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Complement deficiency

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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
#1
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/28086806/age-related-macular-degeneration-associated-polymorphism-rs10490924-in-arms2-results-in-deficiency-of-a-complement-activator
#2
Sven Micklisch, Yuchen Lin, Saskia Jacob, Marcus Karlstetter, Katharina Dannhausen, Prasad Dasari, Monika von der Heide, Hans-Martin Dahse, Lisa Schmölz, Felix Grassmann, Medhanie Alene, Sascha Fauser, Harald Neumann, Stefan Lorkowski, Diana Pauly, Bernhard H Weber, Antonia M Joussen, Thomas Langmann, Peter F Zipfel, Christine Skerka
BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. The polymorphism rs10490924 in the ARMS2 gene is highly associated with AMD and linked to an indel mutation (del443ins54), the latter inducing mRNA instability. At present, the function of the ARMS2 protein, the exact cellular sources in the retina and the biological consequences of the rs10490924 polymorphism are unclear. METHODS: Recombinant ARMS2 was expressed in Pichia pastoris, and protein functions were studied regarding cell surface binding and complement activation in human serum using fluoresence-activated cell sorting (FACS) as well as laser scanning microscopy (LSM)...
January 5, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28071978/nup82-functions-redundantly-with-nup136-in-a-salicylic-acid-dependent-defense-response-of-arabidopsis-thaliana
#3
Kentaro Tamura, Yoichiro Fukao, Noriyuki Hatsugai, Fumiaki Katagiri, Ikuko Hara-Nishimura
The nuclear pore complex (NPC) comprises more than 30 nucleoporins (Nups). NPC mediates macromolecular trafficking between the nucleoplasm and the cytoplasm, but specific roles of individual Nups are poorly understood in higher plants. Here, we show that the novel nucleoporin unique to angiosperm plants (designated as Nup82) functions in a salicylic acid-dependent defense in a redundant manner with Nup136, which is a component of the nuclear basket in the NPC. Arabidopsis thaliana Nup82 had a similar amino acid sequence to the N-terminal half of Nup136 and a Nup82-GFP fusion was localized on the nuclear envelope...
January 10, 2017: Nucleus
https://www.readbyqxmd.com/read/28070672/opposing-effects-of-progranulin-deficiency-on-amyloid-and-tau-pathologies-via-microglial-tyrobp-network
#4
Hideyuki Takahashi, Zoe A Klein, Sarah M Bhagat, Adam C Kaufman, Mikhail A Kostylev, Tsuneya Ikezu, Stephen M Strittmatter
Progranulin (PGRN) is implicated in Alzheimer's disease (AD) as well as frontotemporal lobar degeneration. Genetic studies demonstrate an association of the common GRN rs5848 variant that results in reduced PGRN levels with increased risk for AD. However, the mechanisms by which PGRN reduction from the GRN AD risk variant or mutation exacerbates AD pathophysiology remain ill defined. Here, we show that the GRN AD risk variant has no significant effects on florbetapir positron emission tomographic amyloid imaging and cerebrospinal fluid (CSF) Aβ levels, whereas it is associated with increased CSF tau levels in human subjects of the Alzheimer's disease neuroimaging initiative studies...
January 9, 2017: Acta Neuropathologica
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
#5
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/28061864/identification-of-brassinosteroid-genes-in-brachypodium-distachyon
#6
Claudia Corvalán, Sunghwa Choe
BACKGROUND: Brassinosteroids (BRs) are steroidal phytohormones that are involved in diverse physiological processes and affect many important traits, such as plant stature, stress tolerance, leaf angle, fertility, and grain filling. BR signaling and biosynthetic pathways have been studied in various plants, such as the model dicot Arabidopsis thaliana; however, relatively little is known about these pathways in monocots. RESULTS: To characterize BR-related processes in the model grass Brachypodium distachyon, we studied the response of these plants to the specific BR biosynthesis inhibitor, propiconazole (Pcz)...
