[A MULTICENTER CLINICAL SURVEY ABOUT THE PREVALENCE OF JAPANESE CYPRESS POLLINOSIS AND THE EFFICACY OF SUBLINGUAL IMMUNOTHERAPY WITH JAPANESE CEDAR POLLEN EXTRACT DURING JAPANESE CYPRESS POLLEN DISPERSAL PERIOD].

BACKGROUND: Little is known whether sublingual immunotherapy using Japanese cedar pollen extract (cedar SLIT) is effective for not only Japanese cedar pollinosis but also Japanese cypress pollinosis. We investigated the prevalence rate of Japanese cypress pollinosis, efficacy of cedar SLIT on cypress pollinosis and patients' wish to receive cypress SLIT. METHODS: We investigated a multi-center (31 institutions), cross-sectional survey using a self-administrated questionnaire with four questions for patients received cedar SLIT aged from 5 to 69 years old. RESULTS: 2523 subjects were enrolled for analysis. 83.4% of them had pollinosis symptoms during cypress season before cedar SLIT. In such patients, 37.4% experienced lessened efficacy of cedar SLIT during cypress season. Both the prevalence of cypress pollinosis and the lessened efficacy of cedar SLIT on cypress pollinosis were significantly seen in western Japan as compared to eastern Japan. 76.1% of the subject having cypress pollinosis before SLIT wished to receive cypress SLIT if it is available. CONCLUSION: A lessened efficacy of cedar SLIT during cypress season was broadly seen in Japan, and further showed a regional difference. Together with the finding of high wish by patients, these results suggest a development of cypress SLIT is desirable.

Long-term compliance with nasal continuous positive airway pressure therapy for sleep apnea syndrome in an otorhinolaryngological office.

Continuous positive airway pressure (CPAP) is effective for patients with SAS. CPAP therapy requires long-term usage to prevent recurrence of symptoms. It is, thus, important to examine the level of long-term CPAP use and the factors influencing compliance with CPAP therapy for SAS. Compliance with CPAP therapy was examined in 204 patients in whom such therapy was started between 2003 and 2009. The median follow-up duration was 19 months (IQR = 6.8-37.5). Although the subjective and objective curative effects were significant, 18 patients (8.9%) refused CPAP therapy. Survival analysis showed that the patients' adherence to CPAP after 5 years was 89.8%. Multivariate analysis, including gender, age, BMI, AHI, arousal index, minSpO2, ESS, sleep stage, and LMI, indicated that the degree of improvement of AHI, percentage of deep sleep stage, and LMI were clinical variables independently associated with long-term adherence to CPAP. Furthermore, use of appropriate drugs for the patients with nasal congestion resulted in better satisfaction and adherence to CPAP therapy. We have shown that the rate of compliance and the subjective and objective curative effects of CPAP therapy were high, and detected the independent clinical factors associated with continued CPAP therapy.

Inhibition of histone deacetylase 3 stimulates apoptosis induced by heat shock under acidic conditions in human maxillary cancer.

To elucidate the molecular mechanisms for the enhancement of heat-induced apoptosis on exposure to acidic conditions, human maxillary carcinoma IMC-3 cells were heat-shocked at 44 degrees C for 30 min at either pH 7.4 or 6.7. Analyses with cDNA arrays, the reverse transcription-polymerase chain reaction (RT-PCR), and Western blotting were performed. We found that histone deacetylase 3 (HDAC3) was specifically induced after hyperthermia at 44 degrees C for 30 min at pH 6.7. Although the cytotoxicity of heating at 44 degrees C for 30 min was enhanced by decreasing the pH from 7.4 to 6.7, it was enhanced even more by antisense RNA oligonucleotides for HDAC3. The induction of G2/M arrest after heating occurred earlier at pH 6.7 than at pH 7.4. The inhibition of HDAC3 by the antisense RNA oligonucleotides suppressed partially the induction of G2/M arrest, resulting in an enhancement of the apoptosis caused by the heating under acidic conditions. Antisense RNA oligonucleotides for HDAC3 enhanced apoptosis 48 h after hyperthermia at 43 degrees C for 30 min in vivo. Analyses of p65 activity suggested that NF-kappaB is involved in this enhancement of hyperthermia. HDAC3 may be a novel target enhancing hyperthermia and combined treatment with hyperthermia and HDAC inhibitors is a possible modality for cancer therapy.

