tbuckley/cabot-search huggingface dataset:
ASPECTS OF EPIDURAL MORPHINE
Authors: R.P Husemeyer, M.C O'Connor, H.T Davenport, M.J Cousins, C.J Glynn, P.R Wilson, L.E Mather, J.R Graham, ArunaR Bapat, NilimaA Kshirsagar, R.D Bapat
Journal: The Lancet (1979)
OLFACTORY MEMORY FORMATION IN<i>DROSOPHILA</i>: From Molecular to Systems Neuroscience
Authors: Ronald L. Davis
Journal: Annual Review of Neuroscience (2005)

The olfactory nervous system of insects and mammals exhibits many similarities, which suggests that the mechanisms for olfactory learning may be shared. Molecular genetic investigations of Drosophila learning have uncovered numerous genes whose gene products are essential for olfactory memory formation. Recent studies of the products of these genes have continued to expand the range of molecular processes known to underlie memory formation. Recent research has also broadened the neuroanatomical areas thought to mediate olfactory learning to include the antennal lobes in addition to a previously accepted and central role for the mushroom bodies. The roles for neurons extrinsic to the mushroom body neurons are becoming better defined. Finally, the genes identified to participate in Drosophila olfactory learning have conserved roles in mammalian organisms, highlighting the value of Drosophila for gene discovery.
Statistical Potentials for Improved Structurally Constrained Evolutionary Models
Authors: Claudia L. Kleinman, Nicolas Rodrigue, Nicolas Lartillot, Hervé Philippe
Journal: Molecular Biology and Evolution (2010)

Assessing the influence of three-dimensional protein structure on sequence evolution is a difficult task, mainly because of the assumption of independence between sites required by probabilistic phylogenetic methods. Recently, models that include an explicit treatment of protein structure and site interdependencies have been developed: a statistical potential (an energy-like scoring system for sequence–structure compatibility) is used to evaluate the probability of fixation of a given mutation, assuming a coarse-grained protein structure that is constant through evolution. Yet, due to the novelty of these models and the small degree of overlap between the fields of structural and evolutionary biology, only simple representations of protein structure have been used so far. In this work, we present new forms of statistical potentials using a probabilistic framework recently developed for evolutionary studies. Terms related to pairwise distance interactions, torsion angles, solvent accessibility, and flexibility of the residues are included in the potentials, so as to study the effects of the main factors known to influence protein structure. The new potentials, with a more detailed representation of the protein structure, yield a better fit than the previously used scoring functions, with pairwise interactions contributing to more than half of this improvement. In a phylogenetic context, however, the structurally constrained models are still outperformed by some of the available site-independent models in terms of fit, possibly indicating that alternatives to coarse-grained statistical potentials should be explored in order to better model structural constraints.
Defective B cell tolerance in adult (NZB X MZW)F1 mice.
Authors: E A Goldings, P L Cohen, S F McFadden, M Ziff, E S Vitetta
Journal: The Journal of Experimental Medicine (1980)

Hapten-specific tolerance was induced in vitro by trinitrophenyl-human gamma globulin (TNP32HGG) to a comparable degree in B cells from adult autoimmune (NZB X NZW)F1 (B/W) mice and normal BDF1, CBA/J, and DBA/1J mice. When a lower epitope density tolerogen (TNP7HGG) was used, B/W mice were significantly less sensitive than normal mice to the induction of B cell tolerance. This finding of defective B cell tolerance in adult B/W mice is consistent with previous reports that document other B cell abnormalities that may relate to the expression of autoimmune disease.
Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery
Authors: L. Rubbia-Brandt, E. Giostra, C. Brezault, A.D. Roth, A. Andres, V. Audard, P. Sartoretti, B. Dousset, P.E. Majno, O. Soubrane, S. Chaussade, G. Mentha, B. Terris
Journal: Annals of Oncology (2006)
Clinical Role of Multidrug Resistance Protein 1 Expression in Chemotherapy Resistance in Early-Stage Breast Cancer: The Austrian Breast and Colorectal Cancer Study Group
Authors: Martin Filipits, Gudrun Pohl, Margaretha Rudas, Otto Dietze, Sigurd Lax, Renate Grill, Robert Pirker, Christoph C. Zielinski, Hubert Hausmaninger, Ernst Kubista, Hellmut Samonigg, Raimund Jakesz
Journal: Journal of Clinical Oncology (2005)

