tbuckley/cabot-search huggingface dataset:
Contrast ultrasound molecular imaging: harnessing the power of bubbles
Authors: J. R. Lindner
Journal: Cardiovascular Research (2009)

This editorial refers to ‘Cardiovascular molecular imaging: an overview’ by A. Saraste et al .,2 pp. 643–652, this issue; ‘Ultrasound molecular imaging of atherosclerosis’ by B.A. Kaufmann,3 pp. 617–625, this issue; ‘Contrast ultrasound molecular imaging of inflammation in cardiovascular disease’ by J.R. Lindner,4 forthcoming; ‘Molecular imaging using contrast-enhanced ultrasound: evaluation of angiogenesis and cell therapy’ by H. Leong-Poi,5 doi:10.1093/cvr/cvp248, Advance Access publication July 2009; ‘The utilization of ultrasound and microbubbles for therapy in acute coronary syndromes’ by T.R. Porter,8 pp. 636–642, this issue; and ‘Cardiovascular therapeutic uses of targeted ultrasound contrast agents’ by S.T. Laing et al .,9 pp. 626–635, this issue. 

Over the past decade, there has been an escalating effort by researchers in academic institutions and industry to develop novel, non-invasive medical imaging approaches for evaluating tissue phenotype. These emerging techniques are designed to detect the cellular or molecular mediators of disease rather than structural or functional consequences of disease. The clinical justification for this trend is that molecular imaging provides unique information that could potentially be used to diagnosis disease at a very early stage, … 

*Corresponding author. Tel: +1 503 494 8750; fax: +1 503 494 8550. E-mail address : lindnerj{at}ohsu.edu
Using DNA Microarray to Identify Sp1 as a Transcriptional Regulatory Element of Insulin-Like Growth Factor 1 in Cardiac Muscle Cells
Authors: Tao Li, Yung-Hsiang Chen, Tsun-Jui Liu, Jia Jia, Steven Hampson, Yue-Xin Shan, Dennis Kibler, Ping H. Wang
Journal: Circulation Research (2003)

High throughput gene expression profiling with DNA microarray provides an opportunity to analyze transcriptional regulation of hundreds or thousands of similarly regulated genes. Transcriptional regulation of gene expression plays an important role in myocardial remodeling. We have studied cardiac muscle gene expression with DNA microarray and used a computational strategy to identify common promoter motifs that respond to insulin-like growth factor 1 (IGF-1) stimulation in cardiac muscle cells. The analysis showed that the Sp1 binding site is a likely target of IGF-1 action. Further experiments with gel shift assay indicated that IGF-1 regulated the Sp1 site in cardiomyocytes, by increasing the abundance of Sp1 and Sp3 proteins. Using firefly luciferase as reporter gene, additional experiments showed that IGF-1 activated the promoter of cyclin D3 and Glut1. Both promoters contain one Sp1 site. The effect of IGF-1 on these two promoters was abolished with siRNA for Sp1. Thus, the transcriptional activation of these two promoters by IGF-1 requires the induction of Sp1 protein. These experiments suggest that the global transcriptional regulatory actions of IGF-1 involve activation of the Sp1 site in cardiac muscle. The computational model we have developed is a prototypical method that may be further developed to identify unique cis- and trans-acting elements in response to hormonal stimulation during cardiac muscle growth, repair, and remodeling in normal and abnormal cardiac muscle.
Macrophage-Derived Chemokine In Nasal Washes Is Associated With Asthma Exacerbations and Infections With Rhinovirus In Children
Authors: Carolyn R. Word, Holliday T. Carper, Patricia Jorge, Joshua L. Kennedy, Deborah D. Murphy, Thomas A.E. Platts-Mills, Peter W. Heymann
Journal: Journal of Allergy and Clinical Immunology (2014)
Oxaliplatin plus high-dose folinic acid and 5-fluorouracil i.v. bolus (OXAFAFU) versus irinotecan plus high-dose folinic acid and 5-fluorouracil i.v. bolus (IRIFAFU) in patients with metastatic colorectal carcinoma: a Southern Italy Cooperative Oncology Group phase III trial
Authors: P. Comella, B. Massidda, G. Filippelli, S. Palmeri, D. Natale, A. Farris, F. De Vita, F. Buzzi, S. Tafuto, L. Maiorino, S. Mancarella, S. Leo, V. Lorusso, L. De Lucia, M. Roselli
Journal: Annals of Oncology (2005)
Antithrombotics in pulmonary hypertension: more work needed before we turn to newer agents!
Authors: Laurent Bertoletti, Xavier Delavenne, David Montani
Journal: European Respiratory Journal (2013)

