Hemodynamics of rectal varices.
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Blood Flow Velocity↗
Biomedical subjects
Tooru Shimosegawa
Publications and source records attributed to Tooru Shimosegawa.
Clinical diagnostic criteria of autoimmune pancreatitis: revised proposal.
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Autoimmune Diseases↗
Efficacy and safety of endoscopic balloon dilation for Crohn's strictures.
PURPOSE: This study was designed to investigate retrospectively the efficacy and safety of endoscopic balloon dilation for intestinal strictures in Crohn's disease. METHODS: Sixteen patients with 20 strictures were treated. The stricture sites were as follows: at the ileocolonic (n = 6) or ileoileal (n = 1) anastomosis, in the colon (n = 10), ileum (n = 2), and at the ileocecal valve (n = 1). The dilations were performed with through-the-scope balloons, with diameters of 15 to 20 mm on inflation and lengths of 30 to 80 mm. RESULTS: In 15 of 16 patients, the strictures were successfully dilated and the symptoms caused by the strictures disappeared after the first session. The patients were followed for a median of 38.5 months. Repeat symptomatic stricture formation occurred after a mean of 19.7 months in seven patients. Four patients needed second-round dilation and three patients were treated surgically. Complications occurred in four patients who had primary strictures: bleeding in one, high fever in one, and colorectal perforation in two. One of the patients complicated with colorectal perforation was treated surgically, and the other was treated conservatively. The cumulative nonsurgical rates for the dilation strictures were 93 percent at 12 months and 65 percent at 36 months, respectively. Three patients were treated surgically because of strictures or fistulas that were not related to the procedure of dilation. As a whole, the cumulative nonsurgical rates were 81 percent at 12 months and 46 percent at 36 months. Nine patients (56.3 percent) were able to avoid surgery. CONCLUSIONS: Using endoscopic balloon dilation, it may be possible to avoid or postpone surgery. Primary strictures seem to have increased risk of perforation.
Adult↗
Lack of association between IBD5 and Crohn's disease in Japanese patients demonstrates population-specific differences in inflammatory bowel disease.
OBJECTIVE: Population-specific differences in the genetic susceptibility to inflammatory bowel disease (IBD) are indicated by the fact that Crohn's disease (CD) in Japanese patients does not have any of the common CARD15 variants that are associated with CD in Caucasians. Recently, the disease-causing mutation in the IBD5 haplotype was identified. The TC haplotype, composed of L503F in SLC22A4 and -207G/C in SLC22A5 promoters, was reported to alter the function of the organic cation transporter and to be associated with CD in Caucasians. To determine whether the TC haplotype is also associated with IBD in a Japanese population, we genotyped L503F and -207G/C variants in Japanese subjects. Furthermore, we also performed a case-control association study with all representative single nucleotide polymorphisms (SNPs) in IBD5 using previous information of linkage disequilibrium extension reported in Japanese patients to determine whether there were variants in IBD5 specifically associated with IBD in Japanese patients. MATERIAL AND METHODS: A total of 758 Japanese individuals, 241 patients with CD, 247 patients with ulcerative colitis (UC) and 270 healthy controls, were analyzed in this study. Genotyping for SNPs was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: We found L503F and -207G/C to be very rare (<1% frequency) in CD, UC and HC in the Japanese population. Furthermore, we also found that none of the representative SNPs in IBD5 was associated with CD or UC in the Japanese subjects. CONCLUSIONS: In contrast to Caucasians, IBD5 is not a major component of the susceptibility to IBD in the Japanese population.
Adult↗
Acute pancreatitis due to pancreatic arteriovenous malformation: 2 case reports and review of the literature.
Pancreatic arteriovenous malformation (AVM) is a relatively rare disease. Based on our literature search, 51 cases of pancreatic AVM have been reported since 1968. The gastrointestinal bleeding is the most common presenting symptom (24/51 cases [47%]). There were only 6 cases of pancreatitis in these cases. We describe 2 cases of acute pancretitis with pancreatic AVM. The patients who were diagnosed with acute pancreatitis were admitted to our hospital. Pancreatitis was considered to be caused by pancreatic AVM by some modalities of diagnostic imaging. The respective pancreatic AVM lesions of patients were resected to prevent the recurrence of pancreatitis. They are asymptomatic after the surgery. Pancreatic AVM is thought to be the one of the reasons for acute pancreatitis.
Acute Disease↗
The expression of MUC4 and MUC5AC is related to the biologic malignancy of intraductal papillary mucinous neoplasms of the pancreas.
