tbuckley/cabot-search huggingface dataset:
International Union of Basic and Clinical Pharmacology. LXXXVIII. G Protein-Coupled Receptor List: Recommendations for New Pairings with Cognate Ligands
Authors: Anthony P. Davenport, Stephen P. H. Alexander, Joanna L. Sharman, Adam J. Pawson, Helen E. Benson, Amy E. Monaghan, Wen Chiy Liew, Chidochangu P. Mpamhanga, Tom I. Bonner, Richard R. Neubig, Jean Philippe Pin, Michael Spedding, Anthony J. Harmar
Journal: Pharmacological Reviews (2013)

In 2005, the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) published a catalog of all of the human gene sequences known or predicted to encode G protein-coupled receptors (GPCRs), excluding sensory receptors. This review updates the list of orphan GPCRs and describes the criteria used by NC-IUPHAR to recommend the pairing of an orphan receptor with its cognate ligand(s). The following recommendations are made for new receptor names based on 11 pairings for class A GPCRs: hydroxycarboxylic acid receptors [HCA<sub>1</sub> (<i>GPR81</i>) with lactate, HCA<sub>2</sub> (<i>GPR109A</i>) with 3-hydroxybutyric acid, HCA<sub>3</sub> (<i>GPR109B</i>) with 3-hydroxyoctanoic acid]; lysophosphatidic acid receptors [LPA<sub>4</sub> (GPR23), LPA<sub>5</sub> (<i>GPR92</i>), LPA<sub>6</sub> (<i>P2Y5</i>)]; free fatty acid receptors [FFA4 (<i>GPR120</i>) with omega-3 fatty acids]; chemerin receptor (<i>CMKLR1</i>; ChemR23) with chemerin; <i>CXCR7</i> (<i>CMKOR1</i>) with chemokines CXCL12 (SDF-1) and CXCL11 (ITAC); succinate receptor (<i>SUCNR1</i>) with succinate; and oxoglutarate receptor [<i>OXGR1</i> with 2-oxoglutarate]. Pairings are highlighted for an additional 30 receptors in class A where further input is needed from the scientific community to validate these findings. Fifty-seven human class A receptors (excluding pseudogenes) are still considered orphans; information has been provided where there is a significant phenotype in genetically modified animals. In class B, six pairings have been reported by a single publication, with 28 (excluding pseudogenes) still classified as orphans. Seven orphan receptors remain in class C, with one pairing described by a single paper. The objective is to stimulate research into confirming pairings of orphan receptors where there is currently limited information and to identify cognate ligands for the remaining GPCRs. Further information can be found on the IUPHAR Database website (http://www.iuphar-db.org).
Follicular mucinosis in Hodgkin's disease: A poor prognostic sign?
Authors: M. Stewart, B.R. Smoller
Journal: Journal of the American Academy of Dermatology (1991)

A wide range of nonspecific cutaneous manifestations have been associated with Hodgkin's disease.These include urticaria, erythema multiforme, bullous lesions, erythroderma, and psoriasiform eruptions.I Such paraneoplastic phenomena have been noted in from 17% to 53% of Hodgkin's disease cases.In contrast, specific tumor-relatedinfiltrates are seen in only about 3% ofcases. 2 Follicular mucinosis is often associated with cutaneous T cell lymphomas but rarely with Hodgkin's disease.We report a case of follicular mucinosis in a 20-year-old man with Hodgkin's disease.This case, as well as the only other three we are aware of with this association, had a fatal outcome within 3 years of development of follicular mucinosis.
Y-Box Protein 1 Mediates PDGF-B Effects in Mesangioproliferative Glomerular Disease
Authors: Claudia R.C. van Roeyen, Frank Eitner, Sandra Martinkus, Sabrina R. Thieltges, Tammo Ostendorf, Dirk Bokemeyer, Bernhard Lu[Combining Diaeresis]scher, Juliane M. Lu[Combining Diaeresis]scher-Firzlaff, Juergen Floege, Peter R. Mertens
Journal: Journal of the American Society of Nephrology (2005)

