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In the present study, the natural course of patulous eustachian tube syndrome (PETS) was examined. Fifteen patients (3 males, 12 females, 21 to 79 years old; mean age, 61.1 years) were given the diagnosis of PETS, meeting the criteria of both aural symptoms and hyperpatent eustachian tube findings by sonotubometry and tubo-tympano-aerodynamic graphy. Their aural symptoms were assessed by questionnaire at a mean of 16.7 months after the initial diagnosis in the absence of continuous medical treatment. Based on their answers, 7 patients were subjectively cured or in remission, but the other 8 patients showed intractable aural symptoms. The function of the eustachian tube was then re-examined in 7 of the 15 patients after the questionnaire. Six patients with intractable aural symptoms still showed open tubal function, while the tubal function was improved in another patient with relief from aural symptoms.

The mammalian target of rapamycin complex 1 (mTORC1) is a critical regulator of protein synthesis. The best studied targets of mTORC1 in translation are the eukaryotic initiation factor-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6K1). In this study, we identify the La-related protein 1 (LARP1) as a key novel target of mTORC1 with a fundamental role in terminal oligopyrimidine (TOP) mRNA translation. Recent genome-wide studies indicate that TOP and TOP-like mRNAs compose a large portion of the mTORC1 translatome, but the mechanism by which mTORC1 controls TOP mRNA translation is incompletely understood. Here, we report that LARP1 functions as a key repressor of TOP mRNA translation downstream of mTORC1. Our data show the following: (i) LARP1 associates with mTORC1 via RAPTOR; (ii) LARP1 interacts with TOP mRNAs in an mTORC1-dependent manner; (iii) LARP1 binds the 5′TOP motif to repress TOP mRNA translation; and (iv) LARP1 competes with the eukaryotic initiation factor (eIF) 4G for TOP mRNA binding. Importantly, from a drug resistance standpoint, our data also show that reducing LARP1 protein levels by RNA interference attenuates the inhibitory effect of rapamycin, Torin1, and amino acid deprivation on TOP mRNA translation. Collectively, our findings demonstrate that LARP1 functions as an important repressor of TOP mRNA translation downstream of mTORC1.

SummaryUncoupling protein 1 (Ucp1) contributes to thermogenesis, and its expression is regulated at the transcriptional level. Here, we show that Ucp1 expression is also regulated post-transcriptionally. In inguinal white adipose tissue (iWAT) of mice fed a high-fat diet (HFD), Ucp1 level decreases concomitantly with increases in Cnot7 and its interacting partner Tob. HFD-fed mice lacking Cnot7 and Tob express elevated levels of Ucp1 mRNA in iWAT and are resistant to diet-induced obesity. Ucp1 mRNA has an elongated poly(A) tail and persists in iWAT of Cnot7−/− and/or Tob−/− mice on a HFD. Ucp1 3′-UTR-containing mRNA is more stable in cells expressing mutant Tob that is unable to bind Cnot7 than in WT Tob-expressing cells. Tob interacts with BRF1, which binds to an AU-rich element in the Ucp1 3′-UTR. BRF1 knockdown partially restores the stability of Ucp1 3′-UTR-containing mRNA. Thus, the Cnot7-Tob-BRF1 axis inhibits Ucp1 expression and contributes to obesity.

Cerebrospinal fluid leaks following spinal surgery are relatively common complications. However, subdural hematomas are uncommon, and infratentorial subdural hemorrhages are extremely rare. An 80-year-old man who had a history of myocardial infarction and was being treated with antiplatelet drugs underwent excision of a nerve sheath tumor of the upper cervical spine. Postoperatively, the patient developed headache and experienced weakness in both lower extremities 1 week after the surgery. In addition, he developed vomiting 2 weeks later. Magnetic resonance imaging revealed cerebrospinal fluid retention behind the upper cervical spine, subdural hematomas in the right supra- and infra-tentorial regions, and subdural hygromas in the left supra- and infra-tentorial regions. The chronic subdural hematoma in the right supratentorial region was evacuated through a burr hole. Marked cerebellar ptosis and hydrocephalus developed postoperatively. Thereafter, cerebellar symptoms appeared. The infratentorial subdural hematoma and hygromas diminished in size;however, a posterior fossa cyst was found behind the fourth ventricle. Ten weeks after the burr hole surgery, a ventriculoperitoneal(VP)shunt was installed to decrease the cerebrospinal fluid retention behind the fourth ventricle and to cure the liquorrhea by reducing cerebrospinal fluid flow into the subarachnoid space of the posterior cranial fossa and the spinal canal. The patient's postoperative course was satisfactory, and the liquorrhea disappeared.

