[in Japanese]

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Magnetoencephalographic (MEG) responses to odor (amyl-acetate) and non-odor stimuli for 1 second were recorded in 9 healthy volunteers (right handed) with a dual 37-channel SQUID (Magnes^TM, Bti Co.) and evaluated by fast Fourier transformation analysis, with the following results:
1. On MEG analysis, the spectral density increase in the left mid-central region at a frequency of 7 Hz was significantly greater in response to odor than in response to non-odor stimuli. This greater increase is apparently related to the presence of the odor perception mechanism in the orbital frontal area, a major center of the olfactory system.
2. Both increased and decreased spectral density areas at a frequency of 8 Hz were observed over the right hemisphere when no stimuli was compared with non-odor and no stimulus compared with odor. These changes may reflect a high level of vigilance caused by stimulation.
3. When no stimulus was compared with non-odor stimulation, a significant spectral density increase at a frequency of 11 Hz was noted. Similar trends were observed at frequencies of 11 and 12 Hz when no stimulus was compared with odor. These findings indicated increased attention in response to random presentation of odor and non-odor.
4. Significant differences at frequencies from 14 to 24 Hz were noted in the contralateral hemisphere when no stimulus was compared with odor stimuli. MEG spectral densities at 21 and 22 Hz were also noted in the contralateral hemisphere when no stimulus was compared with non-odor stimulus.
These differences apparently arise from the response of the somato-sensory cortex to non-odor stimuli and amyl-acetate.
Alternation of MEG spectral densities at frequencies from 14 to 17 Hz and 23 to 24 Hz in the left hemisphere was noted when no stimulus was compared with non-odor and no stimulus was compared with odor. These results appear to be related to “emotions” of pleasantness and unpleasantness evoked by non-odor and odor.

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We have previously reported that cisplatin induces caspase-9 activation in head and neck squamous cell carcinoma cells (HNSCCs) in vitro, and the use of a specific inhibitor of caspase-9 blocks cisplatin-induced apoptosis in HNSCCs. Our purpose here was to determine whether HNSCCs selected for resistance to cisplatin fail to exhibit caspase-9 activation in response to cisplatin. Cisplatin-resistant HNSCCs (CRHNSCCs) were selected for growth in the presence of cisplatin. Following cisplatin treatment, no protelyzed caspase-9 subunits were detected in the CRHNSCCs, whereas proteolytic degradation of procaspase-9 was observed in parental cisplatinsensitive HNSCCs (CSHNSCCs). Using a direct enzymatic assay measuring cleavage of the synthetic peptide substrate (LEHD-AFC), caspase-9 activity in cisplatin-treated CRHNSCCs was less than that in cisplatin-treated CSHNSCCs. Because caspase-9 activation requires the release of mitochondorial cytochrome c (Cyt c) into the cytoplasm, we determined the level of cytoplasmic Cyt c in response to cisplatin treatment. Interestingly, following cisplatin treatment, the same extent of increase in cytoplasmic Cyt c was evident and the expression of Bcl-2 family proteins (Bcl-2 and Bcl-XL) remained unchanged in both CRHNSCCs and CSHNSCCs. These results suggest that in certain HNSCC cell types, inhibition of caspase-9 activity represents another mechanism of acquired cisplatin resistance. This inhibition mechanism may be independent of the release of Cyt c into the cytoplasm.