The pivotal role of PDGF-B for mesangioproliferative glomerular disease is well established. Here, Y-box protein-1 (YB-1) was identified as a downstream signaling target of PDGF-B. In healthy kidney cells, YB-1 was located predominantly within the nuclear compartment. Subsequent to PDGF-B infusion and in the course of anti-Thy1.1-induced mesangioproliferative glomerulonephritis, relocalization of YB-1 into the cytoplasm was observed. In experimental models that lack profound mesangial cell proliferation (e.g., Puromycin-nephrosis, passive Heyman nephritis, spontaneous normotensive nephrosclerosis, hyperlipidemic diabetic nephropathy), YB-1 remained nuclear. This translocation coincided with upregulation of YB-1 protein levels within the mesangial compartment. Increased YB-1 expression and subcellular shuttling was dependent on PDGF-B signaling via the mitogen-activated protein kinase pathway because these alterations were prevented by specific PDGF aptamers and the mitogen-activated protein kinase pathway inhibitor U0126. Furthermore, PDGF-B strongly induced YB-1 expression in vitro. This induction was important because RNAi-dependent knockdown of YB-1 abolished the mitogenic PDGF-B effect. Taken together, YB-1 seems to represent a specific and necessary PDGF-B target in mesangioproliferative glomerular disease.
Simple tools for understanding risks: from innumeracy to insight
Authors: G. Gigerenzer
Journal: BMJ (2003)

<b>Objective</b> To investigate the effect of Fluticasone Propionate/Salmeterol on exercise endurance and pulmonary function in patients with moderate-severe COPD. <b>Methods</b> 53 patients with moderate-severe COPD were randomly divided to two groups. Treatment group inhaled dry powder SFC(salmeterol 50ug, fluticasone Propionate 250ug) twice daily for 24 weeks. Control group got symptomatic treatment for 24 weeks. Predose and postdose pulmonary and cycle cardiopulmonary exercise test evaluations were compared. <b>Results</b> There were no difference in predose pulmonary and CPET between two groups. In treatment group, With SFC treatment for 24weeks, FVC, FEV<sub>1</sub>, IC were significient increased; ITGV,RV and TLV were significient decreased(<i>p</i>&lt;0.05); Peak WR increased, but had no statisticly difference. Peak VO<sub>2</sub>, peak VO<sub>2</sub>/Kg, peak VCO<sub>2</sub>, peak O<sub>2</sub> pulse, peak VE were significient increased(<i>p</i>&lt;0.05); VD/VT and lowest VE/VCO2 were decreased from (<i>p</i>&lt;0.05); postdose improvement in IC was significantly correlated with the increase in Peak VO2, Peak VO2/Kg, Peak VE, VD/VT and Lowest VE/VCO<sub>2</sub>,but not with FEV<sub>1</sub>. Predose and postdose pulmonary and CPET were no changes in control group. <b>Conclusion</b> Exercise tolerance in patients with moderate-severe COPD were distinguished impaired. After long term SFC treatment, lung hyperinflation at rest and exercise were decreased, exercise endurance were increased when compared with symptomatic treatment. CPET is useful in COPD patients as it allows objective measurement of the exercise tolerance and evaluation of the response to therapeutic intervention.
Generation of polyclonal plasmablasts from peripheral blood B cells: a normal counterpart of malignant plasmablasts
Authors: Karin Tarte, John De Vos, Thomas Thykjaer, Fenghuang Zhan, Geneviève Fiol, Valérie Costes, Thierry Rème, Eric Legouffe, Jean-François Rossi, John Shaughnessy, Torben F. Ørntoft, Bernard Klein
Journal: Blood (2002)
Remnant Cholesterol, Low-Density Lipoprotein Cholesterol, and Blood Pressure as Mediators From Obesity to Ischemic Heart Disease
Authors: Anette Varbo, Marianne Benn, George Davey Smith, Nicholas J. Timpson, Anne Tybjærg-Hansen, Børge G. Nordestgaard
Journal: Circulation Research (2014)

