Bridging the gap between molecular dynamics and hydrodynamics in nanoscale Brownian motions.

Through molecular dynamics simulations, we examined the hydrodynamic behavior of the Brownian motion of fullerene particles based on molecular interactions. The solvation free energy and velocity autocorrelation function (VACF) were calculated by using the Lennard-Jones (LJ) and Weeks-Chandler-Andersen (WCA) potentials for the solute-solvent and solvent-solvent interactions and by changing the size of the fullerene particles. We also measured the diffusion constant of the fullerene particles and the shear viscosity of the host fluid, and then the hydrodynamic radius aHD was quantified from the Stokes-Einstein relation. The aHD value exceeds that of the gyration radius of the fullerene when the solvation free energy exhibits largely negative values using the LJ potential. In contrast, aHD is similar to the size of bare fullerene when the solvation free energy is positive using the WCA potential. Furthermore, the VACF of the fullerene particles is directly comparable with the analytical expressions utilizing the Navier-Stokes equations both in incompressible and compressible forms. A hydrodynamic long-time tail t-3/2 is demonstrated for timescales longer than the kinematic time of the momentum diffusion over the particle size. However, the VACF at shorter timescales deviates from the hydrodynamic description, particularly for smaller fullerene particles and for the LJ potential. This occurs even though the compressible effect is considered when characterizing the decay of the VACF around the sound-propagation timescale over the particle size. These results indicate that the nanoscale Brownian motion is influenced by the solvation structure around the solute particles originating from the molecular interaction.

M2-like macrophage polarization in high lactic acid-producing head and neck cancer.

Reprogramming of glucose metabolism in tumor cells is referred to as the Warburg effect and results in increased lactic acid secretion into the tumor microenvironment. We have previously shown that lactic acid has important roles as a pro-inflammatory and immunosuppressive mediator and promotes tumor progression. In this study, we examined the relationship between the lactic acid concentration and expression of LDHA and GLUT1, which are related to the Warburg effect, in human head and neck squamous cell carcinoma (HNSCC). Tumors expressing lower levels of LDHA and GLUT1 had a higher concentration of lactic acid than those with higher LDHA and GLUT1 expression. Lactic acid also suppressed the expression of LDHA and GLUT1 in vitro. We previously reported that lactic acid enhances expression of an M2 macrophage marker, ARG1, in murine macrophages. Therefore, we investigated the relationship between the lactic acid concentration and polarization of M2 macrophages in HNSCC by measuring the expression of M2 macrophage markers, CSF1R and CD163, normalized using a pan-macrophage marker, CD68. Tumors with lower levels of CD68 showed a higher concentration of lactic acid, whereas those with higher levels of CSF1R showed a significantly higher concentration of lactic acid. A similar tendency was observed for CD163. These results suggest that tumor-secreted lactic acid is linked to the reduction of macrophages in tumors and promotes induction of M2-like macrophage polarization in human HNSCC.

Imaging findings of primary immunoglobulin G4-related cervical lymphadenopathy.

PURPOSE: The purpose of the present study was to assess imaging findings of primary immunoglobulin G4 (IgG4)-related cervical lymphadenopathy. METHODS: Five consecutive patients with clinically, serologically, and histopathologically confirmed primary IgG4-related cervical lymphadenopathy without any other organ involvement were included. All patients underwent contrast-enhanced computed tomography (CT), and four underwent 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT. We retrospectively reviewed the images and assessed the number, size, location, central necrosis, perinodal infiltration, penetrating vessels, and maximum standardized uptake values (SUVmax) of the enlarged cervical nodes. RESULTS: Thirteen enlarged cervical nodes measuring larger than 10 mm in minimum diameter were identified. The maximum and minimum diameter of enlarged nodes ranged from 1.2 to 3.2 cm (median, 1.8 cm) and from 1.0 to 1.9 cm (median, 1.2 cm), respectively. Lymphadenopathy was unilateral in all patients, and eight enlarged nodes were located at level IB (62%), one at level II (8%), three at level IV (23%), and one at level V (8%). Central necrosis was not seen in any nodes. Perinodal infiltration was seen in only one node (8%), and penetrating vessels were seen in seven nodes (54%). The median SUVmax of nine nodes was 4.45 (range, 2.08-12.44). CONCLUSION: Eight enlarged nodes (62%) were located in the submandibular region. Central necrosis was not observed in any nodes and perinodal infiltration was observed in one node (8%).

