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The mammalian target of rapamycin (mTOR)-composed of multiple complexes, including mTOR complex 1/2 (mTORC1/2)-is a serine-threonine kinase that regulates embryonic development. The transcription factor, hypoxia-inducible factor-1α (HIF-1α), is also involved in embryonic development. As the relationship between mTOR and HIF-1α during embryonic development remains unclear, we investigated the relationship between the two using ex vivo submandibular salivary gland organ cultures. When the expression of HIF-1α increased under hypoxic conditions (1% O

This study investigated olfactory/taste functions in older persons requiring nursing care to clarify whether these functions are associated with appetite or nutritional status. Seventy-two older persons requiring nursing care and 37 unassisted persons were surveyed for olfactory function, taste function, appetite, and nutritional status. Age-adjusted covariance analysis was conducted between the two groups. Both groups showed reduced olfactory and taste functions; these functions were more markedly reduced in participants requiring nursing care compared to those who did not. Both groups had similar appetite and nutritional status findings, suggesting that these factors are not associated with olfactory and taste functions.

Background Aspiration pneumonia is a major complication that occurs in patients with severe cerebral palsy and is associated with their survival prognosis, necessitating appropriate assessment and response. We focused on swallowing frequency as an index of daily swallowing function due to the difficulty in evaluating the risk of pneumonia. The swallowing motion protects the airway by safely directing the food, saliva, and secretions accumulated in the pharynx into the esophagus to prevent aspiration and entry into the trachea. Thus, swallowing frequency may be correlated with the incidence of pneumonia. In this study, we aimed to investigate the relationship between swallowing frequency and history of pneumonia in patients with severe cerebral palsy. Methods Fifty-seven patients with cerebral palsy were included in this study. Swallowing frequency was measured three times for each patient on separate days, and the reproducibility was examined by calculating the intraclass correlation coefficient. Further, the relationship between swallowing frequency and history of pneumonia was investigated using multivariate logistic regression analysis. Results While swallowing frequency differed between participants, it was constant within individuals (intraclass correlation coefficient: 0.941). Furthermore, the swallowing frequencies per hour were 12.2 ± 12.2 and 27.0 ± 20.4 in the patient groups with and without a history of pneumonia, respectively (P P = 0.001) was significantly associated with the incidence of pneumonia in the previous year. Conclusions Swallowing frequency could be used as an index for assessing the risk of dysphagia and pneumonia in patients with severe cerebral palsy.

Background/Aim: Although mucociliary clearance is important for preventing pneumonia, its association with the onset of pneumonia is unclear. The aim of this study is to examine the association between saccharin test results as a potential measure of mucociliary clearance and history of pneumonia in nursing home residents. Patients and Methods: Ninety elderly nursing home residents (elderly group) were selected, 35 of whom had a history of pneumonia. Twenty-five healthy adults (adult group) were also investigated to provide baseline values for this study. We conducted the saccharin test to evaluate mucociliary clearance and compared the saccharin time (ST) between those with and without history of pneumonia. Results: Mean ST in the adult group was 12±6 min. The ST in the pneumonia group was significantly longer than that in the non-pneumonia group (32±23 min vs. 17±13 min) (p

PURPOSE: This study examined whether certain medical complications influence the feasibility of tube removal. METHODS: 42 subjects with dysphagia who were under the age of 2.5 years were nourished entirely through feeding tubes. Additionally, they were judged to have no aspiration. The following data about the infants were collected through a retroactive survey: age at which oral feeding training commenced, gender, and whether certain medical complications (cardiovascular, respiratory, digestive, neurological, or oral) had been present at birth. The data were analyzed to determine which type of medical complication affected the likelihood of removing the feeding tube from the infant at 3 years of age. RESULTS: Of the five medical complications examined, cardiovascular complications significantly affected the feasibility of tube removal (p = 0.049). CONCLUSION: Pediatric dysphagia patients with cardiac complications, compared to those with other complications, may take longer to transition off tube feeding.

Salivary glands act as virus reservoirs in various infectious diseases and have been reported to be targeted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the mechanisms underlying infection and replication in salivary glands are still enigmatic due to the lack of proper in vitro models. Here, we show that human induced salivary glands (hiSGs) generated from human induced pluripotent stem cells can be infected with SARS-CoV-2. The hiSGs exhibit properties similar to those of embryonic salivary glands and are a valuable tool for the functional analysis of genes during development. Orthotopically transplanted hiSGs can be engrafted at a recipient site in mice and show a mature phenotype. In addition, we confirm SARS-CoV-2 infection and replication in hiSGs. SARS-CoV-2 derived from saliva in asymptomatic individuals may participate in the spread of the virus. hiSGs may be a promising model for investigating the role of salivary glands as a virus reservoir.

