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https://www.readbyqxmd.com/read/28216420/evaluation-of-rag1-mutations-in-an-adult-with-combined-immunodeficiency-and-progressive-multifocal-leukoencephalopathy
#1
Claudia Schröder, Niklas Baerlecken, Ulrich Pannicke, Thilo Dörk, Torsten Witte, Roland Jacobs, Matthias Stoll, Klaus Schwarz, Bodo Grimbacher, Reinhold E Schmidt, Faranaz Atschekzei
Here we describe novel mutations in recombination activation gene 1 (RAG1) in a compound heterozygous male patient with combined T and B cell immunodeficiency (CID). Clinical manifestations besides antibody deficiency included airway infections, granulomatosis and autoimmune features. He died at the age of 37 due to PML caused by JC virus infection. By targeted next-generation sequencing we detected post mortem in this patient three mutations in RAG1. One allele harbored two novel mutations (c.1123C>G, p...
February 16, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28210663/maraviroc-in-pml-iris-a-separate-ball-game-under-hiv-infection-and-natalizumab
#2
EDITORIAL
Israel Steiner, Felix Benninger
No abstract text is available yet for this article.
March 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28210661/maraviroc-as-possible-treatment-for-pml-iris-in-natalizumab-treated-patients-with-ms
#3
Sibylle C Hodecker, Klarissa H Stürner, Veit Becker, Birte Elias-Hamp, Brigitte Holst, Manuel A Friese, Christoph Heesen
No abstract text is available yet for this article.
March 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28210660/severe-early-natalizumab-associated-pml-in-ms-effective-control-of-pml-iris-with-maraviroc
#4
Gabriel Bsteh, Michael Auer, Sarah Iglseder, Lisa-Maria Walchhofer, Dietmar Langenscheidt, Stefan Koppi, Gabriele Schauer-Maurer, Guenther Stockhammer, Thomas Berger
No abstract text is available yet for this article.
March 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28202068/the-dna-damage-response-promotes-polyomavirus-jc-infection-by-nucleus-to-cytoplasm-nf-kappab-activation
#5
Martyn K White, Anna Bellizzi, Gabriele Ibba, Valeria Pietropaolo, Anna T Palamara, Hassen S Wollebo
BACKGROUND: Infection of glial cells by human neurotropic polyomavirus JC (JCV), the causative agent of the CNS demyelinating disease progressive multifocal leukoencephalopathy (PML), rapidly inflicts damage to cellular DNA. This activates DNA damage response (DDR) signaling including induction of expression of DNA repair factor Rad51. We previously reported that Rad51 co-operates with the transcription factor NF-κB p65 to activate JCV early transcription. Thus Rad51 induction by JCV infection may provide positive feedback for viral activation early in JCV infection...
February 15, 2017: Virology Journal
https://www.readbyqxmd.com/read/28197915/the-role-of-sumoylation-in-senescence
#6
Lyndee L Scurr, Sebastian Haferkamp, Helen Rizos
Cellular senescence is a program initiated by many stress signals including aberrant activation of oncogenes, DNA damage, oxidative lesions and telomere attrition. Once engaged senescence irreversibly limits cellular proliferation and potently prevents tumor formation in vivo. The precise mechanisms driving the onset of senescence are still not completely defined, although the pRb and p53 tumor suppressor pathways converge with the SUMO cascade to regulate cellular senescence. Sumoylation translocates p53 to PML nuclear bodies where it can co-operate with many sumoylated co-factors in a program that activates pRb and favors senescence...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28183680/diagnosis-of-variant-rara-translocation-using-standard-dual-color-dual-fusion-pml-rara-fish-probes-an-illustrative-report
#7
Manish K Singh, Mayur Parihar, Neeraj Arora, D K Mishra, Saurabh J Bhave, Mammen Chandy
Acute promyelocytic leukemia (APML) with variant RARa translocations comprises 1-2% of APML cases. However, the diagnosis of these cases is challenging as the routine practice includes fluorescence in situ hybridization (FISH) reverse transcription polymerase chain reaction targeting the PML and RARA genes to detect PML/RARA fusions. Here, we report a case highlighting the importance of atypical FISH signal patterns in standard dual-color dual-fusion PML/RARa FISH analysis complimented by karyotyping to detect these variant RARA translocations...
February 1, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28176617/progressive-multifocal-leukoencephalopathy-in-a-kidney-transplant-recipient
#8
Federico Cicora, Javier Roberti
Progressive multifocal leukoencephalopathy (PML) is a debilitating and often fatal viral disease of the central nervous system. A 39-year-old male kidney transplant recipient presented to our hospital with weakness of the left arm and leg, his immunosuppressive regimen consisted of tacrolimus, mycophenolate sodium, and meprednisone. Magnetic resonance imaging of the brain revealed hypercellularity in neural tissue and a lesion affecting the right ventral and lateral areas of the thalamus and the posterior limb of the internal capsule...
