Search results for "Complement"
showing 10 items of 2113 documents
Angioedema due to acquired C1-inhibitor deficiency: spectrum and treatment with C1-inhibitor concentrate
2018
Abstract Background Acquired angioedema due to C1-inhibitor (C1-INH) deficiency (AAE-C1-INH) is a serious condition that may result in life-threatening asphyxiation due to laryngeal edema. It is associated with malignant B-cell lymphoma and other disorders. The purpose of this study was to describe the characteristics and associated disorders of patients with AAE-C1-INH and assess the efficacy of plasma-derived C1-INH concentrate (pdC1-INH) in the treatment of AAE-C1-INH. Forty-four patients with AAE-C1-INH from the Angioedema Outpatient Service of Mainz were assessed for associated disorders. In 32 of these patients, the duration of swelling attacks was measured before and after treatment …
Prognostic Implications of the Complement Protein C1q in Gliomas
2019
The contribution of the complement system in the pathophysiology of brain cancers has been recently considered in light of its well-known involvement in carcinogenesis. Complement system represents an important component of the inflammatory response, which acts as a functional bridge between the innate and adaptive immune response. C1q, the first recognition subcomponent of the complement classical pathway, has recently been shown to be involved in a range of pathophysiological functions that are not dependent on complement activation. C1q is expressed in the microenvironment of various types of human tumors, including melanoma, prostate, mesothelioma, and ovarian cancers, where it can exer…
The complex alteration in the network of IL-17-type cytokines in patients with hereditary angioedema
2018
Hereditary angioedema (HAE) is a rare autosomic-dominant disorder characterized by a deficiency of C1 esterase inhibitor which causes episodic swellings of subcutaneous tissues, bowel walls and upper airways that are disabling and potentially life-threatening. We evaluated n = 17 patients with confirmed HAE diagnosis during attack and remission state and n = 19 healthy subjects. The samples were tested for a panel of IL (Interleukin)-17-type cytokines (IL-1β, IL-6, IL-10, granulocyte–macrophage colony stimulating factor (GM-CSF), IL-17, IL-21, IL-22, IL-23) and transforming growth factor-beta (TGF-β) subtypes. Data indicate that there are variations of cytokine levels in HAE subjects compar…
Genetic prediction of ICU hospitalization and mortality in COVID‐19 patients using artificial neural networks
2021
There is an unmet need of models for early prediction of morbidity and mortality of Coronavirus disease-19 (COVID-19). We aimed to a) identify complement-related genetic variants associated with the clinical outcomes of ICU hospitalization and death, b) develop an artificial neural network (ANN) predicting these outcomes and c) validate whether complement-related variants are associated with an impaired complement phenotype. We prospectively recruited consecutive adult patients of Caucasian origin, hospitalized due to COVID-19. Through targeted next-generation sequencing, we identified variants in complement factor H/CFH, CFB, CFH-related, CFD, CD55, C3, C5, CFI, CD46, thrombomodulin/THBD, …
Mating systems and protein–protein interactions determine evolutionary rates of primate sperm proteins
2013
To assess the relative impact of functional constraint and post-mating sexual selection on sequence evolution of reproductive proteins, we examined 169 primate sperm proteins. In order to recognize potential genome-wide trends, we additionally analysed a sample of altogether 318 non-reproductive (brain and postsynaptic) proteins. Based on cDNAs of eight primate species (Anthropoidea), we observed that pre-mating sperm proteins engaged in sperm composition and assembly show significantly lower incidence of site-specific positive selection and overall lower non-synonymous to synonymous substitution rates ( d N / d S ) across sites as compared with post-mating sperm proteins involved in capac…
Prevention of Hereditary Angioedema Attacks with a Subcutaneous C1 Inhibitor
2017
Prevenció; Atac d'angioedema; Inhibidor C1 Prevención; Ataque de angioedema; Inhibidor C1 Prevention; Angioedema attack; C1 inhibitor BACKGROUND: Hereditary angioedema is a disabling, potentially fatal condition caused by deficiency (type I) or dysfunction (type II) of the C1 inhibitor protein. In a phase 2 trial, the use of CSL830, a nanofiltered C1 inhibitor preparation that is suitable for subcutaneous injection, resulted in functional levels of C1 inhibitor activity that would be expected to provide effective prophylaxis of attacks. METHODS: We conducted an international, prospective, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, phase 3 trial to evaluate the …
Evaluation of low dose anaphylatoxic peptides in the pathogenesis of the adult respiratory distress syndrome (ARDS). Monitoring of early C5a effects …
1986
A guinea-pig in vivo model is presented that allows the infusion of purified C5a via a central vein catheter and the monitoring of its effects on granulocytes and platelets, the most important cells in the pathogenesis of several lung disorders, e.g. shock lung. After the infusion of C5a, which was adjusted to a quantity that caused slight and transient alterations of lung physiology, granulocytes disappeared from circulation within 1 min. Simultaneously the granulocyte content of the lung increased about three-fold as judged by histological evaluations. Morphologic destructions were not observed. After the drop a rebound of circulating Polymorpho-nuclear leucocytes (PMN) occurred, which wa…
Identification and characterization of a gene encoding a putative mouse Rho GTPase activating protein gene 8, Arhgap8.
2003
Rho GTPase activating proteins promote the intrinsic GTP hydrolysis activity of Rho family proteins. We isolated a putative mouse ortholog of the human Rho GTPase activating protein 8, ARHGAP8. The open reading frame encodes a peptide of 387 amino acids with high homology to human ARHGAP8 in its N-terminal domain. Both radiation hybrid mapping and fluorescent in situ hybridization localized the gene to mouse chromosome 15E. The 23 kb genomic Arhgap8 sequence consists of eight exons and seven introns. Northern blot and RT-PCR analyses showed that a transcript of approximately 1.9 kb is ubiquitously expressed in various adult mouse tissues with particularly strong expression in kidney.
Vascular Leakage in Severe Dengue Virus Infections: A Potential Role for the Nonstructural Viral Protein NS1 and Complement
2006
Background Vascular leakage and shock are the major causes of death in patients with dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Thirty years ago, complement activation was proposed to be a key underlying event, but the cause of complement activation has remained unknown. Methods The major nonstructural dengue virus (DV) protein NS1 was tested for its capacity to activate human complement in its membrane-associated and soluble forms. Plasma samples from 163 patients with DV infection and from 19 patients with other febrile illnesses were prospectively analyzed for viral load and for levels of NS1 and complement-activation products. Blood and pleural fluids from 9 patient…
The international WAO/EAACI guideline for the management of hereditary angioedema – the 2017 revision and update
2018
Hereditary Angioedema (HAE) is a rare and disabling disease. Early diagnosis and appropriate therapy are essential. This update and revision of the global guideline for HAE provides up-to-date consensus recommendations for the management of HAE. In the development of this update and revision of the guideline, an international expert panel reviewed the existing evidence and developed 20 recommendations that were discussed, finalized and consented during the guideline consensus conference in June 2016 in Vienna. The final version of this update and revision of the guideline incorporates the contributions of a board of expert reviewers and the endorsing societies. The goal of this guideline up…