Polypharmacy in elderly persons living at home or in a nursing home is an issue. In the field of dentistry, strategies to reduce polypharmacy must be promoted; however, there is insufficient basic data on medications received by elderly persons with dysphagia living at home or in a nursing home. The subjects were 106 elderly persons with dysphagia living at home or in a nursing home. Based on their medical records, the presence of disease and number/type of drugs being administered were investigated. Stroke, dementia, and hypertension were common. The mean number of drugs per person was 6.3 (minimum: 0, maximum: 15). Drugs for digestive ulcers were the most frequently prescribed medication, followed by hypotensive drugs, anti-parkinsonism drugs, and other central nervous drugs. Fifty-nine patients (52.8%) had taken drugs that may cause dysphagia, and 19 (17.9%) had taken drugs that may cause aspiration. Of the subjects, 68.9% had taken ≥5 drugs, demonstrating polypharmacy in elderly persons with dysphagia living at home or in a nursing home. Many drugs that may cause dysphagia or aspiration had been prescribed, suggesting the importance of dentists' reducing polypharmacy from the viewpoint of swallowing.

Background Detecting and addressing aspiration early in children with dysphagia, such as those with cerebral palsy, is important for preventing aspiration pneumonia. The current gold standards for assessing aspiration are swallowing function tests, such as fiberoptic endoscopic evaluation of swallowing (FEES) and videofluorographic swallowing study; however, the relationship between aspiration of secretion vs aspiration of foodstuff and pulmonary injury is unclear. To clarify this relationship, we examined the correlations between pneumonia findings from chest computed tomography (CT) and the presence or absence of aspiration detected by FEES. Methods Eighty-five children (11 years 2 months ±7 years 2 months) underwent FEES and chest CT. Based on the FEES findings, the participants were divided into groups: with and without food aspiration, and with and without saliva aspiration. Correlations between chest CT findings of pneumonia and the presence or absence of each type of aspiration were then examined. Results No significant correlations were observed between food aspiration and chest CT findings of pneumonia, whereas saliva aspiration and chest CT findings of pneumonia were significantly correlated. In addition, saliva aspiration was significantly associated with bronchial wall thickening (p < 0.01) and atelectasis (p < 0.05). Conclusions Our findings in children suggest that: (1) the presence or absence of food aspiration detected by FEES evaluation has little correlation with pneumonia, and (2) the presence or absence of saliva aspiration may be an indicator of aspiration pneumonia risk.

To determine the general condition of elderly xerostomia patients, we collected their background and medication data in order to potentially treat their xerostomia. It is critical to identify the drugs causing xerostomia in elderly patients. A total of 521 patients who were examined at the Xerostomia Clinic of Osaka University Dental Hospital were included in the study. We obtained patients' data on age, sex, number of primary illnesses, Saxon test scores, oral moisture test, subjective symptoms, and drug types from their clinical records.The mean age of the patients was 65.2 ± 13.3 years. Although all patients exhibited xerostomia symptoms, there were a lot of patients without hyposalivation. With respect to medication, each elderly xerostomia patient took an average of 6.8 ± 4.4 medicines. A total of 26.1% of patients in their 70 s took more than ten number of drugs. In addition, the number of frequently used medication medicine was different between elderly and young patients. Most of the medicines had xerostomia as a side effect in medical package inserts. Moreover, the quantity of salivation significantly decreased in patients who took more than seven drugs in comparison with the patients who did not take medicine.As patients age, the number of medications they take tends to increase, subsequently increasing their risk of xerostomia. For the health of the patients, it is critical that an accurate diagnosis is made.To establish therapeutic strategies for treatment of xerostomia, this study provides new and important information that will help in the development of xerostomia medical treatment.

