Eiji Takeshita

Molecular characterization and distribution of motilin family receptors in the human gastrointestinal tract.

BackgroundMotilin and ghrelin have been recognized as important endogenous regulators of gastrointestinal motor function in mammals, mediated respectively by the motilin receptor and by the closely related ghrelin receptor. The aims of this study were to explore the distribution of motilin and ghrelin receptors along the human gastrointestinal tract and to establish the molecular nature of the human motilin receptor.MethodsPost mortem and surgical human tissue specimens with no hemorrhage, necrosis, or tumor were obtained from various parts of the gastrointestinal tract. We analyzed levels of expression of mRNA for motilin and ghrelin receptors and examined their molecular identities. Portions of some specimens were also studied by immunohistochemistry for expression of the motilin and ghrelin receptor.ResultsThe long form of the motilin receptor, but not the short form, was expressed in all parts of the gastrointestinal tract, and expressed at higher levels in muscle than in mucosa. Motilin receptor immunoreactivity was present in muscle cells and the myenteric plexus, but not in mucosal or submucosal cells. In contrast, ghrelin receptor mRNA was expressed equally in all parts of the gastrointestinal tract, with similar levels of expression in mucosal and muscle layers.ConclusionsBoth the motilin and ghrelin receptors are expressed along the human gastrointestinal tract, but they have clearly distinct distributions in regard to both level and layer. The diffuse muscle expression of the motilin receptor, at both the levels of the gene and the protein product, along the entire gastrointestinal tract makes it a useful potential target for motilide drugs for dysmotility.

Esophagogastric varices as a prognostic factor for the determination of clinical stage in patients with primary biliary cirrhosis

BackgroundPrimary biliary cirrhosis (PBC) is usually classified as either asymptomatic PBC (a-PBC) or symptomatic PBC (s-PBC). Although the proportion of a-PBC versus s-PBC patients has been consistently increasing, it is not clear whether the present criteria for the staging of PBC are optimal or not. We investigated the clinical stage of PBC patients from the standpoint of esophagogastric varices (EGV).MethodsOne hundred and nine PBC patients were enrolled in this retrospective study. We investigated the clinical features of PBC based on laboratory data, histological stage, symptoms, and existence of EGV. In addition, the clinical course and prognosis in patients who were periodically followed up were also studied.Results(1) EGV was detected in a-PBC patients, and there was no difference in the grade of EGV between a-PBC and s-PBC patients. (2) a-PBC patients with EGV had more liver damage than those without EGV, and a-PBC patients with EGV had a poorer prognosis than those without EGV. (3) Three of 11 patients who progressed from a-PBC to s-PBC within 3 years had EGV. (4) One of 3 a-PBC patients with EGV had progressed to s-PBC at 3-year follow-up.ConclusionsThese results indicate that EGV is one of the most important factors for evaluating PBC. Therefore, we would like to propose that a-PBC patients with EGV should either be included in the presently defined s-PBC class, or that new prognostic classes of PBC be created that include EGV as a prognostic factor.

Earlier recurrence of esophageal varices, following therapy, in patients with primary biliary cirrhosis (PBC) compared with non-PBC patients.

BackgroundVariceal bleeding is a common, life-threatening complication of primary biliary cirrhosis (PBC). Recently, several reports have suggested that the existence of esophageal varices in patients with PBC is a significant factor in the assessment of disease prognosis. However, there have been no reports on the recurrence of esophageal varices following treatment in patients with PBC. In this study, we investigated the recurrence of esophageal varices in PBC patients and attempted to identify predictive factors for the recurrence of esophageal varices.MethodsBetween April 1993 and August 2003, 138 patients with esophageal varices who had been treated by endoscopic variceal ligation (EVL; 96 men and 42 women; age, 33–83 years; mean, 62.6 ± 10.1 years), were enrolled in the present study. The diagnosis of esophageal varices was made by upper gastrointestinal endoscopy, and the varices were graded according to the criteria of the Japanese Research Society for Portal Hypertension. The relationship between the recurrence of esophageal varices and factors such as biochemical and hematological parameters, as well as the etiology of the liver disease, was analyzed using the Kaplan-Meier method and the multivariate Weibull regression model.ResultsPBC patients had an earlier recurrence of esophageal varices compared to non-PBC patients, and two factors, prothrombin time and etiology (PBC/non-PBC), were indicative of significantly earlier recurrence of esophageal varices.ConclusionsWe should be extra careful in the follow-up of patients with PBC after therapy for esophageal varices.

