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Find video protocols related to scientific articles indexed in Pubmed.
Simultaneous realization of two approaches to white light in single-component phosphors.
Opt Express
PUBLISHED: 11-18-2014
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A novel single-component warm white light-emitting Sr2Ca0.995MoO6: Sm3+ 0.005 phosphor was synthesized by solid-state reaction. The photoluminescence excitation spectra ranging from 300 to 450 nm and 460 to 500 nm broadly are observed. Direct full-color warm white light [(x, y) = 0.3221, 0.3525] was realized in this single-phase phosphor with exposure to 380 nm UV light. When this phosphor is pumped by 466 nm radiation we obtained yellow emission with an intense red component, suggesting that this material is also competitive as a blue-pumped yellow phosphor. Thus two approaches to white light are realized simultaneously in Sm3+ doped single-component phosphor for the first time. The quantum yield and the reliability of the as-synthesized phosphors for White LED applications were also investigated.
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Elevated Fasting Insulin Level Significantly Increases the Risk of Microalbuminuria.
Circ. J.
PUBLISHED: 11-14-2014
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Background:Microalbuminuria is significantly associated with long-term prognosis in the general population as well as in diabetic patients. It is well known that insulin resistance (IR) can induce microalbuminuria, but an elevated fasting insulin level, which is an early clinical manifestation of IR, as a risk factor for microalbuminuria has not been clarified, so we investigated the association between fasting insulin level and the development of microalbuminuria in a general population.Methods?and?Results:A total of 1,192 non-diabetic Korean men without microalbuminuria in 2005 were followed until 2010. They were categorized into 3 groups according to their fasting insulin levels and monitored for the development of microalbuminuria. The incidence of microalbuminuria was compared among groups, and Cox proportional hazards models were used to calculate the hazard ratios for microalbuminuria according to the fasting insulin levels. During 4,013.0 person-years of follow-up, 51 incident cases of microalbuminuria developed between 2006 and 2010. The incidence of microalbuminuria increased in proportion to the fasting insulin levels (tertile 1: 1.8%, tertile 2: 4.5%, tertile 3: 6.5%, P<0.001). Hazard ratios for microalbuminuria also increased in proportion to the fasting insulin levels [tertile 1: reference, tertile 2: 2.44 (1.01-5.89), tertile 3: 3.30 (1.40-7.78), respectively, P for trend 0.013].Conclusions:Elevated fasting insulin level was associated with the future development of microalbuminuria.
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Outcome methods used in clinical studies of Chiari malformation Type I: a systematic review.
J. Neurosurg.
PUBLISHED: 11-08-2014
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OBJECT Chiari malformation Type I (CM-I) is a common and often debilitating neurological disease. Efforts to improve treatment of CM-I are impeded by inconsistent and limited methods of evaluating clinical outcomes. To understand current approaches and lay a foundation for future research, the authors conducted a systematic review of the methods used in original published research articles to evaluate clinical outcomes in patients treated for CM-I. METHODS The authors searched PubMed, Embase, the Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov , and Cochrane databases to identify publications between January 2003 and August 2013 that met the following criteria: 1) reported clinical outcomes in patients treated for CM-I; 2) were original research articles; 3) included at least 10 patients or, if a comparative study, at least 5 patients per group; and 4) were restricted to patients with CM-I. RESULTS Among the 74 papers meeting inclusion criteria, there was wide variation in the outcome methods used. However, all approaches were broadly grouped into 3 categories: 1) "gestalt" impression of overall symptomatic improvement (n = 45 papers); 2) postoperative change in specific signs or symptoms (n = 20); or 3) results of various standardized assessment scales (n = 22). Among standardized scales, 11 general function measures were used, compared with 6 disease-specific tools. Only 3 papers used scales validated in patients with CM-I. To facilitate a uniform comparison of these heterogeneous approaches, the authors appraised articles in multiple domains defined a priori as integral to reporting clinical outcomes in CM-I. Notably, only 7 articles incorporated patient-response instruments when reporting outcome, and only 22 articles explicitly assessed quality of life. CONCLUSIONS The methods used to evaluate clinical outcomes in CM-I are inconsistent and frequently not comparable, complicating efforts to analyze results across studies. Development, validation, and incorporation of a small number of disease-specific patient-based instruments will improve the quality of research and care of CM-I patients.
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DBTMEE: a database of transcriptome in mouse early embryos.
Nucleic Acids Res.
PUBLISHED: 10-23-2014
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DBTMEE (http://dbtmee.hgc.jp/) is a searchable and browsable database designed to manipulate gene expression information from our ultralarge-scale whole-transcriptome analysis of mouse early embryos. Since integrative approaches with multiple public analytical data have become indispensable for studying embryogenesis due to technical challenges such as biological sample collection, we intend DBTMEE to be an integrated gateway for the research community. To do so, we combined the gene expression profile with various public resources. Thereby, users can extensively investigate molecular characteristics among totipotent, pluripotent and differentiated cells while taking genetic and epigenetic characteristics into consideration. We have also designed user friendly web interfaces that enable users to access the data quickly and easily. DBTMEE will help to promote our understanding of the enigmatic fertilization dynamics.
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Radial to axillary nerve neurotization for brachial plexus injury in children: a combined case series.
J Neurosurg Pediatr
PUBLISHED: 09-05-2014
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Object Axillary nerve palsy, isolated or as part of a more complex brachial plexus injury, can have profound effects on upper-extremity function. Radial to axillary nerve neurotization is a useful technique for regaining shoulder abduction with little compromise of other neurological function. A combined experience of this procedure used in children is reviewed. Methods A retrospective review of the authors' experience across 3 tertiary care centers with brachial plexus and peripheral nerve injury in children (younger than 18 years) revealed 7 cases involving patients with axillary nerve injury as part of an overall brachial plexus injury with persistent shoulder abduction deficits. Two surgical approaches to the region were used. Results Four infants (ages 0.6, 0.8, 0.8, and 0.6 years) and 3 older children (ages 8, 15, and 17 years) underwent surgical intervention. No patient had significant shoulder abduction past 15° preoperatively. In 3 cases, additional neurotization was performed in conjunction with the procedure of interest. Two surgical approaches were used: posterior and transaxillary. All patients displayed improvement in shoulder abduction. All were able to activate their deltoid muscle to raise their arm against gravity and 4 of 7 were able to abduct against resistance. The median duration of follow-up was 15 months (range 8 months to 5.9 years). Conclusions Radial to axillary nerve neurotization improved shoulder abduction in this series of patients treated at 3 institutions. While rarely used in children, this neurotization procedure is an excellent option to restore deltoid function in children with brachial plexus injury due to birth or accidental trauma.
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Laparoscopic reconstructive surgery is superior to vaginal reconstruction in the pelvic organ prolapse.
Int J Med Sci
PUBLISHED: 08-10-2014
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Our purpose was to provide the clinical advantages of the laparoscopic approach compare to the vaginal approach in correcting uterine and vaginal vault prolapse.
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Deep vein thrombosis after spine operation in prone position with subclavian venous catheterization: a case report.
Korean J Anesthesiol
PUBLISHED: 07-29-2014
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We experienced a case of deep vein thrombosis after spine surgery in the prone position with a central venous catheter (CVC). Posterior lumbar interbody fusion was performed on a 73-year-old female patient who was diagnosed with spinal stenosis. Accordingly, in the operation room under general anesthesia, two-lumen CVC were inserted into the left subclavian vein. The surgery was performed in the prone position with a Wilson frame. On the next day, there was a sudden occurrence of severe edema in the patient's left arm. By ultrasonography and computed tomography scanning, extensive deep vein thrombosis was observed in the left subclavian vein. The existence of a factor affecting blood flow such as the prone position may increase the risk of thrombus formation. Therefore, careful perioperative evaluation should be implemented.
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Inhibition of osteoclastogenesis and inflammatory bone resorption by targeting BET proteins and epigenetic regulation.
