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https://www.readbyqxmd.com/read/28334823/h3-y-discriminates-between-hira-and-daxx-chaperone-complexes-and-reveals-unexpected-insights-into-human-daxx-h3-3-h4-binding-and-deposition-requirements
#1
Lisa-Maria Zink, Erwan Delbarre, H Christian Eberl, Eva C Keilhauer, Clemens Bönisch, Sebastian Pünzeler, Marek Bartkuhn, Philippe Collas, Matthias Mann, Sandra B Hake
Histone chaperones prevent promiscuous histone interactions before chromatin assembly. They guarantee faithful deposition of canonical histones and functionally specialized histone variants into chromatin in a spatial- and temporally-restricted manner. Here, we identify the binding partners of the primate-specific and H3.3-related histone variant H3.Y using several quantitative mass spectrometry approaches, and biochemical and cell biological assays. We find the HIRA, but not the DAXX/ATRX, complex to recognize H3...
February 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28332630/pml-nuclear-bodies-contribute-to-the-basal-expression-of-the-mtor-inhibitor-ddit4
#2
Jayme Salsman, Alex Stathakis, Ellen Parker, Dudley Chung, Livia E Anthes, Kara L Koskowich, Sara Lahsaee, Daniel Gaston, Kimberly R Kukurba, Kevin S Smith, Ian C Chute, Daniel Léger, Laura D Frost, Stephen B Montgomery, Stephen M Lewis, Christopher Eskiw, Graham Dellaire
The promyelocytic leukemia (PML) protein is an essential component of PML nuclear bodies (PML NBs) frequently lost in cancer. PML NBs coordinate chromosomal regions via modification of nuclear proteins that in turn may regulate genes in the vicinity of these bodies. However, few PML NB-associated genes have been identified. PML and PML NBs can also regulate mTOR and cell fate decisions in response to cellular stresses. We now demonstrate that PML depletion in U2OS cells or TERT-immortalized normal human diploid fibroblasts results in decreased expression of the mTOR inhibitor DDIT4 (REDD1)...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332088/simple-technique-of-repair-for-barlow-syndrome-with-posterior-resection-and-chordal-transfer-via-minimally-invasive-approach-primary-experience-in-a-consecutive-series-of-22-patients
#3
H Kamiya, Payam Akhyari, J-P Minol, A C Ites, T Weinreich, S Sixt, P Rellecke, U Boeken, A Albert, A Lichtenberg
OBJECTIVE: Current techniques for mitral valve repair (MVR) in Barlow's disease require high level of surgical expertise due to a complex anatomy. A novel and simple standardized technique that particularly considers the pathological changes of the mitral valve in Barlow's disease has been developed. METHODS: Between 2009 and 2013, 22 patients underwent minimally invasive MVR for Barlow's disease and severe mitral regurgitation (MR). A simple, standardized technique was applied, including resection of P2 segment of posterior mitral leaflet (PML) with preservation of the shortest chordae, transfer of the preserved chordae to A2, and implantation of a semi-rigid open ring...
March 22, 2017: General Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28323224/progressive-multifocal-leukoencephalopathy-and-rheumatoid-arthritis-treatments
#4
Gaëlle Clavel, Antoine Moulignier, Luca Semerano
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system due to reactivation of the JC virus (JCV). PML is extremely uncommon despite the high prevalence of the virus in the general population. No specific treatment is available, and the prognosis is bleak. The diagnosis is based on brain imaging findings, detection of the JCV genome in cerebrospinal fluid samples and, in some cases, histological studies of the brain lesions. The pathophysiological mechanisms that drive the development of PML are incompletely understood...
March 16, 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/28322482/progressive-multifocal-leukoencephalopathy-associated-with-fumaric-acid-esters-treatment-in-psoriasis-patients
#5
Deepak M W Balak, Enes Hajdarbegovic, Wichor M Bramer, Martino H A Neumann, H Bing Thio
BACKGROUND: Fumaric acid esters (FAEs) are a systemic treatment for psoriasis considered to have a favorable long-term safety profile without an increased risk for immunosuppression. However, progressive multifocal leukoencephalopathy (PML), a rare, opportunistic viral infection of the central nervous system, has been linked anecdotally to FAE treatment. OBJECTIVE: to assess clinical features and outcomes of FAE-associated PML cases. METHODS: Systematic literature search in multiple databases up to February, 25(th) 2016 for reports of PML in psoriasis patients treated with FAEs...
