tbuckley/cabot-search huggingface dataset:
Factor V leiden and prothrombin gene G20210A mutation in children with cerebral thromboembolism
Authors: Mariana Bonduel, Gabriela Sciuccati, Mirta Hepner, Graciela Pieroni, Aurora Feliú Torres, Claudia Mardaraz, Juan Pablo Frontroth
Journal: American Journal of Hematology (2003)

We investigated whether there is an association between factor V Leiden (FVL) and/or prothrombin gene G20210A mutation (PT20210A) and cerebral thromboembolism in a pediatric Argentinean population. From May 1992 to January 2002, 44 consecutive children with arterial ischemic stroke (AIS) and 23 children with cerebral sinovenous thrombosis (SVT) were prospectively studied at a single center. The prevalence of both mutations was compared with a 102 age-matched controls. In children with AIS, the frequencies (patients vs. controls), odds ratio (OR), and 95% confidence interval (95% CI) for the presence of FVL were as follows: 2.3% vs. 2%, OR/95% CI, 1.16/0.2 to 13.2; P value = 0.99. No cases of PT20210A were found in this group. In children with SVT, the frequencies (patients vs. controls), OR, and 95% CI were as follows: FVL (4.3% vs. 2%, OR/95% CI, 2.27/0.22 to 6.2; P value = 0.99) and PT20210A (4.3% vs. 1%; OR/95% CI, 4.6/0.3 to 76.3; P value = 0.3354). One child with PT20210A also had an inherited protein C deficiency. In 12 (18%) out of the 67 children with cerebral thromboembolism, without the aforementioned mutations, other prothrombotic disorders were detected. Although a multi-center prospective study with a large number of Argentinean pediatric patients is needed to obtain considerable evidence, no association between factor V Leiden and/or prothrombin gene G20210A mutation and cerebral thromboembolism was found in this pediatric series.
Primary generation of cytolytic T lymphocytes in the absence of DNA synthesis.
Authors: H R MacDonald, R K Less
Journal: The Journal of Experimental Medicine (1979)

The requirement for DNA synthesis during the primary differentiation of cytolytic T lymphocytes (CTL) had been investigated. CTL were induced polyclonally in vitro by stimulation of normal C57BL/6 spleen cells with concanavalin A (Con A)and their cytolytic activity was tested against 51Cr-labeled target cells in the presence of Bacto Phytohemagglutinin M. With this system, CTL activity could first be detected 48 h after exposure of spleen cells to Con A. Addition of cytosine arabinoside at concentrations sufficient to reduce DNA synthesis by 95-98% in Con A-stimulated cultures did not significantly inhibit the generation of cytolytic activity on a cell-to-cell basis. These results demonstrate that derepression of the genetic information required for the expression of CTL function can occur in the absence of detectable DNA synthesis.
The will: Interpersonal bargaining versus intrapersonal prediction
Authors: Luca Ferrero
Journal: Behavioral and Brain Sciences (2005)

Ainslie is correct in arguing that the force of commitments partly depends on the predictive role of present action, but this claim can be supported independently of the analogy with interpersonal bargaining. No matter whether we conceive of the parties involved in the bargaining as interests or transient selves, the picture of the will as a competitive interaction among these parties is unconvincing.
Cardiopulmonary exercise test and risk stratifications for lung cancer surgery
Authors: Elisabeth Edvardsen, Sigmund A. Anderssen, Fredrik Borchsenius, Silje Rustad, Ole Henning Skjønsberg
Journal: European Respiratory Journal (2014)

Objective:  To identify different factors measured during a cardiopulmonary exercise test (CPET) on a treadmill that might be associated with postoperative cardiopulmonary complications.   Methods:  In a prospective study, 71 candidates for lung cancer surgery (female=35) underwent CPET on a treadmill. Typical CPET variables were evaluated for associations with postoperative cardiopulmonary complications.   Results: Postoperative mortality within 60 days was 4.2% (n=3). They all had abnormal gas-exchange response and the VO 2max  range from 16.7 to 29.3 mL·kg -1· min -1  (68-76% pred). The cardiopulmonary complications were recorded in 28% (n=20), significantly more frequent in men than in women (85% vs 15%).   Conclusion:  VO 2max  in % of predicted seems more suitable than the absolute value (mL·kg -1· min -1 ) for risk stratification prior to lung cancer surgery. This is probably due to gender differences since females in general have significant lower VO 2max  compared to the males. In addition, anaerobic threshold and VE/VCO 2  slope should be considered as a marker for risk stratification, especially in those patients who are not able to exercise until exhaustion.
Unrecognised ventricular dysfunction in COPD
Authors: A. Macchia, J.J. Rodriguez Moncalvo, M. Kleinert, P.D. Comignani, G. Gimeno, D. Arakaki, N. Laffaye, J.J. Fuselli, H.P. Massolin, J. Gambarte, M. Romero, G. Tognoni
Journal: European Respiratory Journal (2011)

