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Biomedical subjects

R W Carrell

Publications and source records attributed to R W Carrell.

At least 199 records · Page 11Linked to original sources
PubMed1974

Studies of hemoglobin denaturation and Heinz body formation in the unstable hemoglobins.

The sequential changes that occur during the precipitation on mild heating of the unstable hemoglobins, Hb Christchurch, Hb Sydney, Hb Köln, and Hb A, were examined with particular attention to the possibility of an accompanying oxidative process. Hb Christchurch, Hb Sydney, and Hb A precipitated with equal amounts of alpha- and beta-chains and full heme complement. Hb Köln, however, was one-half hemedepleted and showed a slight excess of precipitated beta-chains. In all cases the spectrum of the precipitated material was typical of a hemichrome. There was no evidence that sulfhydryl oxidation contributed to the precipitation process. Reduced glutathione was unable to protect the hemoglobin against precipitation, and mixed disulfide formation between the precipitating hemoglobin and glutathione was insignificant, even in the presence of excess glutathione. No blockade of beta93 cysteines could be demonstrated in the unstable hemoglobins. Precipitation of oxyhemoglobin and carboxyhemoglobin in all cases gave nonspecific oxidation of approximately two of the six hemoglobin sulfhydryl groups to give intra- and intermolecular disulfide bonds. Single alpha- and beta-chains, plus polymers of up to five or six chains linked by disulfide bridges, were demonstrated by polyacrylamide gel electrophoresis. This disulfide oxidation was not observed with deoxy- or methemoglobin and did not appear to influence the rate of precipitation. These findings fit the theoretical prediction that autoxidation of oxy- and carboxyhemoglobin is accompanied by formation of a free radical, with the reactions of this free radical being confined intramolecularly.Together, these results are in keeping with predictions based on the known structural abnormalities of the unstable hemoglobins, all of which result in greater molecular flexibility. Our findings support the conclusion that the usual precipitating event is altered bonding at the heme to give the formation of hemichromes. There is no evidence of an accompanying oxidative process that could pose a threat to the integrity of the red cell.

Anemia, Hemolytic, Congenital↗
PubMed1968

Differences between alpha- and beta-chain mutants of human haemoglobin and between alpha- and beta-thalassaemia. Possible duplication of the alpha-chain gene.

Human adult haemoglobin consists of two unlike pairs of polypeptide chains, and can be described as alpha(2)beta(2). Amino-acid substitutions in either of the two types of chain result in alpha- and beta-chain variants. In thalassaemia, which causes a lowered production of haemoglobin, the alpha or the beta chain can be affected, the result being alpha- or beta-thalassaemia. There is a quantitative difference in the proportion of alpha- and beta-chain variants to normal haemoglobin in the respective heterozygotes, and there is also a difference in the pattern of inheritance of alpha- and beta-thalassaemia: these could possibly be explained by assuming that man has one gene for the beta- and two for the alpha-chain.

Hemoglobins↗