Nat Commun
PUBLISHED: 07-28-2014
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Emerging evidence suggests that RANKL-induced changes in chromatin state are important for osteoclastogenesis, but these epigenetic mechanisms are not well understood and have not been therapeutically targeted. In this study, we find that the small molecule I-BET151 that targets bromo and extra-terminal (BET) proteins that 'read' chromatin states by binding to acetylated histones strongly suppresses osteoclastogenesis. I-BET151 suppresses pathologic bone loss in TNF-induced inflammatory osteolysis, inflammatory arthritis and post-ovariectomy models. Transcriptome analysis identifies a MYC-NFAT axis important for osteoclastogenesis. Mechanistically, I-BET151 inhibits expression of the master osteoclast regulator NFATC1 by suppressing expression and recruitment of its newly identified upstream regulator MYC. MYC is elevated in rheumatoid arthritis macrophages and its induction by RANKL is important for osteoclastogenesis and TNF-induced bone resorption. These findings highlight the importance of an I-BET151-inhibited MYC-NFAT axis in osteoclastogenesis, and suggest targeting epigenetic chromatin regulators holds promise for treatment of inflammatory and oestrogen deficiency-mediated pathologic bone resorption.
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Identification and in vivo functional characterization of novel compound heterozygous BMP1 variants in osteogenesis imperfecta.
Hum. Mutat.
PUBLISHED: 07-02-2014
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Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders that are characterized by susceptibility to bone fractures, and range in severity from a subtle increase in fracture frequency to death in the perinatal period. Most patients have defects in type I collagen biosynthesis with autosomal dominant inheritance; but, many autosomal recessive genes have been reported. We applied whole exome sequencing to identify mutations in a Korean OI patient who had an umbilical hernia, frequent fractures, a markedly short stature, delayed motor development, scoliosis, and dislocation of the radial head, with a bowed radius and ulna. We identified two novel variants in the BMP1 gene: c.808A>G and c.1297G>T. The former variant caused a missense change p.(Met270Val) and the latter variant caused the skipping of exon 10. The hypo-functional nature of the two variants was demonstrated in a zebrafish assay. This article is protected by copyright. All rights reserved.
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Myocardium-derived angiopoietin-1 is essential for coronary vein formation in the developing heart.
Nat Commun
PUBLISHED: 06-27-2014
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The origin and developmental mechanisms underlying coronary vessels are not fully elucidated. Here we show that myocardium-derived angiopoietin-1 (Ang1) is essential for coronary vein formation in the developing heart. Cardiomyocyte-specific Ang1 deletion results in defective formation of the subepicardial coronary veins, but had no significant effect on the formation of intramyocardial coronary arteries. The endothelial cells (ECs) of the sinus venosus (SV) are heterogeneous population, composed of APJ-positive and APJ-negative ECs. Among these, the APJ-negative ECs migrate from the SV into the atrial and ventricular myocardium in Ang1-dependent manner. In addition, Ang1 may positively regulate venous differentiation of the subepicardial APJ-negative ECs in the heart. Consistently, in vitro experiments show that Ang1 indeed promotes venous differentiation of the immature ECs. Collectively, our results indicate that myocardial Ang1 positively regulates coronary vein formation presumably by promoting the proliferation, migration and differentiation of immature ECs derived from the SV.
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Acetabular paralabral cyst as a rare cause of obturator neuropathy: a case report.
Ann Rehabil Med
PUBLISHED: 06-26-2014
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An acetabular paralabral cyst is a benign soft tissue cyst usually seen in association with a tear of the acetabular labrum. Acetabular paralabral cysts are often the cause of joint pain, but they rarely cause compression of the adjacent neurovascular structures. We present a case of a 63-year-old male patient who had paresis and atrophy of right hip adductor muscles. Right obturator neuropathy was confirmed through an electrodiagnostic study. In addition, magnetic resonance imaging showed a paralabral cyst in the right acetabulum which extended to the pelvic wall. The patient underwent conservative treatment without surgical procedure. The pain was decreased after 1 month of conservative therapy. The pain was decreased at the 1-month follow-up. Follow-up electromyography showed polyphasic motor unit potentials in adductor magnus and adductor longus muscles. Based on the experience of this case, an acetabular paralabral cyst should be considered as one of the rare causes of obturator neuropathy.
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Prediction of pathologic staging with magnetic resonance imaging after preoperative chemoradiotherapy in rectal cancer: Pooled analysis of KROG 10-01 and 11-02.
Radiother Oncol
PUBLISHED: 06-18-2014
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The reported overall accuracy of MRI in predicting the pathologic stage of nonirradiated rectal cancer is high. However, the role of MRI in restaging rectal tumors after neoadjuvant CRT is contentious. Thus, we evaluate the accuracy of restaging magnetic resonance imaging (MRI) for rectal cancer patients who receive preoperative chemoradiotherapy (CRT).
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Optical coherence tomography shows early loss of the inferior temporal quadrant retinal nerve fiber layer in autosomal dominant optic atrophy.
Graefes Arch. Clin. Exp. Ophthalmol.
PUBLISHED: 06-10-2014
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The aim of the study was to evaluate the relationship between visual function and retinal nerve fiber layer thickness (RNFLT) determined using Stratus optical coherence tomography (OCT) in patients with autosomal dominant optic atrophy (ADOA).
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Strength of footing with punching shear preventers.
ScientificWorldJournal
PUBLISHED: 05-30-2014
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The punching shear failure often governs the strength of the footing-to-column connection. The punching shear failure is an undesirable failure mode, since it results in a brittle failure of the footing. In this study, a new method to increase the strength and ductility of the footing was proposed by inserting the punching shear preventers (PSPs) into the footing. The validation and effectiveness of PSP were verified through a series of experimental studies. The nonlinear finite element analysis was then performed to demonstrate the failure mechanism of the footing with PSPs in depth and to investigate the key parameters that affect the behavior of the footing with PSPs. Finally, the design recommendations for the footing with PSPs were suggested.
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Clinical outcomes of laparoscopic versus open surgery for primary tumor resection in patients with stage IV colorectal cancer with unresectable metastasis.
Surg. Today
PUBLISHED: 05-27-2014
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The aim of this study was to compare the clinical outcomes of laparoscopic surgery with those of open surgery in patients with colorectal cancer and unresectable metastasis.
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Effect of enzyme replacement therapy in late onset Pompe disease: open pilot study of 48 weeks follow-up.
Neurol. Sci.
PUBLISHED: 05-26-2014
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Late-onset Pompe disease (LOPD) is an autosomal recessive disorder caused by deficiency of the enzyme acid glucosidase alfa (GAA). Recently, enzyme replacement therapy (ERT) using recombinant human GAA (rhGAA) became clinically available, and is expected to modify the clinical course in LOPD of various stages. In this study, we evaluated the efficacy and adverse events of ERT for 48 weeks in Korean LOPD patients. Five Korean LOPD patients were included in the study. At baseline, clinical and laboratory features, including muscular and pulmonary function, were assessed, and rhGAA was infused every 2 weeks. Then, patients were examined at every 12-week interval for evaluation of changes in motor and pulmonary function for 48 weeks along with adverse reactions to ERT. The muscular and pulmonary function of the patients varied depending on the baseline condition of the patient after 48 weeks of ERT. However, the overall function of the patients showed stabilization of the disease rather than the improvement seen in infantile-onset Pompe disease. This is the first clinical study on ERT of Korean LOPD patients. Results of our study showed stabilization of muscular and pulmonary function in LOPD patients for 48 weeks with a favorable prognosis for patients who received early diagnosis and ambulatory patients. One of our patients developed a serious anaphylactic reaction, which necessitated the cessation of further ERT. Therefore, our study shows that early diagnosis and ERT are important in preventing further deterioration of the disease.
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Production of ?-particle emitting ²¹¹At using 45 MeV ?-beam.
Phys Med Biol
PUBLISHED: 05-13-2014
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Among the ?-particle emitting radionuclides, (211)At is considered to be a promising radionuclide for targeted cancer therapy due to its decay properties. The range of alpha particles produced by the decay of (211)At are less than 70 µm in water with a linear energy transfer between 100 and 130 keV µm(-1), which are about the maximum relative biological effectiveness for heavy ions. It is important to note that at the present time, only a few of cyclotrons routinely produce (211)At. The direct production method is based on the nuclear reactions (209)Bi(?,2n)(211)At. Production of the radionuclide (211)At was carried out using the MC-50 cyclotron at the Korea Institute of Radiological and Medical Sciences (KIRAMS). To ensure high beam current, the ?-beam was extracted with an initial energy of 45 MeV, which was degraded to obtain the appropriate ?-beam energy. The calculations of beam energy degradation were performed utilizing the MCNPX. Alumina-baked targets were prepared by heating the bismuth metal powder onto a circular cavity in a furnace. When using an E(?, av) of 29.17 MeV, the very small contribution of (210)At confirms the right choice of the irradiation energy to obtain a pure production of (211)At isotope.
