Cholinergic denervation in patients with idiopathic rapid eye movement sleep behaviour disorder.

BACKGROUND AND PURPOSE: Cholinergic dysfunction appears to play a role in the cognitive impairment observed in Parkinson's disease and dementia with Lewy bodies. The occurrence of cholinergic dysfunction in the early stages of these conditions, however, has not been investigated. The objective of this study was to investigate cholinergic function in patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD), a disorder recognized to be an early stage of both Parkinson's disease and dementia with Lewy bodies. METHODS: A total of 21 patients with polysomnography-confirmed iRBD with no evidence of parkinsonism and cognitive impairment and 10 controls underwent positron emission tomography (PET) to assess brain acetylcholinesterase levels (11 C-donepezil PET) and nigrostriatal dopaminergic function (18 F-DOPA PET). Clinical examination included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination and Montreal Cognitive Assessment. RESULTS: The 11 C-donepezil PET was successfully performed in 17 patients with iRBD and nine controls. Compared with controls, patients with iRBD showed a mean 7.65% reduction in neocortical 11 C-donepezil levels (P = 0.005). Bilateral superior temporal cortex, occipital cortex, cingulate cortex and dorsolateral prefrontal cortex showed the most significant reductions at voxel level. CONCLUSION: Reduced neocortical 11 C-donepezil binding in our patients indicates cholinergic denervation and suggests that the projections from the nucleus basalis of Meynert, which supplies cholinergic innervation to the neocortex, are dysfunctional in iRBD. Longitudinal studies will clarify if these changes are predictive of future cognitive impairment in these patients.

Longitudinal changes in 18 F-THK5351 positron emission tomography in corticobasal syndrome.

BACKGROUND AND PURPOSE: Corticobasal syndrome (CBS) is pathologically characterized by tau deposits in neuronal and glial cells and by reactive astrogliosis. In several neurodegenerative disorders, 18 F-THK5351 has been observed to bind to reactive astrocytes expressing monoamine oxidase B. In this study, the aim was to investigate the progression of disease-related pathology in the brains of patients with CBS using positron emission tomography with 18 F-THK5351. METHODS: Baseline and 1-year follow-up imaging were acquired using magnetic resonance imaging and positron emission tomography with 18 F-THK5351 in 10 subjects: five patients with CBS and five age-matched normal controls (NCs). RESULTS: The 1-year follow-up scan images revealed that 18 F-THK5351 retention had significantly increased in the superior parietal gyrus of the patients with CBS compared with the NCs. The median increases in 18 F-THK5351 accumulation in the patients with CBS were 6.53% in the superior parietal gyrus, 4.34% in the precentral gyrus and 4.33% in the postcentral gyrus. In contrast, there was no significant increase in the regional 18 F-THK5351 retention in the NCs. CONCLUSIONS: Longitudinal increases in 18 F-THK5351 binding can be detected over a short interval in the cortical sites of patients with CBS. A monoamine oxidase B binding radiotracer could be useful in monitoring the progression of astrogliosis in CBS.

Improvement of gemcitabine sensitivity of p53-mutated pancreatic cancer MiaPaCa-2 cells by RUNX2 depletion-mediated augmentation of TAp73-dependent cell death.

Pancreatic cancer exhibits the worst prognostic outcome among human cancers. Recently, we have described that depletion of RUNX2 enhances gemcitabine (GEM) sensitivity of p53-deficient pancreatic cancer AsPC-1 cells through the activation of TAp63-mediated cell death pathway. These findings raised a question whether RUNX2 silencing could also improve GEM efficacy on pancreatic cancer cells bearing p53 mutation. In the present study, we have extended our study to p53-mutated pancreatic cancer MiaPaCa-2 cells. Based on our current results, MiaPaCa-2 cells were much more resistant to GEM as compared with p53-proficient pancreatic cancer SW1990 cells, and there existed a clear inverse relationship between the expression levels of TAp73 and RUNX2 in response to GEM. Forced expression of TAp73α in MiaPaCa-2 cells significantly promoted cell cycle arrest and/or cell death, indicating that a large amount of TAp73 might induce cell death even in the presence of mutant p53. Consistent with this notion, overexpression of TAp73α stimulated luciferase activity driven by p53/TAp73-target gene promoters in MiaPaCa-2 cells. Similar to AsPC-1 cells, small interfering RNA-mediated knockdown of RUNX2 remarkably enhanced GEM sensitivity of MiPaCa-2 cells. Under our experimental conditions, TAp73 further accumulated in RUNX2-depleted MiaPaCa-2 cells exposed to GEM relative to GEM-treated non-silencing control cells. As expected, silencing of p73 reduced GEM sensitivity of MiPaCa-2 cells. Moreover, GEM-mediated Tyr phosphorylation level of TAp73 was much more elevated in RUNX2-depleted MiaPaCa-2 cells. Collectively, our present findings strongly suggest that knockdown of RUNX2 contributes to a prominent enhancement of GEM sensitivity of p53-mutated pancreatic cancer cells through the activation of TAp73-mediated cell death pathway, and also provides a promising strategy for the treatment of patients with pancreatic cancer bearing p53 mutation.