[Eight Cases of Small Cell Neuroendocrine Carcinoma of the Head and Neck].

Small cell neuroendocrine carcinoma of the head and neck is a rarely occurring poorly differentiated and high-grade malignant neoplasm characterized by highly active proliferation of neuroendocrine tumor cells. There are no established therapies for this disease. To clarify the clinical course and develop effective treatment(s) for the carcinoma, we reviewed the data of 8 patients of small cell neuroendocrine carcinoma of the head and neck treated by us between 2006 and 2014 at the Department of Otolaryngology, Gifu University School of Medicine and our affiliated hospitals. The patients consisted of 3 men and 5 women, ranging in age from 38 to 84 years old (mean : 60.9 years). The tumor arose from the nasal cavity or the paranasal sinuses in 3 cases, from the parotid grand in 2 cases, from the oropharynx in 2 cases, and from the hypopharynx in 1 case. The tumor that arose from the hypopharynx was a combined small-cell carcinoma with squamous cell carcinomas, and the one that arose from the oropharynx had already metastasized to the brain. Most of the patients were treated by chemotherapy and radiotherapy based on the treatment employed for small cell carcinoma of the lung. Only the patient in whom the tumor arose from a paranasal sinus was treated by surgery despite the definitive diagnosis of small cell carcinoma. We selected CPT-11 and a platinum agent for 4 patients, and VP-16 and a platinum agent for 3 patients as the first-line chemotherapy. Although two patients showed carcinoma-free survival, one died of recurrence of the regional lymph node metastases and five died of distant metastases despite the absence of locoregional recurrence. The 5-year survival rate was a dismal 25%, suggesting that we need to establish effective treatment(s) for the control of distant metastases in cases of the small cell neuroendocrine carcinoma of the head and neck.

Perfusion imaging of parotid gland tumours: usefulness of arterial spin labeling for differentiating Warthin's tumours.

OBJECTIVE: To assess prospectively the efficacy of arterial spin labelling (ASL) against conventional and diffusion-weighted (DW) MR imaging for differentiating parotid gland tumours. METHODS: We included 10 pleomorphic adenomas, 12 Warthin's tumours, and nine malignant tumours of the parotid glands. Only tumours larger than 10 mm were included in this study. All parotid gland tumours underwent T1-weighted, T2-weighted, DW, and ASL imaging. Tumour-to-parotid gland signal intensity ratios (SIRs) and apparent diffusion coefficients (ADCs) of solid components were correlated with these pathologies. RESULTS: SIRs on T2-weighted images and ADCs were higher in pleomorphic adenomas than in Warthin's tumours (p < .01) and malignant tumours (p < .01). SIRs on ASL were higher in Warthin's tumours than in pleomorphic adenomas (p < .01) and malignant tumours (p < .05). Az value of SIRs on ASL for differentiating Warthin's tumours from the other pathologies was 0.982. The sensitivity, specificity, and accuracy of SIRs on ASL for the diagnosis of Warthin's tumours at an optimal SIR threshold of over 8.70 were 91.7%, 94.7%, and 93.5%, respectively. CONCLUSIONS: ASL with SIR measurements could non-invasively evaluate tumour blood flow of parotid gland tumours and differentiate Warthin's tumours from pleomorphic adenomas and malignant tumours. KEY POINTS: • ASL non-invasively evaluates tumour blood flow of parotid gland tumours • ASL differentiates Warthin's tumours from pleomorphic adenomas and malignant tumours • ASL cannot differentiate between pleomorphic adenomas and malignant tumours.

