Outcome of maintenance systemic chemotherapy with drug-free interval for metastatic urothelial carcinoma.

OBJECTIVE: Aiming to achieve long-term disease control, maintenance systemic chemotherapy (MSC) with a 1-3-month drug-free interval is continued in selected patients. We report our experience of MSC for metastatic urothelial carcinoma (UC). METHODS: Of 228 metastatic UC patients treated with systemic chemotherapy, 40 (17.5%, 40/228) had continuously undergone MSC. Data on the regimen, cycle number, and reason for the discontinuation of MSC were also collected. We analyzed OS from the initiation of MSC until death or the last follow-up, using the log-rank test to assess the significance of differences. RESULTS: The median number of cycles of chemotherapy was 6, and the responses were CR in 6, PR in 20, SD in 13, and PD in 1 before MSC. Gemcitabine plus CDDP or carboplatin was mainly performed as MSC (70%, 28/40). MSC was repeated quarterly in 30 (75%, 30/40), every two months in 8 (20%, 8/40), and with other intervals in 2 (5%, 2/40). Overall, a median of 3.5 cycles (range: 1-29) of MSC was performed. The reason for the discontinuation of MSC was PD in 24 (60%, 24/40), favorable disease control in 9 (22.5%, 9/40), and myelosuppression in 3 (7.5%, 3/40), and for other reasons in 2 (5%, 2/40). MSC was ongoing in 2 (5%, 2/40). The median OS was 27 months from the initiation of MSC. PS0 (P = 0.0169), the absence of lung metastasis (P = 0.0387), and resection of the primary site (P = 0.0495) were associated with long-term survival after MSC. CONCLUSIONS: In selected patients, long-term systemic chemotherapy could be performed with a drug-free interval. Our maintenance strategy with cytotoxic drugs may become one of the treatment options for long-term disease control.

The Association Between MCT1 T1470A Polymorphism and Power-Oriented Athletic Performance.

The purpose of this study was to investigate the effects of the MCT1 T1470A polymorphism (rs1049434) on power-oriented performance and lactate concentration during or after cycling sprints in Japanese wrestlers. Participants (199 wrestlers and 649 controls) were genotyped for the MCT1 T1470A genotype (rs1049434) using the TaqMan® Assay. All wrestlers were international (n=77) or national (n=122) level athletes. Among them, 46 wrestlers performed 2 anaerobic performance tests, a 30-s Wingate Anaerobic test (WAnT) and a series of 10 maximal effort 10-s sprints on a cycle ergometer. Blood lactate levels were measured before, during, and after the tests. In the A-allele recessive model (AA vs. TA+TT), the frequency of the AA genotype was significantly higher in all wrestlers than in controls (p=0.037). Wrestlers with AA genotype had lower blood lactate concentrations than those with TA+TT genotype at 10 min after the WAnT and following the 5th and the final set of repeated cycling sprints (p<0.05). The AA genotype of the MCT1 T1470A polymorphism is over-represented in wrestlers compared with controls and is associated with lower blood lactate concentrations after 30-s WAnT and during intermittent sprint tests in Japanese wrestlers.

Sialyl-glycoconjugates in cholesterol-rich microdomains of P388 cells are the triggers for apoptosis induced by Rana catesbeiana oocyte ribonuclease.

SBL/RC-RNase was originally isolated from frog (Rana catesbeiana) oocytes and purified as a novel sialic acid-binding lectin (SBL) that displayed strong anti-cancer activity. SBL was later shown to be identical to a ribonuclease (RC-RNase) from oocytes of the same species. The administration of SBL/RC-RNase induced apoptosis (with nuclear condensation and DNA fragmentation) in mouse leukemia P388 cells but did not kill umbilical vein endothelial or fibroblast cells derived from normal tissues. The cytotoxic activity of SBL/RC-RNase was inhibited by desialylation of P388 cells and/or the co-presence of free bovine submaxillary mucin. FACS analysis showed that SBL/RC-RNase was incorporated into cells after attachment to cholesterol-rich microdomains. Addition of the cholesterol remover methyl-ß-cyclodextrin reduced SBL/RC-RNase-induced apoptosis. Apoptosis occurred through the caspase-3 pathway following activation of caspase-8 by SBL/RC-RNase. A heat shock cognate protein (Hsc70) and a heat shock protein (Hsp70) (each 70 kDa) on the cell membrane were shown to bind to SBL/RC-RNase by mass spectrometric and flow cytometric analyses. Quercetin, an inhibitor of Hsc70 and Hsp70, significantly reduced SBL/RC-RNase-induced apoptosis. Taken together, our findings suggest that sialyl-glycoconjugates present in cholesterol-rich microdomains form complexes with Hsc70 or Hsp70 that act as triggers for SBL/RC-RNase to induce apoptosis through a pathway involving the activation of caspase-3 and caspase-8.