Poly(phenylene sulfide) (PPS) films were modified by Ar, O2, N2 and NH3 plasmas in order to improve their adhesion to copper metal. All four plasmas modified the PPS film surfaces, but the NH3 plasma modification was the most effective in improving adhesion. The NH3 plasma modification brought about large changes in the surface topography and chemical composition of the PPS film surfaces. The peel strength for the Cu/plasma-modified PPS film systems increased linearly with increasing surface roughness, R a or R rms, of the PPS film. The plasma modification also led to considerable changes in the chemical composition of the PPS film surfaces. A large fraction of phenylene units and a small fraction of sulfide groups in the PPS film surfaces were oxidized during the plasma modification process. Nitrogen functional groups also were formed on the PPS film surfaces. The NH3 plasma modification formed S—H groups on the PPS film surfaces by reduction of S—C groups in the PPS film. Not only the mechanical interlo...

A simple method for the formation of microbial biofilms of three species, Pseudomonas fluorescens, Pseudomonas aeruginosa, and Klebsiella pneumoniae, on a small glass slide was established, and its suitability for evaluation of disinfectant efficacy was examined. The biofilms formed were observed in situ by confocal laser scanning microscopy (CLSM). Using the biofilms established, biocidal efficacy of several halogen biocides, such as hypochlorite (HOCl), bromochlorodimethylhydantoin (Br, Cl-DMH), ammonia monochloramine (NH2Cl), a stabilized hypobromite biocide named STABREX®, and a mixed solution of NH4Br and HOCl, was evaluated. The formation of NHBrCl in the mixed solution was indicated by UV spectra analysis. Biofilm cells were more resistant to these biocides than planktonic cells and the extent of resistance varied with the biocide tested. Among the biocides tested, the biocidal potency of HOCl was the most susceptible to the change brought about by biofilm formation. By CLSM observation, differences in biofilm conformation were revealed between the microbial species. The efficacy of the biocide tested varied with the structure of biofilms formed. The assay method developed in the present study would be useful for further investigation on biofilm disinfection.

Mesoporous silica (MPS) was used for poly(ethylene oxide) (PEO)-based solid polymer electrolytes as novel inorganic filler. For improvement in ionic conductivity in solid state, a room temperature ionic liquid (IL), 1-ethyl-3-methylimidazolium tetrafluoroborate, was introduced into periodic nano-tunnels of MPS, and the modified MPS (IL-MPS) was filled with PEO-LiBF4 electrolyte. Ionic conductivity of neat-MPS-filled composites was approximately 4-fold higher than that of the original electrolyte. On the other hand, the conductivity was more than 11-fold enhanced by addition of IL-MPS, to be more than 10−6 S/cm at 30°C and at least 10 wt% silica contents. The conductivity increased with increasing IL-MPS contents, to be a maximum value of approximately 3×10−6 S/cm at 30°C and at 40 wt%. Dynamic mechanical measurements for neat- and IL-MPS composites revealed that the addition of fillers improves storage modulus of PEO-based electrolytes at room temperature. The addition of IL-MPS was able to realize the improvement in both ionic conductivity and storage modulus.

Utilizing a zone model and a ceiling-jet model, a simple calculation method for predicting fire detector's response time is presented. The parameters are the floor area and the ceiling height of the room, the radial distance of the detector from the fire axis, time history of the heat and smoke release rates of the fire, and the response characteristics of the detector. For the heat detector, application of RTI-C model (a modified Response Time Index model) is discussed and a method utilizing two RTI's, one for the sensor element and the other for the detector body, is introduced. The method using two RTI's shows better results than the original RTI-C model, which was derived for predicting the response of sprinkler heads. In addition, a calculation method for predicting the response of rate-of-rise heat detector is presented. For the response of photoelectric smoke detector, a method utilizing a response threshold in the optical smoke concentration and a response threshold in the air velocity is introduced. It is shown that different response thresholds in the smoke concentration are needed for the smoke released from flaming sources and for the smoke released from smoldering sources respectively.

