tbuckley/cabot-search huggingface dataset:
NO in exhaled air is correlated with markers of eosinophilic airway inflammation in corticosteroid‐dependent childhood asthma
Authors: J. Mattes, K. Storm van′s Gravesande, U. Reining, K Alving, G. Ihorst, M. Henschen, J. Kuehr
Journal: European Respiratory Journal (1999)

The relationship between nitric oxide in exhaled air, levels of sputum eosinophils, sputum eosinophil cationic protein (ECP) and urinary eosinophil protein X (EPX) excretion has not yet been investigated in corticosteroid-dependent childhood asthma. Therefore, taking 25 children with stable asthma (mean age 11.2 yrs) treated with inhaled corticosteroids and nine nonatopic healthy control children (mean age 12.8 yrs) the level of exhaled NO was measured by means of a chemiluminescence analyser before and after sputum induction. This was conducted as a slow vital capacity manoeuvre under standardized conditions with a target flow of 70 mL x s(-1) against a resistance of 100 cm H2O x L(-1) x s. Sputum induction was performed by inhalation of hypertonic saline (3, 4, and 5%) in a standardized manner and a single sample of urine was collected. Exhaled NO (p = 0.01), absolute eosinophil cell counts in sputum (p = 0.02), sputum ECP (p = 0.09) and urinary EPX excretion (p = 0.02) were higher in asthmatics compared to control children. Exhaled NO was positively correlated with sputum ECP (r(s) = 0.59, p = 0.002), urinary EPX (r(s) = 0.42, p = 0.03), and sputum eosinophils (r(s) = 0.30, p = 0.15) in the asthmatic children. These correlations appeared to be pronounced after sputum induction, where NO values had decreased (p = 0.01). None of the correlations were observed in the group of nonatopic control subjects. Additionally there were significant correlations between sputum ECP and sputum eosinophils (r(s) = 0.69, p&lt;0.001) as well as between sputum ECP and urinary EPX excretion (r(s) = 0.58, p = 0.003) in the asthmatics. Exhaled NO provides information about the degree of eosinophilic airway inflammation and thus appears to be a useful and easy-to-perform inflammatory marker in corticosteroid-dependent asthma.
Ligands to Nucleic Acid–Specific Toll-Like Receptors and the Onset of Lupus Nephritis
Authors: Rahul D. Pawar, Prashant S. Patole, Andreas Ellwart, Maciej Lech, Stephan Segerer, Detlef Schlondorff, Hans-Joachim Anders
Journal: Journal of the American Society of Nephrology (2006)

Lupus nephritis develops from a combination of genetic and environmental factors such as microbial infection. A role for microbial nucleic acids (e.g., via nucleic acid-specific Toll-like receptors [TLR]) was hypothesized, in this context, because microbial nucleic acids can trigger multiple aspects of autoimmunity in vitro and in vivo. Eight-week-old MRL(lpr/lpr) and MRL wild-type mice received an injection of pI:C RNA (ligand to TLR-3), imiquimod (ligand to TLR-7), or CpG-DNA (ligand to TLR-9) on alternate days for 2 wk. Only CpG-DNA triggered the onset of lupus nephritis in MRL(lpr/lpr) mice, as defined by diffuse proliferative glomerulonephritis associated with glomerular IgG and complement C3 deposition, proteinuria, and glomerular macrophage infiltrates. None of the compounds caused DNA autoantibody production or glomerulonephritis in MRL wild-type mice. The role of CpG-DNA to trigger lupus nephritis in MRL(lpr/lpr) mice was found to relate to its potent immunostimulatory effects at multiple levels: B cell IL12p40 production, B cell proliferation, double-stranded DNA autoantibody secretion, and dendritic cell IFN-alpha production. The induction of lupus nephritis by CpG-DNA is motif specific and could be prevented by co-injection of inhibitory DNA. In summary, among the ligands tested, CpG-DNA triggers lupus nephritis in genetically predisposed hosts. These data support the concept that systemic lupus erythematosus is triggered by pathogens that release CG-rich DNA.
Association of the Metabolic Syndrome With History of Myocardial Infarction and Stroke in the Third National Health and Nutrition Examination Survey
Authors: John K. Ninomiya, Gilbert L’Italien, Michael H. Criqui, Joanna L. Whyte, Anthony Gamst, Roland S. Chen
Journal: Circulation (2003)

