39 results on '"Lapouméroulie C"'
Search Results
2. Analysis of the 5′ flanking sequence of the Gγ globin gene by denaturing gradient gel electrophoresis confirms the heterogeneity of the Bantu βs haplotype
- Author
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Tachdjian, G., Benabdennebi, M., Guidal, C., Sayada, C., Lapouméroulie, C., and Elion, J.
- Published
- 1992
- Full Text
- View/download PDF
3. Haemoglobin D-Ouled Rabah among the Mozabites: A Relevant Variant to Trace the Origin of Berber-Speaking Populations
- Author
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Merghoub T, Alicia SANCHEZ-MAZAS, Tamouza R, Cy, Lu, Bouzid K, Fz, Ardjoun, Labie D, Lapouméroulie C, and Elion J
- Subjects
Genetic Markers ,Polymorphism, Genetic ,Hemoglobins, Abnormal ,DNA Mutational Analysis ,Hemoglobin C ,Hemoglobins ,Gene Frequency ,Haplotypes ,Algeria ,Blood Group Antigens ,Ethnicity ,Genetics ,Humans ,Genetics (clinical) - Abstract
We have studied haemoglobin (Hb) variants and blood groups (ABO, RH, and Kell) in 598 children from the Berber population of the Mzab. Hb D-Ouled Rabah, considered as a private marker of the Kel Kummer Tuaregs, and Hb C were found at the same gene frequency (0.015). Haplotype analysis suggests a single origin to the Hb D mutation. Genetic distances calculated from the blood group data cluster Mozabites and Tuaregs with the other Berber-speaking groups, Arabic-speaking populations being more distant. But, we found no specific relationship between Mozabites and Kel Kummers. Tuaregs in general exhibit features that tend to differentiate them from other Berber-speaking groups. Hb D-Ouled Rabah may be specific of Berber-speaking populations.
- Published
- 1997
4. DNA haplotype distribution in Algerian β thalassaemia patients: An extended evaluation by family studies and representative molecular characterization
- Author
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Rouabhi, F., Lapouméroulie, C., Amselem, S., Krishnamoorthy, R., Adjrad, L., Girot, R., Chardin, P., Benabdji, M., Labie, D., and Beldjord, C.
- Published
- 1988
- Full Text
- View/download PDF
5. [Pathophysiology of sickle cell disease]
- Author
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Elion J, Sandrine LAURANCE, and Lapouméroulie C
- Subjects
Erythrocytes ,Erythrocyte Membrane ,Hemoglobin, Sickle ,Cell Adhesion ,Humans ,Anemia, Sickle Cell ,Endothelium, Vascular ,Vascular Diseases - Abstract
It has been 100 years since Herrick published the first medical case report of sickle cell disease. In 1949, Pauling discovered hemoglobin S (HbS). As early as the 1960-70s, emerged a coherent detailed molecular-level description of pathophysiology of sickle disease. It involved polymerization of deoxyhemoglobin S with formation of long fibers inside red blood cells (RBC) causing a distorted sickle shape and shortened lifespan. These changes constitute the basic disease process and account for hemolytic anemia and for obstructive events underlying vasoocclusive crises (VOC). However, they do not explain the mechanisms that trigger VOC. The purpose of this review is to present recent data on dehydration of sickle cell RBC, abnormalities in RBC adhesion to the vascular endothelium, the role of inflammatory events and of activation of all cells in the vessel, and abnormalities of vascular tone and carbon monoxide metabolism. These data provide new insight into the pathophysiology of the first molecular disease.
- Published
- 2011
6. Hydroxyurée et drépanocytose : rôle des protéines d’adhérence
- Author
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Odièvre, M.-H., primary, Lapouméroulie, C., additional, and Elion, J., additional
- Published
- 2009
- Full Text
- View/download PDF
7. A novel mechanism for thalassaemia intermedia
- Author
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Badens, C, primary, Mattei, MG, additional, Imbert, AM, additional, Lapouméroulie, C, additional, Martini, N, additional, Michel, G, additional, and Lena-Russo, D, additional
- Published
- 2002
- Full Text
- View/download PDF
8. L'analyse phylogénétique du gène CFTR plaide pour l'utilisation du lapin comme modèle animal dans la mucoviscidose
- Author
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Vuillaumier, S, primary, Lapouméroulie, C, additional, Lehn, P, additional, Denamur, E, additional, Hinnrasky, J, additional, Puchelle, E, additional, Lecointre, G, additional, and Koltenboeck, B, additional
- Published
- 1997
- Full Text
- View/download PDF
9. Thalassemia in the Southeastern Part of Sicilya
- Author
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LOMBARDO, M., primary, RAGUSA, A., additional, XIMENES, B., additional, LAPOUMÉROULIE, C., additional, LABIE, D., additional, ELION, J., additional, KRISHNAMOORTHY, R., additional, and LOMBARDO, T., additional
- Published
- 1990
- Full Text
- View/download PDF
10. Homozygous deletional α+ thalassaemia associated with unequal expression of the two remaining α1 genes (α1A and α1Q).
- Author
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Pagnier, J., Elion, J., Lapouméroulie, C., Vigneron, C., and Labie, D.
- Published
- 1982
- Full Text
- View/download PDF
11. Analysis of the 5′ flanking sequence of the Gγ globin gene by denaturing gradient gel electrophoresis confirms the heterogeneity of the Bantu βs haplotype
- Author
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Tachdjian, G., Benabdennebi, M., Guidal, C., Sayada, C., Lapouméroulie, C., and Elion, J.
- Abstract
The GC?TT polymorphism recently described at positions — 1106 and — 1105 in the 5' flanking region of the G? globin gene for the Bantu ß
S haplotype was analysed by denaturing gradient gel electrophoresis. We studied 108 ßS chromosome and 122 ßA chromosomes. The TT sequence was found as follows: in all of 80 chromosomes bearing the Bantu ßS haplotype with the 6-bp deletion -400 nt from the G? gene in 3 out of 5 Bantu ßS chromosomes without the deletion, in 1 out of 122 ßA chromosomes from different ethnic origins but in none of 23 ßS chromosomes bearing the Senegal, Benin or Cameroon haplotypes. These results confirm the heterogeneity of the Bantu ßS haplotype and allow a tentative evolutionary sequence for the different alleles at this locus to be presented.- Published
- 1992
- Full Text
- View/download PDF
12. Thalassemia in the Southeastern Part of Sicilya.
- Author
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LOMBARDO, M., RAGUSA, A., XIMENES, B., LAPOUMÉROULIE, C., LABIE, D., ELION, J., KRISHNAMOORTHY, R., and LOMBARDO, T.
