In 2016, novel H5N6 highly pathogenic avian influenza virus emerged in Korea. During the outbreak, the virus caused the largest culling, especially in brown chicken lines. We determined the pathogenicity and transmissibility of the virus in 2 white chicken lines of the specific pathogen-free chickens, broilers and brown chicken line of Korean native chicken (KNC). A KNC had a longer virus shedding period and longer mean death time than others. Our study showed that this characteristic in the KNC might have contributed to a farm-to-farm transmission of the brown chicken farms.
Agriculture ; Animals ; Chickens ; Influenza in Birds ; Korea ; Virulence ; Virus Shedding

PURPOSE: Immune checkpoint blockades (ICB) have been successful in gastric cancer (GC). However, the majority of unselected patients with GC fail to respond to ICB. It is crucial to identify precise biomarkers to predict response to ICB. METHODS: Gene expression profiling of formalin-fixed and paraffin-embedded GC tissues from 25 patients treated with ICB (pembrolizumab) targeting programmed cell death protein 1 (PD-1) was performed using NanoString (NanoString Technologies). For development of a gene signature to predict response to ICB, differential gene expression analysis with linear regression modeling was performed with area under the curve packages in R. RESULTS: From the analysis, 10 genes were differentially expressed between patients with response and no response to ICB (P<0.01). To identify a biomarker predicting response to ICB, four genes were selected based on |log₂ (foldchange)|≥1. After calculating the IMmunotherapy Against GastrIc Cancer (IMAGiC) score, patients were divided into two groups: to be responder and to be non-responder, according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. The IMAGiC score was significantly associated with RECIST groups (P=0.0057), Epstein-Barr virus (P=0.048), and tumor mutational load (P=0.023); however, was not significantly correlated with microsatellite instability status (P=0.14) and programmed death ligand 1 (PD-L1) expression (P=0.095). To reproduce IMAGiC with different technology, we retested the results with a quantitative real-time polymerase chain reaction (qRT-PCR) method, and the precision of reproduction of 87.5%. In validation cohort with 17 samples from the ongoing trial with nivolumab, the precision of IMAGiC qRT-PCR was 100%. CONCLUSION Our identified gene signatures and proposed IMAGiC model for predicting response to pembrolizumab in patients with GC showed validity.

PURPOSE: The purpose of this study was to assess current levels of awareness of clinical trials (CTs), perceptions regarding their benefits and willingness to participate to CTs among Korean cancer patients. MATERIALS AND METHODS: From December 2012 to August 2015, we distributed questionnaires to cancer patients receiving systemic anti-cancer therapy at Seoul National University Hospital, Seoul, Korea. RESULTS: A total of 397 out of 520 requested patients (76.3%) responded to the survey. Among the 397 patients, 62.5% were female and the median age was 52 years. Overall, 97.4% (387/397) answered that they have at least heard of CTs. When asked about their level of awareness, 23.8% (92/387) answered that they could more than roughly explain about CTs. The average visual analogue scale score of CT benefit in all patients was 6.43 (standard deviation, 2.20). Patients who were only familiar with the term without detailed knowledge of the contents had the least expectation of benefit from CTs (p=0.015). When asked about their willingness to participate in CTs, 56.7% (225/397) answered positively. Patients with higher levels of awareness of CTs showed higher willingness to participate (p < 0.001). Heavily treated patients and patients with previous experience regarding CTs also showed a higher willingness to participate (p < 0.001). The perceived benefit of CTs was higher in the group willing to participate (p=0.026). CONCLUSION: The patient’s level of awareness regarding CTs was positively related to the positive perception and willingness to participate. Although the general awareness of CTs was high, a relatively large proportion of patients did not have accurate knowledge; therefore, proper and accurate patient education is necessary.
Female ; Humans ; Korea ; Patient Education as Topic ; Seoul ; Volition

