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Biomedical subjects

S Kurachi

Publications and source records attributed to S Kurachi.

47 records · Page 3Linked to original sources
PubMed1981

Globin synthesis in erythroid bursts that mature sequentially in culture. I. Studies in cultures of adult peripheral blood BFU-Es.

To study whether the culture time at which the burst populations mature influences the expression of fetal hemoglobin in bursts, we measured hemoglobin synthesis in cohorts of fully hemoglobinized erythroid bursts maturing sequentially in cultures of adult peripheral blood BFU-Es. In 13 of 15 experiments, a decline in gamma/gamma + beta ratio was noted as the culture time advanced. On the average, erythroid bursts that mature during the third culture week showed lower levels of fetal Hb synthesis compared to bursts that are already mature in the second culture week. The decline of gamma/gamma + beta ratio with culture time was also noted in erythroid bursts composed of immature erythroblasts. The enhanced HbF formation in peripheral blood BFU-E cultures is thus most pronounced among the bursts that become hemoglobinized early, and there is a tendency for normalization of HbF synthesis in bursts that mature in late culture days. These results can be interpreted by several alternatives, including the possibility that the expression of high HbF levels in the early days of adult BFU-E cultures is a reflection of premature commitment to terminal differentiation of progenitors that possess an active HbF program. The present data indicate that the variation of HbF synthesis with culture time should be taken into consideration when the influence of various culture conditions of HbF synthesis is studied in BFU-E cultures.

Adult↗
PubMed1979

Hb F production of endogenous colonies of polycythemia vera.

Fetal hemoglobin was studied in endogenous colonies produced in plasma clot and methylcellulose cultures of circulating progenitors from patients with polycythemia vera (PV). Analysis of globin chain synthesis showed that gamma chains constituted from 13% to 42% of the non-alpha chains produced in cultured cells, whereas from 27% to over 50% of the endogenous colonies contained Hb F, as indicated by the fluorescent antibody probe. Since the endogenous colonies in PV cultures originate from the abnormal PV clone, the findings provide direct evidence that a single pluripotent stem cell can have committed progeny that differ in their expressions of the Hb F production program.

Cells, Cultured↗
PubMed1978

Erythroid progenitors circulating in the blood of adult individuals produce fetal hemoglobin in culture.

Erythroid colonies, raised from erythroid stem cells circulating in the peripheral blood of normal adult individuals, synthesize considerable amounts of fetal hemoglobin. In cultures from persons with sickling disorders, amounts of hemoglobin F that are known to inhibit sickling in vivo are produced. The results provide evidence that primitive erythroid progenitors are able to express the hemoglobin F production program and that cultures of mononuclear cells of the adult blood can be used to investigate the mechanisms involved in regulation of gamma-globin gene switching.

Adult↗
PubMed1978

Consistent activation of fetal hemoglobin synthesis in cultured adult bone marrow cells.

The production of fetal hemoglobin was investigated in plasma clot cultures of adult bone marrow cells from normal donors and from individuals with homozygous HbS or HbC disease. Synthesis of gamma and beta chains was assessed either by 35S-methionine labeling of cultures and measurement of the radioactivity incorporated into the methionine-containing tryptic peptides of the gamma and beta subunits or by 3H-leucine labeling and measurement of the radioactivity incorporated into the globin chains of Hbs F0 and A0 isolated by ion-exchange chromatography. The cultures from all individuals responded with increased production of HbF. Cultured cells from subjects without a hemoglobinopathy produced an average of 8.2% gamma chains (range 3.1%-20.3%), while cultured cells from subjects homozygous for HbS or HbC produced an average of 16.6% gamma chains (range 12.2%-20.4%). These findings indicate that fetal Hb production was regularly enhanced in adult bone marrow cells triggered in vitro to clonal growth in the plasma clot culture system.

Adult↗
PubMed1977

The molecular defects of alpha-thalassemia in the Filipino.

Molecular hybridization with synthetic radioactive DNA (cDNA) complementry to alpha globin mRNA sequences shows that, as in most other Southeast Asian populations, the alpha globin structural genes are deleted in Filipinos affected by the alpha-thalassemia syndromes. Thus, all 4 alpha-globin structural genes are deleted in homozygous alpha-thalassemia with hydrops fetalis, 3 and 2 structural genes are deleted in hemoglobin H disease and alpha-thalassemia-1 respectively.

DNA↗
PubMed1977

Frequencies of thalassemia in American blacks.

The frequency of thalassemia was determined in a group of 541 healthy adult black males. Individuals with decreased mean corpuscular hemoglobin (MCH) values were evaluated further with hemoglobin analysis, iron studies, and globin chain synthesis. Of the males screened, 13.4% had MCH levels below 27.0 pg, while 1.4% had heterozygous beta thalassemia, 2.3% had iron deficiency, and 5.7% had globin synthesis findings compatible with the diagnosis of alpha thalassemia trait (alpha thalassemia-1). This study suggests that thalassemia is one of the most frequent hematologically depictable abnormalities in American blacks.

Adolescent↗
PubMedDate not supplied

A haemoglobin switching activity modulates hereditary persistence of fetal haemoglobin.

During human development there is a switch from fetal to adult haemoglobin formation, reflecting the differential expression of fetal (G gamma and A gamma) and adult (beta and delta) globin genes. Mutations that inhibit this switch produce variants of the syndrome of hereditary persistence of fetal haemoglobin (HPFH). Adult heterozygotes for these mutants produce 15-30% fetal haemoglobin (HbF) in their red cells. The general assumption is that the mutations result in a permanent switching on of gamma-globin genes. Here, however, we show that fetal globin expression can be turned off in cultures of HPFH cells by an uncharacterized factor in fetal sheep serum. This is the first demonstration that mutations affecting the developmental expression of globin genes can be modulated by exogenous factors. The findings raise the possibility that the phenotype of HPFH is not simply the direct result of mutations in or around globin genes but the consequence of the mutations on the interaction of globin genes with trans-acting regulatory factors.

Adult↗