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Biomedical subjects

J Constans

Publications and source records attributed to J Constans.

At least 145 records · Page 8Linked to original sources
PubMed1989

Human red-cell acid phosphatase (ACP1): a new mutant (ACP1*KUK) detected by isoelectric focusing, kinetics of thermostability and substrate activity.

A new rare mutant of the red-cell acid phosphatase (ACP1) is described using conventional gel electrophoresis and isoelectric focusing migration. According to the electrophoretic patterns obtained, the new mutant ACP1* KUK is different from the ACP* H and ACP1* A' variants already described. The enzyme activities and the thermostability curves definitively confirm the existence of a new variant. The transmission of this mutant was followed through a pedigree of three generations. The family originated from Czechoslovakia. The frequency of the variant is probably less than 0.001.

Acid Phosphatase↗
PubMed1988

The group specific component/vitamin D binding protein (GC/DBP) system in the analysis of disputed paternities.

The group-specific component (GC) was discovered in 1959, and in the same year a vitamin D binding protein (DBP) in human plasma was found; however, their identity was established as late as 1975. In the GC/DBP system three common alleles, GC*1F, GC*1S, and GC*2, determine six GC phenotypes: 1F, 1S, 2, 1F-1S, 2-1F and 2-1S, these common alleles having been found in all human populations studied. In addition, more than 120 GC variants have been discovered, with varying frequencies in different populations. The distribution of the common GC phenotypes and the presence of rare GC variant phenotypes render the GC/DBP system useful for the analysis of disputed paternities.

Biomarkers↗
PubMed1988

Identification of group specific component/vitamin D-binding protein (GC/DBP) mutants by isoelectric focusing in immobilized pH gradients.

The six common genetic types of the group specific component/vitamin D-binding protein (GC/DBP) system are usually classified by isoelectric focusing in carrier ampholytes, followed by visualization of the GC proteins by immunoprinting with monospecific antiserum. In addition, more than 120 mutant GC types have been discovered. For their identification additional methods were necessary, including polyacrylamide gel electrophoresis, isoelectric focusing in the presence of 3 M urea as well as isoelectric focusing in immobilized pH gradients. The application of the last method is described in detail and several examples of GC/DBP mutants identified thereby are presented.

Gels↗
PubMed1988

The mutants of the vitamin-D-binding protein: more than 120 variants of the GC/DBP system.

In this report 40 newly observed GC/DBP mutants are described. A list of the thus far identified GC mutants is presented: in addition to the three common alleles, a total of 124 Gc variants are recorded. Their population distribution is described and their relationship to the molecular features of the DBP protein is discussed. The methods currently in use for the delineation of GC mutants are briefly considered.

Africa↗
PubMed1988

DNA and protein polymorphism: application to anthropology and human genetics.

In this paper, the author analyses the different approaches of the DNA polymorphism. Mitochondrial DNA, RFLP haplotypes associated with serum protein polymorphism, variability of some small regions of the genome detected by minisatellite probes are now well developed and often adapted to population analysis. The data gathered are used to build phylogenic or genealogic trees. Despite the limited number sampled in these investigations, it is obvious that they were obtained to establish a beginning of geographical map distribution of the DNA polymorphisms and to answer basic questions in Anthropology. In this sense, DNA polymorphism is a new way to obtain a large amount of information not available through the different polymorphisms previously performed. Today, the interpretation of the data on DNA polymorphism is based on archeological and prehistorical hypotheses. It is highly probable that for a long time, no phylogenic analysis will be able to determine the step of speciation, the period of emergence of primitive man and of his geographical origins. In some fields of anthropological investigations, studies on the DNA structure and organisation may bring new information on the genetic of skin pigmentation, eye and hair colours, body size, etc. But the essential aim of studies on humans cannot exist out of multidisciplinary follow up including sociology, biology, linguistics, behaviour and economy. Molecular biology of DNA is an additional method from which we can learn a lot about human genetic heterogeneity but man is a group, a society, a population, a tribe and not a certain amount of allele frequencies.

Anthropology, Physical↗
PubMed1988

Population polymorphism of the GLO1 enzyme. Identification of two new variants.

A new electrophoretic technique for the determination of the glyoxalase I (GLO1) polymorphism on mixed agarose and starch gel is applied to the genetic study of "Provinces Françaises" and some other human populations. Four rare electrophoretic variants are revealed; two of them (GLO1*4, GLO1*5), both new, are discussed. In the "Provinces Françaises" the mating GLO1 2-1 x GLO1 2-1 shows an irregular segregation of the GLO1 alloenzymes.

Africa, Western↗
PubMed1987

Polymorphism of the vitamin D binding protein (DBP) among primates: an evolutionary analysis.

