tbuckley/cabot-search huggingface dataset:
Detrimental Ventricular Remodeling in Patients With Congenital Complete Heart Block and Chronic Right Ventricular Apical Pacing
Authors: Jean-Benoît Thambo, Pierre Bordachar, Stephane Garrigue, Stephane Lafitte, Prashanthan Sanders, Sylvain Reuter, Romain Girardot, David Crepin, Patricia Reant, Raymond Roudaut, Pierre Jaïs, Michel Haïssaguerre, Jacques Clementy, Maria Jimenez
Journal: Circulation (2004)

Although dual-chamber pacing improves cardiac function in patients with complete congenital atrioventricular block (CCAVB) by restoring physiological heart rate and atrioventricular synchronization, the long-term detrimental effect of asynchronous electromechanical activation induced by apical right ventricular pacing (RVP) has not been well clarified.Twenty-three CCAVB adults (24+/-3 years) with a DDD transvenous pacemaker underwent conventional echocardiography before implantation and, after at least 5 years of RVP, an exercise test and echocardiography coupled with tissue Doppler imaging and tissue tracking. They were compared with 30 matched healthy control subjects. After 10+/-3 years of RVP, CCAVB adults had significantly higher values versus controls in terms of intra-left ventricular (LV) asynchrony (respectively, 59+/-18 versus 19+/-9 ms, P<0.001), extent of LV myocardium displaying delayed longitudinal contraction (39+/-15% versus 10+/-7%, P<0.01), and septal-to-posterior wall-motion delay (84+/-26 versus 18+/-9 ms, P<0.01). The ratio of late-activated posterior to early-activated septal wall thickness was higher after long-term RVP than before (1.3+/-0.2 vs 1+/-0.1, P=0.05) and was higher than in controls (1+/-0.1, P<0.05). The percentage of patients with increased LV end-diastolic diameter was higher after long-term RVP than before implantation and was higher than in controls (57% versus 13%, P<0.05, and 57% versus 0%, P<0.01, respectively). CCAVB patients with long-term RVP had a lower cardiac output than controls (3.8+/-0.6 versus 4.9+/-0.8 L/min, P<0.05) and lower exercise performance (123+/-24 versus 185+/-39 W, P<0.001).Prolonged ventricular dyssynchrony induced by long-term endovenous RVP is associated with deleterious LV remodeling, LV dilatation, LV asymmetrical hypertrophy, and low exercise capacity. These new data highlight the importance of the ventricular activation sequence in all patients with chronic ventricular pacing.
The Human Glutathione <b> <i>S</i> </b>-Transferase P1 Protein Is Phosphorylated and Its Metabolic Function Enhanced by the Ser/Thr Protein Kinases, cAMP-Dependent Protein Kinase and Protein Kinase C, in Glioblastoma Cells
Authors: Hui-Wen Lo, Gamil R. Antoun, Francis Ali-Osman
Journal: Cancer Research (2004)

Abstract We report here that the human glutathione S-transferase P1 (GSTP1) protein, involved in phase II metabolism of many carcinogens and anticancer agents and in the regulation of c-Jun NH2-terminal kinase-mediated cell signaling, undergoes phosphorylation by the Ser/Thr protein kinases, cAMP-dependent protein kinase (PKA) and protein kinase C (PKC), resulting in a significant enhancement of its metabolic activity. GSTP1 phosphorylation by PKA was glutathione (GSH)-dependent, whereas phosphorylation by PKC did not require but was significantly enhanced by GSH. In the presence of GSH, the stoichiometry of phosphorylation was 0.4 ± 0.03 and 0.53 ± 0.02 mol incorporated phosphate per mole of dimeric GSTP1 protein. The GSTP1 protein was phosphorylated, in the presence of GSH, by eight different PKC isoforms (α, βΙ, βΙΙ, δ, ε, γ, η, and ζ), belonging to the three major PKC subclasses, albeit with various efficiencies. The catalytic efficiency, kcat/Km, of the phosphorylated GSTP1 was more than double that of the unphosphorylated protein. In MGR3 human glioblastoma cells, PKA and PKC activation resulted in a significant increase in the level of phosphorylation of the GSTP1 protein and was accompanied by a 2.1- and 2.7-fold increase, respectively, in specific GSTP1 activity in the cells. Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. The GSH-dependence of the phosphorylation suggests that under high intracellular GSH conditions, such as is present in most drug-resistant tumors, the GSTP1 protein will exist in a hyper-phosphorylated and enzymatically more active state. In normal cells, the functional activation of the GSTP1 protein by PKA- and PKC-dependent phosphorylation could represent a potentially important mechanism of cellular protection, whereas in tumors, increased phase II metabolism of anticancer drugs by the more active phosphorylated GSTP1 protein could contribute to the drug resistance and therapeutic failure frequently associated with increased activities of these Ser/Thr kinases.
