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Complement alternative pathway

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https://www.readbyqxmd.com/read/28724763/species-specificity-of-vaccinia-virus-complement-control-protein-towards-bovine-classical-pathway-is-governed-primarily-by-direct-interaction-of-its-acidic-residues-with-factor-i
#1
Jitendra Kumar, Viveka Nand Yadav, Swastik Phulera, Ashish Kamble, Avneesh Kumar Gautam, Hemendra Singh Panwar, Arvind Sahu
Poxviruses display species tropism - variola virus is a human-specific virus, while vaccinia virus causes repeated outbreaks in dairy cattle. Consistent with this, variola virus complement regulator SPICE exhibit selectivity in inhibiting the human alternative complement pathway and vaccinia virus complement regulator VCP display selectivity in inhibiting the bovine alternative complement pathway. In the present study, we examined the species-specificity of VCP and SPICE towards the classical pathway (CP). We observed that VCP is ∼43-fold superior in inhibiting bovine CP than SPICE...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28718268/oxymorphone-induced-thrombotic-microangiopathy-mimicking-atypical-haemolytic-uremic-syndrome
#2
Amibhen Gandhi, Saad Ullah, Shani Kotadia, Samer Nasser
Atypical Haemolytic Uremic Syndrome (aHUS) is a rare life threatening entity characterized by thrombocytopenia, haemolytic anaemia and renal dysfunction. It is a thrombotic microangiopathy related to genetic mutations in the alternate complement pathway and has a distinct pathophysiology which makes it harder to distinguish from other microangiopathies. We present a case of a 25-year-old male patient with history of polysubstance abuse who presented with chest pain and dyspnoea. He admitted to using injectable oxymorphone (Opana) two weeks before presentation...
April 2017: Journal of Ayub Medical College, Abbottabad: JAMC
https://www.readbyqxmd.com/read/28712854/c5-nephritic-factors-drive-the-biological-phenotype-of-c3-glomerulopathies
#3
Maria-Chiara Marinozzi, Sophie Chauvet, Moglie Le Quintrec, Morgane Mignotet, Florent Petitprez, Christophe Legendre, Mathilde Cailliez, Georges Deschenes, Michel Fischbach, Alexandre Karras, Francois Nobili, Christine Pietrement, Marie-Agnes Dragon-Durey, Fadi Fakhouri, Lubka T Roumenina, Veronique Fremeaux-Bacchi
C3 Glomerulopathies, which include Dense Deposit Disease and C3 Glomerulonephritis, are associated with genetic and acquired dysregulation of the C3 convertase alternative pathway of complement. The potential role of the activation of the C5 convertase has not been studied extensively. Here we analyzed IgG samples from patients with C3 Glomerulopathies to identify circulating autoantibodies that stabilize the C3 alternative pathway (C3 Nephritic Factors) as well as C5 convertases (C5 Nephritic Factors), thus preventing decay of these enzyme complexes...
July 13, 2017: Kidney International
https://www.readbyqxmd.com/read/28711159/-hemolytic-and-uremic-syndrome-and-related-thrombotic-microangiopathies-epidemiology-pathophysiology-and-clinics
#4
C Rafat, P Coppo, F Fakhouri, V Frémeaux-Bacchi, C Loirat, J Zuber, E Rondeau
Thrombotic microangiopathies (TMA) represent an eclectic group of conditions, which share hemolytic anemia and thrombocytopenia as a common defining basis. Remarkable breakthroughs in the physiopathological setting have allowed for a thorough recomposition of the disparate syndromes, which form the constellation of TMA. In this view, clinicians now discriminate thrombocytopenic thrombotic purpura (TTP) defined by a severe deficiency in ADAMTS13, which is rarely associated with a severe renal involvement and the hemolytic and uremic syndrome (HUS) in which renal impairment is the most prominent clinical feature...
July 12, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28704660/pathway-analysis-of-systemic-transcriptome-responses-to-injected-polystyrene-particles-in-zebrafish-larvae
#5
Wouter J Veneman, Herman P Spaink, Nadja R Brun, Thijs Bosker, Martina G Vijver
Microplastics are a contaminant of emergent concern in the environment, however, to date there is a limited understanding on their movement within organisms and the response of organisms. In the current study zebrafish embryos at different development stages were exposed to 700nm fluorescent polystyrene (PS) particles and the response pathway after exposure was investigated using imaging and transcriptomics. Our results show limited spreading of particles within the larvae after injection during the blastula stage...
