Kazutami Tamura

IL18 polymorphism is associated with an increased risk of Crohn’s disease

Background. The etiology of inflammatory bowel disease, which includes ulcerative colitis and Crohn’s disease, has not yet been made clear. However, inflammatory bowel disease is recognized as a multifactorial disease, and innate genetic factors might contribute to the pathogenesis. Cytokine genes are thought to be important in inflammatory bowel disease. Recently, interleukin 18, cloned as a novel proinflammatory cytokine, has been implicated in inflammatory bowel disease, especially Crohn’s disease. Methods. To identify germline mutations in patients with inflammatory bowel disease, the entire coding region of IL18 was examined using a DNA sequencing procedure. Results. No functional mutations were found, but a novel single nucleotide polymorphism (SNP) was identified as TCA/ TCC at codon 35. In patients with Crohn’s disease, the frequency of TCC allele carriers was significantly higher than in healthy controls (χ2 = 9.35, P = 0.002229, OR = 2.58, 95% CI = 1.39–4.80). Also, the magnitude of the association was more remarkable in females (χ2 = 16.36, P = 0.000052, OR = 8.17, 95% CI = 2.73–24.41). The TCC allele at codon 35 of IL18 may increase the risk for Crohn’s disease, especially in females. Conclusions.IL18 is probably one of several genes that determine susceptibility to Crohn’s disease.

Helicobacter pylori Infection Increases Mucosal Permeability of the Stomach and Intestine

It is important to study the effect of Helicobacter pylori infection on the permeability of the intestine. Permeability was evaluated by oral sucrose tolerance test using sucrose 25 g in 200 ml of water. Existence of H. pylori itself was associated with increased permeability of sucrose. Also, the permeability of sucrose increased as polymorphonuclear and lymphocyte infiltration increased. The increase of mucosal permeability suggests that antigens like protein penetrate into the body and result in systemic reactions. Thus, it is important to study the implication of increased permeability in relation not only to gastric diseases but also certain systemic diseases.

Angiomyolipoma of the colon: A new entity in colonic polypoid lesions

SummaryA 67-year-old man with angiomyolipoma on the sigmoid colon is reported. The colonic polyp was pedunculated and diagnosed histologically after endoscopic polypectomy. Angiomyolipoma is one of the benign hamartomas arising principally in the kidneys of patients with or without tuberous sclerosis. Extrarenal angiomyolipoma is rare and this may be the first report of colonic angiomyolipoma.

Campylobacter pylori in Japan: Bacteriological feature and prevalence in healthy subjects and patients with gastroduodenal disorders

SummaryThe presence ofCampylobacter pylori was investigated in biopsy specimens obtained during gastrofiberscopy from 103 consecutive patients prospectively. Patients included 25 with gastric ulcer, 4 with duodenal ulcer, 5 with coexisting gastroduodenal ulcer, 31 with gastroduodenal ulcer with gastritis, 27 with gastritis, 3 with gastric polyps and 8 with gastric cancer. Results were compared with 20 healthy control subjects who were endoscopically normal. Two specimens each were taken from 3 sites in the stomach. One part was used for a histological study to examine the presence of the organisms. The other part was cultured using Skirrow’s agar microaerophilically. Conventional microflora andC. pylori were examined in gastric contents of some cases. Bacteriological features of isolated strains of C.pylori were identical to the NCTC strain. C.pylori was the most dominant organism in gastric contents at any pH level. Detection rates of C.pylori by bacteriological culture were 96% in gastric ulcer, 100% in duodenal ulcer, 80% in coexisting gastroduodenal ulcer, 84% in gastroduodenal ulcer with gastritis, 70% in gastritis, 100% in gastric polyps and 100% in gastric cancer, and the percentages recognized by histological studies were 81,100,100, 84, 71, 67, and 57%, respectively. The values in healthy controls were 55% by histological and bacteriological methods (P<0.001 compared with overall ulcer patients). These results supported the close association between C.pylori and gastroduodenal diseases.