The combination of cardiovascular risk factors known as the metabolic syndrome is receiving increased attention from physicians, but data on the syndrome's association with morbidity are limited.Applying National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria, we evaluated 10 357 NHANES III subjects for the 5 component conditions of the metabolic syndrome: insulin resistance, abdominal obesity based on waist circumference, hypertriglyceridemia, low HDL cholesterol (HDL-C), and hypertension, as well as the full syndrome, defined as at least 3 of the 5 conditions. Logistic regression was used to estimate the cross-sectional association of the syndrome and each of its 5 component conditions separately with history of myocardial infarction (MI), stroke, and either MI or stroke (MI/stroke). Models were adjusted for age, sex, race, and cigarette smoking. The metabolic syndrome was significantly related in multivariate analysis to MI (OR, 2.01; 95% CI, 1.53 to 2.64), stroke (OR, 2.16; 95% CI, 1.48 to 3.16), and MI/stroke (OR, 2.05; 95% CI, 1.64 to 2.57). The syndrome was significantly associated with MI/stroke in both women and men. Among the component conditions, insulin resistance (OR, 1.30; 95% CI, 1.03 to 1.66), low HDL-C (OR, 1.35; 95% CI, 1.05 to 1.74), hypertension (OR, 1.44; 95% CI, 1.00 to 2.08), and hypertriglyceridemia (OR, 1.66; 95% CI=1.20 to 2.30) were independently and significantly related to MI/stroke.These results indicate a strong, consistent relationship of the metabolic syndrome with prevalent MI and stroke.
Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial
Authors: Claudine Angela Blum, Nicole Nigro, Matthias Briel, Philipp Schuetz, Elke Ullmer, Isabelle Suter-Widmer, Bettina Winzeler, Roland Bingisser, Hanno Elsaesser, Daniel Drozdov, Birsen Arici, Sandrine Andrea Urwyler, Julie Refardt, Philip Tarr, Sebastian Wirz, Robert Thomann, Christine Baumgartner, Hervé Duplain, Dieter Burki, Werner Zimmerli, Nicolas Rodondi, Beat Mueller, Mirjam Christ-Crain
Journal: The Lancet (2015)
Craniomaxillofacial injury in sport: a review of prevention research
Authors: P S Echlin, R E G Upshur, D M Peck, E N Skopelja
Journal: British Journal of Sports Medicine (2005)

Current decision making in prevention of sport related craniomaxillofacial injury is based on available data derived from surveillance and attitude based studies. The literature on this type of injury prevention lacks the high quality scientific design and evidence on which mandatory interventions can be based. Currently available prevention methodology can provide a better understanding of injury mechanisms and produce valid interventions.
Role of Vascular Cell Adhesion Molecule-1 and Fibronectin Connecting Segment-1 in Monocyte Rolling and Adhesion on Early Atherosclerotic Lesions
Authors: Yuqing Huo, Ali Hafezi-Moghadam, Klaus Ley
Journal: Circulation Research (2000)

