70 research outputs found

    A role of DNA-dependent protein kinase for the activation of AMP-activated protein kinase in response to glucose deprivation

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    AbstractThe catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) plays an essential role in double-strand break repair by initially recognizing and binding to DNA breaks. Here, we show that DNA-PKcs interacts with the regulatory Ī³1 subunit of AMP-activated protein kinase (AMPK), a heterotrimeric enzyme that has been proposed to function as a ā€œfuel gaugeā€ to monitor changes in the energy status of cells and is controlled by the upstream kinases LKB1 and Ca2+/calmodulin-dependent kinase kinase (CaMKK). In co-immunoprecipitation analyses, DNA-PKcs and AMPKĪ³1 interacted physically in DNA-PKcs-proficient M059K cells but not in DNA-PKcs-deficient M059J cells. Glucose deprivation-stimulated phosphorylation of AMPKĪ± on Thr172 and of acetyl-CoA carboxylase (ACC), a downstream target of AMPK, is substantially reduced in M059J cells compared with M059K cells. The inhibition or down-regulation of DNA-PKcs by the DNA-PKcs inhibitors, wortmannin and Nu7441, or by DNA-PKcs siRNA caused a marked reduction in AMPK phosphorylation, AMPK activity, and ACC phosphorylation in response to glucose depletion in M059K, WI38, and IMR90 cells. In addition, DNAā€“DNA-PKcsāˆ’/āˆ’ mouse embryonic fibroblasts (MEFs) exhibited decreased AMPK activation in response to glucose-free conditions. Furthermore, the knockdown of DNA-PKcs led to the suppression of AMPK (Thr172) phosphorylation in LKB1-deficient HeLa cells under glucose deprivation. Taken together, these findings support the positive regulation of AMPK activation by DNA-PKcs under glucose-deprived conditions in mammalian cells

    Estimation of Stellate Ganglion Block Injection Point Using the Cricoid Cartilage as Landmark Through X-ray Review

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    BACKGROUND: Stellate ganglion block is usually performed at the transverse process of C6, because the vertebral artery is located anterior to the transverse process of C7. The purpose of this study is to estimate the location of the transverse process of C6 using the cricoid cartilage in the performance of stellate ganglion block. METHODS: We reviewed cervical lateral neutral-flexion-extension views of 48 patients who visited our pain clinic between January and June of 2010. We drew a horizontal line at the surface of the cricoid cartilage in the neutral and extension views of cervical lateral x-rays. We then measured the change in the shortest distance from this horizontal line to the lowest point of the transverse process of C6 between the neutral and extension views. RESULTS: There was a statistically significant difference in the shortest distance from the horizontal line at the surface of the cricoid cartilage to the lowest point of transverse process of C6 between neutral position and neck extension position in both males and females, and between males and females in both neutral position and neck extension position. The cricoid cartilage level was 4.8 mm lower in males and 14.4 mm higher in females than the lowest point of transverse process of C6 in neck extension position. CONCLUSIONS: Practitioners should recognize that the cricoid cartilage has cephalad movement in neck extension. In this way, the cricoid cartilage can be still useful as a landmark for stellate ganglion block.ope

    Enhancement of paclitaxel-induced breast cancer cell death via the glycogen synthase kinase-3 beta-mediated B-cell lymphoma 2 regulation

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    Glycogen synthase kinase-3 beta (GSK-3 beta) is a serine/threonine protein kinase that is known to mediate cancer cell death. Here, we show that B-cell lymphoma 2 (Bcl-2), an anti-apoptotic protein, is regulated by GSK-3 beta and that GSK-3 beta-mediated regulation of Bcl-2 is crucial for mitochondrial-dependent cell death in paclitaxel-stimulated cells. We demonstrate that MCF7 GSK3 beta siRNA cells are more sensitive to cell death than MCF7 GFP control cells and that in the absence of GSK-3 beta, Bcl-2 levels are reduced, a result enhanced by paclitaxel. Paclitaxel-induced JNK (c-Jun N-terminal kinase) activation is critical for Bcl-2 modulation. In the absence of GSK-3 beta, Bcl-2 was unstable in an ubiquitination-dependent manner in both basal-and paclitaxel-treated cells. Furthermore, we demonstrate that GSK-3 beta-mediated regulation of Bcl-2 influences cytochrome C release and mitochondrial membrane potential. Taken together, our data suggest that GSK-3 beta-dependent regulation of Bcl-2 is crucial for mitochondria-dependent cell death in paclitaxel-mediated breast cancer therapy.clos