Study design A retrospective study of 87 patients who underwent posterior lumbar interbody fusion (PLIF) at L4-L5 for L4 degenerative spondylolisthesis. Objective To clarify: 1) the correlation between radiologic degeneration of cranial adjacent segment and clinical results, 2) risk factors for radiologic degeneration of cranial adjacent segment, and 3) preoperative radiologic features of patients who underwent additional surgery with cranial adjacent segment degeneration. Summary of background data Whereas PLIF with pedicle screw fixation has shown satisfactory clinical results, a solid fusion has been reported to accelerate a degenerative change at unfused adjacent levels, especially in the cranial level. Although several authors have reported the adjacent segment degeneration after PLIF, there are no previous reports of risk factors for adjacent segment degeneration after PLIF. Materials and methods Eighty-seven patients who underwent PLIF for L4 degenerative spondylolisthesis and could be followed for at least 2 years were included in this study. We measured lumbar lordosis, scoliosis, laminar inclination angle at L3, facet sagittalization at L3-L4, facet tropism at L3-L4, preexisting disc degeneration at L3-L4, and lordosis at the fused segment. Progression of L3-L4 segment degeneration was defined as a condition in which disc narrowing, posterior opening, and progress of slippage in comparison with preoperative dynamic lateral radiographs. Patients were divided into three groups according to postoperative progression of L3-L4 degeneration: Group 1 with neither progression of L3-L4 degeneration nor neurologic deterioration, Group 2 with progression of L3-L4 degeneration but no neurologic deterioration, and Group 3 with an additional surgery required for neurologic deterioration. Correlation between clinical results and radiologic progression of L3-L4 degeneration, and risk factors for progression of radiologic degeneration were investigated. Further, preoperative radiologic features of Group 3 were studied to detect risk factors for clinical deterioration. Results There were 58 (67%) patients classified into Group 1, 25 (29%) patients into Group 2, and 4 (4%) patients into Group 3. There was no significant difference in average age in each group. No obvious difference was observed in recovery rate between Groups 1 and 2. Laminar inclination angle and facet tropism in Group 3 were more significant than those in Groups 1 and 2. Further, apparent lamina inclination and facet tropism coexisted in Group 3. There were no obvious differences in other factors between each group. Conclusion 1) There was no correlation between radiologic degeneration of cranial adjacent segment and clinical results. 2) Risk factors for postoperative radiologic degeneration could not be detected in terms of each preoperative radiologic factor. 3) Coexistence of horizontalization of the lamina at L3 and facet tropism at L3-L4 may be one of the risk factors for neurologic deterioration resulting from accelerated L3-L4 degenerative change after L4-L5 PLIF.

We report a homozygous case of spinocerebellar ataxia type 17 with 48 glutamines. The age of the patient at disease onset was not lower than those of heterozygotes with the same CAG-repeat sizes, but the clinical manifestations were rapidly progressive dementia and chorea. Neuronal loss was relatively restricted and most prominent in the Purkinje cell layer and striatum; however, intranuclear neuronal polyglutamine accumulation was widespread, with a high frequency in the cerebral cortex and striatum.

We report two patients with motor neuron disease-inclusion dementia, with special reference to the pathology of the motor neuron system and hippocampal formation. The ages of the patients at death were 55 and 62 years, and the disease durations were 8 and 3 years, respectively. The two patients exhibited progressive frontotemporal dementia in the absence of motor neuron signs. At autopsy, both cases exhibited frontotemporal lobar atrophy with ubiquitin-positive, and tau- and alpha-synuclein-negative neuronal inclusions. As expected from the clinical signs, in both cases, the upper and lower motor neuron systems were well preserved: no Bunina bodies or ubiquitinated inclusions were detected in the motor neurons. However, of great importance was that when visualized immunohistochemically, the Golgi apparatus and trans-Golgi network often exhibited fragmentation in the lower motor neurons (the spinal anterior horn cells). In one of the cases, a decrease in the amount of Golgi apparatus was also a frequent feature in the upper motor neurons (Betz cells in the motor cortex). Moreover, in both cases, circumscribed degeneration affecting the CA1-subiculum border zone was evident in the hippocampal formation. These findings further strengthen the idea that, pathologically, motor neuron disease-inclusion dementia is a rare phenotype of amyotrophic lateral sclerosis.

Overestimation or underestimation of functional capacity in community-dwelling older people with cognitive impairment was evaluated between the responses of subjects and family members (proxies) by cognitive function level. Out of all the residents aged 65 years and over living in Yoita town, Niigata Prefecture in 2000 (n = 1,673), 1,544 voluntarily participated in the interview survey held at community halls or at home (92.3% response). They underwent the Mini-Mental State Examination (MMSE) for assessment of cognitive function and answered questionnaires comprising socio-demographic, psychological, physical and medical, and social activity items (2000/11). According to the age of the subject and MMSE score, we defined cognitive decline (MMSE scores 1 SD below age-specific means and CDR (Clinical Dementia Rating) = 0: mild cognitive decline (MCD) (n = 54), 21 0.5. SCD subjects significantly overestimated total and Instrumental Self-Maintenance scores in TMIG-IC more than control or SCD subjects. Multiple logistic regression analyses indicated that complaints of memory by the proxy, response by spouse, and higher levels of education were extracted as significantly independent variables affecting overestimation for functional capacity. On the other hand, aging affected underestimation.

Woodceramics has been studied as an Ecomaterial, and is expected to have applications in a wide variety of fields. In this report, thermogravimetry and differential thermal analysis of Woodceramics with changing concentration of oxygen was conducted. Experiments in chemical reaction kinetics were also performed in order to clarify the thermo-physical and thermo-chemical properties of Woodceramics in the presence of oxygen. The experimental results show that both mass loss curves and differential heat curves are dependent on the concentration of oxygen. In addition, the reaction rate law of the thermal degradation of Woodceramics with change in concentration of oxygen is reported to verify the suitability of the method.