Aberrant human tissue kallikrein levels in the stratum corneum and serum of patients with psoriasis: dependence on phenotype, severity and therapy
Authors: N. Komatsu, K. Saijoh, C. Kuk, F. Shirasaki, K. Takehara, E.P. Diamandis
Journal: British Journal of Dermatology (2007)

Human tissue kallikreins (KLKs) are a family of 15 trypsin-like or chymotrypsin-like secreted serine proteases (KLK1-KLK15). Multiple KLKs have been quantitatively identified in normal stratum corneum (SC) and sweat as candidate desquamation-related proteases.To quantify KLK5, KLK6, KLK7, KLK8, KLK10, KLK11, KLK13 and KLK14 in the SC and serum of patients with psoriasis, and their variation between lesional and nonlesional areas and with phenotype, therapy and severity. The overall SC serine protease activities were also measured.Enzyme-linked immunosorbent assays and enzymatic assays were used.The lesional SC of psoriasis generally contained significantly higher levels of all KLKs. KLK6, KLK10 and KLK13 levels were significantly elevated even in the nonlesional SC. The overall trypsin-like, plasmin-like and furin-like activities were significantly elevated in the lesional SC. Plasmin-like activity was significantly elevated also in the nonlesional SC. The SC chymotrypsin-like activity was only slightly elevated in psoriasis. KLK7 serum levels did not differ between normal volunteers and patients with psoriasis. Serum KLK6, KLK8, KLK10 and KLK13 levels in patients with untreated psoriasis significantly correlated with Psoriasis Area and Severity Index score. Serum KLK5 and KLK11 levels decreased in patients with psoriasis after therapy, especially with etretinate. Patients with erythrodermic psoriasis exhibited significantly higher serum KLK levels than normal subjects or patients with psoriasis vulgaris or arthropathic psoriasis.We found aberrant KLK levels in the SC and serum of patients with psoriasis and suggest that KLKs might be involved in the pathogenesis of this disease.
Penetrance Analysis of the <i>PALB2</i> c.1592delT Founder Mutation
Authors: Hannele Erkko, James G. Dowty, Jenni Nikkilä, Kirsi Syrjäkoski, Arto Mannermaa, Katri Pylkäs, Melissa C. Southey, Kaija Holli, Anne Kallioniemi, Arja Jukkola-Vuorinen, Vesa Kataja, Veli-Matti Kosma, Bing Xia, David M. Livingston, Robert Winqvist, John L. Hopper
Journal: Clinical Cancer Research (2008)

Abstract Purpose: PALB2 is a recently identified breast cancer susceptibility gene. We have previously identified in the Finnish population a PALB2 c.1592delT founder truncation mutation that is associated with an increased risk of breast cancer. In the present study, we wanted to assess in more detail the increased risk (hazard ratio, HR) and the age-specific cumulative risk (penetrance) of c.1592delT with regard to susceptibility to breast and other forms of cancer. Experimental Design: Modified segregation analyses fitted under maximum likelihood theory were used to estimate age-specific cumulative risks and HRs using the families of mutation carriers identified from a consecutive series of breast cancer cases unselected for age at onset or family history. Results: We found a substantially increased risk of breast cancer [HR, 6.1; 95% confidence interval (95% CI), 2.2-17.2; P = 0.01] equivalent to a 40% (95% CI, 17-77) breast cancer risk by age 70 years, comparable to that for carriers of mutations in BRCA2. We found marginal evidence (P = 0.06) that the HR for breast cancer decreased with age by 4.2% per year (95% CI, 0.2-8.1), from 7.5-fold at age 30 years to 2.0-fold at age 60 years. Conclusions: Our results suggest that it may be appropriate to offer PALB2 c.1592delT mutation testing to Finnish women with breast cancer, especially those with an early age at onset or a family history of breast or related cancers, and to offer carriers the option of participation in extended disease surveillance programs.
Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: A multicenter international myeloma working group study
Authors: S K Kumar, J H Lee, J J Lahuerta, G Morgan, P G Richardson, J Crowley, J Haessler, J Feather, A Hoering, P Moreau, X LeLeu, C Hulin, S K Klein, P Sonneveld, D Siegel, J Bladé, H Goldschmidt, S Jagannath, J S Miguel, R Orlowski, A Palumbo, O Sezer, S V Rajkumar, B G M Durie, Niels Abildgaard, Rafat Abonour, Ray Alexanian, Melissa Alsina, Kenneth, C Anderson, Michael Attal, Hervé Avet-Loiseau, Ashraf Badros, Dalsu Baris, Bart Barlogie, Régis Bataille, Meral Beksaç, Andrew Belch, Dina Ben-Yehuda, Bill Bensinger, P Leif Bergsagel, Jenny Bird, Joan Bladé, Mario Boccadoro, Michele Cavo, Asher Chanan-Khan, Wen Ming Chen, Tony Child, James Chim, Wee-Joo Chng, Ray Comenzo, John Crowley, William Dalton, Faith Davies, Cármino de Souza, Michel Delforge, Meletios Dimopoulos, Angela Dispenzieri, Johannes Drach, Matthew Drake, Brian G M Durie, Hermann Einsele, Theirry Facon, Dorotea Fantl, Jean-Paul Fermand, Rafael Fonseca, Gösta Gahrton, Ramón García-Sanz, Christina Gasparetto, Morie Gertz, John Gibson, Sergio Giralt, Hartmut Goldschmidt, Philip Greipp, Roman Hajek, Izhar Hardan, Parameswaran Hari, Jean-Luc Harousseau, Hiroyuki Hata, Yutaka Hattori, Tom Heffner, Joy Ho, Vania Hungria, Shinsuke Ida, Peter Jacobs, Sundar Jagannath, Hans Johnsen, Hou Jian, Douglas Joshua, Artur Jurczyszyn, Michio Kawano, Nicolaus Kröger, Shaji Kumar, Robert A Kyle, Martha Lacy, Juan José Lahuerta, Ola Landgren, Jacob Laubach, Jae Hoon Lee, Xavier LeLeu, Suzanne Lentzsch, Henk Lokhorst, Sagar Lonial, Heinz Ludwig, Angelo Maiolino, María Mateos, Jayesh Mehta, Ulf-Henrik Mellqvist, GiamPaolo Merlini, Joseph Mikhael, Angelina Rodríguez Morales, Philippe Moreau, Gareth Morgan, Hareth Nari, Nikhil Munshi, Ruben Niesvizky, Amara Nouel, Yana Novis, Robert Orlowski, Antonio Palumbo, Santiago Pavlovsky, Linda Pilarski, Raymond Powles, Noopur Raje, S Vincent Rajkumar, Donna Reece, Tony Reiman, Paul G Richardson, David Roodman, Laura Rosiñol, Jesús San Miguel, Orhan Sezer, Jatin J Shah, John Shaughnessy, Kazuyuki Shimizu, Chaim Shustik, David Siegel, Seema Singhal, Pieter Sonneveld, Andrew Spencer, Edward Stadtmauer, Keith Stewart, Evangelos Terpos, Patrizia Tosi, Guido Tricot, Ingemar Turesson, Ben Van Camp, Brian Van Ness, Ivan Van Riet, Isabelle Vande Broek, Karin Vanderkerken, Robert Vescio, David Vesole, Anders Waage, Michael Wang, Donna Weber, Jan Westin, Keith Wheatley, Jeffrey Zonder
Journal: Leukemia (2011)
Coalescent Methods Are Robust to the Simultaneous Effects of Long Branches and Incomplete Lineage Sorting
Authors: L. Liu, Z. Xi, C. C. Davis
Journal: Molecular Biology and Evolution (2014)