To investigate olfactory function in elderly subjects requiring nursing care to clarify its association with appetite and nutritional status. Facility for the elderly requiring nursing care. Participants: The subjects were 158 elderly people requiring nursing care and 37 elderly people not requiring nursing care. Experiment I: Olfactory function and factors (cognitive function, appetite, and nutritional status) that may be associated with it were compared between the elderly subjects requiring nursing care and those not requiring nursing care using covariance analysis in consideration of age. For evaluation, the OSIT-J was used for olfactory function, the HDS-R for cognitive function, the CNAQ for appetite, and BMI for nutritional status. Experiment II: The subjects were the same elderly subjects requiring nursing care in Experiment I, and food intake was surveyed in addition to the OSIT-J, HDS-R, CNAQ, and BMI. A univariate linear regression analysis was performed with OSIT-J as the response variable, and age, HDS-R, CNAQ, BMI, and food intake as the explanatory variables. Experiment I: On covariance analysis, the OSIT-J score was significantly lower for the elderly subjects requiring nursing care than for those not requiring nursing care (p

Organoids generated from pluripotent stem cells are used in the development of organ replacement regenerative therapy by recapitulating the process of organogenesis. These processes are strictly regulated by morphogen signalling and transcriptional networks. However, the precise transcription factors involved in the organogenesis of exocrine glands, including salivary glands, remain unknown. Here, we identify a specific combination of two transcription factors (Sox9 and Foxc1) responsible for the differentiation of mouse embryonic stem cell-derived oral ectoderm into the salivary gland rudiment in an organoid culture system. Following orthotopic transplantation into mice whose salivary glands had been removed, the induced salivary gland rudiment not only showed a similar morphology and gene expression profile to those of the embryonic salivary gland rudiment of normal mice but also exhibited characteristics of mature salivary glands, including saliva secretion. This study suggests that exocrine glands can be induced from pluripotent stem cells for organ replacement regenerative therapy., Functional salivary glands have not been generated from embryonic stem cells (mESCs) to date. Here the authors demonstrate directed in vitro differentiation of mESCs to oral ectoderm and salivary gland rudiments that form mature, functional salivary glands after orthotopic transplantation.

The aim of this study was to investigate the predictors of dental changes associated with long-term treatment with oral appliances (OAs) in patients with obstructive sleep apnea (OSA).This was a retrospective study to investigate Japanese patients with OSA receiving long-term treatment with OAs. Comparisons of cephalometric analysis were carried out between the initial and follow-up assessments of dental and skeletal changes. Based on dental changes, predictors that may cause side effects were investigated.A total of 64 patients (average age at start of treatment: 57.7 ± 14.2 years, 44 males) were included in this study. The average duration of treatment was 4.3 ± 2.1 years. Over the total treatment period, there was a significant reduction in overjet (OJ) (1.5 ± 1.3 mm) and overbite (0.90 ± 1.5 mm), and an increase in the lower incisor line to the mandibular plane (3.1 ± 5.4°). A larger reduction in OJ of ≥ 1 mm was associated with treatment duration, use frequency, and mandibular advancement of the OAs. In addition to these predictive factors, the number of teeth was correlated with the amount of OJ reduction.For long-term treatment with OAs, the risk of dental side effects should be considered, such as a reduction in OJ. A small number of maxillary teeth, as well as the factors associated with OAs, including treatment duration, use frequency, and mandibular advancement of the OAs, was correlated with an increased rate of OJ reduction.A commentary on this article appears in this issue on page 7.

The objective of this study was to determine the utility of nasoendoscopy of the upper airway as a predictor of the efficacy of oral appliance treatment in obstructive sleep apnoea (OSA).A total of 61 consecutive patients with moderate-to-severe polysomnographically diagnosed OSA were recruited for this study. Using nasoendoscopy, we prospectively assessed the velopharynx and oro/hypopharynx in each patient while awake and in the supine position. We measured cross-sectional area (CSA), and anteroposterior and lateral diameters of the airway before and after mandibular advancement, and expressed the changes in dimensions as expansion ratios (after/before). We then compared the measurements of responders and nonresponders with oral appliance treatment.The expansion ratio (median (interquartile range)) for the CSA was greater in responders compared with nonresponders in the velopharynx (2.9 (2.3–5.0)versus1.7 (1.5–1.9), pversus2.4 (1.8–3.7), pThese results indicate that nasoendoscopy may have significant clinical utility in predicting the success of oral appliance treatment.

