Biomedical subjects

Glenn Walter

Publications and source records attributed to Glenn Walter.

5 recordsLinked to original sources

PubMed2006

Nanoparticles for bioimaging.

The emergence of synthesis strategies for the fabrication of nanosized contrast agents is anticipated to lead to advancements in understanding biological processes at the molecular level in addition to progress in the development of diagnostic tools and innovative therapies. Imaging agents such as fluorescent dye-doped silica nanoparticles, quantum dots and gold nanoparticles have overcome many of the limitations of conventional contrast agents (organic dyes) such as poor photostability, low quantum yield, insufficient in vitro and in vivo stability, etc. Such particulates are now being developed for absorbance and emission in the near infrared region, which is expected to allow for real time and deep tissue imaging via optical routes. Other efforts to facilitate deep tissue imaging with pre-existing technologies have lead to the development of multimodal nanoparticles which are both optical and MRI active. The main focus of this article is to provide an overview of properties and design of contrast agents such as dye-doped silica nanoparticles, quantum dots and gold nanoparticles for non-invasive bioimaging.

Contrast Media↗

PubMed2006

Systemic correction of a fatty acid oxidation defect by intramuscular injection of a recombinant adeno-associated virus vector.

Mitochondrial beta-oxidation of fatty acids is required to meet physiologic energy requirements during illness and periods of fasting or physiologic stress, and is most active in liver and striated muscle. Acyl-CoA dehydrogenases of varying chain-length specificities represent the first step in the mitochondria for each round of beta-oxidation, each of which removes two-carbon units as acetyl-CoA for entry into the tricarboxylic acid cycle. We have used recombinant adeno-associated virus (rAAV) vectors expressing short-chain acyl-CoA dehydrogenase (SCAD) to correct the accumulation of fatty acyl-CoA intermediates in deficient cell lines. The rAAV-SCAD vector was then packaged into either rAAV serotype 1 or 2 capsids and injected intramuscularly into SCAD-deficient mice. A systemic effect was observed as judged by restoration of circulating butyryl- carnitine levels to normal. Total lipid content at the injection site was also decreased as demonstrated by noninvasive magnetic resonance spectroscopy (MRS). SCAD enzyme activity in the injected muscle was found at necropsy to be above the normal control mouse level. This study is the first to demonstrate the systemic correction of a fatty acid oxidation disorder with rAAV and the utility of MRS as a noninvasive method to monitor SCAD correction after in vivo gene therapy.

Animals↗

PubMed2005

Rapid and effective labeling of brain tissue using TAT-conjugated CdS:Mn/ZnS quantum dots.

TAT (a cell penetrating peptide)-conjugated CdSratioMn/ZnS quantum dots (Qdots), intra-arterially delivered to a rat brain, rapidly (within a few minutes) labeled the brain tissue without manipulating the blood-brain-barrier (BBB). Qdot loading was sufficiently high that it allowed a gross fluorescent visualization of the whole rat brain using a low power hand-held UV lamp. Histological data clearly showed that TAT-conjugated Qdots migrated beyond the endothelial cell line and reached the brain parenchyma. Qdots without TAT did not label the brain tissue confirming the fact that TAT peptide was necessary to overcome the BBB. The present study clearly demonstrated the possibility of delivering a large amount of Qdot-based imaging agents to the brain tissue.

Animals↗

PubMed2005

Noninvasive monitoring of gene correction in dystrophic muscle.

Gene and stem cell transfer have shown tremendous potential in rescuing dystrophic muscle in animal models. However, monitoring of gene transfer efficacy in clinical settings currently requires invasive muscle biopsies. We determined whether (1)H-magnetic resonance spectroscopy (MRS) and imaging (MRI) could be used to noninvasively monitor gene correction in dystrophic skeletal muscle. MRI/MRS measurements were performed in murine models of Limb Girdle (gammasg(-/-)) and Duchenne muscular dystrophy (mdx). Viral delivery of gammasg into gammasg(-/-) muscles was achieved using both an adenovirus and an adenoassociated virus. T(2)-weighted MRIs consistently revealed hyperintense regions in muscles of dystrophic mice, which agreed well with histologically determined damaged muscle fibers. (1)H-MRS revealed that the increase in T(2) in dystrophic muscle is not due to fatty tissue infiltration. Reintroduction of the gammasg gene in gammasg(-/-) muscles restored normal muscle histology, membrane stability, and T(2) contrast. Expression of gammasg also significantly decreased the number of pixels with increased T(2) values and MRI contrast agent uptake. Our data demonstrate that therapeutic correction of dystrophic lesions can be noninvasively monitored using endogenous MR contrast. This may be particularly relevant for future interventions in children with muscular dystrophy.

Animals↗

PubMed2004

Angiotensin II type 2 receptor gene transfer elicits cardioprotective effects in an angiotensin II infusion rat model of hypertension.

The role of the angiotensin II type 2 receptor (AT2R) in cardiovascular physiology remains elusive. We have developed an in vivo lentiviral vector-mediated gene transfer system to study the physiological functions of the AT2R. Our objectives in this study were to determine whether the AT2R influences cardiac hypertrophy and myocardial and perivascular fibrosis in a nongenetic rat model of hypertension. Lentiviral vector containing the AT2R or saline was injected intracardially in 5-day-old Sprague-Dawley rats. This resulted in a persistent overexpression of the AT2R in cardiac tissues. At 15 wk of age, animals were infused with either 200 ng x kg(-1) x min(-1) of angiotensin II or saline by implantation of a 4-wk osmotic minipump. This resulted in an increase in blood pressure (BP) that reached maximal by 2 wk of treatment and was associated with a 123% increase in left ventricular wall thickness (LVWT) and a 129% increase in heart weight to body weight ratios (HW/BW). In addition, the increase in cardiac hypertrophy was associated with a 300% and 158% increase in myocardial and perivascular fibrosis, respectively. Cardiac transduction of the AT2R resulted in an 85% attenuation of LVWT, 91% attenuation of HW/BW, and a 43% decrease in myocardial fibrosis induced by angiotensin infusion. These improvements in cardiac pathology were observed in the absence of attenuation of high BP. Thus our observations indicate that long-term expression of the AT2R in the heart attenuates cardiac hypertrophy and fibrosis in a nongenetic rat model of hypertension.

Angiotensin II↗