OBJECTIVE: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas show heterogeneous proliferations with latent malignancy. Mucins (MUC) are high-molecular-weight glycoproteins, with an aberrant expression profile in various malignancies. Recently, MUC4 and MUC5AC expressions have been demonstrated to correlate with the unfavorable and the favorable prognosis of pancreatic duct cell carcinoma, respectively. However, little is known about these mucin expressions in IPMNs. METHODS: To clarify the role of MUC4 and MUC5AC expressions in IPMNs, the expression profiles of MUC4 and MUC5AC were investigated in 50 lesions from 17 specimens with 16 IPMNs by immunohistochemistry, using each of their specific antibodies. RESULTS: The expression of MUC4 was found in the lesions ranging from adenoma to cancer lesions of IPMNs, whereas it was undetectable in normal and hyperplastic lesions. Frequent expression of MUC4 is found in the higher grade of IPMNs (borderline and cancer lesions; 16/18 lesions, 94%). The differences were independently significant (P < 0.001) when the cutoff point was set between adenoma and borderline IPMNs. Similarly, frequent expression of MUC5AC was detected in the lesions from adenoma to cancer of IPMNs (32/34, 94%), whereas no intense expression was detected in normal or hyperplastic lesions. The significant difference was found when the cutoff point was set between hyperplasia and adenoma of IPMNs (P < 0.001). CONCLUSIONS: These results indicated that the expressions of MUC4 and MUC5AC are potential markers to distinguish adenoma or above malignant lesions of IPMNs from lesser malignant ones, respectively.
Adenocarcinoma, Mucinous↗
Analysis of the entire nucleotide sequence of hepatitis B virus genotype B in the Philippines reveals a new subgenotype of genotype B.
The entire nucleotide sequences were determined for hepatitis B virus (HBV) genotype B (HBV/B) genomes extracted from five patients in the Philippines and designated GenBank AB219426, AB219427, AB219428, AB219429 and AB219430. The serotype of the first four isolates was ayw and that of GenBank AB219430 was adw. Divergences of entire sequences were 1.0-2.0 % between the first four isolates and 3.8-4.2 % between these four and GenBank AB219430. Phylogenetic-tree analysis revealed that, worldwide, HBV/B comprises five subgenotypes: B1, B2, B3, B4 and the new Philippines group, designated B5. Divergences of the entire genome sequences between four isolates in subgenotype B5 and isolates from other countries (subgenotypes) were 4.4-4.8 % with Vietnam (B4), 2.9-3.5 % with Indonesia (B3), 4.7-5.1 % with China (B2) and 5.4-6.0 % with Japan (B1). Similarly, GenBank AB219430 showed the lowest divergences: 3.4 % with the isolate from Indonesia (B3), 5.0 % with Vietnam (B4), 5.4 % with China (B2) and 6.1 % with Japan (B1). This is the first report of entire nucleotide sequences of HBV/B from the Philippines and the results show that these sequences belong to a new subgenotype, B5. The present study identified that HBV/B isolates throughout the world are divided genetically into five subgenotypes, the relationships between geographical distances and the genetic distances of HBV/B being well-correlated.
Adult↗
Analysis of human and swine hepatitis E virus (HEV) isolates of genotype 3 in Japan that are only 81-83 % similar to reported HEV isolates of the same genotype over the entire genome.
Full-length sequences were determined for a human hepatitis E virus (HEV) isolate (HE-JA04-1911) and two swine HEV isolates (swJ8-5 and swJ12-4) that belong to one of three clusters within genotype 3 in Japan and are close to Spanish isolates according to their partial sequences. The three HEV isolates were 89.7-92.9 % identical to each other, but only 80.7-83.0 % similar to 21 HEV strains of the same genotype isolated in Canada, Kyrgyzstan, the USA and Japan over their entire genome. On comparison with HEV isolates whose partial sequence is known, the HE-JA04-1911, swJ8-5 and swJ12-4 isolates segregated into a phylogenetic cluster consisting of human and swine HEV isolates in Japan and the UK, with identities of 89.8-100 % and 87.9-92.4 %, respectively. Genotype 3 HEV isolates were found to be markedly heterogeneous. The UK-isolate-like HEV strains in Japan may have originated from the UK via the importation of pigs since 1900.
Animals↗
A pilot study to evaluate a new combination therapy for gastric ulcer: Helicobacter pylori eradication therapy followed by gastroprotective treatment with rebamipide.