Application of alkali metal-doped carbons for hydrogen recovery and isotope separation.

Hydrogen-sorption isotherms of alkali metal-doped carbons at 77 K were determined for promoting application of these materials as hydrogen-recovery and isotope-separation agent. The hydrogen-sorption behavior of rubidium-doped Grafoil, with composition of RbC24, showed high sorption ability against hydrogen at low pressure. Taking into account the fact that sorption-desorption was fast and reversible, and the equilibrium pressure at half coverage was very low, i.e., 40 Pa, RbC24 prepared from Grafoil is promising as a recovery agent for hydrogen gas at low pressure. The hydrogen (H2)/deuterium(D2)-sorption isotherms of potassium-doped carbons with composition of KC10, prepared from multi wall carbon nanotube (MWCNT) and carbons derived from petroleum cokes with heat-treatment temperatures of 1000 and 1500 degrees C, were also determined. Isotope separation coefficient was estimated from those isotherms. A very large isotope effect was found for KC10 prepared from MWCNT, comparable to those prepared from carbons with heat-treatment temperatures of 1000 or 1500 degrees C. However, a severe problem was found for KC10 (MWCNT) that repetition of the sorption-desorption cycles resulted in the decrease of the sorbed amount of H2 and D2.

Differentiation in vitro of hybrid eosinophil/basophil granulocytes: autocrine function of an eosinophil developmental intermediate.

Granulocytes with the hybrid characteristics of eosinophils and basophils have been identified in the bone marrow and peripheral blood of humans with myeloid leukemias. We now describe a technique by which such hybrid granulocytes can be developed in vitro from normal cord blood precursors cultured in the presence of recombinant human interleukin (rhIL) 3 (350 pM) and rhIL-5 (200 pM) in a plastic vessel coated with Matrigel. After 14 d in culture, 90 +/- 3% (mean +/- standard error of the mean) of the nonadherent cells cultured in the Matrigel-coated flasks contained both eosinophil and basophil granules, as indicated by staining with Wright's and Giemsa stains. Of the nonadherent cells, 93 +/- 1% contained cyanide-resistant peroxidase, and 88 +/- 2% were toluidine blue-positive, characteristic of eosinophil and basophil granules, respectively. Transmission electron micrographs showed hybrid cells containing ultrastructurally distinct eosinophil granules with developing crystalline cores and basophil granules with reticular structures. These 14-d cord blood-derived cell cultures showed strong hybridization signals for eosinophil-derived neurotoxin by RNA blot analysis and contained 78 ng histamine per 10(6) cells. When the granulocytes were removed from cytokine-containing medium and suspended without Matrigel in RPMI 1640 medium containing 10% fetal calf serum (FCS), more than 80% of the granulocytes excluded trypan blue for as long as 5 d, and 93% had developed into eosinophils at 6 d. Conditioned medium prepared over 48 h from the 14-d cell cultures (hybrid granulocytes) sustained the 4-d viability in vitro of 78% of peripheral blood eosinophils from atopic donors. In comparison, 13% survived in RPMI 1640 containing 10% FCS alone. This viability-sustaining activity was nearly completely neutralized by an anti-granulocyte/macrophage colony-stimulating factor (GM-CSF) antibody and was only minimally reduced by anti-IL-3 or IL-5. Thus, cells possessing both eosinophil and basophil granules by both histochemical and ultrastructural analysis can be developed from normal progenitors in vitro in response to eosinophilopoietic cytokines and Matrigel. Their subsequent spontaneous development into mature eosinophils suggests that hybrid granulocytes are part of a normal developmental sequence during eosinophilopoiesis. Furthermore, these hybrid granulocytes are capable of autoregulation through elaboration of GM-CSF, which sustains their viability.

Transgenic mice expressing a B cell growth and differentiation factor gene (interleukin 5) develop eosinophilia and autoantibody production.

