tbuckley/cabot-search huggingface dataset:
MIP-1α, MCP-1, and Desensitization in Anaphylaxis from Cow's Milk
Authors: Paloma Poza-R. Glez, Yvelise Barrios-A. Franco, Víctor Matheu
Journal: New England Journal of Medicine (2012)

could not find studies on the relationship be tween a physics requirement and aspects of performance in medical school or medical prac tice.However, the justification for a background in chemistry or physics is the same as it is for one in the behavioral and social sciences -it allows professors to move directly into more advanced topics.Given the conceptual breadth and strong clinical relevance of the behavioral and social sciences, it seems unrealistic to ex pect medical schools to adequately train stu dents when many schools are unable to address advanced topics because their curriculum time must be used to remediate poor preparation by some students.Although we appreciate Dienstag's perspec tive, we remain convinced that solid preparatory training and evaluation in the behavioral and social sciences is essential for training tomor row's physicians.
OP0119 Pharmacodynamic Effects of Atacicept in SLE Patients: 52-Week Data from the April-SLE Trial
Authors: D. Wofsy, C. Gordon, D. Licu, S. Copt, C. Pena Rossi, D. Isenberg
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> SLE is associated with abnormal B cell activity, including elevated titers of IgG and anti-dsDNA antibodies (abs), and decreased complement levels. Atacicept is a fusion protein that inhibits the B cell stimulating factors BLyS and APRIL. <h3>Objectives</h3> To analyze changes in biomarkers reflecting disease activity and protective abs in response to atacicept treatment. <h3>Methods</h3> Patients with active SLEdefined as≥1 A and/or B BILAG score, and positive for ANA/anti-dsDNA abs, were treated with a corticosteroid taper for 10 weeks. Patients reaching BILAG C or D in all organ systems, and stable for 2 weeks, were randomized at baseline 1:1:1 to receive placebo (PBO) or atacicept 75 or 150 mg. Study drug was given SC twice weekly for 4 weeks, then weekly for 48 weeks. <h3>Results</h3> 461 subjects were randomized and analyzed. The 150 mg arm was terminated early due to 2 fatal pulmonary infections. Efficacy and safety data are presented elsewhere. One subject in the 75 mg treatment group developed serum IgG levels below 3 g/L and was discontinued from the study. In neither of the 2 fatal pneumonias did the IgG level decrease below 14.6 g/L (ref range, 5.65-17.65 g/L). Atacicept induced changes in pharmacodynamic and disease-related markers as shown in the Table. For treatment completers (analyzed at Week 52), the proportion of patients in the PBO, atacicept 75 mg and 150 mg groups whose anti-tetanus abs fell from above protective threshold at baseline to below at Week 52 were 1.9% (2/107), 9.9% (10/101) and 8.8% (5/57). The corresponding values for anti-pneumococcal abs were 3.9% (4/102), 10.4% (11/106) and 10.5% (6/57) respectively. There were no shifts in anti-diphtheria titer status. <h3>Conclusions</h3> In subjects who received atacicept, but not PBO, following steroid treatment, there were declines in IgG, IgA, and IgM, as well as mature B cells and plasma cells. In subjects with abnormal values at screening, atacicept was associated with favorable effects on anti-dsDNA and complement levels. <h3>Acknowledgements</h3> †An affiliate of Merck KGaA, Darmstadt, Germany <h3>Disclosure of Interest</h3> D. Wofsy Consultant for: Merck Serono SA, C. Gordon Consultant for: Merck Serono SA, D. Licu Employee of: Merck Serono SA, S. Copt Employee of: Merck Serono SA, C. Pena Rossi Employee of: Merck Serono SA, D. Isenberg Consultant for: Merck Serono SA
Mitochondrial Ultrastructure in Reye's Syndrome (Encephalopathy and Fatty Degeneration of the Viscera)
Authors: John C. Partin, William K. Schubert, Jacqueline S. Partin
Journal: New England Journal of Medicine (1971)

Abstract Electron microscopy was performed on liver-biopsy tissue obtained early in the evolution of Reye's syndrome and during recovery in an effort to identify the main site (or sites) of cell injury. Early in the course of encephalopathy, hepatocytes are universally affected by a process that results in mitochondrial swelling and pleomorphism as well as small-droplet triglyceride accumulation. During recovery, mitochondrial morphology improves in parallel with clinical improvement. A chemically mediated, potentially reversible mitochondrial injury may be instrumental in the evolution of Reye's syndrome.
