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PubMed · 4522740

The view box.

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T D Clopper. 1974. The view box.. https://pubmed.ncbi.nlm.nih.gov/4522740/

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The survival characteristics of dense sickle cells.

Sickle red blood cells (RBCs) become depleted of potassium, leading to dehydration and abnormally elevated cellular density. The increased sickling that results is important for both hemolysis and vasocclusion. In this study, sickle cells were subjected to high-speed centrifugation, and the bottom 15% were isolated. This procedure removed light cells and to a variable degree enriched cells that were denser than normal to produce a high-density-enriched (HDE) population of sickle cells. Autologous HDE cells from 3 subjects were labeled with biotin and re-infused. The following determinations were performed: (1) the survival and density changes of HDE cells; (2) the amount of fetal hemoglobin (HbF) in labeled cells after magnetic isolation; (3) the percentage of labeled F cells; (4) the percentage of labeled cells displaying external phosphatidylserine (PS). For patients with 3.5%, 4.5%, and 24% HbF in the HDE RBCs, the circulation half-time was 40, 80, and 180 hours, respectively. The percentage of HbF (measured in all 3 subjects) and of F cells (measured in 2 subjects) in labeled RBCs increased with time after re-infusion, indicating that HDE F cells have longer in vivo survival than HDE non-F cells. The percentage of PS(+), biotin-labeled HDE cells showed no consistent increase or decrease with time after re-infusion. These data provide evidence that HDE sickle cells, especially those that do not contain HbF, have a very short in vivo survival, and that the percentage of PS(+) cells in a re-infused HDE population does not change in a consistent manner as these cells age in the circulation.

Anemia, Sickle Cell↗

Sera of patients suffering from inflammatory diseases contain group IIA but not group V phospholipase A(2).

During recent years, the high phospholipase A(2) (PLA(2)) concentrations at sites of inflammation and in circulation in several life-threatening diseases, such as sepsis, multi-organ dysfunction and acute respiratory distress syndrome, has generally been ascribed to the non-pancreatic group IIA PLA(2). Recently the family of secreted low molecular mass PLA(2) enzymes has rapidly expanded. In some cases, a newly described enzyme appeared to be cross-reactive with antibodies against the group IIA enzyme. For this reason, reports describing the expression of group IIA PLA(2) during inflammatory conditions need to be reevaluated. Here we describe the identification of the PLA(2) activity in sera of acute chest syndrome patients and in sera of trauma victims. In both cases, the PLA(2) activity was identified as group IIA. This classification was based upon cross-reactivity with monoclonal antibodies against group IIA PLA(2) which do not recognize the recombinant human group V enzyme. Moreover, purification of the enzymatic activity from the two sera followed by N-terminal amino acid sequence analyses revealed only the presence of group IIA enzyme.

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Hemoglobin C associated with protection from severe malaria in the Dogon of Mali, a West African population with a low prevalence of hemoglobin S.

The malaria hypothesis proposes a survival advantage for individuals with hemoglobin variants in areas of endemic Plasmodium falciparum malaria. Hemoglobin C (HbC) is a possible example in West Africa, where this hemoglobin has a centric distribution with high frequencies among certain populations including the Dogon ethnic group. To test whether HbC is associated with protection from malaria, we performed a case-control study in the Dogon of Bandiagara, Mali. HbC was present in 68 of 391 (17.4%) of uncomplicated malaria control cases, whereas it was detected in only 3 of 67 cases (4.5%) of severe malaria (odds ratio [OR], 0.22; P =. 01). Further, HbC was present in only 1 of 34 cases (2.9%) with cerebral manifestations, the most common presentation of severe malaria in this population (OR, 0.14; P =.03). Episodes of uncomplicated malaria and parasitemias (4800-205 050/microL) were identified in cases of homozygous HbC (HbCC), which indicates that P falciparum parasites are able to efficiently replicate within HbCC erythrocytes in vivo. These findings suggest that HbC does not protect against infection or uncomplicated malaria but can protect against severe malaria in the Dogon population of Bandiagara, Mali. The data also suggest that the protective effect associated with HbC may be greater than that of HbS in this population.

Anemia, Sickle Cell↗