Gastric mucosal levels of prostaglandins and leukotrienes in patients with gastric ulcer after treatment with rabeprazole in comparison to treatment with ranitidine

AIM : Prostaglandins (PGs) and leukotrienes (LTs) are major factors involved in the defense of the gastric mucosa against ulcer formation. However, little is still known about the gastromucosa-protecting action of proton pump inhibitors (PPIs) and histamine H2 receptor antagonists (H2 blockers) in patients with gastric ulcer. We therefore examined the effectiveness of a PPI in protecting the gastric mucosa. METHODS : We compared the PGE2 and LTB4 levels and the expression levels of cyclooxygenase (COX)-1 and COX-2 mRNA in the gastric mucosa in gastric ulcer patients between the group treated for 8 weeks with a PPI, rabeprazole (PPI group ; n=5), and the group treated for 8 weeks with an H2 blocker, ranitidine (H2 blocker group ; n=6), as well as in nonulcer subjects (control group ; n=5). RESULTS : The mucosal levels of PGE2 and COX-2 mRNA expression were significantly lower in the ulcer patients than those in the nonulcer patients, whereas the LTB4 level was significantly higher in the ulcer patients than that in the nonulcer patients, and it was also significantly lower in the ulcerated mucosa than that in the nonulcerated mucosa. The PPI group had a significantly increased PGE2 and decreased LTB4 levels in comparison to the H2 blocker group during the ulcer-healing stage. The COX-1 mRNA expression showed no difference among the PPI and H2 blocker groups or between before and after the treatment. However, the COX-2 mRNA expression increased in the PPI group more than that in the H2 blocker group during the ulcer-healing stage. CONCLUSION : These findings demonstrated the significant gastric-mucosa-protecting effect of PPI by increasing the PGE2 production and reducing the LTB4 production

A patient with octopus pot-shaped cardial cancer that metastasized to multiple organs

A 71-year-old male was admitted for abdominal fullness. The condition rapidly deteriorated in a short period (3weeks), and the patient died. Autopsy revealed a protruding lesion measuring about 3 cm with erosion measuring 5mmin diameter immediately below the esophago-gastric conjugation site, suggesting primary cardial undifferentiated adenocarcinoma. In the primary focus, changes on the mucosal surface were almost normal. However, below the mucosa, infiltration of cancer cells was observed in an approximately 3 cm area along the gastric wall. Simultaneously, the site of infiltration was markedly increased in deep areas. Extra serous infiltration was observed. The morphology was special, and resembled an octopus pot, a trap used to catch octopuses in Japan, with a narrow top and a broad base. In our patient, metastatic lesions were detected in multiple organs, including the stomach

Intron-loss evolution of hatching enzyme genes in Teleostei

<p>Abstract</p> <p>Background</p> <p>Hatching enzyme, belonging to the astacin metallo-protease family, digests egg envelope at embryo hatching. Orthologous genes of the enzyme are found in all vertebrate genomes. Recently, we found that exon-intron structures of the genes were conserved among tetrapods, while the genes of teleosts frequently lost their introns. Occurrence of such intron losses in teleostean hatching enzyme genes is an uncommon evolutionary event, as most eukaryotic genes are generally known to be interrupted by introns and the intron insertion sites are conserved from species to species. Here, we report on extensive studies of the exon-intron structures of teleostean hatching enzyme genes for insight into how and why introns were lost during evolution.</p> <p>Results</p> <p>We investigated the evolutionary pathway of intron-losses in hatching enzyme genes of 27 species of Teleostei. Hatching enzyme genes of basal teleosts are of only one type, which conserves the 9-exon-8-intron structure of an assumed ancestor. On the other hand, otocephalans and euteleosts possess two types of hatching enzyme genes, suggesting a gene duplication event in the common ancestor of otocephalans and euteleosts. The duplicated genes were classified into two clades, clades I and II, based on phylogenetic analysis. In otocephalans and euteleosts, clade I genes developed a phylogeny-specific structure, such as an 8-exon-7-intron, 5-exon-4-intron, 4-exon-3-intron or intron-less structure. In contrast to the clade I genes, the structures of clade II genes were relatively stable in their configuration, and were similar to that of the ancestral genes. Expression analyses revealed that hatching enzyme genes were high-expression genes, when compared to that of housekeeping genes. When expression levels were compared between clade I and II genes, clade I genes tends to be expressed more highly than clade II genes.</p> <p>Conclusions</p> <p>Hatching enzyme genes evolved to lose their introns, and the intron-loss events occurred at the specific points of teleostean phylogeny. We propose that the high-expression hatching enzyme genes frequently lost their introns during the evolution of teleosts, while the low-expression genes maintained the exon-intron structure of the ancestral gene.</p