Salivary gland tumors of the parotid gland: CT and MR imaging findings with emphasis on intratumoral cystic components.

INTRODUCTION: The purpose of this study was to assess computed tomography (CT) and magnetic resonance (MR) imaging findings of salivary gland tumors of the parotid gland with emphasis on intratumoral cystic components. METHODS: Seventy-two histopathologically confirmed salivary gland tumors of the parotid gland (44 benign and 28 malignant), which underwent both CT and MR imaging including contrast-enhanced study, were included in this study. We retrospectively reviewed images for the presence, number, occupying rate, margin characteristics, distribution, and predominant MR signal intensity of intratumoral cystic components. RESULTS: The prevalence of cystic components was greater in malignant than benign tumors (79 vs. 50%, p < 0.05). The number and occupying rate were similar between benign and malignant tumors. The irregular margins were more frequent in malignant than benign tumors (73 vs. 27%, p < 0.01). The frequency of eccentric location was greater in benign than malignant tumors (91 vs. 55%, p < 0.01), whereas the frequency of centric location was greater in malignant than benign tumors (32 vs. 0%, p < 0.01). On T1-weighted images, the frequency of hyperintensity was greater in benign than malignant tumors (50 vs. 9%, p < 0.01), whereas that of isointensity was greater in malignant than benign tumors (50 vs. 0%, p < 0.01). Multiple logistic regression analysis showed that the absence of irregular margins of cystic components only was significantly correlated with the presence of benign salivary gland tumors (p < 0.01). CONCLUSION: Imaging features of intratumoral cystic components may help to differentiate benign from malignant tumors of the parotid salivary gland.

[A case of idiopathic neck bleeding from a parathyroid cyst].

Bleeding from parathyroid cysts is rare. The retropharyngeal space has a very soft structure and if bleeding spreads to this space, airway obstruction can easily occur. We report on a 50-year-old female case with idiopathic neck bleeding from a left parathyroid cyst without any episode of injury. The patient complained of neck swelling after exercise and went to a nearby hospital. At the hospital, the doctor thought this swelling was caused by retropharyngeal bleeding from a tumor behind the left thyroid gland. Embolization of the left thyroid artery was performed. However, the next day, airway obstruction.was occurred and she was brought to our hospital. An emergency operation was performed to open the left neck swelling region. The operation findings and pathological examination showed that the bleeding was caused by a parathyroid cyst and airway obstruction had occurred because of retropharyngeal edema. In this case, the bleeding may have been caused by torsion of the neck when the patient exercised. The retropharyngeal edema probably resulted from the delay of delivery of the lymphatic and venous return and the arterial embolization. 1 year after the operation, the patient is very well and there has been no recurrence.

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.

Evidence for vestibular dysfunction in orthostatic hypotension.

There is little definitive evidence of the clinical significance of the vestibular-cardiovascular reflex in humans, despite the fact that the vestibular system is known to contribute to cardiovascular control in animals. The present study involved 248 dizzy patients (127 male patients and 121 female patients) aged 65 years and younger. We classified all participants into three groups based on their vestibular evoked myogenic potential (VEMP) responses; absent VEMP, asymmetry VEMP and normal VEMP. To investigate the effect of the otolith disorder, which was estimated by the VEMP, on the orthostatic blood pressure responses, the subjects' systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate were monitored during the orthostatic test after they actively stood up. The male patients in the absent VEMP group had a significant drop in their DBP at 1 min after active standing up (P < 0.05) without any change in their SBP. Conversely, male patients in the asymmetry VEMP and normal VEMP groups showed a significant increase in the SBP at 1 min after active standing up (P < 0.05). Female patients in the absent VEMP group did not show any significant drop in their blood pressure after standing up (P > 0.05). In the entire group of participants, a total of 19.6% of the patients in the absent VEMP group fulfilled the criteria for orthostatic hypotension (OH), which was significantly > the 8.6% of patients in the normal VEMP group and the 7.2% in the asymmetry VEMP group (P < 0.05). Our results suggest that vestibular disorders due to the dysfunction of otolith organs provoke OH.

