Electron microscope studies revealed that the average value for the percentage of erythropoietic cell profiles containing globin chain precipitates in heterozygotes for haemoglobin Constant Spring (HbCS) was similar to that in subjects with alpha-thalassaemia 2 trait and that the average values for this parameter in homozygotes for HbCS and patients with HbCS-H disease were similar to that in individuals with HbH disease. The explanation for the finding that the presence of two alpha cs genes (in homozygotes for HbCS) caused a degree of precipitation corresponding to that seen in patients with HbH disease, who have three deleted alpha genes, rather than to that seen in individuals with alpha-thalassaemia 1 trait, who have two deleted alpha genes, is uncertain. In all the patients with HbCS studied, the majority of the inclusions of precipitated globin chains had a stellate or branching appearance and were considered to consist of beta-chains. However, in the homozygotes for HbCS and to a lesser extent in the patients with HbCS-H disease there were small but significant numbers of erythropoietic cell profiles containing multiple rounded inclusions of the type seen in the beta-thalassaemia syndromes, or both branching and multiple rounded inclusions. It is argued that these rounded inclusions probably consisted either of precipitated HbCS or beta-chains rather than alpha-chains. The distribution of erythroblasts in the different stages of the cell cycle was normal in two homozygotes for HbCS and two patients with HbCS-H disease, indicating that there was little or no cell death during the proliferative phase of erythropoiesis in either of these conditions.

Adult↗

PubMed1986

Comparison of erythrocyte antioxidative enzyme activities between two types of haemoglobin H disease.

The activities of erythrocyte antioxidative enzymes were measured in two groups of patients with different genotypes of haemoglobin (Hb) H disease: 21 with alpha-thalassaemia 1 or alpha-thalassaemia 2 (alpha-thalassaemia 1/2) and 21 with alpha-thalassaemia 1/Hb Constant Spring (HbCS). They were compared with 21 normal subjects. Both genotypes of Hb H disease had increased activities of erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase when compared with those of controls. Comparison of the two genotypes showed that subjects with alpha-thalassaemia 1/Hb CS, the more severe disease, had higher SOD and GSH-Px activities but lower catalase activity than those with alpha-thalassaemia 1/2. This indicates that there are compensatory mechanisms in Hb H erythrocytes to cope with increased generation of oxygen free radicals as a result of increased excess beta chain.

Catalase↗

PubMed1986

Increased phagocytosis of Plasmodium falciparum-infected erythrocytes with haemoglobin E by peripheral blood monocytes.

Erythrocytes from subjects with homozygous and heterozygous haemoglobin E (HbE) infected with Plasmodium falciparum in vitro were phagocytosed to a greater extent by normal human monocytes than infected erythrocytes from normal subjects. Susceptibility to phagocytosis was maximal when the parasites developed to trophozoite and schizont stages in both normal and patients' erythrocytes. The increased susceptibility of P. falciparum-infected HbE erythrocytes to phagocytosis by monocytes may play a role in protection against malaria.

Cells, Cultured↗

PubMed1985

Concomitant inheritance of alpha-thalassemia in beta 0- thalassemia/Hb E disease.

Concomitant inheritance of alpha-thalassemia in patients with beta 0-thalassemia/hemoglobin (Hb) E disease was detected by restriction endonuclease DNA mapping. Among 42 patients with beta 0-thalassemia/Hb E disease, seven were found to have an alpha-thalassemia-2 haplotype. Of these, five belonged to the rightward or 3.7-kb type of alpha-thalassemia-2 and the remaining two the leftward or 4.2-kb type. All the seven patients with alpha-thalassemia-2 haplotype had hemoglobin levels of 7.4 g/dl or above; those without detectable alpha-thalassemia had hemoglobin levels both higher and lower than 7.4 g/dl. The latter attended the clinic regularly, the former did occasionally. These findings suggest that concomitant inheritance of alpha-thalassemia can alleviate the severity of beta 0-thalassemia/Hb E disease. Failure to find alpha-thalassemia-1 haplotype in these patients suggests that concomitant inheritance of alpha-thalassemia-1 with beta 0-thalassemia/Hb E might lead to so mild a condition that the individuals do not present clinically. The fact that many patients without a detectable alpha-thalassemia haplotype also had hemoglobin levels of 7.4 g/dl or higher suggests that there are additional factors responsible for the mildness of beta 0-thalassemia/Hb E disease.