MUCOSAL BLOOD FLOW AND GENERATION OF SUPEROXIDE IN RAT EXPERIMENTAL COLITIS INDUCED BY SUCCINIC ACID

As we consider succinic acid to be an exacerbating factor in ulcerative colitis, we investigated its influence on rat colonic mucosa in terms of mucosal blood flow and superoxide generation. We measured mucosal blood flow by the hydrogen gas clearance method and superoxide generation by the chemiluminescence method, and observed histopathological findings to determine the effects of succinic acid. After the instillation of succinic acid of any concentration tested to the colon, mucosal blood flow decreased. Histopathologically, the higher the concentration of succinic acid, the greater was the erosion formation in the colonic mucosa, while significant polymorpho-nuclear cell infiltration and superoxide generation from colon tissue were observed with 0.01% succinic acid compared with higher or lower concentrations. Succinic acid, at fecal concentrations found in active stage ulcerative colitis, appears to be implicated in mucosal injury, mediated by a decrease in colonic mucosal blood flow and infiltration of superoxide-generating polymorpho-nuclear cells into the mucosa.

Hepatocellular carcinoma complicating autoimmune hepatitis without either hepatitis C viral infection or corticosteroid therapy.

She was readmitted to our hospital in June 2000 because of hematemesis. Endoscopic examination demonstrated rupture of esophageal varix, and sclerotherapy was performed. She was also readmitted in June 2001, for the same reason, and blood transfusion was performed. Serum α-fetoprotein was elevated to 62.3ng/ ml, and serum total bilirubin level also gradually became elevated. She died of liver failure in August 2001. Autopsy demonstrated a hepatoma, measuring 7cm in diameter, in the cirrhotic liver. The tumor was recognized as HCC (Fig. 1). Histology of the nontumorous area showed macronodular cirrhosis with interface hepatitis (Fig. 2). There was a small amount of liver cell rosetting (Fig. 3) and plasmacytic infiltration. Neither hepatitis B virus DNA nor HCV RNA was detected in extraction from paraffin-embedded liver tissue by real-time polymerase chain reaction (PCR) or reverse transcriptase-PCR assay.1 Watanabe et al. described the natural course of a patient with HCV-seronegative AIH who had not received corticosteroid therapy, but had developed HCC, and suggested that the development had been related to the cirrhosis itself rather than to corticosteroid therapy.4 The present patient had not received corticosteroid therapy either and also had cirrhosis, but did not demonstrate HCV RNA in either serum or liver tissue. Therefore, our case further suggests that HCC can occur even in patients with serum and tissue HCV-negative AIH without corticosteroid therapy, and screening for HCC should be performed in patients with AIH complicating cirrhosis, regardless of the results of serum HCV detection. The development of hepatocellular carcinoma (HCC) in patients with autoimmune hepatitis (AIH) is a rare event.1 Hepatitis C virus (HCV) is a carcinogen, and its detection in liver tissue has been reported in two of four HCV RNA-seronegative patients with HCC complicating AIH.1 Corticosteroid has been used in patients with AIH; however, this therapy is regarded as a risk for the development of HCC.2 Herein, we report a woman with HCC complicating HCV-tissue-negative AIH without corticosteroid therapy. An 89-year-old woman was admitted to our hospital in July 1999 because of tarry stool. Endoscopic examination demonstrated hemorrhagic gastritis and esophageal varices without plug. Computed tomography scans showed a mass measuring 4cm in diameter in a cirrhotic liver, suggesting HCC. Laboratory data are shown in Table 1. There was no evidence of any viral hepatitis infection, and she had no history of either a blood transfusion or of drinking liquor. There was no history of using known or suspected hepatotoxic drugs, and she had no remarkable past medical history, except for mild diabetes beginning 3 years earlier. We scored the AIH as 16 in this patient, using a scoring system for the diagnosis of AIH (definite AIH, 15).3 Her family history was not contributory, except that one of her six children, a daughter, has Behçet’s syndrome. The patient was 140cm in height and weighed 51kg. There was foot and face edema, but no ascites and no struma. Thyroid function suggested autoimmune thyroiditis (Table 1). Corticosteroid therapy was not performed because of her advanced age, hemorrhagic gastritis, diabetes, HCC, and absence of severe hepatitis. She was treated with a proton pump inhibitor for the gastritis, and discharged.

