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https://www.readbyqxmd.com/read/28087150/apelin-protects-against-nmda-induced-retinal-neuronal-death-via-an-apj-receptor-by-activating-akt-and-erk1-2-and-suppressing-tnf-%C3%AE-expression-in-mice
#1
Yuki Ishimaru, Akihide Sumino, Daiki Kajioka, Fumiya Shibagaki, Akiko Yamamuro, Yasuhiro Yoshioka, Sadaaki Maeda
Glutamate excitotoxicity mediated by N-methyl-d-aspartate (NMDA) receptors is an important cause of retinal ganglion cell death in glaucoma. To elucidate whether apelin protects against retinal neuronal cell death, we examined protective effects of exogenous and endogenous apelin on neuronal cell death induced by intravitreal injection of NMDA in the retinas of mice. An intravitreal injection of NMDA induced neuronal cell death in both the retinal ganglion cell layer and inner nuclear layer, and reduced the amplitudes of scotopic threshold response (STR) in electroretinography studies...
December 24, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28086930/mannose-binding-lectin-associated-serine-protease-2-masp-2-contributes-to-poor-disease-outcome-in-humans-and-mice-with-pneumococcal-meningitis
#2
E Soemirien Kasanmoentalib, Mercedes Valls Seron, Bart Ferwerda, Michael W Tanck, Aeilko H Zwinderman, Frank Baas, Arie van der Ende, Matthijs C Brouwer, Diederik van de Beek
BACKGROUND: Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the pro-inflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. METHODS: We investigated mannose-binding lectin-associated serine protease (MASP-2) levels in cerebrospinal fluid (CSF) samples derived from the diagnostic lumbar puncture, which was available for 307 of 792 pneumococcal meningitis episodes included in our prospective nationwide cohort study (39%), and the association between these levels and clinical outcome...
January 3, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28079912/intravenous-immunoglobulin-in-the-treatment-of-primary-immunodeficiency-diseases
#3
Deirdre De Ranieri, Nana Sarkoah Fenny
Intravenous immunoglobulin (IVIG) has been used as antibody replacement therapy in primary immunodeficiency diseases (PIDDs) for more than 50 years. Its role as a therapeutic agent has expanded over the past couple of decades as its anti-inflammatory and immune-modulatory mechanisms of action have been elucidated. It is now used "off-label" to treat other autoimmune diseases. This article focuses on the role of IVIG in the treatment of PIDDs characterized by absent or deficient antibody production. Replacement doses are given on a monthly basis in these conditions as a prophylactic measure to prevent acute and serious bacterial infections...
January 1, 2017: Pediatric Annals
https://www.readbyqxmd.com/read/28079608/mortality-and-differential-diagnoses-of-villous-atrophy-without-coeliac-antibodies
#4
Annalisa Schiepatti, Federico Biagi, Giacomo Fraternale, Claudia Vattiato, Davide Balduzzi, Simona Agazzi, Claudia Alpini, Catherine Klersy, Gino R Corazza
OBJECTIVE: Villous atrophy (VA) of the small bowel is mainly related to coeliac disease (CD), whose diagnosis is made on the basis of positive endomysial/tissue transglutaminase antibodies while on a gluten-containing diet in the vast majority of patients. However, VA can also occur in other conditions whose epidemiology is little known. Our aim was to study the epidemiology and clinical features of these rare enteropathies. PATIENTS AND METHODS: Clinical and laboratory data of all the patients with VA directly diagnosed in our centre in the last 15 years were collected and statistically analysed...
January 11, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28079521/isoform-specific-subcellular-localization-and-function-of-protein-kinase-a-identified-by-mosaic-imaging-of-mouse-brain
#5
Ronit Ilouz, Varda Lev-Ram, Eric A Bushong, Travis L Stiles, Dinorah Friedmann-Morvinski, Christopher Douglas, Geoffrey Goldberg, Mark H Ellisman, Susan S Taylor
Protein kinase A (PKA) plays critical roles in neuronal function that are mediated by different regulatory (R) subunits. Deficiency in either RIβ or RIIβ subunits results in distinct neuronal phenotypes. Although RIβ contributes to synaptic plasticity, it is the least studied isoform. Using isoform-specific antibodies we generated high-resolution large-scale immunohistochemical mosaic images of mouse brain that provide global views of several brain regions, including the hippocampus and cerebellum...