It is well known that species with elevated substitution rates can give rise to disproportionately long branches in the species tree. This combination of long and short branches can contribute to long-branch artifacts (LBA). Despite efforts to remedy LBA via increased taxon sampling and methodological improvements in gene tree estimation, it remains unclear how long and short branches affect species tree estimation in the presence of incomplete lineage sorting (ILS). Here, we examine the combined influence of long external and short internal branches on concatenation and coalescent methods using both simulated and empirical data. Our results demonstrate that the presence of long and short branches alone does not obviously confound the consistency of concatenation and coalescent methods. However, when long external and short internal branches occur simultaneously with high ILS, concatenation methods can be misled, especially when two of these long branches are sister lineages. In contrast, coalescent methods are more robust under these circumstances. This is particularly relevant because this topological pattern also characterizes numerous ancient rapid radiations across the tree of life. Because short internal branches can increase the potential for ILS and gene tree discordance, our results collectively suggest that coalescent methods are more likely to infer the correct species tree in cases of ancient rapid radiations where long external and short internal branches are in close phylogenetic proximity.
Role of inducible nitric oxide synthase in trinitrobenzene sulphonic acid induced colitis in mice
Authors: D-M McCafferty, M Miampamba, E Sihota, K A Sharkey, P Kubes
Journal: Gut (1999)

<h3>BACKGROUND</h3> Studies using inhibitors of nitric oxide synthase (NOS) to date are inconclusive regarding the role of inducible NOS (iNOS) in intestinal inflammation. <h3>AIMS</h3> (1) To examine the role of iNOS in the development of chronic intestinal inflammation; (2) to identify the cellular source(s) of iNOS. <h3>METHODS</h3> Colitis was induced by an intrarectal instillation of trinitrobenzene sulphonic acid (TNBS, 60 mg/ml, 30% ethanol), in wild type (control) or iNOS deficient mice. Mice were studied over 14 days; the colons were scored for injury and granulocyte infiltration was quantified. Blood to lumen leakage of<sup>51</sup>Cr-EDTA was measured as a quantitative index of mucosal damage. <h3>RESULTS</h3> At 24 and 72 hours, iNOS deficient mice had significantly increased macroscopic inflammation compared with wild type mice. Granulocyte infiltration increased significantly at 24 hours and remained elevated in iNOS deficient mice at 72 hours, but significantly decreased in controls. However, by seven days post-TNBS macroscopic damage, microscopic histology, granulocyte infiltration, and mucosal permeability did not differ between wild type and iNOS deficient mice. A four- to fivefold increase in iNOS mRNA was observed in wild type mice at 72 hours and seven days post-TNBS and was absent in iNOS deficient mice. Immunohistochemistry techniques showed that iNOS expression was predominantly localised in neutrophils, with some staining also in macrophages. <h3>CONCLUSIONS</h3> These results suggest that leucocyte derived iNOS ameliorates the early phase, but does not impact on the chronic phase of TNBS induced colitis despite the presence of iNOS.
Diagnostic and prognostic characteristics of the enzyme linked immunosorbent rheumatoid factor assays in rheumatoid arthritis.
