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Acid-sensing ion channel-2a (ASIC2a) is an amiloride-blockable proton-gated cation channel, probably contributing to sour-taste detection in rat taste cells. To isolate another subtype of the sour-taste receptor, we screened a rat circumvallate papilla cDNA library and identified ASIC2b, an N-terminal splice variant of ASIC2a. Reverse transcription-PCR analyses confirmed the expression of ASIC2b transcripts in the circumvallate papilla and, moreover, demonstrated its expression in the foliate and fungiform papillae. Immunohistochemical analyses revealed that ASIC2b, as well as ASIC2a, was expressed in a subpopulation of taste cells in the circumvallate, foliate, and fungiform papillae, and some of the cells displayed both ASIC2a and ASIC2b immunoreactivities. Subsequent coimmunoprecipitation studies with circumvallate papillae extracts indicated that ASIC2b associated with ASIC2a to form assemblies and, together with our immunohistochemical findings, strongly suggested that both ASIC2 subunits formed heteromeric channels in taste cells in the circumvallate, foliate, and fungiform papillae. Oocyte electrophysiology demonstrated that the ASIC2a/ASIC2b channel generated maximal inward currents at a pH ofor =2.0, which is in agreement with the in vivo pH sensitivity of rat taste cells, and that the amiloride sensitivity of the heteromer decreased with decreasing pH and was almost completely abolished at a pH of 2.0. These findings provide persuasive explanations for the amiloride insensitivity of acid-induced responses of rat taste cells.

Pungent sensation of hot peppers is thought to be mediated by vanilloid receptor subtype-1 (VR1), which can be activated by capsaicin, but there is little information regarding its histological localization in the tongue. We examined the immunohistochemical distribution of VR1 in the rat tongue. Intensely labeled VR1-immunoreactive (VR1-IR) fibers were concentrated in the circumvallate, foliate, and fungiform papillae, while sparse VR1-IR fibers were scattered throughout the tongue. VR1-positive taste-bud cells were not observed. Many VR1-positive nerve fibers surrounded the furrows of the circumvallate and foliate papillae, forming plexuses. Some of these VR1-positive fibers penetrated the apical epithelium and the trench wall epithelium, while a few of them entered taste buds. These VR1 distribution patterns resembled those of substance P (SP) and the calcitonin gene-related peptide (CGRP). Double-labeling experiments revealed that most of the VR1-immunoreactivity coexisted with SP- or CGRP-immunoreactivity in the nerve terminals in the circumvallate and foliate papillae. On the other hand, in the fungiform papillae, most of the VR1-IR fibers were positive for SP, but fewer were also positive for CGRP. Although VR1-immunoreactivity was not observed in taste-bud cells, our findings that a large number of VR1-IR fibers concentrated in the taste papillae suggest that capsaicin easily reaches the VR1 nerve terminals because of its lipophilic nature.

To the paralyzed or those otherwise enable to move on their own, we have been developing ""muscle suit"" providing muscular support. Muscle suit are worn and use a McKibben actuator driven by compressed air. Because actuators are sewn into a garment, no metal frame is needed, making a muscle suit very light and cheap. Most medical and welfare apparatuses were developing for caregivers rather than patients in need of nursing, causing patients to lose their own identity and a positive attitude. With muscle suit, they could control their movement of their own will. Muscle suit are very helpful for muscular and mental support.

The 20q11.2 microdeletion is a rare chromosomal aberration characterized by intellectual disability (ID), motor developmental delay, neonatal feeding problems, and facial dysmorphism. Here, a 2-year- and 6-month-old Japanese girl with a 1.2 Mb microdeletion of 20q11.2 showed ID, motor developmental delay, and distinctive facial features without feeding problems. The deleted region was identified by array-based comparative genomic hybridization and is the smallest reported for a 20q11.2 microdeletion.

In this paper, the plastic singular stress field for a crack normal to and meeting a bimaterial interface is studied by using FEM. In the analysis, it is assumed that both materials obey Ramberg-Osgood stress-strain formulation, and have different strain hardening exponent n. Detailed results for MODE I under plane strain are investigated. When n1 for the material with a crack is larger than n2 for the other material without the crack, the plastic singular stress field obtained by FEM is almost the same field obtained by asymptotic analysis. However, from the FEM result, it is found that a term which is independent of the distance r from the crack tip is included in the displacement field so as to satisfy the continuity of displacement along the interface. When n1 < n2, the plastic stress singularity exists near the crack tip, but the stress singularity cannot be described as a power-type singularity form.

In our research program for investigating anti-dementia agents from natural plant resources, we screened extracts from 15 spice samples. Among the plant extracts tested, ethyl acetate extract prepared from rhizome of Zingiber zerumbet showed potent activity. Activity-guided purification led to determination of afzelin and its acetylated compound as the active principles. Afzelin showed moderate inhibitory activity against acetylcholinesterase and may also be expected to possess anti-butyrylcholinesterase activity. This is the first report to reveal the anti-cholinesterase activities of ethyl acetate extract of Z. zerumbet and afzelin. Furthermore, Z. zerumbet may be a potential therapeutic agent for the improvement of dementia, especially Alzheimer's disease.

