tbuckley/cabot-search huggingface dataset:
Clinical relevance of transforming growth factor α, epidermal growth factor receptor, p53, and Ki67 in colorectal liver metastases and corresponding primary tumors
Authors: Koert P. De Jong, Rudi Stellema, Arend Karrenbeld, Jan Koudstaal, Annette S. Gouw, Wim J. Sluiter, Paul M. J. G. Peeters, Maarten J. H. Slooff, Elisabeth G. E. De Vries
Journal: Hepatology (1998)

To determine whether the expression of transforming growth factor α (TGF-α), its receptor (epidermal growth factor receptor [EGFr]), p53 nuclear protein, and proliferation influences prognosis of patients with liver metastases, a study was performed in 45 liver metastases and 33 corresponding primary colorectal carcinomas in patients referred for liver surgery. The expression of TGF-α, EGFr, p53 nuclear protein, and proliferation rate was correlated with clinicopathological characteristics and survival after partial liver resection. In liver metastases, TGF-α expression was low in 42%, intermediate in 35%, and high in 23%. TGF-α expression was higher in liver metastases derived from lymph node-positive primary carcinomas, in synchronous and in irresectable liver metastases compared with those derived from lymph node-negative primary carcinomas, metachronous, and resectable liver metastases. Nuclear p53 expression was found in 83% of primary tumors and 71% of liver metastases. p53 expression did not correlate with the various clinicopathological characteristics. Ki67 expression was not associated with clinicopathological characteristics in primary and metastatic tumors. In the 38 patients in whom a partial liver resection was performed, median survival was 25 months in patients with a higher TGF-α expression in the metastasis than in the primary tumor and 60 months in patients with comparable or lower TGF-α expression in the metastasis than in the primary tumor ( P = .036). Median survival after liver resection was 21 months in patients with p53-negative liver metastases and 58 months in patients with p53-positive metastases ( P = .043). By multivariate analysis, p53 and EGFr expression on liver metastases were the best predictors of disease-free survival after partial liver resection, with relative risks of 2.38 and 3.33, respectively. In patients with colorectal liver metastases, referred for liver surgery, a higher TGF-α expression is associated with unfavorable tumor characteristics, whereas p53 and absence of EGFr expression is associated with a better survival after partial liver resection.
EH Domain Proteins Regulate Cardiac Membrane Protein Targeting
Authors: Hjalti Gudmundsson, Thomas J. Hund, Patrick J. Wright, Crystal F. Kline, Jedidiah S. Snyder, Lan Qian, Olha M. Koval, Shane R. Cunha, Manju George, Mark A. Rainey, Farshid E. Kashef, Wen Dun, Penelope A. Boyden, Mark E. Anderson, Hamid Band, Peter J. Mohler
Journal: Circulation Research (2010)

Rationale : Cardiac membrane excitability is tightly regulated by an integrated network of membrane-associated ion channels, transporters, receptors, and signaling molecules. Membrane protein dynamics in health and disease are maintained by a complex ensemble of intracellular targeting, scaffolding, recycling, and degradation pathways. Surprisingly, despite decades of research linking dysfunction in membrane protein trafficking with human cardiovascular disease, essentially nothing is known regarding the molecular identity or function of these intracellular targeting pathways in excitable cardiomyocytes. Objective : We sought to discover novel pathways for membrane protein targeting in primary cardiomyocytes. Methods and Results : We report the initial characterization of a large family of membrane trafficking proteins in human heart. We used a tissue-wide screen for novel ankyrin-associated trafficking proteins and identified 4 members of a unique Eps15 homology (EH) domain–containing protein family (EHD1, EHD2, EHD3, EHD4) that serve critical roles in endosome-based membrane protein targeting in other cell types. We show that EHD1-4 directly associate with ankyrin, provide the first information on the expression and localization of these molecules in primary cardiomyocytes, and demonstrate that EHD1-4 are coexpressed with ankyrin-B in the myocyte perinuclear region. Notably, the expression of multiple EHD proteins is increased in animal models lacking ankyrin-B, and EHD3-deficient cardiomyocytes display aberrant ankyrin-B localization and selective loss of Na/Ca exchanger expression and function. Finally, we report significant modulation of EHD expression following myocardial infarction, suggesting that these proteins may play a key role in regulating membrane excitability in normal and diseased heart. Conclusions : Our findings identify and characterize a new class of cardiac trafficking proteins, define the first group of proteins associated with the ankyrin-based targeting network, and identify potential new targets to modulate membrane excitability in disease. Notably, these data provide the first link between EHD proteins and a human disease model.
Atopic Allergy and Serum IgE Concentrations in Randomly Selected Children Followed Up from 8 to 12 Years of Age
Authors: N.‐I. M. Kjellman
Journal: Allergy (1984)

