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https://www.readbyqxmd.com/read/29150704/evaluation-of-immune-mediated-idiosyncratic-drug-toxicity-using-chimeric-hla-transgenic-mice
#1
Takeshi Susukida, Shigeki Aoki, Kotaro Kogo, Sota Fujimori, Binbin Song, Cong Liu, Shuichi Sekine, Kousei Ito
Immune-mediated idiosyncratic drug toxicity (IDT) is a rare adverse drug reaction, potentially resulting in death. Although genome-wide association studies suggest that the occurrence of immune-mediated IDT is strongly associated with specific human leukocyte antigen (HLA) allotypes, these associations have not yet been prospectively demonstrated. In this study, we focused on HLA-B*57:01 and abacavir (ABC)-induced immune-mediated IDT, and constructed transgenic mice carrying chimeric HLA-B*57:01 (B*57:01-Tg) to determine if this in vivo model may be useful for evaluating immune-mediated IDT...
November 17, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29150511/sulfolobus-acidocaldarius-uptakes-pentoses-via-a-cut2-type-abc-transporter-and-metabolizes-them-through-the-aldolase-independent-weimberg-pathway
#2
Michaela Wagner, Lu Shen, Andreas Albersmeier, Nienke van der Kolk, Sujin Kim, Jaeho Cha, Christopher Bräsen, Jörn Kalinowski, Bettina Siebers, Sonja-Verena Albers
Sulfolobus spp. possess a great metabolic versatility and grow heterotrophically on various carbon sources such as different sugars and peptides. Known sugar transporters in Archaea predominantly belong to ABC transport systems. Although several ABC transporters for sugar uptake have been characterized in the crenarchaeon Sulfolobus solfataricus, only one homologue of these transporters, the maltose/maltooligomer transporter, could be identified in the closely related Sulfolobus acidocaldarius Comparison of the transcriptome of S...
November 17, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29150050/cytogenetic-changes-in-the-bhopal-population-exposed-to-methyl-isocyanate-mic-in-1984-then-and-30-years-later
#3
Bani Bandana Ganguly, Shouvik Mandal
Following the 1984 Bhopal methyl isocyanate (MIC) gas disaster, genetic alterations were sporadically reported on small cohorts. However, the outcome of the multi-center cytogenetic screening conducted at that time remains unknown and no follow-up studies on the long-term effects of MIC exposure have been published. The present work examines genetic changes in the exposed population,with the aim of identifying any long-term effects of MIC. G-Banded metaphases were studied in lymphocytes of 130 individuals. Chromosomal aberrations (CA) were broadly grouped as abnormal cells (Abc), aberrations (Abn), and aberration/abnormal cell (Abn/Abc)...
December 2017: Mutation Research
https://www.readbyqxmd.com/read/29147815/atp-binding-cassette-transporters-limit-the-brain-penetration-of-wee1-inhibitors
#4
Mark C de Gooijer, Levi C M Buil, Jos H Beijnen, Olaf van Tellingen
Introduction Wee1 is an important kinase involved in the G2 cell cycle checkpoint and frequently upregulated in intracranial neoplasms such as glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG). Two small molecules are available that target Wee1, AZD1775 and PD0166285, and clinical trials with AZD1775 have already been started. Since GBM and DIPG are highly invasive brain tumors, they are at least to some extent protected by the blood-brain barrier (BBB) and its ATP-binding cassette (ABC) efflux transporters...
November 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29146563/characterization-of-the-ipec-j2-mdr1-ip-gp-cell-line-as-a-tool-for-identification-of-p-gp-substrates
#5
Burak Ozgür, Lasse Saaby, Kristine Langthaler, Birger Brodin
Recently, we transfected the porcine intestinal cell line IPEC-J2, with human P-glycoprotein (P-gp, ABCB1). The resulting cell line, iP-gp, has a high expression of functional human P-gp in the apical membrane, and a low expression of nonhuman ATP-binding cassette (ABC) transporters. The aim of the present work was to investigate the usability of iP-gp cell line for determining transepithelial transport kinetics of the prototypical P-gp substrates digoxin and rhodamine 123. The cell line generated tight monolayers after 16days of culture, reflected by high transepithelial electrical resistance values (TEER>15,000Ω·cm(2)), immunocytochemistry and low fluxes of the paracellular flux marker [(14)C]-mannitol...
