tbuckley/cabot-search huggingface dataset:
Abstract LB-185: Oxidative damage targets complexes containing DNA methyltransferases, SIRT1 and polycomb members to promoter CpG islands
Authors: Heather M. O'Hagan, Wei Wang, Subhojit Sen, Stella S. Lee, Eriko G. Clements, Yi Cai, Leander Van Neste, Hariharan Easwaran, Stephen B. Baylin
Journal: Cancer Research (2011)

Abstract A key question in cancer epigenetics is how cancers of multiple types simultaneously acquire global losses and gains of DNA methylation. The increases often occur in promoter CpG islands and can be associated with transcriptional inactivation of key tumor suppressor genes. Here we demonstrate a molecular response to oxidative damage, a key factor in cancer risk states, which could help explain the gains and losses of DNA methylation that occur during tumor progression. Within 30 minutes of exposing cells to the reactive oxygen species, hydrogen peroxide (H2O2), the major maintenance enzyme for DNA methylation, DNMT1, becomes notably more tightly bound to chromatin. Concomitantly, DNMT1 targets SIRT1 to chromatin and both proteins become part of a large multi-protein complex(es) which also contains the de novo DNA methyltransferase, DNMT3B. This oxidative damage-induced complex also contains specific polycomb group members, which, in the context of SIRT1, define the Polycomb Repressive Complex 4 (PRC4), previously found only in embryonic and adult stem cells and cancer cells. By examining chromatin on a genome-wide scale, we demonstrate that H2O2 treatment preferentially damages GC-rich regions of DNA. This damage causes a shift in localization of the above complex(es) from non-GC-rich to GC-rich regions of the genome including promoter CpG islands of which some are DNA hypermethylated in cancer cells. Additionally, this treatment causes a decrease in nascent RNA transcript levels of these genes that have oxidative damage-induced enrichment of the silencing complex in their CpG island-containing promoters. Thus, oxidative damage induces formation and localization of a silencing complex that may in part explain cancer specific aberrant losses and gains in DNA methylation associated with gene transcriptional silencing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-185. doi:10.1158/1538-7445.AM2011-LB-185
Abstract 1739: Unexpected complexity in Mcl-1 phosphorylation in response to microtubule inhibitors.
Authors: Rong Chu, Timothy C. Chambers
Journal: Cancer Research (2013)

Abstract Microtubule inhibitors promote phosphorylation and degradation of Mcl-1, and the loss of expression of this key anti-apoptotic Bcl-2 family member appears to be critical for apoptosis induction. While several sites and kinases have been implicated, a phosphorylation/degradation-resistant mutant has not been definitively described. Contrary to previous reports suggesting that Thr92 phosphorylation by Cdk1 regulates Mcl-1 degradation, a Thr92Ala Mcl-1 mutant expressed in HeLa cells was phosphorylated and degraded with the same kinetics as wild-type following vinblastine-treatment. Similarly, when Mcl-1 with alanine replacements of five putative major sites (S64, T70A, T92, S121, T163) was expressed, it was phosphorylated and degraded like the wild-type. These results suggested redundancy or the existence of additional regulatory sites. To analyze Mcl-1 phosphorylation in more detail, cell extracts, made using a novel extraction solution to improve resolution, were subjected to 2D-PAGE/immunoblotting. Extracts from asynchronous control cells showed one major and two minor, more acidic, spots, the latter sensitive to acid phosphatase treatment. Extracts from vinblastine-treated cells showed up to 9 distinct spots all but two of which were eliminated after acid phosphatase treatment. These results reveal an unexpected complexity in Mcl-1 phosphorylation in response to microtubule inhibitors and the existence of many more sites than previously suspected. Identification of the additional sites of phosphorylation, the kinase(s) responsible, and their role in regulation of Mcl-1 degradation are ongoing. Supported by NIH CA109821. Citation Format: Rong Chu, Timothy C. Chambers. Unexpected complexity in Mcl-1 phosphorylation in response to microtubule inhibitors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1739. doi:10.1158/1538-7445.AM2013-1739
Prevalence of human immunodeficiency virus and hepatitis C virus among French prison inmates in 2010: a challenge for public health policy
Authors: C Semaille, Y Le Strat, E Chiron, K Chemlal, M A Valantin, P Serre, L Caté, C Barbier, M Jauffret-Roustide, Collective the Prevacar Group
Journal: Eurosurveillance (2013)