A total of 159 children selected at random were followed up from the age of 8 to 12 years regarding the development and cumulated incidence of atopic disease as well as serum IgE concentrations. The cumulated incidence, including healed cases, rose to 25.8%. The highest prevalence was found for allergic rhinitis (12.2%). Serum IgE concentrations decreased significantly in both healthy and atopic subjects, and indicated a peak in total IgE concentration in early school age. The allergy predictive value of elevated IgE concentrations was confirmed. Low concentrations of allergen‐specific IgE were found in 14.1 % of children healthy before and during the observation period, indicating that transient production of IgE antibodies is a normal phenomenon. Finally, the stability of IgE was excellent during the first 2 years at −20°C but later on concentrations tended to decrease, especially in the lower range.
Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue
Authors: Colin S Cooper, Rosalind Eeles, David C Wedge, Peter Van Loo, Gunes Gundem, Ludmil B Alexandrov, Barbara Kremeyer, Adam Butler, Andrew G Lynch, Niedzica Camacho, Charlie E Massie, Jonathan Kay, Hayley J Luxton, Sandra Edwards, Zsofia Kote-Jarai, Nening Dennis, Sue Merson, Daniel Leongamornlert, Jorge Zamora, Cathy Corbishley, Sarah Thomas, Serena Nik-Zainal, Manasa Ramakrishna, Sarah O'Meara, Lucy Matthews, Jeremy Clark, Rachel Hurst, Richard Mithen, Robert G Bristow, Paul C Boutros, Michael Fraser, Susanna Cooke, Keiran Raine, David Jones, Andrew Menzies, Lucy Stebbings, Jon Hinton, Jon Teague, Stuart McLaren, Laura Mudie, Claire Hardy, Elizabeth Anderson, Olivia Joseph, Victoria Goody, Ben Robinson, Mark Maddison, Stephen Gamble, Christopher Greenman, Dan Berney, Steven Hazell, Naomi Livni, Cyril Fisher, Christopher Ogden, Pardeep Kumar, Alan Thompson, Christopher Woodhouse, David Nicol, Erik Mayer, Tim Dudderidge, Nimish C Shah, Vincent Gnanapragasam, Thierry Voet, Peter Campbell, Andrew Futreal, Douglas Easton, Anne Y Warren, Christopher S Foster, Michael R Stratton, Hayley C Whitaker, Ultan McDermott, Daniel S Brewer, David E Neal
Journal: Nature Genetics (2015)
Minimal residual disease-directed risk stratification using real-time quantitative PCR analysis of immunoglobulin and T-cell receptor gene rearrangements in the international multicenter trial AIEOP-BFM ALL 2000 for childhood acute lymphoblastic leukemia
Authors: T Flohr, A Schrauder, G Cazzaniga, R Panzer-Grümayer, V van der Velden, S Fischer, M Stanulla, G Basso, F K Niggli, B W Schäfer, R Sutton, R Koehler, M Zimmermann, M G Valsecchi, H Gadner, G Masera, M Schrappe, J J M van Dongen, A Biondi, C R Bartram
Journal: Leukemia (2008)
Expression of FcRL4 defines a pro-inflammatory, RANKL-producing B cell subset in rheumatoid arthritis
Authors: L Yeo, H Lom, M Juarez, M Snow, C D Buckley, A Filer, K Raza, D Scheel-Toellner
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> The success of B cell targeting therapies has highlighted the importance of B cells in rheumatoid arthritis pathogenesis. We have previously shown that B cells in the RA synovium are capable of producing pro-inflammatory and bone-destructive cytokines including RANKL. Here we sought to characterise the nature and functional relevance of the RANKL-producing B cell subset in the RA synovium. <h3>Methods</h3> Synovial fluid and peripheral blood B cells from patients with RA were analysed by flow cytometry for markers of B cell differentiation and activation and for chemokine receptors. FcRL4<sup>+</sup> and FcRL4<sup>−</sup> B cells sorted from synovial fluid were analysed for cytokine expression using Taqman low-density arrays. Synovial tissue biopsies obtained from patients with RA were analysed by immunofluorescence for CD20, RANKL and FcRL4. FCRL4 mRNA expression was determined in synovial tissue of RA patients and non-inflammatory control subjects by real-time PCR. <h3>Results</h3> RANKL-producing B cells in RA synovial tissue and fluid were identified as belonging to a distinct subset of B cells defined by expression of the transmembrane protein FcRL4. FcRL4+ B cells express a distinct combination of cytokines and surface proteins indicating a function distinct from that of FcRL4− B cells. Notably, FcRL4+ B cells expressed high levels of TNF-α and RANKL mRNA. <h3>Conclusions</h3> We have identified a novel pro-inflammatory B cell population in the RA synovium which is defined by expression of FcRL4 and responsible for RANKL production. This B cell population expresses high levels of CD20, and its removal by rituximab may contribute to the anti-inflammatory effect of this drug.
Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10 801 women in 17 randomised trials
Authors: S Darby, P McGale, C Correa, C Taylor, R Arriagada, M Clarke, D Cutter, C Davies, M Ewertz, J Godwin, R Gray, L Pierce, T Whelan, Y Wang, R Peto
Journal: The Lancet (2011)
Overexpression of the Cardiac β <sub>2</sub> -Adrenergic Receptor and Expression of a β-Adrenergic Receptor Kinase-1 (βARK1) Inhibitor Both Increase Myocardial Contractility but Have Differential Effects on Susceptibility to Ischemic Injury
Authors: Heather R. Cross, Charles Steenbergen, Robert J. Lefkowitz, Walter J. Koch, Elizabeth Murphy
Journal: Circulation Research (1999)