November 13, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29146558/role-of-his-his-interaction-in-ser-474-his-475-tyr-476-sequence-of-chondroitinase-abc-i-in-the-enzyme-activity-and-stability
#6
Monireh Maleki, Khosro Khajeh, Massoud Amanlou, Abolfazl Golestani
Despite clinical importance of chondroitinase ABC I, its application has been limited due to thermal instability as reported in the literature. There are various approaches to improve thermal stability of enzymes, among them, His-His interactions are believed generally as an effective means. In the present study and for preparing a His-His interaction, various mutations in the sequence of Ser(474)-His(475)-Tyr(476) at catalytic domain of the enzyme were performed using site directed mutagenesis method. The effect of these mutations on activity, stability and structural features of cABC I was assessed...
November 13, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29146535/2017-acc-aha-aapa-abc-acpm-ags-apha-ash-aspc-nma-pcna-guideline-for-the-prevention-detection-evaluation-and-management-of-high-blood-pressure-in-adults-a-report-of-the-american-college-of-cardiology-american-heart-association-task-force-on-clinical-practice
#7
Paul K Whelton, Robert M Carey, Wilbert S Aronow, Donald E Casey, Karen J Collins, Cheryl Dennison Himmelfarb, Sondra M DePalma, Samuel Gidding, Kenneth A Jamerson, Daniel W Jones, Eric J MacLaughlin, Paul Muntner, Bruce Ovbiagele, Sidney C Smith, Crystal C Spencer, Randall S Stafford, Sandra J Taler, Randal J Thomas, Kim A Williams, Jeff D Williamson, Jackson T Wright
No abstract text is available yet for this article.
November 7, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29146534/systematic-review-for-the-2017-acc-aha-aapa-abc-acpm-ags-apha-ash-aspc-nma-pcna-guideline-for-the-prevention-detection-evaluation-and-management-of-high-blood-pressure-in-adults-a-report-of-the-american-college-of-cardiology-american-heart-association-task
#8
David M Reboussin, Norrina B Allen, Michael E Griswold, Eliseo Guallar, Yuling Hong, Daniel T Lackland, Edgar Pete R Miller, Tamar Polonsky, Angela M Thompson-Paul, Suma Vupputuri
OBJECTIVE: To review the literature systematically and perform meta-analyses to address these questions: 1) Is there evidence that self-measured blood pressure (BP) without other augmentation is superior to office-based measurement of BP for achieving better BP control or for preventing adverse clinical outcomes that are related to elevated BP? 2) What is the optimal target for BP lowering during antihypertensive therapy in adults? 3) In adults with hypertension, how do various antihypertensive drug classes differ in their benefits and harms compared with each other as first-line therapy? METHODS: Electronic literature searches were performed by Doctor Evidence, a global medical evidence software and services company, across PubMed and EMBASE from 1966 to 2015 using key words and relevant subject headings for randomized controlled trials that met eligibility criteria defined for each question...
November 7, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29146533/2017-acc-aha-aapa-abc-acpm-ags-apha-ash-aspc-nma-pcna-guideline-for-the-prevention-detection-evaluation-and-management-of-high-blood-pressure-in-adults-executive-summary-a-report-of-the-american-college-of-cardiology-american-heart-association-task-force-on
#9
Paul K Whelton, Robert M Carey, Wilbert S Aronow, Donald E Casey, Karen J Collins, Cheryl Dennison Himmelfarb, Sondra M DePalma, Samuel Gidding, Kenneth A Jamerson, Daniel W Jones, Eric J MacLaughlin, Paul Muntner, Bruce Ovbiagele, Sidney C Smith, Crystal C Spencer, Randall S Stafford, Sandra J Taler, Randal J Thomas, Kim A Williams, Jeff D Williamson, Jackson T Wright
No abstract text is available yet for this article.
November 7, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29145976/not-only-p-glycoprotein-amplification-of-the-abcb1-containing-chromosome-region-7q21-confers-multidrug-resistance-upon-cancer-cells-by-coordinated-overexpression-of-an-assortment-of-resistance-related-proteins
#10
Ilaria Genovese, Andrea Ilari, Yehuda G Assaraf, Francesco Fazi, Gianni Colotti
The development of drug resistance continues to be a dominant hindrance toward curative cancer treatment. Overexpression of a wide-spectrum of ATP-dependent efflux pumps, and in particular of ABCB1 (P-glycoprotein or MDR1) is a well-known resistance mechanism for a plethora of cancer chemotherapeutics including for example taxenes, anthracyclines, Vinca alkaloids, and epipodopyllotoxins, demonstrated by a large array of published papers, both in tumor cell lines and in a variety of tumors, including various solid tumors and hematological malignancies...