Therapeutic research is particularly dynamic in the setting of pulmonary arterial hypertension (PAH). Despite the low prevalence of this rare disease, the efficacy and safety of targeted PAH therapies have been evaluated in randomised controlled trials, providing important data for clinicians, health authorities and patients. Beside these well-studied targeted therapies, “supportive therapy” is also recommended. This includes antithrombotic therapy with vitamin-K antagonists (VKAs) [1]. The background for the use of these agents is principally supported by findings in histopathological and biological studies [2, 3], as well as their potential indirect clinical consequences which may present as perfusion defects evaluated by ventilation/perfusion ( V ′/ Q ′) scan [4]. Clinical studies evaluating VKAs in the setting of PAH are, however, lacking. In the prospective study published by Rich et al. [5], VKA use improved prognosis, but the allocation to VKA treatment followed the demonstration of perfusion defects on V ′/ Q ′ scan, and not from proper randomisation. This explains the low level of the related recommendation in the guidelines from the European Respiratory Society and European Society of Cardiology [1], that being a class IIa recommendation for idiopathic or heritable PAH and for PAH due to anorexigens, and an even lower level of recommendation in patients with associated PAH. By extension, anticoagulant therapy has been proposed in other groups of pulmonary hypertension (groups 2, 3 or 5) despite the absence of specific studies. Paradoxically, whereas only half of patients with a certain indication for VKA therapy (for example, atrial fibrillation) receive VKA [6], most PAH patients are anticoagulated with VKA (90% of the patients included in the French registry) [7]. Conversely, antithrombotic therapy with VKA is the cornerstone of medical therapy in the case of …
Cyclosporin A Is a Broad-Spectrum Multidrug Resistance Modulator
Authors: Misbah Qadir, Kieran L. O'Loughlin, Stacy M. Fricke, Nicole A. Williamson, William R. Greco, Hans Minderman, Maria R. Baer
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Overexpression of the multidrug resistance proteins P-glycoprotein (Pgp), multidrug resistance protein (MRP-1), breast cancer resistance protein (BCRP), and lung resistance protein (LRP) is associated with treatment failure in acute myeloid leukemia (AML) and other malignancies. The Pgp modulator cyclosporin A has shown clinical efficacy in AML, whereas its analogue PSC-833 has not. Cyclosporin A is known to also modulate MRP-1, and we hypothesized that broad-spectrum multidrug resistance modulation might contribute to its clinical efficacy. Experimental Design: We studied the effects of cyclosporin A and PSC-833 on in vitro drug retention and cytotoxicity in resistant cell lines overexpressing Pgp, MRP-1, and BCRP and on nuclear-cytoplasmic drug distribution and cytotoxicity in cells overexpressing LRP. Cellular drug content was assessed by flow cytometry and nuclear-cytoplasmic drug distribution by confocal microscopy. Results: Cyclosporin A enhanced retention of the substrate drug mitoxantrone in cells overexpressing Pgp (HL60/VCR), MRP-1 (HL60/ADR), and BCRP (8226/MR20, HEK-293 482R) and increased cytotoxicity 6-, 4-, 4-, and 3-fold, respectively. Moreover, cyclosporin A enhanced nuclear distribution of doxorubicin in 8226/MR20 cells, which also express LRP, and increased doxorubicin cytotoxicity 12-fold without an effect on cellular doxorubicin content, consistent with expression of wild-type BCRP, which does not efflux doxorubicin. Cyclosporin A also enhanced nuclear doxorubicin distribution in a second cell line with LRP overexpression, HT1080/DR4. PSC-833 enhanced mitoxantrone retention and cytotoxicity in cells overexpressing Pgp, but had no effect in cells overexpressing MRP-1, BCRP, or LRP. Conclusions: Cyclosporin A modulates Pgp, MRP-1, BCRP, and LRP, and this broad-spectrum activity may contribute to its clinical efficacy.
Alveolar proteinosis lung lavage using partial cardiopulmonary bypass.
Authors: A P Freedman, A Pelias, R F Johnston, I P Goel, H I Hakki, T Oslick, J P Shinnick
Journal: Thorax (1981)