Abstract —Atherosclerotic lesion development seems to be inflammatory in nature and involves the recruitment of monocytes to the vessel wall. In this study, we investigated the role of vascular cell adhesion molecule-1 (VCAM-1) and fibronectin (FN) connecting segment-1 containing the amino acid sequence ILDV as functional ligands for α 4 β 1 integrin (VLA-4) in monocyte rolling and adherence to early atherosclerotic lesions. Carotid arteries of apolipoprotein E–deficient mice were isolated and perfused with monocytes or U937 cells. Cell adhesion was reduced 95±4% by monoclonal antibodies HP1/2 and HP2/1, which block VLA-4 binding to both VCAM-1 and FN connecting segment-1. mAb HP1/3 preferentially blocked interaction of VLA-4 with FN but not VCAM-1 and decreased adhesion by 30±8%. In contrast, blocking VCAM-1 by perfusing the isolated carotid artery with mAb MK-2.7 reduced adhesion by 75±12%. Mononuclear cell adhesion to the early atherosclerotic endothelium was inhibited by 68±10% in the presence of EILDVPST but not in the presence of control peptide EIDVLPST. When VLA-4 or VCAM-1 was blocked, more mononuclear cells rolled on early lesions at significantly higher (approximately doubled) rolling velocities. These data demonstrate that (1) blockade of VCAM-1 can abrogate the majority (75±12%) of VLA-4–dependent monocyte adhesion on early atherosclerotic endothelia and (2) ILDV peptide interferes with VLA-4 binding to both VCAM-1 and FN and may be useful in limiting monocyte adhesion to atherosclerotic lesions. (Circ Res. 2000;87:153-159.)
PMLRARα binds to Fas and suppresses Fas-mediated apoptosis through recruiting c-FLIP in vivo
Authors: Rong-Hua Tao, Zuzana Berkova, Jillian F. Wise, Abdol-Hossein Rezaeian, Urszula Daniluk, Xue Ao, David H. Hawke, Judith E. Karp, Hui-Kuan Lin, Jeffrey J. Molldrem, Felipe Samaniego
Journal: Blood (2011)
Interdependence of HIF1α /TGFβ1 activity in induction of pulmonary fibrosis
Authors: Chandru Hanumegowda, Kjetil Ask, Jack Gauldie, Martin Kolb
Journal: European Respiratory Journal (2013)

Introduction:   Pulmonary Fibrosis is a chronic lung disease likely involving multiple microinjuries to alveolar epithelium, resulting in excess deposition of extracellular matrix (ECM) and hardening/stiffening of tissue. Transforming growth factor β1 (TGFβ1) is a key regulator of ECM expression and is linked with the development of pulmonary fibrosis. Activation of Hypoxia inducible factor-1a (HIF1α) under hypoxic conditions in fibrotic lung is expected and could promote perpetuation of the disease.   Objective:   Evaluate if concomitant overexpression of HIF1α / TGFβ1 worsens or improves pulmonary fibrosis.   Methods:   Adenoviral vectors each 6 X 10 8  pfu of AdHIF1α /AdDL-70 (control), AdTGFβ1/AdDL-70 and AdHIF1α /AdTGFβ1 or AdDL70/AdDL70 in combination were administered intratracheally to rats. Lung extracts ELISA, western blot, RT-PCR, collagen assay and lung histopathology, elastance measures and HIF1α DNA binding assays were carried out to assess tissue fibrosis.   Results:   Concomitant administration of AdHIF1α/AdTGFβ1 enhances the fibrotic response. TGFβ1 is able to induce fibrosis with induction of HIF1α. Over expression of HIF1α alone induces limited fibrosis but enhances the ability of TGFβ1 to further develop sustained fibrosis. This study highlights a crucial role of TGFβ1 in mediating the effect of HIF1α and vice versa.   Conclusion:   Combined activation of HIF1α/TGF β1 in lungs enhances inflammation, marked distortion of lung structure, over expression of smooth muscle actin and plasminogen activator inhibitor-1, accumulation of collagen and increases lung elastance, indicating that HIF1α activation may therefore have a role in progression of chronic fibrotic diseases such as IPF.
Different Matrilineal Contributions to Genetic Structure of Ethnic Groups in the Silk Road Region in China
Authors: Y.-G. Yao
Journal: Molecular Biology and Evolution (2004)