Interleukin 5 (IL-5) has been suggested to be involved in the growth and differentiation of B cells and eosinophils. Especially, Ly-1+ B cells, which have been considered to produce autoantibodies, are selectively developed by this lymphokine in long-term bone marrow culture. To envisage the possible engagement of IL-5 in the development of these cells in vivo, transgenic mice carrying the mouse IL-5 gene ligated with a metallothionein promoter were generated. Transgenic mice carrying the IL-5 gene exhibited elevated levels of IL-5 in the serum and an increase in the levels of serum IgM and IgA. A massive eosinophilia in peripheral blood, bone marrow, and spleen, and an infiltration of muscle and liver with eosinophils, were observed. When cadmium-containing saline was injected intraperitoneally into transgenic mice, IL-5 production was augmented about five times within 24 h, and a distinctive Ly-1+ B cell population became apparent in the spleen after 5 d. IL-5 receptors were detected on those cells by monoclonal antibodies against IL-5 receptors. Another interesting finding in these transgenic mice was an increase in polyreactive anti-DNA antibodies of IgM class. It is suggested, therefore, that aberrant expression of the IL-5 gene may induce accumulation of Ly-1+ B cells and eosinophils. Furthermore, this IL-5 transgenic mouse can be a model mouse for eosinophilia, and we can determine the role of IL-5 in the differentiation of Ly-1+ B cells and eosinophils by using this mouse.

Transforming growth factor beta induces IgA production and acts additively with interleukin 5 for IgA production.

Effects of transforming growth factor beta (TGF-beta) on IgA production by LPS-stimulated B cells have been studied. TGF-beta itself could augment polyclonal IgA production in concomitant inhibition of polyclonal IgM and IgG1 production. Furthermore, TGF-beta and IL-5 additively augmented IgA production. TGF-beta exerted its activity early in the culture (by 2 d in a 5-d culture) and IL-5 was required late in the culture. Surface IgA- (sIgA-) B cells responded to TGF-beta for the development of IgA-secreting cells. By contrast, sIgA+ B cells, but not sIgA- B cells, responded to IL-5 for IgA production. These results suggest that TGF-beta has a differential role in the induction of IgA production from IL-5 on murine-activated B cells.

Relationship between the unilateral TMJ osteoarthritis/osteoarthrosis, mandibular asymmetry and the EMG activity of the masticatory muscles: a retrospective study.

The purpose of this retrospective study was to investigate the relationship between the unilateral temporomandibular joint (TMJ) osteoarthritis/osteoarthrosis (OA), mandibular asymmetry and electromyographic (EMG) activity of the masticatory muscles. Twenty-two Japanese women (aged 23.2 +/- 5.4 years) and 10 Japanese men (aged 22.4 +/- 2.8 years) exhibiting unilateral TMJ OA were included in this study. Two angular and seven linear measurements were obtained for the analysis of the skeletal hard tissues. The cephalometric measurement values (CV) were normalized using the CV ratio for the evaluation of the degree of mandibular asymmetry. The EMG was recorded during maximal voluntary clenching efforts for 10 s in the intercuspal position. The average values of integral EMG (iEMG) of three trials were normalized using the iEMG ratio for the evaluation of the functional balance of the masticatory muscles. The mandibular midline was shifted to the TMJ OA side with a median value of 9.85 mm. The CV ratio of the ramus height of the TMJ OA side was significantly smaller than that of the non-OA side. For the masseter muscle, the iEMG ratio of the TMJ OA side was significantly larger than that of the non-OA side (P < 0.05). These results suggest that unilateral TMJ OA is related to the dentofacial morphology, thus resulting in a mandibular midline shift to the affected side and it is associated with a masticatory muscle imbalance.

Mast cells that reside at different locations in the jejunum of mice infected with Trichinella spiralis exhibit sequential changes in their granule ultrastructure and chymase phenotype.