Hypofunction of the salivary gland causes several life-disrupting side effects such as dental caries, oral candidiasis, loss of taste, and swallowing disorders. No satisfactory therapy has been established to treat salivary hypofunction. Pilocarpine represents a potential treatment for dry mouth due to Sjogren's syndrome (SS). Although subjective improvement was consistently observed with pilocarpine therapy, the mechanism was unclear. In this study, we investigated the mechanism of recovery in salivation following treatment with pilocarpine. We first examined the effectiveness of pilocarpine in SS patients as quantified by the Saxon test and the visual analogue scale average. We found that salivation ability and subjective symptoms improved by continuous administration of pilocarpine. These results demonstrated that long-term medication for dry mouth patients was more effective. However, as the mechanism remained unclear, molecular biological mechanisms were analyzed based on the effects of continuous administration of pilocarpine using model mice. In the molecular biological analysis, continuous administration of pilocarpine was effective in both ICR and SS model mice. Gene and protein expression of muscarinic acetylcholine receptor 3 (M3R) increased in salivary glands following continuous administration of pilocarpine compared with single administration. Therefore, continuous administration of pilocarpine effectively induced M3R expression, thereby activating salivation.

BACKGROUND Obstructive sleep apnoea (OSA) is characterised by recurrent episodes of partial or complete upper airway collapse during sleep and is highly prevalent in the general population. The nasopharyngeal airway stent (Nastent) is a specifically designed, preformed silicone tube that intends to maintain the upper airway patency during sleep and reduce snoring and sleep apnoea. OBJECTIVE(S) The purpose of this study was to determine the efficacy of Nastent treatment and examine predictors for Nastent treatment outcomes in patients with OSA. METHODS Consecutive thirty patients were enrolled in this study. Cephalometric radiographs were obtained to analyse the pharyngeal and craniofacial morphology. Before and after Nastent treatment, we evaluated OSA using a portable sleep study. RESULTS Twenty-nine subjects completed this study. There were significant decreases in the respiratory event index (REI) (22.4 ± 14.1 to 15.7 ± 10.4, P 50% compared with baseline REI. We evaluated the ratio of inferior airway width and middle airway width (IAW/MAW) on cephalograms as the index of the narrowest airway site. The IAW/MAW was significantly higher in responders than in non-responders (1.4 ± 0.9 vs 0.9 ± 0.4, P

Radiotherapy is commonly used in patients with head and neck cancer, and usually results in irreversible salivary glands damage and hypofunction. It is therefore important to manage such irradiation to prevent damage to the salivary glands. A previous study showed that Lactoferrin (LF) has a radioprotective effect, but the mechanism was not determined in salivary glands. In the present study, we investigated the detailed radioprotective effect of LF using both ex vivo submandibular salivary gland organ culture and ICR male mice in vivo. We found that LF had effects on both cell proliferation and CyclinD1-mediated cell-cycle progression which were regulated via the ERK1/2 and AKT signal transduction pathways. In addition, LF affected acinar cell structure and function after irradiation. These findings suggest that LF may be a useful agent to prevent irradiation effects in salivary glands.

The excision of malignant tongue tumors often produces tongue defects that can cause dysphagia. A palatal augmentation prosthesis is frequently used to treat such dysphagia. This report describes a patient who received a palatal augmentation prosthesis after a glossectomy for malignant cancer of the tongue; however, no improvement was noted in swallowing function. A lingual augmentation prosthesis was then applied to the mandible, which resulted in improved swallowing function.

Disuse atrophy of swallowing-related organs due to an excessive decrease in swallowing frequency is suspected to occur in patients with poor oral intake, especially elderly people. However, swallowing frequency in daily life has not previously been examined in the elderly. This study examined swallowing frequency in elderly people and compared these findings to those in a younger population and differences in the degree of activity in daily life. (i) We compared swallowing frequency in 20 elderly people (82·0 ± 8·3 year) and 15 healthy young people (26·5 ± 3·5 year). (ii) 20 elderly people were divided into two groups according to the degree of activity in daily life: a semi-bedridden group and bedridden group; the swallowing frequency was compared between these groups. (i) The swallowing frequency in the elderly people was 2-19 times per hour and the mean was 9·4 ± 4·9, and that in the healthy young people was 16-76 times per hour and the mean was 40·7 ± 19·5. Swallowing frequency in elderly people was significantly lower than that in young healthy people (P < 0·0001). (ii) The swallowing frequency in bedridden group was 2-11 times per hour and the mean was 6·8 ± 3·3, and that in semi-bedridden group was 3-19 times per hour and the mean was 11·9 ± 5·1. Swallowing frequency in bedridden group was significantly lower than that in semi-bedridden group (P < 0·05). These results indicate that in daily life, elderly people tend to swallow less frequently than young people. In addition, swallowing frequency was lower in elderly subjects with a low degree of activity in daily life.