The terminal of the sympathetic nerve fibers in the facial nerve.

OBJECTIVE: The terminal of the sympathetic nerve fibers of the rat facial nerve in the temporal bone region was investigated. MATERIAL AND METHODS: We used tyrosine hydroxylase (TH) and the synaptophysin antibody as markers of the sympathetic nerve fiber and the membrane of the synaptic vesicle, respectively. Using immunohistochemistry, we determined whether and where the synapse exists in the facial nerve of the Sprague-Dawley rat. RESULTS: TH-immunoreactive fibers were confirmed as being present in both the epineurium and the nerve fascicle of the facial nerve. A synaptophysin immunoreaction was found in the facial nerve in a region of the temporal bone. These reaction products looked like varicosities. Most TH-positive fibers in the facial nerve disappeared after superior cervical ganglionectomy. CONCLUSIONS: As the synaptophysin immunoreaction indicates the existence of a synapse, we speculate that the sympathetic fibers affect the facial nerve in the region of the temporal bone. Further studies may be needed to elucidate the function of the sympathetic system in the facial nerve.

Inhibitory effect of cyclosporin A on p-glycoprotein function in peripheral nerves of mice treated with doxorubicin and vinblastine.

OBJECTIVE: To investigate the inhibitory effect of cyclosporin A on p-glycoprotein function in peripheral nerves (VIIth, VIIIth and sciatic nerves). MATERIAL AND METHODS: Male mdr1a(-/-) and mdr1a(+/+) FVB mice were used. Doxorubicin (30 mg/kg) was administered intravenously with or without i.p. administration of cyclosporin A (200 mg/kg). Vinblastine (5 mg/kg) was also administered intravenously with or without i.p. administration of cyclosporin A (200 mg/kg). RESULTS: Tissue concentrations of doxorubicin and vinblastine in peripheral nerves of the mdr1a(+/+) mice pretreated with 200 mg/kg cyclosporin A were significantly higher than those in the mdr1a(+/+) mice administered doxorubicin or vinblastine alone, suggesting that cyclosporin A inhibited the efflux pump function of p-glycoprotein in the peripheral nerves. In the mdr1a(-/-) mice, tissue concentrations of doxorubicin and vinblastine in peripheral nerves were also significantly higher than those in the mdr1a(+/+) mice administered doxorubicin or vinblastine alone. Based on these results, it is suggested that p-glycoprotein plays an important role in blood-nerve barrier function by preventing side-effects induced by neurotoxic drugs. CONCLUSION: When doxorubicin and vinblastine are co-administered with cyclosporin A, the patient should be carefully monitored because peripheral nerve disorders may be induced.

Cochlear nerve demyelination causes prolongation of wave I latency in ABR of the myelin deficient (md) rat.

In this study, we examined the auditory brainstem responses (ABRs), distortion product of otoacoustic emissions (DPOAEs) and cochlear morphology of the myelin deficient (md) rat, which completely lacks central myelin but not peripheral myelin. ABRs showed a marked prolongation not only wave II-IV latencies but also wave I latency. Cochlear nerve fibers near the modiolus lost their myelin halfway into the internal auditory canal. DPOAEs also decreased at a lower frequency of the combined tone. Since nerve fibers ending at the apical turn of the cochlea passed through central portion of the cochlear nerve, wave I prolongation of ABRs and decrease of DPOAEs at a lower frequency might originate mainly from the demyelinated CNS part of the cochlear nerve and efferent olivocochlear bundle in the internal auditory canal.

Expression of p27 and apoptosis in oral leukoplakia.

