tbuckley/cabot-search huggingface dataset:
Iron Uptake Promotes Hyperoxic Injury to Alveolar Macrophages
Authors: LEWIS J. WESSELIUS, WADE L. WILLIAMS, KIRSTIN BAILEY, SUSAN VAMOS, AMY R. O'BRIEN-LADNER, THOMAS WIEGMANN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Iron uptake by cells may increase the intracellular pool of prooxidant iron prior to storage of iron within ferritin. Because hyperoxia is toxic to alveolar macrophages (AM) via mechanisms involving oxidant stress, we hypothesized that iron uptake by AM might promote hyperoxia-induced injury. To assess this hypothesis, we cultured AM recovered from healthy volunteers under conditions of normoxia or hyperoxia (60% or 95% oxygen) in media of varying iron content, including control media (3 μ M iron) and media supplemented with iron (FeCl3; total iron 10, 20, or 40 μ M). AM injury was assessed by measuring release of lactate dehydrogenase (LDH), phagocytic activity for yeast, and cytosolic concentrations of calcium ([Ca2 +]i) as determined by ratio image analysis of AM loaded with the fluorescent calcium probe indo-1. There was dose-dependent accumulation of iron and ferritin synthesis in AM exposed to iron-supplemented media. Exposure of AM to hyperoxia (60% and 95% oxygen, 18 h) in control media increased LDH release and impaired phagocytic activity for yeast; however, similar hyperoxic exposures in iron-supplemented media significantly increased the cells' LDH release and decreased phagocytosis. Exposure to 95% oxygen increased the [Ca2 +]i of AM over 18 h, but similar exposure in iron-supplemented media induced greater increases in [Ca2 +]i. As compared with exposure to normoxia, exposure to hyperoxia (60% and 95% oxygen) also decreased iron uptake and, to a greater extent, ferritin synthesis by AM in iron-supplemented media. These data suggest that: (1) iron uptake promotes hyperoxic injury to AM; and (2) hyperoxia impairs the capacity of AM to sequester iron in ferritin.
Impact of Natriuretic Peptide Clearance Receptor (<i>NPR3</i>) Gene Variants on Blood Pressure in Type 2 Diabetes
Authors: Pierre-Jean Saulnier, Ronan Roussel, Jean Michel Halimi, Jeremie Lebrec, Dured Dardari, Sulyia Maimaitiming, Gérard Guilloteau, Xavier Prugnard, Richard Marechaud, Stephanie Ragot, Michel Marre, Samy Hadjadj
Journal: Diabetes Care (2011)

OBJECTIVE Hypertension in diabetes is characterized by abnormal sodium homeostasis, suggesting a particular role of natriuretic peptide pathway. Natriuretic peptides can affect blood pressure (BP) through their plasma concentrations, which are dependent on their receptor activities. We thus assessed the association between nine NPR3 gene polymorphisms and BP levels in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Nine single nucleotide polymorphisms (SNPs) tagging the haplotype structure of the NPR3 gene were genotyped in the 3,126 French Non-insulin-dependent Diabetes, Hypertension, Microalbuminuria or Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) trial participants. We then used a second population (Diabete de type 2, Nephropathie et Genetique [DIAB2NEPHROGENE]/Survie, Diabete de type 2 et Genetique [SURDIAGENE] study) of 2,452 patients for the purpose of replication. Finally, we separately investigated subjects selected according to their rs 2270915SNP genotypes for their BP response to salt restriction. RESULTS In DIABHYCAR patients, three SNPs (rs6889608, rs1173773, and rs2270915) were significantly associated with systolic BP (SBP). The effect of the rs2270915 was replicated in the second step population: AA homozygotes had a lower SBP than G carriers (137.4 ± 19.1 vs. 140.0 ± 20.2 mmHg, P = 0.004). The rs2270915 influenced the response of SBP to salt reduction, with AA homozygous patients showing greater reductions after restriction of salt intake compared with G carriers: −20 mmHg (−43 to −8) vs. −3 (−20 to +7); P = 0.006. CONCLUSIONS We found a consistent and significant association between the rs2270915 polymorphism of the NPR3 gene and SBP in diabetic patients. This genetic variation may affect pressure response to changes in dietary sodium.
(13) Argyria and lead poisoning
Authors: G.E. Allen
Journal: British Journal of Dermatology (1984)

