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https://www.readbyqxmd.com/read/28919990/pharmacological-targeting-of-peptidylarginine-deiminase-4-prevents-cancer-associated-kidney-injury-in-mice
#1
Jessica Cedervall, Anca Dragomir, Falk Saupe, Yanyu Zhang, Johan Ärnlöv, Erik Larsson, Anna Dimberg, Anders Larsson, Anna-Karin Olsson
Renal insufficiency is a frequent cancer-associated problem affecting more than half of all cancer patients at the time of diagnosis. To minimize nephrotoxic effects the dosage of anticancer drugs are reduced in these patients, leading to sub-optimal treatment efficacy. Despite the severity of this cancer-associated pathology, the molecular mechanisms, as well as therapeutic options, are still largely lacking. We here show that formation of intravascular tumor-induced neutrophil extracellular traps (NETs) is a cause of kidney injury in tumor-bearing mice...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28899799/neutrophil-extracellular-traps-nets-in-autoimmune-diseases-a-comprehensive-review
#2
REVIEW
Keum Hwa Lee, Andreas Kronbichler, David Duck-Young Park, YoungMin Park, Hanwool Moon, Hyungdo Kim, Jun Hyug Choi, YoungSeo Choi, Songjoo Shim, Il Suk Lyu, Byung Hwan Yun, Yeonseung Han, Donghee Lee, Sang Yoon Lee, Byung Hun Yoo, Kyung Hwan Lee, Tai Lim Kim, Heonki Kim, Joo Sung Shim, Wonseok Nam, Heesung So, SooYeon Choi, Sangmok Lee, Jae Il Shin
The structures named neutrophil extracellular traps (NETs) are fibrous networks which protrude from the membrane of activated neutrophils. NETs are found in a variety of conditions, such as infection, malignancy, atherosclerosis, and autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), psoriasis, and gout. The impact of NETs on the development mechanisms of autoimmune diseases are proposed to arise from an imbalance between "NETosis" which is a process of NET formation and NET degradation...
September 9, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28863790/anca-associated-vasculitis-pathogenesis-models-and-preclinical-testing
#3
REVIEW
Holly L Hutton, Stephen R Holdsworth, A Richard Kitching
Our understanding of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis has developed greatly since the discovery of ANCA, directed against neutrophil components, in 1982. Observations in human disease, and increasingly sophisticated studies in vitro and in rodent models in vivo, have allowed a nuanced understanding of many aspects of the immunopathogenesis of disease, including the significance of ANCA as a diagnostic and monitoring tool as well as a mediator of microvascular injury. The mechanisms of leukocyte recruitment and tissue injury, and the role of T cells increasingly are understood...
September 2017: Seminars in Nephrology
https://www.readbyqxmd.com/read/28852481/infectious-complications-of-rituximab-therapy-in-renal-disease
#4
Andrew Nixon, Leanne Ogden, Alexander Woywodt, Ajay Dhaygude
Rituximab, an anti-CD20 monoclonal antibody, was originally used to treat B-cell malignancies. Its use has significantly increased in recent years, as it is now also used to treat a variety of autoimmune diseases including rheumatoid arthritis and ANCA-associated vasculitis (AAV). Initial studies suggested that the adverse effects of rituximab were minimal. Though the risk of malignancy with rituximab-based immunosuppressive regimens appears similar to that of the general population, there are now concerns regarding the risk of infectious complications...
August 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/28829051/dopamine-transporter-and-reward-anticipation-in-a-dimensional-perspective-a-multimodal-brain-imaging-study
#5
Manon Dubol, Christian Trichard, Claire Leroy, Anca-Larisa Sandu, Mehdi Rahim, Bernard Granger, Eleni T Tzavara, Laurent Karila, Jean-Luc Martinot, Eric Artiges
Dopamine function and reward processing are highly interrelated and involve common brain regions afferent to the Nucleus Accumbens, within the mesolimbic pathway. While dopamine function and reward system neural activity are impaired in most psychiatric disorders, it is unknown if alterations in the dopamine system underlie variations in reward processing across a continuum encompassing health and these disorders. We explored the relationship between dopamine function and neural activity during reward anticipation in twenty-seven participants including healthy volunteers and psychiatric patients with schizophrenia, depression or cocaine addiction, using functional Magnetic Resonance Imaging (fMRI) and Positron Emission Tomography (PET) multimodal imaging with a voxel-based statistical approach...