The multidrug resistance protein 1 (MRP1) is expressed in human breast cancer cells and may contribute to the clinical drug resistance of breast cancer patients. Therefore, we determined the impact of MRP1 expression on the clinical outcome of adjuvant therapy in patients with early-stage breast cancer.Immunostaining for MRP1 was performed on tissue sections from 516 premenopausal, hormone receptor-positive breast cancer patients with stage I and II disease. Statistical analyses were performed to assess the effect of MRP1 expression on survival and to test for interaction between MRP1 expression and treatment.MRP1 expression independently predicted shorter relapse-free survival (RFS) and overall survival (OS) in patients treated with cyclophosphamide, methotrexate, and fluorouracil (CMF; RFS: hazard ratio [HR] = 1.48; 95% CI, 1.16 to 1.88; P = .002; OS: HR = 1.82; 95% CI, 1.10 to 3.01; P = .02), but it did not predict shorter RFS and OS in patients who received tamoxifen plus goserelin (RFS: HR = 0.99; 95% CI, 0.74 to 1.31; P = .9; OS: HR = 0.68; 95% CI, 0.40 to 1.15; P = .1). Tests for interaction between MRP1 expression and treatment were statistically significant for both RFS (P = .04) and OS (P = .006).Our data suggest that MRP1 expression plays an important role in the clinical resistance to adjuvant CMF chemotherapy but does not seem to affect response to adjuvant endocrine treatment with tamoxifen plus goserelin. Thus, MRP1 may be a useful marker for the selection of patients with early-stage breast cancer for the appropriate adjuvant therapy after prospective confirmatory evaluation.
The Biology of the Eosinophilic Leukocyte
Authors: G J Gleich, C R Adolphson, K M Leiferman
Journal: Annual Review of Medicine (1993)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
The vascular basement membrane in systemic sclerosis skin: heterogeneity of type IV collagen
Authors: J.A. HOYLAND, L. NEWSON, M.I.V. JAYSON, A. J. FREEMONT
Journal: British Journal of Dermatology (1993)

In systemic sclerosis (SS) changes in the dermal microvasculature include endothelial cell damage, a reduction in the number of vessels, and vascular basement membrane thickening. The basement membrane is a critical component of the vessel, and alterations in its structure may lead to changes in the surrounding tissue. In SS the altered basement membrane is associated with the subsequent development of fibrosis. To investigate the relationship between vascular basement membrane changes in affected skin and disease progression, immunohistochemical analyses were performed using both polyclonal and monoclonal antibodies against type IV collagen, the major basement membrane collagen. Using two monoclonal antibodies directed against different conformational epitopes within the (α1)2 (α2) helical domain, type IV collagen was detected in normal skin, and uninvolved SS skin, but not in later grades of disease. Identical results were obtained using a monoclonal antibody against a sequential determinant on the denatured α1 (IV) chain. The use of a polyclonal antibody, however, showed that type IV collagen was present in all grades of disease, suggesting an alteration in the composition of type IV collagen with disease progression.
KEAP1-Dependent Synthetic Lethality Induced by AKT and TXNRD1 Inhibitors in Lung Cancer
Authors: Bingbing Dai, Suk-Young Yoo, Geoffrey Bartholomeusz, Ryan A. Graham, Mourad Majidi, Shaoyu Yan, Jieru Meng, Lin Ji, Kevin Coombes, John D. Minna, Bingliang Fang, Jack A. Roth
Journal: Cancer Research (2013)