While both chronic congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD) impose a substantial disease burden and share aetiological and epidemiological associations, they have largely been studied separately. The aim of our study was to assess the prevalence and the prognostic implications of the coexistence of left ventricular dysfunction in COPD patients and airway obstruction in CHF patients. We used a prospective cohort study including stable ≥ 60-yr-old patients with echocardiographically confirmed CHF (n=201) and stable ≥ 60-yr-old patients with clinically and spirometry-confirmed COPD (n=218). All CHF patients underwent routine spirometry, and all COPD patients underwent routine echocardiographic assessment and B-type natriuretic peptide (BNP) measurement. Patients were followed for 2 yrs. The prevalence of airway obstruction among CHF patients was 37.3% and the prevalence of ventricular dysfunction among COPD patients was 17%. The presence of ventricular dysfunction in patients with COPD tended to increase the risk of mortality during follow-up (hazard ratio 2.34, 95% CI 0.99-5.54; p=0.053). The presence of airway obstruction in patients with CHF did not influence survival. CHF and COPD frequently coexist, and ventricular dysfunction worsens survival in patients with COPD. Considering the high prevalence and the prognostic implications of ventricular dysfunction, routine assessment with either BNP or echocardiogram should be considered in COPD patients.
Pruritus as a manifestation of the dumping syndrome
Authors: A.D. Harries, R. Tredree, R.V. Heatley, J. Rhodes, P.J.A. Holt
Journal: British Journal of Dermatology (1982)

Journal Article Pruritus as a manifestation of the dumping syndrome Get access A.D. HARRIES, A.D. HARRIES Department of Gastroenterology, University Hospital of Wales, Cardiff A.D.Harries, Department of Gastroenterology, University Hospital of Wales, Cardiff CF4 4XW. Search for other works by this author on: Oxford Academic Google Scholar R. TREDREE, R. TREDREE Department of Gastroenterology, University Hospital of Wales, Cardiff Search for other works by this author on: Oxford Academic Google Scholar R.V. HEATLEY, R.V. HEATLEY Department of Gastroenterology, University Hospital of Wales, Cardiff Search for other works by this author on: Oxford Academic Google Scholar J. RHODES, J. RHODES Department of Gastroenterology, University Hospital of Wales, Cardiff Search for other works by this author on: Oxford Academic Google Scholar P.J.A. HOLT P.J.A. HOLT Department of Dermatology, University Hospital of Wales, Cardiff Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 107, Issue 6, 1 December 1982, Pages 707–709, https://doi.org/10.1111/j.1365-2133.1982.tb00533.x Published: 01 December 1982 Article history Accepted: 16 May 1982 Published: 01 December 1982
An opportunity cost model of subjective effort and task performance
Authors: Robert Kurzban, Angela Duckworth, Joseph W. Kable, Justus Myers
Journal: Behavioral and Brain Sciences (2013)

Abstract Why does performing certain tasks cause the aversive experience of mental effort and concomitant deterioration in task performance? One explanation posits a physical resource that is depleted over time. We propose an alternative explanation that centers on mental representations of the costs and benefits associated with task performance. Specifically, certain computational mechanisms, especially those associated with executive function, can be deployed for only a limited number of simultaneous tasks at any given moment. Consequently, the deployment of these computational mechanisms carries an opportunity cost – that is, the next-best use to which these systems might be put. We argue that the phenomenology of effort can be understood as the felt output of these cost/benefit computations. In turn, the subjective experience of effort motivates reduced deployment of these computational mechanisms in the service of the present task. These opportunity cost representations, then, together with other cost/benefit calculations, determine effort expended and, everything else equal, result in performance reductions. In making our case for this position, we review alternative explanations for both the phenomenology of effort associated with these tasks and for performance reductions over time. Likewise, we review the broad range of relevant empirical results from across sub-disciplines, especially psychology and neuroscience. We hope that our proposal will help to build links among the diverse fields that have been addressing similar questions from different perspectives, and we emphasize ways in which alternative models might be empirically distinguished.
Interferon gamma-activated human monocytes downregulate transferrin receptors and inhibit the intracellular multiplication of Legionella pneumophila by limiting the availability of iron.
Authors: T F Byrd, M A Horwitz
Journal: Journal of Clinical Investigation (1989)

