tbuckley/cabot-search huggingface dataset:
Colon Cancer Screening Practices After Genetic Counseling and Testing for Hereditary Nonpolyposis Colorectal Cancer
Authors: Donald W. Hadley, Jean F. Jenkins, Eileen Dimond, Maria de Carvalho, Ilan Kirsch, Christina G.S. Palmer
Journal: Journal of Clinical Oncology (2003)

Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common hereditary form of colon cancer. Cancer screening recommendations differ between individuals identified to carry an HNPCC mutation and those who do not carry a known family mutation. We assessed the impact of genetic counseling and testing (GCT) on the use of endoscopic screening procedures and adherence to recommended endoscopic screening guidelines in 56 asymptomatic at-risk individuals from families known to carry an HNPCC mutation.We analyzed data on colonoscopy and flexible sigmoidoscopy screenings collected before GCT and 6 months and 12 months post-GCT on 17 mutation-positive and 39 true mutation-negative individuals. Main outcome measures were use of endoscopic screening and adherence to recommended guidelines for the relevant mutation status. Mutation status, age, sex, employment, and income were analyzed as predictor variables.Among mutation-negative individuals, use of colonoscopy and flexible sigmoidoscopy decreased significantly between pre- and post-GCT (P <.00001 and P <.0003, respectively). Among mutation-positive individuals, a nonsignificant increase (P =.24) in use was noted. Age was also associated with use of endoscopic screening after GCT (P =.03). Mutation status (odds ratio [OR], 7.5; P =.02) and employment (OR, 8.6; P =.025) were associated with nonadherence to endoscopic screening guidelines. More mutation-negative individuals strictly adhered to guidelines than did mutation-positive individuals (87% v 65%).Genetic counseling and testing for HNPCC significantly influences the use of colonic endoscopy and adherence to recommendations for colon cancer screening.
One Thousand Two Hundred Ninety Nuclear Genes from a Genome-Wide Survey Support Lungfishes as the Sister Group of Tetrapods
Authors: Dan Liang, Xing Xing Shen, Peng Zhang
Journal: Molecular Biology and Evolution (2013)

The only currently unresolved portion of the backbone phylogeny of the vertebrates involves the relationships among coelacanths, lungfishes, and tetrapods. Despite active research on this question over the past three decades, it is still difficult to determine statistically whether lungfishes alone or both lungfishes and coelacanths together are closely related to tetrapods. To resolve this controversy, we assembled a data set comprising 1,290 nuclear genes encoding 690,838 amino acid residues by analyzing available genome and transcriptome data. Phylogenetic analyses of this data set provided overwhelming evidence that the lungfishes are the closest living relatives of the land vertebrates. This result is strongly supported by high bootstrap values from maximum likelihood and maximum parsimony analyses, Bayesian posterior probabilities of CAT model analysis, and topological tests. Additionally, a species tree analysis without data concatenation also strongly supported this result.
840-1 Myocardial fibrosis patterns correlate with adverse right ventricular morphology and function in patients with repaired conotruncal heart defects
Authors: Anne Marie Valente, Salim F Idriss, Peter Cawley, John Heitner, Igor Klem, Jospeh Kay, Ann Marie Nawrocki, Michele Parker, J.Rene' Herlong, Raymond Kim
Journal: Journal of the American College of Cardiology (2004)
High energy phosphate depletion and lactate accumulation in the interventricular septum and left ventricular free wall of the dog after total coronary occlusion.
Authors: R B Dunn
Journal: Circulation Research (1984)

We measured indices of energy metabolism in tissue samples taken from the interventricular septum and left ventricular free wall of open-chest dogs under control conditions and after a 20-second period of no coronary inflow. The heart was paced at 150 beats/min, and arterial pressure was controlled by aortic constriction. Each tissue sample was divided into three transmural regions and analyzed for creatine phosphate, adenosine triphosphate, and lactate. Data were also obtained in animals subjected to ventricular fibrillation, with ventricular pressures reduced to atmosphere and sampling delayed to 70 seconds, and with the pulmonary artery constricted prior to coronary artery occlusion. In control animals, there were no metabolite differences between the free wall and septum. Coronary occlusion produced a lactate gradient across both the free wall and septum, with the highest lactate concentrations occurring in the regions adjacent to the left ventricular cavity. The increase in tissue lactate above control was greater in the septum than in the free wall. Coronary occlusion decreased tissue creatine phosphate but not adenosine triphosphate. The decrease in creatine phosphate was greater in the septum than in the free wall. Coronary occlusion and ventricular fibrillation, or coronary occlusion and ventricular pressures reduced to atmosphere, produced neither transmural metabolite differences nor differences between the free wall and septum. Pulmonary artery constriction increased right and decreased left ventricular pressures.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiac Magnetic Resonance Imaging After Stage I Norwood Operation for Hypoplastic Left Heart Syndrome
Authors: Vivek Muthurangu, Andrew M. Taylor, Sanjeet R. Hegde, Robert Johnson, Robert Tulloh, John M. Simpson, Shakeel Qureshi, Eric Rosenthal, Edward Baker, David Anderson, Reza Razavi
Journal: Circulation (2005)