Previous studies have shown that there were extensive genetic admixtures in the Silk Road region. In the present study, we analyzed 252 mtDNAs of five ethnic groups (Uygur, Uzbek, Kazak, Mongolian, and Hui) from Xinjiang Province, China (through which the Silk Road once ran) together with some reported data from the adjacent regions in Central Asia. In a simple way, we classified the mtDNAs into different haplogroups (monophyletic clades in the rooted mtDNA tree) according to the available phylogenetic information and compared their frequencies to show the differences among the matrilineal genetic structures of these populations with different demographic histories. With the exception of eight unassigned M*, N*, and R* mtDNAs, all the mtDNA types identified here belonged to defined subhaplogroups of haplogroups M and N (including R) and consisted of subsets of both the eastern and western Eurasian pools, thus providing direct evidence supporting the suggestion that Central Asia is the location of genetic admixture of the East and the West. Although our samples were from the same geographic location, a decreasing tendency of the western Eurasian-specific haplogroup frequency was observed, with the highest frequency present in Uygur (42.6%) and Uzbek (41.4%) samples, followed by Kazak (30.2%), Mongolian (14.3%), and Hui (6.7%). No western Eurasian type was found in Han Chinese samples from the same place. The frequencies of the eastern Eurasian-specific haplogroups also varied in these samples. Combined with the historical records, ethno-origin, migratory history, and marriage customs might play different roles in shaping the matrilineal genetic structure of different ethnic populations residing in this region.
Effect of Coronary Vasodilator Drugs on Retrograde Flow in Areas of Chronic Myocardial Ischemia
Authors: WADIE M. FAM, MAURICE MCGREGOR
Journal: Circulation Research (1964)

The effects of two coronary vasodilator drugs, nitroglycerin and dipyridamole, on the coronary collateral flow were studied in twelve dogs with chronic myocardial ischemia and in five normal dogs, by means of the retrograde flow technique. In the ischemic dogs with well developed collateral circulation, both drugs caused a reduction in systemic blood pressure. Dipyridamole caused a significant reduction in both the retrograde flow and peripheral coronary pressure as well. Nitroglycerin, by contrast, did not cause a significant reduction in either retrograde flow or peripheral coronary pressure in spite of a greater fall in mean arterial pressure. When arterial pressure was held constant artificially, nitroglycerin caused a large increase of retrograde flow in chronic "ischemic" dogs while dipyridamole did not. In normal dogs these differences between the two drugs were not observed. Both drugs caused a reduction of retrograde flow and peripheral coronary pressure which paralleled the reduction in systemic pressure. In both ischemic and normal dogs, dipyridamole caused a reduction in the coronary arteriovenous oxygen difference. Nitroglycerin did not change this value. Reported differences between these two drugs, together with these observations, suggest that nitroglycerin may have an action which is to be seen only in the presence of well developed collateral circulation; this is to increase flow through collateral channels without significantly altering total coronary artery flow. Dipyridamole does not seem to alter collateral flow but does increase total coronary flow. The site of action of these two drugs in the coronary vascular tree must thus be different.
Intrinsic TGF-β signaling promotes age-dependent CD8+ T cell polyfunctionality attrition
Authors: Rajarshi Bhadra, Magali M. Moretto, Julio C. Castillo, Constantinos Petrovas, Sara Ferrando-Martinez, Upasana Shokal, Manuel Leal, Richard A. Koup, Ioannis Eleftherianos, Imtiaz A. Khan
Journal: Journal of Clinical Investigation (2014)