Prevalence Rates of Pathogenic Mutations in the <i>BRCA1</i> and <i>BRCA2</i> Genes in Families with Different Disease Histories: Results from the German Consortium for Hereditary Breast and Ovarian Cancer.
Authors: K. Kast, R. Schmutzler, W. Distler, N. Arnold, C. Bartram, U. Bick, U. Froster, T. Grimm, R. Kreienberg, C. Naestle-Kraemling, B. Schlegelberger, P. Wieacker, A. Meindl, C. Engel
Journal: Cancer Research (2009)

Abstract Introduction: In the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC), a large number of families with different histories of breast and ovarian cancers was screened for pathogenic mutations in the tumor-suppressor genes BRCA1/2. We here aimed to analyse the prevalence rates of pathogenic mutations for various familial disease histories.Methods: From 1997-2009 more than 6,000 families were screened for pathogenic mutations in BRCA1/2. Mutation analysis was performed by DHPLC (denaturing high-performance liquid chromatography) pre-screening, direct sequencing of suspect fragments and MLPA (multiplex ligation-dependant probe amplification) in at least one index case of these families. Complete pedigree information over three generations was used for the analysis. All lineages within a pedigree were traced and checked for the presence of several predefined disease histories.Results: Detailed mutation prevalence rates have been determined for a variety of familial risk situations. The highest mutation prevalence rate (78%, 95%CI 67-87%) was seen in families with at least two relatives affected by pre-menopausal breast cancer and at least two affected by ovarian cancer at any age. Importantly, the presence of a single woman affected by breast and ovarian cancer or bilateral breast cancer with first breast cancer under the age of 41 was associated with a BRCA1/2 mutation prevalence of 53% (95%CI 48-59%) and 34% (95%CI 23-47%) respectively. Interestingly, low mutation prevalence rates of &amp;lt;10% were found in families with only one case of male breast cancer (9%, 95%CI 4-19%), and in families with three or more cases of postmenopausal breast cancer (7%, 95%CI 4-14%), the former being only BRCA2 mutations. Overall, the mutation prevalence was 27% (95% CI 26-29%) in the whole cohort.Conclusion: We provide comprehensive estimates for BRCA1/2 mutation prevalence rates that are based on a large number of families with comprehensive pedigree information. Such estimates can be used to develop cost effective screening strategies for public health care providers. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4073.