After the Norwood operation, a patient's suitability for proceeding to a bidirectional cavopulmonary connection (BCPC) is assessed by a combination of echocardiography and diagnostic cardiac catheterization. In this study, we describe the results of 37 patients who underwent cardiovascular magnetic resonance (MR) assessment before BCPC.Cardiovascular MR and echocardiography were performed in 37 infants with hypoplastic left heart syndrome before BCPC, and the findings were compared with surgical findings. MR assessment of ventricular function and valvar regurgitation were compared with echocardiography. MR exhibited high sensitivity and specificity for identification of neoaortic (sensitivity 86%, specificity 97%) and left pulmonary artery (sensitivity 100%, specificity 94%) obstruction. Echocardiography exhibited poor sensitivity for identification of vascular stenosis. The mean right ventricular ejection fraction calculated from the MR data was 50+/-10%. There was general agreement between MR and echocardiographic measures of ventricular function, although patients with good function on echocardiography demonstrated a wide range of ejection fractions. There was good agreement between MR and echocardiography for identification of valvar regurgitation.Cardiovascular MR can be used to define ventricular and valvar function and vascular anatomy in infants with hypoplastic left heart syndrome after the Norwood operation. We have shown how this information can be used to plan the BCPC and identify any revisions or additional valvar surgery.
Signaling Mechanisms Linking Neuronal Activity to Gene Expression and Plasticity of the Nervous System
Authors: Steven W. Flavell, Michael E. Greenberg
Journal: Annual Review of Neuroscience (2008)

Sensory experience and the resulting synaptic activity within the brain are critical for the proper development of neural circuits. Experience-driven synaptic activity causes membrane depolarization and calcium influx into select neurons within a neural circuit, which in turn trigger a wide variety of cellular changes that alter the synaptic connectivity within the neural circuit. One way in which calcium influx leads to the remodeling of synapses made by neurons is through the activation of new gene transcription. Recent studies have identified many of the signaling pathways that link neuronal activity to transcription, revealing both the transcription factors that mediate this process and the neuronal activity-regulated genes. These studies indicate that neuronal activity regulates a complex program of gene expression involved in many aspects of neuronal development, including dendritic branching, synapse maturation, and synapse elimination. Genetic mutations in several key regulators of activity-dependent transcription give rise to neurological disorders in humans, suggesting that future studies of this gene expression program will likely provide insight into the mechanisms by which the disruption of proper synapse development can give rise to a variety of neurological disorders.
World Health Organization Guidelines for Management of Acute Stress, PTSD, and Bereavement: Key Challenges on the Road Ahead
Authors: Wietse A. Tol, Corrado Barbui, Jonathan Bisson, Judith Cohen, Zeinab Hijazi, Lynne Jones, Joop T. V. M. de Jong, Nicola Magrini, Olayinka Omigbodun, Soraya Seedat, Derrick Silove, Renato Souza, Athula Sumathipala, Lakshmi Vijayakumar, Inka Weissbecker, Douglas Zatzick, Mark van Ommeren
Journal: PLoS Medicine (2014)

Wietse Tol and colleagues discuss some of the key challenges for implementation of new WHO guidelines for stress-related mental health disorders in low- and middle-income countries. Please see later in the article for the Editors' Summary
What Will It Take to Eliminate Pediatric HIV? Reaching WHO Target Rates of Mother-to-Child HIV Transmission in Zimbabwe: A Model-Based Analysis
Authors: Andrea L. Ciaranello, Freddy Perez, Jo Keatinge, Ji-Eun Park, Barbara Engelsmann, Matthews Maruva, Rochelle P. Walensky, Francois Dabis, Jennifer Chu, Asinath Rusibamayila, Angela Mushavi, Kenneth A. Freedberg
Journal: PLoS Medicine (2012)