January 12, 2017: ELife
https://www.readbyqxmd.com/read/28077463/novel-method-for-detection-of-glycogen-in-cells
#6
Alexander V Skurat, Dyann Segvich, Anna A DePaoli-Roach, Peter J Roach
Glycogen, a branched polymer of glucose, functions as an energy reserve in many living organisms. Abnormalities in glycogen metabolism, usually excessive accumulation, can be caused genetically, most often through mutation of the enzymes directly involved in synthesis and degradation of the polymer leading to a variety of glycogen storage diseases (GSDs). Microscopic visualization of glycogen deposits in cells and tissues is important for the study of normal glycogen metabolism as well as diagnosis of GSDs...
January 10, 2017: Glycobiology
https://www.readbyqxmd.com/read/28073916/ceramide-cd300f-binding-inhibits-lipopolysaccharide-induced-skin-inflammation
#7
Emiko Shiba, Kumi Izawa, Ayako Kaitani, Masamichi Isobe, Akie Maehara, Koichiro Uchida, Keiko Maeda, Nobuhiro Nakano, Hideoki Ogawa, Ko Okumura, Toshio Kitamura, Toshiaki Shimizu, Jiro Kitaura
Lipopolysaccharide (LPS) triggers inflammatory responses; however, the negative regulation of LPS responses in vivo remains poorly understood. CD300f is an inhibitory receptor among the CD300 family of paired activating and inhibitory receptors. We have previously identified ceramide as a ligand for CD300f and shown that the binding of ceramide to CD300f inhibits IgE-mediated mast cell activation and allergic responses in mouse models. Here we identify the critical role of CD300f in inhibiting LPS-induced skin inflammation...
January 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28070764/serum-25-oh-vitamin-d-levels-in-systemic-sclerosis-analysis-of-140-patients-and-review-of-the-literature
#8
Dilia Giuggioli, M Colaci, G Cassone, P Fallahi, F Lumetti, A Spinella, F Campomori, A Manfredi, C U Manzini, A Antonelli, C Ferri
Hypovitaminosis D is increasingly reported in autoimmune diseases. We investigated the 25-OH-vitamin D (25-OH-vitD) levels in systemic sclerosis (SSc) patients, in correlation with disease's features. We measured the 25-OH-vitD serum levels in 140 consecutive patients (F/M 126/15; mean age 61 ± 15.1 years), 91 without (group A) and 49 with (group B) 25-OH-cholecalciferol supplementation. Patients of group A invariably showed low 25-OH-vitD levels (9.8 ± 4.1 ng/ml vs. 26 ± 8.1 ng/ml of group B); in particular, 88/91 (97%) patients showed vitamin D deficiency (<20 ng/ml), with very low vitamin D levels (<10 ng/ml) in 40 (44%) subjects...
January 9, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28070732/the-clinical-and-laboratory-spectrum-of-dedicator-of-cytokinesis-8-immunodeficiency-syndrome-in-patients-with-a-unique-mutation
#9
Arnon Broides, Amarilla B Mandola, Jacov Levy, Baruch Yerushalmi, Vered Pinsk, Michal Eldan, George Shubinsky, Nurit Hadad, Rachel Levy, Amit Nahum, Miriam Ben-Harosh, Atar Lev, Amos Simon, Raz Somech
Mutations in the dedicator of cytokinesis 8 (DOCK8) gene cause a combined immunodeficiency usually diagnosed as autosomal recessive hyper IgE syndrome. We sought to reveal the varying manifestations in patients with a unique mutation in DOCK8 gene by a retrospective medical record review. Ten patients from five consanguineous families and three tribes were included. Seven patients were homozygous for the c.C5134A, p.S1711X mutation, and the remaining three patients were their siblings manifesting hyper IgE syndrome features without a genetic diagnosis...
January 10, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28070718/first-in-human-trial-of-an-anti-5t4-antibody-monomethylauristatin-conjugate-pf-06263507-in-patients-with-advanced-solid-tumors
#10
Geoffrey I Shapiro, Ulka N Vaishampayan, Patricia LoRusso, Jeremy Barton, Steven Hua, Steven D Reich, Ronald Shazer, Carrie T Taylor, Dawei Xuan, Hossein Borghaei
Background The antibody-drug conjugate PF-06263507 targets the cell-surface, tumor-associated antigen 5T4 and consists of a humanized IgG1 conjugated to the microtubule-disrupting agent monomethylauristatin-F by a non-cleavable maleimidocaproyl linker. In this first-in-human, dose-finding trial (NCT01891669), we evaluated safety, pharmacokinetics, and preliminary antitumor activity of PF-06263507 in pretreated patients with advanced solid tumors, unselected for 5T4 expression. starting at 0.05 mg/kg, with 25, 56, and 95% dose increments, depending on observed dose-limiting toxicities (DLTs), applying a modified continual reassessment method...
