Biomedical subjects

G Mauff

Publications and source records attributed to G Mauff.

At least 19 recordsLinked to original sources

PubMed1992

Improvement of BF typing and of BF F subtyping after neuraminidase treatment in the unconverted and converted factor B.

When neuraminidase-treated sera are analyzed by agarose gel isoelectric focusing, the factor B (BF) banding pattern is reduced to predominantly one major band without cathodically positioned bands. This not only makes unequivocal typing of BF allotypes possible but also the reliable distinction of all BF F subtype phenotypes with delimitation of "BF F subtype variants". With this new method, serum aging affects the BF determination to a lesser extent than when applying methods that separate native sera. We show that sialylation is not responsible for the BF F subtype polymorphism. All of the investigated BF allotype bands, including those characteristic of the subtypes, show functional hemolytic activity. The banding pattern after removal of neuraminic acid residues ranges from pH 6.8 to 7.3 for factor B, from pH 5.3 to 5.9 for the Ba fragment, and from pH 8.2 to 8.7 for the Bb fragment. The protein structure of factor B is also discussed. Eliminating the superimposition of bands in different BF allotypes, as demonstrated by these methods, proved to be necessary for the detection of hypomorphic BF gene products (BF QL), which are expressed by assumed BF*Q0 alleles in heterozygous genotypes. This allows investigation of BF*Q0 alleles on a protein level, which complements molecular genetic approaches.

Blood Preservation↗

PubMed1992

Apparently non-expressed alleles of factor B (BF) code for hypomorphic proteins.

In three families with an apparent non-expressed factor B (BF) allele (BF*Q0), advanced methods of isoelectric focusing for the determination of BF F subtypes revealed different hypomorphic BF products (BF QL) with functional hemolytic activity expressed by the assumed BF*Q0 allele. A Taq I and a Msp I restriction fragment length polymorphism as well as the Ba fragment of the expression products showed banding patterns for the BF*QL alleles corresponding to BF S types, whereas an altered Bb fragment was seen in two BF QL products. In one family an intragenic recombination site within the Bb part of the BF gene was assumed. Investigations of factor B and its conversion fragments, as demonstrated by the used methods, allow to complement molecular genetic investigations of BF*Q0 alleles in heterozygous genotypes on a protein level. We conclude that apparently non-expressed alleles of factor B code for hypomorphic but functionally active proteins.

Alleles↗

PubMed1991

Association of major histocompatibility complex class III complement components C2, BF, and C4 with Brazilian paracoccidioidomycosis.

A genetic influence of the major histocompatibility complex (MHC) on the susceptibility and the development of the different clinical forms of paracoccidioidomycosis (PCM) has been postulated. In the present investigation allotypes of MHC-coded class III gene products (complement components C2, BF, C4A, and B) were determined in 69 Brazilian PCM patients and 225 healthy control individuals matched for ethnic and geographic origin. The frequency of the non-expressed C4B allele (C4B*Q0) was significantly elevated in comparison to the controls (p less than 0.01; Fisher's exact test). Three out of 69 patients had a complete C4B deficiency as against 2 among 223 control individuals. The C4A*Q0 allele was also more frequent in the patients. Other C4 alleles were not seen to differ between the two groups. The analysis of BF allotypes showed a non-significant predominance of the rarer allele BF*S07 in the patients, whereas no difference in the distribution of C2 alleles was seen. The data on MHC class III association may support the hypothesis of immune response modulation in PCM and suggest a functional genetic role of complement action against the fungus and in the outcome of PCM infection. We conclude that MHC class III products, especially C4B*Q0, are associated with chronic uni- or multifocal PCM and may influence the course of the infection.

Adolescent↗

PubMed1990

Restriction fragment length polymorphism for the identification of Campylobacter jejuni-isolates.

