Yumiko Ishino

Aberrant expression of CDX2 in Barrett's epithelium and inflammatory esophageal mucosa

Background: There have been no detailed reports directly comparing the expression of CDX1 with that of CDX2 in the inflammatory esophageal mucosa and Barretts epithelium. The present study was designed to examine the expression of CDX 1/2 in inflammatory esophageal mucosa with or without Barretts epithelium. Methods: The expression of CDX1/2 genes was analyzed using the reverse transcriptase-polymerase chain reaction (RT-PCR) in 34 human esophageal biopsy specimens, and CDX2 expression was also evaluated immunohistochemically, using anti-human CDX2 monoclonal antibody. The biopsy specimens for RNA extraction were taken endoscopically from esophageal mucosa with mucosal break due to gastroesophageal reflux disease (GERD), Barretts epithelium, and normal epithelium. The expressions of mucin markers (MUC2) and intestine-specific genes (sucrase-isomal-tase, human defensin-5, alkaline phosphatase) were also comparatively analyzed. Results: CDX1/2 expression was not found in the normal esophageal mucosa. The prevalence of CDX1/2 mRNA expression was significantly higher in the mucosa with Barretts epithelium than in the mucosa without Barretts epithelium. It is noteworthy, however, that the CDX2 mRNA expression was initiated at the stage of esophagitis, when neither CDX1 nor intestine-specific genes had emerged yet. In contrast to CDX2, CDX1 was expressed only in Barretts epithelium. Immunohistochemical study demonstrated strong and extensive nuclear immunoreactivity for CDX2 in Barretts epithelium. Furthermore, fine granular cytoplasmic staining was also observed in the cytoplasm in Barretts epithelium, as well as in inflammatory esophageal mucosa. Conclusions: We report here, for the first time, that CDX2 is expressed in patients with Barretts epithelium and inflammatory esophageal mucosa. These findings imply that the expression of CDX2 may be an early event leading to the development of Barretts esophagus.

Changes in plasma ghrelin levels, gastric ghrelin production, and body weight after Helicobacter pylori cure

BackgroundGhrelin is a body weight-regulating peptide produced and secreted primarily by the gastric mucosa. Helicobacter pylori infection impairs gastric ghrelin production, leading to a lower plasma ghrelin concentration. However, the effect of H. pylori eradication on plasma ghrelin levels and its relation to body weight change after H. pylori cure are still uncertain. We examined the association of plasma ghrelin levels with gastric ghrelin production and body weight change before and after H. pylori eradication.MethodsPlasma ghrelin concentrations, gastric ghrelin expression, and body weight were determined in a total of 134 consecutive individuals before and 12 weeks after successful H. pylori eradication. Gastric ghrelin expression was evaluated by determining mRNA expression levels and the number of ghrelin-producing cells in gastric mucosa biopsy specimens by real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively.ResultsPlasma ghrelin concentration increased in 50 patients and decreased in 84 patients after H. pylori eradication. After H. pylori cure, however, gastric preproghrelin mRNA expression was increased nearly fourfold (P < 0.0001), and the number of ghrelin-positive cells was increased or unchanged. In contrast, plasma ghrelin changes after H. pylori cure were inversely correlated with both body weight change (P < 0.0001) and initial plasma ghrelin levels (P < 0.0001).ConclusionsChanges in plasma ghrelin concentrations before and after H. pylori cure were inversely correlated with body weight change and initial plasma ghrelin levels but not with gastric ghrelin production in Japanese patients.

Rabeprazole, amoxycillin and low‐ or high‐dose clarithromycin for cure of Helicobacter pylori infection

Rabeprazole sodium is a proton pump inhibitor.

Helicobacter pylori eradication induces marked increase in H+/K+-adenosine triphosphatase expression without altering parietal cell number in human gastric mucosa

