In Vitro Red Blood Cell Segregation in Sickle Cell Anemia

Red blood cells in sickle cell anemia (sRBC) are more heterogeneous in their physical properties than healthy red blood cells, spanning adhesiveness, rigidity, density, size, and shape. sRBC with increased adhesiveness to the vascular wall would trigger vaso-occlusive like complications, a hallmark of sickle cell anemia. We investigated whether segregation occurs among sRBC flowing in micron-sized channels and tested the impact of aggregation on segregation. Two populations of sRBC of different densities were separated, labeled, and mixed again. The mixed suspension was flowed within glass capillary tubes at different pressure-drops, hematocrit, and suspending media that promoted or not cell aggregation. Observations were made at a fixed channel position. The mean flow velocity was obtained by using the cells as tracking particles, and the cell depleted layer (CDL) by measuring the distance from the cell core border to the channel wall. The labeled sRBC were identified by stopping the flow and scanning the cells within the channel section. The tube hematocrit was estimated from the number of fluorescence cells identified in the field of view. In non-aggregating media, our results showed a heterogeneous distribution of sRBC according to their density: low-density sRBC population remained closer to the center of the channel, while the densest cells segregated towards the walls. There was no impact of the mean flow velocity and little impact of hematocrit. This segregation heterogeneity could influence the ability of sRBC to adhere to the vascular wall and slow down blood flow. However, promoting aggregation inhibited segregation while CDL thickness was enhanced by aggregation, highlighting a potential protective role against vaso-occlusion in patients with sickle cell anemia

"LOLF et Justice"

International audienc

Les attentes et besoins des internes face au "Livret pratique" au sein du service de pédiatrie du Centre Hospitalier de Blois

TOURS-BU Médecine (372612103) / SudocSudocFranceF

Phylogénie des rétrovirus, et utilisation de la variabilité génétique du SIV dans l'étude de l'immunopathologie

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Antigenic stimulation specifically reactivates the replication of archived simian immunodeficiency virus genomes in chronically infected macaques.

Human immunodeficiency virus/simian immunodeficiency virus (SIV) diversification is a direct consequence of viral replication and occurs principally in secondary lymphoid organs where CD4(+) T cells are activated and proliferate. However, the evolution of viral quasispecies may also be driven by various nonexclusive mechanisms, including adaptation to specific immune responses and modification of viral fitness. Analysis of viral quasispecies in SIV-infected macaques subjected to repeated antigenic stimulations allowed us to demonstrate transient expansions of SIV populations that were highly dependent upon activation of antigen-specific T cells. T-cell clones expanded in response to a particular antigen were infected by a specific viral population and persisted for prolonged periods. Upon a second stimulation by encounter with the same antigen, these specific genomes were at the origin of a new burst of replication, leading to rapid but transient replacement of the viral quasispecies in blood. Finally, longitudinal analysis of SIV sequence variation during and between antigenic stimulations revealed that viral evolution is mostly constrained to periods of strong immunological activity

Dual mechanical characterisation of red blood cells: role of surface area, internal viscosity and membrane rigidity

International audienc

Dual mechanical characterisation of red blood cells: role of surface area, internal viscosity and membrane rigidity

International audienc

Description of Three New α Variants and Four New β Variants: Hb Montluel [ α 110(G17)Ala → Val; HBA1 : c.332C > T], Hb Cap d’Agde [ α 131(H14)Ser → Cys; HBA2 : c.395C > G] and Hb Corsica [ α 100(G7)Leu → Pro; HBA1 : 302T > C]; Hb Nîmes [ β 104(G6)Arg → Gly; HBB : c.313A > G], Hb Saint Marcellin [ β 112(G14)Cys → Gly; HBB : c.337T > G], Hb Saint Chamond [ β 80(EF4)Asn → 0; HBB : c.241_243delAAC] and Hb Dompierre [ β 29(B11)Gly → Arg; HBB : c.88G > C]

International audienc

Network analysis of human and simian immunodeficiency virus sequence sets reveals massive recombination resulting in shorter pathways

International audienceThe intrinsic recombination rate of human immunodeficiency virus (HIV) exceeds the point mutation rate by a factor of 10. As the majority of infected cells in vivo harbour multiple proviruses, the stage is set for rampant recombination. Therefore, it may be presumed that phylogenic relationships and mutation frequencies will probably be affected by recombination. However, the proportion of homoplasies arising from recombination and mutation is not known. By studying the evolution of the hypervariable regions of the simian immunodeficiency virus envelope gene among four macaques, it is shown that homoplasies arise more from recombination than from point mutation. When recombination is accounted for, the minimum number of substitutions in a sequence set may be reduced by as much as 45 %. In fact, the true number of point mutations in a set of HIV sequences tends to the number of discrete substitutions. Hence, lineages are younger than anticipated previously, although not in proportion to the ratio of the intrinsic recombination/point mutation rate. Recombination also inflates codon polymorphisms

Higher Daily Physical Activity Level Is Associated with Lower RBC Aggregation in Carotid Artery Disease Patients at High Risk of Stroke

Aim: Carotid artery disease (CAD) is an atherosclerotic inflammatory disease that affects the arterial wall, specifically at points of bifurcation where blood flow is disturbed. Abnormal blood rheology could participate in the pathophysiology of ischemic cardiovascular disease. Physical activity (PA) is known to improve blood rheology in several chronic disorders. This study aims to (i) compare the hemorheological profile of CAD patients and controls and (ii) investigate the associations between daily PA and hemorheological parameters in CAD patients.Methods: Blood viscosity, red blood cell (RBC) aggregation and RBC deformability were assessed in 80 patients (15 symptomatic and 65 asymptomatic) and 14 age-matched controls. Patients' PA levels were evaluated using questionnaires.Results: Symptomatic patients showed increased blood viscosity and RBC aggregation compared to healthy controls. RBC aggregation was significantly lower in the most physically active patients compared to the least physically active ones. Blood viscosity and RBC deformability did not vary according to physical activity level.Conclusions: Our results showed greater hemorheological abnormalities (blood hyper-viscosity and hyper-aggregation of red blood cells) in the most severe CAD patients, which could exacerbate the risk of stroke in patients with stenosis. As the most physically active patients had lower RBC aggregation than those who were less physically active, it is possible that regular PA may limit hemorheological alterations in CAD patients