tbuckley/cabot-search huggingface dataset:
Radon and man-made vitreous fibers
Authors: James E Lockey, Clara Sue Ross
Journal: Journal of Allergy and Clinical Immunology (1994)

Epidemiologic studies of miners have established a causal association between radon exposure and development of lung cancer. During the past decade the focus of attention has turned to the potential risks from exposure to radon in indoor air. Governmental involvement thus far has primarily been aimed at gathering further data and issuing voluntary guidelines for radon control in the indoor environment. The federal government's most recent risk assessment for exposure to indoor radon published in 1992 concluded that exposure to indoor radon results in 13,600 radon-induced lung cancer deaths in the United States each year. As public awareness of such environmental issues continues to grow, physicians will be faced with the need to respond to inquiries regarding potential health effects. Man-made vitreous fibers are silicate glass that have a noncrystalline structure. They have been in production for more than 100 years and are used in numerous applications in residential and commercial settings. The health risks from man-made vitreous fibers that are used in residential and commercial settings are limited to skin and occasional respiratory tract irritation under circumstances of improper installation or maintenance. When glass fiber contaminates an indoor environment, proper repair measures and thorough cleaning of the indoor environment will lead to resolution of any resultant irritant symptoms.
Oral N-acetylcysteine reduces bleomycin-induced lung damage and mucin Muc5ac expression in rats
Authors: M. Mata, A. Ruíz, M. Cerdá, M. Martinez-Losa, J. Cortijo, F. Santangelo, A. Serrano-Mollar, A. Llombart-Bosch, E.J. Morcillo
Journal: European Respiratory Journal (2003)

Oxidative stress is involved in the pathogenesis of pulmonary fibrosis, therefore antioxidants may be of therapeutic value. Clinical work indicates that N ‐acetylcysteine (NAC) may be beneficial in this disease. The activity of this antioxidant was examined on bleomycin-induced lung damage, mucus secretory cells hyperplasia and mucin Muc5ac gene expression in rats. NAC (3 mmol·kg −1 ·day −1 ) or saline was given orally to Sprague-Dawley rats for 1 week prior to a single intratracheal instillation of bleomycin (2.5 U·kg −1 ) and for 14 days postinstillation. NAC decreased collagen deposition in bleomycin-exposed rats (hydroxyproline content was 4,257±323 and 3,200±192 µg·lung −1 in vehicle- and NAC‐treated rats, respectively) and lessened the fibrotic area assessed by morphometric analysis. The bleomycin-induced increases in lung tumour necrosis factor‐α and myeloperoxidase activity were reduced by NAC treatment. The numbers of mucus secretory cells in airway epithelium, and the Muc5ac messenger ribonucleic acid and protein expression, were markedly augmented in rats exposed to bleomycin. These changes were significantly reduced in NAC‐treated rats. These results indicate that bleomycin increases the number of airway secretory cells and their mucin production, and that oral N ‐acetylcysteine improved pulmonary lesions and reduced the mucus hypersecretion in the bleomycin rat model.
Stable Peptide of the Endogenous Opioid Enkephalin Precursor and Breast Cancer Risk
Authors: Olle Melander, Marju Orho-Melander, Jonas Manjer, Thomas Svensson, Peter Almgren, Peter M. Nilsson, Gunnar Engström, Bo Hedblad, Signe Borgquist, Oliver Hartmann, Joachim Struck, Andreas Bergmann, Mattias Belting
Journal: Journal of Clinical Oncology (2015)