Rationale: Obesity leads to increased ischemic heart disease (IHD) risk, but the risk is thought to be mediated through intermediate variables and may not be caused by increased weight per se. Objective: To test the hypothesis that the increased IHD risk because of obesity is mediated through lipoproteins, blood pressure, glucose, and C-reactive protein. Methods and Results: Approximately 90 000 participants from Copenhagen were included in a Mendelian randomization design with mediation analyses. Associations were examined using conventional measurements of body mass index and intermediate variables and using genetic variants associated with these. During ≤22 years of follow-up 13 945 participants developed IHD. The increased IHD risk caused by obesity was partly mediated through elevated levels of nonfasting remnant cholesterol and low-density lipoprotein cholesterol, through elevated blood pressure, and possibly also through elevated nonfasting glucose levels; however, reduced high-density lipoprotein cholesterol and elevated C-reactive protein levels were not mediators in genetic analyses. The 3 intermediate variables that explained the highest excess risk of IHD from genetically determined obesity were low-density lipoprotein cholesterol with 8%, systolic blood pressure with 7%, and remnant cholesterol with 7% excess risk of IHD. Corresponding observational excess risks using conventional body mass index were 21%, 11%, and 20%, respectively. Conclusions: The increased IHD risk because of obesity was partly mediated through elevated levels of nonfasting remnant and low-density lipoprotein cholesterol and through elevated blood pressure. Our results suggest that there may be benefit to gain by reducing levels of these risk factors in obese individuals not able to achieve sustained weight loss.
Histamine receptor 2 modifies dendritic cell responses to microbial ligands
Authors: Remo Frei, Ruth Ferstl, Patrycja Konieczna, Mario Ziegler, Tunde Simon, Tulia Mateus Rugeles, Susanne Mailand, Takeshi Watanabe, Roger Lauener, Cezmi A. Akdis, Liam O'Mahony
Journal: Journal of Allergy and Clinical Immunology (2013)
Coffee Consumption Enhances High-Density Lipoprotein-Mediated Cholesterol Efflux in Macrophages
Authors: Harumi Uto-Kondo, Makoto Ayaori, Masatsune Ogura, Kazuhiro Nakaya, Mai Ito, Atsushi Suzuki, Shun-ichi Takiguchi, Emi Yakushiji, Yoshio Terao, Hideki Ozasa, Tetsuya Hisada, Makoto Sasaki, Fumitaka Ohsuzu, Katsunori Ikewaki
Journal: Circulation Research (2010)

Association of habitual coffee consumption with coronary heart disease morbidity and mortality has not been established. We hypothesized that coffee may enhance reverse cholesterol transport (RCT) as the antiatherogenic properties of high-density lipoprotein (HDL).This study was to investigate whether the phenolic acids of coffee and coffee regulates RCT from macrophages in vitro, ex vivo and in vivo.Caffeic acid and ferulic acid, the major phenolic acids of coffee, enhanced cholesterol efflux from THP-1 macrophages mediated by HDL, but not apoA-I. Furthermore, these phenolic acids increased both the mRNA and protein levels of ATP-binding cassette transporter (ABC)G1 and scavenger receptor class B type I (SR-BI), but not ABCA1. Eight healthy volunteers were recruited for the ex vivo study, and blood samples were taken before and 30 minutes after consumption of coffee or water in a crossover study. The mRNA as well as protein levels of ABCG1, SR-BI, and cholesterol efflux by HDL were increased in the macrophages differentiated under autologous sera obtained after coffee consumption compared to baseline sera. Finally, effects of coffee and phenolic acid on in vivo RCT were assessed by intraperitoneally injecting [(3)H]cholesterol-labeled acetyl low-density lipoprotein-loaded RAW264.7 cells into mice, then monitoring appearance of (3)H tracer in plasma, liver, and feces. Supporting in vitro and ex vivo data, ferulic acid was found to significantly increase the levels of (3)H tracer in feces.Coffee intake might have an antiatherogenic property by increasing ABCG1 and SR-BI expression and enhancing HDL-mediated cholesterol efflux from the macrophages via its plasma phenolic acids.
Sleep apnoea in Scheie's syndrome.
Authors: W H Perks, R A Cooper, S Bradbury, P Horrocks, N Baldock, A Allen, W Van't Hoff, G Weidman, K Prowse
Journal: Thorax (1980)

