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J Goetz

Publications and source records attributed to J Goetz.

At least 37 records · Page 2Linked to original sources
PubMed1989

Molecular basis of complete C4 deficiency. A study of three patients.

The highly polymorphic fourth component of human complement (C4) is usually encoded by two genes, C4A and C4B, adjacent to the 21-hydroxylase (21-OH) genes and is also remarkable by the high frequency of the null alleles, C4A*Q0 and C4B*Q0. Complete C4 deficiency is exceptional because this condition appears only in homozygotes for the very rare double-null haplotype C4AQ0,BQ0. This condition in most cases gives rise to systemic lupus erythematosus and an increased susceptibility to infections. The molecular basis for complete C4 deficiency has not yet been established. Therefore we studied the DNA of three previously described C4 deficient patients belonging to unrelated families by restriction fragment length polymorphism analysis using C4 and 21-OH probes. These studies revealed a deletion of the C4B and 21-OHA genes in two patients and no deletion at all in the third patient. Therefore, complete C4 deficiency as a result of homozygosity for the C4AQ0, BQ0 haplotype is not a consequence of a deletion of the C4 genes. The molecular basis of this genetic abnormality is certainly very complex and may vary also from one case to another.

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↗
PubMed1988

Differential utilization of the same reading frame in a Xenopus homeobox gene encodes two related proteins sharing the same DNA-binding specificity.

Xenopus XlHbox 1 produces two transcripts during early development. One encodes a long open reading frame (ORF) and the other a short ORF sharing the same homeodomain, but differing by an 82 amino acid domain at the amino terminus. The long protein amino terminus is conserved with many other homeodomain proteins, and its absence from the short protein could have functional consequences. Some viral genes also utilize a single ORF to encode transcription factors of antagonistic functions. The overall organization of the homologous genes in frog and man is similar, supporting the notion that both transcripts are of functional significance. Studies on XlHbox 1 function show that the region common to the long and short proteins has a sequence-specific DNA-binding activity, and that microinjection of specific antibodies into embryos results in the loss of structures derived from cells normally expressing XlHbox 1.

Amino Acid Sequence↗
PubMed1988

Antigenic determinants expressed by human C4 allotypes; a study of 325 families provides evidence for the structural antigenic model.

The antigenic determinants of human C4 have been defined by human IgG antisera, Rodgers (Rg) and Chido (Ch), in hemagglutination-inhibition assays (HAI). Eight (2 Rg and 6 Ch) are of high frequency, greater than 90%, and 1, WH, is of low frequency, 15%. The phenotypic combinations are complex; generally, C4A expresses Rg, and C4B has Ch, but reverse antigenicities have been established both by HAI and by sequence data of selected C4 allotypes. A study of 325 families provides data on the antigenic expression of each C4 allotype and demonstrates strong associations. A structural model for the antigenic determinants of C4 proteins has been proposed and is completely supported by the family material. Of the 16 possible antigenic combinations for C4 proteins, only 3 are undetected. A new Ch combination has been recorded in two French families. The reported sequence variation within the C4d region can account for the antigenic determinants but leaves the location of electrophoretic variation in C4 still unclear.

Blood Group Antigens↗
PubMed1988

Complement C4 phenotypes in dementia of the Alzheimer type.

Complement C4 phenotype distribution was studied in 64 patients with dementia of the Alzheimer type. In contrast to reported findings we failed to find a significant association between C4B2 gene frequency and Alzheimer's dementia.

Alzheimer Disease↗
PubMed1988

[Polymorphism of C4 and factor B in type I diabetes].