Adolescent↗

PubMed1985

The morphology of redox-dye-treated HbH-containing red cells: differences between cells treated with brilliant cresyl blue, methylene blue and new methylene blue.

The ultrastructure of redox-dye-treated HbH-containing red cells has been shown to be dependent on the nature of the redox dye used. Brilliant cresyl blue causes the formation of a large number of small inclusions which are invariably attached to the inner surface of the red cell membrane. Methylene blue and new methylene blue cause the formation of a much smaller number of larger inclusions only some of which appear to be membrane-bound. These ultrastructural differences are reflected in marked differences in the light microscope appearances of the supravitally-stained cells.

Adult↗

PubMed1985

Thalassemia in southeast Asia: determination of different degrees of severity of anemia in thalassemia.

beta (0)-Thalassemia/Hb E in Southeast Asia varies greatly in severity, with hemoglobin levels ranging from 2.5 to 13.5 g/dl, averaging 7.7 g/dl. Results of systematic investigations to find out what determines different levels of severity are reviewed. Concomitant inheritance of alpha-thalassemia significantly decreases the severity. Different degrees of severity in the majority of cases, however, is not due to alpha-thalassemia. Concordance of hemoglobin levels among patients who are sibs prevails, suggesting polygenic factor determinants. Potential factors ruled out as determinants for different levels of severity are discriminating fetal hemoglobin production, erythrocyte superoxide dismutase activity, reticulo-endothelial function, and failure of erythropoiesis compensation. Red cell survival and globin synthesis studies indicate that different degrees of excess of alpha-chains leading to different red cell pathology and survival are responsible for variable severity. Degrees of excess of alpha-chains in this circumstance are probably mainly determined by erythrocyte proteolytic activity. The relationship between the hemoglobin levels and erythrocyte cytosol proteolytic activity in 15 beta(0) -thalassemia/Hb E disease patients in whom a deletional type of alpha-thalassemia had been ruled out by DNA mapping is striking, with a correlation coefficient of 0.78. This finding suggests that modulation of erythrocyte proteolysis is another approach for treatment of thalassemia.

Asia, Southeastern↗

PubMed1985

Improved technic for detecting intraerythrocytic inclusion bodies in alpha thalassemia trait.

Explore the source record for details and available documents.

Erythrocytes↗

PubMed1985

Prevalence of HTLV-III/LAV antibody in selected populations in Thailand.

Antibody to the human T-lymphotropic virus, type III/lymphadenopathy-associated virus (HTLV-III/LAV) by ELISA test was detected in one (1%) of 101 male homosexual prostitutes (confidence limit 95%:0.03-5.4%, in two (2%) of 100 thalassemia patients, and in none (C.L. 95%:0-3.6%) of 100 female prostitutes, 99 parenteral drug abusers, 100 male VD patients, 100 consecutive blood donors in serum collected from February through June 1985. Serum from the positive homosexual subject was strongly positive on repeated ELISA testing, and was also positive by Western Blot test. The two thalassemia patients, who were repeatedly weakly-positive by ELISA, were negative by Western Blot test and presumed to be false positive reactors. Prevalence of HTLV-III/LAV virus in sexually-active homosexuals in Thailand in 1985 appears to be similar to the 1% rate among homosexuals in San Francisco in 1978 at the start of the AIDS epidemic there.

Acquired Immunodeficiency Syndrome↗

PubMed1985

Intracranial extramedullary hematopoiesis inducing epilepsy in a patient with beta-thalassemia--hemoglobin E.

Generalized epileptiform seizures developed in a 23-year-old patient with beta-thalassemia-hemoglobin E. A computed tomographic scan suggested an intracranial mass. Surgery disclosed an extramedullary hematopoietic mass compressing the brain. Removal of the mass followed by irradiation of the area resulted in disappearance of the convulsions.

Adult↗

PubMed1984

Determination for different severity of anemia in thalassemia: concordance and discordance among sib pairs.

