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Objective This study aimed to verify cutoff values for G width (the width of bimodal peaks for the waveform obtained when measuring conductance at 2000 Hz) in Japanese individuals diagnosed with Meniere’s disease (MD) using multifrequency tympanometry (MFT) and to determine the relationship between the G width and ability to hear low-pitched sounds using measurements over time. Methods The study included 51 patients with clinically diagnosed MD, who had not undergone endolymphatic sac surgery, but had no other known ear disease (57 ears in patients aged 22–80 years were affected, and 45 ears in patients aged 18–83 years were unaffected; mean age: 53.3 ± 16.9 years). We also enlisted 80 healthy controls with no prior history of ear disease (160 ears, aged 22–76 years, mean age: 40.8 ± 15.7 years). MFT was used to measure the bimodal peak width of the waveform obtained when measuring conductance at resonance frequency of 2000 Hz. For patients who had G width measured several times over multiple outpatient visits, we used initial test data to analyze cutoff values. In nine cases with four or more measurements over time, we evaluated a possible correlation between G width and the sum of the hearing threshold for three low-pitched frequencies (125 Hz, 250 Hz, and 500 Hz). We used Student’s t-test to determine significance. Results The both ears in the MD patients had a G width wider than the distribution in the control group. There was a significant difference between G width in the control group and in affected ears with MD (p = 0.00026) and there was also a significant difference between G width in the control group and in unaffected ears of MD patients (p = 0.0056). The cutoff value set with a specificity of 95% was 200 daPa, with a sensitivity of 35.1% and specificity of 95.6%. The cutoff value set with a sensitivity of 50% was 140 daPa, with sensitivity of 50.9% and specificity of 78.8%. There was no significant difference between resonance frequency of ears in the control group and ears with MD (p = 0.41). In nine cases with four or more measurements over time, a case showed a statistically significant positive correlation between the G width and hearing ability threshold for low-pitched sounds (125 Hz, 250 Hz, and 500 Hz) (p = 0.03), while an another case showed a tendency toward a positive correlation, which was not statistically significant (p = 0.08). Further, there were cases that did not show significant differences in the present study, but might have shown a negative correlation if the number of measurements had been increased. Conclusion Measurement of G width using MFT may have accuracy as the traditional endolymphatic hydrops test. MFT is non-invasive, causes little discomfort for patients, requires little time to perform, and can be performed by paramedics. MFT was shown to be useful in screening for MD and it is effective in diagnosing MD to measure the change over time of G width using MFT.

Objectives: Small cell carcinomas in extrapulmonary sites (ESmCCs) are very rare. ESmCCs originating in the head and neck account for approximately 10% of all ESmCCs, and there are few reports about this disease. ESmCCs have an aggressive natural history characterized by widespread metastasis. The aim of this study was to investigate the characteristics and outcomes of patients with ESmCCs of the head and neck. Methods: The outcomes of 21 patients with ESmCCs of the head and neck treated between January 2001 and December 2015 at the authors’ hospital and associated facilities were reviewed. Results: There were 18 men and 3 women, and the median age was 74 years (range, 53-91 years). The tumor site was the larynx in 6 patients; the paranasal sinus in 5; the hypopharynx in 3; the oropharynx in 2; the nasopharynx in 2; and the oral cavity, salivary gland, and primary unknown in 1 patient each. The extent of the disease was staged as follows: stage I or II, 3 cases; stage III, 4 cases; stage IVA, 9 cases; stage IVB, 1 case; and stage IVC, 4 cases. The median observation time was 17 months (range, 1-103 months). Four patients (19%) had distant metastasis at initial treatment, and 13 patients (62%) developed distant metastasis within 3 years. Treatments were administered, including radical surgery (9 patients), radiation therapy (5 patients), chemoradiotherapy (7 patients), and chemotherapy (6 patients). The 1- and 3-year overall survival rates of patients were 56% and 37%, respectively. More than half of the patients died of distant metastasis. Conclusions: ESmCCs of the head and neck have a poor prognosis, similar to those of carcinomas in many other sites. Control of distant metastasis would contribute to improving the prognosis of ESmCCs of the head and neck. Further studies are required for better understanding these disease entities and their response to treatment modalities.