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Background: Interest in the physiological, pathological and therapeutic implications of nitric oxide (NO) have grown exponentially, with human nasal cavity and paranasal sinuses considered a dominant source of NO, indicating that this molecule possesses the diversity of biological effects in the regulation of airway clearance and nonspecific cellular immunity. We previously observed differences in NO synthase (NOS) isoform constitutively expressed in nasal epithelial cells (NECs) from allergic and normal subjects.
Objectives: We extended the previous work to determine whether in vitro stimulation with proinflammatory cytokines influences levels of different NOS isoform expression.
Methods: Nasal epithelial cells were sampled from the inferior turbinate in a group of 16 healthy normal controls and 11 patients with perennial allergic rhinitis against house dust (HD) mite antigen. 1×10⁵ cells were incubated in conditioned medium for 24 hours. Human recombinant interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), or both (cytomix) were added to a final concentration of 10 ng/ml. Cells were then fixed with 4% paraformaldehyde and processed for fluorescence immunocytochemistry. Immunoreactivity for 2 NOS isoforms, inducible NOS (iNOS) and endothelial NOS (eNOS), was studied by laser scanning confocal microscopy and fluorescence intensity was assessed quantitatively.
Results: We observed constitutive eNOS expression in epithelial cells of all subjects. Different treatments with cytokines did not affect eNOS expression. Cytokine treatment, however, significantly augmented iNOS expression in the control group. The average increase induced with IFN-γ, TNF-α, and cytomix was 1.8, 2.33, and 2.31-fold. Nasal epithelial cells in the HD group showed elevated steady-state iNOS expression even in untreated. Cytokine treatment did not affect the degree of iNOS expression in this group.
Conclusion: These results confirm our previous findings that nasal epithelial cells in patients with allergic rhinitis produce higher levels of NO through the concomitant expression of different NOS isoforms. We also demonstrated that nasal epithelial cells have the potential to express iNOS protein spontaneously or upon stimulation with inflammatory cytokines, such as IFN-γ and TNF-α. Because the high level of exhaled NO is considered a potential marker of allergic airway inflammation, preserving the iNOS gene from its unregulated induction may be important for maintenance of nasal homeostasis and may offer a tool for therapeutic intervention.

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We studied whether epithelial cells cultured in serum-free medium contained other cells or not, there were differences in SCF production from cultured nasal epithelial cells between groups of nonallergic and allergic patients, and among degrees of serum mite-CAP RAST classes of allergic patients, and how drugs inhibited SCF production. As a result, no other contaminating cells except mast cell existed in cultured cells. There was a significant difference in SCF production of cultured cells between nonallergic and class 1-2, 3-4, 5-6, and between class 1-2 and 3-4, 5-6 of mite CAP-RAST class. Cyclosporin, prednisolone, fluticasone, ketotifen, and clemastine inhibited SCF production from cultured epithelial cells, but cromoglicate and suplatast did not. Inhibition means the reduction of SCF from cells, not the growth of cultured nasal epithelial cells.

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Enlarged vestibular aqueduct (EVA) is an inner ear anomaly occasionally associated with sensorineural hearing loss (SNHL) and/or dizziness. Recent genetic studies indicate that mutations in the PDS gene may cause EVA. A 10-year-old EVA patient who had undergone annual hearing tests for 7 years had an aunt and cousin who also had hearing loss and EVA, so genetic examinations were conducted for a possible genetic link. Two new PDS gene mutations, S610X and S657N, were found in all 3, including the proband. We discuss the importance of genetic analysis, which offers new insight into SNHL diagnosis and treatment in children.

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We conducted definitive surgery on 45 patients with untreated primary parotid cancer from 1975 to 1995, and evaluated methods of neck dissection and results of treatment. All 14 with clinical neck lymph node metastasis underwent ipsilateral radical neck dissection and only 1 developed neck lymph node recurrence at the peripheral dissected site. Of 31 patients without clinical neck lymph node metastasis, 27 of 19 of 36 with high-grade malignancy and 12 of 24 with T3 or T4 did not undergo prophylactic neck dissection and developed latent neck lymph node metastasis in 2 cases (7.4%). Whereas in most cases we achieved good control of the primary site but neck lymph node recurrences occurred, recurrent sites were observed all around the ipsilateral neck and prognosis were very poor if neck dissection was conducted as secondary treatment. Although histopathological diagnosis was considered feasible for predicting occult neck lymph node metastasis, correct diagnostic with fine needle aspiration cytology revealed only 21.8%. Pathological positive lymph nodes in 15 patients who underwent neck dissection were detected all over (level I to V) the ipsilateral neck and the recurrent positive rate at level II was 100%. Based on the above results, we conclude that (1) in cases with neck lymph node metastasis in preoperative evaluation, ipsilateral radical neck dissection is mandated, and (2) in cases without neck lymph node metastasis, prophylactic neck dissection is not usually needed. When pathological results of frozen section from intraoperative jugulodigastric nodal sampling are positive, ipsilateral radical neck dissection is mandated.

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