Search PubMed⌕ Search

Biomedical subjects

F Galacteros

Publications and source records attributed to F Galacteros.

At least 37 records · Page 2Linked to original sources
PubMed1995

Structural determination of a new electrophoreticaly silent variant: hemoglobin Alzette, beta 104(G6)Arg --> Lys.

A new electrophoreticaly neutral hemoglobin variant was found by ion-exchange high-performance liquid chromatography (HPLC). The molecular mass of the beta-chain was shifted down 28 mass units. The modification was found in the beta T-11 peptide that co-elutes with beta T-14 in the tryptic HPLC profile. Collision-induced decomposition of the protonated modified peptide indicated the Arg --> Lys exchange at the C-terminus. This modifies the fragmentation pattern as charge-remote processes induced by the strong basicity of arginine were replaced by charge-induced mechanisms. The exchanged 104Arg is one of the chloride binding sites in the central cavity of Hb.

Amino Acid Sequence↗
PubMed1994

The involvement of the Ca-dependent K channel and of the KCl co-transport in sickle cell dehydration during cyclic deoxygenation.

We have investigated the mechanisms involved in sickle cell dehydration upon continuous or cyclic deoxygenation: the Ca(2+)-activated K+ channel and the KCl co-transport system. Short-term continuous deoxygenation (1 h) of sickle cells in a Ca(2+)-containing medium promoted a stimulation of the efflux of K+ and cell dehydration. This latter was reduced by the replacement of Ca2+ in the medium by EGTA, but not by addition of [(dihydro-indenyl) oxy] alkanoic acid (DIOA), an inhibitor of the KCl co-transport. During cycles of deoxygenation-reoxygenation, cell dehydration was partly prevented by EGTA and significantly reduced by DIOA only in the presence of Ca2+. The present data support the view that sickle cell dehydration during deoxygenation arises from the stimulation of the Ca(2+)-dependent K+ permeability leading to water loss, whereas during reoxygenation periods, subsequent activation of the KCl co-transport also contributes to cell dehydration.

Anemia, Sickle Cell↗
PubMed1994

Hb Cemenelum [alpha 92 (FG4) Arg-->Trp]: a hemoglobin variant of the alpha 1/beta 2 interface that displays a moderate increase in oxygen affinity.

Hb Cemenelum [alpha 92 (FG4) Arg-->Trp] carries a structural modification at the same position as Hb Chesapeake, a very high oxygen affinity variant. Hb Cemenelum was found in a French diabetic patient with no abnormal hematological features. The purified abnormal hemoglobin, like Hb J Cape Town, another variant of position alpha 92(FG4), displayed only a 1.5- to 2-fold increased oxygen affinity and a reduced cooperativity. This hemoglobin demonstrates that, even for some key residues of the alpha 1/beta 2 interface, the degree at which the functional properties are altered depends upon the specific residue occupying this position.

Amino Acid Sequence↗
PubMed1994

[Extensive bone marrow necrosis and major sickle cell syndromes].

Three cases of extensive bone marrow necrosis in patients with sickle cell disease are reported. All three patients presented severe bone pains with severe anaemia (haemoglobin value less than 5 g/dl) and high increased of LDH serum values (upper than 20 fold normal value). Bone marrow aspirate and biopsy showed typical signs of necrosis. The extent of necrosis was evaluated by reticuloendothelial scan obtained with 111In chloride. Treatment required transfusions of phenotyped red blood cell concentrates. Favourable outcome was observed in all patients.

Adult↗
PubMed1994

[Transfusion and alloimmunization in sickle cell anemia patients].

Transfusion therapy for sickle cell anemia is limited by the development of antibodies to red cell antigens. The aim of this study was to evaluate whether transfusion of blood matched for antigens Rh and Kell would reduce the incidence of alloimmunization. We determined the transfusion history, red cell phenotype and development of alloantibodies in 173 patients with sickle all anemia who received transfusions. Forty nine patients were transfused exclusively with frozen red blood cells (RBL) matched for antigens Rh and Kell; the rate of alloimmunization was 8.2%; antibodies to the Jkb, Jka, Fya and S were developed; 1 patient developed 2 antibodies. In a control group of 124 patients who received standard red blood cells, the rate of alloimmunization was significantly increased to 30.6% (p < 0.05); antibodies against C, E, K, Fya were the most frequently developed and 19 patients (16%) developed antibodies reacting with different antigens. In the 2 groups, alloimmunization occurred after receiving a significantly different number of transfusions: mean 9 in the patients transfused with matched RBC and 32 in the control group. The influence of the kinetics of transfusion was not demonstrated. To assess the effect that racial differences might have on alloimmunization, comparison of the red cell phenotype of patients with that of a panel of unselected blood bank donors was performed: the patients had a significant decrease in the frequency of red cell antigens corresponding to most of the detected alloantibodies JkB, C, S. Fyb, Fya and Kell.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[Potential alternatives to erythrocyte transfusion in hemoglobinopathies: hydroxyurea (HU), erythropoietin (EPO), butyrate derivatives, blood substitutes].

