tbuckley/cabot-search huggingface dataset:
Splicing Patterns in <i>SF3B1</i>-Mutated Uveal Melanoma Generate Shared Immunogenic Tumor-Specific Neoepitopes
Authors: Jeremy Bigot, Ana I. Lalanne, Francesca Lucibello, Paul Gueguen, Alexandre Houy, Stephane Dayot, Olivier Ganier, Jules Gilet, Jimena Tosello, Fariba Nemati, Gaelle Pierron, Joshua J. Waterfall, Raymond Barnhill, Sophie Gardrat, Sophie Piperno-Neumann, Tatiana Popova, Vanessa Masson, Damarys Loew, Pascale Mariani, Nathalie Cassoux, Sebastian Amigorena, Manuel Rodrigues, Samar Alsafadi, Marc-Henri Stern, Olivier Lantz
Journal: Cancer Discovery (2021)

Disruption of splicing patterns due to mutations of genes coding splicing factors in tumors represents a potential source of tumor neoantigens, which would be both public (shared between patients) and tumor-specific (not expressed in normal tissues). In this study, we show that mutations of the splicing factor SF3B1 in uveal melanoma generate such immunogenic neoantigens. Memory CD8+ T cells specific for these neoantigens are preferentially found in 20% of patients with uveal melanoma bearing SF3B1-mutated tumors. Single-cell analyses of neoepitope-specific T cells from the blood identified large clonal T-cell expansions, with distinct effector transcription patterns. Some of these expanded T-cell receptors are also present in the corresponding tumors. CD8+ T-cell clones specific for the neoepitopes specifically recognize and kill SF3B1-mutated tumor cells, supporting the use of this new family of neoantigens as therapeutic targets. SIGNIFICANCE: Mutations of the splicing factor SF3B1 in uveal melanoma generate shared neoantigens that are uniquely expressed by tumor cells, leading to recognition and killing by specific CD8 T cells. Mutations in splicing factors can be sources of new therapeutic strategies applicable to diverse tumors.This article is highlighted in the In This Issue feature, p. 1861.
Temporary left ventricular bypass: factors affecting patient survival.
Authors: W FBernhard, R LBerger, J PStetz, J GCarr, N AColo, J RMcCormick, M CFishbein
Journal: Circulation (1979)

Circulatory support (range, 2 hours-8 days) was undertaken in eight cardiac surgical patients (with two survivors) exhibiting intractable cardiogenic shock. A paracorporeal, pneumatic, xenograft-valve pump was interposed between the left ventricular apex and ascending aorta. Pumping lowered left atrial and ventricular pressure while maintaining cardiac output (1.8--2.6 l/min/m2). Following implantation, plasma hemoglobin and erythrocyte mechanical fragility values were elevated but decreased to normal when renal function was not impaired. Mild thrombocytopenia was noted in three patients and was severe in five others with persistent hemorrhage. Anticoagulation agents were used during tapering of pump flow (three patients) after 100, 105 and 120 hours of bypass. Otherwise, for the major portion of the interval of mechanical circulatory support, anticoagulants were not administered. Despite this fact, no systemic embolization was detected in any of the patients. It appears that assist pump support can be li...
Frequency-dependent effects of calcium antagonists on atrioventricular conduction and refractoriness: demonstration and characterization in anesthetized dogs.
Authors: MTalajic, SNattel
Journal: Circulation (1986)

Calcium-channel blockers are known to affect slow inward current in a frequency-dependent fashion. The purpose of these experiments was to study use-dependent effects of verapamil, diltiazem, and nifedipine on atrioventricular conduction in vivo. Loading and maintenance infusion techniques were developed to study each drug at a series of stable plasma concentrations in autonomically blocked dogs anesthetized with morphine and alpha-chloralose. All three agents produced changes in atrioventricular conduction and refractoriness that increased with increasing stimulation frequency. The time dependence of drug-induced changes in atrioventricular conduction was characterized both by varying the coupling of single test stimuli and by abruptly changing activation frequency. The time constants for onset of (tau on) and recovery from (tau off) block were typical for each drug, with nifedipine having a faster time constant (tau off = 0.36 +/- 0.12 sec) than verapamil (tau off = 3.2 +/- 1.0 sec, tau on = 28 +/- 8 se...
A theoretically and practically more effective method for interruption of ventricular tachycardia: self-adapting autodecremental overdrive pacing.
Authors: G SCharos, C IHaffajee, R LGold, R LBishop, B VBerkovits, J SAlpert
Journal: Circulation (1986)

