Alimentary Pharmacology & Therapeutics Symposium Series最新文献

Summary

Background

We investigated factors that impact γδ T-cell phenotype accumulation in Helicobacter pylori-infected gastric mucosa and peripheral blood.

Aim

To determine whether H. pylori infection induces accumulation of Vδ1 T cells via CC chemokine receptor 2 (CCR2) upregulation.

Methods

Mucosal biopsy samples from 22 H. pylori-free and 75 H. pylori-infected patients were classified into grades I–III gastritis groups as per our previous study. The number of γδ, Vδ1 and Vδ2 T cells was evaluated by immunostaining and then compared with counts in 17 patients after H. pylori eradication. TGF-β, IFN-γ and CCR2 mRNA expression levels in Vδ1 T cells stimulated by H. pylori component were also evaluated.

Results

γδ T-cell count was significantly higher in grade III gastritis patients, who exhibited strong IgA and IgG responses to H. pylori urease, than in other groups. Vδ1 T cells were found dominantly residing in H. pylori-infected gastric mucosa, whereas Vδ2 T cells were mainly found in peripheral blood. Vδ1 T-cell count was significantly reduced after H. pylori eradication therapy. In in vitro studies, H. pylori component stimulation significantly upregulated both TGF-β and IFN-γ production in supernatant from stimulated Vδ1 T cells. Moreover, CCR2 mRNA expression in Vδ1 T cells stimulated with H. pylori components was significantly increased.

Conclusion

Accumulation of Vδ1 T cells may occur through the upregulation of CCR2 expression.

Summary

Background

Ghrelin, growth-hormone-releasing peptide, has been reported to accelerate food intake and gastrointestinal motility.

Aim

The present study was designed to investigate the plasma ghrelin levels in patients with functional dyspepsia (FD).

Patients and Methods

Ninety-seven patients, who showed no evidence of peptic ulcer disease or gastrointestinal cancer on upper gastrointestinal endoscopy, were recruited. Seventeen patients who had no gastrointestinal symptoms were recruited as controls. Forty-seven patients were diagnosed to be suffering from FD, based on the Rome II criteria. The FD patients were further subdivided into those with ulcer-like FD, dysmotility-like FD and non-specific-type FD, based on their Gastrointestinal Symptom Rating Scale (GSRS) scores. Fourteen patients were categorized as having gastro-oesophageal reflux disease, and 19 patients were excluded as having the irritable bowel syndrome, based on the GSRS. The plasma ghrelin levels were measured by radioimmunoassay.

Results

The plasma ghrelin levels were significantly higher in FD patients, especially in those with dysmotility-like FD, as compared with those in controls. The plasma ghrelin levels were also correlated well with the indigestion scores.

Conclusion

Plasma ghrelin levels are significantly higher in patients with dysmotility-like FD, suggesting that this parameter could become useful as a novel supportive marker for the diagnosis of FD.

Summary

Background

Recent reports support the notion that patients with Crohn's disease have a dysregulated innate immune response to endogenous flora.

Aim

To reveal the distinct gene expression clusters of a lipopolysaccharide-stimulated pathway in the peripheral blood monocytes of Japanese patients with Crohn's disease.

Materials and methods

Total RNA was extracted from peripheral blood monocytes of four patients in the remission stage of Crohn's disease as well as four controls, and gene expression profiles before and after lipopolysaccharide stimulation were investigated using a high-density oligonucleotide probe array. To focus on innate immunity, the expression of genes to be studied was narrowed down to 118 probe sets which were selected using the following keywords: lipopolysaccharide, toll, myd and tir along with a software of NetAffx Analysis Center.

Results

Using hierarchical clustering analysis, we picked up to 44 and 36 probe sets for which expression had decreased before and after lipopolysaccharide stimulation, respectively, in patients with Crohn's disease compared with healthy volunteers. The expression of TLR5, 7, MyD88, SIGIRR, and Tollip was decreased both before and after lipopolysaccharide stimulation in patients with Crohn's disease.