August 22, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28807980/cd177-modulates-human-neutrophil-migration-through-activation-mediated-integrin-and-chemoreceptor-regulation
#6
Ming Bai, Ricardo Grieshaber-Bouyer, Junxia Wang, Angela B Schmider, Zachary S Wilson, Liling Zeng, Olha Halyabar, Matthew D Godin, Hung N Nguyen, Anaïs Levescot, Pierre Cunin, Craig T Lefort, Roy J Soberman, Peter A Nigrovic
CD177 is a GPI-anchored protein expressed by a variable proportion of human neutrophils that mediates surface expression of the anti-neutrophil cytoplasmic antibody (ANCA) antigen proteinase 3. CD177 associates with β2 integrins and recognizes PECAM-1, suggesting a role in neutrophil migration. However, CD177(pos) neutrophils exhibit no clear migratory advantage in vivo, despite interruption of transendothelial migration by in vitro CD177 ligation. We sought to understand this paradox. Using a PECAM-1-independent transwell system, we found that CD177(pos) and CD177(neg) neutrophils migrated comparably...
August 14, 2017: Blood
https://www.readbyqxmd.com/read/28790376/global-and-local-excitation-and-inhibition-shape-the-dynamics-of-the-cortico-striatal-thalamo-cortical-pathway
#7
Anca Rădulescu, Joanna Herron, Caitlin Kennedy, Annalisa Scimemi
The cortico-striatal-thalamo-cortical (CSTC) pathway is a brain circuit that controls movement execution, habit formation and reward. Hyperactivity in the CSTC pathway is involved in obsessive compulsive disorder (OCD), a neuropsychiatric disorder characterized by the execution of repetitive involuntary movements. The striatum shapes the activity of the CSTC pathway through the coordinated activation of two classes of medium spiny neurons (MSNs) expressing D1 or D2 dopamine receptors. The exact mechanisms by which balanced excitation/inhibition (E/I) of these cells controls the network dynamics of the CSTC pathway remain unclear...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28781371/t-helper-type-17-cells-in-immune-mediated-glomerular-disease
#8
REVIEW
Christian F Krebs, Tilman Schmidt, Jan-Hendrik Riedel, Ulf Panzer
CD4(+) T cells are important drivers of tissue damage in immune-mediated renal diseases, such as anti-glomerular basement membrane glomerulonephritis, anti-neutrophil cytoplasmic antibody-associated glomerulonephritis, and lupus nephritis. The discovery of a distinct, IL-17-producing CD4(+) T-cell lineage termed T helper type 17 (TH17) cells has markedly advanced current understanding of the pathogenic mechanisms of organ-specific immunity and the pathways that lead to target organ damage. TH17 cells are characterized by the expression of the transcription factor RORγt, the production of the pro-inflammatory cytokines IL-17A, IL-17F, IL-22, and high expression of the chemokine receptor C-C-motif chemokine receptor 6 (CCR6)...
August 7, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28780080/-how-i-treat-autoimmune-diseases-state-of-the-art-on-the-management-of-rare-rheumatic-diseases-and-anca-associated-systemic-idiopathic-vasculitis
#9
EDITORIAL
Dario Roccatello
This Special Issue of Autoimmunity Reviews constitutes summaries of presentations at the 20th International Meeting on Immunopathology and Orphan Diseases, held in Torino, Italy, 25-28th January 2017. As such, these presentations represent the state of the art on the pathophysiology of autoimmune diseases as well as the most recent insights into the management of these pathologic conditions. The latter includes both the optimal use of established drugs and approaches as well as novel knowledge on the means and consequences of targeted blocking of molecules or cellular mechanisms...