Super-atmospheric pressure ionization mass spectrometry and its application to ultrafast online protein digestion analysis.

Pressure is a key parameter for an ionization source. In this Special Feature article, Lee Chuin Chen and colleagues review super-atmospheric pressure ionization MS with electrospray, corona-discharge-based chemical ionization, and field desorption. They routinely run their mass spectrometer with ion source pressures ranging from several to several tens of atmospheres. A number of strategies have been used to preserve the high vacuum of the instrument while working with a high-pressure (HP) ion source. A recent prototype uses a booster pump with variable pumping speed added to the first pumping stage of the mass spectrometer to regulate a constant vacuum pressure. Further, a new HP-ESI source allowing rapid (a few seconds) online protein digestion MS is also reported. Dr. Lee Chuin Chen is Associate Professor in the Department of Interdisciplinary Research at the University of Yamanashi (Yamanashi, Japan). His main research interest is the development of novel mass spectrometric methods for in-situ medical diagnosis.

Desorption of low-volatility compounds induced by dynamic friction between microdroplets and an ultrasonically vibrating blade.

Friction plays an important role in desorption and/or ionization of nonvolatile compounds in mass spectrometry, e.g., sonic spray, easy ambient sonic-spray ionization, solvent-assisted inlet ionization, desorption electrospray, etc. In our previous work, desorption of low molecular weight compounds induced by solid/solid dynamic friction was studied. The objective of this work was to investigate desorption of low-volatility compounds induced by liquid/solid friction. Water/methanol (1/1) microdroplets with ∼30 µm in diameter were generated by using a piezoelectric microdroplet generator. They were injected to analytes deposited on the flat surface of a blade vibrating ultrasonically with the frequency of 40 kHz. Neutral molecules desorbed from the blade were ionized by a helium dielectric barrier discharge (DBD), generating strong signals for samples including drugs, explosives, and insecticides. These signals were not detected when either the blade vibrator or the piezoelectric microdroplet generator was off. In contrast, for ionic compounds such as 1-butyl-3-methylimidazolium bis(trifluoro-methylsulfonyl)imide, p-chlorobenzyl pyridinium chloride, and rhodamine B, strong ion signals were obtained when the vibrator and droplet generator were on, but DBD was off. Sub-nanogram limits of detection were attained for low-volatility compounds.

Electrospray droplet impact secondary ion mass spectrometry using a vacuum electrospray source.

RATIONALE: In electrospray droplet impact (EDI) developed in our laboratory, an atmospheric pressure electrospray source has been used. To increase the ion beam intensity and reduce the evacuation load, a vacuum electrospray cluster ion source using a silica capillary was developed. METHODS: A silica capillary with a tip inner diameter of 8 µm was used for vacuum electrospray using aqueous 10% methanol. To stabilize the flow rate of the liquid for nano-electrospray, a home-made constant pressure liquid pump was also developed. RESULTS: By using the silica tip nano-electrospray emitter and a constant pressure pump, stable electrospray with flow rate of 22 nL/min was realized without using any heating system such as laser irradiation. Comparative study of mass spectra obtained by atmospheric pressure EDI (A-EDI) and vacuum EDI (V-EDI) was made for various samples such as thermometer molecule, peptide, polystyrene, Alq(3), NPD, C(60), indium, and SiO(2). V-EDI showed slightly milder ionization than A-EDI. CONCLUSIONS: Because V-EDI gave higher target current (5-10 nA) than A-EDI (a few nA at most), V-EDI secondary ion mass spectrometry (SIMS) would be a useful technique for the surface and interface analysis.

Atmospheric pressure chemical ionization of explosives using alternating current corona discharge ion source.

