tbuckley/cabot-search huggingface dataset:
Weighting by heritability for detection of quantitative trait loci with microarray estimates of gene expression.
Authors: Kenneth F Manly, Jintao Wang, Robert W Williams
Journal: Genome biology (2005)

Abstract Heritable differences in transcribed RNA levels can be mapped as quantitative trait loci (QTLs). Transcribed RNA levels are often measured by hybridization to microarrays of oligonucleotide probes, in which each transcript is represented by multiple probes. The use of recombinant inbred lines allows an estimate of the heritability of expression measured by individual probes. This heritability varies greatly. We have tested heritability-weighted averages to define expression of a transcript and found that these allow detection of more QTLs than previously described methods.
Pancoast's syndrome due to chronic pneumonia by Pasteurella multocida
Authors: J Ribas, L Lores, J Ruiz, V Ausina, J Morera
Journal: European Respiratory Journal (1997)

Infectious causes of Pancoast's syndrome are extremely rare. We describe the case of a patient with Pancoast's syndrome due to chronic pneumonia resulting from Pasteurella multocida. The patient was not immunosuppressed and had had no contact with animals. The diagnosis was made by transthoracic needle aspiration and institution of therapy with cefuroxime-axetil resulted in resolution of his symptoms.
Accumulation of novel transplatinum complexes in cisplatin and oxaliplatin resistant cell lines overcomes resistance
Authors: Robert F. Murphy, Nick Farrell, Alian Aguila, Masaki Okada, Frank M. Balis, Tito Fojo
Journal: Cancer Research (2005)

4109  We previously identified nine novel groups of platinum compounds based on distinctive activity profiles in the NCI 60 cell line panel (using Clustered Image Maps, the COMPARE algorithm, and other numerical methods) with characteristic chemical structures. A group of transplatin analogs of the general structure trans-[PtX2(L)(L’)] where X = Cl or OAc, L = NH3, L’= a planar, nitrogen-containing heterocycle or L = L ’ = a planar, nitrogen-containing heterocycle were further characterized. Compared to the trans-[PtCl2(L)(L’)] compounds, the trans-[PtOAc2(L)(L’)] analogs are more stable and water-soluble. When the transplanar platinum compounds were incubated with fresh plasma and subjected to ultrafiltration, 39 to 63% of the trans-[PtOAc2(L)(L’)] compounds could be recovered in the ultrafiltrate compared to only 1.8 to 4.1% of the trans-[PtCl2(L)(L’)] compounds. In addition to having a cytotoxicity profile distinct from that of cisplatin, carboplatin and oxaliplatin, all members of this class of compounds retained activity against cisplatin and oxaliplatin-resistant cell lines. A possible explanation for this persistent activity was obtained in studies examining the accumulation of platinum in the drug resistant cells lines. Platinum analogs (33 μM) were incubated for 2 h with the parental (KB) and cisplatin (KBCP20) and oxaliplatin (KBOXO80) resistant cell lines. Intracellular platinum was measured by atomic absorption spectroscopy after extraction. Compared to cisplatin and oxaliplatin whose accumulation in the drug resistant cell lines was 4.8 to 21% of that in parental KB cells (Table), the accumulation of four trans-[PtOAc2(L)(L’)] compounds was 83 to 166%. Thus these trans-[PtX2(L)(L’)] compounds have an activity profile distinct from platinum compounds currently in use, and retain activity in oxaliplatin- and cisplatin-resistant cells lines at least in part by retaining the ability to accumulate in the resistant cells at levels comparable to those in drug sensitive parental cells. 1IC50 of resistant cell line divided by IC50 of parental KB cells 2Percent of parental KB cell accumulation
Tyrosine kinase inhibitor sunitinib relieves systemic and oral antigen‐induced anaphylaxes in mice
Authors: K. Yamaki, S. Yoshino
Journal: Allergy (2011)

