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T Sakagami

Publications and source records attributed to T Sakagami.

At least 19 recordsLinked to original sources
PubMed2004

Local adaptation and population differentiation at the interleukin 13 and interleukin 4 loci.

A 25.6 kb region at chromosome 5q31, covering the entire human interleukin 13 (IL-13) and interleukin 4 (IL-4) genes, has been reported to be associated with bronchial asthma. We have examined nucleotide variations at this locus in African, European American, and Japanese populations, using 120 diallelic variants. A block of strong linkage disequilibrium (LD) (mid R:D'mid R:>0.7) spans a 10 kb region containing IL-4 in European American and Japanese populations, and is present but less clear in African samples. Two major haplotypes at IL-4 account for >80% of haplotypes in European Americans and Japanese. These haplotypes are common and quite diverged from each other and the ancestral haplotype, resulting in highly significant deviations from neutrality. F(ST) statistics show that European American and Japanese populations are unusually distinct at the IL-4 locus. The most common haplotype in the European American population is much less common in the Japanese population, and vice versa. This implies that natural selection has acted on IL-4 haplotypes differently in different populations. This selected variation at IL-4 may account for some genetic variance underlying susceptibility to asthma and other allergic diseases. The strong LD observed in the IL-4 region may allow more efficient disease-association studies using this locus.

Adaptation, Physiological↗
PubMed2002

Successful eradication of Helicobacter pylori prevents relapse of peptic ulcer disease.

BACKGROUND: The NIH consensus conference in 1994 recommended that all patients with peptic ulcers should be tested and treated for Helicobacter pylori. Recent studies have shown that the eradication of H. pylori is associated with a significant reduction in the relapse rate of peptic ulcers, but there are few reports about long-term outcome. AIMS: To evaluate the relapse rate of peptic ulcer in the long-term follow-up of patients after H. pylori eradication therapy. PATIENTS AND METHODS: Patients infected with H. pylori (445; 88 duodenal ulcer, 357 gastric ulcer) were randomly divided into three groups. In group A, patients received 'conventional treatment' including acid decreasing therapy with a histamine H2-receptor antagonist or proton pump inhibitor (PPI). In group B, patients received 'dual therapy' including one antibiotic plus acid-decreasing therapy. In group C, patients received 'triple therapy' with PPI plus amoxicillin and clarithromycin. Eradication of H. pylori infection was assessed by histology of biopsy specimens from both the antrum and body corpus at 4 weeks, and 6 and 12 months after stopping therapy. Endoscopy was performed at intervals of 6 months for 5 years. RESULTS: Intention-to-treat eradication rates for the duodenal ulcer patients were 0% for group A, 46% for group B and 80% for group C; eradication rates for the gastric ulcer patients were 0%, 33% and 83% respectively. No recurrence was noted in the duodenal ulcer patients and only 4% of gastric ulcers recurred after successful eradication during follow-up for 5 years. In contrast, in patients with persistent H. pylori infection all DU and 92% of gastric ulcers recurred. CONCLUSION: Eradication of H. pylori infection changes the natural course of peptic ulcer.

Anti-Bacterial Agents↗
PubMed2001

[The relation between resistance to change and preference in pigeons with concurrent chained schedules].

Two experiments were conducted to investigate the relation between resistance to change and preference. Four pigeons responded in concurrent chained schedules in which variable-interval (VI) 60-s schedules were arranged in the initial link. In Experiment 1, VI and fixed-interval (FI) schedules of equal mean reinforcement rates were arranged in the terminal link. Response rates were higher in the initial link leading to VI terminal link. Under the prefeeding test, the initial-link response rates leading to VI terminal link were more resistant to change than were those leading to FI terminal link, but under the extinction test there were no consistent differences between the two initial-link response rates. In Experiment 2, FI value of the terminal link was manipulated so that pigeons maintained approximately equal responding in the initial link. The two initial-link response rates showed equal resistance to change under the prefeeding and extinction tests. Thus, the data suggest that although the use of extinction as a manipulation to study resistance to change is questioned, resistance to change and preference are different measures of a single object.

Animals↗
PubMed2000

Influence of Helicobacter pylori infection on development of stress-induced gastric mucosal injury.

Immediately after the Great Hanshin Earthquake in Kobe in 1995, the recurrence rate of peptic ulcer in patients infected with Helicobacter pylori was higher than that in patients in whom H. pylori had been eradicated. We evaluated the influence of H. pylori infection on stress-induced gastric mucosal injury in Mongolian gerbils and C57BL/6 mice. These animals were immersed in water for 30, 120, and 720 min 12 weeks after inoculation with H. pylori, and then killed to assess gastric mucosal damage, and to measure cytokine production (interleukin [IL]-1beta, IL-4, IL-6, and IL-10; interferon [IFN]-gamma; and tumor necrosis factor [TNF]-alpha) in the gastric tissue of the mice. The stress treatment for 30 min resulted in a significantly higher bleeding rate and bleeding index among infected gerbils and mice compared with results in uninfected animals. Conversely, the bleeding and ulcer indexes were significantly higher in uninfected gerbils after 720 min of the stress treatment than in infected gerbils. Prior to the stress treatment, gastric IL-1beta and IFN-gamma production was significantly higher in the infected group than in the uninfected group. After 120 min of the stress treatment, TNF-alpha production was increased in the infected group, and IL-1beta and IL-10 production was increased in the uninfected group. However, the production of these cytokines showed no change at 30 min of the stress treatment. These results suggest that H. pylori infection influences the development of gastric mucosal injury in the early phase of stress exposure; cytokines do not play a major role in this process.

