Quantitative Analysis of SMN1 Gene and Estimation of SMN1 Deletion Carrier Frequency in Korean Population based on Real-Time PCR

Spinal muscular atrophy (SMA) is an autosomal recessive disorder, caused by homozygous absence of the survival motor neuron gene (SMN1) in approximately 94% of patients. Since most carriers have only one SMN1 gene copy, several SMN1 quantitative analyses have been used for the SMA carrier detection. We developed a reliable quantitative real-time PCR with SYBR Green I dye and studied 13 patients with SMA and their 24 parents, as well as 326 healthy normal individuals. The copy number of the SMN1 gene was determined by the comparative threshold cycle (Ct) method and albumin was used as a reference gene. The homozygous SMN1 deletion ratio of patients was 0.00 and the hemizygous SMN1 deletion ratio of parents ranged from 0.39 to 0.59. The ΔΔCt ratios of 7 persons among 326 normal individuals were within the carrier range, 0.41-0.57. According to these data, we estimated the carrier and disease prevalence of SMA at 1/47 and 1/8,496 in Korean population, respectively. These data indicated that there would be no much difference in disease prevalence of SMA compared with western countries. Since the prevalence of SMA is higher than other autosomal recessive disorders, the carrier detection method using real-time PCR could be a useful tool for genetic counseling

Human AQP5 Plays a Role in the Progression of Chronic Myelogenous Leukemia (CML)

Aquaporins (AQPs) have previously been associated with increased expression in solid tumors. However, its expression in hematologic malignancies including CML has not been described yet. Here, we report the expression of AQP5 in CML cells by RT-PCR and immunohistochemistry. While normal bone marrow biopsy samples (n = 5) showed no expression of AQP5, 32% of CML patient samples (n = 41) demonstrated AQP5 expression. In addition, AQP5 expression level increased with the emergence of imatinib mesylate resistance in paired samples (p = 0.047). We have found that the overexpression of AQP5 in K562 cells resulted in increased cell proliferation. In addition, small interfering RNA (siRNA) targeting AQP5 reduced the cell proliferation rate in both K562 and LAMA84 CML cells. Moreover, by immunoblotting and flow cytometry, we show that phosphorylation of BCR-ABL1 is increased in AQP5-overexpressing CML cells and decreased in AQP5 siRNA-treated CML cells. Interestingly, caspase9 activity increased in AQP5 siRNA-treated cells. Finally, FISH showed no evidence of AQP5 gene amplification in CML from bone marrow. In summary, we report for the first time that AQP5 is overexpressed in CML cells and plays a role in promoting cell proliferation and inhibiting apoptosis. Furthermore, our findings may provide the basis for a novel CML therapy targeting AQP5

The Usefulness of Percutaneous Transhepatic Cholangioscopy for Identifying Malignancies in Distal Commom Bile Duct Strictures

The diagnostic accuracy of percutaneous transhepatic cholangioscopy (PTCS) was compared to that of three radiologic modalities in distal common bile duct (CBD) strictures for the evaluation of clinical application. Ninety-five patients who underwent PTCS for the evaluation of distal CBD strictures (35 malignant and 60 benign) whose masses were not obvious from radiologic imagings were included. Confirmative diagnosis could not be reached by endoscopic retrograde cholangiopancreatography (ERCP) or radiologic findings in all cases. Specific findings on the computed tomography (CT), magnetic resonance cholangiopancreatography (MRCP) and direct cholangiography were analyzed among 68 (25 malignant and 43 benign) out of the 95 patients in order to determine the sensitivity and specificity of three radiologic studies for the diagnosis of malignant distal CBD strictures, and to compare those results with those by a combination of PTCS-guided biopsy and tumor vessel observation on cholangioscopy. The sensitivity/specificity of CT, MRCP and direct cholangiography including ERCP in diagnosing malignant distal CBD strictures were 42.9%/65.8%, 53.3%/58.3%, and 70.8%/47.6% respectively, while it was 96%/100% for the combination of PTCS-guided biopsy and tumor vessel. PTCS is a useful method for differential diagnosis of distal CBD strictures, particularly when it is difficult to distinguish benign from malignant strictures by radiologic studies and when peroral approach is not feasible

Clinical Features and Prognosis of Spontaneous Bacterial Peritonitis in Korean Patients with Liver Cirrhosis: A Multicenter Retrospective Study