The Face of the Next Generation in China
Authors: Chen Wang, Jinghong Li, Sinan Wu, Atul Malhotra
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

AJRCCM Articles in Press. Published on 04-April-2016 as 10.1164/rccm.201603-0485ED Page 1 of 7 The Face of the Next Generation in China Chen Wang 1,3 Jinghong Li 2 , Sinan Wu 1 and Atul Malhotra 2,3 Department of Respiratory and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China Department of Respiratory Medicine, Capital Medical University Beijing, China National Clinical Research Centre for Respiratory Diseases, Beijing, China University of California, San Diego, Division of Pulmonary Critical Care and Sleep Medicine, La Jolla, CA 92037, United States Correspondence to: Chen Wang, MD, PhD No. 2 East Yinghua Road, Chaoyang District Beijing 100029, China Tel: 86-10-84206166 Fax: 86-10-64289840 Email: cyh-birm@263.net Atul Malhotra, MD 9300 Campus Point Drive, MC 7381 La Jolla, CA 92037 U.S.A. Tel: (858) 657-6159 Fax: (858) 657-5021 Email: amalhotra@ucsd.edu Copyright © 2016 by the American Thoracic Society
INCIDENCE, PREDICTORS AND IMPACT OF MAJOR BLEEDING IN PATIENTS UNDERGOING TRANSFEMORAL TRANSCATHETER AORTIC VALVE REPLACEMENT WITH BIVALIRUDIN OR UNFRACTIONATED HEPARIN: FROM THE EFFECT OF BIVALIRUDIN ON AORTIC VALVE INTERVENTION OUTCOMES (BRAVO) TRIAL
Authors: Didier Tchetche, Gennaro Giustino, Jaya Chandrasekhar, Thierry Lefevre, Roxana Mehran, Eberhard Grube, Christian Kupatt, Nicolas Dumonteil, John Webb, Antonio Colombo, Stephan Windecker, Peter Boekstegers, Axel Linke, Eric Van Belle, Gennaro Sardella, Oliver Husser, David Hildick-Smith, Efthymios Deliargyris, Promodoros Anthopoulos, Raban Jeger, Christophe Tron, Andreas Fach, Anita Asgar, Christian Hengstenberg, George Dangas
Journal: Journal of the American College of Cardiology (2016)
Rota Virus Infection in Adults
Authors: Wanda M. Wenman, Dorothy Hinde, Sheila Feltham, Marc Gurwith
Journal: New England Journal of Medicine (1979)

To study the epidemiologic and clinical features of rotavirus infections, we enrolled 98 families in a prospective study of diarrhea in households with newborn children. Families were seen at three-month intervals and whenever ill. The mean follow-up period was 16.4 months. Rotavirus infections were documented by electron microscopy of feces, indirect fluorescent-antibody assays in serum or both. The 43 infections identified in adults represented an attack rate of 0.17 per adult per year. Ninety-three per cent of these infections occurred from November through May. Seventeen adults had gastrointestinal symptoms, most often diarrhea (in 14) or abdominal cramps (in 11). Rotavirus infections occurred in 36 of 102 adults whose children had rotavirus infection, as compared with four of 86 without infected children (P less than 0.001). Serum rotavirus antibody did not correlate with a reduced risk of infection or symptomatic disease. Rotavirus is a mild but common infection in parents of young children.
Abstract LB-92: Isoflurane increases the metastatic potential of renal cell carcinoma cells via the hypoxia inducible factor pathway- an <i>in vitro</i> study
Authors: Laura L. Benzonana, Nicholas J. Perry, Helena R. Watts, Daqing Ma
Journal: Cancer Research (2011)

