade administration of vector for global cardiac gene delivery. Here we present a translatable cardiac surgical procedure that allows for complete surgical isolation of the heart in situ with retrograde (through the coronary venous circulation) administration of both vector and endothelial permeabilizing agents to increase myocyte transduction efficiency.

Methods: In 6 adult dogs the heart was completely isolated with tourniquets placed around both vena cavae and cannulas and all pulmonary veins.

Uniform scale-independent gene transfer to striated muscle after transvenular extravasation of vector.

Background: The muscular dystrophies exemplify a class of systemic disorders for which widespread protein replacement in situ is essential for treatment of the underlying genetic disorder. Somatic gene therapy will require efficient, scale-independent transport of DNA-containing macromolecular complexes too large to cross the continuous endothelia under physiological conditions. Previous studies in large-animal models have revealed a trade-off between the efficiency of gene transfer and the inherent safety of the required surgical and pharmacological interventions to achieve this.

Myosin gene mutation correlates with anatomical changes in the human lineage.

Powerful masticatory muscles are found in most primates, including chimpanzees and gorillas, and were part of a prominent adaptation of Australopithecus and Paranthropus, extinct genera of the family Hominidae. In contrast, masticatory muscles are considerably smaller in both modern and fossil members of Homo. The evolving hominid masticatory apparatus--traceable to a Late Miocene, chimpanzee-like morphology--shifted towards a pattern of gracilization nearly simultaneously with accelerated encephalization in early Homo.

Modular organization of phylogenetically conserved domains controlling developmental regulation of the human skeletal myosin heavy chain gene family.

The mammalian skeletal myosin heavy chain locus is composed of a six-membered family of tandemly linked genes whose complex regulation plays a central role in striated muscle development and diversification. We have used publicly available genomic DNA sequences to provide a theoretical foundation for an experimental analysis of transcriptional regulation among the six promoters at this locus. After reconstruction of annotated drafts of the human and murine loci from fragmented DNA sequences, phylogenetic footprint analysis of each of the six promoters using standard and Bayesian alignment algorithms revealed unexpected patterns of DNA sequence conservation among orthologous and paralogous gene pairs.