The canonical Wnt pathway is critical for embryonic stem cell (ESC) pluripotency and aberrant control of β-catenin leads to failure of exit from pluripotency and lineage commitments. Hence, maintaining the appropriate level of β-catenin is important for the decision to commit to the appropriate lineage. However, how β-catenin links to core transcription factors in ESCs remains elusive. C-terminal-binding protein (CtBP) in Drosophila is essential for Wnt-mediated target gene expression. In addition, Ctbp acts as an antagonist of β-catenin/TCF activation in mammals. Recently, Ctbp2, a core Oct4-binding protein in ESCs, has been reported to play a key role in ESC pluripotency. However, the significance of the connection between Ctbp2 and β-catenin with regard to ESC pluripotency remains elusive. Here, we demonstrate that C-terminal-binding protein 2 (Ctbp2) associates with major components of the β-catenin destruction complex and limits the accessibility of β-catenin to core transcription factors in undifferentiated ESCs. Ctbp2 knockdown leads to stabilization of β-catenin, which then interacts with core pluripotency-maintaining factors that are occupied by Ctbp2, leading to incomplete exit from pluripotency. These findings suggest a suppressive function for Ctbp2 in reducing the protein level of β-catenin, along with priming its position on core pluripotency genes to hinder β-catenin deposition, which is central to commitment to the appropriate lineage.
Drosophila ; Embryonic Stem Cells ; Gene Expression ; Mammals ; Transcription Factors ; Wnt Signaling Pathway

The original version of this article contained wrong informations of some authors which should be changed.

Replication-independent incorporation of variant histone H3.3 has a profound impact on chromatin function and numerous cellular processes, including the differentiation of muscle cells. The histone chaperone HIRA and H3.3 have essential roles in MyoD regulation during myoblast differentiation. However, the precise mechanism that determines the onset of H3.3 deposition in response to differentiation signals is unclear. Here we show that HIRA is phosphorylated by Akt kinase, an important signaling modulator in muscle cells. By generating a phosphospecific antibody, we found that a significant amount of HIRA was phosphorylated in myoblasts. The phosphorylation level of HIRA and the occupancy of phosphorylated protein on muscle genes gradually decreased during cellular differentiation. Remarkably, the forced expression of the phosphomimic form of HIRA resulted in reduced H3.3 deposition and suppressed the activation of muscle genes in myotubes. Our data show that HIRA phosphorylation limits the expression of myogenic genes, while the dephosphorylation of HIRA is required for proficient H3.3 deposition and gene activation, demonstrating that the phosphorylation switch is exploited to modulate HIRA/H3.3-mediated muscle gene regulation during myogenesis.
Antibodies, Phospho-Specific ; Chromatin ; Histones* ; Muscle Cells* ; Muscle Development ; Muscle Fibers, Skeletal ; Myoblasts ; Phosphorylation* ; Phosphotransferases ; Transcriptional Activation

BACKGROUND AND PURPOSE: Nonmotor symptoms (NMS) in Parkinson's disease (PD) have multisystem origins with heterogeneous manifestations that develop throughout the course of PD. NMS are increasingly recognized as having a significant impact on the health-related quality of life (HrQoL). We aimed to determine the NMS presentation according to PD status, and the associations of NMS with other clinical variables and the HrQoL of Korean PD patients. METHODS: We surveyed patients in 37 movement-disorders clinics throughout Korea. In total, 323 PD patients were recruited for assessment of disease severity and duration, NMS, HrQoL, and other clinical variables including demographics, cognition, sleep scale, fatigability, and symptoms. RESULTS: In total, 98.1% of enrolled PD subjects suffered from various kinds of NMS. The prevalence of NMS and scores in each NMS domain were significantly higher in the PD group, and the NMS worsened as the disease progressed. Among clinical variables, disease duration and depressive mood showed significant correlations with all NMS domains (p<0.001). NMS status impacted HrQoL in PD (rS=0.329, p<0.01), and the association patterns differed with the disease stage. CONCLUSIONS: The results of our survey suggest that NMS in PD are not simply isolated symptoms of degenerative disease, but rather exert significant influences throughout the disease course. A novel clinical approach focused on NMS to develop tailored management strategies is warranted to improve the HrQoL in PD patients.
Cognition ; Demography ; Humans ; Korea ; Movement Disorders* ; Parkinson Disease* ; Prevalence ; Quality of Life*

