tbuckley/cabot-search huggingface dataset:
Germline p53 mutations are frequently detected in young children with rhabdomyosarcoma.
Authors: L Diller, E Sexsmith, A Gottlieb, F P Li, D Malkin
Journal: Journal of Clinical Investigation (1995)

We investigated the possibility that a proportion of children with sporadic rhabdomyosarcoma (RMS) carry constitutional mutations of the p53 tumor suppressor gene. 33 patients with sporadic RMS at two large outpatient pediatric oncology clinics submitted blood samples. Genomic DNA was extracted from peripheral blood leukocytes and PCR was used to amplify exons 2-11 of the p53 gene. Amplified genomic DNA was screened for the presence of germline p53 mutations using single-strand conformation polymorphism (SSCP) analysis. The DNA sequence of those samples that showed aberrant migration of bands on SSCP analysis was determined to identify the precise nature of the gene mutations. Patient records were reviewed to assess clinical correlates of the mutant p53 carrier state. Heterozygous constitutional mutations were detected in 3/33 patient samples screened. Two of these missense mutations are located in exon 7 and one in exon 8 of the p53 gene. The presence of mutations was not correlated with tumor histology, stage, or site. However, an association between young age at diagnosis and presence of a constitutional p53 mutation was noted: 3/13 children under the age of 3 yr at diagnosis carried mutations, whereas none of 20 children over 3 yr of age at diagnosis harbored a detectable constitutional mutation. These results in children with RMS corroborates previous findings in other clinical settings suggesting that the mutant p53 carrier state may predispose individuals to malignancy at an early age. Although this study did not assess whether the mutations were preexisting or new germline alterations, assessment of close relatives of RMS patients for cancer risk and predictive genetic testing may be indicated.
Cardiac Arrhythmias in Children
Authors: R M Campbell, M Dick, A Rosenthal
Journal: Annual Review of Medicine (1984)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Deep vein thrombosis after thoracotomy.
Authors: F R Jackaman, B J Perry, H Siddons
Journal: Thorax (1978)

In a prospective study of 183 patients undergoing lateral thoracotomy the 125 I fibrinogen uptake test and perioperative heparin prophylaxis for deep-vein thrombosis were investigated. There was an incidence of deep vein thrombosis in 51% in untreated control patients. The heparin prophylaxis effectively reduced the incidence of deep venous thrombosis to 28% (P less than 0.005) without increasing postoperative blood loss. Unilateral thrombosis was found to be significantly more frequent in the leg opposite the side of the thoracotomy (P less than 0.005). The 125I fibrinogen test is essential in assessing methods of prophylaxis but is not recommended as a routine.
Tobacco Marketing
Authors: Rep Henry Waxman
Journal: JAMA (1991)

In 1946, the RJ Reynolds Tobacco Co advertised that "More Doctors Smoke Camels Than Any Other Cigarette."<sup>1</sup>Such a message conveyed that it was medically safe to smoke, and the tobacco companies targeted adults to receive that message. In 1991, tobacco companies don't use medical spokespersons to sell their products. Few physicians would attest to the safety of smoking, and tobacco companies are not as interested in adults anymore. In today's cigarette advertisements, physicians in white coats have been replaced by cartoon animals in bright, preschool colors. With straight faces, RJ Reynolds and its industry colleagues report that they've chosen figures like Old Joe Camel because they believe that such figures will appeal to adult smokers and encourage them to change brands. With the same straight faces, they will likely express shock that children respond to this campaign by taking up smoking.
Inhibition of Erythrocyte Cation Channels by Erythropoietin
Authors: Svetlana Myssina, Stephan M. Huber, Christina Birka, Philipp A. Lang, Karl S. Lang, Björn Friedrich, Teut Risler, Thomas Wieder, Florian Lang
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Recombinant human erythropoietin therapy is used to counteract anemia that is the result of renal insufficiency. It stimulates the formation of peripheral blood erythrocytes by inhibiting apoptosis of erythrocyte precursor cells. Mature erythrocytes have similarly been shown to undergo apoptosis. Hyperosmotic shock and Cl − removal activate a Ca 2+ -permeable, ethylisopropylamiloride-inhibitable cation channel. The subsequent increase of cytosolic Ca 2+ activates a scramblase that breaks down cell membrane phosphatidylserine asymmetry, leading to annexin binding. Studied was whether channel activity and erythrocyte cell death are regulated by erythropoietin. Scatchard plot analysis disclosed low-abundance, high-affinity binding of 125 I-erythropoietin to erythrocytes. Whole cell patch clamp experiments revealed significant inhibition of the ethylisopropylamiloride-sensitive current by 1 U/ml erythropoietin. Cl − removal triggered annexin binding, an effect abrogated by erythropoietin (1 U/ml) but not by GM-CSF (10 ng/ml). Osmotic shock (700 mOsm) stimulated annexin binding within 24 h in the majority of the erythrocytes, an effect blunted by erythropoietin (1 U/ml) but not by GM-CSF (10 ng/ml). In the nominal absence of Ca 2+ , the effect of osmotic shock was blunted and the effect of erythropoietin abolished. In hemodialysis patients, intravenous administration of erythropoietin (50 IU/kg) within 4 h decreased the number of annexin binding circulating erythrocytes. Erythropoietin binds to erythrocytes and inhibits volume-sensitive erythrocyte cation channels and thus the breakdown of phosphatidylserine asymmetry after activation of this channel. The effect could prolong the erythrocyte lifespan and may contribute to the enhancement of the erythrocyte number during erythropoietin therapy in dialysis patients. E-mail: florian.lang@uni-tuebingen.de
The capsule of the gonococcus.
Authors: J F James, J Swanson
Journal: The Journal of Experimental Medicine (1977)