January 6, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/28060266/in-vivo-study-of-human-endothelial-pericyte-interaction-using-the-matrix-gel-plug-assay-in-mouse
#7
Ke Yuan, Mark E Orcholski, Ngan F Huang, Vinicio A de Jesus Perez
Angiogenesis is the process by which new blood vessels are formed from existing vessels. New vessel growth requires coordinated endothelial cell proliferation, migration, and alignment to form tubular structures followed by recruitment of pericytes to provide mural support and facilitate vessel maturation. Current in vitro cell culture approaches cannot fully reproduce the complex biological environment where endothelial cells and pericytes interact to produce functional vessels. We present a novel application of the in vivo matrix gel plug assay to study endothelial-pericyte interactions and formation of functional blood vessels using severe combined immune deficiency mutation (SCID) mice...
December 19, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28057640/murine-systemic-thrombophilia-and-hemolytic-uremic-syndrome-from-a-factor-h-point-mutation
#8
Yoshiyasu Ueda, Imran Mohammed, Delu Song, Damodar Gullipalli, Lin Zhou, Sayaka Sato, Yuan Wang, Shuchi Gupta, Zhongjian Cheng, Hong Wang, Jialing Bao, Yingying Mao, Lawrence Brass, X Long Zheng, Takashi Miwa, Matthew Palmer, Joshua Dunaief, Wen-Chao Song
Complement plays a key role in host defense but its dysregulation can cause autologous tissue injury. Complement activation is normally controlled by regulatory proteins including factor H (FH) in plasma and membrane cofactor protein (MCP) on the cell surface. Mutations in FH and MCP are linked to atypical hemolytic uremic syndrome, a type of thrombotic microangiopathy (TMA) that causes renal failure in patients. We describe here that disruption of FH function on the cell surface can also lead to disseminated complement-dependent macrovascular thrombosis...
January 5, 2017: Blood
https://www.readbyqxmd.com/read/28052346/properdin-deficiency-protects-from-5-fluorouracil-induced-small-intestinal-mucositis-in-a-complement-activation-independent-il-10-dependent-mechanism
#9
Umang Jain, Craig A Midgen, Trent M Woodruff, Wilhelm J Schwaeble, Cordula M Stover, Andrew W Stadnyk
Intestinal mucositis is a serious complication of chemotherapy that leads to significant morbidity that may require dose or drug adjustments. Specific mitigating strategies for mucositis are unavailable, partly due to an incomplete understanding of the pathogenic mechanisms. We have previously shown an effect of properdin, a positive regulator of complement activation, in models of colitis. Here we use properdin deficient (P(KO) ) mice to interrogate the role of properdin and complement in small intestinal mucositis...
January 3, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28049704/the-nucleotide-excision-repair-pathway-limits-l1-retrotransposition
#10
Geraldine Servant, Vincent A Streva, Rebecca S Derbes, Madushani I Wijetunge, Marc Neeland, Travis B White, Victoria P Belancio, Astrid M Roy-Engel, Prescott L Deininger
Long interspersed elements 1 (L1) are active mobile elements that constitute almost 17% of the human genome. They amplify through a "copy-and-paste" mechanism termed retrotransposition, and de novo insertions related to these elements have been reported to cause 0.2% of genetic diseases. Our previous data demonstrated that the endonuclease complex ERCC1-XPF, which cleaves a 3' DNA flap structure, limits L1 retrotransposition. Although the ERCC1-XPF endonuclease participates in several different DNA repair pathways, such as single-strand annealing, or in telomere maintenance, its recruitment to DNA lesions is best characterized in the nucleotide excision repair (NER) pathway...
January 2017: Genetics
https://www.readbyqxmd.com/read/28049128/immune-reconstitution-inflammatory-syndrome-associated-with-pulmonary-pathogens
#11
REVIEW
Radha Gopal, Rekha R Rapaka, Jay K Kolls
Immune reconstitution inflammatory syndrome (IRIS) is an exaggerated immune response to a variety of pathogens in response to antiretroviral therapy-mediated recovery of the immune system in HIV-infected patients. Although IRIS can occur in many organs, pulmonary IRIS, associated with opportunistic infections such as Mycobacterium tuberculosis and Pneumocystis jirovecii, is particularly associated with high morbidity and mortality. The pathology of IRIS is associated with a variety of innate and adaptive immune factors, including CD4(+) T-cells, CD8(+) T-cells, γδ T-cells, natural killer cells, macrophages, the complement system and surfactant proteins, Toll-like receptors and pro-inflammatory cytokines and chemokines...
