OBJECTIVE Present study was aimed to verify the effect of granulocyte macrophage-colony stimulating factor (GM-CSF) in the preimplantation development of mouse embryos and the involvement of the mitogen activated protein kiase (MAPK) in the GM-CSF signaling. METHODS: Two-cell embryos were cultured for 96 h in the presence or absence of GM-CSF (0, 0.4, 2, 10 ng/ml) and PD98059, a MEK inhibitor (10 muM). Morphological development, cell number per blastocyst, and apoptotic nuclei, were eamined. MAPK activity of embryonic immunoprecipitate by MAPK (ERK1/2) antibody was measured by in vitro phosphorylation of myelin basic protein. RESULTS: At post hCG 122 h the embryonic development among the experimental groups was significantly different (p=0.018). The rate of blastocyst development and cell number per embryo were the highest in 2 ng/ml GM-CSF treatment group. The percent of apoptotic cells of the GM-CSF-treated embryos was the lowest among the group. in blastocysts, GM-CSF treatment transiently increased MAPK activity. PD098059 attenuated the effect of GM-CSF on the morphological development, increase in cell number per blastocyst, down regulation of apoptosis, and upregulation of MAPK activity, suggesting that activation of MAPK cascade possibly mediated the embryotropic effect of GM-CSF. CONCLUSION: This result suggested that GM-CSF potentiated the development of preimplantation mouse embryos by activation of MAPK.
Animals ; Apoptosis ; Blastocyst ; Cell Count ; Down-Regulation ; Embryonic Development ; Embryonic Structures* ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor ; Granulocytes* ; Mice* ; Myelin Basic Protein ; Phosphorylation ; Pregnancy ; Up-Regulation

OBJECTIVES: Bedtime procrastination is defined as going to bed later than intended, without having external reasons for doing so. Despite various studies investigating the new concept of bedtime procrastination, there have been no studies that have validated the Bedtime Procrastination Scale (BPS). Thus, this study aims to validate the BPS in Korean. METHODS: Two hundred twenty seven participants (mean age 22±2.39 years, 81.1% female) participated in the study. All participants completed the BPS, Insomnia Severity Index, Center for Epidemiologic Studies Depression Scale, Perceived Stress Scale, Depressive Symptom Inventory-Suicidality Subscale, and General Procrastination Scale (GPS). Exploratory factor analysis was used to determine number of factors. RESULTS: Exploratory factor analysis revealed support for one factor, which was consistent with the original study. Goodness of fit was adequate for the one factor model [χ²=59.369(df=27, p<0.001), Comparative Fit Index=0.963, Tucker-Lewis Index=0.951, Root Mean Square Error of Approximation= 0.073, Standardized Root Mean Square Residual=0.042]. Internal consistency was also adequate (Cronbach's alpha=0.86). Convergent validity was also high with the GPS (p<0.001, r=0.411). Correlations were also high with other questionnaires (p<0.05). CONCLUSIONS: The BPS is a reliable and valid measure for bedtime procrastination, and may have important clinical implications for sleep disorders.
Depression ; Epidemiologic Studies ; Factor Analysis, Statistical ; Humans ; Sleep Deprivation ; Sleep Initiation and Maintenance Disorders ; Sleep Wake Disorders ; Young Adult

Despite the therapeutic equivalence between twice-daily and once-daily tacrolimus, patient safety after conversion is still a concern. We reviewed 218 liver transplantation (LT) patients who converted twice-daily to once-daily tacrolimus between May 2011 and January 2014. Thirty (13.8%) patients had adverse events after conversion, with a liver function test (LFT) abnormality being the most common adverse event (n = 17). Despite the decrease in serum tacrolimus of > 30% after conversion, none of the patients who were converted to a dosage ratio (once-daily tacrolimus dosage: twice-daily tacrolimus dosage) > 1 had an LFT abnormality. Most patients with an LFT abnormality improved after increasing the once-daily tacrolimus dosage (n = 2), returned to a previous medication, and/or added another immunosuppressant (n = 15). One patient had acute cellular rejection, which improved after steroid pulse treatment, and another patient had graft failure. In patients with a dosage ratio ≤ 1, the conversion time within 5 years after LT was the only significant risk factor for an LFT abnormality after conversion (odds ratio: 11.850, 95% confidence interval: 1.321–106.325, P = 0.027). In conclusion, the dosage ratio and time after LT should be carefully considered during conversion from twice-daily to once-daily tacrolimus.
Humans ; Liver Function Tests ; Liver Transplantation* ; Liver* ; Patient Safety ; Risk Factors* ; Tacrolimus* ; Transplants

