Biomedical subjects

R Bütler

Publications and source records attributed to R Bütler.

At least 19 recordsLinked to original sources

PubMed2001

A worldwide analysis of AG molecular diversity inferred from serology.

Ten population samples from different geographic origins were tested serologically for the AG polymorphism of human beta-lipoproteins. Their haplotype frequencies were used with previously published data to perform a wide analysis of AG genetic differentiations throughout the world. Coancestry coefficients were computed from weighted F(ST)s among populations by using a matrix of molecular distances among AG haplotypes, which is here determined on the basis of DNA studies. Coancestry coefficients derived from unweighted F(ST)s and more classical Prevosti distances were computed on the same data and used for a comparison. In all cases a highly significant correlation was found between genetics and geography on a worldwide scale, while the significance of the correlation with linguistics differed. A test of significance of the pairwise F(ST)s among populations also gave different results depending on whether the molecular distance matrix among AG haplotypes was included. Globally, this study shows that in spite of being highly significantly correlated to each other, different genetic distance measures can lead to different interpretations of the same data set. Moreover, the elucidation of the molecular models related to the presently known serological polymorphisms may represent an additional tool for analyzing such polymorphisms in human population genetics studies.

Amino Acid Substitution↗

PubMed1995

Two new immunogenetic polymorphisms of the apoB gene and their effect on serum lipid levels and responses to changes in dietary fat intake.

In previous studies, apoB polymorphisms have been shown to modify serum lipid responses to changes in dietary fat intake. The functionally important apoB DNA change or changes underlying these effects have, however, remained unknown. Using a single-strand conformation polymorphism analysis-based screening method, we identified two previously unreported apoB polymorphisms located close to each other in the 5' region of apoB gene exon 26. This DNA segment corresponds to the binding site of monoclonal anti-apoB antibody D7.2. The two A-->G changes at apoB cDNA nucleotides 5869 and 5896 produced an Asn-->Ser change at amino acid 1887 and a His-->Arg change at amino acid 1896. In the Finnish population, allele frequencies of the rare alleles of the apoB 1887 (Asn-->Ser) and apoB 1896 (His-->Arg) polymorphisms were .02 and .11, respectively. Both polymorphisms were shown to have an independent effect on the binding affinity of LDL with monoclonal antibody D7.2. The effect of these polymorphisms on serum lipid levels and responses to changes in dietary fat intake in 102 healthy free-living subjects was assessed. The apoB 1896 Arg allele was associated with a higher serum LDL cholesterol level during a low-fat, low-cholesterol diet in men.

Alleles↗

PubMed1992

Two amino acid substitutions in apolipoprotein B are in complete allelic association with the antigen group (x/y) polymorphism: evidence for little recombination in the 3' end of the human gene.

We report the identification of an A-to-G base change, in exon 29 of the apolipoprotein B (apo B) gene, that results in the substitution of serine for asparagine at residue 4311 of mature apo B100. In a recent publication, Huang et al. have reported a C-to-T base change in exon 26 that causes the substitution of leucine for proline at residue 2712 of apo B. We have found complete linkage disequilibrium between the alleles at both these sites and an immunochemical polymorphism of LDL designated antigen group (x/y) (Ag(x/y)) in a sample of 118 Finnish individuals. This implies that either one of these substitutions--or both of them combined--could be the molecular basis of the Ag(x/y) antigenic determinants, with the allele encoding serine4311 plus leucine2712 representing the Ag(x) epitope, and that encoding asparagine4311 plus proline2712 the Ag(y) epitope. In a sample of 90 healthy Swedish individuals the Leu2712/Ser4311 allele is associated both with reduced serum levels of LDL-cholesterol and apo B and with raised levels of HDL. However, these differences are of smaller effect than those associated with the XbaI RFLP of the apo B gene in this sample. We have also genotyped 523 individuals from European, Asian, Chinese, and Afro-Caribbean populations and have found complete association between the sites encoding residues 2712 and 4311 in all of these samples, although there are large allele frequency differences between these populations. In addition, there is strong linkage disequilibrium with allelic association between the alleles of these sites and those of the XbaI RFLP in all the populations examined. Taken together, these data suggest that, since the divergence of the major ethnic groups, there has been little or no recombination in the 3' end of the human apo B gene.

