tbuckley/cabot-search huggingface dataset:
Correlation of radio- and histomorphological pattern of pulmonary adenocarcinoma
Authors: Mathieu Lederlin, Michael Puderbach, Thomas Muley, Philipp A. Schnabel, Albrecht Stenzinger, Hans-Ulrich Kauczor, Claus Peter Heussel, Felix J. F. Herth, Hans Hoffmann, Hendrik Dienemann, Wilko Weichert, Arne Warth
Journal: European Respiratory Journal (2012)

Recently, a novel classification system based on tumour architecture and with high prognostic impact has been proposed for pulmonary adenocarcinomas (ADCs). For imaging-based prediction of histological ADC subtypes and, thus, prognosis, it is of paramount importance to investigate the correlations of radio- and histomorphological parameters. Associations between histomorphological ADC growth patterns (lepidic, acinar, papillary, micropapillary and solid) and data from pre-operative assessment by computed tomography (CT) imaging of 174 resected pulmonary ADCs were analysed. Margin configuration as well as solidity/ground glass opacity of an ADC was associated with distinct histomorphological ADC growth patterns. Solid-predominant ADCs usually had smooth margins and were also solid in CT scans, while lepidic-predominant ADCs had no predominant margin pattern, were located in the periphery, showed a positive bronchogram and were frequently associated with solidity/ground glass opacity. In addition, nonspherical tumour growth was a negative predictor of overall and disease-specific patient survival. We defined CT morphological parameters that were associated with histomorphological growth patterns of pulmonary ADCs. These data may form the basis for the development of future prognostic algorithms in the palliative setting, which include an integrated evaluation of biopsy histomorphology and CT scan morphology of nonresectable pulmonary ADC.
Enhanced Contractility and Decreased β-Adrenergic Receptor Kinase-1 in Mice Lacking Endogenous Norepinephrine and Epinephrine
Authors: Myeong-Chan Cho, Madhu Rao, Walter J. Koch, Steven A. Thomas, Richard D. Palmiter, Howard A. Rockman
Journal: Circulation (1999)

Background —Elevated circulating norepinephrine (NE) has been implicated in causing the profound β-adrenergic receptor (βAR) downregulation and receptor uncoupling that are characteristic of end-stage human dilated cardiomyopathy, a process mediated in part by increased levels of β-adrenergic receptor kinase (βARK1). To explore whether chronic sustained NE stimulation is a primary stimulus that promotes deterioration in cardiac signaling, we characterized a gene-targeted mouse in which activation of the sympathetic nervous system cannot lead to an elevation in plasma NE and epinephrine. Methods and Results —Gene-targeted mice that lack dopamine β-hydroxylase ( dbh −/− ), the enzyme needed to convert dopamine to NE, were created by homologous recombination. In vivo contractile response to the β 1 AR agonist dobutamine, measured by a high-fidelity left ventricular micromanometer, was enhanced in mice lacking the dbh gene. In unloaded adult myocytes isolated from dbh −/− mice, basal contractility was significantly increased compared with control cells. Furthermore, the increase in βAR responsiveness and enhanced cellular contractility were associated with a significant reduction in activity and protein level of βARK1 and increased high-affinity agonist binding without changes in βAR density or G-protein levels. Conclusions —Mice that lack the ability to generate NE or epinephrine show increased contractility associated primarily with a decrease in the level of βARK1 protein and kinase activity. This animal model will be valuable in testing whether NE is required for the pathogenesis of heart failure through mating strategies that cross the dbh −/− mouse into genetically engineered models of heart failure.
Scalable cell alignment on optical media substrates
Authors: Chukwuemeka G. Anene-Nzelu, Deepak Choudhury, Huipeng Li, Azmall Fraiszudeen, Kah-Yim Peh, Yi- Chin Toh, Sum Huan Ng, Hwa Liang Leo, Hanry Yu
Journal: Biomaterials (2013)
Immunology at the Maternal-Fetal Interface: Lessons for T Cell Tolerance and Suppression
Authors: A. L. Mellor, D. H. Munn
Journal: Annual Review of Immunology (2000)