Companion animals ("pets") are occasionally carriers of organisms pathogenic for man. In the present, study fecal samples of clinically inapparent animals with direct contact to 204 patients, suffering from campylobacter enteritis, were investigated for C. jejuni or C. coli (CJC). CJC positive animals were seen in the environment of only five patients (= 2.4%). By comparison of biotypes and serotypes of thermostable and thermolabile antigens from human and animal isolates no clear epidemiological relationship could be deduced. Using chromosomal DNA of the strains, genetic identity of the isolates was studied for HaeIII-restriction fragment length polymorphism (RFLP), applying a biotinylated commercial CJ probe. The probe was found to be specific for most CJ strains and revealed a pattern of one to four bands. In contrast to biotyping no identity of patient strains and animal isolates was seen in three cases; one case with different biotypes had identical RFLP patterns; one patient CJ strain did not show any pattern with the CJ probe. Serotypes were identical for a larger number of animal strains but differed in HaeIII RFLP and vice versa. Comparing the results from the different technological approaches it seems impossible to give a clear statement on the epidemiology of campylobacter infections or carrier state by biotyping alone. It is concluded that DNA RFLP patterns are a useful additional tool, but for epidemiological analysis a set of different methods should be used.

Animals↗

PubMed1990

Major histocompatibility complex class I to III allotypes in patients with AIDS-related complex/Walter-Reed 5, disseminated Kaposi's sarcoma and in normal controls. The ARC-IVIG Study Group.

In HIV-infected patients major histocompatibility complex (MHC) class I and II (= HLA-A, B, C, DR) association has been controversial. Of the MHC class III coded complement components C2, BF, C4A/C4B especially C4 allotypes appear of major immunogenetic relevance for their potential differences in virus neutralizing potency and immune complex formation. In the present study 29 patients with AIDS-related complex and Walter-Reed 5 ARC/WR5), 35 patients with disseminated Kaposi's sarcoma (KS), and 160 HIV-negative control individuals were compared for MHC class I to III allotypes. Diagnosis of ARC and KS (WR criteria) was done by clinical and laboratory parameters, MHC testing, by standard procedures. An increase in frequency (p less than or equal to 0.05) was observed between ARC/WR5 patients and controls for HLA-B35/CW4, DRW14, a decrease for B16, CW6/DR7. However, values were not significant if corrected for the number of tested antigens. No significant differences were seen between KS and ARC patients or controls for class III allotypes, nor for previously reported associations, e.g. for B8, DR2, DR3, and especially DR5, including the DR5 splits DRW11, 12. The results indicate the lack of a strong MHC association with the investigated antigens in West German Caucasoids, and support the hypothesis of ethnic dependence of HIV-related diseases. The HLA-B35/CW4 increase, also associated with the duplicated C4 A*3 A*2 and the silent C4B*Q0, was more pronounced in ARC patients with progression to AIDS-OI. The increased frequency of C4B*Q0 alleles in these patients was thought to be secondary to a hypothetical increase in 'converted' and dysregulated C4 genes not seen to be associated in this study.

AIDS-Related Complex↗

PubMed1990

Lymphocyte proliferation in AIDS-related complex/Walter-Reed 5 patients: response to herpes simplex virus and tuberculin antigen and mitogen during intravenous immunoglobulin treatment. The ARC-IVIG Study Group.

In a randomized, controlled double-blind study, 15 patients with AIDS-related complex/Walter-Reed 5 (ARC/WR5) were compared during 6 months intravenous immunoglobulin (IVIG) treatment (0.4 g/kg body weight every 2 weeks) with 15 placebo-treated patients. This study was aimed at the lymphocyte response to T and B cell mitogens and antigens. 3H-thymidine uptake was determined after stimulation with the unspecific mitogens phytohemagglutinin (PHA), pokeweed mitogen (PWM), formalinized Staphylococcus aureus-Cowan I (SAC), and with the antigens tuberculin and herpes simplex virus (HSV) at the onset, on days 85, 183, 267 and 351; IgG and IgM antibodies against HSV were measured by ELISA. In addition, 30 untreated HIV-negative controls were tested. For the T cell mitogen PHA, T-cell-dependent B cell mitogen PWM and B cell mitogen SAC, no differences between the two patient groups were observed before therapy nor in the course of therapy or the 6-month observation period thereafter. The entire patient group showed significantly impaired mitogenic response on day 1 as compared to the controls. There was no significant difference in response to tuberculin between the patients and HIV-negative controls, nor for both patients groups before and in the course of treatment. All patients had IgG antibodies against HSV. Three of them showed blastogenic lymphocyte response to HSV on day 1. Among 19 seropositive controls, 7 individuals showed positive HSV lymphocyte response; but for both patient groups, there was no significant difference before and in the course of the treatment and observation period.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Complex↗