August 2, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28768972/extranodal-nk-t-cell-lymphoma-nasal-type-accompanied-by-pr3-anca-associated-glomerulonephritis
#10
Yuta Tamoto, Ryo Ishida, Kazuya Shiogama, Hiroshi Kado, Michitsugu Kamezaki, Yoshiaki Chinen, Yosuke Matsumoto, Tetsuro Kusaba, Eiichi Konishi, Yutaka Tsutsumi, Keiichi Tamagaki
A 62-year-old man exhibiting nasal obstruction and glomerulonephritis with proteinase 3-antineutrophil cytoplasmic antibodies (PR3-ANCAs) was diagnosed with extranodal NK/T-cell lymphoma, nasal type (ENKL) with infiltration of neutrophils with apoptosis. Chemoradiotherapy reduced the tumor, improved the renal function, and decreased the PR3-ANCA levels. ANCA-positivity is observed in immunoinsufficient diseases, in which neutrophils lead to apoptosis and translocate intracellular granules, such as PR3, to the cell surface, triggering the production of ANCAs...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28757683/chemokines-ccl3-ccl4-and-ccl5-inhibit-atp-induced-release-of-il-1%C3%AE-by-monocytic-cells
#11
Anca-Laura Amati, Anna Zakrzewicz, Kathrin Siebers, Sigrid Wilker, Sarah Heldmann, Dariusz Zakrzewicz, Andreas Hecker, J Michael McIntosh, Winfried Padberg, Veronika Grau
Chemokines and ATP are among the mediators of inflammatory sites that can enter the circulation via damaged blood vessels. The main function of chemokines is leukocyte mobilization, and ATP typically triggers inflammasome assembly. IL-1β, a potent inflammasome-dependent cytokine of innate immunity, is essential for pathogen defense. However, excessive IL-1β may cause life-threatening systemic inflammation. Here, we hypothesize that chemokines control ATP-dependent secretion of monocytic IL-1β. Lipopolysaccharide-primed human monocytic U937 cells were stimulated with the P2X7 agonist BzATP for 30 min to induce IL-1β release...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28753257/caffeic-acid-attenuates-the-inflammatory-stress-induced-by-glycated-ldl-in-human-endothelial-cells-by-mechanisms-involving-inhibition-of-age-receptor-oxidative-and-endoplasmic-reticulum-stress
#12
Laura Toma, Gabriela M Sanda, Loredan S Niculescu, Mariana Deleanu, Camelia S Stancu, Anca V Sima
Type 2 diabetes mellitus is a worldwide epidemic and its atherosclerotic complications determine the high morbidity and mortality of diabetic patients. Caffeic acid (CAF), a phenolic acid present in normal diets, is known for its antioxidant properties. The aim of this study was to investigate CAF's anti-inflammatory properties and its mechanism of action, using cultured human endothelial cells (HEC) incubated with glycated low-density lipoproteins (gLDL). Levels of the receptor for advanced glycation end-products (RAGE), inflammatory stress markers (C reactive protein, CRP; vascular cell adhesion molecule-1, VCAM-1; monocyte chemoattractant protein-1, MCP-1), and oxidative stress and endoplasmic reticulum stress (ERS) markers were evaluated in gLDL-exposed HEC, in the presence/absence of CAF...
July 28, 2017: BioFactors
https://www.readbyqxmd.com/read/28752492/pulmonary-involvement-in-systemic-vasculitis
#13
REVIEW
Luis Felipe Flores-Suárez, Marco A Alba, Heidegger Mateos-Toledo, Natllely Ruiz
PURPOSE OF REVIEW: The purpose of this study is to describe the most relevant advances concerning lung involvement in the ANCA-associated vasculitides (excluding eosinophilic granulomatosis with polyangiitis which may have different disease mechanisms). Focus is on pathophysiology, recent important imagenological procedures, treatment, and outcome. RECENT FINDINGS: Emerging information exists on potential newly investigated diagnostic procedures (v.g. transbronchial cryobiopsies), detailed tomographic abnormalities, the potential favorable role of rituximab and the still uncertain one of plasma exchange in the treatment, and the increasing description of interstitial lung disease...
September 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/28745694/-difficulties-in-the-differential-diagnosis-of-kidney-injury-in-a-patient-with-infective-endocarditis-associated-with-antineutrophil-cytoplasmic-antibodies
#14
T V Androsova, L V Kozlovskaya, M V Taranova, L A Strizhakov, S V Gulyaev, A V Russkikh
Infective endocarditis (IE) may be accompanied by the production of a broad spectrum of autoantibodies, including antineutrophil cytoplasmic antibodies (ANCA). ANCA detection creates difficulties in the differential diagnosis of IE, especially in relation to kidney injury, the determination of the mechanism of which is important for choosing a treatment policy and estimating a prognosis. The paper describes a clinical case of a 57-year-old man who was found to have higher proteinase-3 (PR-3) ANCA titers along with the symptoms of anemia, purpura, and kidney injury during his hospitalization; echocardiography revealed vegetation on the aortic valve...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28732837/immune-diffuse-alveolar-hemorrhage-clinical-presentation-and-outcome
#15
Silvia Quadrelli, Diana Dubinsky, Marco Solis, Demelza Yucra, Marcos Hernández, Hugo Karlen, Alejandro Brigante
BACKGROUND: Diffuse alveolar haemorrhage (DAH) is a manifestation of several immune and nonimmune diseases. OBJECTIVE: The objective of this study was to characterize the clinical characteristics and short-term outcomes of patients with immune-mediated DAH requiring hospital admission. METHODS: A retrospective study from December 2010 to December 2015, was conducted by analyzing the clinical records of 39 patients with DAH with a proven immunological origin...
