SUMMARYAim: To investigate the effect of the eradication of Helicobacter pylori on histological gastritis. Methods: Twenty-six patients with moderate to severe atrophy received successful eradication therapy of H. pylori. Four patients dropped out and 22 were followed up prospectively for 5 years. The grades of gastritis were estimated from gastric biopsy specimens. The grade of intestinal metaplasia was also evaluated by dye-endoscopy using methylene blue (methylthioninium chloride). The serum levels of pepsinogen, gastrin and anti-parietal cell antibody were also determined. Results: The grades of atrophy decreased in patients with successful eradication therapy in the gastric corpus (before vs. 5 years after eradication, 2.09 ± 0.15 vs. 0.91 ± 0.17; P < 0.01) and in the antrum (2.14 ± 0.17 vs. 1.36 ± 0.17; P < 0.01). The levels of intestinal metaplasia were also decreased in the corpus (0.91 ± 0.24 vs. 0.50 ± 0.16; P < 0.05) and in the antrum (1.41 ± 0.20 vs. 1.00 ± 0.16; P < 0.05), which was also demonstrated by the methylene blue (methylthioninium chloride) staining method (33.4 ± 8.2% vs. 23.0 ± 6.5%; P < 0.05). The improvement of corpus atrophy correlated well with the high serum level of pepsinogen I (P ¼ 0.005), but showed no correlation with the levels of anti-parietal cell antibody. Conclusions: These results suggest that gastric atrophy and intestinal metaplasia are reversible events in some patients.

The REV1 protein is a member of the growing family of translesion DNA polymerases. A cDNA of the human REV1 gene that we had originally isolated encoded 1250 amino acids residues, which was one amino acid shorter than previously reported ones. The shorter form of REV1 was named REV1S. All individuals examined expressed equivalent amounts of REV1S and REV1 mRNA, suggesting that the REV1S mRNA is a splicing variant. We show that the REV1S protein also possesses deoxycytidyl transferase activity that inserts a dCMP opposite a DNA template apurinic/apyrimidinic site. Deletion and point mutation analysis of the REV1S protein revealed that the domain required for deoxycytidyl transferase and DNA binding activities of the REV1S protein are located in a conserved domain of translesion DNA polymerases. This result indicates that the structure of the catalytic site of the deoxycytidyl transferase closely resembles that of the translesion DNA polymerases. Therefore, the molecular mechanism of the dCMP transfer reaction of the REV1S protein and maybe also the REV1 protein might be the same as that of the dNTP transfer reaction of the translesion DNA polymerases.In yeast Saccharomyces cerevisiae, almost all induced mutations arise during translesion replication, a process that promotes elongation past sites of unrepaired lesions (1). The mutagenesis pathway (rev) mutants were initially isolated by their reduced mutations after UV treatment (2). The REV1, REV3, and REV7 genes are required for the major pathway for translesion replication in yeast (3-6). The REV1 gene encodes a deoxycytidyl transferase that incorporates dCMP opposite apurinic/apyrimidinic (AP) 1 sites in the template (7). The REV3 and REV7 genes encode a translesion DNA polymerase, pol (8, 9), which works together with the REV1 protein for translesion replication (7). Recently, the human orthologues of REV1 (10, 11), REV3 (12, 13), and REV7 (14) have been identified. It has been shown that the human REV1 protein possesses a deoxycytidyl transferase activity (10) and that the human REV1 and REV3 genes are required for mutagenesis induced by UV light in humans (11,12).The REV1 gene is a member of a growing family including umuC (15) (18,(23)(24)(25)(26)(27)(28)(29). However, the REV1 protein does not possess such polymerase activity although it contains the conserved domain in translesion polymerases.In this work, we made various mutants of the human REV1S protein. Biochemical analysis of those mutant proteins showed that the domain required for deoxycytidyl transferase activity and DNA binding is located in a conserved domain of translesion DNA polymerases. EXPERIMENTAL PROCEDURES Isolation of Human REV1 cDNAWe found a partial sequence of a candidate of the human REV1 cDNA in a data base (accession number AJ131720). Based on the sequence, a portion of the cDNA fragment of the human REV1 was amplified by RT-PCR from human breast cancer using primers 5Ј-AA-TCTAGCTGGAGCTGTTGA-3Ј and 5Ј-GTAAAACCACCTGGACATTG-3Ј, and it was used as a probe for screening a human testi...

Vascular endothelial growth factor (VEGF) is associated with the malignant potential of several types of carcinoma. The aim of this study was to elucidate the clinical significance of VEGF expression in gastrointestinal stromal tumor (GIST). Methods: Specimens obtained from 53 patients who had underwent surgical resection for GIST of the stomach were used in this study. Specimens were examined immunohistochemically for VEGF expression and Ki-67 expression. Tumor microvessel density (MVD) was determined immunohistochemically with anti-CD31 antibody, and was estimated by averaging the counts from three high-power fields in the area showing the greatest neovascularization. Results: VEGF expression was detected in 14 (26.4%) of the 53 lesions and correlated significantly with tumor size, liver metastasis, Ki-67 labeling index, and MVD. Prognosis was significantly poorer than in patients with tumors expressing VEGF than in patients with tumors lacking VEGF expression. Multiple logistic regression analysis for 10-year survival showed VEGF expression and high mitotic rate to be independent predictor of a poor outcome. Conclusions: Angiogenesis associated with VEGF may play an important role in the progression of GIST. VEGF expression may serve as an indicator of a poor prognosis.

Tumor angiogenesis is a complicated process for which the mechanisms remain unclear. The aim of this study was to elucidate the clinical significance of several angiogenic factor expression as a predictor of the invasive/metastatic potential and of the prognosis of advanced colorectal carcinoma (CRC) in relation to their intratumoral histologic heterogeneity. One hundred fifty two patients who had undergone surgical resection for advanced CRC entered this study. PD-ECGF, VEGF, and VEGF-C were examined immunohistochemically with antibodies 1C6-203, A-20, and C-20, respectively. Tumor microvessel density (MVD) was determined immunohistochemically with anti-CD34 antibody. Expression of PD-ECGF, of VEGF, and of VEGF-C at the deepest invasive site were detected in 77 (50.7%), 62 (30.8%), and 71 (46.7%) of the 152 lesions, respectively. PD-ECGF, VEGF, and VEGF-C expression at the deepest invasive site in lesions with liver metastasis (77, 67, and 70%) was significantly higher than that in those without liver metastasis (44, 34, and 41%). In cases with curative surgery, patients with PD-ECGF, VEGF, and VEGF-C expression at the deepest invasive site had a significantly poorer prognosis than those without PD-ECGF, VEGF, and VEGF-C expression at the deepest invasive site. PD-ECGF, VEGF, and VEGF-C expression at the deepest invasive site correlated significantly with MVD. Multivariate analysis with logistic regression for 5-year survival in patients with curative surgery showed that lymph node metastasis and VEGF expression were significant risk factors. Expression of PD-ECGF, VEGF, and VEGF-C was correlated significantly with metastatic potential and prognosis in relation to MVD. Of the several angiogenic factors, VEGF expression at the deepest invasive site of tumor was the most statistically significant indicator of prognosis in advanced CRC.

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