tbuckley/cabot-search huggingface dataset:
Who Knows Whether Acrylamide in Food Is Hazardous to Humans?
Authors: F. Granath, M. Tornqvist
Journal: JNCI Journal of the National Cancer Institute (2003)

add tothe toxicologic evidence that acrylamide has the ability to inducegenetic damage in mammalian cells. Acrylamide or probablyglycidamide, its genotoxic metabolite, has a relatively low mu-tagenic potency and is likely to have a relatively small impact onthe overall cancer risk of an individual. However, because ratherhigh concentrations of acrylamide are found in frequently con-sumed foods, the total acrylamide burden to a population islarge. If one is willing to assume that a low-dose linear relation-ship between acrylamide exposure and carcinogenicity exists,then the contribution of acrylamide to the total cancer incidencein a population may be important. The expectedly low carcino-genicity will, however, create difficulties in applying epidemio-logic studies, and the uncertainties associated with extrapola-tions from experimental findings to potential risks make itdifficult to communicate to the general public.Data from cancer tests on rodents have been used to obtain aquantitative cancer risk estimate associated with acrylamide ex-posure
Functional disruption of α4 integrin mobilizes bone marrow–derived endothelial progenitors and augments ischemic neovascularization
Authors: Gangjian Qin, Masaaki Ii, Marcy Silver, Andrea Wecker, Evelyn Bord, Hong Ma, Mary Gavin, David A. Goukassian, Young-sup Yoon, Thalia Papayannopoulou, Takayuki Asahara, Marianne Kearney, Tina Thorne, Cynthia Curry, Liz Eaton, Lindsay Heyd, Deepika Dinesh, Raj Kishore, Yan Zhu, Douglas W. Losordo
Journal: The Journal of Experimental Medicine (2006)

The cell surface receptor α4 integrin plays a critical role in the homing, engraftment, and maintenance of hematopoietic progenitor cells (HPCs) in the bone marrow (BM). Down-regulation or functional blockade of α4 integrin or its ligand vascular cell adhesion molecule-1 mobilizes long-term HPCs. We investigated the role of α4 integrin in the mobilization and homing of BM endothelial progenitor cells (EPCs). EPCs with endothelial colony-forming activity in the BM are exclusively α4 integrin–expressing cells. In vivo, a single dose of anti–α4 integrin antibody resulted in increased circulating EPC counts for 3 d. In hindlimb ischemia and myocardial infarction, systemically administered anti–α4 integrin antibody increased recruitment and incorporation of BM EPCs in newly formed vasculature and improved functional blood flow recovery and tissue preservation. Interestingly, BM EPCs that had been preblocked with anti–α4 integrin ex vivo or collected from α4 integrin–deficient mice incorporated as well as control cells into the neovasculature in ischemic sites, suggesting that α4 integrin may be dispensable or play a redundant role in EPC homing to ischemic tissue. These data indicate that functional disruption of α4 integrin may represent a potential angiogenic therapy for ischemic disease by increasing the available circulating supply of EPCs.
Identification of the E1A-Regulated Transcription Factor p120E4F as an Interacting Partner of the RASSF1A Candidate Tumor Suppressor Gene
Authors: Sarah L. Fenton, Ashraf Dallol, Angelo Agathanggelou, Luke Hesson, Jalal Ahmed-Choudhury, Shairaz Baksh, Claude Sardet, Reinhard Dammann, John D. Minna, Julian Downward, Eamonn R. Maher, Farida Latif
Journal: Cancer Research (2004)