BACKGROUND/AIMS: Although early recognition and treatment with effective antibiotics have lead to improvements in the prognosis of patients with spontaneous bacterial peritonitis (SBP), it remains to be a serious complication in cirrhotic patients. This study was designed to evaluate the clinical manifestations and prognosis of patients with liver cirrhosis and SBP in Korea. METHODS: This was a multicenter retrospective study examining 157 episodes of SBP in 145 patients with cirrhosis. SBP was diagnosed based on a polymorphonuclear cell count in ascitic fluid of >250 cells/mm(3) in the absence of data compatible with secondary peritonitis. RESULTS: The mean age of the cohort was 56 years, and 121 (77%) of the 157 episodes of SBP occurred in men. Microorganisms were isolated in 66 episodes (42%): Gram-negative bacteria in 54 (81.8%), Gram-positive in 11 (16.7%), and Candida in 1. Isolated Gram-negative organisms were resistant to third-generation cephalosporin in 6 cases (17%), to ciprofloxacin in 11 (20.8%), and to penicillin in 33 (62.3%). The treatment failure and in-hospital mortality rates were 12.1% and 21%, respectively. A high Model of End-Stage Liver Disease (MELD) score, SBP caused by extended-spectrum beta-lactamase-producing organisms, and hepatocellular carcinoma were independent prognostic factors of high in-hospital mortality. CONCLUSIONS: SBP remains to be a serious complication with high in-hospital mortality, especially in patients with a high MELD score.ope

Кераміка «terra sigillata» з с. Зимне на Волині

Стаття присвячена публікації чотирьох керамічних посудин типу «terra sigillata», знайдених на дні р. Луги у с. Зимне Володимир-Волинського району Волинської області. Попередній аналіз цих знахідок дозволяє віднести їх до Понтійського центру виробництва такого посуду. Вірогідним шляхом потрапляння цієї колекції на Волинь була готська експансія у Північне Причорномор’я

Vibration-Induced Nystagmus After Acute Peripheral Vestibular Loss: Comparative Study With Other Vestibule-Ocular Reflex Tests in the Yaw Plane

Objective: To validate the role of vibration-induced nystagmus (VIN) detecting vestibular asymmetry by comparing several vestibulo-ocular reflex (VOR) parameters in the yaw plane.Study Design: Prospective validation study for diagnostic test.Setting: Tertiary referral center.Patients: Seventy-four patients with unilateral vestibular loss of acute onset without a history of fluctuating vestibular function and 24 healthy volunteers.Intervention: Spontaneous nystagmus, head-shaking nystagmus (HSN), and VIN using a 100 Hz handheld vibrator were recorded using a videonystagmography system. Canal paresis on the caloric test and the time constant (TC) on the step velocity test were examined as parameters of the laboratory test.Main Outcome Measures: Correlation analysis between horizontal VOR parameters was performed. Receiver operating characteristic (ROC) curves of these parameters were plotted, and the area under the ROC curve (AUC) was compared according to the lower limiting value of TC on step velocity test as well as the presence of unilateral vestibular loss.Results: VIN was observed in 64 (86%) of 74 patients, and it was directed toward the contralesional side in 98%. VIN showed a significant positive correlation with the canal paresis (r = 0.416, p < 0.001) and a negative correlation with the TC (r = -0.351, p < 0.005). ROC curves of several VOR parameters were compared according to the presence of unilateral vestibular loss. The AUC of VIN was 0.882, and the cutoff intensity of VIN was 2.5 degrees per second. The AUCs of the HSN and spontaneous nystagmus were 0.774 and 0.661, respectively.Conclusion: The lateralization value of VIN was comparable with caloric test and superior to HSN. VIN is a useful vestibular test detecting vestibular asymmetry in the evaluation of dizziness.This study was supported by grant no. 02-2008-019 from the SNUBH Research Fund.OAIID:oai:osos.snu.ac.kr:snu2011-01/102/0000005485/1SEQ:1PERF_CD:SNU2011-01EVAL_ITEM_CD:102USER_ID:0000005485ADJUST_YN:YEMP_ID:A076326DEPT_CD:801CITE_RATE:1.904FILENAME:2011VIN_ON.pdfDEPT_NM:의학과EMAIL:[email protected]_YN:YCONFIRM: