Relationships between Lip Seal Strength, Tongue Pressure, and Daytime Sleepiness in Japanese Workers: A Cross-Sectional Study.

This cross-sectional study aimed to examine the relationships between lip seal strength, tongue pressure, and daytime sleepiness in Japanese workers. A self-administered questionnaire which comprised the Epworth Sleepiness Scale (ESS) was completed by 496 workers, and excessive daytime sleepiness was defined by an ESS score of 11 or over. Lip seal strength and tongue pressure were measured in all participants, and multiple regression analyses were performed to examine the effects of lip seal strength and tongue pressure on daytime sleepiness. The median ESS score was 5.0 (25th and 75th percentiles: 2.0 and 8.0), and 42 (8.5%) workers had excessive daytime sleepiness. The median lip seal strength was 13.5 N (11.4, 16.3), and the tongue pressure was 41.7 kPa (35.2, 48.3). Workers with higher ESS scores had significantly lower levels of lip seal strength than those without, following adjustments for age and body mass index (BMI) values (ß (95% confidence interval): -0.043 [-0.081, -0.004]). However, tongue pressure was not significantly associated with ESS score after adjustments for age and/or BMI. These results suggest that maintaining moderate lip seal strength may help prevent excessive daytime sleepiness in Japanese workers regardless of age or BMI.

Effects of interferential current electrical stimulation (IFCS) on mastication and swallowing function in healthy young adults: A preliminary study.

OBJECTIVES: This study aimed to investigate the effects of interferential current electrical stimulation (IFCS) on masticatory and swallowing function. MATERIALS AND METHODS: Twenty healthy young adults were enrolled. The measurement items were spontaneous swallowing frequency (SSF), voluntary swallowing frequency (VSF), saliva secretion volume (SSV), glucose elution volume (GEV), and velocity of chew (VOC). All participants underwent both IFCS and sham stimulation (without stimulation, sham). Two sets of independent IFCS electrodes were placed on the bilateral neck. The precise location of the upper electrodes was just below the angle of the mandible, while the lower electrodes were placed at the anterior border of the sternocleidomastoid muscle. The intensity of IFCS was determined to be one level below the perceptual threshold that all participants felt discomfort. Statistical analysis was performed using a two-way repeated measures analysis of variance. RESULTS: For IFCS, the results of each measurement before and during stimulation were SSF: 1.16 and 1.46, VSF: 8.05 and 8.45, SSV: 5.33 and 5.56 g, GEV: 171.75 and 208.60 mg/dL, and VOC: 87.20 and 95.20, respectively. SSF, GEV, and VOC during stimulation were significantly increased by IFCS (SSF, p = .009; GEV, p = .048; and VOC, p = .007). Following sham stimulation, the results were SSF: 1.24 and 1.34, VSF: 7.75 and 7.90, SSV: 5.65 and 6.04 g, GEV: 176.45 and 187.35 mg/dL, and VOC: 91.35 and 88.25, respectively. CONCLUSION: While no significant differences were observed in the sham group, our findings suggest that IFCS of the superior laryngeal nerve may impact not only the swallowing function but also the masticatory function.

Lip Seal Strength and Tongue Pressure among Japanese Male Workers: Comparison of Different Age Groups.

Lip seal strength and tongue pressure are related to sarcopenia in older adults and are directly linked to the quality of life of workers after retirement. This study examined lip seal strength and tongue pressure among Japanese male workers by age. A self-administered questionnaire survey including alcohol consumption and smoking was conducted on 454 male workers. Height, weight, lip seal strength, and tongue pressure were also measured and then stratified by age (20s, 30s, 40s, 50s, and 60s and over). The mean (25th, 75th percentiles) lip seal strength and tongue pressure for all workers were 13.7 N (11.6, 16.4) and 41.7 kPa (35.2, 48.2), respectively. Both lip seal strength and tongue pressure were lowest in the 20s, at 12.1 N (9.6, 14.0) and 40.6 kPa (33.4, 47.6), respectively. The multiple regression analysis adjusted for smoking showed a significant positive association between lip seal strength and BMI for the 20s, 50s, and 60s and over, and a significant positive association between tongue pressure and BMI for the 30s, 40s, 50s, and 60s and over. To maintain oral health in older adults, it may be useful to measure workers' lip seal strength and tongue pressure and intervene at an earlier stage.