The degree of anemia in beta(0)-thalassemia/hemoglobin E disease is highly variable. As part of an attempt to identify determinants of this variability of severity we studied concordance and discordance of hemoglobin levels among sib pairs. The distribution of differences of hemoglobin levels in 216 sib pairs from 98 families showed a remarkable skewness toward the lower values with a mode at 0-0.5 gm/dl. The prevailing concordance of hemoglobin levels in patients from the same families and the persistence of the patterns indicate that polygenic factors are mainly responsible for the variability of anemia in this disease.

Female↗

PubMed1984

Ultrastructure and cell cycle distribution of erythropoietic cells in heterozygotes and homozygotes for haemoglobin E.

Marrow aspirates from heterozygotes and homozygotes for haemoglobin E (HbE) have been studied by electron microscopy and by the technique of combined Feulgen microspectrophotometry and 3H-thymidine autoradiography. The erythropoietic cells of heterozygotes did not contain any precipitated globin chains and the proliferating erythroblasts of such individuals showed no abnormality in their distribution in the different stages of interphase. By contrast, 0-1.5% of late erythroblast profiles and 3.1-12.8% of marrow reticulocyte profiles of homozygotes contained intracellular inclusions resembling precipitated alpha-chains. Although precipitated globin chains were not seen in the early polychromatic erythroblasts of homozygotes, the number of these cells in the G2 phase relative to that in the S phase was increased. These data indicate that there is probably little or no imbalance of globin chain synthesis in heterozygotes, a substantial degree of imbalance in homozygotes, and a disturbance of erythroblast proliferation in homozygotes which cannot be attributed to the deleterious effects of detectable intracellular alpha-chain precipitates. The electron microscope and cell cycle distribution data in the homozygotes for HbE were similar to those in two heterozygotes for beta thalassaemia.

Bone Marrow↗

PubMed1984

The fate of excess beta-globin chains within erythropoietic cells in alpha-thalassaemia 2 trait, alpha-thalassaemia 1 trait, haemoglobin H disease and haemoglobin Q-H disease: an electron microscope study.

Electron microscope studies have been performed on bone marrow cells from individuals with various alpha-thalassaemia syndromes. Globin chain precipitates were rarely found in the erythropoietic cells of a subject with alpha-thalassaemia 2 trait. By contrast, such precipitates were found in 0.6 - 1.3% of the erythroblast and marrow reticulocyte profiles in two cases of alpha-thalassaemia 1 trait, 2.1 - 13.7% of profiles in five patients with haemoglobin H (HbH) disease and 6.2% of profiles in one patient with haemoglobin Q-H (HbQ-H) disease. In the patient with HbQ-H disease, but not in the others, the nuclei of some erythroblasts displayed the 'Swiss cheese' appearance which has been reported in some forms of congenital dyserythropoietic anaemia. It is proposed that in alpha-thalassaemia 2 trait, where the degree of excess of beta-chains is slight, most of the excess chains are degraded by proteolysis. In alpha-thalassaemia 1 trait, where there is a greater excess of beta-chains, the excess chains can undergo either proteolysis or precipitation, but there is little or no tetramerization to form soluble HbH. Finally, in HbH disease, where the degree of excess is considerable, the excess beta-chains may be subject to proteolysis, precipitation and tetramerization.

Adult↗

PubMed1984

Hematologic and biosynthetic studies in homozygous hemoglobin Constant Spring.

The elongated alpha-globin chains of hemoglobin Constant Spring (alpha cs chain of HbCS ) are produced in low amounts such that the alpha cs-gene acts as a form of alpha-thalassemia; yet in the homozygous state the pathophysiological effects of this mutant are more severe than in the corresponding conditions that result from alpha-globin gene deletions. In studies designed to examine this discrepancy, we have demonstrated that a significant proportion of red cells produced in an HbCS homozygote has a much reduced red cell life span. Contrary to previous reports, we have been able to demonstrate the expected deficit in alpha-chain production in this condition and have shown that both the cessation of globin chain synthesis in vitro and the destruction of the excess beta-chains occur unusually rapidly. Comparison with various deletion forms of alpha-thalassemia suggests that, in terms of intracellular globin chain precipitates and free beta-chain pool, homozygous HbCS red cells more closely resemble those of HbH disease, with three of the four alpha-genes inactivated, than they do the more comparable alpha-thalassemia carriers with only two genes deleted.

Adult↗