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https://www.readbyqxmd.com/read/28087666/dysregulation-of-b-cell-repertoire-formation-in-myasthenia-gravis-patients-revealed-through-deep-sequencing
#1
Jason A Vander Heiden, Panos Stathopoulos, Julian Q Zhou, Luan Chen, Tamara J Gilbert, Christopher R Bolen, Richard J Barohn, Mazen M Dimachkie, Emma Ciafaloni, Teresa J Broering, Francois Vigneault, Richard J Nowak, Steven H Kleinstein, Kevin C O'Connor
Myasthenia gravis (MG) is a prototypical B cell-mediated autoimmune disease affecting 20-50 people per 100,000. The majority of patients fall into two clinically distinguishable types based on whether they produce autoantibodies targeting the acetylcholine receptor (AChR-MG) or muscle specific kinase (MuSK-MG). The autoantibodies are pathogenic, but whether their generation is associated with broader defects in the B cell repertoire is unknown. To address this question, we performed deep sequencing of the BCR repertoire of AChR-MG, MuSK-MG, and healthy subjects to generate ∼518,000 unique VH and VL sequences from sorted naive and memory B cell populations...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28079665/anesthetic-management-of-a-patient-with-antimuscle-specific-kinase-antibody-positive-myasthenia-gravis-undergoing-an-open-cholecystectomy-a-case-report
#2
Masahiko Akatsu, Yukihiro Ikegami, Choichiro Tase, Koichi Nishikawa
Myasthenia gravis (MG) is an autoimmune disease characterized by the production of antibodies against the acetylcholine receptor, muscle-specific kinase (MuSK), or other proteins at the neuromuscular junction. MG with antibodies against MuSK (MuSK-MG) has been described recently. Here, we report the first case of anesthetic management of a patient with MuSK-MG undergoing an open cholecystectomy. In our case, propofol and remifentanil-based anesthesia were used for successful management without using muscle relaxants...
January 11, 2017: A & A Case Reports
https://www.readbyqxmd.com/read/28079271/uptake-and-elimination-kinetics-of-the-biocide-triclosan-and-the-synthetic-musks-galaxolide-and-tonalide-in-the-earthworm-dendrobaena-veneta-when-exposed-to-sewage-sludge
#3
Ivo Havranek, Claire Coutris, Hans Ragnar Norli, Pierre-Adrien Rivier, Erik J Joner
Sewage sludge is an important amendment that enriches soils with organic matter and provides plants with nutrients such as nitrogen and phosphorus. However, knowledge on fate and effects of organic pollutants present in the sludge on soil organisms is limited. In the present study, the uptake of triclosan, galaxolide, and tonalide in the earthworm Dendrobaena veneta was measured one week after amendment of agricultural soil with sewage sludge, while elimination kinetics were assessed over a 21-day period after transferring worms to a clean soil...
January 12, 2017: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/28072465/splicing-regulation-and-dysregulation-of-cholinergic-genes-expressed-at-the-neuromuscular-junction
#4
REVIEW
Kinji Ohno, Mohammad Alinoor Rahman, Mohammad Nazim, Farhana Nasrin, Yingni Lin, Jun-Ichi Takeda, Akio Masuda
We humans have evolved by acquiring diversity of alternative RNA metabolisms including alternative means of splicing and transcribing non-coding genes, and not by acquiring new coding genes. Tissue-specific and developmental stage-specific alternative RNA splicing is achieved by tightly regulated spatiotemporal regulation of expressions and activations of RNA-binding proteins that recognize their cognate splicing cis-elements on nascent RNA transcripts. Genes expressed at the neuromuscular junction (NMJ) are also alternatively spliced...