The high-sensitive detection of explosives is of great importance for social security and safety. In this work, the ion source for atmospheric pressure chemical ionization/mass spectrometry using alternating current corona discharge was newly designed for the analysis of explosives. An electromolded fine capillary with 115 µm inner diameter and 12 mm long was used for the inlet of the mass spectrometer. The flow rate of air through this capillary was 41 ml/min. Stable corona discharge could be maintained with the position of the discharge needle tip as close as 1 mm to the inlet capillary without causing the arc discharge. Explosives dissolved in 0.5 µl methanol were injected to the ion source. The limits of detection for five explosives with 50 pg or lower were achieved. In the ion/molecule reactions of trinitrotoluene (TNT), the discharge products of NOx (-) (x = 2,3), O3 and HNO3 originating from plasma-excited air were suggested to contribute to the formation of [TNT - H](-) (m/z 226), [TNT - NO](-) (m/z 197) and [TNT - NO + HNO3 ](-) (m/z 260), respectively. Formation processes of these ions were traced by density functional theory calculations. Copyright © 2015 John Wiley & Sons, Ltd.

Silencing of RUNX2 enhances gemcitabine sensitivity of p53-deficient human pancreatic cancer AsPC-1 cells through the stimulation of TAp63-mediated cell death.

Runt-related transcription factor 2 (RUNX2) has been considered to be one of master regulators for osteoblast differentiation and bone formation. Recently, we have described that RUNX2 attenuates p53/TAp73-dependent cell death of human osteosarcoma U2OS cells bearing wild-type p53 in response to adriamycin. In this study, we have asked whether RUNX2 silencing could enhance gemcitabine (GEM) sensitivity of p53-deficient human pancreatic cancer AsPC-1 cells. Under our experimental conditions, GEM treatment increased the expression level of p53 family TAp63, whereas RUNX2 was reduced following GEM exposure, indicating that there exists an inverse relationship between the expression level of TAp63 and RUNX2 following GEM exposure. To assess whether TAp63 could be involved in the regulation of GEM sensitivity of AsPC-1 cells, small interfering RNA-mediated knockdown of TAp63 was performed. As expected, silencing of TAp63 significantly prohibited GEM-dependent cell death as compared with GEM-treated non-silencing cells. As TAp63 was negatively regulated by RUNX2, we sought to examine whether RUNX2 knockdown could enhance the sensitivity to GEM. Expression analysis demonstrated that depletion of RUNX2 apparently stimulates the expression of TAp63, as well as proteolytic cleavage of poly ADP ribose polymerase (PARP) after GEM exposure, and further augmented GEM-mediated induction of p53/TAp63-target genes, such as p21 (WAF1) , PUMA and NOXA, relative to GEM-treated control-transfected cells, implying that RUNX2 has a critical role in the regulation of GEM resistance through the downregulation of TAp63. Notably, ablation of TAp63 gave a decrease in number of γH2AX-positive cells in response to GEM relative to control-transfected cells following GEM exposure. Consistently, GEM-dependent phosphorylation of ataxia telangiectasia-mutated protein was remarkably impaired in TAp63 knockdown cells. Collectively, our present findings strongly suggest that RUNX2-mediated repression of TAp63 contributes at least in part to GEM resistance of AsPC-1 cells, and thus silencing of RUNX2 may be a novel strategy to enhance the efficacy of GEM in p53-deficient pancreatic cancer cells.

Non-invasive cerebellar stimulation--a consensus paper.

The field of neurostimulation of the cerebellum either with transcranial magnetic stimulation (TMS; single pulse or repetitive (rTMS)) or transcranial direct current stimulation (tDCS; anodal or cathodal) is gaining popularity in the scientific community, in particular because these stimulation techniques are non-invasive and provide novel information on cerebellar functions. There is a consensus amongst the panel of experts that both TMS and tDCS can effectively influence cerebellar functions, not only in the motor domain, with effects on visually guided tracking tasks, motor surround inhibition, motor adaptation and learning, but also for the cognitive and affective operations handled by the cerebro-cerebellar circuits. Verbal working memory, semantic associations and predictive language processing are amongst these operations. Both TMS and tDCS modulate the connectivity between the cerebellum and the primary motor cortex, tuning cerebellar excitability. Cerebellar TMS is an effective and valuable method to evaluate the cerebello-thalamo-cortical loop functions and for the study of the pathophysiology of ataxia. In most circumstances, DCS induces a polarity-dependent site-specific modulation of cerebellar activity. Paired associative stimulation of the cerebello-dentato-thalamo-M1 pathway can induce bidirectional long-term spike-timing-dependent plasticity-like changes of corticospinal excitability. However, the panel of experts considers that several important issues still remain unresolved and require further research. In particular, the role of TMS in promoting cerebellar plasticity is not established. Moreover, the exact positioning of electrode stimulation and the duration of the after effects of tDCS remain unclear. Future studies are required to better define how DCS over particular regions of the cerebellum affects individual cerebellar symptoms, given the topographical organization of cerebellar symptoms. The long-term neural consequences of non-invasive cerebellar modulation are also unclear. Although there is an agreement that the clinical applications in cerebellar disorders are likely numerous, it is emphasized that rigorous large-scale clinical trials are missing. Further studies should be encouraged to better clarify the role of using non-invasive neurostimulation techniques over the cerebellum in motor, cognitive and psychiatric rehabilitation strategies.

