A 40KDa zinc-binding protein (ZBP), ZBPP-2, was purified to homogeneity from rat intestinal mucosa by a combination of zinc-chelating affinity column, hydroxyapatite column and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by electroelution. This protein was deleted in intestinal crypts after dithizone-treatment of rats, as we reported previously for ZBPP-1, a 90KDa ZBP. Four independent mouse monoclonal antibodies (mAbs) to purified 40KDa ZBP (all μκ isotype) were prepared. In addition to 40KDa ZBP, these mAbs detected several higher molecular size ZBP in Western blot. Although non-zinc binding protein fraction seemed to contain abundant antigens reactive to anti-ZBPP-2 mAbs, immunohistochemistry of rat intestine with these mAbs selectively stained Paneth cells. Moreover, the staining disappeared 6hr after dithizone-treatment and resumed after 3 days as Paneth cells regenerated. Accordingly, the ZBPP-2 was another unique marker for Paneth cells.
ABSTRACT Helicobacter pylori is the major causative agent of chronic antral gastritis and is thought to be involved in the pathogenesis of mucosa-associated lymphoid tissue lymphoma (MALToma) developing in the human stomach. The aim of this study was to clarify whether corporal autoimmune gastritis (AIG), which is known to decrease acidity due to destruction of parietal cells, predisposes mice to H. pylori infection, thereby leading to MALToma-like pathology. BALB/c mice in which AIG had been induced by thymectomy 3 days after birth (AIG mice) were used. The AIG mice were orally administered mouse-adapted H. pylori at the age of 6 weeks and were examined histologically and serologically after 2 to 12 months. The results were compared with those obtained from uninfected AIG mice and infected normal mice. Germinal centers were induced in the corpus in 57% of the H. pylori -infected AIG mice, which elicited anti- H. pylori antibody responses in association with upregulation of interleukin-4 (IL-4) mRNA. In these mice, parietal cells remained in the corpus mucosa. These findings were in contrast to those with the uninfected AIG mice: fundic gland atrophy due to disappearance of parietal cells associated with upregulation of gamma interferon, but not IL-4, mRNA and no germinal center formation in the corpus. These observations suggest that AIG alters the infectivity of H. pylori , leading to MALToma-like follicular gastritis, at an early stage after H. pylori infection.
Musashi‐1, a neural RNA‐binding protein, is important for maintaining neural stem cells. Both Musashi‐1 and Hes1, a transcriptional factor regulated by Musashi‐1, are expressed in the small intestine. Here we show that Musashi‐1 is present in a few epithelial cells just above the Paneth cells in the small intestinal crypt, the putative position of stem cells, whereas Hes1 is expressed in lower crypt cells just above the Paneth cells, including Musashi‐1‐positive cells. Musashi‐1 and Hes1 were not expressed in Paneth cells. Notably, Musashi‐1 and Hes1 were coexpressed in the crypt base columnar cells located between the Paneth cells. These findings suggest that not only the cells just above Paneth cells but also the crypt base columnar cells between the Paneth cells have stem cell characteristics.
<i>Background/Aims:</i> Although <i>regenerating</i><i>gene</i><i>(Reg)</i> Iα protein has a trophic effect on gastric epithelial cells, it is unclear whether Reg Iα protein and its receptor are involved in gastric carcinogenesis. Therefore, we investigated the Reg Iα protein expression in human gastric cancers and assessed its relationship to clinicopathological factors. <i>Methods:</i> Sixty-one gastric cancer specimens were examined, using immunohistochemistry, for Reg Iα protein, p53, and proliferating cell nuclear antigen. The expression of both Reg Iα and Reg receptor mRNA was examined in seven human gastric cancer cell lines (MKN1, MKN28, MKN45, MKN74, KATOIII, GCIY, and AGS) by reverse transcription-polymerase chain reaction and Northern blot analysis. <i>Results:</i> Twenty-three (37.7%) of the 61 gastric cancer tissues samples were positive for Reg Iα protein. The Reg Iα expression was significantly related to the presence of lymphatic invasion but not to tumor size, tumor stage, Lauren’s classification, presence of venous invasion, lymph node metastases, or p53 overexpression. Gastric cancers positive for Reg Iα protein showed a significantly higher proliferating cell nuclear antigen labeling index than negative ones. The expression of both Reg Iα and Reg receptor mRNA was detected in all seven gastric cancer cell lines. <i>Conclusion:</i> Reg Iα protein may play a role in the development of gastric cancers.
Background: The increased use of esophagogastroduodenoscopy has revealed the esophagus to be a common site of occurrence of granular cell tumors (GCT). To clarify the endosonographic features of esophageal GCT, we compared endosonographic findings and histopathological analysis of resected specimens of esophageal GCT and submucosal leiomyomas. Methods: We enrolled a total number of 18 consecutive patients with esophageal submucosal tumors. They were preoperatively examined using 15 MHz or 20 MHz probe endoscopic ultrasonography. The endosonographic findings were retrospectively compared with hisopathological findings of the resected specimens. Results: Five GCT and 13 submucosal leiomyomas were diagnosed histologically as well as endosonographically. Pathological analysis revealed that the dispropotional mixture of tumor cells, fibrosis and muscularis mucosa within the GCT would be endosonographically visualized as a heterogeneous hypoechoic mass. Moreover, the laterally scattered tumor cells, together with adjacent thickened muscularis mucosa, are reflected by the unclear margin of the tumor by endoscopic ultrasonography. In contrast, in the submucosal leiomyomas, tumor cells and fibrosis were uniformly mixed and the margin of the tumor was clearly demarcated. These histological findings would be endosonographically recognized as a homogeneously hypoechoic mass with a clearly demarcated border. Conclusion: A high‐frequency probe endoscopic ultrasonography is useful for differentiating esophageal GCT from submucosal leiomyomas. Considering the histological characteristics, esophageal GCT should be resected with adequate tumor‐free margin when endoscopic treatment is applied.
