tbuckley/cabot-search huggingface dataset:
Adenosine A <sub>2a</sub> and A <sub>2b</sub> Receptors in Cultured Fetal Chick Heart Cells
Authors: Bruce T. Liang, Brett Haltiwanger
Journal: Circulation Research (1995)

Abstract Adenosine exerts pronounced biological effects in the heart cell. The role of multiple adenosine receptor subtypes in regulating the heart cell function is not known. Ventricular cells cultured from chick embryos 14 days in ovo were used to study a novel feature of heart cell regulation by the stimulatory adenosine receptors. The inhibitory adenosine A 1 receptor pathway was first inactivated by pertussis toxin treatment of the cultures, and the effects of adenosine agonists and antagonists on the heart cell contractile amplitude, measured via an opticovideo motion detection system, and on the modulation of cAMP level were determined. Adenosine and N -ethyladenosine-5′-uronic acid (NECA), capable of activating both the adenosine A 2a and A 2b receptors, caused a greater increase in the contractile amplitude than did the A 2a -selective agonist 2-[4-(2-carboxyethyl)phenylethylamino]-5′- N -ethylcarboxamidoadenosine ( CGS21680 ). NECA caused a biphasic increase in cAMP, which became monophasic in the presence of the A 2a receptor–selective antagonist 8-(3-chlorostyryl)caffeine, whereas the CGS21680 -induced cAMP response was monophasic. Blocking with 8-(3-chlorostyryl)caffeine abolished most of the CGS21680 -elicited contractile or cAMP response while attenuating only part of the adenosine- or NECA-stimulated responses. Blocking with the A 2b -selective antagonists 1,3-diethyl-8-phenylxanthine or alloxazine caused a more pronounced inhibition of the contractile or cAMP response by adenosine or NECA than by CGS21680 . Affinity of the A 2a receptor was 60-fold higher than that of the A 2b receptor. These data demonstrate that a functional A 2b receptor is expressed on the heart cell and is capable of mediating augmentation of cardiac myocyte contractility and that adenosine A 2a and A 2b receptors, with greatly different affinity, coexist and are coupled to the same functional responses. Taken together, the data suggest a novel feature of heart cell regulation, where the high-affinity A 2a receptor can play an important modulatory role in the presence of a low level of adenosine, whereas the low-affinity A 2b receptor becomes functionally important when the adenosine level is high.
Squamous Cell Carcinoma of the Lung: Molecular Subtypes and Therapeutic Opportunities
Authors: Pablo Perez-Moreno, Elisabeth Brambilla, Roman Thomas, Jean-Charles Soria
Journal: Clinical Cancer Research (2012)

Abstract Lung cancer is the leading cause of cancer-related deaths worldwide. Next to adenocarcinoma, squamous cell carcinoma (SCC) of the lung is the most frequent histologic subtype in non–small cell lung cancer. Encouraging new treatments (i.e., bevacizumab, EGFR tyrosine kinase inhibitors, and ALK inhibitors) have afforded benefits to patients with adenocarcinoma, but unfortunately the same is not true for SCC. However, many genomic abnormalities are present in SCC, and there is growing evidence of their biologic significance. Thus, in the short term, the molecular characterization of patients with SCC in modern profiling platforms will probably be as important as deciphering the molecular genetics of adenocarcinoma. Patients with SCC of the lung harboring specific molecular defects that are actionable (e.g., fibroblast growth factor receptor 1 amplification, discoidin domain receptor 2 mutation, and phosphoinositide 3-kinase amplification) should be enrolled in prospective clinical trials targeting such molecular defects. Clin Cancer Res; 18(9); 2443–51. ©2012 AACR.
Early growth characteristics and the risk of reduced lung function and asthma: A meta-analysis of 25,000 children
Authors: Herman T. den Dekker, Agnes M.M. Sonnenschein-van der Voort, Johan C. de Jongste, Isabella Anessi-Maesano, S. Hasan Arshad, Henrique Barros, Caroline S. Beardsmore, Hans Bisgaard, Sofia Correia Phar, Leone Craig, Graham Devereux, C. Kors van der Ent, Ana Esplugues, Maria P. Fantini, Claudia Flexeder, Urs Frey, Francesco Forastiere, Ulrike Gehring, Davide Gori, Anne C. van der Gugten, A. John Henderson, Barbara Heude, Jesús Ibarluzea, Hazel M. Inskip, Thomas Keil, Manolis Kogevinas, Eskil Kreiner-Møller, Claudia E. Kuehni, Susanne Lau, Erik Mélen, Monique Mommers, Eva Morales, John Penders, Katy C. Pike, Daniela Porta, Irwin K. Reiss, Graham Roberts, Anne Schmidt, Erica S. Schultz, Holger Schulz, Jordi Sunyer, Matias Torrent, Maria Vassilaki, Alet H. Wijga, Carlos Zabaleta, Vincent W.V. Jaddoe, Liesbeth Duijts
Journal: Journal of Allergy and Clinical Immunology (2015)
SITES OF WATER EXCHANGE BETWEEN THE MATERNAL SYSTEM AND THE AMNIOTIC FLUID OF RABBITS1
Authors: William M. Paul, Theodore Enns, Samuel R. M. Reynolds, Francis P. Chinard
Journal: Journal of Clinical Investigation (1956)

