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Complement alternative pathway

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https://www.readbyqxmd.com/read/29784885/-pseudomonas-aeruginosa-regulated-intramembrane-proteolysis-rip-protease-mucp-can-overcome-mutations-in-the-algo-periplasmic-protease-to-restore-alginate-production-in-nonmucoid-revertants
#1
Camila Delgado, Laura Florez, Ivonne Lollett, Christine Lopez, Shiva Kangeyan, Hansi Kumari, Marios Stylianou, Robert J Smiddy, Lisa Schneper, Robert T Sautter, George Szatmari, Kalai Mathee
The progression of cystic fibrosis (CF) from an acute to a chronic disease is often associated with the conversion of the opportunistic pathogen Pseudomonas aeruginosa from a nonmucoid form to a mucoid form in the lung. This conversion involves the overproduction of the exopolysaccharide alginate, whose production is under control of the AlgT/U sigma factor. This factor is regulated posttranslationally by an extremely unstable process and has been commonly attributed to mutations in the algT/U gene. By exploiting this unstable phenotype, we isolated 34 spontaneous nonmucoid variants arising from the mucoid strain PDO300, a PAO1 derivative containing the mucA22 allele commonly found in mucoid CF isolates...
May 21, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29777623/complement-factor-h-as-a-potential-atherogenic-marker-in-chronic-chagas-disease
#2
Kárita Cláudia Freitas Lidani, Thaisa Lucas Sandri, Fabiana Antunes Andrade, Lorena Bavia, Renato Nisihara, Iara J Messias Reason
AIMS: We aimed to investigate the association between plasma levels of complement Factor H (FH) with cardiac involvement, inflammatory and cardiometabolic parameters in patients with chronic Chagas disease (CD). METHODS: FH plasmatic levels were determined in 80 chronic CD patients. Glycemic index, lipidogram (high-density lipoprotein cholesterol HDL-C, low-density lipoprotein cholesterol LDL-C, triglycerides and total cholesterol), and Ultrasensitive C-Reactive Protein (uCRP) values were obtained from medical records...
May 19, 2018: Parasite Immunology
https://www.readbyqxmd.com/read/29752310/extracellular-histones-inhibit-complement-activation-through-interacting-with-complement-component-4
#3
Yasir Qaddoori, Simon T Abrams, Paul Mould, Yasir Alhamdi, Stephen E Christmas, Guozheng Wang, Cheng-Hock Toh
Complement activation leads to membrane attack complex formation, which can lyse not only pathogens but also host cells. Histones can be released from the lysed or damaged cells and serve as a major type of damage-associated molecular pattern, but their effects on the complement system are not clear. In this study, we pulled down two major proteins from human serum using histone-conjugated beads: one was C-reactive protein and the other was C4, as identified by mass spectrometry. In surface plasmon resonance analysis, histone H3 and H4 showed stronger binding to C4 than other histones, with KD around 1 nM...
May 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29750504/c1q-mediated-complement-activation-and-c3-opsonization-trigger-recognition-of-stealth-poly-2-methyl-2-oxazoline-coated-silica-nanoparticles-by-human-phagocytes
#4
Regina Tavano, Luca Gabrielli, Elisa Lubian, Chiara Fedeli, Silvia Visentin, Patrizia Polverino de Laureto, Giorgio Arrigoni, Alessandra Geffner-Smith, Fangfang Chen, Dmitri Simberg, Giulia Morgese, Edmondo Maria Benetti, Linping Wu, Seyed Moein Moghimi, Fabrizio Mancin, Emanuele Papini
Poly(2-methyl-2-oxazoline) (PMOXA) is an alternative promising polymer to poly(ethylene glycol), (PEG), for design and engineering of macrophage-evading nanoparticles (NPs). Although PMOXA engineered NPs have shown comparable pharmacokinetics, and in vivo performance to PEGylated stealth NPs in the murine model, its interaction with elements of the human innate immune system has not been studied. From a translational angle, we studied the interaction of fully characterized PMOXA-coated vinyl-triethoxysilane-derived organically modified silica NPs (PMOXA-coated NPs) of approximately 100 nm in diameter with human complement system, blood leukocytes and macrophages, and compared their performance with PEGylated and uncoated NP counterparts...