16 strains of Neisseria gonorrhoeae were subjected to several established techniques for capsule demonstration by light microscopy. In all strains examined, encapsulation of the gonococcus was demonstrated. Although the capsules were somewhat more easily seen in strains recently isolated from clinical material, organisms that had been passaged for several years also were encapsulated as were all the colony types within these strains. The gonococcal capsule is easily disrupted by mechanical forces.
Genetic Abnormalities and Patterns of Antigenic Expression in Multiple Myeloma
Authors: Gema Mateo, Mariana Castellanos, Ana Rasillo, Norma C. Gutiérrez, Ma. Angeles Montalbán, Ma. Luisa Martín, Jesús Ma. Hernández, Ma. Consuelo López-Berges, Laura Montejano, Joan Bladé, Ma. Victoria Mateos, Anna Sureda, Javier de la Rubia, Joaquín Díaz-Mediavilla, Atanasio Pandiella, Juan José Lahuerta, Alberto Orfao, Jesús F. San Miguel
Journal: Clinical Cancer Research (2005)

Abstract Myelomatous plasma cells show a high heterogeneity both in their immunophenotypic characteristics as well as in their cytogenetic features. Thus far, no extensive studies have been carried out to explore whether such antigenic diversity is associated with specific genetic characteristics. We have investigated the relationship between the immunophenotypic profile at plasma cell and both their DNA ploidy status (evaluated by flow cytometry) and specific genetic features (ascertained by fluorescence in situ hybridization) in a large series of 915 patients with newly diagnosed multiple myeloma. The non-hyperdiploid multiple myeloma group (n = 454, 52%) was associated with a significantly higher frequency of positivity for CD28 and CD20 as well as a higher incidence of CD56− and CD117− cases (P &amp;lt; 0.001). Remarkably, 13q deletion and immunoglobulin heavy chain (IGH) gene rearrangements, which were significantly more common in non-hyperdiploid multiple myeloma, showed a strong association with CD117− cases. IGH translocation to 11q13 was associated with reactivity for CD20 (P &amp;lt; 0.001), down-regulation of CD56 (P &amp;lt; 0.001), and lack of expression of CD117 (P = 0.001). By contrast, IGH translocations to other chromosome partners were almost exclusively found among CD20− and CD117− cases (P &amp;lt; 0.001). These results suggest that genetic categories in multiple myeloma exhibit particular immunophenotypic profiles which in turn are strongly associated with the DNA ploidy status.
ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension
Authors: Vallerie V. McLaughlin, Stephen L. Archer, David B. Badesch, Robyn J. Barst, Harrison W. Farber, Jonathan R. Lindner, Michael A. Mathier, Michael D. McGoon, Myung H. Park, Robert S. Rosenson, Lewis J. Rubin, Victor F. Tapson, John Varga
Journal: Circulation (2009)
Grid maps for spaceflight, anyone? They are for free!
Authors: Federico Stella, Bailu Si, Emilio Kropff, Alessandro Treves
Journal: Behavioral and Brain Sciences (2013)