January 9, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28069388/vitamin-d-receptor-deficit-induces-activation-of-renin-angiotensin-system-via-sirt1-modulation-in-podocytes
#11
Nirupama Chandel, Kamesh Ayosolla, Hongxiu Wen, Xiqian Lan, Shabirul Haque, Moin A Saleem, Ashwani Malhotra, Pravin C Singhal
Vitamin D receptor (VDR) deficient status has been shown to be associated with the activation of renin angiotensin system (RAS). We hypothesized that lack of VDR would enhance p53 expression in podocytes through down regulation of SIRT1; the former would enhance the transcription of angiotensinogen (Agt) and angiotensinogen II type 1 receptor (AT1R) leading to the activation of RAS. Renal tissues of VDR mutant (M) mice displayed increased expression of p53, Agt, renin, and AT1R. In vitro studies, VDR knockout podocytes not only displayed up regulation p53 but also displayed enhanced expression of Agt, renin and AT1R...
January 6, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28068853/chronic-lung-disease-in-common-variable-immune-deficiency-cvid-a-pathophysiological-role-for-microbial-and-non-b-cell-immune-factors
#12
Denver Mooney, David Edgar, Gisli Einarsson, Damian Downey, Stuart Elborn, Michael Tunney
One of the most common and most severe forms of primary antibody deficiency encountered in the clinical setting is a heterogeneous group of syndromes termed common variable immune deficiency (CVID). This disorder is characterized by reduced immunoglobulin production and increased susceptibility to infection, particularly of the respiratory tract. Infection and subsequent immunological/inflammatory processes may contribute to the development of pulmonary complications such as bronchiectasis and interstitial lung disease...
January 10, 2017: Critical Reviews in Microbiology
https://www.readbyqxmd.com/read/28068342/neuropathogenesis-of-zika-virus-in-a-highly-susceptible-immunocompetent-mouse-model-after-antibody-blockade-of-type-i-interferon
#13
Darci R Smith, Bradley Hollidge, Sharon Daye, Xiankun Zeng, Candace Blancett, Kyle Kuszpit, Thomas Bocan, Jeff W Koehler, Susan Coyne, Tim Minogue, Tara Kenny, Xiaoli Chi, Soojin Yim, Lynn Miller, Connie Schmaljohn, Sina Bavari, Joseph W Golden
Animal models are needed to better understand the pathogenic mechanisms of Zika virus (ZIKV) and to evaluate candidate medical countermeasures. Adult mice infected with ZIKV develop a transient viremia, but do not demonstrate signs of morbidity or mortality. Mice deficient in type I or a combination of type I and type II interferon (IFN) responses are highly susceptible to ZIKV infection; however, the absence of a competent immune system limits their usefulness for studying medical countermeasures. Here we employ a murine model for ZIKV using wild-type C57BL/6 mice treated with an antibody to disrupt type I IFN signaling to study ZIKV pathogenesis...
January 9, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28068286/pathobiochemical-mechanisms-relating-iron-homeostasis-to-parameters-of-inflammatory-activity-and-autoimmune-disorders-in-rheumatoid-arthritis
#14
Katya I Stefanova, Ginka T Delcheva, Ana I Maneva, Anastas Z Batalov, Mariela G Geneva-Popova, Rositza V Karalilova, Kiril K Simitchiev
AIM: To find the correlations between the parameters of iron homeostasis, inflammatory activity and autoimmune disorders in rheumatoid arthritis (RA). MATERIALS AND METHODS: The present study included 114 patients with RA and 42 healthy controls. We determined the parameters of iron homeostasis: serum iron, total iron binding capacity (TIBC), ferritin and soluble transferrin receptor (sTfR), the parameters of inflammatory activity: C-reactive protein (CRP), interleukin-6 (IL-6) and prohepcidin, and the parameters of autoimmune disorders: rheumatoid factor (RF), anti-cyclic citrullinated peptide (antiCCP) antibodies, and DAS 28...
December 1, 2016: Folia Medica
https://www.readbyqxmd.com/read/28067796/combined-effects-of-androgen-and-growth-hormone-on-osteoblast-marker-expression-in-mouse-c2c12-and-mc3t3-e1-cells-induced-by-bone-morphogenetic-protein
#15
Kosuke Kimura, Tomohiro Terasaka, Nahoko Iwata, Takayuki Katsuyama, Motoshi Komatsubara, Ryota Nagao, Kenichi Inagaki, Fumio Otsuka
Osteoblasts undergo differentiation in response to various factors, including growth factors and steroids. Bone mass is diminished in androgen- and/or growth hormone (GH)-deficient patients. However the functional relationship between androgen and GH, and their combined effects on bone metabolism, remains unclear. Here we investigated the mutual effects of androgen and GH on osteoblastic marker expression using mouse myoblastic C2C12 and osteoblast-like MC3T3-E1 cells. Combined treatment with dihydrotestosterone (DHT) and GH enhanced BMP-2-induced expression of Runx2, ALP, and osteocalcin mRNA, compared with the individual treatments in C2C12 cells...
