20 research outputs found
Proteins of the Factor H protein family bind to C-reactive protein and regulate complement activity on apoptotic and necrotic host cells
No full textThe complement system protects the host against foreign organisms and induces a non-inflammatory phagocytosis of damaged or mutated host cells. Complement regulators protect intact host cells against complement attack and prevent inflammatory reactions. Factor H is the main soluble regulator of the alternative complement pathway. Factor H binds to host cells and blocks the alternative complement activation to prevent cell- and tissue damages. In addition, Factor H binds the acute phase protein C-reactive protein (CRP). CRP opsonizes apoptotic and necrotic host cells and microbial invaders for phagocytosis by activating the classical complement cascade. However, the amplification loop via the alternative pathway and the pro-inflammatory terminal complement pathway are inhibited. Here I analyzed the role of Factor H binding to CRP in this limitation of complement. Furthermore, the Factor H related (CFHR) proteins CFHR-1, CFHR-4A, and CFHR-4B, which have a high similarity to Factor H, were functionally characterized. In this work I show, that Factor H, CFHR 4A, and CFHR-4B bind different isoforms of CRP. Factor H binds monomeric CRP (mCRP), while CFHR-4A/4B bind pentameric CRP (pCRP). Moreover, the analyzed proteins of the Factor H protein family regulate complement at the surface of cellular debris. Factor H and CFHR 1 inhibit complement and protect cellular debris from inflammatory complement attack, while CFHR 4A/4B enhance the cell opsonization through recruitment of pCRP. In addition, Factor H enhances the phagocytosis of apoptotic particles and inhibits the release of the pro-inflammatory cytokine TNF-αand the chemokine IL-8. These effects of Factor H are enhanced by mCRP. Thus, Factor H, CFHR-1, CFHR-4A/4B, and CRP maintain a beneficial balance between complement activation and inhibition which is crucial to prevent inflammation and ultimately the development of autoimmune diseases
Dependence of gradient moment based descriptors on affine distortions of the differentiating kernel
No full textComplement analysis 2016 : Clinical indications, laboratory diagnostics and quality control
No full textIn recent years, complement analysis of body fluids and biopsies, going far beyond C3 and C4, has significantly enhanced our understanding of the disease process. Such expanded complement analysis allows for a more precise differential diagnosis and for critical monitoring of complement-targeted therapy. These changes are a result of the growing understanding of the involvement of complement in a diverse set of disorders. To appreciate the importance of proper complement analysis, it is important to understand the role it plays in disease. Historically, it was the absence of complement as manifested in severe infection that was noted. Since then complement has been connected to a variety of inflammatory disorders, such as autoimmune diseases and hereditary angioedema. While the role of complement in the rejection of renal grafts has been known longer, the significant impact of complement. In certain nephropathies has now led to the reclassification of some rare kidney diseases and an increased role for complement analysis in diagnosis. Even more unexpected is that complement has also been implicated in neural, ophtalmological and dermatological disorders. With this level of involvement in some varied and impactful health issues proper complement testing is clearly important; however, analysis of the complement system varies widely among laboratories. Except for a few proteins, such as C3 and C4, there are neither well-characterized standard preparations nor calibrated assays available. This is especially true for the inter-laboratory variation of tests which assess classical, alternative, or lectin pathway function. In addition, there is a need for the standardization of the measurement of complement activation products that are so critical in determining whether clinically relevant complement activation has occurred in vivo. Finally, autoantibodies to complement proteins (e.g. anti-C1q), C3 and C4 convertases (C3 and C4 nephritic factor) or to regulatory proteins (e.g. anti-Clinhibitor, anti-factor H) are important in defining autoimmune processes and diseases based on complement dysregulation. To improve the quality of complement laboratory analysis a standardization commmittee of the International Complement Society (ICS) and the International Union of Immunological Societies (IUIS) was formed to provide guidelines for modern complement analysis and standards for the development of international testing programs.</p
The Rationale of Complement Blockade of the MCPggaac Haplotype following Atypical Hemolytic Uremic Syndrome of Three Southeastern European Countries with a Literature Review
No full textWe present eight cases of the homozygous MCPggaac haplotype, which is considered to increase the likelihood and severity of atypical hemolytic uremic syndrome (aHUS), especially in combination with additional risk aHUS mutations. Complement blockade (CBT) was applied at a median age of 92 months (IQR 36–252 months). The median number of relapses before CBT initiation (Eculizumab) was two. Relapses occurred within an average of 22.16 months (median 17.5, minimum 8 months, and maximum 48 months) from the first subsequent onset of the disease (6/8 patients). All cases were treated with PI/PEX, and rarely with renal replacement therapy (RRT). When complement blockade was applied, children had no further disease relapses. Children with MCPggaac haplotype with/without additional gene mutations can achieve remission through renal replacement therapy without an immediate need for complement blockade. If relapse of aHUS occurs soon after disease onset or relapses are repeated frequently, a permanent complement blockade is required. However, the duration of such a blockade remains uncertain. If complement inhibition is not applied within 4–5 relapses, proteinuria and chronic renal failure will eventually occur
Hemolytic uremic syndrome with Mycoplasma pneumoniae infection and membrane cofactor protein mutation : case report
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Design of an embedded microcomputer based mini quadrotor UAV
No full textThis paper describes the design and realization of a mini quadrotor UAV (Unmanned Aerial Vehicle) that has been initiated in the Systems and Control Laboratory at the Computer and Automation Research institute of the Hungarian Academy of Science in collaboration with control departments of the Budapest University of Technology and Economics. The mini quadrotor UAV is intended to use in several areas such as camera-based air-surveillance, traffic control, environmental measurements, etc. The paper focuses upon the embedded microcomputer-based implementation of the mini UAV, describes the elements of the implementation, the tools realized for mathematical model building, as well as obtains a brief outline of the control design
Annual Incidence and Severity of Acute Episodes in Hereditary Thrombotic Thrombocytopenic Purpura.
No full textHereditary thrombotic thrombocytopenic purpura (hTTP) is a rare thrombotic microangiopathy characterized by severe congenital ADAMTS13 deficiency and recurring acute episodes causing morbidity and premature death. Information on the annual incidence and severity of acute episodes in hTTP patients is largely lacking. This study reports prospective data of 87 patients from the Hereditary TTP Registry (ClinicalTrials.gov NCT01257269) for survival, frequency and severity of acute episodes from enrollment until December 2019. The 87 patients, followed for median 4.2 years (range 0.01-15), had a median age at overt disease onset and at clinical diagnosis of 4.6 years and of 18 years (range 0.0-70 for both), respectively. Forty-three patients received regular plasma prophylaxis, while 22 did not, and treatment changed over time or was unknown in the remaining 22. Forty-three patients experienced 131 acute episodes of which 91 (69%) occurred in patients on regular prophylaxis. This resulted in an annual incidence of acute episodes of 0.36 (95%CI 0.29-0.44) with and of 0.41 (95%CI 0.30-0.56) without regular plasma treatment. More than one third of acute episodes (n=51) were documented in children 40 years of age (1.18 [95% CI 0.88-1.55] vs. 0.14 [95% CI 0.08-0.23]). Prophylactic plasma infusion regimens used were insufficient to prevent acute episodes in many patients. Such regimens are burdensome, caregivers, patients and their guardians are reluctant to start regular plasma infusions, from which particularly children would benefit
SP730PREEMPTIVE PLASMA THERAPY AND ECULIZUMAB RESCUE FOR ATYPICAL HEMOLYTIC UREMIC SYNDROME RELAPSE FOLLOWING KIDNEY TRANSPLANTATION
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