Background: Cognitive impairment is a major health issue, but epidemiological data on mild cognitive decline have been almost absent in Japan. Methods: Of all residents aged 65 years and over living in Yoita town, Niigata Prefecture, Japan in the year 2000 (n = 1673), 1544 participated in the interview survey held at community halls or at home (92.3% response). They underwent the Mini-Mental State Examination (MMSE) for assessment of cognitive function and answered questionnaires comprising socio-demographic, psychological, physical and medical, and social activity items. Higher-level functional capacities were evaluated with the Tokyo Metropolitan Index of Competence (TMIG-Index of Competence). According to subject’s age and MMSE score, all subjects were classified into 3 groups: control (MMSE > 1 SD below age-specific means), mild cognitive decline (MMSE ≥ 21 and ≤ 1 SD below age-specific means), and severe cognitive decline (MMSE ≤ 20), and compared various characteristics among these groups. Results: Mean MMSE score of the subjects showed a linear decline with advancing age. Among the participants, 232 (15.2%) were classified as mild cognitive decline. Compared with the controls, the subjects with mild cognitive decline reported poorer subjective health, more depressive moods, more history of stroke, more prevalence of basic activity of daily living (BADL) disability, and lower higher-level functional capacity, even after controlling for possible confounding factors. They also reported a low level of social activities: both participating in group activities and enjoying hobbies were less frequent. Their food intake pattern tended to be monotonous. Conclusions: Older persons with mild cognitive decline comprised a substantial proportion (15.2%) of the community-dwelling older population. In addition to lower cognitive function, they had lower levels of functional capacity and social activity.

The mechanisms that link environmental and intracellular stimuli to mitochondrial functions, including fission/fusion, ATP production, metabolite biogenesis, and apoptosis, are not well understood. Here, we demonstrate that the nutrient-sensing mechanistic/mammalian target of rapamycin complex 1 (mTORC1) stimulates translation of mitochondrial fission process 1 (MTFP1) to control mitochondrial fission and apoptosis. Expression of MTFP1 is coupled to pro-fission phosphorylation and mitochondrial recruitment of the fission GTPase dynamin-related protein 1 (DRP1). Potent active-site mTOR inhibitors engender mitochondrial hyperfusion due to the diminished translation of MTFP1, which is mediated by translation initiation factor 4E (eIF4E)-binding proteins (4E-BPs). Uncoupling MTFP1 levels from the mTORC1/4E-BP pathway upon mTOR inhibition blocks the hyperfusion response and leads to apoptosis by converting mTOR inhibitor action from cytostatic to cytotoxic. These data provide direct evidence for cell survival upon mTOR inhibition through mitochondrial hyperfusion employing MTFP1 as a critical effector of mTORC1 to govern cell fate decisions.

mRNA translation is the most energy consuming process in the cell. Translation and energy metabolism are dysregulated in a variety of diseases including cancer. However, the mechanisms which coordinate translation and energy metabolism remain largely unknown. The mechanistic/mammalian target of rapamycin complex 1 (mTORC1) stimulates mRNA translation and other anabolic processes in response to a variety of extracellular signals and intracellular cues (e.g., growth factors, nutrients, oxygen), ultimately accelerating cellular growth and proliferation. mTORC1 is frequently hyper-activated in a series of cancer, thereby it is targeted for the cancer treatment. We previously carried out a genome-wide polysome profiling analysis using mTORC1 inhibitors, such as rapamycin and active-site mTOR inhibitors. These experiments revealed that mRNAs whose translation is regulated by mTORC1 are enriched in those encoding mitochondrial proteins. Here, by using a combination of pharmacological, genetic, biochemical and metabolomic approaches, we demonstrate that mTORC1 modulates mitochondrial functions and dynamics through translational regulation of mRNAs encoding mitochondrial proteins. Mechanistically, we indicate that the effects of mTORC1 on mitochondria are mediated by the eukaryotic translation initiation factor 4E (eIF4E) binding proteins (4E-BPs). Stimulation of translation of mitochondria-related mRNAs engendered an increase in ATP production, which is required as an energy source for translation. These data support a feed-forward loop model, whereby the mTORC1/4E-BP pathway promotes translation of mitochondria-related mRNAs to increase mitochondrial ATP production to meet the high energy demand of protein synthesis in proliferating cells. This represents a novel paradigm for understanding how cellular energy homeostasis is maintained via direct coordination of energy consumption (translation) and energy production (ATP production in mitochondrion). Thereby, our findings provide a new mechanism linking aberrant mTOR signaling to conditions of abnormal cellular energy metabolism such as neoplasia. In this presentation, we will introduce our recent data and discuss the role of mTORC1/4E-BP signaling pathway on mitochondrial function, cellular metabolism and proliferation. Citation Format: Masahiro Morita, Julien Prudent, Heidi McBride, John Bergeron, Nahum Sonenberg. Translational control of mitochondria through mTORC1/4E-BP signaling pathway. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr B06.

