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https://www.readbyqxmd.com/read/29346632/diagnostic-and-prognostic-value-of-jc-virus-dna-in-plasma-in-progressive-multifocal-leukoencephalopathy
#1
Francesca Ferretti, Arabella Bestetti, Constantin T Yiannoutsos, Beverly S Musick, Simonetta Gerevini, Laura Passeri, Simona Bossolasco, Antonio Boschini, Diego Franciotta, Adriano Lazzarin, Paola Cinque
Background: Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease caused by the polyomavirus JC (JCV) affecting subjects with impaired immune system. While JCV-DNA detection in cerebrospinal fluid (CSF) is diagnostic of PML, the clinical significance of plasma JCV-DNA is still uncertain. Methods: We retrospectively analyzed plasma samples drawn from patients with PML close to disease onset, and controls without PML. In PML patients, we compared plasma JCV DNA detection and levels to: JCV DNA in the other biological samples, clinical and laboratory parameters and patients' survival...
January 15, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29344139/nls-rar%C3%AE-is-a-novel-transcriptional-factor
#2
Kai-Ling Jiang, Liang Zhong, Xiao-Qun Yang, Peng-Peng Ma, Hui Wang, Xin-Yu Zhu, Bei-Zhong Liu
Acute promyelocytic leukemia (APL) is characterized by the presence of the promyelocytic leukemia (PML)-retinoic acid receptor-α (RAR-α) fusion protein. PML-RARα can be cleaved by neutrophil elastase (NE) in several positions in cells in the promyelocytic stage, nuclear location signal (NLS)-negative PML and NLS-RARα may be the products of PML-RARα by NE. The function of NLS-RARα may be affected by the addition of NLS, which would alter its localization in cells, as the role of NLS is to identify proteins for transport to the nucleus...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343163/magnetic-resonance-imaging-changes-following-natalizumab-discontinuation-in-multiple-sclerosis-patients-with-progressive-multifocal-leukoencephalopathy
#3
Jérôme Hodel, Blanche Bapst, Olivier Outteryck, Sébastien Verclytte, Vincent Deramecourt, Mohamed Amine Benadjaoud, Jean-Pierre Pruvo, Patrick Vermersch, Xavier Leclerc
BACKGROUND: Detecting early progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome (PML-IRIS) is clinically relevant. OBJECTIVE: Evaluating magnetic resonance imaging (MRI) changes following natalizumab (NTZ) discontinuation and preceding PML-IRIS. METHODS: MRIs (including diffusion-weighted imaging (DWI), T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), post-contrast T1-weighted sequences) were performed every week following PML diagnosis in 11 consecutive NTZ-PML patients...
January 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29335545/an-aberrant-srebp-dependent-lipogenic-program-promotes-metastatic-prostate-cancer
#4
Ming Chen, Jiangwen Zhang, Katia Sampieri, John G Clohessy, Lourdes Mendez, Enrique Gonzalez-Billalabeitia, Xue-Song Liu, Yu-Ru Lee, Jacqueline Fung, Jesse M Katon, Archita Venugopal Menon, Kaitlyn A Webster, Christopher Ng, Maria Dilia Palumbieri, Moussa S Diolombi, Susanne B Breitkopf, Julie Teruya-Feldstein, Sabina Signoretti, Roderick T Bronson, John M Asara, Mireia Castillo-Martin, Carlos Cordon-Cardo, Pier Paolo Pandolfi
Lipids, either endogenously synthesized or exogenous, have been linked to human cancer. Here we found that PML is frequently co-deleted with PTEN in metastatic human prostate cancer (CaP). We demonstrated that conditional inactivation of Pml in the mouse prostate morphs indolent Pten-null tumors into lethal metastatic disease. We identified MAPK reactivation, subsequent hyperactivation of an aberrant SREBP prometastatic lipogenic program, and a distinctive lipidomic profile as key characteristic features of metastatic Pml and Pten double-null CaP...
January 15, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29335436/deregulated-pp1%C3%AE-phosphatase-activity-towards-mapk-activation-is-antagonized-by-a-tumor-suppressive-failsafe-mechanism
#5
Ming Chen, Lixin Wan, Jiangwen Zhang, Jinfang Zhang, Lourdes Mendez, John G Clohessy, Kelsey Berry, Joshua Victor, Qing Yin, Yuan Zhu, Wenyi Wei, Pier Paolo Pandolfi
The mitogen-activated protein kinase (MAPK) pathway is frequently aberrantly activated in advanced cancers, including metastatic prostate cancer (CaP). However, activating mutations or gene rearrangements among MAPK signaling components, such as Ras and Raf, are not always observed in cancers with hyperactivated MAPK. The mechanisms underlying MAPK activation in these cancers remain largely elusive. Here we discover that genomic amplification of the PPP1CA gene is highly enriched in metastatic human CaP. We further identify an S6K/PP1α/B-Raf signaling pathway leading to activation of MAPK signaling that is antagonized by the PML tumor suppressor...
