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Alternative complement pathway

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https://www.readbyqxmd.com/read/28811496/genome-wide-expression-differences-in-anti-vegf-and-dexamethasone-treatment-of-inflammatory-angiogenesis-in-the-rat-cornea
#1
Pierfrancesco Mirabelli, Anthony Mukwaya, Anton Lennikov, Maria Xeroudaki, Beatrice Peebo, Mira Schaupper, Neil Lagali
Angiogenesis as a pathological process in the eye can lead to blindness. In the cornea, suppression of angiogenesis by anti-VEGF treatment is only partially effective while steroids, although effective in treating inflammation and angiogenesis, have broad activity leading to undesirable side effects. In this study, genome-wide expression was investigated in a suture-induced corneal neovascularization model in rats, to investigate factors differentially targeted by dexamethasone and anti-Vegf. Topical treatment with either rat-specific anti-Vegf, dexamethasone, or normal goat IgG (sham) was given to sutured corneas for 48 hours, after which in vivo imaging, tissue processing for RNA microarray, and immunofluorescence were performed...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808775/how-novel-structures-inform-understanding-of-complement-function
#2
REVIEW
Elena Goicoechea de Jorge, Hugo Yebenes, Marina Serna, Agustín Tortajada, Oscar Llorca, Santiago Rodríguez de Córdoba
During the last decade, the complement field has experienced outstanding advancements in the mechanistic understanding of how complement activators are recognized, what C3 activation means, how protein complexes like the C3 convertases and the membrane attack complex are assembled, and how positive and negative complement regulators perform their function. All of this has been made possible mostly because of the contributions of structural biology to the study of the complement components. The wealth of novel structural data has frequently provided support to previously held knowledge, but often has added alternative and unexpected insights into complement function...
August 14, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28803115/immunological-response-to-nitroglycerin-loaded-shear-responsive-liposomes-in-vitro-and-in-vivo
#3
Marzia Buscema, Sofiya Matviykiv, Tamás Mészáros, Gabriela Gerganova, Andreas Weinberger, Ute Mettal, Dennis Mueller, Frederik Neuhaus, Etienne Stalder, Takashi Ishikawa, Rudolf Urbanics, Till Saxer, Thomas Pfohl, János Szebeni, Andreas Zumbuehl, Bert Müller
Liposomes formulated from the 1,3-diamidophospholipid Pad-PC-Pad are shear-responsive and thus promising nano-containers to specifically release a vasodilator at stenotic arteries. The recommended preclinical safety tests for therapeutic liposomes of nanometer size include the in vitro assessment of complement activation and the evaluation of the associated risk of complement activation-related pseudo-allergy (CARPA) in vivo. For this reason, we measured complement activation by Pad-PC-Pad formulations in human and porcine sera, along with the nanopharmaceutical-mediated cardiopulmonary responses in pigs...
August 9, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28801815/plasma-levels-of-complement-activation-fragments-c3b-and-sc5b-9-significantly-increased-in-patients-with-thrombotic-microangiopathy-after-allogeneic-stem-cell-transplantation
#4
Jiaqian Qi, Jie Wang, Jia Chen, Jian Su, Yaqiong Tang, Xiaojin Wu, Xiao Ma, Feng Chen, Changgeng Ruan, X Long Zheng, Depei Wu, Yue Han
Transplantation-associated thrombotic microangiopathy (TA-TMA) is an uncommon but severe complication in patients undergoing allogeneic stem cell transplantation (allo-SCT). However, the mechanism is unclear. From 2011 to 2014, 20 patients with TA-TMA, 20 patients without, and 54 patients with various other complications, including veno occlusive disease (VOD), graft-versus-host disease (GVHD), and infection, were recruited in the study. Plasma vWF antigen (vWFAg), vWF activity (vWFAc), and ADAMTS13 activity were determined in these patients by ELISAs and FRETS-vWF73 assay, respectively...
August 11, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28798244/atypical-haemolytic-uremic-syndrome-ahus-and-membranoproliferative-glomerulonephritis-mpgn-different-diseases-or-a-spectrum-of-complement-mediated-glomerular-diseases
#5
Ghada A Ankawi, William F Clark
Historically, patients with kidney diseases caused by genetic or acquired dysregulation of the complement alternative pathway have been grouped into clinical syndromes, C3 glomerulopathy (C3GN/DDD) and thrombotic microangiopathy (TMA), specifically atypical haemolytic uremic syndrome (aHUS). Recent data suggested that these diseases share a common pathophysiology and that patients can transition between glomerulopathies in this spectrum. Histopathologically, the main difference cited is the immunofluorescence (IF) findings, with C3 predominance in C3 glomerulopathy (compared with immunoglobulins and complements in immune complex-mediated membranoproliferative glomerulonephritis (MPGN)) and negative IF in TMA...