We have investigated the role of iron in the intracellular biology of Legionella pneumophila in human monocytes and in the effector arm of cell-mediated immune defense against this intracellular bacterial pathogen. To determine if L. pneumophila intracellular multiplication is iron dependent, we studied the effect of the iron chelator deferoxamine on L. pneumophila infection of monocytes. Deferoxamine at 15 microM completely inhibited L. pneumophila intracellular multiplication. The inhibitory effect of deferoxamine was reversed with equimolar iron-saturated transferrin but not apotransferrin. To examine the potential role of iron in monocyte activation, we investigated the influence of iron-saturated transferrin on L. pneumophila multiplication in IFN gamma-activated monocytes. Iron transferrin, but not apotransferrin, neutralized the capacity of activated monocytes to inhibit L. pneumophila multiplication. To explore a potential mechanism by which activated monocytes might limit the availability of intracellular iron, we examined transferrin receptor expression on nonactivated and activated monocytes cultured in vitro for 5 d. By fluorescence-activated flow cytometry, activated monocytes exhibited markedly fewer transferrin receptors than nonactivated monocytes. By Scatchard analysis of 125I-transferrin binding to monocytes, nonactivated monocytes had 38,300 +/- 12,700 (mean +/- SE) transferrin binding sites, whereas activated monocytes had 10,300 +/- 1,600, a reduction of 73%. Activated and nonactivated monocytes had a similar mean Kd (1.8 +/- 0.2 nM). This study demonstrates that (a) L. pneumophila intracellular multiplication is iron dependent; (b) activated monocytes inhibit L. pneumophila multiplication by limiting the availability of intracellular iron; and (c) transferrin receptors are downregulated on IFN gamma-activated monocytes.
Effects of lipids on the functional and metabolic recovery from global myocardial stunning in isolated rabbit hearts
Authors: M Van de Velde
Journal: Cardiovascular Research (2000)

Objectives: High concentrations of free fatty acids may increase myocardial ischaemic damage. However, the administration of lipid emulsions during reperfusion improves the functional recovery of stunned myocardium. From this apparent controversy we hypothesise that the effect of lipids is related to the time of its administration: we compared the effects of pre- and post-ischaemic administration of Intralipid® on stunned myocardium. We also examined the role of fatty acids and phospholipids, respectively, in the effect of lipid emulsions on stunned myocardium. Methods: Myocardial stunning was produced by 15 min of ischaemia and 90 min of reperfusion in isolated blood perfused rabbit hearts. Intralipid® was administered either prior to ischaemia or during reperfusion. Left ventricular pressure (LVP) and its first derivative (LVdP/dt) were measured to assess functional recovery. High energy phosphates were measured with HPLC. The effects of linoleic acid, phosphatidylcholine and their combination were also studied. Results: Only when Intralipid® was administered during reperfusion, it improved recovery from contractile function and increased high energy phosphate content in globally stunned myocardium. Both linoleic acid and phosphatidylcholine significantly improved myocardial function in stunned myocardium. Conclusions: The effect of lipids on the contractile performance and metabolic state of stunned myocardium depends mainly on the timing of its administration with regard to the ischaemia/reperfusion event. Both free fatty acids and phospholipids contribute to the beneficial effect of lipid emulsions on functional recovery of stunned myocardium.
Characterizing the Epidemiological Transition in Mexico: National and Subnational Burden of Diseases, Injuries, and Risk Factors
Authors: Gretchen Stevens, Rodrigo H Dias, Kevin J. A Thomas, Juan A Rivera, Natalie Carvalho, Simón Barquera, Kenneth Hill, Majid Ezzati
Journal: PLoS Medicine (2008)