PubMed1990

Complement levels and circulating immune complexes in a controlled, longitudinal, multicentre study on effects of intravenous immunoglobulin in adults with AIDS-related complex/Walter-Reed 5. The ARC-IVIG Study Group.

The complement system, as the effector mechanism of the antigen-antibody reaction, and the levels of circulating immune complexes in a 1-year, double-blind, randomized, placebo-controlled study served as laboratory parameters to assess the effect of long-term high-dose intravenous immunoglobulin (IVIG) therapy in 30 adult patients (2 x 15) with AIDS-related complex/Walter-Reed 5 (ARC/WR5). We obtained no evidence of an adverse effect in such patients of high-dose IVIG administered over a 6-month period: none of the parameters studied showed a significant difference between the two groups of patients. In both groups, using data before the first infusion or using data of the whole study, a correlation between circulating immune complexes and classical complement pathway activation was found. The most striking increase was seen in the two groups of patients for functional serum factor D. The accumulation of serum factor D was not paralleled by an increase in serum creatinine. In patients with disease progressing from ARC to AIDS within the study period, an accumulation of serum factor D was not more or less pronounced than in those who remained in the ARC stage. Accumulation of factor D was not related to the clinical score as assessed in this study.

AIDS-Related Complex↗

PubMed1990

Factor B reference typing report.

In a factor B (BF) Reference Typing of the VIth Complement Genetics Workshop and Conference, Mainz, FRG, 1989, 99 samples from 13 laboratories, including 18 families, were investigated with the majority of presently known typing procedures. Among the major ('standard') allotypes BF SO4 was found to be new. For the group of common BF F subtypes samples from 11 laboratories including complete family data from 5 laboratories were compared. The subtypes BF FA and FB were recognized and confirmed to be identical in the samples from all groups. Within a third group rare subtype variants of F and S were compared and characterized. In samples submitted from individuals with assumed non-expressed (BF*QO) alleles unexpected and hypomorphic gene products were seen. The investigation of DNA samples for restriction fragment length polymorphisms from the same set of individuals revealed a correlation of the Msp I 0.7-kb fragment with BF F, and confirmed the correlation of a Taq I 6.6-kb fragment with BF FA.

Alleles↗

PubMed1990

C4 reference typing report.

Human C4 is most polymorphic at the protein level, distinction between allotypes of the C4A and C4B proteins resting on electrophoretic migration patterns and difference in hemolytic activity. The aim of the C4 reference typing has been the definition of reference variants, the assignment of rare variants, and the investigation of duplicated, deleted, or non-expressed and hybrid genes. Samples from 136 individuals, predominantly with known segregation, from 16 laboratories were investigated by standard electrophoretic techniques, for their relative hemolytic activity, reactivity with monoclonal antibodies and Rg/Ch reagents, alpha-, and beta-chain types, relative electrophoretic migration distance, as well as the C4/21-OH-TaqI RFLPs. The results were evaluated in three groups; they consisted in the definition of the eight most common C4 alleles, and the ten Rg/Ch standard phenotypes in group I. In group II twelve C4A and fourteen C4B duplications among 96 complotypes, as well as eighteen deleted/non-expressed C4A and twenty-two C4B alleles, and hybrid alleles were seen by correlation of lytic activity, electrophoretic mobility, and monoclonal and/or Rg/Ch reactivity. Group III consisted of the newly defined allotypes A 8, A 7, A 58, A 55, A 45, B 45, B 35, and B 22, furthermore of alleles subdividing the A 1/A 91, and the B 13/B 12/B 11 regions. The reference typing has allowed reclassification of the majority of described C4 allotypes and resulted in a revision of the C4 nomenclature.