Animals↗
PubMed1999

[Epidemiological study for infection with H. pylori in Japan compared with that in USA, Europe and Asian Pacific area].

The prevalence of infection with H. pylori in developed countries was about 20%, on the other hand in developing countries it reached over 80%. In developed countries 40% of infants already had anti-H. pylori antibody and the prevalence of infection rapidly increased and then reached the peak (80%) in teenager. In contrast in developed countries the rate of infection with H. pylori was below 20% in teenager and gradually increased by age (1% per 1 year). In our country an unique pattern of the prevalence of infection with H. pylori was observed. The rate of infection with H. pylori in young person was low and increased with 1% per 1 year (developed countries pattern). However, middle-aged person had higher rate of infection of H. pylori (over 85%) (developing countries pattern). These results suggested H. pylori infection would be closely associated with childhood living conditions than current living (including socioeconomic) status. From this point of view, the prevention for infection with H. pylori in childhood will be most important to prevent the gastroduodenal disease related with H. pylori in the future.

Adolescent↗
PubMed1999

Comparison of pathologic changes in Helicobacter pylori-infected Mongolian gerbils and humans.

Helicobacter pylori has been recognized as a pathogen causing gastroduodenal disease, with adequate evidence to prove this relation in clinical research. Available animal models, however, were inadequate until 1995, when a new animal model of H. pylori infection was established using Mongolian gerbils. In this study we compared pathological changes in seven H. pylori-infected Mongolian gerbils with ulcers to five patients with gastric ulcer who underwent operation. All of the animals showed positive reactions for both H. pylori culture and serum anti-H. pylori antibody titer. All human subjects had H. pylori on the mucosal surface. Thus, inflammatory cell infiltration in the pyloric gland area was observed throughout almost all layers in the animals. In contrast, inflammation was observed in the surface layer of the mucosa in the pyloric gland area in the human subjects. Lymph follicle formation was observed more often in humans than in the animals. Inflammation of the fundic gland area in both groups was weaker than of the pyloric gland area and was observed within the mucosa. Histological changes observed in both groups were chronic active gastritis, lymph follicles, and intestinal metaplasia in the stomach. H. pylori-associated gastritis in humans is characterized by erosion, inflammation with neutrophil infiltration, lymph follicles, intestinal metaplasia, and atrophy. These findings are similar to those in this animal model. Thus, H. pylori infection might participate in the pathogenesis of gastroduodenal mucosal damage. In conclusion, the Mongolian gerbil is a good animal model for H. pylori-associated gastric diseases, and it might be useful for investigating the pathogenesis of H. pylori infection.

Adult↗
PubMed1998

Pathologic changes in the glandular stomach and duodenum in an H. pylori-infected Mongolian gerbil model.

We have established a Helicobacter pylori-infected Mongolian gerbil model following Hirayama's method to investigate gastric diseases associated with H. pylori infection. We orally administered the culture broth of H. pylori ATCC 43504 to 8-week-old male Mongolian gerbils. After this, the gerbils were fed in a vinyl isolator. Subsequently, over the course of 48 weeks some of them were sacrificed for histopathologic examination and H. pylori culture. H. pylori colonization in the glandular stomach was seen in all the infected gerbils but only a few H. pylori were detected histologically. Acute inflammation, immature epithelium, and erosion were observed 2 weeks after H. pylori infection. Chronic inflammation was noted from 4 weeks after H. pylori infection. In addition, we found intestinal metaplasia and gastric ulcers from 12 and 24 weeks, respectively. There was mild to moderate inflammation in the duodenum but no ulcerative lesions or gastric metaplasia were observed. Some histologic findings were similar to those in humans, but inflammation occurred mainly in the deep mucosa and submucosa. This is a good animal model for H. pylori-associated gastric diseases but not for duodenal ulcers or gastric metaplasia. It might be useful for investigating the pathogenesis of H. pylori infection in the stomach.

Animals↗
PubMed1998

Pathological changes in glandular stomach of Helicobacter pylori-infected Mongolian gerbil model.

