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https://www.readbyqxmd.com/read/28346043/structural-abnormalities-in-the-primary-somatosensory-cortex-and-a-normal-behavioral-profile-in-contactin-5-deficient-mice
#1
Kristel T E Kleijer, Denise van Nieuwenhuize, Henk A Spierenburg, Sara Gregorio-Jordan, Martien J H Kas, J Peter H Burbach
Contactin-5 (Cntn5) is an immunoglobulin cell adhesion molecule that is exclusively expressed in the central nervous system. In view of its association with neurodevelopmental disorders, particularly autism spectrum disorder (ASD), this study focused on Cntn5-positive areas in the forebrain and aimed to explore the morphological and behavioral phenotypes of the Cntn5 null mutant (Cntn5(-/-)) mouse in relation to these areas and ASD symptomatology. A newly generated antibody enabled us to elaborately describe the spatial expression pattern of Cntn5 in P7 wild type (Cntn5(+/+)) mice...
March 27, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28346009/reactions-with-antisera-and-pathological-effects-of-staphylococcus-aureus-gamma-toxin-in-the-cornea
#2
Michael A Bierdeman, Angela M Torres, Armando R Caballero, Aihua Tang, Richard J O'Callaghan
PURPOSE: This study analyzed the toxicity of purified gamma-toxin from Staphylococcus aureus and the protectiveness of antisera to gamma-toxin in the rabbit cornea. MATERIALS AND METHODS: Gamma-toxin was purified from cultures of alpha-toxin deficient S. aureus strain Newman Δhla. Antisera to native gamma-toxin (Hlg) were produced in rabbits. These antisera and a commercial polyclonal antibody to recombinant HlgB (rHlgB) were analyzed for specificity and toxin neutralization...
March 27, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28345289/severe-bleeding-diatheses-in-an-elderly-patient-with-combined-type-autoantibody-against-factor-xiii-a-subunit-novel-approach-to-the-diagnosis-and-classification-of-anti-factor-xiii-antibodies
#3
M Kun, N Szuber, É Katona, K Pénzes, A Bonnefoy, B Bécsi, F Erdődi, G E Rivard, L Muszbek
INTRODUCTION: Acquired factor XIII (FXIII) deficiency due to autoantibody is a rare, severe bleeding diathesis. Its laboratory diagnosis and classification represents a difficult task. AIM: Introduction of novel approaches into the diagnosis and characterization of anti-FXIII autoantibody and demonstration of their use in the diagnosis of a patient with autoimmune FXIII deficiency. METHODS: Factor XIII activity, FXIII antigen levels and the titre of anti-FXIII-A antibody were monitored throughout the course of the disease...
March 26, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28345287/contribution-of-platelet-p2y12-receptors-to-chronic-complete-freund-s-adjuvant-induced-inflammatory-pain
#4
K Bekő, B Koványi, F Gölöncsér, G Horváth, Á Dénes, Zs Környei, B Botz, Zs Helyes, C E Müller, B Sperlágh
BACKGROUND: P2Y12 receptor antagonists are widely used in clinical practice to inhibit platelet aggregation. P2Y12 receptors are also known to regulate different forms of pain as well as local and systemic inflammation. However it is not known if platelet P2Y12 receptors contribute to these effects. OBJECTIVES: In this study, we explored the contribution of platelet P2Y12 receptors to chronic inflammatory pain in mice. METHODS: Complete Freund's adjuvant (CFA)-induced chronic inflammatory pain was induced in wild-type and P2ry12 gene-deficient mice (P2ry12-/-), and the potent, direct-acting and reversible P2Y12 receptor antagonists, PSB-0739, and cangrelor were used...
March 27, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28345023/enhancement-of-psma-directed-car-adoptive-immunotherapy-by-pd-1-pd-l1-blockade
#5
Inna Serganova, Ekaterina Moroz, Ivan Cohen, Maxim Moroz, Mayuresh Mane, Juan Zurita, Larissa Shenker, Vladimir Ponomarev, Ronald Blasberg
Chimeric antigen receptor (CAR) T cell therapy in hematologic malignancies has shown remarkable responses, but the same level of success has not been observed in solid tumors. A new prostate cancer model (Myc-CaP:PSMA(+)) and a second-generation anti-hPSMA human CAR T cells expressing a Click Beetle Red luciferase reporter) were used to study hPSMA targeting and assess CAR T cell trafficking and persistence by bioluminescence imaging (BLI). We investigated the antitumor efficacy of human CAR T cells targeting human prostate-specific membrane antigen (hPSMA), in the presence and absence of the target antigen; first alone and then combined with a monoclonal antibody targeting the human programmed death receptor 1 (anti-hPD1 mAb)...