The haplotypic frequencies of the fourth component of complement (C4) and factor B (Bf) have been determined in 44 Alsatian type 1 diabetics. An increased frequency of the rare allele Bf F1 (9.1% vs 1.5%) and of the silent alleles of C4 (C4 AQO: 21.6% vers 15.5% -C4 BQO: 29.6% vs 16.0%) was observed in diabetics in comparison to the general population of the same geographic area. A complete HLA haplotype determination has been obtained in 24 type 1 French diabetics. Three haplotypes were associated with the diabetic susceptibility: HLA-A30 CW5 B18 BfF1 C4A3BQO DR3 (18.75% vs 0.86%), HLA-A1 CW7 B8 BfS C4AQOB1 DR3 (15.58% vs 4.17%), HLA-A2 CW3 BW62 BfS C4A3B3 DR4 (6.25% vs 0.45%). The authors suggest that the silent alleles of C4 could modulate the expression of the diabetic susceptibility genes by lowering of the serum C4 hemolytic activity.

Alleles↗
PubMed1987

Heterogeneity in the structural basis of the human complement C4A null allele (C4A Q0) as revealed by HindIII restriction fragment length polymorphism analysis.

The highly polymorphic fourth component of human complement (C4) is usually encoded by two genes. C4A and C4B, adjacent to the 21-hydroxylase (21-OH) genes, 21-OHA and 21-OHB, and is also remarkable in the high frequency of the 'null' alleles, C4A Q0 and C4B Q0. The molecular basis for the C4A Q0 allele was studied in 26 families through restriction fragment length polymorphism (RFLP) analysis with C4 and 21-OH cDNA probes after digestion of the DNA with the endonuclease HindIII. The individuals expressing the extended haplotype HLA-A1 (of A2) Cw7 B8 C2C BfS C4AQ0B1 DR3 have a large deletion taking off the C4A and 21-OHA genes.

Alleles↗
PubMed1987

[Components of the classical complement pathway in systemic lupus erythematosus].

Measurements of complement components in sera from patients with systemic lupus erythematosus (SLE) and some of their relatives indicated that decreased levels of CH50, C4 and C2 were mostly related to a genetic deficiency at one or both of the loci coding for C4, at least in those patients in whom decreased C4 levels were associated with normal C1 hemolytic activity. C4 deficiency is either isolated or associated with complement activation. In some patients with C4 deficiency, complement activation could only be demonstrated by measuring plasma level of the C3 cleavage fragment, C3a des Arg. Decreased concentration and/or hemolytic activity of C4 and C2 in SLE cannot be used to assess the activity of the disease.

Complement Activation↗
PubMed1987

The study of a French family with two duplicated C4A haplotypes.

The finding of two duplicated C4A haplotypes in a normal French family led to a detailed study of their C4 polymorphism. The father had an extremely rare A*6A*11, B*QO haplotype inherited by all of his children and the mother had the more common A*3A*2, B*QO haplotype. Two HLA identical daughters only have four C4A alleles. The father's A11 allotype expresses Ch:1 (Chido) rather than Rg:1 (Rodgers) and represents a new Ch phenotype Ch:1,-2,-3,-4,-5,-6. In order to clarify the genetic background in this unusual family, DNA studies of restriction fragment length polymorphisms (RFLPs) were undertaken. The father's rare haplotype, which expresses two C4A allotypes, results from a long and a short C4 gene normally associated with the A*6, B*1 that also exhibits the Bg/II RFLP. As it travels in an extended MHC haplotype HLA A2, B57(17), C2*C, BF*S, DR7 that is most frequently associated with A*6, B*1, we postulate that the short C4B has been converted in the alpha chain region to a C4A gene which produces a C4A protein. This report of a short C4A gene is the first example in the complex polymorphism of C4.

Alleles↗
PubMed1986

Lupus erythematosus panniculitis with partial genetic deficiency of C2 and C4 in a child.

A 7-year-old girl developed recurrent febrile nodules and subcutaneous plaques on her arm, shoulder, and face. Primary acquired toxoplasmosis was diagnosed at onset, because of associated lymphadenopathy and detection of specific IgM. Skin lesions were responsive to therapy with systemic steroids but progressed to atrophy and poikiloderma within a few months. Subsequently, chloroquine therapy has been instituted and no relapse has occurred. Histopathologic findings and direct immunofluorescence studies were diagnostic of lupus erythematosus panniculitis. Electron microscopy showed lamellar inclusions within mast cells. Results of laboratory investigations disclosed leukopenia and hypocomplementemia with low C2 serum levels. A family study of the complement system, including C4 and Bf phenotyping and HLA A, B, and DR haplotyping, revealed the carriage of both C2 and C4A null alleles in the propositus. This observation suggests an additional link between lupus erythematosus panniculitis and the remainder of the lupus erythematosus clinical spectrum.