Advanced age is associated with immune system deficits that result in an increased susceptibility to infectious diseases; however, specific mediators of age-dependent immune dysfunction have not been fully elucidated. Here we demonstrated that aged mice exhibit poor effector CD8+ T cell polyfunctionality, primarily due to CD8+ T cell-extrinsic deficits, and that reduced CD8+ T cell polyfunctionality correlates with increased susceptibility to pathogenic diseases. In aged animals challenged with the parasite Encephalitozoon cuniculi, effector CD8+ T cell survival and polyfunctionality were suppressed by highly elevated TGF-β1. Furthermore, TGF-β depletion reduced effector CD8+ T cell apoptosis in both young and aged mice and enhanced effector CD8+ T cell polyfunctionality in aged mice. Surprisingly, intrinsic blockade of TGF-β signaling in CD8+ T cells was sufficient to rescue polyfunctionality in aged animals. Together, these data demonstrate that low levels of TGF-β1 promote apoptosis of CD8+ effector T cells and high TGF-β1 levels associated with age result in both CD8+ T cell apoptosis and an altered transcriptional profile, which correlates with loss of polyfunctionality. Furthermore, elevated TGF-β levels are observed in the elderly human population and in aged Drosophila, suggesting that TGF-β represents an evolutionarily conserved negative regulator of the immune response in aging organisms.
Whole-gland Ablation of Localized Prostate Cancer with High-intensity Focused Ultrasound: Oncologic Outcomes and Morbidity in 1002 Patients
Authors: Sebastien Crouzet, Jean Yves Chapelon, Olivier Rouvière, Florence Mege-Lechevallier, Marc Colombel, Hélène Tonoli-Catez, Xavier Martin, Albert Gelet
Journal: European Urology (2013)
Supernormal Excitability and Conduction in the His-Purkinje System of the Dog
Authors: Joseph F. Spear, E. Neil Moore
Journal: Circulation Research (1974)

The electrophysiological characteristics of the period of supernormal excitability and supernormal conduction were investigated in the isolated canine His-Purkinje system. Strength-interval curves were determined as the minimum transmembrane current required to bring the impaled fiber to threshold potential following a conducted action potential. During the period of supernormal excitability, 17.0 ± 4.6% (SD) less current than that required during diastole was needed to reexcite fibers throughout the left and right bundle branch-Purkinje system. A period of supernormal excitability was not found in the His bundle proximal to its pseudobifurcation or in ventricular muscle. The period of supernormal excitability was voltage dependent in the bundle branch-Purkinje system; it began during phase 3 at full repolarization (88.8 ± 5.6 [SD] mv) and reached minimum current requirements at about 74.3 ± 5.8 mv. Action potentials evoked during this period were conducted faster than they were during diastole. The maximum rates of depolarization of these supernormally conducted action potentials were not greatly depressed compared with control rates. A period of supernormal conduction was not observed in the His bundle. When the external potassium concentration was increased from 2.7 mM to 5.0 um or 7.5 mM, both the supernormal period of excitability and the period of supernormal conduction were eliminated in Purkinje fibers.
Ulcerative colitis in the South African Bantu
Authors: J. D. Sobel, L. Schamroth
Journal: Gut (1970)

Two cases of ulcerative colitis in the Bantu are reported. One patient presented with fulminant acute colitis with toxic dilatation of the colon and massive rectal haemorrhage, the second with chronic, continuous diarrhoea for over twenty years, culminating ultimately with carcinoma of the colon. The aetiology of ulcerative colitis is discussed, together with the problems of specific diagnosis encountered in a population with a high incidence of parasitic infestation and infective diarrhoea. It is considered that the sparseness of reports and apparent rarity of this disease in the Bantu may reflect a failure of detection rather than a true infrequent occurrence. The natural incidence of the disease may be on the increase.
fMRI Study of Maintenance and Manipulation Processes Within Working Memory in First-Episode Schizophrenia
Authors: Hao-Yang Tan, Wei-Chieh Choo, Calvin S.L. Fones, Michael W.L. Chee
Journal: American Journal of Psychiatry (2005)

