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https://www.readbyqxmd.com/read/27909702/complement-inhibition-enables-tumor-delivery-of-lcmv-glycoprotein-pseudotyped-viruses-in-the-presence-of-antiviral-antibodies
#1
Laura Evgin, Carolina S Ilkow, Marie-Claude Bourgeois-Daigneault, Christiano Tanese de Souza, Lawton Stubbert, Michael S Huh, Victoria A Jennings, Monique Marguerie, Sergio A Acuna, Brian A Keller, Charles Lefebvre, Theresa Falls, Fabrice Le Boeuf, Rebecca A Auer, John D Lambris, J Andrea McCart, David F Stojdl, John C Bell
The systemic delivery of therapeutic viruses, such as oncolytic viruses or vaccines, is limited by the generation of neutralizing antibodies. While pseudotyping of rhabdoviruses with the lymphocytic choriomeningitis virus glycoprotein has previously allowed for multiple rounds of delivery in mice, this strategy has not translated to other animal models. For the first time, we provide experimental evidence that antibodies generated against the lymphocytic choriomeningitis virus glycoprotein mediate robust complement-dependent viral neutralization via activation of the classical pathway...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27899229/development-of-novel-replication-defective-lymphocytic-choriomeningitis-virus-vectors-expressing-siv-antigens
#2
Pablo Penaloza MacMaster, Jennifer L Shields, Quazim A Alayo, Crystal Cabral, Jessica Jimenez, Jade Mondesir, Abishek Chandrashekar, Joseph M Cabral, Matthew Lim, M Justin Iampietro, Nicholas M Provine, Christine A Bricault, Michael Seaman, Klaus Orlinger, Andreas Aspoeck, Gerhard Fuhrmann, Anders E Lilja, Thomas Monath, Bastien Mangeat, Daniel D Pinschewer, Dan H Barouch
An important focus in vaccine research is the design of vaccine vectors with low seroprevalence and high immunogenicity. Replication-incompetent lymphocytic choriomeningitis virus (rLCMV) vectors do not elicit vector-neutralizing antibody responses, and homologous prime-boost regimens with rLCMV vectors induce boostable and protective T cell responses to model antigens in mice. However, cellular and humoral immune responses following homologous rLCMV vaccine regimens have not been rigorously evaluated in non-human primates (NHPs)...
November 26, 2016: Vaccine
https://www.readbyqxmd.com/read/27895178/conserved-region-c-functions-to-regulate-pd-1-expression-and-subsequent-cd8-t-cell-memory
#3
Alexander P R Bally, Yan Tang, Joshua T Lee, Benjamin G Barwick, Ryan Martinez, Brian D Evavold, Jeremy M Boss
Expression of programmed death 1 (PD-1) on CD8 T cells promotes T cell exhaustion during chronic Ag exposure. During acute infections, PD-1 is transiently expressed and has the potential to modulate CD8 T cell memory formation. Conserved region C (CR-C), a promoter proximal cis-regulatory element that is critical to PD-1 expression in vitro, responds to NFATc1, FoxO1, and/or NF-κB signaling pathways. Here, a CR-C knockout mouse was established to determine its role on PD-1 expression and the corresponding effects on T cell function in vivo...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27894806/genetic-divergence-in-the-transcriptional-engram-of-chronic-alcohol-abuse-a-laser-capture-rna-seq-study-of-the-mouse-mesocorticolimbic-system
#4
Megan K Mulligan, Khyobeni Mozhui, Ashutosh K Pandey, Maren L Smith, Suzhen Gong, Jesse Ingels, Michael F Miles, Marcelo F Lopez, Lu Lu, Robert W Williams
Genetic factors that influence the transition from initial drinking to dependence remain enigmatic. Recent studies have leveraged chronic intermittent ethanol (CIE) paradigms to measure changes in brain gene expression in a single strain at 0, 8, 72 h, and even 7 days following CIE. We extend these findings using LCM RNA-seq to profile expression in 11 brain regions in two inbred strains - C57BL/6J (B6) and DBA/2J (D2) - 72 h following multiple cycles of ethanol self-administration and CIE. Linear models identified differential expression based on treatment, region, strain, or interactions with treatment...
October 15, 2016: Alcohol
https://www.readbyqxmd.com/read/27885483/neuroborreliosis
#5
John J Halperin
Appropriate, critical application of evidence-based diagnostic criteria enables both a clear definition of what constitutes neuroborreliosis-nervous system infection with Borrelia burgdorferi sensu stricto in the US, B garinii and less commonly B. afzelii and other species in Europe-and recognition that this disorder is quite similar in Europe and the US. Most commonly evidenced by lymphocytic meningitis and/or multifocal inflammation of the peripheral (common; cranial neuropathy, radiculopathy, mononeuropathy multiplex) or central (rare) nervous system, it is readily diagnosed and highly antibiotic responsive...