The efficacy and safety of a new antitachycardia pacing technique, self-adapting decremental overdrive pacing, was assessed in patients with clinical ventricular tachyarrhythmias who underwent programmed ventricular stimulation and serial drug testing. The three phases of this study involved a learning/experience phase, followed by intrapatient comparison of decremental overdrive pacing with conventional antitachycardia pacing modalities of overdrive burst ventricular pacing, and diastolic scanning with single (S2) and double (S2S3) ventricular extrastimuli. The final phase involved an intrapatient comparison of automated decremental overdrive pacing with overdrive burst ventricular pacing in patients with ventricular tachycardia (VT) cycle lengths of 280 msec or greater. Decremental overdrive pacing was superior to overdrive burst pacing and diastolic scanning (S2S3 and S2) (83% vs 38%, 50%, 9%) in patients with VT cycle lengths of 280 msec or greater. Automated decremental overdrive pacing as applied in...
Endocytosis and uptake of lucifer yellow by cultured atrial myocytes and isolated intact atria from adult rats. Regulation and subcellular localization.
Authors: EPage, G EGoings, JUpshaw-Earley, D AHanck
Journal: Circulation Research (1994)

The time course of endocytic uptake of Lucifer yellow (LY) was followed by fluorescence and electron microscopy after exposure of primary cultures of atrial myocytes from adult rats to LY under conditions that prevented transplasmalemmal LY entry via channels or carriers. After a 2-minute exposure to LY at 37 degrees C, electron microscopy revealed classic clathrin-coated vesicles fused to endosomes, which were absent in LY-free medium or at 2 degrees C, suggesting that LY turns on endocytosis or accelerates a slow constitutive endocytosis. Fluorescence microscopy, which detected no LY entry at 2 minutes in LY, showed punctate cytoplasmic fluorescent densities after 10 minutes, which were readily distinguishable from intrinsic perinuclear fluorescence. Fluorescence microscopy after immunostaining with antibodies against clathrin, vacuolar H(+)-ATPase, atrial peptide, or a marker for acidified compartments suggested LY sorting into an acidified prelysosomal pathway. Using absence of punctate fluorescence a...
Broncho-Pulmonary Squamous Cell Carcinoma Complicated by an Esophago-Bronchial Fistula
Authors: M Oustani, A Zazour, A El Mekkaoui, W Khannoussi, G Kharrasse, MZ Ismaili
Journal: Endoscopy (2021)

A 56-years-old man followed up for a broncho-pulmonary squamous cell carcinoma with a pancreatic metastasis, under chemotherapy. He was admitted for the treatment of an aphagia associated with false routes. Upper gastrointestinal endoscopy showed a large esophago-bronchial fistula at 30cm from the dental arches. The decision in a multidisciplinary meeting was to put a fully covered metallic stent as a palliative treatment.
Rapid reprogramming of tumour cells into cancer stem cells on double-network hydrogels
Authors: Jun Suzuka, Masumi Tsuda, Lei Wang, Shinji Kohsaka, Karin Kishida, Shingo Semba, Hirokazu Sugino, Sachiyo Aburatani, Martin Frauenlob, Takayuki Kurokawa, Shinya Kojima, Toshihide Ueno, Yoshihiro Ohmiya, Hiroyuki Mano, Kazunori Yasuda, Jian Ping Gong, Shinya Tanaka
Journal: Nature Biomedical Engineering (2021)
Metal-Binding Proteins as Metal Pollution Indicators
Authors: H. F.-K. O. Hennig
Journal: Environmental Health Perspectives (1986)