Abstract Epigenetic inactivation of the candidate tumor suppressor gene RASSF1A is a frequent and critical event in the pathogenesis of many human cancers. The RASSF1A protein contains a Ras association domain, suggesting a role in Ras-like signaling pathways, and has also been implicated in cell cycle progression. However, the preliminary data suggests that the RASSF1A gene product is likely to have multiple functions. To identify novel RASSF1A functions, we have sought to identify interacting proteins by yeast two-hybrid analysis in a human brain cDNA library. We identified the E1A-regulated transcription factor p120E4F as a RASSF1A interacting partner in yeast and mammalian cells, and demonstrated that RASSF1A protein and p120E4F form a complex in vivo. The interaction between RASSF1A and p120E4F was confirmed by both in vitro and in vivo pull downs and coimmunoprecipitation assays. In addition, specific inactivation of RASSF1A by short interfering RNA disrupts binding of RASSF1A to p120E4F in coimmunoprecipitation assays. In addition, we demonstrated enhanced G1 cell cycle arrest and S phase inhibition by propidium iodide staining of p120E4F in the presence of RASSF1A. As p120E4F has been reported previously to interact with p14ARF, retinoblastoma, and p53, these findings provide an important link between the function of RASSF1A and other major human tumor suppressor genes.
Giant Multiloculated Left Ventricular Outflow Tract Pseudoaneurysm Causing Severe Extrinsic Compression of Subpulmonic Infundibulum
Authors: Sudarshan Kumar Vijay, Ram Kirti Saran, Deepak Ameta, Rishi Sethi, Sharad Chandra, Sudhanshu Kumar Dwivedi, Varun Shankar Narain, Aniket Puri, Pallavi Aga, Neera Kohli
Journal: Circulation (2013)
The Role of Virus-Specific Cd8+ Cells in Liver Damage and Viral Control during Persistent Hepatitis B Virus Infection
Authors: Mala K. Maini, Carolina Boni, Chun Kyon Lee, Juan R. Larrubia, Stephanie Reignat, Graham S. Ogg, Abigail S. King, Jethro Herberg, Richard Gilson, Akeem Alisa, Roger Williams, Diego Vergani, Nikolai V. Naoumov, Carlo Ferrari, Antonio Bertoletti
Journal: The Journal of Experimental Medicine (2000)

Hepatitis B virus (HBV) is a noncytopathic virus, and the recognition of infected hepatocytes by HBV-specific CD8 cells has been assumed to be the central mechanism causing both liver damage and virus control. To understand the role of cytotoxic T cells in the pathogenesis of HBV infection, we used functional assays that require T cell expansion in vitro and human histocompatibility leukocyte antigen (HLA)-peptide tetramers that allow direct ex vivo quantification of circulating and liver-infiltrating HBV-specific CD8 cells. Two groups of patients with persistent HBV infection were studied: one without liver inflammation and HBV replication, the other with liver inflammation and a high level of HBV replication. Contrary to expectation, a high frequency of intrahepatic HBV-specific CD8 cells was found in the absence of hepatic immunopathology. In contrast, virus-specific T cells were more diluted among liver infiltrates in viremic patients, but their absolute number was similar because of the massive cellular infiltration. Furthermore, inhibition of HBV replication was associated with the presence of a circulating reservoir of CD8+ cells able to expand after specific virus recognition that was not detectable in highly viremic patients with liver inflammation. These results show that in the presence of an effective HBV-specific CD8 response, inhibition of virus replication can be independent of liver damage. When the HBV-specific CD8 response is unable to control virus replication, it may contribute to liver pathology not only directly but by causing the recruitment of nonvirus-specific T cells.
Genetic Disruption of Poly (ADP-Ribose) Synthetase Inhibits the Expression of P-Selectin and Intercellular Adhesion Molecule-1 in Myocardial Ischemia/Reperfusion Injury
Authors: Basilia Zingarelli, Andrew L. Salzman, Csaba Szabó
Journal: Circulation Research (1998)