January 5, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28065678/construction-and-validation-of-a-novel-disease-specific-quality-of-life-instrument-for-patients-with-primary-antibody-deficiency-disease-padqol-16
#16
Mark Ballow, Mark R Conaway, Panida Sriaroon, Rima A Rachid, Filiz O Seeborg, Carla M Duff, Francisco A Bonilla, M Elizabeth M Younger, Ralph Shapiro, Ted M Burns
A disease-specific Health-related Quality of Life survey was developed for adult patients with antibody immune deficiency disorders as a tool (PADQOL-16) for assessing a patient's QOL issues and their relation to clinical status.
January 5, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28062921/targeted-deletion-of-traf2-allows-immunosuppression-free-islet-allograft-survival-in-mice
#17
Jeanette E Villanueva, Stacey N Walters, Mitsuru Saito, Elisabeth K Malle, Nathan W Zammit, Katherine A Watson, Robert Brink, Nicole L La Gruta, Stephen I Alexander, Shane T Grey
AIMS/HYPOTHESIS: Administration of anti-CD40 ligand (CD40L) antibodies has been reported to allow long-term islet allograft survival in non-human primates without the need for exogenous immunosuppression. However, the use of anti-CD40L antibodies was associated with thromboembolic complications. Targeting downstream intracellular components shared between CD40 and other TNF family co-stimulatory molecules could bypass these complications. TNF receptor associated factor 2 (TRAF2) integrates multiple TNF receptor family signalling pathways that are critical for T cell activation and may be a central node of alloimmune responses...
January 6, 2017: Diabetologia
https://www.readbyqxmd.com/read/28061955/the-role-of-cd30-and-cd153-cd30l-in-the-anti-mycobacterial-immune-response
#18
REVIEW
Nancy D Marín, Luis F García
The establishment of a protective T-cell response against mycobacterial infections involves different co-stimulatory molecules and their respective ligands. Among these molecules the Tumor Necrosis Factor Receptor Super-family (TNFRSF) and the Tumor Necrosis Factor Super-family (TNFSF) are known to be important members. This review analyzes the evidence that CD30 and CD153 (CD30L), members of the TNFRSF and TNSF, play key roles in the T cell-dependent anti-mycobacterial immune response. Mice deficient in either CD30 or CD153, or treated with antibodies blocking the effects or CD30 and CD153, and infected with M...
January 2017: Tuberculosis
https://www.readbyqxmd.com/read/28060909/long-term-depletion-of-conventional-dendritic-cells-cannot-be-maintained-in-an-atherosclerotic-zbtb46-dtr-mouse-model
#19
Miche Rombouts, Nathalie Cools, Mandy O J Grootaert, Flore de Bakker, Ilse Van Brussel, An Wouters, Guido R Y De Meyer, Benedicte Y De Winter, Dorien M Schrijvers
BACKGROUND AND AIMS: Increased evidence suggests a pro-atherogenic role for conventional dendritic cells (cDC). However, due to the lack of an exclusive marker for cDC, their exact contribution to atherosclerosis remains elusive. Recently, a unique transcription factor was described for cDC, namely Zbtb46, enabling us to selectively target this cell type in mice. METHODS: Low-density lipoprotein receptor-deficient (Ldlr-/-) mice were transplanted with bone marrow from Zbtb46-diphtheria toxin receptor (DTR) transgenic mice following total body irradiation...
2017: PloS One
https://www.readbyqxmd.com/read/28057924/tyrosine-kinase-c-abl-regulates-the-survival-of-plasma-cells
#20
Yan-Feng Li, Shengli Xu, Yuhan Huang, Xijun Ou, Kong-Peng Lam
Tyrosine kinase c-Abl plays an important role in early B cell development. Its deletion leads to reduced pro- and pre-B cell generation in mice. However, its function in B cell terminal differentiation remains unexplored. Here, we used c-Abl(f/f) Aicda(cre/+) mice, in which c-Abl is ablated only in antigen-activated B cells, to study the role of c-Abl in germinal center (GC) B and antibody-secreting plasma cell formation. Upon challenge with a model antigen, we found normal GC and memory B but reduced plasma cells and antigen-specific antibody response in the mutant mice...
January 6, 2017: Scientific Reports
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