Rapid immunohistochemistry (R-IHC) can contribute to the intraoperative diagnosis of central nervous system (CNS) tumors. We have recently developed a new IHC method based on an alternating current electric field to facilitate the antigen-antibody reaction. To ensure the requirement of R-IHC for intraoperative diagnosis, 183 cases of CNS tumors were reviewed regarding the accuracy rate of diagnosis without R-IHC. The diagnostic accuracy was 90.7 % (166/183 cases) [corrected] in which definitive diagnoses were not provided in 17 cases because of the failure of glioma grading and differential diagnosis of lymphoma and glioma. To establish the clinicopathological application, R-IHC for frozen specimens was compared with standard IHC for permanent specimens. 33 gliomas were analyzed, and the Ki-67/MIB-1 indices of frozen specimens by R-IHC were consistent with the grade and statistically correlated with those of permanent specimens. Thus, R-IHC provided supportive information to determine the grade of glioma. For discrimination between glioma and lymphoma, R-IHC was able to provide clear results of CD20 and Ki-67/MIB-1 in four frozen specimens of CNS lymphoma as well as standard IHC. We conclude that the R-IHC for frozen specimens can provide important information for intraoperative diagnosis of CNS tumors.

To investigate the early events of JC virus (JCV) infection, including attachment, penetration, transport to the nuclei, and replication of the virus, we analyzed the susceptibility of 15 different cell lines to infection using a semiquantitative polymerase chain reaction (PCR) assay, in situ hybridization, laser scanning confocal microscopy, and a viral replication assay. The cell lines examined were human permissive and nonpermissive cells as well as cells of monkey and mouse origin. JCV entry into the nuclei of the all cell lines was observed within 10 min after inoculation, demonstrating that the virus receptor is widely distributed among mammalian cells. Inhibition of viral entry by an anti-JCV VP1 antibody and sialidase treatment to remove sialic acid residues, which are considered a candidate for the JCV receptor, suggested that VP1 may interact with the cellular surface sialic acid. In addition, chlorpromazine, a clathrin-dependent pathway inhibitor, significantly suppressed entry of JCV into nuclei. In spite of the broad spectrum of cells susceptible to JCV entry, replication of the virus occurred exclusively in human neuroblastoma cell lines. These results suggest that whereas JCV can enter a wide variety of cell types and localize to the nuclei, cell-specific intranuclear mechanisms are required for virus replication.

A 75-year-old man who underwent choledochojejunostomy for gallstones 30 years ago was hospitalized for general malaise. Abdominal computed tomography revealed marked dilation of the intrahepatic bile duct in the right lobe and an image of a hypervascular tumor. Endoscopic retrograde cholangiography using double-balloon enteroscopy (DBE) showed a filling defect that was localized to the right hepatic bile duct. Furthermore, the scope was able to readily pass through the anastomosed site of the choledochojejunostomy and, therefore, we observed the interior of the bile duct using the same scope. We obtained an image showing a whitish, papillary-like tumor, and a biopsy of the tumor rendered the pathology of intraductal papillary mucinous carcinoma. Direct cholangioscopy using DBE is a useful diagnostic tool, particularly in patients with a past history of choledochojejunostomy.

Autoimmune pancreatitis (AIP) occurs in association with a variety of multiorgan pathologies. AIP coexists most often with sclerosing cholangitis, and involvement of the lachrymal gland, salivary gland, thyroid gland, lymph nodes, and retroperitoneum has been reported, although these are less common. It has been reported that gastric ulcers are associated with AIP, even though these are actually rare. We encountered a case of IgG4-positive multiple inflammatory gastric polyps in a patient with AIP. We believe that there are no similar previous reports, so we present our findings as a case report.

There are two major hurdles to carrying out endoscopic retrograde cholangiopancreatography (ERCP) in patients with altered gastrointestinal anatomy (Billroth II gastrectomy [B-II], Roux-en-Y anastomosis [R-Y] etc.), post-pancreatoduodenectomy or post-choledochojejunostomy. These are: (i) the endoscopic approach to the afferent loop, blind end, and the site of bilio-pancreatic anastomosis; and (ii) bile duct and/or pancreatic duct cannulation. Balloon-assisted enteroscopy (BAE) became available in recent years and is now being actively used to overcome the first hurdle and, at least, the success rate has improved. However, room for improvement still remains in regards to the second hurdle (i.e. the success rate of cannulation of the bile duct and/or pancreatic duct), and there has been a desire for the development of dedicated devices (ERCP catheters, hoods etc.) and for improvement in the functionality of the enteroscopes etc. In the present review, we explain the basic procedure for bile duct and/or pancreatic duct cannulation with conventional endoscopes and BAE, and modifications of the basic procedure.

