Hemoglobin S

Sickle cell disease was the first human genetic disorder in which a causative mutation was identified at the molecular level, the p-globin chain substitution p6 Glu! Val. When deoxygenated, HbS polymerizes, causing sickling and leading to anemia, acute chest syndrome, stroke, splenic and renal dysfunction, vaso-occlusive painful crises, and susceptibility to bacterial infections. SCD is the most common hemoglobinopathy in the United States, with 8-10% of African-Americans carrying the sickle hemoglobin (HbS) gene. Haplotype analysis has revealed several origins for the HbS mutation in Africa, Asia, and Southern Europe. Haplotype is correlated to some extent with disease severity: individuals with the ''Indian/Arabian haplotype'' have the mildest course, whereas those with the ''Bantu haplotype'' often exhibit severe SCD.

Neonatal screening for SCD has been driven by the demonstration that daily oral penicillin administration prevents early morbidity and mortality from pneumo-coccal septicemia.[17] This is the single instance where newborn screening has been prompted by evidence from a randomized, double-blind, placebo-controlled clinical trial.

In France, a combination of IEF and more sensitive, quantitative cation-exchange HPLC has confirmed the status of 99.7% of newborn infant dried blood spot hemoglobinopathy screening samples. Exceptional cases required reverse-phase HPLC for g- or a-globin chain variants or confirmatory testing by DNA.[18]

Digestion of genomic DNA from uncultured amnio-cytes with MstII results in fragments larger than those produced by some other enzymes and therefore has been particularly useful in prenatal diagnosis of SCD. These genotyping methods are being supplanted by PCR amplification of the relevant segment of the human p-globin gene, followed by hybridization of the amplicon with allele-specific oligonucleotide probes, and, most recently, by direct PCR amplification using allele-specific primers.

A related HbS variant, HbS-Oman, contains the classic HbS p6 Glu! Val mutation as well as a second mutation in the same p-chain, p121 Glu!Lys, i.e., the HbO-Arab mutation. This HbS-Arab double mutation can produce particularly severe sickling. Deoxygenation of HbS-Oman RBCs in vitro induces polymerization and a characteristic ''yarn/knitting-needle'' cell deformation.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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