Conclusion

We found several interesting clusters in monocytes before and after stimulation with lipopolysaccharide. These genes may have been responsible for the immunological differences between the Crohn's disease and control patients.

Summary

Background

Membranous nephropathy is the most common cause of nephrotic syndrome in Japanese adults, and is often precipitated by systemic diseases such as infection, neoplasm, and autoimmune conditions. Recently, the Helicobacter pylori antigen was detected histochemically in the glomeruli of membranous nephropathy patients, raising the possibility that H. pylori may be the pathogen that causes.

Aim

To reveal the p1revalence of H. pylori infection in the Japanese membranous nephropathy population and to test the therapeutic efficacy of H. pylori eradication on the course of disease in membranous nephropathy patients.

Methods

The prevalence of H. pylori infection was investigated by the HM-CAP method in 32 membranous nephropathy patients and an age-matched control group (C: n = 243).

Results

A significantly higher H. pylori infection rate was found in membranous nephropathy patients than in the control group (positive/total: membranous nephropathy 21/32 vs. C 108/243, P < 0.05 by chi-squared test). Eradication of H. pylori was achieved in four membranous nephropathy patients with proteinuria who were receiving glucocorticoid therapy, three of whom experienced a reduction of proteinuria after eradication.

Conclusions

We found a higher prevalence of H. pylori infection in Japanese membranous nephropathy patients than in age-matched control subjects, which suggests the possible involvement of H. pylori infection in the pathogenesis of membranous nephropathy.

Summary

Background

Although recent immunochemical analysis enabled the discrimination of gastrointestinal stromal tumour (GIST) to other mesenchymal tumours, preoperative diagnosis of these tumours is not always easy.

Aim

To discriminate between ectopic pancreas (EP) and mesenchymal tumours, including GIST, 12 years surgical experience at Keio University Hospital was reviewed.

Methods

Clinicopathological findings were analysed for 131 patients with gastric submucosal tumours (SMT), including GIST (67 cases), myogenic tumour (21 cases), Schwannoma (11 cases), EP (12 cases) and others (20 cases) surgically treated at Keio University Hospital since 1993.

Results

Analysis of clinicopathological findings of these tumours showed that GIST, myogenic tumour and Schwannoma mimic each other from the standpoint of size and location of the tumour. In contrast, comparison of mesenchymal tumours showed that, compared with gastrointestinal mesenchymal tumour, EP tends to exist at middle or lower third of the stomach (P = 0.004), and the tumour size was smaller than 3 cm (P = 0.0006). All EPs were laparoscopically resected and no malignant features were evident.

Conclusion

To avoid unnecessary surgery for EP, SMT smaller than 3 cm occurring in the middle or lower third of the stomach should be carefully selected as a candidate of surgical resection.

Summary

Background

Endoscopic classifications were reported to reflect the pathophysiology of gastric mucosa. However, relationship between gastric lesions and classifications has not been examined well.

Aim

To investigate the relationship between endoscopic classifications and cancers or ulcers.

Methods

In this study, 487 patients undergoing upper gastrointestinal endoscopy in Takahashi Clinic and 257 patients with early gastric cancer in Keio University Hospital were enrolled.

Results

Incidence of reflux oesophagitis was higher in Helicobacter pylori-negative patients. K-form was better in the H. pylori-positive patients. Most cancers in the patients with the closed-type or reflux oesophagitis were of undifferentiated types. Incidences of ulcers were highest in C-2 and C-3 in which the borders of atrophy cross the medial oblique muscle bundle, the border circular muscle bundle or both, and 94% of ulcers in C-2 and C-3 stomach were located along the lesser curvature.

Conclusion

The predominant existence of undifferentiated types in patients with reflux oesophagitis or closed-type stomach can be useful information for early diagnosis of cancers. The relationship between the Kimura–Takemoto classification and ulcer location may explain why H. pylori infection is related to ulcer formation along the lesser curvature.