March 21, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28320193/good-outcome-of-brain-stem-progressive-multifocal-leukoencephalopathy-in-an-immunosuppressed-renal-transplant-patient-importance-of-early-detection-and-rapid-immune-reconstitution
#6
Roland Sauer, Philipp Gölitz, Johannes Jacobi, Stefan Schwab, Ralf A Linker, De-Hyung Lee
Progressive multifocal leukoencephalopathy (PML) is a rare, opportunistic and often fatal disease of the CNS which may occur under immunosuppression in transplant patients. Brain stem PML is associated with a particularly bad prognosis. Here, we present a case of a renal transplant patient treated with mycophenolate mofetil (MMF) and tacrolimus who developed brain stem PML with limb ataxia, dysarthria and dysphagia. Diagnosis was established by typical MRI features and detection of JCV-DNA in the CSF. Immune reconstitution after stopping MMF and tacrolimus led to a complete and sustained remission of symptoms with improvement of the brain stem lesion over a follow-up over 20months...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28318370/patient-to-patient-transmission-of-natalizumab-associated-pml
#7
Reinhard Hohlfeld, Joachim Havla, Tania Kümpfel
No abstract text is available yet for this article.
March 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28317833/regulation-of-nf-%C3%AE%C2%BAb-by-pml-and-pml-rar%C3%AE
#8
Abrar Ahmed, Xiaochun Wan, Izaskun Mitxitorena, Andrew J Lindsay, Pier Paolo Pandolfi, Mary W McCaffrey, Karen Keeshan, Youhai H Chen, Ruaidhrí J Carmody
Promyelocytic Leukemia (PML) is a nuclear protein that forms sub-nuclear structures termed nuclear bodies associated with transcriptionally active genomic regions. PML is a tumour suppressor and regulator of cell differentiation. We demonstrate that PML promotes TNFα-induced transcriptional responses by promoting NF-κB activity. TNFα-treated PML(-/-) cells show normal IκBα degradation and NF-κB nuclear translocation but significantly reduced NF-κB DNA binding and phosphorylation of NF-κB p65. We also demonstrate that the PML retinoic acid receptor-α (PML-RARα) oncofusion protein, which causes acute promyelocytic leukemia, inhibits TNFα induced gene expression and phosphorylation of NF-κB...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28296380/cd62l-is-not-a-reliable-biomarker-for-predicting-pml-risk-in-natalizumab-treated-r-ms-patients-author-response
#9
COMMENT
Ellen Cahir-McFarland, Richard M Ransohoff, Linda Lieberman, Tatiana Plavina
No abstract text is available yet for this article.
August 30, 2016: Neurology
https://www.readbyqxmd.com/read/28287040/high-frequency-mri-monitoring-should-be-performed-in-natalizumab-treated-ms-patients-with-higher-risk-of-pml-commentary
#10
Mike P Wattjes, Clemens Warnke
No abstract text is available yet for this article.
March 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28287039/high-frequency-mri-monitoring-should-be-performed-in-natalizumab-treated-ms-patients-with-higher-risk-of-pml-yes
#11
Siew Mei Yap, Christopher McGuigan
No abstract text is available yet for this article.
March 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28287038/high-frequency-mri-monitoring-should-be-performed-in-natalizumab-treated-ms-patients-with-higher-risk-of-pml-no
#12
Christian Enzinger
No abstract text is available yet for this article.
March 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28283109/classifying-pml-risk-with-disease-modifying-therapies
#13
REVIEW
Joseph R Berger
OBJECTIVE: To catalogue the risk of PML with the currently available disease modifying therapies (DMTs) for multiple sclerosis (MS). BACKGROUND: All DMTs perturb the immune system in some fashion. Natalizumab, a highly effective DMT, has been associated with a significant risk of PML. Fingolimod and dimethyl fumarate have also been unquestionably associated with a risk of PML in the MS population. Concerns about PML risk with other DMTs have arisen due to their mechanism of action and pharmacological parallel to other agents with known PML risk...
February 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28282574/long-term-effectiveness-and-safety-of-natalizumab-in-a-portuguese-population
#14
I Correia, S Batista, O Galego, I B Marques, J Jesus-Ribeiro, A I Martins, C Nunes, M C Macário, L Cunha, L Sousa
OBJECTIVES: Natalizumab long-term effectiveness data in real-world relapsing-remitting multiple sclerosis (RRMS) is needed. Our objective is to report the long-term effectiveness and safety of natalizumab in a cohort of RRMS patients. METHODS: This is a retrospective study of natalizumab treatment for two years or longer in RRMS. Annualized relapse rate, Expanded Disability Status Scale (EDSS), brain magnetic resonance imaging T2 lesion volume, JC virus antibody status, previous treatments and adverse events were analysed...