November 24, 2016: Journal of Neurology
https://www.readbyqxmd.com/read/27872905/interferon-driven-deletion-of-antiviral-b-cells-at-the-onset-of-chronic-infection
#6
Benedict Fallet, Kerstin Narr, Yusuf I Ertuna, Melissa Remy, Rami Sommerstein, Karen Cornille, Mario Kreutzfeldt, Nicolas Page, Gert Zimmer, Florian Geier, Tobias Straub, Hanspeter Pircher, Kevin Larimore, Philip D Greenberg, Doron Merkler, Daniel D Pinschewer
Inadequate antibody responses and perturbed B cell compartments represent hallmarks of persistent microbial infections, but the mechanisms whereby persisting pathogens suppress humoral immunity remain poorly defined. Using adoptive transfer experiments in the context of a chronic lymphocytic choriomeningitis virus (LCMV) infection of mice, we have documented rapid depletion of virus-specific B cells that coincided with the early type I interferon response to infection. We found that the loss of activated B cells was driven by type I interferon (IFN-I) signaling to several cell types including dendritic cells, T cells and myeloid cells...
October 21, 2016: Science Immunology
https://www.readbyqxmd.com/read/27868108/inflammatory-monocytes-hinder-antiviral-b-cell-responses
#7
Stefano Sammicheli, Mirela Kuka, Pietro Di Lucia, Nereida Jimenez de Oya, Marco De Giovanni, Jessica Fioravanti, Claudia Cristofani, Carmela G Maganuco, Benedict Fallet, Lucia Ganzer, Laura Sironi, Marta Mainetti, Renato Ostuni, Kevin Larimore, Philip D Greenberg, Juan Carlos de la Torre, Luca G Guidotti, Matteo Iannacone
Antibodies are critical for protection against viral infections. However, several viruses, such as lymphocytic choriomeningitis virus (LCMV), avoid the induction of early protective antibody responses by poorly understood mechanisms. Here we analyzed the spatiotemporal dynamics of B cell activation to show that, upon subcutaneous infection, LCMV-specific B cells readily relocate to the interfollicular and T cell areas of the draining lymph node where they extensively interact with CD11b(+)Ly6C(hi) inflammatory monocytes...
October 21, 2016: Science Immunology
https://www.readbyqxmd.com/read/27864845/activity-of-the-anticonvulsant-lacosamide-in-experimental-and-human-epilepsy-via-selective-effects-on-slow-na-channel-inactivation
#8
Dominik Holtkamp, Thoralf Opitz, Isabelle Niespodziany, Christian Wolff, Heinz Beck
OBJECTIVE: In human epilepsy, pharmacoresistance to antiepileptic drug therapy is a major problem affecting ~30% of patients with epilepsy. Many classical antiepileptic drugs target voltage-gated sodium channels, and their potent activity in inhibiting high-frequency firing has been attributed to their strong use-dependent blocking action. In chronic epilepsy, a loss of use-dependent block has emerged as a potential cellular mechanism of pharmacoresistance for anticonvulsants acting on voltage-gated sodium channels...
November 19, 2016: Epilepsia
https://www.readbyqxmd.com/read/27861803/%C3%AE-4-%C3%AE-1-integrin-promotes-accumulation-of-tissue-resident-memory-cd8-t-cells-in-salivary-glands
#9
Sandra Woyciechowski, Maike Hofmann, Hanspeter Pircher
The salivary glands (SGs) of virus-immune mice contain substantial numbers of tissue-resident memory CD8(+) T cells (TRM cells) that can provide immunity to local infections. Integrins regulate entry of activated T cells into non-lymphoid tissues but the molecules that mediate migration of virus-specific CD8(+) T cells to the SGs have not yet been defined. Here, we found that polyinosinic-polycytidylic acid (poly(I:C)) strongly promoted the accumulation of P14 TCR-transgenic CD8(+) TRM cells in SGs in an α4 β1 integrin-dependent manner...
