Toshiyuki Yanase

Hemoglobin Yoshizuka (G10(108)β asparagine→aspartic acid): a new variant with a reduced oxygen affinity from a Japanese family

During the course of a survey, a new hemoglobin, designated hemoglobin Yoshizuka, has been encountered in a Japanese family. Clinically, mild anemia was noted in five of six heterozygous individuals but no other significant abnormalities were found. Hemoglobin Yoshizuka is characterized by the substitution of aspartic acid for asparagine at the tenth residue of the G helix in the beta-chain. Reduced oxygen affinity with almost normal heme-heme interaction was found to be a property of this abnormal hemoglobin. The asparagine residue G10(108)beta lies in the internal cavity of the tetrameric molecule and its main chain carbonyl is thought to be hydrogen bonded to histidine G10(103)alpha at the region of contact between alpha- and beta-chains. It would appear likely that the introduction of a carboxyl group into the central cavity might result in interactions between the polar groups and the substituted side chain, disrupting the system of hydrogen bonds which contribute to the stability of the contacts between unlike subunits.

Selective IgA Deficiency: Analysis of Ig Production in Vitro

The cellular basis of the pathogenesis of selective IgA deficiency (SIgAD) was investigated by examining surface immunoglobulin (SmIg) andin vitro pokeweed mitogen (PWM)-stimulated immunoglobulin (Ig) synthesis and by assaying in combination the counterpart lymphocytes from individuals with SIgAD and healthy donors. Peripheral blood lymphocytes (PBL) from 14 individuals with SIgAD synthesized normal amounts of IgG and IgM but did not synthesize normal amounts of IgA. Functional defects of lymphocytes for IgA synthesis were classified into four types: (i) B-lymphocyte dysfunction, (ii) increased function of suppressor T lymphocytes (Ts), (iii) decreased function of helper T lymphocytes (Th), and (iv) B-lymphocyte dysfunction and increased Ts function. The cells bearing SmIgG, SmIgM, and SmIgD were demonstrated at normal percentage ratios in all cases by immunofluorescent staining. The cells bearing SmIgA were at normal percentage ratios in the cases of T-lymphocyte dysfunction, while in the cases of B-lymphocyte defect SmIgA-bearing cells were reduced.

Frequency and Distribution of Structural Variants of Hemoglobin and Thalassemic States in Western Japan

Hemolysates from 100,000 people who visited the Kyushu University Hospital and affiliated hospitals during the past 15 years were screened for hemoglobinopathies using electrophoresis on thin-layer starch gel; those exhibiting an abnormality were characterized further on clinical, biochemical, and genetic grounds. Of about 97,000 adult and 3,140 cord blood samples, 29 contained electrophoretically detectable abnormalities in the heterozygous condition. Another 17 samples had quantitative changes in the levels of the minor hemoglobin components. Of the thalassemic conditions, 12 involved beta-thalassemia, 3 alpha-thalassemia, 1 delta beta-thalassemia, and 1 delta-thalassemia. Among 45 carriers of beta-thalassemia from 12 families, 5 were noted to have thalassemia intermedia since they exhibited much more severe hemolytic syndromes than those with typical beta-thalassemia minor. The frequency with which we could detect a structural variant of Hb A in the adults by electrophoresis was one in 3,800 samples. About one in 8,000 carried a beta-thalassemia gene.

Hemoglobin sawara: α 6(A4) aspartic acid → alanine

Abstract In a survey of a Japanese population for abnormal hemoglobins, a new variant of human adult hemoglobin was found: hemoglobin Sawara, in which a residue of aspartic acid in position 6(A 4 ) of the α-chain is replaced by one of alanine. There were no pathological findings associated with this hemoglobin variant.

