Exon skipping is an efficient technique to inhibit specific gene expression induced by a short-sequence peptide nucleic acid (PNA).To date, there has been no study on the effects of PNA on skin pigmentation. In melanocytes, the tripartite complex is responsible for the transport of mature melanosomes from the nucleus to the dendrites. The tripartite complex is composed of Rab27a, Mlph (Melanophilin), and Myosin Va. Defects in the protein Mlph, a melanosome transport-related protein, are known to cause hypopigmentation. Our study shows that Olipass peptide nucleic acid (OPNA), a cell membrane-permeable PNA, targets exon skipping in the Mlph SHD domain, which is involved in Rab27a binding. Our findings demonstrate that OPNA induced exon skipping in melan-a cells, resulting in shortened Mlph mRNA, reduced Mlph protein levels, and melanosome aggregation, as observed by microscopy. Therefore, OPNA inhibits the expression of Mlph by inducing exon skipping within the gene. These results suggest that OPNA, which targets Mlph, may be a potential new whitening agent to inhibit melanosome movement.

Purpose: To investigate the correlation between preoperative De Ritis ratio (aspartate transaminase [AST]/alanine transaminase [ALT]) and postoperative clinical outcome in patients with upper urinary tract carcinoma (UTUC) who underwent radical nephroureterectomy (RNU) and adjuvant chemotherapy (ACH). Materials and Methods: We respectively analyzed the clinical and pathological data of 102 patients who underwent RNU and ACH for UTUC. Patients were divided into 2 groups, according to the optimal value of AST/ALT ratio. The effect of the AST/ALT ratio was analyzed by the Kaplan-Meier method and Cox regression hazard models for patients’ cancer-specific survival (CSS) and overall survival (OS). Results: Mean survival time was 50.5±41.2 months. Mean age was 61.4±9.7years. Forty-one of the patients (46.5%) were in the high AST/ALT group. According to receiver operating characteristic analysis, the optimal AST/ALT ratio was 1.2. In Kaplan-Meier analyses, the high AST/ALT group showed worse outcomes in OS (p=0.007) and CSS (p=0.011). Using Cox regression models of clinical and pathological parameters to predict OS, high AST/ALT ratio (hazard ratio [HR], 5.428; 95% confidence interval [CI]; 1.803–16.334; p=0.002), pathological T3 (pT3) or higher (HR, 1.464; 95% CI; 1.156-1.857; p=0.002), and to predict CSS, high AST/ALT ratio (HR, 4.417; 95% CI; 1.545–12.632; p=0.005), and pT3 or higher (HR, 1.475; 95% CI; 1.172–1.904; p=0.002) were determined as independent prognostic factors. Conclusions Pretreatment AST/ALT ratio is a significant independent predictor of CSS and OS in advanced UTUC patients receiving systemic ACH after RNU.

BACKGROUND: Recently, a new automated inoculating instrument, Previ Isola(R) (bioMerieux, France) was introduced. Although there are many evaluation reports about the inoculation of urine and body fluid samples using Previ Isola(R), no evaluation has been reported for blood samples. The objectives of this study were to evaluate this instrument for the inoculation of blood samples and to compare the microbiological results with the manual loop-to-plate method. METHODS: From March 2014 to July 2014, a total of 296 non-duplicate blood samples showing positive signals on the BacT/Alert 3D system were obtained, and both manual and automated methods were used for sample inoculation. Results of the two methods were compared according to five aspects: the culture result, number of single colonies, morphology of colonies, number of re-inoculations, and time required for inoculation. RESULTS: The sensitivity and specificity of Previ Isola(R) were 98.9% and 96.6%, respectively. The positive and negative predictive values were 99.6% and 90.3%, respectively, and the total concordance rate was 98.6%. For Previ Isola(R) and the manual methods, the number of average usable single colonies per plate was 25 and 16, the number of re-inoculations was 60 and 62, and the inoculation time for 15 blood samples was 30 min and 75 min, respectively. The morphology of colonies showed no differences between the two methods. CONCLUSIONS: The automated inoculation instrument, Previ Isola(R), showed relative good concordance with manual method, with high sensitivity and high specificity for blood sample inoculation. Previ Isola(R) may be useful for inoculating specimens including blood samples.
Automation ; Body Fluids ; Evaluation Studies as Topic ; Sensitivity and Specificity