BACKGROUNDS/AIMS: In hepatocellular carcinoma (HCC), bile duct invasion occurs far more rarely than vascular invasion and is not well characterized. In addition, the pathologic finding of bile duct invasion is not considered an independent prognostic factor for HCC following surgery. In this study, we determined the characteristics of HCC with bile duct invasion, and assessed the clinical significance of bile duct invasion. METHODS: We retrospectively reviewed the medical records of 363 patients who underwent hepatic resection for HCC at Seoul National University Hospital (SNUH) from January 2009 to December 2011. Preoperative, operative, and pathological data were collected. The risk factors for recurrence and survival were analyzed. Subsequently, the patients were divided into 2 groups according to disease stage (American Joint Committee on Cancer/International Union Against Cancer 7th edition): early stage (T1 and 2) and advanced stage (T3 and 4) group; and risk factors in the sub-groups were analyzed. RESULTS: Among 363 patients, 13 showed bile duct invasion on pathology. Patients with bile duct invasion had higher preoperative total bilirubin levels, greater microvascular invasion, and a higher death rate than those without bile duct invasion. In multivariate analysis, bile duct invasion was not an independent prognostic factor for survival for the entire cohort, but, was an independent prognostic factor for early stage. CONCLUSIONS: Bile duct invasion accompanied microvascular invasion in most cases, and could be used as an independent prognostic factor for survival especially in early stage HCC (T1 and T2).
Bile Ducts* ; Bile* ; Bilirubin ; Carcinoma, Hepatocellular* ; Cohort Studies ; Humans ; Joints ; Medical Records ; Mortality ; Multivariate Analysis ; Pathology ; Recurrence ; Retrospective Studies ; Risk Factors ; Seoul

PURPOSE: We evaluated the heterogeneity of steatosis in living donor livers to determine its regional differences. METHODS: Between June 2011 and February 2012, 81 liver donors were selected. Fat fraction was estimated using magnetic resonance triple-echo chemical shifting gradient imaging in 13 different regions: segment 1 (S1), S2, S3, and each peripheral and deep region of S4, S5, S6, S7, and S8. RESULTS: There were differences (range, 3.2%-5.3%) in fat fractions between each peripheral and deep region of S4, S6, S7, and S8 (P < 0.001, P = 0.004, P < 0.001, and P = 0.006). Fat deposit amount in S1, S2, S3 and deep regions of S4-S8 were significantly different from one another (F [4.003, 58.032] = 8.684, P < 0.001), while there were no differences among the peripheral regions of S4-S8 (F [2.9, 5.3] = 1.3, P = 0.272) by repeated measure analysis of variance method. And regional differences of the amount of fat deposit in the whole liver increased as a peripheral fat fraction of S5 increased (R2 = 0.428, P < 0.001). CONCLUSION: Multifocal fat measurements for the whole liver are needed because a small regional evaluation might not represent the remaining liver completely, especially in patients with severe hepatic steatosis.
Fatty Liver ; Humans ; Liver ; Liver Transplantation ; Living Donors* ; Magnetic Resonance Imaging* ; Population Characteristics ; Tissue Donors ; Transplant Donor Site

