PURPOSE: The role of IL28B gene variants and expression in hepatitis B virus (HBV) infections are not well understood. Here, we evaluated whether IL28B gene expression and rs12979860 variations are associated with HBV outcomes. MATERIALS AND METHODS: IL28B genetic variations (rs12979860) were genotyped by pyrosequencing of DNA samples from 137 individuals with chronic HBV infection [50 inactive carriers (IC), 34 chronic hepatitis B (CHB), 27 cirrhosis, 26 hepatocellular carcinoma (HCC)], and 19 healthy controls. IL28A/B mRNA expression in peripheral blood mononuclear cells was determined by qRT-PCR, and serum IL28B protein was measured by ELISA. RESULTS: Patients with IL28B C/C genotype had greater IL28A/B mRNA expression and higher IL28B protein levels than C/T patients. Within the various disease stages, compared to IC and healthy controls, IL28B expression was reduced in the CHB, cirrhosis, and HCC cohorts (CHB vs. IC, p=0.02; cirrhosis vs. IC, p=0.01; HCC vs. IC, p=0.001; CHB vs. controls, p<0.01; cirrhosis vs. controls, p<0.01; HCC vs. controls, p<0.01). When stratified with respect to serum HBV markers in the IC and CHB cohorts, IL28B mRNA and protein levels were higher in HBeAg-positive than negative individuals (p=0.01). Logistic regression analysis revealed that factors associated with high IL28B protein levels were C/C versus C/T genotype [p=0.016, odds ratio (OR)=0.25, 95% confidence interval (CI)=0.08-0.78], high alanine aminotransferase values (p<0.001, OR=8.02, 95% CI=2.64-24.4), and the IC stage of HBV infection (p<0.001). CONCLUSION: Our data suggest that IL28B genetic variations may play an important role in long-term development of disease in chronic HBV infections.
Adult ; Aged ; Alanine Transaminase/blood ; Asian Continental Ancestry Group/*genetics ; Biological Markers/blood ; Carcinoma, Hepatocellular/genetics ; Case-Control Studies ; China ; DNA, Viral/blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Genotype ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/ethnology/*genetics/immunology/*virology ; Humans ; Interleukins/blood/*genetics/metabolism ; Leukocytes, Mononuclear ; Liver Cirrhosis/blood ; Liver Neoplasms/genetics ; Male ; Middle Aged ; RNA, Messenger/*genetics ; Reverse Transcriptase Polymerase Chain Reaction

BACKGROUND/AIMS: The aim was to determine which of three sets of metabolic syndrome (MetS) criteria (International Diabetes Federation [IDF], National Cholesterol Education Program Adult Treatment Panel III [ATP III], and European Group for the Study of Insulin Resistance [EGIR]) best predicts the coronary artery calcification (CAC) score in a cross-sectional study. This has not been evaluated in previous studies. METHODS: A total of 24,060 subjects were screened for CAC by multi-detector computed tomography. The presence of CAC was defined as a CAC score > 0. The odds ratio for the presence of CAC was analyzed for three different sets of MetS criteria and according to number of MetS components. RESULTS: CAC was observed in 12.6% (3,037) of the subjects. Patients with MetS, as defined by the IDF, ATP III, and EGIR criteria, had a CAC rate of 23.0%, 25.1%, and 29.5%, respectively (p < 0.001). Comparisons of C statistics for multivariate regression models revealed no significant difference among the three sets of criteria. After adjustment for risk factors, the ATP III criteria produced a slightly higher odds ratio for CAC compared with the other criteria, but this difference was not significant. The risk factor-adjusted odds ratio for the presence of CAC increased from 1 to 1.679 as the number of MetS components defined by ATP III increased from 0 to > or = 3 (p for trend < 0.001). CONCLUSIONS: The presence of MetS was associated with the presence of CAC. There was no significant difference among the three sets of MetS criteria in terms of the ability to predict CAC. An increase in the number of MetS components was associated with an increased odds of CAC.
Adult ; Asymptomatic Diseases ; Biological Markers/blood ; Calcium/*analysis ; Coronary Angiography/methods ; Coronary Artery Disease/blood/*epidemiology/radiography ; Coronary Vessels/*chemistry/radiography ; Cross-Sectional Studies ; Female ; Humans ; Male ; Metabolic Syndrome X/blood/diagnosis/*epidemiology ; Middle Aged ; Multidetector Computed Tomography ; Multivariate Analysis ; Odds Ratio ; Predictive Value of Tests ; Prevalence ; Republic of Korea/epidemiology ; Risk Assessment ; Risk Factors ; Vascular Calcification/blood/*epidemiology/metabolism/radiography