- Published
- 1990
- Full Text
- View/download PDF
13. Homozygous deletional α+thalassaemia associated with unequal expression of the two remaining α1genes (α1Aand α1Q)
- Author
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Pagnier, J., primary, Elion, J., additional, Lapouméroulie, C., additional, Vigneron, C., additional, and Labie, D., additional
- Published
- 1982
- Full Text
- View/download PDF
14. Homeostasis of extracellular ATP in uninfected RBCs from a Plasmodium falciparum culture and derived microparticles.
- Author
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Alvarez CL, Chêne A, Semblat JP, Gamain B, Lapouméroulie C, Fader CM, Hattab C, Sévigny J, Denis MFL, Lauri N, Ostuni MA, and Schwarzbaum PJ
- Subjects
- Adenosine Triphosphate metabolism, Erythrocytes metabolism, Homeostasis, Humans, Malaria metabolism, Plasmodium falciparum metabolism
- Abstract
Plasmodium falciparum, a dangerous parasitic agent causing malaria, invades human red blood cells (RBCs), causing hemolysis and microvascular obstruction. These and other pathological processes of malaria patients are due to metabolic and structural changes occurring in uninfected RBCs. In addition, infection activates the production of microparticles (MPs). ATP and byproducts are important extracellular ligands modulating purinergic signaling within the intravascular space. Here, we analyzed the contribution of uninfected RBCs and MPs to the regulation of extracellular ATP (eATP) of RBCs, which depends on the balance between ATP release by specific transporters and eATP hydrolysis by ectonucleotidases. RBCs were cultured with P. falciparum for 24-48 h prior to experiments, from which uninfected RBCs and MPs were purified. On-line luminometry was used to quantify the kinetics of ATP release. Luminometry, colorimetry and radioactive methods were used to assess the rate of eATP hydrolysis by ectonucleotidases. Rates of ATP release and eATP hydrolysis were also evaluated in MPs. Uninfected RBCs challenged by different stimuli displayed a strong and transient activation of ATP release, together with an elevated rate of eATP hydrolysis. MPs contained ATP in their lumen, which was released upon vesicle rupture, and were able to hydrolyze eATP. Results suggest that uninfected RBCs and MPs can act as important determinants of eATP regulation of RBCs during malaria. The comparison of eATP homeostasis in infected RBCs, ui-RBCs, and MPs allowed us to speculate on the impact of P. falciparum infection on intravascular purinergic signaling and the control of the vascular caliber by RBCs., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
15. Plasma microparticles of sickle patients during crisis or taking hydroxyurea modify endothelium inflammatory properties.
- Author
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Garnier Y, Ferdinand S, Garnier M, Cita KC, Hierso R, Claes A, Connes P, Hardy-Dessources MD, Lapouméroulie C, Lemonne N, Etienne-Julan M, El Nemer W, and Romana M
- Subjects
- Adolescent, Endothelium, Vascular pathology, Endothelium, Vascular physiopathology, Female, Humans, Inflammation blood, Inflammation drug therapy, Inflammation pathology, Inflammation physiopathology, Male, Anemia, Sickle Cell blood, Anemia, Sickle Cell drug therapy, Anemia, Sickle Cell pathology, Anemia, Sickle Cell physiopathology, Cell-Derived Microparticles metabolism, Endothelium, Vascular metabolism, Hydroxyurea administration & dosage, Intercellular Adhesion Molecule-1 blood, RNA, Messenger blood
- Abstract
Microparticles (MPs) are submicron extracellular vesicles exposing phosphatidylserine (PS), detected at high concentration in the circulation of sickle cell anemia (SS) patients. Several groups studied the biological effects of MPs generated ex vivo. Here, we analyzed for the first time the impact of circulating MPs on endothelial cells (ECs) from 60 sickle cell disease (SCD) patients. MPs were collected from SCD patients and compared with MPs isolated from healthy individuals (AA). Other plasma MPs were purified from SS patients before and 2 years after the onset of hydroxyurea (HU) treatment or during a vaso-occlusive crisis and at steady-state. Compared with AA MPs, SS MPs increased EC ICAM-1 messenger RNA and protein levels, as well as neutrophil adhesion. We showed that ICAM-1 overexpression was primarily caused by MPs derived from erythrocytes, rather than from platelets, and that it was abolished by MP PS capping using annexin V. MPs from SS patients treated with HU were less efficient to induce a proinflammatory phenotype in ECs compared with MPs collected before therapy. In contrast, MPs released during crisis increased ICAM-1 and neutrophil adhesion levels, in a PS-dependent manner, compared with MPs collected at steady-state. Furthermore, neutrophil adhesion was abolished by a blocking anti-ICAM-1 antibody. Our study provides evidence that MPs play a key role in SCD pathophysiology by triggering a proinflammatory phenotype of ECs. We also uncover a new mode of action for HU and identify potential therapeutics: annexin V and anti-ICAM-1 antibodies., (© 2020 by The American Society of Hematology.)
- Published
- 2020
- Full Text
- View/download PDF
16. Insights into determinants of spleen injury in sickle cell anemia.
- Author
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El Hoss S, Cochet S, Marin M, Lapouméroulie C, Dussiot M, Bouazza N, Elie C, de Montalembert M, Arnaud C, Guitton C, Pellegrino B, Odièvre MH, Moati F, Le Van Kim C, Aronovicz YC, El Nemer W, and Brousse V
- Subjects
- Biomarkers, Erythrocyte Deformability drug effects, Erythrocyte Inclusions pathology, Female, Humans, Immunophenotyping, Incidence, Male, Phosphorylation, Radionuclide Imaging methods, Splenic Diseases epidemiology, Anemia, Sickle Cell complications, Disease Susceptibility, Splenic Diseases diagnosis, Splenic Diseases etiology
- Abstract
Spleen dysfunction is central to morbidity and mortality in children with sickle cell anemia (SCA). The initiation and determinants of spleen injury, including acute splenic sequestration (ASS) have not been established. We investigated splenic function longitudinally in a cohort of 57 infants with SCA enrolled at 3 to 6 months of age and followed up to 24 months of age and explored the respective contribution of decreased red blood cell (RBC) deformability and increased RBC adhesion on splenic injury, including ASS. Spleen function was evaluated by sequential
99m Tc heated RBC spleen scintigraphy and high-throughput quantification of RBCs with Howell-Jolly bodies (HJBs). At 6 and 18 months of age, spleen filtration function was decreased in 32% and 50% of infants, respectively, whereas the median %HJB-RBCs rose significantly (from 0.3% to 0.74%). An excellent correlation was established between %HJB-RBCs and spleen scintigraphy results. RBC adhesion to laminin and endothelial cells increased with time. Adhesion to endothelial cells negatively correlated with splenic function. Irreversibly sickled cells (ISCs), used as a surrogate marker of impaired deformability, were detected at enrollment and increased significantly at 18 months. %ISCs correlated positively with %HJB-RBCs and negatively with splenic uptake, indicating a relationship between their presence in the circulation and spleen dysfunction. In the subgroup of 8 infants who subsequently experienced ASS, %ISCs at enrollment were significantly higher compared with the asymptomatic group, suggesting a major role of impaired deformability in ASS. Higher levels of %HJB-RBCs were observed after the occurrence of ASS, demonstrating its negative impact on splenic function., (© 2019 by The American Society of Hematology.)- Published
- 2019
- Full Text
- View/download PDF
17. Prognostic factors of disease severity in infants with sickle cell anemia: A comprehensive longitudinal cohort study.
