The MHC class II transactivator (CIITA) is the master transcriptional regulator of genes involved in MHC class II restricted antigen presentation. Previously we suggested another role of CIITA in Th1/Th2 balance by demonstrating that forced expression of CIITA in murine T cells repressed Th1 immunity both in vitro and in vivo. However, the results were contradictory to the report that CIITA functioned to suppress the production of Th2 cytokine by CD4+T cells in CIITA deficient mice. In this study, we investigated the influence of constitutive expression of CIITA in T cells on Th2 immune response in vivo using murine experimental colitis model. In the dextran sodium sulfate-induced acute colitis, a disease involving innate immunity, CIITA transgenic mice and wild type control mice showed similar progression of the disease. However, the development of oxazolone-induced colitis, a colitis mediated by predominantly Th2 immune response, was aggravated in CIITA-transgenic mice. And, CD4+T cells from the mesenteric lymph node of CIITA-transgenic mice treated with oxazolone exhibited a high level of IL-4 secretion. Together, these data demonstrate that constitutive expression of CIITA in T cells skews immune response to Th2, resulting in aggravation of Th2-mediated colitis in vivo.
Trans-Activators/*physiology ; Th2 Cells/*immunology ; T-Lymphocytes/*metabolism ; Oxazolone/pharmacology ; Nuclear Proteins/*physiology ; Mice, Transgenic ; Mice, Inbred C57BL ; Mice ; Interleukin-4/biosynthesis ; Colitis/*etiology ; Animals

Objectives: The effectiveness of drugs currently used in medication, which is important in the treatment of alcohol use disorders, is limited. Recently, ondansetron which acts as 5-HT3 receptor antagonist, has been studied and proved possibility as new medication for alcohol use disorder. Meanwhile, there are studies supporting that 5-HT1A receptors are related to addictive behavior. Considering those studies, we expect that vortioxetine, which acts as both 5-HT3 receptor antagonist and 5-HT1A receptor agonist, may be effective in treatment of alcohol use disorder. The purpose of this study is to examine the effect of vortioxetine on alcohol intake of C57BL/6 mice. Methods: In this study C57BL/6 mice were randomly assigned to normal saline group, vortioxetine 10 mg/kg group and vortioxetine 1 mg/kg group. To study effect of vortioxetine on alcohol, water, food intake and body weight of mice, we administered each medication for 14 days. Results: The overall alcohol intake was different between the three groups (PGroup=0.021), and alcohol intake in vortioxetine 10 mg/kg group was significantly lower than one in placebo group. Change across time points (PTime<0.001) and the interaction between group and time (PGroup×Time =0.016) were also significant. However, there were no significant differences between the three groups in water, food intake and body weight. Conclusions These results indicated that administration of high dose vortioxetine reduced alcohol intake of mice.Therefore, it is necessary to conduct clinical studies to examine the effectiveness of vortioxetine as a new treatment for alcohol use disorder.

PURPOSE: To investigate the relationship between MUC expression and clinicopathologic factors in advanced gastric cancer.METHODS: A total of 237 tumor specimens were assessed for MUC expression by immunohistochemistry. The clinicopathologic factors were investigated with MUC1, MUC2, MUC5AC, and MUC6.RESULTS: MUC1, MUC2, MUC5AC, and MUC6 expression was identified in 148 of 237 (62.4%), 141 of 237 (59.5%), 186 of 237 (78.5%), and 146 of 237 (61.6%) specimens, respectively. MUC1 expression was correlated with age, human epidermal growth factor receptor 2 (HER2) status, lymphatic invasion, Lauren classification and histology. Further multivariate logistic regression analysis revealed a significant correlation between MUC1expression and lymphatic invasion, diffuse type of Lauren classification. MUC5AC expression was correlated with HER2 status, Lauren classification and histology. Further multivariate logistic regression analysis revealed a significant correlation between MUC5AC expression and HER2 status, diffuse and mixed type of Lauren classification. MUC2 and MUC6 expression were not correlated with clinicopathologic factors. The patients of MUC1 expression had poorer survival than those without MUC1 expression, but MUC2, MUC5AC or MUC6 were not related to survival. In an additional multivariate analysis that used the Cox proportional hazards model, MUC1 expression was not significantly correlated with patient survival independent of age, N-stage, and venous invasion.CONCLUSION: When each of these four MUCs expression is evaluated, in light of clinicopathologic factors, MUC1 expression may be considered as a prognostic factor in patients with advanced gastric cancer. Therefore, careful follow-up may be necessary because the prognosis is poor when MUC1 expression is present.
Classification ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Logistic Models ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Receptor, Epidermal Growth Factor ; Stomach Neoplasms

