Effects of pulsed magnetic stimulation on isolated crayfish heart.

Cardiac muscular contraction of the neurogenic heart that could be excited by pulsed magnetic stimulation (PMS) was investigated using preparation of the isolated crayfish heart. When a figure-eight magnetic coil was set over the isolated heart, cardiac contraction induced by a single PMS was not observed. Cardiac arrest occurred immediately after repetitive PMS and persisted for dozens of seconds depending on the number of stimuli. We concluded that PMS caused neuronal modulation in the neuronal network in the cardiac ganglion.

Neuronal activity in the monkey prefrontal cortex during a duration discrimination task with visual and auditory cues.

To investigate neuronal processing involved in the integration of auditory and visual signals for time perception, we examined neuronal activity in prefrontal cortex (PFC) of macaque monkeys during a duration discrimination task with auditory and visual cues. In the task, two cues were consecutively presented for different durations between 0.2 and 1.8 s. Each cue was either auditory or visual and was followed by a delay period. After the second delay, subjects indicated whether the first or the second cue was longer. Cue- and delay-responsive neurons were found in PFC. Cue-responsive neurons mostly responded to either the auditory or the visual cue, and to either the first or the second cue. The neurons responsive to the first delay showed activity that changed depending on the first cue duration and were mostly sensitive to cue modality. The neurons responsive to the second delay exhibited activity that represented which cue, the first or second cue, was presented longer. Nearly half of this activity representing order-based duration was sensitive to cue modality. These results suggest that temporal information with visual and auditory signals was separately processed in PFC in the early stage of duration discrimination and integrated for the final decision.

[Primary diaphragmatic schwannoma which needed to be distinguished from a liver tumor].

A 55-year-old woman was admitted because of a tumor located in the ventral region of S4 of the liver, just beneath the diaphragm. A CT scan revealed the round tumor to be delineated as a 33 mm in size, with an outer capsule. The tumor was visualized as concentric circles which presented high-, low-, and high- signal patterns on T2-weighted MRI. It also presented a triphasic pattern in which the border and the central part were not contrasted as a low signal pattern, while the middle part was contrasted as a high signal pattern by T1-weighted enhanced imaging with Gd-DTPA. Angiography revealed that the tumor did not originate from the liver but from the diaphragm, so it was surgically resected as a primary diaphragmatic tumor. We report a schwannoma which originated from the diaphragm, that showed characteristic imaging findings and required to be distinguished from a liver tumor.

[Gemcitabine in combination with S-1 or UFT in patients with advanced pancreatic cancer].

The present retrospective study aimed to evaluate the anti-tumor activity and toxicity of combination chemotherapy with gemcitabine (GEM) and oral S-1 or UFT in patients with advanced or metastatic pancreatic cancer. Ninety-four patients received chemotherapy. Among them, sixty-three were treated with GEM alone, twenty-two with UFT and GEM (UFT/GEM), and nine with S-1 and GEM(S-1/GEM). The median survival time was 8.7 months with GEM, 7.3 months with UFT/GEM, and 23.3 months with S-1/GEM. The overall response rate was 11.1%, 10.0%, and 22.2%, respectively. The 1-year survival rate was 29.5%, 36.4%, and 85.7%, respectively. Although the treatment-related adverse effects were not infrequent in patients treated with S-1/GEM, they were moderate in intensity. The combination chemotherapy with S-1/GEM was well tolerated and yielded a high response rate in patients with pancreatic cancer.

Temporal filtering by prefrontal neurons in duration discrimination.

Neural imaging studies have revealed that the prefrontal cortex (PFC) participates in time perception. However, actual functional roles remain unclear. We trained two monkeys to perform a duration-discrimination task, in which two visual cues were presented consecutively for different durations ranging from 0.2 to 2.0 s. The subjects were required to choose the longer cue. We recorded single-neuron activity from the PFC while the subjects were performing the task. Responsive neurons for the first cue period were extracted and classified through a cluster analysis of firing rate curves. The neuronal activity was categorized as phasic, ramping and sustained patterns. Among them, the phasic activity was the most prevailing. Peak time of the phasic activity was broadly distributed about 0.8 s after cue onset, leading to a natural assumption that the phasic activity was related to cognitive processes. The phasic activity with constant delay after cue onset might function to filter current cue duration with the peak time. The broad distribution of the peak time would indicate that various filtering durations had been prepared for estimating C1 duration. The most frequent peak time was close to the time separating cue durations into long and short. The activity with this peak time might have had a role of filtering in attempted duration discrimination. Our results suggest that the PFC contributes to duration discrimination with temporal filtering in the cue period.

Striatal neurons encoded temporal information in duration discrimination task.