BACKGROUND AND AIM: Controversies remain over the need for antiulcer treatment following 1-week eradication triple therapy for Helicobacter pylori-positive peptic ulcers. The usefulness of combination therapy for gastric ulcers in Japanese patients, which consists of H. pylori eradication followed by gastroprotective therapy with rebamipide, was therefore evaluated. METHODS: The study was conducted in 52 H. pylori-positive patients with an endoscopically-proven open gastric ulcer. All patients received 1-week triple therapy (lansoprazole, amoxicillin and clarithromycin) followed by 7-week rebamipide therapy. After completion of the combination therapy, all patients underwent evaluation of ulcer healing by endoscopy, gastric ulcer symptoms and H. pylori eradication by rapid urease test and (13)C-urea breath test. RESULTS: The ulcer healing rates were 85.7% (36/42) at 8 weeks, 83.3% (30/36) in eradicated patients and 100% (6/6) in non-eradicated patients. The overall gastrointestinal symptom-free rate improved from 19.0% at baseline to 88.1% at 8 weeks. H. pylori was effectively eradicated in 85.7% (36/42) of patients. CONCLUSIONS: The results suggested that the combination therapy for open gastric ulcer was safe, well-tolerated and effective. However, data from a double-blind placebo-controlled study is necessary to confirm these findings.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Therapeutic effects of 10 mg/day rabeprazole administration on reflux esophagitis was not influenced by the CYP2C19 polymorphism.
BACKGROUND: The acid suppressive effects of omeprazole (OPZ) and lansoprazole (LPZ) are influenced by the CYP2C19 polymorphism. On the other hand, some investigators have reported that acid suppressive effect of rabeprazole (RPZ) was not significantly affected by CYP2C19. The present study was designed to investigate whether the CYP2C19 genotype is related to the healing of reflux esophagitis (RE) in treatment with RPZ 10 mg. METHODS: One hundred and three Japanese patients with RE were treated with daily oral administration of 10 mg RPZ. At 4 and 8 weeks after the start of treatment, healing of RE was evaluated endoscopically. The CYP2C19 genotype was investigated before the treatment. RESULTS: At 4 weeks after the start of treatment, the healing rates for homo-extensive metabolizer, hetero-extensive metabolizer, and poor metabolizer patients were 83.3% (15/18), 77.3% (17/22), and 88.9% (8/9) [corrected] respectively, and at 8 weeks after the start of treatment, the healing rates were 86.1% (31/36), 92.0% (46/50), and 82.4% (14/17), respectively. There were no significant differences in the healing rate of RE among the three genotypes at either 4 or 8 weeks after the start of treatment. CONCLUSIONS: The therapeutic effects of 10 mg/day RPZ administration on RE may be uninfluenced by the CYP2C19 polymorphism.
2-Pyridinylmethylsulfinylbenzimidazoles↗
SPINK1 gene mutations and pancreatitis in Japan.
SPINK1 can inhibit up to 20% of trypsin activity, and may constitute one major mechanism to protect the pancreas from autodigestion. In 2000, Witt et al. first recognized the association between mutations in the SPINK1 gene and chronic pancreatitis (CP), but the significance of SPINK1 gene mutation in pancreatitis and its relation to alcohol consumption remains unclear in Japan. The aim of the present paper was to clarify the incidence of SPINK1 mutations in CP patients with various etiologies in Japan and, in addition, to examine the relationship between alcohol metabolism and the polymorphisms in the key enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase-2 (ALDH2). A total of 156 patients with CP, and 165 healthy volunteers, all Japanese, were examined for the SPINK1 mutations by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. In Japan, the prevalence of [N34S; IVS1-37T > C] and [-215G > A; IVS3 + 2T > C] was significantly higher in patients with idiopathic CP (10.6% and 12.8%, respectively) than normal subjects (0.6% and 0%). The frequency of the [-215G > A; IVS3 + 2T > C] mutation in Japan was significantly higher than that reported in other populations. Concerning alcoholic CP, the [-215G > A; IVS3 + 2T > C] mutation was found in only a small number of patients (3.9%). On analysis of ADH2 and ALDH2 gene polymorphisms an association was found between ADH2*2 allele and alcoholic CP, and the ADH2*2/2*2 genotype had a tendency to increase the risk of developing pancreatic pseudocyst. In conclusion, in Japan the [-215G > A; IVS3 + 2T > C] mutation in the SPINK1 gene may form a unique genetic background for pancreatitis.
Carrier Proteins↗
Lack of evidence that bone marrow cells contribute to cholangiocyte repopulation during experimental cholestatic ductal hyperplasia.