The morphogenesis of hepatocytes after massive hepatic necrosis to recovery through liver cell regeneration has not been fully understood. Sequential biopsies were performed on the native liver of a 22-year-old man who underwent auxiliary partial orthotopic liver transplantation 1 month after fulminant hepatitis. Auxiliary partial orthotopic liver transplantation was successful, and the biopsy samples permitted us to examine the regenerating process of hepatocytes after massive necrosis. At the time of auxiliary partial orthotopic liver transplantation (postoperative day 0), 95% of hepatocytes were lost and a few ductules were found in the portal areas. The ductules stained with cytokeratin 19. At postoperative day 7, the ductules began to increase in size and number and became dilated over a period of 1 month, when individual hepatocytes with clear cytoplasm appeared from the ductules. As the differentiation of hepatocytes increased, the expression of cytokeratin 19 was found to decrease. From 2 to 3 months, all of the ductules were transformed into hepatocytes, and they began to form round cell clusters. From 3 to 6 months, the round cell clusters became organized into trabecula with fibrosis. From 6 to 12 months, a lobular architecture was established, and by 14 months, the necrotic liver was fully recovered to normal. This study by examination of sequential biopsies demonstrates the progression of the regenerating process from total hepatic necrosis to complete recovery.

The 5-hydroxytryptamine type 3 (5-HT3) receptor is a ligand-gated ion channel and a member of the Cys-loop family of receptors. Previous studies have shown 5-HT3 receptor expression in various neural cells of the central and peripheral nervous systems. Although the function and distribution of the 5-HT3 receptor has been well established, its role in the inner ear is still poorly understood. Moreover, no study has yet determined its localization and function in the peripheral vestibular nervous system. In the present study, we reveal mRNA expression of both 5-HT3A and 5-HT3B receptor subunits in the mouse vestibular ganglion (VG) by RT-PCR and in situ hybridization (ISH). We also show by ISH that 5-HT3 receptor mRNA is only expressed in the VG (superior and inferior division) in the peripheral vestibular nervous system. Moreover, we performed Ca2+ imaging to determine whether functional 5-HT3 receptors are present in the mouse VG, using a selective 5-HT3 receptor agonist, SR57227A. In wild mice, 32% of VG neurons responded to the agonist, whereas there was no response in 5-HT3A receptor knockout mice. These results indicate that VG cells express functional 5-HT3 receptor channels and might play a modulatory role in the peripheral vestibular nervous system.

Small cell glioblastoma is a histological subtype of glioblastoma with characteristic features of highly proliferative, monotonous small glial cells with high nuclear cytoplasm ratio. Morphologically, malignant lymphoma or small cell metastatic carcinoma should be carefully discriminated. Some cases are difficult to differentiate from anaplastic oligodendroglioma. In this report, we present a case of small cell glioblastoma of an elderly man. The lack of IDH1/2 mutation was confirmed by immunohistochemistry and direct sequencing. Fluorescence in situ hybridization revealed the lower rates of chromosome 1p and 19q deletion. Microsatellite analysis disclosed partial 10q alteration near the PTEN locus. Not only morphological and immunohistochemical examinations, but also cytogenetical investigations for IDH1/2 mutation, 1p/19q loss, and PTEN alteration, are strongly supportive methods for the differential diagnosis of small cell glioblastoma and anaplastic oligodendroglioma.

The success of biliary drainage in patients with liver metastases from colorectal cancer and obstructive jaundice influences its prognosis greatly. In this study, we report a retrospective evaluation of endoscopic retrograde biliary drainage in patients with liver metastases from colorectal cancer and obstructive jaundice.From April 2004 to December 2011, 9 patients with liver metastases from colorectal cancer and obstructive jaundice who underwent endoscopic biliary drainage were evaluated retrospectively.The mean serum levels of total bilirubin, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase improved significantly after biliary drainage. The median survival time after biliary drainage was 133 days. Only 4 cases were able to resume chemotherapy after biliary drainage, and their prognosis was significantly better than patients who were not able to resume chemotherapy(p=0.014).Endoscopic biliary drainage in patients with liver metastases from colorectal cancer and obstructive jaundice was effective, led to the resumption of chemotherapy, and improved prognosis. However, sufficient consideration of the patient's prognosis and performance status is required in order to perform biliary drainage.

