tbuckley/cabot-search huggingface dataset:
Polarized monocyte response to cytokine stimulation.
Authors: Dirk Nagorsen, Sara Deola, Kina Smith, Ena Wang, Vladia Monsurro, Paola Zanovello, Francesco M Marincola, Monica C Panelli
Journal: Genome biology (2005)

Abstract Background Mononuclear phagocytes (MPs) stand at the crossroads between the induction of acute inflammation to recruit and activate immune effector cells and the downmodulation of the inflammatory process to contain collateral damage. This decision is extensively modulated by the cytokine microenvironment, which includes a broad array of cytokines whose direct effect on MPs remains largely unexplored. Therefore, we tested whether polarized responses of MPs to pathogens are related to the influence of selected cytokines or represent a mandatory molecular switch through which most cytokines operate. Results Circulating CD14 + MPs were exposed to bacterial lipopolysaccharide (LPS) followed by exposure to an array of cytokines, chemokines and soluble factors involved in the immune response. Gene expression was studied by global transcript analysis. Two main classes of cytokines were identified that induced a classical or an alternative pathway of MP activation. Expression of genes affected by NFκB activation was most predictive of the two main classes, suggesting that this pathway is a fundamental target of cytokine regulation. As LPS itself induces a classical type of activation, the most dramatic modulation was observed toward the alternative pathway, suggesting that a broad array of cytokines may counteract the pro-inflammatory effects of bacterial components. Conclusions This analysis is directly informative of the primary effect of individual cytokines on the early stages of LPS stimulation and, therefore, may be most informative of the way MP maturation may be polarized at the early stages of the immune response.
On the ontogeny of combination-sensitive neurons in speech perception
Authors: Athanassios Protopapas, Paula Tallal
Journal: Behavioral and Brain Sciences (1998)

The arguments for the orderly output constraint concern phylogenetic matters and do not address the ontogeny of combination-specific neurons and the corresponding processing mechanisms. Locus equations are too variable to be strongly predetermined and too inconsistent to be easily learned. Findings on the development of speech perception and underlying auditory processing must be taken into account in the formulation of neural encoding theories.
Usefulness of transbronchial needle aspiration in evaluating patients with lung cancer
Authors: S Gasparini
Journal: Thorax (2005)

There is a need to promote more widespread use of TBNA for evaluating NSCLC

Since the introduction of flexible bronchoscopes in 1968,1 various ancillary related methods of sampling lung tissue have been developed to greatly expand the diagnostic capabilities of the procedure. Perhaps the most important innovation has been the development of needles with the ability to puncture the tracheobronchial wall, allowing the bronchoscopist to go beyond the barrier of the airways to obtain specimens from both hilar and mediastinal structures.

After the publication of Dr Ko-Pen Wang’s initial experience with transbronchial needle aspiration (TBNA) in the 1980s,2,3 it became clear that this technique had great potential in both the diagnosis and staging of lung cancer as well as other diseases. The only limiting requirement is that the lymph node must be in close contact with the airways, which is most frequently the case in patients with lung cancer. Despite numerous publications highlighting the safety and accuracy of this procedure, the technique is still underused by pulmonologists. Based on data compiled from Europe and the United States, it has been estimated that the percentage of pulmonologists using TBNA is between 11% and 30%.4–6

The three most often cited reasons for not performing TBNA are: (1) problems with the technique (30%); (2) a belief that TBNA is not useful …
Effects of calcium on canine Purkinje fiber action potential duration in the presence of agents affecting potassium permeability.
Authors: M S Siegal, B F Hoffman
Journal: Circulation Research (1980)

