Keisuke Mizuta

Motion sickness susceptibility associated with visually induced postural instability and cardiac autonomic responses in healthy subjects.

Conclusions This study supports the hypothesis that postural sway and autonomic responses to moving visual stimuli may be associated with motion sickness susceptibility. Characteristics of the cardiac sympathovagal balance during exposure to provocative stimulation may be a marker of individual susceptibility to motion sickness. Objective To assess the relationship between postural and autonomic responses to a simulated visual motion environment and reported susceptibility to motion sickness. Material and methods Fifteen healthy subjects were exposed to sinusoidally oscillating visual motion in roll at frequencies of 0.1–0.4 Hz. Recordings were made of postural sway and respiratory frequency and electrocardiograms were obtained from which heart rate variability (HRV) was computed in order to probe cardiac sympathetic and parasympathetic activity. Results In subjects with a low susceptibility to motion sickness as rated using a standardized questionnaire, there was no significant effect of visual stimulus on postural sway or HRV at any frequency of motion. Subjects with a high susceptibility to motion sickness showed significant postural instability induced by visual stimuli (p<0.01). Visual stimuli presented at a frequency of 0.1 Hz significantly increased the low-frequency power (LF) of HRV, decreased the high-frequency power (HF) of HRV and increased the LF:HF ratio in these subjects (p<0.05).

Head and neck squamous cell carcinoma: usefulness of diffusion-weighted MR imaging in the prediction of a neoadjuvant therapeutic effect.

The purpose of our study was to evaluate the usefulness of diffusion-weighted imaging in predicting the responses to neoadjuvant therapy for head and neck squamous cell carcinomas. Diffusion-weighted, T2-weighted, and gadolinium-enhanced T1-weighted images were obtained from 28 patients with untreated head and neck squamous cell carcinomas with histological proof. A blinded radiologist evaluated the quantitative and qualitative signal intensities and apparent diffusion coefficients (ADCs) in the lesions on each sequence. All patients were treated by neoadjuvant therapies, and the post-therapeutic tumor regression rate was determined. Both the quantitative and qualitative signal intensities on diffusion-weighted images showed positive correlations (r = 0.367 and 0.412, p < .05), and the ADCs showed a weak, inversed correlation (r = −0.384, p < .05) with the tumor regression rates. Diffusion-weighted imaging including an assessment by ADCs may be able to predict tumor response to neoadjuvant therapy for head and neck squamous cell carcinomas.

Dichloroacetate improves immune dysfunction caused by tumor-secreted lactic acid and increases antitumor immunoreactivity.

The activation of oncogenic signaling pathways induces the reprogramming of glucose metabolism in tumor cells and increases lactic acid secretion into the tumor microenvironment. This is a well‐known characteristic of tumor cells, termed the Warburg effect, and is a candidate target for antitumor therapy. Previous reports show that lactic acid secreted by tumor cells is a proinflammatory mediator that activates the IL‐23/IL‐17 pathway, thereby inducing inflammation, angiogenesis and tissue remodeling. Here, we show that lactic acid, or more specifically the acidification it causes, increases arginase I (ARG1) expression in macrophages to inhibit T‐cell proliferation and activation. Accordingly, we hypothesized that counteraction of the immune effects by lactic acid might suppress tumor development. We show that dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinases, targets macrophages to suppress activation of the IL‐23/IL‐17 pathway and the expression of ARG1 by lactic acid. Furthermore, lactic acid‐pretreated macrophages inhibited CD8+ T‐cell proliferation, but CD8+ T‐cell proliferation was restored when macrophages were pretreated with lactic acid and DCA. DCA treatment decreased ARG1 expression in tumor‐infiltrating immune cells and increased the number of IFN‐γ‐producing CD8+ T cells and NK cells in tumor‐bearing mouse spleen. Although DCA treatment alone did not suppress tumor growth, it increased antitumor immunotherapeutic activity of Poly(IC) in both CD8+ T cell‐ and NK cell‐sensitive tumor models. Therefore, DCA acts not only on tumor cells to suppress glycolysis but also on immune cells to improve the immune status modulated by lactic acid and to increase the effectiveness of antitumor immunotherapy.

