Search results for "C4A"

The human gene for mannan-binding lectin-associated serine protease-2 (MASP-2), the effector component of the lectin route of complement activation, …

2001

The proteases of the lectin pathway of complement activation, MASP-1 and MASP-2, are encoded by two separate genes. The MASP1 gene is located on chromosome 3q27, the MASP2 gene on chromosome 1p36.23-31. The genes for the classical complement activation pathway proteases, C1r and C1s, are linked on chromosome 12p13. We have shown that the MASP2 gene encodes two gene products, the 76 kDa MASP-2 serine protease and a plasma protein of 19 kDa, termed MAp19 or sMAP. Both gene products are components of the lectin pathway activation complex. We present the complete primary structure of the human MASP2 gene and the tight cluster that this locus forms with non-complement genes. A comparison of the …

Combined complete C5 and partial C4 deficiency in humans: clinical consequences and complement-mediated functions in vitro.

1990

A family is described with two siblings who suffered at different times from a single episode of meningococcal meningitis by Neisseria meningitidis groups B and C, respectively. In the two subjects, hemolytically active fifth component of complement (C5) was not detectable and antigenic C5 was less than 0.05% and less than 0.7% of normal, respectively. Repletion of sera by purified human C5 (70 micrograms/ml) restored total complement hemolytic activities. The asymptomatic first degree family members had C5 levels compatible with a heterozygous state of C5 deficiency. C4 allotyping revealed an inherited partial deficiency (Q0) of C4A and C4B in the family with a combined C4AQ0 and C4BQ0 het…

Genetic basis of human complement C4A deficiency. Detection of a point mutation leading to nonexpression.

1993

Abstract The fourth component of the human complement system (C4) is coded for by two genes, C4A and C4B, located within the MHC. Null alleles of C4 (C4Q0) are defined by the absence of C4 protein in plasma. These null alleles are due either to large gene deletions or to nonexpression of the respective genes. In a previous study, evidence was obtained for nonexpressed defective genes at the C4A locus, and for gene conversion at the C4B locus. To further characterize the molecular basis of these non-expressed C4A genes, we selected nine pairs of PCR primers from flanking genomic intron sequences to amplify all 41 exons from individuals with a defective C4A gene. The amplified products were s…

A NEW PCR-BASED TYPING OF THE RODGERS AND CHIDO ANTIGENIC DETERMINANTS OF THE FOURTH COMPONENT OF HUMAN COMPLEMEMT

1994

The Rodgers (Rg) and Chido (Ch) blood groups are antigenic determinants of the fourth component of human complement C4. They are associated with the two isotypes of C4, C4A and C4B, respectively. They serve as markers to distinguish C4A from C4B as well as for the definition of subtypes of common and rare allotypes. As an alternative to the serological typing method using human alloantisera, a PCR typing procedure with sequence-specific primers (PCR-SSP) was designed. The method was tested on selected DNA samples from individuals with well-defined C4 allotypes. No false-positive or false-negative typing results were obtained and all the determinant combinations could be distinguished. The P…

Bgl II restriction fragment length polymorphism of human complement C4A gene coincides with BF*F allele of factor B.

1988

Beneficial effects of C1 esterase inhibitor in ST-elevation myocardial infarction in patients who underwentsurgical reperfusion: a randomized double-…

2007

Background: The inflammatory cascade has been hypothesized to be an important mechanism of post-ischaemic myocardial reperfusion injury and several studies demonstrated that C1 esterase inhibitor (C1 -INH) is effective in post-ischaemia myocardial protection. Therefore, we aimed to investigate prospectively in a randomised double-blind study the cardioprotective effects of C1-INH in ST segment elevation myocardial infarction (STEMI) in patients who underwent emergent reperfusion with coronary artery bypass grafting (CABG). Methods: In this study, we enrolled 80 patients affected with STEMI who underwent emergent CABG. Patients were assigned in two groups (C1-INH group: receive 1000 Ul of C1…

Disruption of Slc4a10 augments neuronal excitability and modulates synaptic short-term plasticity

2015

Slc4a10 is a Na(+)-coupled Cl(-)-HCO3 (-) exchanger, which is expressed in principal and inhibitory neurons as well as in choroid plexus epithelial cells of the brain. Slc4a10 knockout (KO) mice have collapsed brain ventricles and display an increased seizure threshold, while heterozygous deletions in man have been associated with idiopathic epilepsy and other neurological symptoms. To further characterize the role of Slc4a10 for network excitability, we compared input-output relations as well as short and long term changes of evoked field potentials in Slc4a10 KO and wildtype (WT) mice. While responses of CA1 pyramidal neurons to stimulation of Schaffer collaterals were increased in Slc4a1…

Possible protective role for C-reactive protein in atherogenesis: complement activation by modified lipoproteins halts before detrimental terminal se…

2004

Background—Previous work indicated that enzymatically remodeled LDL (E-LDL) might activate complement in atherosclerotic lesions via a C-reactive protein (CRP)–dependent and CRP-independent pathway. We sought to substantiate this contention and determine whether both pathways drive the sequence to completion.Methods and Results—E-LDL was prepared by sequential treatment of LDL with a protease and cholesteryl esterase. Trypsin, proteinase K, cathepsin H, or plasmin was used with similar results. Functional tests were used to assess total complement hemolytic activity, and immunoassays were used to demonstrate C3 cleavage and to quantify C3a, C4a, C5a, and C5b-9. E-LDL preparations activated …

Null alleles of human complement C4. Evidence for pseudogenes at the C4A locus and for gene conversion at the C4B locus

1990

The two genes for the C4A and C4B isotypes of the fourth component of human complement are located in the MHC class III region. Previous studies have demonstrated the unusual expression of C4 genes in the form of aberrant or duplicated haplotypes. Null alleles of C4A or C4B (AQ0 or BQ0) have been defined by the absence of gene products and occur at frequencies of 0.1-0.3. However, only some C4 null alleles are due to gene deletions, the remainder were thought to be nonexpressed genes. We have analyzed the C4 gene structure of 26 individuals lacking either C4A or C4B protein. The DNA of individuals with apparently nonexpressed C4 genes was tested for the presence of C4A- and C4B-specific seq…

Rapid and Standardized Quantitation of Hemolytic Activity of the Fourth Component of Human Complement

1990

Based on a method that uses the fourth component of complement (C4)-deficient guinea pig serum to quantify the hemolytic activity of C4, we developed an assay that allows the processing of a large number of individual samples with high reproducibility. In contrast to the conventional procedure using titration curves of each sample to be determined, we can show that a single appropriate dilution of the sample allows accurate quantitation of hemolytic activity. The reliability of the procedure is demonstrated using either C4A- or C4B- deficient and normal individual samples.