The KFDA (Korea Food & Drug Administration) has performed a collaborative toxicogenomics project since 2003. Its aim is to construct a toxicology database of 12 compounds administered to mice at initial phase. We chose 6-MP (6-mercaptopurine) which has been used in the treatment of childhood leukemia. It was administered at low (0.224 mg/kg) and at high (2.24 mg/kg) dose (5 mice per group) intraperitonealy to the postnatal 6 weeks mice, then the serum and liver were collected at the indicated time (6, 24 and 72 h) after scarification. Serum biochemical markers for liver toxicity were measured and histopathologic studies also were carried out. The gene expression profiling was carried out by using Applied Biosystems 1700 Full Genome Expression Mouse. By self-organization maps (SOM), we identified groups with unique gene expression patterns, some of them are supposed to be related to 6-MP induced toxicity, including lipid metabolism abnormality, inflammatory response, oxidative stress, ATP depletion and cell death. The potential toxic effects appearing as gene expression changes are dependent of the time of 6-MP but independent of the dosage of it. This study would contribute to establishment of international database as well as national one about hepatotoxicity.
Adenosine Triphosphate ; Animals ; Cell Death ; Gene Expression Profiling* ; Gene Expression* ; Genome ; Leukemia ; Lipid Metabolism ; Liver* ; Mice ; Microarray Analysis ; Oxidative Stress ; Toxicogenetics ; Toxicology ; Biomarkers

How personality forms and whether personality genes exist are long-studied questions. Various concepts and theories have been presented for centuries. Personality is a complex trait and is developed through the interaction of genes and the environment. Twin and family studies have found that there are critical genetic and environmental components in the inheritance of personality traits, and modern advances in genetics are making it possible to identify specific variants for personality traits. Although genes that were found in studies on personality have not provided replicable association between genetic and personality variability, more and more genetic variants associated with personality traits are being discovered. Here, we present the current state of the art on genetic research in the personality field and finally list several of the recently published research highlights. First, we briefly describe the commonly used self-reported measures that define personality traits. Then, we summarize the characteristics of the candidate genes for personality traits and investigate gene variants that have been suggested to be associated with personality traits.
Genetic Research ; Humans ; Wills

BACKGROUND/AIMS: The aims of this study are to clarify the morphology of fundic gland polyp (FGP) and to compare the features of FGP between familial adenomatous polyposis-associated group and sporadic development group. METHODS: A total of 15 endo- scopic biopsy specimens of FGP from 13 patients were divided into three groups; Group A(3 cases; familial adenomatous polyposis family, multiple FGPs), Group B(3 cases; sporadic development, multiple FGPs) and Group C(7 cases; sporadic development, single FGP), and their endoseopic /microscopic features including mucin histochemistry and immunohistoc- hemistty(for PCNA) were compared. RESULTS: FGPs were confined to the gastric body and fundus in all 3 groups, and measured 2-8 mm. Their numbers varied even in Group A and Group B, The difference was observed in their median age: 26 years in Group A and 55 years in Group B, respectively, but there were no differences in endoscopic, histologic, mucin histochemical and immunohistochemical(for PCNA) features. Micro-scopically, all FGPs were composed of fundic glands and scattered microcysts with a spectrum of disordered glandular architecture which ranged from convoluted gland to Y-shaped gland, to stellateshaped gland, and to irregular tortuous glancl with dilated lumen. CONCLUSIONS: We assume that diversity af morphologic features of FGP may develop from progression of hyperplastic/hamartomatous fundic glandular proliferation which may end up with microcyst formation as an evolutional change. Familial adenomatous polyosis-associated FGPs were not endoscopically and histologically distingishable from sporadic deveoped FGPs.
Adenomatous Polyposis Coli* ; Biopsy ; Esophagus* ; Humans ; Intestines* ; Mucins ; Polyps* ; Stomach*

