PubMed Health⌕ Search

Biomedical subjects

T Virag

Publications and source records attributed to T Virag.

7 recordsLinked to original sources
PubMed2012

MRI roadmap-guided transendocardial delivery of exon-skipping recombinant adeno-associated virus restores dystrophin expression in a canine model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) cardiomyopathy patients currently have no therapeutic options. We evaluated catheter-based transendocardial delivery of a recombinant adeno-associated virus (rAAV) expressing a small nuclear U7 RNA (U7smOPT) complementary to specific cis-acting splicing signals. Eliminating specific exons restores the open reading frame resulting in translation of truncated dystrophin protein. To test this approach in a clinically relevant DMD model, golden retriever muscular dystrophy (GRMD) dogs received serotype 6 rAAV-U7smOPT via the intracoronary or transendocardial route. Transendocardial injections were administered with an injection-tipped catheter and fluoroscopic guidance using X-ray fused with magnetic resonance imaging (XFM) roadmaps. Three months after treatment, tissues were analyzed for DNA, RNA, dystrophin protein, and histology. Whereas intracoronary delivery did not result in effective transduction, transendocardial injections, XFM guidance, enabled 30&#xb1;10 non-overlapping injections per animal. Vector DNA was detectable in all samples tested and ranged from <1 to >3000 vector genome copies per cell. RNA analysis, western blot analysis, and immunohistology demonstrated extensive expression of skipped RNA and dystrophin protein in the treated myocardium. Left ventricular function remained unchanged over a 3-month follow-up. These results demonstrated that effective transendocardial delivery of rAAV-U7smOPT was achieved using XFM. This approach restores an open reading frame for dystrophin in affected dogs and has potential clinical utility.

Animals↗
PubMed2006

Differentiated dopaminergic MN9D cells only partially recapitulate the electrophysiological properties of midbrain dopaminergic neurons.

The cell line MN9D, a fusion of embryonic ventral mesencephalic and neuroblastoma cells, is extensively used as a model of dopamine (DA) neurons because it expresses tyrosine hydroxylase and synthesizes and releases DA. These cells are also used to test mechanisms and potential therapeutics relevant to the loss of DA neurons in Parkinson's disease. To date, little work has been done to determine whether MN9D cells electrophysiologically resemble mature DA neurons. We examined sodium, calcium and potassium currents in undifferentiated and differentiated MN9D cells, and compared these to those found in acutely dissociated mouse substantia nigra pars compacta DA neurons. It was observed that undifferentiated MN9D cells bore no resemblance to DA neurons. Upon differentiation with butyric acid with or without a prior treatment with glial cell line-derived neurotrophic factor, differentiated MN9D cells produce an electrophysiological profile that more closely resembles substantia nigra pars compacta DA neurons even though the A-type potassium current remains noticeably absent. These observations demonstrate that undifferentiated MN9D cells are not reasonable models of DA neurons. Although differentiated MN9D cells are closer to the mature DA neuronal phenotype, they do not fully mimic DA neurons and are likely to be of questionable value as a model because of their substantive differences, including the lack of the characteristic A-type potassium current. The future use of one or a combination of growth or other factors to differentiate MN9D cells may yield a more useful model system for Parkinson's disease studies in vitro.

Action Potentials↗
PubMed2001

Short-chain phosphatidates are subtype-selective antagonists of lysophosphatidic acid receptors.

Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are members of the phospholipid growth factor family. A major limitation in the field to date has been a lack of receptor subtype-specific agonists and antagonists. Here, we report that dioctylglycerol pyrophosphate and dioctylphosphatidic acid are selective antagonists of the LPA(1) and LPA(3) receptors, but prefer LPA(3) by an order of magnitude. Neither molecule had an agonistic or antagonistic effect on LPA(2) receptor. Consistent with this receptor subtype selectivity, dioctylglycerol pyrophosphate inhibited cellular responses to LPA in NIH3T3 fibroblasts, HEY ovarian cancer cells, PC12 pheochromocytoma cells, and Xenopus laevis oocytes. Responses elicited by S1P in these cell lines that endogenously express S1P(1), S1P(2), S1P(3), and S1P(5) receptors were unaffected by dioctylglycerol pyrophosphate. Responses evoked by the G protein-coupled receptor ligands acetylcholine, serotonin, ATP, and thrombin receptor-activating peptide were similarly unaffected, suggesting that the short-chain phosphatidates are receptor subtype-specific lysophosphatidate antagonists.

3T3 Cells↗
PubMed2000

Pharmacological characterization of phospholipid growth-factor receptors.

The phospholipid growth-factor (PLGE) terminology is proposed to describe a group of endogenous glycerol- and sphingolipid mediators that regulate cell proliferation through plasma membrane receptors. In addition to LPA and SPP, multiple PLGFs are present in blood plasma and serum. PLGF activity is regulated by its stimulus-coupled production and by endogenous inhibitors. In addition to LPA and SPP, alkenyl-glycerophosphate, cyclic-phosphatidic acid, and sphingosylphosphorylcholine were detected in biological fluids using mass spectrometry. Heterologous desensitization studies indicate the expression of multiple LPA-activated receptors in a variety of cell types, which are differentially activated by the different PLGFs. Northern blot and RT-PCR results reinforce the coexpression of PSP24 alpha and different members of the EDG1-7 receptors in the same cell. Stable heterologous expression of the PSP24 alpha, EDG2, and EDG4 receptors in HEK293 cells show distinct PLGF specificities and dose-response properties for each receptor subtype. Thus, both the controlled availability of the different agonists/inhibitors and the regulated expression of their receptors regulate the biological effects of PLGFs.

Animals↗
PubMed1999

[Not Available].

The paper attempts to conceptualise the observations made in therapies of Holocaust survivors. The first case studies of child therapies were published in 1982, demonstrating the induced trauma transference and the three-generational neurosis model, i.e. the transfer of the trauma from the traumatised grandparent through his/her child to the grandchild. The first generation survivor syndrome was first experienced with patients who themselves had suffered deportation or had survived the ghetto, and after several decades, came for treatment to the KUT Psychotherapeutical Clinic. that has been operating for 4 years now.

Adolescent↗