Obesity is a global epidemic resulting from increased energy intake, which alters energy homeostasis and results in an imbalance in fat storage and breakdown. G0/G1 switch gene 2 (G0s2) has been recently characterised in vitro as an inhibitor of adipose triglyceride lipase (ATGL), the rate-limiting step in fat catabolism. In the current study we aim to functionally characterise G0s2 within the physiological context of a mouse model. We generated a mouse model in which G0s2 was deleted. The homozygous G0s2 knockout (G0s2 −/−) mice were studied over a period of 22 weeks. Metabolic variables were measured including body weight and body composition, food intake, glucose and insulin tolerance tests, energy metabolism and thermogenesis. We report that G0s2 inhibits ATGL and regulates lipolysis and energy metabolism in vivo. G0s2 −/− mice are lean, resistant to weight gain induced by a high-fat diet and are glucose tolerant and insulin sensitive. The white adipose tissue of G0s2 −/− mice has enhanced lipase activity and adipocytes showed enhanced stimulated lipolysis. Energy metabolism in the G0s2 −/− mice is shifted towards enhanced lipid metabolism and increased thermogenesis. G0s2 −/− mice showed enhanced cold tolerance and increased expression of thermoregulatory and oxidation genes within white adipose tissue, suggesting enhanced ‘browning’ of the white adipose tissue. Our data show that G0s2 is a physiological regulator of adiposity and energy metabolism and is a potential target in the treatment of obesity and insulin resistance.

mRNA translation plays a central role in the regulation of gene expression and represents the most energy consuming process in mammalian cells. Accordingly, dysregulation of mRNA translation is considered to play a major role in a variety of pathological states including cancer. Ribosomes also host chaperones, which facilitate folding of nascent polypeptides, thereby modulating function and stability of newly synthesized polypeptides. In addition, emerging data indicate that ribosomes serve as a platform for a repertoire of signaling molecules, which are implicated in a variety of post-translational modifications of newly synthesized polypeptides as they emerge from the ribosome, and/or components of translational machinery. Herein, a well-established method of ribosome fractionation using sucrose density gradient centrifugation is described. In conjunction with the in-house developed “anota” algorithm this method allows direct determination of differential translation of individual mRNAs on a genome-wide scale. Moreover, this versatile protocol can be used for a variety of biochemical studies aiming to dissect the function of ribosome-associated protein complexes, including those that play a central role in folding and degradation of newly synthesized polypeptides.

Osteoclastogenesis is under the control of posttranscriptional and transcriptional events. However, posttranscriptional regulation of osteoclastogenesis is incompletely understood. CNOT3 is a component of the CCR4 family that regulates mRNA stability, but its function in bone is not known. Here, we show that Cnot3 deficiency by deletion of a single allele induces osteoporosis. Cnot3 deficiency causes an enhancement in bone resorption in association with an elevation in bone formation, resulting in high-turnover type bone loss. At the cellular level, Cnot3 deficiency enhances receptor activator of NF-κB ligand (RANKL) effects on osteoclastogenesis in a cell-autonomous manner. Conversely, Cnot3 deficiency does not affect osteoblasts directly. Cnot3 deficiency does not alter RANKL expression but enhances receptor activator of NF-κB (RANK) mRNA expression in bone in vivo. Cnot3 deficiency promotes RANK mRNA stability about twofold in bone marrow cells of mice. Cnot3 knockdown also increases RANK mRNA expression in the precursor cell line for osteoclasts. Anti-CNOT3 antibody immunoprecipitates RANK mRNA. Cnot3 deficiency stabilizes luciferase reporter expression linked to the 3′-UTR fragment of RANK mRNA. In contrast, Cnot3 overexpression destabilizes the luciferase reporter linked to RANK 3′-UTR. In aged mice that exhibit severe osteoporosis, Cnot3 expression levels in bone are reduced about threefold in vivo. Surprisingly, Cnot3 deficiency in these aged mice further exacerbates osteoporosis, which also occurs via enhancement of osteoclastic activity. Our results reveal that CNOT3 is a critical regulator of bone mass acting on bone resorption through posttranscriptional down-regulation of RANK mRNA stability, at least in part, even in aging-induced osteoporosis.