Swallowing is an important physiological response that protects the airway. Although aspiration during sleep may cause aspiration pneumonia, the mechanisms responsible have not yet been elucidated. We evaluated the coordination between respiration and swallowing by infusing water into the pharynx of healthy young adults during each sleep stage. Seven normal subjects participated in the study. During polysomnography recordings, to elicit a swallow we injected distilled water into the pharynx during the awake state and each sleep stage through a nasal catheter. We assessed swallow latency, swallow apnea time, the respiratory phase during a swallow, the number of swallows, and coughing. A total number of 79 swallows were recorded. The median swallow latency was significantly higher in stage 2 (10.05 s) and stage 3 (44.17 s) when compared to awake state (4.99 s). The swallow latency in stage 3 showed a very wide interquartile range. In two subjects, the result was predominantly prolonged compared to the other subjects. There was no significant difference in the swallow apnea time between sleep stages. The presence of inspiration after swallowing, repetitive swallowing, and coughing after swallowing was more frequent during sleep than when awake. This study suggests that the coordination between respiration and swallowing as a defense mechanism against aspiration was impaired during sleep. Our results supported physiologically the fact that healthy adult individuals aspirate pharyngeal secretions during sleep.

Food bolus preparation plays an important role in swallowing food. The ability to carry out oral functions varies with age, and the same might be true of the ability to prepare food boluses. Previously developed methods for assessing food bolus preparation were not able to evaluate swallowed boluses; that is, the boluses were spat out before they were swallowed. The aim of the present study was to evaluate food bolus preparation in older adults using videoendoscopy, and to compare the food bolus preparation abilities of older adults and younger healthy adults.The participants were 30 older adults and 30 younger healthy adults. None of the participants showed any symptoms of dysphagia or eating difficulties. In each examination, an endoscope was inserted into the nasal passage, and the participant was instructed to eat cooked rice. The grinding, mixing and aggregation of each bolus was graded from 0 to 2, with higher numbers indicating more marked grinding, mixing and aggregation. We simultaneously investigated the number of chewing cycles.The older adults showed higher grinding scores and lower mixing scores than the younger healthy adults. However, neither of these differences was significant. In contrast, the older adults showed significantly lower aggregation scores and carried out a significantly greater number of chewing cycles than the younger healthy adults.Using videoendoscopy, we found that older adults showed lower aggregation scores and carried out a greater number of chewing cycles than younger healthy adults. These results suggest that older adults are less able to prepare food boluses than younger healthy adults. Geriatr Gerontol Int 2017; 17: 226-231.

It is known that solid food is transported to the pharynx actively in parallel to it being crushed by chewing and mixed with saliva in the oral cavity. Therefore, food bolus formation should be considered to take place from the oral cavity to the pharynx. In previous studies, the chewed food was evaluated after the food had been removed from the oral cavity. However, it has been pointed out that spitting food out of the oral cavity interferes with natural food bolus formation. Therefore, we observed food boluses immediately before swallowing using an endoscope to establish a method to evaluate the food bolus-forming function, and simultaneously performed endoscopic evaluation of food bolus formation and its relationship with the number of chewing cycles. The subject was inserted the endoscope nasally and instructed to eat two coloured samples of boiled rice simultaneously in two ingestion conditions ('as usual' and 'chewing well'). The condition of the food bolus was graded into three categories for each item of grinding, mixing and aggregation and scored 2, 1 and 0. The score of aggregation was high under both ingestion conditions. The scores of grinding and mixing tended to be higher in subjects with a high number of chewing cycles, and the score of aggregation was high regardless of the number of chewing cycles. It was suggested that food has to be aggregated, even though the number of chewing cycles is low and the food is not ground or mixed for a food bolus to reach the swallowing threshold.

Sialolipoma is a new variant of salivary gland lipoma, which was first proposed by Nagao et al. (Histopathology 2001; 38: 30) in 2001. We report this rare case of sialolipoma in the hard palate. A 60-year-old Japanese woman was referred to our department complaining of a painless swelling on the right side of the hard palate. Intra-oral examination revealed a soft, elastic, dome-shaped mass with 1 cm in diameter located in the posterior part of the hard palate. Magnetic resonance imaging examination revealed high intensity on T1-weighted image and isointensity on T2-weighted image. Incisional biopsy revealed that the tumor was encapsulated by fibrous tissue, consisted of adipose tissue, and also contained normal salivary gland tissue peripherally. First diagnosed as an ordinary lipoma of the hard palate, the tumor was excised. According to the recent criteria of histologic findings of sialolipoma, we rediagnosed the tumor as sialolipoma of the hard palate. J Oral Pathol Med (2006) 35: 376–8