March 7, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28277656/biologically-safe-poly-l-lactic-acid-blends-with-tunable-degradation-rate-microstructure-degradation-mechanism-and-mechanical-properties
#15
Hideko T Oyama, Daisuke Tanishima, Ryohei Ogawa
Although poly(L-lactic acid) (PLLA) is reputed to be biodegradable in the human body, its hydrophobic nature lets it persist for ca. 5.5 years. This study demonstrates that biologically safe lactide copolymers, poly(aspartic acid-co-L-lactide) (PAL) and poly(malic acid-co-L-lactide) (PML), dispersed in the PLLA function as detonators (triggers) for its hydrolytic degradation at physiological conditions. The copolymers significantly enhance hydrolysis and consequently the degradation rate of PLLA becomes easily tunable by controlling the amounts of PAL and PML...
March 9, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28268092/droplet-digital-pcr-is-a-reliable-tool-for-monitoring-minimal-residual-disease-in-acute-promyelocytic-leukemia
#16
Claudia Brunetti, Luisa Anelli, Antonella Zagaria, Angela Minervini, Crescenzio F Minervini, Paola Casieri, Nicoletta Coccaro, Cosimo Cumbo, Giuseppina Tota, Luciana Impera, Paola Orsini, Giorgina Specchia, Francesco Albano
Nested PCR (nPCR) and real-time quantitative PCR (qPCR) are well-established methods for monitoring minimal residual disease (MRD) in acute promyelocytic leukemia (APL). Despite their remarkable sensitivity and specificity, both methods have inherent limitations, such as qualitative MRD evaluation and relative quantification. Herein, we used droplet digital PCR (ddPCR) to monitor MRD in 21 APL patients and compared its performance with nPCR and qPCR. After assessing the limit of detection (LOD) for each technique on serial dilutions of PML-RARA bcr1 and bcr3 transcripts, a total of 48 follow-up samples were analyzed and the results compared...
March 4, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28260421/successful-pregnancy-after-natalizumab-associated-progressive-multifocal-leukoencephalopathy-in-a-patient-with-multiple-sclerosis
#17
Kalliopi Pitarokoili, Kerstin Hellwig, Carsten Lukas, Ralf Gold
We report the case of a post-progressive multifocal leukoencephalopathy (PML), multiple sclerosis (MS) patient with an uncomplicated pregnancy and delivery. A 28-year-old woman on natalizumab (total of 49 infusions) was diagnosed with PML due to typical magnetic resonance imaging (MRI) and clinical presentation. John Cunningham virus (JCV) was detected in the cerebrospinal fluid (CSF) during the immune reconstitution inflammatory syndrome (IRIS). Nine months after PML onset, JCV negativity in the CSF was observed...
March 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28250117/the-nd10-component-promyelocytic-leukemia-protein-acts-as-an-e3-ligase-for-sumoylation-of-the-major-immediate-early-protein-ie1-of-human-cytomegalovirus
#18
Nina Reuter, Eva-Maria Schilling, Myriam Scherer, Regina Müller, Thomas Stamminger
Previous studies identified the nuclear domain 10 (ND10) components PML, hDaxx, and Sp100 as factors of an intrinsic immune response against human cytomegalovirus (HCMV). This antiviral function of ND10, however, is antagonized by viral effector proteins like IE1p72, which induces a dispersal of ND10. Furthermore, we have shown that both major immediate-early proteins of HCMV, IE1p72 and IE2p86, transiently co-localize with ND10 subnuclear structures and undergo modification by the covalent attachment of SUMO...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28245526/progressive-multifocal-leukoencephalopathy-driven-from-rarity-to-clinical-mainstream-by-iatrogenic-immunodeficiency
#19
REVIEW
Siraj A Misbah
Advances in immune-mediated targeted therapies have proven to be a double-edged sword for patients by highlighting the risk of iatrogenic infective complications. This has been exemplified by progressive multifocal leukoencephalopathy (PML), a hitherto rare devastating viral infection of the brain caused by the neurotropic JC polyoma virus. While PML achieved prominence during the first two decades of the HIV epidemic, effective anti-retroviral treatment and restitution of T cell function has led to PML being less prominent in this population...
February 28, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28239645/pml-promotes-metastasis-of-triple-negative-breast-cancer-through-transcriptional-regulation-of-hif1a-target-genes
#20
Manfredi Ponente, Letizia Campanini, Roberto Cuttano, Andrea Piunti, Giacomo A Delledonne, Nadia Coltella, Roberta Valsecchi, Alessandra Villa, Ugo Cavallaro, Linda Pattini, Claudio Doglioni, Rosa Bernardi
Elucidating the molecular basis of tumor metastasis is pivotal for eradicating cancer-related mortality. Triple-negative breast cancer (TNBC) encompasses a class of aggressive tumors characterized by high rates of recurrence and metastasis, as well as poor overall survival. Here, we find that the promyelocytic leukemia protein PML exerts a prometastatic function in TNBC that can be targeted by arsenic trioxide. We found that, in TNBC patients, constitutive HIF1A activity induces high expression of PML, along with a number of HIF1A target genes that promote metastasis at multiple levels...
February 23, 2017: JCI Insight
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