For women with a BRCA 1/2 mutation, prophylactic bilateral salpingo-oophorectomy (BSO) is known to reduce the risk of developing both ovarian and breast cancer. The increasing interest in hereditary breast cancer has recently resulted in frequent genetic testing for high-risk patients. Since breast surgeons frequently encounter BRCA-positive breast cancer patients or carriers in the outpatient clinic, it is a prerequisite that the decision of the patients and doctors should be based on a thorough understanding of the objective risk, the medical assessment and the various treatment options, including surgery and anti-cancer therapy. The risk for the ovarian cancer also makes up an important part of genetic counseling; therefore, the breast surgeons should be well aware of this. This report presents the first experience with performing single-port access laparoscopic prophylactic BSO for a BRCA-positive breast cancer patient, and this procedure was technically feasible and the patient had minimal scar. However, a future investigation is needed to properly assess the cosmetic outcome in this approach.
Ambulatory Care Facilities ; Breast ; Breast Neoplasms ; Cicatrix ; Cosmetics ; Female ; Genetic Testing ; Humans ; Laparoscopy ; Ovarian Neoplasms

We report a case of an infected pneumatocele in the course of anaerobic pneumonia in an adult. To the best of our knowledge, anaerobic pneumonia complicated by a pneumatocele in an adult has not previously been described. The pneumatocele occurred on the fifth day of hospitalization, and rapidly increased in size, with the development of a subsequent mixed anaerobe infection. A pig-tail catheter was inserted and the pus drained. The bacterial culture from the pus was positive for three anaerobes: Bacteroid species, Peptostreptococcus asaccharolyticus and Fusobacterium species. Intravenous antibiotics and percutaneous catheter drainage resulted in a successful treatment.
Pneumonia, Bacterial/*complications/microbiology ; Pneumocephalus/*complications/microbiology ; Middle Aged ; Male ; Humans ; Gram-Negative Anaerobic Bacteria/isolation & purification

TCR signaling leading to thymocyte apoptosis is mediated through the expression of the Nur77 family of orphan nuclear receptors. It has been shown that the Nur77 promoter is activated by at least two signaling pathways, one mediated by calcium and the other by protein kinase C (PKC). MEF2D has been known to regulate Nur77 expression in a calcium- dependent manner. The mechanism by which calcium regulates MEF2D is through dissociation of calcium-sensitive MEF2 corepressors (Cabin1/ HDACs, HDAC4/5) and the association with calcineurin-activated transcription factor NF-AT and the coactivator p300. However, little is known about how PKC activates the Nur77 promoter. Herein, we report that PKC theta targets AP-1 like response element in the Nur77 promoter where JunD constitutively binds. PKC theta triggers mitogen-activated protein kinase- inediated phosphorylation of JunD, and increases transcriptional activity of JunD, cooperatively with p300. Menin is identified as the transcriptional corepressor for JunD via recruitment of mSin3-istone deacetylases. In fact, Menin represses PKC theta/ p300-mediated transcriptional activity of JunD in T cell. Its dynamic regulation of histone modifiers with JunD is responsible for PKCq-synergistic effect on Nur77 expression in T cell.
Cell Line, Tumor ; DNA-Binding Proteins/*genetics ; Enzyme Activation ; *Gene Expression Regulation ; Humans ; Isoenzymes/*metabolism ; Mitogen-Activated Protein Kinases/metabolism ; *Multiple Endocrine Neoplasia Type 1 ; Promoter Regions (Genetics)/genetics ; Protein Kinase C/*metabolism ; Proto-Oncogene Proteins/genetics/*metabolism ; Proto-Oncogene Proteins c-jun/*antagonists & inhibitors/metabolism ; Receptors, Cytoplasmic and Nuclear/*genetics ; Receptors, Steroid/*genetics ; Research Support, Non-U.S. Gov't ; Response Elements ; Transcription Factors/*genetics ; Transcription, Genetic/*genetics

OBJECTIVE: The purpose of this study is to evaluate the uroflow parameters of the pregnant women before delivery and immediate postpartum period. METHODS: Forty four patients delivered by spontaneous vaginal delivery (NVD group) and 46 patients by Cesarean section (C/SEC group) and 28 non-pregnant young women (Control group) were included in this study. Uroflow were checked 1 day before and 2 days after delivery by Jupiter 8000 (FM Wiest(R)) uroflowmetry. Mean value of the uroflow parameters in each group was compared using ANOVA t-test. For continuous data, linear associations with each of the uroflow parameters were assessed using a Pearson correlation coefficient. RESULTS: Maximal (18.48+/-5.21 mL/sec) and mean flow rate (9.45+/-3.73 mL/sec) of pregnant women were lower than control group (22.75+/-5.14 mL/sec), and were not changed after delivery (18.79+/-6.03 mL/ sec). Total flow time of pregnant woman (14.06+/-6.09 sec) was longer than control group (8.05+/-5.32 sec) before delivery, and increased after delivery especially after cesarean delivery. Time to peak flow of pregnant women (8.44+/-9.48 sec) was shorter than control group (16.33+/-6.11 sec) before delivery, and was similar to control group after delivery. Total voided volume (121.39+/-50.17 mL) was less than control group before delivery, and was increased after delivery (246.77+/-127.42 mL). Total voided volume after delivery was not different with control group statistically. CONCLUSION: There was no statistically differences before and after delivery in maximal flow rate, but was lower than non-pregnant women. Total flow time was much prolonged after delivery, especially after cesarean delivery. Time to peak flow and voided volume were restored to levels of non-pregnant women after delivery.
Cesarean Section* ; Female ; Humans ; Postpartum Period ; Pregnancy ; Pregnant Women