- Author
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Brousse V, El Hoss S, Bouazza N, Arnaud C, Bernaudin F, Pellegrino B, Guitton C, Odièvre-Montanié MH, Mames D, Brouzes C, Picard V, Nguyen-Khoa T, Pereira C, Lapouméroulie C, Pissard S, Gardner K, Menzel S, Le Van Kim C, Colin-Aronovicz Y, Buffet P, Mohandas N, Elie C, Maier-Redelsperger M, El Nemer W, and de Montalembert M
- Subjects
- Anemia, Sickle Cell complications, Anemia, Sickle Cell therapy, Biomarkers analysis, Blood Transfusion, Cohort Studies, Female, Fetal Hemoglobin analysis, Hemoglobins analysis, Hospitalization, Humans, Infant, Longitudinal Studies, Male, Prognosis, Anemia, Sickle Cell diagnosis, Severity of Illness Index
- Abstract
In order to identify very early prognostic factors that can provide insights into subsequent clinical complications, we performed a comprehensive longitudinal multi-center cohort study on 57 infants with sickle cell anemia (55 SS; 2 Sβ°) during the first 2 years of life (ClinicalTrials.gov: NCT01207037). Time to first occurrence of a severe clinical event-acute splenic sequestration (ASS), vaso-occlusive (VOC) event requiring hospitalization, transfusion requirement, conditional/ abnormal cerebral velocities, or death-was used as a composite endpoint. Infants were recruited at a mean age of 4.4 ±1 months. Median follow-up was 19.4 months. During the study period, 38.6% of infants experienced ≥1 severe event: 14% ASS, 22.8% ≥ 1 VOC (median age: 13.4 and 12.8 months, respectively) and 33.3% required transfusion. Of note, 77% of the cohort was hospitalized, with febrile illness being the leading cause for admission. Univariate analysis of various biomarkers measured at enrollment showed that fetal hemoglobin (HbF) was the strongest prognostic factor of subsequent severe outcome. Other biomarkers measured at enrolment including absolute neutrophil or reticulocyte counts, expression of erythroid adhesion markers, % of dense red cells, cellular deformability or ϒ-globin genetic variants, failed to be associated with severe clinical outcome. Multivariate analysis demonstrated that higher Hb concentration and HbF level are two independent protective factors (adjusted HRs (95% CI) 0.27 (0.11-0.73) and 0.16 (0.06-0.43), respectively). These findings imply that early measurement of HbF and Hb levels can identify infants at high risk for subsequent severe complications, who might maximally benefit from early disease modifying treatments., (© 2018 Wiley Periodicals, Inc.)
- Published
- 2018
- Full Text
- View/download PDF
18. Newborn screening for sickle cell disease in Europe: recommendations from a Pan-European Consensus Conference.
- Author
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Lobitz S, Telfer P, Cela E, Allaf B, Angastiniotis M, Backman Johansson C, Badens C, Bento C, Bouva MJ, Canatan D, Charlton M, Coppinger C, Daniel Y, de Montalembert M, Ducoroy P, Dulin E, Fingerhut R, Frömmel C, García-Morin M, Gulbis B, Holtkamp U, Inusa B, James J, Kleanthous M, Klein J, Kunz JB, Langabeer L, Lapouméroulie C, Marcao A, Marín Soria JL, McMahon C, Ohene-Frempong K, Périni JM, Piel FB, Russo G, Sainati L, Schmugge M, Streetly A, Tshilolo L, Turner C, Venturelli D, Vilarinho L, Yahyaoui R, Elion J, and Colombatti R
- Subjects
- Anemia, Sickle Cell epidemiology, Consensus Development Conferences as Topic, Europe epidemiology, Female, Humans, Infant, Newborn, Male, Neonatal Screening, Practice Guidelines as Topic, Anemia, Sickle Cell diagnostic imaging, Anemia, Sickle Cell genetics
- Abstract
Sickle Cell Disease (SCD) is an increasing global health problem and presents significant challenges to European health care systems. Newborn screening (NBS) for SCD enables early initiation of preventive measures and has contributed to a reduction in childhood mortality from SCD. Policies and methodologies for NBS vary in different countries, and this might have consequences for the quality of care and clinical outcomes for SCD across Europe. A two-day Pan-European consensus conference was held in Berlin in April 2017 in order to appraise the current status of NBS for SCD and to develop consensus-based statements on indications and methodology for NBS for SCD in Europe. More than 50 SCD experts from 13 European countries participated in the conference. This paper aims to summarise the discussions and present consensus recommendations which can be used to support the development of NBS programmes in European countries where they do not yet exist, and to review existing programmes., (© 2018 British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2018
- Full Text
- View/download PDF
19. A microfluidic approach to study the effect of mechanical stress on erythrocytes in sickle cell disease.
- Author
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Lizarralde Iragorri MA, El Hoss S, Brousse V, Lefevre SD, Dussiot M, Xu T, Ferreira AR, Lamarre Y, Silva Pinto AC, Kashima S, Lapouméroulie C, Covas DT, Le Van Kim C, Colin Y, Elion J, Français O, Le Pioufle B, and El Nemer W
- Subjects
- Adolescent, Adult, Biomechanical Phenomena, Child, Child, Preschool, Erythrocyte Deformability, Female, Humans, Male, Middle Aged, Young Adult, Anemia, Sickle Cell blood, Erythrocytes pathology, Lab-On-A-Chip Devices, Stress, Mechanical
- Abstract
The human red blood cell is a biconcave disc of 6-8 × 2 μm that is highly elastic. This capacity to deform enables it to stretch while circulating through narrow capillaries to ensure its main function of gas exchange. Red cell shape and deformability are altered in membrane disorders because of defects in skeletal or membrane proteins affecting protein-protein interactions. Red cell properties are also altered in other pathologies such as sickle cell disease. Sickle cell disease is a genetic hereditary disorder caused by a single point mutation in the β-globin gene generating sickle haemoglobin (HbS). Hypoxia drives HbS polymerisation that is responsible for red cell sickling and reduced deformability. The main clinical features of sickle cell disease are vaso-occlusive crises and haemolytic anaemia. Foetal haemoglobin (HbF) inhibits HbS polymerisation and positively impacts red cell survival in the circulation but the mechanism through which it exerts this action is not fully characterized. In this study, we designed a microfluidic biochip mimicking the dimensions of human capillaries to measure the impact of repeated mechanical stress on the survival of red cells at the single cell scale under controlled pressure. We show that mechanical stress is a critical parameter underlying intravascular haemolysis in sickle cell disease and that high intracellular levels of HbF protect against lysis. The biochip is a promising tool to address red cell deformability in pathological situations and to screen for molecules positively impacting this parameter in order to improve red cell survival in the circulation.