Counting-backward test for executive function in idiopathic normal pressure hydrocephalus.

OBJECTIVES: The aim of this study was to develop and validate a bedside test for executive function in patients with idiopathic normal pressure hydrocephalus (INPH). MATERIALS AND METHODS: Twenty consecutive patients with INPH and 20 patients with Alzheimer's disease (AD) were enrolled in this study. We developed the counting-backward test for evaluating executive function in patients with INPH. Two indices that are considered to be reflective of the attention deficits and response suppression underlying executive dysfunction in INPH were calculated: the first-error score and the reverse-effect index. Performance on both the counting-backward test and standard neuropsychological tests for executive function was assessed in INPH and AD patients. RESULTS: The first-error score, reverse-effect index and the scores from the standard neuropsychological tests for executive function were significantly lower for individuals in the INPH group than in the AD group. The two indices for the counting-backward test in the INPH group were strongly correlated with the total scores for Frontal Assessment Battery and Phonemic Verbal Fluency. The first-error score was also significantly correlated with the error rate of the Stroop colour-word test and the score of the go/no-go test. In addition, we found that the first-error score highly distinguished patients with INPH from those with AD using these tests. CONCLUSION: The counting-backward test is useful for evaluating executive dysfunction in INPH and for differentiating between INPH and AD patients. In particular, the first-error score may reflect deficits in the response suppression related to executive dysfunction in INPH.

Sclerotherapy with monoethanolamine oleate in benign oral vascular lesions.

AIM: The aim of the present study was to carry out a retrospective survey at the Stomatology Clinic of a federal university in Brazil of 411 dental charts for the assessment of vascular tumors. METHODS: After the determination of the sample, the following clinical patient information was recorded: gender, age, ethnic background, marital status, profession, place of birth, clinical diagnosis, anatomic site and tumor size. RESULTS: Among all patients treated, 4.4% had benign vascular tumors in the oral cavity. The majority of these tumors were asymptomatic, with a purplish, bluish or reddish coloration and of variable size. A clinical examination and vitropressure were essential to the diagnosis. The most affected age group was 60 to 75 years. Vascular tumors most often affected white individuals and the female gender. The most common anatomic site was the tongue, followed by the buccal mucosa. Treatment with sclerotherapy proved effective, with complete regression in 94.5% of the tumors. CONCLUSION: The majority of patients demonstrated wholehearted acceptance of the treatment and side effects following the administration of the substance were slight. Sclerotherapy is a simple, low-cost method of safe and easy execution, allowing the elimination of surgical trauma and a lesser risk of hemorrhage.

Finger movement improves ankle control for gait initiation in patients with Parkinson's disease.

The purpose of this study was to investigate the effect of finger movement on ankle control for gait initiation in patients with Parkinson's disease (PD patients). The subjects were 13 PD patients and 6 age-matched healthy adults. The subjects moved fingers before or after gait initiation, or initiated gait without finger movement. Ankle joint movement in the stance leg was recorded to estimate the duration of ankle dorsiflexion (DIF duration), which reflects the degree of disturbance in ankle control for gait initiation in PD patients. In the PD patients with prolonged D/F duration, finger movement that preceded gait initiation shortened the D/F duration, but in the PD patients without prolonged D/F duration and in healthy subjects, the effect was not found. Accordingly, finger movement that precedes gait initiation improves ankle control for gait initiation in PD patients who suffer disturbance in ankle control for gait initiation.