Abstract We show that, given extensive exploration of a three-dimensional volume, grid units can form with the approximate periodicity of a face-centered cubic crystal, as the spontaneous product of a self-organizing process at the single unit level, driven solely by firing rate adaptation.
Talent identification in soccer
Authors: Nader Rahnama
Journal: British Journal of Sports Medicine (2010)

Some studies showed that most professional soccer players were born on the same date. The aim of this study was to investigate talent identification among players of the 2006 FIFA World Cup according to the distribution of their birth date in different playing positions in five continents of the world (Asia, Africa, Europe, North Africa and South America). Information about birth dates of 736 players was collected from FIFA website. χ 2 Test and analysis of variance were used to assess the differences among the players' birth dates. The results showed no significant effect in different positions between players born in the first and second halves of a month and between players born in different months (p&gt;0.05). Although the number of births between August and October were more than other seasons, the difference was not significant (p&gt;0.05). Also, no significant effect was found between different positions and the players' birth season (p&gt;0.05). No significant effect was found between month and season of births in five continents (p&gt;0.05). Although the mean of height and the mean of weight of the players born between August and October were more than other seasons, this difference was not significant (p&gt;0.05). It can be concluded that birth date of players of the 2006 FIFA World Cup was similar to the distribution of playing positions and continents. Talent identification according to the birth date is not reliable.
Constructing an understanding of mind with peers
Authors: Stephanie Zerwas, Geetha Balaraman, Celia Brownell
Journal: Behavioral and Brain Sciences (2004)

Carpendale & Lewis (C&L) stress the importance of social interaction for social understanding, but focus on the adult-child relationship. In the present commentary, we discuss the development of social understanding within early peer relationships. We argue that peer interaction stretches the limits of early social understanding, thereby providing both unique challenges and unique opportunities for constructing an understanding of others' minds.
The Same IκBα Mutation in Two Related Individuals Leads to Completely Different Clinical Syndromes
Authors: Riny Janssen, Annelies van Wengen, Marieke A. Hoeve, Monique ten Dam, Miriam van der Burg, Jacques van Dongen, Esther van de Vosse, Maarten van Tol, Robbert Bredius, Tom H. Ottenhoff, Corry Weemaes, Jaap T. van Dissel, Arjan Lankester
Journal: The Journal of Experimental Medicine (2004)

Both innate and adaptive immune responses are dependent on activation of nuclear factor kappaB (NF-kappaB), induced upon binding of pathogen-associated molecular patterns to Toll-like receptors (TLRs). In murine models, defects in NF-kappaB pathway are often lethal and viable knockout mice have severe immune defects. Similarly, defects in the human NF-kappaB pathway described to date lead to severe clinical disease. Here, we describe a patient with a hyper immunoglobulin M-like immunodeficiency syndrome and ectodermal dysplasia. Monocytes did not produce interleukin 12p40 upon stimulation with various TLR stimuli and nuclear translocation of NF-kappaB was impaired. T cell receptor-mediated proliferation was also impaired. A heterozygous mutation was found at serine 32 in IkappaBalpha. Interestingly, his father has the same mutation but displays complex mosaicism. He does not display features of ectodermal dysplasia and did not suffer from serious infections with the exception of a relapsing Salmonella typhimurium infection. His monocyte function was impaired, whereas T cell function was relatively normal. Consistent with this, his T cells almost exclusively displayed the wild-type allele, whereas both alleles were present in his monocytes. We propose that the T and B cell compartment of the mosaic father arose as a result of selection of wild-type cells and that this underlies the widely different clinical phenotype.
Exon Skipping and Duchenne Muscular Dystrophy Therapy: Selection of the Most Active U1 snRNA Antisense Able to Induce Dystrophin Exon 51 Skipping
Authors: Tania Incitti, Fernanda G De Angelis, Valentina Cazzella, Olga Sthandier, Chiara Pinnarò, Ivano Legnini, Irene Bozzoni
Journal: Molecular Therapy (2010)

