Toshikazu Yamaguchi

Frequent and Significant K- ras Mutation in the Pancreas, the Bile Duct, and the Gallbladder in Autoimmune Pancreatitis

Objectives: To assess the relationship between autoimmune pancreatitis (AIP) and pancreatic cancer, we analyzed K-ras mutation in the pancreatobiliary tissues of patients with AIP. Methods: An analysis of K-ras mutation and an immunohistochemical study were performed on the pancreas of 8 patients with AIP and 10 patients with chronic alcoholic pancreatitis and on the common bile duct and the gallbladder of 9 patients with AIP. K-ras mutation was analyzed in the pure pancreatic juice from 3 patients with AIP. Results: High-frequency K-ras mutation (2+ or 3+) was detected in the pancreas of all the 8 patients and in the pancreatic juice of the other 2 patients. The mutation in codon 12 of the ras gene was GAT in all the 10 patients. High-frequency K-ras mutation was detected in the common bile duct of 5 patients with AIP and in the gallbladder epithelium of 4 patients with AIP. The K-ras mutation was detected in the fibroinflammatory pancreas, the bile duct, and the gallbladder, with abundant infiltrating IgG4-positive plasma and Foxp3-positive cells of patients with AIP with elevated serum IgG4 levels. Conclusions: Significant K-ras mutation occurs most frequently in the pancreatobiliary regions of patients with AIP. Autoimmune pancreatitis may be a risk factor of pancreatobiliary cancer.

Pathologic changes in the non-carcinomatous epithelium of the gallbladder in patients with a relatively long common channel

BACKGROUND Except for pancreaticobiliary maljunction, the relationship between a relatively long common channel and gallbladder carcinoma is unknown. METHODS For purposes of this study, a high confluence of pancreaticobiliary ducts was defined as a common channel that is 6 mm or greater in length, together with occlusion of the communication between the pancreatic and bile ducts during sphincter contraction. Pancreaticobiliary maljunction and high confluence of the pancreaticobiliary ducts were detected in 69 (2.1%) and 54 (1.6%), respectively, of 3300 consecutive patients who underwent ERCP. Proliferation activity and genetic alteration were examined in the non-carcinomatous epithelium of the gallbladder in patients with these two radiographic findings at ERCP. RESULTS The Ki-67 labeling index in the epithelium in cases of a high confluence of the pancreaticobiliary ducts and pancreaticobiliary maljunction without biliary dilatation was significantly greater than that in cases of gallbladder carcinoma without these anomalies (p < 0.01). Overexpression of p53 and K-ras mutations were detected in, respectively, 22.2% and 27.8% of cases of a high confluence of pancreaticobiliary ducts. CONCLUSIONS A relatively long common channel may be an important risk factor for the development of gallbladder carcinoma. Vigilance for the development of gallbladder carcinoma is indicated in patients with a relatively long common channel, in addition to those with pancreaticobiliary maljunction.

Gastric epithelial cell proliferation and apoptosis in Helicobacter pylori-infected mice

Background: Helicobacter pylori causes gastritis and is strongly associated with gastroduodenal ulcer and gastric cancer. The bacterium is associated with an increased rate of epithelial proliferation, which can be reversed by eradication of the organism. The mechanism of this response is not known, but this epithelial proliferation is one of the risk factors for developing gastric carcinoma. Recently, apoptosis also was found to be increased in the gastric mucosa of persons carrying H. pylori.

A case of sexually transmitted acute hepatitis C: confirmation by analysis of viral genome

Abstract We report a case of acute hepatitis C that appears to have been sexually transmitted. The patient was a 21-year-old female with no history of blood transfusion and no personal or family history related to hepatic decease. The patient first had sexual intercourse with her male partner in November 1994 and she visited our hospital with a chief complaint of general weakness in March 1995. She was admitted because of abnormal liver function test results (ALT 329; AST 152 IU l −1 ). She was negative for serum second-generation anti-hepatitis C virus (HCV) antibody, anti-hepatitis A IgM antibody, anti-hepatitis B core IgM antibody, anti-Epstein–Barr virus IgM antibody, anti-nuclear antibody, anti-DNA antibody and anti-mitochondrial antibody at admission. A serum HCV RNA test gave a positive result on the 7th day after admission; her HCV RNA level was 10 3.5 copies 50 μl −1 serum on the 21st day. Her anti-HCV antibody status became positive on the 30th day after admission. A liver needle biopsy specimen taken on the 35th day showed well-preserved lobular architecture and mild necroinflammation within the parenchyma without accompanying fibrosis. Abdominal ultrasound and computed tomography did not show significant change in the liver or spleen. Taking the above findings together a diagnosis of acute hepatitis C was maden. Treatment by interferon-β succeeded in eradicating the HCV and the patient was free of HCV RNA 1 year later. The patients partner had untreated chronic hepatitis C. The HCVs isolated from the patient and her partner both had the 2b genotype and single-strand conformation polymorphism analysis revealed three virtually identical bands. The nucleotide sequences (E1-E2/NS1 region) of the two HCVs showed 98% homology. These genetic findings suggest that the sexual transmission of HCV occurred in this case.

Green tea polyphenols reduce gastric epithelial cell proliferation and apoptosis stimulated by Helicobacter pylori infection

Helicobacter pylori (H. pylori) infection in the human stomach is associated with increased epithelial proliferation, and the increased proliferation is one of the risk factors for developing gastric carcinoma. Recently, cells undergoing apoptosis were found to be increased in human gastric mucosa in persons carrying H. pylori. Green tea polyphenols (polyphenols) have been reported to show a variety of biological activities against various foodborne pathological bacteria. Therefore, we studied the effect of polyphenols on gastric epithelial proliferation and apoptosis in H. pylori infected mice. Methods: We challenged Balb/C mice with I08cfu/mouse of the H. pylori (NCTC 11637) strain for 18 weeks. After this challenge, mice were treated with 0.5% polyphenols dairy in drinking water for 2 weeks, and given 5 mg/kg bromodeoxyuridine (BrdU) by introperitoneal injection, I hour before sacrify. Gastric epithelial cell proliferation was evaluated by immunohistochemical anti-BrdU labeling. Apoptosis was examined by using the Tunel method on tissue sections. Results: The number of BrdUlabeled cells in was significantly increased on the H. pylori challenged mice compared with control. The increased proliferation was reduced by polyphenols administration. The number of apoptosis cells also was increased in H. pylori challenged mice. The increased apoptosis was reduced by polyphenols administration. Conclusions: Green tea polyphenols reduced the gastric epithelial cell proliferation and apoptosis caused by H. pylori infection. Administration of green tea polyphenols may reduce gastric carcinogenesis induced by H. pylori infection. 2803