March 17, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28344998/low-dose-liver-targeted-gene-therapy-for-pompe-disease-enhances-therapeutic-efficacy-of-ert-via-immune-tolerance-induction
#6
Sang-Oh Han, Giuseppe Ronzitti, Benjamin Arnson, Christian Leborgne, Songtao Li, Federico Mingozzi, Dwight Koeberl
Pompe disease results from acid α-glucosidase (GAA) deficiency, and enzyme replacement therapy (ERT) with recombinant human (rh) GAA has clinical benefits, although its limitations include the short half-life of GAA and the formation of antibody responses. The present study compared the efficacy of ERT against gene transfer with an adeno-associated viral (AAV) vector containing a liver-specific promoter. GAA knockout (KO) mice were administered either a weekly injection of rhGAA (20 mg/kg) or a single injection of AAV2/8-LSPhGAA (8 × 10(11) vector genomes [vg]/kg)...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344878/targeting-cytokine-signaling-checkpoint-cis-activates-nk-cells-to-protect-from-tumor-initiation-and-metastasis
#7
Eva M Putz, Camille Guillerey, Kevin Kos, Kimberley Stannard, Kim Miles, Rebecca B Delconte, Kazuyoshi Takeda, Sandra E Nicholson, Nicholas D Huntington, Mark J Smyth
The cytokine-induced SH2-containing protein CIS belongs to the suppressor of cytokine signaling (SOCS) protein family. Here, we show the critical role of CIS in suppressing natural killer (NK) cell control of tumor initiation and metastasis. Cish-deficient mice were highly resistant to methylcholanthrene-induced sarcoma formation and protected from lung metastasis of B16F10 melanoma and RM-1 prostate carcinoma cells. In contrast, the growth of primary subcutaneous tumors, including those expressing the foreign antigen OVA, was unchanged in Cish-deficient mice...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344876/2b4-sap-signaling-is-required-for-the-priming-of-naive-cd8-t-cells-by-antigen-expressing-b-cells-and-b-lymphoma-cells
#8
Yu-Hsuan Huang, Kevin Tsai, Sara Y Tan, Sohyeong Kang, Mandy L Ford, Kenneth W Harder, John J Priatel
Mutations in SH2D1A gene that encodes SAP (SLAM-associated protein) result in X-linked lymphoproliferative disease (XLP), a rare primary immunodeficiency disease defined by exquisite sensitivity to the B-lymphotropic Epstein-Barr virus (EBV) and B cell lymphomas. However, the precise mechanism of how the loss of SAP function contributes to extreme vulnerability to EBV and the development of B cell lymphomas remains unclear. Here, we investigate the hypothesis that SAP is critical for CD8(+) T cell immune surveillance of antigen (Ag)-expressing B cells or B lymphoma cells under conditions of defined T cell receptor (TCR) signaling...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28341640/impaired-b-cell-function-during-viral-infections-due-to-pten-mediated-inhibition-of-the-pi3k-pathway
#9
Andrew Getahun, Scott M Wemlinger, Pratyaydipta Rudra, Mario L Santiago, Linda F van Dyk, John C Cambier
Transient suppression of B cell function often accompanies acute viral infection. However, the molecular signaling circuitry that enforces this hyporesponsiveness is undefined. In this study, experiments identify up-regulation of the inositol phosphatase PTEN (phosphatase and tensin homolog) as primarily responsible for defects in B lymphocyte migration and antibody responses that accompany acute viral infection. B cells from mice acutely infected with gammaherpesvirus 68 are defective in BCR- and CXCR4-mediated activation of the PI3K pathway, and this, we show, is associated with increased PTEN expression...
March 24, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28341440/optimization-and-testing-of-dried-antibody-tube-the-euroflow-lst-and-pidot-tubes-as-examples
#10
V H J van der Velden, J Flores-Montero, Martin Perez, Marta Martin-Ayuso, Oliver Crespo, Elena Blanco, Tomas Kalina, Jan Philippé, Carolien Bonroy, Maaike de Bie, Jeroen Te Marvelde, Cristina Teodosio, Alba Corral Mateos, Veronika Kanderová, Mirjam van der Burg, Dennis Van Hoof, Jacques J M van Dongen, Alberto Orfao
Within EuroFlow, we recently developed screening tubes for hematological malignancies and immune deficiencies. Pipetting of antibodies for such 8-color 12-marker tubes however is time-consuming and prone to operational mistakes. We therefore evaluated dried formats of the lymphocytosis screening tube (LST) and of the primary immune deficiency orientation tube (PIDOT). Both tubes were evaluated on normal and/or on patient samples, comparing the mean fluorescence intensity of specific lymphocyte populations. Our data show that the dried tubes and liquid counterparts give highly comparable staining results, particularly when analyzed in multidimensional plots...