- Published
- 2018
- Full Text
- View/download PDF
20. Erythroid Adhesion Molecules in Sickle Cell Anaemia Infants: Insights Into Early Pathophysiology.
- Author
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Brousse V, Colin Y, Pereira C, Arnaud C, Odièvre MH, Boutemy A, Guitton C, de Montalembert M, Lapouméroulie C, Picot J, Le Van Kim C, and El Nemer W
- Subjects
- Anemia, Sickle Cell physiopathology, Female, Flow Cytometry, Gene Expression Profiling, Humans, Infant, Male, Anemia, Sickle Cell blood, CD58 Antigens blood, Cell Adhesion Molecules blood, Gene Expression Regulation, Lutheran Blood-Group System blood, Reticulocytes metabolism
- Abstract
Sickle cell anaemia (SCA) results from a single mutation in the β globin gene. It is seldom symptomatic in the first semester of life. We analysed the expression pattern of 9 adhesion molecules on red blood cells, in a cohort of 54 SCA and 17 non-SCA very young infants of comparable age (median 144 days, 81-196). Haemoglobin F (HbF) level was unsurprisingly elevated in SCA infants (41.2% ± 11.2) and 2-4 fold higher than in non-SCA infants, yet SCA infants presented significantly decreased Hb level and increased reticulocytosis. Cytometry analysis evidenced a specific expression profile on reticulocytes of SCA infants, with notably an increased expression of the adhesion molecules Lu/BCAM, ICAM-4 and LFA-3, both in percentage of positive cells and in surface density. No significant difference was found on mature red cells. Our findings demonstrate the very early onset of reticulocyte membrane modifications in SCA asymptomatic infants and allow an insight into the first pathological changes with the release of stress reticulocytes expressing a distinctive profile of adhesion molecules.
- Published
- 2014
- Full Text
- View/download PDF
21. Prior exposure of endothelial cells to hydroxycarbamide alters the flow dynamics and adhesion of sickle red blood cells.
- Author
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Verger E, Schoëvaërt D, Carrivain P, Victor JM, Lapouméroulie C, and Elion J
- Subjects
- Anemia, Sickle Cell blood, Anemia, Sickle Cell physiopathology, Cell Line, Endothelial Cells cytology, Endothelium, Vascular cytology, Erythrocytes cytology, Erythrocytes drug effects, Hemodynamics drug effects, Human Umbilical Vein Endothelial Cells, Humans, Vascular Cell Adhesion Molecule-1 analysis, Anemia, Sickle Cell drug therapy, Antisickling Agents pharmacology, Cell Adhesion drug effects, Endothelial Cells drug effects, Erythrocytes pathology, Hydroxyurea pharmacology
- Abstract
The hallmark of sickle cell disease (SCD) is vasoocclusive crisis (VOC). The sickle red blood cells (SS-RBCs) present enhanced adhesion to activated endothelial cells (ECs) as compared to normal RBCs (AA-RBCs) and believed to contribute to VOC. Hydroxycarbamide (HC), the sole drug thus far proven as efficacious at reducing VOC frequency, alters the expression of adhesion proteins both on RBCs and ECs. We investigated the functional effect of HC on the adhesive properties of ECs from the micro- or the macrocirculation (TrHBMEC, HPMEC, and HUVEC). Using a flow chamber, we analyzed RBC dynamics on the treated or untreated EC bed and firm adhesion in basal and inflammatory conditions. Most significant effects were obtained with ECs from the pulmonary microcirculation (HPMEC). HC treatment of ECs affects both transient interactions and firm adhesion of SS-RBCs to the EC bed. Indeed, first, HC-treatment of ECs decreases the number of firmly adherent SS-RBCs to the adhesion level of AA-RBCs in a VCAM-1 independent manner. Second, HC significantly increases the mean velocity of SS-RBCs and reduces the population of SS-RBCs in contact with the EC bed. These data provide additional evidence that modulation of SS-RBCs/ECs interactions by HC represents an important aspect of its mechanism of action.
- Published
- 2014
- Full Text
- View/download PDF
22. [Pathophysiology of sickle cell disease].
- Author
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Elion J, Laurance S, and Lapouméroulie C
- Subjects
- Cell Adhesion, Endothelium, Vascular cytology, Erythrocyte Membrane metabolism, Erythrocytes cytology, Hemoglobin, Sickle metabolism, Humans, Vascular Diseases etiology, Anemia, Sickle Cell physiopathology
- Abstract
It has been 100 years since Herrick published the first medical case report of sickle cell disease. In 1949, Pauling discovered hemoglobin S (HbS). As early as the 1960-70s, emerged a coherent detailed molecular-level description of pathophysiology of sickle disease. It involved polymerization of deoxyhemoglobin S with formation of long fibers inside red blood cells (RBC) causing a distorted sickle shape and shortened lifespan. These changes constitute the basic disease process and account for hemolytic anemia and for obstructive events underlying vasoocclusive crises (VOC). However, they do not explain the mechanisms that trigger VOC. The purpose of this review is to present recent data on dehydration of sickle cell RBC, abnormalities in RBC adhesion to the vascular endothelium, the role of inflammatory events and of activation of all cells in the vessel, and abnormalities of vascular tone and carbon monoxide metabolism. These data provide new insight into the pathophysiology of the first molecular disease.
- Published
- 2010
23. [Effect of hydroxyurea on adhesion proteins in sickle cell anemia].
- Author
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Odièvre MH, Lapouméroulie C, and Elion J
- Subjects
- Anemia, Sickle Cell blood, Humans, Anemia, Sickle Cell drug therapy, Antisickling Agents pharmacology, Cell Adhesion Molecules drug effects, Hydroxyurea pharmacology
- Published
- 2009
- Full Text
- View/download PDF
24. Endothelial cells do not express GSTA1: potential relevance to busulfan-mediated endothelial damage during haematopoietic stem cell transplantation.
