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https://www.readbyqxmd.com/read/28098164/uncovering-the-sumoylation-and-ubiquitylation-crosstalk-in-human-cells-using-sequential-peptide-immunopurification
#1
Frédéric Lamoliatte, Francis P McManus, Ghizlane Maarifi, Mounira K Chelbi-Alix, Pierre Thibault
Crosstalk between the SUMO and ubiquitin pathways has recently been reported. However, no approach currently exists to determine the interrelationship between these modifications. Here, we report an optimized immunoaffinity method that permits the study of both protein ubiquitylation and SUMOylation from a single sample. This method enables the unprecedented identification of 10,388 SUMO sites in HEK293 cells. The sequential use of SUMO and ubiquitin remnant immunoaffinity purification facilitates the dynamic profiling of SUMOylated and ubiquitylated proteins in HEK293 cells treated with the proteasome inhibitor MG132...
January 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28095350/progressive-multifocal-leukoencephalopathy-in-a-patient-with-systemic-mastocytosis-treated-with-cladribine
#2
Karl B Alstadhaug, Randi Fykse Halstensen, Francis Odeh
BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic brain infection caused by the human polyomavirus JC (JCPyV). A particular problem with the drug cladribine seems to be prolonged suppression of the CD4+ T-cells, a well-known risk factor for PML. CASE DESCRIPTION: A 67-year-old male presented with a 3-weeks history of unsteady gait, dysarthria and a dysfunctional right arm. Seven years earlier, he had been diagnosed with urticaria pigmentosa, and 2 years later aggressive systemic mastocytosis...
December 14, 2016: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28088449/the-role-of-sumoylation-in-ageing-and-senescent-decline
#3
REVIEW
Andrea Princz, Nektarios Tavernarakis
Posttranslational protein modifications are playing crucial roles in essential cellular mechanisms. SUMOylation is a reversible posttranslational modification of specific target proteins by the attachment of a small ubiquitin-like protein. Although the mechanism of conjugation of SUMO to proteins is analogous to ubiquitination, it requires its own, specific set of enzymes. The consequences of SUMOylation are widely variable, depending on the physiological state of the cell and the attached SUMO isoform. Accumulating recent findings have revealed a prominent role of SUMOylation in molecular pathways that govern senescence and ageing...
January 11, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28087821/selection-of-first-line-therapy-in-multiple-sclerosis-using-risk-benefit-decision-analysis
#4
David Bargiela, Matthew T Bianchi, M Brandon Westover, Lori B Chibnik, Brian C Healy, Philip L De Jager, Zongqi Xia
OBJECTIVE: To integrate long-term measures of disease-modifying drug efficacy and risk to guide selection of first-line treatment of multiple sclerosis. METHODS: We created a Markov decision model to evaluate disability worsening and progressive multifocal leukoencephalopathy (PML) risk in patients receiving natalizumab (NTZ), fingolimod (FGL), or glatiramer acetate (GA) over 30 years. Leveraging publicly available data, we integrated treatment utility, disability worsening, and risk of PML into quality-adjusted life-years (QALYs)...
January 13, 2017: Neurology
https://www.readbyqxmd.com/read/28075463/expression-of-the-promyelocytic-leukemia-protein-without-the-nuclear-localization-signal-as-a-novel-diagnostic-marker-for-acute-promyelocytic-leukemia
#5
Ting Xu, Xiao-Qun Yang, Kai-Ling Jiang, Hui Wang, Peng-Peng Ma, Liang Zhong, Bei-Zhong Liu
Promyelocytic leukemia-retinoic acid receptor α (PML-RARα) is a fusion protein generated by the t(15;17)(q22;q12) translocation associated with acute promyelocytic leukemia (APL). PML-RARα is cleaved by neutrophil elastase, an early myeloid-specific serine protease, leading to translocation of the nuclear localization signal (NLS) of the PML protein to the N-terminal of RARα, and the mutational product PML(NLS-). The present study was designed to analyze the role of the NLS in mediating PML transport into the nucleus and to evaluate the value of measuring NLS translocation in the early diagnosis of APL...
January 9, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28074026/promyelocytic-leukemia-protein-pml-controls-listeria-monocytogenes-infection
#6
David Ribet, Valérie Lallemand-Breitenbach, Omar Ferhi, Marie-Anne Nahori, Hugo Varet, Hugues de Thé, Pascale Cossart
: The promyelocytic leukemia protein (PML) is the main organizer of stress-responsive subnuclear structures called PML nuclear bodies. These structures recruit multiple interactors and modulate their abundance or their posttranslational modifications, notably by the SUMO ubiquitin-like modifiers. The involvement of PML in antiviral responses is well established. In contrast, the role of PML in bacterial infection remains poorly characterized. Here, we show that PML restricts infection by the pathogenic bacterium Listeria monocytogenes but not by Salmonella enterica serovar Typhimurium...