OBJECTIVES: The American Diabetes Association (ADA) has recently recommended the HbA1c assay as one of four options for making the diagnosis of diabetes mellitus, with a cut-point of > or =6.5%. We compared the HbA1c assay and the fasting plasma glucose level for making the diagnosis of diabetes among Korean adults. METHODS: We analyzed 8710 adults (age 45-74 years), who were not diagnosed as having diabetes mellitus, from the Namwon study population. A fasting plasma glucose level of > or =126 mg/dL and an A1c of > or =6.5% were used for the diagnosis of diabetes. The kappa index of agreement was calculated to measure the agreement between the diagnosis based on the fasting plasma glucose level and the HbA1c. RESULTS: The kappa index of agreement between the fasting plasma glucose level and HbA1c was 0.50. CONCLUSIONS: The agreement between the fasting plasma glucose and HbA1c for the diagnosis of diabetes was moderate for Korean adults.
Adult ; Aged ; Aged, 80 and over ; Anemia, Aplastic/*diagnosis ; Child ; Child, Preschool ; Diagnosis, Differential ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Platelet Count/*standards ; Purpura, Thrombocytopenic, Idiopathic/*diagnosis ; Reference Values ; Reproducibility of Results ; Sex Factors

Carcinosarcoma is a rare malignant, biphasic tumor comprised of carcinoma and sarcoma components. In the gastrointestinal tract, carcinosarcoma is most frequently seen in the esophagus and rarely in the stomach. We report a 51-year-old female patient with 2-month-history of epigastric pain and dyspepsia. Endoscopic finding revealed a huge ulcerative lesion that infiltrated from the antrum to the mid-body. An endoscopically taken biopsy revealed poorly differentiated malignant round cell neoplasm. After the palliative subtotal gastrectomy, immunohistochemical studies showed two positive reactions for the epithelial marker and mesenchymal marker. Based on the above findings, the patient was diagnosed with gastric carcinosarcoma. The immunohistochemical analysis is a critical method in making an accurate diagnosis of carcinosarcoma.
Biopsy ; Carcinosarcoma ; Dyspepsia ; Esophagus ; Female ; Gastrectomy ; Gastrointestinal Tract ; Humans ; Immunohistochemistry ; Sarcoma ; Stomach ; Ulcer

