tbuckley/cabot-search huggingface dataset:
First months of employment and new onset of rhinitis in adolescents
Authors: E. Riu, H. Dressel, D. Windstetter, G. Weinmayr, S. Weiland, C. Vogelberg, W. Leupold, E. von Mutius, D. Nowak, K. Radon
Journal: European Respiratory Journal (2007)

The aim of the present study was to investigate the incidence of rhinitis in adolescents, taking into account the duration and type of employment in holiday and vocational jobs, and to study latency until development of symptoms. Participants of the International Study of Asthma and Allergies in Childhood (ISAAC)-II study in Munich and Dresden (Germany), who were enrolled in 1995, were re-contacted by a postal questionnaire in 2002 (aged 16–18 yrs). The questionnaire focused on allergic rhinitis, type and duration of all jobs, and potential confounders. All jobs held for ≥8 h·week −1 and ≥1 month were coded and occupational exposure was assigned by a job-exposure matrix. Out of the 3,785 participants, 964 reported an employment history. The median (25th–75th percentile) duration of employment was 10 (1–16) months. After adjusting for potential confounders, those working in high-risk occupations (odds ratio (OR) 1.4, 95% confidence interval (CI) 1.0–2.1) had an increased risk for new onset of rhinitis, especially those exposed to low molecular weight agents (OR 1.8, 95% CI 1.1–2.8). The incidence of rhinitis was highest among those currently employed in a high-risk job for &lt;10 months. Teenagers who start working in high-risk occupations have a higher incidence of rhinitis compared with those not working. This increased risk might occur early on during employment.
The risk of lung cancer and mesothelioma after cessation of asbestos exposure: a prospective cohort study of shipyard workers
Authors: A Sandén, B Järvholm, S Larsson, G Thiringer
Journal: European Respiratory Journal (1992)

A prospective cohort study of 3,893 shipyard workers, mainly exposed to chrysotile, indicated no increased risk of lung cancer 7-15 yrs after exposure to asbestos had ceased. The shipyard workers, however, had an increased risk of pleural mesotheliomas with 11 observed cases versus 1.5 expected. An explanation for these observations may be that asbestos may have different carcinogenic mechanisms in causing lung cancer and mesothelioma. A non-increased risk of lung cancer some years after exposure to asbestos has stopped is in accordance with asbestos acting as a promotor. The high risk of mesothelioma, on the other hand, may indicate that asbestos acts as a complete carcinogen in developing this disease.
Indirect representation of grammatical class at the lexeme level
Authors: Michael H. Kelly
Journal: Behavioral and Brain Sciences (1999)

Lexemes supposedly represent phonological but not grammatical information. Phonological word substitutions pose problems for this account because the target and error almost always come from the same grammatical class. This grammatical congruency effect can be explained within the Levelt et al. lexicon given that (1) lexemes are organized according to phonological similarity and (2) lexemes from the same grammatical category share phonological properties.
The effect of plasma low density lipoprotein apheresis on the hepatic secretion of biliary lipids in humans
Authors: C G Hillebrant, B Nyberg, K Einarsson, M Eriksson
Journal: Gut (1997)

Background —The liver is a key organ in the metabolism of cholesterol in humans. It is the only organ by which substantial amounts of cholesterol are excreted from the body, either directly as free cholesterol into the bile or after conversion to bile acids. The major part of cholesterol synthesis in the body occurs in the liver. Cholesterol is also taken up by the liver from plasma lipoproteins. The relative contributions of newly synthesised cholesterol and plasma lipoprotein cholesterol to bile acid synthesis and biliary cholesterol secretion, respectively, are not known in detail. Aims —To determine how a rapid lowering of plasma low density lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterol influences the biliary secretion rates of cholesterol and bile acids in patients with cholesterol gallstones and complete biliary drainage. In this model with a completely interrupted enterohepatic circulation, the secretion of bile acids equals the new synthesis of bile acids in the liver. Patients —Eight patients with common bile duct stones of cholesterol type undergoing conventional cholecystectomy and choledocholithotomy. Methods —At operation a balloon occludable Foley catheter attached to a T tube was inserted into the bile duct with the balloon placed just past the distal limb of the T tube. The T tube was allowed to drain the bile externally. One week after the operation the Foley catheter balloon was inflated, creating complete biliary drainage. Twelve hours following the inflation plasma LDL apheresis was carried out for two hours. Bile was collected for 15 minute periods starting one hour before the apheresis and ending two hours after its termination. During the collection of bile, plasma lipids were analysed on several occasions. Results —The plasma level of LDL cholesterol decreased by 26% from (mean (SEM)) 2.19 (0.29) to 1.63 (0.17) mmol/l during the LDL apheresis while high density lipoprotein (HDL) cholesterol in plasma was unaffected. During LDL apheresis apolipoprotein B containing lipoproteins bind to the column, causing a significant decrease of not only plasma LDL but also of VLDL cholesterol. The secretion rate of bile acids decreased significantly by 31% from 131 (38) to 90 (16) μmol/15 minutes (p=0.045). The output of phospholipids also decreased by 19%. The biliary secretion rate of cholesterol was not, however, affected by the plasma LDL apheresis. Conclusions —The results suggest that, in patients with cholesterol gallstones and complete biliary drainage, lowering of plasma LDL and VLDL cholesterol reduces the biliary secretion rate—synthesis—of bile acids without affecting the biliary secretion rate of cholesterol.
Up-regulation of endothelial stretch-activated cation channels by fluid shear stress
Authors: Susanne Brakemeier, Ines Eichler, Hartmut Hopp, Ralf Köhler, Joachim Hoyer
Journal: Cardiovascular Research (2002)

