Blood
-
Alpha-thalassemia is very common throughout all tropical and subtropical regions of the world. In Southeast Asia and the Mediterranean regions, compound heterozygotes and homozygotes may have anemia that is mild to severe (hemoglobin [Hb] H disease) or lethal (Hb Bart's hydrops fetalis). We have developed a reliable, single-tube multiplex-polymerase chain reaction (PCR) assay for the 6 most frequently observed determinants of alpha-thalassemia. The assay allows simple, high throughput genetic screening for these common hematological disorders. (Blood. 2000;95:360-362)
-
During recovery from intensive chemotherapy with cyclophosphamide (CTX), mice suffer a severe but transitory impairment in spleen cell proliferation to T-cell mitogens (Con A or anti-CD3 plus IL-2). Although CTX treatment reduced spleen T-cell cellularity, this cannot fully account for T-cell unresponsiveness. The results showed that CTX induces the colonization of spleen by an immature myeloid CD11b(+)Ly-6G(+)CD31(+) population. ⋯ Finally, iNOS protein expression was restricted to a heterogeneous population of CD31(+) cells in which CD11b(+)Ly-6G(+) cells were required to suppress T-cell proliferation. These results indicated that CTX might also cause immunosuppression by a mechanism involving the presence of immature myeloid cells with suppressor activity. This may have implications in clinical praxis since inappropriate immunotherapies in patients treated with intensive chemotherapy could lead to deleterious T-cell responses. (Blood. 2000;95:212-220)
-
Following ischemia-reperfusion (I/R), platelet adhesion is thought to represent the initial event leading to remodeling and reocclusion of the vasculature. The mechanisms underlying platelet adhesion to the endothelium have not been completely established. Endothelial cells rendered ischemic acquire a procoagulant phenotype, characterized by fibrinogen accumulation. ⋯ Intracellular adhesion molecule (ICAM)-1 served as a major receptor for fibrinogen, since fibrinogen deposition and platelet adhesion to the endothelial cell surface were markedly decreased in ICAM-1-deficient mice. The platelet alpha(IIb)/beta(3) integrin plays a key role in fibrinogen-dependent platelet accumulation, because (1) platelet adhesion involved RGD-recognition sequences, and (2) platelets isolated from a patient with Glanzmann's disease showed decreased interaction with the postischemic endothelium. Since platelets are demonstrated here to induce tyrosine phosphorylation in endothelial cells, platelet recruitment might contribute to the development of an inflammatory reaction during I/R.
-
Children with sickle cell disease (SCD) and stroke receive chronic transfusions to prevent stroke recurrence. Transfusion risks including infection, erythrocyte allosensitization, and iron overload suggest a need for alternative therapies. We previously used hydroxyurea (HU) and phlebotomy in two young adults with SCD and stroke as an alternative to transfusions. ⋯ These preliminary data suggest some children with SCD and stroke may discontinue chronic transfusions and use HU therapy to prevent stroke recurrence. Phlebotomy is well-tolerated and significantly reduces iron overload. Modifications in HU therapy to raise HbF more rapidly might increase protection against stroke recurrence.
-
Circulating complexes of leukocytes and activated platelets are markers for atherosclerosis, but their interaction with the arterial endothelial lining has not been studied. Therefore, the effect of activated platelets on rolling and adhesion of labeled human THP-1 monocytoid cells to human umbilical vein endothelial cell (HUVEC) monolayers was studied by epifluorescence microscopy in a parallel plate flow chamber. In the absence of activated platelets, THP-1 rolling on resting HUVEC was negligible at shear rates greater than 300 s(-1). ⋯ Sialidase digestion and removal of terminal sialic acid residues from HUVEC or THP-1 cells but not from platelets abolished the platelet mediated augmentation of THP-1 cell adhesion. Thus, THP-1 rolling on HUVEC is shear-dependent and largely mediated by L-selectin. P-selectin expressed on activated platelets increases monocytoid cell adhesion to endothelial cells at shear rates found in coronary arteries through interactions with both endothelial and monocytoid cells and may facilitate macrophage accumulation in the vessel wall.