Evolution of Globin Genes of the Medaka Oryzias latipes (Euteleostei; Beloniformes; Oryziinae)

Recently we cloned two globin gene clusters from the genome of medaka (Oryzias latipes): one designated the embryonic globin gene cluster (E1; 5\u27a03\u27-3\u27b15\u27-5\u27a13\u27-5\u27b23\u27-5\u27a23\u27-3\u27a35\u27-5\u27b33\u27-3\u27b45\u27-5\u27a43\u27-3\u27ya5\u27-5\u27yb3\u27) and the other the adult globin gene cluster (A1; 3\u27ad.a15\u27-5\u27ad.b13\u27-3\u27ad.a25\u27). The E1 and A1 clusters map to linkage groups 8 and 19, respectively. The genes b1/a1, a3/b3, b4/a4, ya/yb and ad.a1/ad.b1 are organized in head-to-head orientation with respect to transcriptional polarity. The genes a0, a1 and a2 are arranged in tandem with the same orientation. The results suggest that a variety of events occurred in globin gene evolution such as chromosomal translocation, duplication of a/b-paired genes, tandem duplication of single a genes and the transformation of one pair of a/b-paired genes into pseudogenes (ya/yb). Amino acid sequences predicted from the genes were compared with those of 42 a and 55 b teleostean globins using the neighbor-joining or maximum likelihood methods. The phylogenetic trees that were generated classified the teleostean globins into at least four groups, tentatively named "Embryonic Hb Group (I)", "Notothenioid Major Adult Hb Group (II)", "Anodic Adult Hb Group (III)" and "Cathodic Adult Hb Group (IV)". The medaka genes a0, b1, a1, a2, a3, b3, b4 and a4 belong to group I, and ad.a1 and ad.b1 to group II. Further analysis suggests that ya/yb and b2/ad.a2 belong to groups III and IV, respectively. Thus, globin genes in the medaka probably were diversified from four ancestral genes, one for each group. On the basis of the gene comparisons, we present a hypothetical pathway for globin gene evolution in the medaka

Globin Gene Enhancer Activity of DNase-I Hypersensitive Site-40 Homolog in Medaka, Oryzias latipes

In medaka, we found a C16orf35 gene-like gene at the 1Kbp-3\u27downstreamregion of the yb end of the 36Kbp embryonic globin gene cluster(5\u27a03\u27-3\u27b15\u27-5\u27a13\u27-5\u27b23\u27-5\u27a23\u27-3\u27a35\u27-5\u27b33\u27-3\u27b45\u27-5\u27a43\u27-3\u27ya5\u27-5\u27yb3\u27). Intron 5 of the gene contained a region having NF-E2 binding siteslocated between GATA boxes. The region was homologous to human HS-40 in theexistence and structure of characteristic transcription factor binding sitesand was named Ol-HS-40. Injection of the fusion gene construct(Ol-HS-40-a0(up-2)GFP) consisting of Ol-HS-40, a 200bp-5\u27upstream minimumpromoter for a0, and GFP showed that Ol-HS-40, as in human HS-40, had theability to strongly enhance GFP expression in erythroid cells of embryos.Further analysis using transgenic technology revealed that Ol-HS-40 had theability to change the embryo-to-young fish expression of GFP into theembryo-to-adult expression. In addition, the results suggest that Ol-HS-40,although its natural function remains unclear, has the strong enhanceractivity for the expression of not only the a-globin gene but also theb-globin gene

Genomic Organization and Evolution of Globin Genes in Medaka, Oryzias latipes

Medaka Genome and Vertebrate Evolutio