August 10, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28794230/analysis-of-factor-d-isoforms-in-malpuech-michels-mingarelli-carnevale-patients-highlights-the-role-of-masp-3-as-a-maturase-in-the-alternative-pathway-of-complement
#6
Rasmus Pihl, Lisbeth Jensen, Annette G Hansen, Ida B Thøgersen, Stephanie Andres, Frederik Dagnæs-Hansen, Konrad Oexle, Jan J Enghild, Steffen Thiel
Factor D (FD), which is also known as adipsin, is regarded as the first-acting protease of the alternative pathway (AP) of complement. It has been suggested that FD is secreted as a mature enzyme that does not require subsequent activation. This view was challenged when it was shown that mice lacking mannose-binding lectin (MBL)-associated serine protease-1 (MASP-1) and MASP-3 contain zymogenic FD (pro-FD), and it is becoming evident that MASP-3 is implicated in pro-FD maturation. However, the necessity of MASP-3 for pro-FD cleavage has been questioned, because AP activity is still observed in sera from MASP-1/3-deficient Malpuech-Michels-Mingarelli-Carnevale (3MC) patients...
August 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28764571/increased-c4d-and-bb-immunoreactivity-and-decreased-mbl-immunoreactivity-characterise-first-time-pathologic-first-trimester-miscarriage-a-case-control-study
#7
M Tunc Canda, Latife Doganay Caglayan, Namik Demir, Ragıp Ortaç
The role of the complement system in first-time pathologic first-trimester miscarriage was investigated. In this case-control study, tissue samples of 126 women with pathologic miscarriage and termination of normal pregnancies were assessed. The pathologic pregnancy group consisted of 40 women with missed miscarriage, 13 women with incomplete miscarriage and 10 women with a blighted ovum. The control group consisted of 63 normal-appearing pregnancies. Immunoreactivity for C4d, Bb and MBL was evaluated in the deciduas and villous trophoblasts separately using a semi-quantitative histological scoring system (H-score)...
August 1, 2017: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28757372/magnetic-bead-based-assays-for-complement-component-c5
#8
Richard G DiScipio, Ingrid U Schraufstatter
Two novel magnetic agarose bead based assays have been developed to measure complement component C5 interaction with C3b and the Factor I Modules (FIMs) of C7. One innovation was to couple C3b onto the magnetic agarose bead using the alternative pathway C3 convertase, which resulted in a linkage of the ligand by a covalent ester bond. A second innovation was to employ nickel ion charged N,N,N'-tris(carboxymethyl)ethylene-diamine-magnetic agarose to capture recombinantly prepared C7 FIMs that were expressed with an oligo-histidine linker followed by an acidic domain that provided a spacer enabling the C7 modules exposure to C5...
July 27, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28753630/double-impact-natural-molluscicide-for-schistosomiasis-vector-control-also-impedes-development-of-schistosoma-mansoni-cercariae-into-adult-parasites
#9
Ronaldo de Carvalho Augusto, Guillaume Tetreau, Philippe Chan, Marie-Laure Walet-Balieu, Clélia Christina Mello-Silva, Claudia Portes Santos, Christoph Grunau
BACKGROUND: Schistosomiasis has been reported in 78 endemic countries and affects 240 million people worldwide. The digenetic parasite Schistosoma mansoni needs fresh water to compete its life cycle. There, it is susceptible to soluble compounds that can affect directly and/or indirectly the parasite's biology. The cercariae stage is one of the key points in which the parasite is vulnerable to different soluble compounds that can significantly alter the parasite's life cycle. Molluscicides are recommended by the World Health Organization for the control of schistosomiasis transmission and Euphorbia milii latex is effective against snails intermediate hosts...
July 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28748900/dense-deposit-disease-in-a-child-with-febrile-sore-throat
#10
Giovanni Conti, Dominique De Vivo, Agata Vitale, Carmelo Fede, Domenico Santoro
Dense deposit disease or membranoproliferative glomerulonephritis type II is a rare glomerulopathy characterized on renal biopsy by deposition of abnormal electron-dense material in the glomerular basement membrane. The pathophysiologic basis is uncontrolled systemic activation of the alternate pathway of the complement cascade. C3 nephritic factor, an autoantibody directed against the C3 convertase of the alternate pathway, plays a key role. In some patients, complement gene mutations have been identified...