PURPOSE: To describe the CT findings and charicteristic clinical manifestation of primary malignant pulmonarymesenchymal tumors. MATERIALS AND METHODS: This study involved nine histopathologically proven cases of malignantprimary pulmonary mesenchymal tumors, as follows : MFH(n=2), leiomyosarcoma(n=2), pulmonary blastoma(n=1),neurogenic sarcoma(n=1), rhabdomyosarcoma(n=1), liposarcoma(n=1) and hemangiopericytoma(n=1). Two patients weremale and seven were female; their median age was 45. We retrospectively analyzed tumor size, location,characteristic of the peripheral margin, relationship to airways, and whether there was distal atelectasis orobstructive pneumonitis and lymph node involvement. We also reviewed distant metastasis, tumor growth rate and theinterval between surgery and recurrence, as seen on follow-up CT scans(n=6). RESULTS: Lesions were located at theright upper (n=2), right middle (n=1), right lower (n=1) and left lower lobe (n=2); in three cases, the whole leftlung (left upper + left lower lobe) was involved. CT findings showed that in all cases, the largest diameter ofmasses ranged from 3 to 15 cm; a well-demarcated margin was seen (smooth in eight cases, psiculated in one) andthis was well enhanced(inhomogeneous in six cases, homogeneous in three). In six cases, masses encircled ordisplaced the peritumoral small bronchus, and in five cases, were located in the peripheral lung field. In fourpatients who underwent endobronchoscopy, no endobronchial lesions were present, and in six cases scans initial CTscans showed no lymph-node involvement. In two cases, mass size doubled within one month. On initial diagnosis,distant metastasis was seen in seven cases, and in three, recurrent lesions were detected within postoperative sixmonths. CONCLUSION: If in the differential diagnosis of lung cancer, a mass seen on CT images is well demarcated,large, peripheral, inhomogeneously enhanced, encircles or displaces the peritumoral small bronchus, shows earlydistant metastasis, is high locally invasive, and recurs early with relative sparing of the lymph nodes, thepossibility of primary malignant pulmonary mesenchymal tumor shouldbe considered.
Bronchi ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Lung ; Lung Neoplasms ; Lymph Nodes ; Neoplasm Metastasis ; Pneumonia ; Pulmonary Atelectasis ; Recurrence ; Retrospective Studies

We examined the effect of class II transactivator (CIITA) down-modulation on allograft rejection. To inhibit the function of CIITA, we constructed a series of CIITA mutants and found one exhibiting the dominant-negative effect on the regulation of major histocompatibility complex (MHC) class II expression. To test whether the CIITA dominant-negative mutant reduces immunogenecity, CIITA-transfected melanoma cells were injected into allogeneic host and assessed for immune evading activity against host immune cells. We demonstrated that the CIITA dominant-negative mutant allowed tumor nodules to develop earlier in the lung than control by this tumor challenge study. Furthermore, skin grafts deficient for CIITA also survived longer than wild-type in allogeneic hosts. Both the tumor challenge and skin graft studies suggest the inhibition of CIITA molecules in donor tissue would be beneficial to the control of allo-response.
Transplantation, Homologous ; Transfection ; Trans-Activators/genetics/*immunology/metabolism ; Trans-Activation (Genetics)/genetics/immunology ; Skin Transplantation ; Nuclear Proteins/genetics/*immunology/metabolism ; Mutation ; Mice, Transgenic ; Mice, Knockout ; Mice, Inbred C57BL ; Mice, Inbred BALB C ; Mice ; Melanoma, Experimental/genetics/immunology/pathology ; Male ; Interferon Type II/pharmacology ; Humans ; Histocompatibility Antigens Class II/genetics/*immunology/metabolism ; Graft Survival/genetics/immunology ; Graft Rejection/genetics/*immunology ; Genes, MHC Class II/genetics/immunology ; Flow Cytometry ; DNA, Complementary/genetics ; Cell Proliferation/drug effects ; Cell Line, Tumor ; Animals