In experimental studies, enkephalins (ENKs) and related opioids have been implicated as negative regulators of breast cancer development by enhancing immune-mediated tumoral defense as well as directly inhibiting cancer cells. We hypothesized that plasma levels of ENKs are predictive of the long-term breast cancer risk. Therefore, our objective was to measure pro-ENK A, a surrogate for mature ENK, and evaluate its predictive value for the development of breast cancer in a large population of middle-aged women and an independent study population.We related pro-ENK in fasting plasma samples from 1,929 healthy women (mean age, 57.6 ± 5.9 years) of the Malmö Diet and Cancer study to breast cancer incidence (n = 123) during a median follow-up of 14.7 years. For replication, pro-ENK was related to risk of breast cancer (n = 130) in an older independent sample from the Malmö Preventive Project consisting of 1,569 women (mean age, 70.0 ± 4.4 years).In the Malmö Diet and Cancer study, pro-ENK was inversely related to the risk of incident breast cancer, with a hazard ratio per each standard deviation increment of logarithm-transformed pro-ENK of 0.72 (95% CI, 0.62 to 0.85; P < .001). The linear elevation of risk over pro-ENK quartiles 3, 2, and 1, with the fourth quartile as a reference, was 1.38 (95% CI, 0.73 to 2.64), 2.29 (95% CI, 1.26 to 4.15), and 3.16 (95% CI, 1.78 to 5.60; for the trend, P < .001), respectively. These results were replicated in the Malmö Preventive Project, where the continuous odds ratio for incident breast cancer was 0.63 (95% CI, 0.52 to 0.76; P < .001) and the risk over pro-ENK quartiles 3, 2, and 1, where the fourth quartile was the reference, was 2.48 (95% CI, 1.25 to 4.94), 2.94 (95% CI, 1.50 to 5.77), and 4.81 (95% CI, 2.52 to 9.18; for the trend, P < .001), respecitvely.Low fasting plasma concentration of the opioid precursor peptide pro-ENK is associated with an increased risk of future breast cancer in middle-aged and postmenopausal women.
Elimination In Vivo of Developing T Cells by Natural Killer Cells
Authors: Eckart Schott, Roberto Bonasio, Hidde L. Ploegh
Journal: The Journal of Experimental Medicine (2003)

Natural killer cells gauge the absence of self class I MHC on susceptible target cells by means of inhibitory receptors such as members of the Ly49 family. To initiate killing by natural killer cells, a lack of inhibitory signals must be accompanied by the presence of activating ligands on the target cell. Although natural killer cell–mediated rejection of class I MHC–deficient bone marrow (BM) grafts is a matter of record, little is known about the targeting in vivo of specific cellular subsets by natural killer cells. We show here that development of class I MHC–negative thymocytes is delayed as a result of natural killer cell toxicity after grafting of a class I MHC–positive host with class I MHC–negative BM. Double positive thymocytes that persist in the presence of natural killer cells display an unusual T cell receptor–deficient phenotype, yet nevertheless give rise to single positive thymocytes and yield mature class I MHC–deficient lymphocytes that accumulate in the class I MHC–positive host. The resulting class I MHC–deficient CD8 T cells are functional and upon activation remain susceptible to natural killer cell toxicity in vivo. Reconstitution of class I MHC–deficient BM precursors with H2-Kb by retroviral transduction fully restores normal thymic development.
An unusual case of refractory asthma
Authors: W.-T. N. Lee, A. Brown, S. Banham, H. Walker, M. Johnson
Journal: Thorax (2010)