It is well established that there is rapid ex- change of water between the maternal circulation and the amniotic fluid in the guinea pig and the human (1-4).It has been suggested that amni- otic fluid may be formed, partly or entirely, by the amnion (5), by the fetal kidney (6, 7), by the fetal lung (8, 9) and in the buccal and nasal cavi- ties (10).It has been implied that the calculated rates of exchange of water represent real volumes of water crossing the barriers and that the sites of formation and of removal of amniotic fluid are not necessarily the same (7).Some of these sug- gestions and concepts would lead to the hypothesis that water entered the amniotic fluid by way of the placenta and the fetus and left by way of some other route, possibly across the fetal mem- branes; the system as a whole would then be a series one for water with "feed-back" from the amniotic fluid to the maternal system.Mainte- nance of the relative constancy of volume of the amniotic fluid would be the result of a steady state rather than of equilibrium with respect to water between amniotic and maternal fluids.3
Improved diagnosis of Duchenne/Becker muscular dystrophy.
Authors: A H Beggs, L M Kunkel
Journal: Journal of Clinical Investigation (1990)

Molecular genetics has revolutionized the way one should con- sider a patient with muscular dystrophy.The purpose of this Perspectives article is to set the parameters by which physi- cians may judge their neuromuscular patients in the context of recent advances in the understanding of both genetic and bio- chemical aspects of muscular dystrophy.We will first review some of the progress that has occurred over the past 5 years.This will illustrate how advances at the basic science level have led directly to powerful new diagnostic tests and, hence, to a new "molecular definition" of Duchenne and Becker muscu- lar dystrophies (DMD and BMD).'After discussing the strengths and weaknesses and appropriate use of these tests, we will end with specific examples of their use in a clinical setting.We hope this review will aid in the rapid transition of these tests from the research laboratory to routine clinical use.
Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening
Authors: E K O Ng, W W S Chong, H Jin, E K Y Lam, V Y Shin, J Yu, T C W Poon, S S M Ng, J J Y Sung
Journal: Gut (2009)

<h3>Objective:</h3> MicroRNAs (miRNAs) have been shown to offer great potential in the diagnosis of cancer. We investigated whether plasma miRNAs could discriminate between patients with and without colorectal cancer (CRC). <h3>Methods:</h3> This study was divided into three phases: (1) marker discovery using real-time PCR-based miRNA profiling on plasma, corresponding cancerous and adjacent non-cancerous colonic tissues of five patients with CRC, along with plasma from five healthy individuals as controls; (2) marker selection and validation by real-time quantitative RT-PCR on a small set of plasma; and (3) independent validation on a large set of plasma from 90 patients with CRC, 20 patients with gastric cancer, 20 patients with inflammatory bowel disease (IBD) and 50 healthy controls. <h3>Results:</h3> Of the panel of 95 miRNAs analysed, five were upregulated both in plasma and tissue samples. All the five miRNAs were validated on the plasma of 25 patients with CRC and 20 healthy controls. Both miR-17-3p and miR-92 were significantly elevated in the patients with CRC (p&lt;0.0005). The plasma levels of these markers were significantly reduced after surgery in 10 patients with CRC (p&lt;0.05). Further validation with an independent set of plasma samples (n = 180) indicated that miR-92 differentiates CRC from gastric cancer, IBD and normal subjects. This marker yielded a receiver operating characteristic curve area of 88.5%. At a cut-off of 240 (relative expression in comparison to RNU6B snRNA), the sensitivity was 89% and the specificity was 70% in discriminating CRC from control subjects. <h3>Conclusion:</h3> MiR-92 is significantly elevated in plasma of patients with CRC and can be a potential non-invasive molecular marker for CRC screening.
MECHANISM OF EOSINOPHILIA
Authors: Antony Basten, Paul B. Beeson
Journal: The Journal of Experimental Medicine (1970)

