Atsuko Maki

Concomitant Chemoradiotherapy as a Standard Treatment for Squamous Cell Carcinoma of the Temporal Bone

We sought to characterize the effectiveness of concomitant chemoradiotherapy (CCRT) for patients with squamous cell carcinoma of the temporal bone. We performed a retrospective chart review of 14 patients with cancer of the temporal bone who were provided initial treatment in our hospital from December 2001 to November 2008. Four patients with stage I tumors were treated by radiation therapy alone or with oral administration of S1. One patient with a stage II tumor was treated by radiation therapy concomitant with low dose docetaxel. Nine patients with stage IV tumors were treated by CCRT using the TPF regimen (docetaxel, cisplatin, and 5-fluorouracil). As an initial treatment, all patients but one were treated by radiation therapy with or without chemotherapy. Grade 4 adverse events of patients who received CCRT using the TPF regimen involved the leukopenia in one patient and the neutropenia in two patients. Local recurrences were observed in three patients including two patients with T4 tumors. Five-year disease-specific survival rates for all patients and for patients with T4 tumors were 78% and 67%, respectively. CCRT using the TPF regimen is safe and effective as the first treatment for patients with cancer of the temporal bone.

Toll-Like Receptor 9-Dependent Activation of Bone Marrow-Derived Dendritic Cells by URA5 DNA from Cryptococcus neoformans

ABSTRACT Cryptococcus neoformans is an opportunistic fungal pathogen that causes meningoencephalitis in immunocompromised patients. Recently, we reported that Toll-like receptor 9 (TLR9) is involved in host defense against C. neoformans: specifically, it detects the pathogens DNA. In the present study, we aimed to elucidate the mechanisms underlying TLR9-mediated activation of innate immune responses by using the URA5 gene, which encodes a virulent component of this fungal pathogen. A PCR-amplified 345-bp URA5 gene fragment induced interleukin-12 p40 (IL-12p40) production by bone marrow-derived dendritic cells (BM-DCs) in a TLR9-dependent manner. Similar activity was detected in the 5′ 129-bp DNA fragment of URA5 and in a synthesized oligodeoxynucleotide (ODN) with the same sequence. Shorter ODN fragments, which contained GTCGGT or GACGAT but had only 24 or 21 bases, induced IL-12p40 production and CD40 expression by BM-DCs, but this activity vanished when the CG sequence was replaced by GC or when a phosphorothioate modification was introduced. IL-12p40 production caused by active ODN was strikingly enhanced by treatment with DOTAP, a cationic lipid that increases the uptake of DNA by BM-DCs, though DOTAP failed to induce IL-12p40 production by inactive ODN and did not affect the activity of an ODN-containing canonical CpG motif. There was no apparent difference in intracellular trafficking between active and inactive ODNs. Finally, an extremely high dose of inactive ODN suppressed IL-12p40 production by BM-DCs that had been stimulated with active ODN. These results suggest that the C. neoformans URA5 gene activates BM-DCs through a TLR9-mediated signaling pathway, using a mechanism possibly independent of the canonical CpG motif.

Bimodal audio-visual training enhances auditory adaptation process

Effects of auditory training with bimodal audio–visual stimuli on monomodal aural speech intelligibility were examined in individuals with normal hearing using highly degraded noise-vocoded speech sound. Visual cue simultaneously presented with auditory stimuli during the training session significantly improved auditory speech intelligibility not only for words used in the training session, but also untrained words, when compared with the auditory training using only auditory stimuli. Visual information is generally considered to complement insufficient speech information conveyed by the auditory system during audio–visual speech perception. However, the present results showed another beneficial effect of audio–visual training that the visual cue enhances the auditory adaptation process to the degraded new speech sound, which is different from those given during bimodal training.

Effects of contralateral noise on 40-Hz and 80-Hz auditory steady-state responses.

Objectives: The amplitude of 40-Hz auditory steady-state response (ASSR) in response to repeated click or tone pips at levels of 45 to 60 dB SL is reduced by up to 50% by the central masking mechanism if white noise at levels of 40 to 60 dB SL is applied contralaterally. However, the effect of contralateral noise on the elevation of the threshold of ASSR is unknown. The present study investigated the effects of contralateral noise on the threshold measurements of ASSR for 40- and 80-Hz amplitude modulated tones that are widely used in clinical examinations. Design: The effects of contralateral noise on the 40- and 80-Hz ASSRs for amplitude modulated tones at 500 Hz and 2000 Hz were examined in 11 healthy volunteers (10 men and 1 woman, mean age 26.1 years). Contralateral noise consisted of white noise low-pass filtered at 700 and 4000 Hz in the measurements of ASSR at a carrier frequency of 500 and 2000 Hz, respectively. Results: Contralateral noise at a level of 40 dB SL caused no significant psychophysical threshold elevation, caused significant threshold elevation of the 40-Hz ASSR (average 10 to 15 dB), and caused no significant threshold elevation of the 80-Hz ASSR. Conclusions: The different effects on the 40- and 80-Hz ASSRs were probably related to the differences in sources because the 40-Hz ASSR contains more components from the upper auditory pathway that are affected by contralateral masking, whereas the 80-Hz ASSR contains more components from the brain stem. The present results suggest that threshold elevation of the 40-Hz ASSR may occur during clinical measurements using binaural presentation of sounds and cause a possible discrepancy between psychophysical threshold and 40-Hz ASSR measurements.

Contralateral white noise attenuates 40-Hz auditory steady-state fields but not N100m in auditory evoked fields

The different response characteristics of the different auditory cortical responses under conventional central masking conditions were examined by comparing the effects of contralateral white noise on the cortical component of 40-Hz auditory steady state fields (ASSFs) and the N100 m component in auditory evoked fields (AEFs) for tone bursts using a helmet-shaped magnetoencephalography system in 8 healthy volunteers (7 males, mean age 32.6 years). The ASSFs were elicited by monaural 1000 Hz amplitude modulation tones at 80 dB SPL, with the amplitude modulated at 39 Hz. The AEFs were elicited by monaural 1000 Hz tone bursts of 60 ms duration (rise and fall times of 10 ms, plateau time of 40 ms) at 80 dB SPL. The results indicated that continuous white noise at 70 dB SPL presented to the contralateral ear did not suppress the N100 m response in either hemisphere, but significantly reduced the amplitude of the 40-Hz ASSF in both hemispheres with asymmetry in that suppression of the 40-Hz ASSF was greater in the right hemisphere. Different effects of contralateral white noise on these two responses may reflect different functional auditory processes in the cortices.