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1.
Proc Natl Acad Sci U S A ; 105(3): 991-6, 2008 Jan 22.
Article in English | MEDLINE | ID: mdl-18192399

ABSTRACT

Sickle trait, the heterozygous state of normal hemoglobin A (HbA) and sickle hemoglobin S (HbS), confers protection against malaria in Africa. AS children infected with Plasmodium falciparum are less likely than AA children to suffer the symptoms or severe manifestations of malaria, and they often carry lower parasite densities than AA children. The mechanisms by which sickle trait might confer such malaria protection remain unclear. We have compared the cytoadherence properties of parasitized AS and AA erythrocytes, because it is by these properties that parasitized erythrocytes can sequester in postcapillary microvessels of critical tissues such as the brain and cause the life-threatening complications of malaria. Our results show that the binding of parasitized AS erythrocytes to microvascular endothelial cells and blood monocytes is significantly reduced relative to the binding of parasitized AA erythrocytes. Reduced binding correlates with the altered display of P. falciparum erythrocyte membrane protein-1 (PfEMP-1), the parasite's major cytoadherence ligand and virulence factor on the erythrocyte surface. These findings identify a mechanism of protection for HbS that has features in common with that of hemoglobin C (HbC). Coinherited hemoglobin polymorphisms and naturally acquired antibodies to PfEMP-1 may influence the degree of malaria protection in AS children by further weakening cytoadherence interactions.


Subject(s)
Erythrocytes/cytology , Erythrocytes/metabolism , Hemoglobin, Sickle/metabolism , Plasmodium falciparum/physiology , Animals , Cell Adhesion , Cells, Cultured , Endothelial Cells/cytology , Erythrocytes/ultrastructure , Hemoglobin SC Disease/metabolism , Hemoglobin SC Disease/parasitology , Hemoglobin SC Disease/pathology , Humans , Microcirculation/cytology , Microscopy, Electron, Transmission , Monocytes/cytology , Protozoan Proteins/metabolism , Sickle Cell Trait/metabolism , Sickle Cell Trait/parasitology , Sickle Cell Trait/pathology
2.
Sleep Breath ; 9(2): 50-6, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15803318

ABSTRACT

We determined the prevalence of concomitant sleep disorders in patients with a primary diagnosis of obstructive sleep apnea (OSA). We retrospectively analyzed 643 patients, aged > or =18, with a primary diagnosis of OSA, evaluated by sleep specialists, in whom clinical and polysomnographic data were derived using standardized techniques by reviewing data from a standardized database and clinical charts. Concomitant sleep disorders were listed according to the International Classification of Sleep Disorders (American Academy of Sleep Medicine, 2000). The mean age was 48.5+/-13.5 years and 55% were male. Racial distributions were African-Americans 51.8% and Caucasian 47%. Indices of disordered breathing were respiratory disturbance index 32.4+/-30.4/h sleep and time <90% O(2) saturation 44.5+/-81.6 min. Thirty-one percent of patients had a concomitant sleep disorder. The most common were inadequate sleep hygiene (14.5%) and periodic limb movement disorder (PLMD, 8.1%). Of patients with other sleep disorders, 66.8% had treatment initiated for these disorders. Predictors of inadequate sleep hygiene (logistic regression) were: age (each decade OR=0.678, P=0.000000), gender (for M, OR=0.536), and the presence of at least one other major system disorder (OR=2.123, P=0.0015). Predictors of PLMD were: age (each decade OR=0.794, P=0.0005), gender (for M, OR=0.433, P=0.004), and total sleep time (for each 10 min, OR=0.972, P=0.0013). We conclude that approximately one third of patients with sleep apnea have another identifiable sleep disorder, usually requiring treatment. This suggests that practitioners evaluating and treating sleep apnea ought to be prepared to deal with other sleep disorders as well.


Subject(s)
Sleep Apnea, Obstructive/epidemiology , Sleep Wake Disorders/epidemiology , Female , Humans , Male , Middle Aged , Prevalence , Severity of Illness Index , Sleep, REM/physiology
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