To cite this article: Yamaki K, Yoshino S. Tyrosine kinase inhibitor sunitinib relieves systemic and oral antigen‐induced anaphylaxes in mice. Allergy 2012; 67 : 114–122. Abstract Background: Systemic and oral antigen‐induced anaphylaxes are mediated by immunoglobulin (Ig) E and mast cells, but there is no satisfactory treatment for the life‐threatening allergic reaction. We investigated the potential of the multitargeted receptor tyrosine kinase inhibitor sunitinib to relieve anaphylactic reactions in food allergy and systemic anaphylaxis. Methods: Efficacy of oral sunitinib on oral and parenteral antigen‐induced anaphylaxes in Balb/c mice was evaluated. IgE‐dependent degranulation and growth of rat basophilic leukemia RBL2H3 and bone marrow‐derived mast cells (BMMCs) in response to sunitinib were investigated. Results: Daily administration of sunitinib throughout antigen challenges prevented oral antigen‐induced anaphylaxis including diarrhea, anaphylactic symptoms, and hypothermia. The mouse mast cell protease (MMCP)‐1 concentration in serum and mast cell number in intestinal tissue after challenge were also decreased by the treatment. Spleen cells from sunitinib‐treated mice contained smaller numbers of antigen‐specific IgG‐producing cells and secreted lower amounts of both Th1 and Th2 cytokines than those of the control mice, whereas the levels of antigen‐specific antibodies in serum were not decreased. The reactions and MMCP‐1 release in oral antigen‐induced anaphylaxis and passive systemic anaphylaxis were attenuated even by a single predose of sunitinib. Degranulation and growth of RBL2H3 cells and BMMCs were greatly reduced by sunitinib. Conclusion: These results suggested that sunitinib relieves systemic and oral antigen‐induced anaphylaxes by the prevention of mast cell activation and hyperplasia in intestinal tissue directly and indirectly through an immunosuppressive effect. Sunitinib and its related kinase inhibitors might be potential drugs for the treatment of food allergy and systemic anaphylaxis.
Abstract 1045: E-ntpdase-1/Cd39 Confers Anti-inflammatory And Immunomodulatory Properties To Circulating Membrane-derived Microparticles
Authors: Yara Banz, Guido Beldi, Yan Wu, Anny Usheva, Simon C Robson
Journal: Circulation (2007)

Background: Microparticles (MPs, &lt;1.5ÂμM) are circulating, membrane-derived micro-vesicles shed from cells and platelets under physiological conditions as well as following stress, such as post-myocardial infarction. MPs have been implicated in inflammation, coagulation and vascular function. CD39, the prototype nucleoside triphosphate diphosphohydrolase (NTP-Dase1) within the vasculature modulates extracellular purinergic signalling through ATP and ADP hydrolysis, conferring anti-inflammatory, anti-thrombotic properties to the intravascular space. The aim of this study was to determine if CD39 is present on MPs and whether this impacts MP phenotype and function. Methods: The proteome, absolute numbers as well as cellular origin of circulating MPs from wild type (wt) and cd39-null C57Bl6 mice were compared by 2D-gel electrophoresis, western blot and flow cytometry. Isolated MPs were incubated with endothelial cells (EC) to analyze their intrinsic pro-inflammatory potential. Results: CD39 can be demonstrated and has ecto-enzymatic activity on circulating MPs from wt mice. 2D-gel analysis revealed that cd39-null MPs express lower levels of talin (component of focal adhesion) and ATP synthase, when compared to wild type MPs. Mutant mice have increased numbers of circulating MPs, with significantly higher fractions derived from platelets and endothelium as compared to wt mice (p&lt;0.05). The presence of CD39 on wt MPs significantly attenuates inflammatory responses following incubation with EC as compared to cd39-null MPs (reduced IL-6 and TNF-alpha secretion, ICAM-1 and VCAM-1 expression, vWF release and NF-kappa B activation, p&lt;0.05). Conclusions: CD39 confers anti-inflammatory and immunomodulatory properties upon circulating MPs. These results highlight the protective potential of CD39; a finding that may be exploited therapeutically, with the prospective of administering soluble CD39 (apyrase) to the site of intravascular injury to ameliorate inflammation, as occurs for instance in acute coronary syndromes.
Imetelstat, a Telomerase Inhibitor, Therapy for Myelofibrosis: A Pilot Study
Authors: Ayalew Tefferi, Betsy R. LaPlant, Kebede Begna, Mrinal M. Patnaik, Terra L Lasho, Darci Zblewski, Christy Finke, Lauren Schimek, Adam Pettinger, Curtis A. Hanson, Naseema Gangat, Animesh Pardanani
Journal: Blood (2014)
Poly(ADP-ribose) polymerase (PARP) decreases apoptosis and stimulates growth of HeLa cells by decreasing stability of P2X7 mRNA
Authors: Lingyin Zhou, Xiaoping Qi, Liping Luo, Mukesh Agarwal, Olena Skomorovska-Prokvolit, Wen Fu, Judith Potashkin, George Gorodeski
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