Adult↗

PubMed1990

A worldwide population study of the Ag-system haplotypes, a genetic polymorphism of human low-density lipoprotein.

The aim of this investigation is to examine the distribution of the Ag immunological polymorphism in human populations on a worldwide scale and to look for possible explanations of this distribution in the field of modern human peopling history and Ag-system evolution. Extensive Ag-antigene typings were carried out on 13 human population samples, including sub-Saharan African, European, west and east Asiatic, Melanesian, Australian aborigine, and Amerindian groups. Complete Ag-haplotype frequencies were estimated by maximum-likelihood-score procedures, and the data were analyzed by genetic distance computations and principal coordinate projections. With the exception of the Amerindian sample, the Ag polymorphism is shown to be highly polymorphic in all the populations tested. Their genetic relationships appear to be closely correlated to their geographical distribution. This suggests that the Ag system has evolved as a neutral or nearly neutral polymorphism and that it is highly informative for modern human peopling history studies. From the worldwide Ag haplotypic distributions, a model for the Ag molecular structure is derived. According to this model and to the most recent results obtained from molecular data, the establishment of the Ag polymorphism could be explained by several mutations and recombination events between the haplotypes most frequently found in human populations today. As a conclusion, genetic and paleontological data suggest that the genetic structure of caucasoid populations (located from North Africa to India) may be the least differentiated from an ancestral genetic stock. Worldwide genetic differentiations are properly explained as the results of westward and eastward human migrations from a Near East-centered but undefined geographical area where modern humans may have originated. The importance of Ag polymorphism analyses for the reconstruction of human settlement history and origins is discussed in the light of the main conclusions of the most recent genetic polymorphism studies.

Antigens↗

PubMed1990

Apolipoprotein B signal peptide insertion/deletion polymorphism is associated with Ag epitopes and involved in the determination of serum triglyceride levels.

We have investigated the insertion/deletion polymorphism in the signal peptide region of the apoB gene in 106 Finnish individuals from North Karelia. The relative frequency of the insertion allele in this sample was 0.73. Strong linkage disequilibrium was detected between this apoB insertion/deletion polymorphism and the Ag(c/g) epitope pair of apoB, while weak linkage disequilibrium was detected between the polymorphism and the four other reported Ag epitope pairs [(a1/d), (x/y), (h/i) and (t/z)], as well as the apoB PvuII and the XbaI RFLPs. Using one-way analysis of variance there was a statistically significant association (P less than 0.05) between the apoB insertion/deletion polymorphism and serum triglyceride levels in this sample. Individuals homozygous for the insertion allele had higher triglyceride levels than individuals homozygous for the deletion allele, while individuals heterozygous for the polymorphism had intermediate levels. These differences were reduced when individuals were consuming a low fat diet but were statistically significant when the individuals returned to their normal diet. It is possible that insertion or deletion of three hydrophobic amino acids (leu-ala-leu) from the signal peptide of apoB may have a direct effect on plasma triglyceride levels by altering the intracellular processing of apoB or apoB-containing lipoproteins in the liver or intestine.

Adult↗

PubMed1989

Apolipoprotein B amino acid 3611 substitution from arginine to glutamine creates the Ag (h/i) epitope: the polymorphism is not associated with differences in serum cholesterol and apolipoprotein B levels.

A G- to A-DNA sequence change in exon 26 of the human apolipoprotein B (apo B) gene leads to a glutamine substitution for arginine at codon 3611 of the mature apolipo-protein B100 and causes a loss of an MspI site. In 106 Finnish individuals, a complete correspondence exists between this MspI polymorphic site and the Ag (h/i) immunochemical polymorphism. Linkage disequilibrium was found between this MspI polymorphic site and the apo B XbaI and EcoRI variable sites and the Ag (al/d) and (c/g) epitope pairs; there is apparent linkage equilibrium with the apo B PvuII variable site. Based on three population studies (samples from London. Finland and Italy), no significant association was found between this RFLP and serum cholesterol and apo B levels. These data suggest that the arginine 3611----glutamine 3611 substitution has no significant effect on apo B function.

Adult↗

PubMed1988

[2-year anti-HIV donor screening in the Central Laboratory of the Swiss Red Cross Blood Transfusion Service].