August 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28674364/diffuse-cerebral-vasoconstriction-in-a-intravascular-lymphoma-patient-with-a-high-serum-mpo-anca-level
#16
Atsuhiko Sugiyama, Makoto Kobayashi, Ayaka Daizo, Miyako Suzuki, Hirotoshi Kawashima, Shin-Ichiro Kagami, Hiroaki Tanaka, Yoshio Suzuki, Takashi Matsunaga, Satoshi Kuwabara
An 87-year-old woman presented with a 3-month history of fever, edema of the lower legs, and gait disturbance. A laboratory examination revealed high serum levels of myeloperoxidase-specific antineutrophil cytoplasmic antibody (MPO-ANCA). Although microscopic polyangiitis was initially suspected and treated, the patient subsequently developed transient hemiparesis and disturbed consciousness. Brain magnetic resonance imaging/angiography revealed infarct-like lesions, pachymeningeal involvement, and diffuse cerebral vasoconstriction...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28660014/apolipoprotein-e-a-multifunctional-protein-with-implications-in-various-pathologies-as-a-result-of-its-structural-features
#17
REVIEW
Irina Florina Tudorache, Violeta Georgeta Trusca, Anca Violeta Gafencu
Apolipoprotein E (apoE), a 34 kDa glycoprotein, mediates hepatic and extrahepatic uptake of plasma lipoproteins and cholesterol efflux from lipid-laden macrophages. In humans, three structural different apoE isoforms occur, with subsequent functional changes and pathological consequences. Here, we review data supporting the involvement of apoE structural domains and isoforms in normal and altered lipid metabolism, cardiovascular and neurodegenerative diseases, as well as stress-related pathological states...
2017: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/28649674/synovial-fibroblast-neutrophil-interactions-promote-pathogenic-adaptive-immunity-in-rheumatoid-arthritis
#18
Carmelo Carmona-Rivera, Philip M Carlucci, Erica Moore, Nithya Lingampalli, Hannes Uchtenhagen, Eddie James, Yudong Liu, Kevin L Bicker, Heidi Wahamaa, Victoria Hoffmann, Anca Irinel Catrina, PaulR Thompson, Jane H Buckner, William H Robinson, David A Fox, Mariana J Kaplan
Rheumatoid arthritis (RA) is characterized by synovial joint inflammation and by development of pathogenic humoral and cellular autoimmunity to citrullinated proteins. Neutrophil extracellular traps (NETs) are a source of citrullinated autoantigens and activate RA synovial fibroblasts (FLS), cells crucial in joint damage. We investigated the molecular mechanisms by which NETs promote proinflammatory phenotypes in FLS, and whether these interactions generate pathogenic anti-citrulline adaptive immune responses...
April 2017: Science Immunology
https://www.readbyqxmd.com/read/28636133/association-of-chronic-hypertension-with-birth-of-small-for-gestational-age-neonates
#19
Anca M Panaitescu, Ahmet A Baschat, Ranjit Akolekar, Argyro Syngelaki, Kypros H Nicolaides
OBJECTIVE: To examine the effect of chronic hypertension (CH), with and without superimposed preeclampsia (PE), on the incidence of small for gestational age (SGA) neonates, and explore possible mechanisms for such association. METHODS: The data for the study were derived from prospective screening for adverse pregnancy outcomes in women with singleton pregnancies attending for their first routine hospital visit at 11-13 weeks' gestation, which included recording of maternal characteristics and medical history and measurement of mean arterial pressure (MAP)...
June 21, 2017: Ultrasound in Obstetrics & Gynecology
https://www.readbyqxmd.com/read/28632894/flavonoids-as-modulators-of-metabolic-enzymes-and-drug-transporters
#20
REVIEW
Anca Miron, Ana Clara Aprotosoaie, Adriana Trifan, Jianbo Xiao
Flavonoids, natural compounds found in plants and in plant-derived foods and beverages, have been extensively studied with regard to their capacity to modulate metabolic enzymes and drug transporters. In vitro, flavonoids predominantly inhibit the major phase I drug-metabolizing enzyme CYP450 3A4 and the enzymes responsible for the bioactivation of procarcinogens (CYP1 enzymes) and upregulate the enzymes involved in carcinogen detoxification (UDP-glucuronosyltransferases, glutathione S-transferases (GSTs))...
June 2017: Annals of the New York Academy of Sciences
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