PURPOSE: Gastrokine 1 plays an important role in gastric mucosal defense. Additionally, the Gastrokine 1-miR-185-DNMT1 axis has been shown to suppress gastric carcinogenesis through regulation of epigenetic alteration. Here, we investigated the effects of Gastrokine 1 on DNA methylation and gastritis. MATERIALS AND METHODS: Expression of Gastrokine 1, DNMT1, EZH2, and c-Myc proteins, and the presence of Helicobacter pylori CagA protein were determined in 55 non-neoplastic gastric mucosal tissue samples by western blot analysis. The CpG island methylation phenotype was also examined using six markers (p16, hMLH1, CDH1, MINT1, MINT2 and MINT31) by methylation-specific polymerase chain reaction. Histological gastritis was assessed according to the updated Sydney classification system. RESULTS: Reduced Gastrokine 1 expression was found in 20 of the 55 (36.4%) gastric mucosal tissue samples and was closely associated with miR-185 expression. The Gastrokine 1 expression level was inversely correlated with that of DNMT1, EZH2, and c-Myc, and closely associated with the degree of gastritis. The H. pylori CagA protein was detected in 26 of the 55 (47.3%) gastric mucosal tissues and was positively associated with the expression of DNMT1, EZH2, and c-Myc. In addition, 30 (54.5%) and 23 (41.9%) of the gastric mucosal tissues could be classified as CpG island methylation phenotype-low and CpG island methylation phenotype-high, respectively. Reduced expression of Gastrokine 1 and miR-185, and increased expression of DNMT1, EZH2, and c-Myc were detected in the CpG island methylation phenotype-high gastric mucosa. CONCLUSIONS: Gastrokine 1 has a crucial role in gastric inflammation and DNA methylation in gastric mucosa.
Axis, Cervical Vertebra ; Blotting, Western ; Carcinogenesis ; Classification ; CpG Islands ; DNA Methylation* ; DNA* ; Epigenomics ; Gastric Mucosa* ; Gastritis* ; Helicobacter pylori ; Humans* ; Inflammation ; Methylation ; Mucous Membrane ; Phenotype ; Polymerase Chain Reaction ; Proto-Oncogene Proteins c-myc

OBJECTIVES: The aim of this study is to investigate correlation between the location of white matter hyperintensities (WMH) and neurocognitive dysfunction in non-demented Korean vascular depression patients. METHODS: A total of 148 subjects diagnosed with first major depressive episode after the age of 60 were included in this study. Subjects were divided into the vascular depression group (n=83) and the non-vascular depression group (n=65) according to the degree of WMH. The degree and location of WMH on T2-weighted images were measured using the Scheltens scale. In addition, several clinical features, including cognitive functions and depression severities, were evaluated. Correlation analysis was performed for examination of the relationships between the location of WMH and neuropsychological functions. RESULTS: Capsular frontal periventricular hyperintensities showed correlation with poorer performance of the word list memory test, constructional recall test, and trail making test A and B. Lateral ventricular hyperintensities showed correlation with poorer performance of verbal fluency test, word list recognition test, and trail making test B. Deep WMH, especially parietal and occipital lesions, showed an association with poorer performance on trail making test B. In addition, deep WMH, but not periventricular WMH, showed an association with Hamilton Depression Scale score. CONCLUSION: Our results suggest that subjects with vascular depression showed significantly poorer performance on neurocognitive tests than those with non-vascular depression. In addition, WMH, depending on their locations, showed different correlations according to details of cognitive dysfunction and severity of depressive symptoms.
Depression ; Humans ; Memory ; Trail Making Test