Objective: Stretch-activated cation channels (SAC) have been suggested to act as endothelial mechanosensors for hemodynamic forces. Ca2+ influx through SAC could induce an intracellular Ca2+ signal stimulating Ca2+-dependent synthesis of vasodilators like NO, prostacyclin, or EDHF. In the present study we tested whether laminar shear stress (LSS) regulates SAC function. Methods: Electrophysiological properties of SAC were investigated in human umbilical vein endothelial cells (HUVEC) subjected to defined levels of LSS in a flow-cone apparatus. Results: In HUVEC, we identified a Ca2+ permeable SAC that was activated by membrane stretch. Single-channel current densities of SAC in cell-attached patches were significantly increased in HUVEC exposed to an LSS of 5 dyn/cm2 for 4 h (1.15±0.17 SAC/patch) compared to HUVEC kept in stationary culture (0.46±0.07 SAC/patch). Exposure of HUVEC to a higher LSS of 15 dyn/cm2 for 4 h induced similar up-regulation of SAC (1.27±0.21 SAC/patch). After 24 h exposure to LSS of 15 dyn/cm2, single-channel current densities of SAC remained up-regulated (1.07±0.18 SAC/patch) compared to controls. In addition, stretch-sensitivity of SAC (channel activity NPo at −30 mmHg) significantly increased after 2 h of exposure to LSS of 5 and 15 dyn/cm2 and remained up-regulated after 24 h. Inhibition of protein kinases and tyrosine kinases by H7 and genistein, respectively, prevented LSS-induced alteration of SAC function. Conclusion: Single-channel current density and mechanosensitivity of SAC in HUVEC is up-regulated by LSS. Up-regulation of SAC function leads to enhanced mechanosensitive Ca2+ influx, and represents a novel adaptive mechanism of the endothelium in the presence of altered hemodynamic forces.
Nonmalignant Diagnoses in Patients
Authors: Ann Partridge, Selim Nasser, Sunny Dzik
Journal: Journal of Clinical Oncology (2000)

Article Tools Nonmalignant Diagnoses in Patients Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.13.2635 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10893297 Nonmalignant Diagnoses in Patients Ann PartridgexAnn PartridgeSearch for articles by this author , Selim NasserxSelim NasserSearch for articles by this author , Sunny DzikxSunny DzikSearch for articles by this author Show More Departments of Medicine and Pathology; Dana-Farber Cancer Institute, Massachusetts General Hospital, and Harvard Medical School; Boston, MA https://doi.org/10.1200/JCO.2000.18.13.2635 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
Presenilin-1 regulates induction of hypoxia inducible factor-1α: altered activation by a mutation associated with familial Alzheimer's disease
Authors: Rita De Gasperi, Miguel A Gama Sosa, Stella Dracheva, Gregory A Elder
Journal: Molecular Neurodegeneration (2010)