The fact that metal-binding proteins are a consequence of elevated metal concentration in organisms is well known.What has been overlooked is that the presence of these proteins provides a unique opportunity to reformulate the criteria of metal pollution.The detoxification effect of metal-binding proteins in animals from polluted areas has been cited, but there have been only very few studies relating metal-binding proteins to pollution.This lack is due partly to the design of most experiments, which were aimed at isolation of metal-binding proteins and hence were of too short duration to allow for correlation to adverse physiological effects on the organism.In this study metal-binding proteins were isolated and characterized from five different marine animals (rock lobster, Jasus lalandii; hermit crab, Diogenes brevirostris; sandshrimp, Palaemon pacificus; black mussel, Choromytius meridionalis; and limpet, Patella granularis).These animals were kept under identical metal-enriched conditions, hence eliminating differences in method and seasons.The study animals belonged to different phyla; varied in size, mass, age, behavior, food requirements and life stages; and accumulated metals at different rates.It is possible to link unseasonal moulting in crustacea, a known physiological effect due to a metal- enriched environment, to the production of the metal-binding protein without evidence of obvious metal body burden.Thus a new concept of pollution is defined: the presence of metal-binding proteins confirms toxic metal pollution.This concept was then tested under field conditions in the whelk Bullia digitalis and in metal- enriched grass.
Antiphospholipid Antibodies and Risk for Recurrent Vascular Events
Authors: Denis Wahl, Véronique Regnault, Philippe de Moerloose, Thomas Lecompte
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
THE OPERATIVE LENGTHENING OF THE FEMUR
Journal: JAMA (1921)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Non-compliance with colonoscopy after a positive faecal immunochemical test doubles the risk of dying from colorectal cancer
Authors: Manuel Zorzi, Jessica Battagello, Kevin Selby, Giulia Capodaglio, Susanna Baracco, Silvia Rizzato, Enrico Chinellato, Stefano Guzzinati, Massimo Rugge
Journal: Gut (2021)

The risk of colorectal cancer (CRC) among subjects with a positive faecal immunochemical test (FIT) who do not undergo a colonoscopy is unknown. We estimated whether non-compliance with colonoscopy after a positive FIT is associated with increased CRC incidence and mortality.
Rapid and reversible inhibition by low density lipoprotein of the endothelium-dependent relaxation to hemostatic substances in porcine coronary arteries. Heat and acid labile factors in low density lipoprotein mediate the inhibition.
Authors: TTomita, MEzaki, MMiwa, KNakamura, YInoue
Journal: Circulation Research (1990)

The effects of hemostatic substances on the vascular tone in porcine coronary arteries and the influence of low density lipoprotein on tension were investigated. Thrombin induced a marked concentration-dependent relaxation in prostaglandin F2 alpha-precontracted strips with intact endothelium, whereas it produced a modest constriction in endothelium-denuded arteries. Methylene blue abolished the relaxation, but indomethacin did not affect it significantly. An exposure of the intact strips to low density lipoprotein resulted in a marked inhibition of the relaxation to thrombin but did not interfere with vasodilation by sodium nitroprusside. The inhibition by low density lipoprotein was reversed completely by washing. In contrast, high density lipoprotein lacked such inhibitory effects. Adenosine diphosphate, calcium ionophore A23187, and platelet-activating factor also produced relaxation in the intact strips. An exposure of the strips to low density lipoprotein almost abolished relaxation to these substan...
Laser-induced endothelial damage inhibits endothelium-dependent relaxation in the cerebral microcirculation of the mouse.
Authors: W IRosenblum, G HNelson, J TPovlishock
Journal: Circulation Research (1987)

This study demonstrates endothelium-dependent relaxation in the surface arterioles of the brain. A helium-neon laser was used to injure endothelium in situ following i.v. injection of Evans blue dye, which sensitizes the bed to the laser. Areas 18 or 36 micron in diameter were injured and no longer relaxed to either 1 ml of acetylcholine chloride or bradykinin triacetate, 80 micrograms/ml delivered for 60 seconds. Dilations to sodium nitroprusside (30 micrograms/ml) were unaffected. Normal responses to nitroprusside, plus electron microscopy, established that vascular smooth muscle was uninjured. Endothelium-dependent relaxation was impaired when only minor ultrastructural damage was present. Dilation was inhibited downstream and upstream as far as 80 micron from the center of the laser beam. This suggests a spread of endothelium injury around the site of laser impact. However, inhibition was somewhat more marked downstream than upstream, implying that a portion of the downstream response was dependent on...
<i>NT5E</i>Mutations and Arterial Calcifications
Journal: New England Journal of Medicine (2011)

