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Biomedical subjects

T Shimoyama

Publications and source records attributed to T Shimoyama.

At least 181 records · Page 10Linked to original sources
PubMed1996

Atrophic gastric changes in both Helicobacter felis and Helicobacter pylori infected mice are host dependent and separate from antral gastritis.

BACKGROUND/AIMS: The role of host factors has been neglected in studies of the pathogenesis of Helicobacter associated disease. The aim of this study was to assess the response of different mouse strains to infection with a single strain of Helicobacter felis. METHOD: Six strains of inbred mice were infected with the identical H felis culture and were killed at one month, two months, and six months after infection to assess histopathological changes. In addition, two strains of mice were infected with a mouse adapted strain of H pylori and examined at six months after infection. RESULTS: In SJL, C3H/He, DBA/2, and C57BL/6 infected mice, severe to moderate chronic active gastritis was observed only in the body of the stomach, which increased in severity over time with specialised cells in the body glands being replaced. As the severity of this damage in the body increased and atrophic changes were seen, the level of bacterial colonisation of the antrum decreased. In contrast, in BALB/c and CBA mice, there was only mild gastritis in the antrum, no remarkable changes were detected in their body mucosa, and no atrophy was seen over time. In both these strains of mice, heavy bacterial colonisation was seen, which tended to increase over the period of the experiment. Of particular importance in this experiment was that bacterial colonisation was mainly restricted to the antrum yet the atrophy, when present, was only observed in the body of the stomach. H pylori infected C3H/He mice showed moderate colonisation of the antrum, which persisted up to six months with little development of atrophy. In contrast, H pylori in C57BL/6 mice showed excellent colonisation of the antrum at two months but six months after infection there was moderate to severe body atrophy, which was associated with a loss of bacteria from the antrum. CONCLUSIONS: These findings challenge current concepts of the development of Helicobacter induced atrophy in that active chronic gastritis of antrum or the body mucosa, or both, is not a prerequisite. They also suggest an autoimmune basis for the pathology although no autoantibody or antibody to the H+/K+ ATPase was detected. Loss of infecting helicobacters from the stomach together with development of an atrophic gastritis in the body of the stomach is similar to the pattern found in certain H pylori infected human subjects.

Animals↗
PubMed1996

[LY188011 phase I study. Research Group of Gemcitabine (LY188011)].

LY188011 (Gemcitabine hydrochloride) is a new derivative of deoxycytidine. Phase I study was carried out by a cooperative study group. LY188011 was administered weekly for 3 consecutive weeks starting with an initial dose of 60 mg/m2 (1n) and then increasing the dosage to 1,000 mg/m2 (16.7n). Dose limiting factor was found to be myelosuppression (decreases of WBC, neutrophils and platelet), and MTD was considered to be 1,000 mg/m2. The nadir of WBC and platelet were observed after about 1-3 weeks. It took 1-2 weeks for their recovery. Other adverse reactions included fever, fatigue, anorexia, nausea/vomiting, anemia and transient elevations of GOT and GPT. However, those adverse reactions were mild. T1/2 rho of plasma concentration was about 19 min and the C5min was dependent on the dose. Anti-cancer effects were observed in one gastric cancer and two colon cancer patients. It is recommended that the dosing schedule for an early phase II study is 800 mg/m2 weekly for 3 weeks with 1 week of rest as one cycle, in multiple cycles.

Adult↗
PubMed1996

[Helicobacter pylori and gastric cancer].

H. pylori has been included as a definite biological carcinogen by WHO/ IARC. H. pylori is thought to play a role in the gastritis-metaplasia-carcinoma sequence by inducing atrophic gastritis. Clinical and epidemiological studies have shown a close association between H. pylori infection and gastric cancer. Yet, experimental evidence is equivocal. Epidemiological evidence also suggests that there are significant variable(s) other than H. pylori infection in gastric carcinogenesis. Clearly many questions regarding the role of H. pylori in gastric carcinogenesis have been left for further study. The authors have summarized these aspects together with their experimental results.

Animals↗
PubMed1996

Helicobacter pylori in Japan.