Mammalian reproduction poses an immunological paradox because fetal alloantigens encoded by genes inherited from the father should provoke responses by maternal T cells leading to fetal loss. Current understanding of T cell immunobiology and the critical role of inflammatory processes during pregnancy is reviewed and discussed. Lessons derived from studies on the regulation of T cell responsiveness during mammalian gestation are considered in the wider context of T cell tolerance toward some microbial infections and tumors, avoidance of autoimmunity, and tissue allograft rejection.
Polygenic risk and the development and course of asthma: an analysis of data from a four-decade longitudinal study
Authors: Daniel W Belsky, Malcolm R Sears, Robert J Hancox, HonaLee Harrington, Renate Houts, Terrie E Moffitt, Karen Sugden, Benjamin Williams, Richie Poulton, Avshalom Caspi
Journal: The Lancet Respiratory Medicine (2013)

BackgroundGenome-wide association studies (GWAS) have discovered genetic variants that predispose individuals to asthma. To integrate these new discoveries with emerging models of asthma pathobiology, we aimed to test how genetic discoveries relate to developmental and biological characteristics of asthma.MethodsIn this prospective longitudinal study, we investigated a multilocus profile of genetic risk derived from published GWAS of asthma case status. We then tested associations between this genetic risk score and developmental and biological characteristics of asthma in participants enrolled in a population-based long-running birth cohort, the Dunedin Multidisciplinary Health and Development Study (n=1037). We used data on asthma onset, asthma persistence, atopy, airway hyper-responsiveness, incompletely reversible airflow obstruction, and asthma-related school and work absenteeism and hospital admissions obtained during nine prospective assessments spanning the ages of 9 to 38 years. Analyses included cohort members of European descent from whom genetic data had been obtained.FindingsOf the 880 cohort members included in our analysis, those at higher genetic risk developed asthma earlier in life than did those with lower genetic risk (hazard ratio [HR] 1·12, 95% CI 1·01–1·26). Of cohort members with childhood-onset asthma, those with higher genetic risk were more likely to develop life-course-persistent asthma than were those with a lower genetic risk (relative risk [RR] 1·36, 95% CI 1·14–1·63). Participants with asthma at higher genetic risk more often had atopy (RR 1·07, 1·01–1·14), airway hyper-responsiveness (RR 1·16, 1·03–1·32), and incompletely reversible airflow obstruction (RR 1·28, 1·04–1·57) than did those with a lower genetic risk. They were also more likely to miss school or work (incident rate ratio 1·38, 1·02–1·86) and be admitted to hospital (HR 1·38, 1·07–1·79) because of asthma. Genotypic information about asthma risk was independent of and additive to information derived from cohort members' family histories of asthma.InterpretationOur findings confirm that GWAS discoveries for asthma are associated with a childhood-onset phenotype. Genetic risk assessments might be able to predict which childhood-onset asthma cases remit and which become life-course-persistent, who might develop impaired lung function, and the burden of asthma in terms of missed school and work and hospital admissions, although these predictions are not sufficiently sensitive or specific to support immediate clinical translation.FundingUS National Institute on Aging and UK Medical Research Council.
Asymptomatic primary Epstein-Barr virus infection occurs in the absence of blood T-cell repertoire perturbations despite high levels of systemic viral load
Authors: Sharon L. Silins, Martina A. Sherritt, Jodie M. Silleri, Simone M. Cross, Suzanne L. Elliott, Mandvi Bharadwaj, Thuy T. T. Le, Leanne E. Morrison, Rajiv Khanna, Denis J. Moss, Andreas Suhrbier, Ihor S. Misko
Journal: Blood (2001)
Drug-Related Hepatotoxicity
Authors: Victor J. Navarro, John R. Senior
Journal: New England Journal of Medicine (2006)

Given its rarity, drug-related hepatotoxicity may not be seen during the initial clinical trials of a new medication. After approval, when many more patients are exposed, toxic effects that are very infrequent may emerge. This review explains the difficulties in identifying the cause of hepatotoxic effects in such situations and provides clinical guidance with regard to the detection, evaluation, and possible prevention of drug-related hepatotoxicity.
Automated measurement of unsaturated iron binding capacity is an effective screening strategy for C282Y homozygous haemochromatosis
Authors: P E Hickman
Journal: Gut (2000)