We used intracellular microelectrodes to study the effect of changes in extracellular calcium ion concentration [Ca 2+ ] o on the transmembrane potentials of canine cardiac Purkinje fibers in control Tyrode's solution and in the presence of agents thought to modify membrane permeability to potassium.In Tyrode's solution, decreasing [Ca 2+ ] o from 2.7 to 0.9 mM increased action potential duration measured at -60 mv (APD «,) and at full repolarization (APDioo) but did not significantly modify the normal linear relationship between cycle length and APD between cycle lengths of 500 to 4000 msec.We used 9-aminoacridine (9-AA) to decrease potassium permeability.At concentrations between 0.01 and 1.5 x 10" 5 M, 9-AA caused a concentration-dependent increase in APD-M and APD 1O o and a significant increase in the slope of the line relating APD to cycle length.The usual effects of changes in [Ca z+ ] o on APD were potentiated by 9-AA.We then used lidocaine (L) to increase potassium permeability.At concentrations between 0.75 and 1.5 x 10~5 M, L significantly increased the slope of the line relating APD and cycle length.In the presence of L an increase in [Ca 2+ ] o increased both APD_eo and APD,oo, and a decrease in [Ca 2+ ] o decreased both parameters.9-AA thus potentiated and L reversed the effects of changing [Ca 2+ ] o on APD.The results suggest that changes in [Ca 2+ ] o modify repolarization by modifying both slow inward current and potassium permeability and that the extent to which the latter changes can determine the effect of [Ca 2+ ] o on APD.
Role of neuronal NO synthase in regulating vascular superoxide levels and mitogen-activated protein kinase phosphorylation
Authors: G.-X. Zhang, S. Kimura, K. Murao, J. Shimizu, H. Matsuyoshi, M. Takaki
Journal: Cardiovascular Research (2008)

The present study is designed to investigate the role of neuronal nitric oxide synthase (nNOS) in the regulation of vascular mitogen-activated protein kinase (MAPK) activity under basal and angiotensin II (Ang II)-stimulated conditions.Incubation with a potent nNOS inhibitor (L-VNIO) significantly increased superoxide (O2(-)) levels, with increased MAPK phosphorylation, in isolated aorta and vascular smooth muscle cells (VSMCs) from wild-type mice. Both increases were inhibited by the superoxide dismutase mimetic, tempol, but not by the peroxynitrite scavenger, FeTPPS. The levels of O2(-) and MAPK phosphorylation were higher in aorta from nNOS(-/-) mice than from wild-type mice. These parameters were suppressed by tempol and oxypurinal (a xanthine oxidase inhibitor). In isolated VSMCs or aorta from wild-type mice, Ang II stimulation markedly increased the levels of O2(-) and MAPK phosphorylation. L-VNIO significantly reduced Ang II-induced increases of these parameters. Apocynin, an NAD(P)H oxidase inhibitor, further inhibited Ang II-induced increases of these parameters compared with the L-VNIO-treated group. FeTPPS did not suppress the Ang II-induced increase of O2(-) levels, but markedly inhibited Ang II-induced MAPK phosphorylation. In contrast to the wild-type, in isolated aorta or VSMCs from nNOS(-/-) mice, Ang II failed to increase O2(-) levels and MAPK phosphorylation.Under basal conditions, nNOS-derived NO acting as antioxidant reduces O2(-) accumulation and suppresses vascular MAPK phosphorylation. Under Ang II-stimulated conditions, NAD(P)H oxidase-derived O2(-), inducing nNOS uncoupling, potentiates the Ang II-induced increase of O2(-) generation. The generated O2(-) may react with NO to form peroxynitrite (ONOO(-)). Both O2(-) and ONOO(-) participate in Ang II-induced activation of vascular MAPK.
Fyn kinase initiates complementary signals required for IgE-dependent mast cell degranulation
Authors: Valentino Parravicini, Massimo Gadina, Martina Kovarova, Sandra Odom, Claudia Gonzalez-Espinosa, Yasuko Furumoto, Shinichiroh Saitoh, Lawrence E. Samelson, John J. O'Shea, Juan Rivera
Journal: Nature Immunology (2002)
Graded Autonomy in Medical Education — Managing Things That Go Bump in the Night
Authors: Scott D. Halpern, Allan S. Detsky
Journal: New England Journal of Medicine (2014)

Interview with Dr. Allan Detsky on the ACGME rules about resident supervision and the need for graded autonomy in medical education. (14:29)Download The level of supervision of residents is increasing, with an attendant perceived loss of autonomy in decision making. However, as with duty-hour restrictions, there is no evidence regarding the effects of increased supervision on educational value or future quality of care.
Insulin Resistance and Progression to Type 1 Diabetes in the European Nicotinamide Diabetes Intervention Trial (ENDIT)
Authors: Terence J. Wilkin
Journal: Diabetes Care (2008)