- Author
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Vassord C, Lapouméroulie C, Koumaravelou K, Srivastava A, and Krishnamoorthy R
- Subjects
- Cells, Cultured, Endothelial Cells metabolism, Genotype, Glutathione Transferase genetics, Glutathione Transferase metabolism, Humans, Promoter Regions, Genetic genetics, Busulfan pharmacology, Endothelial Cells drug effects, Hematopoietic Stem Cell Transplantation
- Abstract
Busulfan-mediated endothelial damage is believed to be a common mechanism in a variety of vascular disorders that occur during haematopoietic stem cell transplantation. The alkylating capacity of busulfan is compromised in vivo by enzymatic conjugation with glutathione, principally catalysed by glutathione S-transferase alpha (GST alpha). We investigated whether the susceptibility of endothelial cells to busulfan-mediated damage is related to their intrinsic deficiency in GST alpha expression. We tested for the expression of GST alpha mRNA by real-time quantitative PCR and the GST protein by enzyme-linked immunosorbent assay in various independently derived endothelial cell types (human bone marrow-derived endothelial cell line and endothelial cells from human vein umbilical cord ) and in a control hepatic cell line, HepG2. We demonstrate that endothelial cells, contrary to hepatic cells do not express GST alpha either at mRNA or protein levels and hence are potentially susceptible to busulfan-mediated cytotoxic damage.
- Published
- 2008
- Full Text
- View/download PDF
25. Modulation of erythroid adhesion receptor expression by hydroxyurea in children with sickle cell disease.
- Author
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Odièvre MH, Bony V, Benkerrou M, Lapouméroulie C, Alberti C, Ducrocq R, Jacqz-Aigrain E, Elion J, and Cartron JP
- Subjects
- Africa South of the Sahara ethnology, Anemia, Sickle Cell blood, Anemia, Sickle Cell complications, Arterial Occlusive Diseases drug therapy, Arterial Occlusive Diseases metabolism, Basigin metabolism, CD36 Antigens metabolism, CD47 Antigen metabolism, Cell Adhesion Molecules metabolism, Child, Erythrocytes chemistry, Erythroid Precursor Cells chemistry, Erythropoiesis drug effects, Follow-Up Studies, France, Gene Expression Regulation drug effects, Humans, Hydroxyurea pharmacology, Integrin alpha4beta1 metabolism, Lutheran Blood-Group System, Neoplasm Proteins metabolism, Reticulocytes chemistry, Sialic Acid Binding Ig-like Lectin 1, Signal Transduction drug effects, Anemia, Sickle Cell drug therapy, Arterial Occlusive Diseases etiology, Cell Adhesion drug effects, Cell Adhesion Molecules blood, Erythrocyte Aggregation drug effects, Hydroxyurea therapeutic use, Membrane Glycoproteins blood, Receptors, Immunologic blood
- Abstract
Background: We investigated adhesion receptor levels on red blood cells, reticulocytes and erythroid progenitors from children with sickle cell disease treated or not with hydroxyurea., Design and Methods: Four groups of patients were investigated: (i) children receiving hydroxyurea for severe vaso-occlusive events (n=26); (ii) untreated children with a history of vaso-occlusive events (n=20); (iii) children with no history of vaso-occlusive events (n=28); and (iv) healthy African controls (n=27). Expression of adhesion receptors was analyzed by flow cytometry with specific mono-clonal antibodies., Results: Reticulocytes and/or red blood cells from the children with sickle cell disease showed significantly higher expression of CD36, alpha 4beta 1, Lu/BCAM than those from controls, whatever the severity of the disease, as well as less marked increases in expression of ICAM-4, CD47 and CD147. Under hydroxyurea treatment, the expression of CD36, alpha 4beta 1 and ICAM-4 (to a lesser extent) was decreased, but surprisingly the expression of Lu/BCAM (and also CD47 and CD147 to a lesser extent) was significantly increased. Alterations of levels of adhesion receptors could be recapitulated in two-phase liquid cultures of erythroid progenitors from controls and untreated children with a history of vaso-occlusive disease, grown in the absence or presence of hydroxyurea., Conclusions: Our results suggest that hydroxyurea acts during erythroid development and modulates adhesion receptor expression and function differently, possibly by acting on gene expression and the signaling cascade leading to receptor activation.
- Published
- 2008
- Full Text
- View/download PDF
26. Sodium phenyl butyrate downregulates endothelin-1 expression in cultured human endothelial cells: relevance to sickle-cell disease.
- Author
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Odièvre MH, Brun M, Krishnamoorthy R, Lapouméroulie C, and Elion J
- Subjects
- Anemia, Sickle Cell drug therapy, Anemia, Sickle Cell physiopathology, Cell Line, Transformed drug effects, Cell Line, Transformed metabolism, Drug Evaluation, Preclinical, Drug Synergism, Endothelial Cells metabolism, Endothelin-1 genetics, Humans, Hydroxyurea pharmacology, Intercellular Adhesion Molecule-1 biosynthesis, Intercellular Adhesion Molecule-1 genetics, Interferon-gamma pharmacology, RNA, Messenger biosynthesis, Solubility, Tumor Necrosis Factor-alpha pharmacology, Vascular Cell Adhesion Molecule-1 biosynthesis, Vascular Cell Adhesion Molecule-1 genetics, Endothelial Cells drug effects, Endothelin-1 biosynthesis, Gene Expression Regulation drug effects, Phenylbutyrates pharmacology
- Abstract
As hydroxyurea (HU), sodium phenyl butyrate (SPB) is known to induce fetal hemoglobin (HbF) expression and thus shows potentials for sickle-cell disease (SCD) treatment. More recently, few studies suggested that endothelial cells (ECs), a major pathophysiological actor of SCD, are also a target of SPB. Here, we show that SPB, as HU, reduces endothelin-1 mRNA expression and peptide release by human ECs in culture. SPB increases VCAM-1 and ICAM-1 mRNAs and soluble ICAM-1 release. Both drugs have a cumulative effect on ICAM-1 expression. We conclude that SPB, as HU, also affects the expression of molecules important to the pathophysiology of SCD, in addition to its effect on HbF. Its potential as an alternative or adjuvant drug in SCD treatment warrants further investigations., ((c) 2007 Wiley-Liss, Inc.)
- Published
- 2007
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27. Decreased plasma endothelin-1 levels in children with sickle cell disease treated with hydroxyurea.
