BACKGROUND: The relaxative response of blood vessels to acetylcholine (ACh) is known to be abnormal in diabetic rat due to changes in endothelium-derived relaxing factor (EDRF) and/or endothelium-derived hyperpolarizing factor (EDHF)-mediated action. Oxygen free radical (OFR) interferes with endothelium dependent relaxation to ACh in diabetic rats; this effect rnay be prevented by superoxide dismutase (SOD), OFR scavenger. Then, we determined the effect of SOD on modulation of OFR-induced damage to EDRF and EDHF-mediated relaxations to ACh in diabetic rat aortas. METHODS: After aortas were incubated with free radical generating system for 15 min with or without SOD pretreatment (150 U/mL) and contracted submaximally by norepinephrine (10 (-5) M), relaxative responses to cumulative concentrations (10 (-9) M to 10 (-5) M) of ACh were measured in aortas isolated from the control and 6-8 week streptozotocin-induced diabetic rat. We measured relaxative responses to ACh in these aortas treated with calmidazolium (100uM) or N-nitro-L-arginine methyl ester (luM) after exposure to OFR with/without SOD pretreatment, RESULTS: The ACh-induced relaxation (10 (-9)M to 10 (-5) M) was significantly decreased in diabetic than in control rat aortas (p<0.05). ACh-induced relaxation in diabetic rat aortas was significantly impaired from 79.3% to 71.2% after exposure to OFR (p<0.05), and the degree of ACh-induced relaxation was recovered from 71.2% to 84.0% after pretreatment with SOD (p<0.05). EDRF-mediated relaxation to ACh in diabetic rat aortas was significantly impaired from 71.2% to 61.6% after exposure to OFR (p<0.05), and the degree of impairment of ACh-induced EDRF-mediated relaxation was recovered from 61.6% to 76.0% after pretreatment with SOD. After exposure to OFR, EDHF-mediated relaxation to ACh in diabetic rat aortas was not significanlty impaired. However, the degree of impairment of EDHF-mediated relaxation to ACh was recovered from 46.0% to 59.5% after pretreatment with SOD. CONCLUSION: This study suggests that OFR may impair mainly EDRF-mediated relaxation to ACh and SOD may protect rnainly OFR-induced damage to EDRF-mediated relaxation to ACh in diabetic rat aortas.
Acetylcholine ; Animals ; Aorta* ; Blood Vessels ; Endothelium ; Endothelium-Dependent Relaxing Factors ; Free Radicals* ; Norepinephrine ; Oxygen* ; Rats* ; Relaxation* ; Superoxide Dismutase* ; Superoxides*

Nesidioblastosis is characterized by a diffuse proliferation of islet cells arising from pancreatic ducts and is the most common cause of hyperinsulinemic hypoglycemia in newborns and infantile. It is exceedingly rare in adults and no concensus regarding its diagnosis and management is available. We herein describe an elderly man with fasting hypoglycemia, inappropriate insulin hypersecretion. And pathologic examination of his pancreas revealed the characteristic finding of nesidioblastosis confirmed by immunohistochemical stain.
Adult ; Aged* ; Diagnosis ; Humans ; Hypoglycemia* ; Infant, Newborn ; Insulin ; Islets of Langerhans ; Nesidioblastosis* ; Pancreas ; Pancreatic Ducts

PURPOSE: Caspase 2, a member of the family of ICE-like proteases, is activated by the Fas pathway and induces apoptosis by triggering the caspase cascade. The purpose of this study was to determine whether the expression pattern of caspase 2 might be associated with gastric cancer development and if so, to determine to which pathologic parameter it is linked. MATENRIALS AND METHODS: For the construction of the gastric cancer tissue microarray, 78 paraffin-embedded tissues containing gastric cancer areas were cored 3 times and transferred to the recipient master block. The expression pattern of caspase 2 was examined on tissue microarray slides by using immunohistochemistry and was compared with pathologic parameters, including histologic type, depth of invasion, lymph node metastasis, and peritoneal dissemination. RESULTS: Caspase 2 was expressed on superficial and foveolar epithelial cells and lymphocytes in the gastric mucosa, mainly in cytoplasm. We found loss of caspase 2 expression in 41 (52.6%) of the 78 gastric cancer tissues. Statistically, histologic type and other pathologic parameters were not related with loss of caspase 2 expression. CONCLUSION: Our findings provide enough evidence that loss of caspase 2 expression may contribute to the development of Korean gastric cancer and that it might be one of the possible escape mechanisms from apoptosis in gastric cancer.
Apoptosis ; Caspase 2* ; Cytoplasm ; Epithelial Cells ; Gastric Mucosa ; Humans ; Immunohistochemistry ; Lymph Nodes ; Lymphocytes ; Neoplasm Metastasis ; Peptide Hydrolases ; Stomach Neoplasms* ; United Nations

Recently, the -160 C/A polymorphism, located within the regulatory region of E-cadherin promoter, has been shown to influence E-cadherin transcription by altering transcription factor binding. We examined the effect of this polymorphism on risk of gastric cancer and on histological classification of intestinal- and diffuse-type gastric cancer in 146 normal healthy individuals and 292 Korean gastric cancer patients. Genomic DNA samples were examined by polymerase chain reaction (PCR)-single strand conformational polymorphism (SSCP)-sequencing and confirmed by restriction fragment length polymorphism (RFLP). Unexpectedly, there was no significant difference in the genotype frequencies of the polymorphism between normal control and gastric cancer patients (x(2) test, p=0.433). The estimated odd ratio of C/C to A/A genotype in gastric cancer cases was 1.07 (95% confidence interval, 0.396-2.870). We also found no evidence for differences in risk for the intestinal- and diffuse-type gastric cancer. These results suggest that the -160 C/A polymorphism of the E-cadherin has no direct effect on the risk of Korean gastric cancer development and on its histological classification.
Alleles ; Cadherins/*genetics ; DNA/metabolism ; Genetic Predisposition to Disease ; Genotype ; Homozygote ; Human ; Korea ; Odds Ratio ; Polymerase Chain Reaction ; Polymorphism (Genetics) ; Polymorphism, Restriction Fragment Length ; *Polymorphism, Single Nucleotide ; Polymorphism, Single-Stranded Conformational ; *Promoter Regions (Genetics) ; Risk ; Stomach Neoplasms/*genetics ; Transcription, Genetic