July 4, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28698081/in-vitro-immunological-and-anti-complementary-activities-of-two-water-soluble-lignins-from-zizyphus-jujube-cv-jinchangzao
#6
Yuqing Cai, Xinping Zhou, Aizhi Han, Peng Chen, Hongjin Bai
Two homogenous biological macromolecules, designated as JJC1 and JJC2 were extracted from Zizyphus jujube cv. Jinchangzao. Their molecular weights were determined to be 56.03 and 112.11kDa by high performance gel permeation chromatography (HPGPC), respectively. Chemical and spectral analysis indicated that both JJC1 and JJC2 mainly consisted of lignin, along with carbohydrates (∼18%). Both JJC1 and JJC2 could stimulate the proliferation of spleen lymphocytes, and enhance phagocytosis and NO production of RAW264...
July 8, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28683450/acute-kidney-injury-and-hemolytic-anemia-secondary-to-mycoplasma-pneumoniae-infection
#7
Camillo Carrara, Mauro Abbate, Ettore Sabadini, Giuseppe Remuzzi
Glomerulonephritis as well as kidney injury secondary to fulminant intravascular hemolysis are rare extrapulmonary manifestations of Mycoplasma pneumoniae infection. We describe a 50-year-old female diagnosed with M. pneumoniae infection-associated hemolytic anemia, characterized by negative cold agglutinin tests but with laboratory evidence of complement alternative pathway activation. The patient presented both with anemia and severe kidney failure and she was treated with steroids and red blood cell transfusions along with plasmapheresis...
July 7, 2017: Nephron
https://www.readbyqxmd.com/read/28683197/immobilization-strategies-for-functional-complement-convertase-assembly-at-lipid-membrane-interfaces
#8
Saziye Yorulmaz Avsar, Joshua Alexander Jackman, Min Chul Kim, Bo Kyeong Yoon, Walter Hunziker, Nam-Joon Cho
The self-assembly formation of complement convertases - essential biomacromolecular complexes which amplify innate immune responses - is triggered by protein adsorption. Herein, a supported lipid bilayer platform was utilized in order to investigate the effects of covalent and noncovalent tethering strategies on the self-assembly of alternative pathway C3 convertase components, starting with C3b protein adsorption followed by addition of factors B and D. Quartz crystal microbalance-dissipation (QCM-D) experiments measured the real-time kinetics of convertase assembly onto supported lipid bilayers...
July 6, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28682564/-complement-factor-b-mutation-in-atypical-hemolytic-uremic-syndrome-rare-cause-of-rare-disease
#9
Luca Visconti, Valeria Cernaro, Gianluigi Ardissino, Martina Sgarbanti, Domenico Ferrara, Giuseppe Visconti, Domenico Santoro, Michele Buemi
Hemolytic uremic syndrome (HUS) is a rare disease characterized by microangiopathic hemolysis, platelet consumption and multiple organ failure with predominant renal involvement. In the most of cases (85-90%), it is associated with enteric infection due to Shiga-toxin or verocytotoxin (STEC-VTEC)-producer Escherichia coli. Rarely, in about 10-15% of cases, HUS develops in the presence of a disorder of alternative complement pathway regulation and it is defined atypical (aHUS). We describe the case of a 65-year-old man who came to our attention with a clinical presentation of aHUS and a clinical course characterized by rapidly progressive acute renal failure (ARF), which required renal replacement treatments, and by a stable clinical picture of hematological impairment as a marker of a non-severe and self-limiting form...