Transfusion is associated with improvement of life expectancy in beta thalassemia and sickle cell disease (SCD). Bone marrow transplantation concerns only a few patients. Among potentially useful therapeutic agents which can induce fetal hemoglobin (HbF) production, hydroxyurea (HU) stands out in particular for SCD. In our sickle cell center, 10 patients with SCD received HU for chronic leg ulcer with good results in terms of healing (7 among 10, who required no additional transfusion). A few patients, most of them over 30 years, received HU for chronic organ failure at the onset. HU on long term therapy over one year improved general status, Hb level, in 7 patients with beta thalassemia intermedia. A major challenge in the coming years will be the effective evaluation of clinical efficiency and the comparison of risks and benefits of such compounds versus transfusion.

Adolescent↗
PubMed1994

The use of Staphylococcus V8 protease in the structural determination of human hemoglobin variants: HB Valparaiso [alpha 88(F9)Ala-->Gly] example.

In human hemoglobin, enzymic cleavage with the protease from Staphylococcus aureus strain V8 (protease V8) is a convenient method for the study of variants that involve large peptides such as alpha T-9 and alpha T-12b. We report here on Hb Valparaiso [alpha 88(F9)Ala-->Gly], a new neutral variant with a slight increase in oxygen affinity, that was identified by use of this strategy.

Female↗
PubMed1994

Hb Taybe (alpha 38 or 39 THR deleted): an alpha-globin defect, silent in the heterozygous state and producing severe hemolytic anemia in the homozygous.

Several alpha-chain hemoglobin variants have been described as responsible, in homozygous or compound heterozygous patients, for a chronic hemolytic disease that overlaps thalassemia and Heinz bodies hemolytic anemia phenotypes. These variants are present in trace amounts together with some Hb H in the lysate of the patients. In the asymptomatic heterozygous carriers, they are usually not detected by electrophoretic methods. Hb Taybe is an example of such an unstable and thalassemic alpha-hemoglobin variant. This hemoglobin was observed in a young Israeli Arab woman having suffered since birth from a severe and highly regenerative hemolytic anemia for which she was splenectomized at age sixteen. The structural abnormality was characterized by protein chemistry as the deletion of a threonine residue at position alpha 38 or 39 and assigned to the alpha 1 gene by selective DNA sequencing. This structural modification is localized in helix C, which is a highly conserved 3(10) helix participating in the alpha 1 beta 2 contact and close to the alpha 1 beta 1 interface. The propositus and two siblings, who were also anemic, were found to be homozygous for the molecular defect, although the abnormal Hb was not detected in the latters. Consanguinity in this family demonstrated the threshold effect in the clinical manifestations of such alpha-gene disorders since heterozygotes were clinically and biologically normal.

Adult↗
PubMed1993

Hb Villaverde [beta 89 (F5) Ser-->Thr]: the structural modification of an intrasubunit contact is responsible for a high oxygen affinity.

Hb Villaverde [beta 89 (F5) Ser-->Thr], identified in a Spanish patient, is a new human hemoglobin variant, electrophoreticaly silent, responsible for a severe erythrocytosis. This abnormal hemoglobin displays a very high oxygen affinity and a markedly reduced cooperativity that is partly restored in the presence of IHP. Determination of the structural abnormality was achieved on a mixture of the normal and abnormal beta-chains. After isolation of the abnormal tryptic peptide by RP-HPLC, its sequence was determined by mass spectrometry. The structural abnormality disturbs the intrasubunit interaction between helices F and H and, thus, may weaken the C-terminal bonds of the deoxy conformation and the heme contacts of several hydrophobic residues. Hb Villaverde demonstrates that this intrasubunit contact between helices F and H is essential for the cohesion of the hemoglobin molecule.

Adult↗
PubMed1993

[Acute aseptic arthritis in major sickle cell syndromes].

We report 9 cases of febrile aseptic arthritis which occurred in 6 adults presenting with major sickle cell disease. The monoarticular arthritis affected the knee in 8 cases and the ankle in 1 case. Body temperature ranged from 38 degrees C to 39.5 degrees C in 7 cases, and neutrophilia (12.7 to 24 x 10(9)/l) was noted on six occasions. The always sterile synovial fluid contained 100 to 1700 cells/mm3 in 6 cases and 5200 to 12,500 cell/mm3 in 3 cases. Uricacidaemia was normal, and a search for crystals in the synovial fluid gave negative results. Bone scintigraphy and magnetic resonance imaging, performed in 3 patients, revealed the presence of a juxta-articular cortical bone infarct, whereas standard radiography was normal. In all patients, a brief immobilization and treatment with non-steroidal anti-inflammatory drugs resulted in complete cure in less than 10 days. These cases illustrate the characteristics of sickle cell arthritis, a rare complication of major sickle cell disease. Clinically, the condition resembles septic arthritis, being febrile and showing granulocytosis, but articular needle aspiration corrects the diagnosis. The mechanisms underlying these disorders have not yet been elucidated, but the bone scintigraphy and MRI performed in our patients are in favour of a reaction to a juxta-articular bone infarct.