<h3>Background and Objectives:</h3> Hypertriglyceridemia is perceived to promote atherosclerotic pathology, but its role in stroke has not been well defined. We aimed to assess the contribution of hypertriglyceridemia to residual vascular risk in patients with atherothrombotic stroke. <h3>Methods:</h3> The Tokyo Women’s Medical University Stroke Registry is an ongoing prospective, observational registry, in which 870 patients with acute ischemic stroke or TIA within 1 week of onset were consecutively enrolled and followed up for 1 year. Hypertriglyceridemia was defined as serum triglycerides levels of ≥150 mg/dL under fasting conditions. Significant stenosis of the cervicocephalic arteries was defined as having 50% or greater stenosis or occlusion. The primary outcome was major adverse cardiovascular events, including nonfatal stroke, nonfatal acute coronary syndrome, and vascular death. <h3>Results:</h3> Of 870 patients (mean age, 70.1 years; male, 60.9%), 217 (24.9%) had hypertriglyceridemia. High triglycerides levels were significantly associated with an increased prevalence of intracranial artery stenosis, particularly in the anterior circulation, rather than extracranial artery stenosis. Patients with hypertriglyceridemia had a greater risk of major adverse cardiovascular events than those without (annual rate, 20.9% vs. 9.7%; <i>P</i>&lt;0.001), even after adjustment for potential confounders, including baseline low-density lipoprotein cholesterol and statin use (adjusted hazard ratio, 2.46; 95% confidence interval, 1.62-3.74). The higher risk of vascular events in hypertriglyceridemia versus non-hypertriglyceridemia patients was observed among patients with stroke of atherothrombotic origin (n=174; annual rate, 35.1% vs. 14.2%; <i>P</i>=0.001), those with significant intracranial artery stenosis (n=247; annual rate, 29.9% vs. 14.7%; <i>P</i>=0.006), and those with significant extracranial carotid artery stenosis (n=123; annual rate, 23.0% vs. 9.4%; <i>P</i>=0.042). In contrast, hypertriglyceridemia was not predictive of recurrent vascular events in patients with cardioembolic stroke (n=221; annual rate, 19.1% vs. 10.5%; <i>P</i>=0.18). <h3>Discussion:</h3> Hypertriglyceridemia is an important modifiable risk factor that drives residual vascular risk in patients with stroke of atherothrombotic origin, even while on statin therapy. <h3>Trial Registration Information:</h3> The Tokyo Women’s Medical University Stroke Registry is registered at UMIN000031913 (https://upload.umin.ac.jp). <h3>Classification of Evidence:</h3> This study provides Class I evidence that in patients with atherothrombotic stroke, hypertriglyceridemia is associated with an increased risk of major cardiovascular events.
Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial
Authors: Eric Lawitz, Fred F Poordad, Phillip S Pang, Robert H Hyland, Xiao Ding, Hongmei Mo, William T Symonds, John G McHutchison, Fernando E Membreno
Journal: The Lancet (2013)
Upregulation of Steroidogenic Acute Regulatory Protein by Hypoxia Stimulates Aldosterone Synthesis in Pulmonary Artery Endothelial Cells to Promote Pulmonary Vascular Fibrosis
Authors: Bradley A. Maron, William M. Oldham, Stephen Y. Chan, Sara O. Vargas, Elena Arons, Ying-Yi Zhang, Joseph Loscalzo, Jane A. Leopold
Journal: Circulation (2014)

The molecular mechanism(s) regulating hypoxia-induced vascular fibrosis are unresolved. Hyperaldosteronism correlates positively with vascular remodeling in pulmonary arterial hypertension, suggesting that aldosterone may contribute to the pulmonary vasculopathy of hypoxia. The hypoxia-sensitive transcription factors c-Fos/c-Jun regulate steroidogenic acute regulatory protein (StAR), which facilitates the rate-limiting step of aldosterone steroidogenesis. We hypothesized that c-Fos/c-Jun upregulation by hypoxia activates StAR-dependent aldosterone synthesis in human pulmonary artery endothelial cells (HPAECs) to promote vascular fibrosis in pulmonary arterial hypertension.Patients with pulmonary arterial hypertension, rats with Sugen/hypoxia-pulmonary arterial hypertension, and mice exposed to chronic hypoxia expressed increased StAR in remodeled pulmonary arterioles, providing a basis for investigating hypoxia-StAR signaling in HPAECs. Hypoxia (2.0% FiO2) increased aldosterone levels selectively in HPAECs, which was confirmed by liquid chromatography-mass spectrometry. Increased aldosterone by hypoxia resulted from enhanced c-Fos/c-Jun binding to the proximal activator protein-1 site of the StAR promoter in HPAECs, which increased StAR expression and activity. In HPAECs transfected with StAR-small interfering RNA or treated with the activator protein-1 inhibitor SR-11302 [3-methyl-7-(4-methylphenyl)-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenoic acid], hypoxia failed to increase aldosterone, confirming that aldosterone biosynthesis required StAR activation by c-Fos/c-Jun. The functional consequences of aldosterone were confirmed by pharmacological inhibition of the mineralocorticoid receptor with spironolactone or eplerenone, which attenuated hypoxia-induced upregulation of the fibrogenic protein connective tissue growth factor and collagen III in vitro and decreased pulmonary vascular fibrosis to improve pulmonary hypertension in vivo.Our findings identify autonomous aldosterone synthesis in HPAECs attributable to hypoxia-mediated upregulation of StAR as a novel molecular mechanism that promotes pulmonary vascular remodeling and fibrosis.
Control of Hemoglobin Synthesis in Fetal Erythroid Cells by L‐Thyroxine
Authors: J. E. Fuhr, C. D. R. Dunn
Journal: American Journal of Hematology (1978)