Recently, a close relationship between the cell cycle and apoptosis was confirmed in oral squamous cell carcinoma (SCC). To clarify the expression of cell cycle-related proteins and apoptosis in the oral premalignant state, we investigated the expression of p27, cyclin D1 and proliferating cell nuclear antigen (PCNA) using immunohistochemical staining, and apoptotic index (AI) using ApopTag in situ staining. The positive expression-score of p27 was 42.0% in leukoplakia (34.8% in hyperplasia, 55.4% in dysplasia) and 31.1% in SCC (43.3% in the early stage of SCC, 25.9% in the advanced stage of SCC). The level of p27 expression showed a peak in dysplasia and decreased in SCC. The expression of cyclin D1 was almost constant between hyperplasia and SCC. The expression of PCNA increased sequentially with disease progression. The apoptotic index (AI) in the p27-positive leukoplakia group was significantly higher than that in the p27-negative leukoplakia group (3.9 +/- 3.6 vs. 1.5 +/- 1.6, p = 0.026). From these results, we suggest that the abundance of p27 in oral leukoplakia may inhibit cell proliferation and lead premalignant tumor cells to apoptosis, and thus is concerned with prevention of tumor progression.

Gene expression analysis of human middle ear cholesteatoma using complementary DNA arrays.

OBJECTIVE: To identify genes regulated in human cholesteatoma compared with normal skin tissue using complementary DNA arrays. STUDY DESIGN: In vitro analysis. METHODS: Eight cholesteatoma and retroauricular skin samples were obtained from the same patients during surgery. Upregulated and downregulated genes were highlighted using complementary DNA arrays for screening. Reverse transcriptase-polymerase chain reaction and immunohistochemical staining were performed to confirm the results of the complementary DNA array. RESULTS: Twelve genes were found to be induced or upregulated in cholesteatoma compared with skin samples. These included genes involved in cell proliferation and differentiation (eg, calgranulin A, calgranulin B, psoriasin, thymosin beta-10) and cell invasion (eg, cathepsin C, cathepsin D, cathepsin H). Analyses by means of reverse transcription-polymerase chain reaction showed enhanced expression of several genes including calgranulin A, calgranulin B, psoriasin, thymosin beta-10, cathepsin C, cathepsin D, and cathepsin H in cholesteatoma, supporting the findings from the gene array. In addition, it was verified by immunohistochemical analysis that the expressions of Calgranulin A, Calgranulin B, and Cathepsin D were mainly located in cholesteatoma epithelium. CONCLUSION: The observed alteration in gene expression may play a role in various mechanisms of pathogenesis in cholesteatoma.

Analysis of heat-shock related gene expression in head-and-neck cancer using cDNA arrays.

PURPOSE: The aim of the present study was to identify genes regulated in the early response to heat-shock in human head-and-neck cancer cells using a cDNA array. METHODS AND MATERIALS: IMC-3 cells were heat-shocked at 44 degrees C for 30 min, then incubated for 6 h. After 6 h incubation, mRNAs were extracted. Early gene expressions in IMC-3 cells were analyzed using a cDNA array after heat-shock. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was performed to identify the expressions of mRNA for confirming features by cDNA array analysis in several other cell lines (KB, T3M-1, SCC-TF) as well as in IMC-3 cells. RESULTS: Twenty-eight genes were found to be induced or upregulated by heat-shock in IMC-3 cells. These included genes involved in the apoptosis (e.g., CC3, caspase10), tumor invasion (e.g., CC3, TIMP-3), cell cycle checkpoint control (e.g., DP-1, CDC25A), signal transduction (e.g., MEK1) as well as genes associated with heat stress (e.g., Hsp70B', Hsp40). Gene expressions of CC3 and MEK1 were recognized to be induced by heat-shock in pharyngeal cancer cells (KB, T3M-1) and lingual cancer cells (SCC-TF). CONCLUSION: The observed alteration in gene expression may play a role in various biochemical pathways of cancer cells exposed to heat-shock.