The distribution of the DBP (vitamin D binding protein) polymorphism is now well characterized among human populations but for primates only limited results are known. The aim of this paper is to describe the electrophoretic polymorphism of this protein among various species. Using three different electrophoretic methods, we are able to detect an unknown polymorphism and to classify the different alleles observed. These results may be used to set an international nomenclature for further comparisons. The different electrophoretic mobilities between Old and New World Monkeys show that: 1) the Cercopithecoïdea are presenting the largest genetic heterogeneity; 2) the DBP among the Galago corresponds to the lowest isoelectric points observed among Primates; 3) during the evolution from nonhuman Primates to Man, the DBP is able to keep its affinity for vitamin D derivatives despite the occurrence of significant molecular modifications; 4) among Anthropoïdea, the electrophoretic patterns of DBP are very close to the human Gc1 proteins. These results show that evolution at the DBP level can be considered as a continuous mechanism of structural modifications. A significant transition occurs during the differentiation between Cercopithecoïdea and Anthropoïdea. It is not too speculative to consider that some electrophoretic forms detected among Gorilla, Pongo, or Pan may be identical to rare variants observed among humans.

Animals↗
PubMed1987

Biochemical and biological properties of an alpha 1-antitrypsin concentrate.

alpha 1-Antitrypsin (AAT) has been purified from human plasma supernatant A (equivalent to COHN fraction II + III) by a large-scale chromatographic procedure involving anion-exchange adsorption on DEAE Sepharose CL-6B fast flow and size-exclusion chromatography on Sephacryl S-200. Before freeze-drying, the liquid concentrate was heat-treated at 60 degrees C for 10 h to reduce the risk of transmission of blood-born viral diseases. Using this procedure, AAT is recovered with 80-90% purity in 65-75% yield from supernatant A. The heterogeneity of AAT is preserved across the purification steps. In addition, purified AAT exhibits inhibitory activities against trypsin and elastase equivalent to that of the serum protein. The mean association rate constant for elastase was found as high as 2.15 X 10(5) M-1 s-1. Thus, purifying active AAT from supernatant A contributes to improving the availability of this protein which may be potentially useful in the treatment of hereditary emphysema.

Chromatography, DEAE-Cellulose↗
PubMed1987

Large scale chromatographic purification of alpha 1-antitrypsin from human plasma supernatant II + III.

We describe a large-scale chromatographic method to purify alpha 1-antitrypsin (AAT) from human plasma supernatant II + III. Supernatant II + III was injected onto DEAE sepharose CL 6B to get an albumin-rich fraction as well as a fraction that contained about 45% AAT. This intermediate purity AAT fraction was further purified by size-exclusion chromatography on Sephacryl S-200. The product was heated in solution at 60 degrees C for 10 hours in the presence of a stabilizer to lower the risk of transmission of viral diseases. Purity of the AAT concentrate is over 85%; clinical testing of its safety and efficacy in the treatment of PiZ patients is underway.

Blood Proteins↗
PubMed1986

Effects of serum vitamin-D-binding protein on actin in the presence of plasma gelsolin.

The interaction of serum vitamin-D-binding protein (DBP) and plasma gelsolin with actin was studied using fluorescent 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole-actin or N-pyrenylcarboxyamidomethyl-actin. DBP and gelsolin formed very tight complexes with one or two monomeric actin subunits respectively. Kd values of about 10 nm have been found for both complexes. When DBP and gelsolin were added simultaneously to G-actin no ternary complex was observed and the DBP-actin complex was formed preferentially. In the presence of CaCl2 no transfer of actin occurred from the 1:2 gelsolin:actin molar complex to free DBP while in the presence of EGTA one actin monomer could be transferred. DBP did not affect the severing activity of gelsolin. The effects of a mixture of gelsolin and DBP on F-actin suggest that only individual interactions of these two plasma proteins with actin occurred in solution.

Actins↗
PubMed1986

Complete amino acid sequence of human vitamin D-binding protein (group-specific component): evidence of a three-fold internal homology as in serum albumin and alpha-fetoprotein.

The complete amino acid sequence (458 amino acid residues) of human group-specific component 2 (Gc2) protein was determined. Computer analyses established a three-fold internal homology of Gc2 protein as well as an extensive homology between the overall structures of Gc2 protein, human serum albumin and human alpha-fetoprotein.

Amino Acid Sequence↗
PubMed1986

Gene flow across tribal barriers and its effect among the Amazonian Içana river Indians.