Blood Grouping and Crossmatching↗

PubMed1990

C6 reference typing report.

Various C6 protein allotypes were examined using polyacrylamide gel isoelectric focusing followed by immunoblotting or hemolytic overlay. For several 'difficult' allotypes, neuraminidase treatment of samples and long-distance isoelectric focusing gels were applied. Nineteen different allotypes were distinguished besides the two common allotypes C6 A and C6 B. They were designated basically according to the previous statement on C6 nomenclature [Mauff et al., 1980].

Complement C6↗

PubMed1990

Factor B (BF) nomenclature statement.

A common nomenclature for factor B (BF) allotypes is recommended as a result of the BF Reference Typing of the VIth Complement Genetics Workshop and Conference, Mainz, FRG, 1989. It has generally been agreed that the alphanumeric BF nomenclature according to Mauff et al. should also be used in the future for all major BF allotypes distinguishable by standard agarose gel electrophoresis (AGE). The common BF F subtypes and further described rarer subtype variants are not detectable by standard AGE. Therefore, the nomenclature had to be extended. For the subtypes of BF F an alphabetical designation with capital letters will now be used: FA and FB. The designation of the five rarer subtype variants was modified after the reference typing to FB1, FB2, SB1, SB2, and SB3. Hyposynthetic variants detected in samples with previously assumed non-expressed (BF*Q0) alleles are now designated as SQL, M1QL, and M2QL, HQL' characterizing their lower concentration.

Complement Factor B↗

PubMed1990

C4 nomenclature statement (1990).

A common and revised nomenclature of the allotypes of the fourth component (C4) of human complement has been proposed. It is based on the results of the C4 Reference Typing of the VIth Complement Genetics Workshop and Conference, Mainz, FRG, 1989, the previous C4 nomenclature and the guidelines for human gene nomenclature (ISGN). The designation of allotypes derives from their relative electrophoretic mobility, the distinction between C4A and C4B proteins from their relative hemolytic activity. Common alleles retain their single digit numeric designation, intermediate variants their two- or three-digit designations; newly discovered alleles should not interfere with already described variants. At least 13 C4A alleles, 16 C4B alleles as well as non-expressed genes at each C4 locus are presently known. There are also duplicated loci of each C4 gene; they should be designated by repetition of the locus symbol at the haplotype or genotype level. As a phenotype they will be placed in parenthesis without repetition of the locus symbol. Aberrant allotypes or hybrid genes should be explained by a special suffix. No special nomenclature is recommended for restriction fragment length polymorphisms. Their designation should follow the general rules of the ISGN.

Alleles↗

PubMed1990

Relative electrophoretic migration distances for the classification of C4 allotypes.

For the definition of common C4 allotypes relative electrophoretic migration (RM) values were determined. A set of standard C4 variants were investigated by prolonged agarose gel electrophoresis and subsequent immunofixation with specific antiserum. RM distances were measured by laser densitometry. Using an arbitrary standard of 100 units for the migration distance between the C4B 1 and C4A 3 bands a total deviation of +/- 6.45% in more than 108 single determinations was found. The common C4 alleles used for standardization were C4A*6, C4A*4, C4A*3, C4A*2, C4B*5, C4B*3, C4B*2, C4B*1. In addition, side by side comparison and admixture of known variants will be necessary for the differentiation of some of the closely migrating allotypes. RM values are now available for eight alleles frequently found in all populations for future comparison and designation of newly discovered C4 allotypes.

Complement C4↗

PubMed1990

Early onset sensorineural hearing loss: association studies with major histocompatibility class III (complement) markers.