OBJECTIVES: To evaluate the effects of chronic kidney disease (CKD) and hemodialysis (HD) on the inner ear using the G width (the width between the bimodal peaks of the conductance (G) tympanogram at 2,000 Hz), which reflects the inner ear pressure and/or the existence of endolymphatic hydrops. MATERIALS AND METHODS: We selected five patients (10 ears) from the patients with CKD who were hospitalized for creation of arteriovenous fistula prior to initiation of HD (non-HD group), and we selected seven patients (14 ears) from the patients with CKD who were undergoing HD (the HD group). As a control group, we selected 80 healthy individuals (160 ears); these were mainly the medical staff of the hospital. We measured the G width of the control group and that of patients with CKD using multifrequency tympanometry. RESULTS: The mean G widths of the HD (measured just before an HD session), non-HD, and control groups were 210.7, 128.4, and 97.0 daPa, respectively. The G width of the HD group was significantly greater than that of the control and non-HD groups (p

We herein report a case of posterior semicircular canal dehiscence (SCD) syndrome who had been audiologically followed up for eight years. The patient originally had sensorineural hearing loss. The audiogram had gradually transformed to pure conductive hearing loss. The posterior SCD was identified in CT scan. The reported case showed the possibility to distinguish the mechanism at play underlying the typical conductive hearing loss in SCD patients by tracing the transition of the hearing loss pattern. This information is of much help to predict the hearing outcomes if surgical intervention were chosen for the treatment.

Objective:The aim of this study was to determine whether allergic rhinitis can induce structural changes in the synapse formation in the hippocampus of BALB/c mice immunocytochemically.Methods:Allergic rhinitis was induced in mice by two intra-peritoneal injections of ovalbumin administered with a one-week interval. After two weeks, the sensitised mice were challenged with an intra-nasal injection of ovalbumin for two weeks. To analyse the hippocampal synaptic structures, sections were immunostained with antibodies against glutamic acid decarboxylase 65 and glutamic acid decarboxylase 67 (for γ-aminobutyric acid-ergic terminals), synaptophysin (for glutamatergic and γ-aminobutyric acid-ergic terminals) and spinophilin (for dendritic spines). The number of nasal rubbing movements was significantly greater in the allergic rhinitis mice than in the control mice. However, the expression patterns of the four above-mentioned synaptic markers in the hippocampus showed no detectable difference between the allergic rhinitis and control mice.Results and Conclusion:These data indicate that the synaptic structure in the hippocampus might remain unaltered in allergic rhinitis patients.

Bisphenol A (BPA) is an environmental endocrine disrupter (EED). Previous studies by our group showed that pre- and postnatal administration of low-level BPA induced depression-like behavior in rats. In this study, we evaluated the effects of prenatal BPA on behavioral responses to a predator odor by using a novel cross-form apparatus consisting of 4 plastic chambers. On the first day, nothing was placed into the chambers (Session 1). On the second day, a predator odor (fox odor) was located in separate chambers at 2 opposite corners of the apparatus (Session 2). Pregnant Wistar rats were exposed to low-dose BPA (less than the reference dose) during the 7 days just before birth, and the offspring of the treated rats were evaluated as adults. The locomotor activity and avoidance response of each rat on both test days were compared. The control and BPA groups showed reduced locomotor activity in the presence of the predator odor, but the odor-avoidance response was significant only in the BPA rats. The BPA-exposed rats were obviously sensitive to the predator odor. These results suggest that prenatal BPA exposure has an amplifying effect on avoidance responses to predator odor stress.

Objective Among many immunotherapeutic approaches, oral immunotherapy (OIT) is thought to be an effective route for desensitization against a variety of allergens. However, there is little evidence that OIT is effective for airway allergic diseases such as pollen allergy. Thus, in the present study, we assessed the safety, efficacy and immune response of OIT using the Cry j1–galactomannan conjugate for Japanese cedar pollen allergy. Methods An open trial was conducted over a period of 4 months. The OIT group comprised of 23 subjects. Treatment was initiated 1 month before the estimated pollen season and continued for 1 month. The control group (the pharmacological treatment group without OIT) comprised of 11 subjects. The symptoms and medication score, levels of allergen-specific serum antibodies, cellular components of lymphocytes and cytokine production from peripheral blood mononuclear cells (PBMCs) were evaluated throughout the pollen season. Results The participants receiving OIT treatment showed significant improvements in total symptom scores and symptom–medication scores during the pollen season compared with the control group. The levels of allergen-specific serum IgG4 and IL-10 production in PBMCs were significantly increased in the OIT group compared with that in the control group. Importantly, no severe adverse effects were observed in the participants receiving OIT treatment. Conclusion Short-term OIT using the Cry j1–galactomannan conjugate is effective, relatively safe and induces tolerant immune responses such as increased allergen-specific serum IgG4 and IL-10 production in PBMCs. These results suggest that OIT using allergen–galactomannan conjugates may provide a rapid, effective, and safe immunotherapy regimen for cedar pollen allergy.