Abstract Background: Patients with solid tumours are likely to have to undergo surgery during the course of their disease. Surgery and anaesthesia may influence the tumour's metastatic potential. Isoflurane is known to up-regulate hypoxia inducible factors (HIFs). HIFs are heavily implicated in tumorigenesis and may play an important role in tumour cell proliferation, migration, invasion and angiogenesis (VEGF signaling). Our aim was to investigate the potential impact of isoflurane on tumour cell progression in vitro. Methods: Human Renal Cell Carcinoma (RCC4) cells were exposed to 2% isoflurane for 2 hours at 37°C. HIF-1α, HIF-2α, p-Akt, and VEGFA protein levels were measured by Western Blotting at different time points (0, 2, 4, 8 and 24 hours) following isoflurane exposure. HIF-1α was also measured by fluorescent immunocytochemistry after cell fixation. Cell proliferation was measured by MTT and trypan blue exclusion assays. Cell migration was measured using an Oris cell migration assay. Results: Isoflurane up-regulated HIF-1α in a time-dependent manner, with the highest levels being detected at 8 hours post gas exposure (p&amp;lt;0.001). These results were confirmed by immunofluorescence, showing a significant accumulation of HIF-1 α in the nucleus at 8 hours. Isoflurane also up-regulated HIF-2α, maximal levels were detected at 24 hours (p&amp;lt;0.01). Isoflurane activated the PI3K pathway, as indicated by significantly raised levels of p-Akt from 4 to 24 hours, with highest levels at 8 hours (p&amp;lt;0.001). An increase in VEGFA accumulation was seen at 24 hours (p&amp;lt;0.01). MTT assays performed 8 hours following gas exposure demonstrated that isoflurane increased the rate of cell proliferation (p&amp;lt;0.01), as confirmed by immunofluorescence findings at this time point. Cell migration assays showed an increased migration of Isoflurane treated cells 8 hours post exposure (p&amp;lt;0.01), as confirmed by immunofluorescence, where an increased number of cells showing filipodia (cells migrating) was observed. Conclusion: Isoflurane at clinically relevant concentrations up-regulates HIF-1α and HIF-2α, which may be due to upstream PI3K pathway activation. Isoflurane up-regulates the major pro-angiogenic factor VEGFA and increases the rate of proliferation and migration in RCC4 cells in vitro. These findings may have major clinical implications for patients undergoing cancer surgery under general isoflurane anaesthesia. 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-92. doi:10.1158/1538-7445.AM2011-LB-92
Poster session 6. Phase 1 studies
Authors: D. Pollyea, L. Gore, J. Gutman, S. G. Eckhardt, N. Hagelstrom, S. Coutre, M. Thirman, J. Byrd, G. Massimini, B. Laffranchi, N. Rejeb, E. Asatiani, A. Milner, O. von Richter, G. Locatelli, J. A. Ogden, B. Osterwalder, R. Meng, L. R. Molife, L. de Mattos-Arruda, A. Hollebecque, S. J. Isakoff, D. Roda, Y. Yan, A. Cervantes, J. C. Soria, J. Mateo, G. Argiles, J. C. Bendell, A. Hollebecque, A. El-Khoueiry, D. J. Jonker, M. B. Sawyer, L. Wong, C. R. Becerra, J. C. Soria, J. M. Chemidlin, G. Kollia, D. S. A. Nuyten, C. J. Twelves, D. K. Wilkins, A. Anthoney, J. Chappell, W. T. Ng, P. T. Turner, R. Kristeleit, O. Schoenborn-Kellenberger, A. Suder
Journal: Annals of Oncology (2013)
EARLY GADOLINIUM ENHANCEMENT OVERESTIMATES HUMAN INFARCT SIZE IN ACUTE MYOCARDIAL INFARCTION: A QUANTITATIVE AND KINETIC STUDY
Authors: Sophia Hammer-Hansen, W. Patricia Bandettini, Li-Yueh Hsu, Steve Leung, Sujata Shanbhag, Christine Mancini, Anders Greve, Lars Kober, Jens Jakob Thune, Peter Kellman, Andrew Arai
Journal: Journal of the American College of Cardiology (2015)
Abstract 609: Novel techniques for identifying apoptosis with pSIVA-IANBD in live and fixed cells.