BACKGROUND: The tumor necrosis factor (TNF) is believed to play an important role in the pathophysiology of osteoarthritis (OA). Evidence shows that genetic polymorphisms make substantial contributions to the etiology of OA. METHODS: We investigated the genotypes TNF-alpha and TNF-beta in 301 OA patients and 291 healthy subjects as controls. We employed a polymerase chain reaction-restriction fragment length polymorphism and a polymerase chain reaction-single strand conformation polymorphism assay to identify the genotypes TNFA -G308A and TNFB +G252A, respectively. RESULTS: For TNFA -G308A, the percentages of genotypes GG, AG, and AA were 26.3% (79/301), 62.5% (188/301), and 11.3% (34/301) in OA patients and 88.7% (258/291), 11.3% (33/291), and 0% (0/291) in controls. For TNFB +G252A, the percentages of genotypes GG, AG, and AA were 15.3% (46/301), 41.9% (126/301), and 42.9% (129/301) in OA patients and 12% (35/291), 52.6% (153/291), and 35.4% (103/291) in controls. There were significant differences in genotypes and alleles of TNFA -308 between OA patients and controls (p<0.0001) and in alleles of TNFB +252 (p=0.0325). The risk of OA was significantly higher for carriers of the TNFA -308A allele and the TNFB +252 AA homozygote (p=0.0224). CONCLUSIONS: The results suggest close relationships between TNFA -G308A and TNFB +G252A polymorphisms and individual susceptibility to OA in the Korean population.
Alleles ; Genetic Predisposition to Disease ; Genotype ; Homozygote ; Humans ; Lymphotoxin-alpha ; Osteoarthritis ; Polymorphism, Genetic ; Tumor Necrosis Factor-alpha

BACKGROUND: Osteoarthritis (OA) is a common disease characterized by degenerating joint cartilage in the knee, hip, and hand. A functional single nucleotide polymorphism (SNP) +104T/C; rs143383 in the 5' untranslated region of the growth differentiation factor 5 (GDF5) gene was recently associated with susceptibility to OA in the Japanese and Chinese populations. METHODS: To investigate whether this association is present in the Korean population, the frequency of the polymorphism was investigated in 276 patients with knee OA and 298 healthy subjects as controls. Polymorphism analysis was performed by amplifying the core promoter region of the GDF5 gene and digesting it with the BsiEI restriction enzyme. RESULTS: The frequency of the TT, CT, and CC genotypes was 54.3% (150/276), 41.7% (115/276), and 4.0% (11/276), respectively, in patients with OA, and 53.4% (159/298), 37.9% (113/298), and 8.7% (26/298), respectively, in healthy controls. No significant differences in genotypic or allelic frequencies of the +104T/C SNP of the GDF5 gene were observed between patients with OA and controls. Also, no significant differences in allelic and genotypic frequencies were found when the individuals were stratified by age and gender. CONCLUSIONS: The results suggest that the +104T/C; rs143383 GDF5 core promoter polymorphism is not a risk factor for OA in the Korean population.
5' Untranslated Regions ; Asian Continental Ancestry Group ; Cartilage ; Genotype ; Growth Differentiation Factor 5 ; Hand ; Hip ; Humans ; Joints ; Knee ; Osteoarthritis ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Risk Factors

PURPOSE: Silent mating-type information regulation 2 homologue 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase. SIRT1 plays an important role in the regulation of cell death/survival and stress response in mammals. The aim of this study was to investigate whether the SIRT1 gene is involved in the development or progression of gastric cancers. MATERIALS AND METHODS: SIRT1 and p53 genes in 86 gastric cancers were examined for genetic alterations by PCR-single strand conformation polymorphism sequencing, as well as SIRT1 protein expression in 170 gastric cancers by immunohistochemistry. RESULTS: In the genetic analysis, we found SIRT1 and p53 mutations in two and 12 cases, respectively. Two missense mutations, c.599 C>T (T200I) and c.1258 G>A (E420K), were detected in the SIRT1 gene coding region. The SIRT1 and p53 mutation were found in mutually exclusive gastric cancers. The immunohistochemistry revealed that SIRT1 overexpression was found in 95 (55.9%) of 170 gastric cancers. Altered SIRT1 expression was not statistically associated with clinicopathological parameters, including tumor differentiation, location, lymph node metastasis, or p53 expression. Two cases with an SIRT1 mutation showed increased SIRT1 expression. CONCLUSIONS: These results suggest that genetic alterations and overexpression of the SIRT1 gene may contribute to gastric cancer development.
Adenine ; Clinical Coding ; Genes, p53 ; Immunohistochemistry ; Lymph Nodes ; Mammals ; Mutation, Missense ; Neoplasm Metastasis ; Niacinamide ; Stomach Neoplasms