One promising approach for the gene therapy of Duchenne muscular dystrophy (DMD) is exon skipping. When thinking of possible intervention on human, it is very crucial to identify the most appropriate antisense sequences able to provide the highest possible skipping efficiency. In this article, we compared the exon 51 skipping activity of 10 different antisense molecules, raised against splice junctions and/or exonic splicing enhancers (ESEs), expressed as part of the U1 small nuclear RNA (snRNA). The effectiveness of each construct was tested in human DMD myoblasts carrying the deletion of exons 48–50, which can be treated with skipping of exon 51. Our results show that the highest skipping activity and dystrophin rescue is achieved upon expression of a U1 snRNA-derived antisense molecule targeting exon 51 splice sites in combination with an internal exon sequence. The efficacy of this molecule was further proven on an exon 45–50 deletion background, utilizing patient's fibroblasts transdifferentiated into myoblasts. In this system, we showed that the selected antisense was able to produce 50% skipping of exon 51. One promising approach for the gene therapy of Duchenne muscular dystrophy (DMD) is exon skipping. When thinking of possible intervention on human, it is very crucial to identify the most appropriate antisense sequences able to provide the highest possible skipping efficiency. In this article, we compared the exon 51 skipping activity of 10 different antisense molecules, raised against splice junctions and/or exonic splicing enhancers (ESEs), expressed as part of the U1 small nuclear RNA (snRNA). The effectiveness of each construct was tested in human DMD myoblasts carrying the deletion of exons 48–50, which can be treated with skipping of exon 51. Our results show that the highest skipping activity and dystrophin rescue is achieved upon expression of a U1 snRNA-derived antisense molecule targeting exon 51 splice sites in combination with an internal exon sequence. The efficacy of this molecule was further proven on an exon 45–50 deletion background, utilizing patient's fibroblasts transdifferentiated into myoblasts. In this system, we showed that the selected antisense was able to produce 50% skipping of exon 51.
Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies
Authors: Nadeem Sarwar, Adam S. Butterworth, Daniel F. Freitag, John Gregson, Peter Willeit, Donal N. Gorman, Pei Gao, Danish Saleheen, Augusto Rendon, Christopher P. Nelson, Peter S. Braund, Alistair S. Hall, Daniel I. Chasman, Anne Tybjaerg-Hansen, John C. Chambers, Emelia J. Benjamin, Paul W. Franks, Robert Clarke, Arthur A. M. Wilde, Mieke D. Trip, Maristella Steri, Jacqueline C. M. Witteman, Lu Qi, C. Ellen van der Schoot, Ulf de Faire, Jeanette Erdmann, Heather M. Stringham, Wolfgang Koenig, Daniel J. Rader, David Melzer, David Reich, Bruce M. Psaty, Marcus E. Kleber, Demosthenes B. Panagiotakos, Johann Willeit, Patrik Wennberg, Mark Woodward, Svetlana Adamovic, Eric B. Rimm, Tom W. Meade, Richard F. Gillum, Jonathan A. Shaffer, Albert Hofman, Altan Onat, Johan Sundstrom, Sylvia Wassertheil-Smoller, Dan Mellstrom, John Gallacher, Mary Cushman, Russell P. Tracy, Jussi Kauhanen, Magnus Karlsson, Jukka T. Salonen, Lars Wilhelmsen, Philippe Amouyel, Bernard Cantin, Lyle G. Best, Yoav Ben-Shlomo, JoAnn E. Manson, George Davey-Smith, Paul I. W. de Bakker, Christopher J. O'Donnell, James F. Wilson, Anthony G. Wilson, Themistocles L. Assimes, John-Olov Jansson, Claes Ohlsson, Asa Tivesten, Osten Ljunggren, Muredach P. Reilly, Anders Hamsten, Erik Ingelsson, Francois Cambien, Joseph Hung, G. Neil Thomas, Michael Boehnke, Heribert Schunkert, Folkert W. Asselbergs, John J. P. Kastelein, Vilmundur Gudnason, Veikko Salomaa, Tamara B. Harris, Jaspal S. Kooner, Kristine H. Allin, Borge G. Nordestgaard, Jemma C. Hopewell, Alison H. Goodall, Paul M. Ridker, Hilma Holm, Hugh Watkins, Willem H. Ouwehand, Nilesh J. Samani, Stephen Kaptoge, Emanuele Di Angelantonio, Olivier Harari, John Danesh
Journal: The Lancet (2012)
Human TRIM71 and Its Nematode Homologue Are Targets of let-7 MicroRNA and Its Zebrafish Orthologue Is Essential for Development
Authors: You-Chin Lin, Li-Ching Hsieh, Ming-Wei Kuo, John Yu, Huan-Hsien Kuo, Wan-Lin Lo, Ruey-Jen Lin, Alice L. Yu, Wen-Hsiung Li
Journal: Molecular Biology and Evolution (2007)