March 21, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28337237/relationship-between-helicobacter-pylori-infection-and-celiac-disease-a-cross-sectional-study-and-a-brief-review-of-the-literature
#11
Sebahat Basyigit, Oktay Unsal, Metin Uzman, Ferdane Sapmaz, Ozlem Ceylan Dogan, Ayse Kefeli, Zeliha Asilturk, Abdullah Ozgur Yeniova, Yasar Nazligul
INTRODUCTION: Whether Helicobacter pylori triggers celiac disease (CD) or protects against CD is currently the subject of research. In the literature, there are epidemiologic studies that have reported conflicting results regarding the association between H. pylori and CD. AIM: To compare the prevalence of CD autoantibody positivity and the levels of CD autoantibodies between H. pylori-positive and H. pylori-negative subjects. MATERIAL AND METHODS: This study was prospectively designed and included 240 dyspeptic patients who underwent upper gastrointestinal endoscopy with gastric and duodenal biopsies...
2017: Przegla̜d Gastroenterologiczny
https://www.readbyqxmd.com/read/28335329/nanoparticle-based-delivery-of-anaplasma-marginale-membrane-proteins-virb9-1-and-virb10-produced-in-the-pichia-pastoris-expression-system
#12
Bing Zhang, Antonio S Cavallaro, Karishma T Mody, Jun Zhang, James R Deringer, Wendy C Brown, Timothy J Mahony, Chengzhong Yu, Neena Mitter
Bovine anaplasmosis or cattle-tick fever is a tick-borne haemolytic disease caused by the rickettsial haemoparasite Anaplasma marginale in tropical and subtropical areas of the world. While difficult to express, the proteins VirB9-1 and VirB10 are immunogenic components of the outer membrane type IV secretion system that have been identified as candidate antigens for vaccines targeting of A. marginale. Soluble VirB9-1 and VirB10 were successfully expressed using Pichia pastoris. When formulated with the self-adjuvanting silica vesicles, SV-100 (diameter: 50 nm, and pore entrance size: 6 nm), 200 µg of VirB9-1 and VirB10 were adsorbed per milligram of nanoparticle...
November 5, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28334791/isolated-acth-deficiency-probably-induced-by-autoimmune-related-mechanism-evoked-with-nivolumab
#13
Keiko Kitajima, Kenji Ashida, Naoko Wada, Ryoko Suetsugu, Yukina Takeichi, Shohei Sakamoto, Hiroshi Uchi, Takamitsu Matsushima, Motoaki Shiratsuchi, Keizo Ohnaka, Masutaka Furue, Masatoshi Nomura
Nivolumab, an anti-programmed death-1 antibody, is a breakthrough treatment for several malignancies. Its specific adverse effects caused by autoimmunity are termed immune-related adverse events, which involve several endocrine dysfunctions. Herein, we report two cases of isolated adrenocorticotropic hormone (ACTH) deficiency induced by nivolumab for the treatment of metastatic malignant melanoma. Case 1 was a 39-year-old man and Case 2 was a 50-year-old woman, both of whom presented with progressive melanoma...
February 18, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28330983/gamma-delta-t-cells-mediate-angiotensin-ii-induced-hypertension-and-vascular-injury
#14
Antoine Caillon, Muhammad Oneeb Rehman Mian, Julio C Fraulob-Aquino, Ku-Geng Huo, Tlili Barhoumi, Sofiane Ouerd, Peter R Sinnaeve, Pierre Paradis, Ernesto L Schiffrin
Background -Innate antigen-presenting cells and adaptive immune T cells have been implicated in the development of hypertension. However, the T-lymphocyte subsets involved in the pathophysiology of hypertension remain unclear. A small subset of "innate-like" T cells expressing the γδ T cell receptor (TCR) rather than the αβ TCR could play a role in the initiation of the immune response in hypertension. We aimed to determine whether angiotensin (Ang) II caused kinetic changes in γδ T cells, whether deficiency in γδ T cells blunted Ang II-induced hypertension, vascular injury and T-cell activation, and whether γδ T cells are associated with human hypertension...
March 22, 2017: Circulation
https://www.readbyqxmd.com/read/28330862/when-tlrs-fail-igg-has-your-back
#15
Tiffany C Scharschmidt
Inherited TIRAP deficiency confers susceptibility to staphylococcal disease via impaired TLR2 and TLR4 responses, which can be rescued by bacteria-specific antibodies.