Abstract —Cardiac β 2 -adrenergic receptor (β 2 AR) overexpression is a potential contractile therapy for heart failure. Cardiac contractility was elevated in mice overexpressing β 2 ARs (TG4s) with no adverse effects under normal conditions. To assess the consequences of β 2 AR overexpression during ischemia, perfused hearts from TG4 and wild-type mice were subjected to 20-minute ischemia and 40-minute reperfusion. During ischemia, ATP and pH fell lower in TG4 hearts than wild type. Ischemic injury was greater in TG4 hearts, as indicated by lower postischemic recoveries of contractile function, ATP, and phosphocreatine. Because β 2 ARs, unlike β 1 ARs, couple to G i as well as G s , we pretreated mice with the G i inhibitor pertussis toxin (PTX). PTX treatment increased basal contractility in TG4 hearts and abolished the contractile resistance to isoproterenol. During ischemia, ATP fell lower in TG4+PTX than in TG4 hearts. Recoveries of contractile function and ATP were lower in TG4+PTX than in TG4 hearts. We also studied mice that overexpressed either βARK1 (TGβARK1) or a βARK1 inhibitor (TGβARKct). Recoveries of function, ATP, and phosphocreatine were higher in TGβARK1 hearts than in wild-type hearts. Despite basal contractility being elevated in TGβARKct hearts to the same level as that of TG4s, ischemic injury was not increased. In summary, β 2 AR overexpression increased ischemic injury, whereas βARK1 overexpression was protective. Ischemic injury in the β 2 AR overexpressors was exacerbated by PTX treatment, implying that it was G s not G i activity that enhanced injury. Unlike β 2 AR overexpression, basal contractility was increased by βARK1 inhibitor expression without increasing ischemic injury, thus implicating a safer potential therapy for heart failure.
Anticoagulation in atrial fibrillation
Authors: B. A. Steinberg, J. P. Piccini
Journal: BMJ (2014)

