SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
A study of the family of a patient who had an SLE-like syndrome and an extremely low serum C4 revealed an inheritance of C4 types and HLA region markers which indicated that the patient had 60--70% of "normal" C4 level prior to the onset of disease. Thus the extremely low C4 level during her disease may result from a combination of genetically determined low normal C4 and increased consumption/hyposynthesis secondary to her SLE.
The frequency of duplicated and non-expressed C4 alleles was determined by segregation analysis in 31 German and five French families with altogether 274 individuals by submitting the complete data from C4 protein phenotyping, including C4 beta chains, and the other classical MHC markers to the family analysis programme (FAP). From 120 unrelated German haplotypes the following frequencies were derived for silent alleles: C4A*Q0 0.2000, C4B*Q0 0.2083, and for the total of homo- and heteroduplicated C4A resp. C4B alleles: C4"DA"* 0.1333, C4"DB"* 0.1000. The true occurrence of the duplicated C4A*2, "DB*21" haplotype, first observed in French families, was found to be 0.0250 in the German sample. While the frequency of duplicated C4 haplotypes confirms earlier estimates, the increase in the frequency of silent alleles corresponds to those assumed from investigations at the DNA level. The results demonstrate classical protein typing with inclusion of C4 beta chain types to be an indispensable and powerful tool for haplotype recognition; they support the hypothesis that deletion at one C4 locus is accompanied by duplication at the other in a majority of haplotypes.
Twenty-five Tunisian families were analyzed for their complement alleles in order to detect duplications at the C4 loci. In this population, the most characteristic duplications are C4A2, B1.12 or C4A1, B1,12 always associated with BFS07 and C2C. This previously undescribed C4B1,12 duplication was found in seven families, five times in association with HLA-A2, B50.
We have shown that the first component of complement C1 is present in an active form on the surface of washed human peripheral lymphocytes but not on platelets or erythrocytes. This active C1 (C-1) was detected by its ability to transfer to sensitized cells carrying C4, i.e., EAC4, forming EAC-1,4. Active C1 was also able to consume C4. Treatment of these lymphocytes with 0.02 M EDTA removed C-1. EDTA-treated lymphocytes were able to bind exogenous purified human C-1. Comparative studies with sentized erythrocytes (EA) and EDTA treated lymphocytes showed that although fewer molecules of exogenous C1 could bind to the EDTA-treated lymphocytes than to EA, the consumption of C4 by C-1 bound to lymphocytes was significantly higher than that observed with EAC-1. When lymphocytes obtained from 2 patients with chronic lymphocytic leukemia and hypocomplementemia were tested, the release of C1, the C4 consumption and the binding of C-1 to EDTA-treated cells were highly inefficient.
Activation of the alternative pathway of complement by Candida albicans was examined using a chemotactic assay. Two serologically defined strains and eight clinical isolates of Candida albicans were used in these experiments. The results showed that all ten strains of Candida albicans were capable of alternative complement pathway activation. These findings may provide an insight into host resistance to this infection.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Tryptic digests of acid-treated Fc from normal human IgG were separated into four peaks (I-IV) by gel filtration on Sephadex G-100. The second peak was further divided into two fractions (II and II'). Peak I was indistinguishable from intact Fc on electrophoresis, immunodiffusion, and reactivity to protein A. The protein A reactive fragments of fractions II, II', and III were shown to contain antigenic determinants of both the CH2 and CH3 domains, to interact with the anti-Gm (1) specific rheumatoid factor, and to fix complement. These results, together with SDS-electrophoresis, showed that protein A reactive fragments are all composed of an intact Fc chain with shorter chains covalently linked to it. The protein A non-reactive fragments of fractions II' and III were homogeneous, fixed complement and showed no interaction with the Gm (1) rheumatoid factor. These results, in addition to the observed antigenic determinants, localized the fragments to the CH2 region.
The uptake of aggregated IgG by type 12, M protein positive (M + ve) streptococci was high in the presence of fresh serum, while the uptake by type 12, M-ve, type 1 and type 2, M + ve or M-ve streptococci was inhibited. Serum heated to 56 degrees C for 30 min inhibited the uptake of aggregated IgG by all strains tested. Purified C1q or macromolecular C1 added to heat-treated serum restituted the uptake of aggregated IgG. It was shown that C1 and C4 in fresh serum influenced the uptake of aggregated IgG by streptococci, resulting in the distinct reaction patterns observed.