Visible-laser desorption/ionization on gold nanostructures.

In this report, we describe the visible-laser desorption/ionization of biomolecules deposited on gold-coated porous silicon and gold nanorod arrays. The porous silicon made by electrochemical etching was coated with gold using argon ion sputtering. The gold nanorod arrays were fabricated by electrodepositing gold onto a porous alumina template, and the subsequent partial removal of the alumina template. A frequency-doubled/tripled Nd : YAG laser was used to irradiate the gold nanostructured substrate, and the desorbed molecular ions were mass-analyzed by a time-of-flight mass spectrometer. The desorption/ionization of biomolecules for both substrates was favored by the use of the 532-nm visible-laser, which is in the range of the localized surface plasmon resonance of the gold nanostructure. The present technique offers a potential analytical method for low-molecular-weight analytes that are rather difficult to handle in the conventional matrix-assisted laser desorption/ionization (MALDI) mass spectrometry.

Detailed images of asteroid 25143 Itokawa from Hayabusa.

Rendezvous of the Japanese spacecraft Hayabusa with the near-Earth asteroid 25143 Itokawa took place during the interval September through November 2005. The onboard camera imaged the solid surface of this tiny asteroid (535 meters by 294 meters by 209 meters) with a spatial resolution of 70 centimeters per pixel, revealing diverse surface morphologies. Unlike previously explored asteroids, the surface of Itokawa reveals both rough and smooth terrains. Craters generally show unclear morphologies. Numerous boulders on Itokawa's surface suggest a rubble-pile structure.

Transcriptional targeting of adenovirus vectors with the squamous cell carcinoma-specific antigen-2 promoter for selective apoptosis induction in lung cancer.

Squamous cell carcinoma antigens SCCA1 and SCCA2 are highly homologous serine proteinase inhibitors which have been widely utilized as serological markers for squamous cell cancers, but it has recently been demonstrated that only SCCA2 is truly specific for certain forms of lung cancer. Using a construct containing the 5'-flanking region of the SCCA2 gene between -460 and +0 bp and the luciferase reporter gene, SCCA2 promoter activity was detected in SCCA2-producing SCC cell lines (LK-2, LC-1), but not in SCCA2-nonproducing lung adenocarcinoma cell lines (A549, ABC-1, and RERF-LC-MS) or normal cells (WI-38, SAEC, and NHEK-Adult). Infection with a recombinant adenovirus vector, Ad-SCCA2-DsRed, resulted in cell-specific expression of the SCCA2 promoter-driven DsRed marker gene only in LK-2 and LC-1 cells. The same strategy was used for SCCA2-driven expression of a proapoptotic gene, (KLAKLAK)2, which can cause mitochondrial disruption by triggering mitochondrial permeabilization and swelling, resulting in the release of cytochrome c and induction of apoptosis. Infection with Ad-SCCA2-KLAKLAK2 specifically reduced the growth of the two human lung SCC cell lines compared to the SCCA2 nonproducing cell lines both in vitro and in vivo, suggesting that the SCCA2 promoter had a tumor-specific effect. These results suggest that transduction of SCCA2 promoter-controlled suicide genes by adenoviral vectors can confer transcriptionally targeted cytotoxicity in SCCA2-producing lung SCC cells, and represents a novel strategy for gene transfer specifically targeted to SCC in the lung.

Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable prognostic factor in non-small-cell lung carcinoma.

The purpose of this study was to clarify the relationship between the number of tumour-infiltrating T lymphocytes and the clinicopathological features and clinical outcome in patients with non-small-cell lung cancer (NSCLC). Tissue specimens from 109 patients who underwent surgical resection for NSCLC were immunohistochemically analysed for CD4 and CD8 expression. Patients were classified into two groups according to whether their tumours exhibited a 'high' or 'low' level of CD8(+) or CD4(+) lymphocyte infiltration. Although the level of infiltration by CD8(+) T cells alone had no prognostic significance, the survival rate for patients with both 'high' CD8(+) and 'high' CD4(+) T-cell infiltration was significantly higher than that for the other groups (log-rank test, P=0.006). Multivariate analysis indicated that concomitant high CD8(+) and high CD4(+) T-cell infiltration was an independent favourable prognostic factor (P=0.0092). In conclusion, the presence of high levels of both CD8(+) T cells and CD4(+) T cells is a significant indicator of a better prognosis for patients with NSCLC, and cooperation between these cell populations may allow a significantly more potent antitumour response than either population alone.