Authors: Lisa S. Heiden, Stan Krajewski, Payton D. Quintel, Sujay K. Singh
Journal: Cancer Research (2013)

Abstract Historically, flow cytometry has been the primary technique for identifying individual cells undergoing apoptosis. However, imaging is becoming increasingly important for analyzing cell death and underlying mechanisms in living cell populations. In this study, we developed new techniques for using the polar sensitive pSIVA-IANBD Annexin XII probe to identify apoptosis in mixed populations of cells by multiple imaging of viable primary neuronal cultures over 0-72h. The pSIVA-IANBD probe was added to living cultures at time=0. pSIVA-IAND binds to exposed phosphatidylserine (PS) residues and fluoresces (in the FITC channel) only when bound to cells. Cultures were fixed and permeabilized at the end of their respective time courses and immunostained with MAP2 or NeuN neuronal markers to identify neurons, and counterstained with Hoeschst dye to visualize nuclei. The results were imaged by an IFL multichannel inverted digital microscope (EVOS; AMG Inc, USA). They showed that bound pSIVA-IANBD was fixation resistant and the single (pSIVA-IANBD), double (pSIVA-IANBD + Hoescht) and as well as the triple (pSIVA-IANBD + Hoescht + antibody) stained cells were readily identifiable in the mixed cell population. They suggested that pSIVA-IANBD enables detection of PS, a hallmark of apoptosis by imaging of viable as well as post-fixed cells. Furthermore, since pSIVA-IANBD is not toxic to cells and does not require a washing step, it can be maintained in cultures with only a single application and no medium change for up to 72h. This allows continuous live monitoring of cells for apoptosis, cells can then be fixed and labeled with additional biomarkers of interest and imaged. These features render pSIVA-IANBD a particularly useful tool for toxicological studies of novel drugs in cell-based assays. pSIVA-IANBD is also suitable for flow cytometry and may supercede the widely used Annexin V-FITC PS probe which has has limited applications outside of flow cytometry. Citation Format: Lisa S. Heiden, Stan Krajewski, Payton D. Quintel, Sujay K. Singh. Novel techniques for identifying apoptosis with pSIVA-IANBD in live and fixed cells. [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 609. doi:10.1158/1538-7445.AM2013-609
Older Women Underutilize Breast Cancer Screening
Authors: S. Jenks
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Older Women Underutilize Breast Cancer Screening Get access Susan Jenks Susan Jenks Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 6, 17 March 1993, Pages 438–439, https://doi.org/10.1093/jnci/85.6.438 Published: 17 March 1993
SP0150 Helping doctors and their patients make better decisions about health
Authors: R. Garcia-Retamero
Journal: Annals of the Rheumatic Diseases (2013)

Recent research on health literacy and medical decision making has shown that in most cultures doctors and their patients have severe problems grasping a host of numerical concepts that are prerequisites for understanding and communicating health-relevant risk information. However, there is a dearth of published research comparing risk communication in cultures with different health systems. We present the results of three studies conducted in three different countries (US, Germany, and Spain), which converge to demonstrate that problems associated with risk illiteracy are not simply the result of cognitive biases preventing good decision making. Rather, errors occur because ineffective information formats complicate and mislead adaptive decision makers. In particular, we report the effectiveness of visual aids to enhance risk understanding and communication (Study 1), to eliminate biases such as denominator neglect (Study 2) and errors induced by framed messages (Study 3). We conclude that information formats that exploit people's inherent capacity to recognize relationships in naturally occurring problems (so-called transparent information formats) can dramatically enhance risk comprehension, communication, and recall and foster better decisions about health regardless of culture. We provide some guidelines for transparent communication of health-relevant information. <h3>Disclosure of Interest</h3> None Declared
Abstract 4968: TNF-alpha promotes genome-wide replacement of TAp73 chromatin occupancy by cREL and DeltaNp63
Authors: Hai Lu, Han Si, Xinping Yang, Jeffery Burnett, Sean Davis, Hongwei Sun, Wenming Xiao, Lai Wei, Paul Meltzer, Carter Van Waes, Zhong Chen
Journal: Cancer Research (2011)