612526 blood donations collected by the Central Laboratory of the Swiss Red Cross Blood Transfusion Service between July 1985 and June 1987 were routinely tested for antibodies to HIV.96 donations (82 men, 14 women were anti-HIV positive (0.157%, 1 of 6369 donations). The prevalence of anti-HIV positive donations was higher in men (0.172%, 1/5814) than in women (0.104%, 1/9615). Donations collected in military units were markedly more frequently seropositive (0.570%, 1/1754 in refresher courses, 0.261%, 1/3831 in recruit training). Excluding military donations, donations from men (0.077%) were less frequently HIV-seropositive than donations from women (0.104%). The prevalence of seropositive donations was 4.4 times higher in new donors than in repeat donors. Regarding age distribution, the peak of seropositive donations was observed, as expected, in the third decade. Donations from French speaking Swiss had a clearly higher HIV prevalence than those of German speaking Swiss. As a result of continuous donor information and selection, the number of anti-HIV positive results decreased during the 4 half years covered by our study. It was lowest at the end of the observation period (0.098% or 1/10200 between January and June 1987). Doubtful positive results were recorded chiefly among women, at a rate increasing with age. The majority of such results are presumably due to antibodies with other specificities and must therefore be considered false positive.

Blood Donors↗

PubMed1988

[Hepatitis B screening in late pregnancy and results of immunization in newborn infants].

Screening for hepatitis Bs antigen in late pregnancy was introduced in mid-1983 at the University Women's Hospital, Berne. 4118 pregnant women had been investigated by the end of 1986, of whom 26 (0.63%) turned out to be HBsAg positive. The prevalence of HBsAg carriers was 0.12% in Swiss women, 0.65% in other European women, 12.5% in women from the Far East and 5.6% and 4.9% in women from the Near East and Africa respectively. Newborns of HBsAg positive mothers simultaneously received hepatitis B immunoglobulin (400 IU anti-HBs) and a first injection of hepatitis B vaccine (Hevac B 5 mg) in the first hours of life, followed by vaccinations after two, three and twelve months. Of 18 children investigated after the first year of life none was HBsAg positive. 14 children (78%) were shown to have HBs antibodies. Two of the four anti-HBs-negative unfortunately received only the first vaccine injection after birth. Taking this fact into account, the "success rate" of the immunoprophylaxis is 88%.

Female↗

PubMed1988

Study of five haemogenetic markers (Gc, C3, Bf, Ag, and GALT) in six Indonesian populations and in 12 subgroups of Balinese.

In various ethnic groups of the Indonesian archipelago and of Bali, the polymorphisms of the serum proteins Gc globulin (vitamin D-binding protein), C3 (complement component 3), Bf (complement factor B), Ag x,y (lipoprotein allotypes), and of the red cell enzyme system GALT (galactose-1P-uridyltransferase) were analysed. Among the studied proteins, the Gc system was the most informative one for the anthropologist. Besides considerable differences of frequencies of the common alleles Gc*1F, Gc*1S and Gc*2, a number of rare alleles (1A1, 1A3, 1A8, 1A9, 1A12, 1C2, 1C21, 1C24, and 2C8) and some new ones (1C28, 1C29, 1C30, 2C9) were observed. The presence of Gc*1A1 demonstrates the relationship to the Australo-Melanesian populations, but Mongolian variants (1A3, 1A8, 1A9, 1C2) were also encountered. Within the C3 system a very high frequency of the C3*S allele was observed in all populations. The rare alleles C3*F0.55, C3S1, and C3*S0.5 were observed in some groups. A new allele (C3*F0.35) was detected in a Chinese individual and in a nobleman from Bali. The frequency of the Bf*F allele was rather low in general, and the Bf*S0.7 allele was found in three Indonesian individuals only. The Ag*(x) frequencies were rather high, as it is known for Asiatic populations. Variability among subgroups was not very pronounced. The GALT*2 allele (Duarte variant of the enzyme) was observed very rarely; however, it was present in several populations. Enzyme activities could not be determined, and therefore we cannot tell whether the galactosaemia gene (GALT*0) was present or not.

Complement C3↗

PubMed1988

Relationships between DNA and protein polymorphisms of apolipoprotein B.