January 10, 2017: MBio
https://www.readbyqxmd.com/read/28070163/development-of-reverse-transcription-loop-mediated-isothermal-amplification-for-simple-and-rapid-detection-of-promyelocytic-leukemia-retinoic-acid-receptor-%C3%AE-mrna
#7
Yuki Hashimoto, Yuki Hatayama, Nao Kojima, Shota Morishita, Satoko Matsumoto, Yuzuru Hosoda, Ayako Hara, Toru Motokura
BACKGROUND: Acute promyelocytic leukemia (APL) is a disease characterized by expression of Promyelocytic Leukemia-Retinoic Acid Receptor α (PML-RARα) chimeric mRNA. Although APL is curable, early death due to hemorrhage is a major problem. Here, we report the development of a simple and rapid diagnostic method for APL based on reverse transcription loop-mediated isothermal amplification (RT-LAMP). METHODS: An RT-LAMP primer set was designed to detect three types of PML-RARα mRNA in a single reaction...
December 2016: Yonago Acta Medica
https://www.readbyqxmd.com/read/28063140/regulatory-mechanism-and-functional-analysis-of-s100a9-in-acute-promyelocytic-leukemia-cells
#8
Yonglan Zhu, Fang Zhang, Shanzhen Zhang, Wanglong Deng, Huiyong Fan, Haiwei Wang, Ji Zhang
S100A9, a calcium-binding protein, participates in the inflammatory process and development of various tumors, thus attracting much attention in the field of cancer biology. This study aimed to investigate the regulatory mechanism of S100A9 and its function involvement in APL. We used real-time quantitative PCR to determine whether PML/RARα affects the expression of S100A9 in NB4 and PR9 cells upon ATRA treatment. ChIP-based PCR and dual-luciferase reporter assay system were used to detect how PML/RARα and PU...
January 6, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28036121/study-of-the-anti-jcv-antibody-levels-in-a-spanish-multiple-sclerosis-cohort
#9
María I Dominguez-Mozo, Macarena Rus, Jose L Santiago, Guillermo Izquierdo, Ignacio Casanova, Victoria Galan, M Angel Garcia-Martinez, Ana M Arias-Leal, Marta García-Montojo, Silvia Pérez-Pérez, Rafael Arroyo, Roberto Alvarez-Lafuente
One of the risk factor to develop progressive multifocal leukoencephalopathy (PML) among natalizumab-treated patients is the presence and high levels of anti-JCV antibodies. Our purpose was to test the association of different clinical and demographic variables with the presence and levels of anti-JCV antibodies in a Spanish cohort of multiple sclerosis (MS) patients during natalizumab treatment MATERIALS AND METHODS: All MS patients from two hospitals with at least one measure of the anti-JCV antibodies levels (2011-2014) were recruited, among them two PML cases...
December 30, 2016: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28035072/%C3%AE-np73-overexpression-promotes-resistance-to-apoptosis-but-does-not-cooperate-with-pml-rara-in-the-induction-of-an-apl-leukemic-phenotype
#10
Antonio R Lucena-Araujo, Juan L Coelho-Silva, Diego A Pereira-Martins, Carolina Thomé, Priscila S Scheucher, Ana P Lange, Helder H Paiva, Benjamin T Hemmelgarn, Mariana C Morais-Sobral, Elisa A Azevedo, Pedro L Franca-Neto, Rafael F Franca, Cleide L Silva, Alexandre Krause, Eduardo M Rego
Here, we evaluated whether the overexpression of transcriptionally inactive ΔNp73 cooperates with PML/RARA fusion protein in the induction of an APL-leukemic phenotype, as well as its role in vitro in proliferation, myeloid differentiation, and drug-induced apoptosis. Using lentiviral gene transfer, we showed in vitro that ΔNp73 overexpression resulted in increased proliferation in murine bone marrow (BM) cells from hCG-PML/RARA transgenic mice and their wild-type (WT) counterpart, with no accumulation of cells at G2/M or S phases; instead, ΔNp73-expressing cells had a lower rate of induced apoptosis...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28030795/aml-associated-oncofusion-proteins-pml-rara-aml1-eto-and-cbfb-myh11-target-runx-ets-factor-binding-sites-to-modulate-h3ac-levels-and-drive-leukemogenesis
#11
Abhishek A Singh, Amit Mandoli, Koen H M Prange, Marko Laakso, Joost H A Martens
Chromosomal translocations are one of the hallmarks of acute myeloid leukemia (AML), often leading to gene fusions and expression of an oncofusion protein. Over recent years it has become clear that most of the AML associated oncofusion proteins molecularly adopt distinct mechanisms for inducing leukemogenesis. Still these unique molecular properties of the chimeric proteins converge and give rise to a common pathogenic molecular mechanism. In the present study we compared genome-wide DNA binding and transcriptome data associated with AML1-ETO, CBFB-MYH11 and PML-RARA oncofusion protein expression to identify unique and common features...