Involvement of ghrelin in the regulation of swallowing motor activity in an arterially perfused rat preparation.

Ghrelin, a peripheral peptide produced in the stomach, is involved in the neural networks that control food intake. Alterations in motor components, such as swallowing, are believed to be significant in the regulation food intake by orexigenic signals. However, there has been no detailed investigation of the relationship between ghrelin and swallowing activities induced in motor nerves innervating the pharyngeal and laryngeal muscles. In this study, we examined the effects of ghrelin administration on swallowing motor activity in arterially perfused rats. Injection of distilled water (0.5 ml) into the oral cavity or electrical stimulation of the superior laryngeal nerve evoked swallowing motor activity in the cervical vagus nerve. Administration of ghrelin (6 nM), but not des-acylated ghrelin (6 nM), into the perfusate increased the peak burst amplitude and burst duration, and shortened the first burst interval of water injection-induced swallowing. These ghrelin-induced changes in swallowing motor activity were blocked by the administration of JMV2959 (6 µM), a growth hormone secretagogue receptor antagonist. In preparations in which the hypothalamus was removed, ghrelin had no effect on swallowing motor activity. Furthermore, ghrelin-induced changes were counteracted by the administration of BIBO3304 (1 µM) or L-152,804 (1 µM), antagonists of neuropeptide Y Y1 and Y5 receptors, respectively, which are essential for ghrelin-induced enhancement of food intake. Ghrelin also increased the peak burst amplitude and burst duration of the swallowing motor activity evoked by electrical stimulation of the superior laryngeal nerve, although the effects of ghrelin on the number of swallowing bursts and burst intervals varied with stimulus intensity. These results suggest that ghrelin enhances the magnitude and frequency of bursts of swallowing motor activity by acting via the hypothalamic neural network, and that neuropeptide Y Y1 and Y5 receptors are involved in this enhancement.

Changes in oral function, swallowing function, and quality of life in patients with head and neck cancer: a prospective cohort study.

BACKGROUND: Head and neck cancer (HNC) treatment can cause oral morbidities, such as oral dryness and dysphagia, affecting the patient's quality of life (QOL). The relationship between oral functions and QOL in patients with early-stage HNC remains poorly studied. This study aimed to evaluate changes in the QOL of patients with early-stage HNC and identify factors that affect the QOL of these patients. METHODS: In this prospective cohort study, 37 patients who underwent early-stage (Stage I/Stage II) HNC treatment were evaluated for their oral function, swallowing function, and the QOL score at baseline (BL) and 12 months after surgical treatment (12 M). The participants were divided into two groups: patients who returned to the BL QOL score at 12 M (RE; n = 26) and those who did not (NR; n = 11). RESULTS: In total, 29.7% (11/37) patients with early-stage HNC did not return to the BL QOL score at 12 M. There was no significant difference between the RE and NR groups regarding the oral and swallowing function. Moreover, oral and swallowing function of all patients returned to the BL at 12 M. The NR group showed lower QOL scores than the RE group in the global health status, and "sticky saliva" parameters in the questionnaires. CONCLUSION: Restoration of the oral function is insufficient to improve the QOL of patients with early-stage HNC. The treatment of these patients should instead consider several factors that affect their QOL.

A study of acoustic characteristics of voluntary expiratory sounds produced before and immediately after swallowing.