The accelerator hypothesis proposes that type 1 and type 2 diabetes are both driven by insulin resistance (1), and its principle prediction is an inverse correlation between BMI and age at onset in children with type 1 diabetes. Bingley et al. (2) examined ENDIT data and found evidence for an inverse correlation only among those with advanced β-cell loss (low first-phase insulin response) (FPIR). They conclude that insulin …
Clinical Pharmacology of the Dietary Supplement Creatine Monohydrate
Authors: Adam M. Persky, Gayle A. Brazeau
Journal: Pharmacological Reviews (2001)

Creatine is a dietary supplement purported to improve exercise performance and increase fat-free mass. Recent research on creatine has demonstrated positive therapeutic results in various clinical applications. The purpose of this review is to focus on the clinical pharmacology and therapeutic application of creatine supplementation. Creatine is a naturally occurring compound obtained in humans from endogenous production and consumption through the diet. When supplemented with exogenous creatine, intramuscular and cerebral stores of creatine and its phosphorylated form, phosphocreatine, become elevated. The increase of these stores can offer therapeutic benefits by preventing ATP depletion, stimulating protein synthesis or reducing protein degradation, and stabilizing biological membranes. Evidence from the exercise literature has shown athletes benefit from supplementation by increasing muscular force and power, reducing fatigue in repeated bout activities, and increasing muscle mass. These benefits have been applied to disease models of Huntington's, Parkinson's, Duchenne muscular dystrophy, and applied clinically in patients with gyrate atrophy, various neuromuscular disorders, McArdle's disease, and congestive heart failure. This review covers the basics of creatine synthesis and transport, proposed mechanisms of action, pharmacokinetics of exogenous creatine administration, creatine use in disease models, side effects associated with use, and issues on product quality.
Cardiovascular and sympathetic responses reflexly elicited through the excitation with bradykinin of sympathetic and vagal cardiac sensory endings in the cat
Authors: F. LOMBARDI, C. P PATTON, P. D. BELLA, M. PAGANI, A. MALLIANI
Journal: Cardiovascular Research (1982)

The intracoronary administration of bradykinin (30 ng·kg−1) was used to study the reflex responses to the excitation of sympathetic and vagal cardiac sensory endings in anaesthetised cats. The left main coronary artery was perfused with a constant flow pump to administer the drug without concomitant manipulations of the heart. The reflex effects were assessed by recording simultaneously target haemodynamic functions and the impulse activity of sympathetic preganglionic fibres, isolated from an outflow largely directed to the heart. In eight out of 13 cats with intact cardiovascular innervation the intracoronary injection of bradykinin produced a consistent and significant increase in systemic mean arterial pressure (MAP), left ventricular pressure (LVP) and LVdP/dtmax along with a significant increase in the sympathetic efferent impulse activity. In the remaining five animals, bradykinin caused a significant haemodynamic depressor response concomitant with a slight increase in sympathetic impulse activity. In eight additional cats with sinoaortic denervation, excitatory or inhibitory haemodynamic reflex responses were also observed, the types of response being consistent in each individual animal. However, in the case of inhibitory responses the sympathetic impulse activity was simultaneously decreased. After vagotomy, bradykinin induced a significant increase in MAP, LVP, LVdP/dtmax and in cardiac sympathetic efferent activity in all 21 cats. These excitatory responses were abolished after the interruption of a large part of the cardiac sympathetic afferents. Thus the intracoronary administration of bradykinin induced haemodynamic and sympathetic reflex responses that were dependent upon the interaction of opposite influences mediated by the simultaneous activation of cardiac vagal and sympathetic afferents.
Beyond patient safety Flatland
Authors: Jeffrey Braithwaite, Enrico Coiera
Journal: Journal of the Royal Society of Medicine (2010)

When Edwin A Abbott published in 1884 his famous fantasy in geometry, Flatland: A romance of many dimensions, his imagination sparked not so much a revolution in mathematics or physics as of perspective. Flatland is a universe in two dimensions – length and width – and the inhabitants (lines, triangles, squares and multisided polygons) in the plane cannot apprehend the complexities of the third dimension: height. It remains beyond their cognitive reach. This analogously describes the problem of patient safety, where we know a lot about two dimensions – the magnitude of the predicament (the length of the problem) and the categories of harm (its width) – but the nature of the third dimension, the lofty heights of what to do, and how to address problems, has proven elusive. We are on the brink of understanding this dimension more thoroughly, and thus better positioned to tackle the challenges it presents.
The basics of epithelial-mesenchymal transition
Authors: Raghu Kalluri, Robert A. Weinberg
Journal: Journal of Clinical Investigation (2009)

