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Articles 1 - 6 of 6
Full-Text Articles in Medicine and Health Sciences
An Analysis Of The Use Of Dogs In Predicting Human Toxicology And Drug Safety, Jarrod Bailey, Michelle Thew, Michael Balls
An Analysis Of The Use Of Dogs In Predicting Human Toxicology And Drug Safety, Jarrod Bailey, Michelle Thew, Michael Balls
Jarrod Bailey, PhD
Dogs remain the main non-rodent species in preclinical drug development. Despite the current dearth of new drug approvals and meagre pipelines, this continues, with little supportive evidence of its value or necessity. To estimate the evidential weight provided by canine data to the probability that a new drug may be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive dataset of 2,366 drugs with both animal and human data, including tissue-level effects and Medical Dictionary for Regulatory Activities (MedDRA) Level 1–4 biomedical observations. The resulting LRs show that the absence of toxicity in dogs provides virtually no …
Identification Of Genetic Variation And Haplotype Structure Of The Canine Abca4 Gene For Retinal Disease Association Studies, Barbara Zangerl, Sarah J. Lindauer, Gregory M. Acland, Gustavo D. Aguirre
Identification Of Genetic Variation And Haplotype Structure Of The Canine Abca4 Gene For Retinal Disease Association Studies, Barbara Zangerl, Sarah J. Lindauer, Gregory M. Acland, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Over 200 mutations in the retina specific member of the ATP-binding cassette transporter superfamily (ABCA4) have been associated with a diverse group of human retinal diseases. The disease mechanisms, and genotype–phenotype associations, nonetheless, remain elusive in many cases. As orthologous genes are commonly mutated in canine models of human blinding disorders, canine ABCA4 appears to be an ideal candidate gene to identify and study sequence changes in dogs affected by various forms of inherited retinal degeneration. However, the size of the gene and lack of haplotype assignment significantly limit targeted association and/or linkage approaches. This study assessed the naturally observed …
Targeting Gene Expression To Cones With Human Cone Opsin Promoters In Recombinant Aav, András M. Komáromy, John J. Alexander, Anne E. Cooper, Vince A. Chodo, Gregory M. Acland, William W. Hauswirth, Gustavo D. Aguirre
Targeting Gene Expression To Cones With Human Cone Opsin Promoters In Recombinant Aav, András M. Komáromy, John J. Alexander, Anne E. Cooper, Vince A. Chodo, Gregory M. Acland, William W. Hauswirth, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Specific cone-directed therapy is of high priority in the treatment of human hereditary retinal diseases. However, not much information exists about the specific targeting of photoreceptor subclasses. Three versions of the human red cone opsin promoter (PR0.5, 3LCR-PR0.5 and PR2.1), and the human blue cone opsin promoter HB569, were evaluated for their specificity and robustness in targeting green fluorescent protein (GFP) gene expression to subclasses of cones in the canine retina when used in recombinant adeno-associated viral vectors of serotype 5. The vectors were administered by subretinal injection. The promoter PR2.1 led to most effective and specific expression of GFP …
A Kutya Mint Modell Az Örökletes Retinadegenerációk Kutatásában / The Dog As A Model In Research Into Inherited Retinal Degenerations, Ágnes I. Berta, Ágoston Szél, Gustavo D. Aguirre
A Kutya Mint Modell Az Örökletes Retinadegenerációk Kutatásában / The Dog As A Model In Research Into Inherited Retinal Degenerations, Ágnes I. Berta, Ágoston Szél, Gustavo D. Aguirre
Gustavo D. Aguirre, VMD, PhD
Összefoglalás: A kutya mint modellállat csak az elmúlt 15 évben került az érdeklődés középpontjába. A kutya retinája különösen érdekes, mivel számos örökletes retinadegeneráció szoros homológiát mutat az ember hasonló betegségeivel. Röviden összefoglaljuk a kutya retinájának sajátosságait és azokat az alapkutatásban használt módszereket, melyek segítségével a retina degenerációja leírható kutyában. A kutya örökletes retinadegenerációi közül a szemészek számára a legérdekesebb csoport a progresszív retinalis atrophia (PRA), mivel genetikai, patológiai és klinikai szempontból is nagyon hasonló a retinitis pigmentosa különböző típusaihoz. A PRA csoport tagjai élő modellrendszerek, melyek alkalmazhatók az örökletes retinadegenerációk alap- és klinikai kutatásában egyaránt. Ezekben a súlyos és mindenekelőtt …
A Non-Stop S-Antigen Gene Mutation Is Associated With Late Onset Hereditary Retinal Degeneration In Dogs, Orly Goldstein, Julie Ann Jordan, Gustavo D. Aguirre, Gregory M. Acland
A Non-Stop S-Antigen Gene Mutation Is Associated With Late Onset Hereditary Retinal Degeneration In Dogs, Orly Goldstein, Julie Ann Jordan, Gustavo D. Aguirre, Gregory M. Acland
Gustavo D. Aguirre, VMD, PhD
Purpose: To identify the causative mutation of canine progressive retinal atrophy (PRA) segregating as an adult onset autosomal recessive disorder in the Basenji breed of dog. Methods: Basenji dogs were ascertained for the PRA phenotype by clinical ophthalmoscopic examination. Blood samples from six affected cases and three nonaffected controls were collected, and DNA extraction was used for a genome-wide association study using the canine HD Illumina single nucleotide polymorphism (SNP) array and PLINK. Positional candidate genes identified within the peak association signal region were evaluated. Results: The highest -Log10(P) value of 4.65 was obtained for 12 single nucleotide polymorphisms on …
A Digital Atlas Of The Dog Brain, Ritobrato Datta, Jongho Lee, Jeffrey Duda, Brian B. Avants, Charles H. Vite, Ben Tseng, Jim C. Gee, Gustavo D. Aguirre, Geoffrey K. Aguirre
A Digital Atlas Of The Dog Brain, Ritobrato Datta, Jongho Lee, Jeffrey Duda, Brian B. Avants, Charles H. Vite, Ben Tseng, Jim C. Gee, Gustavo D. Aguirre, Geoffrey K. Aguirre
Gustavo D. Aguirre, VMD, PhD
There is a long history and a growing interest in the canine as a subject of study in neuroscience research and in translational neurology. In the last few years, anatomical and functional magnetic resonance imaging (MRI) studies of awake and anesthetized dogs have been reported. Such efforts can be enhanced by a population atlas of canine brain anatomy to implement group analyses. Here we present a canine brain atlas derived as the diffeomorphic average of a population of fifteen mesaticephalic dogs. The atlas includes: 1) A brain template derived from in-vivo, T1-weighted imaging at 1 mm isotropic resolution at 3 …