2692 

Introduction: The P2X7 receptor is a membrane-bound ligand-operated channel, and in epithelia its main function is regulation of apoptosis. Recent studies showed that protein and mRNA levels of P2X7 are lower in cancer epithelial tissues than in the corresponding normal tissues, and that P2X7-mediated apoptosis is abrogated in epithelial cancer cells compared to normal cells. These data suggest that decreased expression of P2X7 predisposes epithelial cells to the effects of carcinogens and may lead to the development of cancer. In this study, we tested the hypothesis that regions of the 3’UTR of P2X7 mRNA confer instability to the transcript.    Methods: Normal (hEVEC) and cancerous human uterine cervical epithelial cells (HeLa) were transfected with a reporter plasmid containing luciferase - 3’ untranslated region (3’UTR)-P2X7 cDNA. RNA-Protein Pull-Down experiments involved incubation of biotin-labeled, in-vitro - transcribed (3’UTR)-P2X7 mRNA with nuclear extract of HeLa cells, followed by fractionation using SDS-PAGE. RNA was quantified by one-step qPCR and levels were normalized to GAPDH. Apoptosis was quantified using commercially available kits.    Results: (1) Steady-state levels of luciferase mRNA were higher in hEVEC cells transfected with the 3’UTR-P2X7-luciferase vector than in HeLa cells transfected with the reporter plasmid. (2) Pull-Down experiments using (3’UTR)-P2X7 mRNA revealed significant interaction with a 115 kDa band in nuclear extracts of HeLa but only minimally in hEVEC cells. (3) Mass spectrometry of the band revealed the presence of human poly(ADP-ribose) polymerase (PARP). (4) Treatment of HeLa cells with the PARP inhibitor 4-HQN resulted in a dose-related increase in P2X7 mRNA and apoptosis.    Conclusions: The data suggest that (1) cancerous epithelial cells degrade P2X7 mRNA by activation of instability domains located at the 3’UTR of the P2X7; (2) PARP interacts with transcribed P2X7 mRNA and de-stabilizes the (3’UTR)-P2X7 mRNA; (3) inhibition of PARP augments P2X7-related apoptosis by increasing stability of the P2X7 mRNA.    Support: NIH (AG15955) and CytoCore Inc. unrestricted grant to GIG.
Multiple traces or Fuzzy Traces? Converging evidence for applications of modern cognitive theory to psychotherapy
Authors: Valerie F. Reyna, Yulia Landa
Journal: Behavioral and Brain Sciences (2015)

Neurobiologically informed integration of research on memory, emotion, and behavior change in psychotherapy is needed, which Lane at al. advance. Memory reconsolidation that incorporates new emotional experience plays an important role in therapeutic change, converging with evidence for Fuzzy Trace Theory. Applications of Fuzzy Trace Theory to Cognitive Behavioral Therapy (CBT) for youth at risk for psychosis, and to other aspects of behavior change, are discussed.
Abstract 117: Mild Induced Hypothermia and Emergency Percutaneous Coronary Intervention After Out-of-Hospital Cardiac Arrest Complicating ST-Elevation Myocardial Infarction: Long-Term Survival and Neurological Outcome
Authors: Stefan Zimmermann, Frank A Flachskampf, Reinhard Schneider, Anna Alff, Katharina Dechant, Lutz Klinghammer, Werner G Daniel, Stephan Achenbach
Journal: Circulation (2011)

