tbuckley/cabot-search huggingface dataset:
Energetically Optimal Left Ventricular Pressure for the Failing Human Heart
Authors: Hidetsugu Asanoi, Tomoki Kameyama, Shinji Ishizaka, Takashi Nozawa, Hiroshi Inoue
Journal: Circulation (1996)

An energy-starved failing heart would benefit from more effective transfer of the mechanical energy of ventricular contraction to blood propulsion. However, the energetically optimal loading conditions for the failing heart are difficult to establish. In the present study, we analyzed the optimal left ventricular pressure to achieve maximal mechanical efficiency of the failing heart in humans.We determined the relation between left ventricular pressure-volume area and myocardial oxygen consumption per beat (VO2), stoke work, and mechanical efficiency (stroke work/VO2) in 13 patients with different contractile states. We also calculated the optimal end-systolic pressure that would theoretically maximize mechanical efficiency for a given end-diastolic volume and contractility. Left ventricular pressure-volume loops were constructed by plotting the instantaneous left ventricular pressure against the left ventricular volume at baseline and during pressure loading. The contractile properties of the ventricle were defined by the slope of the end-systolic pressure-volume relation. In patients with less compromised ventricular function, the operating end-systolic pressure was close to the optimal pressure, achieving nearly maximal mechanical efficiency. As the heart deteriorated, however, the optimal end-systolic pressure became significantly lower than normal, whereas the actual pressure remained within the normal range. This discrepancy resulted in worsening of ventriculoarterial coupling and decreased mechanical efficiency compared with theoretically maximal efficiency.Homeostatic mechanisms to maintain arterial blood pressure within the normal range cause the failing heart to deviate from energetically optimal conditions.
Abstract 3063: Molecular characterization of individual circulating tumor cells by RNA sequencing
Authors: Jaymala Patel, Brad Foulk, Vipul Bhargava, Denis A. Smirnov
Journal: Cancer Research (2014)

Abstract Background: Numbers of circulating tumor cells (CTC) measured with the CellSearch system in patients with metastatic carcinomas are associated with poor survival. Such association with clinical outcome suggests that CTCs play an important role in metastatic process. Molecular characterization of CTCs can provide important insights into phenotypic characteristics of cells necessary to participate in this process. Moreover, detailed molecular characterization of CTCs at various points of the disease course may be useful in understanding of evolution of tumors and aid in selection of optimal therapeutic regimens. Like most other CTC isolation instruments CellSearch is a CTC-enrichment device that efficiently captures CTCs while also retaining few thousands non-specifically captured white blood cells. To obtain deep molecular profiles of CTCs isolation of single cells is required and development of specialized next-generation sequencing protocols is necessary. Method/Results: We developed a workflow to enable isolation of single CTCs or pools of few CTCs following enrichment with the FDA approved CellSearch platform. Experiments with cancer cell lines spiked into donor blood showed 80% cellular recovery from blood using CellSearch and subsequent 40-50% capture of individual cancer cells using Fluidigm C1 Single Cell system. Following analysis of gene expression via RNAseq expression of ∼5000 genes can be detected in isolated tumor cells. We will discuss reagents and molecular approaches utilized to ensure efficient isolation and quality assessment of nucleic acids recovered from isolated tumor cells. We will discuss impact of sample preservation has on transcriptome profiling. We will share insights into prostate and lung cancers that one can gain from such analysis. Conclusion: Characterization of individual CTCs by RNA sequencing is a promising approach to characterize metastatic processes and tumor evolution. Citation Format: Jaymala Patel, Brad Foulk, Vipul Bhargava, Denis A. Smirnov. Molecular characterization of individual circulating tumor cells by RNA sequencing. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3063. doi:10.1158/1538-7445.AM2014-3063
Diaphragm Recruitment during Nonrespiratory Activities
Authors: FADI AL-BILBEISI, F. DENNIS McCOOL
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We previously found that weight lifters could generate greater inspiratory pressures and had more diaphragm mass than control subjects. We postulated that the weight-lifting activity itself provided a strength-training stimulus to the diaphragm. To evaluate the extent to which the diaphragm is recruited during strenuous nonrespiratory activities, we measured transdiaphragmatic pressure (Pdi) in six healthy subjects during biceps curls, bench press, power lift, and sit-ups. Each maneuver was performed with and without added weight (control), and with and without an abdominal binder. The weighted maneuvers were performed either during inspiration or expiration. Maximal static transdiaphragmatic pressure (Pdi(max)) was measured during a combined inspiratory and expulsive maneuver. Group mean values of Pdi increased during all activities when compared with control (57 +/- 24 versus 18 +/- 10 cm H(2)O [mean +/- SD] [p < 0.001]), as task intensity increased (98 +/- 14 versus 35 +/- 13 cm H(2)O for high- and low-intensity activities, respectively) (p < 0.001), and with abdominal binding (75 +/- 25 versus 59 +/- 25 cm H(2)O) (p < 0.05). Peak levels of Pdi attained during the activities were 126 +/- 11 cm H(2)O or 0.65 +/- 0.09 of Pdi(max). Changes in gastric pressure accounted for 85 +/- 4% of the increase in Pdi during the activities whereas it accounted for only 58 +/- 9% of the rise in Pdi during the control activities (p < 0.001). We conclude that during a range of weight-lifting activities, the diaphragm is recruited and Pdi is raised to a level that may provide a significant strength-training stimulus to the diaphragm.
Effects of Complementarity Determining Region Mutations on the Affinity of an α/β T Cell Receptor: Measuring the Energy Associated with CD4/CD8 Repertoire Skewing
Authors: Thomas C. Manning, Evan A. Parke, Luc Teyton, David M. Kranz
Journal: The Journal of Experimental Medicine (1999)