Abstract —The nuclear enzyme poly (ADP-ribose) synthetase (PARS) has been shown to play an important role in the pathogenesis of ischemia/reperfusion injury and circulatory shock. The aim of this study was to investigate whether PARS activity may modulate endothelial-neutrophil interaction. We present evidence that genetic disruption of PARS provides protection against myocardial ischemia and reperfusion injury by inhibiting the expression of P-selectin and intercellular adhesion molecule-1 (ICAM-1) and, consequently, by inhibiting the recruitment of neutrophils into the jeopardized tissue. Furthermore, using in vitro studies, we demonstrate that in fibroblasts lacking a functional gene for PARS, cytokine-stimulated expression of ICAM-1 is significantly reduced compared with fibroblasts from animals with a normal genotype. Similarly, in cultured human endothelial cells, oxidative- or cytokine-dependent expression of P-selectin and ICAM-1 is reduced by pharmacological inhibition of PARS by 3-aminobenzamide. These findings provide the first direct evidence that PARS activation participates in neutrophil-mediated myocardial damage by regulating the expression of P-selectin and ICAM-1 in ischemic and reperfused myocardium, and they also provide the basis for a novel therapeutic approach for the treatment of reperfusion injury.
Improving Conventional Enhanced Permeability and Retention (EPR) Effects; What Is the Appropriate Target?
Authors: Hisataka Kobayashi, Rira Watanabe, Peter L. Choyke
Journal: Theranostics (2014)

Nano-sized therapeutic agents have several advantages over low molecular weight agents such as a larger loading capacity, the ability to protect the payload until delivery, more specific targeting due to multivalency and the opportunity for controlled/sustained release. However, the delivery of nano-sized agents into cancer tissue is problematic because it mostly relies on the enhanced permeability and retention (EPR) effect that depends on the leaky nature of the tumor vasculature and the prolonged circulation of nano-sized agents, allowing slow but uneven accumulation in the tumor bed. Delivery of nano-sized agents is dependent on several factors that influence the EPR effect; 1. Regional blood flow to the tumor, 2. Permeability of the tumor vasculature, 3. Structural barriers imposed by perivascular tumor cells and extracellular matrix, 4. Intratumoral pressure. In this review, these factors will be described and methods to enhance nano-agent delivery will be reviewed.
Two-Year Prospective Evaluation of the Relationship Between Acute Stress Disorder and Posttraumatic Stress Disorder Following Mild Traumatic Brain Injury
Authors: Allison G. Harvey, Richard A. Bryant
Journal: American Journal of Psychiatry (2000)

To assess the ability of acute stress disorder to predict posttraumatic stress disorder (PTSD), the relationship between acute stress disorder and PTSD over the 2 years following mild traumatic brain injury was determined.Survivors of motor vehicle accidents who sustained mild traumatic brain injuries were assessed for acute stress disorder within 1 month of the trauma (N=79) and for PTSD at 6 months (N=63) and 2 years (N=50) posttrauma.Acute stress disorder was diagnosed in 14% of the patients. Among the patients who participated in all three assessments, 80% of the subjects who met the criteria for acute stress disorder were diagnosed with PTSD at 2 years. Of the total initial group, 73% of those diagnosed with acute stress disorder had PTSD at 2 years.This study provides further support for the utility of the acute stress disorder diagnosis as a predictor of PTSD but indicates that the predictive power of the diagnostic criteria can be increased by placing greater emphasis on reexperiencing, avoidance, and arousal symptoms.
The diagnostic capacity of forced oscillation and forced expiration techniques in identifying asthma by isocapnic hyperpnoea of cold air
Authors: B Schmekel, HJ Smith
Journal: European Respiratory Journal (1997)