Hypoglycemia is a major barrier to achieving the glycemic goal in patients with type 2 diabetes. In particular, severe hypoglycemia, which is defined as an event that requires the assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions, is a serious clinical concern in patients with diabetes. If severe hypoglycemia is not managed promptly, it can be life threatening. Hypoglycemia-associated autonomic failure (HAAF) is the main pathogenic mechanism behind severe hypoglycemia. Defective glucose counter-regulation (altered insulin secretion, glucagon secretion, and an attenuated increase in epinephrine during hypoglycemia) and a lack of awareness regarding hypoglycemia (attenuated sympathoadrenal activity) are common components of HAAF in patients with diabetes. There is considerable evidence that hypoglycemia is an independent risk factor for cardiovascular disease. In addition, hypoglycemia has a significant influence on the quality of life of patients with diabetes. To prevent hypoglycemic events, the setting of glycemic goals should be individualized, particularly in elderly individuals or patients with complicated or advanced type 2 diabetes. Patients at high-risk for the future development of severe hypoglycemia should be selected carefully, and intensive education with reinforcement should be implemented.
Autonomic Nervous System/physiopathology ; Biological Markers/blood ; Blood Glucose/*drug effects/metabolism ; Diabetes Mellitus, Type 2/blood/complications/diagnosis/*drug therapy/physiopathology ; Health Knowledge, Attitudes, Practice ; Humans ; Hypoglycemia/blood/chemically induced/epidemiology/physiopathology/*prevention & control ; Hypoglycemic Agents/*adverse effects ; Incidence ; Patient Education as Topic ; Prevalence ; Prognosis ; Risk Assessment ; Risk Factors

PURPOSE: This study aimed to compare the regulatory T cells in cord blood of appropriate for gestational age (AGA) neonates with those of small for gestational age (SGA) neonates. MATERIALS AND METHODS: Umbilical cord blood was collected upon labor in 108 healthy full-term (between 37 and 41 gestational weeks) neonates, who were born between November 2010 and April 2012. Among them, 77 samples were obtained from AGA neonates, and 31 samples were obtained from SGA neonates. Regulatory T cells and lymphocyte subsets were determined using a flow cytometer. Student's t-test for independent samples was used to compare differences between AGA and SGA neonates. RESULTS: Regulatory T cells in cord blood were increased in the SGA group compared with normal controls (p=0.041). However, cytotoxic T cells in cord blood were significantly decreased in the SGA group compared with normal controls (p=0.007). CONCLUSION: This is the first study to compare the distribution of lymphocyte subsets including regulatory T cells in cord blood between AGA neonates and SGA neonates.
Biological Markers/metabolism ; Female ; Fetal Blood/*immunology ; Gestational Age ; Humans ; Infant, Newborn/*blood ; Infant, Small for Gestational Age/*blood ; Lymphocyte Count ; T-Lymphocytes, Cytotoxic/metabolism ; T-Lymphocytes, Regulatory/*metabolism