Whether or not a nontransformed, mature mouse mast cell (MC) or its committed progenitor can change its granule protease phenotype during inflammatory responses, has not been determined. To address this issue, the granule morphology and protease content of the MC in the jejunum of BALB/c mice exposed to Trichinella spiralis were assessed during the course of the infection. Within 1 wk after helminth infection of the mice, increased numbers of MC appeared in the crypts at the base of the villi, and by wk 2 the number of MC throughout the villi increased by approximately 25-fold. Shortly after the peak of the mastocytosis, the intraepithelial population of MC disappeared, followed by a progressive loss of lamina propria MC. The presence of stellate-shaped granules containing crystalline structures in intraepithelial MC at the height of infection and the retention of such granules with fragmented crystals in lamina propria MC during resolution of the mastocytosis suggest that MC migrate during the various phases of the inflammation. As assessed by immunohistochemical analyses of serial sections, predominant chymase phenotypes were observed at the height of the infection in the muscle that expressed mouse MC protease (mMCP) 5 without mMCP-1 or mMCP-2 and in the epithelium that expressed mMCP-1 and mMCP-2 without mMCP-5. Accompanying these two MC populations were transitional forms in the submucosa that expressed mMCP-2 and mMCP-5 without mMCP-1 and in the lamina propria that expressed mMCP-2 alone. These data suggest that jejunal MC sequentially express mMCP-2, cease expressing mMCP-5, and finally express mMCP-1 as the cells progressively appear in the submucosa, lamina propria, and epithelium, respectively. In the recovery phase of the disease, MC sequentially cease expressing mMCP-1, express mMCP-5, and finally cease expressing mMCP-2 as they present at the tips of the villi, the base of the villi, and the submucosa, respectively. That MC can reversibly alter their protease phenotypes suggests that a static nomenclature with fixed functional implications is inadequate to describe MC populations during an inflammatory process within a particular tissue.

Purification and biochemical characterization of a D-galactose binding lectin from Japanese sea hare (Aplysia kurodai) eggs.

A lectin was purified from Japanese sea hare Aplysia kurodai by lactosyl-agarose affinity chromatography. The molecular mass of the lectin was determined to be 56 and 32 kDa by SDS-PAGE under non-reducing and reducing conditions, respectively. It was found to agglutinate trypsinized and glutaraldehyde-fixed rabbit and human erythrocytes in the absence of divalent cations. The lectin exhibited stable thermo-tolerance as it retained hemagglutinating activity for 1 h even at 80 degrees C and showed stability at pH 10. By contrast, it was very sensitive at pH less than 5 and in the presence of the sulfhydryl-group preserving reagent, beta-mercaptoethanol. The hemagglutinating activity by the lectin was specifically inhibited by D-galactose, galacturonic acid, methyl-alpha- and methyl-beta-D-galactopyranoside, lactose, melibiose, and asialofetuin. The association rate constant (k(ass)) and dissociation rate constant (k(diss)) were determined for the lectin to be 4.3 x 10(5) M(-1) x sec(-1) and 2.2 x 10(-3) sec(-1), respectively, using a surface plasmon resonance biosensor. The lectin moderately inhibited cell proliferation in the P388 cell line dose dependently. Interestingly, lectin-treated cells did not show a fragmented DNA ladder as is caused by apoptosis, suggesting that the cell proliferation inhibition was caused by another unknown mechanism.

Hemispheric asymmetry of the arcuate fasciculus: a preliminary diffusion tensor tractography study in patients with unilateral language dominance defined by Wada test.

OBJECTIVE: Lateralization of language function is a prominent feature of human brain function, and its underlying structural asymmetry has been recently reported in normal right-handed subjects. By means of diffusion tensor tractography (DTT), we investigated the asymmetry of the language network, namely, the arcuate fasciculus in patients in whom the unilateral language dominance was defined by Wada test. METHODS: DTT was performed in 24 patients with a focal lesion or an epileptic focus outside the C-shaped segment of the arcuate fasciculus. The arcuate fasciculus was reconstructed by placing two regions-of-interest in the deep white matter lateral to the corona radiata. The pathway was then divided into one terminating in the temporal lobe (FT tract) and the other in the parietal lobe (FP tract). The relative number and volume of the FT and FP tracts in each hemisphere were submitted to repeated measure ANOVA separately, with the hemisphere as a within-subject factor and with the side of pathology as a between subject factor. RESULTS: The FT tract showed a significantly larger number and volume in the language dominant hemisphere than in the non-dominant hemisphere, while, for the FP tract, no significant hemispheric difference was observed in the relative number or volume. There was a tendency that the FT tract was less lateralized when the pathology was located in the dominant hemisphere than in the non-dominant hemisphere. CONCLUSION: Dominance of the FT tract in the language dominant hemisphere was demonstrated for the first time in a patient population and implicated a clinical utility of DTT for non-invasive evaluation of language lateralization. Our preliminary study might indicate reorganization of the language network in conjunction with pathology.