Atrial fibrillation increases the risk of stroke, which is a leading cause of death and disability worldwide. The use of oral anticoagulation in patients with atrial fibrillation at moderate or high risk of stroke, estimated by established criteria, improves outcomes. However, to ensure that the benefits exceed the risks of bleeding, appropriate patient selection is essential. Vitamin K antagonism has been the mainstay of treatment; however, newer drugs with novel mechanisms are also available. These novel oral anticoagulants (direct thrombin inhibitors and factor Xa inhibitors) obviate many of warfarin's shortcomings, and they have demonstrated safety and efficacy in large randomized trials of patients with non-valvular atrial fibrillation. However, the management of patients taking warfarin or novel agents remains a clinical challenge. There are several important considerations when selecting anticoagulant therapy for patients with atrial fibrillation. This review will discuss the rationale for anticoagulation in patients with atrial fibrillation; risk stratification for treatment; available agents; the appropriate implementation of these agents; and additional, specific clinical considerations for treatment.
Treatment of polymyalgia rheumatica and giant cell arteritis. II. Relation between steroid dose and steroid associated side effects.
Authors: V Kyle, B L Hazleman
Journal: Annals of the Rheumatic Diseases (1989)

In a prospective study of 74 patients and a retrospective study of 35 patients with polymyalgia rheumatica/giant cell arteritis steroid related side effects occurred in at least one third of patients, and in two thirds if weight gain was included. Side effects were significantly related to an initial prednisolone dose of more than 30 mg and to the cumulative prednisolone dose. Patients taking a mean daily dose of 5 mg prednisolone or less were significantly less likely to develop side effects.
Modeling Protein Evolution with Several Amino Acid Replacement Matrices Depending on Site Rates
Authors: S. Q. Le, C. C. Dang, O. Gascuel
Journal: Molecular Biology and Evolution (2012)

Most protein substitution models use a single amino acid replacement matrix summarizing the biochemical properties of amino acids. However, site evolution is highly heterogeneous and depends on many factors that influence the substitution patterns. In this paper, we investigate the use of different substitution matrices for different site evolutionary rates. Indeed, the variability of evolutionary rates corresponds to one of the most apparent heterogeneity factors among sites, and there is no reason to assume that the substitution patterns remain identical regardless of the evolutionary rate. We first introduce LG4M, which is composed of four matrices, each corresponding to one discrete gamma rate category (of four). These matrices differ in their amino acid equilibrium distributions and in their exchangeabilities, contrary to the standard gamma model where only the global rate differs from one category to another. Next, we present LG4X, which also uses four different matrices, but leaves aside the gamma distribution and follows a distribution-free scheme for the site rates. All these matrices are estimated from a very large alignment database, and our two models are tested using a large sample of independent alignments. Detailed analysis of resulting matrices and models shows the complexity of amino acid substitutions and the advantage of flexible models such as LG4M and LG4X. Both significantly outperform single-matrix models, providing gains of dozens to hundreds of log-likelihood units for most data sets. LG4X obtains substantial gains compared with LG4M, thanks to its distribution-free scheme for site rates. Since LG4M and LG4X display such advantages but require the same memory space and have comparable running times to standard models, we believe that LG4M and LG4X are relevant alternatives to single replacement matrices. Our models, data, and software are available from http://www.atgc-montpellier.fr/models/lg4x.
Association between bone mass and injuries in professional jumpers
Authors: Mahdi Haydari, Nader Rahnama, Khalil Khayambashi, Mohammad Marandi
Journal: British Journal of Sports Medicine (2010)