Demographic information was obtained from 622 individuals of five communities of primarily Baniwa Amerindians living near the Içana river in Brazil. Four of these populations, plus another from the same area, were also studied genetically. The latter investigation included the blood and, in some cases, saliva of 531 subjects, variously tested in relation to 40 genetic systems. Demographically these groups are characterized by young age, high intertribal admixture, low non-Indian admixture, high exogamy but low marital distance and high inbreeding, high fertility but low variance in offspring number, and relatively low mortality. Their gene pool shows a peptidase B variant (PEPB2BAN1) and "private" polymorphism of carbonic anhydrase2 (CA2BAN1) until now observed only among them. Other distinctive characteristics are the low frequencies of LNS (0.08), LNs (0.09), RZ (0.01), RO or r(0.02), ACPA (0.08), GALTD (0.01), and the relatively high prevalences of Gm (0.05) and Gc1 (0.82). TfDchi occurs with a low prevalence (0.01). Genetic distance analysis reveals that the one Baniwa sample by history comprised of minimally admixed individuals is quite similar genetically to the Wapishana, another Arawak-speaking tribe some 900 km to the east, and that the genetic distances between the Baniwa communities reflect the amount of historical admixture in a way that indicates which should be excluded from considerations of intertribal genetic distances. Finally, the genetic relation of the Baniwa to the nearby tribes is examined.

Adolescent↗
PubMed1985

Population distribution of the human vitamin D binding protein: anthropological considerations.

The polymorphism of the serum vitamin D binding protein (DBP) in humans is based on the existence of three common alleles, Gc1F, Gc1S, and Gc2, and 84 rare alleles. The geographical distribution of Gc1F, Gc1S, and Gc2 alleles shows north to south clines, together with a balanced equilibrium between the Gc1F or Gc1S allele frequency and the Gc2 frequency. The distribution of the FST values shows high variability within a geographical area. For European and North Asiatic groups, the FST values are the lowest observed, and the reason may be a long process of homogenization. Aboriginal populations from Australia and New Guinea and groups from both North Africa and South America show the greatest heterogeneity of their allele frequencies. Systematic factors such as genetic drift and selection may account for this distribution. In contrast with the three main DBP alleles, the distribution of the rare alleles corresponds to patterns of human migrations that occurred during prehistoric and historic periods. Thus, the rare mutants are of particular relevance to anthropological and genetical investigations.

Alleles↗
PubMed1985

Unusual sialilation of three different rare genetic variants of serum DBP: Gc1A17, Gc1A16, and Gc1A11.

The proteins of three anodal Gc1 variants, Gc1A16, 1A11, and 1A17, are characterized by the most acidic isoelectric points observed so far among the different Gc mutants. Stepwise removal of N-acetylneuraminic acid (NANA) by treatment with neuraminidase was performed to estimate the degree of sialilation of these Gc variants. The results indicate that both proteins, the anodal and the cathodal component of these Gc1 mutants, carry sialic acid residues. This observation is remarkable in so far as usually only the anodal component of the Gc1 protein contains NANA and only a single residue. From the experiments carried out it can be deduced that Gc1A16 has two NANA residues in the anodal and one NANA residue in the cathodal component. Gc1A16 was found in four members of three generations in a Danish family; the variant segregated as a Mendelian trait. More difficult to interpret are the results obtained with the variants Gc1A11 and Gc1A17. Gc1A11 probably has three NANA residues in the anodal and two NANA residues in the cathodal component. Gc1A11 has been observed in two mother-child pairs and is presumably also a simple genetic trait. Gc1A17 has also several NANA residues in both Gc proteins; it is suggested that the anodal component has either three or four NANA residues and the cathodal component either two or three NANA residues. Family information on this variant is not yet available.

Alleles↗
PubMed1983

Isolation and characterization of the O-glycan chain of the human vitamin-D binding protein.

On a highly purified preparation, the structure of the carbohydrate chain of the human vitamin D-binding protein was investigated and two genetic forms of this protein were considered (Gc 2 and Gc 1 proteins). It was found that only the Gc 1 protein (Gc1a isoform) was glycosylated, the glycan moiety representing about 1% of the protein. The structure of this O-glycosidically linked glycan was determined to be: Neu Ac alpha (2 leads to 3) Gal beta (1 leads to 3) GaINAc alpha (1 leads to 0) Ser (or Thr). A tetrasaccharidic O-glycan with two N-acetylneuraminic residues was also characterized. The vitamin D-binding protein is a rare example of a serum protein O-glycosylated only on some genetic forms.

Carrier Proteins↗
PubMed1983

The effect of serum vitamin D-binding protein on polymerization and depolymerization of actin is similar to the effect of profilin on actin.

The mechanism of the interaction between two genetically determined serum vitamin D-binding protein forms and the muscle skeletal actin was investigated. Vitamin D-binding protein was isolated in a good yield from human serum, using immunoaffinity chromatography. 16 mg of pure vitamin D-binding protein were obtained from 100 ml of serum. The interaction between purified vitamin D-binding protein and skeletal muscle actin was studied by viscosity, delta A (232 nm) measurements and by electron microscopy. The effect of vitamin D-binding protein on actin polymerization is characterized by the decrease of the nucleation and elongation rates and by the decrease of the final concentration of polymerized actin in the steady state. The depolymerizing effect is not the result of direct action on vitamin D-binding protein on F-actin but rather of an increased concentration of the complex of the former protein with G-actin. The characteristics of the vitamin D-binding protein and profilin interactions with actin are similar. Both proteins seem to react only with G-actin.

Actins↗