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Biomedical subjects

Y Beuzard

Publications and source records attributed to Y Beuzard.

At least 145 records · Page 8Linked to original sources

[The antenatal diagnosis of haemoglobinopathies. A preliminary study (author's transl)].

From now on antenatal diagnosis of haemoglobinopathies is possible. Fetal blood can be taken from the uterus from the 17th to the 20th week of the pregnancy by direct puncture of the placenta or placentocentesis or by selective puncture of a straight vein close to its insertion in the cord on the fetal surface of the placenta, using a fetoscope. Biochemical techniques today allow us to detect beta thalassaemia major (with total absence of synthesis or with synthesis of less than 2 per cent of the beta A chain of haemoglobin by the fetus) and drepanocytosis (which is the synthesis of the chain beta S by the in the absence of production of the chain beta A). It is possible in cases where the fetal blood that has been taken is seriously contaminated by maternal blood (which is often the case with direct punctures) by using purification methods to increase the proportion of fetal red blood cells in the sample by eliminating adult reticulocytes which could cause errors in diagnosis. There are several centres where this type of diagnosis is being carried out. Some of them now have two years' experience and their results are encouraging. In spite of their difficulty these methods of investigation can allow couples at risk to have normal children or heterozygous infants. They can help them to avoid the need for termination of pregnancy or permanent contraception.

Anemia, Sickle Cell↗

Structural and functional studies of hemoglobin J Cala-bria: beta64 (E8) Gly leads to Asp.

A hemoglobin of high electrophoretic mobility was detected in a French male suffering from an acute leukemia; this hemoglobin was also present in his family. The variant was unstable and possessed an abnormal beta chain, in which a glycyl residue in position 64 (E8) was replaced by an aspartyl residue. This variant constitutes a new case of Hb J Calabria. Since the substituted E8 residue is in close spatial contact with that at B6, it was of interest to compare the properties of Hb J Calabria with those of other hemoglobins bearing substitutions at the same site.

Adult↗

Inhibition of erythrocyte sickling by cystamine, a thiol reagent.

Incubation of sickle cells with cystamine, a thiol reagnet, resulted in the formation of an intracellular S-ethylamine derivative. The rate of the reaction was dependent upon the cystamine concentration, the temperature, and the duration of the incubation. The cystamine-treated cells demonstrated a marked inhibition of sickling under hypoxic conditions, a decrease in their mean corpuscular hemoglobin concentration, and a significant increase in their oxygen affinity. The oxygen affinity of these cells was less dependent on their mean corpuscular hemoglobin concentration than that of untreated sickle cells. The minimum gelling concentration of S-ethylamine doxyhemoglobin S was slightly increased. Cystamine did not affect the intracellular pH nor the 2,3-diphosphoglycerate level. The exact contribution of the interrelated factors in cystamine inhibition of sickling (changes in oxygen affinity, mean corpuscular hemoglobin concentration, and minimum gelling concentration) has yet to be determined.

Anemia, Sickle Cell↗

Mapping of several abnormal hemoglobins by horizontal polyacrylamide gel isoelectric focusing.

The relative mobilities of serveral human hemoglobin variants were studied by use of an isoelectric focusing method in a thin-layer horizontal polyacrylamide gel. The technic is described in detail and a preliminary mapping of these variants is presented. It appears that thin-layer gel isoelectric focusing is a method that is rapid, highly reproducible and easily applicable in laboratories concerned with the study of hemoglobinopathies.

Amino Acid Sequence↗

Haemoglobin Saki alpha 2 beta 2 14 Leu-Pro(a11) structure and function.

The characterization of haemoglobin Saki alpha 2 beta 2 14 Leu-Pro(a11) is described. This new mutation is unique since it only induces modification of the stability of the molecule. In vitro precipitation of haemoglobin Saki upon heat or in the presence of chemicals is compared to the stability of haemoglobin A and haemoglobin S.

Adult↗

The effects of hemin and double-stranded RNA on alpha and beta globin synthesis in reticulocyte and Krebs II ascites cell-free systems and the relationship of these effects to an initiation factor preparation.

Protein synthesis in reticulocyte lysates ceases abruptly in the absence of added hemin or in the presence of double-stranded RNA. A similar effect of double-stranded RNA is observed in Krebs II ascites cell-free systems translating exogenous globin mRNA. The shut-off of protein synthesis is due to inhibition of initiation and can be prevented or reversed by addition of the initiation factor preparation M(3). Preparations of M(1), M(2), and dissociation factor are ineffective under these conditions. The effects of added hemin, M(3), and globin mRNA on the synthesis of alpha and beta globin chains have been studied in the reticulocyte and ascites cell extracts. When the concentration of M(3) is rate limiting, the synthesis of beta chains exceeds that of alpha chains. When the concentration of mRNA is rate limiting, synthesis of alpha and beta chains is more nearly equal.

Animals↗

Effect of hemin on the synthesis of hemoglobin and other proteins in mammalian cells.

The initiation of globin synthesis in intact reticulocytes and in reticulocyte lysates is maintained by the addition of hemin. The specificity of this effect has been studied to determine whether it is restricted to hemoglobin and erythroid cells. In intact reticulocytes, hemin (500 muM) enhances the synthesis of carbonic anhydrase as well as of hemoglobin. Similar enhancement of protein synthesis is observed on addition of hemin (500 muM) to intact Krebs II ascites tumor cells, in cell-free extracts of these cells, added hemin (50 muM) increases endogenous protein synthesis and the translation of exogenous rabbit globin messenger RNA. These results provide evidence that the effect of hemin is not restricted to globin, and they suggest that hemin may enhance protein synthesis in at least some nonerythroid cells.

Alanine↗

Oxygen tension and a pharmacological switch in the regulation of transgene expression for gene therapy.

BACKGROUND: The combination of physiologically and pharmacologically controlled elements may provide a means to ensure both the regulation and the safety of transgene expression--two major goals in gene therapy. METHODS: A two-gene modulation system was developed that uses the following three levels of control: (i) the hypoxia-responsive element directing the transcription of the tetracycline-controlled transactivator (tTA); (ii) part of the oxygen-degradation domain limiting the production of tTA in normoxia; and (iii) the tetracycline switch of the transactivator activity (the tet-off system). RESULTS: This triple-control system allowed high expression of the gene of interest (luciferase or erythropoietin) by transfected cells upon hypoxia and low expression under normoxia or in the presence of tetracycline. This control of transgene expression was also obtained in mouse tumors. CONCLUSIONS: This multiple-control system is of interest for spatially restricting transgene expression into hypoxic tumors, and for finely adjusting the expression level of a therapeutic protein to the oxygen supply in medical applications such as neoangiogenesis or the erythropoietin-mediated treatment of anemia.

Adenoviridae↗

Red blood cell indices, cation content, and membrane cation transports.

In sickle cell disease, in the homozygous state, the increased heterogeneity of erythrocytes results mainly from membrane defects secondary to Hb S polymerization and the increased survival of F cells. The density distribution curve, using phthalate esters or the red blood cell indices measured with the H*3 system, are useful methods for the hematological follow-up of patients under specific therapies. The methods evaluating the red blood cell cation contents and the abnormal membrane potassium transport pathways are also described, in order to evaluate agents which can restore normal hemoglobin concentration and water content in dehydrated sickle cells.

Anemia, Sickle Cell↗