Objective assessment of mastication predominance in healthy dentate subjects and patients with unilateral posterior missing teeth.

We aimed to investigate mastication predominance in healthy dentate individuals and patients with unilateral posterior missing teeth using objective and subjective methods. The sample comprised 50 healthy dentate individuals (healthy dentate group) and 30 patients with unilateral posterior missing teeth (partially edentulous group). Subjects were asked to freely chew three kinds of test foods (peanuts, beef jerky and chewing gum). Electromyographic activity of the bilateral masseter muscles was recorded. The chewing side (right side or left side) was judged by the level of root mean square electromyographic amplitude. Mastication predominance was then objectively assessed using the mastication predominant score and the mastication predominant index. Self-awareness of mastication predominance was evaluated using a modified visual analogue scale. Mastication predominance scores of the healthy dentate and partially edentulous groups for each test food were analysed. There was a significant difference in the distribution of the mastication predominant index between the two groups (P < 0·05). The mastication predominant score was weakly correlated with self-awareness of mastication predominance in the healthy dentate group, whereas strong correlation was observed in the partially edentulous group (P < 0·05). The results suggest that the individuals with missing unilateral posterior teeth exhibited greater mastication predominance and were more aware of mastication predominance than healthy dentate individuals. Our findings suggest that an objective evaluation of mastication predominance is more precise than a subjective method.

Effect of visual biofeedback of posterior tongue movement on articulation rehabilitation in dysarthria patients.

Articulation is driven by various combinations of movements of the lip, tongue, soft palate, pharynx and larynx, where the tongue plays an especially important role. In patients with cerebrovascular disorder, lingual motor function is often affected, causing dysarthria. We aimed to evaluate the effect of visual biofeedback of posterior tongue movement on articulation rehabilitation in dysarthria patients with cerebrovascular disorder. Fifteen dysarthria patients (10 men and 5 women; mean age, 70.7 ± 10.3 years) agreed to participate in this study. A device for measuring the movement of the posterior part of the tongue was used for the visual biofeedback. Subjects were instructed to produce repetitive articulation of [ka] as fast and steadily as possible between a lungful with/without visual biofeedback. For both the unaffected and affected sides, the range of ascending and descending movement of the posterior tongue with visual biofeedback was significantly larger than that without visual biofeedback. The coefficient of variation for these movements with visual biofeedback was significantly smaller than that without visual biofeedback. With visual biofeedback, the range of ascent exhibited a significant and strong correlation with that of descent for both the unaffected and affected sides. The results of this study revealed that the use of visual biofeedback leads to prompt and preferable change in the movement of the posterior part of the tongue. From the standpoint of pursuing necessary rehabilitation for patients with attention and memory disorders, visualization of tongue movement would be of marked clinical benefit.

Marked improvement of insulin sensitivity without enhancement of GLP-1 and insulin secretion after Roux-en-Y gastric bypass surgery in a mildly obese patient with diabetes.

Roux-en-Y gastric bypass is an option of treatment for morbidly obese patients with diabetes. However, the value of the operation in mildly obese patients is not established. We report the first prospective systematic endocrine and metabolic analysis in a mildly obese patient who underwent a Roux-en-Y gastric bypass. In a 49-year-old man with BMI 32.6 kg/m(2) having type 2 diabetes, intramucosal gastric cancer was treated by partial gastrectomy with Roux-en-Y gastric bypass. Pre-operatively, he received 53 U/day insulin and the HbA1c value was 63 mmol/mol: meal tolerance test showed diabetic hyperglycemia and low insulin sensitivity with attenuated insulin secretion and normal glucagon-like peptide 1(7-36) secretion. After the operation, hypoglycemic agent was stopped. Body weight reduced from 84.0 to 77.0 kg within 2 weeks and increased thereafter to 79.4 kg at 4 months later, when the degree of hyperglycemia was unchanged as indexed by a HbA1c value of 62 mmol/mol. Upon repeated meal tolerance test, no increase of glucagon-like peptide 1 and insulin secretion, but significantly improved hepatic and peripheral insulin sensitivity were found, compared to the preoperative meal tolerance test. Marked dissociation of endocrine and metabolic effects of Roux-en-Y gastric bypass, that is, absence of increased glucagon-like peptide 1/insulin secretion with improvement of insulin sensitivity, was found in a mildly obese patient with type 2 diabetes.