The health benefits of exercise are well established. Research has shown that exercise has a positive effect on bone health. Sport injuries are associated with several physical and physiological changes that lead to increased disability. Examples of these changes are deteriorations in bone and muscle tissues, referred, respectively, as osteopenia and sarcopenia. High peak bone mass in early adulthood is an important protective factor against osteoporotic fractures in later life, but relation between bone mass and sports injuries has been less documented. The main aim of this study was to determine the association between femoral neck, trochanter and lumbar spines bone mineral density (BMD) and bone mineral content (BMC) and injuries in professional jumpers. Thirty professional men jumpers (10 long, 10 high and 10 triple jumpers) with no history of bone disease participated in this study (mean±SD, aged 21.27±3.52 years, height 182±6 cm, weight 69.93±6.01 kg). BMD and BMC of femoral neck, trochanter for right and left sides and also lumbar spines were measured by dual-energy x-ray absorptiometry. Injury data of these professional jumpers over a 1-year time period (2008–2009) were collected using a standard questionnaire retrospectively. Data were analysed using Pearson correlation test. Results of this study showed an indirect but non-significant correlation between BMD and bone-related injuries (r=0.306, p&gt;0.05). A significant negative association between BMC and bone-related injuries was observed (r=0.359, p&lt;0.05). There were no significant correlations between BMD or BMC and ligamentous, muscular and tendinous injuries (r=0.123, p&gt;0.05; r=0.264, p&gt;0.05), respectively. It can be concluded that long time jumping results in high BMC and decreased risk of bone-related injuries in elite jumpers.
JAK2 p.V617F detection and allele burden measurement in peripheral blood and bone marrow aspirates in patients with myeloproliferative neoplasms
Authors: Koichi Takahashi, Keyur P. Patel, Hagop Kantarjian, Rajyalakshmi Luthra, Sherry Pierce, Jorge Cortes, Srdan Verstovsek
Journal: Blood (2013)
Impact of Adjuvant Chemotherapy and Surgical Staging in Early-Stage Ovarian Carcinoma: European Organisation for Research and Treatment of Cancer-Adjuvant ChemoTherapy in Ovarian Neoplasm Trial
Authors: J. B. Trimbos, I. Vergote, G. Bolis, J. B. Vermorken, C. Mangioni, C. Madronal, M. Franchi, S. Tateo, G. Zanetta, G. Scarfone, L. Giurgea, P. Timmers, C. Coens, S. Pecorelli
Journal: JNCI Journal of the National Cancer Institute (2003)

All randomized trials of adjuvant chemotherapy for early-stage ovarian cancer have lacked the statistical power to show a difference in the effect on survival between adjuvant chemotherapy and no adjuvant chemotherapy. They have also not taken into account the adequacy of surgical staging. We performed a prospective unblinded, randomized phase III trial to test the efficacy of adjuvant chemotherapy in patients with early-stage ovarian cancer, with emphasis on the extent of surgical staging.Between November 1990 and January 2000, 448 patients from 40 centers in nine European countries were randomly assigned to either adjuvant platinum-based chemotherapy (n = 224) or observation (n = 224) following surgery. Endpoints were overall survival and recurrence-free survival, and the analysis was on an intention-to-treat basis. The Kaplan-Meier method was used to perform time-to-event analysis, and the log-rank test was used to compare differences between treatment arms. Statistical tests were two-sided.After a median follow-up of 5.5 years, the difference in overall survival between the two trial arms was not statistically significant (hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.44 to 1.08; P =.10). Recurrence-free survival, however, was statistically significantly improved in the adjuvant chemotherapy arm (HR = 0.63, 95% CI = 0.43 to 0.92; P =.02). Approximately one-third of patients (n = 151) had been optimally staged and two-thirds (n = 297) had not. Among patients in the observation arm, optimal staging was associated with a statistically significant improvement in overall and recurrence-free survival (HR = 2.31 [95% CI = 1.08 to 4.96]; P =.03 and HR = 1.82 [95% CI = 1.02 to 3.24] P =.04, respectively). No such association was observed in the chemotherapy arm. In the non-optimally staged patients, adjuvant chemotherapy was associated with statistically significant improvements in overall and recurrence-free survival (HR = 1.75 [95% CI = 1.04 to 2.95]; P =.03 and HR = 1.78 [95% CI = 1.15 to 2.77]; P =.009, respectively). In the optimally staged patients, no benefit of adjuvant chemotherapy was seen.Adjuvant chemotherapy was associated with statistically significantly improved recurrence-free survival in patients with early-stage ovarian cancer. The benefit of adjuvant chemotherapy appeared to be limited to patients with non-optimal staging, i.e., patients with more risk of unappreciated residual disease.
Hygiene and Public Health.
Authors: Benjamin Arthur Whitelegge
Journal: JAMA (1907)

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