It has been proposed that the generally low affinities of T cell receptors (TCRs) for their peptide–major histocompatibility complex (pMHC) ligands (Kd ∼10−4 to 10−7 M) are the result of biological selection rather than an intrinsic affinity limitation imposed by the TCR framework. Using a soluble version of the 2C TCR, we have used complementarity determining region (CDR)-directed mutagenesis to investigate whether the affinity of this receptor for its allogeneic pMHC ligand can be improved upon. We report that several mutants at positions lying within CDR3α and CDR2β showed increased affinities for pMHC compared with the wild-type receptor. Additionally, we have investigated whether Vα mutations that have been implicated in the phenomenon of CD8+ repertoire skewing achieve this skewing by means of generalized increases in affinity for MHC-I molecules. Two mutants (S27F and S51P), which each promote skewing toward a CD8+ phenotype, exhibited significantly reduced affinity for pMHC-I, consistent with a quantitative-instructional model of CD4/CD8 lineage commitment. This model predicts that CD8 is downregulated on thymocytes that have TCR–ligand interactions above a minimal energy threshold. Together, the results (a) demonstrate that engineering higher affinity TCRs is feasible, and (b) provide TCR–pMHC energy values associated with CD4/CD8 repertoire skewing.
Publication bias does not play a role in the reporting of the results of endoscopic ultrasound staging of upper gastrointestinal cancers
Authors: E. van Vliet, M. Eijkemans, E. Kuipers, J. Poley, E. Steyerberg, P. Siersema
Journal: Endoscopy (2007)

See also: Commentaire de travail de P. M. van Vliet et al., pp. 325Endoscopy 2007; 39(04): 383-383DOI: 10.1055/s-0032-1306924
Clinical judgment in rheumatoid arthritis. IV. Rheumatologists' assessments of disease remain stable over long periods.
Authors: J R Kirwan, H L Currey
Journal: Annals of the Rheumatic Diseases (1984)

Seven rheumatologists made judgments about the improvement or deterioration of identical sets of 50 'paper' patients on two occasions one year apart. The stability of their judgments over one year (rs = 0.70) compared favourably with the reliability of duplicate judgments on each occasion (rs = 0.76). Multiple regression analysis of the patient data in relation to the disease assessments provided a model of each clinician's underlying judgment policy. The stability of judgments predicted by these policy models was even higher (rs = 0.83).
CD14 is required for MyD88-independent LPS signaling
Authors: Zhengfan Jiang, Philippe Georgel, Xin Du, Louis Shamel, Sosathya Sovath, Suzanne Mudd, Michael Huber, Christoph Kalis, Simone Keck, Chris Galanos, Marina Freudenberg, Bruce Beutler
Journal: Nature Immunology (2005)
Developmental neurotoxicity induced by therapeutic and illicit drugs.
Authors: C V Vorhees
Journal: Environmental Health Perspectives (1994)