To evaluate the expiratory sounds produced during swallowing recorded simultaneously with videofluorographic examination of swallowing (VF) using fast Fourier transform (FFT), and to examine the relationship between dysphagia and its acoustic characteristics. A total of 348 samples of expiratory sounds were collected from 61 patients with dysphagia whose expiratory sounds were recorded during VF. The VF results were evaluated by one dentist and categorized into three groups: safe group (SG), penetration group (PG), and aspiration group (AG). The duration and maximum amplitude of expiratory sounds produced were measured as the domain characteristics on the time waveform of these sounds and compared among the groups. Time window-length appropriate for FFT and acoustic discriminate values (AD values) of SG, PG, and AG were also investigated. The groups were analyzed using analysis of variance and Scheffé's multiple comparison method. The maximum amplitude of SG was significantly smaller than those of PG and AG. The mean duration in SG (2.05 s) was significantly longer than those in PG (0.84 s) and AG (0.96 s). The AD value in SG was significantly lower than those in PG and AG. AD value detects penetration or aspiration, and can be useful in screening for dysphagia.

Developmental changes in GABAergic and glycinergic synaptic transmission to rat motoneurons innervating jaw-closing and jaw-opening muscles.

Trigeminal motoneurons (MNs) innervating the jaw-closing and jaw-opening muscles receive numerous inhibitory synaptic inputs from GABAergic and glycinergic neurons, which are essential for oromotor functions, such as the orofacial reflex, suckling, and mastication. The properties of the GABAergic and glycinergic inputs of these MNs undergo developmental alterations during the period in which their feeding behavior proceeds from suckling to mastication; however, the detailed characteristics of the developmental patterns of GABAergic and glycinergic transmission in these neurons remain to be elucidated. This study was conducted to investigate developmental changes in miniature inhibitory postsynaptic currents (mIPSCs) in masseter (jaw-closing) and digastric (jaw-opening) MNs using brainstem slice preparations obtained from Wistar rats on postnatal day (P)2-5, P9-12, and P14-17. The frequency and amplitude of glycinergic mIPSCs substantially increased with age in both the masseter and digastric MNs. The rise time and decay time of glycinergic mIPSCs in both MNs decreased during development. In contrast, the frequency of GABAergic components in masseter MNs was higher at P2-5 than at P14-17, whereas that in the digastric MNs remained unchanged throughout the postnatal period. The proportion of currents mediated by GABA-glycine co-transmission was higher at P2-5, and then it decreased with age in both MNs. These results suggest that characteristics related to the development of inhibitory synaptic inputs differ between jaw-closing and jaw-opening MNs and between GABAergic and glycinergic currents. These distinct developmental characteristics may contribute to the development of feeding behaviors.

The Device of Ethylene Vinyl Acetate Sheet for Trismus Caused by Bilateral Mandible Fractures.

Trismus is commonly caused by temporomandibular joint disorders and maxillofacial fractures. We report the case of a 62-year-old woman with trismus and difficulty in mastication caused by bilateral mandibular fractures. She had a maximal interincisal opening distance (MID) of 22 mm. Mouth-opening training was administered using a novel dental mouth-training device custom-made using ethylene vinyl acetate sheets and according to the dentition and extent of mouth-opening of the patient. After 2 months of training, the MID increased to 42 mm. With adequate training, this device is effective in treating trismus due to scarring.

Changes in Oral Function and Quality of Life in Tongue Cancer Patients Based on Resected Area.

