An unusual case of polypoid angiodysplasia.
Explore the source record for details and available documents.
Angiodysplasia↗
Biomedical subjects
M Omata
Publications and source records attributed to M Omata.
Comparison of various submucosal injection solutions for maintaining mucosal elevation during endoscopic mucosal resection.
BACKGROUND AND STUDY AIMS: One of the major complications of endoscopic mucosal resection (EMR) for gastrointestinal tumors is perforation, and the most effective way of preventing perforation is to elevate the lesion sufficiently by endoscopic injection of fluid into the submucosa. MATERIALS AND METHODS: In order to compare the lesion-lifting properties of several different solutions, 1 ml of each of the following solutions was injected into the submucosa of the resected porcine stomach: normal saline, 3.75 % NaCl, 20 % dextrose water, 10 % glycerin with 0.9 % NaCl plus 5 % fructose, and two sodium hyaluronate (SH) solutions. RESULTS: Significantly higher initial elevation was produced by both SH solutions, and it remained higher than that achieved by the other solutions at all times. Hypertonic solutions, especially 10 % glycerin with 0.9 % NaCl plus 5 % fructose, tended to produce and maintain greater mucosal elevation than normal saline, but the difference was not significant. CONCLUSIONS: SH solutions were the most suitable ones for producing and maintaining long-term mucosal elevation, while the superiority of hypertonic solutions over normal saline was not clearly demonstrated.
Animals↗
Different mixtures of sodium hyaluronate and their ability to create submucosal fluid cushions for endoscopic mucosal resection.
BACKGROUND AND STUDY AIMS: Sodium hyaluronate (SH) is a promising submucosal injection solution during endoscopic mucosal resection, but its high cost is an obstacle to more widespread use. The aim of this study was to identify an appropriate low-cost SH solution by varying the molecular weight of SH and mixing various solutions with it. MATERIALS AND METHODS: The viscoelasticity of various SH solutions was first measured. The concentrations of two 1 % SH preparations with different molecular weights (800 kDa and 1900 kDa) were adjusted to 0.5 %, 0.25 %, and 0.125 %, using 0.9 %/3.75 % normal saline (NS), 5 %/20 % dextrose water (DW), and a glycerin solution (Glyceol): 10 % glycerin with 0.9 % normal saline plus 5 % fructose. The ability of these SH solutions to create submucosal fluid cushions (SFCs) was then investigated in the stomachs of two live minipigs. RESULTS: The 0.25 % 1900 kDa SH/NS solution and the 0.125 % 1900 kDa SH/20 % DW solution created a similar viscoelasticity to that of the 0.5 % 800 kDa SH/NS solution. The ability of these solutions to create SFCs was also similar. In addition, the 0.125 % 1900 kDa SH/Glyceol solution created similar SFCs, with a synergistic effect of increased viscoelasticity and the hypertonic nature of glycerin. CONCLUSIONS: A mixture of higher molecular weight sodium hyaluronate with a sugar solution (particularly 20 % dextrose), with or without glycerin, should be regarded as a cost-effective option for creating SFCs instead of the conventional SH solution made with the same amount of a 1 % 800 kDa SH preparation and normal saline.
Animals↗
A prospective randomised study of "covered" versus "uncovered" diamond stents for the management of distal malignant biliary obstruction.
