PubMed · 5433271
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
R W Mowry. 1970. "Asplenia"?. https://doi.org/10.7326/0003-4819-73-1-140_2
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Prevention of erythrocyte dehydration is a potential therapeutic strategy for sickle cell disease. Increasing erythrocyte magnesium (Mg) could inhibit sickle cell dehydration by increasing chloride (CI) and water content and by inhibiting potassium chloride (K-CI) cotransport. In transgenic SAD 1 and (control) C57BL/6 normal mice, we investigated the effect of 2 weeks of diet with either low Mg (6 +/- 2 mg/kg body weight/d) or high Mg (1,000 +/- 20 mg/kg body weight/ d), in comparison with a diet of standard Mg (400 +/- 20 mg/ kg body weight/d). The high-Mg diet increased SAD 1 erythrocyte Mg and K contents and reduced K-CI cotransport activity, mean corpuscular hemoglobin concentration (MCHC), cell density, and reticulocyte count. SAD 1 mice treated with low-Mg diet showed a significant reduction in erythrocyte Mg and K contents and increases in K-CI cotransport, MCHC, cell density, and reticulocyte counts. In SAD 1 mice, hematocrit (Hct) and hemoglobin (Hb) decreased significantly with low Mg diet and increased significantly with high-Mg diet. The C57BL/6 controls showed significant changes only in erythrocyte Mg and K content, and K-CI cotransport activities, similar to those observed in SAD 1 mice. Thus, in the SAD 1 mouse, changes in dietary Mg modulate K-CI cotransport, modify erythrocyte dehydration, and ultimately affect Hb levels.
We investigated the effects of hypoxia on red blood cell (RBC)-endothelial cell (EC) adherence and the potential mechanism(s) involved in mediating this effect. We report that hypoxia significantly increased sickle RBC adherence to aortic EC when compared with the normoxia controls. However, hypoxia had no effect on the adherence of normal RBCs. In additional studies, we found that the least dense sickle RBCs containing CD36+ and VLA-4+ reticulocytes were involved in hypoxia-induced adherence. We next evaluated the effects of hypoxia on the expression of EC surface receptors involved in RBC adherence to macrovascular ECs, including vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), and the vitronectin receptor (VnR). Hypoxia upregulated the expression of both VCAM-1 and ICAM-1, whereas no effect on VnR was noted. Potential involvement of VCAM-1 and ICAM-1 in mediating hypoxia-induced sickle RBC-EC adhesion was next investigated using monoclonal antibodies against these receptors. Whereas anti-VCAM-1 had no effect on basal adherence, it inhibited hypoxia-induced sickle RBC adherence in a concentration-dependent manner, with 50% to 75% inhibition noted at 10 to 60 micrograms/mL antibody (n = 6, P < .05 to P < .01). Anti-ICAM-1 (10 to 60 micrograms/mL, n = 8) had no effect on either basal or hypoxia-induced adherence. As noted in the bovine aortic ECs, hypoxia stimulated the adherence of sickle RBCs to human retinal capillary ECs, and this response appeared to be mediated via mechanisms similar to those observed with macro-endothelium, ie, via the adhesive receptor combination VCAM-1-VLA-4. Our studies show that hypoxia enhances sickle RBC adhesion to both macrovascular and human microvascular ECs via the adhesive receptor VCAM-1. Our findings are of interest because hypoxia is an integral part of the pathophysiology of the vaso-occlusive phenomenon in sickle cell anemia.
Hematological disorders underlie a small proportion of all ischemic strokes. The association of these coagulation abnormalities with ischemic stroke is not always clear. The etiology of stroke still remains uncertain in a large number of cases and proper screening for coagulation abnormalities and the discovery of new coagulation disorders will probably increase the rate of strokes attributable to these causes. Since large case-control studies with unselected and consecutive stroke patients from different ethnic origins have not yet been performed to determine the role of coagulation abnormalities in ischemic stroke, our knowledge is dependent on case reports and small series of mostly younger patients. Extensive hematologic evaluation of unselected stroke patients will likely yield little useful information and be too expensive. Every stroke patients needs a careful evaluation, and in selected cases, this should include coagulation parameters. Patients with unexplained strokes after a careful evaluation, previous thrombotic episodes, or a positive family history for thrombosis, are good candidates for further coagulation studies. As long as the hypercoagulable state persists, both arterial and venous thromboembolic recurrences can be expected. Many of these patients may benefit from anticoagulants. In patients with hereditary coagulation disorders, studies should be extended to close relatives. Since some coagulation tests are fairly expensive, provide only equivocal data, and are not widely available, we advise a step-by-step approach starting with the patient and family history.