We have established a Helicobacter pylori-infected Mongolian gerbil model, following Hirayama's method, to clarify gastric diseases associated with H. pylori infection. We administered the culture broth of H. pylori ATCC 43504 orally to 8-week-old male Mongolian gerbils. After H. pylori inoculation, the gerbils were fed in a vinyl isolator. Subsequently, over the course of 48 weeks, they were killed for histopathological examination, H. pylori culture, and serum antibody measurement. H. pylori colonization in the glandular stomach was seen in all the infected gerbils, but only a few H. pylori were detected histologically. The serum antibody titer in the H. pylori-inoculated group increased gradually in comparison with controls. Acute inflammation, immature epithelium, and erosion were observed 2 weeks after H. pylori infection. Chronic inflammation was noted from 4 weeks after H. pylori infection. We also found intestinal metaplasia and gastric ulcers from 12 and 24 weeks after inoculation, respectively. Some histological findings were similar to those in humans, but the chronic inflammation in the gerbils was present mainly in the deep mucosa and submucosa. This appears to be a good animal model for H. pylori-associated gastric diseases and it may be useful for investigating the pathogenesis of H. pylori infection.

Animals↗
PubMed1997

The endotoxin of Helicobacter pylori is a modulator of host-dependent gastritis.

Atrophic gastritis caused by Helicobacter pylori is the precursor lesion in the development of intestinal-type gastric adenocarcinoma. In animal models, atrophic gastritis induced by Helicobacter felis has been shown to be host dependent, developing in some mouse strains and not in others. The lipopolysaccharide (LPS) of H. pylori has been suggested to play a role in the induction of gastritis. The goal of this study was to compare the inflammation induced by long-term infection of the C3H/He and the C3H/HeJ strains of mice with H. felis. C3H/HeJ mice are unresponsive to LPS. Six months after infection, severe atrophic gastritis had developed in the body mucosae of all infected C3H/He mice, with replacement of parietal and chief cells. Atrophy was associated with a loss of the H. felis from the antral mucosa. In contrast, no atrophy was seen in the infected C3H/HeJ non-LPS responder animals, and heavy colonization of the antrum remained. There were no significant differences between both the quantitative and qualitative serum immunoglobulin G (IgG) and salivary IgA levels in both strains of mice. The main difference between the two strains of long-term-infected mice was a lack of macrophage infiltration in the lamina propria. Immunization induced good protective immunity to challenge with viable H. felis. Helicobacter-induced, host-dependent gastritis is likely to be cell mediated. The C3H/He and C3H/HeJ mouse model provides an excellent opportunity to investigate the cellular basis of atrophic gastritis.

Animals↗
PubMed1997

[Critical review on the WHO/IARC report regarding carcinogenicity of Helicobacter pylori].

Helicobacter pylori has been defined as a "definite carcinogen" at the WHO/IARC meeting in 1994. H. pylori causes histological gastritis. Long-lasting infection may induce atrophic gastritis, which is considered to be the first step in the gastritis-metaplasia-carcinoma sequence of the stomach. In a pooled analysis of the three prospective epidemiological studies, the relative risk for developing gastric cancer with H. pylori infection was 3.8, which was statistically significant. Thus, it was concluded that there was sufficient evidence in humans for the carcinogenicity of infection with H. pylori. However, there was no evidence experimentally for the carcinogenicity of infection with H. pylori. Further study is necessary to elucidate the role of H. pylori in gastric carcinogenesis.

Animals↗
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

[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↗
PubMed1994

Structure and chromosomal locus of the mouse gene encoding a cerebellar Purkinje cell-specific helix-loop-helix factor Hes-3.

HES-3 is a cerebellar Purkinje cell-specific helix-loop-helix factor structurally related to the products of the Drosophila hairy and Enhancer of split genes. Here, we report the nucleotide sequence and chromosomal locus of the mouse Hes-3 gene. This gene consists of four exons and the exon-intron boundaries are well conserved when compared with those of the mouse Hes-1 and Drosophila hairy genes. Southern blot and interspecies backcross analyses show that the mouse Hes-3 gene is a single-copy gene and is located around position 80 on chromosome 4. Further analysis indicates that this locus is close to the Hes-5 locus, which is different from the Hes-1 locus (position 26 on chromosome 16). These results suggest that the Hes-3 and Hes-5 genes may be clustered on chromosome 4 while the Hes-1 gene is not.

Amino Acid Sequence↗
PubMed1994

[Advances in the experimental analysis of behavior: issues of choice behavior, comparative cognition, and human language].

As the opportunity to contact with related areas has increased, the study of of the experimental analysis of behavior has experienced revolutionary changes. Some of the most active and important areas-studies of choice, comparative cognition, and human language--are reviewed to acquaint readers. Studies of CHOICE have linked to the molar theories of behavioral economics and behavioral ecology, which promoted research of choice by animals under uncertainty conditions. Further approach has been made to integrate the molar and molecular analyses on the basis of the ideas of behavior dynamics. COMPARATIVE COGNITION is a part of a larger field including cognitive science, behavioral neuroscience, and biological science. Recent developments, aided with a comparative perspective, made significant contributions to our understanding of the phylogeny and ontogeny of cognition. Advances in analysis of human behavior provided tools to study behavioral aspects of semantics, syntax, and pragmatics of HUMAN LANGUAGE. Using the paradigm of stimulus equivalence, the emergence of stimulus relations, stimulus-stimulus networks, hierarchical structure of verbal behavior, and other language-related behaviors have been investigated.

Choice Behavior↗