Triple A syndrome is a rare genetic disorder caused by mutations in the achalasia-addisonianism-alacrima syndrome (AAAS) gene which encodes a tryptophan aspartic acid (WD) repeat-containing protein named alacrima-achalasia-adrenal insufficiency neurologic disorder (ALADIN). Northern blot analysis shows that the 2.1 kb AAAS mRNA is expressed in various tissues with stronger expression in testis and pancreas. We show that human ALADIN is a protein with an apparent molecular weight of 60 kDa, and expressed in the adrenal gland, pituitary gland and pancreas. Furthermore, biochemical analysis using anti-ALADIN antibody supports the previous finding of the localization of ALADIN in the nuclear membrane. The mutations S544G and S544X show that alteration of S544 residue affects correct targeting of ALADIN to the nuclear membrane.
Adrenal Insufficiency/*genetics ; Antibodies/immunology ; Cloning, Molecular ; DNA, Complementary/genetics ; Esophageal Achalasia/*genetics ; Gene Expression Profiling ; Hela Cells ; Humans ; Lacrimal Apparatus Diseases/*genetics ; Mutagenesis, Site-Directed ; Nerve Tissue Proteins/*analysis/*genetics/immunology ; Nuclear Pore/chemistry ; Nuclear Pore Complex Proteins/*analysis/*genetics/immunology ; RNA, Messenger/analysis/genetics ; Syndrome ; Tissue Distribution

BACKGROUND: Rocuronium bromide is a monoquaternary amino steroidal muscle relaxant. Rocuronium is structurally stable and no metabolites of rocuronium have not been observed in humans. The manufacturer recommends that rocuronium can be stored in room temperature for 12 weeks. The aim of this study was to determine if the storage temperature of rocuronium could influence the pharmacodynamics of rocuronium. METHODS: One hundred of patients with a class I or II ASA physical status were enrolled in this study. It was divided to two groups. One (Group '0', n = 50) consists of those who had intravenously administered the rocuronium which had been stored in refrigerator and the other (Group '14', n = 50) consists of those who had intravenously administered the rocuronium which had been stored in room temperature (20-29degrees C, median 25.1degrees C) for 14 days. Before an anesthesia was induced, TOF-Watch(R) was attached and calibrated. The anesthesia was induced with 1microgram/kg of fentanyl and 1.5 mg/kg of propofol intravenously. While the 0.1 Hz of single twitch was applied, 0.45 mg/kg of rocuronium, which is appointed to each group, was injected. Intubation is performed 90 seconds after injection of rocuronium and evaluated the intubating condition as excellent, good, poor, and impossible. RESULTS: There was a statistically significant difference in intubating condition at 90 seconds between two groups. The onset time to twitch depression of 0% in group '14' was prolonged compared to group '0' (P < 0.05). Clinical duration was also shortened in group '14' (P < 0.05). CONCLUSIONS: Compared with the use of rocuronium stored in refrigerator, that stored at room temperature can be expected to have unfavorable intubating condition at 90 seconds after rocuronium injection. Therefore, the storage temperature has some influences on the efficacy of rocuronium.
Anesthesia ; Depression ; Fentanyl ; Humans ; Intubation ; Propofol