BACKGROUND: Many studies document the presence of abnormalities in amino acids metabolism in chronic uremia. These abnormalities have been attributed to low protein intake, deficiency of excretory and metabolic functions of the diseased kidneys, toxic effects of uremia on the intermediary metabolism of amino acids and in dialysis patients, loss of protein and amino acids by the dialytic procedure. METHODS: This study was designed to compare anthropometric measurement, biochemical characteristics and plasma amino acid concentration between patients with end stage renal disease on maintenance hemodialysis (HD) and normal controls. A cross sectional study of overnight fasting plasma amino acids and plasma albumin, prealbumin, triglyceride (TG), cholesterol, transferrin concentration were performed on 20 hemodialysis patients and 20 normal controls, matched by age and sex. RESULTS: The concentrations of prealbumin (25.60+/-7.05 mg/dL vs 35.08+/-8.11 mg/dL, p<0.005), transferrin (158.30+/-39.66 mg/dL vs 275.50+/-55.46 mg/dL, p<0.001) were found to be lower in HD patients. No differences in albumin, cholesterol and TG were observed between the two groups. Several amino acids (taurine, cystine, phosphoserine) were found to be higher in the HD patients, while the concentrations of other five amino acids (serine, alanine, valine, leucine, tyrosine) were lowered in HD patients. No differences in nine amino acids (asparagine, glutamine, proline, glycine, methionine, isoleucine, lysine, histidine, arginine) were observed between the two groups. CONCLUSION: Our results suggest that chronic renal failure patients have malnutrition and amino acids abnormalities. To correct the amino acids abnormalities and improve nitrogen utilization in hemodialysis patients, correction of acidosis and supplementation of the diet with serine should be considered.
Acidosis ; Alanine ; Amino Acids ; Cholesterol ; Cystine ; Dialysis ; Diet ; Fasting ; Glutamine ; Glycine ; Histidine ; Humans ; Isoleucine ; Kidney ; Kidney Failure, Chronic ; Leucine ; Lysine ; Malnutrition ; Metabolism ; Methionine ; Nitrogen ; Nutritional Status* ; Plasma* ; Prealbumin ; Proline ; Renal Dialysis* ; Serine ; Serum Albumin ; Transferrin ; Triglycerides ; Uremia ; Valine

PURPOSE: The purpose of this article is to analyze the results of combined agioplasity and femorofemoral bypass in patients with unilateral iliac arterial occlusive disease. METHOD: During the 11-year period from 1990 to 2000, 44 patients with iliac artery occlusion and a hemodynamically significant contralateral iliac artery stenosis were treated by using a combination of percutaneous transluminal angioplasity (PTA) and femorofemoral bypass (n=18) as well as aortobifemoral bypass (n=12) and iliofemoral bypass (n=14) at Korea university medical center. PTA was performed if the lesions in the donor iliac artery were less than 3 cm in length with no more than one well-localized lesion in either the common or external iliac artery, or both. Stent was deployed for suboptimal PTAs. The femorofemoral bypass was done within 3 to 5 days after PTA or stenting. RESULT: The mean age was 61.2 years. The Indications of femorofemoral bypass were hypertension, ischemic heart disease, chronic obstructive lung disease, old age (>75), cancer, and previous abdominal operation. The complication rate of the combination treatment was lower than that of the others. Primary patency rate at 1 and 3 years were 89%, 78% for aortobifemoral bypass, 83%, 66% for iliofemoral bypass, and 77%, 65% for femorofemoral bypass, respectively. CONCLUSION: The combination of PTA with or without stent deployment and femorofemoral bypass can be a useful option for treating iliac occlusion and contralateral iliac stenosis in patients with severe comorbid illness, advanced age, and intra-abdominal pathology. Angioplasity can allow more widespread use of femorofemoral bypass in these patients.
Academic Medical Centers ; Angioplasty* ; Arterial Occlusive Diseases* ; Constriction, Pathologic ; Humans ; Hypertension ; Iliac Artery ; Korea ; Myocardial Ischemia ; Pathology ; Pulmonary Disease, Chronic Obstructive ; Stents ; Tissue Donors