Yuko Saitoh

Transient evoked otoacoustic emissions in newborn infants: Effects of ear asymmetry, gender, and age.

Our aim was to examine the effects of gender, ear asymmetry, and age of infants on various parameters of transient evoked otoacoustic emissions (TEOAEs). Three hundred thirty-two infants (181 males, 151 females) were tested using the ILO292 Otodynamics Analyzer (Otodynamics Ltd, England) as a screening procedure. The subjects were divided into two age groups: group 1, newborn infants prior to hospital discharge (mean age of 4 days), and group 2, infants at the 1-month-old health checkup (mean age of 35 days). Responses to TEOAE stimuli were recorded at 1.0, 1.5, 2.0, 3.0, and 4.0 kHz. There were significant effects of gender and ear (left/right) on the signal-to-noise ratio, response level, and whole-wave and band reproducibility values in TEOAEs. The right ear had higher values of whole-wave reproducibility, response level, signal-to-noise ratio, and band reproducibility than the left ear. Females displayed higher whole-wave reproducibility, response level, band reproducibility, and signal-to-noise ratio values than males. There was no significant difference in response level, signal-to-noise ratio, and band reproducibility between the two age groups. The findings of the present investigation may contribute toward future improvements in neonatal hearing screening based on the community.

Reduced expression of MAb6B4 epitopes on chondroitin sulfate proteoglycan aggrecan in perineuronal nets from cerebral cortices of SAMP10 mice: A model for age‐dependent neurodegeneration

The accelerated senescence‐prone SAMP10 mouse strain is a model for age‐dependent neurodegeneration and is characterized by brain atrophy and deficits in learning and memory. Because perineuronal nets play an important role in the synaptic plasticity of adult brains, we examined the distributions of molecules that constitute perineuronal nets in SAMP10 mouse brain samples and compared them with those in control SAMR1 mouse samples. Proteoglycan‐related monoclonal antibody 6B4 (MAb6B4) clearly immunostained perineuronal nets in SAMR1 mice cortices, but the corresponding immunostaining in SAMP10 mice was very faint. MAb6B4 recognizes phosphacan/PTPζ in immature brains. However, this antibody recognized several protein bands, including a 400‐kDa core glycoprotein from chondroitin sulfate proteoglycan in homogenates of mature cortices from SAMR1 mice. The 400‐kDa band was also recognized by antiaggrecan antibodies. The aggrecan core glycoprotein band was also detectable in samples from SAMP10 mice, but this glycoprotein was faintly immunostained by MAb6B4. Because MAb6B4 recognized the same set of protein bands that the monoclonal antibody Cat‐315 recognized in mature cerebral cortices of SAMR1 mice, the MAb6B4 epitope appears to be closely related to that of Cat‐315 and presumably represents a novel type of oligosaccharide that attaches to aggrecans. The Cat‐315 epitope colocalized with aggrecan in perineuronal nets from SAMR1 mouse brain samples, whereas its expression was prominently reduced in SAMP10 mouse brain samples. The biological significance of the MAb6B4/Cat‐315 epitope in brain function and its relationship to the neurodegeneration and learning disabilities observed in SAMP10 mice remain to be elucidated.

Germline PTCH1 mutations in Japanese basal cell nevus syndrome patients

Basal cell nevus syndrome (BCNS or Gorlin syndrome, OMIM: 109400) is a rare autosomal dominant disorder with high penetrance. It is characterized by developmental anomalies and predisposition to tumors (for example, basal cell carcinoma (BCC) and medulloblastoma). PTCH1, the human homolog of the Drosophila patched gene, was identified as a gene responsible for BCNS. The PTCH1 protein is a Hedgehog (Hh) protein receptor and is pivotal for early development, stem cell maintenance and/or differentiation. We analyzed the six Japanese families with BCNS and identified six germline mutations in the PTCH1 gene. One family had a nonsense mutation (c.1196G>A), one had a 1-bp deletion (c.2029delA), two had 2-bp deletions (c.239_240delGA and c.1670_1671delCA) and one had a 58-bp duplication (c.1138_1195dup). They caused premature termination, resulting in the truncation of the PTCH1 protein. Analysis of a high-density single nucleotide polymorphism (SNP) mapping array showed a large ∼1.2-Mb deletion, including the PTCH1 gene in one allele, in a family in which PTCH1 mutations were not identified at the sequence level. These data indicated that all the six families who were diagnosed with BCNS had mutations in the PTCH1 gene and that a single copy of a PTCH1 mutation causes BCNS.