Background: Therapeutic hypothermia has been integrated into international resuscitation guidelines to improve survival after out-of-hospital cardiac arrest (OHCA). Data on long-term results are li...
Abstract 3748: Transcriptome landscape of brain tumor progression at single-cell resolution
Authors: Kyu-Tae Kim, Jin-Ku Lee, Dong-Hyun Park, Do-Hyun Nam, Hae-Ock Lee, Woong-Yang Park
Journal: Cancer Research (2015)

Abstract BACKGROUND: Tumor progression within a brain is the process of acquiring malignant genetic mutations from glial progenitor cells, dodging their original developmental fate and deteriorating functional connectivity of CNS. In order to devise effective targeted therapeutic strategies, understanding distinct molecular and phenotypic evolutionary features of cancer clones is eminent. METHODS: To examine molecular signatures associated with malignant glioma progression, we analyzed transcriptome dynamics of 311 single-cells derived from 3 patients showing distinct disease patterns. Combined with single-cell level signatures, clonal architecture of tumors was reconstructed based on Bayesian-model clustering with integrated information of SSNVs and SCNAs identified from bulk population-level using aCGH and WES. RESULTS: We found evidence of branched evolutionary patterns within and across two histopathological separated tumor regions. Both tumors have high clonal probable somatic mutations, and evolutionary inference showed clonal lineage between two tumor regions was divided at early time during tumor progression. For all patients, the gene expression signatures within a tumor were heterogeneous but converged towards mesenchymal phenotype in the aggressive region. In the first case, the left tumor was self-limiting and showed mixed proneural and classical gene expression signatures whereas the right side tumor has expanded to the corpus callosum with EGFR overexpression and mesenchymal gene expression. In a case of a monocentric tumor with PDGFRA amplification, cancer cells disseminated from the core mass with massive immune cell infiltration underwent transcriptome switching from proneural to mesenchymal gene expression, with a concomitant FGFR1 copy number gain and mutation. Lastly, in a secondary glioblastoma with IDH1 mutation, GLIOLAN positive glioblastoma was surrounded by grade III oligodendroglioma. The two tumor areas showed intermingled heterogeneous gene expression signatures, with upregulation of astrocytic/mesenchymal genes in the GLIOLAN positive tumor cells. CONCLUSIONS: Our results show distinct genetic patterns of clonal expansion across patients undergoing malignant glioma progression. We also provide the transcriptome-wide view of gene expression signatures directed by genomic alterations. Overall our study reveals heterogeneity of individual tumor but elucidates common genomic features of glioblastoma progression. Citation Format: Kyu-Tae Kim, Jin-Ku Lee, Dong-Hyun Park, Do-Hyun Nam, Hae-Ock Lee, Woong-Yang Park. Transcriptome landscape of brain tumor progression at single-cell resolution. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3748. doi:10.1158/1538-7445.AM2015-3748
931. Correction of ADA-SCID by Stem Cell Gene Therapy Combined with a Non-Myeloablative Conditioning
Authors: Scott H. Sicherer
Journal: Molecular Therapy (2002)

Aiuti A, Slavin S, Aker M, et al. Science. 2002;296:2410–2413 

To use improved gene therapy techniques to correct adenoside deaminase (ADA)-deficient severe combined immunodeficiency (SCID).

Two patients (7 months old and 2.5 years) with ADA-SCID who lacked an HLA-identical sibling donor and for whom polyethylene glycol conjugated (PEG)-ADA was unavailable.