January 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29326799/molecular-heterogeneity-in-acute-promyelocytic-leukemia-a-single-center-experience-from-india
#6
Nikhil Rabade, Goutham Raval, Shruti Chaudhary, P G Subramanian, Rohan Kodgule, Swapnali Joshi, Prashant Tembhare, Syed K Hasan, Hasmukh Jain, Manju Sengar, Gaurav Narula, Shripad Banavali, Pratibha Amare Kadam, Dhanalaxmi Shetty, Sumeet Gujral, Nikhil Patkar
Atypical breakpoints and variant APL cases involving alternative chromosomal aberrations are seen in a small subset of acute promyelocytic leukemia (APL) patients. Over seven different partner genes for RARA have been described. Although rare, these variants prove to be a diagnostic challenge and require a combination of advanced cytogenetic and molecular techniques for accurate characterization. Heterogeneity occurs not only at the molecular level but also at clinico-pathological level influencing treatment response and outcome...
2018: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/29323725/serum-igg-antibodies-from-healthy-subjects-up-to-100-years-old-react-to-jc-polyomavirus
#7
Ilaria Bononi, Elisa Mazzoni, Silvia Pietrobon, Marco Manfredini, Elena Trregiani, Marika Rossini, Francesca Lotito, Giovanni Guerra, Paola Rizzo, Fernanda Martini, Mauro Tognon
JC polyomavirus (JCPyV) was identified in 1971 in the brain tissue of a patient (J.C.) affected by the progressive multifocal leukoencephalopathy (PML). JCPyV encodes for the oncoproteins large T antigen (Tag) and small t-antigen (tag). These oncoproteins are responsible of the cell transformation and tumorigenesis in experimental animals. JCPyV is ubiquitous in human populations. After the primary infection, which is usually asymptomatic, JCPyV remains lifelong in the host in a latent phase. Its reactivation may occur in heathy subjects and immunocompromised patients...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29323056/role-of-salivary-biomarkers-in-early-detection-of-oral-squamous-cell-carcinoma
#8
Nidhi Awasthi
INTRODUCTION: Oral cancer is prevalent worldwide and is a common cause of morbidity and mortality. Despite advances in treatment, the survival of patients with oral cancer has not significantly improved over the past several decades owing to late detection and treatment failures. The present study was undertaken with an objective to explore the role of salivary CYFRA 21-1, CA 19-9, lactate dehydrogenase (LDH), total proteins, and amylase as biochemical markers of oral squamous cell carcinoma (OSCC) and premalignant lesions (PML)...
October 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/29322824/detection-and-analysis-of-variants-of-jc-polyomavirus-in-urine-samples-from-hiv-1-infected-patients-in-china-s-zhejiang-province
#9
Caiqin Hu, Ying Huang, Junwei Su, Mengyan Wang, Qihui Zhou, Biao Zhu
Objectives Human JC polyomavirus (JCPyV) infection has an increased risk of developing progressive multifocal leukoencephalopathy (PML). Different JCPyV subtypes differ in the virulence with which they cause PML. Currently, the JCPyV infection status and subtype distribution in patients with human immunodeficiency virus-1 (HIV-1) in China are still unclear. This study aimed to investigate the epidemiology and subtype distribution of JCPyV in HIV-1-infected patients in China. Methods Urine samples from 137 HIV-1-infected patients in Zhejiang Province in China were tested for the presence of JCPyV DNA...
January 1, 2018: Journal of International Medical Research
https://www.readbyqxmd.com/read/29321332/erk-is-a-critical-regulator-of-jc-polyomavirus-infection
#10
Jeanne K DuShane, Michael P Wilczek, Colleen L Mayberry, Melissa S Maginnis
The human JC polyomavirus (JCPyV) infects the majority of the population worldwide and presents as an asymptomatic, persistent infection in the kidney. In individuals who are immunocompromised, JCPyV can become reactivated and cause a lytic infection in the central nervous system resulting in the fatal, demyelinating disease progressive multifocal leukoencephalopathy (PML). Infection is initiated by interactions between the capsid protein viral protein 1 (VP1) and the α2,6-linked sialic acid on LSTc, while JCPyV internalization is facilitated by 5-hydroxytryptamine 2 receptors (5-HT2Rs)...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321229/the-national-incidence-of-pml-in-sweden-1988-2013
#11
Ellen Iacobaeus, Sarah Burkill, Shahram Bahmanyar, Ramil Hakim, Camilla Byström, Michael Fored, Tomas Olsson, Lou Brundin, Scott Montgomery
OBJECTIVE: To investigate the incidence of progressive multifocal leukoencephalopathy (PML) and patient characteristics in Sweden between 1988 and 2013. METHODS: All PML diagnoses in Sweden between 1988 and 2013 were identified in the National Patient Register. Information to validate the diagnosis and patient characteristics was obtained from medical records. RESULTS: Medical record review classified 108 out of 250 patients (43%) as definite (n = 84), probable (n = 4), or possible (n = 20) PML according to diagnostic criteria...