Abstract Fetal mouse liver cells were incubated in the presence of L‐thyroxine. Globin synthesis by cells from the 13th to 15th days of gestation was stimulated by the presence of the hormone. Although protein synthesis by cells from the 17th day of gestation was stimulated, the protein was not identified as globin. A tentative conclusion was drawn that fetal erythroid tissue may be preferentially stimulated by thyroid hormone.
Polymyositis/dermatomyositis: the current position.
Authors: A Urbano-Marquez, J Casademont, J M Grau
Journal: Annals of the Rheumatic Diseases (1991)

Polymyositis/dermatomyositis are a hetero- geneous group of diseases characterised by skeletal muscle inflammation and necrosis.' 2 Since an excellent clinical description in 1903 by Steiner of dermatomyositis, which is essentially still valid,3 much progress has been made towards our understanding of this group of diseases.The most widely used clinical classification of idiopathic inflammatory myopathies is the one proposed by Bohan and Peter in 1975.4That was a landmark, providing guidelines in clinical practice to accurate diagnosis of inflammatory myopathies and standardisation of studies.Nonetheless, the classification was based on clinical data.In view of recent histological and immunological studies the clas- sification proposed by Karpati et al in 1987 seems better to fit our current view of such diseases5 (table 1).In this review we focus on recent developments in polymyositis/dermato- myositis, analysing separately the currently considered third major form of inflammatory myopathy-inclusion body myositis. EpidemiologyPolymyositis/dermatomyositis are the most commonly acquired myopathies in developed countries6 if we do not consider subclinical forms of toxic myopathies,7 but still fairly uncommon.No more than 5-10 new cases per million persons per year are diagnosed in the United States.8We have found a similar inci- dence in a large teaching hospital with dermato- logical clinic and muscle research unit.Never- theless, the true incidence of polymyositis/ dermatomyositis remains unknown for several reasons.Firstly, some patients with dermato- myositis are currently treated by their general practitioner because diagnosis is 'easy'.Secondly, some cases of polymyositis may have such an indolent clinical course that diagnosis is only made when a muscle biopsy is performed; some patients with polymyositis undergo diagnostic muscle biopsy after persistently raised serum creatine kinase activity with minimal or no clinical symptoms.Thirdly, there are few or no prospective studies of connective tissue disease associated myositis; fourthly, not all laboratories Muscle Research Unit, Tabl I Classification of idiopathic inflammatory
Relaxin Suppresses Atrial Fibrillation by Reversing Fibrosis and Myocyte Hypertrophy and Increasing Conduction Velocity and Sodium Current in Spontaneously Hypertensive Rat Hearts
Authors: Ashish Parikh, Divyang Patel, Charles F. McTiernan, Wenyu Xiang, Jamie Haney, Lei Yang, Bo Lin, Aaron D. Kaplan, Glenna C.L. Bett, Randall L. Rasmusson, Sanjeev G. Shroff, David Schwartzman, Guy Salama
Journal: Circulation Research (2013)

Rationale: Atrial fibrillation (AF) contributes significantly to morbidity and mortality in elderly and hypertensive patients and has been correlated to enhanced atrial fibrosis. Despite a lack of direct evidence that fibrosis causes AF, reversal of fibrosis is considered a plausible therapy. Objective: To evaluate the efficacy of the antifibrotic hormone relaxin (RLX) in suppressing AF in spontaneously hypertensive rats (SHR). Methods and Results: Normotensive Wistar-Kyoto (WKY) and SHR were treated for 2 weeks with vehicle (WKY+V and SHR+V) or RLX (0.4 mg/kg per day, SHR+RLX) using implantable mini-pumps. Hearts were perfused, mapped optically to analyze action potential durations, intracellular Ca 2+ transients, and restitution kinetics, and tested for AF vulnerability. SHR hearts had slower conduction velocity (CV; P &lt;0.01 versus WKY), steeper CV restitution kinetics, greater collagen deposition, higher levels of transcripts for transforming growth factor-β, metalloproteinase-2, metalloproteinase-9, collagen I/III, and reduced connexin 43 phosphorylation ( P &lt;0.05 versus WKY). Programmed stimulation triggered sustained AF in SHR (n=5/5) and SHR+V (n=4/4), but not in WKY (n=0/5) and SHR+RLX (n=1/8; P &lt;0.01). RLX treatment reversed the transcripts for fibrosis, flattened CV restitution kinetics, reduced action potential duration at 90% recovery to baseline, increased CV ( P &lt;0.01), and reversed atrial hypertrophy ( P &lt;0.05). Independent of antifibrotic actions, RLX (0.1 µmol/L) increased Na + current density, I Na (≈2-fold in 48 hours) in human cardiomyocytes derived from inducible pluripotent stem cells (n=18/18; P &lt;0.01). Conclusions: RLX treatment suppressed AF in SHR hearts by increasing CV from a combination of reversal of fibrosis and hypertrophy and by increasing I Na . The study provides compelling evidence that RLX may provide a novel therapy to manage AF in humans by reversing fibrosis and hypertrophy and by modulating cardiac ionic currents.
Change in Neurocognitive Functioning After Treatment With Cranial Radiation in Childhood
Authors: Brenda J. Spiegler, Eric Bouffet, Mark L. Greenberg, James T. Rutka, Donald J. Mabbott
Journal: Journal of Clinical Oncology (2004)