BACKGROUND AND AIM: Covered self-expandable metal stents (EMS) were recently developed to overcome tumour ingrowth in conventional EMS. However, supporting evidence for the efficacy of covered EMS is lacking. PATIENTS AND METHODS: We enrolled 112 patients with unresectable distal biliary malignancies. They were randomly assigned to polyurethane covered (n = 57) or original diamond stent (n = 55). RESULTS: Stent occlusion occurred in eight patients (14%) after a mean of 304 days in the covered group, and in 21 patients (38%) after a mean of 166 days in the uncovered group. The incidence of covered EMS occlusion was significantly lower than that of uncovered EMS (p = 0.0032). The cumulative stent patency of covered stents was significantly higher than that of uncovered stents (p = 0.0066). No tumour ingrowth occurred in the covered group while it was observed in 15 patients in the uncovered group. In subgroup analysis, the cumulative patency of the covered EMS was significantly higher in pancreatic cancer (p = 0.0363) and metastatic lymph nodes (p = 0.0354). There was no significant difference in survival between the two groups. Acute cholecystitis was observed in two of the covered group and in none of the uncovered group. Mild pancreatitis occurred in five of the covered group and in one of the uncovered group. CONCLUSIONS: Covered diamond stents successfully prevented tumour ingrowth and were significantly superior to uncovered stents for the treatment of patients with distal malignant biliary obstruction. However, careful attention must be paid to complications specific to covered self-expandable metal stents, such as acute cholecystitis and pancreatitis.
Acute Disease↗
Incidence and recurrence rates of colorectal adenomas estimated by annually repeated colonoscopies on asymptomatic Japanese.
BACKGROUND: Whereas high recurrence rates of colorectal adenomas after polypectomy are widely recognised, little is known of the natural incidence in those with no neoplastic lesions initially. It is also known that single colonoscopy has a significant miss rate. AIMS: To elucidate the incidence and recurrence rates of colorectal neoplasms from a large cohort of asymptomatic Japanese patients on the basis of annually repeated colonoscopies. METHODS: A total of 6225 subjects (4659 men and 1566 women) participating in an annual colonoscopic screening programme and completing three or more colonoscopies were analysed during the 14 year period between 1988 and 2002. Patients were divided into three groups according to the findings of the initial two colonoscopies: 4084 subjects with no neoplasm, 1818 with small adenomas <10 mm, and 323 with advanced lesions, including carcinoma in situ, severe dysplasia, or large adenomas > or =10 mm. Mean age at the second colonoscopy was 48.8 years. RESULTS: For all types of colorectal neoplasms, the incidence rate in those with no initial neoplasm was 7.2%/year whereas recurrence rates in those with small adenomas and advanced lesions were 19.3% and 22.9%/year, respectively. For advanced colorectal lesions, the incidence rate was 0.21%/year whereas recurrence rates in those with small adenomas and advanced lesions were 0.64% and 1.88%/year, respectively. Colorectal neoplasms were in general more likely to develop in males and older subjects. CONCLUSIONS: Although recurrence rates after polypectomy were elevated, the incidence rates in subjects with no neoplastic lesions initially were quite high.
Adenoma↗
Benefit of interferon therapy in hepatocellular carcinoma prevention for individual patients with chronic hepatitis C.
BACKGROUND: An increase in the incidence of hepatocellular carcinoma (HCC) in Japan since the 1980s suggests an imminent outbreak in other countries where viral spread occurred more recently. Interferon therapy for chronic hepatitis C, in general, has been shown to prevent HCC. AIMS: To determine the scale of benefit in individual patients. SUBJECTS: Histologically proven chronic hepatitis C patients in the Inhibition of Hepatocarcinogenesis by Interferon Therapy (IHIT) cohort (Ann Intern Med 1999;131:174), as updated in March 2003. METHODS: The lifetime risk for HCC was calculated based on HCC incidence rates, stratified by sex, age, fibrosis stage, and outcome of interferon therapy. The gain in HCC free survival was defined as the difference between expected HCC free survival with sustained virological response and that without. RESULTS: The gain in HCC free survival was greater when a patient was younger and fibrosis was more advanced. For example, a 30 year old male with F3 fibrosis gained 12.4 years by attaining sustained response while a patient with F1 fibrosis older than 60 years gained less than one year. For a treatment protocol with a given sustained response rate, prior estimation of the gain can be obtained by multiplying the calculated HCC free survival for responders by the response rate. CONCLUSIONS: The gain in HCC free survival may serve as an indicator of the benefit of interferon therapy in terms of HCC prevention and be useful in the consideration of indication and selection of treatment protocol for individual patients.