Complement-dependent serum-mediated cytotoxicity (CDC) was measured in a 51-chromium release assay against autologous tumor cells from 7 non-invasive and 9 invasive transitional-cell tumors of the urinary bladder. CDC was demonstrated against tumor cells from invasive tumors. Heat-inactivation of autologous sera lead to complete loss of cytotoxicity. There were no differences in CDC of autologous sera from patients and allogenic sera from controls. The cytotoxic response seems to be strongly dependent on the target cell. CDC was significantly reduced by use of an allogenic C 2 deficient serum. Direct immunofluorescence did not reveal any tumor cell associated immunoglobulins of IgG or IgM classes. Indirect immunofluorescence with autologous heat-inactivated sera demonstrated in most cases both IgG and IgM attachment to the tumor cells, but there were no obvious relations between indirect immunofluorescence and CDC. Absorption of allogenic sera to trypsin- or neuraminidase-treated erythrocytes did not affect CDC of these sera against invasive tumor targets. The results indicate a complement-dependent cytotoxicity against target cells from invasive bladder tumors. Complement seems to be activated through the classical pathway, but the possible role of naturally-occurring antibodies against invasive tumor targets is not clarified.
Rg and Ch typing was performed, by serum inhibition, on 145 families that had been typed for HLA/C4/BF/C2 with a view to assessing partial inhibition (p.i.) of anti-Rg/Ch and its haplotype associations. Rg p.i. was found predominantly with the C4A*3A*2,B*QO homoduplicated C4 haplotype and BFF. The original type of Ch p.i. (Nordhagen et al., 1980) was closely associated with the allotype C4B 2, which also occasionally exhibited complete inhibition (c.i.), but this Ch p.i. was also found with the C4A*1,B*QO haplotype (Rittner et al., 1984a). The second type of Ch p.i. (Giles, 1984) was closely associated with the C4B 1 allotype most frequently in the haplotype C4A*6,B*1 but also with C4A*3,B*1. Both types of Ch p.i. are usually found with BF S. The present data indicate that the determinants of Rg and Ch are not directly related to any particular C4 allotype or extended haplotype. Further examples of C4A 1 with Ch and C4B 5 without Ch determinants have been detected and theoretical considerations are discussed as to how they might have arisen from unequal crossovers in homologous regions that result in hybrid protein molecules.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Tuberculosis is the leading cause of death due to an infectious organism, killing an estimated 3 million people annually. Mycobacterium tuberculosis, the causative agent of tuberculosis, and other pathogenic mycobacteria require entry into host macrophages to initiate infection. An invasion mechanism was defined that was shared among pathogenic mycobacteria including M. tuberculosis, M. leprae, and M. avium but not by nonpathogenic mycobacteria or nonmycobacterial intramacrophage pathogens. This pathway required the association of the complement cleavage product C2a with mycobacteria resulting in the formation of a C3 convertase. The mycobacteria-associated C2a cleaved C3, resulting in C3b opsonization of the mycobacteria and recognition by macrophages.
Interleukin-1 (IL-1) is a product of mononuclear phagocytes that mediates changes characteristic of the response to inflammation or tissue injury (the acute-phase response). One of two structurally and functionally homologous major histocompatibility complex (MHC) class III genes encodes a positive acute-phase protein, complement factor B. The closely linked complement C2 gene is not affected during the acute-phase response. Purified human IL-1, pH 7.0, and recombinant-generated murine IL-1, pH 5.0, increased the expression of factor B and other positive acute-phase proteins in human hepatoma cells but decreased the expression of albumin, a negative acute-phase reactant. Furthermore, in a murine fibroblast L-cell line transfected with cosmid DNA bearing the human C2 and factor B genes, IL-1 mediated a reversible dose- and time-dependent increase in factor B expression in the transfected cells. Expression of the C2 gene was not affected by IL-1. The effect of IL-1 on factor B expression involves a mechanism acting at a pre-translational level as demonstrated by an increase in specific messenger RNA content and a corresponding increase in biosynthesis and secretion of factor B. The structural basis and mechanism for selective and independent regulation of these genes provides insight into the molecular control of the inflammatory response.