Motowo Mizuno

The effect of eradicating Helicobacter pylori on the development of gastric cancer in patients with peptic ulcer disease

OBJECTIVES:Infection with Helicobacter pylori is a risk factor for the development of gastric cancer. However, it is not known whether eradication therapy can prevent the development of gastric cancer in persons in whom the cancer is not yet established. In the present study, we investigated whether the eradication of H. pylori in patients with peptic ulcer disease reduces the likelihood of their developing gastric cancer.METHODS:Prospective posteradication evaluations were conducted in 1,342 consecutive patients (1,191 men and 151 women; mean age: 50 yr) with peptic ulcer diseases who had received H. pylori eradication therapy. After confirmation of eradication, endoscopy and a urea breath test were performed yearly.RESULTS:A total of 1,120 patients completed more than 1-yr follow-up and were followed for up to 8.6 yr (a mean of 3.4 yr). Gastric cancer developed in 8 of 944 patients cured of infection and 4 of 176 who had persistent infection (p = 0.04; log-rank test). All the gastric cancer developed in patients with gastric ulcer, but none in patients with duodenal ulcer (p = 0.005; Fishers exact test). In patients with gastric ulcer, persistent infection was identified as a significant factor for the risk of developing gastric cancer (hazard ratio: 3.35; 95% confidence interval: 1.00–11.22; p = 0.04; Coxs proportional-hazards model).CONCLUSION:H. pylori eradication may reduce their risk of developing gastric cancer in patients with gastric ulcer. Large-scale studies in additional populations of this important international public-health issue are warranted.

Baseline gastric mucosal atrophy is a risk factor associated with the development of gastric cancer after Helicobacter pylori eradication therapy in patients with peptic ulcer diseases

Background We previously reported that eradication of Helicobacter pylori could reduce the risk of developing gastric cancer in patients with peptic ulcer diseases. In the present study, we further followed up our patient groups to identify factors associated with the development of gastric cancer.MethodsProspective posteradication evaluations were conducted in 1342 consecutive patients (1191 men and 151 women; mean age, 50 years) with peptic ulcer disease who had received H. pylori eradication therapy. The patients had undergone endoscopic examination before eradication therapy to evaluate peptic ulcers, background gastric mucosa, and H. pylori infection. After confirmation of eradication, follow-up endoscopy was performed yearly.ResultsA total of 1131 patients were followed for up to 9.5 years (mean, 3.9 years). Gastric cancer developed in 9 of 953 patients cured of infection and in 4 of 178 who had persistent infection (P = 0.04). The risk of developing gastric cancer after receiving H. pylori eradication therapy was increased according to the grade of baseline gastric mucosal atrophy (P = 0.01). In patients with peptic ulcer diseases, persistent infection of H. pylori (hazard ratio, 3.9; P = 0.03), the grade of baseline gastric mucosal atrophy (3.3, P = 0.01) and age (2.0, P = 0.04) were identified as significant risk factors for developing gastric cancer.ConclusionsThe grade of gastric atrophy was closely related to the development of gastric cancer after receiving H. pylori eradication therapy. Thus, eradication of H. pylori before the significant expansion of atrophy is most beneficial to prevent gastric cancer.

Randomized open trial for comparison of proton pump inhibitors in triple therapy for Helicobacter pylori infection in relation to CYP2C19 genotype

Abstract Background and aims : Genetic polymorphism of cytochrome P450 (CYP) 2C19 influences the efficacy of Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI) and amoxicillin. However, in triple therapy (PPI plus amoxicillin and clarithromycin), little is known about the impact of CYP2C19 polymorphism, or the use of rabeprazole, which is not well metabolized by CYP2C19. The efficacy of three PPI (omeprazole, lansoprazole, and rabeprazole) in a 1‐week triple regimen were compared in relation to CYP2C19 polymorphism.

Eradication of Helicobacter pylori increases platelet count in patients with idiopathic thrombocytopenic purpura in Japan.

Background  The effect of Helicobacter pylori eradication on the platelet count in patients with thrombocytopenic purpura is controversial. In this multicentre study, we prospectively assessed the effect of H. pylori eradication therapy in idiopathic thrombocytopenic purpura patients.

Interleukin-1β genetic polymorphism influences the effect of cytochrome P 2C19 genotype on the cure rate of 1-week triple therapy for Helicobacter pylori infection

Interleukin-1β genetic polymorphism influences the effect of cytochrome P 2C19 genotype on the cure rate of 1-week triple therapy for Helicobacter pylori infection

A randomized open trial for comparison of proton pump inhibitors, omeprazole versus rabeprazole, in dual therapy for Helicobacter pylori infection in relation to CYP2C19 genetic polymorphism

Background and Aim: The genetic polymorphism of cytochrome P450 (CYP) 2C19 has been shown to influence the efficacy of Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI) and amoxicillin (so‐called dual therapy). Omeprazole, a widely used PPI, and rabeprazole, a new PPI, are metabolized in different pathways in terms of CYP2C19 genetic polymorphisms. In this study, we compared the efficacy of omeprazole and rabeprazole in a 2‐week dual therapy in relation to CYP2C19 polymorphism.