Binary file ES_Abstracts_Final_ECDC.txt matches
SP0066 Satellite Cells in Adult Muscle Repair, Adaptation and Disease.
Authors: C. A. Peterson
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Satellite cells are clearly necessary for postnatal muscle growth and muscle regeneration in the adult. Satellite cells are normally quiescent and in response to damage become activated, proliferate and differentiate into myocytes that fuse with each other to replace lost myofibers, or fuse with existing myofibers for repair. Following injury, and in neuromuscular degenerative diseases, central nucleation is the hallmark of regenerating myofibers. The role of satellite cells in inflammatory myopathies is less clear, although infiltrating immune cells influence satellite cell activity. The necessity of satellite cells in adult muscle adaptability is equivocal. Although satellite cells are known to participate in adult myofiber hypertrophy, several different mouse models of muscle growth show that they are dispensable; the myonuclear domain is flexible, enlarging to accommodate growth in the absence of satellite cell fusion. Satellite cells are not involved in muscle re-growth following disuse atrophy, as no change in myonuclear number occurs during those processes; myonuclear domain size is reduced with unloading due to decreased cytoplasmic volume and is restored following reloading, independent of satellite cells. Currently, there is also no direct evidence that satellite cells are involved in normal muscle maintenance. Our recent work demonstrates that lifelong satellite cell depletion does not exacerbate sarcopenia; neither the loss of muscle mass nor the attenuated hypertrophic response to overload, both apparent in aged mice, is affected by satellite cells. Thus, whereas satellite cell or stem cell-based therapies for muscle degenerative diseases holds promise, therapies for atrophy focused on increasing satellite cell number or activity are unfounded. The extent to which results from studies of mouse satellite cell properties will be translatable to human muscle remains to be determined. <h3>Disclosure of Interest</h3> None Declared
572 CARDIAC FUNCTION AND DYNAMICS OF QT INTERVAL IN PATIENTS WITH MILD CIRRHOSIS DURING MAXIMAL BETA-ADRENERGIC DRIVE: A DOBUTAMIN STRESS STUDY
Authors: E.K. Dahl, S. Möller, F. Bendtsen, A. Kjœr, C.L. Petersen, A. Krag
Journal: Journal of Hepatology (2012)
Nine Bahraini medical professionals are sentenced to five years in prison
Authors: S. Arie
Journal: BMJ (2012)

The US government and human rights groups have expressed deep disappointment after nine Shia medical professionals in Bahrain were sentenced to up to five years in prison on 14 June for crimes against the state during last year’s uprising.

The doctors and nurses were among a group of 20 whose cases were reviewed by an appeals court after international outcry over harsher sentences given by a military judge last September.1

Nine others were cleared of charges, and sentences of 15 years were upheld against two doctors who have gone …
Role of the high-affinity IgE receptor (Fc∈RI) in the development of airway hyperresponsiveness (AHR)
Authors: C. Taube, X. Wei, A. Joetham, J. Park, K. Takeda, N. Miyahara, T. Kodama, J. Loader, G.L. Larsen, A. Balhorn, A. Dakhama, E.W. Gelfand, C. Taube
Journal: Journal of Allergy and Clinical Immunology (2003)
Life-threatening gastrointestinal bleeding in Klippel-Trenaunay syndrome
Authors: N. Thosani, Y. Ghouri, S. Shah, S. Reddy, G. Arora, L. Scott
Journal: Endoscopy (2013)