BACKGROUND: The aim of this study was to investigate the current status and identify any existing problems in the allocation system of liver transplantation (LT) for children in Korea. METHODS: The information for the period between January 2006 and March 2012 contained in the Korean Network for Organ Sharing (KONOS) database, and the 2008 and 2010 annual reports from KONOS were analyzed. Detailed information about split LT (SLT) was analyzed using the SLT database which contains data collected since 2010. RESULTS: Of 4,462 cases of LT between January 2006 and December 2010, 243 were pediatric cases (5.4%). Of these pediatric cases, 195 (80.2%) were living donor LT. Of the liver grafts from deceased pediatric donors, 68% were donated to adults and 3.9% were shared with children. Of the 104 splittable donors from January 2010 to March 2012, a split was performed only in 4.6% of cases. The main reason for the low split rate was few pediatric candidate(s) in the waiting list due to strict Korean regulatory requirements for split candidate registration. CONCLUSIONS: Under the current liver transplant allocation system, Korean children have less chance to receive a liver graft from a deceased donor. With improvement of the allocation system and the rules governing SLT, children in need may have greater opportunity to receive a deceased donor graft without negatively affecting adult recipients.
Adult ; Child ; Humans ; Korea ; Liver ; Liver Transplantation ; Living Donors ; Tissue Donors ; Transplants ; Waiting Lists

Hepatitis C virus (HCV) recurrence after liver transplantation (LT) is universal and progressive. Here, we report recent results of response-guided therapy for HCV recurrence based on early protocol biopsy after LT. We reviewed patients who underwent LT for HCV related liver disease between 2010 and 2012. Protocol biopsies were performed at 3, 6, and 12 months after LT in HCV recurrence (positive HCV-RNA). For any degree of fibrosis, > or = moderate inflammation on histology or HCV hepatitis accompanying with abnormal liver function, we treated with pegylated interferon and ribavirin. We adjusted treatment period according to individual response to treatment. Among 41 HCV related recipients, 25 (61.0%) who underwent protocol biopsies more than once were enrolled in this study. The mean follow-up time was 43.1 (range, 23-55) months after LT. Genotype 1 and 2 showed in 56.0% and 36.0% patients, respectively. Of the 25 patients, 20 (80.0%) started HCV treatment after LT. Rapid or early virological response was observed in 20 (100%) patients. Fifteen (75.0%) patients finished the treatment with end-of-treatment response. Sustained virological response (SVR) was in 11 (55.0%) patients, including 5 (41.7%) of 12 genotype 1 and 6 (75.0%) of 8 non-genotype 1 (P = 0.197). Only rapid or complete early virological response was a significant predictor for HCV treatment response after LT (100% in SVR group vs. 55.6% in non-SVR group, P = 0.026). Overall 3-yr survival rate was 100%. In conclusion, response-guided therapy for HCV recurrence based on early protocol biopsy after LT shows encouraging results.
Adult ; Aged ; Antiviral Agents/*administration & dosage ; Biopsy ; Drug Monitoring/*methods ; Female ; Hepatitis C/etiology/*pathology/*prevention & control ; Humans ; Liver Transplantation/*adverse effects ; Male ; Middle Aged ; Recurrence ; Reproducibility of Results ; Retrospective Studies ; Sensitivity and Specificity ; Treatment Outcome ; Watchful Waiting/methods