May 11, 2018: ACS Nano
https://www.readbyqxmd.com/read/29743491/classical-and-alternative-complement-activation-on-photoreceptor-outer-segments-drives-monocyte-dependent-retinal-atrophy
#5
Kenneth J Katschke, Hongkang Xi, Christian Cox, Tom Truong, Yann Malato, Wyne P Lee, Brent McKenzie, Rommel Arceo, Jianhua Tao, Linda Rangell, Mike Reichelt, Lauri Diehl, Justin Elstrott, Robby M Weimer, Menno van Lookeren Campagne
Geographic atrophy (GA), the advanced form of dry age-related macular degeneration (AMD), is characterized by progressive loss of retinal pigment epithelium cells and photoreceptors in the setting of characteristic extracellular deposits and remains a serious unmet medical need. While genetic predisposition to AMD is dominated by polymorphisms in complement genes, it remains unclear how complement activation contributes to retinal atrophy. Here we demonstrate that complement is activated on photoreceptor outer segments (POS) in the retina peripheral to atrophic lesions associated with GA...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29743365/dengue-virus-induces-increased-activity-of-the-complement-alternative-pathway-in-infected-cells
#6
Sheila Cabezas, Gustavo Bracho, Amanda L Aloia, Penelope J Adamson, Claudine S Bonder, Justine R Smith, David L Gordon, Jillian M Carr
Severe dengue virus (DENV) infection is associated with overactivity of the complement alternative pathway (AP) in patient studies. Here, the molecular changes in components of the AP during DENV infection in vitro are investigated. mRNA for factor H (FH) a major negative regulator of the AP, is significantly increased in DENV-infected endothelial cells (EC) and macrophages but in contrast production of extracellular FH protein is not. This discord is not seen for the AP activator, factor B (FB), with DENV induction of both FB mRNA and protein, nor with Toll-like receptor 3 or 4 stimulation of EC and macrophages, which induces both FH and FB mRNA and protein...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29740447/high-complement-factor-h-related-fhr-3-levels-are-associated-with-the-atypical-hemolytic-uremic-syndrome-risk-allele-cfhr3-b
#7
Richard B Pouw, Irene Gómez Delgado, Alberto López Lera, Santiago Rodríguez de Córdoba, Diana Wouters, Taco W Kuijpers, Pilar Sánchez-Corral
Dysregulation of the complement alternative pathway (AP) is a major pathogenic mechanism in atypical hemolytic-uremic syndrome (aHUS). Genetic or acquired defects in factor H (FH), the main AP regulator, are major aHUS drivers that associate with a poor prognosis. FH activity has been suggested to be downregulated by homologous FH-related (FHR) proteins, including FHR-3 and FHR-1. Hence, their relative levels in plasma could be disease-relevant. The genes coding for FH, FHR-3, and FHR-1 ( CFH, CFHR3 , and CFHR1 , respectively) are polymorphic and located adjacent to each other on human chromosome 1q31...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29738834/interaction-of-complement-system-and-microglia-activation-in-retina-and-optic-nerve-in-a-nmda-damage-model
#8
Sandra Kuehn, Sabrina Reinehr, Gesa Stute, Cara Rodust, Pia Grotegut, Alexander-Tobias Hensel, H Burkhard Dick, Stephanie C Joachim
It is known that intravitreally injected N-methyl-d-aspartate (NMDA) leads to fast retina and optic nerve degeneration and can directly activate microglia. Here, we analyzed the relevance for microglia related degenerating factors, the proteins of the complement system, at a late stage in the NMDA damage model. Therefore, different doses of NMDA (0 (PBS), 20, 40, 80 nmol) were intravitreally injected in rat eyes. Proliferative and activated microglia/macrophages (MG/Mϕ) were found in retina and optic nerve 2 weeks after NMDA injection...
May 5, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29732228/de-novo-atypical-haemolytic-uremic-syndrome-after-kidney-transplantation
#9
Arnaud Devresse, Martine de Meyer, Selda Aydin, Karin Dahan, Nada Kanaan
De novo thrombotic microangiopathy (TMA) can occur after kidney transplantation. An abnormality of the alternative pathway of complement must be suspected and searched for, even in presence of a secondary cause. We report the case of a 23-year-old female patient who was transplanted with a kidney from her mother for end-stage renal disease secondary to Hinman syndrome. Early after transplantation, she presented with 2 episodes of severe pyelonephritis, associated with acute kidney dysfunction and biological and histological features of TMA...