Objective The aim of this study was to determine whether aryl hydrocarbon receptor (AhR) and AhR nuclear translocators (ARNTs) are expressed in human adenoid tissue. Methods Paraffin-embedded human adenoid tissue specimens were obtained from eight children with adenoid hypertrophy. Sections were stained immunohistochemically with specific polyclonal antibodies to evaluate the expression pattern of AhR, ARNT1 and ARNT2 were evaluated. Results AhR-immunoreactivity was ubiquitously seen in human adenoid tissue such as the epithelium, subepithelial layer, germinal center, mantle zone and interfollicular area. ARNT1 was also widely expressed in the same regions as AhR. Although ARNT2 was expressed in the human adenoid, the expression level was significantly lower than that of ARNT1. Conclusion These data suggest that the relationship between AhR and ARNTs may play an important role in the local immune response in adenoid and that ARNT1 may be more important than ARNT2 especially in adenoid tissue.

Vertigo is one of most common complaints among emergency department patients. It is most important to check the nystagmus when emergency doctors see patients with vertigo. However, there are many cases where we cannot make any diagnosis in the otorhinolaryngological clinic the day following a patient's vertigo attack because the nystagmus has already vanished. In order to resolve this medical problem, we developed a novel method that could record nystagmus anywhere and anytime. This system is very easy for any doctor to record and save the nystagmus in the dark. As a result, we have been able to make a true diagnosis even if patients had nystagmus transiently. We expect that this recording system may lead in the future to a more fulfilling medical practice in the case of patients with vertigo.

Objective:Our aim was to determine if stapes surgery is useful for treating inflammatory ear diseases.Materials and methods:Thirteen patients underwent single-stage or staged surgery for stapes fixation due to tympanosclerosis alone or with cholesteatoma. Operative criteria were: no tympanic membrane retraction, perforation or adhesion; middle-ear cavity with aeration >1 year; a fixed stapes. Computed tomography was used to analyse the relation between operative success and pre-operative pneumatisation.Results:Success rate at six months was 75 per cent. Hearing results were stable with little deterioration and no complications. Patients with poor pneumatisation had good results (with improved air–bone gap) only after staged surgery. Well-aerated ears heard better even with single-stage surgery.Conclusions:Pre-operative computed tomography and intra-operative findings are necessary to determine the pneumatisation status of tympanic mastoid cavities. If criteria approved, poorly pneumatised patients underwent staged surgery. Stapedectomy achieved good hearing results for inflammatory middle-ear disease with stapes fixation.

Perinatal exposure to bisphenol A (BPA, 0.1 and 1 ppm in drinking water applied to mother rats for 6 weeks) has been shown to impair the sexual differentiation in exploratory behavior, but the exact critical period of this disrupting effect is still unknown. In this study, we examined the effects of prenatal exposure to BPA (0.1 ppm in drinking water applied to dams during the final week of pregnant) on emotional and learning behaviors in addition to exploratory behavior. Estimated daily intake was 15 microg/kg/day, below the reference dose (RfD) in the United States and the daily tolerable intake (TDI) in Japan (50 microg/kg/day). The rats were successively tested in open-field test, elevated plus maze test, passive avoidance test and forced swimming test during development from 6 to 9 weeks of juvenile period. Prenatal exposure to BPA mainly affected male rats and abolished sex differences in rearing behavior in the open-field test and struggling behavior in the forced swimming test. BPA increased the immobility of male rats in the forced swimming test. The avoidance learning and behaviors in the elevated plus maze were not affected. The present study demonstrates that male rats at the final week of prenatal period are sensitive to BPA, which impairs sexual differentiation in rearing and struggling behavior and facilitate depression-like behavior.

The central nervous system is highly sensitive to endogenous and exogenous chemicals. Catecholamines, norepinephrine (NE) and dopamine (DA), regulate many different brain functions including learning and memory, emotion, stress responses and homeostatic control of physiological systems. NE and DA are differently involved in reward-related neuronal activity and other task-related neuron activities in the prefrontal cortex, amygdala and the lateral hypothalamic area. During inflammatory and non-inflammatory stress conditions, NE levels are locally regulated at terminal levels by proinflammatory cytokines such as interleukin-1β in which prostanoid and nitric oxide are involved. NE system has been shown to express estrogen receptors and is highly sensitive to endocrine disrupters such as bisphenol A during sexual differentiation. These findings suggest that higher brain functions such as learning and emotional control are under the influence of chemical impacts via catecholamines, cytokines and environmental chemicals.