November 11, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27861537/modelling-and-simulation-of-the-dynamics-of-the-antigen-specific-t-cell-response-using-variable-structure-control-theory
#10
Anet J N Anelone, Sarah K Spurgeon
Experimental and mathematical studies in immunology have revealed that the dynamics of the programmed T cell response to vigorous infection can be conveniently modelled using a sigmoidal or a discontinuous immune response function. This paper hypothesizes strong synergies between this existing work and the dynamical behaviour of engineering systems with a variable structure control (VSC) law. These findings motivate the interpretation of the immune system as a variable structure control system. It is shown that dynamical properties as well as conditions to analytically assess the transition from health to disease can be developed for the specific T cell response from the theory of variable structure control...
2016: PloS One
https://www.readbyqxmd.com/read/27858316/clinical-outcomes-linked-to%C3%A2-expression%C3%A2-of-gene-subsets-for-protein-hormones-and-their-cognate-receptors-from-lcm-procured-breast%C3%A2-carcinoma-cells
#11
Michael W Daniels, Guy N Brock, James L Wittliff
PURPOSE: Certain peptide hormones and/or their cognate receptors influencing normal cellular pathways also have been detected in breast cancers. The hypothesis is that gene subsets of these regulatory molecules predict risk of breast carcinoma recurrence in patients with primary disease. METHODS: Gene expression levels of 61 hormones and 81 receptors were determined by microarray with LCM-procured carcinoma cells of 247 de-identified biopsies. Univariable and multivariable Cox regressions were determined using expression levels of each hormone/receptor gene, individually or as a pair...
November 17, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27855284/development-of-live-attenuated-arenavirus-vaccines-based-on-codon-deoptimization-of-the-viral-glycoprotein
#12
Benson Y H Cheng, Aitor Nogales, Juan Carlos de la Torre, Luis Martínez-Sobrido
Several arenaviruses, chiefly Lassa (LASV) in West Africa, cause hemorrhagic fever (HF) disease in humans and pose important public health problems in their endemic regions. To date, there are no FDA-approved arenavirus vaccines and current anti-arenaviral therapy is limited to the use of ribavirin that has very limited efficacy. In this work we document that a recombinant prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) with a codon deoptimized (CD) surface glycoprotein (GP), rLCMV/CD, exhibited wild type (WT)-like growth properties in cultured cells despite barely detectable GP expression levels in rLCMV/CD-infected cells...
November 14, 2016: Virology
https://www.readbyqxmd.com/read/27854111/the-risk-of-hypotension-and-seizures-in-patients-receiving-prophylactic-anti-epileptic-drugs-for-supratentorial-craniotomy
#13
Julius Höhne, Karl M Schebesch, Christian Ott, Alexander Brawanski, Max Lange
BACKGROUND: Perioperative seizure prophylaxis with antiepileptic drugs (AED) has been advocated in patients undergoing supratentorial craniotomy. The practice remains controversial. The reasoning presupposes that the possibility of an adverse drug reaction from the AED is lower than the probability of harm from a seizure. Even short periods of hypotension during the operation can lead to acute kidney and myocardial injury. We retrospectively evaluated cardiovascular effects and tolerability of Levetiracetam (LEV) alone, LEV and Lacosamid (LCM) as compared to Phenytoin (PHT)...
November 17, 2016: Journal of Neurosurgical Sciences
https://www.readbyqxmd.com/read/27852793/dampened-antiviral-immunity-to-intravaginal-exposure-to-rna-viral-pathogens-allows-enhanced-viral-replication
#14
Shahzada Khan, Erik M Woodruff, Martin Trapecar, Krystal A Fontaine, Ashley Ezaki, Timothy C Borbet, Melanie Ott, Shomyseh Sanjabi
Understanding the host immune response to vaginal exposure to RNA viruses is required to combat sexual transmission of this class of pathogens. In this study, using lymphocytic choriomeningitis virus (LCMV) and Zika virus (ZIKV) in wild-type mice, we show that these viruses replicate in the vaginal mucosa with minimal induction of antiviral interferon and inflammatory response, causing dampened innate-mediated control of viral replication and a failure to mature local antigen-presenting cells (APCs). Enhancement of innate-mediated inflammation in the vaginal mucosa rescues this phenotype and completely inhibits ZIKV replication...
November 16, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27851926/local-cellular-and-cytokine-cues-in-the-spleen-regulate-in-situ-t-cell-receptor-affinity-function-and-fate-of-cd8-t-cells
#15
Young-Jin Seo, Prithiviraj Jothikumar, Mehul S Suthar, Cheng Zhu, Arash Grakoui
T cells rapidly undergo contraction upon viral clearance, but how T cell function and fate are determined during this phase is unclear. During the contraction phase of an acute infection with lymphocytic choriomeningitis virus, we found that virus-specific CD8(+) T cells within the splenic red pulp (RP) had higher two-dimensional (2D) effective affinity than those within the white pulp (WP). This increased antigen recognition of RP-derived CD8(+) T cells correlated with more efficient target cell killing and improved control of viremia...
