The HCV Core Protein Acts as a Positive Regulator of Fas-Mediated Apoptosis in a Human Lymphoblastoid T Cell Line

AbstractHepatitis C virus (HCV) is a major human pathogen causing mild to severe liver disease worldwide and is remarkably efficient at establishing persistent infections. Previously, we have shown that the core protein has an immunomodulatory function including the suppression of T lymphocyte responses to viral infection. To investigate the underlying mechanism for the role of core protein in immune modulation, we examined the effect of core on the sensitivity of the human T cell line, Jurkat, to Fas-mediated apoptosis. The transient and stable expression of core protein in Jurkat cells increased the sensitivity of cells to Fas-mediated apoptosis when compared to control cells expressing vector DNA alone. In addition, we demonstrated that the core protein binds to the cytoplasmic domain of Fas which may enhance the downstream signaling event of Fas-mediated apoptosis. The expression of core protein did not alter the cell surface expression of Fas, indicating that the increased sensitivity of core-expressing cells to Fas ligand was not due to upregulation of Fas. Furthermore, we observed the augmentation of caspase-3 activity in core-expressing cells. These results suggest that the core protein may promote the apoptosis of immune cells during HCV infection via the Fas signaling pathway, thus facilitating HCV persistence

Semi-Automatic Measurement of the Airway Dimension by Computed Tomography Using the Full-With-Half-Maximum Method: a Study of the Measurement Accuracy according to the Orientation of an Artificial Airway

parameters on the correct measurement of the airway dimension. Materials and Methods: An airway phantom with 11 poly-acryl tubes of various lumen diameters and wall thicknesses was scanned using a 16-MDCT (multidetector CT) at various tilt angles (0, 30, 45, and 60 ). The CT images were reconstructed at various reconstruction kernels and thicknesses. The axis of each airway was determined using the 3D thinning algorithm, with images perpendicular to the axis being reconstructed. The luminal radius and wall thickness was measured by the full-width-half-maximum method. The influence of the CT parameters (the size of the airways, obliquity on the radius and wall thickness) was assessed by comparing the actual dimension of each tube with the estimated values. Results: The 3D thinning algorithm correctly determined the axis of the oblique airway in all tubes (mean error: 0.91+-0.82 ). A sharper reconstruction kernel, thicker image thickness and larger tilt angle of the airway axis resulted in a significant decrease of the measured wall thickness and an increase of the measured luminal radius. Use of a standard kernel and a 0.75-mm slice thickness resulted in the most accurate measurement of airway dimension, which was independent of obliquity. Conclusion: The airway obliquity and imaging parameters have a strong influence on the accuracy of the airway wall measurement. For the accurate measurement of airway thickness, the CT images should be reconstructed with a standard kernel and a 0.75 mm slice thickness.This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (No. R01-2006-000-11244-0)

Superficial Endobronchial Lung Cancer: Radiologic-Pathologic Correlation

Objective: To analyze the plain chest radiographic and CT findings of superficial endobronchial lung cancer and to correlate these with the findings of histopathology. Materials and Methods: This study involved 19 consecutive patients with pathologically proven lung cancer confined to the bronchial wall. Chest radiographs and CT scans were reviewed for the presence of parenchymal abnormalities, endobronchial nodules, bronchial obstruction, and bronchial wall thickening and stenosis. The CT and histopathologic findings were compared. Results: Sixteen of the 19 patients had abnormal chest radiographic findings, while in 15 (79%), CT revealed bronchial abnormalities: an endobronchial nodule in seven, bronchial obstruction in five, and bronchial wall thickening and stenosis in three. Histopathologically, the lesions appeared as endobronchial nodules in 11 patients, irregular thickening of the bronchial wall in six, elevated mucosa in one, and carcinoma in situ in one. Conclusion: CT helps detect superficial endobronchial lung cancer in 79 % of these patients, though there is some disagreement between the CT findings and the pathologic pattern of bronchial lesions. Although nonspecific, findings of bronchial obstruction or bronchial wall thickening and stenosis should not be overlooked, and if clinically necessary, bronchoscopy should be performed. Index terms: Lung, radiograph