The developmental neurotoxicity of phenytoin, isotretinoin, and methamphetamine has been reviewed to illustrate effects from both therapeutic and illicit drugs to which people are exposed and which either induce or show the potential for inducing learning disabilities following in utero exposure. In each case both human and experimental animal data are presented and compared where possible. The findings point to several conclusions. First, some drugs in current use induce developmental neurotoxicity, and it cannot safely be assumed that there are not more as yet unidentified. Second, of the types of neurotoxicity induced by drugs, learning disabilities figure prominently. Third, the effects observed are dependent on both the drug's mechanism of action and the period of brain development during which exposure occurs. Fourth, with the exception of CNS teratogens, it is not yet possible to predict which periods of brain development are the most vulnerable for the induction of learning disabilities, as seen by the different patterns of critical periods for phenytoin and isotretinoin compared to methamphetamine. Fifth, as seen with isotretinoin, existing drugs that cause developmental neurotoxicity are not the only problem; new drugs with such effects are still being introduced. Sixth, only a small fraction of the drugs currently in use have ever been examined for developmental neurotoxicity; hence, the full scope of the problem cannot even be accurately estimated based on current information. It is concluded that prevention of new cases caused by drugs such as isotretinoin should be a high priority for future regulatory action.
THE PREVENTIVE EFFECT OF POST-PROCEDURAL STATIN THERAPY ON THE DEVELOPMENT OF CONTRAST-INDUCED NEPHROPATHY IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION UNDERGOING PRIMARY CORONARY INTERVENTION
Authors: Pyung Chun Oh, Woong Chol Kang, Jong Goo Seo, Soon Yong Suh, Kyounghoon Lee, Seung Hwan Han, Taehoon Ahn, Eak Kyun Shin
Journal: Journal of the American College of Cardiology (2014)
Thrombotic Thrombocytopenic Purpura
Authors: Simon Soumerai, William F. MacGillivray
Journal: New England Journal of Medicine (1956)

THROMBOCYTOPENIC purpura, anemia and manifestations of severe involvement of the central nervous system constitute the clinical triad of thrombotic thrombocytopenic purpura.1 , 2 Fibrinoid "degeneration" of the arterioles and capillaries, without inflammatory changes, and eventual bland thrombosis of the affected vessels form its histologic counterpart.3 4 5 Polyvalent immunoallergic mechanisms still unproved have been suspected of causing this disease.6 , 7 The purpose of this paper is to report another case of thrombotic thrombocytopenic purpura in which the signs of cortical irritation with epileptiform seizures were associated with electroencephalographic changes and overshadowed the anemia and bleeding tendency and led to a diagnosis of possible brain tumor. . . .
Mechanisms of carcinogenesis by crystalline silica in relation to oxygen radicals.
Authors: U Saffiotti, L N Daniel, Y Mao, X Shi, A O Williams, M E Kaighn
Journal: Environmental Health Perspectives (1994)

The carcinogenic effects of crystalline silica in rat lungs were extensively demonstrated by many experimental long-term studies, showing a marked predominance for adenocarcinomas originating from alveolar type II cells and associated with areas of pulmonary fibrosis (silicosis). In contrast with its effects in rats, silica did not induce alveolar type II hyperplasia and lung tumors in mice and hamsters, pointing to a critical role for host factors. Using these animal models, we are investigating the role of cytokines and other cellular mediators on the proliferation of alveolar type II cells. Immunohistochemical localization of TGF-beta 1 precursor in alveolar type II cells adjacent to silicotic granulomas was shown to occur in rats, but not in mice, and hamsters, suggesting a pathogenetic role for this regulatory growth factor. Recent investigations in our laboratory on the biologic mechanisms of crystalline silica included determination of anionic sites on crystalline silica surfaces by binding of the cationic dye Janus Green B; binding of crystalline silica to DNA, demonstrated by infrared spectrometry; production of oxygen radicals by crystalline silica in aqueous media; induction of DNA strand breakage and base oxidation in vitro and its potentiation by superoxide dismutase and by hydrogen peroxide; and induction by crystalline silica of neoplastic transformation and chromosomal damage in cells in culture. On the basis of these in vitro studies, we propose that DNA binding to crystalline silica surfaces may be important in silica carcinogenesis by anchoring DNA close to sites of oxygen radical production on the silica surface, so that the oxygen radicals are produced within a few A from their target DNA nucleotides.
Role of the Mast Cell in the Pulmonary Pressor Response to Hypoxia
Authors: Francois Haas, Edward H. Bergofsky
Journal: Journal of Clinical Investigation (1972)