Recent international consensus statements have concluded that Helicobacter pylori is a causal factor in peptic ulcer disease and a Group 1 carcinogen in humans, and that all patients with peptic ulcer associated with H. pylori infection should receive eradication therapy. There are marked differences in the presentation of peptic ulcer disease between Japanese patients and those from other countries, however, and thus a committee of the Japanese Society of Gastroenterology has been set up to develop guidelines for clinical trials in patients with gastric or duodenal ulcers associated with H. pylori. According to these guidelines, eradication therapy should normally consist of dual therapy with a proton pump inhibitor, such as omeprazole, and an antibiotic; a nitroimidazole can be added, however, if necessary. The diagnosis of H. pylori should be made on the basis of a positive culture of the organism or histological examination of gastric biopsies, together with a positive urease test or 13C-urea breath test. Eradication should be confirmed by the same means 4-6 weeks after treatment. Other research is investigating the relationship between H. pylori and gastric cancer, an important issue in view of the high incidence of this condition in Japan. There is evidence that the Mongolian gerbil may be a useful animal model to investigate this question.

Helicobacter Infections↗
PubMed1996

Strain differentiation and phylogenic relationships, in terms of base sequence of the ure B gene, of Helicobacter pylori.

We constructed a phylogenetic tree based on the nucleotide sequence of the ure B gene of Helicobacter pylori strains, amplified by polymerase chain reaction (PCR). We analyzed the tree in terms of the relationship between the PCR-restriction fragment length polymorphism (RFLP)-genotype and the sequevar. The main frame of ure B (928 bp) was amplified by PCR from 38 strains of clinical isolates and reference species. The amplified probes were sequenced and processed into matrix and phylogenic trees. Homogeneity of the strains of "intra-case" origin and heterogeneity in "inter-cases" was parallel to clustering on the phylogenic tree. Sequevars in a cluster showed an identical RFLP-genotype in one case, indicating the clonal origin of H. pylori flora in an individual.

Base Sequence↗
PubMed1996

Ecabet sodium eradicates Helicobacter pylori infection in gastric ulcer patients.

Ecabet sodium (ecabet), a new agent that has protective effects on the gastric mucosa has anti-Helicobacter pylori effects, binding with urease to inhibit H. pylori activity, and causing the bacterial to become non-viable. Ecabet monotherapy eradicates H. pylori infection in Japanese monkeys. We investigated a new regimen that included ecabet to eradicate H. pylori infection in gastric ulcer patients. Fifty-five H. pylori-positive patients with gastric ulcer were randomly assigned to one of two groups: group 1 received dual therapy with lansoprazole (30 mg o.d.) for 8 weeks plus clarithromycin (200 mg b.i.d.) or amoxicillin (250 mg q.i.d.) for 2 weeks. Group 2 received triple therapy with lansoprazole (30 mg o.d.) and ecabet sodium (1.0 g b.i.d.) for 8 weeks plus clarithromycin (200 mg b.i.d.) or amoxicillin (250 mg q.i.d.) for 2 weeks. Four weeks after the treatment was withdrawn, H. pylori status was evaluated by histological examination, rapid urease test, and culture. The eradication rate was 26% (7 out of 27 patients) in group 1 and 79% (22 out of 28 patients) in group 2. All patients completed the treatment. The addition of ecabet to the regimen increased the eradication rate of H. pylori infection, and there were no associated major side effects.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

Eradication of Helicobacter pylori followed by reinfection.

Eradication therapy for Helicobacter pylori is now common, since eradication of this organism reduces the recurrence rate of peptic ulcer. We evaluated the eradication of H. pylori 4 weeks after the cessation of eradication treatment, and encountered recolonization in patients in whom eradication had been confirmed. Using a urease probe, we analyzed the Ure B restriction fragment length polymorphism (RFLP) of the DNA of the recolonized H. pylori by Southern blotting and compared it with that of the H. pylori strain cultured before eradication therapy. RFLP patterns before and after the treatment were identical, indicating that the recolonization of H. pylori was an exacerbation of the primary infection, rather than a reinfection.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

The effects of dietary fiber from Lagenaria scineraria (yugao-melon) on colonic carcinogenesis in mice.