An adult case of pulmonary alveolar proteinosis presented with an arterial oxygen tension of 27 mmHg (3.6 kPa) while breathing air. Dangerous hypoxaemia during lung lavage was avoided by using partial cardiopulmonary bypass.
α4β7 Integrin is essential for contact hypersensitivity by regulating migration of T cells to skin
Authors: Hanako Ohmatsu, Takafumi Kadono, Makoto Sugaya, Manabu Tomita, Hiromichi Kai, Tomomitsu Miyagaki, Hidehisa Saeki, Kunihiko Tamaki, Douglas A. Steeber, Thomas F. Tedder, Shinichi Sato
Journal: Journal of Allergy and Clinical Immunology (2010)
Brain Structure Abnormalities in Early-Onset and Adolescent-Onset Conduct Disorder
Authors: Graeme Fairchild, Luca Passamonti, Georgina Hurford, Cindy C. Hagan, Elisabeth A.H. von dem Hagen, Stephanie H.M. van Goozen, Ian M. Goodyer, Andrew J. Calder
Journal: American Journal of Psychiatry (2011)

The developmental taxonomic theory proposes that neurodevelopmental factors play a critical role in the etiology of early-onset conduct disorder, whereas adolescent-onset conduct disorder arises as a result of social mimicry of deviant peers. Recent studies have challenged this theory by demonstrating that adolescents with both early- and adolescent-onset forms of conduct disorder show impaired emotional learning and abnormal neural activation during facial expression processing. The present study extends this work by investigating brain structure in both subtypes of conduct disorder.Voxel-based morphometry was used to compare gray matter volumes in four regions of interest (amygdala, insula, anterior cingulate, and orbitofrontal cortex) in male adolescents with early-onset (N=36) or adolescent-onset (N=27) conduct disorder and in healthy comparison subjects (N=27). Whole-brain structural analyses were also performed.The combined conduct disorder group displayed gray matter volume reductions in the bilateral amygdala, extending into the insula, relative to healthy comparison subjects. Separate comparisons between healthy subjects and each conduct disorder subgroup revealed lower amygdala volume in both subgroups and reduced right insula volume in the adolescent-onset subgroup. Regression analyses within the conduct disorder subjects alone demonstrated a negative correlation between conduct disorder symptoms and right insula volume.The results demonstrate that gray matter volume reductions in brain regions involved in processing socioemotional stimuli are associated with conduct disorder, regardless of age of onset. Brain structural abnormalities may contribute to the emergence of adolescent-onset as well as early-onset conduct disorder.
PARALLELISM IN THE LETHAL AND HEMOLYTIC ACTIVITY OF THE TOXIN OF CLOSTRIDIUM SEPTICUM
Authors: Alan W. Bernheimer
Journal: The Journal of Experimental Medicine (1944)

The relation of the lethal toxin to the hemolysin produced by Clostridium septicum, strain 44, has been investigated. The following results suggest that the hemolytic and lethal actions of crude toxin are functions of a single substance or that they are functions of two substances which have similar physical, chemical, and antigenic properties. (1) Within the limits of experimental error, the lethal activity of cultures is directly proportional to their hemolytic activity. (2) Treatment of a culture supernate with hydrogen peroxide diminishes to the same extent its hemolytic and lethal activities. (3) The hemolytic principle and the lethal toxin are adsorbed to approximately the same extent by charcoal. (4) The hemolytic principle and the lethal toxin are adsorbed to approximately the same extent by kaolin. (5) Treatment of culture supernate with erythrocytes results in the removal of most of the lethal activity as well as of most of the hemolytic activity. (6) Both lethal toxin and hemolytic principle are partially destroyed in dilute solution at 36°C. The loss in lethal and hemolytic activities occurs in parallel. (7) The lethal and hemolytic activities of cultures are found to be inseparable by fractional precipitation with ammonium sulfate. (8) The antihemolytic capacity of antitoxic horse serum is found to be directly proportional to the antilethal capacity.
Primary lymphoproliferative conditions of lung.
Authors: A R Gibbs, R M Seal
Journal: Thorax (1978)

<b>Summary:</b> We report the case of an asymptomatic 2-month-old infant with 6-pyruvoyltetrahydropterin synthetase deficiency detected through a neonatal phenylketonuria screening program. MR imaging revealed symmetrical lesions in the central tegmental tract with reduced diffusion, which resolved after treatment. A possible explanation for these lesions is intramyelinic edema resulting from brain insults in utero.
Per cent of predicted as the limit of normal in pulmonary function testing: a statistically valid approach.
Authors: B J Sobol, P G Sobol
Journal: Thorax (1979)

Per cent of predicted as the limit of normal in pulmonary function testing: a statistically valid approach It has been traditional in pulmonary function testing to set the limits of normal as the predicted -4-20%.Since most pulmonary function tests, and all spirometric tests, are abnormal only when below predicted, the rule of thumb for the limit of normal becomes 80% of predicted.How this
Genome-Wide Association Studies: Results from the First Few Years and Potential Implications for Clinical Medicine
Authors: Joel N. Hirschhorn, Zofia K. Z. Gajdos
Journal: Annual Review of Medicine (2010)