A randomized clinical study on postoperative pain comparing between the supraglottic airway device and endotracheal tubing in transabdominal preperitoneal repair (TAPP).

BACKGROUND: Transabdominal preperitoneal (TAPP) repair is the most widely used laparoscopic technique for the treatment of inguinal hernia in Japan. Many studies have shown that in comparison with open hernia repair, laparoscopic repair results in less pain and a shorter convalescence. However, postoperative pain remains a concern. One possible cause of postoperative pain in the early postoperative phase is strain or cough on removal of the endotracheal tube. Use of a supraglottic airway (SGA) device helps to avoid such complaints. We evaluated postoperative pain after TAPP repair using the SGA for general anesthesia. METHODS: We evaluated the postoperative pain in 146 patients with inguinal hernia repaired by TAPP in our hospital between May 2013 and May 2016. A total of 144 adult patients of American Society of Anesthesiologists physical status I and II who underwent needlescopic TAPP surgery were randomly allocated to one of two groups of 72 patients: group A (SGA), in which the patient's airway was secured with an appropriately sized I-gel, and group B (endotracheal tube), in which the airway was secured under laryngoscopy. RESULTS: There was no significant difference between the groups regarding patient background, postoperative hospital stay, and operation time, and TAPP was performed safely in all cases. In the analysis of postoperative pain, the mean Numerical Rating Scale score of peak pain in group A was significantly less than that of group B (2.10 ± 2.05 vs 2.90 ± 2.65; p = 0.043). In group A, the percentage of patients who had an NRS score of 0 was 51.4% 30 min after surgery, 62.5% after 6 h and 68.1% at POD1, and compared to group B, the NRS scores were significantly higher at POD1 (p = 0.003), and the level of postoperative pain in group A tended to decrease earlier than that in group B. CONCLUSIONS: The results of this study are the first to show that an SGA device can reduce postoperative pain after laparoscopic surgery.

Selective sensitivity to radiation of cerebral glioblastomas harboring p53 mutations.

Recent studies suggest that a balance may exist between the cell cycle arrest and apoptosis-inducing functions of the p53 tumor suppressor gene. Adenoviral p21 transduction attenuates apoptosis, whereas deletion of the p21 gene promotes it, and p21-null xenografts respond better than isogenic p21-wild type tumors to irradiation. Hence, the role of p53 in dictating the clinical response to radiotherapy and chemotherapy may be more complex than previously thought. We have analyzed survival and radiation response (regrowth-free period) of 42 patients with glioblastomas whose p53 status was determined by a sensitive yeast functional assay. Multivariate analysis revealed that p53 mutation is associated with longer survival (P < 0.02). Among 36 radiation-treated patients, the regrowth-free period after treatment was significantly longer for tumors with p53 mutations (P < 0.0001), and p53 mutation was the sole independent factor predictive of radiotherapeutic response (P < 0.01). Survival time after regrowth was independent of p53 status, suggesting that the difference in survival was related to the treatment rather than to the intrinsic aggressiveness of the tumor. Thus, in this Northern Japanese population, p53 mutation is a marker for better radiation response in glioblastomas, and this results in significantly longer survival.

Short alternative splice transcripts of the mdm2 oncogene correlate to malignancy in human astrocytic neoplasms.

The mdm2 oncogene encodes a 90-kDa nuclear phosphoprotein that binds and inhibits the function of the p53 tumor suppressor protein. It was recently reported that the expression of alternatively spliced variants of mdm2 correlated with malignancy in ovarian tumors and bladder carcinomas. We analyzed the presence of alternatively spliced mdm2 variants and studied their correlation to p53 status in a total of 66 human astrocytic tumors, including 32 glioblastomas multiforme, 17 anaplastic astrocytomas, 12 astrocytomas, and 5 pilocytic astrocytomas, using a specific nested reverse transcription-PCR technique. The full-length mdm2 transcript was demonstrated in all of the cases. Multiple-sized PCR products were found in 29 cases. Two of 5 pilocytic astrocytomas (40%), none of 12 astrocytomas, and 5 of 17 anaplastic astrocytomas (29%) showed alternative splice variants. In contrast, 22 of 32 glioblastomas (69%) showed the presence of splice variants, demonstrating a significantly higher frequency than in lower-grade astrocytomas (P < 0.0003). A majority of the splice variants were 707 base-type (mdm2-b), which was confirmed by sequence analysis. There was no apparent correlation of the presence of mdm2 splice variants with p53 gene status. These results suggest a new role for mdm2, independent of p53 gene status, as an oncogene in the development of malignant astrocytic tumors.

