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M B Coleman

Publications and source records attributed to M B Coleman.

29 records · Page 2Linked to original sources
PubMed1986

A new gene deletion in the alpha-like globin gene cluster as the molecular basis for the rare alpha-thalassemia-1(--/alpha alpha) in blacks: HbH disease in sickle cell trait.

A novel deletion of at least 26 kilobase of DNA, including both alpha-globin genes, the psi alpha- and psi zeta-globin genes, but sparing the functional zeta-gene was found in a 10-year-old black boy with HbH disease and sickle cell trait. This particular deletion has not previously been described in blacks. Its existence makes it likely that the absence of Hb Barts hydrops fetalis in blacks is due to the rarity of the chromosome lacking two alpha-globin genes rather than a result of early embryonic death due to the failure to synthesize embryonic hemoglobins because of deletion of functional zeta-globin genes.

Anemia, Sickle Cell↗
PubMed1984

Interaction between HBS-beta-o-thalassemia and alpha-thalassemia.

We have defined the clinical and laboratory characteristics of a group of patients with HbS-beta o-thalassemia plus alpha-thalassemia, by analysis of erythrocyte indices, hemoglobin A2 and F levels, globin biosynthesis studies and alpha-globin gene mapping. Patients with HbS-beta o + alpha-thalassemia closely resembled individuals with HbS-beta o-thalassemia except for balanced globin synthesis ratios and a lower HbF level. The frequency of painful crises, leg ulceration, aseptic necrosis of bone and acute chest syndrome was similar in HbS-beta o + alpha-thalassemia patients and controls with sickle cell anemia (HbSS), HbSS-alpha-thalassemia and HbS-beta o-thalassemia. These findings are consistent with previous work which failed to show a reduction in the vaso-occlusive severity of sickle cell disease by the coexistence of alpha-thalassemia.

Adolescent↗
PubMed1984

Effects of thalassemia and microcytosis on the hematologic and vasoocclusive severity of sickle cell anemia.

The characteristic clinical heterogeneity of sickle cell anemia (HbSS) may be, in part, a result of its interactions with alpha-thalassemia. Although alpha-thalassemia clearly affects some hematologic features of HbSS, its role in modulating the vasoocclusive severity of disease is not clear. To further explore this relationship, we examined the incidence of painful episodes, acute chest syndrome, aseptic bone necrosis, and leg ulcers in 3 patient groups with sickle cell disease: (1) 2,147 patients over age 2 yr, stratified according to mean corpuscular volume (MCV); (2) 183 patients selected on the basis of microcytosis and elevated HbA2, on whom globin biosynthesis studies were done; and (3) 125 patients who had alpha-globin genotype assigned by restriction endonuclease gene mapping. When patients were stratified by MCV, there was a reciprocal relationship between HbA2 levels and MCV, reflecting the presence of patients with beta o and alpha-thalassemia in the low MCV groups. The erythrocyte indices and HbA2 levels in patients classified as HbSS-alpha-thalassemia, by either globin synthesis studies or gene mapping, were very similar to those previously reported by others. Neither microcytosis, beta o, or alpha-thalassemia appeared to provide any clear protection from the vasoocclusive complication evaluated, and the prevalence of aseptic necrosis was increased in patients with microcytosis over age 20 yr and in groups with alpha-thalassemia. The effects of a reduced MCV and mean corpuscular hemoglobin concentration (MCHC), of possible benefit by themselves, when accompanied by a reduction in hemolysis and rise in hemoglobin concentration, as in HbSS-alpha-thalassemia, may cause sufficient rise in blood viscosity in critical vascular beds to impair blood flow and negate any amelioration of vasoocclusive complications in HbSS.

Adolescent↗
PubMed1983

The effects of alpha-thalassaemia in HbSC disease.

In HbSC disease, as in sickle cell anaemia, there is a spectrum of clinical severity. A reduced mean corpuscular volume and haemoglobin concentration, traits typical of thalassaemia, might retard sickling. We therefore ascertained the prevalence of alpha-thalassaemia in 53 adults with HbSC disease and related alpha-globin gene deletion to the haematologic and clinical findings. Alpha-globin genotype was identified by restriction endonuclease gene mapping. Indirect ophthalmoscopy and fluorescein angiography were used to document the presence of proliferative retinopathy. Bone necrosis and infarction were determined roentgenographically or by radionuclide scanning. Either heterozygous or homozygous alpha-thalassaemia-2 was present in 26% of patients. There was no relationship between alpha-globin genotype and haematocrit, pain crises, bone lesions, proliferation retinopathy or clinical severity score.

Adolescent↗
PubMed1982

Beta-thalassemia with exceptionally high hemoglobin A2. Differential expression of the delta-globin gene in the presence of beta-thalassemia.

Hemoglobin A2 levels in normal adults are rarely greater than 3.5%. In patients heterozygous for beta-thalassemia, they average about 5% but do not usually exceed 7%. We studied a family in which four patients with heterozygous beta-thalassemia had HbA2 levels of 8.4% to 11.2%. Globin biosynthesis studies and restriction endonuclease mapping of the alpha-globin loci showed homozygous or heterozygous alpha-thalassemia-2 as well as beta-thalassemia in some family members. The delta- and beta-globin genes were examined by using the restriction enzymes Eco RI, Pvu II, and Xba I, which cut both within and outside the coding portions of the delta- and beta-loci. Only the expected delta- and beta-globin gene containing fragments were present, excluding a crossover event producing a fusion gene that would code for delta-globin but possibly be under the regulatory influence of nucleotide sequences that control the expression of the beta-gene. This kindred provides evidence that in the presence of beta-thalassemia, expression of the delta-gene, beyond that commonly seen, is possible. This could be a direct result of the gene defect producing beta-thalassemia or be due to differences in the delta-globin gene linked to this beta-thalassemia gene. The interactions of alpha- and beta-thalassemia may alter tetramer assembly and increase HbA2 levels; however, this possibility seems less likely.