Summary Background The frequent insertion of self-tapping screws for securing the proximal positioning plate in bimaxillary osteotomy often cause loosening of screws and plate, which produces incorrect repositioning. In this article, a newly developed base-attachment for a T-shaped proximal positioning plate for bimaxillary osteotomy is presented. Material The base-attachment set consists of a titanium base-attachment and two titanium tapped screws. The attachment has a shallow depression having the same shape as the basal part of the positioning plate. Method The base-attachment is secured by self-tapping screws until the end of the procedure, and the T-shaped proximal positioning plate is placed and secured by two titanium-tapped screws. Result By using this base-attachment, the T-shaped plate can be easily placed repeatedly without difficulty. Conclusion This base-attachment set may be useful for the frequently repositioned proximal plate in bimaxillary osteotomy.

In treatment for obstructive sleep apnea (OSA), oral appliance (OA) therapy is indicated in patients with mild–moderate OSA. However, since patients with severe OSA in whom OA therapy was effective have also been reported, it may not be possible to determine indications for OA therapy based on the severity alone. The purpose of this study was to determine indications for OA therapy using endoscopy during wakefulness in patients with severe OSA. The subjects consisted of 36 patients (27 males and 9 females) diagnosed with severe OSA using all-night polysomnography. In each patient, a nasoendoscope was inserted in a horizontal position during nasal breathing, and morphological changes in the airway of the velopharynx and oro-hypopharynx with mandibular advancement were evaluated. With mandibular advancement, the oro-hypopharynx was widened in all patients while the velopharynx was widened in 29 patients, but not in 7. The apnea hypopnea index (AHI) reduction rate after OA application was 79.8 % (SD, 13.0 %) in the group with and 40.6 % (SD, 27.0 %) in the group without velopharyngeal widening, being significantly different between the two groups. In the group showing velopharyngeal widening, evaluation of the direction of widening revealed two types: the “all-round type”, which is circumferential widening in the anteroposterior–lateral directions, and the “lateral dominant type”, which is widening mainly in the lateral direction. The AHI reduction rate was 80.1 % (SD, 15.0 %) for the all-round type and 79.3 % (SD, 10.6 %) for the lateral dominant type showing no significant difference. (1) Concerning indications for OA therapy, findings in the velopharynx rather than those in the hypopharynx may be important. (2) The effects of OA therapy can be expected in the presence of velopharyngeal widening irrespective of its direction. Thus, to determine whether OA therapy is indicated, endoscopic evaluation of morphological changes in the velopharynx with mandibular advancement may be important.

Summary This study examined the aspect of the regulation of velum movement in the transition from the oral to pharyngeal phases of swallowing in relation to changes in the swallowing volume and viscosity by means of measurment of levator veli palatini muscle activity. The subjects were nine normal adults, ranging in age from 24 to 30 years. The swallowing volume was set at 1/4, 1/2 and 1 volume of the optimum volume of green tea for swallowing determined in each subject, and the viscosity was adjusted to 0, 2·0 and 4·6 Pa·s by mixing with thickener. Nine test foods were prepared in total. The electromyographic activity of the levator veli palatini muscle was monitored using bipolar hooked wire electrodes. The levator veli palatini muscle activity was defined as the integrated electromyographic wave. The mean in swallowing each test food was determined in each subject. The levator veli palatini muscle activity increased with the swallowing volume for all subjects (P

The hyoid bone moves during swallowing due to contraction of suprahyoid muscles, which are critical components of normal swallowing function. It has been reported that the muscle force and shortening velocity decline gradually with age. Reduced hyoid velocities may delay the sealing of the laryngeal vestibule and opening of the cricopharyngeal muscle. We hypothesised that the hyoid velocity could be a factor influencing aspiration. This study evaluated effects of bolus volume changes on the hyoid distance and velocity in normal swallowing. The subjects were 21 healthy young adults. Lateral projection videofluorography was recorded while each subject swallowed 2·5, 5·0, 10 and 20 mL of liquid barium. We evaluated the maximum hyoid distance (Max d), anterior and superior distance (Max ad, Max sd). And, we evaluated the maximum velocity (Max v), anterior and superior velocity (Max av, Max sv). Two-way anova test revealed that Max d, Max ad and Max sd for different bolus volumes are not significantly different. But, two-way anova test showed statistically significant difference in Max v, Max av and Max sv among different bolus volume (P < 0·01). Tukey's test showed that there are significant differences in Max v between 2·5 and 20 mL, 5·0 and 20 mL, 10 and 20 mL, and 2·5 and 10 mL swallowing. And, Tukey's test showed significant differences in Max av and Max sv between 2·5 and 20 mL, 5·0 and 20 mL, and 10 and 20 mL swallowing. It is possible that a larger bolus volume requires greater maximum hyoid velocity. We plan to study hyoid velocity in elderly subjects and in those with dysphagia.

