Comparison of Electroaudiometry with cochlear implant in children with inner ear anomaly.

The promontory stimulation test (PST) using a needle electrode has been used to evaluate the sense of the auditory nerve as a preoperative examination for cochlear implant in adults. Because this is a painful test, it is not suitable for children. It has been reported that children with inner ear anomaly showed poorer outcomes of hearing after cochlear implant. Electroaudiometry developed by Med-El Corporation, which is noninvasive, is a more suitable procedure for young children. Patients were three children less than five years old with inner ear anomaly. Two patients showed common cavity, and one showed narrow IAC with hypoplastic cochlear anomaly. By using Electroaudiometry, we analyzed electro-neural hearing of these children before cochlear implant, and compared their hearing after cochlear implant. Three children seemed to have residural electro-neural hearing because the dynamic range between stimulus level (SL) and uncomfortable level (UCL) was detected by using Electroaudiometry. After cochlear implant, their pure-tone audiograms showed moderate hearing thresholds, and their hearing detection and speech perception improved. These results suggest that Electroaudiometry is available for evaluating electro-neural hearing in young children with inner ear anomaly. It can provide useful information for a successful cochlear implant and evaluation of postoperative performances.

Hyper-resistance of meiotic cells to radiation due to a strong expression of a single recA-like gene in Caenorhabditis elegans.

Sensitivity of meiotic cells to DNA damaging agents is little understood. We have demonstrated that the meiotic pachytene nuclei in the Caenorhabditis elegans gonad are hyper-resistant to X-ray irradiation, but not to UV irradiation, whereas the early embryonic cells after fertilization and the full grown oocytes are not. The Ce-rdh-1 gene [RAD51, DMC1 (LIM15), homolog 1 or Ce-rad-51], which is essential for the meiotic recombination, is the only bacterial recA-like gene in the nematode genome, and is strongly expressed in the meiotic cells. Following silencing of the Ce-rdh-1 gene by RNA interference, the meiotic cells become more sensitive to X-ray irradiation than the early embryonic cells. This is the first report that meiotic cells are hyper-resistant to DNA strand breaks due to the high level of expression of the enzyme(s) involved in meiotic homologous recombination.

Caenorhabditis elegans Chk2-like gene is essential for meiosis but dispensable for DNA repair.

A Chk2-like gene was identified in the genome of Caenorhabditis elegans. The putative gene product, termed Ce-chk-2 consists of 450 amino acid residues, and shows good homology with the Chk2/Cds1 gene family. The results of RNA-mediated interference (RNAi) indicated that the F1 generation from dsRNA injected animals grew to adulthood, but approximately 95% of their eggs (F2) died during early embryogenesis. Among the few surviving progeny, males (XO animals) arose at an abnormally high frequency (30%). In addition, 12 univalents were observed in full grown oocytes of the F1, while six bivalents were normally observed in wild-type oocytes. Ce-chk-2 gene expression increased in the adult stage, and their expression level decreased in the glp-4 mutant, which is defective in germ line proliferation. The radiation sensitivity of F1 embryos carrying Ce-chk-2 RNAi was not significantly affected.

Characterization of Ce-atl-1, an ATM-like gene from Caenorhabditis elegans.

An ATM-like gene was identified in the genome of Caenorhabditis elegans. The putative product of the gene, termed Ce-atl-1 (C. elegans ATM-like 1) consists of 2514 amino acid residues. The C-terminal sequence, which contains a PI-3 kinase-like domain, showed good homology with the products of the gene MEC1/ESR1 from budding yeast, the rad3+ gene of fission yeast and mammalian ATM (ataxia-telangiectasia and rad3+ related) genes. The results of RNA-mediated interference indicated that the major phenotype associated with repression of Ce-atl-1 was lethality (approximately 50-80%) during early embryogenesis. Among the surviving progeny, males (XO animals) arose at a high frequency (2-30%). In addition, 5% of oocyte chromosomes demonstrated aneuploidy due to a defect in pre-meiotic chromosomal segregation. Gene expression analyses indicated that Ce-atl-1 mRNA was expressed in all larval stages and that its level increased about fivefold in the adult stage. The adult expression level was decreased in the glp-4 mutant, which is defective in germ line proliferation. Ce-atl-1 was strongly expressed in both the mitotic and meiotic cells of adult gonads. In summary, Ce-atl-1 appears to be important for early embryogenesis, and loss of its function results in a defect in chromosome segregation, similar to what has been observed for AT-related proteins.

Characterization of a Caenorhabditis elegans recA-like gene Ce-rdh-1 involved in meiotic recombination.

A recA-like gene was identified in the Caenorhabditis elegans genome project database. The putative product of the gene, termed Ce-rdh-1 (C. elegans RAD51 and DMC1/LIM15 homolog 1), consists of 357 amino acid residues. The predicted amino acid sequence of Ce-rdh-1 showed 46-60% identity to both RAD51 type and DMC1/LIM15 type genes in several eukaryote species. The results of RNAi (RNA-mediated interference) indicated that repression of Ce-rdh-1 blocked chromosome condensation of six bivalents and dissociation of chiasmata in oocytes of F1 progeny. Oogenesis did not proceed to the diakinesis stage. Accordingly, all the eggs produced (F2) died in early stages. These results suggest that Ce-rdh-1 participates in meiotic recombination.