February 7, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28174598/review-on-the-role-of-the-human-polyomavirus-jc-in-the-development-of-tumors
#9
REVIEW
Serena Delbue, Manola Comar, Pasquale Ferrante
Almost one fifth of human cancers worldwide are associated with infectious agents, either bacteria or viruses, and this makes the possible association between infections and tumors a relevant research issue. We focused our attention on the human Polyomavirus JC (JCPyV), that is a small, naked DNA virus, belonging to the Polyomaviridae family. It is the recognized etiological agent of the Progressive Multifocal Leukoencephalopathy (PML), a fatal demyelinating disease, occurring in immunosuppressed individuals...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/28168372/high-b-value-diffusion-weighted-imaging-in-progressive-multifocal-leukoencephalopathy-in-hiv-patients
#10
Claudia Godi, Enrico De Vita, Enrico Tombetti, Indran Davagnanam, Lewis Haddow, Hans Rolf Jäger
OBJECTIVES: An ill-defined hyperintense edge and hypointense core on diffusion-weighted imaging (DWI) is typical of progressive multifocal leukoencephalopathy (PML). We aimed to investigate whether a b-value of 3,000 s/mm(2) (b3000) can improve visualisation of PML, or provide different structural information compared to 1,000 s/mm(2) (b1000). METHODS: We retrospectively identified HIV-positive patients with confirmed PML studied under a clinical protocol including both b1000 and b3000 DWI...
February 6, 2017: European Radiology
https://www.readbyqxmd.com/read/28165319/progressive-multifocal-leukoencephalopathy-in-two-natalizumab-treated-stepsisters-an-intriguing-coincidence
#11
Frédéric Bacchetta, Amandine Mathias, Myriam Schluep, Renaud Du Pasquier
BACKGROUND: Natalizumab, a treatment used in multiple sclerosis (MS), is associated with cases of progressive multifocal leukoencephalopathy (PML). OBJECTIVE: We describe two cases of PML in related but not genetically apparented natalizumab-treated MS patients who are stepsisters. Reported cases/outcomes: While Patient 1 developed PML, Patient 2 was on natalizumab and had contacts with Patient 1. Patient 2 was diagnosed with PML 5 months after Patient 1. CONCLUSION: The clinical and temporal data highly suggest that there was JC virus (JCV) transmission from one patient to the other with development of PML as primo-infection in Patient 2...
February 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28147629/contribution-of-leaky-modes-in-the-modal-analysis-of-unbounded-problems-with-perfectly-matched-layers
#12
Matthieu Gallezot, Fabien Treyssède, Laurent Laguerre
The modal analysis of wave problems of unbounded type involves a continuous sum of radiation modes. This continuum is difficult to handle mathematically and physically. It can be approximated by a discrete set of leaky modes, corresponding to improper modes growing to infinity. Perfectly matched layers (PMLs) have been widely applied in numerical methods to efficiently simulate infinite media, most often without considering a modal approach. This letter aims to bring insight into the modal basis computed with PMLs...
January 2017: Journal of the Acoustical Society of America
https://www.readbyqxmd.com/read/28147349/leukocyte-anti-trafficking-strategies-current-status-and-future-directions
#13
REVIEW
Bruce E Sands
BACKGROUND: In inflammatory bowel diseases (IBD), a pivotal step in the initiation and perpetuation of mucosal inflammation entails the recruitment of inflammatory leukocytes to the gut. Understanding the carefully coordinated series of molecular events that culminate in the recruitment of leukocytes to the gut has resulted in novel interventions with new capabilities in treating both Crohn's disease and ulcerative colitis. Key Messages: Natalizumab, an anti-α4 integrin antibody, was the first agent to demonstrate the efficacy of this approach for the induction and maintenance of response and remission in Crohn's disease...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28143738/manipulating-pml-sumoylation-via-silencing-ubc9-and-rnf4-regulates-cardiac-fibrosis
#14
Yu Liu, Dan Zhao, Fang Qiu, Ling-Ling Zhang, Shang-Kun Liu, Yuan-Yuan Li, Mei-Tong Liu, Di Wu, Jia-Xin Wang, Xiao-Qing Ding, Yan-Xin Liu, Chang-Jiang Dong, Xiao-Qi Shao, Bao-Feng Yang, Wen-Feng Chu
The promyelocytic leukemia protein (PML) is essential in the assembly of dynamic subnuclear structures called PML nuclear bodies (PML-NBs), which are involved in regulating diverse cellular functions. However, the possibility of PML being involved in cardiac disease has not been examined. In mice undergoing transverse aortic constriction (TAC) and arsenic trioxide (ATO) injection, transforming growth factor β1 (TGF-β1) was upregulated along with dynamic alteration of PML SUMOylation. In cultured neonatal mouse cardiac fibroblasts (NMCFs), ATO, angiotensin II (Ang II), and fetal bovine serum (FBS) significantly triggered PML SUMOylation and the assembly of PML-NBs...