Adult↗
Hepatitis A virus VP3 may activate serum response element associated transcription.
BACKGROUND: Hepatitis A virus (HAV) infection is a major public health problem worldwide. The infection does not induce any visible cytopathic effects or interfere with macromolecular synthesis in host cells. However, the hepatitis B and C viruses have recently been reported to activate intracellular signals. To clarify the effects of HAV infection on intracellular signalling, we examined the influence of 9 FLAG-tagged HAV proteins (VP2, VP3, VP1-2A, 2B, 2C, 3A, 3BC, 3C and 3D) on signal transduction pathways. METHODS: Viral protein expression vectors were co-transfected into HeLa cells with reporter plasmids controlled by a synthetic promoter containing direct repeats of the cyclic AMP response element (CRE), serum response factor (SRF), activator protein 1 (AP-1), nuclear factor kappaB (NF-kappaB) or serum response element (SRE). Cells were harvested 42 h after transfection and luciferase assays were performed. Viral protein activation twice that of the control was defined as significant. RESULTS: VP3 induced an SRE-associated signal 2.2 +/- 0.3 times higher than that of control. VP3 did not activate CRE-, SRF-, AP-1- or NF-kappaB- associated signalling. The other HAV proteins tested also failed to induce these pathways. CONCLUSIONS: HAV interacts with the host signalling mechanism, and HAV VP3, different from HBX and hepatitis C core protein, may activate only SRE-associated intracellular signalling, a pathway associated with cell proliferation and differentiation.
Blotting, Western↗
Resolution of liver cirrhosis and prevention of hepatocellular carcinoma by interferon therapy against chronic hepatitis C.
Hepatocellular carcinoma (HCC) is one of the most important medical problems facing the Asian-Pacific region, where the prevalence of chronic hepatitis B and C is so high. Every year, we have approximately 500 admissions to our department due to this malignancy. It is of utmost importance that we have efficient screening, diagnosis and treatment. Over the past several years, there has been steady improvement in elucidating the super-high risk group for HCC, and in the management of these patients. I discuss how effectively we can screen patients by using three tests, conventional AFP, AFP-L3 (lectin fraction) and DCP (des-gamma-carboxy-prothrombin). With these tests we can detect HCC as small as 10 mm. In addition, imaging technology including CT-angiography can effectively pick up small cancer nodules. However, they are not always readily available in all Asian countries. Thus, diagnostic procedures and treatment methods can be modified in each country depending on the situation. One such treatment modality is the percutaneous therapy. The recent introduction of radiofrequency ablation (RFA) has dramatically changed our daily clinical practice. The time needed to treat cancer nodules of 2 to 3 cm in size has been reduced from 1 month or longer with ethanol injection to less than a week with RFA. However, the most important issue is to prevent infection and progression from chronic hepatitis to HCC. The recent introduction of improved antiviral therapy makes us feel optimistically that we might eventually have a comprehensive strategy for HCC in the region where it is most needed.
Antiviral Agents↗
Thoracoscopic radiofrequency ablation therapy for hepatocellular carcinoma above the diaphragm associated with intractable hemothorax.
Explore the source record for details and available documents.
Carcinoma, Hepatocellular↗
Endoscopic spraying of sucralfate using the outer sheath of a clipping device.
Explore the source record for details and available documents.
Administration, Topical↗
Weak response of helicobacter pylori antibody is high risk for gastric cancer: a cross-sectional study of 10,234 endoscoped Japanese.