PURPOSE: The EphB2 receptor, a member of the receptor tyrosine kinase family, is a target gene of the Wnt signaling pathway and may achieve a tumor suppressor function through regulation of cell growth and migration. Our aim was to determine whether an altered expression of EphB2 might be associated with gastric cancer development and, if so, to determine to which pathologic parameter it is linked. MATERIALS AND METHODS: For the construction of the gastric cancer tissue microarray, 83 paraffin-embedded tissues containing gastric cancer areas were cored 3 times and transferred to the recipient master block. The expression patterns of EphB2 were examined on tissue microarray slides by using immunohistochemistry and were compared using pathologic parameters, including histological type, depth of invasion, lymph node metastatsis, and peritoneal dissemination. RESULTS: The EphB2 protein was expressed in the normal gastric mucosal epithelium, especially in the bottom of the mucosa. We found loss of EphB2 expression in 30 (36.1%) of the 83 gastric cancer tissues. Statistically, loss of EphB2 expression was more common in gastric cancer with lymph-node metastasis. There was no significant correlation between EphB2 expression and depth of invasion, histologic type, or peritoneal dissemination. CONCLUSION: Our findings suggest that loss of EphB2 expression may represent a critical step in gastric carcinogenesis.
Carcinogenesis ; Epithelium ; Genes, Tumor Suppressor ; Humans ; Immunohistochemistry ; Lymph Nodes ; Mucous Membrane ; Neoplasm Metastasis ; Protein-Tyrosine Kinases ; Receptor, EphB2 ; Stomach Neoplasms* ; Wnt Signaling Pathway

The potassium channels are ubiquitous multisubunit membrane proteins, and potassium-dependent alterations in the membrane potential play an important role in the proliferation of many types of cells. This study analyzed the mutation, allelic loss and expression patterns of the KCNRG gene in 77 HCCs in order to determine if the KCNRG gene, which encodes the potassium channel regulating protein, is involved in the tumorigenesis of hepatocellular carcinoma (HCC). One KCNRG missense mutation, CGT->CAT (Arg->His) was found at codon 92 within the T1 domain. Hep3B hepatoma cells were transfected with the wild- or mutant-KCNRG to determine the effect of this mutation in KCNRG. Interestingly, the suppressive cell growth activity of the mutant-type KCNRG was significantly lower than that of the wild-type KCNRG. In addition, allelic loss was detected in 17 out of 64 (26.5%) informative HCC cases, and all were hepatitis B virus (HBV)-positive. Moreover, the allelic loss was closely related to an intrahepatic metastasis (P=0.0247), higher grade (P=0.0078) and clinical stage (P=0.0071). Expression analysis revealed 22 tumor tissues to have a loss of expression of the KCNRG transcript. These results suggest that genetic alterations and the expression of KCNRG might play an important role in the development and/or progression of a subset of HCCs.
Transfection ; Reverse Transcriptase Polymerase Chain Reaction ; Potassium Channels/*genetics/metabolism ; Polymorphism, Single-Stranded Conformational ; Mutation/genetics ; Middle Aged ; Membrane Potentials/genetics/physiology ; Male ; Loss of Heterozygosity/genetics ; Liver Neoplasms/*genetics/metabolism/pathology ; Humans ; Gene Expression Regulation, Neoplastic/genetics ; Female ; DNA Mutational Analysis ; Cell Proliferation ; Cell Line, Tumor ; Carcinoma, Hepatocellular/*genetics/metabolism/pathology ; Blotting, Western ; Aged, 80 and over ; Aged ; Adult

PURPOSE: The protein kinase Chk1 is required for cell cycle arrest in response to DNA damage and is shown to play an important role in the G2/M checkpoint. The aim of this study was to investigate the relationship between microsatellite instability and frameshift mutation of the Chk1 gene in gastric cancers. MATERIALS AND METHODS: The microsatellite instability was analyzed in 95 primary gastric carcinomas by using microdissection and 6 microsatellite markers. We also performed single strand conformational polymorphism and sequencing to detect frameshift mutation of the Chk1 gene. RESULTS: We found positive microsatellite instability in 19 (20%) of the 95 gastric cancers, 13 high- and 6 low-frequency microsatellite instability cases. The frameshift mutation of Chk1, which resulted in a truncated Chk1 protein, was detected in two high-frequency microsatellite instability cases. CONCLUSION: These data suggest that the microsatellite instability may contribute to the development of gastric carcinomas through inactivation of Chk1.
Cell Cycle ; Cell Cycle Checkpoints ; DNA Damage ; Frameshift Mutation ; Microdissection ; Microsatellite Instability* ; Microsatellite Repeats* ; Protein Kinases ; Stomach Neoplasms*