This study investigated the role of the mast cell in the pulmonary arterial pressor response to hypoxia. We found that pulmonary arteries 50-500 mu in diameter have a predictable distribution of perivascular mast cells; that such pulmonary mast cells are degranulated in vivo during alveolar hypoxia; that hypoxia releases histamine from mast cells isolated from the peritoneal cavity without apparent injury to the cells; and that histamine is released from the lung of intact guinea pigs during alveolar hypoxia, with the rise in pulmonary vascular resistance during this period proportional to the amount of histamine released. These data point to the perivascular pulmonary mast cell in the rat and guinea pig as an important structure in the mediation of the pulmonary pressor response to hypoxia, even though the responsible humoral vasoconstrictor released from such a cell may not be histamine, or histamine alone.
Effects of respiratory syncytial virus persistence on airway responsiveness and inflammation in guinea-pigs
Authors: AM Bramley, TZ Vitalis, BR Wiggs, RG Hegele
Journal: European Respiratory Journal (1999)

Recurrent wheezing and asthma often develop after acute respiratory syncytial virus (RSV) bronchiolitis, but the mechanisms of these sequelae are poorly understood. Using a guinea-pig model of human RSV lung infection, the effects of long-term viral persistence on three hallmarks of asthma: nonspecific airway responsiveness, airway inflammation and airway remodelling were examined. Guinea-pigs were studied 100 days after intranasal instillation of either human RSV or uninfected vehicle, using: 1) acetylcholine challenge to test for airway hyperresponsiveness (AHR); 2) lung histology to quantify the numbers of airway eosinophils and metachromatic cells (mast cells/basophils); 3) airway morphometry of the areas of the airway subepithelial connective tissue, smooth muscle and adventitia, to test for airway remodelling; and 4) immunohistochemistry to identify lung cells containing RSV antigens. The RSV-inoculated group had significantly elevated AHR and airway eosinophils compared to uninfected control animals (p&lt;0.05). There were no significant differences between the two groups in terms of numbers of airway metachromatic cells, or the areas of subepithelial connective tissue, smooth muscle or adventitia. Viral proteins were identified by immunohistochemistry within several types of lung cells. In conclusion, long-term persistence of respiratory syncytial virus in the guinea-pig lung is associated with airway hyperresponsiveness and airway eosinophilia, and these changes may be pertinent to the pathogenesis of postbronchiolitis wheezing and asthma in children.
IL-17C regulates the innate immune function of epithelial cells in an autocrine manner
Authors: Vladimir Ramirez-Carrozzi, Arivazhagan Sambandam, Elizabeth Luis, Zhongua Lin, Surinder Jeet, Justin Lesch, Jason Hackney, Janice Kim, Meijuan Zhou, Joyce Lai, Zora Modrusan, Tao Sai, Wyne Lee, Min Xu, Patrick Caplazi, Lauri Diehl, Jason de Voss, Mercedesz Balazs, Lino Gonzalez, Harinder Singh, Wenjun Ouyang, Rajita Pappu
Journal: Nature Immunology (2011)
Implantable defibrillator events in patients with hypertrophic cardiomyopathy: low incidence of ventricular and high incidence of supraventricular events during intermediate term follow-up
Authors: Andrea M. Russo, Christa Schorr, Jamie Springman, David Callans, Henry Hsia, Bindi Shah, Erica Zado, Francis E. Marchlinski
Journal: Journal of the American College of Cardiology (2002)
An Experimental Study on Intercoronary Reflexes
Authors: HSUEH-HWA WANG, CHARLES W. FRANK, DONALD M. KANTER, RENÉ WÉGRIA
Journal: Circulation Research (1957)

There is no evidence in the anesthetized dog that occlusion of one of the three coronary arteries leads to vasoconstriction in the vascular areas irrigated by the other two arteries. On the contrary, occlusion of one coronary artery appears to lead to a decrease in the resistance of the two adjacent vascular beds in most experiments. The mechanisms and the implications of this effect are discussed.
Coronary Angioplasty Compared with Bypass Grafting
Authors: L. D. Hillis, J. D. Rutherford
Journal: New England Journal of Medicine (1994)