A possible role for the lymphocyte in the mechanism of eosinopoiesis has been examined. Procedures known to deplete or inactivate the pool of recirculating lymphocytes such as neonatal thymectomy, administration of antilymphocyte serum, and prolonged thoracic duct drainage, either singly or in combination, resulted in a highly significant reduction in the eosinophil response to trichinosis. Irradiated animals exposed to parasitic challenge did not develop eosinophilia unless reconstituted with lymphocytes as well as bone marrow cells. When "memory" cells were used instead of normal lymphocytes, a "secondary" type of eosinophil response was observed. Transfer of a primary eosinophilia was achieved adoptively with a population of living large lymphocytes from thoracic duct lymph and peripheral blood, but not with blood plasma or cell-free lymph. The potency of the active lymphocytes was not impaired by enclosing them in cell-tight diffusion chambers, indicating that they exerted an effect on bone marrow by agency of a diffusible factor. The demonstration of a role for lymphocytes in induction of the eosinophil response to this kind of stimulus supports the conclusion that eosinophilia belongs in the category of immunologic phenomena.
18F-Fluoroethylcholine PET/CT Identifies Lymph Node Metastasis in Patients with Prostate-Specific Antigen Failure After Radical Prostatectomy but Underestimates Its Extent
Authors: Derya Tilki, Oliver Reich, Anno Graser, Marcus Hacker, Jürgen Silchinger, Armin J. Becker, Wael Khoder, Peter Bartenstein, Christian G. Stief, Wolfgang Loidl, Michael Seitz
Journal: European Urology (2012)
P83 Validation of a novel Porcine-Resin thorax model for Chest drain insertion training
Authors: T. R. Naicker, E. A. Hughes, D. T. McLeod
Journal: Thorax (2010)

<h3>Objective</h3> Our poster at the 2009 winter BTS meeting described the Chest drain training module for CMT1 and CMT2 trainees in West Midlands Deanery. We have proceeded further to formally validate our novel Porcine–Resin thorax model for Chest drain insertion training by assessing the face, content, and construct validity of the model. <h3>Methods</h3> We recruited 82 doctors who work in General Medicine and Allied Specialties in Hospitals across West Midlands Deanery in UK. They were further divided into three groups as novice, intermediate and expert depending on the number of chest drains they had performed previously. During the study, they were asked to insert a chest drain using seldinger technique in the Porcine–Resin thorax model and their performance was recorded and marked anonymously using checklist scoring system. We developed the model using porcine ribs mounted on a resin cast of human thorax. All participants completed a questionnaire regarding the realism of the simulator after they completed 2 h of training and updated their skills using the model. In addition, the intermediate and expert groups also have given their views regarding the appropriateness of the simulator for training and assessment purposes. <h3>Results</h3> The expert group performed better than the intermediate group (p&lt;0.0001), which in turn performed better than the novices (p&lt;0.0001).The expert group rated the overall realism of the simulator at 5.2, Intermediate group at 5.4 and the Novice group at 5.26 on a seven-point Likert scale. No statistically significant differences were observed between the group mean scores. <h3>Conclusion</h3> Through this study we have demonstrated that our Porcine–Resin thorax model was able to discriminate between different levels of expertise (construct validity) in seldinger chest drain insertion. All the three groups have agreed that this offers a realistic experience in chest drain insertion training for residents (face validity) and in addition the experts believe that this model can also be used competency assessments.
Cachectin, Cachexia, and Shock
Authors: B Beutler, A Cerami
Journal: Annual Review of Medicine (1988)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Oncogenic Kit controls neoplastic mast cell growth through a Stat5/PI3-kinase signaling cascade
Authors: Noria Harir, Cédric Boudot, Katrin Friedbichler, Karoline Sonneck, Rudin Kondo, Séverine Martin-Lannerée, Lukas Kenner, Marc Kerenyi, Saliha Yahiaoui, Valérie Gouilleux-Gruart, Jean Gondry, Laurence Bénit, Isabelle Dusanter-Fourt, Kaïss Lassoued, Peter Valent, Richard Moriggl, Fabrice Gouilleux
Journal: Blood (2008)
Hepatocyte growth factor activates CCAAT enhancer binding protein and cell replication via PI3-kinase pathway
Authors: Min Kyung Cho, Sang Geon Kim
Journal: Hepatology (2003)