An 18-year-old student presented with a two-year history of daytime sleepiness and noisy breathing during sleep. Both he and his brother, aged 25 years, had Scheie9s syndrome, a mucopolysaccharidosis characterised by small stature, micrognathia, corneal clouding, hepatosplenomegaly, raised urinary mucopolysaccharides, and undetectable levels of alpha-L-iduronidase assayed in cultured fibroblasts. Both brothers had sleep apnoea (apnoea index, 59 and 35 respectively) during which there was a significant fall in heart rate and arterial oxygen saturation. One brother had EEG changes suggestive of cerebral hypoxia and the other had ventricular extrasystoles at the end of several episodes. Tracheostomy in the younger brother produced a dramatic symptomatic improvement and reduced the number and severity of apnoeic episodes (post-tracheostomy apnoea index 2.4).
Influence of initial severity of depression on effectiveness of low intensity interventions: meta-analysis of individual patient data
Authors: P. Bower, E. Kontopantelis, A. Sutton, T. Kendrick, D. A. Richards, S. Gilbody, S. Knowles, P. Cuijpers, G. Andersson, H. Christensen, B. Meyer, M. Huibers, F. Smit, A. van Straten, L. Warmerdam, M. Barkham, L. Bilich, K. Lovell, E. T.-H. Liu
Journal: BMJ (2013)

Objective To assess how initial severity of depression affects the benefit derived from low intensity interventions for depression. Design Meta-analysis of individual patient data from 16 datasets comparing low intensity interventions with usual care. Setting Primary care and community settings. Participants 2470 patients with depression. Interventions Low intensity interventions for depression (such as guided self help by means of written materials and limited professional support, and internet delivered interventions). Main outcome measures Depression outcomes (measured with the Beck Depression Inventory or Center for Epidemiologic Studies Depression Scale), and the effect of initial depression severity on the effects of low intensity interventions. Results Although patients were referred for low intensity interventions, many had moderate to severe depression at baseline. We found a significant interaction between baseline severity and treatment effect (coefficient −0.1 (95% CI −0.19 to −0.002)), suggesting that patients who are more severely depressed at baseline demonstrate larger treatment effects than those who are less severely depressed. However, the magnitude of the interaction (equivalent to an additional drop of around one point on the Beck Depression Inventory for a one standard deviation increase in initial severity) was small and may not be clinically significant. Conclusions The data suggest that patients with more severe depression at baseline show at least as much clinical benefit from low intensity interventions as less severely depressed patients and could usefully be offered these interventions as part of a stepped care model.
Role of Computerized Physician Order Entry Systems in Facilitating Medication Errors
Authors: Ross Koppel, Joshua P Metlay, Abigail Cohen, Brian Abaluck, A Russell Localio, Stephen E Kimmel, Brian L Strom
Journal: JAMA (2005)