<h3>BACKGROUND</h3> C282Y hereditary haemochromatosis is an appropriate condition for population screening. Transferrin saturation, the best screening test to date, is relatively expensive, labour intensive, and cannot be automated. Unsaturated iron binding capacity is a surrogate marker of transferrin saturation and its measurement can be automated. <h3>AIMS</h3> To evaluate a screening strategy for C282Y hereditary haemochromatosis in a tertiary hospital environment based on unsaturated iron binding capacity as the initial screening test. <h3>METHODS</h3> Measurement of unsaturated iron binding capacity was adapted to the main laboratory analyser. An unsaturated iron binding capacity of less than 30 μmol/l was identified as an appropriate decision point and 5182 consecutive subjects were screened over 28 consecutive days. <h3>RESULTS</h3> Of those screened, 697 had an unsaturated iron binding capacity less than 30 μmol/l. Of these, transferrin saturation was greater than 40% in 294. A total of 227 were able to be genotyped for the C282Y mutation. Nine subjects homozygous for C282Y were identified. Based on full cost recovery, affected persons were identified at a cost of Aus$2268·77 per case (approximately US$1496). <h3>CONCLUSION</h3> Automated measurement of unsaturated iron binding capacity enables a cost effective, large scale population screening programme for C282Y hereditary haemochromatosis to be developed.
Placebo-controlled trial of vaccination with recombinant glycoprotein D of herpes simplex virus type 2 for immunotherapy of genital herpes
Authors: S.E Straus, B Savarese, P.R Krause, R.G Kost, J.L Meier, L Corey, G Barnum, R.L Burke, R Sekulovich, S.F Adair, C.L Dekker
Journal: The Lancet (1994)
Soluble Intercellular Adhesion Molecule-1, Soluble Vascular Adhesion Molecule-1, and the Development of Symptomatic Peripheral Arterial Disease in Men
Authors: Aruna D. Pradhan, Nader Rifai, Paul M. Ridker
Journal: Circulation (2002)