May 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/29145636/localization-and-functional-characterization-of-the-p-asn965ser-n965s-abca4-variant-in-mice-reveal-pathogenic-mechanisms-underlying-stargardt-macular-degeneration
#11
Laurie L Molday, Daniel Wahl, Marinko Sarunic, Robert S Molday
ABCA4 is a member of the superfamily of ATP-binding cassette (ABC) proteins that transports N-retinylidene-phosphatidylethanolamine (N-Ret-PE) across outer segment disc membranes thereby facilitating the removal of potentially toxic retinoid compounds from photoreceptor cells. Mutations in the gene encoding ABCA4 are responsible for Stargardt disease (STGD1), an autosomal recessive retinal degenerative disease that causes severe vision loss. To define the molecular basis for STGD1 associated with the p.Asn965Ser (N965S) mutation in the Walker A motif of nucleotide binding domain 1 (NBD1), we generated a p...
November 14, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29145194/deficiency-of-functional-iron-sulfur-domains-in-abce1-inhibits-the-proliferation-and-migration-of-lung-adenocarcinomas-by-regulating-the-biogenesis-of-beta-actin-in-vitro
#12
Qian Yu, Xu Han, Da-Li Tian
BACKGROUND/AIMS: ATP-binding cassette transporter E1 (ABCE1), a unique ABC superfamily member that bears two Fe-S clusters, is essential for metastatic progression in lung cancer. Fe-S clusters within ABCE1 are crucial for ribosome dissociation and translation reinitiation; however, whether these clusters promote tumor proliferation and migration is unclear. METHODS: The interaction between ABCE1 and β-actin was confirmed using GST pull-down. The lung adenocarcinoma (LUAD) cell line A549 was transduced with lentiviral packaging vectors overexpressing either wild-type ABCE1 or ABCE1 with Fe-S cluster deletions (ΔABCE1)...
November 17, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29144855/pain-intensity-and-sexual-functioning-in-men-with-genital-pain-the-mediation-role-of-sexually-related-thoughts
#13
Raquel Pereira, Cátia M Oliveira, Pedro J Nobre
The comorbidity between male genital pain and sexual dysfunction is highly prevalent. Previous studies have indicated that men with genital pain share some cognitive characteristics with men experiencing other sexual dysfunctions. However, there is little information on the role of these cognitive factors in understanding the relationship between pain intensity and sexual functioning. This study aims to test if negative sexually-related thoughts mediate the relationship between pain intensity and sexual functioning in men with genital pain...
November 16, 2017: Journal of Sex & Marital Therapy
https://www.readbyqxmd.com/read/29143928/systematic-literature-review-of-the-impact-of-endocrine-monotherapy-and-in-combination-with-targeted-therapy-on-quality-of-life-of-postmenopausal-women-with-hr-her2-advanced-breast-cancer
#14
REVIEW
Zhou Zhou, Derek H Tang, Jipan Xie, Rajeev Ayyagari, Eric Wu, Polly A Niravath
INTRODUCTION: A major treatment goal for advanced breast cancer (ABC) is to maintain or ideally improve patient quality of life (QoL). Given the changing disease landscape, this systematic literature review (SLR) aims to assess the impact of endocrine therapies (ET), including ET monotherapy (ET mono) and ET combined with targeted therapy (ET + TT), on QoL of women with HR+/HER2- ABC. METHODS: A SLR was conducted to identify randomized controlled trials (RCTs) meeting the following criteria: (1) included ET mono or ET + TT, (2) reported QoL outcomes, (3) focused on women with HR+/HER2- ABC, and (4) published after 2007 (when standardized HER2 testing became available)...
November 16, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/29139553/distinct-b-subunits-of-pp2a-regulate-the-nf-%C3%AE%C2%BAb-signaling-pathway-through-dephosphorylation-of-ikk%C3%AE-i%C3%AE%C2%BAb%C3%AE-and-rela
#15
Yoshihiro Tsuchiya, Keiko Osaki, Mayu Kanamoto, Yuki Nakao, Ena Takahashi, Toru Higuchi, Hideaki Kamata
PP2A is composed of a scaffolding subunit (A), a catalytic subunit (C), and a regulatory subunit (B) that is classified into four families including B, B', B'', and B'''/striatin. Here, we found that a distinct PP2A complex regulates NF-κB signaling by dephosphorylation of IKKβ, IκBα, and RelA/p65. The PP2A core enzyme AC dimer and the holoenzyme AB'''C trimer dephosphorylate IKKβ, IκBα, and RelA, whereas the ABC trimer dephosphorylates IκBα but not IKKβ and RelA in cells. In contrast, AB'C and AB''C trimers have little effect on dephosphorylation of these signaling proteins...