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Incidence and risk factors of metachronous colorectal neoplasm after curative resection of colorectal cancer in Korean patients.
J Dig Dis
PUBLISHED: 04-30-2014
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Early detection and endoscopic removal of metachronous neoplasms are important preventive strategies for patients with colorectal cancer (CRC) after curative tumor resection. We aimed to determine the incidence of and the risk factors for metachronous colorectal neoplasms after curative resection for CRC.
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Clinical significance of non-alcoholic fatty liver disease as a risk factor for prehypertension.
J. Korean Med. Sci.
PUBLISHED: 04-24-2014
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Previous epidemiologic studies have shown the clinical association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). However, there is only limited information about the effect of NAFLD on the development of hypertension. Accordingly, we investigated the clinical association between NAFLD and prehypertension. A prospective cohort study was conducted on the 11,350 Korean men without prehypertension for 5 yr. The incidences of prehypertension were evaluated, and Cox proportional hazard model was used to measure the hazard ratios (HRs) for the development of prehypertension according to the degree of NAFLD (normal, mild, moderate to severe). The incidence of prehypertension increased according to NAFLD states (normal: 55.5%, mild: 63.7%, moderate to severe: 70.3%, P<0.001). Even after adjusting for multiple covariates, the HRs (95% confidence interval) for prehypertension were higher in the mild group (1.18; 1.07-1.31) and moderate to severe group (1.62; 1.21-2.17), compared to normal group, respectively (P for trend <0.001). The development of prehypertension is more potentially associated with the more progressive NAFLD than normal and milder state. These findings suggest the clinical significance of NAFLD as one of risk factors for prehypertension.
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Clinical association between non-alcoholic fatty liver disease and the development of hypertension.
J. Gastroenterol. Hepatol.
PUBLISHED: 04-17-2014
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Non-alcoholic fatty liver disease (NAFLD) is getting an increasing attention for its clinical implications on cardiovascular disease (CVD). However, epidemiologic data are not so evident to sustain the causative association between NAFLD and hypertension, the major cause of CVD. Accordingly, we designed this study to investigate the clinical association between NAFLD and the development of hypertension.
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Nondispersive optical activity of meshed helical metamaterials.
Nat Commun
PUBLISHED: 04-10-2014
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Extreme optical properties can be realized by the strong resonant response of metamaterials consisting of subwavelength-scale metallic resonators. However, highly dispersive optical properties resulting from strong resonances have impeded the broadband operation required for frequency-independent optical components or devices. Here we demonstrate that strong, flat broadband optical activity with high transparency can be obtained with meshed helical metamaterials in which metallic helical structures are networked and arranged to have fourfold rotational symmetry around the propagation axis. This nondispersive optical activity originates from the Drude-like response as well as the fourfold rotational symmetry of the meshed helical metamaterials. The theoretical concept is validated in a microwave experiment in which flat broadband optical activity with a designed magnitude of 45° per layer of metamaterial is measured. The broadband capabilities of chiral metamaterials may provide opportunities in the design of various broadband optical systems and applications.
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Angiopoietin 2 induces pericyte apoptosis via ?3?1 integrin signaling in diabetic retinopathy.
Diabetes
PUBLISHED: 04-10-2014
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Pericyte loss is an early characteristic change in diabetic retinopathy (DR). Despite accumulating evidence that hyperglycemia-induced angiopoietin 2 (Ang2) has a central role in pericyte loss, the precise molecular mechanism has not been elucidated. This study investigated the role of Ang2 in pericyte loss in DR. We demonstrated that pericyte loss occurred with Ang2 increase in the diabetic mouse retina and that the source of Ang2 could be the endothelial cell. Ang2 induced pericyte apoptosis via the p53 pathway under high glucose, whereas Ang2 alone did not induce apoptosis. Integrin, not Tie-2 receptor, was involved for Ang2-induced pericyte apoptosis under high glucose as an Ang2 receptor. High glucose changed the integrin expression pattern, which increased integrin ?3 and ?1 in the pericyte. Furthermore, Ang2-induced pericyte apoptosis in vitro was effectively attenuated via p53 suppression by blocking integrin ?3 and ?1. Although intravitreal injection of Ang2 induced pericyte loss in C57BL/6J mice retina in vivo, intravitreal injection of anti-integrin ?3 and ?1 antibodies attenuated Ang2-induced pericyte loss. Taken together, Ang2 induced pericyte apoptosis under high glucose via ?3?1 integrin. Glycemic control or blocking Ang2/integrin signaling could be a potential therapeutic target to prevent pericyte loss in early DR.
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Association between family history of malignant neoplasm with colorectal adenomatous polyp in 40s aged relative person.
Cancer Epidemiol
PUBLISHED: 04-03-2014
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We assessed the association between a family history of malignancy and risk of colorectal adenoma among individuals aged 40-49 years.
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A case of malignant granular cell tumor in the sigmoid colon.
Clin Endosc
PUBLISHED: 03-31-2014
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Granular cell tumor (GCT) is an uncommon, usually benign neoplasm; however, a malignant potential has been described. Malignant GCT is an extremely rare neoplasm showing rapid growth and invasion into adjacent muscles, lymph nodes, or vessels, or even distant metastasis. We recently experienced a case of a histologically benign or atypical but clinically malignant GCT, with invasion of the lymph nodes and vessels in the sigmoid colon, diagnosed by segmental colon resection with lymph node dissection. We also performed a review of relevant medical literature.
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Does cardiac catheterization laboratory activation by electrocardiography machine auto-interpretation reduce door-to-balloon time?
Am J Emerg Med
PUBLISHED: 03-21-2014
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In an attempt to begin ST-segment elevation myocardial infarction (STEMI) treatment more quickly (referred to as door-to-balloon [DTB] time) by minimizing preventable delays in electrocardiogram (ECG) interpretation, cardiac catheterization laboratory (CCL) activation was changed from activation by the emergency physician (code heart I) to activation by a single page if the ECG is interpreted as STEMI by the ECG machine (ECG machine auto-interpretation) (code heart II). We sought to determine the impact of ECG machine auto-interpretation on CCL activation.
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Reliability of the percent density in digital mammography with a semi-automated thresholding method.
J Breast Cancer
PUBLISHED: 03-17-2014
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The reliability of the quantitative measurement of breast density with a semi-automated thresholding method (Cumulus™) has mainly been investigated with film mammograms. This study aimed to evaluate the intrarater reproducibility of percent density (PD) by Cumulus™ with digital mammograms.
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Risk of secondary cancers from scattered radiation during intensity-modulated radiotherapies for hepatocellular carcinoma.
Radiat Oncol
PUBLISHED: 03-17-2014
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To evaluate and compare the risks of secondary cancers from therapeutic doses received by patients with hepatocellular carcinoma (HCC) during intensity-modulated radiotherapy (IMRT), volumetric arc therapy (VMAT), and tomotherapy (TOMO).
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Dual modulation of the mitochondrial permeability transition pore and redox signaling synergistically promotes cardiomyocyte differentiation from pluripotent stem cells.
J Am Heart Assoc
PUBLISHED: 03-15-2014
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Cardiomyocytes that differentiate from pluripotent stem cells (PSCs) provide a crucial cellular resource for cardiac regeneration. The mechanisms of mitochondrial metabolic and redox regulation for efficient cardiomyocyte differentiation are, however, still poorly understood. Here, we show that inhibition of the mitochondrial permeability transition pore (mPTP) by Cyclosporin A (CsA) promotes cardiomyocyte differentiation from PSCs.
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A beneficial effect of purse-string skin closure after ileostomy takedown: a retrospective cohort study.
Int J Surg
PUBLISHED: 03-11-2014
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The aim of this study was to investigate the clinical benefits of purse-string skin closure (PS) in daily practice compared with conventional linear skin closure (CL) after ileostomy takedown in Korean population.
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Parkinson's disease-linked human PARK9/ATP13A2 maintains zinc homeostasis and promotes ?-Synuclein externalization via exosomes.
Hum. Mol. Genet.