Patients underwent collection of autologous CD34+ cells (stem cells) from bone marrow that were …
Abstract 1355: Functional inactivation of LKB1 increases the production of pro-inflammatory cytokines and governs response to immune modulation
Authors: Esra A. Akbay, Shohei Koyama, Yvonne Li, Grit S. Herter-Sprie, Tran C. Thai, Amir R. Aref, Margaret Soucheray, Takeshi Shimamura, David A. Barbie, Glenn Dranoff, Peter S. Hammerman, Kwok-Kin Wong
Journal: Cancer Research (2015)

Abstract LKB1/STK11 is one of the most commonly mutated tumor suppressors in non-small cell lung cancers. Inactivation of LKB1/STK11 is common in lung cancers with mutated KRAS alleles (1) and results in a clinically more aggressive and metastatic phenotype (2-5). Here, we show in genetically engineered mouse models (GEMMs) and in primary human cancer specimens that loss of LKB1/STK11 in the context of mutated KRAS has a marked effect on the tumor immune microenvironment characterized by accumulation of neutrophils and of tumor promoting cytokines including interleukin (IL)-6. Importantly, Kras/Lkb1 tumors also carry reduced number of tumor-infiltrating lymphocytes with the infiltrating lymphocytes expressing higher levels of T cell exhaustion markers and greater proportions of regulatory T cells as compared to KRAS-driven (Kras) tumors. We also found that presence of LKB1 mutation was negatively correlated with programmed death-1 ligand-1 (PD-L1) expression in mouse and human lung tumors and that antibodies therapeutically targeting this immune checkpoint were ineffective in Kras/Lkb1 mice. In contrast, an IL-6 neutralizing antibody showed clinical benefit in the Kras/Lkb1 model via the reduction of neutrophil accumulation and proinflammatory cytokines. These findings suggest that LKB1 loss of function exacerbates the tumor inflammatory microenvironment in lung cancers and that targeting the aberrant cytokine signaling in LKB1-deficient tumors could be a viable therapeutic option. Citation Format: Esra A. Akbay, Shohei Koyama, Yvonne Li, Grit S. Herter-Sprie, Tran C. Thai, Amir R. Aref, Margaret Soucheray, Takeshi Shimamura, David A. Barbie, Glenn Dranoff, Peter S. Hammerman, Kwok-Kin Wong. Functional inactivation of LKB1 increases the production of pro-inflammatory cytokines and governs response to immune modulation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1355. doi:10.1158/1538-7445.AM2015-1355
Short-term results of a registered smoking cessation clinic with patients referred by ALO 171 Quitline
Authors: Dorina Rama Esendagli, Ozge Ozturk, Derya Ersel, Seha Akduman, Deniz Koksal, Salih Emri
Journal: European Respiratory Journal (2014)

According to the Global Adult Tobacco Survey 2012 in Turkey overall smoking rate is 27.1%. Within the MPOWER package, one of the main issues is to offer help by referring smokers to registered smoking cessation clinics. Here, the results of a follow up of patients with tobacco addiction referred from the ALO 171 official quitline of Ministry of Health are presented. This smoking cessation clinic is functional for over 1 year.  Each patient underwent a survey asking demographic information, motivation to quit, Fagerstrom test (FT), physical examination, amount of exhaled CO, pulmonary function test, chest x-ray, and treatment given.  A total of 192 patients (63% male) was followed. Mean age was 43±13 (Avg±SD). Mean packet/year consumed was 25.80±20.05 and 54% were heavy-smokers. Majority of the patients (87%) participated to a cessation program for the first time and 27.1% never tried to quit before. According to FT 43.8% of the patients were highly addicted. Yet, 69.8% were highly motivated and confident for quitting. Only 34.9% heard about the pharmacotherapy.  The patients were identified with chronic cough 40.6%, sputum 43.8%, hemoptysis 2.6%, dyspnea 33.9%, angina 17.7%, diabetes 4.7%, and hypertension and high cholesterol 6.8%. The patients had exhaled CO 9.3±4.9; FEV1, 2.9±0.9L; FEV1/FVC 80.9±11.2 values.  Only 44.3% of patients took the treatment correctly. Unfortunately, 45.3% who did notquit smoking had either refused or inappropriately used the treatment. Following the treatment, there was an overall quittance rate of 18.2% (varenycline 38.2%; 29.4% NRT; 26.5% bupropione, and 5.7% drugs combination). There was no significant difference between the treatment modalities.
A double-blind, comparative facial tolerance study of a new 10% sodium sulfacetamide &amp; 5% sulfur aqueous gel (in a 10% urea vehicle) vs. a 10% sodium sulfacetamide &amp; 5% sulfur topical suspension in rosacea &amp; acne subjects with sensitive skin
Authors: James J. Leyden, Gary Grove, Charles Zerweck
Journal: Journal of the American Academy of Dermatology (2004)
Prevalence and characterization of extended-spectrum β-lactamase-producing clinical Salmonella enterica isolates in Dakar, Senegal, from 1999 to 2009
Authors: D. Harrois, S. Breurec, A. Seck, A. Delauné, S. Le Hello, M. Pardos de la Gándara, L. Sontag, J.-D. Perrier-Gros-Claude, J.-M. Sire, B. Garin, F.-X. Weill
Journal: Clinical Microbiology and Infection (2013)
Abstract 235: Therapeutic Levels of Anticoagulation Do Not Increase Embolic Risk Early in the Course of S. Aureus Infective Endocarditis
Authors: Stuart Dickerman, Michael Gurin, Bruno Barsic, Magid Halim, Vivian Chu, Ralph Corey, Tsung-Cheng Hsieh, Arnold Bayer
Journal: Circulation (2009)