Development of a speech-discriminating electromyogram system for routine ambulatory recordings for the low-level masseter muscle activity.

Previous work suggests a relationship between sustained low-level tooth clenching and the aetiology of myogenous temporomandibular disorder (TMD) pain. This study aimed to establish a reliable system with which to evaluate low-level electromyographic (EMG) activity related to low-level tooth clenching while discriminating speech activity, which is one of the most common facial muscle activities to be discriminated from low-level clenching. This device should facilitate the clinical evaluation of awake muscle activity in TMD patients. Eight female and eight male subjects (38.9 ± 11.3 years) participated in the study to evaluate the validity of estimation of speech duration. Actual speech duration was defined by one examiner by pointing out the timing of beginning and end point of each speech on wave-editing software. Speech duration, as detected by a voice sensor system, which was activated by a voice loudness of 54.71 ± 5.00 dB, was significantly correlated with the above actual speech duration (P < 0.01, R(2) = 0.9935). An actual recording with the system was carried out in one TMD patient and one healthy volunteer and revealed that the duration of diurnal EMG activity higher than 5% MVC was 1649.16 s and 95.99 s, respectively. As the voice sensor system adopted in this study could define the exact onset and offset of each segment of speech, EMG activity during speech could be precisely discriminated. The results of this study demonstrate that the EMG system with voice sensor system would be an effective tool for the evaluation of low-level masticatory muscle activity.

Dynamics of posterior tongue during pronunciation and voluntary tongue lift movement in young adults.

The lifting-up movement of the posterior part of the tongue to touch the palate, which is a requirement for performing physiological functions such as deglutition and speech, is an important phenomenon that is difficult to objectively evaluate. The purpose of this study was to develop a new modality to evaluate the tongue-lifting function, especially in the posterior part of the tongue, and to elucidate the dynamic properties of the tongue in normal subjects. Twenty-three healthy volunteers (9 men and 14 women; mean age, 27·6years) participated in this study. A new device was developed that could evaluate the up-down movement of the posterior part of the tongue in a non-invasive manner. The experimental tasks were as follows: (i) /a/ pronunciation for 1s followed by /ka/ pronunciation (a-ka task), (ii) /a/ pronunciation for 1s followed by /ga/ pronunciation (a-ga task) and (iii) /a/ pronunciation for 1s followed by a voluntary push-up movement of the posterior part of the tongue (a-lift task). Maximum upward velocity in the a-ga task was larger than that in the a-ka task (P<0·05). The a-lift task showed the highest tongue lift range among the three tasks, and the a-ga task showed a higher range than that of the a-ka task (P<0·05). This study revealed that precise quantification of the motility of the posterior part of the tongue, which would be useful in rehabilitation of articulation and/or swallowing, could be achieved using this new device in a non-invasive manner.

Manifestation of preferred chewing side for hard food on TMJ disc displacement side.

The purpose of this study was to reveal the relationship between chewing-side preference and anterior disc displacement (ADD) of the TMJ. Thirty-two healthy subjects with ages ranging from 26 to 34 years were selected from volunteer students at the Okayama University Dental School. Subjects were asked to chew freely with two kinds of test foods, beef jerky (hard food) and chiffon cake (soft food), thus expecting different amounts of mechanical loading on the TMJ. One, 4, and 7 s after starting the mastication, subjects were asked to open their mouth momentarily to have a digital image of their mouth taken. The bolus placement area was measured by processing the digital images, calculated as the number of pixel of bolus area. Area asymmetry index was used for the determination of preferred chewing side (PCS). Oblique sagittal MRI scanning in the closed mouth position was taken to evaluate the articular disc position. In asymptomatic subjects with ADD, a significant predominance of the PCS on the ipsilateral side of ADD was observed during the mastication of hard food. On the contrary, no correlation was found between unilateral ADD and PCS for the soft food. From the results of this study, it is suggested that ADD is the associating factor of PCS for hard food. Therefore, it would be necessary to break down the concept of PCS into at least two categories, one for hard food and one for soft food, considering the mechanical loading on the TMJ.

Anti-fibrotic effect of adipose-derived mesenchymal stem cell conditioned medium in muscle fibrosis.