PUBLISHED: 03-06-2014
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?-Synuclein plays a central causative role in Parkinson's disease (PD). Increased expression of the P-type ATPase ion pump PARK9/ATP13A2 suppresses ?-Synuclein toxicity in primary neurons. Our data indicate that ATP13A2 encodes a zinc pump; neurospheres from a compound heterozygous ATP13A2(-/-) patient and ATP13A2 knockdown cells are sensitive to zinc, whereas ATP13A2 over-expression in primary neurons confers zinc resistance. Reduced ATP13A2 expression significantly decreased vesicular zinc levels, indicating ATP13A2 facilitates transport of zinc into membrane-bound compartments or vesicles. Endogenous ATP13A2 localized to multi-vesicular bodies (MVBs), a late endosomal compartment located at the convergence point of the endosomal and autophagic pathways. Dysfunction in MVBs can cause a range of detrimental effects including lysosomal dysfunction and impaired delivery of endocytosed proteins/autophagy cargo to the lysosome, both of which have been observed in cells with reduced ATP13A2 function. MVBs also serve as the source of intra-luminal nanovesicles released extracellularly as exosomes that can contain a range of cargoes including ?-Synuclein. Elevated ATP13A2 expression reduced intracellular ?-Synuclein levels and increased ?-Synuclein externalization in exosomes >3-fold whereas ATP13A2 knockdown decreased ?-Synuclein externalization. An increased export of exosome-associated ?-Synuclein may explain why surviving neurons of the substantia nigra pars compacta in sporadic PD patients were observed to over-express ATP13A2. We propose ATP13A2's modulation of zinc levels in MVBs can regulate the biogenesis of exosomes capable of containing ?-Synuclein. Our data indicate that ATP13A2 is the first PD-associated gene involved in exosome biogenesis and indicates a potential neuroprotective role of exosomes in PD.
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Beta-lapachone inhibits pathological retinal neovascularization in oxygen-induced retinopathy via regulation of HIF-1?.
J. Cell. Mol. Med.
PUBLISHED: 02-18-2014
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Retinal neovascularization in retinopathy of prematurity (ROP) is the most common cause of blindness for children. Despite evidence that hypoxia inducible factor (HIF)-1? -VEGF axis is associated with the pathogenesis of ROP, the inhibitors of HIF-1? have not been established as a therapeutic target in the control of ROP pathophysiology. We investigated the hypothesis that degradation of HIF-1? as a master regulator of angiogenesis in hypoxic condition, using ?-lapachone, would confer protection against hypoxia-induced retinopathy without affecting physiological vascular development in mice with oxygen-induced retinopathy (OIR), an animal model of ROP. The effects of ?-lapachone were examined after intraocular injection in mice with OIR. Intraocular administration of ?-lapachone resulted in significant reduction in hypoxia-induced retinal neovascularization without retinal toxicity or perturbation of developmental retinal angiogenesis. Our results demonstrate that HIF-1?-mediated VEGF expression in OIR is associated with pathological neovascularization, not physiological angiogenesis. Thus, strategies blocking HIF-1? in the developing eye in the pathological hypoxia could serve as a novel therapeutic target for ROP.
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G-749, a novel FLT3 kinase inhibitor, can overcome drug resistance for the treatment of acute myeloid leukemia.
Blood
PUBLISHED: 02-14-2014
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Aberrant activations of Fms-like tyrosine receptor kinase (FLT) 3 are implicated in the pathogenesis of 20% to 30% of patients with acute myeloid leukemia (AML). G-749 is a novel FLT3 inhibitor that showed potent and sustained inhibition of the FLT3 wild type and mutants including FLT3-ITD, FLT3-D835Y, FLT3-ITD/N676D, and FLT3-ITD/F691L in cellular assays. G-749 retained its inhibitory potency in various drug-resistance milieus such as patient plasma, FLT3 ligand surge, and stromal protection. Furthermore, it displayed potent antileukemic activity in bone marrow blasts from AML patients regardless of FLT3 mutation status, including those with little or only minor responses to AC220 or PKC412. Oral administration of G-749 yielded complete tumor regression and increased life span in animal models. Thus, G-749 appears to be a promising next-generation drug candidate for the treatment of relapsed and refractory AML patients with various FLT3-ITD/FLT3-TKD mutants and further shows the ability to overcome drug resistance.
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Usefulness of Digital Tomosynthesis for the Detection of Airway Obstruction: A Case Report of Bronchial Carcinosarcoma.
Cancer Res Treat
PUBLISHED: 02-11-2014
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Bronchial carcinosarcoma is a very rare malignant tumor that is composed of carcinomatous and sarcomatous elements. We describe the first case in which digital tomosynthesis was useful for the evaluation of airway obstruction by bronchial carcinosarcoma that was overlooked on initial chest radiography.
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GABARBP down-regulates HIF-1? expression through the VEGFR-2 and PI3K/mTOR/4E-BP1 pathways.
Cell. Signal.
PUBLISHED: 01-28-2014
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Human ?-aminobutyrate type A (GABAA) receptor-binding protein (GABARBP), a tumor suppressor protein with apoptotic function, can be inhibited in response to angiogenesis through the PI3K/Akt signaling cascades. Here, we investigated whether GABARBP over-expression could regulate vascular endothelial growth factor (VEGF)/hypoxia-inducible factor-1? (HIF-1?) expression and angiogenic activity in a carcinoma model system. GABARBP dramatically inhibited VEGF-induced endothelial cell proliferation, migration, and tube formation, as well as VEGFR-2 phosphorylation in vitro. At the same time, GABARBP exposed potent anti-angiogenic activity and remarkably down-regulated the levels of VEGF and HIF-1? protein expression, key components for angiogenesis. In addressing its biological molecular mechanism, GABARBP was found to effectively inhibit the phosphorylation of down-stream PI3K components, such as PDK1, Akt, mTOR, TSC-2, p70S6K, and 4E-BP1 by directly binding with VEGFR-2. In contrast, p38/JNK phosphorylation was not suppressed by GABARBP. These findings disclose a novel function of GABARBP in suppressing VEGF and HIF-1? protein expression, which is important for tumor angiogenesis and tumor growth. Thus, our data strongly provides novel biological mechanistic insights into the regulatory function of GABARBP in ovarian tumor progression, and the important of pre-clinical certification of GABARBP as a potential angiogenesis agent targeting ovarian tumorigenesis.
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Impact of enzyme replacement therapy on linear growth in Korean patients with mucopolysaccharidosis type II (Hunter syndrome).
J. Korean Med. Sci.
PUBLISHED: 01-28-2014
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Hunter syndrome (or mucopolysaccharidosis type II [MPS II]) arises because of a deficiency in the lysosomal enzyme iduronate-2-sulfatase. Short stature is a prominent and consistent feature in MPS II. Enzyme replacement therapy (ERT) with idursulfase (Elaprase®) or idursulfase beta (Hunterase®) have been developed for these patients. The effect of ERT on the growth of Korean patients with Hunter syndrome was evaluated at a single center. This study comprised 32 patients, who had received ERT for at least 2 yr; they were divided into three groups according to their ages at the start of ERT: group 1 (<6 yr, n=14), group 2 (6-10 yr, n=11), and group 3 (10-20 yr, n=7). The patients showed marked growth retardation as they got older. ERT may have less effect on the growth of patients with the severe form of Hunter syndrome. The height z-scores in groups 2 and 3 revealed a significant change (the estimated slopes before and after the treatment were -0.047 and -0.007, respectively: difference in the slope, 0.04; P<0.001). Growth in response to ERT could be an important treatment outcome or an endpoint for future studies.
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Prognostic impact of circumferential resection margin in rectal cancer treated with preoperative chemoradiotherapy.
Ann. Surg. Oncol.
PUBLISHED: 01-28-2014
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The circumferential resection margin (CRM) is a strong prognostic factor in rectal cancer. The purpose of this study was to investigate the relationship between CRM distance and recurrence in patients with locally advanced rectal cancer who received preoperative chemoradiotherapy (CRT).
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Intracellular amyloid beta alters the tight junction of retinal pigment epithelium in 5XFAD mice.