Hepatocyte growth factor (HGF), a ligand of c–Met receptor, stimulates activation of cellular kinases via phosphatidylinositol 3–kinase (PI3–kinase). CCAAT/enhancer binding protein (C/EBP) controls cell cycle progression. The present study was designed to determine whether HGF activates C/EBP in association with the S–phase entrance for cell replication and whether PI3–kinase contributes to the activation of C/EBP. Treatment of H4IIE cells, a hepatocyte–derived cell line, with HGF increased protein binding to the C/EBP binding site at an early time. Immunodepletion, subcellular fractionation, and confocal microscopic analyses showed that the HGF–induced C/EBP DNA binding activity depended on nuclear translocation of C/EBPβ. Whereas stable transfection of the p110 catalytic subunit of PI3–kinase enhanced HGF–mediated nuclear translocation of C/EBPβ and DNA binding, stable transfection of p85 subunit or chemical inhibition of PI3–kinase completely blocked C/EBP activation. HGF increased luciferase reporter activity in cells transfected with a mammalian cell expression vector containing -1.65 kilobase rGSTA2 promoter comprising C/EBP response element (pGL–1651). Whereas transfection with pCMV500, a control vector, allowed pGL–1651 to respond to HGF, expression of dominant negative mutant C/EBP completely inhibited the ability of HGF to stimulate the reporter gene expression. Flow cytometric analysis showed that HGF caused an increase in the area of S phase with a reciprocal decrease in that of G 1 phase, suggesting that HGF promoted cell cycle progression to S phase. In conclusion, HGF induces nuclear translocation of C/EBPβ via the PI3–kinase pathway and stimulates C/EBP DNA binding and gene transcription and that the PI3–kinase-mediated C/EBP activation by HGF may contribute to cell replication.
GSK-3α Promotes Oncogenic KRAS Function in Pancreatic Cancer via TAK1–TAB Stabilization and Regulation of Noncanonical NF-κB
Authors: Deepali Bang, Willie Wilson, Meagan Ryan, Jen Jen Yeh, Albert S. Baldwin
Journal: Cancer Discovery (2013)

Mutations in KRAS drive the oncogenic phenotype in a variety of tumors of epithelial origin. The NF-κB transcription factor pathway is important for oncogenic RAS to transform cells and to drive tumorigenesis in animal models. Recently, TGF-β-activated kinase 1 (TAK1), an upstream regulator of IκB kinase (IKK), which controls canonical NF-κB signaling, was shown to be important for chemoresistance in pancreatic cancer and for regulating KRAS-mutant colorectal cancer cell growth and survival. Here, we show that mutant KRAS upregulates glycogen synthase kinase 3α (GSK-3α), leading to its interaction with TAK1 to stabilize the TAK1-TAB complex to promote IKK activity. In addition, GSK-3α is required for promoting critical noncanonical NF-κB signaling in pancreatic cancer cells. Pharmacologic inhibition of GSK-3 suppresses growth of human pancreatic tumor explants, consistent with the loss of expression of oncogenic genes such as c-myc and TERT. These data identify GSK-3α as a key downstream effector of oncogenic KRAS via its ability to coordinately regulate distinct NF-κB signaling pathways.
The sugar hypothesis of heart disease never gathered supportive data
Authors: A. S. Truswell
Journal: BMJ (2013)

Although “sugar causes heart disease” might become a little more fashionable after Pure, White and Deadly is reissued, the scientific data and constructs will not change. Evidence for the fat hypothesis is massive and has increased since Yudkin’s book went out of print.

I think Watts conveys two wrong impressions about Yudkin’s disappointment that the sugar hypothesis was not confirmed.1 I was …
Duration of protection with RTS,S/AS02A malaria vaccine in prevention of Plasmodium falciparum disease in Mozambican children: single-blind extended follow-up of a randomised controlled trial
Authors: Pedro L Alonso, Jahit Sacarlal, John J Aponte, Amanda Leach, Eusebio Macete, Pedro Aide, Betuel Sigauque, Jessica Milman, Inacio Mandomando, Quique Bassat, Caterina Guinovart, Mateu Espasa, Sabine Corachan, Marc Lievens, Margarita M Navia, Marie-Claude Dubois, Clara Menendez, Filip Dubovsky, Joe Cohen, Ricardo Thompson, W Ripley Ballou
Journal: The Lancet (2005)
Association of β-Blocker Therapy With Risks of Adverse Cardiovascular Events and Deaths in Patients With Ischemic Heart Disease Undergoing Noncardiac Surgery
Authors: Charlotte Andersson, Charlotte Mérie, Mads Jørgensen, Gunnar H. Gislason, Christian Torp-Pedersen, Charlotte Overgaard, Lars Køber, Per Føge Jensen, Mark A. Hlatky
Journal: JAMA Internal Medicine (2013)