To clarify the roles of the basal ganglia in time perception, single-unit activity was recorded from both sides of the striatum of a monkey performing a duration discrimination task. In the task, two visual cues were presented successively in different durations (0.2 approximately 1.6 s). Each cue presentation was followed by a 1-s delay period. The subject was instructed to choose a longer presented cue after the second delay period. There were two types of trials for sequence of cue duration, the long-short (LS) trials in which the first cue (C1) was longer than the second cue (C2) and the short-long (SL) trials in which the C1 was shorter than the C2. Striatal neurons phasically responded during the first delay (D1) and second delay (D2) periods. Responses during the D1 period changed depending on C1 duration. Activity of populations of D1-response neurons correlated with C1 duration positively or negatively. Responses during the D2 period differed between the LS and SL trials. Activity of population of D2-response neurons also changed depending on C2 duration. But the dependence on C2 duration was affected by the trial type, that is, whether the C2 was longer or shorter compared to the C1. These findings suggest that striatal neurons could encode cue durations with monotonically changing responses in the D1 period and discrimination results between the two cue durations in the D2 period.

A high-throughput sequence analysis of Japanese patients revealed 11 candidate genes associated with type 1 autoimmune pancreatitis susceptibility.

The pathogenesis of autoimmune pancreatitis is unknown. In the present study we used high-throughput sequencing with next generation sequencing to identify the candidate genes associated with AIP. A total of 27 type 1 AIP patients and 30 healthy blood donors were recruited, and DNA samples were isolated from their mononuclear cells. A high-throughput sequencer with an original custom panel of 1031 genes was used to detect the genetic variants in each sample. Polymorphisms of CACNA1S (c.4642C>T), rs41554316, rs2231119, rs1042131, rs2838171, P2RX3 (c.195delG), rs75639061, SMAD7 (c.624delC) and TOP1 (c.2007delG), were identified as candidate genetic variants in patients with type 1 AIP. P2RX3 and TOP1 were significantly associated with AIP, even after adjusting bay means of Bonferroni's correction. In addition, we also identified eight candidate genetic variants that were associated with the relapse of type 1 AIP, namely: rs1143146, rs1050716, HLA-C (c.759_763delCCCCCinsTCCCG), rs1050451, rs4154112, rs1049069, CACNA1C (c.5996delC) and CXCR3 (c.630_631delGC). Finally polymorphisms of rs1050716 and rs111493987 were identified as candidate genetic variants associated with extra-pancreatic lesions in patients with type 1 AIP. These candidates might be used as markers of AIP susceptibility and could contribute to the pathogenesis of type 1 AIP.

Neuronal representation of duration discrimination in the monkey striatum.

Functional imaging and lesion studies in humans and animals suggest that the basal ganglia are crucial for temporal information processing. To elucidate neuronal mechanisms of interval timing in the basal ganglia, we recorded single-unit activity from the striatum of two monkeys while they performed a visual duration discrimination task. In the task, blue and red cues of different durations (0.2-2.0 sec) were successively presented. Each of the two cues was followed by a 1.0 sec delay period. The animals were instructed to choose the longer presented colored stimulus after the second delay period. A total of 498 phasically active neurons were recorded from the striatum, and 269 neurons were defined as task related. Two types of neuronal activity were distinguished during the delay periods. First, the activity gradually changed depending on the duration of the cue presented just before. This activity may represent the signal duration for later comparison between two cue durations. The activity during the second cue period also represented duration of the first cue. Second, the activity changed differently depending on whether the first or second cue was presented longer. This activity may represent discrimination results after the comparison between the two cue durations. These findings support the assumption that striatal neurons represent timing information of sensory signals for duration discrimination.

Magnetically evoked EMGs in rats.

Magnetic stimulation of the brain and spinal cord was carried out in rats to record electromyogram (EMGs) from the gastrocnemius. A figure-eight coil was set over the middle of the dorsum, and shifted from the cervical vertebrae to the sacrum. The motor evoked potentials (MEPs) with 4.8 msec latency by transcranial magnetic stimulation and the descending wave with 4.7 msec latency by C3-C4 stimulation were recorded. In evoked EMGs by magnetic stimulation over T9-T10, L4-L5, S2-S3 and Ca2-Ca3 spinal cord levels, the causes of these two evoked components with short (1.5 msec) and long (4.1 msec) latencies were estimated to be the eddy current generated from the rostral to the caudal portion of the spinal cord. With the increase in magnetic stimuli, the relative sizes and disappearance of H- and M-like responses were comparable with the ordinary M- and H-responses in electrically evoked EMGs. The magnetic stimulation of the spinal cord activated the sciatic nerve at their vertebral exit, because the latencies of the H- and M-responses were constant despite the changing stimulus sites. Although magnetic stimulation with the figure-eight coil can be focused on the target, it is necessary to take into consideration the influence of the eddy current flowing in the body.