Authors: H Visser, L B Gelinck, A H Kampfraath, F C Breedveld, J M Hazes
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVE: To determine the diagnostic and prognostic test qualities of the enzyme linked immunosorbent assays (ELISA) for rheumatoid factor isotypes in rheumatoid arthritis (RA), and to compare them with the latex fixation test. METHODS: Rheumatoid factor tests were performed in 1988 consecutive new rheumatology outpatients within two months after their first visit to the outpatient clinic of the Department of Rheumatology of Leiden University hospital. The sensitivity, specificity, accuracy, and predictive values of the tests in discriminating RA from non-rheumatoid arthritis and erosive from non-erosive disease after two years of follow up were determined and presented as receiver operating characteristic curves and post-test probability curves. RESULTS: The sensitivity of the ELISA for IgG, IgA, and IgM rheumatoid factor for RA versus all controls at optimal cut off titres was 72%, 44%, and 69%, respectively; the specificity was 52%, 84%, and 86%. For the latex fixation test the sensitivity was 66% and the specificity 91%. The post-test probability of RA, at a clinical prevalence rate of 12%, given a positive test result in the ELISAs for IgG, IgA, and IgM rheumatoid factor and the latex fixation test, was 17%, 27%, 40%, and 49%, respectively; with negative test results the probability was 7%, 8%, 5%, and 5%, respectively. The specificity of all tests in discriminating erosive from non-erosive RA at two years was low: 41%, 44%, 47%, and 58% for the ELISAs for IgG, IgA, and IgM rheumatoid factor and the latex fixation test, respectively. CONCLUSION: The ELISAs for IgG and IgA rheumatoid factor are of no significance in diagnosing RA and in the prediction of erosive disease. The ELISA for IgM rheumatoid factor is a reasonable alternative for the latex fixation test when age and gender are taken in to consideration. The specificity of all rheumatoid factor tests in discriminating erosive from non-erosive RA is low.
Identification of TRAIL-inducing compounds highlights small molecule ONC201/TIC10 as a unique anti-cancer agent that activates the TRAIL pathway
Authors: Joshua E Allen, Gabriel Krigsfeld, Luv Patel, Patrick A Mayes, David T Dicker, Gen Sheng Wu, Wafik S El-Deiry
Journal: Molecular Cancer (2015)

We previously reported the identification of ONC201/TIC10, a novel small molecule inducer of the human TRAIL gene that improves efficacy-limiting properties of recombinant TRAIL and is in clinical trials in advanced cancers based on its promising safety and antitumor efficacy in several preclinical models.
Importance of the SDF-1:CXCR4 Axis in Myocardial Repair
Authors: Marc S. Penn
Journal: Circulation Research (2009)

3][4][5][6] In this issue of Circulation Research, Tang et al investigate the role of the SDF-1:CXCR4 axis in the recruitment of exogenously derived cardiac stem cells. 7They further investigate how cardiac stem cell exposure to hypoxia before their intravenous administration alters cardiac stem cell engraftment and subsequent effects on myocardial repair.Cardiac stem cells were derived from cardiosphere cultures and were defined by as CLK (cardiosphere-derived c-Kit ϩ Lin Ϫ ) cells.The cells were shown to have evidence of cardiac potential through the expression of green fluorescent protein under control of the Nkx2.5 promoter.The cells were administered intravenously 1 hour following permanent left anterior descending coronary artery ligation in the murine model of myocardial infarction.