- Author
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Lapouméroulie C, Benkerrou M, Odièvre MH, Ducrocq R, Brun M, and Elion J
- Subjects
- Anemia, Sickle Cell blood, Case-Control Studies, Child, Fetal Hemoglobin analysis, Humans, Anemia, Sickle Cell drug therapy, Endothelin-1 blood, Hydroxyurea therapeutic use
- Abstract
Plasma endothelin-1 (ET-1) is elevated in patients with sickle cell disease (SCD). Hydroxyurea (HU) is the only drug with demonstrated clinical efficacy in SCD. Here we show that treatment with HU results in a decreased concentration of circulating ET-1 which is not correlated with the HU-induced increase in HbF level. Blunting of the ET-1 vasoconstrictive stimulus could contribute to the beneficial effects of HU.
- Published
- 2005
28. Genetic polymorphism of the mannose-binding protein gene in children with sickle cell disease: identification of three new variant alleles and relationship to infections.
- Author
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Neonato MG, Lu CY, Guilloud-Bataille M, Lapouméroulie C, Nabeel-Jassim H, Dabit D, Girot R, Krishnamoorthy R, Feingold J, Besmond C, and Elion J
- Subjects
- Adolescent, Alleles, Child, Child, Preschool, Chromosomes, Human, Pair 10, Collectins, Exons, Female, Genetic Variation, Genotype, Homozygote, Humans, Male, Models, Genetic, Polymorphism, Restriction Fragment Length, Promoter Regions, Genetic, Anemia, Sickle Cell genetics, Carrier Proteins genetics, Polymorphism, Genetic
- Abstract
Mannose-binding protein (MBP) is a serum lectin that participates in the innate immune response. MBP deficiency may constitute a risk factor in the development of infections. Three MBP structural variants have been identified with a dominant effect on MBP serum concentration. Similarly, polymorphisms in the promoter of the corresponding gene (HSMBP1B) have been related to variations of MBP concentration in serum. Children with sickle cell disease (SCD) have an increased susceptibility to infections with encapsulated organisms resulting in meningitis, septicaemia, and osteomyelitis. We have investigated the HSMBP1B genotype in 242 children with SCD living in Paris. Apart from the known variant alleles, we identified three novel ones and report their distribution in our sample population. In addition, we found rather unexpectedly an increased frequency of the variant alleles in patients who had not suffered severe infections.
- Published
- 1999
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29. CFTR regions containing duodenum specific DNase I hypersensitive sites drive expression in intestinal crypt cells but not in fibroblasts.
- Author
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Dixméras I, Lapouméroulie C, Tallec LP, Bens M, Elion J, Vandewalle A, and Denamur E
- Subjects
- 3T3 Cells, Animals, Cystic Fibrosis genetics, Cystic Fibrosis physiopathology, Mice, Rats, Transfection, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Deoxyribonuclease I genetics, Gene Expression Regulation, Intestines physiology
- Abstract
We have investigated CFTR specific intestinal expression by transfection assays in mouse cultured fibroblasts and transimmortalized intestinal crypt m-ICc12 cells using the beta-galactosidase gene linked to rat CFTR non-coding regions. Two constructs were studied, one encompassing a 5.3 kb region 5' to the gene where numerous duodenum-specific DNase I hypersensitive sites (DHSs) were previously mapped and the other including a 1.3 kb 3' region in which novel DHSs had been identified. In transient transfection assays, transgenes were expressed in m-ICc12 cells but not in fibroblasts. In m-ICc12 cells, the pattern of expression of the chromosomally integrated transgenes paralleled the endogenous expression of CFTR and beta-galactosidase activity was detected in cells containing villin and forming domes. Thus, a 6.6 kb region encompassing 5' and 3' non-coding parts of rat CFTR is able to drive specific expression of a reporter gene in cultured mouse intestinal cells having kept a crypt phenotype.
- Published
- 1998
- Full Text
- View/download PDF
30. Cross-species characterization of the promoter region of the cystic fibrosis transmembrane conductance regulator gene reveals multiple levels of regulation.
- Author
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Vuillaumier S, Dixmeras I, Messaï H, Lapouméroulie C, Lallemand D, Gekas J, Chehab FF, Perret C, Elion J, and Denamur E
- Subjects
- Activating Transcription Factor 1, Animals, Base Sequence, Caco-2 Cells, Cattle, Cyclic AMP metabolism, Cystic Fibrosis Transmembrane Conductance Regulator metabolism, DNA Footprinting, DNA-Binding Proteins metabolism, Deoxyribonucleases, Type I Site-Specific metabolism, Fos-Related Antigen-2, Haplorhini, Humans, Mice, Molecular Sequence Data, Nucleic Acid Conformation, Phylogeny, Proto-Oncogene Proteins c-jun metabolism, Rats, Species Specificity, Tetradecanoylphorbol Acetate metabolism, Transcription Factors metabolism, Transcription, Genetic, Chromatin genetics, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Gene Expression, Gene Expression Regulation, Promoter Regions, Genetic
- Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR) gene is highly conserved within vertebrate species. Its pattern of expression in vivo seems to be tightly regulated both developmentally and in a tissue-specific manner, but shows differences with species. To identify transcriptional regulatory elements in the CFTR promoter region, we have used a combined approach based both on the analysis of the chromatin structure in vivo in rat tissues and on evolutionary clues (i.e. phylogenetic footprinting). In CFTR-expressing tissues, 15 DNase I-hypersensitive sites were identified within a 36 kb region encompassing exon 1. Eleven of them are clustered in a 3.5 kb region that exhibits eleven phylogenetic footprints observed when comparing sequences from eight mammalian species representing four orders (Primates, Artiodactylia, Lagomorpha and Rodentia). Comparison of the two sets of data allows the identification of two types of regulatory elements. Some are conserved between species, such as a non-consensus cAMP response element (CRE) and a PMA-responsive element (TRE) located respectively at positions -0.1 and -1.3 kb relative to ATG. Some are species-specific elements such as a 300 bp purine.pyrimidine (Pu.Py) stretch that is present only in rodents. Analysis of protein/DNA interactions in vitro with rat tissue protein extracts on the conserved elements revealed that the TRE site binds a specific heterodimeric complex composed of Fra-2, Jun D and a protein immunologically related to Jun/CRE-binding protein in the duodenum, whereas the CRE-like site binds ATF-1 ubiquitously. Functional analysis in Caco-2 cells showed that the CRE-like site supports a high basal transcriptional activity but is not able by itself to induce a response to cAMP, whereas the TRE site acts as a weak transactivator stimulated by PMA. Lastly, we found that the rodent-specific Pu.Py stretch confers nuclease S1 hypersensitivity under conditions of acidic pH and supercoiling. This indicates a non-B DNA conformation and thus reinforces the biological significance of non-random Pu.Py strand asymmetry in the regulation of transcription. Thus the tight transcriptional regulation of CFTR expression involves the combination of multiple regulatory elements that act in the chromatin environment in vivo. Some of them are conserved throughout evolution, such as the CRE-like element, which is clearly involved in the basal level of transcription; others are species-specific.