Neurobiol. Aging
PUBLISHED: 01-21-2014
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Extracellular deposit of amyloid beta (A?) is a common pathologic feature in both age-related macular degeneration (AMD) and Alzheimer's disease, but the role of intracellular A? on the tight junction of the retinal pigment epithelium (RPE) is unknown. In this study, we investigated the intracellular A? expression and its role on the outer blood retinal barrier in the retina of 5XFAD mice, a mouse model of Alzheimer's disease. The retina of 5XFAD mice showed the pathologic features of AMD with intracellular A? in the RPE. As intracellular A? accumulated, zonular occludens-1 and occludin were markedly attenuated and lost their integrity as tight junctions in the RPE of 5XFAD mice. Also, A?42 uptake by ARPE-19 cells induced the tight junction breakdown of zonular occludens-1 and occludin without cell death. These results implicate that intracellular A?42 could play a role in the breakdown of the outer blood retinal barrier in 5XFAD mice. Thus, we suggested that 5XFAD mice could be a mouse model of dry AMD with regard to the A?42 related pathology.
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Vascular RhoJ is an effective and selective target for tumor angiogenesis and vascular disruption.
Cancer Cell
PUBLISHED: 01-18-2014
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Current antiangiogenic therapy is limited by its cytostatic nature and systemic side effects. To address these limitations, we have unveiled the role of RhoJ, an endothelial-enriched Rho GTPase, during tumor progression. RhoJ blockade provides a double assault on tumor vessels by both inhibiting tumor angiogenesis and disrupting the preformed tumor vessels through the activation of the RhoA-ROCK (Rho kinase) signaling pathway in tumor endothelial cells, consequently resulting in a functional failure of tumor vasculatures. Moreover, enhanced anticancer effects were observed when RhoJ blockade was employed in concert with a cytotoxic chemotherapeutic agent, angiogenesis-inhibiting agent, or vascular-disrupting agent. These results identify RhoJ blockade as a selective and effective therapeutic strategy for targeting tumor vasculature with minimal side effects.
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Evaluation of effective dose conversion coefficients for Korean adults during medical x-ray examinations up to 150 keV through comparison with ICRP Publication 74 and ICRP Publication 116.
J Radiol Prot
PUBLISHED: 01-17-2014
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A Monte Carlo program for calculating organ doses for patients undergoing medical x-ray examination (PCXMC) was used to calculate effective dose conversion coefficients for Korean adults. Two sets of effective dose results were calculated based on tissue weighting factors recommended in International Commission on Radiological Protection (ICRP) Publications 60 and 103 for monochromatic energy photons of 10, 15, 20, 30, 40, 50, 60, 70, 80, 100 and 150 keV. The results were obtained for monoenergetic photons, since effective dose conversion coefficients recommended in ICRP Publications 74 and 116 were given for monochromatic energies, thereby enabling the comparison of our result to those suggested by the ICRP publications. The areas of comparison include: to observe effects due to changes in tissue weighting factors, modification within Medical Internal Radiation Dose (MIRD) phantoms and differences in phantom types. The phantom employed in the PCXMC program is a modified version of the phantom used in ICRP Publication 74, with additional organs that were added in order to take into account the updated tissue weighting factors given in ICRP Publication 103. Both use MIRD phantoms but our study modified the phantom size to the average physical condition of Korean adults, while ICRP Publication 74 uses the phantom size of the reference man defined in ICRP Publication 23. On the other hand, the effective dose suggested in ICRP 116 was calculated using an entirely different type of phantom: a voxel phantom with the size of reference man. Although significant differences were observed for certain organ doses in the lateral beam directions, differences in the effective doses were within 5% for the anterior-posterior (AP) and posterior-anterior (PA) directions, and within 16% in lateral directions when tissue weighting factors were applied and the variations were adjusted for all three comparisons. The results show that calculation of effective doses for Korean adults using the PCXMC (Caucasian-based phantom) is acceptable for the AP and PA directions, but care should be taken for lateral directions.
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Elevated fasting serum insulin level predicts future development of hypertension.
Int. J. Cardiol.
PUBLISHED: 01-16-2014
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Studies have investigated clinical association between fasting insulin level and hypertension. However, it is still debatable whether elevated fasting insulin actually increases the risk of hypertension with the passage of time. Thus, this study was aimed at investigating the association between baseline fasting insulin level and the development of hypertension.
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Hirayama disease with juvenile myoclonic epilepsy: A case report.
Ann Indian Acad Neurol
PUBLISHED: 01-10-2014
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Hirayama disease (HD) is rare, but benign anterior horn cell disease, predominantly affecting young men. One of the symptoms, besides weakness, is abnormal movement in the hand. Juvenile myoclonic epilepsy (JME) is one of the most common types of generalized epilepsies and can be recognized by a myoclonic jerk and electroencephalography (EEG) features. We report the case of a 19-year-old male who had HD, with unilateral abnormal movement in the hand, which was diagnosed as JME. We should consider performing an EEG in patients with HD, who present with atypical hand movements, in order to differentiate it from seizure.
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Parkinson's disease-associated human ATP13A2 (PARK9) deficiency causes zinc dyshomeostasis and mitochondrial dysfunction.
Hum. Mol. Genet.
PUBLISHED: 01-07-2014
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Human ATP13A2 (PARK9), a lysosomal type 5 P-type ATPase, has been associated with autosomal recessive early-onset Parkinson's disease (PD). ATP13A2 encodes a protein that is highly expressed in neurons and is predicted to function as a cation pump, although the substrate specificity remains unclear. Accumulation of zinc and mitochondrial dysfunction are established aetiological factors that contribute to PD; however, their underlying molecular mechanisms are largely unknown. Using patient-derived human olfactory neurosphere cultures, which harbour loss-of-function mutations in both alleles of ATP13A2, we identified a low intracellular free zinc ion concentration ([Zn(2+)]i), altered expression of zinc transporters and impaired sequestration of Zn(2+) into autophagy-lysosomal pathway-associated vesicles, indicating that zinc dyshomeostasis occurs in the setting of ATP13A2 deficiency. Pharmacological treatments that increased [Zn(2+)]i also induced the production of reactive oxygen species and aggravation of mitochondrial abnormalities that gave rise to mitochondrial depolarization, fragmentation and cell death due to ATP depletion. The toxic effect of Zn(2+) was blocked by ATP13A2 overexpression, Zn(2+) chelation, antioxidant treatment and promotion of mitochondrial fusion. Taken together, these results indicate that human ATP13A2 deficiency results in zinc dyshomeostasis and mitochondrial dysfunction. Our data provide insights into the molecular mechanisms of zinc dyshomeostasis in PD and its contribution to mitochondrial dysfunction with ATP13A2 as a molecular link between the two distinctive aetiological factors of PD.
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Silver Wire Amplifies the Signaling Mechanism for IL-1beta Production More Than Silver Submicroparticles in Human Monocytic THP-1 Cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Silver materials have been widely used in diverse fields. However, their toxicity and their mechanism, especially in different forms, have not been studied sufficiently. Thus, cytotoxicity, apoptosis, and interleukin-1beta (IL-1?) production were investigated using macrophage-like THP-1 cells in the presence of Ag microparticles (AgMPs, 2.7 µm), Ag submicroparticles (AgSMPs, 150 nm), and Ag wires (AgWs, 274 nm×5.3 µm). The levels of cytotoxicity, apoptosis, and IL-1? production by AgWs were higher than those by the other two AgSMPs and AgMPs. This trend was also observed with each step of the signaling mechanism for IL-1? production, which is a single pathway affiliated with ROS generation or lysosomal rupture or both, cathepsin B, caspase-1 (NALP3 inflammasome), and finally IL-1? production in THP-1 cells. All these results suggest that, for development of safe and effective silver materials, the shape or form of silver materials should be considered, especially for macrophage cell lines because epithelial cell lines are not overly sensitive to silver materials.
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Computational promoter modeling identifies the modes of transcriptional regulation in hematopoietic stem cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Extrinsic and intrinsic regulators are responsible for the tight control of hematopoietic stem cells (HSCs), which differentiate into all blood cell lineages. To understand the fundamental basis of HSC biology, we focused on differentially expressed genes (DEGs) in long-term and short-term HSCs, which are closely related in terms of cell development but substantially differ in their stem cell capacity. To analyze the transcriptional regulation of the DEGs identified in the novel transcriptome profiles obtained by our RNA-seq analysis, we developed a computational method to model the linear relationship between gene expression and the features of putative regulatory elements. The transcriptional regulation modes characterized here suggest the importance of transcription factors (TFs) that are expressed at steady state or at low levels. Remarkably, we found that 24 differentially expressed TFs targeting 21 putative TF-binding sites contributed significantly to transcriptional regulation. These TFs tended to be modulated by other nondifferentially expressed TFs, suggesting that HSCs can achieve flexible and rapid responses via the control of nondifferentially expressed TFs through a highly complex regulatory network. Our novel transcriptome profiles and new method are powerful tools for studying the mechanistic basis of cell fate decisions.