Note: Novel diamond anvil cell for electrical measurements using boron-doped metallic diamond electrodes.

A novel diamond anvil cell suitable for electrical transport measurements under high pressure has been developed. A boron-doped metallic diamond film was deposited as an electrode on a nano-polycrystalline diamond anvil using a microwave plasma-assisted chemical vapor deposition technique combined with electron beam lithography. The maximum pressure that can be achieved by this assembly is above 30 GPa. We report electrical transport measurements of Pb up to 8 GPa. The boron-doped metallic diamond electrodes showed no signs of degradation after repeated compression.

The 'when' and 'where' of semantic coding in the anterior temporal lobe: Temporal representational similarity analysis of electrocorticogram data.

Electrocorticograms (ECoG) provide a unique opportunity to monitor neural activity directly at the cortical surface. Ten patients with subdural electrodes covering ventral and lateral anterior temporal regions (ATL) performed a picture naming task. Temporal representational similarity analysis (RSA) was used, for the first time, to compare spatio-temporal neural patterns from the ATL surface with pre-defined theoretical models. The results indicate that the neural activity in the ventral subregion of the ATL codes semantic representations from 250 msec after picture onset. The observed activation similarity was not related to the visual similarity of the pictures or the phonological similarity of their names. In keeping with convergent evidence for the importance of the ATL in semantic processing, these results provide the first direct evidence of semantic coding from the surface of the ventral ATL and its time-course.

Extra-anatomical Meso-portal Venous Jump Graft Repair for Early Portal Vein Thrombosis After Liver Transplant in an Infant With a Hypoplastic Portal Vein: A Case Report.

BACKGROUND AND PURPOSE: Small infants with biliary atresia and hypoplastic portal veins (PV) are at risk for portal vein thrombosis (PVT) after liver transplantation (LT), which can lead to graft loss and mortality. Extra-anatomical PV reconstruction techniques have been established for adult cases of PVT; however, they have not been widely accepted for infants. METHODS: Here, we report the successful use of an extra-anatomical meso-portal venous jump graft to treat early PVT after LT in a 6-month-old infant with biliary atresia and PV hypoplasia. At the time of LT, despite a reduced-sized left lateral graft, we had to create a temporary abdominal closure with silastic mesh. FINDINGS: On postoperative day 1, PVT was detected by Doppler ultrasound of the liver. Surgical thrombectomy was attempted. We removed the blood clots and reconstructed the PV using an interposition venous graft. As the PV flow was still not sufficient, we performed an extra-anatomical meso-portal venous jump graft procedure from the recipient superior mesenteric vein to the donor PV. This resulted in a significant improvement in PV flow. CONCLUSION: For small infants at high risk for PVT, a detailed pretransplantation surgical plan and treatment options for possible early PVT are mandatory. An extra-anatomical meso-portal venous jump graft is a viable surgical technique for early PVT in infants.

Increased synchronization of cortical oscillatory activities between human supplementary motor and primary sensorimotor areas during voluntary movements.

In human, both primary and nonprimary motor areas are involved in the control of voluntary movements. However, the dynamics of functional coupling among different motor areas has not been fully clarified yet. Because it has been proposed that the functional coupling among cortical areas might be achieved by the synchronization of oscillatory activity, we investigated the electrocorticographic coherence between the supplementary motor and primary sensorimotor areas (SMA and S1-M1) by means of event-related partial coherence analysis in 11 intractable epilepsy patients. We found premovement increase of coherence between the SMA proper and S1-M1 at the frequency of 0-33 Hz and between the pre-SMA and S1-M1 at 0-18 Hz. Coherence between the SMA proper and M1 started to increase 0.9 sec before the movement onset and peaked 0.3 sec after the movement. There was no systematic difference within the SMA (SMA proper vs pre-SMA) or within the S1-M1, in terms of the time course as well as the peak value of coherence. The phase spectra revealed near-zero phase difference in 57% (20 of 35) of region pairs analyzed, and the remaining pairs showed inconsistent results. This increase of synchronization between multiple motor areas in the preparation and execution of voluntary movements may reflect the multiregional functional interactions in human motor behavior.