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Biomedical subjects

F Galacteros

Publications and source records attributed to F Galacteros.

At least 91 records · Page 5Linked to original sources
PubMed1990

Hemoglobin Calais [beta 76 (E20) Ala----Pro]: a hemoglobin variant with decreased intrinsic oxygen affinity.

Hb Calais [beta 76 (E20) Ala----Pro] is a new human hemoglobin variant displaying a decreased oxygen affinity. The only electrophoretical difference with Hb A was a slightly more acidic isoelectric point. A 2-fold decrease in the oxygen affinity was found by equilibrium measurements performed in a suspension of intact red blood cells and in the lysate. It was confirmed by kinetic studies of the purified abnormal hemoglobin. The rate of methemoglobin formation at 37 degrees C of Hb Calais was also increased relative to Hb A. The mechanism by which the Pro for Ala substitution of an external residue in the beta-chains results in these profound functional abnormalities is unclear. Subtle changes at the heme pocket, at a distance from the mutation, may be a plausible explanation for the effects observed.

Adult↗
PubMed1990

[Transfusion in sickle cell anemia].

Transfusion is one of the fundamental treatments in complications of sickle cell anaemia, a disease with peculiar features requiring an appropriate transfusion policy. Owing to the higher risk of vascular occlusion it carries, simple blood transfusion is indicated only for acute anaemia and for the very rare long-term transfusion programmes. In patients with severe occlusive and/or septic accidents, the risk of decompensation makes it mandatory to promptly reduce the sickle cell concentration; this is achieved by exchange transfusion the modalities of which are described by the authors. General anaesthesia also requires exchange transfusion in volumes that depend on the risk incurred. Finally, some patients benefit from a long-term transfusion programme. Potentially repeatable transfusions imply the use of phenotypes and leucocyte-freed red cell concentrates as well as detection and prevention of viral infections transmitted by transfusion. This article summarizes the recommendations that can now be made concerning the use of perfusion in the management of sickle cell anaemia.

Anemia, Sickle Cell↗
PubMed1990

A new hemoglobin variant found during investigations of diabetes mellitus: Hb Pavie [alpha 135 (H18) Val----Glu].

Hb Pavie [alpha 135 (H18) Val----Glu], found during HbA1c measurement in a patient of Italian origin investigated for diabetes mellitus, exemplifies how the presence of an abnormal hemoglobin interferes with the measurement of glycated hemoglobin. This variant hemoglobin migrates as Hb A1c on polyacrylamide gel isoelectric focusing (IEF) and therefore hindered the estimation of glycated hemoglobin by this method. By ion-exchange high-performance liquid chromatography (IE-HPLC) Hb Pavie was eluted as a shoulder of the major component and the corresponding glycated fraction together with Hb A1b. Hb Pavie was purified in order to determine how its functional properties may modify red cell survival. The only functional abnormality observed was a slight decrease of the oxygen affinity, and therefore the total amount of glycated hemoglobin was not expected to be decreased by a shortening of the red cell survival.

Amino Acid Sequence↗
PubMed1990

Hemoglobin Dhonburi alpha 2 beta 2 126 (H4) Val----Gly: a new unstable beta variant producing a beta-thalassemia intermedia phenotype in association with beta zero-thalassemia.

While investigating the mechanism of a beta-thalassemia intermedia phenotype in a 34 year old Thai male, a new Hb variant beta 126 Val----Gly named Hb Dhonburi was discovered. Genetic and structural studies revealed the existence of a beta zero-thalassemia genotype in association with the beta variant. The new variant is unstable but exhibits normal oxygen binding properties. Hb Dhonburi was also discovered in the mother of the propositus in association with Hb E.

1-Propanol↗
PubMed1990

Fate of alpha-hemoglobin chains and erythrocyte defects in beta-thalassemia.

The fate of alpha-hemoglobin chains and the cause of membrane protein defects in thalassemic erythrocytes have been studied in: (1) human beta-thalassemia syndromes, (2) mouse beta-thalassemia, and (3) normal human erythrocytes loaded with purified alpha-hemoglobin chains. The similarity and differences observed in these three systems underline the importance of insoluble alpha chains and the direct relationship between the amount of these chains and the membrane protein defects. Indeed, in addition to the alpha/non-alpha ratio of globin chain synthesis, the proteolysis and instability of alpha chains are major factors in modulating the cellular defects.

Animals↗
PubMed1989

Hemoglobin Nouakchott [alpha 114(GH2)Pro----Leu]: a new hemoglobin variant displaying an unusual increase in hydrophobicity.

The most striking fact in Hb Nouakchott [alpha 114(GH2)Pro----Leu] is the highly increased hydrophobicity of the abnormal chain. In comparison to other variants carrying the same amino-acid substitution, but at another position, the involvement of the environmental domains in the expression of the hydrophobicity is shown. Even though the substitution concerned a proline residue, it was without consequences on the oxygen binding and the stability of the molecule.

Adult↗
PubMed1989

Hemoglobin Athens-Georgia [alpha 2 beta 2 40(C6)Arg----Lys] in association with beta 0-thalassemia in Tunisia.

We describe an Hb Athens-Georgia (Hb A-Ga)/beta 0-thalassemia compound heterozygosity, found in a Tunisian patient. Oxygen binding studies of red cell suspensions of this patient, containing approximately 95% Hb A-Ga, revealed an almost normal oxygen affinity. Nevertheless, dilute solutions of Hb A-Ga showed an increased overall oxygen affinity and decreased heme-heme interaction. This could be explained by a tetrameric hemoglobin with normal oxygen binding properties but with increased dissociation into monomers or dimers, as a consequence of a structural abnormality within the alpha 1 beta 2 interface. Such an interpretation would explain the increased oxygen affinity reported in previous studies performed on heterozygous Hb A/Hb A-Ga patients.