OBJECTIVE: Recent investigations have demonstrated that the administration of MSC in mouse model of diseases provided beneficial effects. On the other hand, human adipose-derived MSC condition medium (ADSC-CM) is reported as containing beneficial secreted factors, but its role in muscle fibrosis has not been identified. The aim of this study was to investigate the inhibitory effects of MSC-CM in muscle fibrosis in vitro using the C2C12 murine muscle, myoblast cell line. MATERIALS AND METHODS: C2C12 cells were cultured overnight in 0.1% albumin-Dulbecco's Modifies Eagle's Medium (DMEM). The cells were then pre-incubated in ADSC-CM for 20 min, treated with 2.5-10 ng/mL human TGFß1 for 8-72 hours and analyzed using RT-qPCR, Western blot and immunofluorescent staining. RESULTS: Treatment with 20% ADSC-CM for 3 days suppressed αSMA protein expression in TGFß1 treated C2C12 cells. ADSC-CM stimulated the proliferation of C2C12 cells in a dose-dependent manner. Furthermore, TGFß1 induced Acta2/αSMA mRNA expression which was inhibited by ADSC-CM treatment for 8 hours. Decorin, one of the dermatan sulfate proteoglycans and an endogenous inhibitor of TGFß1, was expressed in ADSC-CM, but not in TGFß1 pre-incubated ADSC-CM. CONCLUSIONS: Our studies provide useful information for establishing anti-fibrotic mechanism(s) of ADSC-CM, thus facilitating potential application to prevent muscle fibrosis.

Long-term survival of a patient with amyotrophic lateral sclerosis (ALS) who received autologous adipose-derived mesenchymal stem cells.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a progressive debilitating neurodegenerative disease with a life expectancy of 3-5 years from initial symptoms. We report a case of ALS who received autologous adipose-derived mesenchymal stem cells (ADSC) and was followed up for 7 years. CASE REPORT: A 46-year-old man noticed weakness of his legs, difficulties on going down the stairs and coughing during eating in 2009. After complete workout, a diagnosis of ALS was confirmed. His ALS Functional Rating Scale-R (ALSFS-R) was 43. Symptoms rapidly progressed and he coughed and choked during eating. Starting in 2013, the patient received a total of six intravenous infusions of autologous ADSC. Changes in electromyogram, nerve conduction, and ALSFS-R were assessed. RESULTS: Soon after the administration, he noticed that he did not cough during conversation or eating food. Although he had difficulty in walking down the stairs, he remained well without coughing, dysarthria, or dysphagia. His ALSFS-R increased up to 45. Fascicular potentials were not detected in any muscles examined including trapezius muscle and rectus femoris muscles. The patient was well for 7 years after ADSC therapy by the time of this report and more than 10 years from the time of onset. CONCLUSIONS: The present case suggests that autologous ADSC can be administered safely and may be potentially useful in patients with ALS. Further investigations are warranted in order for the results to be generalized to other ALS patients.

Novel mutation of the Notch3 gene in a Japanese patient with CADASIL.

We report a novel missense mutation of the Notch3 gene in a Japanese family with CADASIL. The Cys49Gly mutation in this family is located in exon 2 of the Notch3 gene. Most of the documented Notch3 gene mutations occur in exons 3 or 4. On the other hand, there are few reports around the world of mutations in exon 2 of the Notch3 gene, and this is the first report of a mutation in exon 2 of the gene in a Japanese family. In general, CADASIL mutations involve a cysteine residue. Such mutations may influence the tertiary structure of the Notch3 protein, resulting in protein dysfunction. Thus, the CADASIL in the present case may be a consequence of the mutation in exon 2 causing a structural change in the Notch3 protein.

Effects of mitogen-activated protein kinase inhibitors or phosphodiesterase inhibitors on interleukin-1-induced cytokines production in synovium-derived cells.