Effect of lyophilized powder made from enzymolyzed honeybee larvae on tinnitus-related symptoms, hearing levels, and hypothalamus-pituitary-adrenal axis-related hormones.

OBJECTIVES: Tinnitus interferes with sleep and concentration which is associated with depression; however, no drug has been effective in treating tinnitus. Our purpose is to evaluate our hypothesis that the treatment with lyophilized powder of enzymolyzed honeybee larvae as a complementary medicine may provide a therapeutic effect on tinnitus-related symptoms. DESIGN: Sixty tinnitus sufferers participated in a randomized double-blind placebo-controlled trial using the lyophilized powder of enzymolyzed honeybee larvae or a placebo. The Tinnitus Handicap Inventory, a visual analog scale to rate the severity of tinnitus, hearing levels, and hypothalamus-pituitary-adrenal axis-related hormones drawn early in the morning were measured upon entry into the study and after 12 wk of follow-up. RESULTS: The lyophilized powder of enzymolyzed honeybee larvae was not superior to placebo with regard to the total score on the Tinnitus Handicap Inventory and the visual analog scale. However, subjects in the honeybee larvae group showed significant improvements in some items about depression associated with tinnitus, whereas subjects in the placebo group showed no improvement in any items. The honeybee larvae group showed significant improvements in the hearing levels at 2 and 4 kHz in the audiogram of the better ear. The intervention of the lyophilized powder of enzymolyzed honeybee larvae was associated with lower serum cortisol levels, serum prolactin levels, and cortisol/dehydroepiandrosterone sulfate ratios. The ratios in the placebo group significantly were increased. CONCLUSIONS: Our results suggest that the lyophilized powder of enzymolyzed honeybee larvae represents an effective complementary medicine to alleviate depression associated with tinnitus by regulating the activity of the hypothalamus-pituitary-adrenal axis.

[Surgery in the lateral area of the cervicothoracic border].

Surgery is not usually indicated for the involvement of cervical lymph node metastasis to the subclavian vein. Although surgery is indicated for the involvement of cervical lymph node metastasis to the venous angle, the usual visual field associated with cervical lymph node dissection cannot sufficiently visualize the subclavian vein, and the possibility exists of causing great vessel injury when involved lymph nodes are large and their mobility is restricted. In such cases, surgical excision may be avoided based on the expectation that ligating or cutting the internal jugular vein will be difficult. We examined 10 patients who underwent surgery for the adhesion or invasion of the primary tumor or involved lymph nodes to the venous angle or subclavian vein. The clavicle was removed or displaced to secure the visual field. The sternoclavicular joint was conserved and the clavicle, separated from the first rib, was lifted in 4 patients, while the medial two thirds of the clavicle was removed in 6 patients. Involved lymph nodes could be securely dissected without causing great vessel injury. A chylous leak occurred in one patient undergoing the procedure on the left side.

The relevance of hypothalamus-pituitary-adrenocortical axis-related hormones to the cochlear symptoms in Ménière's disease.