Oral fibroblasts stimulated invasion of oral-carcinoma cells into the collagen matrix. The mechanisms of the fibroblast-induced stimulation of invasiveness was further investigated by examining cell motility and proteolytic activity of tumor cells, using mainly an adenoid-cystic-carcinoma cell line (ACCS) and normal fibroblasts from gingival tissues. Conditioned medium from the fibroblasts grown in serum-free medium was fractionated on a Superdex 200 pg column, and Peak 1 eluted at 200 to 300 kDa and Peak 2 eluted at 50 to 100 kDa were found to contain different specific activity. Treatment of ACCS cells with Peak 1 resulted in an increase in the production of proteolytic enzymes. Peak 2 stimulated both chemotaxis and chemokinesis of ACCS cells. A chemotactic factor was purified from the heparin-unbound fraction of Peak 2 by anion exchange and hydrophobic chromatography, and was named "fibroblast-derived motility factor (FDMF)". At 1 microg/ml, FDMF stimulated chemotaxis of ACCS cells by 4-fold compared with unstimulated controls. Characterization of the physicochemical properties of FDMF suggested that it might be different from any known motility factors. Exposure of ACCS cells to FDMF resulted in reduced amounts of actin stress fiber in the cytoplasm and induction of tyrosine phosphorylation of several cellular proteins detectable 30 to 60 min after treatment. These FDMF-induced changes were blocked by pre-treatment either with genistein or with pertussis toxin. These findings suggest that FDMF may be a novel protein which stimulates cell motility via a signaling pathway mediated by a pertussis-toxin-sensitive G protein and tyrosine phosphorylation.

It has been reported that the levator veli palatini muscles of speakers with velopharyngeal incompetence tend to demonstrate muscle fatigue during speech. This study examined whether a speech aid prosthesis might reduce levator muscle fatigue in such speakers. Eight individuals with post-surgical cleft palates, and who wore a speech aid prosthesis, were studied. Each person was asked to pronounce the syllable [pu] more than 50 times. Mean power frequency (MPF) of one syllable was obtained from electromyographic data from the levator muscle. The MPF regression line was calculated during the course of syllable repetition. The absolute values of the slopes of the regression lines with the prosthesis were significantly smaller than those without the prosthesis. It was shown that the prosthesis reduced the decrease in MPF during speech. These results suggested that speech aid prostheses reduce levator muscle fatigue during speech in persons with velopharyngeal incompetence.

We report a case of osseous dysplasia (OD) showing extremely rare clinical features. A 37-year-old Japanese woman was referred to our clinic complaining of a left alveolar bony swelling at an impacted canine. Radiographic examinations revealed a mixed radiopaque lesion involving the impacted left canine and also revealed an impacted left wisdom tooth with a cystic change and a clear radiopaque lesion suspected to be odontoma. All the extracted upper teeth and odontoma showed hypercementosis and the canine was fully involved in it. Histopathologically, they showed the same features and were diagnosed as OD. The findings of multiple OD from incompletely erupted teeth and odontoma in our case may well show that OD can arise from any tooth with periodontal ligaments and that focal OD can show expansive growth like the ossifying fibroma.

The velopharynx closes during swallowing and pneumatic activities. Pneumatic closure, which is acquired, prevents expiratory air from passing into the nasal cavity, whereas during swallowing, velopharyngeal closure is achieved innately, preventing regurgitation into the nasal cavity. These findings suggest that velopharyngeal closure during swallowing is a different mechanism from that during pneumatic activity. The purpose of this study was to clarify activity differences of the levator veli palatini muscle during swallowing, speech, and blowing using power spectra analysis. Five normal adults served as subjects. Each subject was instructed to speak, blow, and swallow. Electromyograms of the levator muscle were recorded and the spectrum analyzed for each task to calculate the mean power frequency (MPF) of EMG signals. There was no significant difference in MPF between speech and blowing for all subjects. MPF was significantly greater during swallowing than during pneumatic activities for all subjects. The MPF value can reflect the composition of active motor units during muscle contraction. It was therefore indicated that the motor units of the levator muscle participating in contraction were different during swallowing and respiratory activities.