Working memory, a critical cognitive capacity that is affected in schizophrenia, can be divided into maintenance and manipulation processes. Previous behavioral research suggested that manipulation is more affected than maintenance in patients with chronic schizophrenia. In this study of first-episode schizophrenia patients, the authors evaluated the extent to which the two working memory processes are affected early in the course of schizophrenia.Study subjects were 11 first-episode schizophrenia patients and 11 matched healthy comparison subjects. Each group performed two verbal working memory tasks while undergoing functional magnetic resonance imaging. One task required maintenance of information; the other required manipulation of information in addition to maintenance.Under behaviorally matched conditions, both groups activated a predominantly left-sided frontal-parietal network. The manipulation plus maintenance task elicited activation of greater magnitude and spatial extent. With both tasks, patients showed less bilateral dorsolateral prefrontal cortex activation and greater ventrolateral prefrontal cortex activation, relative to the comparison subjects. A group-by-task interaction was observed for activation at the left dorsolateral and ventrolateral prefrontal cortex. The increase in activation when patients engaged in the manipulation plus maintenance task was disproportionately less in the dorsolateral prefrontal cortex and greater in the ventrolateral prefrontal cortex.These functional neuroanatomical findings add support to earlier suggestions that manipulation of information is selectively more affected than maintenance of information in persons with schizophrenia. They also suggest the presence of interacting regions of dysfunctional and compensatory prefrontal responses in the dorsolateral and ventrolateral prefrontal cortex, respectively, that are more prominent when information is manipulated. This disrupted prefrontal network is present relatively early in the course of schizophrenia.
Human monoclonal antibody as prophylaxis for SARS coronavirus infection in ferrets
Authors: Jan ter Meulen, Alexander BH Bakker, Edward N van den Brink, Gerrit J Weverling, Byron EE Martina, Bart L Haagmans, Thijs Kuiken, John de Kruif, Wolfgang Preiser, Willy Spaan, Hans R Gelderblom, Jaap Goudsmit, Albert DME Osterhaus
Journal: The Lancet (2004)

SARS coronavirus continues to cause sporadic cases of severe acute respiratory syndrome (SARS) in China. No active or passive immunoprophylaxis for disease induced by SARS coronavirus is available. We investigated prophylaxis of SARS coronavirus infection with a neutralising human monoclonal antibody in ferrets, which can be readily infected with the virus. Prophylactic administration of the monoclonal antibody at 10 mg/kg reduced replication of SARS coronavirus in the lungs of infected ferrets by 3·3 logs (95% Cl 2·6–4·0 logs; p<0·001), completely prevented the development of SARS coronavirus-induced macroscopic lung pathology (p=0·013), and abolished shedding of virus in pharyngeal secretions. The data generated in this animal model show that administration of a human monoclonal antibody might offer a feasible and effective prophylaxis for the control of human SARS coronavirus infection.
Lung deposition of budesonide from a pressurized metered-dose inhaler attached to a spacer
Authors: L Thorsson, S Edsbacker
Journal: European Respiratory Journal (1998)

The absolute systemic availability and pulmonary deposition of budesonide inhaled from a pressurized metered-dose inhaler (pMDI) attached to a Nebuhaler spacer was determined in 15 healthy subjects. The study was of an open cross-over design. Each subject randomly received three single doses of budesonide on separate days: 0.5 mg given intravenously and 1.0 mg (0.2 mg x 5) by inhalation from a pMDI with a Nebuhaler, with or without concomitant oral charcoal intake to prevent gastrointestinal absorption. Charcoal intake did not significantly affect the systemic availability or deposition of budesonide. The systemic availability was 36+/-14% (metered dose, mean+/-SD) with charcoal and 35+/-10% without. The pulmonary deposition was 36+/-14% with charcoal and 34+/-11% without. Erroneous administration, in which the canister was shaken only before the first of the five actuations, halved the systemic availability. In conclusion, the pulmonary deposition of budesonide from a pressurized metered-dose inhaler with Nebuhaler is high under optimum conditions. The small discrepancy between the systemic availability and pulmonary deposition indicates that the contribution from deposition in the oropharynx and subsequent absorption from the gastrointestinal tract is negligible. The marked reduction in the systemic availability of budesonide with the unshaken canisters confirms that the performance of a pressurized metered-dose inhaler is very much dependent on proper handling.