The World Health Organization (WHO) has called for the "virtual elimination" of pediatric HIV: a mother-to-child HIV transmission (MTCT) risk of less than 5%. We investigated uptake of prevention of MTCT (PMTCT) services, infant feeding recommendations, and specific drug regimens necessary to achieve this goal in Zimbabwe.We used a computer model to simulate a cohort of HIV-infected, pregnant/breastfeeding women (mean age, 24 y; mean CD4, 451/µl; breastfeeding duration, 12 mo). Three PMTCT regimens were evaluated: (1) single-dose nevirapine (sdNVP), (2) WHO 2010 guidelines' "Option A" (zidovudine in pregnancy, infant nevirapine throughout breastfeeding for women without advanced disease, lifelong combination antiretroviral therapy for women with advanced disease), and (3) WHO "Option B" (pregnancy/breastfeeding-limited combination antiretroviral drug regimens without advanced disease; lifelong antiretroviral therapy with advanced disease). We examined four levels of PMTCT uptake (proportion of pregnant women accessing and adhering to PMTCT services): reported rates in 2008 and 2009 (36% and 56%, respectively) and target goals in 2008 and 2009 (80% and 95%, respectively). The primary model outcome was MTCT risk at weaning. The 2008 sdNVP-based National PMTCT Program led to a projected 12-mo MTCT risk of 20.3%. Improved uptake in 2009 reduced projected risk to 18.0%. If sdNVP were replaced by more effective regimens, with 2009 (56%) uptake, estimated MTCT risk would be 14.4% (Option A) or 13.4% (Option B). Even with 95% uptake of Option A or B, projected transmission risks (6.1%-7.7%) would exceed the WHO goal of less than 5%. Only if the lowest published transmission risks were used for each drug regimen, or breastfeeding duration were shortened, would MTCT risks at 95% uptake fall below 5%.Implementation of the WHO PMTCT guidelines must be accompanied by efforts to improve access to PMTCT services, retain women in care, and support medication adherence throughout pregnancy and breastfeeding, to approach the "virtual elimination" of pediatric HIV in Zimbabwe. Please see later in the article for the Editors' Summary.
Combined use of rapid D-dimer testing and estimation of clinical probability in the diagnosis of deep vein thrombosis: systematic review
Authors: Tonya L Fancher, Richard H White, Richard L Kravitz
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To summarise the evidence supporting the use of rapid D-dimer testing combined with estimation of clinical probability to exclude the diagnosis of deep venous thrombosis among outpatients. <b>Data sources</b> Medline (June 1993 to December 2003), the Database of Abstracts and Reviews (DARE), and reference lists of studies in English. <b>Selection of studies</b> We selected 12 studies from among 84 reviewed. The selected studies included more than 5000 patients and used a rapid D-dimer assay and explicit criteria to classify cases as having low, intermediate, or high clinical probability of deep vein thrombosis of the lower extremity among consecutive outpatients. <b>Review methods</b> Diagnosis required objective confirmation, and untreated patients had to have at least three months of follow up. The outcome was objectively documented venous thromboembolism. Two authors independently abstracted data by using a data collection form. <b>Results</b> When the less sensitive SimpliRED D-dimer assay was used the three month incidence of venous thromboembolism was 0.5% (95% confidence interval 0.07% to 1.1%) among patients with a low clinical probability of deep vein thrombosis and normal D-dimer concentrations. When a highly sensitive D-dimer assay was used, the three month incidence of venous thromboembolism was 0.4% (0.04% to 1.1%) among outpatients with low or moderate clinical probability of deep vein thrombosis and a normal D-dimer concentration. <b>Conclusions</b> The combination of low clinical probability for deep vein thrombosis and a normal result from the SimpliRED D-dimer test safely excludes a diagnosis of acute venous thrombosis A normal result from a highly sensitive D-dimer test effectively rules out deep vein thrombosis among patients classified as having either low or moderate clinical probability of deep vein thrombosis.
Recent evidence of underestimated circulation of hepatitis C virus intergenotypic recombinant strain RF2k/1b in the Rhône-Alpes region, France, January to August 2014: implications for antiviral treatment
Authors: C Ramière, P Tremeaux, A Caporossi, M A Trabaud, F Lebossé, F Bailly, M A Thélu, J Nana, V Leroy, P Morand, P André, S Larrat
Journal: Eurosurveillance (2014)