January 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/28045880/targeted-complement-inhibition-protects-vascularized-composite-allografts-from-acute-graft-injury-and-prolongs-graft-survival-when-combined-with-subtherapeutic-cyclosporine-a-therapy
#12
Peng Zhu, Stefanie R Bailey, Biao Lei, Chrystal M Paulos, Carl Atkinson, Stephen Tomlinson
BACKGROUND: Recipients of vascularized composite allografts require aggressive and life-long immunosuppression, and since the surgery is usually performed in nonlife threatening situations, the development of strategies to minimize immunosuppression is especially pertinent for this procedure. We investigated how complement affects acute graft injury, alloimmunity, and immunosuppressive therapy. METHODS: Vascularized composite allografts were transplanted from Balb/C to C57BL/6 mice that were complement deficient (C3 or double C3a Receptor (R)/C5aR), or treated with a targeted complement inhibitor (CR2-Crry)...
December 30, 2016: Transplantation
https://www.readbyqxmd.com/read/28045448/molecular-cloning-characterization-and-functional-analysis-of-acetyl-coa-c-acetyltransferase-and-mevalonate-kinase-genes-involved-in-terpene-trilactone-biosynthesis-from-ginkgo-biloba
#13
Qiangwen Chen, Jiaping Yan, Xiangxiang Meng, Feng Xu, Weiwei Zhang, Yongling Liao, Jinwang Qu
Ginkgolides and bilobalide, collectively termed terpene trilactones (TTLs), are terpenoids that form the main active substance of Ginkgo biloba. Terpenoids in the mevalonate (MVA) biosynthetic pathway include acetyl-CoA C-acetyltransferase (AACT) and mevalonate kinase (MVK) as core enzymes. In this study, two full-length (cDNAs) encoding AACT (GbAACT, GenBank Accession No. KX904942) and MVK (GbMVK, GenBank Accession No. KX904944) were cloned from G. biloba. The deduced GbAACT and GbMVK proteins contain 404 and 396 amino acids with the corresponding open-reading frame (ORF) sizes of 1215 bp and 1194 bp, respectively...
January 2, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28040558/complement-in-autoimmune-diseases
#14
REVIEW
Pandiarajan Vignesh, Amit Rawat, Madhubala Sharma, Surjit Singh
The complement system is an ancient and evolutionary conserved element of the innate immune mechanism. It comprises of more than 20 serum proteins most of which are synthesized in the liver. These proteins are synthesized as inactive precursor proteins which are activated by appropriate stimuli. The activated forms of these proteins act as proteases and cleave other components successively in amplification pathways leading to exponential generation of final effectors. Three major pathways of complement pathways have been described, namely the classical, alternative and lectin pathways which are activated by different stimuli...
December 28, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28032637/nitrogen-limitation-adaptation-nla-is-involved-in-source-to-sink-remobilization-of-nitrate-by-mediating-the-degradation-of-nrt1-7-in-arabidopsis
#15
Wenwen Liu, Qing Sun, Kai Wang, Qingguo Du, Wen-Xue Li
Recent studies on nitrate transporters (NRTs) have greatly increased our knowledge of the mechanisms regulating nitrogen (N) homeostasis in plants. However, an understanding of how these NRTs are regulated is still lacking. The nitrogen limitation adaptation (nla) mutant is hypersensitive to N limitation. In the nla mutant, (15) N-nitrate spotted on old leaves preferentially accumulated in the youngest leaves. Analysis of leaf cross-sections indicated that NLA expression was expressed in the sieve element and companion cell system...
