Takashi Takashima

Increased expression of cytokines and adhesion molecules in rat chronic esophagitis.

Background/Aims: Cytokines and adhesion molecules regulate many inflammatory processes in several gastrointestinal diseases. The dynamics of cytokines and adhesion molecules in reflux esophagitis are unknown in detail. We examined the expression and dynamics of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), MIP-2, GRO/cytokine-induced neutrophil chemoattractant-2α (CINC-2α), intercellular adhesion molecule-1 (ICAM-1), leukocyte function-associated antigen 1 (LFA-1; CD11a/CD18), and Mac-1 (CD11b/CD18) in rat chronic reflux esophagitis. Methods: Chronic acid reflux esophagitis was induced in Wistar rats by ligating the transitional region between the forestomach and the glandular portion and wrapping the duodenum near the pylorus with a small piece of an 18-Fr Nélaton catheter. Rats were killed 3 or 21 days after operation. The levels of mRNA expression of cytokines and ICAM-1 were determined by real-time quantitative RT-PCR. Localization of adhesion molecules and cytokines was investigated by immunohistochemical staining, and numbers of LFA-1- or Mac-1-positive cells were quantified. Results: IL-1β, TNF-α, MCP-1, MIP-1α, MIP-2, CINC-2α, and ICAM-1 mRNA expression was significantly increased in esophageal lesions compared with normal esophagus. There were few these cytokines- or adhesion molecule-positive cells in normal esophagus. In regions of esophagitis, numerous inflammatory leukocytes in lamina propria and the submucosal layer exhibited positive reactions for these cytokines and endothelial cells were intensely stained for ICAM-1. Numbers of LFA-1- and Mac-1-positive cells were significantly increased in rat chronic esophagitis. Treatment with rabeprazole almost completely inhibited development of chronic acid reflux esophagitis and significantly decreased expression of cytokines and ICAM-1 mRNA in esophageal tissue compared with control. Conclusion: Cytokines and adhesion molecules play important roles in the pathogenesis of chronic reflux esophagitis in this rat model.

Increased expression of transforming growth factor-alpha and epidermal growth factor receptors in rat chronic reflux esophagitis

Background and Aim:  Transforming growth factor‐alpha (TGF‐α), which binds to epidermal growth factor receptors (EGF‐R), stimulates esophageal epithelial cell proliferation, enabling rapid repair after mucosal injury. The aim of the present study was to examine epithelial proliferation and dynamics of TGF‐α and EGF‐R gene and protein expression in rat chronic acid reflux esophagitis.

Comparison of the effects of rebamipide with those of cimetidine on chronic gastritis associated with Helicobacter pylori in Mongolian gerbils

Background and Aims : The effects of rebamipide on chronic gastritis associated with Helicobacter pylori have not been well‐defined. We compared these effects of rebamipide with those of cimetidine in Mongolian gerbils infected with H. pylori.

Increased expression of epidermal growth factor receptors in basal cell hyperplasia of the oesophagus after acid reflux oesophagitis in rats

Epidermal growth factor (EGF), which binds to EGF receptors (EGF‐R), stimulates oesophageal epithelial cell proliferation, enabling rapid repair after mucosal injury. In the normal human oesophageal epithelium, EGF‐R expression is present and confined to the basal layer.

High molecular protein of Helicobacter pylori responsible for inhibition of ornithine decarboxylase activity of human gastric cultured cells

Ornithine decarboxylase (ODC), a rate‐limiting enzyme of polyamine biosynthesis, mediates epithelial cell proliferation and plays a critical role in the optimal repair of gastric mucosal damage. Several studies have shown that Helicobacter pylori inhibits the growth and proliferation of gastric cells in vitro.

Lansoprazole inhibits the development of dextran sodium sulfate-induced colitis in rats

was not preventing the activated T cells from proliferating as the numbers were not reduced in the ASM981relative to vehicle-treated mice Conclusions:ASM981 is highly effective in a dlerapeutic setting. ASM981 has strong effects on some of the downstream systemic inthmmatory reactions in this model. The data from th~s severe chronic model of IBD together with the already impressive findings in chronic inflammatory skin disorders lead as to expect ASM981 to be effective in IBD in man