To evaluate the pattern of stability and change over time across multiple domains of neurocognitive function in radiated survivors of posterior fossa (PF) tumors.Thirty-four children (25 males) treated for malignant PF tumors were observed with serial clinical neuropsychologic assessments. Thirty patients were treated for medulloblastoma and four patients were treated for ependymoma. Twelve patients were treated with reduced-dose and 21 patients were treated with standard-dose cranial radiation. All patients received an additional boost to the PF. One patient was treated with PF radiation only. Standardized neuropsychologic tests were administered at different times after diagnosis for each child. The rate of change in scores was determined using a mixed model regression.Results showed a 2- to 4-point decline per year in intelligence scores. For our relatively young sample, intellectual function declined quickly in the first few years after treatment, and then more gradually. Significant declines in visual-motor integration, visual memory, verbal fluency, and executive functioning were also documented. No decline was evident for verbal memory and receptive vocabulary.Cranial radiation is associated with a decline in multiple neurocognitive domains, with a few notable exceptions. Our results must be interpreted in the context of common limitations of clinical research, including patient variability, changes in test versions, small sample size, and clinical referral bias.
A tight control treatment strategy aiming for remission in early rheumatoid arthritis is more effective than usual care treatment in daily clinical practice: a study of two cohorts in the Dutch Rheumatoid Arthritis Monitoring registry
Authors: Lydia G Schipper, Marloes Vermeer, Hillechiena H Kuper, Monique O Hoekstra, Cees J Haagsma, Alfons A Den Broeder, Piet van Riel, Jaap Fransen, Mart AFJ van de Laar
Journal: Annals of the Rheumatic Diseases (2011)

There is strong evidence from clinical trials that a 'treat to target' strategy is effective in reaching remission in rheumatoid arthritis (RA). However, the question is whether these results can be translated into daily clinical practice and clinical remission is a reachable target indeed. <h3>Objective</h3> The study aims to investigate whether in early RA a treatment strategy aiming at Disease Activity Score (DAS) 28 &lt;2.6 is more effective than 'usual care' treatment for reaching clinical remission after 1 year. <h3>Methods</h3> Two early RA inception cohorts from two different regions including patients who fulfilled the American College of Rheumatology criteria for RA were compared. Patients in the tight-control cohort (n=126) were treated according to a DAS28-driven step-up treatment strategy starting with methotrexate, addition of sulphasalazine (SSZ) and exchange of SSZ by anti-tumour necrosis factor in case of failure. Patients in the usual-care cohort (n=126) were treated with methotrexate or SSZ, without DAS28-guided treatment decisions. The primary outcome was the percentage remission (DAS28&lt;2.6) at 1 year. Time to first remission and change in DAS28 were secondary outcomes. <h3>Results</h3> After 1 year, 55% of tight-control patients had a DAS28&lt;2.6 versus 30% of usual care patients (OR 3.1, 95% CI 1.8 to 5.2). The median time to first remission was 25 weeks for tight control and more than 52 weeks for usual care (p&lt;0.0001). The DAS28 decreased with −2.5 in tight control and −1.5 in usual care (p&lt;0.0001). <h3>Conclusion</h3> In early RA, a tight control treatment strategy aiming for remission leads to more rapid DAS28 remission and higher percentages of remission after 1 year than does a usual care treatment.