Journal Article (13) Argyria and lead poisoning Get access G.E. Allen G.E. Allen Ulster Hospital, Dundonald Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 111, Issue s26, 1 July 1984, Pages 57–59, https://doi.org/10.1111/j.1365-2133.1984.tb05283.x Published: 01 July 1984
Beyond Malaria — Causes of Fever in Outpatient Tanzanian Children
Authors: Valérie D'Acremont, Mary Kilowoko, Esther Kyungu, Sister Philipina, Willy Sangu, Judith Kahama-Maro, Christian Lengeler, Pascal Cherpillod, Laurent Kaiser, Blaise Genton
Journal: New England Journal of Medicine (2014)

As the incidence of malaria diminishes, a better understanding of nonmalarial fever is important for effective management of illness in children. In this study, we explored the spectrum of causes of fever in African children.
Instability of Prefrontal Signal Processing in Schizophrenia
Authors: Georg Winterer, Francesco Musso, Christian Beckmann, Venkata Mattay, Michael F. Egan, Douglas W. Jones, Joseph H. Callicott, Richard Coppola,, Daniel R. Weinberger
Journal: American Journal of Psychiatry (2006)

Objective: Prefrontal dysfunction is considered a fundamental characteristic of schizophrenia. Recent electrophysiological evidence points to a major instability of signal processing in prefrontal cortical microcircuits because of reduced phase-synchronization (i.e., an increased stimulus-related variability [noise] of single-trial responses in the spatial and time domain). The authors used functional magnetic resonance imaging (fMRI) during a visual two-choice reaction task in order to measure, with higher topographic accuracy, signal stability in patients with schizophrenia and its relationship to more traditional measures of activation. Method: Twelve clinically stable inpatients with schizophrenia and 16 matched comparison subjects were evaluated. Event-related blood-oxygen-level-dependent responses were subjected to an analysis of residual noise variance and to independent data dimension independent component analysis in the medial prefrontal cortex. Results: In patients with schizophrenia, the authors found increased residual noise variance of the blood-oxygen-level-dependent response that predicted the level of prefrontal activation in these subjects. In the left hemisphere, residual noise variance strongly correlated with psychotic symptoms. Independent component analysis revealed a "fractionized" and unfocussed pattern of activation in patients. Conclusions: These findings suggest that unstable cortical signal processing underlies classic abnormal cortical activation patterns as well as psychosis in schizophrenia.
Risk of hospital admission for COPD following smoking cessation and reduction: a Danish population study
Authors: N S Godtfredsen
Journal: Thorax (2002)

Little is known about the effects of changes in smoking habits on the subsequent risk of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the relationship between smoking cessation and reduction and admission to hospital for COPD in a general population sample.A total of 19,709 participants from three prospective population studies in Copenhagen were followed with record linkage for date of first hospital admission for COPD until 1998 (mean follow up 14 years). Heavy smokers (>/=15 cigarettes/day) who reduced their tobacco consumption by at least 50% between the two initial examinations without quitting and smokers who stopped smoking during this time were compared with continuous heavy smokers using a Cox proportional hazards model.During the follow up period 1,260 subjects (741 men and 519 women) were admitted to hospital for COPD. After multivariate adjustment, quitting smoking was associated with a significant reduction in the risk of hospital admission. The relative hazard (HR) was 0.57 (95% confidence interval (CI) 0.33 to 0.99). Those who reduced smoking did not show a significantly lower risk of hospitalisation than continuing heavy smokers (HR 0.93 (95% CI 0.73 to 1.18)). Exclusion of events during the first 5 study years, detailed adjustment for lung function, or restriction of analyses to participants with impaired pulmonary function did not reverse the observed trend.Self-reported smoking cessation is associated with a reduction in the risk of COPD morbidity of approximately 40%; the benefit of smoking reduction is questionable.
Effects of Dexamethasone on Antigen-Induced Airway Eosinophilia and M<sub>2</sub> Receptor Dysfunction
Authors: CHRISTOPHER M. EVANS, DAVID B. JACOBY, ALLISON D. FRYER
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