There is an endocrinological concern that environmental endocrine disrupters (EEDs) may influence sexual differentiation. Bisphenol A (BPA), one of EEDs, is released from polycarbonate plastics, and has been detected in the human umbilical cord. In this study, we examined the effect of BPA on the sexual differentiation of open-field behavior and the sexually dimorphic nuclei in the brain in the offspring of rats exposed to BPA during the fetal and suckling periods at a dosage below the human tolerable daily intake (TDI) level. In the control group, females were more active in the open field and had a larger locus coeruleus (LC) volume than males. BPA abolished and inverted the sex differences of the open-field behavior and the LC volume, respectively, without affecting the reproductive system. We also compared the effects of estrogenic compounds, diethylstilbestrol (DES) and resveratrol (RVT), to that of BPA because of their structural similarities. DES affected the open-field behavior, LC volume and reproductive system, while RVT affected the LC volume and the reproductive system. These results suggest that the brain is highly sensitive to BPA at a dosage below TDI and that the disrupting effects of BPA on sexual differentiation may vary from those of RVT and DES.

Several effects of neonatal handling on brain and behavior have been reported. We investigated the effects of neonatal handling on behaviors that have been shown to be sexually dimorphic in rats using an open-field test. "Gender differences" were observed in locomotor activity, exploratory behavior and grooming in the handled group. However, clear gender differences in these behaviors were not observed in the non-handled group. Our findings show that brief daily handling sessions (~ 1 min) in the first 2 weeks of postnatal life increased locomotor activity and exploratory behavior, and that these effects were more pronounced in females. Moreover, many rats in the non-handling group exhibited an increase in defecation relative to the handling group during the 10-min observation period. This suggests that the non-handling group experienced more stress in response to the novel open-field arena, and that this resulted in the absence of gender differences. Notably, this anxiety-related response was attenuated by neonatal handling. Our study underscores the impact of brief neonatal handling on sexually dimorphic behaviors, and indicates that caution should be exercised in controlling for the effects of handling between experimental groups, particularly in neurotoxicological studies that evaluate gender differences.

This study tested the effect of exposure to bisphenol A (BPA) early in life on the sexual differentiation in the brain and behavior in Wistar rats. We administered BPA only to mother rats during pregnancy and lactation at a dosage of approximately 1.5 mg/kg per day far less than the no-observed-adverse-effect level (NOAEL; 50 mg/kg per day). Control female offspring showed a higher activity, a lower avoidance memory, and larger locus coeruleus than the male controls, while the BPA-exposed group did not show any sexual dimorphism. BPA did not affect the reproductive organs or sex hormones. Our results suggest that the current methods to determine the NOAEL of artificial industrial chemicals may not be sufficient to detect a disruption of the sexual differentiation in the brain.

The distribution of tributyltin (TBT) and its metabolites, dibutyltin (DBT) and monobutyltin (MBT), was examined in the liver, brain and fat tissues in a two-generation reproductive toxicity study of tributyltin chloride (TBTCl) in rats using dietary supplementation at concentrations of 5, 25 and 125 ppm. In the liver, irrespective of TBTCl dietary concentration, gender or generation, the highest concentration of metabolite was consistently MBT, followed by DBT, and then TBT. In contrast, TBT was consistently present at the highest concentration in the brain, nearly always followed by DBT and MBT. In fat tissues, the concentrations of the three butyltin compounds showed similar relationships to those observed in the brain, although the concentrations were much lower. In the liver, the concentration of TBT was higher in females, and those of DBT and MBT were higher in males. Factorial ANOVA also suggested the effect of gender on the concentrations of the three butyltin compounds in the liver. The results of this study suggest tissue-dependent distribution of TBT, DBT and MBT and gender-dependent distribution of the three metabolites in the liver of rats.

A two-generation reproductive toxicity study of the effects of tributyltin chloride (TBTCl) was conducted in female rats using dietary concentrations of 5, 25, and 125 ppm TBTCl. Reproductive outcomes of dams (number and body weight of pups and the percentage of live pups) and the growth of female pups (the day of eye opening and body weight gain) were significantly decreased in the 125 ppm TBTCl group. A delay in vaginal opening and impaired estrous cyclicity were also observed in the 125 ppm TBTCl group. However, an increase in anogenital distance was found in all TBTCl groups on postnatal d 1. A dose-effect relationship was observed in TBTCl-induced changes in anogenital distance. These results indicate that the whole-life exposure to TBTCl affects the sexual development and reproductive function of female rats. In addition, the TBTCl-induced increase in anogenital distance seems to suggest it may exert a masculinizing effect on female neonates. However, the concentrations of TBTCl used in this study are not environmentally relevant.