BACKGROUND: The increasing trend of colon cancer in Japan is attributed to changes in dietary habits, that is, increased amounts of fat and decreased amounts of fiber in the diet. The effects of Japanese dietary fiber from Lagenaria scineraria (yugao-melon) on colonic carcinogenesis in mice were examined. METHODS: Eighteen ICR mice in each group were fed with either a basal diet or a diet containing 5%, 10%, or 20% of yugao powder for 35 weeks. All the mice received a weekly intraperitoneal injection of 1,2-dimethylhydrazine (DMH), 10 mg/kg body weight for 10 weeks. The effects of yugao powder on the mucosal and luminal variables involved in colonic carcinogenesis were then compared with those of wheat bran in the mice without any carcinogen treatment. RESULTS: The incidence of colon tumors (adenocarcinomas) was lower in the yugao powder diet groups than in the basal diet group at week 35 (24% vs. 50%, P < 0.05). The bile acid concentration in the colon was reduced in all the fiber diet groups except for the 5% yugao powder diet group. The colonic luminal pH acidified as yugao powder contents also increased in the yugao powder diet groups. The findings on the colonic short chain fatty acids, microflora, and mucosal fatty acids and ornithine decarboxylase activity were all inconsistent with a tendency to either develop or to inhibit carcinogenesis in both the fiber diet groups. CONCLUSIONS: Dietary fiber from yugao-melon suppressed DMH-induced colonic carcinogenesis in mice by lowering the bile acid concentration and pH in the colon. The results of the luminal and mucosal variables examined also suggested that the mechanisms of action of yugao powder against colonic carcinogenesis differed from those of wheat brain.

Adenocarcinoma↗
PubMed1995

Detection of immunoreactive antigen, with a monoclonal antibody to measles virus, in tissue from a patient with Crohn's disease.

Using immunofluorescence (IF), we investigated reactive antigens present in Crohn's disease patients with monoclonal antibodies derived from cells infected with measles virus, but not with the subacute sclerosing panencephalitis virus. During immunoblotting, one monoclonal antibody (mAb 86) reacted with a polypeptide with a molecular weight of 36,000 dalton (M; matrix protein) in measles virus-infected cells. This monoclonal antibody displayed a positive reaction only with tissues from patients with Crohn's disease by the IF test. It did not react with samples from patients with other chronic inflammatory bowel diseases, such as ulcerative colitis. Other monoclonal antibodies to the measles virus protein, and monoclonal antibodies to Herpes simplex virus type 1 did not react with the same tissue samples. The role of measles virus infection and/or a viral antigen (possibly the M protein) as a causative agent in Crohn's disease poses a challenging avenue for further research.

Antibodies, Monoclonal↗
PubMed1995

Effect of leukotriene C4D4 antagonist on colonic damage induced by intracolonic administration of trinitrobenzene sulfonic acid in rats.

We examined the effects of eicosanoid antagonists on colonic damage induced by trinitrobenzene sulfonic acid (TNB) in a rat inflammatory bowel model. TNB (30 mg) dissolved in 0.25 ml of 50% ethanol, was given intrarectally. The appropriate doses of ONO-1078 (a leukotriene C4D4 antagonist), ONO-4057 (a leukotriene B4 antagonist), and OKY-046 (a thromboxane A2 synthetase inhibitor) were given to obtain the same blood level, either 4 h before (pre-treatment model) or 24 h after (the post-treatment model) the administration of TNB (n = 8 in all groups). Drugs were given once daily for 6 days through a gastric feeding tube. Autopsy was performed on the 7th day. Colonic damage was assessed in terms of colonic damage scores, and myeloperoxidase (MPO) activity and eicosanoid concentrations in colonic tissues were measured. Compared with the group given TNB alone, the colonic damage score was reduced to 10% in the pre-treatment model with ONO-1078, but the score was not reduced in other groups, MPO activity was not changed in any group. The concentration of leukotriene C4 was reduced with ONO-1078 treatment, in both pre- and post-treatment models. These results demonstrated that a leukotriene C4D4 antagonist reduced colonic inflammation; however, its anti-inflammatory effect was limited in this colitis model.

Animals↗
PubMed1995

Proton pump inhibitors for Helicobacter pylori eradication in patients with peptic ulcer.

