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.
Using specific immune sera, C7, C9, and C3 activator were detected in sera from human fetuses more than 16 weeks old and in newborn samples. Levels of C9 in cord sera ranged between 10 and 30% of those present in sera from adult subjects. The mean value of Ce activator was about half that in maternal blood. The mean level of C7 in newborns was nearly 70% of the amount in normal adults.
A 20-year old man had three episodes of meningococcal meningitis. Complement assays showed a complete deficiency of the seventh component of the complement system. This case emphasizes the need to perform complement assays in young patients with recurrent bacterial meningitis.
Explore the source record for details and available documents.
The serum of a 29-year old woman with a recent episode of disseminated gonococcal infection and a history of meningococcal meningitis and arthritis as a child was found to lack serum hemolytic complement activity. The seventh component of complement (C7) was not detected by functional or immunochemical assays, whereas other components were normal by hemolytic and immunochemical assessment. Her fresh serum lacked complement-mediated bactericidal activity against Neisseria gonorrhoeae, but the addition of fresh normal serum or purified C7 restored bactericidal activity as well as hemolytic activity. The absence of functional C7 activity could not be accounted for on the basis of an inhibitor. Opsonization and generation of chemotactic activity functioned normally. Complete absence of C7 was also found in one sibling who had the clinical syndrome of meningococcal meningitis and arthritis as a child and in this sibling's clinically well eight-year-old son. HLA histocompatibility typing of the family members did not demonstrate evidence for genetic linkage of C7 deficiency with the major histocompatibility loci. This report represents the first cases of C7 deficiency associated with infectious complications and suggests that bactericidal activity may be important in host defense against bacteremic neisseria infections.
The serum of a 44-yr-old woman of French-Canadian descent having a B-27 positive ankylosing spondylitis was deficient in the seventh component of complement (C7) as determined by hemolytic and immunochemical methods. No inhibitor against C7 was detected, and the levels of all other complement components were normal. No deficiency in the opsonic activity of the serum was found, and the results of basic coagulation studies of the plasma were normal. On investigation of the patient's family, two sisters were found to have the same deficiency but were otherwise in good health. The seven other siblings were heterozygous for C7 deficiency, while the paternal aunt had a normal C7 level. In the third generation, six children of the three homozygous sisters and five children of heterozygotes were available for testing. Studies of the HLA antigens in all the 22 subjects and in three spouses indicated no close linkage between the CM deficienty and the HLA system. In addition, the simultaneous occurrence of two hereditary complement deficiencies (C2 and C7) was discovered in one family of this remarkable kindred.
Distributions of complement phenotypes, C6, C7, and C8(1) were studied using thin agarose gel isoelectric focusing (AGIEF) or ultra-thin polyacrylamide gel isoelectric focusing (PAGIEF) and subsequent immunoblotting techniques in 203 Chinese Han population in Liaoning Province of northeast China. The gene frequencies were as follows: C6*A 0.4704, C6*B 0.5049, C6*B2 0.0148, C6*B3 0.0049, and C6*M 0.0049; C7*1 0.8251, C7*2 0.1108, C7*3 0.0320, and C7*4 0.0320; C8(1)*A 0.5567 and C8(1)B 0.4433, respectively. All the observed numbers of the phenotypes were in agreement with the expected numbers under the Hardy-Weinberg equilibrium. The gene frequencies among Chinese subpopulations and other various populations were compared.
In this report we describe the linkage between genes encoding human complement components C6, C7, and C9. Polymorphisms have been described at the DNA level for the C7 and C9 genes. We have studied 20 individuals by Southern blot analysis with four C6 cDNA subclones to detect restriction fragment length polymorphisms (RFLPs). We have found a Taq I polymorphism defined by two alleles of 8.0 (C6 H) and 6.0 (C6 L) kilobases (kb). RFLP segregation for the C6, C7, and C9 loci in informative families allowed us to estimate the maximum Lod scores at a recombination fraction of theta = 0.0 (C6-C7), theta = 0.0 (C7-C9), and theta = 0.0 (C6-C9). Significant linkage disequilibrium was found between C6 and C7 and between C7 and C9 loci in directly determined haplotypes of unrelated parents. Data from this study show that the genes encoding the human terminal complement components C6, C7, and C9 define a cluster in the short arm of chromosome 5. We propose that the clusters involving the C8A and C8B and the C6, C7, and C9 genes be referred to as MACI and MACII, respectively.
A new method for the isolation of C6 and C7 by affinity chromatography of human serum with anti-C6 and anti-C7 coupled to Sepharose is described. C6 and C7 prepared by this method are hemolytically fully active, homogeneous proteins obtained in 25% yield. A comparison of the properties of isolated C6 and C7 gave the following results: The amino acid composition of the two proteins is very similar. The m.w. calculated from the amino acid content is 124,800 for C6 and 120,800 for C7. Both components are single chain glycoproteins migrating upon electrophoresis at pH 8.6 as beta 2-globulins, Both proteins are polymorphic as detected by isoelectrofocusing in polyacrylamide gels and range in their isoelectric points from pH 6.15 to 6.7. The UV spectra reveal only minor differences; the extinction coefficients are: EC6 = 1.71 cm2 X mg-1 and EC7 = 1.92 cm2 X mg-1. CD-spectra show 8% alpha-helix and 10% beta-structure for C6 and 10% alpha-helix and 14% beta-structure for C7. The structural similarities of C6 and C7 suggest their evolution from a common ancestral gene.