No abstract available.
Adult ; Biological Markers/blood ; Female ; Humans ; Mouth Floor ; *Neck/radiography/radionuclide imaging/ultrasonography ; Predictive Value of Tests ; Radiopharmaceuticals/diagnostic use ; Sodium Pertechnetate Tc 99m/diagnostic use ; Thyroid Dysgenesis/blood/*diagnosis/drug therapy ; Thyroid Function Tests ; *Thyroid Gland/drug effects/metabolism/radiography/radionuclide imaging/ultrasonography ; Thyrotropin/blood ; Thyroxine/blood/therapeutic use ; Tomography, X-Ray Computed

No abstract available.
Biopsy ; Blood Glucose/metabolism ; C-Peptide/blood ; Calcium Gluconate/administration & dosage/*diagnostic use ; Female ; Humans ; Immunohistochemistry ; Injections, Intra-Arterial ; Insulin/blood ; Insulinoma/blood/*blood supply/pathology/surgery ; Middle Aged ; Pancreatic Neoplasms/blood/*blood supply/pathology/surgery ; Pancreaticoduodenectomy ; Splenic Artery/*radiography ; *Tomography, X-Ray Computed ; Treatment Outcome ; Tumor Markers, Biological/blood

PURPOSE: The function of regulatory B lymphocytes is known to be abnormal in inflammatory diseases. However, a recent study indicates that IL-10+ B cells seem to be expanded in rheumatoid arthritis (RA). Therefore, the state of IL-10+ B cells in the peripheral blood from RA patients and healthy controls were investigated. MATERIALS AND METHODS: CD19+ cells in peripheral blood mononuclear cells were purified from blood samples of RA patients and age and gender-matched healthy controls, and stimulated with CD40 ligand and CpG for 48 hours. Then, intracellular IL-10 in CD19+ cells was analyzed using flow cytometry. RESULTS: There was no significant difference in the proportion of IL-10+ B cells between 10 RA patients and 10 healthy controls (RA, 0.300+/-0.07 vs. healthy control 0.459+/-0.07, p=0.114). The proportion of induced IL-10+ B cells to total B cells in RA patients was significantly higher than those in controls (RA, 4.44+/-3.44% vs. healthy control 2.44+/-1.64%, p=0.033). However, the proportion of IL-10+ B cells to total B cells correlated negatively with disease activity in RA patients (r=-0.398, p=0.040). Erythrocyte sedimentation rate or C-reactive protein or medication was not associated with the proportion of IL-10+ B cells. CONCLUSION: The proportion of induced IL-10+ B cell increased in RA patients compared to healthy control, however, negatively correlated with disease activity in RA.
Adult ; Aged ; Antigens, CD19/metabolism ; Arthritis, Rheumatoid/blood/*immunology/pathology ; B-Lymphocytes, Regulatory/metabolism/*physiology ; Biological Markers/blood ; Female ; Humans ; Interleukin-10/metabolism ; Male ; Middle Aged ; Severity of Illness Index

BACKGROUND/AIMS: We investigated the efficacy and safety of tenofovir disoproxil fumarate (TDF)-based treatment in chronic hepatitis B (CHB) patients who failed previous antiviral therapies. METHODS: Seventeen patients who failed to achieve virological responses during sequential antiviral treatments were included. The patients were treated with TDF monotherapy (four patients) or a combination of TDF and lamivudine (13 patients) for a median of 42 months. Hepatitis B virus (HBV) DNA and hepatitis B e antigen (HBeAg) were measured, and renal function was also monitored. RESULTS: Prior to TDF therapy, 180 M, 204 I/V/S, 181 T/V, 236 T, and 184 L mutations were detected. After TDF therapy, the median HBV DNA level decreased from 4.6 log10 IU/mL to 2.0 log10 IU/mL and to 1.6 log10 IU/mL at 12 and 24 months, respectively. HBV DNA became undetectable (< or =20 IU/mL) in 14.3%, 41.7%, and 100% of patients after 12, 24, and 48 months of treatment, respectively. HBeAg loss was observed in two patients. Viral breakthrough occurred in five patients who had skipped their medication. No significant changes in renal function were observed. CONCLUSIONS: TDF-based rescue treatment is effective in reducing HBV DNA levels and is safe for patients with CHB who failed prior antiviral treatments. Patients' adherence to medication is related to viral rebound.
Adenine/*analogs & derivatives/therapeutic use ; Adult ; Biological Markers/metabolism ; DNA, Viral/blood ; Drug Resistance, Viral/drug effects ; Drug Therapy, Combination ; Female ; Hepatitis B e Antigens/blood ; Hepatitis B, Chronic/*drug therapy ; Humans ; Lamivudine/*therapeutic use ; Male ; Middle Aged ; Organophosphonates/*therapeutic use ; Reverse Transcriptase Inhibitors/*therapeutic use ; Treatment Outcome