Base Composition↗
PubMed1981

Effects of dexamethasone on fetal hemoglobin synthesis in peripheral blood erythroid burst-forming units.

Colonies derived from erythroid burst-forming units (BFU-E) synthesize fetal hemoglobin (HbF) in amounts that far exceed in vivo levels. There is some evidence that HbF synthesis is controlled at the level of a primitive erythroid precursor cell. Dexamethasone may potentiate the development of BFU-E. Since a means of augmenting HbF production in sickle cell anemia or severe beta-thalassemia would be of great therapeutic value, we studied the effects of dexamethasone on HbF and gamma-globin chain synthesis in BFU-E from patients with sickle cell anemia and controls. HbF was measured by radioimmunoassay of BFU-E lysate and gamma-chain synthesis by the incorporation of 3H-leucine into globin, which was then purified by gel filtration and column chromatography. Dexamethasone (10(-9) M) produced an increase in the number of BFU-E in 16 of 19 subjects when compared with numbers of BFU-E cultured with only erythropoietin. The individual BFU-E were larger and contained more subcolonies. Dexamethasone did not increase HbF or gamma-chain synthesis, and there was no relationship between proliferation of BFU-E and augmented HbF production. Thus, although dexamethasone augmented the development of erythroid bursts, there was no increment in HbF.

Anemia, Sickle Cell↗
PubMed1981

Globin biosynthesis in erythroid bursts of heterozygous alpha or beta thalassaemia.

We examined globin chain synthesis in erythroid bursts (BFU-E) of patients with heterozygous alpha or beta thalassaemia. BFU-E were cloned from circulating mononuclear cells, labelled with [3H]leucine and globin chains purified by gel filtration and column chromatography. In six patients heterozygous for beta thalassaemia, globin synthesis in BFU-E was nearly balanced, with an alpha/non alpha ratio of 1.05 +/- 0.12. These BFU-E produced 33.8 +/- 12.7% gamma globin chain, an amount similar (P > 0.05) to that found in 10 controls with sickle cell anaemia (25.6 +/- 6.7) but greater (P > 0.05) than that of five normal controls (17.2 +/- 2.2). The balanced globin synthesis appeared due to the large amounts of gamma chain made by BFU-E. In two alpha thalassaemia carriers, who also had sickle cell trait, the BFU-E alpha/non-alpha ratio was 0.67 and 0.79. These BFU-E produced 15% and 20% gamma chain and 39% and 45% betaS globin. The synthesis of betaS globin in BFU-E exceeded the erythrocyte levels of 20% and 29% HbS and indicated nearly equal expression of betaA and betaB globin genes in these proliferating erythroid precursors. This provides further evidence that the low levels of HbS in sickle cell carriers with alpha thalassaemia are due to post-translational events resulting from the differing affinity of betaS and betaA globin for alpha chain and the destruction of excessive betaS chain.

Blood Cell Count↗
PubMed1979

Isolation of Plasmodium berghei by hemolysin lysis of infected erythrocytes and evidence for a parasite hexokinase.

A rapid and simple procedure has been developed for the isolation of Plasmodium berghei parasites from infected-mouse erythrocytes employing the heat stable hemolysin produced by Pseudomonas aeruginosa. Using parasites isolated by this method, the presence of a parasite specific hexokinase has been demonstrated, providing an explanation for the increased glucose consumption observed with infected cells. Enzyme assays and serology were employed in determining the purity and yield of purified parasites. The enzyme assays showed that about 25% of the parasites in infected RBCs were recovered in the purified state. The purified parasites were not agglutinated by rabbit-anti-mouse RBC serum which indicated the purified parasites were not contaminated by RBC components.

Animals↗
PubMed1978

Erythroleukemia: in vitro studies of erythropoiesis.

We studied the growth of erythroid burst-forming units (BFU-E) and erythroid colony forming units (CFU-E) from bone marrow and blood in six patients with erythroleukemia. Five patients grew CFU-E, while BFU-E were found in the marrow of two and in the peripheral blood of only one patient. In all cases with colony growth, the numbers of colonies were markedly decreased with respect to normal controls. Patient BFU-E were composed of fewer clusters than those of controls. BFU-E and CFU-E growth was dependent on the addition of erythropoietin to the medium, and no growth was observed in absence of erythropoietin. At present it is not known if the growth obtained is derived from residual normal erythropoietic stem cells or from abnormal erythroid precursors of the leukemic cells.

Adult↗
PubMed1978

Erythrocyte calcium abnormalities and the clinical severity of sickling disorders.

We studied erythrocyte calcium levels and uptake in a group of patients with sickle haemoglobinopathies of different clinical severity in an attempt to relate these measurements to the production of irreversibly sickled cells and disease severity. Erythrocyte calcium levels were measured by atomic absorption spectroscopy and calcium uptake by isotopic means. In sickle cell anaemia, erythrocyte calcium content was elevated and the uptake of isotopic calcium increased under both oxygenated and deoxygenated conditions. There was a direct correlation between the numbers of irreversibly sickled cells and calcium uptake and an inverse relationship between calcium uptake and red cell potassium level. The clinical course of disease was milder in patients with high fetal haemoglobin levels, but there was no relationship between clinical course and calcium levels, calcium flux or irreversibly sickled cells. Our observations suggest that calcium accumulation and irreversibly sickled cell formation are related processes. The absence of good correlation between various biochemical and clinical parameters emphasizes the complexity of factors which modify the clinical course of this disorder.

Adolescent↗