January 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28069867/the-carboxyl-terminal-region-of-dok-7-plays-a-key-but-not-essential-role-in-activation-of-muscle-specific-receptor-kinase-musk-and-neuromuscular-synapse-formation
#5
Ryo Ueta, Tohru Tezuka, Yosuke Izawa, Sadanori Miyoshi, Satoru Nagatoishi, Kouhei Tsumoto, Yuji Yamanashi
As the synapse between a motor neuron and skeletal muscle, the neuromuscular junction (NMJ) is required for muscle contraction. The formation and maintenance of NMJs are controlled by the muscle-specific receptor kinase MuSK. Dok-7 is the essential cytoplasmic activator of MuSK, and indeed mice lacking Dok-7 form no NMJs. Moreover, DOK7 gene mutations underlie DOK7 myasthenia, an NMJ synaptopathy. Previously, we failed to detect MuSK activation in myotubes by Dok-7 mutated in the N-terminal pleckstrin homology (PH) or phosphotyrosine binding (PTB) domain or that lacked the C-terminal region (Dok-7-ΔC)...
January 7, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28042656/the-emetic-activity-of-staphylococcal-enterotoxins-sek-sel-sem-sen-and-seo-in-a-small-emetic-animal-model-house-musk-shrew
#6
Hisaya K Ono, Shouhei Hirose, Ikunori Naito, Yusuke Sato'o, Krisana Asano, Dong-Liang Hu, Katsuhiko Omoe, Akio Nakane
Staphylococcal enterotoxins (SEs) produced by Staphylococcus aureus are the most recognizable causative agents of emetic food poisoning in humans. New types of SEs and SE-like (SEl) toxins have been reported. Several epidemiological investigations have shown that the SEs and SEls genes, particularly, SEK, SEL, SEM, SEN and SEO genes, were highly detected in the strains isolated from food poisoning cases. The purpose of the present study was to evaluate the emetic activity of the recently identified SEs using a small emetic animal model, house musk shrew...
January 2, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28040339/novel-pollutants-in-the-moscow-atmosphere-in-winter-period-gas-chromatography-high-resolution-time-of-flight-mass-spectrometry-study
#7
D M Mazur, O V Polyakova, V B Artaev, A T Lebedev
The most common mass spectrometry approach analyzing contamination of the environment deals with targeted analysis, i.e. detection and quantification of the selected (priority) pollutants. However non-targeted analysis is becoming more often the method of choice for environmental chemists. It involves implementation of modern analytical instrumentation allowing for comprehensive detection and identification of the wide variety of compounds of the environmental interest present in the sample, such as pharmaceuticals and their metabolites, musks, nanomaterials, perfluorinated compounds, hormones, disinfection by-products, flame retardants, personal care products, and many others emerging contaminants...
December 28, 2016: Environmental Pollution
https://www.readbyqxmd.com/read/27998790/a-15-gene-signature-for-prediction-of-colon-cancer-recurrence-and-prognosis-based-on-svm
#8
Guangru Xu, Minghui Zhang, Hongxing Zhu, Jinhua Xu
OBJECTIVE: To screen the gene signature for distinguishing patients with high risks from those with low-risks for colon cancer recurrence and predicting their prognosis. METHODS: Five microarray datasets of colon cancer samples were collected from Gene Expression Omnibus database and one was obtained from The Cancer Genome Atlas (TCGA). After preprocessing, data in GSE17537 were analyzed using the Linear Models for Microarray data (LIMMA) method to identify the differentially expressed genes (DEGs)...