A 28-year-old Hispanic man was brought to the hospital by emergency medical services after several hours of passing bright red blood per rectum. He complained of feeling dizzy and at the emergency center, he continued to pass a large amount of bright red blood per rectum. On admission his hemoglobin was 6.0 g/dL. He had a similar episode of bleeding at age 16, which stopped spontaneously and no further investigation was done at that time. On examination, he had extensive varicose veins and hypertrophy of the left lower extremity ([Fig. 1]). He reported that these varicose veins were first noticed in early infancy. Colonoscopy showed extensive varicosities with bluish discoloration throughout the rectum and sigmoid colon ([Fig. 2]) and large hemorrhoids. He had emergent hemorrhoidectomy to control bleeding. Based on the physical examination findings, he was diagnosed as having Klippel–Trenaunay syndrome (KTS). At 2-year follow-up, he continues to do well without any further episodes of bleeding.
Abstract PR13: Systems and structural biology approaches to elucidate new effectors in KRAS mutant tumors
Authors: Joshua Broyde, David Simpson, David A. Wah, Federico M. Giorgi, Donald Petrey, Mariano J. Alvarez, Antonina Silkov, Alexander Lachmann, David E. Hill, Marc Vidal, Peter Jackson, Barry Honig, Alejandro Sweet-Cordero, Andrea Califano
Journal: Cancer Research (2015)

Abstract Activated KRAS interacts directly and indirectly with numerous downstream effector pathways that are still elusive or poorly characterized. Furthermore, it has become clear over the past few years that the KRAS regulatory gene network (interactome) is highly cell-context dependent and thus tumor specific. We sought to computationally elucidate novel KRAS effectors, modulators, and interactors in Lung Adenocarcinomas (LUAD) and Colon Adenocarcinomas (COAD) by integrating computational and biochemical reverse engineering methods. Specifically, results from ARACNe and MINDy based analysis of KRAS networks were combined with Protein-protein interaction (PPI) predictions based on the PrePPI algorithm. These algorithms detect, respectively, transcriptional, post-translational, and protein-protein interactions respectively. The MARINa/VIPER algorithm was used to analyze the networks resulting from these analyses to identify key modulators and effectors of KRAS activity, including modulators harboring genetic alterations that phenocopy aberrant KRAS activity. In addition, we collaborated with the Jackson (Stanford) and Vidal (Harvard) labs to include high-throughput tandem affinity mass spectrometry data and yeast 2 hybrid screens in these analyses. Validation of computationally inferred effectors, using pooled shRNA silencing assays in primary lung cancer cells isolated from a KrasLSL/p53f/f mouse model of LUAD validated novel genes as likely KRASmut effectors and putative synthetic lethal genes. At least two hairpins against RNF43, E4F1, HMCN1, MYO9A, RHOT2, SETD1B and MAP3K2 scored in this assay. These results suggest that KRAS network analyses using computational methods can identify novel members of the KRAS interactome. Citation Format: Joshua Broyde, David Simpson, David A. Wah, Federico M. Giorgi, Donald Petrey, Mariano J. Alvarez, Antonina Silkov, Alexander Lachmann, David E. Hill, Marc Vidal, Peter Jackson, Barry Honig, Alejandro Sweet-Cordero, Andrea Califano. Systems and structural biology approaches to elucidate new effectors in KRAS mutant tumors. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr PR13.
Abstract 4097: Targeting of mTOR mediated signaling pathways in papillary thyroid cancer cell.
Authors: Maqbool Ahmed, Azhar R. Hussain, Fouad Al Dayel, Shahab Uddin, Khawla S. Al-Kuraya
Journal: Cancer Research (2013)