The effects of mitogen-activated protein (MAP) kinase inhibitors or phosphodiesterase (PDE) inhibitors on interleukin (IL)-1-induced cytokines production in synovium-derived cells were investigated. Human synoviocyte (HS) or synovial sarcoma (SW982) stimulated by IL-1beta (100 ng/ml) produced various cytokines including IL-6, IL-8, GROalpha, VEGF, basic FGF and tumor necrosis factor alpha (TNFalpha) in vitro. SB202190 or SB203580, an inhibitor of p38 MAP kinase, inhibited all cytokines production in both cells. PD98059, an inhibitor of MAP kinase kinase (MEK), inhibited IL-6, IL-8 and basic FGF production in HS and all cytokines production except basic FGF in SW982. However, many of its effects were weaker than those of SB202190 or SB203580. Quazinone, an inhibitor of cyclic GMP-inhibited PDE, scarcely affected cytokines production in both cells. Rolipram or R0201724, an inhibitor of cyclic AMP-specific PDE, inhibited IL-8 and basic FGF production in HS and TNFalpha production in SW982, however, it enhanced the other cytokines production in SW982. These results suggest that the activation of MAP kinase cascade may be important for IL-1-induced cytokines production in synovium-derived cells. On the other hand, the role of cyclic AMP may be dependent on cell and cytokine types.

Laryngostrobovideography using a flexible laryngofiberscope performed in conjunction with the phonatory examination.

The phonatory examination was performed while monitoring vocal fold vibration by laryngostrobovideography. Vocal fold vibration was video-taped by a laryngostroboscope and flexible laryngofiberscope inserted through the nasal cavity. Simultaneously, the phonatory examination was conducted with a phonation analyzer. The data were entered into a personal microcomputer via an A/D converter and analyzed to obtain the parameters of sound pitch, sound intensity and mean expiratory air flow volume, which were superimposed on the color video monitor screen.

Striatal [3H]GTP binding in developing rats: involvement of sulfhydryl residues, Ca2+ and Mg2+.

The influence of sulfhydryl reagents and cations on specific [3H]GTP binding to striatal membranes was investigated in developing rats. Two components of non-cooperative [3H]GTP binding sites were observed in 15, 30, 70 and 360 day old rats but only a single component in 1 and 7 day old ones. The KD for low affinity binding increased with age. Bmax values for both high and low affinity binding increased with age and reached a peak at 30 days, followed by a decrease at 70 and 360 days. At 7 and 70 days, NaCl 1-100 mM did not affect [3H]GTP binding but CaCl2 and MgCl2 significantly inhibited the binding over a concentration range of 1-100 mM. TLC analysis of [3H]GTP and the metabolites in the binding medium and membranes showed that [3H]GTP in both membranes and in the medium was decreased by addition of 1 mM CaCl2 and 1 mM MgCl2 into the binding medium. On days 7 and 70, p-chloromercuriphenyl sulfonate strongly inhibited [3H]GTP binding, and dithiothreitol significantly increased binding but dopamine, apomorphine, spiperone and alpha-flupenthixol did not increase binding up to 0.1 mM. It is suggested that sulfhydryl residues, Ca2+ and Mg2+ are involved in the regulation of guanine nucleotide binding and that the regulatory mechanism becomes functional at 7 days. Ca2+ and Mg2+ seem to act by stimulating degradation of [3H]GTP. In addition, the density of GTP binding sites reaches a peak at around 30 days and the affinity decreases with age.

A new quadruple therapy for the eradication of Helicobacter pylori. Effect of pretreatment with omeprazole on the cure rate.

To elucidate whether pretreatment with omeprazole decreases the cure rate of Helicobacter pylori infection with a new quadruple therapy, and thus, whether this pretreatment should not be used in clinical practice, we conducted a randomized trial. Ninety patients with chronic peptic ulcer disease and nonulcer dyspepsia, with biopsy-proven H. pylori infection were randomly assigned to the two following regimens: Group 1 (n = 45) received omeprazole 20 mg once daily for 2 weeks (days 1-14), and 500 mg amoxicillin granules and 250 mg metronidazole thrice daily, and roxithromycin 150 mg twice daily for 1 week (days 8-14), Group 2 (n = 45) received the same antibiotic treatment as group 1 for 1 week (days 1-7), in addition to omeprazole treatment for 2 weeks (days 1-14). Four weeks after the treatment ended, endoscopy was repeated, with two biopsy specimens each taken from the antrum and the corpus (total of four specimens) for a urease test, histological analysis, and culture to establish cure of infection. A patient was regarded as cured only if all three methods gave negative results for H. pylori. In the intention-to-treat analysis, 42 of 45 patients (93.3%; 95% confidence intervals [CI], 81.7%-98.6%) in group 1 were cured compared with 43 of 45 patients (95.6%; 95% CI, 84.9%-99.5%) in group 2. In the per-protocol analysis, the corresponding figures were 42/44 (95.5%; 95% CI 84.5%-99.4%) and 43/44 (97.7%; 95% CI, 88.0%-99.9%). There were no significant differences in the cure rate between the two groups on either analysis. All patients, except for one who had an allergic reaction, completed the treatment regimens. Fifty to sixty percent of the patients had no side effects while the rest had mild to moderate side effects. The new quadruple therapy consisting of omeprazole, amoxicillin, metronidazole, and roxithromycin appears suitable for use in clinical practice, as the cure rate was 95% and no severe side effects were observed. Pretreatment with omeprazole did not reduce the cure rate for this new quadruple therapy.