Acute Disease↗
PubMed1993

Unstable alpha-chain hemoglobin variants with factitious beta-thalassemia biosynthetic ratio: Hb Questembert (alpha 131[H14]Ser-->Pro) and Hb Caen (alpha 132[H15]Val-->Gly).

Hb Questembert [alpha 131(H14)Ser-->Pro] was found in several members of a French family suffering from congenital Heinz body anemia. The unstable hemoglobin was expressed in the peripheral red blood cells at a very low level. Globin biosynthetic studies revealed a high specific activity of the abnormal chain and an alpha-/beta-labeling ratio similar to that of beta-thalassemia trait. Hb Caen [alpha 132(H15) Val-->Gly] is another unstable variant with the same globin biosynthesis abnormality. In both cases the structural modification is localized at the end of the H helix, a region encoded by the third exon. The mechanism for the unbalanced globin synthesis is not yet clear. It may be related 1) to a defect in chain assembly, 2) to an increased rate of degradation of the variant chain followed by the release of unlabeled beta-chains from the abnormal hemoglobin, thus leading to an apparent suppression of beta-chain synthesis, or 3) to a modified stability of the abnormal alpha-globin mRNA.

Adult↗
PubMed1993

Hb Saint Nazaire (beta 103[G5]Phe-->Ile): a new example of polycythemia due to a hemoglobin variant with increased oxygen affinity.

Hb Saint Nazaire [beta 103 (G5) Phe-->Ile] was found in four apparently unrelated French families. The five patients carrying this hemoglobin have been detected because of a moderate erythrocytosis. The structural abnormality of Hb Saint Nazaire concerns the same residue as in Hb Heathrow [beta 103 (G5) Phe-->Leu). A comparative functional study between these two variants showed that the increase in oxygen affinity is much lower in Hb Saint Nazaire than in Hb Heathrow. The replacement of phenylalanine G5, which is localized within the heme pocket, by a leucine abolishes several contacts between the heme and the globin and leads to an environment of the heme having some similarities with that observed in myoglobin. In contrast, the replacement of G5 by an isoleucine is likely to introduce less structural modifications.

Adolescent↗
PubMed1993

Comparative evaluation of laser Doppler flux metering, bulbar conjunctival angioscopy, and nail fold capillaroscopy in sickle cell disease.

Eleven adult patients with stable sickle cell disease (SCD) were investigated twice at a 15-day interval by nail fold capillaroscopy (NFC), bulbar conjunctival angioscopy (BCA), and laser Doppler flux metering (LDF). NFC and BCA are essentially descriptive. NFC revealed, in some patients, network patterns similar to those observed in vasculitis. BCA provides a reproducible method for the visual assessment of the microcirculation. When using a rating scale with five criteria it identified abnormalities related to both altered red blood cells and vascular morphology but failed to discriminate between patients. LDF, in contrast, is quantifiable and showed reproducible characteristic reactive alterations of vasomotion in response to ischemia after 3 min of occlusion. The SCD patients had a delayed response, best measured by the recovery half time, which was four to five times longer than that of normal subjects. In addition, the cold provocative test was always abnormal, as evidenced by a significant drop in the contralateral flux, and was often poorly tolerated. The observed trends suggest that BCA and LDF should be performed in a large cohort of patients, both in the steady state and during vasoocclusive crises. These methods seem to be useful complementary noninvasive procedures to cellular and clinical evaluation monitoring for therapeutic trials.

Adult↗
PubMed1993

Improvement of microcirculation abnormalities in sickle cell patients upon buflomedil treatment.

The efficacy of the vasoactive compound buflomedil on previously described microcirculation abnormalities observed in sickle cell disease (SCD) was investigated using bulbar conjunctival angioscopy (BCA) and laser doppler flux metering. Eleven sickle cell disease patients at steady state were studied in a double-blind randomized parallel-versus-placebo study (5 patients were given placebo and 6 patients received 600 mg buflomedil per day for 21 days after a washout period of 15 days). The blood flux score measured by BCA improved, indicating reduced entrapment of sickle red blood cells. There was a striking improvement of reactive alterations of vasomotion in the buflomedil group, particularly in postocclusive reactive hyperemia; the half return time was also significantly reduced. These results encourage further studies with buflomedil to investigate long-term effects of this compound in SCD, potential prevention of acute vaso-occlusive events, and degenerative complications.

Adult↗