The origins of the mesenchymal cells participating in tissue repair and pathological processes, notably tissue fibrosis, tumor invasiveness, and metastasis, are poorly understood. However, emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) represent one important source of these cells. As we discuss here, processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias. The identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions.
The Evolution of Genes within Genes and the Control of DNA Replication in Microviruses
Authors: S. M. Doore, C. D. Baird, A. P. Roznowski, B. A. Fane
Journal: Molecular Biology and Evolution (2014)

Single-stranded DNA(ssDNA) viral life cycles must balance double-stranded DNA (dsDNA) and ssDNA biosynthesis. Previously published in vitro results suggest that microvirus C and host cell SSB proteins play antagonistic roles to achieve this balance. To investigate this in vivo, microvirus DNA replication was characterized in cells expressing cloned C or ssb genes, which would presumably alter the C:SSB protein ratios. Representatives of each microvirus clade (ϕX174, G4, and α3) were used in these studies. α3 DNA replication was significantly more complex. Results suggested that the recognized α3 C gene (CS: small) is one of two C genes. A larger 5′ extended gene could be translated from an upstream GTG start codon (CB: big). Wild-type α3 acquired resistance to elevated SSB levels by mutations that exclusively frameshifted the CB reading frame, whereas mutations in the origin of replication conferred resistance to elevated C protein levels. Expression of either the cloned CB or CS gene complemented am(C) mutants, demonstrating functional redundancy. When the CS start codon was eliminated, strains were only viable if an additional amber mutation was placed in gene C and propagated in an informational suppressing host. Thus, CB protein likely reaches toxic levels in the absence of CS translation. This phenomenon may have driven the evolution of the CS gene within the larger CB gene and could constitute a unique mechanism of regulation. Furthermore, cross-complementation data suggested that interactions between the α3 C and other viral proteins have evolved enough specificity to biochemically isolate its DNA replication from G4 and ϕX174.
NHS shows 1.5bn surplus but quarter of trusts have weak financial arrangements
Authors: A. O'Dowd
Journal: BMJ (2011)

The NHS in England made a surplus of £1.5bn (€1.7bn; $2.4bn) last year, but around a quarter of acute trusts have been rated as having weak financial arrangements, according to a report from the national public spending watchdog.

An Audit Commission report published on 11 August says that trusts managed to make savings through a combination of improving clinical productivity—including managing demand, reducing length of stay, moving to day case surgery or outpatient treatments, and bed closures—and reducing workforce costs.

Substantial savings came from the 7274 redundancies and resignations in the financial year 2010-11 from NHS organisations, most of …
Epigenetic Inactivation of Wnt Inhibitory Factor-1 Plays an Important Role in Bladder Cancer through Aberrant Canonical Wnt/β-Catenin Signaling Pathway
Authors: Shinji Urakami, Hiroaki Shiina, Hideki Enokida, Toshifumi Kawakami, Takashi Tokizane, Tatsuya Ogishima, Yuichiro Tanaka, Long-Cheng Li, Leopoldo A. Ribeiro-Filho, Masaharu Terashima, Nobuyuki Kikuno, Hiroyuki Adachi, Tatsuaki Yoneda, Hirofumi Kishi, Kazushi Shigeno, Badrinath R. Konety, Mikio Igawa, Rajvir Dahiya
Journal: Clinical Cancer Research (2006)