March 22, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28330461/impaired-liver-regeneration-is-associated-with-reduced-cyclin-b1-in-natural-killer-t-cell-deficient-mice
#16
Ami Ben Ya'acov, Hadar Meir, Lydia Zolotaryova, Yaron Ilan, Eyal Shteyer
BACKGROUND: It has been shown that the proportion of natural killer T cells is markedly elevated during liver regeneration and their activation under different conditions can modulate this process. As natural killer T cells and liver injury are central in liver regeneration, elucidating their role is important. METHODS: The aim of the current study is to explore the role of natural killer T cells in impaired liver regeneration. Concanvalin A was injected 4 days before partial hepatectomy to natural killer T cells- deficient mice or to anti CD1d1-treated mice...
March 23, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28329908/re-evaluating-the-roles-of-myosin-18a%C3%AE-and-f-actin-in-determining-golgi-morphology
#17
Kyle Bruun, Jordan R Beach, Sarah M Heissler, Kirsten Remmert, James R Sellers, John A Hammer
The peri-centrosomal localization and morphology of the Golgi apparatus depends largely on the microtubule cytoskeleton and the microtubule motor protein dynein. Recent studies proposed that myosin 18Aα (M18Aα) also contributes to Golgi morphology by binding the Golgi protein GOLPH3 and walking along adjacent actin filaments to stretch the Golgi into its classic ribbon structure. Biochemical analyses have shown, however, that M18A is not an actin-activated ATPase and lacks motor activity. Our goal, therefore, was to define the precise molecular mechanism by which M18Aα determines Golgi morphology...
March 22, 2017: Cytoskeleton
https://www.readbyqxmd.com/read/28328326/interleukin-12-and-interleukin-23-blockade-in-leukocyte-adhesion-deficiency-type-1
#18
Niki M Moutsopoulos, Christa S Zerbe, Teresa Wild, Nicolas Dutzan, Laurie Brenchley, Giovanni DiPasquale, Gulbu Uzel, Karen C Axelrod, Andrea Lisco, Lucia D Notarangelo, George Hajishengallis, Luigi D Notarangelo, Steven M Holland
A patient with leukocyte adhesion deficiency type 1 (LAD1) had severe periodontitis and an intractable, deep, nonhealing sacral wound. We had previously found a dominant interleukin-23-interleukin-17 signature at inflamed sites in humans with LAD1 and in mouse models of the disorder. Blockade of this pathway in mouse models has resulted in resolution of the immunopathologic condition. We treated our patient with ustekinumab, an antibody that binds the p40 subunit of interleukin-23 and interleukin-12 and thereby blocks the activity of these cytokines, inhibiting interleukin-23-dependent production of interleukin-17...
March 23, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28326060/microbial-neuraminidase-induces-a-moderate-and-transient-myelin-vacuolation-independent-of-complement-system-activation
#19
Pablo Granados-Durán, María Dolores López-Ávalos, Manuel Cifuentes, Margarita Pérez-Martín, María Del Mar Fernández-Arjona, Timothy R Hughes, Krista Johnson, B Paul Morgan, Pedro Fernández-Llebrez, Jesús M Grondona
AIMS: Some central nervous system pathogens express neuraminidase (NA) on their surfaces. In the rat brain, a single intracerebroventricular (ICV) injection of NA induces myelin vacuolation in axonal tracts. Here, we explore the nature, the time course, and the role of the complement system in this damage. METHODS: The spatiotemporal analysis of myelin vacuolation was performed by optical and electron microscopy. Myelin basic protein-positive area and oligodendrocyte transcription factor (Olig2)-positive cells were quantified in the damaged bundles...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28323124/cd44-is-a-key-player-in-non-alcoholic-steatohepatitis
#20
Stéphanie Patouraux, Déborah Rousseau, Stéphanie Bonnafous, Cynthia Lebeaupin, Carmelo Luci, Clémence M Canivet, Anne-Sophie Schneck, Adeline Bertola, Marie-Christine Saint-Paul, Antonio Iannelli, Jean Gugenheim, Rodolphe Anty, Albert Tran, Béatrice Bailly-Maitre, Philippe Gual
BACKGROUND: CD44 is expressed on many immune cells that contribute to inflammation. It has been shown, mainly through animal data, that CD44 regulates adipose tissue inflammation in obesity and hepatic leukocyte recruitment in a lithogenic context. However, its role in hepatic inflammation in a mouse model of steatohepatitis and its relevance in humans have not yet been investigated. METHODS: The role of CD44 was evaluated in CD44-/- mice and after injections of an αCD44 antibody in Wild-type mice challenged with a methionine- and choline-deficient diet (MCDD)...
March 16, 2017: Journal of Hepatology
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