OBJECTIVE: To investigate the association of the HPA (hypothalamus-pituitary-adrenocortical) axis-related hormones with the progression of cochlear symptoms in patients with Ménière's disease. DESIGN: Clinical assessments (Tinnitus Handicap Inventory: THI, visual analog scale to rate the degree of the tinnitus: VAS, hearing levels in pure-tone audiometry) were conducted upon entry into the study (baseline) and at 12 weeks follow-up (week 12). Blood sampling to measure HPA axis-related hormones took place between 9:00 and 10:00 a.m. at baseline and at 12 weeks follow-up. STUDY SAMPLES: This study consisted of 20 unilateral Ménière's disease patients and 21 patients with other diseases with unilateral sensorineural hearing loss and tinnitus. RESULTS: A significant deterioration of the hearing level at high frequency range, especially at 2 kHz, was found during the 12 weeks follow-up in the Ménière's disease group (p < 0.05). The average hearing levels significantly correlated with the serum cortisol level at baseline and week 12 in the Ménière's disease group, especially regarding the high frequency levels (p < 0.01). CONCLUSIONS: Our results suggest that the cortisol levels influence the endolymphatic homeostasis resulting in a deterioration of hearing at high frequency with upstaging of Ménière's disease.

[Superior semicircular canal dehiscence syndrome treated by calcium phosphate cement canal plugging: a case report].

Superior semicircular canal dehiscence (SCD) syndrome exhibits pressure- and/or sound-induced oscillopsia and vertigo due to an absence of bone overlaying the superior semicircular canal. A 33-year-old man with right-ear SCD reported dizziness in a noisy hall three years earlier followed by dizziness during flatulence, straining or coughing, and right-ear autophony. Audiography showed a right-ear low-frequency air-bone gap, with positive Tullio phenomenon and a Valsalva maneuver against closed glottis causing torsional-vertical nystagmus. Temporal-bone computed tomography (CT) led to a diagnosis of right-ear SCD syndrome. Surgical dehiscence plugging with calcium phosphate cement via the middle fossa resolved vestibular and cochlear symptoms in the more than two years since.

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.

"Flow-void" sign at MR imaging: a rare finding of extracranial head and neck schwannomas.

The authors present two cases of extracranial head and neck schwannomas that exhibited the "flow-void" sign at MR imaging. In the described cases, MR images showed intratumoral signal voids, which corresponded to dilated vessels. Dynamic contrast-enhanced CT also demonstrated dilated vessels within the tumors on the arterial phase and tumor parenchymal enhancement on the delayed phase. Histopathologic examinations of excised specimens revealed thin-walled, dilated abnormal vessels with or without hyaline degeneration. Schwannoma should be considered when MR images demonstrate the "flow-void" sign in extracranial head and neck tumors.

The association of the plasma vasopressin level during attacks with a prognosis of Meniere's disease.

An elevation of the plasma arginine vasopressin (AVP) level has frequently been observed in Meniere's disease patients. However, little is known regarding the mechanism behind this elevation. The plasma AVP levels in acute phase were determined in 21 Meniere's disease patients and 16 patients with other types of vertigo. The plasma AVP levels of Meniere's disease patients in the acute phase were significantly higher than in those of other vertigo patients (p < 0.01). In Meniere's disease patients with abnormally high levels of AVP (more than 3.5 pg/ml) in the acute phase, 36% of patients were resistant to conservative treatments for frequent vertigo attacks for the follow-up period of at least 2years. A significant correlation was observed between the plasma AVP in the acute phase and the highest hearing threshold level at a frequency of 1kHz for the follow-up period of at least 1 year (r=0.45, p < 0.05). These results suggest that the elevation in plasma AVP level in the acute phase is associated with the prognosis of Meniere's disease.

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.

[Studies on the largest Lyapunov exponents of the standing posture in patients with unilateral vestibular dysfunction].