Most common diseases and quantitative traits are heritable: determined in part by genetic variation within the population. The inheritance is typically polygenic in that combined effects of variants in numerous genes, plus nongenetic factors, determine outcome. The genes influencing common disease and quantitative traits remained largely unknown until the implementation in 2006 of genome-wide association (GWA) studies that comprehensively surveyed common genetic variation (frequency>5%). By 2010, GWA studies identified>1,000 genetic variants for polygenic traits. Typically, these variants together account for a modest fraction (10%-30%) of heritability, but they have highlighted genes in both known and new biological pathways and genes of unknown function. This initial effort prefigures new studies aimed at rarer variation and decades of functional work to decipher newly glimpsed biology. The greatest impact of GWA studies may not be in predictive medicine but rather in the development over the next decades of therapies based on novel biological insights.
Regulation of E-cadherin expression by dexamethasone and tumour necrosis factor-α in nasal epithelium
Authors: N. Carayol, I. Vachier, A. Campbell, L. Crampette, J. Bousquet, P. Godard, P. Chanez
Journal: European Respiratory Journal (2002)

Asthma and rhinitis often coexist and share many clinical features. The extent of epithelial alteration in nasal inflammation is controversial. Cell-cell adhesion plays an important role in tissue morphogenesis and homeostasis and is mediated by the cadherin family. In human bronchial epithelial cells the authors have shown that tumour necrosis factor (TNF)-α induced a significant decrease of E-cadherin and β-catenin expression. The addition of dexamethasone inhibited this decrease. The aim of the present study was to investigate the effect of TNF-α and dexamethasone on the regulation of E-cadherin, γ-catenin and β-catenin in human nasal epithelial cells (HNEC). A primary culture of HNEC, obtained from human nasal turbinates after surgery, was used. The quantitative and qualitative modulation of E-cadherin, γ-catenin and β-catenin expression was assessed by Western blot and immunofluorescence analysis. In order to assess the TNF-α-induced activation of HNEC, interleukin-8 and RANTES (regulated on activation, normal T-cell expressed and secreted) release was assessed by enzyme-linked immunosorbent assay. The results showed that TNF-α induced, a decrease in γ-catenin and β-catenin expression, but had no effect on E-cadherin expression. Immunofluorescence showed that TNF-α induced cytoplasmic localisation of E-cadherin, γ-catenin and β-catenin. Dexamethasone inhibited the effect of TNF-α and induced a three-fold increase in E-cadherin expression. These results suggest that the difference in nasal and bronchial epithelial cohesion may be due to the differential effect of tumour necrosis factor-α and dexamethasone on E-cadherin expression.
Vertebral osteomyelitis caused by thoracic empyema, or vice versa?
Authors: KR Liesker, WK Taconis, CM Plasmans, AJ Schreurs
Journal: European Respiratory Journal (1996)

Thoracic empyema and vertebral osteomyelitis is a rare combination. We report a case of vertebral osteomyelitis possibly caused by a progressive thoracic empyema. The causative pathogen was Escherichia coli. Computed tomographic (CT) scan and magnetic resonance imaging (MRI) suggested the diagnosis of vertebral osteomyelitis, confirmed by transthoracic needle aspiration and operative findings. Aetiology and treatment are discussed.
Relationship Between Early Diastolic Intraventricular Pressure Gradients, an Index of Elastic Recoil, and Improvements in Systolic and Diastolic Function
Authors: Michael S. Firstenberg, Nicholas G. Smedira, Neil L. Greenberg, David L. Prior, Patrick M. McCarthy, Mario J. Garcia, James D. Thomas
Journal: Circulation (2001)

