Search

Helicobacter pylori (H. pylori) causes pathological changes of gastric epithelial cells induced by pathogenic factors such as CagA and VacA, namely hummingbird cells (HBC) formation and vacuolization, respectively, in cultured cell lines. Cytopathic effects of other pathogenic factors produced by H. pylori have not been reported. In this study, we examined whether H. pylori induces unique morphological changes other than HBC formation and vacuolization, and we established a new marker of the bacterial infection in vitro. The cytotoxicity of H. pylori was examined in the AGS cell line, and a new morphological change, namely multinuclear giant cells (MNGC) formation, was observed in this cell line. The enhancement of MNGC formation was observed following H. pylori infection but was not associated with CagA, which causes HBC formation. We characterized the factor causing MNGC formation enhancement as heat-stable and water-soluble, and finally considered the factor to be H. pylori lipopolysaccharide (LPS). We considered that H. pylori LPS enhances MNGC formation in vitro. The cytopathic effect may provide an important marker that may clarify the mechanism of H. pylori pathogenesis in human gastric epithelial cells.

We investigated the effect of Helicobacter pylori (H. pylori) infection on development of early differentiated gastric cancer with regard to mucin phenotypic expression and cancer’s surrounding mucosa. The H. pylori antibody (HP-Ab) positive rate of patients with gastric cancer was significantly higher than that of control. Furthermore, we classified the gastric cancer group according to mucin histochemistry and immunohistochemistry into 3 types, namely gastric type, intestinal type and gastric-intestinal type whose occurrence rates were 34%, 35% and 31%, respectively. The surrounding mucosa of the intestinal phenotype cancer showed severe atrophy and high degree of intestinal metaplasia but its H. pylori density was very low. On the contrary, the surrounding mucosa of the gastric phenotype cancer revealed mild atrophy and mild intestinal metaplasia whereas the H. pylori density was relatively high. However, no statistically significant difference was observed in HP-Ab positive rate between these cancer types. Moreover, we found that the tumor diameter was inversely correlated with the incidence of the gastric phenotype cancer. These results indicate that intestinal phenotype cancer is related to atrophy and intestinal metaplasia of surrounding mucosa caused by H. pylori infection. Furthermore, we conclude that gastric phenotype cancer is associated with the early stage of H. pylori infection but not atrophy nor intestinal metaplasia.

Natural gardenia pigment has been known from old times as a dye and colorant and is presently used widely in that area as a food colorant and its safety has already been established. We have comparatively investigated the application of Techno Color blue P, which is the natural gardenia pigment, against normal pigments in contrast endoscopy. Techno Color blue P coagulated thereby decreasing its solubility as the pH of the solvent became acidic. For the upper gastrointestinal tract, 10% and the lower gastrointestinal tract 20% of the Techno Color blue P solution is appropriate. In upper gastrointestinal endoscopy, Techno Color blue P coagulates in the acid secreting areas, and is therefore unsuitable as a contrast method. However, in the pyloric gland, atrophied areas of the gastric mucosa, and duodenal villi, it was superior to Indigocarmine as a contrast method. In colonoscopy, intestinal fluids is alkaline and so Techno Color blue P showed a stable dyeing property with clearer contrasting compared to Indigocarmine. Contrast endoscopy with Techno Color blue P, is useful as a contrast method for accentuated surface morphology of the gastric mucosa, duodenal mucosa, and colonic mucosa.

We focused on the fact that ammonia induces gastric mucosal damage by Helicobacter pylori, and investigated the effect of ammonia water administration in two kinds of concentration of rat gastric mucosa, by allowing rats free access to ammonia water for 6 weeks. No atrophy developed in the rat gastric mucosa and mucus was maintained in the low concentration group of 0.02% ammonia water, while atrophy was observed in the antral mucosa after 4 weeks and in the body mucosa after 6 weeks of administration in the high concentration group of 0.1% ammonia water. The course of atrophy was similar to that of human atrophic gastritis due to H. pylori infection. Furthermore, both superficial and deep mucus significantly decreased. On the contrary, coadministration of geranylgeranylacetone (GGA), one of gastric mucosal protective agents, inhibited decrease in gastric mucus as well as gastric mucosal atrophy in the 0.1% ammonia water group. In that way, myeloperoxidase (MPO) activity, which is an index of tissue disorders in gastric mucosa, and lipid peroxidation (LPO) activity were significantly increased due to access to ammonia water, while GGA suppressed these activities. It was suggested that gastric mucus may act as a radical scavenger to prevent gastric mucosal damage by ammonia.

Recently, Fibro scan was developed as a non-invasive device for measuring liver fibrosis. Progression of liver fibrosis has been reported to increase the measurement value (elasticity). We have performed the Fibro scan for liver diseases.[ ;normal liver (n=33), hepatitis C (n=156), hepatitis B(n=36), non-alcoholic fatty liver disease (n=24), auto immune hepatitis (n=9), primary biliary cirrhosis (n=10), alcoholic liver disease (n=7), acute hepatitis (n=3), other liver disease (n=14), recipient of living donor liver transplantation (n=11)] Elasticity, blood test, and indirect fibrosis diagnostic score were comparatively investigated. In the hepatitis C group, the mean value for elasticity was 14.7±12.0 kPa. Elasticity was found to be significantly correlated with the hepatobiliary enzymes, fibrosis markers and indirect fibrosis diagnostic score. When elasticity was divided into ≧14.6kPa(liver cirrhosis) and<14.6kPa(non liver cirrhosis) groups for the investigation, liver inflammation and fibrosis markers were correlated in the progress of fibrosis in non liver cirrhosis, and it could be speculated that if liver cirrhosis is reached, progression of fibrosis reflects decreased liver function.

Type 2 diabetes mellitus is frequently complicated by hyperlipidemia, which is closely related to the occurrence of atherosclerotic disorders. The small intestine, which absorbs dietary lipids, plays an important role in the regulation of the serum lipid concentrations. We confirmed morphological changes in small intestinal villi in the progression of diabetes mellitus and evaluated intestinal lipid absorption by the 13C-trioctanoin breath test in model rats with type 2 diabetes mellitus (OLETF rats). We measured the height of the intestinal villous epithelium and serially measured the expiratory 13CO2 concentration after the administration of 13C-trioctanoin in OLETF rats at the ages of 28, 36, and 44 weeks. The serum total cholesterol and triglyceride concentrations were significantly higher in the OLETF rats than in the control LETO rats. The height of the small intestinal villi was increased, indicating hyperplastic change. The 13CO2 concentration was significantly increased, suggesting hyperplasia of the small intestinal villi and enhancement of lipid absorption or increased total amount absorption. Excessive lipid absorption from the small intestine was suggested to be one of the causes of hyperlipidemia (particularly hypertriglyceridemia) complicating diabetes mellitus.