The associations between four restriction fragment length polymorphisms (RFLPs) of the gene for human apolipoprotein B (apo B) and five antigen group (Ag) protein-polymorphisms of apo B have been investigated in 24 unrelated Finnish individuals. In this sample a complete correlation exists between the EcoRI RFLP and the Ag(t/z) polymorphism. There is strong association between the alleles of the XbaI RFLP and Ag(c/g) and a weaker one of the same XbaI site with Ag(x/y). Linkage disequilibrium is observed between the PvuII RFLP and the Ag(a1/d) polymorphism. These associations confirm that the Ag variants are true protein sequence polymorphisms of apo B.

Apolipoproteins B↗

PubMed1987

Detection of two apolipoprotein B species (apoBc and apoBg) by a monoclonal antibody.

A monoclonal antibody (MB-19) was used to investigate the polymorphism of apolipoprotein B in a large East Finnish family and in unrelated subjects. Apolipoprotein B was shown to exhibit high, intermediate or low affinity binding to this antibody. Thus, MB-19 bound strongly to the Ag(c) epitope, an Ag antigenic domain previously characterized by human antisera, while it bound only weakly to the allelic epitope Ag(g). It proved useful for the detection of the two corresponding allelic apoB species designated apoBc (= high affinity binding) and apoBg (= low affinity binding), and for confirming their co-dominant transmission. Intermediate binding resulted from the presence of a mixture of both apoB populations in heterozygous subjects.

Adolescent↗

PubMed1987

Two monoclonal antibodies that discriminate between allelic variants of human low density lipoprotein.

Human low density lipoprotein shows a genetic polymorphism, the so-called Ag-system. it consists of 5 pairs of allelic epitopes, x/y, al/d, c/g, t/z, and h/i, which are localized on apolipoprotein B. We have generated a large number of monoclonal antibodies against low density lipoprotein. Two of them, D2E1 and H11G3, recognize epitopes related to this genetic polymorphism. Direct ELISA and ELISA inhibition experiments with different low density lipoproteins of known phenotype showed that D2E1 is directed against the allelic epitope c and H11G3 against d. The two antibodies were used for the characterization of low density lipoprotein in sera from different blood donors and the results compared to those obtained by passive hemagglutination using human allotypic anti-sera. Sera from homo- or heterozygous donors (which display the relevant epitope) could be distinguished from the sera of homozygous donors (which lack the epitope) with the monoclonal antibodies described.

Alleles↗

PubMed1986

[Post-transfusion hepatitis in the Zürich region].

In the years 1979 to 1983 approximately 350,000 units of blood were transfused in the area of Zurich. During the same period 45 cases of posttransfusion hepatitis were reported. In 12 of these cases transfusion could be excluded as cause of the hepatitis. In another 26 cases it was not possible to prove a connection between the blood transfusion and the hepatitis. Only in 7 cases was blood transfusion proved to be responsible for posttransfusion hepatitis: in 3 cases blood positive for HBs-Ag was transfused. In 3 other cases donors who had donated HBs-Ag negative blood developed hepatitis-B shortly after their blood donation: it is assumed that their blood at the time of donation was carrying infectious hepatitis-B-virus particles at a concentration too small to be detected by routine HBs-Ag screening. In one case only was transmission of non-A-non-B-hepatitis virus suspected. Due to improved HBs-Ag-screening, the incidence of posttransfusion hepatitis has been reduced by nearly 70% during the last 10 years. Nevertheless, efforts must continue to reduce the incidence of this important transfusion complication.

Blood Donors↗

PubMed1986

Monoclonal antibody detects Ag polymorphism of apolipoprotein B.

A monoclonal antibody (MB-19) was used to investigate the polymorphism of apolipoprotein B in a large family and in unrelated subjects. Apolipoprotein B was shown to exhibit high-, intermediate- or low-affinity binding to this antibody. Thus, MB-19 bound strongly to the Ag(c) epitope, An Ag antigenic domain previously characterized by human antisera, while it bound only weakly to the allelic epitope Ag(g). It proved therefore useful for the detection of the two corresponding allelic apoB species designated apoBc (high-affinity binding) and apoBg (low-affinity binding), and for confirming their co-dominant transmission. Intermediate binding resulted from the presence of a mixture of both apoB populations in heterozygous subjects.