Mutations in presenilin-1 (Psen1) cause familial Alzheimer's disease (FAD). Both hypoxia and ischemia have been implicated in the pathological cascade that leads to amyloid deposition in AD. Here we investigated whether Psen1 might regulate hypoxic responses by modulating induction of the transcription factor hypoxia inducible factor 1-α (HIF-1α).In fibroblasts that lack Psen1 induction of HIF-1α was impaired in response to the hypoxia mimetic cobalt chloride, as well as was induction by insulin and calcium chelation. Reintroduction of human Psen1 using a lentiviral vector partially rescued the responsiveness of Psen1-/- fibroblasts to cobalt chloride induction. HIF-1α induction did not require Psen1's associated γ-secretase activity. In addition, the failure of insulin to induce HIF-1α was not explicable on the basis of failed activation of the phosphatidylinositol 3-kinase (PI3K/Akt) pathway which activated normally in Psen1-/- fibroblasts. Rather we found that basal levels of HIF-1α were lower in Psen1-/- fibroblasts and that the basis for lower constitutive levels of HIF-1α was best explained by accelerated HIF-1α degradation. We further found that Psen1 and HIF-1α physically interact suggesting that Psen1 may protect HIF-1α from degradation through the proteasome. In fibroblasts harboring the M146V Psen1 FAD mutation on a mouse Psen1 null background, metabolic induction of HIF-1α by insulin was impaired but not hypoxic induction by cobalt chloride. Unlike Psen1-/- fibroblasts, basal levels of HIF-1α were normal in FAD mutant fibroblasts but activation of the insulin-receptor pathway was impaired. Interestingly, in Psen1-/- primary neuronal cultures HIF-1α was induced normally in response to cobalt chloride but insulin induction of HIF-1α was impaired even though activation of the PI3K/Akt pathway by insulin proceeded normally in Psen1-/- neuronal cultures. Basal levels of HIF-1α were not significantly different in Psen1-/- neurons and HIF-1α levels were normal in Psen1-/- embryos.Collectively these studies show that Psen1 regulates induction of HIF-1α although they indicate that cell type specific differences exist in the effect of Psen1 on induction. They also show that the M146V Psen1 FAD mutation impairs metabolic induction of HIF-1α, an observation that may have pathophysiological significance for AD.
Current and Potential Fields Generated by Two Dipoles
Authors: LUIGI DE AMBROGGI, BRUNO TACCARDI
Journal: Circulation Research (1970)

The distribution of currents and potentials in a circular conducting medium surrounding two eccentric dipoles was studied to establish how much information on the number, location, and orientation of the dipoles could be deduced from measurements of potential in the medium at various distances from the generators. When a single, eccentric dipole was active, the curve illustrating the distribution of potentials along the boundary exhibited different kinds of asymmetry, which revealed that the dipole was eccentric and gave some information about its orientation. When both dipoles were active, two maxima and two minima, revealing the presence of two generators, appeared along the boundary when the angle between dipole moments was 150° or more. Along internal circumferences two maxima and two minima appeared at smaller angles between dipole moments and the location of the maxima was closely related to that of the dipole anodes. When the dipoles lay on the same diameter and had opposite polarity, the presence of two generators was clearly detectable from boundary measurements, whereas vector representation was zero. These data improve our understanding of electrical signals recorded from the body surface, whether in the form of electrocardiograms, vectorcardiograms, or equipotential contour maps.
Identification of Lymphomyeloid Primitive Progenitor Cells in Fresh Human Cord Blood and in the Marrow of Nonobese Diabetic–Severe Combined Immunodeficient (NOD-SCID) Mice Transplanted with Human CD34+ Cord Blood Cells
Authors: Catherine Robin, Françoise Pflumio, William Vainchenker, Laure Coulombel
Journal: The Journal of Experimental Medicine (1999)