BACKGROUND: Ductopenia is observed in end-stage human cholestatic diseases. The limited capability of cholangiocytes for proliferation is suggested to be the principal reason. Recently, bone marrow cells (BMCs) have been reported to behave as hepatic stem cells; however, their capability to differentiate into cholangiocytes in cholestasis remains unclear. METHODS: Normal mice were lethally irradiated to suppress the proliferation of self-BMCs; thereafter, the BMCs from enhanced green fluorescent protein (EGFP)-transgenic mice were transferred to recipients. Chronic cholestasis was induced by 0.1%alpha-naphtylisothiocyanate (ANIT) feeding. The proliferation of cholangiocytes and oval cells was assessed morphologically and immunohistchemically (cytokeratin-7 (CK-7), A6). Proliferative activity (proliferating cell nuclear antigen (PCNA) protein expression), hepatic growth factor (HGF) receptor (c-Met), stem cell factor receptor (c-kit), Notch2 and Hes1 expression were also evaluated. RESULTS: Marked cholangiocyte proliferation was observed in ANIT-fed mice. However, no EGFP/CK-7 double positive cells were identified in any of the liver specimens after BMCs transfer (Tx). In hepatic parenchyma, there were scattered EGFP-positive cells, although none of them were positive for CK-7. CONCLUSIONS: In spite of the significant ductular proliferations after ANIT feeding, no EGFP-positive cholangiocytes were confirmed by any other means in this chronic cholestasis model. Thus, different from hepatocytes, BMCs Tx seems not to contribute to the differentiation of cholangiocytes. Future studies are feasible to clarify the origin of proliferative cholangiocytes observed in this chronic cholestatic ductular hyperplasia model.
1-Naphthylisothiocyanate↗
Preservation of gastric acid secretion may be important for the development of gastroesophageal junction adenocarcinoma in Japanese people, irrespective of the H. pylori infection status.
BACKGROUND: We have previously reported that Helicobacter pylori infection prevents reflux esophagitis (RE) and Barrett's esophagus (BE) by decreasing gastric acid secretion. Gastroesophageal (GE) junction adenocarcinoma, including Barrett's adenocarcinoma, has been thought to be a complication of gastroesophageal reflux disease (GERD). However, the relationship between H. pylori infection, gastric acid secretion, and GE junction adenocarcinoma has not yet been investigated in Japan. The aim of this study was to evaluate this relationship in the Japanese population. METHODS: A total of 168 Japanese patients (RE alone: 80, short-segment BE (SSBE): 16, long-segment BE (LSBE): 20, GE junction adenocarcinoma: 12, distal early gastric cancer (EGC): 40; male/female = 106/62; mean age 61.5 yr) and 80 Japanese control subjects who had no localized lesions in the upper gastrointestinal tract (male/female = 43/37, mean age 58.1 yr) were enrolled for this study. The prevalence of H. pylori infection was determined by biopsy, the rapid urease test, and measurement of the serum H. pylori IgG antibody. Gastric acid secretion was assessed by the endoscopic gastrin test (EGT). RE was diagnosed according to the Los Angeles classification. RESULTS: The prevalence of H. pylori infection in the patients with RE alone (30%) was significantly lower than that in control subjects (71.2%). There was also a tendency for the prevalence of H. pylori infection to be lower in patients with BE (SSBE, 18.7%; LSBE, 0%) when compared to that in patients with RE alone. On the other hand, while the prevalence of H. pylori infection in patients with GE junction adenocarcinoma (58.3%) was significantly lower than that in patients with EGC (87.5%), it tended to be higher than that in patients with RE alone or BE. The mean EGT value in patients with RE alone (3.74 mEq/10 min) was significantly higher than that in control subjects (1.83). The mean EGT value in patients with BE (SSBE, 4.74; LSBE, 4.76) tended to be even higher than that in patients with RE alone. The mean EGT value in patients with GE junction adenocarcinoma (3.94) was significantly higher than that in control subjects and patients with EGC (0.67), but it was comparable to that independent of the H. pylori infection status in patients with RE alone or BE. CONCLUSION: Preservation of gastric acid secretion may be important for the development of GE junction adenocarcinoma in Japanese people, irrespective of the H. pylori infection status.
Adenocarcinoma↗
Sustained clinical improvement of a patient with decompensated hepatitis B virus-related cirrhosis after treatment with lamivudine monotherapy.
Hepatitis B virus (HBV) infection, which causes liver cirrhosis and hepatocellular carcinoma, remains a major health problem in Asian countries. Recent development of vaccine for prevention is reported to be successful in reducing the size of chronically infected carriers, although the standard medical therapies have not been established up to now. In this report, we encountered a patient with decompensated HBV-related cirrhosis who exhibited the dramatic improvements after antiviral therapy. The patient was a 50-year-old woman. Previous conventional medical treatments were not effective for this patient, thus this patient had been referred to our hospital. However, the administration of lamivudine, a reverse transcriptase inhibitor, for 23 months dramatically improved her liver severity. During this period, no drug resistant mutant HBV emerged, and the serum HBV-DNA level was continuously suppressed. These virological responses were also maintained even after the antiviral therapy was discontinued. Moreover, both hepatitis B surface antigen and e antigen were observed to have disappeared in this patient. The administration of lamivudine to patients with HBV-related cirrhosis, like our present case, should be considered as an initial medical therapeutic option, especially in countries where liver transplantation is not reliably available.