Abstract Intrinsic resistance to agents targeting phosphoinositide 3-kinase (PI3K)/AKT pathway is one of the major challenges in cancer treatment with such agents. The objective of this study is to identify the genes or pathways that can be targeted to overcome the resistance of non–small cell lung carcinoma (NSCLC) to the AKT inhibitor MK2206, which is currently being evaluated in phase I and II clinical trials. Using a genome-wide siRNA library screening and biologic characterization, we identified that inhibition of thioredoxin reductase-1 (TXNRD1), one of the key antioxidant enzymes, with siRNAs or its inhibitor, auranofin, sensitized NSCLC cells to MK2206 treatment in vitro and in vivo. We found that simultaneous inhibition of TXNRD1 and AKT pathways induced robust reactive oxygen species production, which was involved in c-jun-NH2-kinase (JNK; MAPK8) activation and cell apoptosis. Furthermore, we found that the synthetic lethality interaction between the TXNRD1 and AKT pathways occurred through the KEAP1/NRF2 cellular antioxidant pathway. Finally, we found that synthetic lethality induced by TXNRD1 and AKT inhibitors relied on wild-type KEAP1 function. Our study indicates that targeting the interaction between AKT and TXNRD1 antioxidant pathways with MK2206 and auranofin, a U.S. Food and Drug Administration-approved drug, is a rational strategy to treat lung cancer and that KEAP1 mutation status may offer a predicative biomarker for such combination approaches. Cancer Res; 73(17); 5532–43. ©2013 AACR.
Abstract 14381: Preliminary Results from the SPECULATE Randomized Study: Effect of Amiodarone on the Procedure Outcome in Long-Standing Persistent Atrial Fibrillation Undergoing Extended Pulmonary Vein Antrum Isolation
Authors: Luigi Di Biase, Pasquale Santangelli, Prasant Mohanty, J. David Burkhardt, Javier E. Sanchez, Rodney Horton, Raimondo Massaro, Domenico Potenza, Gemma Pelargonio, Dhanunjay Lakkireddy, Subba Reddy Vanga, Giovanni Forleo, Rong Bai, Sanghamitra Mohanty, Sakis Themistoklakis, Antonio Raviele, Salwa Beheiry, Richard Hongo, Douglas Gibson, Michela Casella, Antonio Dello Russo, Claudio Tondo, Andrea Natale
Journal: Circulation (2011)

Introduction: Long standing persistent (LSP) atrial fibrillation (AF) is the most challenging type of AF to treat. Many centers perform ablation without discontinuation of Amiodarone (AM). Our stud...
IMPACT OF PLAQUE CHARACTERIZATION ON SUBSEQUENT DEVELOPMENT OF PERI–STENT CONTRAST STAINING AFTER SIROLIMUS–ELUTING STENT IMPLANTATION
Authors: Akihiro Suzuki, Hirohiko Ando, Hiroaki Takashima, Katsuhisa Waseda, Kenji Asai, Yasushi Kuhara, Yasuo Kuroda, Takashi Kosaka, Akiyoshi Kurita, Kazuyuki Maeda, Shinichirou Sakurai, Daiki Kato, Shigeko Sato, Masanobu Fujimoto, Tetsuya Amano
Journal: Journal of the American College of Cardiology (2013)
Motexafin gadolinium and involved field radiation therapy for intrinsic pontine glioma of childhood: A Children's Oncology Group phase I study
Authors: Kristin A. Bradley, Ian F. Pollack, Joel M. Reid, Peter C. Adamson, Matthew M. Ames, Gilbert Vezina, Susan Blaney, Percy Ivy, Tianni Zhou, Mark Krailo, Gregory Reaman, Minesh P. Mehta
Journal: Neuro-Oncology (2008)

The purpose of this study was to determine the dose-limiting toxicities, maximum tolerated dose, pharmacokinetics, and intratumor and brain distribution of motexafin gadolinium (MGd) with involved field radiation therapy in children with newly diagnosed intrinsic pontine gliomas. MGd was administered as a 5-min intravenous bolus 2-5 h prior to standard radiation. The starting dose was 1.7 mg/kg. After first establishing that 5 doses/week for 6 weeks was tolerable, the dose of MGd was escalated until dose-limiting toxicity was reached. Radiation therapy was administered to 54 Gy in 30 once-daily fractions. Forty-four children received MGd at doses of 1.7 to 9.2 mg/kg daily prior to radiation therapy for 6 weeks. The maximum tolerated dose was 4.4 mg/kg. The primary dose-limiting toxicities were grade 3 and 4 hypertension and elevations in serum transaminases. Median elimination half-life and clearance values were 6.6 h and 25.4 ml/kg/h, respectively. The estimated median survival was 313 days (95% confidence interval, 248-389 days). The maximum tolerated dose of MGd and the recommended phase II dose was 4.4 mg/kg when administered as a daily intravenous bolus in conjunction with 6 weeks of involved field radiation therapy for pediatric intrinsic pontine gliomas.
Toxin-Resistant Sodium Channels: Parallel Adaptive Evolution across a Complete Gene Family
Authors: M. C. Jost, D. M. Hillis, Y. Lu, J. W. Kyle, H. A. Fozzard, H. H. Zakon
Journal: Molecular Biology and Evolution (2008)