December 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/28028303/dismal-outcome-of-therapy-related-myeloid-neoplasm-associated-with-complex-aberrant-karyotypes-and-monosomal-karyotype-a-case-report
#12
Y L Tang, W K Chia, E C S W Yap, M I Julia, C F Leong, S Salwati, C L Wong
INTRODUCTION: Individuals who are exposed to cytotoxic agents are at risk of developing therapyrelated myeloid neoplasms (t-MN). Cytogenetic findings of a neoplasm play an important role in stratifying patients into different risk groups and thus predict the response to treatment and overall survival. CASE REPORT: A 59-year-old man was diagnosed with acute promyelocytic leukaemia. Following this, he underwent all-trans retinoic acid (ATRA) based chemotherapy and achieved remission...
December 2016: Malaysian Journal of Pathology
https://www.readbyqxmd.com/read/28028302/acute-promyelocytic-leukaemia-with-a-novel-translocation-t-16-17-q12-p13-a-case-report
#13
H Bhat, S Geelani, M Rashid, T Bhat, M Qadri, N Bashir N, F Manzoor, S Bhat, F Rather, J Rasool
Acute promyelocytic leukaemia (APML) is characterised by the t(15;17)(q22;q21), that results in the fusion of the promyelocytic leukaemia (PML) gene at 15q22 with the retinoic acid α-receptor (RARA) gene at 17q21. The current case report describes a 13-year-old male with APML, who was negative for PML/RARA fusion signal but reported to have an atypical translocation t(16;17). To the best of our knowledge this is the first case report of APML responsive to ATRA with such a translocation.
December 2016: Malaysian Journal of Pathology
https://www.readbyqxmd.com/read/28025581/pml-rara-associated-cooperating-mutations-belong-to-a-transcriptional-network-that-is-deregulated-in-myeloid-leukemias
#14
C Ronchini, A Brozzi, L Riva, L Luzi, A M Gruszka, G E M Melloni, E Scanziani, G Dharmalingam, M Mutarelli, V Belcastro, S Lavorgna, V Rossi, O Spinelli, A Biondi, A Rambaldi, F Lo-Coco, D di Bernardo, P G Pelicci
It has been shown that individual Acute Myeloid Leukemia (AML) patients are characterized by one of few initiating DNA mutations and 5-10 cooperating mutations not yet defined among hundreds identified by massive sequencing of AML genomes. We report an in vivo insertional mutagenesis screen for genes cooperating with one AML initiating mutations (PML-RARA, oncogene of acute promyelocytic leukemia, APL), which allowed identification of hundreds of genetic cooperators. The cooperators are mutated at low frequency in APL or AML patients but are always abnormally expressed in a cohort of 182 APLs and AMLs analyzed...
December 27, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28024467/-features-of-immunophenotypes-and-characteristics-of-molecular-biology-and-cellular-genetics-of-aml-patients-with-cd4-and-cd7-expression
#15
Tie-Qiang Liu, Shan Huang, Bo Yao, Zhi-Qing Liu, Chang-Lin Yu, Jian-Hui Qiao, Qi-Yun Sun, Kai-Xun Hu, Ya-Jing Huang, Rui Zhang, Yu-Fang Li, Juan Bai, Yu-Jing Sun, Bing-Xia Li, Dong-Mei Wang, Yi Wang, Mei Guo
OBJECTIVE: To explore the features of immunophenotypes and the characteristics of molecular biology and cellular genetics of AML patients with CD7 and CD4 expression. METHODS: The immunophenotypical markers of AML cells were detected by multiple parameter flow cytometry; the expression of WT1, MDK, ETO, PML-RaRa and BCR-ABL were detected by RT-PCR; and cellular features were analyzed by R-band in 304 patients. The patients were divided into three groups according to their immunophenotypes: AML with CD7 expression (CD7 group), AML with CD4 expression(CD4 group) and AML without CD7 and CD4 expression (common AML group)...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28018952/change-in-thermal-transitions-and-water-uptakes-of-poly-l-lactic-acid-blends-upon-hydrolytic-degradation
#16
Hideko T Oyama, Daisuke Tanishima, Shintaro Maekawa
This article reports experimental data related to the research article entitled "Poly(malic acid-co-l-lactide) as a Superb Degradation Accelerator for Poly(l-lactic acid) at Physiological Conditions" (H.T. Oyama, D. Tanishima, S. Maekawa, 2016) [1]. Hydrolytic degradation of poly(l-lactic acid) (PLLA) blends with poly(aspartic acid-co-l-lactide) (PAL) and poly(malic acid-co-l-lactide) (PML) oligomers was investigated in a phosphate buffer solution at 40 °C. It was found in the differential scanning calorimetry measurements that upon hydrolysis the cold crystallization temperature (Tc ) and the melting temperature (Tm ) significantly shifted to lower temperature...