Hospital computerized physician order entry (CPOE) systems are widely regarded as the technical solution to medication ordering errors, the largest identified source of preventable hospital medical error. Published studies report that CPOE reduces medication errors up to 81%. Few researchers, however, have focused on the existence or types of medication errors facilitated by CPOE.To identify and quantify the role of CPOE in facilitating prescription error risks.We performed a qualitative and quantitative study of house staff interaction with a CPOE system at a tertiary-care teaching hospital (2002-2004). We surveyed house staff (N = 261; 88% of CPOE users); conducted 5 focus groups and 32 intensive one-on-one interviews with house staff, information technology leaders, pharmacy leaders, attending physicians, and nurses; shadowed house staff and nurses; and observed them using CPOE. Participants included house staff, nurses, and hospital leaders.Examples of medication errors caused or exacerbated by the CPOE system.We found that a widely used CPOE system facilitated 22 types of medication error risks. Examples include fragmented CPOE displays that prevent a coherent view of patients' medications, pharmacy inventory displays mistaken for dosage guidelines, ignored antibiotic renewal notices placed on paper charts rather than in the CPOE system, separation of functions that facilitate double dosing and incompatible orders, and inflexible ordering formats generating wrong orders. Three quarters of the house staff reported observing each of these error risks, indicating that they occur weekly or more often. Use of multiple qualitative and survey methods identified and quantified error risks not previously considered, offering many opportunities for error reduction.In this study, we found that a leading CPOE system often facilitated medication error risks, with many reported to occur frequently. As CPOE systems are implemented, clinicians and hospitals must attend to errors that these systems cause in addition to errors that they prevent.
A Compendium of Genome-Wide Associations for Cancer: Critical Synopsis and Reappraisal
Authors: John P. A. Ioannidis, Peter Castaldi, Evangelos Evangelou
Journal: JNCI Journal of the National Cancer Institute (2010)

Since 2007, genome-wide association (GWA) studies have identified numerous well-supported, novel genetic risk loci for common cancers; however, there are concerns that this technology is reaching its limits. We provide an overview of GWA-identified genetic associations with solid tumors. We simulated the distribution of population risk alleles for colorectal, prostate, testicular, and thyroid cancers based on genetic variants identified in GWA studies. We also evaluated whether statistical power to detect typical genetic effects could be improved with studies performing GWA analyses of all available samples rather than multistage designs. Fifty-six eligible articles yielded 92 eligible associations between cancer phenotypes and genetic variants with a median per-allele odds ratio (OR) of 1.22 (interquartile range = 1.15-1.36). Half of the associations pertained to prostate, colorectal, or breast cancer. Individuals at the upper quartile of simulated risk had only 2.1- to 4.2-fold higher relative risk than those in the lower quartile. Comprehensive evaluation of currently available samples with GWA platforms would yield few additional variants with per-allele OR = 1.4, but many more variants with OR = 1.2 could be detected; statistical power to detect weak associations (OR = 1.07) would still be negligible. The GWA approach is effective in identifying common genetic variants with moderate effect; however, identifying loci with very small effects and rare variants will require major new efforts. At present, the utility of GWA-identified risk loci in risk stratification for cancer is limited.
Survival and effectiveness of leflunomide compared with methotrexate and sulfasalazine in rheumatoid arthritis: a matched observational study
Authors: D Aletaha
Journal: Annals of the Rheumatic Diseases (2003)