March 10, 2017: Gene
https://www.readbyqxmd.com/read/27965060/igg4-autoantibodies-against-muscle-specific-kinase-undergo-fab-arm-exchange-in-myasthenia-gravis-patients
#9
Inga Koneczny, Jo A A Stevens, Anna De Rosa, Saif Huda, Maartje G Huijbers, Abhishek Saxena, Michelangelo Maestri, Konstantinos Lazaridis, Paraskevi Zisimopoulou, Socrates Tzartos, Jan Verschuuren, Silvère M van der Maarel, Philip van Damme, Marc H De Baets, Peter C Molenaar, Angela Vincent, Roberta Ricciardi, Pilar Martinez-Martinez, Mario Losen
Autoimmunity mediated by IgG4 subclass autoantibodies is an expanding field of research. Due to their structural characteristics a key feature of IgG4 antibodies is the ability to exchange Fab-arms with other, unrelated, IgG4 molecules, making the IgG4 molecule potentially monovalent for the specific antigen. However, whether those disease-associated antigen-specific IgG4 are mono- or divalent for their antigens is unknown. Myasthenia gravis (MG) with antibodies to muscle specific kinase (MuSK-MG) is a well-recognized disease in which the predominant pathogenic IgG4 antibody binds to extracellular epitopes on MuSK at the neuromuscular junction; this inhibits a pathway that clusters the acetylcholine (neurotransmitter) receptors and leads to failure of neuromuscular transmission...
December 10, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27964993/laminin-is-instructive-and-calmodulin-dependent-kinase-ii-is-non-permissive-for-the-formation-of-complex-aggregates-of-acetylcholine-receptors-on-myotubes-in-culture
#10
Raphael Vezina-Audette, Mathieu Tremblay, Salvatore Carbonetto
Previous work has shown that myotubes cultured on laminin-coated substrates form complex aggregates of synaptic proteins that are similar in shape and composition to neuromuscular junctions (NMJs). Here we show that laminin instructs the location of complex aggregates which form only on the lower surface when laminin is coated onto culture dishes but over the entire cell when laminin is added in solution. Silencing of myotubes by agents that block electrical activity (tetrodotoxin, verapamil) or by inhibitors of calmodulin dependent kinase (CaMKII) render the myotube permissive for the formation of complex aggregates...
December 10, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27964759/voluntary-resistance-wheel-exercise-from-mid-life-prevents-sarcopenia-and-increases-markers-of-mitochondrial-function-and-autophagy-in-muscles-of-old-male-and-female-c57bl-6j-mice
#11
Zoe White, Jessica Terrill, Robert B White, Christopher McMahon, Phillip Sheard, Miranda D Grounds, Tea Shavlakadze
BACKGROUND: There is much interest in the capacity of resistance exercise to prevent the age-related loss of skeletal muscle mass and function, known as sarcopenia. This study investigates the molecular basis underlying the benefits of resistance exercise in aging C57BL/6J mice of both sexes. RESULTS: This study is the first to demonstrate that long-term (34 weeks) voluntary resistance wheel exercise (RWE) initiated at middle age, from 15 months, prevents sarcopenia in selected hindlimb muscles and causes hypertrophy in soleus, by 23 months of age in both male and female C57BL/6J mice...
December 13, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27939665/musk-xylene-induces-malignant-transformation-of-human-liver-cell-line-l02-via-repressing-the-tgf-%C3%AE-signaling-pathway
#12
Youyu Zhang, Lixing Huang, Yujie Zhao, Tianhui Hu
Musk xylene (MX) is a widely used synthetic nitro musk. Although the persistence and bioaccumulation of the synthetic musks are of concern since the nineteenth century, knowledge concerning the toxicity and environmental risks, especially the carcinogenicity is still limited. In the present study, the normal human hepatic cell line L02 was used to investigate the long-term carcinogenicity of MX. L02 cells were exposed to MX with different concentrations (10, 100, and 1000 μg/L) for 24 h, then with conventional culture...