Abstract cREL, DeltaNp63, and TAp73, members of NFkappaB and TP53 transcription factor (TF) families, together regulate broad biological processes critical for inflammation and cancer survival. However, the underlying mechanisms explaining their cross-regulation of transcriptome and interactive signal network have not been revealed. Here, we demonstrate that inflammatory cytokine TNF-alpha induces a dynamic, genome-wide increase in cREL and DeltaNp63 chromatin occupancy after replacing TAp73 binding activity, using ChIP-seq and fitting the data into a negative binomial distribution model integrated in CisGenome. Globally, most of the binding peaks were localized in intergenic and intronic areas, with 4.2% and 5.6% peaks significantly enriched into promoter regions (3000 bp upstream of transcription starting sites) of cREL and DeltaNp63 bound DNAs in response to TNF-alpha respectively, and co-localized peaks for any of the two TFs are prevalent within a distance of ∼200 bp. De novo motif search using Gibbs Sampler identified TP53 and novel binding motifs. A total of 188 differentially expressed genes are associated with the TNF-alpha-induced chromatin occupancy shift by the three TFs. These genes are enriched in cancer-related transcription factors and TP53 signaling pathways. Our data reveal a novel mechanism of genome-wide replacement of TAp73 by cREL and DeltaNp63, supporting cross-regulation and an interactive network between NFkappaB and TP53 families. 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 4968. doi:10.1158/1538-7445.AM2011-4968
S113 The influenza virus activates TGFss via an Vss6-integrin mediated pathway
Authors: A. S. Stavrou, L. J. Jolly, J. P. Porte, P. W. Weinreb, A. T. Tatler, A. J. John, A. K. Knox, S. V. Violet, T. H. Hussel, S. K. Kuchipudi, S. D. Dunham, G. J. Jenkins
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> Idiopathic pulmonary fibrosis is a chronic progressive lung disease of unknown cause. Its pathogenesis is poorly understood but activation of latent TGFß on lung epithelium is an important factor. TGFß must be activated, as it is secreted in a latent complex with its propeptide, the latency associated peptide, and the avß6 integrin is a key activator in the lung. The <i>Influenza A</i> virus is a single-stranded segmented RNA virus that infects epithelial cells leading to cell death and injury. Toll-like receptors (TLRs) detect pathogens, such as influenza. TLR3 activation has been found to increase RhoA activity. We previously showed that RhoA is a key intermediary in avß6 integrin-mediated TGFß activation. The aim of this study is to investigate whether influenza can activate TGFß and stimulate TLR3 leading to activation of TGFß through the avß6 integrin in epithelial cells. <h3>Materials and Methods</h3> Immortalised human bronchial epithelial cells (iHBECs) were infected with influenza A (H2N3) virus at a multiplicity of infection 1 with, or without, the avß6 blocking antibody 6.3G9. iHBECs were also stimulated with the synthetic TLR3 ligand poly(I:C). TGFß activity was determined by: (1) immunoblotting for phosphorylated (phospho-) Smad2, and (2) Transformed mink lung cells (TMLC)-iHBEC cocultures. Infection efficiency was measured by Interferon ß mRNA levels by real-time qPCR. <h3>Results</h3> Infection with H2N3 and stimulation with poly(I:C) led to increase in phospho-smad2 and luciferase activity in coculture indicating increase in TGFß activation levels in a dose- and time-dependent manner. In both cases this was blocked with the addition of 6.3G9. qPCR data following infection showed increased IFNß1 and PAI-1, indicating the ability of the virus to infect the cells and activate TGFß. <h3>Conclusions</h3> Influenza infection and poly(I:C) activates TGFß in iHBECs in an avß6 integrin dependent manner. The data suggests a novel mechanism by which influenza infection of epithelial cells may promote lung fibrosis.
Synchronous sporadic gastrointestinal stromal tumors (GISTs) of the colon
Authors: Fabio Accarpio, Linda Cerbone, Simone Sibio, Marialuisa Framarino, Daniele Biacchi, Francesco Borrini, Maurizio Cardi, Sabrina Rossi, Luisa Toffolatti, Franco Iafrate, Andrea Laghi, Angelo Di Giorgio, Paolo Sammartino
Journal: Endoscopy (2014)

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors of the gastrointestinal tract originating from the cell of Cajal [1]. Up to 75 % of cases are driven by constitutional activation of the proto-oncogene cKIT; 10 % by a mutation of the gene encoding for the platelet-derived growth factor receptor (PDGFRA); 12 % are wild-type and their pathogenesis has been related to mutations of the succinate dehydrogenase complex, BRAF or NF1 genes. Commonly GISTs arise as a solitary lesion; multiple spread is extremely rare and usually associated with familial GIST, type 1 neurofibromatosis (NF-1), or Carney's triad [2].