Background— Elevated levels of soluble cellular adhesion molecules have been linked to the development of occlusive coronary events in otherwise healthy individuals. It is not certain, however, whether similar relationships exist for the development of early systemic atherosclerosis. Methods and Results— In a prospective, nested case-control study conducted among 14 916 middle-aged men, we evaluated the relationship between baseline levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and the subsequent development of symptomatic peripheral arterial disease (PAD) during a 9-year follow-up period. Median levels of sICAM-1 but not sVCAM-1 were significantly higher at baseline among men who developed PAD than among those who did not (285.2 versus 267.8 ng/mL [ P =0.005] for sICAM-1 and 701.0 versus 709.3 ng/mL [ P =0.8] for sVCAM-1). In analyses adjusted for age and smoking, the odds ratio in the highest compared with the lowest quartile of sICAM-1 was 3.9 (95% CI 1.7 to 8.6; P trend =0.001). After additional adjustment for lipid and nonlipid risk factors, including C-reactive protein, elevated sICAM-1 remained significantly associated with subsequent PAD (OR 3.5, 95% CI 1.4 to 8.5, P trend =0.008). Whereas a monotonic dose-response relationship was evident over the full spectrum of ICAM-1 levels, elevated sVCAM-1 was not associated with future PAD in either age- and smoking-adjusted or fully adjusted models. Conclusions— Elevated levels of sICAM-1 are independently associated with the development of accelerated atherosclerosis among otherwise healthy men even in the absence of acute coronary occlusion.
HLA-B27 and gender independently determine the likelihood of a positive MRI of the sacroiliac joints in patients with early inflammatory back pain: a 2-year MRI follow-up study
Authors: M. van Onna, A. G. Jurik, D. van der Heijde, A. van Tubergen, L. Heuft-Dorenbosch, R. Landewe
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> To describe how inflammation on MRI of the sacroiliac joints in patients with recent-onset inflammatory back pain (IBP) evolves over time, and to study determinants of activity on MRI of the sacroiliac joint. <h3>Methods</h3> A 2-year follow-up study with annual MRI of the sacroiliac joints was conducted in patients with IBP of less than 2 years9 duration. Images were scored for bone marrow oedema on short τ inversion recovery and enhancement after administration of gadolinium on T1. <h3>Results</h3> Of the 68 patients (38% male; mean age 34.9±10.3 years) enrolled, 44 had a negative baseline MRI. Of these 44 patients, 39 patients had at least one follow-up MRI of whom six patients (15%) developed activity on MRI during follow-up. 24 patients (35%) had an abnormal MRI at baseline. In 23 of these 24 patients follow-up MRI was available. The MRI became negative in seven of these 23 patients (30%) during follow-up. Human leucocyte antigen B27 (HLA-B27) positivity and male gender determined independently the likelihood of a positive MRI at any time point. In an HLA-B27-positive patient the likelihood of a positive MRI during follow-up is 88% if the baseline MRI is positive and 27% if the baseline MRI is negative. In an HLA-B27-negative patient with a negative MRI at baseline the likelihood of a positive MRI during follow-up is less than 5%. <h3>Conclusions</h3> A positive MRI at baseline predicts a positive MRI during follow-up in HLA-B27-positive patients. A negative MRI at baseline in HLA-B27-negative patients strongly predicts a negative MRI during follow-up.
Women’s Ischemic Syndrome Evaluation
Authors: Elizabeth G. Nabel, Harry P. Selker, Robert M. Califf, John G. Canto, Jie J. Cao, Patrice Desvigne-Nikkens, Robert J. Goldberg, John R. Finnegan, Viola Vaccarino, Renu Virmani
Journal: Circulation (2004)

T he WISE workshop was convened to review results from the Women's Ischemic Syndrome Evaluation (WISE) study and other studies of ischemic heart disease to examine the nature and scope of gender differences in both chronic and acute cardiac ischemia, in terms of clinical manifestations, detection, and treatment.This section addresses research needs in the diagnosis and treatment of acute coronary syndromes in women and in the effective implementation of these findings into the community.
Musculoskeletal pain in Europe: its impact and a comparison of population and medical perceptions of treatment in eight European countries
Authors: A D Woolf
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objectives:</b> To describe the impact of musculoskeletal pain (MP); to compare management of MP by the population and by primary care physicians; and to identify misconceptions about treatment. <b>Methods:</b> 5803 people with MP and 1483 primary care physicians, randomly selected, in eight European countries were interviewed by telephone. A structured questionnaire was used to ask about usual management of MP and perceived benefits and risks of treatment. Current health status (SF-12) was also assessed. <b>Results:</b> From primary care physicians' perceptions, MP appears to be well managed. All presenting patients are offered some form of treatment, 90% or more doctors are trying to improve patients' quality of life, and most are aware and concerned about the risks of treatment with NSAIDs. From a population perspective, up to 27% of people with pain do not seek medical help and of those who do, several wait months/years before seeing a doctor. 55% or fewer patients who have seen a doctor are currently receiving prescription treatment for their pain. Communication between doctors and patients is poor; few patients are given information about their condition; and many have misconceptions about treatment. <b>Conclusions:</b> Management of MP is similar across eight European countries, but there is discordance between physician and patient perspectives of care. Some people with pain have never sought medical help despite being in constant/daily pain. Those who do seek help receive little written information or explanation and many have misperceptions about the benefits and risks of treatment that limit their ability to actively participate in decisions about their care.
1301 ENDOTOXIN CAUSES HIGH MORTALITY AND REDUCED HEPATIC SYNTHESIS OF ACUTE PHASE PROTEINS IN RATS WITH EXPERIMENTAL NON-ALCOHOLIC FATTY LIVER DISEASE
Authors: K.L. Thomsen, E. Glavind, J. George, H. Vilstrup, A. Clouston, L. Hebbard, H. Gronbak
Journal: Journal of Hepatology (2013)
Role of kinins and nitric oxide in the effects of angiotensin converting enzyme inhibitors on neointima formation.
Authors: R D Farhy, O A Carretero, K L Ho, A G Scicli
Journal: Circulation Research (1993)

