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Biomedical subjects

J Constans

Publications and source records attributed to J Constans.

At least 127 records · Page 7Linked to original sources

Localization of a vitamin-D-binding protein interaction site in the COOH-terminal sequence of actin.

The serum vitamin D binding protein is the carrier of vitamin D and its derivatives in the plasma. One of the known roles of this protein is to sequester monomeric actin in the blood, therefore implicating this protein in actin elimination. However, its binding site at the surface of actin is poorly delimited. We report here the results of a study which locates, using several actin fragments together with immunological probes, a vitamin D binding protein site near the COOH-terminal extremity. Thus, the interface is delimited by the sequence 360-372 in subdomain I of actin.

Actins↗

A new polymorphism of thyroxin-binding globulin in three African groups (Mali) with endemic nodular goitre.

The thyroxin-binding globulin (TBG) polymorphism was investigated in three African groups: two belonged to the Bwa villages of Mali, and the third was a Dogon group living in the same area. The Bwa groups were characterized by the occurrence of nodular goitres, whereas the Dogon population did not show similar pathological symptoms. Females were more affected by goitre than males in the affected villages. The TBG polymorphism enabled us to demonstrate the presence of an undescribed allele (TBG C1) in these populations. The frequency of the TBG S allele was also higher than previously published in other African groups. We observed a disequilibrium in the distribution of the C and S alleles in the population, with an excess of homozygous TBG S individuals. No clear relationship between the TBG polymorphism and the number of nodules can be drawn.

Alleles↗

Human red-cell acid phosphatase (ACP1): kinetic and thermodynamic characterization of the KUK variant.

The Km constant and the sensitivity to inhibitors were determined for the rare variant KUK of red cell acid phosphatase. At the same time, the thermodynamic energies of activation and of inactivation were measured. The kinetic parameters were not very different from those of the usual ACP1 C alloenzymes. However, they differed in their thermodynamic energies: the conformational structure of the ACP1 KUK protein being less stable.

Acid Phosphatase↗

Clinical pharmacokinetics of alpha 1-antitrypsin in homozygous PiZ deficient patients.

A pharmacokinetic study of alpha 1-antitrypsin (ATT) was performed in 2 groups of homozygous PiZ-deficient patients (treated and untreated) and 1 group of healthy volunteers. The distribution of the 131I-labelled protein corresponds to a 3-compartment model. The intravenously administered protein diffused quickly to the extravascular compartment where some retention occurred. No significant difference in AAT metabolism was observed between the 3 groups. The half-life of the injected protein is slightly longer than 2.5 days. The AAT protein was not stored. These results confirm the observations collected during the clinical trials. That is, a weekly infusion is necessary to obtain stable serum AAT concentrations. Monthly infusions are unable to maintain a 'plateau' phase. The periodicity may be limited to every 2 weeks.

Adult↗

Group-specific component is not only a vitamin-D-binding protein.

The vitamin-D-binding protein (DBP), also called group-specific component, is well known for two main reasons: its genetic polymorphism, and its binding affinities for actin and vitamin D compounds. In recent years, additional binding affinities have been described for this puzzling molecule, without any significant biological explanations being given for these observations. The molecular genetic data for DBP are analyzed in order to show that the affinities for vitamin D are supported by the genetic variability. The molecular evolution of the protein shows that the ancestral gene was present long before the development of related genes, such as those for albumin and alpha-fetoprotein. Other affinities for actin, C5a-desArg and for a B lymphocyte mitogen are also discussed. DBP is mainly present in the circulating blood as an apoprotein. The cytoplasmic presence of DBP has not been confirmed, and the major question today is to understand the biological role of this protein. In the last part of the review, the discussion focuses on relating the different binding affinities of DBP to its biological activities. Avenues for future research are also outlined: these include DBP metabolism, the differentiation of macrophages, and the activity of DBP during embryonic development.

Amino Acid Sequence↗

[Coronary disease and peripheral arterial disease: contribution of echo-Doppler in the study of the arteries of the neck and lower limbs before the age of 60. Apropos of 76 cases].

Echo-duplex exploration of heart and inferior limbs arteries is performed in 76 patients less than 60 years old, with angiographically established coronary heart disease. Peripheral vascular lesions are found in 15 cases (20%), they are more frequent in patients with tritrunkular coronary disease (35%) than in those with one (16%) or two-vessel lesions (10%). Mean encephalic circulatory resistance index is higher in patients with tritrunkular lesions (p less than 0.03). Vascular echo-duplex should be performed in case of coronary disease in order to avoid catheterism complications and to purpose combined surgical procedure (coronary bypass and carotid endarterectomy).

Adult↗

Genetic similarity maps and immunoglobulin allotypes of eleven populations from the Pyrenees (France).

The genetic heterogeneity of eleven populations from the Pyrenees (France) based on the polymorphism of the immunoglobulin allotypes is studied by means of a 'genetic similarity map'. The method described here, called 'Mobile Node Method', allows the deformation of a square grid, in which the studied region is represented, by moving the nodes at each step in order to reduce the difference between the geographic and genetic distances. This tool allows the overall quantification of the genetic heterogeneity of a population set and possibly the study of its dynamics. Other maps constructed to complete the interpretation are 'map of moving vectors', 'iso-displacement curves' and 'site displacements'. This study identified an overall genetic homogeneity among the Pyrenean populations and several local genetic heterogeneities in different regions.