BACKGROUND: Effective treatment and monitoring of tuberculosis (TB) requires biomarkers that can be easily evaluated in blood samples. The aim of this study was to analyze the serum proteome of patients with TB and to identify protein biomarkers for TB. METHODS: Serum samples from 26 TB patients and 31 controls were analyzed by using nano-flow ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry in data-independent mode, and protein and peptide amounts were calculated by using a label-free quantitative approach. The generated data were analyzed by using principal component analysis and partial least squares discriminant analysis, a multivariate statistical method. RESULTS: Of more than 500 proteins identified, alpha-1-antitrypsin was the most discriminative, which was 4.4 times higher in TB patients than in controls. Peptides from alpha-1-antitrypsin and antithrombin III increased in TB patients and showed a high variable importance in the projection scores and coefficient in partial least square discriminant analysis. CONCLUSIONS: Sera from patients with TB had higher alpha-1-antitrypsin levels than sera from control participants. Alpha-1-antitrypsin levels may aid in the diagnosis of TB.
Adult ; Aged ; Antithrombin III/analysis ; Biological Markers/blood ; Chromatography, High Pressure Liquid ; Discriminant Analysis ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Proteome/*analysis ; *Proteomics ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Tuberculosis/*blood/genetics/metabolism ; alpha 1-Antitrypsin/analysis

OBJECTIVE: The purpose of this study was to evaluate the expression of epidermal growth factor-like domain 7 (EGFL7) in epithelial ovarian cancer, and to assess its relevance to clinicopathological characteristics and patients' survival. METHODS: A total of 177 patients with epithelial ovarian cancer were enrolled in the current study. For each patient, a retrospective review of medical records was conducted. Immunohistochemical staining for EGFL7 was performed using tissue microarrays made with paraffin-embedded tissue block. EGFL7 expression levels were graded on a grade of 0 to 3 based on the percentage of positive cancer cells. We analyzed the correlations between the expression of EGFL7 and various clinical parameters, and also analyzed the survival outcome according to the EGFL7 expression. RESULTS: The expression of EGFL7 in ovarian cancer tissues was observed in 98 patients (55.4%). High expression of EGFL7 (grade 2 or 3) was significantly correlated with pathologic type, differentiation, stage, residual tumor after debulking surgery, lymphovascular space involvement, lymph node metastasis, high cancer antigen 125, peritoneal cytology, and ascites. Among these clinicopathologic factors, differentiation was significantly correlated with EGFL7 expression in multivariate analysis (p<0.05). Survival analysis showed that the patients with high EGFL7 expression had a poorer disease free survival than those with low EGFL7 expression (p=0.002). CONCLUSION: Our data suggest that EGFL7 expression is a novel predictive factor for the clinical progression of epithelial ovarian cancer, and may constitute a therapeutic target for antiangiogenesis therapy in patients with epithelial ovarian cancer.
Adult ; CA-125 Antigen/blood ; Cell Differentiation/physiology ; Endothelial Growth Factors/*metabolism ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Proteins/metabolism ; Neoplasm Staging ; Neoplasm, Residual ; Neoplasms, Glandular and Epithelial/*diagnosis/pathology/surgery ; Ovarian Neoplasms/*diagnosis/pathology/surgery ; Prognosis ; Retrospective Studies ; Survival Analysis ; Tumor Markers, Biological/*metabolism