February 2017: Chemosphere
https://www.readbyqxmd.com/read/27932188/successful-single-lung-transplant-for-severe-lung-graft-versus-host-disease-two-years-after-sibling-allograft-for-acute-lymphoblastic-leukemia-a-case-report
#13
M R Irhimeh, M Musk, J P Cooney
Bone marrow transplantation (BMT) has been performed as a successful life-saving treatment for hematological and neoplastic diseases. Despite the predictable long-term survival rates in BMT, pulmonary complications reduce the survival rates significantly mainly because of chronic graft-versus-host disease (GVHD). This report briefly discusses a successful lung transplantation case for severe lung GVHD after allograft for acute lymphoblastic leukemia. This case report supports the scarce evidence in the literature for the importance of lung transplantation as a therapeutic option for patients who develop respiratory failure secondary to BMT...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27931220/native-musk-and-synthetic-musk-ketone-strongly-induced-the-growth-repression-and-the-apoptosis-of-cancer-cells
#14
Ling Xu, Yi Cao
BACKGROUND: Musk is widely used in clinical practice for its anti-cancer properties. Here, we treated various types of cancer using musk to determine which cancers are sensitive to musk treatment. We also compared effects of native musk and synthetic musk ketone in cancer cells. Furthermore, we investigated mechanisms underlying effects of musk. METHODS: Twenty two cancer cell lines were treated with musk. Cell proliferation and apoptosis analyses were carried out...
December 8, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27919060/estimation-of-quantitative-levels-of-diesel-exhaust-exposure-and-the-health-impact-in-the-contemporary-australian-mining-industry
#15
Susan Peters, Nicholas de Klerk, Alison Reid, Lin Fritschi, Aw Bill Musk, Roel Vermeulen
OBJECTIVES: To estimate quantitative levels of exposure to diesel exhaust expressed by elemental carbon (EC) in the contemporary mining industry and to describe the excess risk of lung cancer that may result from those levels. METHODS: EC exposure has been monitored in Western Australian miners since 2003. Mixed-effects models were used to estimate EC levels for five surface and five underground occupation groups (as a fixed effect) and specific jobs within each group (as a random effect)...
November 15, 2016: Occupational and Environmental Medicine
https://www.readbyqxmd.com/read/27909849/monitoring-contaminants-of-emerging-concern-from-tertiary-wastewater-treatment-plants-using-passive-sampling-modelled-with-performance-reference-compounds
#16
Tamanna Sultana, Craig Murray, M Ehsanul Hoque, Chris D Metcalfe
The Lake Simcoe watershed in Ontario, Canada is an important recreational area and a recharge zone for groundwater resources. Lake Simcoe is a relatively shallow lotic system that has been impacted by urban development, recreation, industry and agriculture. As part of a watershed management plan, six wastewater treatment plants (WWTPs) located in this catchment basin were selected to measure the inputs of contaminants of emerging concern (CECs) of wastewater origin. These WWTPs were recently upgraded to tertiary treatment for phosphorus removal...
December 2016: Environmental Monitoring and Assessment
https://www.readbyqxmd.com/read/27905551/corrigendum-musk-kinase-activity-is-modulated-by-a-serine-phosphorylation-site-in-the-kinase-loop
#17
B Z Camurdanoglu, C Hrovat, G Dürnberger, M Madalinski, K Mechtler, R Herbst
No abstract text is available yet for this article.
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27901396/effects-of-dobutamine-hydrochloride-on-cardiovascular-function-in-horses-anesthetized-with-isoflurane-with-or-without-acepromazine-maleate-premedication
#18
RANDOMIZED CONTROLLED TRIAL
Mara F Schier, Anthea L Raisis, Cristy J Secombe, Giselle Hosgood, Gabrielle C Musk, Guy D Lester
OBJECTIVE To determine the effects of acepromazine maleate premedication on cardiovascular function before and after infusion of dobutamine hydrochloride for 30 minutes in isoflurane-anesthetized horses. ANIMALS 6 healthy adult horses. PROCEDURES Each horse was anesthetized once following premedication with acepromazine (0.02 mg/kg, IV) administered 30 minutes prior to anesthetic induction (ACP+ treatment) and once without premedication (ACP- treatment). Anesthesia was induced with IV administration of xylazine hydrochloride (0...