At present, the endoscopic approach is the most commonly adopted method for stenting in patients with unresectable malignant hilar biliary stricture. This procedure is important, as it determines the quality of life and prognosis of the patient. Regarding the quality of the stent material, self-expandable metallic stents (SEMS) are expected to show longer-term stent patency than plastic stents (PS), and their use as devices of first choice has been increasing. However, complications such as stent occlusion due to tumor ingrowth or biliary sludge formation occur at a considerably high frequency, necessitating reintervention in a considerable number of patients. In the case of dysfunction of an implanted PS, the stent is removed, and the lumen of the bile duct is cleaned, followed by placement of a new stent. In the event of dysfunction of a SEMS, cleaning of the lumen of the SEMS and placement of a second stent (PS is preferable) are carried out. Nevertheless, the results have not been entirely gratifying. Development of SEMS or PS suited to multidisciplinary treatment that would enable uncomplicated reintervention is anticipated.

Detailed endoscopic findings of the bile duct mucosa, even of the non-neoplastic mucosa, have not yet been established. The aim of the present study was to compare a currently used video cholangioscope (CCS) with a magnifying endoscope (ME) that is commonly used for the gastrointestinal tract, for visualization of the bile duct mucosa.Ten freshly resected common bile ducts were used in this study. We observed the non-neoplastic bile duct mucosa with CCS and ME, and carried out both conventional white light imaging and narrow band imaging. After histological diagnosis, the 10 specimens were classified into three categories according to the degree of histological inflammation: normal to mild, moderate, and severe. Then, we examined the relationship between the magnifying endoscopic findings and the histopathological findings.In eight of the 10 cases, the visualization obtained with CCS was inferior to that obtained by ME. Five specimens were classified as normal to mild inflammation, and many oval-shaped, depressed areas and a fine, regular network of the microvessels were observed by ME on the mucosal surfaces of these specimens. The remaining specimens were classified as moderate or severe inflammation, and the aforementioned findings could not be clearly visualized.CCS does not allow visualization of the bile duct mucosa with high sensitivity. Oval-shaped depressed areas and a fine, regular network of microvessels are characteristic endoscopic features of non-neoplastic bile duct mucosa without inflammation.

The patient was a 69 year old man who had been diagnosed with alcoholic chronic pancreatitis and lower common bile duct (CBD) stricture. He subsequently developed cholangitis 2-3 times a year, and we replaced the endoscopic biliary stent (EBS) each time. In April 2010, he was admitted because of complication by a liver abscess and acute cholangitis. We performed percutaneous transhepatic liver abscess drainage. The inflammatory findings then rapidly improved, but the patient developed acute cholangitis due to the sludge and the stones. Then, we placed a partially covered self-expandable metallic stent (C-SEMS) in the lower CBD and performed endoscopic lithotripsy through the C-SEMS, and the cholangitis subsequently improved. Two weeks after, we removed the C-SEMS endoscopically and replaced it with a 10 Fr plastic stent; since then there have been no recurrences of cholangitis. Our experience in this case suggested that when a plastic stent is placed long-term to treat a biliary stricture associated with chronic pancreatitis, it might be useful to also control biliary sludge and stones using a C-SEMS.

Aims Acinar cell carcinomas (ACCs) are rare tumours of the exocrine pancreas accounting for about 1–2% of all pancreatic neoplasms in adults. It is therefore difficult to come across a large number of ACC cases in a single medical institution, and only a few serial studies have been published. Since ACCs present a wide variety of morphological patterns, immunohistochemical analysis is useful. In this study, the authors established a novel monoclonal antibody 2P-1-2-1 by means of a subtractive immunisation method. Methods Immunohistochemical staining was performed using 50 primary pancreatic tumors, including 7 ACCs, 7 neuroendocrine tumours (NETs), 5 solid-pseudopapillary neoplasms (SPNs), and 31 ductal carcinomas and organs other than the pancreas. Results Non-neoplastic acinar cells were stained diffusely, but epithelial cells of the pancreatic duct and the islets of Langerhans were not stained. In pancreatic tumours, all the seven ACCs were diffusely positive for the 2P-1-2-1 antibody. However, no positive staining was found in other pancreatic tumours including NETs, SPNs and ductal adenocarcinomas. The sensitivity and specificity of the 2P-1-2-1 antibody for ACCs were both 100%. In other organs studied, positive staining was observed only in the ectopic pancreas. Conclusions It was shown that the 2P-1-2-1 antibody specifically stained the pancreatic acinar cells and tumours of acinar cell origin, such as ACCs. Although it remains unclear at this time to which proteins the monoclonal antibody 2P-1-2-1 is directed, it is suggested to be useful for the pathological diagnosis of ACCs and for the exclusion of other pancreatic tumours.