January 28, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28130920/interdisciplinary-risk-management-in-the-treatment-of-multiple-sclerosis
#15
Joachim Havla, Clemens Warnke, Tobias Derfuss, Ludwig Kappos, Hans-Peter Hartung, Reinhard Hohlfeld
BACKGROUND: Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system. There are at least 150 000 persons with MS in Germany. Recent years have seen the approval of new drugs against. METHODS: This article is based on pertinent literature retrieved by a selective search in PubMed as well as on documentation of relevant risks and adverse effects in "red hand letters" (information bulletins from pharmaceutical companies to physicians about adverse drug effects) and elsewhere, along with data provided by the German Multiple Sclerosis Competence Network...
December 26, 2016: Deutsches Ärzteblatt International
https://www.readbyqxmd.com/read/28130412/update-on-disease-modifying-therapies-for-multiple-sclerosis
#16
Diana L Vargas, William R Tyor
Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system (CNS). It predominantly affects young women and is one of the most common causes of disability in young adults. MS is characterized by formation of white matter lesions in the CNS as a result of inflammation, demyelination, and axonal loss. Treatment has been a focus of neurological research for over 60 years. A number of disease-modifying therapies (DMTs) have become available making MS a treatable disease. These compounds target the inflammatory response in MS...
January 27, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28130038/autophagy-contributes-to-4-amino-2-trifluoromethyl-phenyl-retinate-induced-differentiation-in-human-acute-promyelocytic-leukemia-nb4-cells
#17
Yue Li, Ge Li, Ke Wang, Ya-Ya Xie, Ren-Peng Zhou, Yao Meng, Ran Ding, Jin-Fang Ge, Fei-Hu Chen
As a classic differentiation agent, all-trans retinoic acid (ATRA) has been widely used in treatment of acute promyelocytic leukemia (APL). However, clinical application of ATRA has limitations. Our previous studies suggested that 4-Amino-2-Trifluoromethyl-Phenyl Retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative designed and synthesized by our team, could induce differentiation of APL cells in vivo and in vitro. To explore the underlying mechanism of ATPR, the effect of ATPR on autophagy of APL cells was observed in the present study...
January 25, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28129653/rxr%C3%AE-ligand-z-10-induces-pml-rar%C3%AE-cleavage-and-apl-cell-apoptosis-through-disrupting-pml-rar%C3%AE-rxr%C3%AE-complex-in-a-camp-independent-manner
#18
Lin Xu, Zhiping Zeng, Weidong Zhang, Gaoang Ren, Xiaobin Ling, Fengyu Huang, Peizhen Xie, Ying Su, Xiao-Kun Zhang, Hu Zhou
The major oncogenic driver of acute promyelocytic leukemia (APL) is the fusion protein PML-RARα originated from the chromosomal translocation t(15;17). All-trans retinoic acid (ATRA) and arsenic trioxide cure most patients by directly targeting PML-RARα. However, major issues including the resistance of ATRA and arsenic therapy still remain in APL clinical management. Here we showed that compound Z-10, a nitro-ligand of retinoid X receptor α (RXRα), strongly promoted the cAMP-independent apoptosis of both ATRA- sensitive and resistant NB4 cells via the induction of caspase-mediated PML-RARα degradation...
January 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28125133/acute-wt1-positive-promyelocytic-leukemia-with-hypogranular-variant-morphology-bcr-3-isoform-of-pml-rar%C3%AE-and-flt3-itd-mutation-a-rare-case-report
#19
Xi Zhang, Cheng Yang, Xiangui Peng, Xinghua Chen, Yimei Feng
CONTEXT: Acute promyelocytic leukemia (APL) accounts for 8% to 10% of cases of acute myeloid leukemia (AML). Remission in cases of high-risk APL is still difficult to achieve, and relapses occur readily. CASE REPORT: Here, we describe a case of APL with high white blood cell counts in blood tests and hypogranular variant morphology in bone marrow, together with fms-like tyrosine kinase-3 with internal tandem duplication mutations (FLT3-ITD), and bcr-3 isoform of PML-RARα...
January 23, 2017: São Paulo Medical Journal, Revista Paulista de Medicina
https://www.readbyqxmd.com/read/28125064/phenylarsine-oxide-can-induce-the-arsenite-resistance-mutant-pml-protein-solubility-changes
#20
Yu Han Jiang, Ye Jia Chen, Chao Wang, Yong Fei Lan, Chang Yang, Qian Qian Wang, Liaqat Hussain, Yasen Maimaitiying, Khairul Islam, Hua Naranmandura
Arsenic trioxide (As₂O₃) has recently become one of the most effective drugs for treatment of patient with acute promyelocytic leukemia (APL), and its molecular mechanism has also been largely investigated. However, it has been reported that As₂O₃ resistant patients are frequently found in relapsed APL after consolidation therapy, which is due to the point mutations in B-box type 2 motifs of promyelocytic leukemia (PML) gene. In the present study, we for the first time establish whether organic arsenic species phenylarsine oxide (PAO) could induce the mutant PML-IV (A216V) protein solubility changes and degradation...
January 25, 2017: International Journal of Molecular Sciences
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