OBJECTIVE: Treatment of tongue cancer caused oral morbidities such as oral dryness, and dysphagia. The purpose of this study is to examine the time course of oral function and QOL based on resected area for patients after tongue cancer resection. METHODS: 31 patients who underwent tongue cancer resection at the Showa University Head and Neck Oncology Center. The participants were divided into two groups; 24 participants in partial/hemi glossectomy group (PG), and seven in subtotal/total glossectomy group (TG). Participants were evaluated swallowing function (FOIS and MASA-C), tongue pressure (TP: kPa), BMI, whole body muscle mass (kg), and QOL evaluation (EORTC QLQ-C30, H & N35). Participants were measured at baseline (before surgical treatment), 1, 3, and 6 months after surgical treatment (1M, 3M, and 6M). RESULTS: At baseline, tongue pressure and FOIS score of PG were significant higher than that of TG. At 1M, TP, MASA-C, and FOIS score of PG were significant higher than that of TG. At 3M, TP, MASA-C, and FOIS score of PG were significant higher than that of TG. At 6M, TP and MASA-C were significantly higher than that of TG. QOL measurements did not noted any significant difference between groups before 6M. At 6M, Some QOL measurements of TG related tongue function (Swallowing, Senses, Speech, Social contact) were significantly lower than PG. CONCLUSIONS: The resected area had significant effects on oral morbidities and feeding function. It is necessary to develop more effective rehabilitation methods to improve patients QOL who had functional impairment remained.
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Effects of Neuromuscular Electrical Stimulation (NMES) on salivary flow in healthy adults.

BACKGROUND: Neuromuscular electrical stimulation (NMES) is a method used for enhancing suprahyoid muscle activity and is widely applied as a treatment for dysphagia. Patients often complain of saliva pooling in the pharynx during NMES. Therefore, the purpose of this study was to investigate the changes in salivary flow during NMES. MATERIAL AND METHODS: Twenty healthy adults participated in this study. Electrical stimulation was applied at constant strength for 60 minutes to the suprahyoid muscles using VitalStim®. Participants were examined under three conditions of NMES: sensory threshold plus 75% of the difference between sensory and pain thresholds (75% Stim), SensoryStim, and Sham. Saliva collections, using a 10-min spitting method, were performed seven times: before stimulation (S1), during stimulation (S2-S6), and 5 min after stimulation ended (S7). RESULTS: Significant differences were observed in saliva flow between S1 and S7, as well as S2 and S7 in 75% Stim. CONCLUSIONS: This study indicates that an increase in saliva flow was promoted after NMES. Therefore, NMES may have effects on patients with xerostomia. Key words:Neuromuscular electrical stimulation, suprahyoid muscle, sensory threshold, pain threshold, saliva flow.

Sole-ground contact and sitting leg position influence suprahyoid and sternocleidomastoid muscle activity during swallowing of liquids.

Clinically, the stable sole-ground contact in the diet is considered as important for achieving safe swallows in the dysphagic patients. However, the effects of varied sole-ground contacts on swallow-related muscles activities remain unclear. The aim of this study was to investigate the effects of sole-ground contacts on the muscle activities during swallow for various materials; 26 healthy adult subjects participated in this study. Three different sole-ground contact conditions were investigated; sole-ground contact with knees bent to 90° (KB 90°), sole-ground contact with knees bent to 135° (KB 135°), and sole-ground off the floor (Off). Participants swallowed four bolus materials (saliva, 5-ml water, 10-ml water, and 5-ml yogurt) in each sole-ground contact condition. The muscular activities of the suprahyoid (SH) muscle and the sternocleidomastoid muscle during swallowing were detected and recorded using surface electromyography. The sole-ground contact pressure was evaluated using the data acquisition system. Duration of SH during 10-ml water swallow for Off was significantly longer than that for KB 90°. Duration of SH during 5-ml yogurt swallow for Off was significantly longer than that for KB 90°. Integration of SH during 10-ml water swallow for Off was significantly greater than that for KB 135°. Integration of SH during 5-ml yogurt swallow for Off was significantly greater than that for KB 90°. No significant differences were found in peak of SH. Sole-ground contact conditions had significant effect on swallow-related muscles activities. The stable sitting positions might be more advantageous for performing effective swallows compared with less stable sitting positions.

Acute Stage Longitudinal Change of Quality of Life from Pre- to 3 Months after Surgical Treatment in Head and Neck Cancer Patients.

