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Research Article Free access | 10.1172/JCI106010
Department of Clinical Laboratories, Atomic Bomb Casualty Commission,* Hiroshima, Japan*
Department of Clinical Pathology, Kawasaki Hospital, Okayama, Japan
Third Division of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan
** The Commission is a cooperative research agency of the U. S. A. National Academy of Sciences—National Research Council, and the Japanese National Institute of Health of the Ministry of Health and Welfare, with funds provided by the United States Atomic Energy Commission, the Japanese Institute of Health, and the U. S. Public Health Service.
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Department of Clinical Laboratories, Atomic Bomb Casualty Commission,* Hiroshima, Japan*
Department of Clinical Pathology, Kawasaki Hospital, Okayama, Japan
Third Division of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan
** The Commission is a cooperative research agency of the U. S. A. National Academy of Sciences—National Research Council, and the Japanese National Institute of Health of the Ministry of Health and Welfare, with funds provided by the United States Atomic Energy Commission, the Japanese Institute of Health, and the U. S. Public Health Service.
Find articles by Iuchi, I. in: JCI | PubMed | Google Scholar
Department of Clinical Laboratories, Atomic Bomb Casualty Commission,* Hiroshima, Japan*
Department of Clinical Pathology, Kawasaki Hospital, Okayama, Japan
Third Division of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan
** The Commission is a cooperative research agency of the U. S. A. National Academy of Sciences—National Research Council, and the Japanese National Institute of Health of the Ministry of Health and Welfare, with funds provided by the United States Atomic Energy Commission, the Japanese Institute of Health, and the U. S. Public Health Service.
Find articles by Miyaji, T. in: JCI | PubMed | Google Scholar
Department of Clinical Laboratories, Atomic Bomb Casualty Commission,* Hiroshima, Japan*
Department of Clinical Pathology, Kawasaki Hospital, Okayama, Japan
Third Division of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan
** The Commission is a cooperative research agency of the U. S. A. National Academy of Sciences—National Research Council, and the Japanese National Institute of Health of the Ministry of Health and Welfare, with funds provided by the United States Atomic Energy Commission, the Japanese Institute of Health, and the U. S. Public Health Service.
Find articles by Shibata, S. in: JCI | PubMed | Google Scholar
Published March 1, 1969 - More info
During a survey for hemoglobinopathies in over 9000 residents of Hiroshima Prefecture, Japan, a fast moving hemoglobin was identified in eight members of three generations in a Japanese family. The abnormal hemoglobin, named Hb Hiroshima, constitutes about 50% of the total hemoglobin in hemolysates from the carriers who have a mild erythremia but are otherwise apparently clinically unaffected. All preparations of Hb Hiroshima have increased affinity for oxygen, by either tonometric or oxygen electrode determinations. At pH 7.0, the oxygen pressure, P50 required to half saturate an unfractionated hemolysate from a carrier was one-half that of Hb A, and the P50 of a purified sample containing no Hb A was one-fourth that of Hb A. The pH dependence of the oxygen equilibrium (Bohr effect) is below normal, as shown by the absolute value of the Bohr effect factor which is about half that of Hb A, in the pH range between 7.0 and 7.4. The Hill constant, n, for Hb Hiroshima between pH 7.0 and 7.4 is 2-2.4, compared to 2.8-3 for Hb A under the same conditions, indicating reduction of, but not complete abolition of heme-heme interaction. Urea dissociation and canine hybridization tests located the biochemical lesion in the beta chain. Fingerprints (Ingram), carboxypeptidase digestion, and amino acid analysis demonstrated that the substitution was at residue 143 in the beta chain, where histidine was replaced by aspartic acid.
In contrast to other recently described high oxygen affinity mutants that show intact Bohr effects, all three of the major characteristics of the reversible combination of hemoglobin with oxygen (oxygen equilibrium, heme-heme interaction, and pH dependence) are affected in Hb Hiroshima. A tentative interpretation of these effects, relating structure to function, is offered in terms of recently developed models of normal hemoglobin.
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