Since the beginning of 2014, hepatitis C virus (HCV) recombinant forms RF2k/1b have been detected in the Rhône-Alpes French region in 10 patients originating from the Caucasus area. Circulation of this particular HCV strain is very likely to be underestimated. It is also prone to be misgenotyped when using genotyping methods based on the 5' region of the viral genome, which may lead to suboptimal treatment.
Biological Activity, Lipoprotein-binding Behavior, and In Vivo Disposition of Extracted and Native Forms of Salmonella typhimurium Lipopolysaccharides
Authors: Robert S. Munford, Catherine L. Hall, J. M. Lipton, John M. Dietschy
Journal: Journal of Clinical Investigation (1982)

Although phenol-extracted gram-negative bacterial lipopolysaccharides (LPS) have been used to study the properties of endotoxins for many years, nothing is known about the behavior of native (unextracted) LPS in vivo. Accordingly, we have compared extracted and native forms of LPS with regard to their biological activity, their ability to bind to plasma high density lipoproteins (HDL), and their fate after intravenous injection into rats. The LPS of Salmonella typhimurium G-30 were labeled with [3H]galactose, and whole bacteria, bacterial outer membranes, outer membrane fragments (harvested from the bacterial culture supernatant), and phenol extracts of the bacteria were prepared. After defining the LPS, phospholipid, and protein composition of these preparations, we compared the activity of the LPS in phenol extracts and membrane fragments in two assays. In both the limulus lysate assay and the rabbit pyrogen test, the LPS in phenol extracts were slightly more potent than the LPS in membrane fragments. We next studied the ability of the LPS in each preparation to bind to rat lipoproteins in vitro, and each preparation was then injected intravenously into rats for measurements of LPS-HDL binding and tissue uptake in vivo. Two patterns of lipoprotein binding were observed. Less than 25% of the LPS in both outer membranes and whole bacteria bound to HDL in vitro. When the outer membranes and whole bacteria were injected into rats, their LPS again bound poorly to HDL and they were rapidly removed from plasma into the liver and spleen. In contrast, >50% of the LPS in both culture supernatant membrane fragments and phenol-water extracts bound to HDL in vitro. When these preparations were injected into rats, ∼50% of the LPS in the membrane fragments and phenol-water extracts bound to HDL and remained in the plasma over the 10-min study period. Moreover, the LPS in these preparations accumulated in the ovary and the adrenal gland, two tissues that use HDL-cholesterol for hormone synthesis. Binding to HDL thus greatly influenced the plasma half-life and tissue uptake of both extracted and native LPS.
J chain biosynthesis in pre-B cells and other possible precursor B cells.
Authors: J M McCune, S M Fu, H G Kunkel
Journal: The Journal of Experimental Medicine (1981)

Human cell lines that resemble precursors in the B cell lineage have been found to synthesize J chain. In vivo pulse labeling, together with in vitro translation of total cellular RNA in a wheat germ cell-free system, detected the synthesis of J chain in immunoglobulin-secreting cell lines, in a cell line with only surface IgM, as well as in the pre-B-like cell line Josh 4 and the round cell lines Josh 7 and KLM 2. The primary translation products of J chain from all of these cell lines were found to be indistinguishable from one another by serologic criteria, by relative mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, by charge as judged by alkaline-urea gel electrophoresis, and by peptide mapping. These findings suggest that the onset of J chain biosynthesis represents a relatively early event in B cell ontogeny, occurring before the development of immunoglobulin polymer-secreting cells. Its role may, consequently, be fundamental to the biosynthesis of all immunoglobulins, at different stages of B cell differentiation.
Natural history of contractile abnormalities after acute myocardial infarction in man: severity and response to nitroglycerin as a function of time.
Authors: K Ramanathan, M M Bodenheimer, V S Banka, R H Helfant
Journal: Circulation (1981)

The natural history of contraction abnormalities and their response after acute myocardial infarction in man were studied using radionuclide angiography. Sixteen patients were studied before and after sublingual nitroglycerin within 24 hours, 5-7 days and 4-6 weeks after the onset of chest pain. Within 24 hours, central chord shortening in the zone of infarction was reduced to 13.1 +/- 9.8%, but improved 27.2 +/- 18.4% (p less than 0.001) after nitroglycerin. After 5-7 days, central chord shortening improved similarly, but less markedly, from 12.9 +/- 9.2% to 24.4 +/- 13.2% (p less than 0.001). After nitroglycerin 4--6 weeks after the acute myocardial infarction, the central chord showed no response to nitroglycerin; it was 13.9 +/- 10.9% before and 13.4 +/- 2.5% after nitroglycerin. Changes in the lateral chords paralleled changes in the central chords in the three studies. Nonischemic zone improvement after nitroglycerin in all three studies. Global ejection fraction improved and end-diastolic and end-systolic volumes decreased in all three studies after nitroglycerin. These data indicate that after acute myocardial infarction, there is a significant reduction in hemiaxis shortening in the central and lateral chords that remains essentially unchanged over 4-6 weeks. However, the asynergic ischemic area improves considerably after nitroglycerin within 24 hours and 5-7 days, but fails to improve after 6 weeks.
Neuronal guidance molecule netrin-1 attenuates inflammatory cell trafficking during acute experimental colitis
Authors: Carol M Aherne, Colm B Collins, Joanne C Masterson, Marco Tizzano, Theresa A Boyle, Joseph A Westrich, Jason A Parnes, Glenn T Furuta, Jesús Rivera-Nieves, Holger K Eltzschig
Journal: Gut (2011)