BACKGROUND AND OBJECTIVES: Excessive catecholamine causes the alteration of cardiac structure and function. This study evaluated if there is any difference in left ventricular hypertrophy (LVH) and QTc prolongation in conditions with pheochromocytoma and Takotsubo cardiomyopathy (TC). SUBJECTS AND METHODS: We reviewed the medical records of 20 pheochromocytoma patients for cardiovascular events prior to diagnosis. The patient's clinical history and electrocardiographic and echocardiographic findings were compared to those of 20 patients diagnosed with TC. RESULTS: Left ventricular (LV) mass index (133.3+/-37.8 vs. 113.3+/-17.3, p=0.031), relative wall thickness (0.55+/-0.15 vs. 0.47+/-0.07, p=032) and elevated blood pressure (BP) were more prominent in pheochromocytoma compared to TC. The mean creatinine kinase-MB elevation, reduced LV systolic function and ST segment changes were more prominent in the TC group compared to the pheochromocytoma groups (all p<0.05). The prevalence of QTc prolongation was high in patients with pheochromocytoma (45%) and TC (55%), and TC male patients appeared to have a more prolonged QTc interval. Urine epinephrine (r=0.844, p=0.004) and norepinephrine level (r=0.782, p=0.013) were significantly correlated with LV mass index, and the predictors for the QTc prolongation were male gender and the presence of LVH. CONCLUSION: A prolonged QTc was prominent in pheochromocytoma and TC regardless of BP and systolic LV function, and LVH was more prominent in pheochromocytoma than TC.
Blood Pressure ; Catecholamines ; Diagnosis ; Echocardiography ; Electrocardiography ; Epinephrine ; Humans ; Hypertrophy, Left Ventricular* ; Long QT Syndrome ; Male ; Medical Records ; Norepinephrine ; Pheochromocytoma* ; Prevalence ; Takotsubo Cardiomyopathy*

BACKGROUND AND OBJECTIVES: Carotid intima-media thickness (IMT) is associated with chronic inflammation, and C-reactive protein (CRP) level is elevated in patients with atrial fibrillation (AF). We investigated the impacts of CRP and AF on carotid atherosclerosis and ischemic stroke in patients with suspected ischemic cerebrovascular disease. SUBJECTS AND METHODS: One-hundred forty patients (78 males) with suspected ischemic cerebrovascular disease underwent carotid ultrasonography. The mean common carotid artery IMT, mean internal carotid artery (ICA) IMT, and plaque score were measured. Patients were divided into four groups according to the presence of AF and elevated CRP level {n=46 for AF(-)CRP(-), n=38 for AF(-)CRP(+), n=43 for AF(+)CRP(-), and n=13 for AF(+)CRP(+)}. RESULTS: Common carotid artery IMT was significantly higher in the AF(-)CRP(+) (0.98+/-0.51 mm) and AF(+)CRP(+) (0.96+/-0.27 mm) groups compared to the AF(-)CRP(-) (0.80+/-0.32 mm) and AF(+)CRP(-) (0.77+/-0.19 mm) groups (p=0.027). Although there was no significant difference in mean ICA IMT among the groups, plaque score was the highest in the AF(+)CRP(+) (4.18+/-3.84 mm) group, followed by AF(-)CRP(+) (3.87+/-2.78 mm), AF(+)CRP(-) (1.34+/-2.61 mm), and AF(-)CRP(-) (1.17+/-2.02 mm) (p<0.001). The AF(+)CRP(+) group showed significantly higher incidence of ischemic stroke than the other groups (all p<0.05). Binary logistic regression analysis showed that age {odds ratio (OR)=1.033, p=0.001}, elevated CRP (OR=3.884, p=0.001), and the presence of AF (OR=1.375, p=0.018) were significantly correlated with incidence of ischemic stroke. CONCLUSION: Elevated plasma CRP concentration may be a reliable surrogate marker for predicting carotid atherosclerosis in patients with AF, which may be related to increased risk of ischemic stroke.
Atrial Fibrillation* ; Biomarkers ; C-Reactive Protein* ; Carotid Artery Diseases* ; Carotid Artery, Common ; Carotid Artery, Internal ; Carotid Intima-Media Thickness ; Cohort Studies* ; Humans ; Incidence ; Inflammation ; Logistic Models ; Plasma ; Retrospective Studies* ; Stroke* ; Ultrasonography