Semi-Automatic Measurement of the Airway Dimension by Computed Tomography Using the Full-Width-Half-Maximum Method: a Study on the Measurement Accuracy according to the CT Parameters and Size of the Airway

Objective: To assess the influence of variable factors such as the size of the airway and the CT imaging parameters such as the reconstruction kernel, field-ofview (FOV), and slice thickness on the automatic measurement of airway dimension. Materials and Methods: An airway phantom was fabricated that contained eleven poly-acryl tubes of various lumen diameters and wall thicknesses. The measured density of the poly-acryl wall was 150 HU, and the measured density of the airspace filled with polyurethane foam was 900 HU. CT images were obtained using a 16-MDCT (multidetector CT) scanner and were reconstructed with various reconstruction kernels, thicknesses and FOV. The luminal radius and wall thickness were measured using in-house software based on the fullwidth- half-maximum method. The measured values as determined by CT and the actual dimensions of the tubes were compared. Results: Measurements were most accurate on images reconstructed with use of a standard kernel (mean error: 0.03+-0.21 mm for wall thickness and 0.12 0.11 mm for the luminal radius). There was no significant difference in accuracy among images with the use of variable slice thicknesses or a variable FOV. Below a 1-mm threshold, the measurement failed to represent the change of the real dimensions. Conclusion: Measurement accuracy was strongly influenced by the specific reconstruction kernel utilized. For accurate measurement, standardization of the imaging protocol and selection of the appropriate anatomic level are essential.This work was supported by a Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (No. R01-2006-000-11244-0)

Prevalence of BRCA1 and BRCA2 Mutations in Korean Breast Cancer Patients

The incidence of breast cancer in Korea has been increasing in recent years, such that it is now the most common female cancer. Breast cancer in Korea is characterized by an earlier age of onset than in Western countries, suggesting that it would be related with genetic background. We assayed germline mutations in the BRCA genes to evaluate their genetic pathology in Korean breast cancer patients. The study subjects consisted of 173 patients at clinically higher risk and 109 unselected patients. Germline mutations in the entire coding sequences of the BRCA1 and BRCA2 genes were analyzed by Conformation-Sensitive Gel Electrophoresis (CSGE), and any aberrantly-sized band was sequenced. BRCA mutations were present in 12.7% of the high risk patients, compared with 2.8% of the unselected patients. Among high risk patients, mutations were most prevalent in patients with a family history of breast or first-degree ovarian cancer (22.1%), followed by those with male breast cancer (20%), bilateral breast cancer (20%), multiple organ cancer including breast (13%) and younger breast cancer patients (aged <35 yr) (8.1%). Moreover, BRCA mutations were detected in 34.8% of patients having two high-risk factors. These findings suggest that BRCA gene mutation analysis should be performed on Korean patients with high-risk factors for breast cancer

Calcific tendinitis of the shoulder in the Korean population: demographics and its relation with coexisting rotator cuff tear

Background To evaluate the demographics, clinical and radiographic features of calcific tendinitis of the shoulder in the Korean population, specifically focusing on the incidence of coexisting rotator cuff tear. Methods Between October 2014 and January 2015, we performed a prospective multicenter study with 506 patients from 11 training hospitals in Korea. We collected data of demographics and radiographic analysis based on simple radiographs, clinical assessments based on visual analog scale (VAS) and the American Shoulder Elbow Surgeons (ASES) score, and treatment modalities that are used currently. We also evaluated coexisting rotator cuff tear by ultrasonography (US) or magnetic resonance imaging (MRI) images. Results There were 402 female patients (79%) with mean age of 55 years (range, 31–87 years). Mean duration of symptoms was 16 months. Mean size of calcific materials was 11.4 mm (range, 0–35 mm). Mean value of VAS and ASES scores were 6.5 (range, 1–10) and 47 (range, 8–95), respectively. Of 383 patients (76%), 59 (15%) had rotator cuff tear including 15 full-thickness tears on US or MRI. Patients with rotator cuff tears were significantly associated with older age, recurrent symptoms, menstrual disorders in females, and having undergone calcification removal surgery and rotator cuff repair (all p<0.05). Conclusions This study reported demographic, radiographic, and clinical features of calcific tendinitis of the shoulder in Korean population, which were not different from those of Western population. Coexisting rotator cuff tear was found with 15% incidence in this large series, suggesting that further radiographic study to evaluate rotator cuff tear might be needed in some calcific tendinitis patients of older age and presenting with recurrent symptoms