Therapeutic levels of anticoagulation do not increase embolic risk early in the course of S.aureus infective endocarditis Introduction  Current guidelines recommend temporary discontinuation of ongoing anticoagulant therapy early in the course of S. aureus (SA) infective endocarditis (IE). This guideline is based on limited data in patients with SA prosthetic valve IE demonstrating a significant risk of adverse events when anticoagulation is continued. These studies, however, do not stratify the risk of clinical events according to the level of anticoagulation as measured by the INR. We hypothesized that therapeutic levels of anticoagulation do not increase the risk of embolic events in this group of patients.   Methods:  This study used the database of the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS) to address the relationship between the level of anticoagulation as measured by the INR and the risk of stroke and other embolic events in anticoagulated patients with SA IE. Of the 5593 patients enrolled in ICE-PCS between January 2000 and December 2006, there were 104 patients with SA IE who were anticoagulated at the time of admission, and had data available on the INR and incidence of stroke and other embolic events at admission.   Results:  In patients with SA IE admitted with an INR >3.5, more patients had stroke or other embolic events at admission compared to those admitted with an INR    Conclusion:  An excess risk of stroke and other embolic events in anticoagulated patients early in the course of SA IE appears limited to those patients who are overanticoagulated as measured by the INR. Consideration should be given to the continuation of therapeutic levels of anticoagulation even early in the course of SA IE.
Charting Unique Signatures of Somatic Hypermutation Amongst Chronic Lymphocytic Leukemia Patients Expressing IGHV4-34 Clonotypic B Cell Receptors
Authors: Aliki Xochelli, Ioannis Kavakiotis, Andreas Agathangelidis, Dirk Kienle, Zadie Davis, Xiao J. Yan, Tait Shanafelt, Myriam Boudjogra, Karla Plevova, Maria Chatzouli, Lone Bredo Pedersen, Silvio Veronese, Monica Facco, Denis Moreno, Charles C Chu, Veronique Giudicelli, Panagiotis Panagiotidis, Ioannis Vlahavas, Achilles Anagnostopoulos, Nikolaos Maglaveras, Livio Trentin, Mark Catherwood, Marco Montillo, Christian H. Geisler, Anton W Langerak, Sarka Pospisilova, Marie-Paule Lefranc, Nicholas Chiorazzi, David Oscier, Diane F. Jelinek, Stephan Stilgenbauer, Chrysoula Belessi, Paolo Ghia, Frederic Davi, Richard Rosenquist, Nikos Darzentas, Ioanna Chouvarda, Lesley-Ann Sutton, Anastasia Hadzidimitriou, Kostas Stamatopoulos
Journal: Blood (2014)