Thermochemical stabilities and structures of the cluster ions OCS+, S2+, H+(OCS), and C2H5+ with OCS molecules in the gas phase.

The gas-phase clustering reactions of OCS+, S2+, H+(OCS), and C2H5+ ions with carbonyl sulfide (OCS) molecules were studied using a pulsed electron-beam high-pressure mass spectrometer and applying density functional theory (DFT) calculations. In the cluster ions OCS+(OCS)(n) and H+(OCS)(OCS)(n), a moderately strong, here referred to as "semi-covalent", bond was formed with n = 1. However, the nature of bonding changed from semi-covalent to electrostatic with n = 1 --> 2. The bond energy of S2(+)(OCS) was determined experimentally to be 12.9 +/- 1 kcal/mol, which is significantly smaller than that of the isovalent S2(+)(CS2) complex (30.9 +/- 1.5 kcal/mol). DFT based calculations predicted the presence of several isomeric structures for H+(OCS)(OCS)(n) complexes. The bond energies in the C2H5+(OCS)(n) clusters showed an irregular decrease for n = 1 --> 2 and 7 --> 8. The nonclassical bridge structure for the free C2H5+ isomerized to form a semi-covalent bond with one OCS ligand, [H3CCH2...SCO]+, i.e., reverted to classical structure. However, the nonclassical bridge structure of C2H5+ was preserved in the cluster ions C2H5+(OCS)(n) below 140 K attributable to the lack of thermal energy for the isomerization. DFT calculations revealed that stability orders of the geometric isomers of H+(OCS)(OCS)(n) and C2H5+(OCS)(n) changed with increasing n values.

Gas-phase ion/molecule reactions in C5F8.

Gas-phase ion-molecule reactions in octafluorocyclopentene (C5F8) were studied with a pulsed electron beam mass spectrometer. When a few Torr of major gas, CH4, Ar, or N2, containing approximately 10 mTorr C5F8 was ionized by 2 keV electrons, C5F8+, C5F7+, C4F6+, C4F5+, and C3F3+ were formed as major fragment ions. The interaction between those ions and C5F8 is found to be a weak electrostatic interaction. The cation...C5F8 bonding energies are around 10 kcal/mol, which were reproduced well by (U)B3LYP/6-311+G(d) calculations. The proton affinity of C5F8 (=148.6 kcal/mol by B3LYP/6-311+G(d)) was found to be smaller than that of C2H4 (=162.8 kcal/mol). In the negative mode of operation, the intense signal of C5F8- was observed during the electron pulse. This indicates that C5F8 has a positive electron affinity (1.27 eV by (U)B3LYP/6-311+G(d)). The C5F8- ion was quickly converted to a complex C10F16-. This complex did not react further with C5F8 down to 170 K. The theoretical calculation revealed that a C5F7-F-...C5F8 interaction mode in (C5F8)2- was converted to a C5F7*...C5F9- one via fluoride-ion transfer. The F- ion was found to form a strong covalent bond with C5F8, but the interaction in F-(C5F8)- - -C5F8 is a weak electrostatic interaction due to the charge dispersal in F-(C5F8). The halide ions except F- interact with C5F8 only weakly. Thermochemical stabilities for the cluster ions I-(CH3I)n (n = 1, 2) were also determined.

Changes in masseter muscle activity associated with swallowing.

The purpose of this study was to investigate masseter muscle activity during swallowing in seven healthy humans. In order to observe both the increase and the decrease of masseter muscle activity, the subjects performed voluntary saliva swallowing while low-intensity tonic clenching was maintained. Electromyograms (EMG) were recorded from the right masseter muscle and the suprahyoid muscle complex. For six of seven subjects, the masseter EMG amplitude increased above the pre-swallow baseline level at the initial phase of swallowing. This increase was initiated 0.1 +/- 0.3 s before the suprahyoid EMG onset and was terminated 0.6 +/- 0.4 s after the suprahyoid EMG onset. For six of seven subjects, the masseter EMG amplitude decreased below the pre-swallow baseline level during swallowing. This decrease was initiated 0.6 +/- 0.3 s after the suprahyoid EMG onset and was terminated 1.3 +/- 0.4 s after the suprahyoid EMG onset. These findings indicate that biphasic modulation of masseter motoneuron excitability occurs during swallowing in humans. Further investigations are needed to determine whether these findings are extensively applicable to swallowing as it occurs under natural conditions.