Digital Accessible Information System (DAISY) content is expected to gain popularity gradually among the visually impaired according to the prevalence of e-book reading devices and the development of text-to-speech (TTS) technology. However, the development of DAISY-formatted e-books, which is undertaken by volunteers, is a time-consuming process, making it difficult to meet end user requirements. In this report, we propose a content transliteration system that can convert plain text to DAISY content including formatted HTML and audio data via automatic TTS technology. Furthermore, using the graphic user interface of the proposed system, users can correct text and accent information by inputting ruby-type data. Through this functionality, we aim to target support for transliteration workers such as volunteers, teachers, and parents to make and edit contents easily and quickly for the visually impaired. Finally, we present the results of a preliminary evaluation using the proposed method in order to compare it with the conventional method.

本報では, 未延伸および幅拘束1軸延伸したフィルムに熱処理, 熱水処理を施し, 結晶化度の値をいろいろと変化させ, これらフィルムの引っ張りによる応力-ひずみ曲線を検討する. ポリエチレンテレフタラート (PET) のフィルムは温度80℃附近で延伸が行われるので, 未延伸フィルムでは, 室温とこの温度による応力-ひずみ曲線を解析した. また, 幅拘束1軸延伸フイルムのOff-axis angle再延伸は室温で行っているので, この後者は, 室温での応力-ひずみ曲線を解析した. 以上の結果により, PETの未延伸, 幅拘束1軸延伸フィルムの結晶相, 非結晶相の値列モデルにもとづき解析され, その結晶相, 非結晶相のヤング率および降伏応力の値の比を得られた.

We compared effects of α-galactosylceramide (α-GalCer) and its 3α- or 3β-galactosylated derivatives on the proliferation of murine spleen cells. The 3α-galactosylated α-GalCer showed stongger proliferative response than the parental α-GalCer, but the 3β-galactosylated α-GalCer possessed weaker activity than the α-GalCer. In addition, α-Gal-3-Cer did not show immunostimulatory activity.

We have developed a new technique for analyzing the rotation vector of eye movement in three dimensions with an infrared CCD camera based on the following four assumptions; i) the eye rotates on a point; ii) the pupil edge is a circle; iii) the distance from the center of eye rotation to pupil circle remains unchanged despite the rotation; iv) the image of the eye by the CCD camera is projected onto a plane which is perpendicular to the camera axis. After taking digital images of voluntary circular eye movements, we first constructed a three-dimensional frame of reference fixed on the orbita of the subject wearing a goggle equipped with an infrared CCD camera, and determined the space coordinates of the center of eye rotation, the center of the pupil, and an iris freckle. We then took digital images of the eye movements during a saccade or vestibulo-ocular reflex (VOR) and analyzed the axis and angle of the eye movements by the trajectories of the center of the pupil and the iris freckle. Finally, Listing's plane of saccade and the gain and the phase of VOR were obtained. The suitability of this technique is examined.

Benign Paroxysmal positioning vertigo and acoustic tumors are thought to be related to the function of the vertical semicircular canal (VSCC). Therefore, we developed a new test to assess VSCC function by analyzing VSCC-induced nystagmus. We examined 11 healthy subjects, wearing goggles equipped with an infrared CCD camera and sitting on a chair designed to bilaterally stimulate the VSCCs by tilting the head backward during 45° rotation to the right on the sagital plane. The stimuli used were sinusoidal rotation with a maximal angular velocity of 100°/sec at a frequency of 0.033 Hz. The result was that the maximum slow phase eye velocity (MSPEV) of horizontal nystagmus decreased parallel to the head-tilted angle and the MSPEV of the vertical nystagmus was maximal when the head was tilted 60° or 70° backward. From the perspective of VSCC anatomy, the direction of horizontal nystagmus is reversed when head is tilted 60° backward. However, we could not observe the reverse of the direction of horizontal nystagmus even when head tilted 80° backward. We considered that vertical nystagmus was maximal when the head was tilted 60-70° backward because this position applied the optimal stimulation to the VSCC. This finding is in agreement with the position of the vertical VSCC in skull. We concluded that rotational test with respect to the VSCC can be used to analyze VSCC function.

von Recklinghausen's disease is characterized by cafe-au-lait spots and multipleneurofibromas as major findings and eye lesions, bone lesions, and endocrine abnormalities as associated findings. A 23-year-old male with von Rechlinghausen's disease associated with mandibular retrognathia was reported. He visited our clinic due to malocclusion and retrognathia.In the abdomen and the back, multiple small tumors and cafe-au-lait spots were observed. Severe deep bite (overbite: 7mm; overjet: 13mm) and narrowing of the maxillary and mandibular dental arches were noted. The interincisal distance was 41 mm, and the maximum ranges of the mandibular movements were 10 mm anteriorly, 9.5 mm to the right, and 12.0mm to the left. Microglossia showing geographical fissured tongue was observed.Intraoral radiographic examination revealed congenital dental missing of 21|2 and impaction of but no other findings in the jaw characteristic of this disease. He was treated by anterior movement of the mandible (12 mm) via bilateral sagittal split ramus osteotomy of the mandible and overcorrection in consideration of possible relapse after operation (overbite: 1 mm; overjet: 1 mm). Subsequently, occlusion was restored by prosthetic treatment. The final measurement values 6months after operation were as follows: overbite: 4.5 mm; overjet: 5 mm; interincisal distance: 41 mm; amount of jaw movements: 7 mm anteriorly, 10 mm on theright side, and 10 mm on the left side. After that, skeletal relapse was not noted. However, atrophic changes and underdevelopment of the mandible appear to be involved in the development of retrognathism in this case.