BACKGROUND: A large number of endoscoped members of the general Japanese population were surveyed to investigate the relationship between Helicobacter pylori infection and gastric cancer. Special attention was given to antibody titer and age of the subjects. METHODS: We performed gastrointestinal endoscopy and measured serum anti-H. pylori antibody in 10,234 consecutive Japanese who participated in a health examination program. Gastric cancer, when suspected, was confirmed by histology. We graded the H. pylori antibody titer into three groups in accordance with optical density values by ELISA: 'strongly positive', 'weakly positive', and 'negative'. RESULTS: Among the 10,234 subjects (men/women, 7.021/3,213; mean age, 49.1 years), 4,909 (48%) were strongly positive, 1,750 (17%) were weakly positive, and 3,575 (35%) were negative for H. pylori antibody. Thirty-seven cases of gastric cancer were found among the 10,234 subjects (0.36%); 23/4,909 (0.47%) in the strongly positive group, 9/1,750 (0.51%) in the weakly positive group, and 5/3,575 (0.14%) in the negative group. Both the strongly and weakly positive groups showed a higher risk of gastric cancer than the negative group. In the subjects over age 60, the weakly positive group seemed to show the highest risk for gastric cancer. CONCLUSIONS: In this investigation of 10,234 Japanese, based on endoscopy results, those with serum H. pylori antibody had an increased risk for gastric cancer, while those 'weakly positive' showed a high risk, particularly in the elderly.
Antibodies, Bacterial↗
Analysis of apoptotic and antiapoptotic signalling pathways induced by Helicobacter pylori.
BACKGROUND AND AIMS: Although it is reported that Helicobacter pylori induces apoptosis on gastric epithelial cells, the mechanism remains unknown. Antiapoptotic effects generated by H pylori have not yet been evaluated. METHODS: (1) H pylori strains (type 1 wild, TN2-DeltacagE, TN2-DeltavacA) were cocultured with MKN45, TMK1, and HeLa cells, and cell viability and apoptosis were assessed by trypan blue exclusion and DNA laddering, respectively. (2) Activation of caspases-3, 7, and 8, cytochrome c release from the mitochondria, and Fas, Fas associated death domain protein (FADD), Bax, Bak, and Bcl-X expression were evaluated by immunoblot analysis. (3) To investigate whether nuclear factor kappa B (NFkappaB) activation induced by cag pathogenicity island (PAI) positive H pylori affects antiapoptosis, MKN45 cells stably expressing super-repressor Ikappabetaalpha were cocultured with H pylori, and cell viability and caspase activation were evaluated. NFkappaB regulated gene expression was also evaluated by ribonuclease protection assay. RESULTS: (1) Wild-type and DeltavacA mutant H pylori induced apoptosis more potently than the DeltacagE mutant. Inhibition of cell contact between H pylori and cancer cells and heat killing H pylori diminished cell death. (2) Caspases-3, 7, and 8 were activated time dependently by H pylori as well as by the agonist anti-Fas. Cytochrome c release from mitochondria was observed and was not inhibited by caspase-8 inhibitor. Although protein expression of Fas, FADD, Bax, Bak, and Bcl-X in the whole cell lysates was not changed by H pylori, Bax was decreased from mitochondria free cytosol suggesting that Bax was translocated into mitochondria. (3) Cell death and the activities of caspases-3 and 8 were promoted in MKN45 cells stably expressing super-repressor Ikappabetaalpha that inhibits NFkappaB activation. Antiapoptotic proteins c-IAP1 and c-IAP2 were upregulated by the wild-type strains. CONCLUSION: cag PAI positive H pylori is capable of inducing apoptotic effects mainly through the mitochondrial pathway. Antiapoptotic effects mediated by NFkappaB activation were also observed.
Adaptor Proteins, Signal Transducing↗
Effects of N-alpha-methyl-histamine on human H(2) receptors expressed in CHO cells.