Polaprezinc prevents oral mucositis associated with radiochemotherapy in patients with head and neck cancer

Oral mucositis is frequent but serious adverse event associated with radiotherapy or radiochemotherapy in head and neck cancer severely impairs health‐related quality of life, leading to poor prognosis due to discontinuation of the therapy. Although a number of compounds have been tested for prophylaxis of oral mucositis, few of them are satisfactory. We investigated the effect of polaprezinc (zinc L‐carnosine), a gastric mucosal protective drug, on radiochemotherapy‐induced oral mucositis, pain, xerostomia and taste disturbance in patients with head and neck cancer. Patients were randomly assigned to receive polaprezinc (n = 16) or azulene oral rinse as the control (n = 15). The incidence rates of mucositis, pain, xerostomia and taste disturbance were all markedly lower in polaprezinc group than in control. Moreover, the use of analgesics was significantly (p = 0.003) less frequent and the amount of food intake was significantly (p = 0.002) higher in polaprezinc group than in control. On the other hand, tumor response rate in patients with neoadjuvant radiochemotherapy was not significantly affected by polaprezinc, in which the response rate (complete plus partial response) was 88% for polaprezinc and 92% for control (p = 1.000). Therefore, it is highly assumable that polaprezinc is potentially useful for prevention of oral mucositis and improvement of quality of life without reducing the tumor response.

The association of antidiuretic hormone levels with an attack of Meniere's disease

Objectives:  An elevation of the plasma antidiuretic hormone (ADH) levels has frequently been observed in Menieres disease patients. However, little is known regarding the mechanism behind such an elevation of ADH level in Menieres disease patients. Therefore, we measured the plasma ADH in Menieres disease patients and other vertigo patients to elucidate the association between the ADH levels, stress levels and the development of Menieres symptom.

Subclinical deviation of the subjective visual vertical in patients affected by a primary headache

Conclusion. Our results suggest that patients with migraine or tension-type headache have subclinical deviations of the subjective visual vertical, which may be associated with their subjective imbalance Objectives. Patients affected by migraine or tension-type headache often complain of unsteadiness. However, they rarely show a clinical significance in the objective examinations of their equilibrium. We investigated the equilibrium functions in patients affected by migraine or tension-type headache Subjects and methods. We investigated the neurotological findings of 17 patients with migraine, 20 patients with tension-type headaches, and 16 patients without headache. All patients in this study experienced vertigo or dizziness before they underwent the examination; however, they never had vertigo attacks for more than 1 month before the examination. All patients in this study were tested during headache-free intervals Results. There was no significant difference in the hearing levels of pure tone audiometry, the canal palsy percentage of bithermal caloric test, and the body sway in posturography among the three groups (p>0.05, Mann-Whitney U test). The average values in absolute deviations of subjective visual vertical (SVV) in patients with tension-type headache (1.3±1.1°) and patients with migraine (1.5±1.2°) were significantly larger in comparison with those of patients without headache (0.6±0.4) (p<0.05, Mann-Whitney U test). Intra-individual varaiances of the SVV in patients with primary headache were significantly larger than those in patients without headache (p<0.05, Mann-Whitney U test).

Increased expression of phospholipase D1 mRNA during cAMP- or NGF- induced differentiation in PC12 cells

The rat pheochromocytoma PC12 cells have been employed as a useful model to study neuronal differentiation. To gain insight into the molecular events involved in extension of neurites, the differential expression of phospholipase D (PLD) isozymes were examined in cyclic AMP- or nerve growth factor (NGF)-treated PC12 cells. When the cells were incubated with dibutyryl cyclic AMP (dbcAMP), almost all the cells displayed prominent neurite outgrowth at 24 h. The neurites developed in NGF-treated cells at 24 h were shorter than those in the cells treated with dbcAMP. However, most of the NGF-treated cells extended long neurites at day 5. The rPLD1b mRNA increased within 6 h following dbcAMP treatment and maintained a high level up to 24 h. In contrast, the levels of rPLD1a and rPLD2 mRNAs were rather consistent throughout the time course examined. However, when the cells were treated with NGF, rPLD1a and rPLD1b mRNAs, but not rPLD2 mRNA, increased within 2 days and remained elevated up to 5 days. These results suggest the possible implication of PLD1 in PC12 cell differentiation.