UNLABELLED: In the present study, we investigated the body sway in patients with unilateral vestibular dysfunction by the largest Lyapunov exponents using a chaotic time series analysis. The largest Lyapunov exponent is regarded as a parameter indexing an orbital instability. MATERIALS AND METHODS: Subjects consisted of 55 normal healthy subjects, 11 patients diagnosed as having vestibular neuritis (VN), 6 patients diagnosed as having sudden deafness (SD) with vertigo, 23 patients diagnosed as having Meniere disease (MD), 11 patients diagnosed as having benign paroxysmal positional vertigo (BPPV) and 14 patients diagnosed as having other vestibular disorders. Using a stabilometer, the sway of the body center of gravity in an upright standing position was recorded with eyes open and closed for 60 seconds under each condition. From the time series data obtained, the largest Lyapunov exponents were calculated using a chaos analysis program. RESULTS: In normal healthy subjects and patients with unilateral vestibular dysfunction, the largest Lyapunov exponents on right-left sway were larger than those on forward-backward sway with eyes open and closed. The largest Lyapunov exponents in patients with unilateral vestibular dysfunction on forward-backward sway with eyes closed were significantly larger than those in normal healthy subjects. A few patients with the instability of standing posture judged from conventional analysis (area of sway, locus length per time) showed higher values of the LLE. We investigated the variation of the values of the largest Lyapunov exponents in patients with unilateral vestibular dysfunction at each stage during recovery from their vestibular damage. The largest Lyapunov exponents at the early stage with stable standing posture were significantly higher than those at the late stable stage with stable standing posture. Some patients at the very early stage had lower values of the largest Lyapunov exponents. CONCLUSION: We speculate that the orbital instability indicated by the values of the largest Lyapunov exponents has a different significance from instability of standing posture indicated by a conventional analysis. We propose that the largest Lyapunov exponents may be an useful subsidiary measure to evaluate postural stability and its change due to vestibular dysfunction.

Involvement of platelet-derived growth factor receptor-beta in maintenance of mesenchyme and sensory epithelium of the neonatal mouse inner ear.

Platelet-derived growth factor receptor (PDGFR) signaling has been demonstrated to play a pivotal role in early embryonic development. Although the expression of PDGF in the inner ear has been studied by RT-PCR, how PDGFR is involved there remains largely unclear. In the current study, we used the antagonistic anti-PDGFR-beta antibody, APB5, to investigate the role of PDGFR-beta in the neonatal mouse inner ear. PDGFR-beta was detected immunohistochemically in the mesenchymal tissue adjacent to the sensory epithelium of the inner ear, and a ligand for PDGFR-beta was detected around the sensory epithelium. To determine whether this expression plays a functional role, we injected APB5 into neonates to block the function of PDGFR-beta. Mesenchymal tissue defects and abnormal capillaries with irregular shapes, especially in the cochlear lateral wall, were detected in APB5-treated mice. The results of a TUNEL assay revealed that not only the adjacent mesenchymal cells but also the sensory epithelial cells underwent cell death. These results indicate that PDGFR-beta signals are required for the survival of the capillary and mesenchymal cells in the neonatal mouse inner ear and also indirectly implicate these signals in the survival of the sensory epithelium.

The orthostatic dysregulation of blood pressure in dizzy patients.

OBJECTIVES: A number of animal studies have confirmed that the otolith organs may contribute to the maintenance of blood pressure during positional change; however, the contribution of such organs remains to be elucidated in humans. METHODS: This study investigated whether acute dizzy patients (n = 11) with an abnormal deviation of the subjective visual vertical (SVV) show an abnormality in the orthostatic regulation of blood pressure in comparison to acute dizzy patients with a normal deviation of the SVV (n = 11) and control subjects (n = 11). RESULTS: The average change in the systolic blood pressure (SBP) at 1 minute after active standing in comparison to that at baseline in dizzy patients with an abnormal deviation of the SVV was -6.8 +/- 3.0 mmHg. The change was significantly lower than that in the control subjects (2.1 +/- 2.6 mmHg, p < 0.05), while the change in dizzy patients with a normal deviation of the SVV (2.6 +/- 2.2 mmHg) was not significantly different from that in the control subjects (p > 0.05). Active standing significantly increased the heart rate (HR) in all participants (p < 0.01) and there was no significant difference in the change of the HR among the 3 groups (p > 0.05). CONCLUSIONS: These results suggest that dizzy patients in the acute phase of recovery from vestibular dysfunction have an orthostatic dysregulation of the blood pressure, thus resulting in such patients suffering from orthostatic intolerance.