Pharmacological characterization of central alpha-adrenoceptors which mediate clonidine-induced locomotor hypoactivity in the developing rat.

The present experiment was designed to pharmacologically characterize receptors which mediate the clonidine-induced locomotor change in the developing rat. A subcutaneous injection of clonidine (0.78 mumol/kg) produced locomotor hyperactivity in 7-day-old rats but hypoactivity in 20-day-old rats. Phenoxybenzamine (1.5 mumol/kg, 5.9 mumol/kg and 15 mumol/kg) decreased spontaneous activity in a dose-dependent manner but did not antagonize clonidine-induced hypoactivity in 20-day-old rats. By contrast, the significant reversal of the clonidine-induced hypoactivity by pretreatment with phentolamine (1.6 mumol/kg and 6.3 mumol/kg), yohimbine (1.3 mumol/kg and 5.1 mumol/kg) and piperoxan (7.4 mumol/kg) was observed at such doses when the blockers did not cause any hypoactivity by themselves. It is suggested that clonidine could induce locomotor hypoactivity by activating presynaptic (alpha 2-type) alpha-adrenoceptors in the CNS of 20-day-old rat.

Involvement of leukotriene B4 in arthritis models.

We investigated the role of leukotriene B4 (LTB4) in murine arthritis models using a leukotriene A4 (LTA4) hydrolase inhibitor, SA6541. SA6541 inhibited the severity of collagen-induced arthritis and muramyl dipeptide (MDP)-induced hyperproliferation of synovial cells in vivo. SA6541 also inhibited LTA4-induced hyperproliferation of synovial stromal cells in vitro. These results suggest that LTB4 may play an important role in arthritis models.

TRH-induced behavioral arousal in developing rats pretreated with 6-hydroxydopa.

The behavioral effect of thyrotropin releasing hormone (TRH) was investigated in the developing rat pretreated with 6-OHDOPA at birth. An IP injection of TRH (20 mg/kg) increased walking with sniffing, rearing, body shaking, grooming, chewing and licking in the 7-, 14-, 20- and 30-day-old as well as in the adult rat. TRH-induced locomotor stimulation began a few minutes after the injection and lasted for approximately 60 min. But on Day 7, TRH produced locomotor stimulation betwen 1.5 hr and 3.5 hr after the injection. Neonatal treatment with 6-OHDOPA markedly potentiated TRH-induced locomotor stimulation and behavioral arousal in the 7-day-old rat but not in the 14-day-old and adult rat. The marked potentiation of TRH-induced locomotor stimulation by 6-OHDOPA in the 7-day-old rat was reduced by alpha-flupenthixol (pA2=5.9) and phenoxybenzamine (pA2=4.4). These results suggest that central dopamine neurons are involved in TRH-induced behavioral arousal in the infant rat.

A single oral administration of conjugated linoleic acid enhanced energy metabolism in mice.

We investigated the effect of a single oral administration of conjugated linoleic acid (CLA) on energy metabolism in mice. Male Std ddY mice were orally administered CLA (5 mL/kg weight) or linoleic acid (5 mL/kg weight) (both solutions at concentrations of 73.5%) as a control. Oxygen consumption was significantly greater in the CLA-administered mice than in the control mice. Respiratory quotient was slightly lower in the CLA-adminis-tered mice than in the control mice. We calculated fat and carbohydrate oxidation from oxygen consumption and respiratory quotient. Fat oxidation in the CLA-administered mice was significantly higher than in the control mice, and there was no difference in carbohydrate oxidation. Serum concentrations of noradrenalin and adrenalin in the CLA administered mice were significantly higher than in the control mice. These results suggested that CLA enhanced sympathetic nervous activity and energy metabolism.