Many organs, including salivary glands, lung and kidney, are formed during embryonic development by epithelial branching. In branching morphogenesis, repetitive epithelial cleft and bud formation create the complex three-dimensional branching structures characteristic of many organs. Although the mechanisms are poorly understood, one might involve the site-specific accumulation of some regulatory protein. Here we show that the extracellular matrix protein fibronectin is essential for cleft formation during the initiation of epithelial branching. Fibronectin messenger RNA and fibrils appeared transiently and focally in forming cleft regions of submandibular salivary-gland epithelia, accompanied by an adjacent loss of cadherin localization. Decreasing the fibronectin concentration by using small interfering RNA and inhibition by anti-fibronectin or anti-integrin antibodies blocked cleft formation and branching. Exogenous fibronectin accelerated cleft formation and branching. Similar effects of fibronectin suppression and augmentation were observed in developing lung and kidney. Mechanistic studies revealed that fibrillar fibronectin can induce cell-matrix adhesions on cultured human salivary epithelial cells with a local loss of cadherins at cell-cell junctions. Thus, fibronectin expression is required for cleft formation in branching morphogenesis associated with the conversion of cell-cell adhesions to cell-matrix adhesions.

In this unit, the authors describe a new technique, T7-SAGE, in which a high-fidelity T7 amplification step is combined with SAGE analysis. In order to avoid extra PCR or other forms of amplification, the authors incorporate only two cycles of T7-based RNA amplification as the initial step. This T7-based amplification step has high accuracy. In addition, T7 RNA polymerase has high processivity and functions effectively even when broad stretches of nucleotides are being amplified. Although no protocol that includes an amplification step can claim to permit determination of absolute transcript number, since slight changes in estimated transcript frequency are always possible, T7 procedures appear to be the safest to date. This new T7-SAGE procedure should facilitate application of SAGE for gene-expression profiling using minimal quantities of starting material, such as from embryonic tissues and microdissected cells from histological sections of tissues.

We recently showed that mouse semaphorin H (MSH), a secreted semaphorin molecule, acts as a chemorepulsive factor on sensory neurites. In this study, we found for the first time that MSH induces neurite outgrowth in PC12 cells in a dose-dependent manner. Comparison of Ras-mitogen-activated protein kinase (MAPK) signaling pathways between MSH and nerve growth factor (NGF) revealed that these pathways are crucial for MSH action as well as NGF. K-252a, an inhibitor of tyrosine autophosphorylation of tyrosine kinase receptors (Trks), did not inhibit the action of MSH, suggesting that MSH action occurs via a different receptor than NGF. L- and N-types of voltage-dependent Ca(2+) channel blockers, diltiazem and omega-conotoxin, inhibited MSH-induced neurite outgrowth and MAPK phosphorylation in a Ca(2+)-dependent manner. A transient elevation in intracellular Ca(2+) level was observed upon MSH stimulation. These findings suggest that extracellular Ca(2+) influx, followed by activation of the Ras-MAPK signaling pathway, is required for MSH induced PC12 cell neurite outgrowth.

Semaphorins/collapsins, a family of genes with a semaphorin domain conserved from insects through to mammals, are believed to be involved in axon guidance during neuronal development. We report the expression patterns of mouse semaphorin messenger RNAs. Among secreted semaphorins, mouse semaphorin H is structurally most similar to semaphorin III/D, the first semaphorin identified as a collapsing factor for sensory axons. However, its expression patterns apparently differ from those of semaphorin III/D. The messenger RNAs are distributed in the brain widely but unevenly during development, in particular, in the main olfactory bulb, hippocampus and pontine nucleus. In the trunk, the expression level is high in mesodermal tissues surrounding the dorsal root ganglia, while it is low in the spinal cord. Moreover, we examined whether this molecule has activity to collapse growth cones of sensory neurons, as well as semaphorin III/D. Mouse semaphorin H collapsed growth cones of sensory neurons of the dorsal root ganglion in a dose-dependent manner, and anti-neuropilin antibodies inhibited this activity. Taken together, these results suggest that mouse semaphorin H can function as a chemorepellent to guide sensory peripheral nerves, most likely via neuropilin as a receptor.