April 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28676844/genetic-characterization-of-coenzyme-a-biosynthesis-reveals-essential-distinctive-functions-during-malaria-parasite-development-in-blood-and-mosquito
#10
Robert J Hart, Amanah Abraham, Ahmed S I Aly
Coenzyme A (CoA) is an essential universal cofactor for all prokaryotic and eukaryotic cells. In nearly all non-photosynthetic cells, CoA biosynthesis depends on the uptake and phosphorylation of vitamin B5 (pantothenic acid or pantothenate). Recently, putative pantothenate transporter (PAT) and pantothenate kinases (PanKs) were functionally characterized in P. yoelii. PAT and PanKs were shown to be dispensable for blood stage development, but they were essential for mosquito stages development. Yet, little is known about the cellular functions of the other enzymes of the CoA biosynthesis pathway in malaria parasite life cycle stages...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28673452/circulating-complement-factor-h-related-proteins-1%C3%A2-and-5-correlate-with-disease-activity-in-iga-nephropathy
#11
Nicholas R Medjeral-Thomas, Hannah J Lomax-Browne, Hannah Beckwith, Michelle Willicombe, Adam G McLean, Paul Brookes, Charles D Pusey, Mario Falchi, H Terence Cook, Matthew C Pickering
IgA nephropathy (IgAN) is a common cause of chronic kidney disease and end-stage renal failure, especially in young people. Due to a wide range of clinical outcomes and difficulty in predicting response to immunosuppression, we need to understand why and identify which patients with IgAN will develop progressive renal impairment. A deletion polymorphism affecting the genes encoding the complement factor H-related protein (FHR)-1 and FHR-3 is robustly associated with protection against IgAN. Some FHR proteins, including FHR-1 and FHR-5, antagonize the ability of complement factor H (fH), the major negative regulator of the complement alternative pathway, to inhibit complement activation on surfaces, a process termed fH deregulation...
June 30, 2017: Kidney International
https://www.readbyqxmd.com/read/28671968/systemic-complement-activation-in-central-serous-chorioretinopathy
#12
Elon H C van Dijk, Roula Tsonaka, Ngaisah Klar-Mohamad, Diana Wouters, Aiko P J de Vries, Eiko K de Jong, Cees van Kooten, Camiel J F Boon
PURPOSE: A clear link between several variants in genes involved in the complement system and chronic central serous chorioretinopathy (CSC) has been described. In age-related macular degeneration, a disease that shows clinical features that overlap with CSC, both genetic risk factors and systemic activation of the complement system have previously been found. In this case-control study, we assessed whether there is evidence of either systemic activation or inhibition of the complement system in patients with chronic CSC...
2017: PloS One
https://www.readbyqxmd.com/read/28671303/increased-complement-activation-during-platelet-storage
#13
Jian Chen, Michael Losos, Shangbin Yang, Junan Li, Haifeng Wu, Spero Cataland
BACKGROUND: It has been shown that platelet transfusion carries a higher incidence of transfusion-related adverse events than any other blood components, and prolonged platelet storage is associated with more transfusion reactions, most of which are considered to be inflammatory responses. However, the role of complement, which has very important proinflammatory activities, in the pathogenesis of platelet-related adverse events has not been fully understood. STUDY DESIGN AND METHODS: Three units of platelets collected by apheresis were stored on a platelet rotator with the temperature controlled between 22 and 24°C...
July 3, 2017: Transfusion
https://www.readbyqxmd.com/read/28670985/-changes-in-diagnostic-criteria-of-thrombotic-microangiopathy-after-stem-cell-transplantation
#14
Orsolya Horváth, Zoltán Prohászka, Krisztián Kállay, Csaba Kassa, Anita Stréhn, Katalin Csordás, János Sinkó, Gergely Kriván
Hematopoietic stem cell transplantation associated thrombotic microangiopathy is a multifactorial complication, and has variable incidence in study populations due to different diagnostic criteria. The diversity of activity parameters, like elevated laktát-dehidrogenáz, hematological parameters and kidney function are not specific variables after stem cell transplantation. Dysregulation of the classical and alternative pathway can play an important role in the pathomechanism of thrombotic microangiopathy, but the understanding of the role of complement activation under transplantation conditions requires further investigation...
July 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28670268/serping1-c1-inhibitor-affects-cortical-development-in-a-cell-autonomous-and-non-cell-autonomous-manner
#15
Anna Gorelik, Tamar Sapir, Trent M Woodruff, Orly Reiner
Current knowledge regarding regulation of radial neuronal migration is mainly focused on intracellular molecules. Our unbiased screen aimed at identification of non-cell autonomous mechanisms involved in this process detected differential expression of Serping1 or C1 inhibitor, which is known to inhibit the initiation of the complement cascade. The complement cascade is composed of three pathways; the classical, lectin, and the alternative pathway; the first two are inhibited by C1 inhibitor, and all three converge at the level of C3...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28662037/activation-of-complement-factor-b-contributes-to-murine-and-human-myocardial-ischemia-reperfusion-injury
#16
Nicholas Chun, Ala S Haddadin, Junying Liu, Yunfang Hou, Karen A Wong, Daniel Lee, Julie I Rushbrook, Karan Gulaya, Roberta Hines, Tamika Hollis, Beatriz Nistal Nuno, Abeel A Mangi, Sabet Hashim, Marcela Pekna, Amy Catalfamo, Hsiao-Ying Chin, Foramben Patel, Sravani Rayala, Ketan Shevde, Peter S Heeger, Ming Zhang
The pathophysiology of myocardial injury that results from cardiac ischemia and reperfusion (I/R) is incompletely understood. Experimental evidence from murine models indicates that innate immune mechanisms including complement activation via the classical and lectin pathways are crucial. Whether factor B (fB), a component of the alternative complement pathway required for amplification of complement cascade activation, participates in the pathophysiology of myocardial I/R injury has not been addressed. We induced regional myocardial I/R injury by transient coronary ligation in WT C57BL/6 mice, a manipulation that resulted in marked myocardial necrosis associated with activation of fB protein and myocardial deposition of C3 activation products...