BACKGROUND-Arterial calcifications are associated with increased cardiovascular risk, but the genetic basis of this association is unclear.METHODS-We performed clinical, radiographic, and genetic studies in three families with symptomatic arterial calcifications.Single-nucleotide-polymorphism analysis, targeted gene sequencing, quantitative polymerase-chain-reaction assays, Western blotting, enzyme measurements, transduction rescue experiments, and in vitro calcification assays were performed.RESULTS-We identified nine persons with calcifications of the lower-extremity arteries and hand and foot joint capsules: all five siblings in one family, three siblings in another, and one patient in a third family.Serum calcium, phosphate, and vitamin D levels were normal.Affected members of Family 1 shared a single 22.4-Mb region of homozygosity on chromosome 6 and had a homozygous nonsense mutation (c.662C→A, p.S221X) in NT5E, encoding CD73, which converts AMP to adenosine.Affected members of Family 2 had a homozygous missense mutation (c.1073G→A, p.C358Y) in NT5E.The proband of Family 3 was a compound heterozygote for c. 662C→A and c.1609dupA (p.V537fsX7).All mutations found in the three families result in nonfunctional CD73.Cultured fibroblasts from affected members of Family 1 showed markedly reduced expression of NT5E messenger RNA, CD73 protein, and enzyme activity, as well as increased alkaline phosphatase levels and accumulated calcium phosphate crystals.Genetic rescue experiments normalized the CD73 and alkaline phosphatase activity in patients' cells, and adenosine treatment reduced the levels of alkaline phosphatase and calcification.
The 2020 Nobel Prize for Medicine or Physiology for the Discovery of Hepatitis C Virus: A Triumph of Curiosity and Persistence
Authors: Marc G. Ghany, Anna S.F. Lok, Jules L. Dienstag, Stephen M. Feinstone, Jay H. Hoofnagle, T. Jake Liang, Leonard B. Seeff, David E. Cohen, Jorge A. Bezerra, Raymond T. Chung
Journal: Hepatology (2021)

The 2020 Nobel Prize in Medicine or Physiology was awarded to Drs. Harvey Alter, Michael Houghton, and Charles Rice for their contributions to the discovery and characterization of the hepatitis C virus (HCV). Their achievements represent a remarkable triumph of biomedical science which allowed the development of curative therapy for HCV, that will save countless lives. This tribute provides a historical perspective of the laureates' seminal work leading to the discovery of the HCV and a synopsis of a forum hosted by the American Association for the Study of Liver Diseases to honor the laureates in which they offered their perspectives, advice for young investigators and what's left to accomplish in the field. Finally, others in the research community who have worked closely with one or more of the laureates, share some of their personal reflections and anecdotes.
Exercise testing in children before and after surgical treatment of aortic stenosis.
Authors: J TWhitmer, F WJames, SKaplan, D CSchwartz, M JKnight
Journal: Circulation (1981)

Twenty-three children with valvar or discrete subvalvar aortic stenosis underwent a controlled, progressive bicycle exercise test within 6 months before and 3-30 months after surgery for left ventricular outflow tract obstruction. The patients were divided into three groups according to the preoperative resting gradient of left ventricular to aortic peak systolic pressure: 30-69 mm Hg (group A), 70-99 mm Hg (group B), and greater than or equal to 100 mm Hg (group C). Preoperatively, 19 of 23 patients (83%) developed significant ST depression (greater than or equal to 1.0 mm) during exercise, whereas only seven (30%) had abnormal ST depression at rest. Postoperatively, mean exercise-induced ST depression regressed to less than 1 mm in all three groups. In the total population the frequency of ST depression greater than 1 mm was significantly reduced after surgical treatment and mean total work and peak exercise systolic blood pressure were significantly increased within 12 months after surgery. Total work ...
Bayesian analysis of data from radionuclide angiocardiograms for diagnosis of coronary artery disease.
Authors: T DChristopher, GKonstantinow, R HJones
Journal: Circulation (1984)