<h3>Background</h3> Inflammatory bowel diseases, encompassing Crohn9s disease and ulcerative colitis, are characterised by persistent leucocyte tissue infiltration leading to perpetuation of an inappropriate inflammatory cascade. The neuronal guidance molecule netrin-1 has recently been implicated in the orchestration of leucocyte trafficking during acute inflammation. We therefore hypothesised that netrin-1 could modulate leucocyte infiltration and disease activity in a model of inflammatory bowel disease. <h3>Design</h3> DSS-colitis was performed in mice with partial genetic netrin-1 deficiency (<i>Ntn-1<sup>+/−</sup></i> mice) or wild-type mice treated with exogenous netrin-1 via osmotic pump to examine the role of endogenous and therapeutically administered netrin-1. These studies were supported by in vitro models of transepithelial migration and intestinal epithelial barrier function. <h3>Results</h3> Consistent with our hypothesis, we observed induction of netrin-1 during intestinal inflammation in vitro or in mice exposed to experimental colitis. Moreover, mice with partial netrin-1 deficiency demonstrated an exacerbated course of DSS-colitis compared to littermate controls, with enhanced weight loss and colonic shortening. Conversely, mice treated with exogenous mouse netrin-1 experienced attenuated disease severity. Importantly, permeability studies and quantitative assessment of apoptosis reveal that netrin-1 signalling events do not alter mucosal permeability or intestinal epithelial cell apoptosis. In vivo studies of leucocyte transmigration demonstrate suppression of neutrophil trafficking as a key function mediated by endogenous or exogenously administered netrin-1. Finally, genetic studies implicate the A2B adenosine receptor in netrin-1-mediated protection during DSS-colitis. <h3>Conclusions</h3> The present study identifies a previously unrecognised role for netrin-1 in attenuating experimental colitis through limitation of neutrophil trafficking.
Tumor Promotion by Intratumoral Plasmacytoid Dendritic Cells Is Reversed by TLR7 Ligand Treatment
Authors: Isabelle Le Mercier, Dominique Poujol, Amélien Sanlaville, Vanja Sisirak, Michael Gobert, Isabelle Durand, Bertrand Dubois, Isabelle Treilleux, Jacqueline Marvel, Jaromir Vlach, Jean-Yves Blay, Nathalie Bendriss-Vermare, Christophe Caux, Isabelle Puisieux, Nadège Goutagny
Journal: Cancer Research (2013)

Plasmacytoid dendritic cells (pDC) are key regulators of antiviral immunity. In previous studies, we reported that pDC-infiltrating human primary breast tumors represent an independent prognostic factor associated with poor outcome. To understand this negative impact of tumor-associated pDC (TApDC), we developed an orthotopic murine mammary tumor model that closely mimics the human pathology, including pDC and regulatory T cell (Treg) infiltration. We showed that TApDC are mostly immature and maintain their ability to internalize antigens in vivo and to activate CD4(+) T cells. Most importantly, TApDC were specifically altered for cytokine production in response to Toll-like receptor (TLR)-9 ligands in vitro while preserving unaltered response to TLR7 ligands (TLR7L). In vivo pDC depletion delayed tumor growth, showing that TApDC provide an immune-subversive environment, most likely through Treg activation, thus favoring tumor progression. However, in vivo intratumoral administration of TLR7L led to TApDC activation and displayed a potent curative effect. Depletion of pDC and type I IFN neutralization prevented TLR7L antitumoral effect. Our results establish a direct contribution of TApDC to primary breast tumor progression and rationalize the application of TLR7 ligands to restore TApDC activation in breast cancer. Cancer Res; 73(15); 4629-40. ©2013 AACR.