Background Rates of diseases and injuries and the effects of their risk factors can have substantial subnational heterogeneity, especially in middle-income countries like Mexico. Subnational analysis of the burden of diseases, injuries, and risk factors can improve characterization of the epidemiological transition and identify policy priorities. Methods and Findings We estimated deaths and loss of healthy life years (measured in disability-adjusted life years [DALYs]) in 2004 from a comprehensive list of diseases and injuries, and 16 major risk factors, by sex and age for Mexico and its states. Data sources included the vital statistics, national censuses, health examination surveys, and published epidemiological studies. Mortality statistics were adjusted for underreporting, misreporting of age at death, and for misclassification and incomparability of cause-of-death assignment. Nationally, noncommunicable diseases caused 75% of total deaths and 68% of total DALYs, with another 14% of deaths and 18% of DALYs caused by undernutrition and communicable, maternal, and perinatal diseases. The leading causes of death were ischemic heart disease, diabetes mellitus, cerebrovascular disease, liver cirrhosis, and road traffic injuries. High body mass index, high blood glucose, and alcohol use were the leading risk factors for disease burden, causing 5.1%, 5.0%, and 7.3% of total burden of disease, respectively. Mexico City had the lowest mortality rates (4.2 per 1,000) and the Southern region the highest (5.0 per 1,000); under-five mortality in the Southern region was nearly twice that of Mexico City. In the Southern region undernutrition and communicable, maternal, and perinatal diseases caused 23% of DALYs; in Chiapas, they caused 29% of DALYs. At the same time, the absolute rates of noncommunicable disease and injury burdens were highest in the Southern region (105 DALYs per 1,000 population versus 97 nationally for noncommunicable diseases; 22 versus 19 for injuries). Conclusions Mexico is at an advanced stage in the epidemiologic transition, with the majority of the disease and injury burden from noncommunicable diseases. A unique characteristic of the epidemiological transition in Mexico is that overweight and obesity, high blood glucose, and alcohol use are responsible for larger burden of disease than other noncommunicable disease risks such as tobacco smoking. The Southern region is least advanced in the epidemiological transition and suffers from the largest burden of ill health in all disease and injury groups.
NF-κB activity marks cells engaged in receptor editing
Authors: Emily J. Cadera, Fengyi Wan, Rupesh H. Amin, Hector Nolla, Michael J. Lenardo, Mark S. Schlissel
Journal: The Journal of Experimental Medicine (2009)

Because of the extreme diversity in immunoglobulin genes, tolerance mechanisms are necessary to ensure that B cells do not respond to self-antigens. One such tolerance mechanism is called receptor editing. If the B cell receptor (BCR) on an immature B cell recognizes self-antigen, it is down-regulated from the cell surface, and light chain gene rearrangement continues in an attempt to edit the autoreactive specificity. Analysis of a heterozygous mutant mouse in which the NF-κB–dependent IκBα gene was replaced with a lacZ (β-gal) reporter complementary DNA (cDNA; IκBα+/lacZ) suggests a potential role for NF-κB in receptor editing. Sorted β-gal+ pre–B cells showed increased levels of various markers of receptor editing. In IκBα+/lacZ reporter mice expressing either innocuous or self-specific knocked in BCRs, β-gal was preferentially expressed in pre–B cells from the mice with self-specific BCRs. Retroviral-mediated expression of a cDNA encoding an IκBα superrepressor in primary bone marrow cultures resulted in diminished germline κ and rearranged λ transcripts but similar levels of RAG expression as compared with controls. We found that IRF4 transcripts were up-regulated in β-gal+ pre–B cells. Because IRF4 is a target of NF-κB and is required for receptor editing, we suggest that NF-κB could be acting through IRF4 to regulate receptor editing.
TIM-2 soaks up ferritin
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

TIM-2 soaks up ferritinThe TIM (T cell immunoglobulin mucin) proteins have emerged as key regulators of allergic and autoimmune diseases due to their influence on T helper (Th)-1 and Th-2 responses.On page 955, Chen and colleagues show that one member of this family, TIM-2, multitasks as a receptor for H-ferritin, a component of the iron storage protein ferritin.Ferritin was not what the group expected to find when they launched a search for TIM-2 ligands."Ferritin is not something immunologists think about much," says senior author William Seaman.Although circulating H-ferritin had been shown to increase during inflammation and to bind to T and B cells, the consequences of these observations were largely unknown.Chen et al. now show that although TIM-2 is most highly expressed in the liver, the primary iron storage organ, this protein is also found on splenic B cells.TIM-2 expression was particularly high on germinal center B cells that were actively responding to antigenic stimulation.Using a TIM-2 reporter cell line, they showed that a soluble product of activated macrophages bound to TIM-2.That product was H-ferritin.Binding triggered endocytosis of the receptor-ligand pair, suggesting that the interaction was functional.The authors are now investigating the consequences of the ferritin-TIM-2 interaction.A recent study showed that intracellular H-ferritin is required for the antiapoptotic effect of NF-B activation in fibroblasts, prompting Seaman to speculate that H-ferritin uptake in activated germinal center B cells might have a similar antiapoptotic effect.
A Clinical Trial of a Whole-Virus H5N1 Vaccine Derived from Cell Culture
Authors: Hartmut J. Ehrlich, Markus Müller, Helen M.L. Oh, Paul A. Tambyah, Christian Joukhadar, Emanuele Montomoli, Dale Fisher, Greg Berezuk, Sandor Fritsch, Alexandra Löw-Baselli, Nina Vartian, Roman Bobrovsky, Borislava G. Pavlova, Eva Maria Pöllabauer, Otfried Kistner, P. Noel Barrett
Journal: New England Journal of Medicine (2008)

