Stable restoration of the sarcoglycan complex in dystrophic muscle perfused with histamine and a recombinant adeno-associated viral vector.

Limb-girdle muscular dystrophies 2C-F represent a family of autosomal recessive diseases caused by defects in sarcoglycan genes. The cardiomyopathic hamster is a naturally occurring model for limb-girdle muscular dystrophy caused by a primary deficiency in delta-sarcoglycan. We show here that acute sarcolemmal disruption occurs in this animal model during forceful muscle contraction. A recombinant adeno-associated virus vector encoding human delta-sarcoglycan conferred efficient and stable genetic reconstitution in the adult cardiomyopathic hamster when injected directly into muscle. A quantitative assay demonstrated that vector-transduced muscle fibers are stably protected from sarcolemmal disruption; there was no associated inflammation or immunologic response to the vector-encoded protein. Efficient gene transduction with rescue of the sarcoglycan complex in muscle fibers of the distal hindlimb was also obtained after infusion of recombinant adeno-associated virus into the femoral artery in conjunction with histamine-induced endothelial permeabilization. This study provides a strong rationale for the development of gene therapy for limb-girdle muscular dystrophy.

Electron-phonon interactions in ce3+-doped yttrium aluminum garnet nanophosphors.

Ce 3+-doped yttrium aluminum garnet nanophosphors with sizes near 30 and 250 nm have been synthesized by using chemical gelation and solvothermal methods, respectively. The size-dependent electron-longitudinal-optical-phonon coupling is investigated by fitting measured photoluminescence spectra within the framework of the Brownian oscillator model. Results show that the coupling strength is in a decreasing order from the bulk material to the nanophosphors of much smaller sizes.

Homogeneous precipitation of Dy2O3 nanoparticles-effects of synthesis parameters.

The experimental parameters that control the size and size distribution of dysprosium oxide nanoparticles synthesized by homogeneous precipitation technique have been systematically investigated. The particles were characterized with respect to their size, shape, and thermal decomposition behavior. It was found that the precipitated particles were spherical, uniform in size, and amorphous, which upon heating in air, decomposed into the oxide form with no change in morphology. The size and size distribution of the particles showed strong dependence on the metal cation concentration ([Dy3+]) and weak dependence on urea concentration and aging time. In addition, the presence of chlorine ions (Cl-) was found to have significant effect on the growth and agglomeration of the particles. Aggregation mechanism as the growth mechanism is offered to explain the effects of these synthesis parameters on the morphology, size, and size distribution of dysprosium oxide particles.

Preparation and evaluation of a hyaluronate-collagen film for preventing post-surgical adhesion.

Post-surgical adhesion occurs when fibrous strands of scar tissue form, leading to the abnormal joining of anatomical structures. Patients undergoing abdominal surgery are at risk of the complications associated with intraperitoneal adhesions. Hyaluronic acid (HA) is a biocompatible, biodegradable and non-toxic natural polymer, which is gaining popularity as a barrier agent for preventing post-surgical adhesions. As HA is water-soluble and rapidly degraded in vivo, chemical modification is required to produce a non-soluble sheet that might be used to prevent tissue adhesion. We developed a range of biocompatible cross-linked HA-collagen composites and then evaluated them in a rat model of post-surgical adhesion. The results showed that cross-linked HA-collagen was almost totally resistant to hyaluronidase digestion. HA-collagen membranes induced minimal tissue reactions and were bioresorbed within 14 days post-surgery. These results suggest that cross-linked HA-collagen membrane may be a valuable anti-adhesion material to prevent post-surgical intraperitoneal adhesion.

Decreasing carotid endarterectomy length of stay at a university hospital.

In 1995, a clinical pathway for carotid endarterectomy patients was instituted at the authors' institution. The effect of this program on length of stay and patient outcomes was investigated. Records of 152 consecutive carotid endarterectomies performed by a single surgeon over a 45-month period with identical technique (general anesthesia, routine shunting, closure with a dacron patch) were reviewed. Comparison of patients treated under the pathway (n = 119) and those prior to that policy (n = 33) revealed no significant differences (P>0.05) in age, sex, co-morbid conditions, or surgical indication. No difference (P>0.05) was found for occurrence of complications, which included two fatal perioperative strokes (1.3%) and two myocardial infarctions (1.3%) (one fatal). No complications occurred after discharge and no patients required readmission to the hospital. Average length of stay was reduced from 6.0 to 3.3 days, with 78% of patients discharged within 48 h. Preoperative hospitalization decreased from 100 to 21%. A decrease in the use of preoperative arteriography from 100 to 10% was noted. The cost of vascular studies decreased from $2451 to $1228. Cost-saving measures, including early discharge of stable patients, elimination of preoperative hospitalization and decreased use of arteriography, can be accomplished while maintaining acceptable complication rates following carotid endarterectomy in a university hospital setting.

Identification of a mouse thiamine transporter gene as a direct transcriptional target for p53.

p53 tumor suppressor is a transcription factor that functions, in part, through many of its downstream target genes. We have identified a p53-inducible gene by performing mRNA differential display on IW32 murine erythroleukemia cells containing a temperature-sensitive p53 mutant allele, tsp53(Val-135). Sequence analysis of the full-length cDNA revealed its identity as the mouse homologue of the human thiamine transporter 1 (THTR-1). Induction of the mouse THTR-1 (mTHTR-1) mRNA was detectable as early as 1 h at 32.5 degrees C; upon shifting back to 38.5 degrees C, mTHTR-1 transcript was rapidly degraded with a half-life of less than 2 h. Elevation of mTHTR-1 expression was found in DNA damage-induced normal mouse embryonic fibroblast cells, but not in p53(-/-) mouse embryonic fibroblast cells, suggesting that mTHTR-1 induction was p53-dependent. A region within the first intron of the mTHTR-1 gene bound to p53 and conferred the p53-mediated transactivation. Furthermore, increased thiamine transporter activities were found in cells overexpressing mTHTR-1 and under conditions of DNA damage or p53 activation. Our findings indicate that p53 may be involved in maintaining thiamine homeostasis through transactivation of THTR-1.