December 2016: American Journal of Veterinary Research
https://www.readbyqxmd.com/read/27876822/a-principal-component-meta-analysis-on-multiple-anthropometric-traits-identifies-novel-loci-for-body-shape
#19
Janina S Ried, Janina Jeff M, Audrey Y Chu, Jennifer L Bragg-Gresham, Jenny van Dongen, Jennifer E Huffman, Tarunveer S Ahluwalia, Gemma Cadby, Niina Eklund, Joel Eriksson, Tõnu Esko, Mary F Feitosa, Anuj Goel, Mathias Gorski, Caroline Hayward, Nancy L Heard-Costa, Anne U Jackson, Eero Jokinen, Stavroula Kanoni, Kati Kristiansson, Zoltán Kutalik, Jari Lahti, Jian'an Luan, Reedik Mägi, Anubha Mahajan, Massimo Mangino, Carolina Medina-Gomez, Keri L Monda, Ilja M Nolte, Louis Pérusse, Inga Prokopenko, Lu Qi, Lynda M Rose, Erika Salvi, Megan T Smith, Harold Snieder, Alena Stančáková, Yun Ju Sung, Ioanna Tachmazidou, Alexander Teumer, Gudmar Thorleifsson, Pim van der Harst, Ryan W Walker, Sophie R Wang, Sarah H Wild, Sara M Willems, Andrew Wong, Weihua Zhang, Eva Albrecht, Alexessander Couto Alves, Stephan J L Bakker, Cristina Barlassina, Traci M Bartz, John Beilby, Claire Bellis, Richard N Bergman, Sven Bergmann, John Blangero, Matthias Blüher, Eric Boerwinkle, Lori L Bonnycastle, Stefan R Bornstein, Marcel Bruinenberg, Harry Campbell, Yii-Der Ida Chen, Charleston W K Chiang, Peter S Chines, Francis S Collins, Fracensco Cucca, L Adrienne Cupples, Francesca D'Avila, Eco J C de Geus, George Dedoussis, Maria Dimitriou, Angela Döring, Johan G Eriksson, Aliki-Eleni Farmaki, Martin Farrall, Teresa Ferreira, Krista Fischer, Nita G Forouhi, Nele Friedrich, Anette Prior Gjesing, Nicola Glorioso, Mariaelisa Graff, Harald Grallert, Niels Grarup, Jürgen Gräßler, Jagvir Grewal, Anders Hamsten, Marie Neergaard Harder, Catharina A Hartman, Maija Hassinen, Nicholas Hastie, Andrew Tym Hattersley, Aki S Havulinna, Markku Heliövaara, Hans Hillege, Albert Hofman, Oddgeir Holmen, Georg Homuth, Jouke-Jan Hottenga, Jennie Hui, Lise Lotte Husemoen, Pirro G Hysi, Aaron Isaacs, Till Ittermann, Shapour Jalilzadeh, Alan L James, Torben Jørgensen, Pekka Jousilahti, Antti Jula, Johanne Marie Justesen, Anne E Justice, Mika Kähönen, Maria Karaleftheri, Kay Tee Khaw, Sirkka M Keinanen-Kiukaanniemi, Leena Kinnunen, Paul B Knekt, Heikki A Koistinen, Ivana Kolcic, Ishminder K Kooner, Seppo Koskinen, Peter Kovacs, Theodosios Kyriakou, Tomi Laitinen, Claudia Langenberg, Alexandra M Lewin, Peter Lichtner, Cecilia M Lindgren, Jaana Lindström, Allan Linneberg, Roberto Lorbeer, Mattias Lorentzon, Robert Luben, Valeriya Lyssenko, Satu Männistö, Paolo Manunta, Irene Mateo Leach, Wendy L McArdle, Barbara Mcknight, Karen L Mohlke, Evelin Mihailov, Lili Milani, Rebecca Mills, May E Montasser, Andrew P Morris, Gabriele Müller, Arthur W Musk, Narisu Narisu, Ken K Ong, Ben A Oostra, Clive Osmond, Aarno Palotie, James S Pankow, Lavinia Paternoster, Brenda W Penninx, Irene Pichler, Maria G Pilia, Ozren Polašek, Peter P Pramstaller, Olli T Raitakari, Tuomo Rankinen, D C Rao, Nigel W Rayner, Rasmus