CT and MR imaging findings of palatal tumors.

Palatal tumors commonly arise from the minor salivary glands, and benign tumors account for approximately half of all minor salivary gland tumors. Minor salivary gland tumors have an affinity for the posterior hard palate and soft palate and virtually never arise in the midline, probably because of the distribution of palatal salivary glands. The majority of benign salivary gland tumors of the palate are pleomorphic adenomas, while the most common malignant salivary gland tumor is adenoid cystic carcinoma, followed by mucoepidermoid carcinoma, adenocarcinoma, and polymorphous low-grade adenocarcinoma. Epithelial tumors frequently arise from the soft palate. The majority of benign epithelial tumors of the palate are papillomas, while most malignant epithelial tumors are squamous cell carcinomas. Various types of mesenchymal tumors, including fibromas, lipomas, schwannomas, neurofibromas, hemangiomas, and lymphangiomas, also involve the palate. This article describes the CT and MR findings of benign and malignant palatal tumors.

Tracing Sox10-expressing cells elucidates the dynamic development of the mouse inner ear.

The inner ear is constituted by complicated cochlear and vestibular compartments, which are derived from the otic vesicle, an embryonic structure of ectodermal origin. Although the inner ear development has been analyzed using various techniques, the developmental events have not been fully elucidated because of the intricate structure. We previously developed a Sox10-IRES-Venus mouse designed to express green fluorescent protein under the control of the Sox10 promoter. In the present study, we showed that the Sox10-IRES-Venus mouse enabled the non-destructive visualization and understanding of the morphogenesis during the development of the inner ear. The expression of the transcription factor Sox10 was first observed in the invaginating otic placodal epithelium, and continued to be expressed in the mature inner ear epithelium except for the hair cells and mesenchymal cells. We found that Sox10 was expressed in immature hair cells in the developing inner ear, suggesting that hair cells were generated from the Sox10-expressing prosensory cells. Furthermore, we demonstrated that scattered Sox10-expressing cells existed around the developing inner ear, some of which differentiated into pigmented melanocytes in the stria vascularis, suggesting that they were neural crest cells. Further analyzing the Sox10-IRES-Venus mice would provide important information to better understand the development of the inner ear.

A characteristic pattern in the postural sway of unilateral vestibular impaired patients.

The statistical properties of the center of pressure (COP) change over time, and -invariant methods of the COP analysis is not sufficient to monitor the changes. Therefore, dynamic temporal information of the COP signals has been important in assessing the postural stability. The purpose of this study was to evaluate the characteristic pattern of time-frequency dynamics during the upright stance in patients with unilateral vestibular dysfunction (UVD). This study included 20 dizzy patients with UVD and age-matched 20 control subjects without any vestibular disorder. The COP signals were collected using a single standard force platform and a spectral analysis including the time-frequency dynamics was carried out on the basis of the maximum entropy method (MEM) by using a segment time series analysis. The power spectral density (PSD) analysis exhibited an exponential decreasing shape (1/f (-)(β)) when plotted on a double logarithmic scale. The average value of β in the low frequency range of less than 1 Hz in the UVD group was significantly lower than that in the control group (p < 0.05) in the medial-lateral (ML) direction under eyes closed condition. In the segment time series analysis, the peak frequency of the COP signals in the patients with UVD gradually converged to the frequency range of 0.1-0.2 Hz in the ML direction under EC condition. Our results suggest that the segment time series analysis of the COP signals can derive a characteristic pattern related to the UVD. It may indicate an increased reflexivity of the COP fluctuation by the UVD, resulting in inducing the instability.