The measurement of forced expiratory volume in one second (FEV1) is often used to assess the effect of bronchial provocations, and deep inspiration is required beforehand. This may briefly alter the bronchial tone in a variable way in some subjects. The forced oscillation technique (FOT) is a test used to characterize the mechanical impedance of the respiratory system, and prior deep inspiration is not required. We tested the hypothesis that measurable bronchoconstriction would occur in all asthmatic subjects stimulated with isocapnic hyperventilation of dry cold air (IHCA). Twenty patients with mild asthma and nine healthy controls were exposed to IHCA, at 70% of their maximal voluntary ventilatory capacity for 4 min and the results were assessed both by applying the FOT and by measuring FEV1. Optimal cut-off levels were defined by receiver operating characteristic (ROC) curve analyses of the changes in respiratory resistance and reactance at 5-35 Hz, resonant frequency (fres) and FEV1. A positive result was present in the asthmatics when measured by FOT, and using ROC analyses the discriminative capacity to correctly diagnose asthma was greatest for responses in fres; the sensitivity was 89% and the specificity 100%. The sensitivity of FEV1 to correctly diagnose asthma was only 73%, and the specificity 88%. In conclusion, the results of this study suggest that the use of forced expiratory volume in one second for bronchial provocation tests by isocapnic hyperventilation of dry cold air may be misleading and that the bronchoconstriction thus elicited is measured with greater sensitivity and specificity by the forced oscillation technique than by forced expiratory volume in one second.
Epithelial-to-Mesenchymal Transition Activates PERK–eIF2α and Sensitizes Cells to Endoplasmic Reticulum Stress
Authors: Yu-xiong Feng, Ethan S. Sokol, Catherine A. Del Vecchio, Sandhya Sanduja, Jasper H.L. Claessen, Theresa A. Proia, Dexter X. Jin, Ferenc Reinhardt, Hidde L. Ploegh, Qiu Wang, Piyush B. Gupta
Journal: Cancer Discovery (2014)

Epithelial-to-mesenchymal transition (EMT) promotes both tumor progression and drug resistance, yet few vulnerabilities of this state have been identified. Using selective small molecules as cellular probes, we show that induction of EMT greatly sensitizes cells to agents that perturb endoplasmic reticulum (ER) function. This sensitivity to ER perturbations is caused by the synthesis and secretion of large quantities of extracellular matrix (ECM) proteins by EMT cells. Consistent with their increased secretory output, EMT cells display a branched ER morphology and constitutively activate the PERK-eIF2α axis of the unfolded protein response (UPR). Protein kinase RNA-like ER kinase (PERK) activation is also required for EMT cells to invade and metastasize. In human tumor tissues, EMT gene expression correlates strongly with both ECM and PERK-eIF2α genes, but not with other branches of the UPR. Taken together, our findings identify a novel vulnerability of EMT cells, and demonstrate that the PERK branch of the UPR is required for their malignancy.EMT drives tumor metastasis and drug resistance, highlighting the need for therapies that target this malignant subpopulation. Our findings identify a previously unrecognized vulnerability of cancer cells that have undergone an EMT: sensitivity to ER stress. We also find that PERK-eIF2α signaling, which is required to maintain ER homeostasis, is also indispensable for EMT cells to invade and metastasize.
A BOLD statement on how to case-find moderate/severe COPD
Authors: Irene Steenbruggen, Jan Zielinski, Peter Lange, David Price, Joan B. Soriano
Journal: European Respiratory Journal (2013)

Screening and case-finding strategies in chronic obstructive pulmonary disease (COPD) remain controversial, with strong opinions all over, and with any statement raising both interest and criticism. Yet, the success of an earlier diagnosis would undoubtedly produce substantial public health benefits. Expert consensus states that there are 210 million people in the world suffering from COPD [1], although these world estimates could be soon modified [2, 3]. Whatever the number, the vast majority of individuals with COPD (70–90%) are as yet undiagnosed [4], and therefore not receiving any medical care whatsoever. Even more importantly, many continue to smoke and/or are exposed to other risk factors. Therefore, any effective strategy to reduce COPD underdiagnosis is urgently needed.