Gradual tilting of crystallographic orientation and configuration of dislocations in GaN selectively grown by vapour phase epitaxy methods

Cross-sectional transmission electron microscope (TEM) observation was performed for selectively grown gallium nitride (GaN) in order to examine the dependence of GaN microstructure on the growth conditions. The GaN films were grown by hydride vapour phase epitaxy (HVPE) or metalorganic vapour phase epitaxy (MOVPE) on GaN covered with a patterned mask. Thin foil specimens for TEM observation were prepared with focused ion beam (FIB) machining apparatus. It was demonstrated that the c-axis of GaN grown over the terrace of the mask tilts towards the centre of the terrace when the GaN is grown in a carrier gas of N2. The wider terrace results in a larger tilting angle if other growth conditions are identical. The tilting is attributed to 'horizontal dislocations' (HDs) generated during the overgrowth of GaN on the mask terrace. The HDs in HVPE-GaN have a semi-loop shape and are tangled with one another, while those in MOVPE-GaN are straight and lined up to form low-angle grain boundaries.

Mercury contamination in the Yatsushiro Sea, south-western Japan: spatial variations of mercury in sediment.

Mercury-contaminated effluent was discharged into Minamata Bay from a chemical plant over a 20-year period until 1965 (from 1958 to 1959, effluent was discharged into Minamata River), causing Minamata disease. In an effort to characterize the extent of the contamination in the Yatsushiro Sea, the vertical and horizontal distributions of mercury in sediment were investigated. Sediment was sampled at 62 locations in the southern part of the sea from 4 to 6 March 1996. In the lower layers of the long cores of sediment, the total amount of mercury was at a relatively uniform low concentration. We interpret these low values to represent the background concentration absent of anthropogenic influence. The background value thus estimated for the Yatsushiro Sea was 0.059 +/- 0.013 mg kg(-1) (mean +/- S.D., n = 51). The highest concentration in each sample ranged from 0.086 to 3.46 mg kg(-1) (mean, 0.57 mg kg(-1)). The higher values were obtained at stations near Minamata Bay and the Minamata River (the sources of the pollution). Concentrations decreased with distance from the source. An inspection of the vertical profiles of mercury concentration in cores suggested that the deposited mercury had not been fixed in sediment but had been transported, despite 30 years having past since the last discharge of contaminated effluent. At nine stations, extractable inorganic and organic mercury concentrations were determined differentially. Inorganic mercury is the predominant species in sediment and organic mercury comprising approximately 1% of the total.

Small intestine transplantation: a logical solution for short bowel syndrome?

The purpose of this study is to determine whether small intestine transplantation could be considered as an alternative treatment in infants and children with short bowel syndrome. The potential nutritional consequence of orthotopic small intestine transplantation was evaluated in a rat model. Young Lewis strain rats (weighing 250 to 275 g) were used. Lewis rats with resection of 90% of the small intestine were studied as short bowel group (group I, n = 5). In the transplant group rats, 90% of the original small intestine was transplanted orthotopically using microvascular techniques (group II, n = 5). During the study period of 8 weeks, group II gained weight at rates equal to that of normal age matched rats (+30% of the preoperative weight), whereas rats with short bowel (group I) lost 10% of their weight. Two weeks following transplantation, serum albumin levels were maintained in the normal range in group II. However, group I rats showed decreased albumin levels. Serum cholesterol levels showed no significant difference between the two groups. Maltose absorption was evaluated as a functional test of small intestinal graft absorption (1.0 mg/g body weight of maltose was orally administered, and serum glucose levels were measured). The glucose level at 45 minutes was significantly blunted in group I in comparison with group II. The data from this study suggested that small intestine transplantation can produce adequate nutritional support to sustain growth and development in this rat model. It would be anticipated that small intestine transplantation in patients with short bowel syndrome would also benefit nutritionally.