Marked neointima formation occurs after balloon injury to the intima of rat arteries. Angiotensin II has been implicated as a growth factor in this process, since angiotensin converting enzyme (ACE) inhibitors block neointima formation after injury. However, ACE is an important kininase, and its inhibitors may act in part by a kinin-mediated mechanism. Kinins are also known to stimulate synthesis of endothelium-derived relaxing factor/nitric oxide (EDRF/NO) and prostacyclin, both of which have antigrowth effects. To determine whether the effect of ACE inhibitors on neointima formation is due to blockade of angiotensin II synthesis alone and/or inhibition of kinin inactivation, we followed two approaches. First, we compared the inhibition of neointima formation induced by the AT1-type angiotensin II receptor antagonist losartan with that caused by the ACE inhibitor ramipril. We also studied whether a kinin receptor antagonist, Hoe 140, blocks the effect of two different ACE inhibitors, ramipril and enalapril, on neointima formation. In addition, we studied whether the effect of ramipril is blocked by an NO synthesis inhibitor, N omega-nitro-L-arginine-methyl ester (L-NAME). Although both ramipril and losartan significantly reduced neointima formation, ramipril had a more marked effect (p &lt; 0.05 for ramipril versus losartan). The kinin antagonist Hoe 140 reduced the inhibitory effect of ramipril and enalapril by 73% and 62%, respectively. The remaining effect of the ACE inhibitors was now similar to that of losartan. Inhibition of neointima formation by ramipril was also blocked by the NO synthesis inhibitor L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)
Side Population Is Enriched in Tumorigenic, Stem-Like Cancer Cells, whereas ABCG2+ and ABCG2− Cancer Cells Are Similarly Tumorigenic
Authors: Lubna Patrawala, Tammy Calhoun, Robin Schneider-Broussard, Jianjun Zhou, Kent Claypool, Dean G. Tang
Journal: Cancer Research (2005)

Abstract Recently, several human cancers including leukemia and breast and brain tumors were found to contain stem-like cancer cells called cancer stem cells (CSC). Most of these CSCs were identified using markers that identify putative normal stem cells. In some cases, stem-like cancer cells were identified using the flow cytometry-based side population technique. In this study, we first show that ∼30% of cultured human cancer cells and xenograft tumors examined (∼30 in total) possess a detectable side population. Purified side population cells from two cell lines (U373 glioma and MCF7 breast cancer) and a xenograft prostate tumor (LAPC-9) are more tumorigenic than the corresponding non–side population cells. These side population cells also possess some intrinsic stem cell properties as they generate non–side population cells in vivo, can be further transplanted, and preferentially express some “stemness” genes, including Notch-1 and β-catenin. Because the side population phenotype is mainly mediated by ABCG2, an ATP-binding cassette half-transporter associated with multidrug resistance, we subsequently studied ABCG2+ and ABCG2− cancer cells with respect to their tumorigenicity in vivo. Although side population cells show increased ABCG2 mRNA expression relative to the non–side population cells and all cancer cells and xenograft tumors examined express ABCG2 in a small fraction (0.5-3%) of the cells, highly purified ABCG2+ cancer cells, surprisingly, have very similar tumorigenicity to the ABCG2− cancer cells. Mechanistic studies indicate that ABCG2 expression is associated with proliferation and ABCG2+ cancer cells can generate ABCG2− cells. However, ABCG2− cancer cells can also generate ABCG2+ cells. Furthermore, the ABCG2− cancer cells form more and larger clones in the long-term clonal analyses and the ABCG2− population preferentially expresses several “stemness” genes. Taken together, our results suggest that (a) the side population is enriched with tumorigenic stem-like cancer cells, (b) ABCG2 expression identifies mainly fast-cycling tumor progenitors, and (c) the ABCG2− population contains primitive stem-like cancer cells.