January 10, 2018: Neurology
https://www.readbyqxmd.com/read/29309427/distinct-temporal-roles-for-the-promyelocytic-leukaemia-pml-protein-in-the-sequential-regulation-of-intracellular-host-immunity-to-hsv-1-infection
#12
Thamir Alandijany, Ashley P E Roberts, Kristen L Conn, Colin Loney, Steven McFarlane, Anne Orr, Chris Boutell
Detection of viral nucleic acids plays a critical role in the induction of intracellular host immune defences. However, the temporal recruitment of immune regulators to infecting viral genomes remains poorly defined due to the technical difficulties associated with low genome copy-number detection. Here we utilize 5-Ethynyl-2'-deoxyuridine (EdU) labelling of herpes simplex virus 1 (HSV-1) DNA in combination with click chemistry to examine the sequential recruitment of host immune regulators to infecting viral genomes under low multiplicity of infection conditions...
January 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29309416/long-term-safety-of-rituximab-induced-peripheral-b-cell-depletion-in-autoimmune-neurological-diseases
#13
Anza B Memon, Adil Javed, Christina Caon, Shitiz Srivastawa, Fen Bao, Evanthia Bernitsas, Jessica Chorostecki, Alexandros Tselis, Navid Seraji-Bozorgzad, Omar Khan
BACKGROUND: B-cells play a pivotal role in several autoimmune diseases, including patients with immune-mediated neurological disorders (PIMND), such as neuromyelitis optica (NMO), multiple sclerosis (MS), and myasthenia gravis (MG). Targeting B-cells has been an effective approach in ameliorating both central and peripheral autoimmune diseases. However, there is a paucity of literature on the safety of continuous B-cell depletion over a long period of time. OBJECTIVE: The aim of this study was to examine the long-term safety, incidence of infections, and malignancies in subjects receiving continuous therapy with a B-cell depleting agent rituximab over at least 3 years or longer...
2018: PloS One
https://www.readbyqxmd.com/read/29309058/diverse-genetic-driven-immune-landscapes-dictate-tumor-progression-through-distinct-mechanisms
#14
Marco Bezzi, Nina Seitzer, Tomoki Ishikawa, Markus Reschke, Ming Chen, Guocan Wang, Caitlin Mitchell, Christopher Ng, Jesse Katon, Andrea Lunardi, Sabina Signoretti, John G Clohessy, Jiangwen Zhang, Pier Paolo Pandolfi
Multiple immune-cell types can infiltrate tumors and promote progression and metastasis through different mechanisms, including immunosuppression. How distinct genetic alterations in tumors affect the composition of the immune landscape is currently unclear. Here, we characterized the immune-cell composition of prostate cancers driven by the loss of the critical tumor suppressor gene Pten, either alone or in combination with the loss of Trp53, Zbtb7a or Pml. We observed a striking quantitative and qualitative heterogeneity that was directly dependent on the specific genetic events in the tumor and ranged from 'cold', noninflamed tumors to massively infiltrated landscapes-results with important therapeutic implications...
January 8, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29307859/zn2-transporters-zip7-and-znt7-play-important-role-in-progression-of-cardiac-dysfunction-via-affecting-sarco-endo-plasmic-reticulum-mitochondria-coupling-in-hyperglycemic-cardiomyocytes
#15
Erkan Tuncay, Verda Bitirim, Yusuf Olgar, Aysegul Durak, Guy A Rutter, Belma Turan
Functional contribution of S(E)R-mitochondria coupling to normal cellular processes is crucial and any alteration in S(E)R-mitochondria axis may be responsible for the onset of diseases. Mitochondrial free Zn2+ level in cardiomyocytes ([Zn2+]Mit) is lower comparison to either its cytosolic or S(E)R level under physiological condition. However, there is little information about distribution of Zn2+-transporters on mitochondria and role of Zn2+-dependent mitochondrial-function associated with [Zn2+]Mit. Since we recently have shown how hyperglycemia (HG)-induced changes in ZIP7 and ZnT7 contribute to Zn2+-transport across S(E)R and contribute to S(E)R-stress in the heart, herein, we hypothesized that these transporters can also be localized to mitochondria and affect the S(E)R-mitochondria coupling, and thereby contribute to cellular Zn2+-muffling between S(E)R-mitochondria in HG-cells...