Metabolic syndrome (MetS) is a complex disorder related to insulin resistance, obesity, and inflammation. Genetic and environmental factors also contribute to the development of MetS, and through genome-wide association studies (GWASs), important susceptibility loci have been identified. However, GWASs focus more on individual single-nucleotide polymorphisms (SNPs), explaining only a small portion of genetic heritability. To overcome this limitation, pathway analyses are being applied to GWAS datasets. The aim of this study is to elucidate the biological pathways involved in the pathogenesis of MetS through pathway analysis. Cohort data from the Korea Associated Resource (KARE) was used for analysis, which include 8,842 individuals (age, 52.2 +/- 8.9 years; body mass index, 24.6 +/- 3.2 kg/m2). A total of 312,121 autosomal SNPs were obtained after quality control. Pathway analysis was conducted using Meta-analysis Gene-Set Enrichment of Variant Associations (MAGENTA) to discover the biological pathways associated with MetS. In the discovery phase, SNPs from chromosome 12, including rs11066280, rs2074356, and rs12229654, were associated with MetS (p < 5 x 10(-6)), and rs11066280 satisfied the Bonferroni-corrected cutoff (unadjusted p < 1.38 x 10(-7), Bonferroni-adjusted p < 0.05). Through pathway analysis, biological pathways, including electron carrier activity, signaling by platelet-derived growth factor (PDGF), the mitogen-activated protein kinase kinase kinase cascade, PDGF binding, peroxisome proliferator-activated receptor (PPAR) signaling, and DNA repair, were associated with MetS. Through pathway analysis of MetS, pathways related with PDGF, mitogen-activated protein kinase, and PPAR signaling, as well as nucleic acid binding, protein secretion, and DNA repair, were identified. Further studies will be needed to clarify the genetic pathogenesis leading to MetS.
Body Mass Index ; Chromosomes, Human, Pair 12 ; Cohort Studies* ; Dataset ; DNA Repair ; Genome-Wide Association Study* ; Inflammation ; Insulin Resistance ; Korea ; Metabolic Syndrome X ; Obesity ; Peroxisome Proliferator-Activated Receptors ; Peroxisomes ; Phosphotransferases ; Platelet-Derived Growth Factor ; Polymorphism, Single Nucleotide ; Protein Binding ; Protein Kinases ; Quality Control

OBJECTIVE: The objective of the study was to estimate socioeconomic burden of polycystic ovary syndrome (PCOS) during the reproductive life span using current definitions and prevalence or incidence data. METHODS: Questionnaires were given to 8,588 reproductive women reviewed at Ewha Womans University Mokdong hospital. The PCOS affected approximately 10.4% of reproductive-aged women (11 million women in Korea, prevalence rate according to 1990 National Institutes of Health PCOS diagnosis criteria). We tied general societal cost data for the different health consequences to reproductive-age PCOS costs, using prevalence data. RESULTS: We estimated the mean annual cost of the initial evaluation to be 76 hundred million won, that of hormonally treating menstrual dysfunction, providing infertility care, diagnosis/treatment of endometrial hyperplasia, GDM, type 2 DM, and hypertension to be 280 billion won. The total annual socioeconomic cost of evaluating and providing care to reproductive-aged PCOS women in Korea is 350 billion won. CONCLUSION: Because the cost of the diagnostic evaluation accounted for a relatively minor part of the total socioeconomic costs, more widespread screening for PCOS appears be a cost-effective strategy, leading to earlier diagnosis and intervention and possibly the amelioration and prevention of serious sequelae.
Endometrial Hyperplasia ; Female ; Humans ; Hypertension ; Incidence ; Infertility ; Korea ; Mass Screening ; National Institutes of Health (U.S.) ; Polycystic Ovary Syndrome ; Prevalence ; Surveys and Questionnaire

Granular corneal dystrophy, type II (CGD2; Avellino corneal dystrophy) is the most common corneal dystrophy among Koreans, but its pathophysiology is still poorly understood. Many reports showed that even though the causative mutation is the same TGFBI R124H mutation, there are severe and mild phenotypes of the corneal dystrophy. We also observed the phenotype differences in our samples. For this reason, we focused our effort on the identification of unknown genetic factor related to phenotype variation. A total 551 individuals from 59 families were genotyped with SNP chip and used in genome-wide linkage analysis. From single-point linkage analyses, we confirmed the known 5q31 region for TGFBI gene, and selected novel nine candidate loci for CGD2. In simulation analysis, the only 3q26.3 region including neuroligin 1 gene (NLGN1) was supported by empirical statistic significance. To investigate the effect of genetic heterogeneity in linkage analysis, we classified CGD2 families into two subgroups. Although we could not find a significant evidence for correlation between the 3q26.3 region and CGD2 phenotypes, this first genome-wide analysis with CGD2 families in Korea has a very important value for offering insights in genetics of CGD2. In addition, the co-segregating loci with CGD2 including 3q26.3 would be a good target for further study to understand the pathophysiology of CGD2.
Cell Adhesion Molecules, Neuronal/genetics ; Chromosomes, Human, Pair 3/*genetics ; Chromosomes, Human, Pair 5/*genetics ; Computer Simulation ; Corneal Dystrophies, Hereditary/*genetics ; Female ; Genetic Linkage ; *Genetic Loci ; *Genome-Wide Association Study ; Genotype ; Humans ; Male ; Models, Genetic ; Polymorphism, Single Nucleotide ; Transforming Growth Factor beta1/genetics

