Hiroshi Hosoi

Transfection with mutant p53 gene inhibits heat-induced apoptosis in a head and neck cell line of human squamous cell carcinoma

PURPOSE To confirm that human cancer cells show p53-dependent heat sensitivity through an apoptosis-related mechanism, we examined the heat sensitivity and Bax-mediated apoptosis after heating in a human squamous cell carcinoma cell line, SAS, with identical genetic backgrounds except for the p53 status. MATERIALS AND METHODS We performed colony formation assay, Western blotting and analyses of apoptosis, using the SAS cells transfected with pC53-248 vector with mutant p53 gene (SAS/Trp248 cells) or the cells transfected with pCMV-Neo-Bam vector (SAS/neo cells) as a control. RESULTS SAS/Trp248 cells showed heat resistance due to the dominant negative nature of mp53, compared with SAS/neo cells. The incidence of DNA ladders and apoptotic bodies increased markedly after heating in SAS/neo cells, but increased very little in SAS/Trp248 cells. CONCLUSION These results suggest that heat resistance brought by mp53-transfection is p53-dependent and closely correlates with the induction of apoptosis in human squamous cell carcinomas.

Regeneration of peripheral motor nerve gaps with a polyglycolic acid-collagen tube: technical case report.

OBJECTIVEAfter previous success in regenerating canine peripheral nerves over 80 mm gaps using a bioabsorbable nerve guide tube, we have extended this method to the treatment of patients experiencing various types of nerve injury. This report describes the treatment of two cases of motor nerve disorder. METHODSThe bioabsorbable nerve tube was a cylindrically woven polyglycolic acid (PGA) tube filled with collagen. A peripheral motor nerve defect (the frontalis branch of the facial nerve) was reconstructed using this PGA-collagen tube in two patients who experienced posttraumatic unilateral eyebrow ptosis for 3 months. RESULTSFive months after surgery, both patients regained their ability to voluntarily lift their eyebrows symmetrically. Electrophysiological examination at 5 months revealed recovery of compound muscle action potential and disappearance of distal latency on the affected side. CONCLUSIONThis is the first clinical report of motor nerve recovery achieved using the PGA-collagen nerve guide tube. The results suggest that use of a PGA-collagen tube is a promising option for the repair of motor nerve defects.

Osteoporosis as a risk factor for the recurrence of benign paroxysmal positional vertigo.

Benign paroxysmal positional vertigo (BPPV) frequently occurs in females over 50 years old, suggesting that a postmenopausal decrease in estrogen secretion might be involved in its onset. An estrogen deficiency is generally known to cause osteoporosis through a reduction in bone mass. This study was designed to investigate a clinical association between idiopathic BPPV and osteoporosis.

Glycerol as a chemical chaperone enhances radiation-induced apoptosis in anaplastic thyroid carcinoma cells

IntroductionAnaplastic thyroid carcinoma, which is one of the most aggressive, malignant tumors in humans, results in an extremely poor prognosis despite chemotherapy and radiotherapy. The present study was designed to evaluate therapeutic effects of radiation by glycerol on p53-mutant anaplastic thyroid carcinoma cells (8305c cells). To examine the effectiveness of glycerol in radiation induced lethality for anaplastic thyroid carcinoma 8305c cells, we performed colony formation assay and apoptosis analysis.ResultsApoptosis was analyzed with Hoechst 33342 staining and DNA ladder formation assay. 8305c cells became radiosensitive when glycerol was added to culture medium before X-ray irradiation. Apoptosis was induced by X-rays in the presence of glycerol. However, there was little apoptosis induced by X-ray irradiation or glycerol alone. The binding activity of whole cell extracts to bax promoter region was induced by X-rays in the presence of glycerol but not by X-rays alone.ConclusionThese findings suggest that glycerol is effective against radiotherapy of p53-mutant thyroid carcinomas.

Social Participation and Cognitive Decline Among Community-dwelling Older Adults: A Community-based Longitudinal Study

Objective To examine whether social participation (SP) by older individuals is associated with cognitive decline (CD). Method Participants were community-dwelling older adults aged 65 or older with both independent activities of daily living and normal cognitive performance at baseline (2,768 men and 3,325 women). CD was evaluated using the Cognitive Performance Scale. Logistic regression analysis stratified by gender was used to examine CD in relation to SP, with nonparticipation as reference. Age, family, body mass index, pensions, comorbidities, medications, alcohol, smoking, depression, self-rated health, and instrumental activities of daily living were used as covariates. Results During the 3-year follow-up, 16.7% of eligible participants reported CD. After covariate adjustments, greater social group participation was associated with CD prevention for women only. Lessened negative CD effects were found in respondents active in these particular types of social outlets: neighborhood associations (odds ratio = 0.81, 95% confidence interval = 0.66-0.99) and local event groups (0.79, 0.63-0.99) for men, and hobby groups (0.70, 0.54-0.91) and volunteer groups (0.66, 0.45-0.96) for women. Discussion Our results suggest that greater social group participation prevents CD in women, while the beneficial effect of each type of SP on cognition differs between genders. Determining which types of social groups are best for community-dwelling older peoples participation based on gender may help them maintain their cognitive functioning abilities.

Glutamate release in the rat medial vestibular nucleus following unilateral labyrinthectomy using in vivo microdialysis.