Transplantation of genetically marked donor cells in mice have unambiguously identified individual clones with full differentiative potential in all lymphoid and myeloid pathways. Such evidence has been lacking in humans because of limitations inherent to clonal stem cell assays. In this work, we used single cell cultures to show that human cord blood (CB) contains totipotent CD34+ cells capable of T, B, natural killer, and granulocytic cell differentiation. Single CD34+ CD19−Thy1+ (or CD38−) cells from fresh CB were first induced to proliferate and their progeny separately studied in mouse fetal thymic organotypic cultures (FTOCs) and cocultures on murine stromal feeder layers. 10% of the clones individually analyzed produced CD19+, CD56+, and CD15+ cells in stromal cocultures and CD4+CD8+ T cells in FTOCs, identifying totipotent progenitor cells. Furthermore, we showed that totipotent clones with similar lymphomyeloid potential are detected in the bone marrow of nonobese diabetic severe combined immunodeficient (NOD-SCID) mice transplanted 4 mo earlier with human CB CD34+ cells. These results provide the first direct demonstration that human CB contains totipotent lymphomyeloid progenitors and transplantable CD34+ cells with the ability to reconstitute, in the marrow of recipient mice, the hierarchy of hematopoietic compartments, including a compartment of functional totipotent cells. These experimental approaches can now be exploited to analyze mechanisms controlling the decisions of such primitive human progenitors and to design conditions for their ampification that can be helpful for therapeutic purposes.
Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group
Authors: Lieke H J Simkens, Harm van Tinteren, Anne May, Albert J ten Tije, Geert-Jan M Creemers, Olaf J L Loosveld, Felix E de Jongh, Frans L G Erdkamp, Zoran Erjavec, Adelheid M E van der Torren, Jolien Tol, Hans J J Braun, Peter Nieboer, Jacobus J M van der Hoeven, Janny G Haasjes, Rob L H Jansen, Jaap Wals, Annemieke Cats, Veerle A Derleyn, Aafke H Honkoop, Linda Mol, Cornelis J A Punt, Miriam Koopman
Journal: The Lancet (2015)
PGD and heteroplasmic mitochondrial DNA point mutations: a systematic review estimating the chance of healthy offspring
Authors: D.M.E.I. Hellebrekers, R. Wolfe, A.T.M. Hendrickx, I.F.M. de Coo, C.E. de Die, J.P.M. Geraedts, P.F. Chinnery, H.J.M. Smeets
Journal: Human Reproduction Update (2012)

Mitochondrial disorders are often fatal multisystem disorders, partially caused by heteroplasmic mitochondrial DNA (mtDNA) point mutations. Prenatal diagnosis is generally not possible for these maternally inherited mutations because of extensive variation in mutation load among embryos and the inability to accurately predict the clinical expression. The aim of this study is to investigate if PGD could be a better alternative, by investigating the existence of a minimal mutation level below which the chance of an embryo being affected is acceptably low, irrespective of the mtDNA mutation. We performed a systematic review of muscle mutation levels, evaluating 159 different heteroplasmic mtDNA point mutations derived from 327 unrelated patients or pedigrees, and reviewed three overrepresented mtDNA mutations (m.3243A>G, m.8344A>G and m.8993T>C/G) separately. Mutation levels were included for familial mtDNA point mutations only, covering all affected (n = 195) and unaffected maternal relatives (n = 19) from 137 pedigrees. Mean muscle mutation levels were comparable between probands and affected maternal relatives, and between affected individuals with tRNA- versus protein-coding mutations. Using an estimated a priori prevalence of being affected in pedigrees of 0.477, we calculated that a 95% or higher chance of being unaffected was associated with a muscle mutation level of 18% or less. At a mutation level of 18%, the predicted probability of being affected is 0.00744. The chance of being unaffected was lower only for the m.3243A>G mutation (P < 0.001). Most carriers of mtDNA mutations will have oocytes with mutation levels below this threshold. Our data show, for the first time, that carriers of heteroplasmic mtDNA mutations will have a fair chance of having healthy offspring, by applying PGD. Nevertheless, our conclusions are partly based on estimations and, as indicated, do not provide absolute certainty. Carriers of mtDNA should be informed about these constraints.
Defect of Pro-Hepatocyte Growth Factor Activation by Fibroblasts in Idiopathic Pulmonary Fibrosis
Authors: Sylvain Marchand-Adam, Aurélie Fabre, Arnaud André Mailleux, Joelle Marchal, Christophe Quesnel, Hiroaki Kataoka, Michel Aubier, Monique Dehoux, Paul Soler, Bruno Crestani
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Hepatocyte growth factor (HGF) protects against lung fibrosis in several animal models. Pro-HGF activation to HGF is subjected to regulation by its activator (HGFA), a serine protease, and HGFA-specific inhibitors (HAI-1 and HAI-2). Our hypothesis was that fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) had an altered capacity to activate pro-HGF in vitro compared with control fibroblasts.We measured the kinetics of pro-HGF activation in human lung fibroblasts from control subjects and from patients with IPF by Western blot. HGFA, HAI-1, and HAI-2 expression was evaluated by immunohistochemistry, RNA protection assay, and Western blot. We evaluated the effect of TGF-beta(1) and PGE(2) on pro-HGF activation and HGFA, HAI-1, and HAI-2 expression.Lung fibroblasts activated pro-HGF in vitro. Pro-HGF activation was inhibited by serine protease inhibitors, by an anti-HGFA antibody, as well as by HAI-1 and HAI-2. Pro-HGF activation by IPF fibroblasts was reduced compared with control fibroblasts. In IPF fibroblasts, HGFA expression was lower and HAI-1 and HAI-2 expression was higher compared with control fibroblasts. PGE(2) stimulated pro-HGF activation through increased expression of HGFA and decreased expression of its inhibitor HAI-2. In contrast, TGF-beta(1) reduced the ability of lung fibroblasts to activate pro-HGF through decreased expression of HGFA and increased expression of its inhibitors.IPF fibroblasts have a low capacity to activate pro-HGF in vitro via a low level of HGFA expression and high levels of HAI-1 and HAI-2 expression, and PGE(2) is able to partially correct this defect.
The IL-17A/IL-17RA Axis Plays a Proatherogenic Role via the Regulation of Aortic Myeloid Cell Recruitment
Authors: Matthew J. Butcher, Breanne N. Gjurich, Tracy Phillips, Elena V. Galkina
Journal: Circulation Research (2012)