Aberrant activation of the Wingless-type (Wnt) pathway plays a significant role in the pathogenesis of several human cancers. Wnt inhibitory factor-1 (Wif-1) was identified as one of the secreted antagonists that can bind Wnt protein. We hypothesize that Wif-1 plays an important role in bladder cancer pathogenesis.To test this hypothesis, epigenetic and genetic pathways involved in the Wif-1 gene modulation and expression of Wnt/beta-catenin-related genes were analyzed in 4 bladder tumor cell lines and 54 bladder tumor and matched normal bladder mucosa.Wif-1 mRNA expression was significantly enhanced after 5-aza-2'-deoxycytidine treatment in bladder tumor cell lines. Wif-1 promoter methylation level was significantly higher and Wif-1 mRNA expression was significantly lower in bladder tumor samples than in bladder mucosa samples. In the total bladder tumor and bladder mucosa samples, an inverse correlation was found between promoter methylation and Wif-1 mRNA transcript levels. However, loss-of-heterozygosity at chromosome 12q14.3 close to the Wif-1 gene loci was a rare event (3.7%). Nuclear accumulation of beta-catenin was significantly more frequent in bladder tumor than in bladder mucosa and inversely correlated with Wif-1 expression. In addition, known targets of the canonical Wnt/beta-catenin signaling pathway, such as c-myc and cyclin D1, were up-regulated in bladder tumor compared with bladder mucosa, and this up-regulation was associated with reduced Wif-1 expression at both mRNA and protein levels. Furthermore, transfection of Wif-1 small interfering RNA into bladder tumor cells expressing Wif-1 mRNA transcripts had increased levels of c-myc and cyclin D1 and accelerated cell growth.This is the first report showing that CpG hypermethylation of the Wif-1 promoter is a frequent event in bladder tumor and may contribute to pathogenesis of bladder cancer through aberrant canonical Wnt/beta-catenin signaling pathway. The present study elucidates novel pathways that are involved in the pathogenesis of bladder cancer.
Pediatric Euthanasia in Belgium
Authors: Andrew M. Siegel, Dominic A. Sisti, Arthur L. Caplan
Journal: JAMA (2014)

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Sports-related acute and chronic avulsion injuries in children and adolescents with special emphasis on tennis
Authors: Everhard J M Vandervliet, Filip M Vanhoenacker, Annemie Snoeckx, Jan L Gielen, Pieter Van Dyck, Paul M Parizel
Journal: British Journal of Sports Medicine (2007)

Acute and chronic sports-related muscle and tendon injuries are not infrequent in youngsters. In particular, the physis is prone to trauma as it constitutes the weakest part of the immature skeleton. The type of sports activity determines the location of the lesion. Most commonly, apophyses of the hip and pelvis are subject to avulsion. The purpose of this paper is to give a short overview of the pathogenesis, location, prevalence and imaging characteristics of acute and chronic avulsion injuries in the immature skeleton, with special emphasis on tennis-related injuries. Tennis-related injuries particularly involve apophyses of the ischial tuberosity, the anterior inferior or superior iliac spine and the iliac crest.
Response to Comment on: Hardikar et al. Spuriously High Prevalence of Prediabetes Diagnosed by HbA1c in Young Indians Partly Explained by Hematological Factors and Iron Deficiency Anemia. Diabetes Care 2012;35:797-802
Authors: Pallavi S. Hardikar, Suyog M. Joshi, Dattatray S. Bhat, Deepa A. Raut, Prachi A. Katre, Himangi G. Lubree, Abhay Jere, Anand N. Pandit, Caroline H.D. Fall, Chittaranjan S. Yajnik
Journal: Diabetes Care (2013)

We are grateful to Schindhelm et al. (1) for their interest in our article. We measured HbA1c during follow-up of a birth cohort in the hope of substituting it for an oral glucose tolerance test. We found a discrepancy between the results of the oral glucose tolerance test (World Health Organization, 1999) and HbA1c (American Diabetes Association, 2009): A large number of individuals were classified as having “prediabetes” by HbA1c when considered normal glucose tolerant by oral glucose tolerance test (2). This prompted us to investigate possible causes of this discrepancy. We found that a number of hematological parameters (lower hemoglobin …
Progesterone receptor loss identifies Luminal B breast cancer subgroups at higher risk of relapse
Authors: G. Cancello, P. Maisonneuve, N. Rotmensz, G. Viale, M.G. Mastropasqua, G. Pruneri, E. Montagna, M. Iorfida, M. Mazza, A. Balduzzi, P. Veronesi, A. Luini, M. Intra, A. Goldhirsch, M. Colleoni
Journal: Annals of Oncology (2012)