France↗

Detection of Mycoplasma hominis antibodies by three different techniques, application to women with pelvic inflammatory disease.

Mycoplasma hominis, a mycoplasma potentially isolated from the genital tract of healthy women, seems to have some role in pelvic inflammatory diseases (PID). Three serologic techniques were developed to detect antibodies to M. hominis: ELISA (IgG, IgM), microimmunofluorescence (MIF) and Western blot. Rabbit and human control sera were used to establish the standard assay conditions. ELISA proved to be more sensitive but less specific than MIF. Cross-reactivity with antibodies to M. pneumoniae existed with ELISA but not with MIF. Twenty six and 60 kDa proteins were responsible for that cross-reactivity, as assessed by Western blot analysis. Among 33 patients with PID, 18 to 35 year old, 67% had antibodies to M. hominis by ELISA and 33% by MIF. Among 52 age comparable healthy women, 44 and 13% were positive for M. hominis by ELISA and MIF respectively. The Western blot analysis showed heterogeneity in the antibody response to M. hominis, but a 76 kDa protein reacted with half of the tested sera. Our study agrees with some role for M. hominis in PID. M. hominis was certainly the primary pathogen in one case, played a role that was probable in seven cases, and possible in three patients.

Adult↗

Consequences of moderate hypoxia on red cell glycolytic metabolism in polycythemia rubra vera.

Red blood cell metabolism was studied in male patients with polycythemia rubra vera (Vaquez disease) and compared to a reference sample of 74 healthy adults. A total of seventeen enzyme activities and seventeen metabolite concentrations were determined. In addition to the modifications of the hematological parameters among the polycytemic patients significant variations were detected: a decreased content of hemoglobin in the cells; significantly decreased levels of ATP, ADP and AMP associated to an accelerated turn over of these metabolites; an acceleration of the glycolytic pathway associated with an increase of the energetic charge and levels of 2-3BPG and G1-6BP. In polycythemia rubra vera patients, the modifications of the hematological and biochemical parameters were compared to previous results obtained in high altitude residents (adaptative hypoxia) and in red cells belonging to new borns.

Adult↗

[Evaluation after 2 years of substitutive treatment of PiZZ emphysema with alpha-1 antitrypsin. 9 cases].

Homozygous PiZZ individuals with a serum deficiency due to a defect in the secretion of the alpha 1-antitrypsin protein are at risk of developing severe panlobular emphysema. Tobacco smokers are particularly exposed to the disease which begins at an earlier age. Treatment by substitutive therapy with alpha 1-antitrypsin concentrates seems to be the only possibility. A two years' clinical trial was performed in 9 PiZZ patients, with more than 1,500 infusions being administered weekly. Serum AAT levels were used as guidelines to follow biochemical changes in the protease-antiprotease balance. From 0.16 g/l initially, the AAT level rose to 0.57 g/l after 7 months. No adverse reaction was observed during the trial; the concentrated protein was well accepted, ant the antielastase activity of the protein recovered after injection was equivalent to the activity injected. An attempt to administer the infusions monthly was stopped when we observed a dramatic decrease of the serum AAT level. Clinically, stabilization of the symptoms was noted. No degradation was observed in the patients who took part in the trial, even if no real improvement was detected.

Adult↗

The Gm-Pi linkage in 843 French families: effect of the alleles Pi Z and Pi S.

Linkage analysis was performed between Gm and Pi in 843 French families. The overall recombination fraction is equal to 0.25 with a sex difference ratio of 1.4 (recombination fraction of 0.20 in males and 0.29 in females), confirming previous results in the literature. Our study does not confirm the existence of a heterogeneity in recombination rate of Pi S versus non-S alleles, but it confirms the previous finding that the presence of the Pi Z allele tends to decrease the recombination rate between the two loci. This decrease appears to be similar in both sexes, and not uniquely in males as previously noted. This result suggests a possible linkage disequilibrium between the Pi Z allele and a presumably large inversion between the two loci Gm and Pi.

Alleles↗

Polymorphism of haptoglobin (HP), group specific component (GC) and alpha-1-antitrypsin (PI) in the resident population of the Basque Country (Spain).

The Basque Country is inhabited by three populations: indigenous inhabitants, immigrants from other regions of the Iberian peninsula and descendants from a mixture of both groups. The principal component analysis of gene frequencies at HP, GC and PI loci shows two groups in the Basque Country: one comprising the indigenous inhabitants and those of mixed descent, the other of immigrants. The first group presents gene frequencies similar to those of inhabitants of the Pyrenees and Central Europe areas, while the second group has frequencies similar to other European and Mediterranean inhabitants.

Ethnicity↗

BamHI and SacI RFLPs of the human immunoglobulin IGHG genes with reference to the Gm polymorphism in African people. Evidence for a major polymorphism.

In this paper, we extend the study of the IGHG gene RFLPs in black African persons and in some other individuals characterized by a Negroid admixture. We demonstrate a polymorphism that is much more important in black Africans, than in Caucasoids, mainly for the IGHG3 and G1 genes, the most 5' members of the IGHG multigene family. These genes encode for the IgG3 and IgG1 subclasses, which are of crucial biological importance.

Alleles↗