Since coronary-artery bypass grafting was introduced by Favaloro in 1969,1 its results have improved steadily even though the procedure has been performed increasingly in patients whose operative risk is relatively high because of advanced age, impaired left ventricular systolic performance, or extensive coronary artery disease.2 The improvement has been due, at least in part, to the routine use of internal-thoracic-artery conduits3 and antiplatelet therapy,4 as well as better intraoperative protection of the heart. When the procedure is performed electively in patients at low risk, mortality is only about 1 percent.5 In randomized comparisons with medical therapy in patients with stable . . .
It's Over, Debbie
Authors: Harold Y. Vanderpool
Journal: JAMA (1988)

To the Editor.  —The story entitled It's Over,  1 raises profoundly troubling ethical issues—the more so because its sentimental surface masks a dark and worrisome underside.  On the surface of the story, a hassled but resolutely caring resident physician ends the hollow-eyed suffering of a young woman named Debbie by putting a stop to the cruel, gallows-like technology that mocks her youth and former vitality.  Just beneath the surface of these heartwarming themes lies the real point of the story—that in cases like this it is ethical for physicians to kill patients. Unfortunately, It's Over,  only disguises and distorts the debate and clarification that are necessary for a moral assessment of mercy killing. First, the story's rhetoric (which is equated with the way the physician thinks) masks the act of killing Debbie with such euphemisms as doing one's job, giving Debbie the rest she needs, and enabling her
Defining the Role of Computed Tomographic Pulmonary Angiography in Suspected Pulmonary Embolism
Authors: Shaun D. Frost
Journal: Annals of Internal Medicine (2005)

Letters3 May 2005Defining the Role of Computed Tomographic Pulmonary Angiography in Suspected Pulmonary EmbolismShaun D. Frost, MDShaun D. Frost, MDFrom HealthPartners Medical Group and Clinics, Minneapolis, MN 55101.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-142-9-200505030-00025 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I am concerned that the article by Moores and colleagues (1) conveys an ambiguous message about the utility of spiral computed tomographic pulmonary angiography (CTPA) for diagnosing pulmonary embolism (PE). The ambiguity results from seemingly different conclusions in the abstract, discussion, and Editors' synopsis sections of the manuscript. The authors concluded their discussion by stating that withholding anticoagulation seems to be safe in patients managed by negative results on CTPA performed concurrently with imaging of the lower extremities (either ultrasonography or computed tomographic venography). The abstract that accompanies the manuscript, however, fails to mention the importance of ...References1. Moores LK, Jackson WL, Shorr AF, Jackson JL. Meta-analysis: outcomes in patients with suspected pulmonary embolism managed with computed tomographic pulmonary angiography. Ann Intern Med. 2004;141:866-74. [PMID: 15583229] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Shaun D. Frost, MDAffiliations: From HealthPartners Medical Group and Clinics, Minneapolis, MN 55101.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoMeta-Analysis: Outcomes in Patients with Suspected Pulmonary Embolism Managed with Computed Tomographic Pulmonary Angiography Lisa K. Moores , William L. Jackson Jr. , Andrew F. Shorr , and Jeffrey L. Jackson Defining the Role of Computed Tomographic Pulmonary Angiography in Suspected Pulmonary Embolism Philippe Girard Defining the Role of Computed Tomographic Pulmonary Angiography in Suspected Pulmonary Embolism Pieter W. Kamphuisen and Giancarlo Agnelli Defining the Role of Computed Tomographic Pulmonary Angiography in Suspected Pulmonary Embolism Lisa K. Moores and William L. Jackson Jr Metrics Cited byOutcomes following a negative computed tomography pulmonary angiography according to pulmonary embolism prevalence: a meta‐analysis of the management outcome studiesUpdate in the diagnosis of deep-vein thrombosis and pulmonary embolism 3 May 2005Volume 142, Issue 9 Page: 800-801 Keywords Angiography Computed axial tomography Conflicts of interest Pulmonary embolism Thrombosis Ultrasound imaging ePublished: 3 May 2005 Issue Published: 3 May 2005 Copyright & PermissionsCopyright © 2005 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...