November 15, 2017: FEBS Letters
https://www.readbyqxmd.com/read/29139179/involvement-of-lemrp-an-atp-binding-cassette-transporter-in-shikonin-transport-and-biosynthesis-in-lithospermum-erythrorhizon
#16
Yu Zhu, Shu-Juan Chu, Yue-Lin Luo, Jiang-Yan Fu, Cheng-Yi Tang, Gui-Hua Lu, Yan-Jun Pang, Xiao-Ming Wang, Rong-Wu Yang, Jin-Liang Qi, Yong-Hua Yang
·Shikonin and its derivatives are important medicinal secondary metabolites accumulating in the roots of Lithospermum erythrorhizon. Although some membrane proteins have been identified as transporters of secondary metabolites, the mechanisms underlying shikonin transport and accumulation in L. erythrorhizon cells still remain largely unknown. ·In this study, we isolated a cDNA encoding LeMRP, an ATP-binding cassette transporter from L. erythrorhizon and further investigated its functions in the transport and biosynthesis of shikonin with the yeast transformation and transgenic hairy root method, respectively...
November 15, 2017: Plant Biology
https://www.readbyqxmd.com/read/29138424/structure-function-relationships-in-abcg2-insights-from-molecular-dynamics-simulations-and-molecular-docking-studies
#17
Ricardo J Ferreira, Cátia A Bonito, M Natália D S Cordeiro, Maria-José U Ferreira, Daniel J V A Dos Santos
Efflux pumps of the ATP-binding cassette transporters superfamily (ABC transporters) are frequently involved in the multidrug-resistance (MDR) phenomenon in cancer cells. Herein, we describe a new atomistic model for the MDR-related ABCG2 efflux pump, also named breast cancer resistance protein (BCRP), based on the recently published crystallographic structure of the ABCG5/G8 heterodimer sterol transporter, a member of the ABCG family involved in cholesterol homeostasis. By means of molecular dynamics simulations and molecular docking, a far-reaching characterization of the ABCG2 homodimer was obtained...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29137272/immunological-cytokine-profiling-identifies-tnf-%C3%AE-as-a-key-molecule-dysregulated-in-autistic-children
#18
Jiang Xie, Li Huang, Xiaohong Li, Hua Li, Yongmei Zhou, Hua Zhu, Tianying Pan, Keith M Kendrick, Wenming Xu
Recent studies have suggested that the etiology of autism spectrum disorder (ASD) may be caused by immunological factors, particularly abnormalities in the innate immune system. However, it is still unclear which specific cytokines may be of most importance. The current study therefore investigated which cytokines showed altered concentrations in blood in ASD compared with healthy control children and which were also correlated with symptom severity. Our study sample included 32 children diagnosed with ASD and 28 age and sex-matched typically developing children...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137222/pi3k%C3%AE-inhibition-causes-feedback-activation-of-pi3k%C3%AE-in-the-abc-subtype-of-diffuse-large-b-cell-lymphoma
#19
Georgios N Pongas, Christina M Annunziata, Louis M Staudt
Cell line models of the activated B cell-like (ABC) subtype of diffuse large B cell (DLBCL) depend on both NF-κB and phosphatidylinositol 3-kinase (PI3K) signaling pathways for survival, especially those with gain-of-function B cell receptor (BCR) mutations. Here we show that these cells depend specifically on the PI3Kδ isoform, but that PI3K pathway interruption by PI3Kδ inhibitors is short-lived due to feedback activation of the PI3Kα isoform. PI3Kδ and PI3Kα inhibition cooperated in killing ABC DLBCL lines, and genetic knockdown of PI3Kα sensitized cells to PI3Kδ inhibition and prolonged the interruption of PI3K signaling...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136146/the-abc-death-risk-score-is-it-time-to-start-measuring-gdf-15
#20
M Benjamin Shoemaker, William G Stevenson
No abstract text is available yet for this article.
November 10, 2017: European Heart Journal
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