Animal microRNAs (miRNAs) are short RNAs that function as posttranscriptional regulators of gene expression by binding to the target mRNAs. Noting that some miRNAs are highly conserved in evolution, we explored the possibility of evolutionary conservation of their targets. We identified human orthologues of experimentally verified let-7 miRNA target genes in Caenorhabditis elegans and used the luciferase reporter system to examine whether these human genes are still the targets of let-7 miRNA. We found that in some cases, the miRNA–target relationship has indeed been conserved in human. Interestingly, human TRIM71, an orthologue of C. elegans let-7–target lin-41 gene, can be repressed by hsa-let-7a and hsa-let-7c. This repression was abolished when both predicted let-7 target sites of TRIM71 were mutated. Moreover, the zebrafish lin-41 orthologue was also repressed by let-7 to a similar degree as was TRIM71. When the expression of zebrafish lin-41 orthologue was silenced by microinjection of RNA interference or morpholino into zebrafish zygotes, retarded embryonic development was observed, providing direct evidence for an essential role of lin-41 in zebrafish development. Taken together, our results suggest that the regulation of TRIM71 expression by let-7 has been evolutionarily conserved and that TRIM71 likely plays an important role in development.
Assessment of myocardial perfusion in the empty beating porcine heart with laser Doppler flowmetry
Authors: H C AHN, R EKROTH, J HEDENMARK, G E NILSSON, R SVEDJEHOLM
Journal: Cardiovascular Research (1988)

Laser Doppler flowmetry was applied to the empty beating heart of six pigs. Cardiopulmonary bypass was instituted and the preparation allowed continuous and simultaneous measurement of coronary sinus blood flow and local tissue perfusion. An epicardial and an intramuscular probe were used. Significant linear correlation coefficients were obtained between changes of laser Doppler signal and coronary sinus blood flow changes in all seven experiments in four animals (r from 0.71 to 0.94, p less than 0.005) and between laser Doppler signal and changes of extracorporeal bypass in five out of six experiments in four animals (r from 0.82 to 0.99, p less than 0.001). The correlation between coronary sinus flow and bypass flow of four pigs was significant (r from 0.81 to 0.98, p less than 0.001), the coronary flow being about 10% of bypass flow. Muscular activity of the heart contributed to the laser Doppler signal, the magnitude of this "noise level" varying between different experiments even in the same animal. A key question for the applicability of laser Doppler flowmetry to the beating heart is whether it will become possible to discriminate between flow and muscular contribution to the laser Doppler output.
Early diagnosis of airways obstruction
Authors: G. M. Cochrane, F. Prieto, B. Hickey, S. R. Benatar, T. J. H. Clark
Journal: Thorax (1974)

<b>Cochcrane, G. M., Prieto, F., Hickey, B., Benatar, S. R., and Clark, T. J. H.</b><i>Thorax</i>, <b>29</b>, 389-393. <b>Early diagnosis of airways obstruction.</b> Three simple tests, maximum expiratory flow volume curve, maximum expiratory volume time curve and `closing volume9, were used to detect early airways obstruction in 21 smokers. A high proportion had abnormal values for MEF<sub>75%</sub>, MEF<sub>50%</sub>, and FET (86%, 71%, and 62% respectively) with a relatively normal FEV<sub>1</sub>. There was a good correlation between tests of small airways obstruction obtained from the forced expiratory manoeuvre. The measurement of `closing volume9 (phase 4/VC%) was less satisfactory as there were difficulties with interpretation of the records in half of the studies. We conclude that the forced expiratory manoeuvre can be used to detect early airways obstruction as well as providing FEV<sub>1</sub> and vital capacity. The importance of early diagnosis of airways obstruction is not yet clear and further information is required about its natural history, and its relation to smoking habits and to the more advanced and less reversible stages of airways obstruction. It may be possible to use early detection to prevent the development of disabling chronic obstructive bronchitis.