Antibodies, Monoclonal↗

PubMed1984

[Immune complexes in the serum of patients with acute myeloblastic leukemia].

This study was performed to determine whether the nature of the hemolytic factor present in 54% of sera collected from patients during the active stage of acute myeloid leukemia (AML) [1] is immune complex (IC)-like. The fluid phase C1q-binding test (C1q-BT) served to analyze 92 sera from 24 patients with AML. In a first study the C1q-BT as modified by Carpentier [2] was compared to the universally accepted C1q-BT as described by Zubler [3]. Binding of C1q to heat aggregated human IgG, to tetanus toxoid (Te)/anti-Te complexes, and to serum containing heparin or fibrinogen was to a similar extent concentration-dependent; however, the binding values obtained with the method of Carpentier were always higher than with the method of Zubler. The same was found for the binding of C1q to sera from patients suffering from various diseases: using Carpentier's method approximately a 20% higher C1q-binding activity was found for all samples compared to binding activities found with Zubler's original method. The higher C1q binding did not depend on higher sensitivity of Carpentier's assay system, as the binding to sera from 60 healthy individuals was also elevated (8.1 +/- 6.0% vs 1.2 +/- 1.0% with the method of ZUBLER). In a second study AML sera were analyzed by the "extended" C1q-BT [4]. The "extended" C1q-BT uses two different C1q preparations and the assay follows the procedure described by ZUBLER. This test is able to detect immune-aggregate-mediated and non-immune-aggregate-mediated C1q binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen-Antibody Complex↗

PubMed1984

C1 inhibitor functional activities in hereditary angioedema plasma of patients under therapy with attenuated androgens.

The effects of therapy with danazol or stanozolol on complement component C4 and on C1 inhibitor concentrations and functions in 6 patients suffering from the common form of hereditary angioedema are described. Whereas the mean C4 concentration was found within the normal range, the therapy with attenuated androgens resulted in a subnormal mean of C1 inhibitor concentration, but an almost normal mean of functional activity.

Angioedema↗

PubMed1984

Quantification of C1-inhibitor functional activities by immunodiffusion assay in plasma of patients with hereditary angioedema--evidence of a functionally critical level of C1-inhibitor concentration.

The relationship of C1-inhibitor (C1-INH) concentration and apparent functional activity was investigated in 111 plasma samples from 21 patients with the common form of hereditary angioedema (HAE). Functional C1-INH was analyzed by means of a modified version of immunodiffusion assay. Down to a C1-INH level of approximately 0.075 g/l (38% of normal) apparent C1-INH functions were found within the normal range, while below this level functional adequacy of C1-INH could no longer be ascertained. When C4 concentrations, considered to reflect approximately functional C1-INH, were related to C1-INH antigen levels of individual samples, a relationship emerged which was identical to that between C1-INH concentration and apparent function. No attacks of edema could be associated with C1-INH concentrations above 0.075 g/l, while it was possible to associate attacks with concentrations below this level. In experiments where patient plasma and normal plasma were mixed in various ratios or where HAE plasma was replaced by purified C1-INH, an increase in C1-INH antigen to concentrations of 0.06-0.08 g/l was followed by a sharp rise in apparent functions to normal values. The rise of functional C1-INH became moderate when C1-INH antigen further increased. The results supported the idea of a functionally critical level of C1-INH in the common form of HAE.

Angioedema↗

PubMed1982

Genetic polymorphism of glycine-rich beta-glycoprotein in the Italian population.

Genetic polymorphism of glycine-rich beta-glycoprotein (GBG) was studied in populations from northern and southern Italy, respectively. Gene frequencies were as follows: northern Italy (n = 431): GbS = 0.7675, GbF = 0.2049, GbS 0.7 = 0.0127, GbF1 = 0.0139; southern Italy (n = 161): GbS = 0.7050, GbF = 0.2360, GbS 0.7 = 0.0373, GbF1 = 0.0217. Comparison of these two populations with the Swiss population revealed a significant drift in gene frequencies from north to south. A new GBG phenotype, supposedly heterozygous, with a slow migrating F band and a regular S band in agarose electrophoresis was observed.

Complement Factor B↗