2018: Case Reports in Nephrology
https://www.readbyqxmd.com/read/29729982/c3-glomerulopathy-associated-with-monoclonal-ig-is-a-distinct-subtype
#10
Aishwarya Ravindran, Fernando C Fervenza, Richard J H Smith, Sanjeev Sethi
Monoclonal immunoglobulins (MIg) may play a causal role in C3 glomerulopathy (C3G) by impairing regulation of the alternative pathway of complement. Ninety-five patients with C3G were tested for MIg of which 36 were positive. Their mean age at diagnosis was 60 years and among patient 50 years and older, 65.1% had a MIg. At presentation, median serum creatinine and proteinuria were 1.9 mg/dL and 3.0 g/24 hours. Hematuria was present in 32 (88.9%) patients. Twelve (34.3%) patients had low C3 levels. C3 nephritic factor was detected in 45...
May 2, 2018: Kidney International
https://www.readbyqxmd.com/read/29729954/complement-activation-in-patients-with-diabetic-nephropathy
#11
X-Q Li, D-Y Chang, M Chen, M-H Zhao
AIM: Emerging evidence has indicated a role of the complement system in the pathogenesis of diabetic nephropathy (DN), although the pathways of complement activation and their clinicopathological relevance in DN are as yet unclear. The present study aimed to investigate levels of various complement components in plasma and urine of DN patients, and their correlation with clinicopathological parameters. METHODS: A total of 68 biopsy-proven DN patients with plasma samples were recruited, including 50 patients who also had urine samples available...
April 16, 2018: Diabetes & Metabolism
https://www.readbyqxmd.com/read/29728803/acquired-thrombotic-thrombocytopenic-purpura-with-isolated-cfhr3-1-deletion-rapid-remission-following-complement-blockade
#12
Martin Bitzan, Rawan M Hammad, Arnaud Bonnefoy, Watfa Shahwan Al Dhaheri, Catherine Vézina, Georges-Étienne Rivard
BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is caused by the abundance of uncleaved ultralarge von Willebrand factor multimers (ULvWF) due to acquired (autoantibody-mediated) or congenital vWF protease ADAMTS13 deficiency. Current treatment recommendations include plasma exchange therapy and immunosuppression for the acquired form and (fresh) frozen plasma for congenital TTP. CASE-DIAGNOSIS/TREATMENT: A previously healthy, 3-year-old boy presented with acute microangiopathic hemolytic anemia, thrombocytopenia, erythrocyturia and mild proteinuria, but normal renal function, and elevated circulating sC5b-9 levels indicating complement activation...
May 4, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29725647/progressive-iga-nephropathy-is-associated-with-low-circulating-mannan-binding-lectin-associated-serine-protease-3-masp-3-and-increased-glomerular-factor-h-related-protein-5-fhr5-deposition
#13
Nicholas R Medjeral-Thomas, Anne Troldborg, Nicholas Constantinou, Hannah J Lomax-Browne, Annette G Hansen, Michelle Willicombe, Charles D Pusey, H Terence Cook, Steffen Thiel, Matthew C Pickering
Introduction: IgA nephropathy (IgAN) is characterized by glomerular deposition of galactose-deficient IgA1 and complement proteins and leads to renal impairment. Complement deposition through the alternative and lectin activation pathways is associated with renal injury. Methods: To elucidate the contribution of the lectin pathway to IgAN, we measured the 11 plasma lectin pathway components in a well-characterized cohort of patients with IgAN. Results: M-ficolin, L-ficolin, mannan-binding lectin (MBL)-associated serine protease (MASP)-1 and MBL-associated protein (MAp) 19 were increased, whereas plasma MASP-3 levels were decreased in patients with IgAN compared with healthy controls...
March 2018: KI Reports
https://www.readbyqxmd.com/read/29724182/favorable-effect-of-bortezomib-in-dense-deposit-disease-associated-with-monoclonal-gammopathy-a-case-report
#14
Shuma Hirashio, Ayaka Satoh, Takahiro Arima, Kouichi Mandai, Tadasuke Awaya, Kumi Oshima, Shigeo Hara, Takao Masaki
BACKGROUND: Complement component 3 (C3) glomerulopathy, which includes dense deposit disease (DDD) and C3 glomerulonephritis, is caused by dysregulation of the alternative complement pathway. In most cases, C3 glomerulopathy manifests pathologically with membranoproliferative glomerulonephritis-like features. An association between C3 glomerulopathy and monoclonal gammopathy was recently reported in several cases, raising the possibility that C3 glomerulopathy is the underlying pathological process in monoclonal gammopathy of renal significance...