Intrahepatic cholangiocarcinoma (ICC) is one of the life-threatening complications of primary sclerosing cholangitis (PSC). However, the incidence of ICC in Japanese PSC patients is low, and the association between the development of ICC and morbidity duration of PSC is largely unknown. Here, we describe a case of ICC that developed after a long-term follow-up of a patient with PSC and ulcerative colitis (UC). At the age of 10 years, the patient was first diagnosed with UC and its remission was achieved with systemic steroid therapy. Since then, he was routinely followed-up. At the age of 19 years, laboratory tests showed abnormalities in liver function parameters, and the patient was diagnosed with PSC. Although treatment with ursodeoxycholic acid improved the abnormalities in serum levels of biliary enzymes and no PSC-related symptoms were seen for 13 years, calculous cholecystitis frequently occurred in the patient since the age of 32 years. He developed ICC, which expressed some hepatic progenitor cell markers such as CD133, neural cell adhesion molecule, keratin 7, and keratin 19 at the age of 33 years. ICC was treated by curative partial hepatectomy and adjuvant chemotherapy with gemcitabine. Eight months later, however, the patient developed multiple metastases in the abdominal lymph nodes and lungs, and died 21 months after the onset of ICC. Here, we report a case of ICC that developed after a 14-year follow-up of a patient with PSC and UC.

Type 1 autoimmune pancreatitis (AIP) is characterized by the increase of serum immunoglobulin (Ig)G4 and abundant IgG4 plasma cell infiltration in the pancreas and various extrapancreatic lesions (EPL), which are proposed as IgG4-related disease. We assessed the correlation between serum IgG4 and the number of EPL, and the association between serum IgG4 and the distribution of EPL in type 1 AIP patients.Serum IgG4 was measured in 35 type 1 AIP patients and 71 non-AIP patients. The clinical characteristics and distribution of eight EPL were determined in 35 type 1 AIP patients.Serum IgG4 in type 1 AIP was significantly higher than in non-AIP (P0.001). A total of 33 patients had EPL among 35 patients with type 1 AIP (94.3%). There was a significant correlation between serum IgG4 and the number of EPL (ρ = 0.75, P0.001). Further, to assess the association between serum IgG4 and the distribution of EPL, type 1 AIP patients were divided into two groups: as abdominal localized EPL and systemic EPL. Both serum IgG4 and total numbers of EPL in systemic EPL were remarkably higher than those in abdominal localized EPL. Serum IgG4 cut-off value was 346 mg/dL to distinguish between abdominal localized EPL and systemic EPL according to the receiver-operator characteristic curve data.Our findings indicated that serum IgG4 was useful in both the diagnosis of type 1 AIP and the detection of systemic EPL. Our finding may help the concept and diagnostic criteria of IgG4-related disease with type 1 AIP.

Diagnosis of cystic lesions of the pancreas is made by clinical history taking, physical examination, blood biochemical tests and diagnostic imaging, such as transabdominal ultrasound, endoscopic ultrasound (EUS), cross-sectional imaging (computed tomography and/or magnetic resonance imaging) and endoscopic retrograde cholangiopancreatography, bearing in mind the known characteristic features of the various cystic lesions that can occur in this organ. Among others, EUS, endowed with a sharp local resolving power, has been described as a highly useful examination method, because it enables concurrent fine-needle aspiration (FNA). EUS has an important role in the differential diagnosis and tumor grading (benign, premalignant or malignant) of cystic lesions. Although the differential diagnosis of cystic lesions of the pancreas based on EUS morphology is practicable to some extent, there have also been reports showing that the diagnosis might vary with the endosonographer and that the diagnostic performance of this method for tumor grading is not necessarily high. In countries overseas, differential diagnosis and tumor grading of cystic lesions of the pancreas are actively undertaken not merely by EUS morphology, but also by cyst-fluid EUS-guided FNA (EUS-FNA) cytology and measurements of pancreatic enzymes and tumor markers, and importance is attached to EUS-FNA in the latest version of the American Society for Gastrointestinal Endoscopy Guideline and in the diagnostic strategies for cystic diseases of the pancreas. Meanwhile, the current Japanese consensus is that EUS-FNA is not recommended in cases of mucinous cystic lesions suspected as being intraductal papillary mucinous neoplasm or mucinous cystic neoplasm.

This paper presents a new IGBT based AC drive inverter and its DC source converter, which were developed for industrial applications. AC drive inverter provides some benefits to customer, very large capacity for an induction motor, a compact footprint and a secured safety stop sequence which is compliant with ISO/IEC functional safety standard. And DC source converter to supply DC input power to AC drive system also provides some benefits as same as AC drive inverter. In addition, it is expected that new PWM control "Instantaneous Current Control PWM (IccPWM)" can improve performance to suppress a harmful harmonics against other surrounding devices and provide a simple harmonic filter to comply with IEEE-519 harmonic limits.

A 75-year-old man who underwent choledochojejunostomy for gallstones 30 years ago was hospitalized for general malaise. Abdominal computed tomography revealed marked dilation of the intrahepatic bile duct in the right lobe and an image of a hypervascular tumor. Endoscopic retrograde cholangiography using double-balloon enteroscopy (DBE) showed a filling defect that was localized to the right hepatic bile duct. Furthermore, the scope was able to readily pass through the anastomosed site of the choledochojejunostomy and, therefore, we observed the interior of the bile duct using the same scope. We obtained an image showing a whitish, papillary-like tumor, and a biopsy of the tumor rendered the pathology of intraductal papillary mucinous carcinoma. Direct cholangioscopy using DBE is a useful diagnostic tool, particularly in patients with a past history of choledochojejunostomy.