Successful eradication of Helicobacter pylori prevents relapse of peptic ulcer disease

The NIH consensus conference in 1994 recommended that all patients with peptic ulcers should be tested and treated for Helicobacter pylori. Recent studies have shown that the eradication of H. pylori is associated with a significant reduction in the relapse rate of peptic ulcers, but there are few reports about long‐term outcome.

Proton Pump Inhibitors for helicobacter pylori Eradication in Patients with Peptic Ulcer

We investigated the effects of omeprazole or lansoprazole on peptic ulcer healing, eradication of Helicobacter pylori (Hp) and abdominal symptoms. A prospective, randomized study was performed for the administration of omeprazole or lansoprazole. Hp-positive peptic ulcer patients (n=86) were randomly assigned to two groups. Gastric ulcer patients received omeprazole 20 mg once daily or lansoprazole 30 mg once daily for 8 weeks. Duodenal ulcer patients were given omeprazole 20 mg once daily or lansoprazole 30 mg once daily for 6 weeks. Endoscopy was performed at baseline, at the end of therapy, and 4 weeks after stopping therapy. The colony factor units (CFUs) of Hp in biopsy specimens were examined. The CFUs of Hp in gastric and duodenal ulcer were significantly decreased at 4 weeks after stopping lansoprazole therapy. We conclude that Hp eradication by combined use of lansoprazole with antibiotics appears to be a promising therapy

N-nitrosamines in the stomach with special reference toin vitro formation, and kinetics after intragastric or intravenous administration in rats

SummaryTo study the implications of nitrosation in the stomach, the formation of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) from nitrite and secondary amines was examinedin vitro under conditions simulating gastric juice. Kinetics of NDMA were investigated after intragastric or intravenous administration of 0.2mg/kg of NDMA in rats. NDMA and NDEA were measured using combined gas chromatography and thermal energy analyzer. Nitrite levels in human gastric juice were less than 10µg/ml. Optimal pH for nitrosation was between 2.0 to 3.5. Nitrosamine formation reached maximum concentration at 3 to 6 hours. The maximum ratios of nitrosation were 0.15 and 0.11% in NDMA/nitrite and NDEA/nitrite, respectively. In the kinetic study, the highest blood levels of NDMA were observed at 5 min, reaching 174±40 and 374±40 ng/ml after administration into the stomach and duodenum, respectively. Then they decreased exponentially and were not detectable after 4 hours. Tissue levels of NDMA in the liver, spleen, kidney, lung and brain showed 70% of the blood levels. Urinary excretion of intravenously administered NDMA during the first 4 hours was less than 0.2%. These results supported the hypothesis that nitrosation occurred in gastric juice under optimal conditions, and indicated that nitrite levels were the limiting factor for nitrosation. Quick disappearance from the gastrointestinal tract suggested that the pathologic implication of nitrosamines formed in the stomach could be important for other organs.

N-Nitrosamines in gastric juice of patients with gastric ulcer before and during treatment with histamine H2-receptor antagonists

SummaryThe clinical implications of N-nitrosamines (NAs) were studied by analyzing their concentration in the gastric juice of 72 healthy subjects and 279 patients with gastric ulcer before and during treatment with histamine H2-receptor antagonists. NAs were measured by combined gas chromatography and thermal energy analyzer. The detection ratios of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) in the patients were 35.3% and 34.6%, respectively, which were significantly higher than the corresponding values in healthy subjects (19.4% and 16.7%, P<0.01). Analysis among the patients showed that this trend was mainly due to higher values in patients who were given histamine H2-receptor antagonists, as their detection ratios increased to 40.2% (NDMA) and 39.9% (NDEA). Patients without histamine H2receptor antagonists showed moderate increases of detection ratios (NDMA; 24.2% NDEA; 22.6%) compared with healthy controls. The differences in these values between those receiving and not receiving histamine H2-receptor antagonists were statistically significant (P<0.01). The maximum concentrations of NDMA and NDEA were 7.9 and 9.8 ng/ml in patients, and 1.2 and 1.3 ng/ml in healthy subjects (the difference between the 2 groups P<0.02). These results indicated that patients with gastric ulcer had higher detection ratios and concentrations of NDMA and NDEA in gastric juice and that, while significant increases occurred during treatment with histamine H2-receptor antagonists, the extent of increase was below toxic or experimental carcinogenic levels.