We investigated the changes in glutamate release from the ipsi- and contra-lesional medial vestibular nucleus (MVN) following unilateral labyrinthectomy (UL) by in vivo microdialysis study. The concentration of glutamate in the ipsi-lesional MVN was decreased until 4 h. Twelve hours after UL, the concentration of glutamate was restored back to the basal level, after which the release did not show any change between 24 and 48 h post-UL. In contrast, the concentration of glutamate in the contra-lesional MVN, which increased immediately after UL, decreased gradually to the basal level until 3-4 h post-UL, followed by no further change. The difference in the glutamate concentration between ipsi- and contra-lesional MVN increased immediately after UL and gradually decreased accompanied by a reduction in the frequency of nystagmus, although spontaneous nystagmus had not disappeared by the time the imbalance of glutamate release diminished. These results suggest that the imbalance of glutamate release between bilateral nuclei induced the nystagmus, and the change in release is concerned with the rapid development of vestibular compensation.

Social Participation and the Prevention of Decline in Effectance among Community-Dwelling Elderly: A Population-Based Cohort Study

Background We examined the association between a decline in effectance and social participation (SP) from the perspective of the number and the type of SP in a prospective cohort study. Methods Included in this analysis were community-dwelling elderly aged ≥65 without dependency on the basic activities of daily living and reporting a perfect baseline effectance score (n = 4,588; mean age 72.8±5.7). SP was categorized into 5 types: neighborhood associations, hobby groups, local event groups, senior citizen clubs, and volunteer groups. Effectance was evaluated using the Tokyo Metropolitan Institute of Gerontology Index of Competence. Using logistic regression analysis, odds ratio (OR) and a 95% confidence interval (CI) for a decline in effectance were calculated. Age, family, BMI, pensions, medical history, medications, alcohol, smoking, cognitive function, depression, social support, ADL, and IADL were used as covariates. Results During the 3-year follow-up, 17.8% of eligible participants reported a decline in effectance. After adjustment for covariates, participation in various groups was associated with the preservation of effectance for both genders. Regarding the type of SP, among females, participation in neighborhood associations (OR: 0.62, 95%CI: 0.48–0.81), hobby groups (0.58, 0.43–0.77), local event groups (0.63, 0.47–0.86), and volunteer groups (0.53, 0.35–0.82) was inversely associated with a decline in effectance. Among males, the beneficial effect was more likely limited to hobby groups (0.59, 0.43–0.81) and volunteer groups (0.57, 0.39–0.83). Conclusions Our results suggest that participation in a variety of social groups is effective for maintenance of older people’s effectance, while the beneficial effect of each type of SP on effectance is stronger for females than for males. Recommending community-dwelling elderly to participate in social groups appropriate for their gender may be effective for successful aging.

Benefit of a new hearing device utilizing cartilage conduction

OBJECTIVE Our previous study demonstrated that sound was effectively transmitted by attaching a transducer to the aural cartilage even without fixation pressure. This new method for sound transmission was found by Hosoi in 2004, and was termed cartilage conduction (CC). CC can be utilized even in hearing-impaired patients who cannot use air-conduction hearing aids owing to continuous otorrhea or aural atresia. A prototype hearing aid employing CC was investigated in this study. METHODS Four patients with conditions such as continuous otorrhea and acquired aural atresia after surgery participated in this study. The CC hearing aid was fitted, and its benefits were assessed by audiometric tests and interview. RESULTS Thresholds and speech recognition scores improved in all subjects. However, in subjects with continuous otorrhea, it was difficult to obtain the gains according to the target gains owing to their severe hearing loss and the limitation of the output level. On the other hand, unexpectedly large gains were obtained below 2kHz in the patient with acquired aural atresia. These large gains were probably caused by soft tissue filling the postoperative space. No subjects complained of pain associated with the attachment of the transducer, although such problems are usually observed for a bone-conduction (BC) hearing aid. This feature is considered one of the advantages of the CC hearing aid. CONCLUSION The results of the audiometric tests and interview suggest that the CC hearing aid has potential as a useful amplification device for hearing disability. Unfortunately, if the soft tissue pathway is not involved, the current device is insufficient for the patients with severe hearing loss. The improvement of the output level will lead to develop a reliable CC hearing aid as an alternative to BC hearing aids or bone anchored hearing aids.

Peripheral perception mechanism of ultrasonic hearing

Ultrasound can be perceived by bone conduction, and its characteristics differ from those of air-conducted audible sound (ACAS) in some respects. Despite many studies on ultrasonic hearing, the details have not yet been clarified. In this study, to elucidate the perception mechanism, the masking of bone-conducted ultrasound (BCU) produced by ACAS and the sensitivity of BCU in hearing impaired subjects were evaluated. We found that BCU was masked by high frequency ACAS, especially in the frequency range of 10-14 kHz. The most effective masker frequency depended on masker intensity. For hearing impaired subjects, the pure tone thresholds at 1-8 kHz and the maximum audible frequencies at cut-off intensities of 70-100 dB HL were significantly associated with the BCU threshold (p < 0.01 or p < 0.05). No subjects with estimated total loss of the inner hair cell system in the cochlear basal turn could hear BCU. These results suggest the peripheral perceptual region to be located in the cochlea. The results of masking show the faster excitation spread to the lower frequency range, depending on the intensity. This faster excitation spread may be due to nonlinearity in cochlear mechanics, which may work even without cochlear amplifier, and induce unique characteristics of BCU.

Association Between Social Participation and 3‐Year Change in Instrumental Activities of Daily Living in Community‐Dwelling Elderly Adults

To investigate whether social participation (SP) in older adults is associated with ability to perform instrumental activities of daily living (IADLs).