In patients with choledocholithiasis, a stone can sometimes become impacted in the ampulla of Vater, potentially resulting in the complications of acute cholangitis and acute pancreatitis. Endoscopic sphincterotomy and needle knife papillotomy are very effective for the removal of an impacted stone in the ampulla of Vater. Dramatic improvement of the symptoms may be expected if these procedures are performed sufficiently early after the occurrence of the impaction. However, depending on the size, site and situation of the impacted stone, we have often encountered difficulties during endoscopic treatment. We encountered two interesting cases of choledocholithiasis with impaction of large stones in the ampulla of Vater. In Case 1, treatment with radial incisions was added to the usual treatment of needle knife papillotomy, because of the large size of the stone, and the combined treatment was effective. In Case 2, a large periampullary choledochoduodenal fistula was created at the ampulla of Vater, and an indwelling double pigtail tube was placed in the ampulla; the stone then discharged via the tube without additional need for endoscopic sphincterotomy or needle knife papillotomy. Our experience in these cases indicates that innovations in treatment according to the situation of the impacted stone may be needed for the treatment of giant impacted stones in the ampulla of Vater.

Computational methods of enumerating chemical graphs have attained great importance in chemoinformatics since they lead to a variety of useful applications including structure determination of novel chemical compounds. Recently, Fujiwara et al. have presented an efficient branch-and-bound algorithm for enumerating treelike chemical graphs with given path frequency. In this paper, we augment Fujiwara et al.'s algorithm by introducing a new bounding operation called detachment-cut to reduce further the search space in the branch-and-bound framework. Experimental results on much chemical compound data show that our proposed algorithm achieves better performance than Fujiwara et al.'s algorithm in computation time. A program that implements our algorithm can be used freely via Web server.

The aim of this study was to compare multidetector-row computed tomography (MDCT) findings between cases of sclerosing cholangitis with autoimmune pancreatitis (SC-AIP) and infiltrative extrahepatic cholangiocarcinoma (IEC). We retrospectively assessed MDCT findings from 16 IEC cases and 13 SC-AIP cases. MDCT findings were analyzed with regard to location, length, wall thickness, contour, stricture wall enhancement pattern, proximal duct diameter, and the presence of diffuse concentric thickening in the proximal duct and gallbladder wall thickness. Stricture length, stricture wall thickness, and proximal duct diameter were significantly smaller for SC-AIP than for IEC: 19.3 ± 8.7 vs. 31.8 ± 12.0 mm (P = 0.004), 2.1 ± 1.3 vs. 4.1 ± 1.3 mm (P < 0.001), and 9.2 ± 3.9 vs. 13.3 ± 5.0 mm (P = 0.012), respectively. SC-AIP was correlated with stricture location in both the intrapancreatic and hilar hepatic bile ducts, concentric stricture contour (P < 0.001), and diffuse concentric thickening of the proximal bile duct (P = 0.010). Overall values of sensitivity, specificity, and accuracy used to distinguish between SC-AIP and IEC for stricture wall thickness of

Proximally migrated biliary plastic stent and migrated stent in the pancreatic pseudocyst are relatively rare complications. A migrated stent causes poor drainage conditions, which leads to secondary complications such as infection, abscess, perforation and, moreover, becomes a foreign object in the body, and retrieval or re-stenting is therefore necessary. The retrieval of a migrated stent includes surgical, percutaneous and endoscopic approaches, and the most non-invasive method is endoscopic retrieval. However, because very few devices are exclusively designed for retrieval, the current situation is that the available devices are used while taking advantage of various ideas and techniques. From previously reported cases and our experiences of such cases, we herein describe the methods of endoscopic retrieval for stents that have migrated into a bile duct or pancreatic pseudocysts.