Several studies have suggested that a positive lymphocyte cross-matching (XM) is associated with low graft survival rates and a high prevalence of acute rejection after adult living donor liver transplantations (ALDLTs) using a small-for-size graft. However, there is still no consensus on preoperative desensitization. We adopted the desensitization protocol from ABO-incompatible LDLT. We performed desensitization for the selected patients according to the degree of T lymphocyte cross-match titer, model for end-stage liver disease (MELD) score, and graft liver volume. We retrospectively evaluated 230 consecutive ALDLT recipients for 5 yr. Eleven recipients (4.8%) showed a positive XM. Among them, five patients with the high titer (> 1:16) by antihuman globulin-augmented method (T-AHG) and one with a low titer but a high MELD score of 36 were selected for desensitization: rituximab injection and plasmapheresis before the transplantation. There were no major side effects of desensitization. Four of the patients showed successful depletion of the T-AHG titer. There was no mortality and hyperacute rejection in lymphocyte XM-positive patients, showing no significant difference in survival outcome between two groups (P=1.000). In conclusion, this desensitization protocol for the selected recipients considering the degree of T lymphocyte cross-match titer, MELD score, and graft liver volume is feasible and safe.
ABO Blood-Group System/immunology ; Adult ; Antibodies, Monoclonal, Murine-Derived/therapeutic use ; Desensitization, Immunologic/*methods ; End Stage Liver Disease/surgery ; Female ; Graft Rejection/immunology ; Graft Survival/*immunology ; Histocompatibility Testing ; Humans ; Liver/surgery ; *Liver Transplantation ; Living Donors ; Male ; Middle Aged ; Plasmapheresis ; Preoperative Care ; Retrospective Studies ; Severity of Illness Index ; Survival Rate ; T-Lymphocytes/*immunology ; *Transplant Recipients

Pretransplant alpha-fetoprotein (AFP) is a useful tumor marker predicting recurrence of hepatocellular carcinoma (HCC). Little is known, however, about the relationship between changes in AFP concentration and prognosis. This study investigated the clinical significance of change in peri-transplant AFP level as a predictor of HCC recurrence. Data from 125 HCC patients with elevated pretransplant AFP level who underwent liver transplantation (LT) between February 2000 and December 2010 were retrospectively reviewed. Patients with AFP normalization within 1 month after LT were classified into the rapid normalization group (n = 97), with all other patients classified into the non-rapid normalization group (n = 28). Tumor recurrence was observed in 17 of the 97 patients (17.5%) with rapid normalization; of these, 11 patients had high AFP levels and six had normal levels at recurrence. In contrast, tumor recurrence was observed in 24 of the 28 patients (85.7%) without rapid normalization, with all 24 having high AFP levels at recurrence. Multivariate analysis showed that non-rapid normalization (harzard ratio [HR], 4.41, P < 0.001), sex (HR, 3.26, P = 0.03), tumor size (HR, 1.15, P = 0.001), and microvascular invasion (HR, 2.65, P = 0.005) were independent risk factors for recurrence. In conclusion, rapid normalization of post-LT AFP level at 1 month is a useful clinical marker for HCC recurrence. Therefore, an adjuvant strategy and/or intensive screening are needed for patients who do not show rapid normalization.
Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Carcinoma, Hepatocellular/blood/mortality/*pathology/therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Liver Neoplasms/blood/mortality/*pathology/therapy ; *Liver Transplantation ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; alpha-Fetoproteins/analysis

To adopt the model for end-stage liver disease (MELD) score-based system in Korea, the feasibility should be evaluated by analysis of Korean database. The aim of this study was to investigate the feasibility of the MELD score-based system compared with the current Child-Turcotte-Pugh (CTP) based-system and to suggest adequate cut-off to stratify waiting list mortality among Korean population. We included 788 adult patients listed in waiting list in Seoul National University Hospital from January 2008 to May 2011. The short-term survival until 6 months after registration was evaluated. Two hundred forty six (31.2%) patients underwent live donor liver transplantation and 353 (44.8%) patients were still waiting and 121 (15.4%) patients were dropped out due to death. Significant difference was observed when MELD score 24 and 31 were used as cut-off. Three-months survival of Status 2A was 70.2%. However, in Status 2A patients whose MELD score less than 24 (n=82), 86.6% of patients survived until 6 month. Furthermore, patients with high MELD score (> or =31) among Status 2B group showed poorer survival rate (45.8%, 3-month) than Status 2A group. In conclusion, MELD score-based system can predict short term mortality better and select more number of high risk patients in Korean population.
Area Under Curve ; Cohort Studies ; End Stage Liver Disease/*mortality/therapy ; Humans ; *Liver Transplantation ; *Models, Statistical ; ROC Curve ; Registries ; *Severity of Illness Index ; Survival Rate ; Time Factors ; Waiting Lists