Uno, A., N. Takeda, A. Horii, M. Morita, Y. Yamamoto, A. Yamatodani and T. Kubo. Histamine release from the hypothalamus induced by gravity change in rats and space motion sickness. Physiol Behav 61(6) 883–887, 1997.—Freely moving rats were exposed to 2 g hypergravity in an animal centrifuge device to produce motion sickness. Histamine release from the anterior hypothalamus of the rats was measured in vivo with a microdialysis technique. After a 2-h load of 2 g hypergravity, rats ate kaolin. Because pica, eating a nonnutritive substance such as kaolin, is a behavioral index of motion sickness in rats, this finding indicates that the rats suffered from motion sickness. During 2 g hypergravity for 2-h, histamine release from the hypothalamus was transiently increased. In contrast, neither the transient increase of histamine release nor the kaolin consumption were induced by 2 g hypergravity in bilaterally labyrinthectomized rats. Pretreatment with α -fluoromethylhistidine, an inhibitor of histamine-synthesizing enzyme, decreased both the basal and hypergravity-induced releases of histamine from the hypothalamus and suppressed the kaolin consumption induced by hypergravity. Taken together, these findings suggest that the vestibular information of changes in gravity activate the histaminergic neuron system, resulting in the development of motion sickness. More prolonged stimulation, a 4-h load of 2 g hypergravity, induced significant increase of kaolin consumption on postdays 1–3, though rats ate kaolin on postdays 1–2 after 2 g hypergravity for 2 h. During 2 g hypergravity for 4 h, the initial transient increase of histamine release was followed by the gradual increase of histamine release after the end of centrifugation. It is suggested that rats adapted to the hypergravity environment after centrifugation for 4 h, but not 2 h, so that the change in gravity from 2 g to 1 g became a provocative stimulation. We, therefore, concluded that motion sickness in rats induced by a negative change in gravity can be used as a simulation of space motion sickness, which is induced by exposure to microgravity. Histaminergic activation in the development of motion sickness induced by negative change in gravity might be an underlying mechanism of space motion sickness.

Theoretical and experimental numerical analysis have proposed the capable of being executed computational finite difference method for fire induced natural convective heat flow using the viscous heat conductive compressible fluid with K-e model in the fire compartment. Because two-point upwind difference scheme give the numerical viscosity, the computational results are different from the approximate solutions at the large velocity. The practical stability and the truncation errors for computing finite difference equations approximating fire governing equations have been introduced by theoretical numerical analysis. The sensitivities of numerical solutions have been evaluated by the theoretical and experimental numerical analysis. As the results of numerical experiments we proposed that the reasonable time interval and space mesh size are chosen considering the CPU time. Furthermore we have introduced the Re* for the equation of motion or Pe*for the equation of energy. We proposed that the values of Re* and Pe* indicate the trust in the approximate solutions in consequence of the numerical experiments.

The therapeutic effects of amezinium, an indirect sympathomimetic, was evaluated in 71 patients with vertigo or dizziness. The patients were given a 10mg tablet of amezinium two times a day for over four weeks. In 39 patients (54.9%), the symptoms were reduced. Mild side effects were noted in 4 patients (5.6%). These findings suggest that amenizium is a clinically useful drug for the treatment of vertigo or dizziness. The administration of amezinium tended to be more effective in patients with orthostatic dysregulation (OD), as diagnosed by an OD questionnaire and a Schellong test, than in patients without OD. These findings suggest that amezinium improved the sympathetic nervous system dysfunction in these patients, leading to its therapeutic effect.

After examination of the ill-natured stress sensitivity of the conventional creep damage model of Kachanov-Rabotnov, first the intrinsic limitations in the applicability of the damage model to reliable analyses of creep fracture processes are discussed. Then, improvement of the damage evolution equation and the development of a new constitutive equation based on micromechanics are ciscussed to facilitate rational creep fracture analyses and to suppress the mesh-dependence in Finite Element Analysis. Finally, the proposed model is applied to creep crack growth analysis, and the improvement in the mesh dependence of the numerical results is demonstrated.