2017: PloS One
https://www.readbyqxmd.com/read/28661399/systematic-bacterialization-of-yeast-genes-identifies-a-near-universally-swappable-pathway
#17
Aashiq Hussain Kachroo, Jon Michael Laurent, Azat Akhmetov, Madelyn Szilagyi-Jones, Claire Darnell McWhite, Alice Zhao, Edward Michael Marcotte
Eukaryotes and prokaryotes last shared a common ancestor ~2 billion years ago, and while many present-day genes in these lineages predate this divergence, the extent to which these genes still perform their ancestral functions is largely unknown. To test principles governing retention of ancient function, we asked if prokaryotic genes could replace their essential eukaryotic orthologs. We systematically replaced essential genes in yeast by their 1:1 orthologs from Escherichia coli. After accounting for mitochondrial localization and alternative start codons, 31 out of 51 bacterial genes tested (61%) could complement a lethal growth defect and replace their yeast orthologs with minimal effects on growth rate...
June 29, 2017: ELife
https://www.readbyqxmd.com/read/28656244/a-genome-wide-analysis-of-the-gene-expression-profiles-and-alternative-splicing-events-during-the-hypoxia-regulated-osteogenic-differentiation-of-human-cartilage-endplate-derived-stem-cells
#18
Yuan Yao, Qiyue Deng, Chao Sun, Weiling Song, Huan Liu, Yue Zhou
It has been hypothesized that intervertebral disc degeneration is initiated by degeneration of the cartilage endplate (CEP), which is characterized by cartilage ossification. CEP‑derived stem cells (CESCs), with the potential for chondro‑osteogenic differentiation, may be responsible for the balance between chondrification and ossification in the CEP. The CEP remains in an avascular and hypoxic microenvironment; the present study observed that hypoxia was able to markedly inhibit the osteogenic differentiation of CESCs...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28652401/interaction-between-multimeric-von-willebrand-factor-and-complement-a-fresh-look-to-the-pathophysiology-of-microvascular-thrombosis
#19
Serena Bettoni, Miriam Galbusera, Sara Gastoldi, Roberta Donadelli, Chiara Tentori, Giuseppina Spartà, Elena Bresin, Caterina Mele, Marta Alberti, Agustin Tortajada, Hugo Yebenes, Giuseppe Remuzzi, Marina Noris
von Willebrand factor (VWF), a multimeric protein with a central role in hemostasis, has been shown to interact with complement components. However, results are contrasting and inconclusive. By studying 20 patients with congenital thrombotic thrombocytopenic purpura (cTTP) who cannot cleave VWF multimers because of genetic ADAMTS13 deficiency, we investigated the mechanism through which VWF modulates complement and its pathophysiological implications for human diseases. Using assays of ex vivo serum-induced C3 and C5b-9 deposits on endothelial cells, we documented that in cTTP, complement is activated via the alternative pathway (AP) on the cell surface...
June 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28649250/immunity-in-protochordates-the-tunicate-perspective
#20
REVIEW
Nicola Franchi, Loriano Ballarin
Tunicates are the closest relatives of vertebrates, and their peculiar phylogenetic position explains the increasing interest toward tunicate immunobiology. They are filter-feeding organisms, and this greatly influences their defense strategies. The majority of the studies on tunicate immunity were carried out in ascidians. The tunic acts as a first barrier against pathogens and parasites. In addition, the oral siphon and the pharynx represent two major, highly vascularized, immune organs, where circulating hemocytes can sense non-self material and trigger immune responses that, usually, lead to inflammation and phagocytosis...
2017: Frontiers in Immunology
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