BACKGROUND: Since various hematology analyzers apply common or different principles in complete blood counting, difference between measured values could developed according to the control material used in external quality assessment. Diagnostic Hematology Subcommittee has been using formalin fixed blood and Liquichek(TM) Hematology-16 (Bio-Rad, USA) as control material of external quality assessment alternately but recently significant difference of test results was found in some analyzers. We intended to select adequate control material showing similar test results in most analyzers. METHODS: Using fresh whole blood, formalin fixed blood, Liquichek(TM) Hematology-16 and CBC-4K (R&D, USA), 5 parameters (WBC, RBC, Hb, Hct, platelet) were measured in 4 hematology analyzers; CELL-DYN sapphire (Abbott Diagnostics, USA), Coulter LH750 (Beckman Coulter, USA), ADVIA 2120 (Siemens Diagnostics, USA) and Sysmex XE-2100 (Sysmex Co., Japan). Linearity, within-run precision and between-day precision of 4 materials for each parameter were evaluated at different analyzers. RESULTS: The between-day precisions for WBC of formalin fixed blood showed very high CVs of 6.5~13.5% in all 4 hematology analyzers. The within-run and between-day precisions for WBC and platelet of Liquichek(TM) Hematology-16 showed high CVs of 9.3%, 16% and 19.8%, 18%, respectively in CELL-DYN analyzer. But, CBC-4K showed a good linearity (r2=0.9953~0.9993) and precision (within-run CVs, 0~1.5% and between-day CVs, 0~2.0%) in all analyzers. CONCLUSIONS: Fresh whole blood, formalin fixed blood and Liquichek(TM) Hematology-16 are not appropriate for standardization of external quality control materials because of some different test results among analyzers. We conclude that CBC-4K with good performance in all hematology analyzer is adequate as external quality control material.
Aluminum Oxide ; Blood Cell Count ; Blood Platelets ; Formaldehyde ; Hematology ; Quality Control

PURPOSE: Patient delays in seeking treatment of stroke and Emergency Department delays are major factors in preventing the use of thrombolytic therapy for stroke. For the achievement of rapid diagnosis and treatment in the emergency center, a unified and systematic confrontation of symptoms and good team cooperation are essential. METHODS: Various departments involved in the management of acute stroke in the ED conferred to discuss ways to minimize door-to-CT and door-to-drug times in the ED. This team formulated the BEST (Brain salvage through Emergent Stroke Therapy) protocol to optimize the treatment of acute stroke patients. Our study employed the BEST protocol for four month during the period from October, 2004 to February, 2005. Inclusion criteria for the protocol were admission to our Hospital's ED with an acute neurologic symptoms and an onset time of less than 12 hours. RESULTS: Ninety-six patients, including fifty-eight men were enrolled in the study. Reasons for acute neurologic changes were ischemic stroke (66 patients), hemorrhagic stroke (22 patients), and metabolic causes (8 patients). Of the 66 ischemic stroke patients, 11 received tissue plasminogen activator (tPA) and 2 were administered Intraarterial Urokinase (IAUK). Door-to-CT times before and after initiation of the BEST protocol were 47+/-19 minutes and 26+/-12 minutes, respectively (p-value=0.024). And door-to-drug times before and after the BEST protocol were 96+/-16 minutes and 67+/-28 minutes, respectively (pvalue=0.035). CONCLUSION: Assembly of a specific "stroke team"and implementation of a well-designed protocol allows the most efficient evaluation and treatment of patients with acute stroke, thus minimizing both door-to-CT and door-to-drug times.
Cerebral Infarction ; Diagnosis* ; Emergencies ; Emergency Service, Hospital ; Humans ; Male ; Medical Records ; Neurologic Manifestations* ; Stroke ; Thrombolytic Therapy ; Tissue Plasminogen Activator ; Urokinase-Type Plasminogen Activator

PURPOSE: Many inborn errors of metabolism can be completely cured with early detection and early treatment. This is why neonatal screening on inborn errors of metabolism is implemented worldwide. In this study, a cost-benefit analysis was performed on the neonatal screening of phenylketonuria and congenital hypothyroidism in Korea. METHODS: This study included 2,908,231 neonates who took the neonatal screening on phenylketonuria and congenital hypothyroidism in Korea from January 1991 to December 2003. From those neonates, the incidence rates of phenylketonuria and congenital hypothyroidism were measured. Furthermore, based on 495,000 babies born in 2002, were calculated and compared the total costs in case when neonatal screening on phenylketonuria and congenital hypothyroidism is implemented, and when not. RESULTS: If the neonatal screening on phenylketonuria and congenital hypothyroidism is implemented, benefits far exceed costs at a ratio of 1.77:1 in phenylketonuria, and 11.11:1 in congenital hypothyroidism. In terms of wons, the present neonatal screening on phenylketonuria and congenital hypothyroidism will gain us more than 29 billion wons every year. CONCLUSION: This study only concerns the monetary aspects of the neonatal screening. Therefore, the benefits of the neonatal screening is underestimated by ignoring precious but not measurable values such as quality of life. However, the present neonatal screening on phenylketonuria and congenital hypothyroidism is found to be beneficial and should continue for the good of the nation as well as that of the patients.
Congenital Hypothyroidism* ; Cost-Benefit Analysis* ; Humans ; Incidence ; Infant, Newborn ; Korea* ; Metabolism, Inborn Errors ; Neonatal Screening* ; Phenylketonurias* ; Quality of Life

