Rin Chang

Interleukin-1B (IL-1B) polymorphisms and gastric mucosal levels of IL-1β cytokine in Korean patients with gastric cancer

Interleukin‐1B and IL‐1 receptor antagonist gene polymorphisms are associated with an increased risk of gastric cancer (GC) in Caucasian populations. However, recent studies could not find any association between IL‐1B‐511T polymorphism and the risk of GC in Asians. We tested for an association between IL‐1 loci polymorphisms with increased gastric mucosal levels of IL‐1β and an increased risk of developing GC in a Korean population. Polymorphisms of IL‐1A‐889, IL‐1B‐31, IL‐1B‐511 and IL‐1RN were genotyped in 434 controls and 234 patients with GC. Mucosal IL‐1β cytokine was measured using an ELISA. The frequencies of IL‐1A, IL‐1B‐511, IL‐1B‐31 and IL‐1RN were not statistically different between controls and all patients with GC. After subclassification of GC, only patients with intestinal‐type GC showed a higher frequency of IL‐1B‐31T homozygotes (OR = 2.2; 95% CI = 1.1–4.3) compared with controls. Risk was also significantly increased in these patients for IL‐1B‐31T homozygotes compared with patients with diffuse‐type GC (OR = 3.4; 95% CI = 1.5–7.7). As in Caucasian populations, linkage disequilibrium between IL‐1B‐31 and IL‐1B‐511 was nearly complete, but the pattern of haplotype related to the risk of GC (IL‐1B‐31T/IL‐1B‐511C) was opposite (IL‐1B‐511T/IL‐1B‐31C). Mucosal IL‐1β levels in H. pylori‐infected GC patients were higher in patients homozygous for IL‐1B‐31T compared with IL‐1B‐31C/T and IL‐1B‐31C/C. Thus, the combined effects of H. pylori infection and IL‐1B‐31T/IL‐1B‐511C polymorphisms with enhanced mucosal IL‐1β production contributed to the development of intestinal‐type GC in this Korean population.

The incidence and clinical characteristics of symptomatic propylthiouracil-induced hepatic injury in patients with hyperthyroidism: a single-center retrospective study

OBJECTIVES:Although symptomatic propylthiouracil (PTU)-induced hepatic injury is known to be rare, there have been few reports about its exact incidence in patients with hyperthyroidism. We tried to evaluate its incidence in a single center and its clinical course.METHODS:Medical records of 912 hyperthyroid patients who had been diagnosed between March 1990 and December 1998 were reviewed about clinical characteristics, management, and laboratory findings. Symptomatic PTU-induced hepatic injury was defined as the development of jaundice or hepatitis symptoms with at least a 3-times elevation of liver function tests (LFT) without other causes.RESULTS:Four hundred ninety-seven patients (age 42.6 ± 10.7 yr, male/female 140/357) were included. Clinically overt hepatitis developed in six patients (1.2%; age, 43.7 ± 14.8 yr; male:female ratio, 3:3) between 12 and 49 days after PTU administration. Jaundice and itching developed in five patients, fever in two, rash in two, and arthralgia in one. Bilirubin, ALT, and ALP increased in five, four, and six patients, respectively (293 ± 288 μmol/L, 143 ± 111 U/L, and 265 ± 81 U/L; normal, <117 U/L). The type of hepatic injury was cholestatic in three, hepatocellular in one, and mixed in two patients. None resulted from viral hepatitis. There were no statistical differences in age, sex, PTU dose, or T4 and T3 levels at initial diagnosis between patients with and without hepatic injury. LFT normalized in all patients between 16 and 145 (72.8 ± 46.4) days after the PTU withdrawal.CONCLUSIONS:Symptomatic hepatic injury develops usually within the first few months of PTU administration with rare frequency, but its clinical course is relatively benign once the drug is withdrawn. However, it may be difficult to predict its development, so all patients should be monitored for rise in LFTs at regular intervals, especially during the early period.

Role of Helicobacter pylori infection among offspring or siblings of gastric cancer patients

A positive family history is an increased risk factor for gastric cancer within family members, and one of the possible causes of this is the intrafamilial clustering of Helicobacter pylori infection. Our study examined the prevalence of H. pylori infection, serum antibodies to CagA and VacA and atrophic gastritis and/or intestinal metaplasia in the offspring or siblings of gastric cancer patients. A total of 726 subjects included 300 relatives of 300 separate gastric cancer patients and 426 controls. All subjects underwent upper gastrointestinal endoscopic examination with a rapid urease test. Blood samples were obtained to test for the presence of serum antibodies to the CagA and VacA proteins of H. pylori. The prevalence of H. pylori infection was higher in relatives of cancer patients (75.3%) than in controls (60.1%), and the adjusted odds ratio was 2.1 (95% CI 1.5–2.9). When either siblings or 2 or more family members were gastric cancer patients, the prevalence of H. pylori infection was much higher compared to the prevalence in controls. There was no specific relationship between CagA and VacA, and H. pylori infection. Atrophic gastritis and/or intestinal metaplasia were more frequently found in H. pylori‐infected relatives of cancer patients (26.1%) than in H. pylori‐infected controls (12.9%). These results strongly support a role for H. pylori infection in familial aggregation of gastric cancer. The prophylactic eradication of H. pylori infection in the offspring or siblings of gastric cancer patients may be clinically beneficial.