July 2017: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/28748184/complement-in-non-antibody-mediated-kidney-diseases
#11
REVIEW
Andrea Angeletti, Joselyn Reyes-Bahamonde, Paolo Cravedi, Kirk N Campbell
The complement system is part of the innate immune response that plays important roles in protecting the host from foreign pathogens. The complement components and relative fragment deposition have long been recognized to be strongly involved also in the pathogenesis of autoantibody-related kidney glomerulopathies, leading to direct glomerular injury and recruitment of infiltrating inflammation pathways. More recently, unregulated complement activation has been shown to be associated with progression of non-antibody-mediated kidney diseases, including focal segmental glomerulosclerosis, C3 glomerular disease, thrombotic microangiopathies, or general fibrosis generation in progressive chronic kidney diseases...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28745692/-changes-in-the-complement-system-in-membranoproliferative-glomerulonephritis
#12
V A Yurova, L A Bobrova, N L Kozlovskaya, Yu V Korotchaeva, A G Serova, L V Kozlov, S S Andina, K A Demyanova, A M Kuchieva, S V Roshchupkina
AIM: To compare the clinical manifestations membranoproliferative glomerulonephritis (MPGN) in its idiopathic variant, lupus nephritis (LN), and C3 glomerulopathy (C3-GP), by comparing them with changes in the complement system. SUBJECTS AND METHODS: The clinic of nephrology followed up 42 patients with different types of MPGN in 2013 to 2015. The study included 35 patients divided into 3 groups: 1) 8 patients with C3-GP, 2) 13 with idiopathic MPGN; 3) 14 with Class IV LN...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28743624/russian-sturgeon-cultured-in-a-subtropical-climate-shows-weaken-innate-defences-and-a-chronic-stress-response
#13
Mauricio Castellano, Valeria Silva-Álvarez, Elena Fernández-López, Verónica Mauris, Daniel Conijeski, Andrea Villarino, Ana M Ferreira
Russian sturgeon (Acipenser gueldenstaedtii) has been successfully farmed in Uruguay for the past ten years. However, during the Uruguayan summer fish endure high water temperatures and increased bacterial infections that threaten aquaculture. Our understanding of sturgeon's immune system and its interplay with environmental factors like temperature is almost unknown. This study analysed the way in which seasonal variations affect enzymatic blood components of Russian sturgeon's innate defences, including the serum alternative complement pathway (ACP), ceruloplasmin (Cp) and lysozyme activities...
July 22, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28742158/human-tamm-horsfall-protein-a-renal-specific-protein-serves-as-a-cofactor-in-complement-3b-degradation
#14
Diana C J Rhodes
Tamm-Horsfall protein (THP) is an abundant urinary protein of renal origin. We hypothesize that THP can act as an inhibitor of complement since THP binds complement 1q (C1q) of the classical complement pathway, inhibits activation of this pathway, and is important in decreasing renal ischemia-reperfusion injury (a complement-mediated condition). In this study, we began to investigate whether THP interacted with the alternate complement pathway via complement factor H (CFH). THP was shown to bind CFH using ligand blots and in an ELISA (KD of 1 × 10-6 M)...
2017: PloS One
https://www.readbyqxmd.com/read/28739878/deconstructing-the-lectin-pathway-in-the-pathogenesis-of-experimental-inflammatory-arthritis-essential-role-of-the-lectin-ficolin-b-and-mannose-binding-protein-associated-serine-protease-2
#15
Nirmal K Banda, Sumitra Acharya, Robert I Scheinman, Gaurav Mehta, Minoru Takahashi, Yuichi Endo, Wuding Zhou, Conrad A Farrar, Steven H Sacks, Teizo Fujita, Hideharu Sekine, V Michael Holers
Complement plays an important role in the pathogenesis of rheumatoid arthritis. Although the alternative pathway (AP) is known to play a key pathogenic role in models of rheumatoid arthritis, the importance of the lectin pathway (LP) pattern recognition molecules such as ficolin (FCN) A, FCN B, and collectin (CL)-11, as well as the activating enzyme mannose-binding lectin-associated serine protease-2 (MASP-2), are less well understood. We show in this article that FCN A(-/-) and CL-11(-/-) mice are fully susceptible to collagen Ab-induced arthritis (CAIA)...
July 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28739825/neisseria-cinerea-expresses-a-functional-factor-h-binding-protein-which-is-recognised-by-immune-responses-elicited-by-meningococcal-vaccines
#16
Hayley Lavender, Katy Poncin, Christoph M Tang
Neisseria meningitidis is a major cause of bacterial meningitis and sepsis worldwide. Capsular polysaccharide vaccines are available against meningococcal serogroups A, C, W and Y. More recently two protein based vaccines, Bexsero® and Trumenba®, have been licenced against meningococcal serogroup B strains; both vaccines contain meningococcal factor H binding protein (fHbp). fHbp is a surface exposed lipoprotein which binds the negative complement regulator, complement factor H (CFH), thereby inhibiting the alternative pathway of complement activation...
July 24, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28729035/a-novel-cfhr1-cfhr5-hybrid-leads-to-a-familial-dominant-c3-glomerulopathy
#17
Shambhuprasad K Togarsimalemath, Sidharth K Sethi, Rajan Duggal, Moglie Le Quintrec, Pranaw Jha, Régis Daniel, Florence Gonnet, Shyam Bansal, Lubka T Roumenina, Veronique Fremeaux-Bacchi, Vijay Kher, Marie-Agnes Dragon-Durey
The intrinsic similarity shared between the members of the complement factor H family, which comprises complement factor H and five complement factor H-related (CFHR) genes, leads to various recombination events. In turn these events lead to deletions of some genes or abnormal proteins, which are found in patients with atypical hemolytic uremic syndrome or C3 glomerulopathies. Here we describe a novel genetic rearrangement generated from a heterozygous deletion spanning 146 Kbp involving multiple CFHR genes leading to a CFHR1-R5 hybrid protein...
July 17, 2017: Kidney International
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
#18
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
#19
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
#20
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
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