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Association between serum ferritin levels and the incidence of obesity in Korean men: A prospective cohort study.
Endocr. J.
PUBLISHED: 12-29-2013
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Elevated serum ferritin levels are associated with insulin resistance, type 2 diabetes, cardiovascular disease, and metabolic syndrome. To date, however, no cohort studies have examined whether serum ferritin levels are an independent risk factor for the obesity. Therefore, we conducted a prospective cohort study to evaluate the temporal relationship between serum ferritin levels and obesity development in Korean men. Total 17,812 healthy Korean men who participated in a medical health check-up program in 2005 were followed-up until 2010. Obesity was defined as a body mass index ? 25 kg/m(2). Cox proportional hazards model was used to measure the hazard ratio of the quartile groups of serum ferritin levels. During 64,446.5 person-years of follow-up carried out, 2,627 patients became obese. After adjusting for multiple covariates, we found that the hazard ratios (95% confidence interval) for incident obesity when we compared the second, third and fourth quartiles of serum ferritin levels with the first quartile were 1.08 (0.95-1.23), 1.14 (1.00-1.30), and 1.24 (1.09-1.41), respectively (p for trend = 0.003). Both severe obesity (body mass index ? 30 kg/m(2)) and abdominal obesity based on waist circumference (>90 cm) showed consistent longitudinal associations (p for trend <0.001). Elevated serum ferritin levels may have been a predictive factor for obesity during the 5-year follow-up in 17,812 Korean men.
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Inferring the choreography of parental genomes during fertilization from ultralarge-scale whole-transcriptome analysis.
Genes Dev.
PUBLISHED: 12-20-2013
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Fertilization precisely choreographs parental genomes by using gamete-derived cellular factors and activating genome regulatory programs. However, the mechanism remains elusive owing to the technical difficulties of preparing large numbers of high-quality preimplantation cells. Here, we collected >14 × 10(4) high-quality mouse metaphase II oocytes and used these to establish detailed transcriptional profiles for four early embryo stages and parthenogenetic development. By combining these profiles with other public resources, we found evidence that gene silencing appeared to be mediated in part by noncoding RNAs and that this was a prerequisite for post-fertilization development. Notably, we identified 817 genes that were differentially expressed in embryos after fertilization compared with parthenotes. The regulation of these genes was distinctly different from those expressed in parthenotes, suggesting functional specialization of particular transcription factors prior to first cell cleavage. We identified five transcription factors that were potentially necessary for developmental progression: Foxd1, Nkx2-5, Sox18, Myod1, and Runx1. Our very large-scale whole-transcriptome profile of early mouse embryos yielded a novel and valuable resource for studies in developmental biology and stem cell research. The database is available at http://dbtmee.hgc.jp.
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High Normal Urine Albumin-to-Creatinine Ratio Predicts Development of Hypertension in Korean Men.
Circ. J.
PUBLISHED: 12-13-2013
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Background:?Microalbuminuria is known as a risk factor for hypertension. Recently it was suggested that urine albumin-to-creatinine ratio (UACR), even within the normal range, can be associated with hypertension, but the temporal relationship between normal range UACR and hypertension was not confirmed. Therefore the aim of this study was to verify an association between normal range UACR and the development of hypertension in Korean men. Methods and Results:?This prospective cohort study was performed on 1,284 initially non-hypertensive Korean men. The total follow-up period was 4,109.5 person-years and the mean follow-up period was 3.2±1.51 years. Cox proportional hazards model was used to estimate the hazard ratios (HR) for the risk of hypertension development. After adjusting for multiple covariates, the HR (95% confidence interval [CI]) for incident hypertension, comparing the second to the fourth quartiles of UACR level to the first quartile, were 1.35 (95% CI: 0.93-1.97), 1.55 (95% CI: 1.07-2.25) and 1.89 (95% CI: 1.31-2.71), respectively (P for trend=0.001). Conclusions:?High UACR within the normal range was significantly associated with hypertension development. Furthermore, this association remained significant after adjusting for multiple baseline covariates.
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Motion-map constrained image reconstruction (MCIR): Application to four-dimensional cone-beam computed tomography.
Med Phys
PUBLISHED: 12-11-2013
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Purpose: Utilization of respiratory correlated four-dimensional cone-beam computed tomography (4DCBCT) has enabled verification of internal target motion and volume immediately prior to treatment. However, with current standard CBCT scan, 4DCBCT poses challenge for reconstruction due to the fact that multiple phase binning leads to insufficient number of projection data to reconstruct and thus cause streaking artifacts. The purpose of this study is to develop a novel 4DCBCT reconstruction algorithm framework called motion-map constrained image reconstruction (MCIR), that allows reconstruction of high quality and high phase resolution 4DCBCT images with no more than the imaging dose as well as projections used in a standard free breathing 3DCBCT (FB-3DCBCT) scan.Methods: The unknown 4DCBCT volume at each phase was mathematically modeled as a combination of FB-3DCBCT and phase-specific update vector which has an associated motion-map matrix. The motion-map matrix, which is the key innovation of the MCIR algorithm, was defined as the matrix that distinguishes voxels that are moving from stationary ones. This 4DCBCT model was then reconstructed with compressed sensing (CS) reconstruction framework such that the voxels with high motion would be aggressively updated by the phase-wise sorted projections and the voxels with less motion would be minimally updated to preserve the FB-3DCBCT. To evaluate the performance of our proposed MCIR algorithm, we evaluated both numerical phantoms and a lung cancer patient. The results were then compared with the (1) clinical FB-3DCBCT reconstructed using the FDK, (2) 4DCBCT reconstructed using the FDK, and (3) 4DCBCT reconstructed using the well-known prior image constrained compressed sensing (PICCS).Results: Examination of the MCIR algorithm showed that high phase-resolved 4DCBCT with sets of up to 20 phases using a typical FB-3DCBCT scan could be reconstructed without compromising the image quality. Moreover, in comparison with other published algorithms, the image quality of the MCIR algorithm is shown to be excellent.Conclusions: This work demonstrates the potential for providing high-quality 4DCBCT during on-line image-guided radiation therapy (IGRT), without increasing the imaging dose. The results showed that (at least) 20 phase images could be reconstructed using the same projections data, used to reconstruct a single FB-3DCBCT, without streak artifacts that are caused by insufficient projections.
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Suppression of VEGF expression through interruption of the HIF?1? and Akt signaling cascade modulates the anti?angiogenic activity of DAPK in ovarian carcinoma cells.
Oncol. Rep.
PUBLISHED: 11-01-2013
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Death-associated protein kinase (DAPK) plays an important role in apoptosis regulation and has been shown to maintain antitumor and metastasis suppressor properties. In the present study, we investigated whether DAPK overexpression may mediate vascular endothelial growth factor (VEGF)/hypoxia-inducible factor-1? (HIF-1?) expression and angiogenic activity in the human carcinoma cell model system. VEGF plays a pivotal role in tumor angiogenesis and tumorigenesis. We found that DAPK significantly downregulated VEGF-induced endothelial cell proliferation, migration and tube formation as well as VEGF receptor-2 (VEGFR-2) phosphorylation in vitro. In addition, DAPK exhibited potent anti-angiogenic activity and clearly decreased the levels of VEGF and HIF-1? expression, a key regulator for angiogenesis. Notably, our results strongly indicated that DAPK can disturb VEGFR-2 transcriptional activity by inhibiting VEGFR-2 phosphorylation through the PI3K/Akt signaling cascade. Collectively, our study identified a novel function of DAPK in regulating cellular VEGF/HIF-1? activity during tumorigenesis, which may act together with its anti-angiogenic function to inhibit tumor progression.