Background and aims: Gastric acid secretion is downregulated by Helicobacter pylori infection and upregulated after its eradication, but the mechanisms are still unclear. We examined the effects of H pylori eradication on the number of parietal cells and on expression of molecules functioning in acid secretion in the human gastric mucosa. Methods: We enrolled 111 consecutive men with chronic gastritis induced by H pylori. Biopsy specimens were endoscopically obtained before and 12 weeks after successful eradication of H pylori and parietal cell numbers were counted. mRNA expression levels of H+/K+-adenosine triphosphatase (H+/K+-ATPase), anion exchanger 2, M3 muscarinic receptor, intrinsic factor, and interleukin 1β were determined with a real time reverse transcriptase-polymerase chain reaction method. The severity of gastric atrophy was evaluated using the serum pepsinogen I/II ratio. Results: No significant difference was observed in parietal cell numbers before and after H pylori eradication. Median mRNA expression levels of H+/K+-ATPase in the gastric mucosa increased 250-fold after H pylori eradication accompanied by attenuation of interleukin 1β. A large increase in H+/K+-ATPase expression was observed even in patients with severe atrophic gastritis. In contrast, fold increases in mRNA expression levels, including intrinsic factor, anion exchanger 2, and M3 muscarinic receptor, after eradication therapy, were limited to 1.4, 2.3, and 2.5 times, respectively. Conclusions: In the absence of alteration of parietal cell number, gastric H+/K+-ATPase mRNA expression was markedly restored after successful H pylori eradication, suggesting a central role for the restoration of H+/K+-ATPase expression in gastric acid secretion recovery after H pylori eradication.

p53 expression in the gastric mucosa before and after eradication of Helicobacter pylori.

Accumulation of p53 has been recognized in the gastric mucosa infected with Helicobacter pylori. We investigated the prevalence of p53‐positive cells in the gastric mucosa before and one month after eradication of H. pylori and the relationship between p53 positivity and inflammation and cell proliferation.

Change in apoptosis in the gastric surface epithelium and glands after eradication of Helicobacter pylori.

BACKGROUND Change in apoptosis in gastric glands after eradication of Helicobacter pylori has never been reported. AIMS The purpose of this paper is to investigate the change in apoptosis in gastric glands after eradication of Heliobacter pylori. PATIENTS AND METHODS We studied 23 Heliobacter pylori-positive patients with duodenal and gastric ulcers, who were monitored for 6-12 months after eradication, and eight controls. Biopsies were taken from the antrum and body. Apoptosis was evaluated immunohistochemically using anti-single stranded DNA antibody. Apoptotic index was calculated by counting immunostained cells in surface epithelial and glandular cells. RESULTS In the surface epithelium, Apoptotic indexes were significantly higher in patients than in controls. In the upper portion of fundic glands, apoptotic indexes were significantly higher in patients with gastric ulcers (14.2% (9.3, 17.8)) (median (1st quartile, 3rd quartile)) than in controls (8.0% (2.0, 9.0), p < 0.01) and decreased significantly after eradication (3.4% (2.0, 5.3)), p < 0.01). In pyloric glands, apoptotic indexes were no different between patients and controls. In the lower portion of fundic glands, apoptotic indexes were very low, both in patients and in controls. CONCLUSIONS Our results showed that apoptosis, not only of surface epithelial cells but also of glandular cells in the upper portion of fundic glands, increased in Heliobacter pylori-positive patients with gastric ulcers and decreased to normal levels after eradication of Heliobacter pylori.

Deficiencies of automatic endoscopic reprocessors: a method to achieve high-grade disinfection of endoscopes

BACKGROUND We show that disinfection using the automatic endoscopic reprocessor is not complete and propose a method for high-grade disinfection of endoscopes. METHODS We used an automatic endoscopic reprocessor, Pyser System 83, and 2% glutaraldehyde. After each endoscopic procedure, the endoscopes were divided into three groups. Endoscopes in group A were washed only by the reprocessor. Group B endoscopes were washed by the reprocessor after the connectors were soaked in glutaraldehyde for 5 minutes. The channels, valves, connecting sections of group C endoscopes, and the connectors of the machine were sprayed with glutaraldehyde before machine-washing. Swabs were taken from all 13 parts of each endoscope and machine for microbiologic culture. RESULTS Six endoscopes were positive, cumulatively, for bacterial contamination in group A. Among group B endoscopes, one remained contaminated. No endoscope was positive in group C. The difference between group A and C was statistically significant (p < .05). CONCLUSIONS Machine washing by automatic endoscopic reprocessors may not achieve complete disinfection. Additional procedures are necessary. High-grade disinfection of the connectors is critical. Disinfection of the interface between the connectors is important.

Histamine‐2 receptor expression in gastric mucosa before and after Helicobacter pylori cure

Background : Helicobacter pylori infection prevents the occurrence of the tolerance phenomenon of Histamine‐2 (H2) receptor antagonists. Gastro‐esophageal reflux disease develops in some cases with the restoration of acid secretion after H. pylori eradication therapy.