Approximately 75% of vertebrate proteins belong to protein families encoded by multiple evolutionarily related genes, a pattern that emerged as a result of gene and genome duplications over the course of vertebrate evolution. In families of genes with similar or related functions, adaptation to a strong selective agent should involve multiple adaptive changes across the entire gene family. However, we know of no evolutionary studies that have explicitly addressed this point. Here, we show how 4 taxonomically diverse species of pufferfishes (Tetraodontidae) each evolved resistance to the guanidinium toxins tetrodotoxin (TTX) and saxitoxin (STX) via parallel amino acid replacements across all 8 sodium channels present in teleost fish genomes. This resulted in diverse suites of coexisting sodium channel types that all confer varying degrees of toxin resistance, yet show remarkable convergence among genes and phylogenetically diverse species. Using site-directed mutagenesis and expression of a vertebrate sodium channel, we also demonstrate that resistance to TTX/STX is enhanced up to 15-fold by single, frequently observed replacements at 2 sites that have not previously been implicated in toxin binding but show similar or identical replacements in pufferfishes and in distantly related vertebrate and nonvertebrate animals. This study presents an example of natural selection acting upon a complete gene family, repeatedly arriving at a diverse but limited number of adaptive changes within the same genome. To be maximally informative, we suggest that future studies of molecular adaptation should consider all functionally similar paralogs of the affected gene family.
A SPECIFIC FLOCCULATION REACTION OCCURRING BETWEEN ALCOHOLIC EXTRACTS OF PNEUMOCOCCI AND ANTIPNEUMOCOCCUS SERUM
Authors: C. W. Jungeblut
Journal: The Journal of Experimental Medicine (1927)

1. A flocculation reaction has been described which occurs between alcoholic extracts of pneumococci and antipneumococcus serum. 2. The reaction appears to be species-specific. It is not strictly type-specific, as slight or moderate cross-reactions occurred between Type I serums and Type II and Type III extracts. 3. The flocculating power of the serum from five horses undergoing immunization with pneumococcus, Type I, did not develop to any extent before the end of the 4th or 5th month. 4. In the case of two of these horses in which it was possible to carry out parallel tests on a larger number of subsequent bleedings until the end of immunization, some relationship was suggested between the flocculating power and the protective titer as ascertained by the routine method of standardization in mice.
Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1): an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study to investigate the effect of once daily nitisinone on 24-h urinary homogentisic acid excretion in patients with alkaptonuria after 4 weeks of treatment
Authors: Lakshminarayan R Ranganath, Anna M Milan, Andrew T Hughes, John J Dutton, Richard Fitzgerald, Michael C Briggs, Helen Bygott, Eftychia E Psarelli, Trevor F Cox, James A Gallagher, Jonathan C Jarvis, Christa van Kan, Anthony K Hall, Dinny Laan, Birgitta Olsson, Johan Szamosi, Mattias Rudebeck, Torbjörn Kullenberg, Arvid Cronlund, Lennart Svensson, Carin Junestrand, Hana Ayoob, Oliver G Timmis, Nicolas Sireau, Kim-Hanh Le Quan Sang, Federica Genovese, Daniela Braconi, Annalisa Santucci, Martina Nemethova, Andrea Zatkova, Judith McCaffrey, Peter Christensen, Gordon Ross, Richard Imrich, Jozef Rovensky
Journal: Annals of the Rheumatic Diseases (2014)

Alkaptonuria (AKU) is a serious genetic disease characterised by premature spondyloarthropathy. Homogentisate-lowering therapy is being investigated for AKU. Nitisinone decreases homogentisic acid (HGA) in AKU but the dose-response relationship has not been previously studied.Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1) was an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study. The primary objective was to investigate the effect of different doses of nitisinone once daily on 24-h urinary HGA excretion (u-HGA24) in patients with AKU after 4 weeks of treatment. Forty patients were randomised into five groups of eight patients each, with groups receiving no treatment or 1 mg, 2 mg, 4 mg and 8 mg of nitisinone.A clear dose-response relationship was observed between nitisinone and the urinary excretion of HGA. At 4 weeks, the adjusted geometric mean u-HGA24 was 31.53 mmol, 3.26 mmol, 1.44 mmol, 0.57 mmol and 0.15 mmol for the no treatment or 1 mg, 2 mg, 4 mg and 8 mg doses, respectively. For the most efficacious dose, 8 mg daily, this corresponds to a mean reduction of u-HGA24 of 98.8% compared with baseline. An increase in tyrosine levels was seen at all doses but the dose-response relationship was less clear than the effect on HGA. Despite tyrosinaemia, there were no safety concerns and no serious adverse events were reported over the 4 weeks of nitisinone therapy.In this study in patients with AKU, nitisinone therapy decreased urinary HGA excretion to low levels in a dose-dependent manner and was well tolerated within the studied dose range.EudraCT number: 2012-005340-24. Registered at ClinicalTrials.gov: NCTO1828463.
Acute mountain sickness susceptibility, fitness and hypoxic ventilatory response
Authors: JS Milledge, JM Beeley, J Broome, N Luff, M Pelling, D Smith
Journal: European Respiratory Journal (1991)