Seventeen patients with sporadic meningococcal meningitis, registered in Fukuoka city, were studied for complement deficiency. Four of the seventeen had a selective deficiency of the ninth component of the complement (C9), four had a deficiency of the seventh component of the complement (C7), and one had a deficiency of the fifth component of the complement (C5) as determined by both hemolytic and antigenic assay. Family studies suggested that these complement deficiencies in the present study were hereditary. Based on the incidence (0.036% of homozygous C9 deficiency in Fukuoka (171 C9 deficient individuals of 475, 886 blood donors), we have concluded that patients with C9 deficiency are more susceptible to meningococcal meningitis than normal individuals (p less than 0.001). In addition, the present study further supports that complement deficiency is common in patients with sporadic meningococcal meningitis.
C7 M/N typing, the determination of the complement component C7 M/N phenotypes, was successfully used in family studies to trace haplotypes bearing C7 deficiency genes. Furthermore, it was shown to be preferable to C7 allotyping based on isoelectric focusing (IEF) since it distinguishes two common alleles (C7*M and C7*N), whereas one common C7 IEF allele (C7*1) predominates in most populations. It is also the more sensitive method, as it enabled detection of very low amounts of abnormal C7 molecules in the third generation of a combined subtotal C6/C7-deficient subject and thus confirmed that this partial deficiency gene is not silent in heterozygotes. In this respect C7 M/N typing is even more informative than DNA restriction fragment length polymorphism typing which will assess the presence but not necessarily the functional status of a gene. C6 and C7 genes are tightly linked and therefore C7 M/N typing was also applied to tracing C6 deficiency genes in families. C6/C7 haplotype analysis of South African C6-deficient (C6Q0) subjects revealed a strong allelic association of C6*Q0 and C7*M.
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.
The possible contribution of additional immunologic variables to the susceptibility of late complement component-deficient individuals to meningococcal disease has not been systematically examined in previous studies. Thus, we studied three groups of patients: (1) 24 healthy individuals, (2) 8 complement-sufficient individuals with a history of recurrent bacterial meningitis, and (3) 19 complement-deficient individuals with prior meningococcal infection. No statistical differences were noted among the three groups for the following parameters: the absolute number and the percentage of lymphocytes; CD3+, CD4+, CD8+, CD20+, and CD16+ cells; and the CD4+/CD8+ ratio. The concentration of C4 and circulating immune complexes was also similar among the groups. The concentrations of IgG, IgM, and IgA were slightly, but significantly, decreased in the complement-deficient individuals. Of interest, the coefficient of spontaneous and lipopolysaccharide-stimulated activation of neutrophils was significantly depressed in the deficient individuals. We hypothesize that the terminal complement components may participate in maximal neutrophil activation.
Explore the source record for details and available documents.
Resealed erythrocyte ghosts have been used to define the kinetics of tracer exchange across the membrane-bound terminal complex of the complement cascade (C5b-9). Under steady-state conditions and at net chemical equilibrium, C5b-9 ghosts showed no significant lysis above control levels as measured by hemoglobin efflux. In 1 mM sucrose at 37 degrees C, [14C]sucrose isotopic exchange diffusion into C5b-9 ghosts occurred at 4.8 (+/- 0.5, SEM) X 10(-20) mol sec-1 per functional lesion, equivalent to an apparent permeability coefficient of 4.8 X 10(-14) cm3 sec-1 for the single C5b-9 lesion. No significant uptake of [14C]sucrose above control levels was observed in C5b67 ghosts. The apparent rate of tracer permeation through the complement lesion is one to two orders of magnitude slower than predicted by a model of a transmembrane channel of dimensions permitting free diffusion of sucrose. The data support earlier assertions from this laboratory that diffusion of small molecules across the complement lesion in biological membranes is significantly restricted.
Lipid vesicles carrying the purified membrane C5b-9 complex [C5b-9(m)] of complement were analyzed immunochemically and in the electron microscope after treatment with a combination of trypsin and alpha-chymotrypsin. Under reducing conditions, the externally oriented annulus was removed. The remaining part of the C5b-9(m), representing approximately half of the total mass of the macromolecular complex, was visualized in the electron microscope as a hollow cylindrical structure with walls of 1-nm thickness. This structure remained tenaciously attached to the lipid bilayer, projecting 8-9 nm from the external membrane surface into the aqueous environment. Cleavage of C5b-9(m) by proteolysis and reduction resulted in a sharp reduction of tis antigenic determinants. One hydrophilic protease-resistant C5 derivative was released from the membrane and recovered in the fluid phase. The membrane-bound residue almost totally lacked antigens precipitable with antisera to C5, C6, C9, and C5b-9(m).