A 70-year old man presented with postprandial upper abdominal pain of two months duration, accompanied by indigestion, weight loss, and anorexia. There was no abnormality noted in the lab results. Abdominal CT showed a 3-cm round cystic mass in the tail of the pancreas. A distal pancreatectomy was done. The patient was discharged in 9 days. The cystic wall was composed of a keratinizing squamous epithelium surrounded by subepithelial, dense lymphoid tissue. Some clusters of the sebaceous gland were noted but there was no sweat gland or hair follicle. These findings were consistent with a lymphoepiethelial cyst with sebaceous differentiation. The patient was followed up for 12 months post operatively, and no recurrence was noted.
Abdominal Pain ; Aged ; Anorexia ; Dermoid Cyst* ; Dyspepsia ; Epithelium ; Hair Follicle ; Humans ; Lymphoid Tissue ; Pancreas* ; Pancreatectomy ; Pancreatic Neoplasms ; Recurrence ; Sebaceous Glands ; Sweat Glands ; Tomography, X-Ray Computed ; Weight Loss

A 70-year old man presented with postprandial upper abdominal pain of two months duration, accompanied by indigestion, weight loss, and anorexia. There was no abnormality noted in the lab results. Abdominal CT showed a 3-cm round cystic mass in the tail of the pancreas. A distal pancreatectomy was done. The patient was discharged in 9 days. The cystic wall was composed of a keratinizing squamous epithelium surrounded by subepithelial, dense lymphoid tissue. Some clusters of the sebaceous gland were noted but there was no sweat gland or hair follicle. These findings were consistent with a lymphoepiethelial cyst with sebaceous differentiation. The patient was followed up for 12 months post operatively, and no recurrence was noted.
Abdominal Pain ; Aged ; Anorexia ; Dermoid Cyst* ; Dyspepsia ; Epithelium ; Hair Follicle ; Humans ; Lymphoid Tissue ; Pancreas* ; Pancreatectomy ; Pancreatic Neoplasms ; Recurrence ; Sebaceous Glands ; Sweat Glands ; Tomography, X-Ray Computed ; Weight Loss

Human gut microbial community is playing a critical role in human health and associated with different human disease. In parallel, probiotics, antibiotics, and antipyretic analgesics (AAs) were developed to improve human health or cure human diseases. We therefore examined how probiotics, antibiotics, and AAs influence to the gut microbiota. Three independent case/control studies were designed from the cross-sectional cohort data of 1,463 healthy Koreans. The composition of the gut microbiota in each case and control group was determined via 16S ribosomal RNA Illumina next-generation sequencing. The correlation between microbial taxa and the consumption of each drug was tested using zero-inflated Gaussian mixture models, with covariate adjustment of age, sex, and body mass index (BMI). Probiotics, antibiotics, and AAs consumption yielded the significant differences in the gut microbiota, represented the lower abundance of Megasphaera in probiotics, the higher abundance of Fusobacteria in antibiotics, and the higher abundance of Butyrivibrio and Verrucomicrobia in AAs, compared to each control group. The reduction of Erysipelotrichaceae family was common in three drugs consumption.
Analgesics* ; Anti-Bacterial Agents* ; Body Mass Index ; Butyrivibrio ; Cohort Studies ; Fusobacteria ; Gastrointestinal Microbiome* ; Humans ; Megasphaera ; Probiotics* ; RNA, Ribosomal, 16S ; Verrucomicrobia

PURPOSE: To evaluate the efficacy and safety of vinorelbine and carboplatin in advanced non- small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Between August 1998 and July 1999, 25 patients were enrolled. The median age was 68 (range, 46~77) years and male:female ratio was 23:2. Two patients had stage IIIa, 15 had stage IIIb and 8 had stage IV. Sixteen patients had ECOG performance status of 0 or 1 and 9 had 2 or 3. Sixteen patients had squamous cell carcinoma, 8 had adenocarcinoma and 1 had undifferentiated NSCLC. Treatment consists of intravenous carboplatin 400 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1 and 8. The treatment was repeated every 28 days. RESULTS: Twenty-three of 25 patients were evaluable. Partial response were observed in 11 patients. The overall response rate was 48% (95% confidence interval: 27~69%) and the median response duration was 19 (range 7 ~44 ) weeks. The median survival of 25 patients was 52 (range 3~53 ) weeks. Toxicities were evaluated by WHO criteria. During a total of 108 cycles, granulocytopenia worse than WHO grade 3 occurred in 2%, thrombocytopenia in 4% and anemia in 10%, respectively. Treatment-related death occurred in 1 patient due to sepsis during cytopenic period. Non-hematologic toxicity was minor and easily controlled. CONCLUSION: A combination chemotherapy of intravenous vinorelbine and carboplatin has relatively high activity with acceptable toxicities in patients with advanced NSCLC.
Adenocarcinoma ; Agranulocytosis ; Anemia ; Carboplatin* ; Carcinoma, Non-Small-Cell Lung* ; Carcinoma, Squamous Cell ; Drug Therapy ; Drug Therapy, Combination ; Humans ; Lung Neoplasms ; Sepsis ; Thrombocytopenia