In a party of 17 subjects who travelled together to 4,500 m, hypoxic ventilatory response (HVR) and maximum oxygen consumption (VO2max) were measured before departure. HVR was measured under constant and varying alveolar carbon dioxide tension (PACO2) conditions. VO2max was measured by both standard expired gas collection technique on a treadmill and using the "shuttle run" technique. On arrival at altitude, symptoms of acute mountain sickness (AMS) were scored daily for three days. There were no cases of severe AMS but half of the party had mild to moderate degrees of AMS. There was no correlation between AMS scores and HVR by either method of measurement or with VO2max measured by either method of measurement or with VO2max measured by treadmill or shuttle run.
Surfactant proteins in pulmonary alveolar proteinosis in adults
Authors: F. Brasch, J. Birzele, M. Ochs, S.H. Guttentag, O.D. Schoch, A. Boehler, M.F. Beers, K.M. Müller, S. Hawgood, G. Johnen
Journal: European Respiratory Journal (2004)

Pulmonary alveolar proteinosis (PAP) is a rare disorder characterised histologically by an intra-alveolar accumulation of fine granular eosinophilic and periodic acid-Schiff positive material. In a retrospective study, the composition of the intra-alveolarly accumulated material of adult patients with PAP was analysed by means of immunohistochemistry and Western blotting. In patients with PAP, the current authors found an intra-alveolar accumulation of surfactant protein (SP)-A, precursors of SP-B, SP-B, variable amounts of mono-, di-, and oligomeric SP-C forms, as well as SP-D. Only in one patient was a precursor of SP-C detected. By means of immuno-electron microscopy, the current authors identified not only transport vesicles labelled for precursors of SP-B and SP-C, but also transport vesicles containing either precursors of SP-B or SP-C in type-II pneumocytes in normal human lungs. It is concluded that pulmonary alveolar proteinosis in adults is characterised by an intra-alveolar accumulation of surfactant protein A, precursors of surfactant protein B, and surfactant proteins B, C and D. The current data provide evidence that not only an impairment of surfactant clearance by alveolar macrophages, but also an abnormal secretion of transport vesicles containing precursors of surfactant protein B (but not surfactant protein C) and an insufficient palmitoylation of surfactant protein C, which may lead to the formation of di- and oligomeric surfactant protein C forms, play a role in the pathogenesis of pulmonary alveolar proteinosis.
Time Delay to Treatment and Mortality in Primary Angioplasty for Acute Myocardial Infarction
Authors: Giuseppe De Luca, Harry Suryapranata, Jan Paul Ottervanger, Elliott M. Antman
Journal: Circulation (2004)

Although the relationship between mortality and time delay to treatment has been demonstrated in patients with acute ST-segment elevation myocardial infarction (STEMI) treated by thrombolysis, the impact of time delay on prognosis in patients undergoing primary angioplasty has yet to be clarified. The aim of this report was to address the relationship between time to treatment and mortality as a continuous function and to estimate the risk of mortality for each 30-minute delay.The study population consisted of 1791 patients with STEMI treated by primary angioplasty. The relationship between ischemic time and 1-year mortality was assessed as a continuous function and plotted with a quadratic regression model. The Cox proportional hazards regression model was used to calculate relative risks (for each 30 minutes of delay), adjusted for baseline characteristics related to ischemic time. Variables related to time to treatment were age >70 years (P<0.0001), female gender (P=0.004), presence of diabetes mellitus (P=0.002), and previous revascularization (P=0.035). Patients with successful reperfusion had a significantly shorter ischemic time (P=0.006). A total of 103 patients (5.8%) had died at 1-year follow-up. After adjustment for age, gender, diabetes, and previous revascularization, each 30 minutes of delay was associated with a relative risk for 1-year mortality of 1.075 (95% CI 1.008 to 1.15; P=0.041).These results suggest that every minute of delay in primary angioplasty for STEMI affects 1-year mortality, even after adjustment for baseline characteristics. Therefore, all efforts should be made to shorten the total ischemic time, not only for thrombolytic therapy but also for primary angioplasty.