In antigen-challenged guinea pigs, airway hyperreactivity is due to recruitment of eosinophils to the airway nerves and dysfunction of M2 muscarinic receptors. M2 receptor dysfunction is caused by eosinophil major basic protein, which is an allosteric antagonist at the receptor. Because glucocorticoids inhibit airway hyperreactivity in humans and in animal models of asthma, we tested whether dexamethasone treatment (6 μ g · kg− 1 · d− 1 for 3 d, intraperitoneal) before antigen challenge prevents M2 receptor dysfunction and airway hyperreactivity. Guinea pigs were sensitized to ovalbumin via intraperitoneal injections, and were challenged with ovalbumin via inhalation. Twenty-four hours later, hyperreactivity and M2 receptor function were tested. Antigen-challenged animals were hyperreactive to vagal stimulation, and demonstrated loss of M2 receptor function. Dexamethasone pretreatment prevented hyperreactivity and M2 receptor dysfunction in antigen-challenged guinea pigs. Antigen challenge resulted in recruitment of eosinophils to the airways and to the airway nerves. Dexamethasone prevented recruitment of eosinophils to the airway nerves but did not affect total eosinophil influx into the airways. These results demonstrate that dexamethasone prevents antigen-induced hyperreactivity by protecting neuronal M2 muscarinic receptors from antagonism by eosinophil major basic protein, and this protective mechanism appears to be by specifically inhibiting eosinophil recruitment to the airway nerves.
Purkinje Cells From RyR2 Mutant Mice Are Highly Arrhythmogenic But Responsive to Targeted Therapy
Authors: Guoxin Kang, Steven F. Giovannone, Nian Liu, Fang-Yu Liu, Jie Zhang, Silvia G. Priori, Glenn I. Fishman
Journal: Circulation Research (2010)

The Purkinje fiber network has been proposed as the source of arrhythmogenic Ca(2+) release events in catecholaminergic polymorphic ventricular tachycardia (CPVT), yet evidence supporting this mechanism at the cellular level is lacking.We sought to determine the frequency and severity of spontaneous Ca(2+) release events and the response to the antiarrhythmic agent flecainide in Purkinje cells and ventricular myocytes from RyR2(R4496C/+) CPVT mutant mice and littermate controls.We crossed RyR2(R4496C/+) knock-in mice with the newly described Cntn2-EGFP BAC transgenic mice, which express a fluorescent reporter gene in cells of the cardiac conduction system, including the distal Purkinje fiber network. Isolated ventricular myocytes (EGFP(-)) and Purkinje cells (EGFP(+)) from wild-type hearts and mutant hearts were distinguished by epifluorescence and intracellular Ca(2+) dynamics recorded by microfluorimetry. Both wild-type and RyR2(R4496C/+) mutant Purkinje cells displayed significantly slower kinetics of activation and relaxation compared to ventricular myocytes of the same genotype, and tau(decay) in the mutant Purkinje cells was significantly slower than that observed in wild-type Purkinje cells. Of the 4 groups studied, RyR2(R4496C/+) mutant Purkinje cells were also most likely to develop spontaneous Ca(2+) release events, and the number of events per cell was also significantly greater. Furthermore, with isoproterenol treatment, although all 4 groups showed increases in the frequency of arrhythmogenic Ca(2+(i)) events, the RyR2(R4496C/+) Purkinje cells responded with the most profound abnormalities in intracellular Ca(2+) handling, including a significant increase in the frequency of unstimulated Ca(2+(i)) events and the development of alternans, as well as isolated and sustained runs of triggered beats. Both Purkinje cells and ventricular myocytes from wild-type mice showed suppression of spontaneous Ca(2+) release events with flecainide, whereas in RyR2(R4496C/+) mice, the Purkinje cells were preferentially responsive to drug. In contrast, the RyR2 blocker tetracaine was equally efficacious in mutant Purkinje cells and ventricular myocytes.Purkinje cells display a greater propensity to develop abnormalities in intracellular Ca(2+) handling than ventricular myocytes. This proarrhythmic behavior is enhanced by disease-causing mutations in the RyR2 Ca(2+) release channel and greatly exacerbated by catecholaminergic stimulation, with the development of arrhythmogenic triggered beats. These data support the concept that Purkinje cells are critical contributors to arrhythmic triggers in animal models and humans with CPVT and suggest a broader role for the Purkinje fiber network in the genesis of ventricular arrhythmias.
Clergymen's Role in Community Health Clinics
Authors: E. Mansell Pattison
Journal: JAMA (1968)