Widespread infections of avian species with avian influenza H5N1 virus and its limited spread to humans suggest that the virus has the potential to cause a human influenza pandemic. An urgent need exists for an H5N1 vaccine that is effective against divergent strains of H5N1 virus.In a randomized, dose-escalation, phase 1 and 2 study involving six subgroups, we investigated the safety of an H5N1 whole-virus vaccine produced on Vero cell cultures and determined its ability to induce antibodies capable of neutralizing various H5N1 strains. In two visits 21 days apart, 275 volunteers between the ages of 18 and 45 years received two doses of vaccine that each contained 3.75 microg, 7.5 microg, 15 microg, or 30 microg of hemagglutinin antigen with alum adjuvant or 7.5 microg or 15 microg of hemagglutinin antigen without adjuvant. Serologic analysis was performed at baseline and on days 21 and 42.The vaccine induced a neutralizing immune response not only against the clade 1 (A/Vietnam/1203/2004) virus strain but also against the clade 2 and 3 strains. The use of adjuvants did not improve the antibody response. Maximum responses to the vaccine strain were obtained with formulations containing 7.5 microg and 15 microg of hemagglutinin antigen without adjuvant. Mild pain at the injection site (in 9 to 27% of subjects) and headache (in 6 to 31% of subjects) were the most common adverse events identified for all vaccine formulations.A two-dose vaccine regimen of either 7.5 microg or 15 microg of hemagglutinin antigen without adjuvant induced neutralizing antibodies against diverse H5N1 virus strains in a high percentage of subjects, suggesting that this may be a useful H5N1 vaccine. (ClinicalTrials.gov number, NCT00349141.)
Evaluation of the Mutagenicity and DNA-Modifying Activity of Carcinogens and Noncarcinogens in Microbial Systems&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: H S Rosenkranz, L A Poirier
Journal: JNCI Journal of the National Cancer Institute (1979)

The mutagenicity of 99 chemicals was determined in a standard Salmonella typhimurium assay with the use of strains TA1535 and TA1538; the DNA-modifying capacity was determined with normal and DNA polymerase-deficient Escherichia coli strains. The following categories of chemicals were studied: alkylating agents (15); nitrosamines, hydrazines, and related substances (8); heterocyclics (10); aromatic amines (36); polycyclic aromatic hydrocarbons (11); amides, ureas, and acylating agents (7); antimetabolites (5); inorganics (4); and promoters (3). Of the substances studied, 21 were known noncarcinogens, 21 were ultimate carcinogens, and 45 were procarcinogens. Of the noncarcinogens, 35, 30, and 25% were positive in the Salmonella, E. coli, and both systems, respectively. All of the ultimate carcinogens were detectable as mutagens of DNA-modifying agents; 79, 100, and 79% gave positive tests in the Salmonella, E. coli, and both systems, respectively. Of the procarcinogens 72% were identifiable by these procedures: 52, 67, and 48% in the Salmonella, E. coli, and both assays, respectively. A tabulation of the combined data for ultimate carcinogens and procarcinogens indicates that 77% of the carcinogens gave positive results: 61, 74, and 59% in the Salmonella, E. coli, and both assays, respectively. We suggest that, for prescreening procedures with microbial assays, S. typhimurium strains TA98 and TA100 be included and the standard E. coli DNA polymerase-deficient assay be run in tandem with the Salmonella mutagenicity assay. When the standard E. coli DNA polymerase-deficient assay does not give interpretable results because of the lack of zones of growth inhibition, a modified assay with the use of liquid suspension should be performed.