We examined the effect and aftereffect of acute or chronic load of hypergravity produced by an animal centrifuge, on pica (that is, kaolin intake) in the rat as an index of motion sickness. Although the degree of pica initially induced by acute or chronic hypergravity was not different, the rate of decline of increased kaolin intake over poststimulus days was different. Pica after a 1-h load of 2g decreased rapidly. On the other hand, pica lasted 3 days after a 48-h load of 2g. These findings suggest that the aftereffects of chronic hypergravity application on pica are due to motion sickness induced by readaptation to normal gravity, and they support our idea that after adaptation to a hypergravity environment, return and readaptation to the normal gravity can simulate exposure and adaptation to microgravity. We concluded that motion sickness in rats induced by the aftereffects of chronic hypergravity stimulation can be used as a ground-based animal model of space adaptation syndrome.

To test vertical semicircular canal function, we developed a new and convenient type of rotation-chair, in which subjects sat with their heads and backs tilting backward 60°and with their heads rolling laterally 45°. A CCD camera and infrared video system was used to record eye movement in the dark. Normal subjects were rotated with an acceleration of 2°/sec2 until the angular velocity reached 60°/sec. The rotation was then stopped with a deceleration of 100°/sec2 after per-rotation nystagmus subsided. The maximal slow phase eye velocity (MSPEV) of vertical components of vertical semicircular canal (VSCC)-induced post-rotatory nystagmus (PRN) were analysed.Subjects were first rotated with laterally rolling head angles of 30°, 45° and 60°to examine the optimal angle for stimulating VSCC.MSPEV of posterior semicircular canal (PSCC)-induced PRN was largest with a head angle of 60°. While MSPEV of anterior semicircular canal (ASCC)-induced PRN did not vary with the laterally rolling head angle. MSPEV of the vertical components of VSCC-induced PRN was then compared with that of the horizontal components of lateral semicircular canal (LSCC)-induced PRN. MSPEV of both PSCC- and ASCC-induced PRN were significantly smaller than that of LSCC-induced PRN.MSPEV of ASCC-induced PRN was slightly smaller than that of PSCC-induced PRN, though individual differences varied widely. However, there were very small leftright differences in MSPEV of both PSCC- and ASCC-induced PRN. Therefore, it is suggested that our PRN function test involving VSCC can diagnose vestibular diseases.

We present a 41-year-old male with vertigo due to orthostatic hypotension caused by diabetic neuropathy. Autonomic function test showed no increase in either plasma noradrenaline or sympathetic activity in response to standing up. During head up tilting, vertebral blood flow measured by Doppler flowmeter decreased with a decrease in blood pressure and asymmetrical vertebral blood flow was evident. Head up tilting also induced nystagmus and vertigo. After the patient was treated for orthostatic hypotension by L-threo-3, 4-dihydroxyphenylserine, a precursor of noradrenaline, neither asymmetrical vertebral blood flow nor nystagmus were observed during head up tilt. It is suggested that asymmetrical vertebral blood flow induced by sympathetic dysfunction causes asymmetrical excitability of the vestibular system, resulting in nystagmus and vertigo.

We evaluated the efficacy of treatment with roxithromycin (RXM: new derivative of erythromycin) for OME patients with tympanostomy tube (TT) from the perspective of reducing refractory OME and preventing complications.Seventeen ears of 15 patients were treated for 6 months with a single daily dose (150mg) of RXM starting on the day of TT insertion. The other 23 ears of 20 patients were treated by TT insertion only.The rate of improvement, including “good” improvement, for ears with mucous fluid in the middle ear and poor mastoid pneumatization was significantly higher in ears treated with RXM (50%, 60%) than in ears treated with TT insertion alone (0%, 25%).These results indicate that low-dose RXM treatment may be useful for OME requiring TT insertion, and in reducing complications caused by TT insertion.

We examined the life-span-prolonging effects of five kinds of α-Galactosylceramides (α-GalCers) on mice irradiated with lethal dose (9 Gy) of X ray, and found that they show strong radioprotective activities even when they are administered to mice after the irradiation. These results suggest that α-GalCers are useful as radioprotective agents.

Agelasphin-9b, (2S,3S,4R)-1-O-(alpha-D-galactopyranosyl)-16-methyl-2- [N-((R)-2- hydroxytetracosanoyl)-amino]- 1,3,4-heptadecanetriol, is a potent antitumor agent isolated from the marine sponge Agelas mauritianus. Various analogues of agelasphin-9b (a lead compound) were synthesized, and the relationship between their structures and biological activities was examined using several assay systems. From the results, KRN7000, (2S,3S,4R)-1-O-(alpha-D- galactopyranosyl)-2-(N-hexacosanoylamino)-1,3,4-octadecanetriol , was selected as a candidate for clinical application.

To examine antitumor activities of monoglycosylceramide, we synthesized α-, β-galactosylceramides and α-, β-glucosylceramides which have the same ceramide portion, and four kinds of diastereomers of the ceramide portion in an α-galactosylceramide.