Multicellular living organisms and unmodified parts thereof and – Nonhuman animal – The nonhuman animal is a model for human disease
Patent
1996-08-09
1999-07-27
Crouch, Deborah
Multicellular living organisms and unmodified parts thereof and
Nonhuman animal
The nonhuman animal is a model for human disease
800 3, 435243, C12N 500, C12N 1500, C12N 100
Patent
active
059292997
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention relates to Helicobacter pylori-colonized Mongolian gerbils usable for (1) screening the therapeutic effect of a drug for Helicobacter pylori which is considered to be the pathogen of gastric ulcer and duodenal ulcer, recurrence thereof, and diseases such as gastric carcinoma, or (2) for the elucidation of pathology in the above-mentioned diseases caused by infection with Helicobacter pylori, and to a method for preparation thereof. The present invention also relates to a medium for isolation of Helicobacter pylori, and further to a method for screening an anti-Helicobacter pylori substances comprising the use thereof.
DESCRIPTION OF THE RELATED ART
Helicobacter pylori (hereinafter sometimes referred to as H. pylori) is a Gram negative bacterium isolated from gastric mucosa of patients with active chronic gastritis (Warren, J. R. & Marshall, B. J. Lancet i: 1273-1275, 1983). H. pylori is a 0.5 .mu.m wide, 3-5 .mu.m long Gram negative spirally curved rod having several polar flagella and flagella sheaths at one or both ends of the cell. H. pylori grows in a microaerophilic environment, cannot grow under aerobic conditions and grows poorly under the anaerobic conditions. It grows at 37.degree. C. and scarcely grows at a temperature lower than 25.degree. C. and higher than 42.degree. C. The bacterium is notably characterized in that it evidently produces urease (Mobley, H. L. et al., Clin. Microbiol., 26, 831-8369 1988).
H. pylori is present in the mucous layer in the gastric mucosal epithelium of humans and swims in the viscous mucous layer using the characteristic flagella. H. pylori specifically resides in the surface layer of the epithelium cells and the crevice therein, which provide the most comfortable living environment where gastric acidity is neutral, and lives by utilizing hemin, urea and so on (Hazell, S. L., Adrian, L., J. Infect. Dis., 153, 658-663, 1986).
As to the pathogenesis of the diseases caused by H. pylori, mucous membrane disorder concept (Hazell, S. L., Adrian, L., J. Infect. Dis., 153, 658-663, 1986), leaking roof concept (Goodwin C. S., Lancet ii, 1467-1469, 1988) and gastrin link concept (Levi, S. et al., Lancet i, 1167-1168, 1989) have been proposed.
The mucous membrane disorder caused by H. pylori is mostly ascribed to its strong urease activity (Hazell, S. L., Adrian, L., J. Infects Dis., 153, 658-663, 1986). The urea present in the gastric juice is decomposed by the urease of H. pylori and converted to a large amount of ammonium and carbon dioxide. The ammonium concentration in the gastric juice is significantly high in the H. pylori positive groups and histological epitheliocyte disorder and an increased ulcer coefficient have also been reported in the experiments where ammonium was orally administered to rats (Murakami, M. et al., Clin. Gastroenterol. 12 (Suppl. 1), S104-109, 1990).
Also, there is a report on reduced amounts of PAS (periodic acid schiff)-positive mucosal juice in the gastric mucosa of patients who tested positive to H. pylori suggesting possible degradation of a gastric mucosa-protective activity due to the decomposition of mucosal juice by the protease of H. pylori (Nakajima, ,M et al., Drug Investigation, (Suppl. 1), 60, 1990). It has been further reported that leukotriene B4 activity is high in the gastric mucosa where striking infiltration of leukocytes by H. pylori is observed (Uchida, T. et al., Therapeutic Research, 12, 85-90, 1991) and that the mucous membrane disorder is caused by the action of phospholipase A2 on bile acid which flows reversely into the stomach.
In 1988, Leunk et al. reported the presence of a cytovacuolating toxin in the supernatant of H. pylori culture. The toxin was isolated and purified by Cover et al (Cover, T. L. & Blaser, M. J., J. Biol. Chem. 267, 10570-10575, 1992). Reports on the toxin have documented that it delays cure of ulcer by hindering the rotation of cells near the ulcer (Chang, K. et al., Gastroenterology, 104 (Suppl), A52, 1993) and that it acts synergistically
REFERENCES:
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Hirayama Fumihiro
Ikeda Yoshifumi
Takagi Shiro
Crouch Deborah
Wilson Michael C.
Yoshitomi Pharmaceutical Industries Ltd.
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