<h3>Importance</h3> Clinical guidelines have been criticized for encouraging the use of β-blockers in noncardiac surgery despite weak evidence. Relevant clinical trials have been small and have not convincingly demonstrated an effect of β-blockers on hard end points (ie, perioperative myocardial infarction, ischemic stroke, cardiovascular death, and all-cause death). <h3>Objective</h3> To assess the association of β-blocker treatment with major cardiovascular adverse events (MACE) and all-cause mortality in patients with ischemic heart disease undergoing noncardiac surgery. <h3>Design, Setting, Participants, and Exposure</h3> Individuals with ischemic heart disease with or without heart failure (HF) and with and without a history of myocardial infarction undergoing noncardiac surgery between October 24, 2004, and December 31, 2009, were identified from nationwide Danish registries. Adjusted Cox regression models were used to calculate the 30-day risks of MACE (ischemic stroke, myocardial infarction, or cardiovascular death) and all-cause mortality associated with β-blocker therapy. <h3>Main Outcomes and Measures</h3> Thirty-day risk of MACE and all-cause mortality. <h3>Results</h3> Of 28 263 patients with ischemic heart disease undergoing surgery, 7990 (28.3%) had HF and 20 273 (71.7%) did not. β-Blockers were used in 4262 (53.3%) with and 7419 (36.6%) without HF. Overall, use of β-blockers was associated with a hazard ratio (HR) of 0.91 (95% CI, 0.81-1.02) for MACE and 0.95 (0.85-1.06) for all-cause mortality. Among patients with HF, use of β-blockers was associated with a significantly lower risk of MACE (HR, 0.78; 95% CI, 0.67-0.90) and all-cause mortality (0.80; 0.70-0.92), whereas among patients without HF, there was no significant association of β-blocker use with MACE (1.11; 0.94-1.31) or mortality (1.15; 0.98-1.35) (<i>P</i>&lt; .001 for interactions). Among patients without HF, β-blockers were also associated with a lowered risk among those with a recent myocardial infarction (&lt;2 years), with HRs of 0.60 (95% CI, 0.42-0.86) for MACE and 0.80 (0.53-1.21) for all-cause mortality (<i>P</i>&lt; .02 for interactions between β-blockers and time period after myocardial infarction), but with no significant association in the remaining patients. Results were similar in propensity score–matched analyses. <h3>Conclusions and Relevance</h3> Among patients with ischemic heart disease undergoing noncardiac surgery, use of β-blockers was associated with lower risk of 30-day MACE and mortality only among those with HF or recent myocardial infarction.
Colorectal Cancer Risk Associated with Hormone Use Varies by Expression of Estrogen Receptor-β
Authors: Anja Rudolph, Csaba Toth, Michael Hoffmeister, Wilfried Roth, Esther Herpel, Peter Schirmacher, Hermann Brenner, Jenny Chang-Claude
Journal: Cancer Research (2013)

The risk of colorectal cancer is reduced among users of oral contraceptives or menopausal hormone therapy, but associations with reproductive characteristics that are markers of a woman's endogenous hormone milieu have not been consistently observed. To help understand possible mechanisms through which exogenous and endogenous hormonal exposures are involved in colorectal cancer, we assessed the risk of these malignancies according to tumor expression of estrogen receptor-β (ESR2). In a population-based study of postmenopausal women (503 cases and 721 controls matched for sex and age), immunohistochemical expression of ESR2 was determined in 445 cases of incident colorectal cancer. Unconditional logistic regression was used in case-case analyses to assess heterogeneity between risk associations according to ESR2 status and in case-control analyses to estimate associations separately for ESR2-negative and ESR2-positive tumors. For ESR2-positive tumors but not ESR2-negative tumors, colorectal cancer risk significantly decreased with duration of oral contraceptive use [per five-year increments OR ESR2-positive, 0.87, 95% confidence interval (CI), 0.77-0.99; OR ESR2-negative, 1.02, 95% CI, 0.91-1.15; Pheterogeneity = 0.07] and with duration of menopausal hormone therapy use (per five-year increments OR ESR2-positive, 0.84, 95% CI, 0.74-0.95; OR ESR2-negative, 0.94, 95% CI 0.84-1.05; Pheterogeneity = 0.06). Significant heterogeneity according to ESR2 expression was found for the association with current use of menopausal hormone therapy (<0.5 years ago; Pheterogeneity = 0.023) but not for associations with reproductive factors. In conclusion, our results suggest that hormone use decreases risk for ESR2-positive but not ESR2-negative colorectal cancer.