Effect of pre-stroke statin use on stroke severity and early functional recovery: a retrospective cohort study

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background Experimental studies suggest that pre-stroke statin treatment has a dual effect of neuroprotection during ischemia and neurorestoration after ischemic injury. The aim of this study was to evaluate the effect of pre-stroke statin use on initial stroke severity and early clinical outcome. Methods We used a prospective database enrolling patients with acute ischemic stroke from 12 hospitals in Korea between April 2008 and January 2012. Primary endpoint was the initial stroke severity as measured by the National Institutes of Health Stroke Scale (NIHSS) score. Secondary endpoints were good outcome (modified Rankin Scale [mRS], 0–2) and overall mRS distribution at discharge. Multivariable regression model and propensity score (PS) matching were used for statistical analyses. Results Among the 8340 patients included in this study, 964 patients (11.6 %) were pre-stroke statin users. The initial NIHSS score (mean [95 % CI]) was lower among pre-stroke statin users vs. non-users in multivariable analysis (5.7 [5.2–6.3] versus 6.4 [5.9–6.9], p = 0.002) and PS analysis (5.2 [4.7–5.7] versus 5.7 [5.4–6.0], p = 0.043). Pre-stroke statin use was associated with increased achievement of mRS 0–2 outcome (multivariable analysis: OR [95 % CI], 1.55 [1.25–1.92], p < 0.001; PS matching: OR [95 % CI], 1.47 [1.16-1.88]; p = 0.002) and favorable shift on the overall mRS distribution (multivariable analysis: OR [95 % CI], 1.29 [1.12-1.51], p = 0.001; PS matching: OR [95 % CI], 1.31 [1.11-1.54]; p = 0.001). Conclusions Pre-stroke statin use was independently associated with lesser stroke severity at presentation and better early functional recovery in patients with acute ischemic stroke

Physiological effects of KDM5C on neural crest migration and eye formation during vertebrate development

Background: Lysine-specific histone demethylase 5C (KDM5C) belongs to the jumonji family of demethylases and is specific for the di- and tri-demethylation of lysine 4 residues on histone 3 (H3K4 me2/3). KDM5C is expressed in the brain and skeletal muscles of humans and is associated with various biologically significant processes. KDM5C is known to be associated with X-linked mental retardation and is also involved in the development of cancer. However, the developmental significance of KDM5C has not been explored yet. In the present study, we investigated the physiological roles of KDM5C during Xenopus laevis embryonic development. Results: Loss-of-function analysis using kdm5c antisense morpholino oligonucleotides indicated that kdm5c knockdown led to small-sized heads, reduced cartilage size, and malformed eyes (i.e., small-sized and deformed eyes). Molecular analyses of KDM5C functional roles using whole-mount in situ hybridization, -galactosidase staining, and reverse transcription-polymerase chain reaction revealed that loss of kdm5c resulted in reduced expression levels of neural crest specifiers and genes involved in eye development. Furthermore, transcriptome analysis indicated the significance of KDM5C in morphogenesis and organogenesis. Conclusion: Our findings indicated that KDM5C is associated with embryonic development and provided additional information regarding the complex and dynamic gene network that regulates neural crest formation and eye development. This study emphasizes the functional significance of KDM5C in Xenopus embryogenesis; however, further analysis is needed to explore the interactions of KDM5C with specific developmental genes