PURPOSE: Head and neck cancer (HNC) patients experience various posttreatment side effects that decrease quality of life (QOL). Some previous study reported that QOL of HHC patients were returned baseline (before treatment) after a year post treatment. However, acute stage longitudinal changes of QOL in HNC patients remains unclear. This point might be important for early reintegration of HNC patients. This study aimed to investigate the acute stage longitudinal change of the relationship between QOL and oral function in HNC patients had surgery. METHODS: 45 HNC patients (23 men) scheduled for surgical treatment were enrolled in this study. Primary tumor sites were 22 tongue, 5 maxilla, 4 mandible, 3 pharynx and others. Weight, body mass index (BMI), whole body soft lean mass (SLM), and skeletal muscle mass (SMM) were evaluated as muscle mass-related measurements. Lip closure force (LC) and tongue pressure (TP) were evaluated as oral function measurements. Feeding function was evaluated using the Functional Oral Intake Scale (FOIS). QOL was assessed using the European Organization for Research and Treatment of Cancer QOL Questionnaire QLQ-C30 and H&N 35. Measures were evaluated at pre-surgical treatment (PT), and 1 month (1M) and 3 months (3M) after surgery. The change of QOL parameters and relationships between measurements were assessed. RESULTS: For QOL assessments, role functioning, fatigue, speech problems, trouble with social eating, trouble with social contact, and opening mouth significantly decreased from PT to 1M, but significantly increased from 1M to 3M. Weight, BMI, SLM, SMM, LC, TP, and FOIS demonstrated significant relationships with QOL from PT to 1M. Meanwhile, from 1M to 3M, weight, BMI, SLM, SMM, LC, and FOIS showed significant relationships with QOL assessments. CONCLUSIONS: Both oral function and muscle mass-related measurements significantly affected QOL in HNC patients.

Male Gender and High Trait Anxiety Are 2 Major Factors Associated With Severe Dental Fear and Avoidance.

The purpose of this article is to investigate the association between the background characteristics of patients with severe fear of dental treatment who frequently avoid dental care and the degree of difficulty in treating them. At the time of initial presentation at a dental phobia clinic, each of 321 subjects was asked to complete the State-Trait Anxiety Inventory, the Dental Anxiety Scale, and a health questionnaire related to phobic objects. Subjects who rejected oral examination with a dental mirror were categorized as being severely difficult to treat, whereas those who were able to undergo examination were categorized as being moderately difficult to treat. In the statistical analysis, assessment items that were correlated with difficulty to treat were designated as independent variables for a logistic regression analysis. In the logistic regression analysis, significant correlations were observed for gender (male > female with adjusted odds ratio, 4.121; 95% CI, 1.96-8.65) and level of trait anxiety (2.401; 1.01-5.73). Male gender and a high trait anxiety were identified as major factors associated with severe dental fear and avoidance.

Dysphagia and Oral Morbidities in Chemoradiation-Treated Head and Neck Cancer Patients.

This study prospectively evaluated relationships between oral morbidities and swallowing ability in head/neck cancer patients following chemoradiation therapy (CRT) and at 3 months following CRT. Thirty patients with confirmed head/neck cancer undergoing chemoradiation were assessed with a battery of swallowing measures and measures of oral morbidities related to chemoradiation (xerostomia, mucositis, pain, taste/smell, oral moisture). All measures were completed at baseline (within the first week of CRT), at 6 weeks (end of treatment), and at 3 months following chemoradiation. Descriptive and univariate statistics were used to depict change over time in swallowing and each oral morbidity. Correlation analyses evaluated relationships between swallowing function and oral morbidities at each time point. Most measures demonstrated significant negative change at 6 weeks with incomplete recovery at 3 months. At 6 weeks, mucositis ratings, xerostomia, and retronasal smell intensity demonstrated significant inverse relationships with swallowing function. In addition, oral moisture levels demonstrated significant positive relationships with swallowing function. At 3 months, mucositis ratings maintained a significant, inverse relationship with swallow function. Taste and both orthonasal and retronasal smell intensity ratings demonstrated inverse relationships with measures of swallow function. Swallow functions and oral morbidities deteriorate significantly following CRT with incomplete recovery at 3 months post treatment. Furthermore, different patterns of relationships between swallow function measures and oral morbidities were obtained at the 6-week versus the 3-month assessment point suggesting that different mechanisms may contribute to the development versus the maintenance of dysphagia over the trajectory of treatment in these patients.

Coordinated control of the tongue during suckling-like activity and respiration.

The tongue can move freely and is important in oral motor functions. Tongue movement must be coordinated with movement of the hyoid, mandible, and pharyngeal wall, to which it is attached. Our previous study using isolated brainstem-spinal cord preparations showed that application of N-methyl-D-aspartate induces rhythmic activity in the hypoglossal nerve that is coincident with rhythmic activity in the ipsilateral trigeminal motor nerve. Partial or complete midline transection of the preparation only abolishes activity in the trigeminal motor nerve; therefore, the neuronal network contributing to coordinated activity of the jaw/tongue muscles is located on both sides of the preparation and sends motor commands to contralateral trigeminal motoneurons. Arterially perfused decerebrate rat preparations exhibit stable inspiratory activity in the phrenic nerve, with efferent nerves innervating the upper airway muscles (the hypoglossal nerve, a branch of the cervical spinal nerve, the external branch of the superior laryngeal nerve, and the recurrent laryngeal nerve) under normocapnic conditions (5% CO2). During hypercapnia (8% CO2), pre-inspiratory discharges appear in all nerves innervating upper airway muscles. Such coordinated activity in the pre-inspiratory phase contributes to dilation of the upper airway and improves hypercapnia.

Accuracy of cervical auscultation in detecting the presence of material in the airway.

Several studies have investigated the accuracy of cervical auscultation (CA). However, both the sensitivities and the specificities of CA in detecting dysphagic conditions varied widely among these studies. These wide variations of the accuracy of CA might be caused by differences of the targeted sounds, such as the expiratory sound (ES) and/or swallowing sound (SS). Forty-six dysphagic patients were served as subjects. Patients who had unoccluded tracheostoma and patients who could not follow the instructions were excluded. During the videofluorographic swallowing study (VFSS), the subjects swallowed 3 ml of yogurt containing barium sulfate. The VFSS images were recorded with acoustic signals including both the swallowing and respiratory sounds detected by our method. Classification of the VFSS images was decided by consensus of the three dentists using a penetration-aspiration scale (PAS). Recorded VFSS images were classified into the following 2 groups based on PAS: "no or minimum risk group": PAS1-2; and "possible risk group": PAS3-8. As a result of the classification of VFSS findings, 30 samples were evaluated as no or minimum risk group and 16 as possible risk group. Twelve observers including 10 dentists other than 3 dentists who evaluated VFSS images and 2 speech pathologists auditorily diagnosed "negative" and "positive." Sensitivity, specificity, and intra-rater reliability was calculated for the 3 types of acoustic samples. The sensitivity of the intra-rater reliability was 60.3% for ES, 76.6% for SS, and 89.9% for ES + SS. The sensitivity of intra-rater reliability of ES + SS samples was significantly higher than that of ES (p < .01) and SS (p < .05). The sensitivity of intra-rater reliability of SS was significantly higher than that of ES (p < .01). The specificity of the intra-rater reliability was 53.7% for ES, 50.3% for SS, and 44.5% for ES + SS. ES + SS might be most useful for detecting the presence of material in the airway.

Clinical inter-rater reliability of postural control techniques.

Effectiveness of postural control techniques to compensate for oropharyngeal dysphagia have been recommended and used by several clinicians. However, the inter-rater reliability of these techniques is not well understood. The purpose of this study was to clarify the ambiguity of postural control techniques using statistical analyses. A total of 50 clinicians involved in dysphagia treatment participated in this study, where a healthy male served as the simulated patient. The following clinically used postures were measured by two investigators on two separate days: chin down, right/left incline, and right/left rotation. Postural angles were measured twice by two investigators on each day. Data obtained for the angle of each posture were visually displayed. Data from both investigators were assessed for each posture using the Youden plot, which analyzes data variability for systematic errors and accidental errors separately. The correlation coefficient for examining the measurement error between investigators was calculated. The results showed considerable variation between clinicians regarding the postures used, and significant differences were noted each day. The correlation coefficient for a total of four measurements was more often lower on Day 2 than that on Day 1. The details of the instructions provided by clinicians were not fixed, and the same specified posture was not reproduced even when instructions were provided to the same subject. These findings suggest poor inter-rater reliability because of the variability of selected postures when using statistical analyses. Therefore, standardized postures need to be developed that can be easily measured and reproduced.

Coordination of NMDA-induced rhythmic activity in the trigeminal and hypoglossal nerves of neonatal mice in vitro.

Suckling is a rhythmic jaw movement that is symmetrical on the left and right side and is highly coordinated with tongue movement. Thus, we investigated the neuronal mechanisms of the left/right and jaw/tongue coordinations during N-methyl-d-aspartate (NMDA)-induced fictive suckling using isolated brainstem-spinal cord preparations obtained from neonatal mice. We observed synchronous low-frequency rhythmic activity in the left/right trigeminal motor nerves, which differed from respiration, and high-frequency rhythmic trigeminal activity, which was side-independent. The low-frequency rhythmic trigeminal activity was also synchronized with the hypoglossal nerve activity. After a complete midline separation of the preparation or a partial midline transection of the brainstem from the anterior inferior cerebellar artery to the junction of the vertebral artery, the low-frequency rhythmic trigeminal activity disappeared, whereas the high-frequency rhythmic trigeminal activity and low-frequency rhythmic hypoglossal activity still remained. These results suggest that the neuronal network that generates low-frequency rhythmic activity likely contributes to the synchronized activity of the left/right jaw muscles and to the jaw/tongue muscles, where it sends its command to the trigeminal motoneurons mainly via the commissural pathway that crosses the transected midline region. Such a neuronal network may underlie the coordinated movements of the jaw and tongue during suckling.

Growth stimulating antibody, as another predisposing factor of Graves' disease (GD): analysis using monoclonal TSH receptor antibodies derived from patients with GD.

TSH receptor antibody (TRAb) is clinically classified into thyroid stimulating antibody (TSAb) and thyroid-stimulation blocking antibody (TSBAb). Although the former is considered to cause Graves' disease (GD), its activity does not necessarily reflect hormone production and goiter size. Moreover, uptake of 99mTcO4(-), the best indicator for GD, is correlated with activity of TSH binding inhibitor immunoglobulin better than activity of TSAb. Because uptake of 99mTcO4(-) reflects thyroid volume, these observations suggest that there exist TRAb with thyrocyte growth stimulating activity (GSA) other than TSAb. In this study, we analyzed GSA of monoclonal TRAb established from patients with GD or idiopathic myxedema (IME). GSA was measured as the degree of FRTL-5 cell growth stimulated by each TRAb. The signaling pathways of the cell growth were pharmacologically analyzed. The cell growth stimulated by TSH was strongly suppressed by protein kinase A (PKA) inhibitor, but was not affected by extracellular signal regulated kinase kinase (MEK) inhibitor. Although TSAb from GD stimulated the cell growth, both inhibitors suppressed it. Surprisingly, the cell growth was also induced by TSBAb from GD and was only suppressed by MEK inhibitor. TSBAb from IME did not have GSA and attenuated the cell growth stimulated by TSH. We concluded that 1; in GD, not only TSAb but some TSBAb could stimulate thyrocyte growth. 2; TSBAb might be classified with respect to their effects on thyrocyte growth; i.e., thyrocyte growth stimulating antibody and thyrocyte growth-stimulation blocking antibody.