BACKGROUND/AIMS: It is difficult to clinically and endoscopically differentiate intestinal tuberculosis (ITB) and Crohn's disease (CD). The aim of this study was to evaluate the usefulness of in vitro interferon-gamma (INF-gamma) assay for differential diagnosis between ITB and CD. METHODS: Sixty patients for whom differential diagnosis between ITB and CD was difficult were enrolled between January 2007 and January 2009. The INF-gamma-producing T-cell response to early secreted antigenic target 6 and culture filtrate protein 10 were measured by T-SPOT.TB blood test in vitro. We evaluated the usefulness of T-SPOT.TB blood test by comparing its results with the final diagnosis. RESULTS: Twenty and forty patients were revealed to be positive and negative in T-SPOT.TB blood test, respectively. Of the 20 patients found to be positive, 12 patients (60%) were finally diagnosed as ITB, 6 patients as CD, and 2 patients as Behcet's enterocolitis. Of the 40 patients with negative results, 38 patients (95%) were diagnosed as CD; one as Behcet's enterocolitis; one as nonspecific colitis; none as ITB. The sensitivity and specificity of T-SPOT.TB blood test for ITB were 100% and 83.3%, respectively. Positive and negative predictive values of T-SPOT.TB blood test for ITB were 60.0% and 100%, respectively. CONCLUSIONS: When differential diagnosis between ITB and CD is difficult, T-SPOT.TB blood test may be a helpful and rapid diagnostic tool to exclude ITB. Prospective large-scaled studies are required for further evaluation of the usefulness of T-SPOT.TB blood test for differential diagnosis between ITB and CD.
Adolescent ; Adult ; Aged ; Crohn Disease/*diagnosis ; Diagnosis, Differential ; Female ; Humans ; Interferon-gamma/*blood ; Male ; Middle Aged ; Polymerase Chain Reaction ; Reagent Kits, Diagnostic ; Retrospective Studies ; Tuberculosis, Gastrointestinal/*diagnosis

BACKGROUND: Rescently, the immunotherapy against infectious disease and cancer is being actively studied, and high yield of pure CD14+ monocytes is a key of concern. In this study, we optimized the percoll gradient method to increase the purity and yield of monocytes from peripheral mononuclear cells. METHODS: We separated mononuclear cells (MNC) from healthy donors, and monocytes from MNC were separated with the various density of percoll gradient. After centrifugation, we determined the most efficient density of the percoll gradient to get the highest yield and purity of monocytes. We also obtained monocytes by the plastic absorption method. Monocytes were differentiated into dendritic cells (DC) and the efficacy of differentiation to DC is confirmed and compared by morphological characteristics and using a flowcytometer. RESULTS: The purity of monocytes was 51.3+/-8.3% by the 35% percoll gradient method and the purity was improved to 82.9+/-4.2% with 100% of yield by repeating the same method. Therefore, the yield of mature dendritic cells was 3.6+/-0.9% of the total input MNC by the 35% percoll repetition method, which was 1.7 times higher than the plastic adherent method (2.1+/-0.5%). CONCLUSION: This study shows a cost-effective method to isolate CD14+ monocytes and these cells demonstrate high differentiation rate to DC. This process will be valuable for obtaining a sufficient number of DC.
Absorption ; Centrifugation ; Communicable Diseases ; Dendritic Cells ; Humans ; Immunotherapy ; Monocytes ; Plastics ; Povidone ; Silicon Dioxide ; Tissue Donors

Various cell types in higher multicellular organisms are genetically homogenous, but are functionally and morphologically heterogeneous due to the differential expression of genes during development, which appears to be controlled by epigenetic mechanisms. However, the exact molecular mechanisms that govern the tissue-specific gene expression are poorly understood. Here, we show that dynamic changes in histone modifications and DNA methylation in the upstream coding region of a gene containing the transcription initiation site determine the tissue-specific gene expression pattern. The tissue-specific expression of the transgene correlated with DNA demethylation at specific CpG sites as well as significant changes in histone modifications from a low ratio of methylated H3- lysine 4 or acetylated H3-lysine 9, 14 to acetylated H4 to higher ratios. Based on the programmed status of transgene silenced in cloned mammalian ear-derived fibroblasts, the transgene could be reprogrammed by change of histone modification and DNA methylation by inhibiting both histone deacetylase and DNA methylation, resulting in high expression of the transgene. These findings indicate that dynamic change of histone modification and DNA methylation is potentially important in the establishment and maintenance of tissue-specific gene expression.
Transgenes/*genetics ; Swine ; Organ Specificity/genetics ; Methylation ; Lysine/*metabolism ; Histones/*metabolism ; Histone Deacetylases/metabolism ; Gene Silencing ; *Gene Expression ; Fibroblasts ; Ear ; *DNA Methylation ; Cells, Cultured ; Animals, Genetically Modified ; Animals ; Acetylation