Hemoglobins, Abnormal↗
PubMed1989

Hemoglobin Villejuif [beta 123(H1) Thr----Ile]: a new variant found in coincidence with polycythemia vera.

A new abnormal hemoglobin, Hb Villejuif [beta 123(H1) Thr----Ile] has been discovered during the exploration of a polycythemia in a 87-year-old patient of French origin. The isoelectric focusing of the lysate revealed the presence of a variant hemoglobin with an isoelectric point very close to that of HbA. The oxygen binding properties of the patient's red blood cells being normal, it was clear that the polycythemia was not a consequence of the presence of this hemoglobin. In fact, the red blood cell morphology and the involvement of the other blood cell lines, demonstrating excessive hemopoiesis, led to the diagnosis of polycythemia vera.

Aged↗
PubMed1989

Inhibition of K+ efflux and dehydration of sickle cells by [(dihydroindenyl)oxy]alkanoic acid: an inhibitor of the K+ Cl- cotransport system.

[(Dihydroindenyl)oxy]alkanoic acid (DIOA) was recently introduced as a potent inhibitor of the K+Cl- cotransport system without side effects on other cation transport systems [Garay, R. P., Nazaret, C., Hannaert, P.A. & Cragoe, E. J., Jr. (1988) Mol. Pharmacol. 33, 696-701]. In sickle cells, an abnormal activation of this K+Cl- cotransport system was proposed to be involved in cell K+ loss and dehydration. We found that DIOA inhibited the abnormal sickle cell K+ loss and specifically reduced sickle cell density upon stimulation of the net outward K+Cl- cotransport--i.e., low pH, hypoosmolarity, and activation by N-ethylmaleimide. DIOA opens another therapeutic approach to sickle cell disease by inhibiting cell dehydration, which favors HbS polymerization and reduces erythrocyte deformability.

Anemia, Sickle Cell↗
PubMed1989

Inhibition of oxygen-linked anion binding in Hb Camperdown [alpha 2 beta 2(104)(G6)Arg----Ser].

Oxygen equilibrium studies of purified Hb Camperdown [beta 104(G6) Arg----Ser] have revealed an increased oxygen affinity at acid pH, while it is decreased for pH values above 7.4. This accounts for an almost 40% reduction in the alkaline Bohr effect. The effects of chloride and organophosphate effectors on the oxygen affinity of Hb Camperdown are inhibited by 40-50%. In chloride-free Hepes buffer, Hb Camperdown exhibits a lower oxygen affinity than normal Hb A. The present results confirm the important role of the positively charged residues lining the beta 1 beta 2 interface in regulating the functional properties of hemoglobin.

2,3-Diphosphoglycerate↗
PubMed1989

Hb Fontainebleau [alpha 21(B2)Ala----pro], a new silent mutant hemoglobin.

Hb Fontainebleau [alpha 21(B2)Ala----Pro] was found in a family of Italian origin. This new variant has electrophoretic properties identical to those of Hb A with the exception of isoelectrofocusing in which it migrates like Hb A1c. The introduction of a prolyl residue at the beginning of the B helix in the alpha chain does not lead to a change in the stability or oxygen binding properties of the hemoglobin molecule.

Adolescent↗
PubMed1989

Hb Luxembourg [alpha 24(B5) Tyr----His]: a new unstable variant.

Hb Luxembourg [alpha 24(B5)Tyr----His] was found in association with mild hemolytic anemia and increased indirect bilirubinemia in a family originating from the Netherlands. The slight instability of this variant may be the consequence of an indirect effect of the substitution on the alpha 1 beta 1 contact since position alpha 24 (B5) is internal and in contact with several residues involved in this interface.

Adolescent↗
PubMed1989

Hb Bruxelles: alpha 2A beta (2)41 or 42(C7 or CD1)Phe deleted.

Hb Bruxelles is a new beta-globin variant producing severe congenital Heinz body anemia. It results from the deletion of one of the two adjacent phenylalanines, beta 41 or beta 42, presumably by frameshift mutagenesis. Its whole blood oxygen affinity is significantly lowered.

Amino Acid Sequence↗
PubMed1989

Structure-function of Hb Marseille-Long Island [alpha 2 beta 2 N-methionyl-2(NA2) His----Pro].

Suspensions of red cells containing Hb Marseille-Long Island showed decreased oxygen affinity and low interaction with 2,3-diphosphoglycerate. Oxygen equilibrium studies of the purified component confirmed these abnormalities. Oxidation rate measurements of carbonmonoxy-Hb Marseille and carbonmonoxy-Hb A by ferricyanide showed an increased rate for the former, suggesting an increased dissociation constant for carbon monoxide. Nuclear Magnetic Resonance spectra in the high field region revealed small changes in the proximal region of the heme pocket. These results indicated that the mutation causes a perturbation at a distance from the mutation site.

2,3-Diphosphoglycerate↗
PubMed1989

Filterability of sickle cells as a function of pO2: role of physico-chemical factors.

A rigidity index (RI) related to red blood cell deformability was measured by using the hemorheometre. The RI for 13 patients homozygous for sickle cell disease was 109 +/- 44 at 37 degrees C and at atmospheric pO2. The filtration time curve as a function of pO2 is biphasic for sickle cell suspensions. The pO2 at which filtration time is maximum, pO2max., correlated with the rigidity index measured at atmospheric pO2. This pO2max. value was very sensitive to small changes in physico-chemical parameters such as osmolality, pH, temperature, hematocrit, and cell density. Conditions which reduced the Hb S polymerization induced a leftward shift of pO2max.. The experimental curves are in agreement with theoretical models based on the presence of two abnormal cell types: filtrable "slow cells" and infiltrable "sickled cells".

Anemia, Sickle Cell↗