Summary

Background

Both adenomatous polyposis coli (APC) gene mutation and cyclo-oxygenase (COX)-2 are thought to play key roles in colorectal carcinogenesis. Nuclear accumulation of β-catenin results from APC gene mutation, which leads to enhanced transcription and activation of target genes, including cyclin D1. In vitro studies suggest that Cox-2 transcription is directly regulated by β-catenin/TCF complexes.

Aim

To investigate the relationship between cellular localization of β-catenin and COX-2 in colorectal cancer.

Methods

We performed immunohistochemical analysis of β-catenin, cyclin D1 and COX-2 expression in 50 resected colorectal cancer cases.

Results

The proportion of cases positive for cyclin D1 was higher in nuclear β-catenin-positive cases than in negative cases (P < 0.001). Serial sections revealed that the co-localization of cyclin D1 and nuclear β-catenin was most frequently evident in the tumour cells at the advancing margin of invasive carcinoma. Conversely, there was no association between COX-2 and nuclear β-catenin expression, either topographically or statistically. The staining patterns for COX-2 and nuclear β-catenin differed; COX-2 was diffuse and homogeneous, whereas nuclear β-catenin was focal and preferentially distributed at the invasive margin of cancer cells.

Conclusions

These two important modulators of colorectal tumourigenesis are differentially expressed. Cox-2 and β-catenin transcription may be activated by different pathways.

Summary

Aim

To examine whether Helicobacter pylori induces structural chromosomal aberrations, such as loss of heterozygosity (LOH) and microsatellite instability (MSI) in the infected gastric mucosa.

Methods

Subjects were 13 patients with H. pylori-positive and 9 with H. pylori-negative gastric cancer and 20 patients with H. pylori-positive and 4 patients with H. pylori-negative chronic gastritis. Gastric mucosal tissues were endoscopically sampled from each subject. Each sample was checked for structural chromosomal aberrations (LOH and MSI) by PCR and microsatellite analysis, using a total of 31 primers corresponding to the regions containing the major genes of chromosomes 1q, 5q, 7q, 17p, 17q, 18q and 21q.

Results

All tissue samples obtained from cancer-affected regions of the stomach had structural chromosomal aberrations (LOH or MSI), irrespective of H. pylori infection. The degree of structural chromosomal aberration was greater in poorly differentiated than well-differentiated adenocarcinoma. In addition, structural chromosomal aberrations were also found in a few samples obtained from the chronic atrophic gastritis group, irrespective of H. pylori infection.

Conclusions

It seems unlikely that H. pylori serves as a direct promoter of gastric cancer, and H. pylori-positive chronic gastritis may not always be a precancerous state.

Summary

Background

Ghrelin stimulates food intake and body weight gain. The stomach is the major source of circulating ghrelin, but controversy exists over the relationship between ghrelin release and Helicobacter pylori infection.

Aim

To assess the relationship between H. pylori infection and ghrelin, leptin and gastrin release in adult shepherds and their children, and to measure the effect of H. pylori eradication on gastric ghrelin content.

Methods

H. pylori prevalence was compared in 42 shepherds with full contact with sheep, 148 farmers without sheep contact and in 61 age-matched urban adult controls as well as in 58 shepherd children with sheep contact, 88 mountain children without contact and 141 urban children controls. Serum levels of ghrelin, leptin and gastrin in adult shepherds and their children with and without H. pylori infection were measured.

Results

The major source of circulating ghrelin was gastric corpus mucosa, as ghrelin content was severalfold higher than that in antral mucosa and was significantly higher in the H. pylori-eradicated than that in H. pylori-infected mucosa. Serum levels of ghrelin were greatly increased, while gastrin levels were significantly decreased in H. pylori-negative as compared with H. pylori-positive subjects. In mountain children, serum levels of ghrelin and leptin were about twofold higher in H. pylori-negative than in H. pylori-positive children, whereas gastrin levels were significantly reduced in H. pylori-negative children.

Conclusions

The high incidence of H. pylori infection in shepherds and their children seems to contribute to the decreased serum levels of ghrelin and increased levels of gastrin in H. pylori-infected mountain children and to their decreased appetite and dyspeptic symptoms.