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Neuromuscular junction in a microfluidic device.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
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Malfunctions at the site of neuromuscular junction (NMJ) of post-injuries or diseases are major barriers to recovery of function. The ability to efficiently derive motor neurons (MN) from embryonic stem cells has indicated promise toward the development of new therapies in increasing functional outcomes post injury. Recent advances in micro-technologies have provided advanced culture platforms allowing compartmentalization of sub-cellular components of neurons. In this study, we combined these advances in science and technology to develop a compartmentalized in vitro NMJ model. The developed NMJ system is between mouse embryonic stem cell (mESC)-derived MNs and c2c12 myotubes cultured in a compartmentalized polydimethylsiloxane (PDMS) microfluidic device. While some functional in vitro NMJ systems have been reported, this system would further contribute to research in NMJ-related diseases by providing a system to study the site of action of NMJ aimed at improving promoting better functional recovery.
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Laparoscopic versus open surgery for stage I rectal cancer: long-term oncologic outcomes.
World J Surg
PUBLISHED: 08-16-2013
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Laparoscopic resection is increasingly being performed for rectal cancer. However, few data are available to compare long-term outcomes after open versus laparoscopic surgery for early-stage rectal cancer.
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Safety and efficacy of single-port colectomy for sigmoid colon cancer: a phase II clinical trial.
J Laparoendosc Adv Surg Tech A
PUBLISHED: 08-12-2013
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Recently, single-port surgery for colon cancer has been increasingly attempted. However, prospective studies investigating the efficacy of single-port colectomy for colon cancer are lacking. The aim of this study is to determine whether single-port colectomy for sigmoid colon cancer is a safe and effective surgical option.
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Clinical availability of nonalcoholic fatty liver disease as an early predictor of type 2 diabetes mellitus in Korean men: 5-year prospective cohort study.
Hepatology
PUBLISHED: 07-06-2013
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There have been several reports about the clinical association between type 2 diabetes mellitus (DM) and nonalcoholic fatty liver disease (NAFLD). However, most of the studies were about the unilateral effects of type 2 DM on NAFLD, and studies on the reverse relation are rare. Thus, this study was designed to investigate the effect of NAFLD on type 2 DM. We conducted a prospective cohort study on 25,232 Korean men without type 2 DM for 5 years. We serially checked the various metabolic factors including fasting glucose and hemoglobin A1c (HbA1c), and monitored the development of type 2 DM. The incidence rate of type 2 DM was compared according to the degree of NAFLD (normal, mild, and moderate to severe), and a Cox proportional hazards model was used to measure the hazard ratios (HRs) of NAFLD on type 2 DM. The incidence rate of type 2 DM increased according to the degree of NAFLD (normal: 7.0%, mild: 9.8%, moderate to severe: 17.8%, P < 0.001). Even after adjusting for other multiple covariates, the HRs (95% confidence interval [CI]) for type 2 DM development was higher in the mild group (1.09; 0.81-1.48) and moderate to severe group (1.73; 1.00-3.01) compared to the normal group, respectively (P for trend <0.001).
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Factors influencing hepatocellular carcinoma prognosis after hepatectomy: a single-center experience.
Korean J. Intern. Med.
PUBLISHED: 07-01-2013
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Recurrence after hepatic resection is one of the most important factors impacting the prognosis and survival of patients with hepatocellular carcinoma (HCC). We identified prognostic factors affecting overall survival (OS) and disease-free survival (DFS) in patients with HCC after hepatic resection.
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Impact of body mass index on the risk of colorectal adenoma in a metabolically healthy population.
Cancer Res.
PUBLISHED: 05-16-2013
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Metabolically healthy obese (MHO) states exist that seem to be protected from cardiovascular risks. Although obesity is a risk factor for colorectal adenoma (CRA), there has yet to be any study of the risks of CRA in MHO individuals. In this study, we compared CRA prevalence in MHO individuals versus metabolically healthy individuals who were normal in weight. This cross-sectional study involved 18,085 Korean adults (39.1 ± 6.7 years) who had a health checkup including a colonoscopy. High-risk CRA was defined as any adenoma over 1 cm, 3 or more adenomas, adenoma with a villous component, or high-grade dysplasia. Multinomial logistic regression models were used to measure the associations between body mass index (BMI) and the risk of low-risk and high-risk CRA. Low-risk and high-risk CRA were present in 9.3% and 1.4% of the study population, respectively. After adjusting for age, sex, smoking, drinking, exercise, family history of colorectal cancer, education, and use of analgesic and aspirin, compared with normal healthy individuals, the prevalence of low-risk and high-risk CRA was increased in MHO individuals [OR = 1.44; 95% confidence interval (CI), 1.23-1.69 and OR = 1.62; 95% CI, 1.09-2.41, respectively]. In fully adjusted models, the prevalence of low-risk and high-risk CRA was associated with increasing categories of BMI in a dose-response manner (P for trend < 0.001 and 0.01, respectively). Thus, excess body weight, even in the absence of a metabolic unhealthy state, was found to be positively associated with increased presence of CRAs.
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Partial visual rehabilitation using a toric implantable collamer lens in a patient with keratoconus: a case report with 20 months of follow-up.
Korean J Ophthalmol
PUBLISHED: 04-30-2013
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We report the case of a 37-year-old man with a high myopic keratoconus eye that was treated with a posterior chamber toric implantable collamer lens (ICL) in Korea. The patient had a history of contact lens intolerance and did not want to have a corneal transplantation. His uncorrected visual acuity (UCVA) and best spectacle corrected visual acuity were 0.02 and 0.4 in the left eye, respectively. Preoperatively, the manifest refraction was -12.0 -3.5 × 30A. Postoperatively, the manifest refraction was -1.75 × 180A. UCVA improved markedly after implantation. No intraoperative or postoperative complications were observed during 20 months of follow-up. Toric ICL implantation may be a possible alternative surgical option for the visual rehabilitation of high myopic astigmatism in keratoconus patients with rigid gas permeable contact lens intolerance and in patients who do not want to get a corneal transplant.
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Association of Serum ?-Glutamyltransferase Level and Incident Prehypertension in Korean Men.
J. Korean Med. Sci.
PUBLISHED: 04-29-2013
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Several lines of evidence indicate that prehypertension is more atherogenic than normal blood pressure. Serum ?-glutamyltransferase (GGT) is known to be positively associated with prehypertensive status and the progression of hypertension. However, there have been no prospective studies of serum GGT level as a predictor of prehypertension. Apparently 13,435 healthy men (mean age 42.0 ± 6.6 yr) with normal blood pressure were included in a prospective cohort study in 2005 and were followed up to 2010 with the endpoint being incident of prehypertension. During the follow up period (median 2.80 ± 1.44 yr; actual follow-up 37,679.1 person-year), prehypertension was developed in 7,867 (58.6%) participants. Risk estimations for incident prehypertension were analyzed based on quartiles of serum GGT levels using multivariate adjusted Cox proportional hazards model. In unadjusted model, the hazard ratio for incident prehypertension for the highest 3 quartiles of baseline serum GGT level was 1.21 (1.13-1.29), 1.29 (1.21-1.38), and 1.57 (1.47-1.67) compared the lowest quartile of serum GGT level, respectively (P for trend < 0.001). These associations still remained statistically significant, even after adjusting for multiple covariates. These findings indicate that increased serum GGT level is independently associated with incident prehypertension in Korean men.
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Preoperative plasma hyperfibrinogenemia is predictive of poor prognosis in patients with nonmetastatic colon cancer.
Ann. Surg. Oncol.
PUBLISHED: 04-25-2013
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The outcomes of colorectal cancer are determined by host factors, including systemic inflammation. The purpose of this study was to evaluate the prognostic significance of fibrinogen and inflammation-based scores, as markers of the inflammatory response, in colon cancer.
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A recurrent longitudinally extensive transverse myelitis with Aquaporin-4(AQP4) antibody after herpes zoster.
J. Neurol. Sci.
PUBLISHED: 04-16-2013
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Longitudinally extensive transverse myelitis (LETM) is a syndrome that involves three or more vertebral segments in the spinal cord lesion, and it is one of the characteristic features of neuromyelitis optica (NMO) differentiating it from multiple sclerosis. Many studies proved the importance of aquaporin-4 (AQP4) antibody, which plays a vital role in the pathogenesis of NMO. Recent reports suggest that recurrent LETM patients with positive anti-AQP4 antibody titers have a higher chance of converting to NMO, and they are now termed as NMO spectrum disorders (NMOSD). The specific role of AQP4 antibody in NMO is yet to be elucidated but there are reports to bring up the pathogenesis in relation with infectious events. Interestingly, parainfectious NMOSD tends to spare the optic nerve unlike classic NMOSD. Here we report a young woman who was once diagnosed as herpes zoster-related LETM, but later developed as recurrent LETM with positive AQP4 antibody titers, which renders the diagnosis of parainfectious LETM without optic neuritis.