It is contemplated that a community mental health center will be established in our city in the near future. It is my understanding that experience in other established community health centers indicates that the clergy do not refer many individuals who approach them with emotional problems to these centers, or indeed to psychiatric personnel in any facility. What is the explanation for this lack of rapport between clergy and mental health personnel? Specifically, what role do you visualize that the clergy can play in the community health centers? What training is necessary for a clergyman to assume the responsibilities of a chaplain? How can we utilize patient contact with clergy to assist in most efficacious case referral?
Brief Report: <i>IFIH1</i> Mutation Causes Systemic Lupus Erythematosus With Selective IgA Deficiency
Authors: Lien Van Eyck, Lien De Somer, Diana Pombal, Simon Bornschein, Glynis Frans, Stéphanie Humblet‐Baron, Leen Moens, Francis de Zegher, Xavier Bossuyt, Carine Wouters, Adrian Liston
Journal: Arthritis & Rheumatology (2015)

Objective To identify the underlying genetic defect in a 16‐year‐old girl with severe early‐onset and refractory systemic lupus erythematosus (SLE), IgA deficiency, and mild lower limb spasticity without neuroradiologic manifestations. Methods Whole‐exome sequencing and extensive immunologic analysis were performed on samples from the index patient. Results We identified a de novo p.R779H IFIH1 gain‐of‐function mutation in a patient with severe early‐onset SLE, selective IgA deficiency, and mild lower limb spasticity. The same mutation in IFIH1 was recently identified in patients with Aicardi‐Goutières syndrome, a rare neuroimmunologic disorder associated with elevated levels of type I interferon (IFN). IFN induced with helicase C domain 1 functions as an intracellular innate immune receptor that senses viral nucleic acids and leads to the induction of type I IFN and proinflammatory cytokines. Despite systemic immunosuppressive treatment, disease activity persisted in the patient and was associated with elevated serum levels of IFNα and up‐regulation of IFIH1 itself. Conclusion This finding adds a new genetic causation for Mendelian lupus and greatly extends the disease spectrum associated with mutations in IFIH1 (ranging from inflammatory encephalopathy to prototypic systemic autoimmune disease). This marked phenotypic heterogeneity, despite an identical mutation, demonstrates the importance of modifying factors in type I IFN–dependent pathologies caused by mutations in IFIH1 .
A rare cause of Ortner's syndrome (cardiovocal hoarseness)
Authors: J T Annema, J J Brahim, K F Rabe
Journal: Thorax (2004)

A group of seven patients with increased transradiancy of one lung included four with chronic bronchitis. The function of the two lungs combined was assessed by measurement of the lung volumes, airway resistance, and carbon monoxide uptake at rest, and by measurement of pulmonary ventilation, gas exchange, blood gases, and cardiac output at rest and during steady state exercise. The contribution of the hypertransradiant lung to the overall functional abnormalities at rest was estimated using a radioactive gas technique. All the patients had airway obstruction. Pulmonary gas exchange was only mildly affected at rest because of equal reduction of ventilation and perfusion in the abnormal lung, but during exercise ventilation-perfusion inequality increased in some of the patients. Cardiac output was low in five patients during exercise and in four there was excessive lactate production. The greatest physiological abnormalities were seen in two of the chronic bronchitics who had abnormalities of ventilation and perfusion in both lungs. We suggest that a pulmonary vascular abnormality resulting in reduced cardiac output, as well as ventilatory impairment due to airway obstruction, may contribute to the limited exercise capacity of these patients.
Intake of Fruit, Vegetables, and Fruit Juices and Risk of Diabetes in Women
Authors: Lydia A. Bazzano, Tricia Y. Li, Kamudi J. Joshipura, Frank B. Hu
Journal: Diabetes Care (2008)