In this issue of the European Respiratory Journal , Jithoo et al . [5] report on a collateral work from the landmark Burden of Lung Disease (BOLD) study, this time with a particular focus on the cost-effectiveness of different population case-finding strategies for COPD. They conclude that screening by using a simple pre-bronchodilator (BD) peak expiratory flow (PEF) measurement has the potential to serve as a cost-effective way to identify individuals most likely to benefit from confirmatory spirometry. Following the guidance of an earlier report [6], these authors expand on the PEF option with a sophisticated analysis, by …
Selective Suppression of Humoral Immunity by Antineoplastic Drugs
Authors: G H Heppner, P Calabresi
Journal: The Annual Review of Pharmacology and Toxicology (1976)

Since the spread of tobacco from the Americas hundreds of years ago, tobacco cigarettes and, more recently, alternative tobacco products have become global products of nicotine addiction. Within the evolving alternative tobacco product space, electronic ...Read More
Can Skin Prick Testing Thresholds Replace Oral Food Challenges In Population-based Studies And Community Screening Of Infants?
Authors: L.C. Gurrin, P.E. Martin, J.J. Koplin, R. Peters, N.J. Osborne, N.A. Bertalli, M.C. Matheson, A.J. Lowe, A. Ponsonby, M. Wake, M.L. Tang, S.C. Dharmage, K.J. Allen
Journal: Journal of Allergy and Clinical Immunology (2011)
Nonstochastic Coexpression of Activation Receptors on Murine Natural Killer Cells
Authors: Hamish R.C. Smith, Hubert H. Chuang, Lawrence L. Wang, Margarita Salcedo, Jonathan W. Heusel, Wayne M. Yokoyama
Journal: The Journal of Experimental Medicine (2000)

Murine natural killer cells (NK) express lectin-like activation and inhibitory receptors, including the CD94/NKG2 family of receptors that bind Qa-1, and the Ly-49 family that recognizes major histocompatibility complex class I molecules. Here, we demonstrate that cross-linking of NK cells with a new specific anti-Ly-49H mAb induced NK cell cytotoxicity and cytokine production. Ly-49H is expressed on a subset of NK cells and can be coexpressed with Ly-49 inhibitory receptors. However, unlike Ly-49 inhibitory receptors, Ly-49H is not detectable on naive splenic CD3(+) T cells, indicating that Ly-49H may be an NK cell-specific activation receptor. In further contrast to the stochastically expressed Ly-49 inhibitory receptors, Ly-49H is preferentially expressed with the Ly-49D activation receptor, and expression of both Ly-49H and Ly-49D is augmented on NK cells that lack receptors for Qa-1 tetramers. On developing splenic NK1.1(+) cells, Ly-49D and Ly-49H are expressed later than the inhibitory receptors. These results directly demonstrate that Ly-49H activates primary NK cells, and suggest that expression of Ly-49 activation receptors by NK cells may be specifically regulated on NK cell subsets. The simultaneous expression of multiple activation receptors by individual NK cells contrasts with that of T cell antigen receptors and is relevant to the role of NK cells in innate immunity.
Remission of asthma in the middle aged and elderly: report from the Obstructive Lung Disease in Northern Sweden study
Authors: E. Ronmark, E. Jonsson, B. Lundback
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Remission of asthma in adults has been considered to be low but is still not well documented. In children remission occurs with a rate estimated at approximately 50%. Remission of asthma in middle aged and elderly subjects was investigated as part of a population based study of respiratory diseases in Northern Sweden. <h3>METHODS</h3> In 1986 86% of 6610 subjects participated in a questionnaire survey. After a clinical validation study 300 subjects were diagnosed as having current asthma. In 1996 5935 subjects of the cohort could be traced for a third survey and 87% participated. Of the subjects with current asthma in 1986, 267 participated. In addition, 60 symptomatic subjects were classified as suspected asthma and 58 of them participated in 1996. Remission of asthma was defined as no recurrent wheeze, no attacks of shortness of breath, and no use of asthma medicines in 1996. <h3>RESULTS</h3> Remission of asthma during the 10 year period under study was 6%. In subjects with suspected asthma, remission occurred in 22%. The average annual remission rate was less than 1%. Remission was associated with previously mild disease and cessation of smoking. <h3>CONCLUSION</h3> Remission of asthma or the disappearance of its symptoms to an asymptomatic latent phase appeared to be rare in middle aged and elderly subjects.
Population Income and Longitudinal Trends in Living Kidney Donation in the United States
Authors: Jagbir Gill, Jianghu Dong, John Gill
Journal: Journal of the American Society of Nephrology (2014)