Comparison between real‐time tissue elastography and vibration‐controlled transient elastography for the assessment of liver fibrosis and disease progression in patients with primary biliary cholangitis

Assessing disease progression in patients with primary biliary cholangitis (PBC) is necessary in order to evaluate therapeutic effectiveness. Therefore, the aims of this study were to evaluate both the diagnostic accuracy of both real‐time tissue elastography (RTE) and vibration‐controlled transient elastography (VCTE), and the usefulness of hepatic and splenic elasticity as predictive markers for the progression of symptomatic PBC.

Usefulness of a New Three-Dimensional Simulator System for Radiofrequency Ablation

Multipuncture radiofrequency ablation is expected to produce a large ablated area and reduce intrahepatic recurrence of hepatocellular carcinoma; however, it requires considerable skill. This study evaluated the utility of a new simulator system for multipuncture radiofrequency ablation. To understand positioning of multipuncture electrodes on three-dimensional images, we developed a new technology by expanding real-time virtual ultrasonography. We performed 21 experimental punctures in phantoms. Electrode insertion directions and positions were confirmed on computed tomography, and accuracy and utility of the simulator system were evaluated by measuring angles and intersections for each electrode. Moreover, to appropriately assess placement of the three electrodes, puncture procedures with or without the simulator were performed by experts and non-experts. Technical success was defined as maximum angle and distance ratio, as calculated by maximum and minimum distances between electrodes. In punctures using 2 electrodes, correlations between angles on each imaging modality were strong (ultrasound vs. simulator: r = 0.991, p<0.001, simulator vs. computed tomography: r = 0.991, p<0.001, ultrasound vs. computed tomography: r = 0.999, p<0.001). Correlations between distances in each imaging modality were also strong (ultrasound vs. simulator: r = 0.993, p<0.001; simulator vs. computed tomography: r = 0.994, p<0.001; ultrasound vs. computed tomography: r = 0.994, p<0.001). In cases with 3 electrodes, distances between each electrode correlated strongly (yellow-labeled vs. red-labeled: r = 0.980, p<0.001; red-labeled vs. blue-labeled: r = 0.953, p<0.001; yellow-labeled vs. blue-labeled: r = 0.953, p<0.001). Both angle and distance ratio (expert with simulator vs. without simulator; p = 0.03, p = 0.02) were significantly smaller in procedures performed by experts using the simulator system. The new simulator system appears to accurately guide electrode positioning. This simulator system could allow multipuncture radiofrequency ablation to be performed more effectively and comfortably.

Usefulness of laparoscopy and intraductal ultrasonography in a patient with isolated immunoglobulin G4-related sclerosing cholangitis

Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is often associated with type 1 autoimmune pancreatitis, and the frequency of isolated IgG4-SC seems to be quite low, making the diagnosis of isolated IgG4-SC challenging. A 63-year-old male was admitted to our hospital for frequent fever. Abdominal magnetic resonance cholangiopancreatography showed diffuse narrowing of the common bile duct and post-stenotic dilatation of the right posterior bile duct. Laboratory tests showed abnormalities in the levels of hepatobiliary enzymes and serum IgG4 levels. Endoscopic retrograde cholangiopancreatography showed diffuse narrowing of intrahepatic bile ducts and post-stenotic dilatation of the right posterior bile duct but no abnormalities in the pancreas. Intraductal ultrasonography showed symmetric circumferentially thickened walls of both narrowed and non-narrowed common bile ducts. Histologic examination of the common bile duct mucosa showed infiltration of IgG4-positive plasma cells. Laparoscopic observations showed discoloration with red lobular markings and multiple small depressed lesions. Liver histology showed mild cholangitis with infiltration of IgG4-positive plasma cells around the bile ducts. From these findings, the patient was diagnosed with isolated IgG4-SC. After treatment with a steroid, bile duct dilatations improved. Laparoscopy and intraductal ultrasonography were useful to diagnose isolated IgG4-SC.

Carbonic Anhydrate I Epitope Peptide Improves Inflammation in a Murine Model of Inflammatory Bowel Disease.