Early diastolic intraventricular pressure gradients (IVPGs) have been proposed to relate to left ventricular (LV) elastic recoil and early ventricular "suction." Animal studies have demonstrated relationships between IVPGs and systolic and diastolic indices during acute ischemia. However, data on the effects of improvements in LV function in humans and the relationship to IVPGs are lacking.Eight patients undergoing CABG and/or infarct exclusion surgery had a triple-sensor high-fidelity catheter placed across the mitral valve intraoperatively for simultaneous recording of left atrial (LA), basal LV, and apical LV pressures. Hemodynamic data obtained before bypass were compared with those with similar LA pressures and heart rates obtained after bypass. From each LV waveform, the time constant of LV relaxation (tau), +dP/dt(max), and -dP/dt(max) were determined. Transesophageal echocardiography was used to determined end-diastolic (EDV) and end-systolic (ESV) volumes and ejection fractions (EF). At similar LA pressures and heart rates, IVPG increased after bypass (before bypass 1.64+/-0.79 mm Hg; after bypass 2.67+/-1.25 mm Hg; P<0.01). Significant improvements were observed in ESV, as well as in apical and basal +dP/dt(max), -dP/dt(max), and tau (each P<0.05). Overall, IVPGs correlated inversely with both ESV (IVPG=-0.027[ESV]+3.46, r=-0.64) and EDV (IVPG=-0.027[EDV]+4.30, r=-0.70). Improvements in IVPGs correlated with improvements in apical tau (Deltatau =5.93[DeltaIVPG]+4.76, r=0.91) and basal tau (Deltatau =2.41[DeltaIVPG]+5.13, r=-0.67). Relative changes in IVPGs correlated with changes in ESV (DeltaESV=-0.97[%DeltaIVPG]+23.34, r=-0.79), EDV (DeltaEDV=-1.16[%DeltaIVPG]+34.92, r=-0.84), and EF (DeltaEF=0.38[%DeltaIVPG]-8.39, r=0.85).Improvements in LV function also increase IVPGs. These changes in IVPGs, suggestive of increases in LV suction and elastic recoil, correlate directly with improvements in LV relaxation and ESV.
THE EFFECTS OF HIGH EXPLOSIVES ON THE EAR
Authors: J. G. Wilson
Journal: BMJ (1917)

<h3>Background</h3> Giant cell arteritis (GCA) is a chronic vasculitis of medium- and large-size vessels, especially the cranial branches of arteries originating from the aortic arch. The most feared complication of GCA is visual loss if not treated promptly. The finding of at least three of the five diagnostic criteria has a sensitivity of 93% and a specificity of 91% for the diagnosis of GCA. <h3>Objective</h3> To describe a patient with GCA and its consideration in the differential diagnosis of headache in an elder with risk of visual loss if not treated promptly. <h3>Case Report</h3> An 89-year-old woman came to hospital with loss of vision in the left eye since 3 days before arrival. The patient developed a pain that started on the cervical region with radiation to the occipital and frontal head during 3 weeks prior to arrival at hospital. The patient was evaluated by community physicians with imaging tests showing normal findings. On evaluation, the patient had hard and nonpulsatile temporal arteries bilaterally, neurologic dysfunction in the left eye, and elevated erythrocyte sedimentation rate by the Westerngren method (ESR, 122 mm/hr). Corticosteroid therapy was started promptly. On admission to hospital, she was evaluated by the ophthalmology and rheumatology services. Two days after admission, the patient was discharged home with oral daily prednisone and follow-up in rheumatology clinics. A left temporal artery biopsy confirmed the diagnosis. <h3>Discussion</h3> The patient had all five diagnostic criteria for GCA: disease onset at or more than 50 years of age, new headache, temporal artery abnormality, ESR at 50 mm/hr or higher, and abnormal artery biopsy. The effective starting dose of corticosteroid should be continued until all reversible symptoms and findings have disappeared and laboratory tests have reverted to normal. <h3>Conclusion</h3> GCA must be considered in the differential diagnosis of new headache in an elder. Corticosteroid should be instituted once the diagnosis of GCA is suspected because of increased risk of visual loss. Temporal artery biopsy should be obtained promptly, but its performance is independent of the clinical suspicion and prompt therapy for GCA.
Liver-resident NK cells confer adaptive immunity in skin-contact inflammation
Authors: Hui Peng, Xiaojun Jiang, Yonglin Chen, Dorothy K. Sojka, Haiming Wei, Xiang Gao, Rui Sun, Wayne M. Yokoyama, Zhigang Tian
Journal: Journal of Clinical Investigation (2013)

Liver natural killer (NK) cells were recently reported to possess memory-like properties in contact hypersensitivity (CHS) models. However, the phenotype and origin of these “memory” NK cells cannot be distinguished from other NK cell subpopulations. Here, we define the transcriptional, phenotypic, and functional features of liver NK cell subsets and their roles in mediating CHS. Liver NK cells can be divided into two distinct subsets: CD49a+DX5– and CD49a–DX5+. Substantial transcriptional and phenotypic differences existed between liver CD49a+DX5– NK cells and other NK cell subsets. CD49a+DX5– NK cells possessed memory potential and conferred hapten-specific CHS responses upon hapten challenge. Importantly, CD49a+DX5– NK cells were liver resident and were present in the liver sinusoidal blood, but not the afferent and efferent blood of the liver. Moreover, they appeared to originate from hepatic hematopoietic progenitor/stem cells (HPCs/HSCs) but not from the bone marrow, and maintained their phenotypes in the steady state. Our findings of liver-resident NK cells shed new light on the acquisition of memory-like properties of NK cells.