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Tumor suppressor BLU promotes paclitaxel antitumor activity by inducing apoptosis through the down-regulation of Bcl-2 expression in tumorigenesis.
Biochem. Biophys. Res. Commun.
PUBLISHED: 04-16-2013
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In this current work, we investigated whether BLU could enhance pro-apoptotic activity of chemotherapeutic drugs in ovarian carcinoma cells. A combination with a chemotherapeutic drug showed an additive effect, and this additive effect was supplemented by the enhancement of caspase-3 and -9 activities. BLU and paclitaxel induced cell cycle arrest in the G2/M phase through the reduction of cyclin dependent kinase 1, cyclin B1, while promoting both p16 and p27 expression. In addition, both BLU and paclitaxel enhanced the expression of the pro-apoptotic protein Bax together with the suppression of anti-apoptotic protein Bcl-2, a protein which is well-known for its function as a regulator in protecting cells from apoptosis. As expected, the Bax and p21 activities were enhanced by BLU or paclitaxel, while a combination of BLU and paclitaxel were additively promoted, whereas Bcl-xL and NF-?B including Bcl-2 activity were inactivated. This study has yielded promising results, which evidence for the first time that BLU could suppress the growth of carcinoma cells. Furthermore, both BLU and paclitaxel inhibited the phosphorylation of signaling components downstream of phosphoinositide 3-kinase, such as 3-phosphoinositide-dependent protein kinase 1, and Akt. Also, BLU plus paclitaxel decreased phosphorylation of p70 ribosomal S6 kinase, as well as decreasing the phosphorylation of glycogen synthase kinase-3?, which is one of the representative targets of the mammalian target of rapamycin signaling cascade. These results provide evidence that BLU enhances G2/M cell cycle arrest and apoptotic cell death through the up-regulation of Bax, p21 and p53 expression.
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High-normal albuminuria predicts metabolic syndrome in middle-aged Korean men: A prospective cohort study.
Maturitas
PUBLISHED: 04-10-2013
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High-normal albuminuria has recently been associated with an elevated risk of cardiovascular disease. However, it is uncertain whether high-normal albuminuria is associated with metabolic syndrome (MetS). The objective of this prospective cohort study was to investigate whether a temporal relationship exists between a high-normal urine albumin-to-creatinine ratio (UACR) and the development of MetS.
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Serum uric acid level is associated with the development of microalbuminuria in Korean men.
Eur. J. Clin. Invest.
PUBLISHED: 04-08-2013
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Elevated serum uric acid (UA) could be a risk factor for hypertension, type 2 diabetes mellitus and cardiovascular disease. In addition, elevated serum UA may be associated with impaired renal function. However, it is unclear whether elevated serum UA is a cause of microalbuminuria or not. Therefore, we performed a prospective cohort study of the temporal relationship between baseline elevated serum UA and the development of microalbuminuria in Korean men.
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Capillary flow of amorphous metal for high performance electrode.
Sci Rep
PUBLISHED: 03-18-2013
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Metallic glass (MG) assists electrical contact of screen-printed silver electrodes and leads to comparable electrode performance to that of electroplated electrodes. For high electrode performance, MG needs to be infiltrated into nanometer-scale cavities between Ag particles and reacts with them. Here, we show that the MG in the supercooled state can fill the gap between Ag particles within a remarkably short time due to capillary effect. The flow behavior of the MG is revealed by computational fluid dynamics and density funtional theory simulation. Also, we suggest the formation mechanism of the Ag electrodes, and demonstrate the criteria of MG for higher electrode performance. Consequently, when Al85Ni5Y8Co2 MG is added in the Ag electrodes, cell efficiency is enhanced up to 20.30% which is the highest efficiency reported so far for screen-printed interdigitated back contact solar cells. These results show the possibility for the replacement of electroplating process to screen-printing process.
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Synchronous activation of gonadotropin-releasing hormone gene transcription and secretion by pulsatile kisspeptin stimulation.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 03-18-2013
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Pulsatile release of hypothalamic gonadotropin-releasing hormone (GnRH) is essential for pituitary gonadotrope function. Although the importance of pulsatile GnRH secretion has been recognized for several decades, the mechanisms underlying GnRH pulse generation in hypothalamic neural networks remain elusive. Here, we demonstrate the ultradian rhythm of GnRH gene transcription in single GnRH neurons using cultured hypothalamic slices prepared from transgenic mice expressing a GnRH promoter-driven destabilized luciferase reporter. Although GnRH promoter activity in each GnRH neuron exhibited an ultradian pattern of oscillations with a period of ?10 h, GnRH neuronal cultures exhibited partially synchronized bursts of GnRH transcriptional activity at ?2-h intervals. Surprisingly, pulsatile administration of kisspeptin, a potent GnRH secretagogue, evoked dramatic synchronous activation of GnRH gene transcription with robust stimulation of pulsatile GnRH secretion. We also addressed the issue of hierarchical interaction between the circadian and ultradian rhythms by using Bmal1-deficient mice with defective circadian clocks. The circadian molecular oscillator barely affected basal ultradian oscillation of GnRH transcription but was heavily involved in kisspeptin-evoked responses of GnRH neurons. In conclusion, we have clearly shown synchronous bursts of GnRH gene transcription in the hypothalamic GnRH neuronal population in association with episodic neurohormone secretion, thereby providing insight into GnRH pulse generation.
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Association of cytomegalovirus with idiopathic chronic anterior uveitis with ocular hypertension in Korean patients.
Ocul. Immunol. Inflamm.
PUBLISHED: 03-12-2013
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To investigate the association between cytomegalovirus and idiopathic chronic recurrent anterior uveitis with ocular hypertension.
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Phase I/II clinical trial of enzyme replacement therapy with idursulfase beta in patients with mucopolysaccharidosis II (Hunter syndrome).
Orphanet J Rare Dis
PUBLISHED: 03-09-2013
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Mucopolysaccharidosis II (MPS II, Hunter syndrome) is a rare X-linked lysosomal storage disorder caused by the deficiency of iduronate-2-sulfatase (IDS). In affected patients, glycosaminoglycan (GAG) accumulates in the lysosomes of many organs and tissues contributing to the pathology associated with MPS II. The objective of this phase I/II clinical study was to evaluate the efficacy and safety of recombinant human iduronate-2-sulfatase (idursulfase beta, Hunterase®) in the treatment of MPS II.
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A known expressed sequence tag, BM742401, is a potent lincRNA inhibiting cancer metastasis.
Exp. Mol. Med.
PUBLISHED: 03-08-2013
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Long intergenic non-coding RNAs (lincRNAs) have historically been ignored in cancer biology. However, thousands of lincRNAs have been identified in mammals using recently developed genomic tools, including microarray and high-throughput RNA sequencing (RNA-seq). Several of the lincRNAs identified have been well characterized for their functions in carcinogenesis. Here we performed RNA-seq experiments comparing gastric cancer with normal tissues to find differentially expressed transcripts in intergenic regions. By analyzing our own RNA-seq and public microarray data, we identified 31 transcripts, including a known expressed sequence tag, BM742401. BM742401 was downregulated in cancer, and its downregulation was associated with poor survival in gastric cancer patients. Ectopic overexpression of BM742401 inhibited metastasis-related phenotypes and decreased the concentration of extracellular MMP9. These results suggest that BM742401 is a potential lincRNA marker and therapeutic target.
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Risk of second cancer from scattered radiation of intensity-modulated radiotherapies with lung cancer.
Radiat Oncol
PUBLISHED: 02-24-2013
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To compare the risk of secondary cancer from scattered and leakage doses following intensity-modulated radiotherapy (IMRT), volumetric arc therapy (VMAT) and tomotherapy (TOMO) in patients with lung cancer.
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Association between CASR polymorphisms, calcium intake, and colorectal cancer risk.
PLoS ONE
PUBLISHED: 02-15-2013
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The current study aimed to assess the effect of dietary calcium intake and possible interactions with calcium-sensing receptor (CASR) gene polymorphisms on colorectal cancer risk.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.