BACKGROUND: Production of N-alpha-methyl-histamine (NAMH), a histamine H(3) receptor (H3R) agonist, is reportedly promoted in Helicobacter pylori infected human gastric mucosa. NAMH was suggested to act directly on histamine H(2) receptors (H2Rs) in animals to stimulate acid secretion and to be a H2R agonist. As H2Rs and H3Rs play different roles in gastric acid secretion, it is very important to verify that NAMH is a H2R agonist. AIMS: To determine whether NAMH is a H2R agonist, as well as a H3R agonist. METHODS: We used a Chinese hamster ovary (CHO) cell line expressing human H2Rs (CHO-H2R) and control CHO cells. Expression of human H2Rs was confirmed by tiotidine binding. cAMP production in CHO-H2R and control cells in response to histamine or NAMH was measured. cAMP production in response to 10(-7) M NAMH was also measured in the presence or absence of the H2R antagonist famotidine and the H3R antagonist thioperamide. RESULTS: NAMH dose dependently stimulated cAMP productions in CHO-H2R cells. This production was inhibited by famotidine but not by thioperamide. Control CHO cells were unresponsive to either histamine or NAMH. In addition, the effect of NAMH, in terms of cAMP production in CHO-H2R cells, was more potent than that of histamine-that is, with a lower EC(50) concentration and higher maximal cAMP production. Both NAMH and histamine, but not R-alpha-methyl-histamine, effectively inhibited [(3)H] tiotidine binding to CHO-H2R cells. CONCLUSIONS: NAMH, which is produced in the gastric mucosa by H pylori, is a potent H2R agonist as well as a H3R agonist.
Animals↗
Association between severity of type A hepatitis and nucleotide variations in the 5' non-translated region of hepatitis A virus RNA: strains from fulminant hepatitis have fewer nucleotide substitutions.
BACKGROUND: Type A hepatitis is still a considerable problem in both underdeveloped and developed countries. Why some patients progress to fulminant type A hepatitis and others do not is unclear. AIMS: To determine if nucleotide differences in the genome of hepatitis A virus (HAV) are responsible for the range of clinical severities, we analysed the 5' non-translated region (5'NTR) of the HAV genome, which has an internal ribosomal entry site and is important for cap independent translation of the viral message. METHODS: Serum samples from 84 Japanese patients with sporadic type A hepatitis from five distant regions of Japan, comprising 12 patients with fulminant hepatitis (FH), 13 with severe acute hepatitis (AHs), and 59 with acute hepatitis (AH), were examined for HAV RNA. The fragment between nucleotides 75 and 638 of the 5'NTR was amplified by reverse transcription-polymerase chain reaction, and the nucleotide sequence was determined by direct sequencing. RESULTS: Comparison of sequences of the 5'NTR revealed relatively fewer nucleotide substitutions in FH and AHs patients compared with the considerable sequence variations found in strains of AH. This tendency was most prominent between nucleotides 200 and 500. Strains from FH and AHs cases had fewer nucleotide substitutions (p<0.001) in this region. CONCLUSIONS: Nucleotide variations in the central portion of the 5'NTR of HAV may influence the severity of type A hepatitis.
5' Untranslated Regions↗
Analysis of apoptotic and antiapoptotic signalling pathways induced by Helicobacter pylori.
BACKGROUND AND AIMS: Although it is reported that Helicobacter pylori induces apoptosis on gastric epithelial cells, the mechanism remains unknown. Antiapoptotic effects generated by H pylori have not yet been evaluated. METHODS: (1) H pylori strains (type 1 wild, TN2-deltacagE, TN2-deltavacA) were cocultured with MKN45, TMK1, and HeLa cells, and cell viability and apoptosis were assessed by trypan blue exclusion and DNA laddering, respectively. (2) Activation of caspases-3, 7, and 8, cytochrome c release from the mitochondria, and Fas, Fas associated death domain protein (FADD), Bax, Bak, and Bcl-X expression were evaluated by immunoblot analysis. (3) To investigate whether nuclear factor kappa B (NFkappaB) activation induced by cag pathogenicity island (PAI) positive H pylori affects antiapoptosis, MKN45 cells stably expressing super-repressor IkappaBalpha were cocultured with H pylori, and cell viability and caspase activation were evaluated. NFkappaB regulated gene expression was also evaluated by ribonuclease protection assay. RESULTS: (1) Wild-type and deltavacA mutant H pylori induced apoptosis more potently than the deltacagE mutant. Inhibition of cell contact between H pylori and cancer cells and heat killing H pylori diminished cell death. (2) Caspases-3, 7, and 8 were activated time dependently by H pylori as well as by the agonist anti-Fas. Cytochrome c release from mitochondria was observed and was not inhibited by caspase-8 inhibitor. Although protein expression of Fas, FADD, Bax, Bak, and Bcl-X in the whole cell lysates was not changed by H pylori, Bax was decreased from mitochondria free cytosol suggesting that Bax was translocated into mitochondria. (3) Cell death and the activities of caspases-3 and 8 were promoted in MKN45 cells stably expressing super-repressor IkappaBalpha that inhibits NFkappaB activation. Antiapoptotic proteins c-IAP1 and c-IAP2 were upregulated by the wild-type strains. CONCLUSION: cag PAI positive H pylori is capable of inducing apoptotic effects mainly through the mitochondrial pathway. Antiapoptotic effects mediated by NFkappaB activation were also observed.