Atherosclerosis is a disease of large- and medium-sized arteries that is characterized by chronic vascular inflammation. While the role of Th1, Th2, and T-regulatory subsets in atherogenesis is established, the involvement of IL-17A-producing cells remains unclear.To investigate the role of the IL-17A/IL-17RA axis in atherosclerosis.We bred apolipoprotein-E-deficient (Apoe(-/-)) mice with IL-17A-deficient and IL-17 receptor A-deficient mice to generate Il17a(-/-)Apoe(-/-) and Il17ra(-/-)Apoe(-/-) mice. Western diet fed Il17a(-/-)Apoe(-/-) and Il17ra(-/-)Apoe(-/-) mice had smaller atherosclerotic plaques in the aortic arch and aortic roots, but showed little difference in plaque burden in the thoracoabdominal aorta in comparison with Apoe(-/-) controls. Flow cytometric analysis of Il17a(-/-)Apoe(-/-) and Il17ra(-/-)Apoe(-/-) aortas revealed that deficiency of IL-17A/IL-17RA preferentially reduced aortic arch, but not thoracoabdominal aortic T cell, neutrophil, and macrophage content in comparison with Apoe(-/-) aortic segments. In contrast to ubiquitous IL-17RA expression throughout the aorta, IL-17A was preferentially expressed within the aortic arch of WD-fed Apoe(-/-) mice. Deficiency of IL-17A or IL-17RA reduced aortic arch, but not thoracoabdominal aortic TNFα and CXCL2 expression. Aortic vascular IL-17RA supports monocyte adherence to explanted aortas in ex vivo adhesion assays. Short-term homing experiments revealed that the recruitment of adoptively transferred monocytes and neutrophils to the aortas of Il17ra(-/-)Apoe(-/-) mice is impaired in comparison with Apoe(-/-) recipients.The IL-17A/IL-17RA axis increases aortic arch inflammation during atherogenesis through the induction of aortic chemokines, and the acceleration of neutrophil and monocyte recruitment to this site.
Nomogram to predict the presence of<i>EGFR</i>activating mutation in lung adenocarcinoma
Authors: Prasanta Raghab Mohapatra, Sachin Punatar, Kumar Prabhash
Journal: European Respiratory Journal (2012)

To the Editors:

Girard et al. [1] developed a nomogram to predict the presence of epidermal growth factor receptor ( EGFR ) activating mutations. Before using it in practice, however, the precision and limitations must be considered. Patient selection for tyrosine kinase inhibitors (TKIs) based exclusively on EGFR mutations is still controversial, because clinical response rates to TKI are nearly 70% in tumours harbouring EGFR activating mutations. Other factors, such as amplification of the EGFR gene and the activity of molecules downstream of EGFR, such as phosphorylated protein kinase B, and mutations of KRAS …
High prevalence of IgA class anti-neutrophil cytoplasmic antibodies (ANCA) is associated with increased risk of bacterial infection in patients with cirrhosis
Authors: Maria Papp, Nora Sipeki, Zsuzsanna Vitalis, Tamas Tornai, Istvan Altorjay, Istvan Tornai, Miklos Udvardy, Kai Fechner, Silvia Jacobsen, Bianca Teegen, Andrea Sumegi, Gabor Veres, Peter Laszlo Lakatos, Janos Kappelmayer, Peter Antal-Szalmas
Journal: Journal of Hepatology (2013)