To determine the survival and clinical effectiveness of leflunomide (LEF) compared with methotrexate (MTX) and sulfasalazine (SSZ) for RA in an observational study.An observational database of 1088 patients and 5141 patient years of DMARD treatment (2680 courses) from two academic hospitals was filtered for treatment with LEF, MTX, and SSZ. LEF treatment groups were matched for patients' age, baseline ESR, number of previous DMARDs, and hospital cohort with MTX and SSZ treatment groups. For these treatments, Kaplan-Meier analyses of time until the drug was discontinued (drug "survival"), and the effectiveness and safety of continuation of treatment, were performed. The change in disease activity markers (CRP, ESR) was compared between the groups.The median dose during the study increased from 10 to 15 mg MTX/week and from 1.5 to 2.0 g SSZ/day. Matched survival analysis showed better retention rates for MTX (mean (SEM) survival 28 (1) months) than for LEF (20 (1) months; p=0.001), whereas retention rates of SSZ (23 (1) months) were similar to those of LEF (p=NS). Treatments were stopped earlier because of adverse events (AEs, 3 months) than because of ineffectiveness (IE, 10 months; p<0.001). LEF and MTX were less likely to be stopped because of AEs than SSZ. LEF courses were stopped earlier for AEs (p<0.001) than MTX.Current dosing strategies should be re-evaluated, and coping strategies for common AEs should be investigated. This will be necessary to achieve better drug retention of LEF. At present, MTX continues to be the most effective drug in clinical practice.
HIV-1 in trophoblastic and villous Hofbauer cells, and haematological precursors in eight-week fetuses
Authors: S.H. Lewis, H.E. Fox, S.H. Lewis, S.H. Lewis, C. Reynolds-Kohler, J.A. Nelson
Journal: The Lancet (1990)

AIDS in children is usually caused by vertical transmission of human immunodeficiency virus type 1 (HIV-1). Aborted eight-week fetal and placental tissue from HIV-1 positive and negative (enzyme-linked immunosorbent assay and Western blot) women was analysed by immunocytochemistry and in-situ hybridisation. Maternal decidual leucocytes, villous trophoblastic derivatives, villous mesenchymal cells, and embryonic blood cell precursors in tissues from seropositive patients all stained for HIV-1 antigen and hybridised for nucleic acids. These observations suggest that a cytological pathway for vertical transmission of HIV-1 is established by eight weeks gestational age.
Nontraditional atherosclerotic risk factors and extent of coronary atherosclerosis in patients with combined impaired fasting glucose and impaired glucose tolerance
Authors: Andrzej Surdacki, Ewa Stochmal, Magdalena Szurkowska, Stefanie M. Bode-Böger, Jens Martens-Lobenhoffer, Anna Stochmal, Artur Klecha, Kalina Kawecka-Jaszcz, Jacek S. Dubiel, Bohdan Huszno, Zbigniew Szybiński
Journal: Metabolism (2006)
Risk of Recurrent Venous Thromboembolism and Mortality in Patients With Cancer Incidentally Diagnosed With Pulmonary Embolism: A Comparison With Symptomatic Patients
Authors: Paul L. den Exter, José Hooijer, Olaf M. Dekkers, Menno V. Huisman
Journal: Journal of Clinical Oncology (2011)

Purpose The routine use of modern computed tomography scanners has led to an increased detection of incidental pulmonary embolism (PE), in particular in patients with cancer. The clinical relevance of these incidental findings is unknown. Patients and Methods In this retrospective cohort study, oncology patients in whom PE was objectively proven between 2004 and 2010 and anticoagulant treatment was started, were included. Fifty-one patients with incidental PE and 144 with symptomatic PE were observed for 1 year to compare the risks of recurrent venous thromboembolism (VTE), bleeding complications, and mortality. Kaplan-Meier and Cox survival analyses were performed. Results Incidental and symptomatic patients did not differ with respect to mean age, sex, cancer type and stage, and risk factors for VTE. As a result from evolving treatment guidelines, approximately half of the patients in both groups received long-term treatment with vitamin K antagonists in stead of currently recommended low-molecular-weight heparin. The 12-month cumulative incidence of recurrent VTE was 13.3% in the incidental group versus 16.9% in the symptomatic group (P = .77). Notably, 20% VTE events recurred after premature termination of anticoagulant therapy. The risk of major bleeding complications was also comparable in the two groups (12.5% for incidental patients and 8.6% for symptomatic patients; P = .5). The respective 12-month mortality risks were 52.9% and 53.3% (P = .7). Conclusion Our findings suggest that oncology patients diagnosed with and treated for incidental PE, have similar high rates of recurrent VTE, bleeding complications, and mortality, as compared with oncology patients who develop symptomatic PE.