December 29, 2016: New Phytologist
https://www.readbyqxmd.com/read/28025641/itraq-based-proteomics-identification-of-serum-biomarkers-of-two-chronic-hepatitis-b-subtypes-diagnosed-by-traditional-chinese-medicine
#16
Jiankun Yang, Lichao Yang, Baixue Li, Weilong Zhou, Sen Zhong, Zhenhua Zhuang, Bin Yang, Maoshan Chen, Quansheng Feng
Background. Chronic infection with hepatitis B virus (HBV) is a leading cause of cirrhosis and hepatocellular carcinoma. By traditional Chinese medicine (TCM) pattern classification, damp heat stasis in the middle-jiao (DHSM) and liver Qi stagnation and spleen deficiency (LSSD) are two most common subtypes of CHB. Results. In this study, we employed iTRAQ proteomics technology to identify potential serum protein biomarkers in 30 LSSD-CHB and 30 DHSM-CHB patients. Of the total 842 detected proteins, 273 and 345 were differentially expressed in LSSD-CHB and DHSM-CHB patients compared to healthy controls, respectively...
2016: BioMed Research International
https://www.readbyqxmd.com/read/28025012/catabolism-of-c1-inhibitor-influences-the-response-to-replacement-therapy-in-hereditary-angioedema
#17
Marco Cicardi, Andrea Zanichelli, Chiara Suffritti, Maddalena A Wu, Thomas Machnig, Annalisa De Silvestri, Mario Regazzi, Carmine Tinelli
Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a disabling and life-threatening disease for which plasma-derived C1 inhibitor (pdC1-INH) is an effective treatment. Poor responses to pdC1-INH are rare. The aim of this prospective study was to evaluate the pharmacokinetics and pharmacodynamics of C1 inhibitor (C1-INH) in a C1-INH-HAE patient with poor response to treatment to investigate the mechanism underlying poor response to pdC1-INH. Seventeen C1-INH-HAE patients with normal responses to treatment served as retrospective controls...
December 23, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28008679/zxakt1-is-essential-for-k-uptake-and-k-na-homeostasis-in-the-succulent-xerophyte-zygophyllum-xanthoxylum
#18
Qing Ma, Jing Hu, Xiang-Rui Zhou, Hui-Jun Yuan, Tanweer Kumar, Sheng Luan, Suo-Min Wang
The inward rectifying K(+) channel AKT1 constitutes an important pathway for K(+) acquisition in plant roots. In glycophytes, excessive accumulation of Na(+) is accompanied by K(+) deficiency under salt stress. However, in the succulent xerophyte Zygophyllum xanthoxylum, which exhibits excellent adaptability to adverse environments, K(+) concentration remains at a relatively constant level despite increased levels of Na(+) under salinity and drought conditions. In this study, the contribution of ZxAKT1 to maintaining K(+) and Na(+) homeostasis in Z...
December 23, 2016: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28005826/porous-polyethylene-implant-as-aesthetic-complement-in-orthognathic-surgery
#19
Juliana Dreyer da Silva de Menezes, Lucas Borin Moura, Renato Parsekian Martins, Eduardo Hochuli-Vieira
Porous polyethylene implants have been used as an alternative in the treatment of patients with zygomatic and paranasal projections deficiency. These implants promote a facial rejuvenating effect due to the attenuation of the nasal and chin prominences. The advantages of porous polyethylene include biocompatibility, dimensional stability, easy adaptation and fixation, low complication rate, and its availability in different sizes and shapes. A 27-year-old woman presenting vertical deficiency associated with midface hypoplasia was treated with orthognathic surgery...
November 2016: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28005440/effect-of-a-single-dose-vitamin-d3-on-postprandial-arterial-stiffness-and-inflammation-in-vitamin-d-deficient-women
#20
Marijke A de Vries, Noëlle van der Meulen, Gert-Jan M van de Geijn, Boudewijn Klop, Ellen M van der Zwan, Lenneke Prinzen, Erwin Birnie, Elsbeth M Westerman, Wouter W de Herder, Manuel Castro Cabezas
CONTEXT: Cholecalciferol (vitamin D3) may improve vascular function and reduce inflammation, potentially providing an explanation for the proposed cardiovascular protection by vitamin D . OBJECTIVE: We investigated whether cholecalciferol supplementation reduces postprandial arterial dysfunction and inflammation. DESIGN: This was a randomized 1:1, double blind trial. SETTING: The study was conducted in the Diabetes and Vascular Center of the Franciscus Gasthuis, Rotterdam, The Netherlands...
December 22, 2016: Journal of Clinical Endocrinology and Metabolism
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