    Etiology of Invasive Bacterial Infections in Immunocompetent Children in Korea (1996-2005): A Retrospective Multicenter Study

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    The purpose of this study was to identify the major etiological agents responsible for invasive bacterial infections in immunocompetent Korean children. We retrospectively surveyed invasive bacterial infections in immunocompetent children caused by eight major pediatric bacteria, namely Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pyogenes, Listeria monocytogenes, and Salmonella species that were diagnosed at 18 university hospitals from 1996 to 2005. A total of 768 cases were identified. S. agalactiae (48.1%) and S. aureus (37.2%) were the most common pathogens in infants younger than 3 months. S. agalactiae was a common cause of meningitis (73.0%), bacteremia without localization (34.0%), and arthritis (50%) in this age group. S. pneumoniae (45.3%) and H. influenzae (20.4%) were common in children aged 3 months to 5 yr. S. pneumoniae was a common cause of meningitis (41.6%), bacteremia without localization (40.0%), and bacteremic pneumonia (74.1%) in this age group. S. aureus (50.6%), Salmonella species (16.9%), and S. pneumoniae (16.3%) were common in older children. A significant decline in H. influenzae infections over the last 10 yr was noted. S. agalactiae, S. pneumoniae, and S. aureus are important pathogens responsible for invasive bacterial infections in Korean children

    Prognostic influence of body mass index and body weight gain during adjuvant FOLFOX chemotherapy in Korean colorectal cancer patients

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    This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Background: Asian population has different body mass index (BMI) profile compared to Caucasian population. However, the effect of obesity and body weight gain in Asian colorectal cancer patients treated with adjuvant chemotherapy has not been studied thus far. Methods: We have analyzed the association between disease-free survival (DFS) and obesity/body weight change during treatment in Korean stage III or high-risk stage II colorectal cancer patients treated with adjuvant 5-fluorouracil/leucovorin/oxaliplatin. BMI was classified according to WHO Asia-Pacific classification. Weight change was calculated by comparing body weights measured at the last chemotherapy cycle and before surgery. Results: Among a total of 522 patients, 35.7 % of patients were obese (BMI >= 25 kg/m(2)) and 29.1 % were overweight (BMI, 23-24.9 kg/m(2)) before surgery. 18.0 % of patients gained = 5 kg and 26.1 % gained 2-4.9 kg during the adjuvant chemotherapy period. Baseline BMI or body weight change was not associated with DFS in the overall study population. However, body weight gain (>= 5 kg) was associated with inferior DFS (adjusted hazard ratio 2.04, 95 % confidence interval 1.02-4.08, p = 0.043) in overweight and obese patients (BMI >= 23.0 kg/m(2)). Conclusion: In Korean colorectal cancer patients treated with adjuvant FOLFOX chemotherapy, body weight gain during the treatment period has a negative prognostic influence in overweight and obese patients

    The Causative Organisms of Bacterial Meningitis in Korean Children in 1996-2005

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    Bacterial meningitis remains a serious cause of morbidity and mortality in childhood, despite the availability of effective vaccines against Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae. The purpose of this study was to analyze data on bacterial meningitis cases in Korea from 1996 through 2005. The information of all hospitalized bacteria-proven meningitis cases was obtained from 17 university hospitals nationwide. A total of 402 cases were identified. Of these, 125 (29.9%) cases were neonates. Streptococcus agalactiae was the most common bacteria responsible for 99 (24.6%) of all cases regardless of age, followed by S. pneumoniae for 91 (22.6%) and H. influenzae for 67 (16.7%) patients. The common etiology beyond the neonatal period was S. pneumoniae for 91 (33.0%) followed by H. influenzae for 63 (22.8%) patients. The overall case fatality rate was 9.4%, which was similar with that in 1986-1995. In conclusion, S. agalactiae, S. pneumoniae and H. influenzae were important etiologic agents of bacterial meningitis in children in the last 10 yrs. It is required to establish the preventive strategy of the three bacteria. The nationwide epidemiologic study should be continued to evaluate immunization strategy and efficacy