- Published
- 1997
- Full Text
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31. Molecular basis of alpha-thalassemia in Sicily.
- Author
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Fichera M, Spalletta A, Fiorenza F, Lombardo T, Schilirò G, Tamouza R, Lapouméroulie C, Labie D, and Ragusa A
- Subjects
- Adolescent, Base Sequence, Child, Child, Preschool, DNA, DNA Mutational Analysis, Gene Deletion, Gene Frequency, Genotype, Humans, Molecular Sequence Data, Phenotype, Sicily epidemiology, alpha-Thalassemia epidemiology, Mutation, alpha-Thalassemia genetics
- Abstract
To evaluate the allelic frequency and genetic diversity of alpha-thalassemia defects in Sicily, both epidemiological and patient-oriented studies were carried out. For the epidemiological study, phenotypic data were collected on more than 1000 Sicilian individuals. Among them, 427 were explored at the molecular level for nine alpha-thalassemic variants known to be common in the Mediterranean region. Our data reveal an allele frequency of 4.1% for alpha(+)-thalassemia matching that of beta-thalassemia in this region. The presence of alpha0-thalassemia (--MEDI and --CAL) was observed only in the group of referred patients. Newly acquired nucleotide sequence data on the deletional breakpoint of --CAL allowed us to design a simple PCR-based procedure for exploring this allele. The data also provide additional information concerning the genetic mechanisms involved in such large deletions.
- Published
- 1997
- Full Text
- View/download PDF
32. Sequence correction and reassignment of the TaqI polymorphic site in the human inter-gamma-globin gene region, an African-specific marker.
- Author
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Guidal C, Lapouméroulie C, Krishnamoorthy R, and Elion J
- Subjects
- Chromosome Mapping, Gene Amplification, Genetic Markers, Genotype, Humans, Polymerase Chain Reaction, Sequence Analysis, DNA, Sequence Tagged Sites, Black People genetics, DNA Probes analysis, Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor genetics, Multigene Family genetics, Polymorphism, Genetic
- Abstract
We report here that the assignment of nt 37504 in the human inter-gamma-globin gene region of the HUMHBB locus sequence as a C is incorrect and should be replaced by a T. Accordingly, the polymorphic TaqI site, originally described at position 37503 as an African-specific marker, is actually located at position 37992. A PCR-based assay for this anthropologically important genetic marker is described.
- Published
- 1994
33. Inter-ethnic polymorphism of the beta-globin gene locus control region (LCR) in sickle-cell anemia patients.
- Author
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Périchon B, Ragusa A, Lapouméroulie C, Romand A, Moi P, Ikuta T, Labie D, Elion J, and Krishnamoorthy R
- Subjects
- Algeria, Base Sequence, Benin, Cameroon, Central African Republic, Haplotypes, Humans, India, Linkage Disequilibrium, Molecular Sequence Data, Nucleic Acid Conformation, Polymerase Chain Reaction, Regulatory Sequences, Nucleic Acid, Repetitive Sequences, Nucleic Acid, Senegal, Sequence Analysis, DNA, Sicily, Anemia, Sickle Cell ethnology, Anemia, Sickle Cell genetics, Black People genetics, Globins genetics, Polymorphism, Genetic
- Abstract
Sequence polymorphisms within the 5'HS2 segment of human locus control region is described among sickle cell anemia patients. Distinct polymorphic patterns of a simple sequence repeat are observed in strong linkage disequilibrium with each of the five major beta s haplotypes. Potential functional relevance of this polymorphic region in globin gene expression is discussed.
- Published
- 1993
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34. A novel sickle cell mutation of yet another origin in Africa: the Cameroon type.
- Author
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Lapouméroulie C, Dunda O, Ducrocq R, Trabuchet G, Mony-Lobé M, Bodo JM, Carnevale P, Labie D, Elion J, and Krishnamoorthy R
- Subjects
- Base Sequence, Blotting, Southern, Cameroon, Fetal Hemoglobin, Humans, Linkage Disequilibrium, Molecular Sequence Data, Mutation genetics, Polymerase Chain Reaction, Recombination, Genetic genetics, Anemia, Sickle Cell genetics, Hemoglobin, Sickle genetics, Polymorphism, Restriction Fragment Length
- Abstract
The sickle cell mutation (beta s) arose as at least three independent events in Africa and once in Asia, being termed the Senegal, Benin, Bantu and Indian types respectively. An investigation in Cameroon was carried out to determine whether the atypical sickle genes observed in the neighboring countries are the result of recombination or the presence of a sickle cell mutation of a different genetic origin. It was conducted on 40 homozygous SS patients followed at the Blood Transfusion Center in the capital city of Yaoundé. On 80 beta s chromosomes, 13 exhibited a novel polymorphic pattern that was observed three times in the homozygous state. This chromosome contains an A gamma T gene. The restriction fragment length polymorphism haplotype is different from all the other beta s chromosomes in both the 5' and 3' regions, but has previously been reported in sporadic cases. The (AT)8(T)5 sequence in the -500 region of the beta gene is specific and different from that of the Senegal, Benin, Bantu or Indian beta s genes. All the carriers of this specific chromosome belong to the Eton ethnic group and originate from the Sanaga river valley. This observation strongly argues for yet another independent origin of the sickle cell mutation in Africa, here referred to as the "Cameroon type". The Benin haplotype and a Benin/Bantu recombinant haplotype have been observed in the other studied populations: Ewondo, Bamiléké, Bassa, Yambassa and Boulou.
- Published
- 1992
- Full Text
- View/download PDF
35. DNA sequence variation in a negative control region 5' to the beta-globin gene correlates with the phenotypic expression of the beta s mutation.