Clinical problems related to eating, reproduction, emotion, and immunity have been demonstrated to be influenced by environmental changes including temperature and meteorological phenomena. The hypothalamus is well known to be involved in homeostatic control of body temperature, ingestion, reproduction, and biodefense to allow survival for both individuals and species. The hypothalamus contains specific neurons responding to changes in temperature, glucose, and sex hormones. Warm-sensitive neurons and glucoreceptor neurons have been shown to be excited by pyrogen and estrogen. Bidirectional facilitative control of glucose utility and estrogen receptors is found in the hypothalamus and this modulates thermoregulation. These findings suggest that the different homeostatic mechanisms link together in the hypothalamus. Environmental problems, such as global warming and environmental endocrine disrupters, may disturb our adaptive function in which the hypothalamus plays an essential role.

Shuji Aou1, Masaharu Mizuno1, Yuko Matsunaga2, Kazuhiko Kubo2, Xue-Liang Li2 and Akikazu Hatanaka3 1Department of Brain Science and Engineering, Kyushu Institute of Technology, Kitakyushu 808-0196, Japan, 2Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan and 3Department of Applied Biological Chemistry, Yamaguchi University, Yamaguchi 753-8511, Japan

This paper describes a new excellent video detector IC for color television receivers with phase lock loop ( PLL ) operating at the intermediate frequency of 58.75 MHz generator. The IC includes IF amplifier, AGC circuit, VCO, video processing circuit, video detector, automatic phase control ( APC ) circuit, lock-unlock condition detector and AFC circuit. Using this system, better performance than a traditional diode detector or a quasi synchronous detector has been achieved with no increase of manufacturing cost.

The thermodynamic quantities associated with the formation of the complexes of tetraphosphate ion with Mg(II), Ca(II) and Sr(II)are determined and compared with those obtained brevious1y fer pyrophosphate and triphosphate complexes of these 41kaline-eart-b m-et-41-ions 1) The thermodynamic stability constants of the complexes of the types ML, MHL and MsL (where M, H and L are a metal ion, hydrogen ion and tetraphosphate ion, respectively)are evaluated from pH titration data obtained at various ionic strengths at 25C.2) The enthalpy changes associated with the fermation of the 1: 1 complexes (ML) at.25C are determinedmined by direct calorimetric method. From these values and the thermodynamic stability constantsi of the 1: 1 complexes, the corresponding entropy changes are calculated.As shown in Table 2, the eomplex formation is always endothermic and entropieally favored. The dSe increases considerably with decreasing radius of the metal cations (r) and with increasing chain length of the polyphosphates (1). The dH, on the o-ther hand, depends only sligfitl y on both r and 1. All these results are explained in terms of present theories of metal c helate formation in aqueous solution.

The mixture of silica powder and milk of lime was stirred in an autoclave and treated hydrothermally under the following conditions; molar ratio of CaO/SiO2 0.80, weight ratio of water/total-solid 12, pressure 8kg/cm2, temperature 175°C, for 4-8hrs. Thus milky slurry consisting of tobermorite was prepared.The slurry contains 8% of total solid matter and its viscosity is 1.5-2.0 poise. Crystals are tobermorite whose (002) spacings are 11.2-11.3A. Grains are spherical aggregates with 5-70μm diameter having inter-twining structures of plate-like tobermorite crystals as shown in Fig. 5, 6 and Fig. 8.The slurry is easily dehydrated and shaped in a mold under pressure and the molded material can be hardened only by drying. The properties of thus obtained light molded material are following as shown in Table 1; density 0.2, bending strength 3-4kg/cm2, thermal durability 900°C, shrinkage at 1000°C 2-3%.

The thermodynamic stability constants of the complexes of pyrophosphate and triphosphate ions with Mg (II), Ca (II) and Sr (IL) are evaluated by the pH titration method. The enthalpy changes associated with the formation of the 1 : 1 complexes at 25°C are determined by a direct calorimetric method or calculated from the variation of the thermodynamic stability constants with temperature. From these values of the themodynamic stability constants and enthalpies, the corresponding entropy changes are calculated. The results are as follows (Table 2); (a) in all cases the complex formation is endotherm and entropically favored, (b) the ΔS0 decreases with increasing radius of the metal cations, while the ΔH0 does not, (c) theΔS0 of a triphos- phate complex is always larger than that of the corresponding pyrophosphate complex. All these results are explained in terms of present theories of metal chelate formation in aqueous solution.