May 3, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29722072/htert-promotes-tumor-progression-by-enhancing-tspan13-expression-in-osteosarcoma-cells
#15
Rishi Kumar Jaiswal, Pramod Kumar, Manoj Kumar, Pramod Kumar Yadava
Telomerase complex maintains the length of the telomere and protects erosion of the physical ends of the eukaryotic chromosome in all actively dividing cells including cancer cells. Telomerase activation extends the lifespan of cells in culture by maintaining the length of the telomere. Compared to terminally differentiated somatic cells, telomerase activity remains high in over 90% of cancer cells. It has now become clear that the role of telomerase is much more complex than just telomere lengthening. The remaining 10% of cancers deploy ALT (alternative lengthening of telomeres) pathway to maintain telomere length...
May 2, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29721924/alterations-in-extracellular-matrix-bruch-s-membrane-can-cause-the-activation-of-the-alternative-complement-pathway-via-tick-over
#16
Rosario Fernandez-Godino
Given the complex etiology of age-related macular degeneration (AMD), treatments are developed to target intermediate/late stages of the disease. Unfortunately, the design of therapies for early stages of the disease is limited by our understanding of the mechanisms involved in the formation of basal deposits and drusen, the first clinical signs of AMD. During the last decade, the identification of common and rare alleles in complement genes as risk AMD variants in addition to the presence of active complement components in basal deposits and drusen has provided compelling evidence that the complement system plays a key role in the pathobiology of AMD...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29720234/two-independent-proteomic-approaches-provide-a-comprehensive-analysis-of-the-synovial-fluid-proteome-response-to-autologous-chondrocyte-implantation
#17
Charlotte H Hulme, Emma L Wilson, Heidi R Fuller, Sally Roberts, James B Richardson, Pete Gallacher, Mandy J Peffers, Sally L Shirran, Catherine H Botting, Karina T Wright
BACKGROUND: Autologous chondrocyte implantation (ACI) has a failure rate of approximately 20%, but it is yet to be fully understood why. Biomarkers are needed that can pre-operatively predict in which patients it is likely to fail, so that alternative or individualised therapies can be offered. We previously used label-free quantitation (LF) with a dynamic range compression proteomic approach to assess the synovial fluid (SF) of ACI responders and non-responders. However, we were able to identify only a few differentially abundant proteins at baseline...
May 2, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29719782/beneficial-effects-of-houttuynia-cordata-polysaccharides-on-two-hit-acute-lung-injury-and-endotoxic-fever-in-rats-associated-with-anti-complementary-activities
#18
Yan Lu, Yun Jiang, Lijun Ling, Yunyi Zhang, Hong Li, Daofeng Chen
Houttuynia cordata Thunb. is a traditional herb used for clearing heat and eliminating toxins, and has also been used for the treatment of severe acute respiratory syndrome (SARS). In vitro, the crude H. cordata polysaccharides (CHCP) exhibited potent anti-complementary activity through both the classical and alternative pathways by acting on components C3 and C4 of the complement system without interfering with the coagulation system. This study was to investigate the preventive effects of CHCP on acute lung injury (ALI) induced by hemorrhagic shock plus lipopolysaccharide (LPS) instillation (two-hit) and LPS-induced fever in rats...
March 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/29718732/avacopan-in-the-treatment-of-anca-associated-vasculitis
#19
Vladimir Tesar, Zdenka Hruskova
ANCA-associated vasculitis (AAV) is a rare but potentially life-threatening disease. Currently used induction treatment (cyclophosphamide or rituximab with high-dose corticosteroids) has significantly improved outcome of AAV, but is associated with high toxicity. Alternative complement pathway activation was shown to play a role in the pathogenesis of AAV, thus providing rationale for the use of avacopan, a selective inhibitor of C5a receptor, in the treatment of AAV. Areas Covered: Pharmacokinetic and pharmocodynamic properties of avacopan, clinical efficacy and safety and tolerability of avacopan in so far performed clinical trials in patients with AAV are reviewed and discussed...
May 2, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29717384/the-complement-alternative-pathway-and-preeclampsia
#20
REVIEW
Layan Alrahmani, Maria Alice V Willrich
PURPOSE OF REVIEW: Significant and intricate immune adaptations are essential for the establishment and maintenance of normal pregnancy. Preeclampsia is a morbid, potentially life-threatening disease for both mother and neonate that occurs uniquely in pregnancy, at least in part, due to maternal immune maladaptation. We aim to review the literature that focuses on case reports, diagnostic approaches, and treatment strategies for disorders of the complement alternative pathway (CAP) as related to preeclampsia...
May 1, 2018: Current Hypertension Reports
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