Apoptosis↗
False positive uptake of metaiodobenzylguanidine in hepatocellular carcinoma.
We present the case of a patient who showed increased accumulation of (123)I-metaiodobenzylguanidine (MIBG) in hepatocellular carcinoma, leading to a false presumptive diagnosis of intrahepatic neuroendocrine tumour. The increase in uptake was not seen on images obtained 4 h after tracer injection but was evident on those taken after 24 h, suggesting slower washout from the liver tumour than from non-tumoural liver parenchyma. Our observations indicate that a non-neuroendocrine malignant tumour may exhibit high accumulation of MIBG associated with prolonged retention.
3-Iodobenzylguanidine↗
Differential expression of the L-plastin gene in human colorectal cancer progression and metastasis.
To identify molecular alterations in the progression of colorectal carcinoma, we analyzed gene expression profiles of colon cancer cell lines derived from primary and metastatic tumors from a single patient. Of 2280 cDNAs investigated using our in-house microarray, the expression of 6 genes (tumor-associated antigen L6, L-plastin, the human homologue of yeast ribosomal protein S28, the B-cell translocation gene, mitochondrial aspartate-aminotransferase, and HLA-A) increased, while that of 2 genes (keratin 5 and phosphoglucomutase) decreased in metastatic-tumor-derived cells compared with primary-tumor-derived cells. Of these genes, we assessed the L-plastin gene, an actin-bundling protein, at the protein level using a tissue microarray consisting of 58 clinically stratified colorectal cancer specimens. Consistent with our microarray results, the expression of L-plastin was significantly correlated with the progression of cancer staging. Therefore, our results suggest that the L-plastin gene is a potential metastatic marker. In addition, combining cDNA microarrays and tissue arrays, as shown here, is thought to facilitate the rapid characterization of candidate biomarkers.
Antigens, Surface↗
Systematic analysis of the TGF-beta-Smad signaling pathway in gastrointestinal cancer cells.
The transforming growth factor-beta (TGF-beta)-Smad signaling pathway has an important role in carcinogenesis. To study the frequency and mechanism of functional impairment of this pathway in human gastrointestinal cancers, we used a reporter assay to examine the response of 38 cell lines (11 colorectal, 9 pancreatic, 10 gastric, and 8 hepatic cancers) to TGF-beta. We then analyzed TGF-beta type II receptor (T beta RII) gene, immunoblots of Smad4, and restoration of the pathway by rescuing T beta R or Smad. We observed impaired signaling in 91% of colorectal, 67% of pancreatic, and 40% of gastric cancer cell lines, but in none of the hepatic cancer cells. We suggest that this pathway does not function as a tumor suppressor in hepatic carcinogenesis. The impairment is due to inactivation of T beta RII and Smad4 in colorectal and pancreatic cancers. However, because the signal was not recovered by rescuing T beta R or Smad genes in TGF-beta-response-defective gastric cancer cell lines, we suggest that novel molecules or mechanisms are involved in the impaired pathway in some gastric cancers.
Blotting, Western↗