TRPM8 and TRPA1 are cold-activated transient receptor potential (TRP) cation channels. TRPM8 is activated by moderate cooling, while TRPA1 is activated by extreme, noxious cold temperatures. These cold receptors are expressed in different subpopulations of primary afferent neurons. TRPA1 is co-expressed in a subpopulation of somatosensory neurons expressing TRPV1, which is activated by heat. However, the distribution and co-expression of these channels in the nodose-petrosal ganglion complex, which contains the jugular (JG), petrosal (PG), and nodose ganglia (NG) (mainly involved in putative somatic, chemo- and somato-sensation, and somato and visceral sensation, respectively), remain unknown. Here, we conducted in situ hybridization analysis of the rat nodose-petrosal ganglion complex using specific riboprobes for TRPM8, TRPA1, and TRPV1 to compare the features of the cranial sensory ganglia. Hybridization signals for TRPA1 were diffusely observed throughout these ganglia, whereas TRPM8 transcripts were seen in the JG and PG but not in the NG. We retrogradely labeled cranial nerve X with Fast Blue (fluorescent dye) and found TRPM8 transcripts in the jugular-vagal ganglion but not the NG neurons. TRPA1 transcripts were not detected in TRPM8-expressing neurons but were present in the subpopulation of TRPV1-expressing visceral sensory neurons. Taken together, these findings support that in the vagal system the expression of cold-activated TRP channels differs between nodose- and jugular-ganglion neurons suggesting different mechanisms of cold-transduction and that the TRPA1 distribution is consistent with its proposed function as a cold-sensing receptor in the visceral system.

G-protein-coupled receptors (GPCRs) are important therapeutic targets for many areas of drug research and development. Although chimeric Galpha16 proteins are valuable tools for detecting the activation of Galpha(i/o)-coupled receptors, the details of the activation process remain unclear. The authors introduce a series of chimeras that combine both Galpha16 and Galpha(i/o) (Galpha(16/o), Galpha(16/i2), and Galpha(16/i3)) into a well-established transient expression system to examine the ability of these chimeras to interact with D2 long-form (D2L) dopamine and 5-HT1A serotonin receptors. The pEC50 data obtained for known agonists were similar to results from previous studies that used other cell-based assays, thus indicating sufficient sensitivity for the assay. Moreover, quinpirole exhibited similar intrinsic activity to dopamine at the D2L receptor, whereas S-(-)-3-PPP displayed partial activity of dopamine and quinpirole in the presence of the Galpha(16/o) chimera. The potency of dopamine for D2L receptors was similar among Galpha(16/o), Galpha(16/i2), and Galpha(16/i3). In contrast, the 5-HT1A receptor exhibited a significantly preferential coupling for Galpha(16/i3) compared with Galpha(16/i2) when serotonin was used as a ligand. This finding was in close agreement with the results of previous reports. The present system could therefore be used as a rapid functional assay for high-throughput screening and deorphanization.

The subtype 2 and subtype 3 ionotropic purinergic receptors (P2X receptors) are crucial for gustation, but the distribution of these receptors in the geniculate ganglion (GG) and their colocalization in tongue papillae remain unknown. Here we investigated the expression and colocalization of P2X(2) and P2X(3) receptors in the GG and fungiform papillae in rats and mice by using in situ hybridization and immunohistochemistry. In both species, P2X(2) transcripts and immunoreactivity were detected in approximately 50-60% of GG neuronal somata, whereas those of P2X(3) were observed in almost all neurons. In each fungiform papilla, immunoreactivity for both receptors was mostly colocalized and was seen in nerve fibers and their bundles concentrated in the taste buds. Because it is well known that the P2X receptors are involved in not only taste but also nociception, we determined whether the expression originated from the chorda tympani nerve (CT, gustatory) or trigeminal nerve (somatosensory) by cutting the CT in both animals. Most P2X(2) and P2X(3) immunoreactivity in the fungiform papillae was abolished after transection, although the nerve fiber immunoreactivity of transient receptor potential V1 (a marker of somatosensory nerve fibers) remained unchanged, indicating that most fungiform papillae nerve fibers with P2X(2) and P2X(3) receptors were derived from CT. Taken together, these findings suggest that most P2X(2) and P2X(3) receptors in fungiform papillae are used for gustation rather than somatosensation.

The P2X7 receptor is a member of the P2X family of adenosine triphosphate-gated ion channels. It is expressed in the central nervous system and is associated with several pathological conditions. Here, we examined the expression of P2X7 with immunohistochemistry after cryogenic injury to the rat cortex. One day after cortical cryogenic injury, P2X7 immunoreactive cells were increased in regions surrounding the cold-injured site. These P2X7 positive cells were also immunoreactive for OX42, a microglial marker, and possessed the short, thick processes that are characteristic of activated microglia. These results suggest that the increased local expression of P2X7 may be associated with microglial activation, contributing to detrimental and/or protective functions around the cold-injured site.

Dry-eye syndrome affects millions of individuals and it is essential to develop effective therapeutic agents for the treatment of this complex condition. The goal of this study was to evaluate the effect of apolipoprotein A (ApoA)-1 and its synergistic action with d-pantethine (DP) on corneal epithelial disorders in dry-eye mouse model.Aqueous tear production of C57BL/6J Jms Slc male mice aged 10 to 12 weeks were inhibited by subcutaneous scopolamine injection and mice were placed in a continuous airflow blower to create desiccating environmental stress. During desiccation, 1 eye of each mouse was treated with ApoA-1 (0.01%, 0.04%, or 0.1%) or ApoA-1 (0.04%) + DP (0.05%, 0.1%, or 0.2%) and the other control eye was instilled with phosphate-buffered saline 4 times daily for 5 days. Phenol red thread test, corneal fluorescein staining (score, 0-4), and measurement of corneal epithelial thickness measurements were performed.Significant reductions of staining scores and higher corneal epithelial thickness values were observed in both ApoA-1- and ApoA-1 + DP-treated groups compared with untreated dry-eye mouse and phosphate-buffered saline-treated group.These results suggest that ApoA-1 and DP may be potential therapeutic agents for ocular surface epithelial disorders in patients with dry eye.