Virion-like structures in HeLa G cells transfected with the full-length sequence of the hepatitis C virus genome

Abstract Background & Aims: The process and the site of hepatitis C virus (HCV) particle formation in cells after infection remain unknown. The aim of this study was to create an in vitro model for the study of HCV particle formation. Methods: HeLa G cells were transfected with the full-length sequence of the HCV genome. Viral protein expression was analyzed using immunoblotting. The cells were examined using immunoelectron and conventional electron microscopy. Results: Core, E2, NS3, NS5a, and NS5b proteins were identified using immunoblotting. Immunoelectron microscopy showed that the core antigen was located along the membrane of the endoplasmic reticulum (ER) and occasionally in its cisternae. Core antigen-positive particles of 30 nm in diameter were found in the cytosol and in the cisternae of the ER. The particles in the cisternae were coated with an outer membrane that was connected to the ER membrane. Conventional electron microscopy revealed particles of 45 nm in diameter with electrondense cores in the cisternae of the ER. The outer membrane of the particles was occasionally connected to the ER membrane. Conclusions: The findings suggest that HCV core proteins are synthesized and assembled into particles in the cytosol and that they bud into the cisternae of the ER to form coated particles.

Antibodies to human gastric epithelial cells and heat shock protein 60 in Helicobacter pylori positive mucosa associated lymphoid tissue lymphoma.

BACKGROUND Development of gastric mucosa associated lymphoid tissue (MALT) lymphoma is thought to be closely associated with host immune reactions toHelicobacter pylori. AIM To investigate humoral immune responses in patients with MALT lymphoma to antigens shared by H pylori and human gastric epithelial cells. METHODS Sera were obtained from H pylori positive patients with MALT lymphoma (n = 11) or other gastroduodenal diseases (peptic ulcer, n = 40; non-ulcer dyspepsia, n = 20) and fromH pylori negative healthy control subjects (n = 10). Antibodies to HGC-27 human gastric epithelial cells and human recombinant heat shock protein (Hsp) 60 were examined using an enzyme linked immunosorbent assay (ELISA) and immunoblotting. RESULTS Antibody titres to HGC-27 cells were significantly elevated inH pylori positive patients with MALT lymphoma when compared with titres in patients with other gastroduodenal diseases and in healthy subjects. Immunoblotting of sera from patients with MALT lymphoma often detected a band with a molecular mass corresponding to Hsp60, and both ELISA and immunoblotting showed elevated antibody titres to the recombinant human Hsp60. Antigenic similarity between Hsp60 and H pylori HspB was documented by immunoblotting experiments. CONCLUSIONS Autoantibodies reactive with host gastric epithelial cells are often increased in MALT lymphoma, and Hsp60 is a major target antigen. Immune responses induced by immunological cross reactivity between H pylori HspB and human Hsp60 in gastric epithelium may be involved in the development of MALT lymphoma.

Distribution of activated complement, C3b, and its degraded fragments, iC3b/C3dg, in the colonic mucosa of ulcerative colitis (UC)

The third component of complement (C3) is central to both the classical and alternative pathways in complement activation. In this study, involvement of C3 activation in the mucosal injury of UC was investigated. We examined the distribution of activated (C3b) and degraded fragments (iC3b/C3dg) of C3, terminal complement complex (TCC), and complement regulatory proteins in normal and diseased colonic mucosa including UC and other types of colitis using immunohistochemical techniques at the level of light and electron microscopy. While C3b and iC3b/C3dg staining was negligible in the normal mucosa, iC3b/C3dg and, to a lesser extent, C3b were deposited in UC mucosa along the epithelial basement membrane. The deposition was enhanced in relation to the severity of mucosal inflammation (C3b, P < 0.05; iC3b/C3dg, P < 0.01). Epithelial deposition of TCC was not observed in most UC mucosa. Immunoelectron microscopy showed that C3b and iC3b/C3dg were distributed mainly along the epithelial basement membrane and the underlying connective tissue in a granular, studded manner, and weakly present along the basolateral surface of epithelial cells. These C3 fragments were also deposited in inflammatory control mucosa such as ischaemic and infectious colitis. Our findings suggest that deposition of the C3 fragments occurs in inflamed colonic mucosa of diverse etiologies, including UC, but to define a role of the deposition in the development of mucosal injury in UC awaits direct study.

Electron and Immunoelectron Microscopic Study of Dane Particle Formation in Chronic Hepatitis B Virus Infection

The site of Dane particle formation in hepatocytes was studied by routine electron and immunoelectron microscopy of liver biopsy specimens from 10 patients with hepatitis B e antigen-positive chronic active hepatitis. With routine electron microscopy, core particles were abundant in cytosol, often adjacent to the cell membrane, and occasionally in the microvilli. Figures suggestive of budding of endoplasmic reticulum with a core particle into the cisternae of endoplasmic reticulum were observed frequently. There were also figures suggestive of direct budding with a core particle from the surface of the cell. With the immunoelectron microscopy, the core particles were found to be positive for hepatitis B core antigen and the endoplasmic reticulum and the plasma membrane were positive for hepatitis B surface antigen. These findings suggest that the most plausible mode of formation of the Dane particle is by budding of hepatitis B surface antigen-positive endoplasmic reticulum membrane into the cisternae. In addition, formation of the Dane particle may also take place at the surface of the hepatocyte by a similar mechanism.