The purpose of this study was to examine the association between fruit, vegetable, and fruit juice intake and development of type 2 diabetes.A total of 71,346 female nurses aged 38-63 years who were free of cardiovascular disease, cancer, and diabetes in 1984 were followed for 18 years, and dietary information was collected using a semiquantitative food frequency questionnaire every 4 years. Diagnosis of diabetes was self-reported.During follow-up, 4,529 cases of diabetes were documented, and the cumulative incidence of diabetes was 7.4%. An increase of three servings/day in total fruit and vegetable consumption was not associated with development of diabetes (multivariate-adjusted hazard ratio 0.99 [95% CI 0.94-1.05]), whereas the same increase in whole fruit consumption was associated with a lower hazard of diabetes (0.82 [0.72-0.94]). An increase of 1 serving/day in green leafy vegetable consumption was associated with a modestly lower hazard of diabetes (0.91 [0.84-0.98]), whereas the same change in fruit juice intake was associated with an increased hazard of diabetes (1.18 [1.10-1.26]).Consumption of green leafy vegetables and fruit was associated with a lower hazard of diabetes, whereas consumption of fruit juices may be associated with an increased hazard among women.
Characteristics of the Temporal and Spatial Excitable Gap in Anisotropic Reentrant Circuits Causing Sustained Ventricular Tachycardia
Authors: Nicholas S. Peters, James Coromilas, Michael S. Hanna, Mark E. Josephson, Constantinos Costeas, Andrew L. Wit
Journal: Circulation Research (1998)

The excitable gap of a reentrant circuit has both temporal (time during the cycle length that the circuit is excitable) and spatial (length of the circuit that is excitable at a given time) properties. We determined the temporal and spatial properties of the excitable gap in reentrant circuits caused by nonuniform anisotropy. Myocardial infarction was produced in canine hearts by ligation of the left anterior descending coronary artery. Four days later, reentrant circuits were mapped in the epicardial border zone of the infarcts with a multielectrode array during sustained ventricular tachycardia induced by programmed stimulation. During tachycardia, premature impulses were initiated by stimulation at sites around and in the reentrant circuits, and their conduction characteristics in the circuit were mapped. All circuits had a temporal excitable gap in at least part of the circuit, which allowed premature impulses to enter the circuit. Completely and partially excitable segments of the temporal gap were identified by measuring conduction velocity of the premature impulses; conduction was equal to the native reentrant wave front in completely excitable regions and slower than the reentrant wave front in partially excitable regions. In some circuits, a temporal gap existed throughout the circuit, permitting the entire circuit to be reset over a range of premature coupling intervals, although the size of the gap varied at different sites. In other circuits, the gap became so small at local sites that even though premature impulses could enter the circuit, the circuit could not be reset. Premature impulses could terminate reentry in circuits that could be reset or not. We also found a significant spatial gap, which was identified by determining the distance between the head of the circulating wave front, which could be located on the activation map, and its tail, which was the site most distal from the head as located by the site of entry of the premature wave front into the circuit. The spatial gap could also vary in different parts of the circuit. Therefore, nonuniform anisotropic reentrant circuits have both a temporal and spatial excitable gap with fully and partially excitable components that change in different parts of the circuit.
The Early History of Modern Birds Inferred from DNA Sequences of Nuclear and Mitochondrial Ribosomal Genes
Authors: Marcel van Tuinen, Charles G. Sibley, S. Blair Hedges
Journal: Molecular Biology and Evolution (2000)

The traditional view of avian evolution places ratites and tinamous at the base of the phylogenetic tree of modern birds (Neornithes). In contrast, most recent molecular studies suggest that neognathous perching birds (Passeriformes) compose the oldest lineage of modern birds. Here, we report significant molecular support for the traditional view of neognath monophyly based on sequence analyses of nuclear and mitochondrial DNA (4.4 kb) from every modern avian order. Phylogenetic analyses further show that the ducks and gallinaceous birds are each other's closest relatives and together form the basal lineage of neognathous birds. To investigate why other molecular studies sampling fewer orders have reached different conclusions regarding neognath monophyly, we performed jackknife analyses on our mitochondrial data. Those analyses indicated taxon-sampling effects when basal galloanserine birds were included in combination with sparse taxon sampling. Our phylogenetic results suggest that the earliest neornithines were heavy-bodied, ground-dwelling, nonmarine birds. This inference, coupled with a fossil bias toward marine environments, provides a possible explanation for the large gap in the early fossil record of birds.