We present a case of hepatocellular carcinoma (HCC), showing an atypical "nodule-in-nodule" appearance on ultrasonogram (US). In general, a "nodule-in-nodule" appearance is found as a hyperechoic tumor containing a hypoechoic nodule. In the present case, however, there was a hyperechoic subnodule in the center of the tumor, which was surrounded by a hypoechoic tumor area. Histologically, the subnodule consisted of moderately differentiated HCC with a markedly dilated pseudoglandular structure, and the outer tumor consisted of well-differentiated HCC with a thin-trabecular pattern. It should be noted that there is a rare HCC with dilated pseudoglandular structure showing the inversed "nodule-in-nodule" appearance.

Nickel(0) triethyl phosphite complex-promoted reaction of allylic acetates with thiols produced allylic sulfides with retention of configuration without allylic rearrangement. A similar reaction of allylic acetates with alcohols and phenols also proceeded with retention of regio- and stereochemistry.

Human beings remember plans concerning typical motions which occur frequently as schema, and by selecting suitable schema depending on conditions, generate muscular motion almost unconsciously. Though a motor schema represents typical motions, it is equipped with superior plan structure taking into consideration the concurrency and seriality of motions as seen in grasping actions and walking motions, and the structure of plans can be acquired by learning. In this paper, a study is made of the modeling of such motor schema with the use of neural networks. For this purpose, the neural network is structured beforehand into the part which generates action sequences in the form containing concurrency (concurrent action generation part) and the part which modifies the action sequences to satisfy constraints which cannot be executed concurrently (constraint representation part). After learning in each part model the neural network can generate motion sequences while taking into consideration the seriality and concurrency of motion by combining the parts at the time of execution. Finally, this model is applied to the formation of typewriting action motor schema, and it is demonsted that generates motion sequences which take into consideration the constraint of the motion system accompanying the execution of motion.

Nickel(0) triethyl phosphite complex-promoted reaction of allylic acetates with thiols produced allylic sulfides with retention of configuration without allylic rearrangement. A similar reaction of allylic acetates with alcohols and phenols also proceeded with retention of regio- and stereochemistry.

We electrophysiologically investigated the effects of nafamostat mesilate (NM: 6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfonate) and its two metabolites, 6-amidino-2-naphthol (AN) and p-guanidinobenzoic acid (PGBA), on three distinct types of human acid-sensing ion channels (ASICs). Acid-evoked inward currents at a holding potential of -60mV in ASIC1a- and ASIC2a-expressing oocytes were decreased by extracellular application of NM in a concentration-dependent manner with IC(50) (inhibition constant) values of approximately 13.5 and 70.6microM, respectively. The NM application also produced concentration-dependent inhibition of the initial-phase transient component of biphasic ASIC3 currents with an IC(50) value of approximately 2.5microM. Application of AN showed weak blocking effects on the ASIC1a, ASIC2a, and transient ASIC3 currents with IC(50) values of approximately 1.2, 1.3, and 0.14mM, respectively, whereas PGBA was insensitive to their currents.

We investigated whether amiloride-blockable proton-gated cation channels ASIC1a (acid-sensing ion channel-1a) and ASIC1b are expressed in the stereocilia of mouse cochlear hair cells. In-situ hybridization studies showed that ASIC1b transcripts, but not ASIC1a transcripts, were expressed in the inner and outer hair cells. Fluorescent immunohistochemical and immunogold electron microscopic analyses revealed that the ASIC1b channels were located at the insertions of the stereocilia into the hair cells. Our findings provide a novel molecular key to the understanding of cochlear physiology and pathophysiology.

Sequence comparison is a fundamental task in pattern matching. Its applications include file comparison, spelling correction, information retrieval, and computing (dis)similarities between biological sequences. A common scheme for sequence comparison is the longest common subsequence (LCS) metric. This paper considers the fully incremental LCS computation problem as follows: For any strings A,B and characters a,b, compute LCS(aA, B), LCS(A, bB), LCS(Aa, B), and LCS(A, Bb), provided that L=LCS(A, B) is already computed. We present an efficient algorithm that computes the four LCS values above, in O(L) or O(n) time depending on where a new character is added, where n is the length of A. Our algorithm is superior in both time and space complexities to the previous known methods.