Motor evoked potentials in rats with congenital hydrocephalus.

Motor evoked potential (MEP) by focal transcranial magnetic stimulation was used to test the functional integrity of the motor cortex in congenital hydrocephalic rats. Magnetic MEPs, using a figure-eight coil above the head, were recorded in the tibialis anterior muscle. The latency of transcranial magnetic MEP was 3.4 msec in nonhydrocephalic rats. In the hydrocephalic rats, the MEP had a lower threshold than in nonhydrocephalic rats, and showed two peaks. Latencies of early and late peaks were 3.9 msec and from 5.4 msec to 10.0 msec, respectively. Our findings suggest that hydrocephalus in rats is associated with changes in pyramidal cell excitability in the motor cortical area, probably induced by the fluctuations in cortical excitability and synaptic interaction in hydrocephalic rats.

Successful curative resection of gallbladder cancer following S-1 chemotherapy: A case report and review of the literature.

The symptoms of gallbladder cancer (GBC) are vague and non-specific. Therefore, GBC is often detected at an advanced or metastatic stage. The most effective treatment for GBC is surgical resection, however the majority of GBC cases are unresectable at the time of diagnosis. Therefore, numerous GBC patients undergo chemotherapy. This study reports the case of a 60-year-old female with GBC who underwent successful surgical curative resection following a single dose of the chemotherapeutic agent, S-1, twice daily for 4 weeks followed by a 14-day rest period for 36 months. S-1 is a novel orally administered drug composed of a combination of the 5-fluorouracil (5-FU) prodrug, tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP) and oteracil potassium in a 1:0.4:1 molar concentration ratio. The focus of the present study was the candidate factors that affect the therapeutic efficacy of S-1-based chemotherapy. In particular, the gene expression involved in the S-1 metabolic pathway was investigated by assessing the intratumoral dihydropyrimidine dehydrogenase (DPD), thymidylate synthase (TS) and orotate phosphoribosyltransferase gene expression. The surgical specimen exhibited high intratumoral DPD gene expression levels compared with those observed in previously reported non S-1 responsive cases of biliary tract cancer. Due to the results obtained in the current study, we hypothesize that CDHP enhanced the antitumor efficacy of 5-FU by inhibiting the excess DPD protein produced by the tumor.

Unruptured cystic artery pseudoaneurysm accompanied by Mirizzi syndrome: a report of a case.

Pseudoaneurysm of the cystic artery is a rare complication of cholecystitis. 34 cases have been reported from 1976 to 2012, searched on MEDLINE and most of the cases have presented with gastrointestinal bleeding. We report the third case of an unruptured pseudoaneurysm of the cystic artery associated with calculous cholecystitis. An 85-year-old female presented to the emergency unit with epigastric pain and jaundice. Laboratory data and contrast-enhanced computed tomography (CT) revealed calculous cholecystitis and Mirizzi syndrome accompanied by a pseudoaneurysm in the gallbladder. Color Doppler ultrasonography (US) clearly demonstrated the pulsatile pseudoaneurysm. After biliary drainage and antimicrobial therapy, selective hepatic angiography with the aim of providing transcatheter arterial embolization was performed but the pseudoaneurysm had already thrombosed spontaneously. Open cholecystectomy was successfully carried out. Histological specimens demonstrated the pseudoaneurysm with organized thrombus in the epithelial wall of the gallbladder thickened with severe fibrosis. It is suggested that cholecystitis with unusual symptoms such as gastrointestinal bleeding requires immediate enhanced CT and US with Doppler imaging in order not to overlook a rare but life-threatening pseudoaneurysm.

Vps33a mediates RANKL storage in secretory lysosomes in osteoblastic cells.

Previous studies have indicated that the amount of RANKL expressed on the cell surface of osteoblasts or bone marrow stromal cells (BMSCs) is considered an important factor determining the extent of osteoclast activation. However, subcellular trafficking of RANKL and its regulatory mechanisms in osteoblastic cells is still unclear. In this study, we showed that RANKL is predominantly localized in lysosomal organelles, but little is found on the cell surface of osteoblastic cells. We also showed that RANKL is relocated to the plasma membrane in response to stimulation with RANK-Fc-coated beads, indicating that the lysosomal organelles where RANKL is localized function as secretory lysosomes. In addition, using a protein pull-down method, we identified vacuolar protein sorting (Vps)33a as interacting with the cytoplasmic tail of RANKL. Furthermore, knockdown of Vps33a expression reduced the lysosomal storage of RANKL and caused the accumulation of newly synthesized RANKL in the Golgi apparatus, indicating that Vps33a is involved in transporting RANKL from the Golgi apparatus to secretory lysosomes. We also showed that suppression of Vps33a affects the cell surface expression level of RANKL and disrupts the regulated behavior of RANKL. These results suggest that RANKL storage in secretory lysosomes is important to control osteoclast activation and to maintain bone homeostasis.

