Biomedical subjects

Andy J Beynon

Publications and source records attributed to Andy J Beynon.

5 recordsLinked to original sources

PubMed2006

Kidney failure in mice lacking the tetraspanin CD151.

The tetraspanin CD151 is a cell-surface molecule known for its strong lateral interaction with the laminin-binding integrin alpha3beta1. Patients with a nonsense mutation in CD151 display end-stage kidney failure associated with regional skin blistering and sensorineural deafness, and mice lacking the integrin alpha3 subunit die neonatally because of severe abnormalities in the lung and kidney epithelia. We report the generation of Cd151-null mice that recapitulate the renal pathology of human patients, i.e., with age they develop massive proteinuria caused by focal glomerulosclerosis, disorganization of the glomerular basement membrane, and tubular cystic dilation. However, neither skin integrity nor hearing ability are impaired in the Cd151-null mice. Furthermore, we generated podocyte-specific conditional knockout mice for the integrin alpha3 subunit that show renal defects similar to those in the Cd151 knockout mice. Our results support the hypothesis that CD151 plays a key role in strengthening alpha3beta1-mediated adhesion in podocytes.

Animals↗

PubMed2006

No hearing loss associated with the use of artemether-lumefantrine to treat experimental human malaria.

Artemisinin derivatives are becoming the first-line treatment for uncomplicated malaria in areas with widespread resistance to chloroquine. Although generally safe and well tolerated, it has been suggested from animal experiments, and more recently from one human study with artemether-lumefantrine, that these compounds are potentially neurotoxic, affecting particularly the brainstem auditory pathways. We report here the auditory analyses of 15 volunteers who underwent an experimental human malaria infection and were treated with artemether-lumefantrine. The subjects underwent audiological examination before the start of the study, during infection, and after treatment. Examination included standard tone audiometry, high frequency tone audiometry and auditory brainstem response (ABR). No effects on hearing loss that were deemed to be caused by drug treatment were found using tone audiometry. ABR analysis similarly failed to demonstrate any auditory pathway damage in the volunteers after treatment. We have thus not found any clear evidence of a detrimental effect on the auditory system by artemether-lumefantrine treatment in uncomplicated malaria. Our results support the continued implementation of artemisinin derivatives in the fight against drug-resistant malaria.

Adolescent↗

PubMed2005

Identification of a rat model for usher syndrome type 1B by N-ethyl-N-nitrosourea mutagenesis-driven forward genetics.

The rat is the most extensively studied model organism and is broadly used in biomedical research. Current rat disease models are selected from existing strains and their number is thereby limited by the degree of naturally occurring variation or spontaneous mutations. We have used ENU mutagenesis to increase genetic variation in laboratory rats and identified a recessive mutant, named tornado, showing aberrant circling behavior, hyperactivity, and stereotypic head shaking. More detailed analysis revealed profound deafness due to disorganization and degeneration of the organ of Corti that already manifests at the onset of hearing. We set up a single nucleotide polymorphism (SNP)-based mapping strategy to identify the affected gene, revealing strong linkage to the central region of chromosome 1. Candidate gene resequencing identified a point mutation that introduces a premature stopcodon in Myo7a. Mutations in human MYO7A result in Usher syndrome type 1B, a severe autosomal inherited recessive disease that involves deafness and vestibular dysfunction. Here, we present the first characterized rat model for this disease. In addition, we demonstrate proof of principle for the generation and cloning of human disease models in rat using ENU mutagenesis, providing good perspectives for systematic phenotypic screens in the rat.

Animals↗

PubMed2003

Comparison of different speech coding strategies using a disability-based inventory and speech perception tests in quiet and in noise.

OBJECTIVE: Intraindividual comparison of two cochlear implant speech coding strategies implemented in the Nucleus 24M system (SPEAK versus ACE). Reasons for subjective preference were evaluated using a combination of speech perception scores and a disability-based inventory. STUDY DESIGN: Cross-over study with two groups of cochlear implant subjects, assigned to first receive ACE or SPEAK strategy. SETTING: Cochlear implant program. SUBJECTS: Twelve postlingually deaf adults using a Nucleus 24M cochlear implant system. INTERVENTION: Subjects consecutively used the two different speech coding strategies and completed speech perception tests in quiet and in noise and a disability-based inventory (Abbreviated Profile of Hearing Aid Benefit). MAIN OUTCOME MEASURES: Individual differences between the two different speech coding strategies and the relation with subjective strategy preference. RESULTS: The ACE strategy produced somewhat better speech recognition scores in quiet and in noise, although the difference in the scores in noise did not reach the 95% level of significance. The first coding strategy chosen did not affect the results or subjective preference. Preference according to the APHAB results were not a priori in conformity with the speech recognition scores. CONCLUSION: Most subjects preferred the ACE strategy. Subjective preference was in agreement with the APHAB results in three subjects, in agreement with speech recognition in two subjects, and in agreement with both in seven subjects. The present results support the use of both speech recognition tests and questionnaires to evaluate different speech coding strategies.

Adult↗

PubMed2002

Evaluation of cochlear implant benefit with auditory cortical evoked potentials.

Endogenous P300 and exogenous slow vertex potentials were obtained with tone and speech stimuli in a group of five children using a cochlear implant (CI) with poor speech recognition (group A) and compared with those from another group of five children using a CI with good speech recognition (group B). The responses were also compared to those of children with normal hearing (n= 14) and a group of adult CI users (n=9). N1 and P2 latencies of CI group A and group B were prolonged compared to those of normally-hearing children. In group A, P300 was present when contrasts with tone stimuli were used. When speech stimuli were used, P300 potentials were absent or delayed. P300 potentials obtained in group B were no different from those obtained in normally-hearing children. It is suggested that the poor results evoked with speech stimuli in contrast to those evoked with pure-tone stimuli in group A are due to the immaturity of (sub) cortical generators associated with acoustical and phonetic processing. In contrast to the children in group B, all children in group A suffered from congenital deafness.

Adolescent↗