Background:Carbonic anhydrase I (CA I), a major cecal bacterial antigen, improves inflammatory bowel disease (IBD) symptoms in a murine model. The aim of this study was to identify the responsible epitope region within the CA I protein and evaluate its effect on inflammation using a murine IBD model. Methods:Candidate peptides within the CA I protein sequence that interact with major histocompatibility complex class II were chosen and their immune responses were evaluated using mesentery lymph nodes (MLNs) from a CD4+CD25− T-cell transfer murine colitis model. Mice were treated with regulatory dendritic cells (Reg-DCs)–pulsed CA I peptide. We assessed their clinical signs, histopathology, induction of cytokines and transcription factors, and generation of CD103+CD11c+ dendritic cells and regulatory T cells (Tregs). Results:We identified 4 candidate epitope peptides of CA I. Among these, Reg-DCs pulsed with CA I 58-73 peptide (Reg-DCsCA I 58-73) alone ameliorated colitis. Reg-DCsCA I 58-73-treated mice showed higher mRNA expression levels of forkhead box protein 3, aldehyde dehydrogenase family 1a2, transforming growth factor-&bgr;, and interleukin (Il)10, when compared with lower mRNA expression of retinoic acid–related orphan receptor gamma and Il17a in MLNs. Compared with control mice, these mice also showed higher numbers of Foxp3+CD4+CD25+ Tregs and CD103+CD11c+ dendritic cells in MLNs and colon. Administration of Reg-DCsCA I 58-73 induced antigen-specific Tregs in MLNs of colitic mice. Conclusions:CA I 58-73 peptide induces antigen-specific therapeutic effect in a murine IBD model using Reg-DCs, indicating that CA I 58-73 is a candidate epitope for IBD immunotherapy.

Diagnostic Challenge in Pancreatic Sarcoidosis using Endoscopic Ultrasonography.

We herein report a 55-year-old woman who presented with erythema and bilateral hilar lymphadenopathy 4 months prior to the detection of pancreatic lesions on an ultrasound. A skin biopsy showed evidence of sarcoidosis. The largest lesion in the tail of the pancreas was hypoechoic on endoscopic ultrasonography (EUS). The lesion was initially iso-enhanced on contrast enhanced-EUS (CE-EUS) but subsequently became hypoenhanced. The lesion revealed heterogeneous components of both soft and hard tissue on EUS elastography. She was ultimately diagnosed with pancreatic sarcoidosis based on the presence of noncaseating granulomas seen on pancreatic tissue retrieved through an EUS-guided fine needle aspiration biopsy.

Histological assessment of the efficacy of drug-eluting beads in portal tumor thrombosis of hepatocellular carcinoma

A 58-year-old man was diagnosed with advanced hepatocellular carcinoma with portal vein tumor thrombosis (PVTT). The tumors were multiple and existed in both lobes. Drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) was performed for the tumors in the left lobe. Embosphere and Hepasphere were selected for embolization of the arterioportal shunt, followed by loaded epirubicin infusion into the left hepatic artery. Computed tomography showed reduction of PVTT. However, liver failure progressed, and the patient died 67 days after DEB-TACE. Autopsy showed that the beads reached the tumor thrombosis in the portal vein. The prognosis of hepatocellular carcinoma with PVTT is poor. Although there are no established treatments for unresectable PVTT, DEB-TACE might be a useful option for such cases.

Case of AIDS-related cholangitis treated by endoscopic sphincterotomy

A 21‐year‐old man with an 8‐year history of acquired immunodeficiency syndrome (AIDS) presented with abdominal pain, jaundice and dark urine. Laboratory data on admission revealed cholestasis. The total bilirubin concentration was 10.0 mg/dL. Alanine transaminase and aspartate transaminase were 198 IU/L and 195 IU/L, respectively. The serum alkaline phosphatase level was 2724 IU/L. γ‐Glutamyl transferase was 1770 IU/L. Abdominal ultrasonography and computed tomography revealed dilation of the common bile duct and intrahepatic ducts without gallstones. Endoscopic retrograde cholangiopancreatography showed dilation of the common bile duct up to the level of the ampulla of Vater with partial stenosis. Endoscopic sphincterotomy was performed. The abdominal pain and jaundice resolved immediately and the liver function tests were significantly improved. The patient developed a subarachnoid hemorrhage and died of respiratory arrest 2 months after the endoscopic sphincterotomy.