Anti-HIV Agents↗
[Diagnosis of pancreatic cancer from laboratory data].
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Alkaline Phosphatase↗
Th1 response during ribavirin and interferon-alpha combination therapy in chronic hepatitis C.
Ribavirin and interferon-alpha induce Th1 polarization of human CD4+ T cells. The study was conducted to investigate the whether cellular immune response during ribavirin/interferon-alpha therapy is associated with viral eradication by examining mRNA expression of molecules relevant to Th1 and Th2 polarization in CD4+ cells of 13 patients with chronic hepatitis C (seven patients with sustained viral response and six with transient response). Peripheral CD4+ T lymphocytes at 0, 4 and 24 weeks of treatment were tested. There were no significant differences in the mRNA levels at each point of time of the treatment between patients with sustained viral response and those with transient response. The percent increase in mRNA level of the IL-12R beta2 chain from the baseline to the end of the treatment was significantly higher in patients with sustained viral response (15.3+/-6.1%) than in those with transient response (-1.6+/-4.7%, p<0.05). There was no significant difference in percent changes in level of IL-12R beta1 chain mRNA between the two groups. In conclusion, the results of this study indicate that the increase of Th1 response is related to the inflammatory activity in the liver and possibly to ribavirin and interferon-alpha therapy. It is also suggested that the measurement of Th1 response has the potential to distinguish patients with relapse from those with sustained virus response.
Journal Article↗
Galectin-1 induces chemokine production and proliferation in pancreatic stellate cells.
Galectin-1 is a beta-galactoside-binding lectin. Previous studies have shown that galectin-1 was expressed in fibroblasts of chronic pancreatitis and of desmoplastic reaction associated with pancreatic cancer. These fibroblasts are now recognized as activated pancreatic stellate cells (PSCs). Here, we examined the role of galectin-1 in cell functions of PSCs. PSCs were isolated from rat pancreatic tissue and used in their culture-activated phenotype unless otherwise stated. Expression of galectin-1 was assessed by Western blot analysis, RT-PCR, and immunofluorescent staining. The effects of recombinant galectin-1 on chemokine production and proliferation were evaluated. Activation of transcription factors was assessed by EMSA. Activation of MAPKs was examined by Western blot analysis using anti-phosphospecific antibodies. Galectin-1 was strongly expressed in culture-activated but not freshly isolated PSCs. Recombinant galectin-1 increased proliferation and production of monocyte chemoattractant protein-1 and cytokine-induced neutrophil chemoattractant-1. Galectin-1 activated ERK, JNK, activator protein-1, and NF-kappaB, but not p38 MAPK or Akt. Galectin-1 induced proliferation through ERK and chemokine production mainly through the activation of NF-kappaB and in part by JNK and ERK pathways. These effects of galectin-1 were abolished in the presence of thiodigalactosie, an inhibitor of beta-galactoside binding. In conclusion, our results suggest a role of galectin-1 in chemokine production and proliferation through its beta-galactoside binding activity in activated PSCs.
Animals↗
MSX2 overexpression inhibits gemcitabine-induced caspase-3 activity in pancreatic cancer cells.
AIM: To evaluate the effect of MSX2 on gemcitabine-induced caspase-3 activation in pancreatic cancer cell line Panc-1. METHODS: Using V5-tagged MSX2 expression vector, stable transfectant of MSX2 was generated from Panc-1 cells (Px14 cells). Cell viability under gemcitabine administration was determined by MTT assay relative to control cell line (empty-vector transfected Panc-1 cells; P-3EV cells). Hoechst staining was used for the detection of apoptotic cell. Activation of caspase-3 was assessed using Western blotting analysis and direct measurement of caspase-3 specific activities. RESULTS: MSX2 overexpression in Panc-1 cells resulted in decreased gemcitabine-induced caspase-3 activation and increased cell viability under gemcitabine treatment in Px14 cells. CONCLUSION: MSX2 exerts repressive effects on gemcitabine-induced apoptotic pathway. This novel apoptosis-regulating function of MSX2 may provide a new therapeutic target for pancreatic cancer.
Antimetabolites, Antineoplastic↗