    Clinical Characteristics of a Nationwide Hospital-based Registry of Mild-to-Moderate Alzheimer's Disease Patients in Korea: A CREDOS (Clinical Research Center for Dementia of South Korea) Study

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    With rapid population aging, the socioeconomic burden caused by dementia care is snowballing. Although a few community-based studies of Alzheimer's disease (AD) have been performed in Korea, there has never been a nationwide hospital-based study thereof. We aimed to identify the demographics and clinical characteristics of mild-to-moderate AD patients from the Clinical Research Center for Dementia of Korea (CREDOS) registry. A total of 1,786 patients were consecutively included from September 2005 to June 2010. Each patient underwent comprehensive neurological examination, interview for caregivers, laboratory investigations, neuropsychological tests, and brain MRI. The mean age was 74.0 yr and the female percentage 67.0%. The mean period of education was 7.1 yr and the frequency of early-onset AD (< 65 yr old) was 18.8%. Among the vascular risk factors, hypertension (48.9%) and diabetes mellitus (22.3%) were the most frequent. The mean score of the Korean version of Mini-Mental State Examination (K-MMSE) was 19.2 and the mean sum of box scores of Clinical Dementia Rating (CDR-SB) 5.1. Based on the well-structured, nationwide, and hospital-based registry, this study provides the unique clinical characteristics of AD and emphasizes the importance of vascular factors in AD in Korea

    Efficacies of the new Paclitaxel-eluting Coroflex Pleaseā„¢ Stent in percutaneous coronary intervention; comparison of efficacy between Coroflex Pleaseā„¢ and Taxusā„¢ (ECO-PLEASANT) trial: study rationale and design

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    <p>Abstract</p> <p>Background</p> <p>Previous randomized trials have showed the superiority of Paclitaxel-eluting stent over bare metal stent in angiographic and clinical outcomes. Coroflex Pleaseā„¢ stent is a newly developed drug eluting stent using the Coroflexā„¢ stent platform combined with the drug paclitaxel contained in a polymer coating. PECOPS I trial, one-arm observational study, showed that the clinical and angiographic outcomes of Coroflex Pleaseā„¢ stent were within the range of those of Taxus, the 1<sup>st </sup>generation paclitaxel-eluting stent (PES). However, there have been no studies directly comparing the Coroflex Pleaseā„¢ stent with the Taxus Liberteā„¢ stent that is the newest version of Taxus. Therefore, prospective, randomized trial is required to demonstrate the non-inferiority of Coroflex Pleaseā„¢ stent compared with Taxus Liberteā„¢ stent in a head-to-head manner.</p> <p>Methods</p> <p>In the comparison of Efficacy between COroflex PLEASeā„¢ ANd Taxusā„¢ stent(ECO-PLEASANT) trial, approximately 900 patients are being prospectively and randomly assigned to the either type of Coroflex Pleaseā„¢ stent and Taxus Liberteā„¢ stent via web-based randomization. The primary endpoint is clinically driven target vessel revascularization at 9 months. The secondary endpoints include major cardiac adverse events, target vessel failure, stent thrombosis and angiographic efficacy endpoints.</p> <p>Discussion</p> <p>The ECO-PLEASANT trial is the study not yet performed to directly compare the efficacy and safety of the Coroflex Pleaseā„¢ versus Taxus Liberteā„¢ stent. On the basis of this trial, we will be able to find out whether the Coroflex Pleaseā„¢ stent is non-inferior to Taxus Liberteā„¢ stent or not.</p> <p>Trial registration</p> <p>ClinicalTrials.gov number, NCT00699543.</p
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