February 2017: Data in Brief
https://www.readbyqxmd.com/read/28017614/fto-plays-an-oncogenic-role-in-acute-myeloid-leukemia-as-a-n-6-methyladenosine-rna-demethylase
#17
Zejuan Li, Hengyou Weng, Rui Su, Xiaocheng Weng, Zhixiang Zuo, Chenying Li, Huilin Huang, Sigrid Nachtergaele, Lei Dong, Chao Hu, Xi Qin, Lichun Tang, Yungui Wang, Gia-Ming Hong, Hao Huang, Xiao Wang, Ping Chen, Sandeep Gurbuxani, Stephen Arnovitz, Yuanyuan Li, Shenglai Li, Jennifer Strong, Mary Beth Neilly, Richard A Larson, Xi Jiang, Pumin Zhang, Jie Jin, Chuan He, Jianjun Chen
N(6)-Methyladenosine (m(6)A) represents the most prevalent internal modification in mammalian mRNAs. Despite its functional importance in various fundamental bioprocesses, the studies of m(6)A in cancer have been limited. Here we show that FTO, as an m(6)A demethylase, plays a critical oncogenic role in acute myeloid leukemia (AML). FTO is highly expressed in AMLs with t(11q23)/MLL rearrangements, t(15;17)/PML-RARA, FLT3-ITD, and/or NPM1 mutations. FTO enhances leukemic oncogene-mediated cell transformation and leukemogenesis, and inhibits all-trans-retinoic acid (ATRA)-induced AML cell differentiation, through regulating expression of targets such as ASB2 and RARA by reducing m(6)A levels in these mRNA transcripts...
January 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28017371/mixed-model-association-with-family-biased-case-control-ascertainment
#18
Tristan J Hayeck, Po-Ru Loh, Samuela Pollack, Alexander Gusev, Nick Patterson, Noah A Zaitlen, Alkes L Price
Mixed models have become the tool of choice for genetic association studies; however, standard mixed model methods may be poorly calibrated or underpowered under family sampling bias and/or case-control ascertainment. Previously, we introduced a liability threshold-based mixed model association statistic (LTMLM) to address case-control ascertainment in unrelated samples. Here, we consider family-biased case-control ascertainment, where case and control subjects are ascertained non-randomly with respect to family relatedness...
January 5, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28005037/-a-case-of-progressive-multifocal-leukoencephalopathy-in-a-hiv-infected-female-patient
#19
E A Samotolkina, A V Pokrovskaya, E S Samotolkina, S L Voznesensky, E V Petrova
Progressive multifocal leukoencephalopathy (PML) caused by JC virus is a severe central nervous lesion developing in the presence of obvious immunodeficiency. In most cases, the disease results in a fatal outcome within a few months. Antiretroviral therapy is currently considered to be the only method for the prevention and treatment of PML in HIV-infected patients. The paper describes a positive experience in treating the HIV-infected female patient with the established diagnosis of PML.
2016: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28001298/drug-induced-pml-in-multiple-sclerosis-european-regulators-perspective
#20
REVIEW
Ruxandra Anton, Manuel Haas, Peter Arlett, Martina Weise, Pavel Balabanov, Giampiero Mazzaglia, Luis Prieto, Brigitte Keller-Stanislawski, June Raine
Progressive multifocal leukoencephalopathy (PML) has been associated with the use of a number of multiple sclerosis (MS) immunomodulatory therapies and has assumed a critical place in the evaluation of their benefit/risk. In this review, we discuss the EU regulatory approach to drug-induced PML in MS, highlight a number of key issues related to the current knowledge on PML and outline possible paths to help progress the risk management of MS patients at risk of PML. This article is protected by copyright. All rights reserved...
December 21, 2016: Clinical Pharmacology and Therapeutics
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