A prospective randomized controlled multicenter trial of duodenoscopes with 5 degrees and 15 degrees backward-oblique angle using wire-guided cannulation: effects on selective cannulation of the common bile duct in endoscopic retrograde cholangiopancreatography.

BACKGROUND: In duodenoscopy, during endoscopic retrograde cholangiopancreatography (ERCP), a backward-oblique angle duodenoscope (BOAD) is generally used. In Japan, 15 degrees BOAD are mainly used, but in Western countries, 5 degrees BOAD are mostly used. In bile duct cannulation associated with ERCP, a catheter for contrast imaging is used in Japan, but wire-guided cannulation (WGC) using a papillotome is standard in Western countries. We conducted a randomized controlled multicenter trial to evaluate the contributions of different duodenoscopes using WGC to selective common bile duct cannulation. METHODS: Subjects comprised 179 consecutive patients who underwent ERCP. Patients were randomized into the 15 degrees BOAD group (15 degrees group, n = 90) or the 5 degrees BOAD group (5 degrees group, n = 89). RESULTS: The duodenal papilla could not be accessed endoscopically in two cases from each group. Success rates for bile duct cannulation by WGC without bow-up for the 15 degrees and 5 degrees groups were 85.6 and 56.2%, respectively (P < 0.01). Success rates for bile duct cannulation by WGC with bow-up for the 15 degrees and 5 degrees groups were 88.9 and 78.7%, respectively. Total rates of bile duct cannulation for the 15 degrees and 5 degrees groups were 94.4 and 92.1%, respectively. As for accidents, incidences of acute pancreatitis for the 15 degrees and 5 degrees groups were 5.6 and 9.0%, respectively, with no significant difference seen. CONCLUSIONS: With 15 degrees BOAD, bile duct cannulation was favorable without papillotome bow-up. With 5 degrees BOAD, the success rate of WGC may be improved by adjusting the angle based on papillotome bow-up.

Delay period activity of monkey prefrontal neurones during duration-discrimination task.

Evidence from brain imaging studies has indicated involvement of the prefrontal cortex (PFC) in time perception; however, the role of this area remains unclear. To address this issue, we recorded single neuronal activity from the PFC of two monkeys while they performed a duration-discrimination task. In the task, two visual cues (a blue or red square) were presented consecutively followed by delay periods and subjects then chose the cue presented for the longer duration. Durations of both cues, order of cue duration [long-short (LS) or short-long (SL)] and order of cue colour (blue-red or red-blue) were randomized on a trial-by-trial basis. We found that subjects responded differently between LS and SL trials and that most prefrontal neurones showed significantly different activity during either the first or the second delay period when comparing activity in LS and SL trials. The present result offers new insights into neural mechanisms of time perception. It appears that, during the delay periods, the PFC contributes to implement a strategic process in temporal processing associated with a trial type (LS or SL) such as representation of the trial type, retention of cue information and anticipation of the forthcoming cue.

Phosphate metabolites in muscular contraction caused by magnetic stimulation.

The metabolism of high energy phosphates during muscular contraction due to direct electrical stimulation, indirect stimulation via nerve excitation, and magnetic stimulation was studied in isolated muscles (frog sartorius muscles) by (31)P nuclear magnetic resonance ((31)P-NMR). Twitch amplitudes elicited by each stimulus were measured alternatively at 3 mm displacement loading and 5 g weight. Both the creatine/inorganic phosphate (PCr/Pi) and pH changes were more marked in direct electrical stimulation than in magnetic stimulation. The muscular contraction caused by magnetic stimulation showed less fatigue than that caused by direct electrical muscular stimulation.

Surgical approach to tumor recurrence and metastatic lesions of the liver in a patient with malignant endocrine tumors of the pancreas: case report.

We describe herein a 72-year-old woman with tumor recurrence in the residual pancreas and metastasis to the liver following a pylorus-preserving pancreatoduodenectomy for multiple endocrine tumors in the head of the pancreas. Abdominal ultrasonography performed 7 years after the initial surgery detected new lesions in the residual pancreas and liver. After recurrence of endocrine tumors of the pancreas and metastasis to the liver were diagnosed, the lesions were successfully resected by total pancreatectomy with distal gastrectomy and both lateral segmentectomy and partial resection of segment 8. Genetic analysis using a blood specimen showed that this patient carried the multiple endocrine neoplasia type 1 (MEN1) gene mutation. One year after the second resection, the patient remains in good health using insulin and has not shown any sign of recurrence. This case report describes successful surgical resection for recurrence and metastasis of malignant endocrine tumors in a patient with the MEN1 gene mutation.