Mutational abrogation of the PTEN/MMAC1 gene in gastrointestinal polyps in patients with Cowden disease

BACKGROUND & AIMS To understand the molecular etiology of Cowden disease-associated gastrointestinal polyps, we analyzed the mutational status of PTEN/MMAC1, a recently identified Cowden disease gene located at 10q23, in gastric hamartomas, colonic adenoma, and juvenile polyps of 3 patients with Cowden disease. METHODS Messenger RNA expression, gene deletion, and sequence alteration of PTEN/MMAC1 were evaluated by quantitative polymerease chain reaction (PCR), PCR-single-strand conformation polymorphism, and sequencing analysis. RESULTS Germline missense mutation at codon 289 (AAA to GAA, Lys to Glu) and deletion of the wild-type allele were detected in the polyps of 2 patients with Cowden disease in the same family. Germline allelic deletion and transcriptional silencing of the remaining allele, probably caused by abnormal methylation, were also observed in a gastric hamartoma of 1 patient. CONCLUSIONS The germline mutation and alteration of the remaining allele observed in this study strongly support that PTEN/MMAC1 functions as a tumor suppressor in Cowden disease. This study is the first to show that the mutational abrogation of PTEN/MMAC1 plays a causal role in the genesis of gastrointestinal polyps in Cowden disease, providing molecular genetic evidence that colonic adenoma, juvenile polyp, and gastric hamartoma could be included in the manifestations of Cowden disease.

Dedifferentiation of conditionally immortalized hepatocytes with long-term in vitro passage.

The rat hepatocytes were immortalized using a temperature-sensitive mutant of SV40 large T antigen (tsT) to develop as a possible substitute for primary hepatocytes. Four rat hepatocyte lines that have been developed and maintained more than passage 50, were characterized for their cellular morphology, T antigen and p53 expression, chromosomes, liver-specific differentiation, telomerase activity and anchorage independent growth. All of four cell lines showed a typical epithelial cell morphology, but the population-doubling time became short with passage: 18 to 60%. T antigen expression was increased with passage about 3 to 65 times at permissive temperature but decreased significantly at non-permissive temperature. The expression level of p53 unchanged during passages was also decreased at non-permissive temperature. The distribution of chromosome number changed somewhat with passage. The production levels of albumin and urea in four cell lines were 2.4 to 13.0% and 7.5 to 19.9% of those produced in primary hepatocytes, respectively and were decreased to an undetectable level with passage. Telomerase activity was increased 10 fold following immortalization of cells, but anchorage independent growth of cells did not develop. These results indicate that conditionally immortalized hepatocytes become dedifferentiated with in vitro passage, which may be caused by marked chromosomal damages that occur with compulsive and continuous replications by the increment of T antigen content with passage and its sequential inhibition of p53 function.

Decreased trabecular bone mineral density in newly diagnosed inflammatory bowel disease patients in Korea

Background : Decreased bone mineral density (BMD) is common in Western patients with inflammatory bowel disease (IBD). However, BMD has never been studied in Asia where the demographic and socio‐economic status are different from the West. The aim of this study was to investigate the prevalence and mechanisms of osteopenia in newly diagnosed Korean patients with IBD.

Liver cirrhosis developed after ketoconazole‐induced acute hepatic injury

Abstract  We describe a previously healthy woman who developed liver cirrhosis as a sequela of acute hepatic injury that was induced by ketoconazole administration to treat onychomycosis. The initial presentation of the disease was of a typical acute hepatitis, characterized by nausea, anorexia, fatigue, and jaundice that developed during the administration of ketoconazole. Many other causes of hepatitis were absent in the patient. Even though the hepatic injury was gradually resolved for several months after cessation of the drug, the liver function was not completely restored. Six months after the onset of illness, a follow‐up abdominal computed tomography and peritoneoscopic liver biopsy were performed. They revealed a marked reduction in the liver volume and a definite cirrhotic change, which persisted for more than 5 years. The case suggests that the administration of ketoconazole can cause liver cirrhosis through acute hepatic injury within a short time under certain circumstances.

Delta 13C-urea breath test value is a useful indicator for Helicobacter pylori eradication in patients with functional dyspepsia

Background: Eradication of Helicobacter pylori is not routinely recommended for the symptomatic relief and the prevention of gastric cancer in patients with functional dyspepsia. The present study investigated a useful indicator of H. pylori eradication in such patients by determining the optimal cutoff value of a 13C‐urea breath test (UBT).

Extrahepatic Biliary Schwannomas : A Case Report

Benign schwannomas arise in neural crest-derived Schwann cells. They can occur almost anywhere in the body, but their most common locations are the central nervous system, extremities, neck, mediastinum, and retroperitoneum. Schwannomas occurring in the biliary tract are extremely rare and mostly present with obstructive jaundice. We recently experienced a case of extrahepatic biliary schwannomas in a 64-yr-old female patient who presented with intra- and extrahepatic bile duct and gallbladder stones during a screening program. To the best of our knowledge, extrahepatic biliary schwannomas associated with bile duct stones have not been reported previously in the literature.

Autoimmune Hepatitis in a Patient with Myasthenia Gravis and Thymoma – a Report on the First Case in Korea

Myasthenia gravis is an autoimmune disease that results from an antibody-mediated reaction and occurs with thymoma in 15% of patients. It is very rarely associated with autoimmune hepatitis. Four cases of myasthenia gravis with autoimmune hepatitis have been reported in the world, We recently experienced a case of 30-year-old man with myasthenia gravis associated with thymoma and autoimmune hepatitis. This condition is the first case that has not been reported previously in Korea. We report this rare condition along with a brief review of the literature.