January 4, 2018: Mitochondrion
https://www.readbyqxmd.com/read/29302031/a-non-cell-autonomous-role-for-pml-in-the-maintenance-of-leukemia-from-the-niche
#16
Jlenia Guarnerio, Lourdes Maria Mendez, Noboru Asada, Archita Venugopal Menon, Jacqueline Fung, Kelsey Berry, Paul S Frenette, Keisuke Ito, Pier Paolo Pandolfi
Disease recurrence after therapy, due to the persistence of resistant leukemic cells, represents a fundamental problem in the treatment of leukemia. Elucidating the mechanisms responsible for the maintenance of leukemic cells, before and after treatment, is therefore critical to identify curative modalities. It has become increasingly clear that cell-autonomous mechanisms are not solely responsible for leukemia maintenance. Here, we report a role for Pml in mesenchymal stem cells (MSCs) in supporting leukemic cells of both CML and AML...
January 4, 2018: Nature Communications
https://www.readbyqxmd.com/read/29299133/domain-retention-in-transcription-factor-fusion-genes-and-its-biological-and-clinical-implications-a-pan-cancer-study
#17
Pora Kim, Leomar Y Ballester, Zhongming Zhao
Genomic rearrangements involving transcription factors (TFs) can form fusion proteins resulting in either enhanced, weakened, or even loss of TF activity. Functional domain (FD) retention is a critical factor in the activity of transcription factor fusion genes (TFFGs). A systematic investigation of FD retention in TFFGs and their outcome (e.g. expression changes) in a pan-cancer study has not yet been completed. Here, we examined the FD retention status in 386 TFFGs across 13 major cancer types and identified 83 TFFGs involving 67 TFs that retained FDs...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296850/progressive-multifocal-leukoencephalopathy-and-hematologic-malignancies-a-single-cancer-center-retrospective-review
#18
Elizabeth C Neil, Lisa M DeAngelis
Progressive multifocal leukoencephalopathy (PML) is an uncommon opportunistic infection with high morbidity and mortality. This is an institutional review board-approved retrospective review of medical records identified by diagnostic coding for PML or John Cunningham virus (JCV) from 2000 to 2015. Inclusion criteria were cerebrospinal fluid (CSF) positive for JCV by polymerase chain reaction or brain biopsy-proven PML in non-HIV patients. There were 16 patients, 12 of whom were men (75%); the median age was 56 years (range, 31-71 years)...
October 24, 2017: Blood Advances
https://www.readbyqxmd.com/read/29287955/remodeling-of-ca2-signaling-in-cancer-regulation-of-inositol-1-4-5-trisphosphate-receptors-through-oncogenes-and-tumor-suppressors
#19
REVIEW
Hideaki Ando, Katsuhiro Kawaai, Benjamin Bonneau, Katsuhiko Mikoshiba
The calcium ion (Ca2+) is a ubiquitous intracellular signaling molecule that regulates diverse physiological and pathological processes, including cancer. Increasing evidence indicates that oncogenes and tumor suppressors regulate the Ca2+ transport systems. Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are IP3-activated Ca2+ release channels located on the endoplasmic reticulum (ER). They play pivotal roles in the regulation of cell death and survival by controlling Ca2+ transfer from the ER to mitochondria through mitochondria-associated ER membranes (MAMs)...
December 20, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29274134/a-distinct-immunophenotype-identifies-a-subset-of-npm1-mutated-aml-with-tet2-or-idh1-2-mutations-and-improved-outcome
#20
Emily F Mason, Frank C Kuo, Robert P Hasserjian, Adam C Seegmiller, Olga Pozdnyakova
Recent work has identified distinct molecular subgroups of acute myeloid leukemia (AML) with implications for disease classification and prognosis. NPM1 is one of the most common recurrently mutated genes in acute myeloid leukemia (AML). NPM1 mutations often co-occur with FLT3-ITDs and mutations in genes regulating DNA methylation, such as DNMT3A, TET2, and IDH1/2. It remains unclear whether these genetic alterations are associated with distinct immunophenotypic findings or affect prognosis. We identified 133 cases of NPM1-mutated AML and correlated sequencing data with immunophenotypic and clinical findings...
December 23, 2017: American Journal of Hematology
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