Proton Pump Inhibitors and Gastritis

Proton pump inhibitors (PPIs) are novel compounds that strongly inhibit the H+/K+-ATPase in the gastric parietal cells to cause profound suppression of acid secretion. Acid-generating ATPase, also known as vacuolar-type ATPase, is located in the lysozomes of leukocytes and osteoclasts and its activity is also reportedly influenced by treatment with PPIs. This concept is supported by the results of studies using autoradiography in which 3H-Lansoprazole uptake sites were clearly detected in the cytoplasmic granules of neutrophils infiltrating the gastric mucosa. In vitro studies indicate that PPIs increase the intra-vacuolar pH in the lysosomes of purified neutrophils and attenuate the adherence of neutrophils to the vascular endothelium. In clinical practice, the acidic environment in the stomach plays a critical role in the development of gastritis induced by Helicobacter pylori (H. pylori). This is worthy of note, because persistent gastritis often results in atrophic and metaplastic changes in the gastric mucosa, which are believed to be preneoplastic abnormalities. In patients with H. pylori-infection, PPI therapy causes corpus-predominant gastritis, which is frequently found in the background mucosa in patients with gastric cancer. The efficacy and safety of long-term PPI-treatment have not been conclusive, thus we need to pay more attention to the additional pharmacological actions of PPIs

Gastric Epithelial Cell Modality and Proton Pump Inhibitor

Proton pump inhibitors (PPIs) are now commonly used for the treatment of acid related diseases such as peptic ulcer and reflux esophagitis. Because of their ability to produce direct inhibition of the proton pump, PPIs provide more sustained increase of the gastric pH than H2-receptor (H2R) antagonists. Diverse reports have been published on gastric epithelial cell modality associated with PPI treatment both in animal models and clinical settings. The present review summarizes the recent accumulated evidence on gastric epithelial cell modality associated with PPI treatment, including the formation of gastric carcinoid tumors and fundic gland polyps, and the development of gastric mucosal atrophy. Long-term PPI treatment has been reported to cause enlargement of the parietal cells and enterochromaffin-like cells, and to decrease the number of chief cells without affecting A-like cell. Although the development of gastric carcinoid tumors after chronic PPI treatment has been reported in animal studies, no such occurrences have been demonstrated in humans. The effect of PPIs on the formation of fundic gland polyps and the development of atrophic gastritis should be investigated in future studies

Helicobacter pylori: present status and future prospects in Japan

The discovery of Helicobacter pylori has already changed the natural history of peptic ulcer disease, with most patients being cured at their first presentation. Similarly, the incidence of gastric cancer and other diseases related to H. pylori are likely to be greatly reduced in the near future. Isolation of the spiral intragastric bacterium H. pylori totally reversed the false dogma that the stomach was sterile, and it taught us that chronic infectious disease can still exist in modern society. Helicobacter pylori’s unique location, persistence, and evasion of the immune system offer important insights into the pathophysiology of the gut. Also, the fact that it was overlooked for so long encourages us to think “outside the box” when investigating other diseases with obscure etiologies. We should consider such provocative scientific ideas as bridges to the future disease control

Prenatal diagnosis of Jacobsen syndrome with cystic hygroma

Jacobsen syndrome (JBS) is a rare, contiguous genetic deletion syndrome caused by partial deletion of chromosome 11q. It is difficult to diagnose JBS by ultrasonography during the prenatal period because it has atypical clinical findings. Although nuchal thickening is associated with JBS, cystic hygroma has not been previously reported in conjunction with this syndrome. We describe the first prenatal diagnosis of JBS with cystic hygroma, which was clinically diagnosed at 13 weeks gestation in a Japanese woman, although it had not been detectable at the 11th week of gestation. In addition, a single ventricle fetal heart defect was suspected. Amniocentesis was performed, and G-banded karyotype evaluation revealed 46,XX,del(11)(q23), which is consistent with JBS. Cystic hygroma and congenital heart malformation have been reported to be associated with chromosomal anomalies. The present case indicates that a fetal cystic hygroma without increased nuchal thickness might be associated with JBS

H. pylori-Eradication Therapy Increases RUNX3 Expression in the Glandular Epithelial Cells in Enlarged-Fold Gastritis

Helicobacter pylori (HP)-eradication therapy increases Runt domain transcription factor 3 (RUNX3) expression in the glandular epithelial cells in enlarged-fold gastritis. The aim of this study is to evaluate expression of the RUNX3 protein, the product of a gastric tumor suppression gene, and mutagenic oxidative stress in human gastric mucosal specimens obtained from patients with HP-induced enlarged-fold gastritis. Methods. RUNX3 expression was immunohistochemically scored and the degree of the mucosal oxidative stress was directly measured by the chemiluminescense (ChL) assay in the biopsy specimens. Results. RUNX3 expression was detected in the gastric epithelial cells. HP-eradication significantly increased RUNX3 expression in the glandular epithelium of the corpus, however, no change was observed in those of the antrum. A fourfold higher mucosal ChL value was observed in the corpus as compared with that in the antrum. HP-eradication significantly decreased the mucosal ChL values in both portions of the stomach to nearly undetectable levels. Conclusion. The glandular epithelium is exposed to a high level of carcinogenic oxidative stress and shows low levels of expression of the tumor suppressive molecule, RUNX3; however, this expression was restored after HP-eradication, suggesting the high risk of carcinogenesis associated with HP-induced enlarged-fold gastritis of the corpus

Nested introns in an intron: Evidence of multi-step splicing in a large intron of the human dystrophin pre-mRNA

AbstractThe mechanisms by which huge human introns are spliced out precisely are poorly understood. We analyzed large intron 7 (110199 nucleotides) generated from the human dystrophin (DMD) pre-mRNA by RT-PCR. We identified branching between the authentic 5′ splice site and the branch point; however, the sequences far from the branch site were not detectable. This RT-PCR product was resistant to exoribonuclease (RNase R) digestion, suggesting that the detected lariat intron has a closed loop structure but contains gaps in its sequence. Transient and concomitant generation of at least two branched fragments from nested introns within large intron 7 suggests internal nested splicing events before the ultimate splicing at the authentic 5′ and 3′ splice sites. Nested splicing events, which bring the authentic 5′ and 3′ splice sites into close proximity, could be one of the splicing mechanisms for the extremely large introns