BACKGROUND/AIMS: This study assessed the antibiotic resistance organisms isolated from the blood and bile of acute cholangitis and evaluated risk factors associated with them and their impact on clinical outcomes. METHODS: The identities and antibiotic resistance profiles of bacteria isolated from 433 cases of acute cholangitis from 346 patients were analyzed. Risk factors and the outcomes of patients infected with them were assessed. RESULTS: Microorganisms were isolated from 266 of 419 blood cultures and 256 of 260 bile cultures. Isolates from bile and blood were identical in 71% of the cases. A total of 20 extended spectrum-beta-lactamase (ESBL)-producers and 4 carbapenemase-producing organisms were isolated from blood, and 34 ESBL-producers and 13 carbapenemase-producers were isolated from bile. Sixty-four (14.8%) cases were infected with any one of these bacteria isolated from blood or bile. Risk factors associated with them in blood were nosocomial infection and prior biliary intervention. In bile, indwelling biliary device was a risk factor associated with them. Antibiotic-resistant bacteria were associated with mortality, independent of other prognostic factors. CONCLUSIONS: ESBL or carbapenemase-producing bacteria were frequently isolated in acute cholangitis patients especially with prior biliary intervention and nosocomial infection. Isolation of antibiotic-resistant bacteria was an independent risk factor of mortality.
Bacteria ; Bacterial Proteins ; beta-Lactamases ; Bile ; Cholangitis ; Cross Infection ; Drug Resistance, Microbial ; Humans ; Risk Factors

PURPOSE: We aimed to determine whether Autism Spectrum Disorder (ASD) would show neural abnormality of the social reward system using functional MRI (fMRI). MATERIALS AND METHODS: 27 ASDs and 12 typically developing controls (TDCs) participated in this study. The social reward task was developed, and all participants performed the task during fMRI scanning. RESULTS: ASDs and TDCs with a social reward learning effect were selected on the basis of behavior data. We found significant differences in brain activation between the ASDs and TDCs showing a social reward learning effect. Compared with the TDCs, the ASDs showed reduced activity in the right dorsolateral prefrontal cortex, right orbitofrontal cortex, right parietal lobe, and occipital lobe; however, they showed increased activity in the right parahippocampal gyrus and superior temporal gyrus. CONCLUSION: These findings suggest that there might be neural abnormality of the social reward learning system of ASDs. Although this study has several potential limitations, it presents novel findings in the different neural mechanisms of social reward learning in children with ASD and a possible useful biomarker of high-functioning ASDs.
Brain/*physiopathology ; Brain Mapping ; Case-Control Studies ; Child ; Child Development Disorders, Pervasive/*physiopathology ; Female ; Functional Neuroimaging/*methods ; Humans ; Magnetic Resonance Imaging/methods ; Male ; Neural Pathways/*physiopathology ; Psychiatric Status Rating Scales ; Republic of Korea ; *Reward ; *Social Behavior

PURPOSE: This study was conducted to evaluate the systemic inflammatory response in colorectal cancer patients, and to estimate the usefulness of the Glasgow prognostic score (GPS) as a prognostic factor. METHODS: Patients with biopsy-proven colorectal adenocarcinoma who were operated between April 2005 and December 2008 were enrolled in this study. The GPS was estimated based on the measurement of CRP and serum albumin level. The GPS was compared with other clinicopathological factors. Univariate and multivariate analyses were performed to evaluate the factors affecting cancer-specific survival. RESULTS: GPS was significantly higher in patients with anemia, thrombocytosis, a high neutrophil to lymphocyte ratio, tumor of the colon, and large tumor. Patient age, gender, serum CEA level, tumor gross appearance, TNM stage, and tumor differentiation were not related with the GPS. In univariate analysis, hemoglobin, CEA, gross appearance of tumor, TNM stage, tumor differentiation, and GPS were associated with cancer-specific survival. In multivariate analysis, TNM stage (III or IV : I or II; hazard ratio [HR], 12.322; P = 0.015), tumor differentiation (poorly differentiated : well or moderately differentiated; HR, 3.112; P = 0.021), and GPS (GPS 2 : GPS 0 or 1; HR, 5.168; P = 0.003) were identified as independent prognostic factors in colorectal cancer. CONCLUSION: Our study showed that the GPS was an independent variable from tumor stage and a good and convenient prognostic factor in colorectal cancer patients.
Adenocarcinoma ; Anemia ; Colon ; Colorectal Neoplasms* ; Humans ; Inflammation ; Lymphocytes ; Multivariate Analysis ; Neutrophils ; Prognosis ; Serum Albumin ; Thrombocytosis