Green and Blue Spaces and Behavioral Development in Barcelona Schoolchildren: The BREATHE Project
Authors: Elmira Amoly, Payam Dadvand, Joan Forns, Mónica López-Vicente, Xavier Basagaña, Jordi Julvez, Mar Alvarez-Pedrerol, Mark J. Nieuwenhuijsen, Jordi Sunyer
Journal: Environmental Health Perspectives (2014)

Background: Green spaces have been associated with improved mental health in children; however, available epidemiological evidence on their impact on child behavioral development is scarce.Objectives: We investigated the impact of contact with green spaces and blue spaces (beaches) on indicators of behavioral development and symptoms of attention deficit/hyperactivity disorder (ADHD) in schoolchildren.Methods: This study was based on a sample of 2,111 schoolchildren (7–10 years of age) from 36 schools in Barcelona in 2012. We obtained data on time spent in green spaces and beaches and Strengths and Difficulties Questionnaires (SDQ) from parents, and ADHD/DSM-IV questionnaires from teachers. Surrounding greenness was abstracted as the average Normalized Difference Vegetation Index (NDVI) in buffers of 100 m, 250 m, and 500 m around each home address. Proximity to green spaces was defined as living within 300 m of a major green space (≥ 0.05 km2). We applied quasi-Poisson mixed-effects models (with school random effect) to separately estimate associations between indicators of contact with green spaces and SDQ and ADHD total and subscale scores.Results: We generally estimated beneficial associations between behavioral indicators and longer time spent in green spaces and beaches, and with residential surrounding greenness. Specifically, we found statistically significant inverse associations between green space playing time and SDQ total difficulties, emotional symptoms, and peer relationship problems; between residential surrounding greenness and SDQ total difficulties and hyperactivity/inattention and ADHD/DSM-IV total and inattention scores; and between annual beach attendance and SDQ total difficulties, peer relationship problems, and prosocial behavior. For proximity to major green spaces, the results were not conclusive.Conclusion: Our findings support beneficial impacts of contact with green and blue spaces on behavioral development in schoolchildren.Citation: Amoly E, Dadvand P, Forns J, López-Vicente M, Basagaña X, Julvez J, Alvarez-Pedrerol M, Nieuwenhuijsen MJ, Sunyer J. 2014. Green and blue spaces and behavioral development in Barcelona schoolchildren: the BREATHE Project. Environ Health Perspect 122:1351–1358; http://dx.doi.org/10.1289/ehp.1408215
Phase II Study of Palifermin and Concurrent Chemoradiation in Head and Neck Squamous Cell Carcinoma
Authors: David M. Brizel, Barbara A. Murphy, David I. Rosenthal, Kishan J. Pandya, Stefan Glück, Herbert E. Brizel, Ruby F. Meredith, Dietmar Berger, Mon-Gy Chen, William Mendenhall
Journal: Journal of Clinical Oncology (2008)

Acute mucositis is a dose-limiting toxicity of concurrent chemoradiotherapy regimens for locally advanced head and neck cancer. Palifermin (a recombinant human keratinocyte growth factor; DeltaN23-KGF) stimulates the proliferation and differentiation of mucosal epithelium to reduce mucositis in patients receiving intensive therapy for hematologic cancers. This study assessed the efficacy and safety of palifermin in patients receiving concurrent chemoradiotherapy for advanced head and neck squamous cell carcinoma.In a phase II trial, standard radiotherapy was delivered in daily 2-Gy fractions to 70 Gy, or hyperfractionated radiotherapy was delivered in 1.25-Gy fractions twice daily to 72 Gy, over 7 weeks. Chemotherapy included cisplatin 20 mg/m(2) for 4 days and continuous-infusion fluorouracil 1,000 mg/m(2)/d for 4 days on weeks 1 and 5 of irradiation. Patients were randomly assigned 2:1 to palifermin 60 microg/kg or placebo once weekly for 10 doses. A follow-up trial evaluated long-term survival.Sixty-seven patients received palifermin and 32 received placebo. The median duration of grade >or= 2 mucositis was 6.5 and 8.1 weeks in the palifermin and placebo groups, respectively (P = .157). Palifermin appeared to reduce mucositis, dysphagia, and xerostomia during hyperfractionated radiotherapy (n = 40) but not standard radiation therapy (n = 59). Adverse events were similar between treatment groups. Palifermin did not alter tumor response or survival.Ten once-weekly doses of palifermin at 60 microg/kg were well tolerated. Most patients completed treatment, but palifermin did not reduce the morbidity of concurrent chemotherapy and radiotherapy. Future studies should evaluate higher palifermin doses with longer and more standardized assessment of acute mucositis.