A continuous Bayesian model was developed by fitting a beta-function to the frequency distributions of resting ejection fraction, exercise ejection fraction, and change in end-systolic volume during exercise measured by radionuclide angiocardiography in a group of 249 men with coronary artery disease (CAD) and in a group of 56 men without disease. This model, then prospectively applied to 250 men with chest pain, did not increase the overall accuracy of the test but did increase the diagnostic content for individual patients. The diagnostic efficacy of the continuous Bayesian model was compared with previously determined optimal discrete criteria of a positive or negative test. Patients with CAD showed a maximum and mean increase in probability of disease of +0.58 and +0.11, respectively, by the continuous Bayesian model and +0.14 and +0.05, respectively, by discrete criteria. Men without significant disease showed a maximum and mean decrease in probability of disease of -0.73 and -0.38, respectively, by ...
Responsiveness of iliac collateral vessels to constrictor stimuli in atherosclerotic primates.
Authors: J ALopez, M LArmstrong, D GHarrison, D JPiegors, D DHeistad
Journal: Circulation Research (1988)

This study was performed to examine, first, the protective effects and responses of collateral vessels of the hind limb in normal and atherosclerotic monkeys and, second, the effects of chronic arterial occlusion on the development of atherosclerosis. The iliac artery was ligated on one side in cynomolgus monkeys. Sixteen months later, we recorded the pressure gradient across the limb collaterals and measured blood flow with microspheres. Collateral conductance was fivefold greater after chronic ligation of the iliac artery than after acute ligation. Despite dilatation or growth of collateral vessels after chronic ligation, iliac pressure was reduced distal to the ligation. Blood flow to the limb was normal after chronic ligation in both normal and atherosclerotic monkeys. Collateral vessels constricted in response to infusion of phenylephrine and serotonin in normal and atherosclerotic monkeys. Thus, one conclusion of this study is that collateral vessels restore limb blood flow to normal after chronic v...
Coronary vasodilator reserve. Comparison of the effects of papaverine and adenosine on coronary flow, ventricular function, and myocardial metabolism.
Authors: C WChristensen, L BRosen, R AGal, MHaseeb, T ALassar, S CPort
Journal: Circulation (1991)

To evaluate coronary flow reserve during cardiac catheterization, intracoronary adenosine and papaverine have been used in the clinical setting. Although papaverine maximizes coronary blood flow, it induces several toxic side effects that reduce its desirability as a coronary dilator. This investigation was designed to compare the subselective intracoronary administration of papaverine with that of adenosine in an animal model. In dogs (n = 34), we studied the effects of each agent on hemodynamics, regional myocardial blood flow, contractility (sonomicrometric and echocardiographic), metabolism (coronary arterial and venous lactate and tissue high-energy phosphates), and electrocardiographic (ST and QT intervals) parameters. Barbiturate and morphine anesthesia/analgesia was induced, and a left thoracotomy was performed. An arterial shunt was created from the left carotid artery to the left anterior descending coronary artery. Two separate groups were studied: group 1 (n = 16) for regional myocardial blood...
The genesis of the diastolic murmur of complete heart block. Phono-echocardiographic observations.
Authors: MJelveh, MBerger, EGoldberg
Journal: Circulation (1978)

A 72-year-old man with calcific aortic stenosis and complete heart block was noted to have an intermittent diastolic murmur. Using combined echocardiography and phonocardiography, it was demonstrated that the murmur occurred while the mitral valve was closing. This suggested that antegrade flow across a closing mitral orifice is of etiologic importance in the production of the murmur. Atrial sounds were also recorded and probably have a similar etiology. It is postulated that reduced ventricular compliance resulting in a more rapid rate of mitral valve closure was of etiologic importance in the genesis of the murmur.