We investigated the effects of omeprazole or lansoprazole on peptic ulcer healing, eradication of Helicobacter pylori (Hp) and abdominal symptoms. A prospective, randomized study was performed for the administration of omeprazole or lansoprazole. Hp-positive peptic ulcer patients (n = 86) were randomly assigned to two groups. Gastric ulcer patients received omeprazole 20 mg once daily or lansoprazole 30 mg once daily for 8 weeks. Duodenal ulcer patients were given omeprazole 20 mg once daily or lansoprazole 30 mg once daily for 6 weeks. Endoscopy was performed at baseline, at the end of therapy, and 4 weeks after stopping therapy. The colony factor units (CFUs) of Hp in biopsy specimens were examined. The CFUs of Hp in gastric and duodenal ulcer were significantly decreased at 4 weeks after stopping lansoprazole therapy. We conclude that Hp eradication by combined use of lansoprazole with antibiotics appears to be a promising therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Eradication of Helicobacter pylori with lansoprazole and clarithromycin in gastric ulcer patients.

This study attempted to determine the efficacy of lansoprazole plus clarithromycin therapy in the eradication of Helicobacter pylori in gastric ulcer patients. The influence of H. pylori eradication on healing and relapse of ulcers was also studied. Thirty-nine patients received either lansoprazole 30 mg daily for 8 weeks (group 1) or clarithromycin 200 mg twice daily for 2 weeks and lansoprazole 30 mg daily for 8 weeks (group 2). Before treatment, H. pylori status was evaluated by a rapid urease test and histologic examination. H. pylori clearance and eradication were evaluated by a rapid urease test, polymerase chain reaction, and a [13C]urea breath test. Clearance of H. pylori was 0% in group 1 and was 33% in group 2. Eradication of H. pylori was 0% in group 1 and 21% in group 2. Although all five ulcers were healed in patients with H. pylori eradication, ulcers were not healed in the five patients without eradication. Relapse of ulcer was observed in three patients in whom eradication had failed. In this study, for H. pylori-positive gastric ulcer patients, better results were obtained when lansoprazole plus clarithromycin therapy was used, and H. pylori eradication was achieved.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Combination therapies with a proton pump inhibitor for Helicobacter pylori-infected gastric ulcer patients.

We investigated the eradication and recurrence rate of Helicobacter pylori-infected gastric ulcer patients by combination therapies. Eighty-six H. pylori-positive gastric ulcer patients were assigned randomly to one of seven groups: I, omeprazole 20 mg (n = 9); II, lansoprazole (LPZ) 30 mg (n = 16); III, LPZ 30 mg plus plaunotol 480 mg (n = 13); IV, LPZ 30 mg plus ecabet sodium 2 g (n = 11); V, LPZ 30 mg plus clarithromycin 600 mg (the first 2 weeks; n = 11); VI, LPZ 30 mg plus plaunotol 480 mg plus clarithromycin 600 mg (the first 2 weeks; n = 13); and VII, LPZ 30 mg plus ecabet sodium 2 g plus amoxicillin 1,500 mg (the first 2 weeks; n = 13). All therapy was for 8 weeks except where otherwise noted. H. pylori eradication rates as diagnosed by culture, histology, urease test, and [13C]urea breath test 4 weeks after stopping therapy were 0, 0, 8, 45, 6, 46, and 62%, respectively, in groups I-VII. No patient achieving H. pylori eradication suffered recurrence. The combination therapies with proton pump inhibitors in addition to antibiotics and antiulcer agents are safe and effective in H. pylori eradication.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Occurrence of Graves' disease during retreatment with interferon-alpha 2a for chronic hepatitis C.

The present report describes a patient who developed Graves' disease 3 months after inception of retreatment with higher doses of interferon-alpha 2a for chronic hepatitis C, although the initial 6-month treatment caused no serious adverse reactions. Severe hyperthyroidism continued despite discontinuation of interferon-alpha 2a, and the patient was subsequently treated with 131I. This case suggests careful evaluation of the safety of retreatment to prevent manifestation of such a complication in the retreatment of chronic hepatitis C with interferon.

Adult↗