Ribel-Madsen, Treva K Rice, Marcus Richards, Paul M Ridker, Fernando Rivadeneira, Kathy A Ryan, Serena Sanna, Mark A Sarzynski, Salome Scholtens, Robert A Scott, Sylvain Sebert, Lorraine Southam, Thomas Hempel Sparsø, Valgerdur Steinthorsdottir, Kathleen Stirrups, Ronald P Stolk, Konstantin Strauch, Heather M Stringham, Morris A Swertz, Amy J Swift, Anke Tönjes, Emmanouil Tsafantakis, Peter J van der Most, Jana V Van Vliet-Ostaptchouk, Liesbeth Vandenput, Erkki Vartiainen, Cristina Venturini, Niek Verweij, Jorma S Viikari, Veronique Vitart, Marie-Claude Vohl, Judith M Vonk, Gérard Waeber, Elisabeth Widén, Gonneke Willemsen, Tom Wilsgaard, Thomas W Winkler, Alan F Wright, Laura M Yerges-Armstrong, Jing Hua Zhao, M Carola Zillikens, Dorret I Boomsma, Claude Bouchard, John C Chambers, Daniel I Chasman, Daniele Cusi, Ron T Gansevoort, Christian Gieger, Torben Hansen, Andrew A Hicks, Frank Hu, Kristian Hveem, Marjo-Riitta Jarvelin, Eero Kajantie, Jaspal S Kooner, Diana Kuh, Johanna Kuusisto, Markku Laakso, Timo A Lakka, Terho Lehtimäki, Andres Metspalu, Inger Njølstad, Claes Ohlsson, Albertine J Oldehinkel, Lyle J Palmer, Oluf Pedersen, Markus Perola, Annette Peters, Bruce M Psaty, Hannu Puolijoki, Rainer Rauramaa, Igor Rudan, Veikko Salomaa, Peter E H Schwarz, Alan R Shudiner, Jan H Smit, Thorkild I A Sørensen, Timothy D Spector, Kari Stefansson, Michael Stumvoll, Angelo Tremblay, Jaakko Tuomilehto, André G Uitterlinden, Matti Uusitupa, Uwe Völker, Peter Vollenweider, Nicholas J Wareham, Hugh Watkins, James F Wilson, Eleftheria Zeggini, Goncalo R Abecasis, Michael Boehnke, Ingrid B Borecki, Panos Deloukas, Cornelia M van Duijn, Caroline Fox, Leif C Groop, Iris M Heid, David J Hunter, Robert C Kaplan, Mark I McCarthy, Kari E North, Jeffrey R O'Connell, David Schlessinger, Unnur Thorsteinsdottir, David P Strachan, Timothy Frayling, Joel N Hirschhorn, Martina Müller-Nurasyid, Ruth J F Loos
Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes...
November 23, 2016: Nature Communications
https://www.readbyqxmd.com/read/27854225/myasthenia-gravis-unusual-presentations-and-diagnostic-pitfalls
#20
Carmelo Rodolico, Daniela Parisi, Simona Portaro, Fiammetta Biasini, Stefano Sinicropi, Annamaria Ciranni, Antonio Toscano, Sonia Messina, Olimpia Musumeci, Giuseppe Vita, Paolo Girlanda
BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder presenting with fluctuating, fatigable muscle weakness. Initial symptoms classically involve ocular and proximal limb muscles. Rarely, MG may onset with unusual features, so it can be misdiagnosed with other neuromuscular diseases. OBJECTIVE: To describe unusual and atypical presentations of MG in a large cohort of patients, considering and discussing diagnostic difficulties and pitfalls. METHODS: We report on 21 out of 508 MG patients, coming to our department in the last 27 years and presenting with atypical or unusual features...
August 30, 2016: Journal of Neuromuscular Diseases
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