Living kidney donation is declining in the United States. We examined longitudinal trends in living donation as a function of median household income and donor relation to assess the effect of financial barriers on donation in a changing economic environment. The zip code-level median household income of all 71,882 living donors was determined by linkage to the 2000 US Census. Longitudinal changes in the rate of donation were determined in income quintiles between 1999 and 2004, when donations were increasing, and between 2005 and 2010, when donations were declining. Rates were adjusted for population differences in age, sex, race, and ESRD rate using multilevel linear regression models. Between 1999 and 2004, the rate of growth in living donation per million population was directly related to income, increasing progressively from the lowest to highest income quintile, with annualized changes of 0.55 (95% confidence interval [95% CI], 0.14 to 1.05) for Q1 and 1.77 (95% CI, 0.66 to 2.77) for Q5 (P<0.05). Between 2005 and 2010, donation declined in Q1, Q2, and Q3; was stable in Q4; and continued to grow in Q5. Longitudinal changes varied by donor relationship, and the association of income with longitudinal changes also varied by donor relationship. In conclusion, changes in living donation in the past decade varied by median household income, resulting in increased disparities in donation between low- and high-income populations. These findings may inform public policies to support living donation during periods of economic volatility.
Phase Ib Trial Trial of Rg7116, a Glycoengineered Monoclonal Antibody Targeting Her3, in Combination with Cetuximab or Erlotinib in Patients with Advanced/Metastatic Tumors of Epithelial Cell Origin Expressing Her3 Protein
Authors: U.N. Lassen, A. Cervantes Ruiperez, T. Fleitas, D. Meulendijks, J. Schellens, M. Lolkemar, M.J.A. De Jonge, S. Sleijfer, M. Mau-Soerensen, A. Taus, C. Adessi, A. Keelara, F. Michielin, B. Bossenmaier, G. Meneses-Lorente, I. James, W. Jacob, M. Weisser, M. Martinez-Garcia
Journal: Annals of Oncology (2014)
Neuregulin-1 Induces a Negative Inotropic Effect in Cardiac Muscle
Authors: Katrien Lemmens, Paul Fransen, Stanislas U. Sys, Dirk L. Brutsaert, Gilles W. De Keulenaer
Journal: Circulation (2004)

Background— Deficient cardiac neuregulin/ErbB signaling increases susceptibility to heart failure. In this study, we examined the effects of neuregulin-1 (NRG-1) on myocardial contractility. Methods and Results— NRG-1 (α and β isoforms) induced a negative inotropic effect in isolated rabbit papillary muscles and a rightward shift of the dose-response curve to isoproterenol. Both effects were attenuated by L-NMMA, which suggests a role for NO synthase. In cultured rat cardiomyocytes, NRG-1β enhanced nitrite production and resulted in phosphorylation of endothelial NO synthase and the serine/threonine kinase Akt. Conclusions— NRG-1 has negative inotropic effects that are preserved during β-adrenergic stimulation and activates endothelial NO synthase in cardiomyocytes.
Renal Inhibition of Pressor Responses to Drugs
Authors: J. W. MCCUBBIN, IRVINE H. PAGE
Journal: Circulation Research (1954)

Bilateral nephrectomy selectively augments reactivity to pressor drugs and affects that to angiotonin the most prominently. This change is not mediated through the central nervous system, does not depend upon mechanical exclusion of the renal vascular bed, and is not modified by change in sodium intake. The inhibitory action on pressor responsiveness is independent of renal excretory function.