Abstract The mammalian target rapamycin (mTOR) signaling cascade is a key regulatory pathway controlling initiation of mRNA in mammalian cells. Torin2 is a potent, selective and orally available mTOR inhibitor for treatment of cancer. Dysregulation of mTOR signaling has been found in many cancers, however its role Papillary Thyroid Cancer (PTC) has not been explained. Therefore in this study, we investigated the role of mTOR and its associated molecules in PTC cell lines using MTT, flow cytometry and DNA fragmentation assays and western blotting. Our data showed that Torin2 caused a dose dependent growth inhibition in all cell lines studied. Cell cycle assay showed that the sub-G1 population in TPC-1 cell increased from 12.44% in untreated control sample to 31.50% after 200nM of Torin2 treatment and 44.08% after 400nM of Torin2 treatment for 48 hours. Similarly BCPAP cells increased from 8.47% in untreated control sample to 33.54% after 200nM of Torin2 treatment and 41.16% after 400nM of Torin2 treatment for 48 hours. Further confirmation using FITC-conjugated Annexin V and PI assay showed that apoptotic cell increased from 8.89% in untreated cells to 58.54% and 73.54% after 200nM and 400nM treatment in TPC-1 cells, and from 13.24% in control to 46.74% and 70.64% in BCPAP cells, indicating a dose dependent apoptosis induced in both cell lines. Treatment of PTC cell lines with Torin2 inactivated downstream targets of mTOR; p70S6 and 4E-BP1. Torin2 treatment of PTC cell lines also induced mitochondrial dependent apoptosis via activation and cleavage of caspase-9, and 3, and cleavage of PARP. Furthermore Torin2 positively regulated autophagy by disrupting the Beclin-1 complex, releasing Beclin-1 to induce autophagy. Our results suggest mTOR and its associated signaling pathway play a critical role in PTC tumorigenesis, therefore targeting of mTOR expression may be a viable therapeutic intervention for treatment of these cancers. Citation Format: Maqbool Ahmed, Azhar R. Hussain, Fouad Al Dayel, Shahab Uddin, Khawla S. Al-Kuraya. Targeting of mTOR mediated signaling pathways in papillary thyroid cancer cell. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4097. doi:10.1158/1538-7445.AM2013-4097
Diagnostic Yield of Advanced Colorectal Neoplasia at Colonoscopy, According to Indications: An Investigation from the Korean Association for the Study of Intestinal Diseases (KASID)
Authors: D. Park, Y. Kim, H. Kim, W. Kim, T. Kim, H. Kim, S. Yang, J. Byeon, M. Lee, I. Jung, M. Chung, S. Jung, Y. Jeen, J. Choi, H. Choi, D. Han, J. Song
Journal: Endoscopy (2006)

Corrected by: Diagnostic Yield of Advanced Colorectal Neoplasia at Colonoscopy, According to Indications: An Investigation from the Korean Association for the Study of Intestinal Diseases (KASID)Endoscopy 2006; 38(08): 852-852DOI: 10.1055/s-2006-944761
Abstract 2126: Quantitative trait locus analysis of tumor morphology in a mouse model of human colorectal cancer
Authors: David J. Bautz, Joshua M. Uronis, David W. Threadgill
Journal: Cancer Research (2010)

Abstract Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. Early detection has frequently been cited as contributing to a favorable outcome. However, detection of CRC is impacted by tumor morphology, with the classical polypoid lesions being detected at a much higher rate than flat lesions. Recently, mouse models of CRC that consistently and almost exclusively develop flat lesions have been developed, indicating that specific host genetic modifiers exist that influence tumor morphology. Using the azoxymethane (AOM) model of human CRC we find that I/LNJ mice develop approximately 85% flat tumors while KK/HlJ mice develop approximately 85% polypoid tumors. To determine what genetic factors contribute to these phenotypic differences, we established an F2 genetic cross between these two mouse strains consisting of 119 animals. After a standardized AOM treatment regimen, these mice developed approximately 40% flat tumors. The mice were genotyped at 80 SNP's evenly spaced across the genome. Statistical analysis revealed two suggestive QTL for tumor morphology, one located on chromosome 12 (LOD 3.45) and the other on chromosome 9 (LOD 2.67). Follow up work has begun to fine map and identify candidate genes at these QTL through high dense SNP genotyping in an additional 300 F2 animals and eQTL analysis of normal colon tissue. These results indicate that tumor morphology is controlled by host genetic factors and we anticipate future studies focusing on the identification of these factors for development of therapeutic interventions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2126.
Cathedrals, symphony orchestras, and iPhones: The cultural basis of modern technology
Authors: Daniel E Moerman
Journal: Behavioral and Brain Sciences (2012)