Shaken baby syndrome develop as a form of child abuse, with the majority of cases occurring during the first year of life. It results from extreme rotational cranial acceleration and deceleration effects induced by violent shaking of an infant. The characteristic injuries include subdural and subarachnoid hemorrhages, and retinal hemorrhages. We experienced three cases of shaken baby syndrome. Although the history of trauma was little known, all of these cases had subdural hemorrhages. We present the cases with a review of related literature.
Acceleration ; Child ; Child Abuse ; Deceleration ; Hematoma, Subdural ; Humans ; Infant ; Retinal Hemorrhage ; Shaken Baby Syndrome* ; Subarachnoid Hemorrhage

Systemic lupus erythematosus(SLE), a rheumatic disease of unknown causes, is characterized by autoantibodies directed against self-antigens, resulting in inflammatory damages to target organs including kidney, blood-forming cells, and central nervous system. The prevalence rates are higher in Native Americans, Asians, Latin Americans and black people. A female to male ratio of approximately 2 : 1 occurs before puberty, and 4 : 1 after puberty. Children of SLE most frequently present with fever, fatigue, arthralgia or arthritis, and rashes. The diagnosis is confirmed by clinical and also laboratory manifestations satisfying at least 4 out of 11 criteria. A central nervous system is not rarely involved in children of SLE with the prevalence rate of 23-44%. However, cerebral infarcts are not a common phenomenon and can be seen only for 6% of children with SLE. There have been no cases reported in Korea. This is why we present a case of basal ganglia infarct associated with SLE in a 19-month old girl. We report this case with a brief review of related literature.
Adolescent ; Arthralgia ; Arthritis ; Asian Continental Ancestry Group ; Autoantibodies ; Autoantigens ; Basal Ganglia* ; Central Nervous System ; Child ; Diagnosis ; Exanthema ; Fatigue ; Female ; Fever ; Humans ; Indians, North American ; Infant ; Kidney ; Korea ; Lupus Erythematosus, Systemic ; Male ; Prevalence ; Puberty ; Rheumatic Diseases

Deranged expression of cell cycle modulators has been reported to contribute to the development and progression of hepatocellular carcinoma (HCC). However, their expression patterns remain poorly understood in hepatitis B virus (HBV)-related HCC, which constitutes about 65-70% of HCC in Korea. The aims of this study were to evaluate the expressions of G1-S modulators in HBV-related HCCs and dysplastic nodules (DNs), and to correlate with the histopathologic features of HCCs. Immunohistochemical expressions of cyclin D1, cyclin E, p53, p27, p21, p16, Rb, and PCNA proteins were investigated in 80 HCCs and 22 DNs. Cyclin D1 overexpression showed positive relationships with advanced tumor stage, poor differentiation, larger tumor size, microvascular invasion, intrahepatic meta-stasis, no tumor capsule formation, infiltrative growth, aberrant p53 expression, and high PCNA labeling index (LI) of HCC (p<0.05). Aberrant p53 expression showed positive relationship with poor differentiation of HCC (p<0.01). Expression of cyclin D1 or p53 was not observed in DNs. The p27 LI and p16 LI were lower in HCCs with intrahepatic metastasis (p<0.05). Cyclin D1 overexpression and aberrant p53 expression could be associated with the progression of HBV-related HCC, and might have a less crucial role in the DN-HCC sequence. In addition, elevated expression of p27 and p16 proteins might have inhibitory action to the intrahepatic metastasis of HBV-related HCC.
Adult ; Aged ; Carcinoma, Hepatocellular/chemistry/etiology/*pathology ; Cyclin D1/*analysis ; Female ; G1 Phase ; Hepatitis B/*complications ; Human ; Immunohistochemistry ; Liver Neoplasms/chemistry/etiology/*pathology ; Male ; Microfilament Proteins/analysis ; Middle Age ; Precancerous Conditions/*virology ; Proliferating Cell Nuclear Antigen/analysis ; Protein p16/analysis ; Protein p53/*analysis ; Retinoblastoma Protein/analysis ; S Phase

Hypertensive encephalpathy is defined as severe hypertension in association with headache, nausea and vomiting, visual disturbances, confusion, stupor and coma. The pathophysiological mechanism is incompletely understood and causing as a result of failure of the upper limit of cerebral vascular autoregulation. Magnetic resonance imaging shows a characteristics posterior leukoencephalopathy, predominantly affects the white matter of the parietal and occipital lobes. Hypertensive encephalopathy are potentially reversible with timely and appropriate treatment. We experienced a case of hypertensive encephalopathy after normal vaginal delivery and report this case with a brief review of the literatures.
Coma ; Headache ; Hemorrhage* ; Homeostasis ; Hypertension ; Hypertensive Encephalopathy* ; Leukoencephalopathies ; Magnetic Resonance Imaging ; Nausea ; Occipital Lobe ; Postpartum Period* ; Rabeprazole ; Stupor ; Vomiting