Distribution of α2-macroglobulin in normal, inflammatory, and tumor tissues in rats

Distribution of uptake and catabolism of intravenously administered125l-labeled rat α2-macroglobulin(125I-α2MG) were examined in normal, inflammatory, and tumor tissues of rats. Clearance of intravenously administered [125l]α2MG from the circulation was rapid. Accumulation of this compound into inflammatory tissue was 2–3 times more extensive than in normal tissues. The accumulation into sarcoma tissue was much less. Radioactivity in TCA-PTA precipitates remained fairly constant for the first 12 h in inflammatory tissue and for the first 24 h in sarcoma. These patterns of accumulation were never observed in the normal tissues. As the kidney preferentially accumulated large amounts of [125l]α2MG in the nondegraded form and its degradation products, the tissue may play a special role in the metabolism of α2MG. Rapid clearance from the circulation and relatively small amounts of accumulation in tissues suggest that α2MG may function as a protease inhibitor, mainly in the circulation rather than in the tissues.

Increased oxygen affinity for hemoglobin Sawara: alphaA4(6) aspartic acid replaced by alanine.

Abstract The oxygen binding property of Hb Sawara ( α A 4 Asp a Ala ) was studied at different pH values with and without addition of 2,3-diphosphoglycerate. The oxygen affinity of Hb Sawara was shown to be increased, the difference of the log P50 value between normal and abnormal hemoglobins being 0.37 at pH 7.0. Both the magnitude of the alkaline Bohr effect and the effect of 2,3-diphosphoglycerate upon oxygen affinity of Hb Sawara were comparable to those of Hb A. The amino acid substitution of alanine for αA4 aspartic acid might result in the loss of a stabilizing force for ionic interaction between the α-amino group of NA(1)α1 valine and the α-carboxyl of HC3(141)α2 arginine in the deoxy-form.

The reactive unit of hemoglobin in hemoglobin-haptoglobin complex formation

Abstract The intermediate and saturated forms of human hemoglobin-haptoglobin 1-1 complex were isolated and characterized using rabbit antisera to hemoglobin α and β chains. These two complexes were ascertained to be pure and stable enough for the present purpose. The intermediate and saturated complexes gave immunoprecipitation reaction with antisera to hemoglobin α and β chains, indicating that both of the hemoglobin chains are involved in these complexes. Furthermore, these antisera were demonstrated to be specific to their proper antigens and they do not cross-react with their opposite types of hemoglobin chains. From these findings and results previously reported, it was concluded that the intermediate and saturated complexes may be expressed as hemoglobin αβ-haptoglobin α2β2 and hemoglobin α2β2-haptoglobin α2β2, respectively, and the basic unit of hemoglobin which enters into complex with haptoglobin will be hemoglobin αβ-dimers, when haptoglobin is progressively saturated by hemoglobin.

Identification of an abnormal hemoglobin with reduced oxygen affinity by high-performance liquid chromatography

Abstract High-performance liquid chromatography on a reversed-phase column was applied to the structural study of the rare hemoglobin variant found in a Japanese family, which was then identified as Hb New York [113(G15) β valine → glutamic acid]. A reduced oxygen affinity is associated with this amino acid substitution, the difference in log P 50 being 0.1 at pH 7.46. The substitution of a glutamyl residue for valine may destabilize the α 1 β 1 contacts in the oxyhemoglobin structure, shifting the allosteric equilibrium towards the T form.

A new electrophoretic variant of hemoglobin (Ogi) in which a leucine residue is replaced by an arginine residue at position 34 of the α-chain

Hemoglobin Ogi, in which an arginine is substituted for a leucine residue at position 34 of the alpha-chain, was detected in a Japanese family. Although slightly increased oxygen affinity is associated with this amino acid substitution in the alpha 1 beta 1 contact, it is without obvious deleterious effect on the hematological parameters of the individuals heterozygous for this variant.

Kinetics of peroxidase activity, absorption spectra and oxygen affinity of human hemoglobin-haptoglobin 1-1 complexes

Abstract Some functional properties of the intermediate and saturated forms of human hemoglobin-haptoglobin 1-1 complex were studied to clucidate the interaction between these two proteins. No significant difference was demonstrated in the kinetics of peroxidase activity and the Soret band spectra of these two complexes under the various conditions studied. Furthermore, both of the complexes have a very high affinity for oxygen, with values of n approximately I, indicating the absence of heme-heme interaction. These results seem to indicate that the similar changes in the configurations of hemoglobin moieties are induced by the binding with haptoglobin in these complexes. Therefore, the same type of molecular interaction between hemoglobin αβ-dimers and haptoglobin will be involved in both complexes.