November 15, 2016: Immunity
https://www.readbyqxmd.com/read/27844464/the-safety-and-effectiveness-of-intravenous-lacosamide-for-refractory-status-epilepticus-in-the-critically-ill
#16
C R Newey, N M Le, C Ahrens, P Sahota, S Hantus
BACKGROUND: Status epilepticus (SE) often does not respond to initial treatment. A second-line agent with a less established safety and efficacy profile is then required. This study examined the safety of intravenous (IV) lacosamide (LCM) in a critically ill population and obtained an estimate of effectiveness in patients with refractory SE on continuous video EEG monitoring (cEEG). METHODS: Retrospective review of critically ill patients in SE on cEEG treated with IV LCM from June 2009 to April 2011...
November 14, 2016: Neurocritical Care
https://www.readbyqxmd.com/read/27835637/transcriptomic-variation-during-spermiogenesis-in-mouse-germ-cells
#17
Haiyang Zuo, Junfang Zhang, Liuguang Zhang, Xiaoxia Ren, Xiaoli Chen, Haisheng Hao, Xueming Zhao, Dong Wang
To explore variations in the transcription activity during spermiogenesis, round and elongated spermatids were collected from ICR/CD1 model mice using laser capture microdissection (LCM) and cauda epididymal sperm samples. The transcripts were sequenced using RNA-seq, and the reads were mapped to mm9. The majority of the reads (70%) in the round and elongated spermatids were mappable to known and predicted exons, but that in sperm was only 9%. The results of the distribution of reads suggested that alternative splicing was more complicated in sperm than in round and elongated spermatids...
2016: PloS One
https://www.readbyqxmd.com/read/27827906/t%C3%AE-riii-expression-in-human-breast-cancer-stroma-and-the-role-of-soluble-t%C3%AE-riii-in-breast-cancer-associated-fibroblasts
#18
Bojana Jovanović, Michael W Pickup, Anna Chytil, Agnieszka E Gorska, Kimberly C Johnson, Harold L Moses, Philip Owens
The TGF-β pathway plays a major role in tumor progression through regulation of epithelial and stromal cell signaling. Dysfunction of the pathway can lead to carcinoma progression and metastasis. To gain insight into the stromal role of the TGF-β pathway in breast cancer, we performed laser capture microdissection (LCM) from breast cancer patients and reduction mammoplasty patients. Microdissected tumor stroma and normal breast stroma were examined for gene expression. Expression of the TGF-β type III receptor (TGFBR3) was greatly decreased in the tumor stroma compared to control healthy breast tissue...
November 4, 2016: Cancers
https://www.readbyqxmd.com/read/27825696/a-pilot-study-exploring-the-molecular-architecture-of-the-tumor-microenvironment-in-human-prostate-cancer-using-laser-capture-microdissection-and-reverse-phase-protein-microarray
#19
Elisa Pin, Steven Stratton, Claudio Belluco, Lance Liotta, Ray Nagle, K Alex Hodge, Jianghong Deng, Ting Dong, Elisa Baldelli, Emanuel Petricoin, Mariaelena Pierobon
The cross-talk between tumor epithelium and surrounding stromal/immune microenvironment is essential to sustain tumor growth and progression and provides new opportunities for the development of targeted treatments focused on disrupting the tumor ecology. Identification of novel approaches to study these interactions is of primary importance. Using laser capture microdissection (LCM) coupled with reverse phase protein microarray (RPPA) based protein signaling activation mapping we explored the molecular interconnection between tumor epithelium and surrounding stromal microenvironment in 18 prostate cancer (PCa) specimens...
October 14, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27812556/type-i-interferon-suppresses-virus-specific-b-cell-responses-by-modulating-cd8-t-cell-differentiation
#20
E Ashley Moseman, Tuoqi Wu, Juan Carlos de la Torre, Pamela L Schwartzberg, Dorian B McGavern
Studies have established a role for T cells in resolving persistent viral infections, yet emerging evidence indicates that both T and B cells are required to control some viruses. During persistent infection, a marked lag or failure to generate neutralizing antibodies is commonly observed and likely contributes to an inability to control certain pathogens. Using lymphocytic choriomeningitis virus (LCMV) as a model, we have examined how a persistent viral infection can suppress neutralizing humoral immunity...
October 2016: Science Immunology
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