Adolescent↗
PubMed1985

[Drugs inhibiting complement activation].

Complement may be activated by anaesthetic agents as well as contrast media, and so could anaphylactoid reactions be induced. Efficient and harmless complement blocking agents were still lacking. The only agents actually used by anaesthetists were steroids and/or antifibrinolytic drugs. Other agents were not indicated in surgical patients because of their adverse effects and the impossibility of giving them by the intravenous route.

Adrenal Cortex Hormones↗
PubMed1985

Detection of the genetic polymorphism of human C2 (native protein and C2a fragment) by immunoblotting after polyacrylamide gel isoelectric focusing.

The polymorphism of the second component of human complement (C2) was studied by means of isoelectric focusing in polyacrylamide gels followed by immunoblotting with a specific antihuman C2 antibody. The polymorphism was studied in native C2 and in the C2a fragment obtained by activation of the classical pathway with heat-aggregated human IgG. Serum samples previously typed with the hemolytic overlay technique were analyzed. They comprised samples of homozygous C2*C, C2*B, C2*Q0, heterozygous C2*BC and C2*CQ0 individuals. The patterns obtained by immunoblotting corresponded to those obtained by the hemolytic overlay technique. As expected, the homozygous C2*Q0 sample (complement C2 deficiency) did not show any band pattern. The C2a fragment presented also a polymorphic variation which correlated exactly with the native C2 polymorphism. It appears thus that the polymorphic site of the C2 protein is carried by the C2a fragment for the C2*C and C2*B variants. In addition, this method is easier to perform than the common hemolytic overlay technique and the rare C2-deficient serum is not needed.

Complement C2↗
PubMed1983

Genetic deficiency of C4 presenting with recurrent infections and a SLE-like disease. Genetic and immunologic studies.

A young girl presenting with recurrent pulmonary infections and atypical lupus erythematosus was totally deficient in C4. In one sister, also deficient in C4, the same symptoms developed. Results of family studies were consistent with an autosomal recessive mode of transmission and with linkage of the genes determining C4 deficiency to those of the major histocompatibility complex. The patient's serum and red cells were Chido- and Rodgers-negative. Humoral and cellular immunity were normal, except for a low lymphocyte response in mixed lymphocyte culture. The cellular function of the patient's polymorphonuclear leukocytes was normal, for both phagocytosis and bactericidal activity using Candida albicans. However, in the presence of C4-deficient serum, opsonin generation and bactericidal indexes were diminished. These defects were completely reversible upon addition of purified C4.

Child, Preschool↗
PubMed1983

HLA A*, B*-BF* and C4 A*, B* allele associations, with special reference to BF*S07, in the Tunisian population.

The HLA A*2, Bw*50-BF*S07-C4 A*2, B*1 linkage group was transmitted unambiguously in four unrelated Tunisian families. In one of these, another allele association, also carrying BF*S07, HLA A*9, Bw*50-BF*S07-C4 A*1, B*1, was encountered. The previously reported linkage disequilibrium between BF*S07 and HLA Bw*50, a subtypic specificity of HLA Bw*21, is confirmed in our study. The C4 A*2, B*1 haplotype, rare in the other populations until now studied, seems more frequent in Tunisia since it has been also found linked to HLA A*11, B*27 and BF*S in one of these families. Other allele associations were unambiguously demonstrated with predominantly the C4 A*3, B*1 haplotype, particularly a rare HLA A*3, B*18-BF*F1-C4 A*3, B*1 linkage group. A silent gene at the C4 A locus was found linked to HLA B*8.

Alleles↗