Abstract The distinctions drawn by Vaesen are plausible when we are comparing chimpanzees and human beings somewhere between the middle Paleolithic and the Neolithic. But since then new kinds of organization have vastly outstripped these neurological differences to account for the enormous advancement of human technology – from cuneiform to the iPhone – leaving our remarkable evolutionary cousins far behind.
Use of Doppler Ultrasonography to Predict the Outcome of Therapy for Renal-Artery Stenosis
Authors: Jörg Radermacher, Ajay Chavan, Jörg Bleck, Annabel Vitzthum, Birte Stoess, Michael Jan Gebel, Michael Galanski, Karl Martin Koch, Hermann Haller
Journal: New England Journal of Medicine (2001)

Prospectively identifying patients whose renal function or blood pressure will improve after the correction of renal-artery stenosis has not been possible. We evaluated whether a high level of resistance to flow in the segmental arteries of both kidneys (indicated by resistance-index values of at least 80) can be used prospectively to select appropriate patients for treatment.
Habitually Wandering Patients
Authors: Loren Pankratz, James Jackson
Journal: New England Journal of Medicine (1994)

Physicians are sometimes confronted with patients who gain admission to one hospital after another, sometimes referred to as "wandering patients." Little is known about the presenting symptoms of these patients, their use of hospital resources, or the costs of their medical care. We analyzed the demographic and clinical characteristics of wandering patients served by Department of Veterans Affairs medical centers (VAMCs).For each patient they admit, all 159 hospitals in the Veterans Affairs medical system submit demographic and diagnostic information to a central data base at the Data Processing Center in Austin, Texas. We searched these records to identify patients who were admitted to four or more VAMCs within each year from fiscal year 1988 through 1992. Patients so identified in any one year were called "wanderers"; those identified in all five years were designated "habitual wanderers."We identified 1013 wanderers in 1988. The number gradually declined each year to 729 in 1993. In 1991 there were 810 wandering patients, who averaged about eight admissions per year and over 100 days of inpatient care; they accounted for about $26.5 million in costs for inpatient and outpatient care in that year. Only 35 patients wandered in all five years from 1988 through 1992. The most common discharge diagnoses of these 35 men were related to substance abuse (mostly alcoholism) and mental disorders. Their 2268 admissions and 7832 outpatient visits cost an estimated $6.5 million over the five-year period.Patients who are repeatedly admitted to different hospitals--wandering patients--accumulate high numbers of admissions, cause diagnostic confusion, and receive uncoordinated care. Because of the complexity of their disorders, such patients require case management on a regional or national basis.
First description of eosinophilic esophagitis using confocal laser endomicroscopy (with video)
Authors: H. Neumann, M. Vieth, R. Atreya, J. Mudter, M. Neurath
Journal: Endoscopy (2011)

Confocal laser endomicroscopy enables in vivo microscopic imaging of the mucosal layer of the gut at a subcellular resolution [1]. Various studies have addressed the potential of endomicroscopy for the in vivo diagnosis of esophageal squamous cell carcinoma, Barrett’s esophagus, and esophageal adenocarcinoma [2] [3] [4]. Currently, no data are available on the utility of endomicroscopy for the in vivo diagnosis of eosinophilic esophagitis.
A case of IgG4-related disease complicated by duodenal bulbitis with IgG4-positive plasma cell infiltration
Authors: Kazuhiro Matsunaga, Ranji Hayashi, Toshimi Otsuka, Daisuke Kaida, Nobuhiko Ueda, Takeo Kosaka, Tomiyasu Arisawa
Journal: Endoscopy (2014)

Duodenal papillitis is a gastrointestinal lesion commonly complicating IgG4-related diseases. Lesions of the esophagus, stomach, and colon with IgG4-positive plasma cell infiltration also complicate IgG4-related diseases. However, few reports have been published on complicating duodenal bulbitis. We encountered a patient with an IgG4-related disease complicated by duodenal bulbitis.