- Author
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Elion J, Berg PE, Lapouméroulie C, Trabuchet G, Mittelman M, Krishnamoorthy R, Schechter AN, and Labie D
- Subjects
- Africa ethnology, Base Sequence, DNA-Binding Proteins metabolism, Gene Expression Regulation, Genetics, Population, Haplotypes, Humans, India ethnology, Molecular Sequence Data, Oligodeoxyribonucleotides chemistry, Phenotype, Polymorphism, Restriction Fragment Length, Regulatory Sequences, Nucleic Acid, Anemia, Sickle Cell genetics, Globins genetics, Hemoglobin, Sickle genetics
- Abstract
The clinical diversity of sickle cell anemia is strongly related to the degree of intracellular hemoglobin S (Hb S) polymerization, which in turn is dependent on the intracellular concentration of Hb S. We have recently defined a region of DNA approximately 500 bp 5' to the human beta-globin gene that acts as a silencer for the transcription of this gene and have shown that a polymorphism in this sequence is associated with a thalassemic phenotype of the beta-globin gene. In this work we have examined the correlation of DNA sequence polymorphisms in this silencer with binding of a previously identified putative repressor protein, BP1, and with the expression of Hb S in individuals heterozygous for the beta s allele. It was found that specific configurations of the motif, (AT)x(T)y, are homogeneous for the major haplotypes of the beta-globin gene cluster described on beta s chromosomes. Binding of BP1 was measured to DNA of three haplotypes: Indian, Benin, and Bantu. BP1 binds most tightly to DNA of the Indian haplotype, and these patients produce less beta s protein than Benin patients, whose DNA exhibits weaker affinity for BP1. Binding of BP1 is the weakest to DNA of the Bantu haplotype, which is associated with clinically more severe sickle cell symptoms. These data are consistent with the hypothesis that these polymorphisms may not be neutral and that the DNA sequence at this site may affect the expression of the beta s gene. Such an effect may be synergistic with other genetic variables, such as fetal hemoglobin levels, F-cell numbers, and the number of alpha-globin genes, in determining intracellular polymerization and, thus, the severity of the sickle cell syndromes.
- Published
- 1992
36. Nucleotide sequence evidence of the unicentric origin of the beta C mutation in Africa.
- Author
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Trabuchet G, Elion J, Dunda O, Lapouméroulie C, Ducrocq R, Nadifi S, Zohoun I, Chaventre A, Carnevale P, and Nagel RL
- Subjects
- Africa, Base Sequence, DNA, Haplotypes, Humans, Molecular Sequence Data, Polymorphism, Restriction Fragment Length, Repetitive Sequences, Nucleic Acid, Globins genetics, Mutation
- Abstract
The origin of the beta C mutation was studied by characterizing nucleotide sequence polymorphisms on beta C chromosomes of patients from various African countries. In the majority of cases, the beta C mutation was found in linkage disequilibrium with a single chromosomal structure as defined by classical RFLP haplotypes, intergenic nucleotide sequence polymorphisms immediately upstream of the beta-globin gene, and intragenic beta-globin gene polymorphisms (frameworks). In addition, three atypical variant chromosomes carrying the beta C mutation were observed, and are most probably explained either by a meiotic recombination (two cases) or by one nucleotide substitution occurring in an unstable array of tandemly repeated sequences (one case). These data demonstrate the unicentric origin of the beta C mutation in central West Africa, with subsequent mutational modification in a small number of instances. The data also supports gene flow of the beta C chromosome from subsaharan Africa to North Africa.
- Published
- 1991
- Full Text
- View/download PDF
37. Four new haplotypes observed in Algerian beta-thalassemia patients.
- Author
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Beldjord C, Lapouméroulie C, Baird ML, Girot R, Adjrad L, Lenoir G, Benabadji M, and Labie D
- Subjects
- Algeria, DNA Restriction Enzymes genetics, Homozygote, Humans, Polymorphism, Genetic, Globins genetics, Haploidy, Thalassemia genetics
- Abstract
beta-Thalassemia, a heterogeneous group of human anemias affecting the expression of beta-globin, is caused by a number of molecular defects. Restriction endonuclease mapping of ethnic populations has revealed many polymorphisms within and around the beta-like globin genes, combinations of which are assigned as haplotypes. Several haplotypes appear to be strongly linked with the molecular defects causing thalassemia in Greek and Italian patients (Orkin et al. 1982). We describe here haplotypes from 40 Algerian beta-thalassemic patients and eight normals determined by restriction endonuclease mapping at seven polymorphic sites. Four haplotypes previously unreported were observed in these thalassemic patients; this argues the existence in this population of undescribed beta-thalassemia alleles. The knowledge of the haplotypes in thalassemic families could be used for prenatal diagnosis of homozygote forms.
- Published
- 1983
- Full Text
- View/download PDF
38. Glucose-6-phosphate dehydrogenase and hemoglobin variants in Kel Kummer Tuareg and related groups. Indirect evidence for alpha-thalassemia trait.
- Author
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Junien C, Chaventré A, Fofana Y, Lapouméroulie C, Floury B, Duflo B, Labie D, and Kaplan JC
- Subjects
- Black People, Consanguinity, Female, Gene Frequency, Humans, Male, Mali, Pedigree, White People, Genetic Variation, Glucosephosphate Dehydrogenase genetics, Hemoglobins genetics
- Abstract
A field study of glucose-6-phosphate dehydrogenase (G6PD) and hemoglobin polymorphisms was performed in 327 subjects belonging to the Kel Kummer, a highly inbred Tuareg tribe of North-East Mali, and to the contact populations. In the Kel Kummer group 11% of the investigated subjects carried the nondeficient G6PD A+ variant. No other G6PD variant was found. Hemoglobin D Ouled-Rabah was found in 21% of the subjects of this group. The presence of an alpha-thalassemic trait was also inferred from indirect evidence. The contact groups (Inedän, Iklan, Kel es Suq and Dausahaq) exhibited different polymorphisms at the G6PD and globin loci, substantiating their belonging to different ethnic stock.
- Published
- 1982
- Full Text
- View/download PDF
39. Homozygous deletional alpha + thalassaemia associated with unequal expression of the two remaining alpha 1 genes (alpha 1A and alpha 1Q).
- Author
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Pagnier J, Elion J, Lapouméroulie C, Vigneron C, and Labie D
- Subjects
- DNA blood, Electrophoresis, Cellulose Acetate, Female, Hemoglobins, Abnormal analysis, Homozygote, Humans, Infant, Newborn, Isoelectric Focusing, Male, Pedigree, Thalassemia blood, Chromosome Deletion, Gene Expression Regulation, Genes, Thalassemia genetics
- Abstract
A Cambodian family presenting several haemoglobinopathies, Hb E, Hb Q and alpha + thalassaemia, has been investigated. DNA analysis showed that the thalassaemia syndrome corresponds to a leftward type (4.2 kb) deletional form of alpha + thalassaemia. Genotypes found in the family are: propositus -alpha A/-alpha Q, beta A/beta E., mother and older sister alpha A alpha A/-alpha Q, beta A/beta E., father alpha A alpha A/-alpha A, beta A/beta A. The propositus consistently presents an alpha Q/alpha A chain ratio of 60/40 although both chains are products of alpha 1 loci. The relatively higher expression of the alpha Q chain is not observed in the mother and therefore makes it unlikely to reflect anything other than differential expression of the maternal -alpha Q/ and paternal -alpha A/ haplotypes. This observation raises the possibility that both haplotypes are not strictly identical and that the region of the cross-over event is important for alpha gene expression.
- Published
- 1982
- Full Text
- View/download PDF
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