In 39 families with at least one child suffering from moderate or severe bilateral sensorineural hearing loss (SNHL), major histocompatibility complex (MHC) class III complement phenotypes were retrospectively determined by standard methods; MHC class I segregation data was also available. The families were treated in the Hospital for Communication Disorders and selected for the HLA-B16 and B18 specificities, respectively. Haplotype and allele frequencies were derived from segregation analysis in the families. From 31 unrelated children with random and familiar forms of SNHL significant deviations in the distribution were seen for the following MHC class III alleles using as a control population 60 German healthy individuals: duplicated C4A alleles (C4"DA") p = 0.009, silent C4A alleles (C4A*Q0) p = 0.006, duplicated heavy C4 beta-chain alleles (C4 beta"DHH") p = 0.0003, and silent C4 beta-chain alleles (C4 beta*Q0) p = 0.0075. In serum samples from patients with an assumed genetic disposition according to clinical criteria indications for an association were found for C4"DA" (p = 0.03), C4A*Q0 (p = 0.003), C4B*3 (p = 0.046), C4 beta"DHH" (p = 0.004), and C4 beta*Q0 (p = 0.02). The underrepresentation of C4A*Q0 may be an indicator for aberrant or duplicated C4 alleles on the same haplotype or exhibit a protection mechanism for acquiring the inheritable forms of early onset SNHL.

Adolescent↗

PubMed1989

Human BF*F-subtypes: segregation analysis with inclusion of MHC haplotypes.

The segregation of factor B(BF)F subtypes was analyzed in conjunction with other MHC markers in 15 families with 89 offspring. Informative data for BF F subtypes were obtained from 11 families, 6 of them with known recombinant individuals for the HLA-B/DR/GLO region. The subtypes did not contribute further to the localization of the cross-overs, but followed the known segregation of conventional BF allotypes. In 2 families of one kinship, the recognition of heterozygous BF*FAFB individuals could be established following the inclusion of three generations. The rarer of the two BF F subtype alleles, BF*FA, is positively associated with the HLA haplotypes BW62, CW3, C4A*3 and A29, CWX, B44, C4A*3, B*1, DR7. BF F subtypes are regarded as a very useful additional tool for studies of MHC organization and disease association.

Alleles↗

PubMed1989

The BF F subtypes are detectable in the Ba fragment of factor B.

The unanimous recognition of the two subtypes FA and FB of the BF*F allele has repeatedly been challenged. In the present investigation we are reporting about the unequivocal and simple detection of the subtypes on the Ba fragment of factor B by immunofixation isoelectric focusing after conversion with inulin. The common BF phenotypes F, S, and FS could be diagnosed in addition to the subtypes of BF*F which were observed in two regions acidic of the F major band. By comparison of standard phenotypes the subtypes in the Ba fragment corresponded to those of native factor B. All BF bands could be attributed to the Ba fragment by developing Western Blots with monoclonal antibodies directed against Ba. The distribution of the major BF phenotypes and alleles and the BF F subtypes in a population sample of 527 unrelated individuals from F.R.G. was in Hardy-Weinberg equilibrium. The allele frequency was determined to be 0.0731 for BF*FA, and 0.1053 for BF*FB. The advantages of determining the subtypes on the Ba fragment are: broadening of the FA/FB corridor, a more reliable diagnosis of phenotypes, improved distinction between homozygous FA and heterozygous FAFB types, and recognition of common BF phenotypes as well as subtypes in aged sera. It is suggested that the problem in the designation of BF F subtypes by different groups should be resolved by an international reference typing.

Alleles↗

PubMed1989

An estimate on the frequency of duplicated haplotypes and silent alleles of human C4 protein polymorphism. I. Investigations in healthy Caucasoid families.

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.

Alleles↗

PubMed1989

[Serological diagnosis of Campylobacter jejuni infections].

Antibody level to Campylobacter in 28 sera of patients of whom Campylobacter infection was confirmed by germ isolation from feces was tested. The investigation was performed using passive haemagglutination technique and as antigens heated and acid glycine extraction prepared from homologous and reference strains. For the method used the heated antigen proved to be superior. Out of 28 tested patients of whom 92.8% were children, 8 sera were positive, 9 doubtful and 9, derived mainly from neonates (0-14 month of age), were negative.

Adult↗