Biomedical subjects

D Roos

Publications and source records attributed to D Roos.

At least 307 records · Page 17Linked to original sources

PubMed1981

Haemolytic disease of the newborn and chronic anaemia induced by gamma beta thalassaemia in a Dutch family.

Severe haemolytic anaemia with hyperbilirubinaemia and erythroblastaemia was observed in nine newborn infants belonging to one large family. One infant was still-born, two died shortly after birth, five recorded after receiving one or more exchange transfusions and one improved without transfusional therapy. In four out of six newborns whose bilirubin levels were determined, a mixed hyperbilirubinaemia was found with high concentrations of both free and conjugated bilirubin. At the end of the first year of life the surviving children, although in satisfactory general condition, showed a mild microcytic hypochromic anaemia with decreased red cell osmotic fragility and morphological abnormalities of the erythrocytes consisting of microcytosis, anisopoikilocytosis and target cells. The serum iron levels were normal. The same haematological picture was also present in those parents of the affected children that are members of this family; these adult had normal levels of Hbs A2 and F. Incorporation of [3H]leucine into the globin chains of two adults with this syndrome revealed a reduced beta-chain synthesis (beta/alpha ratio of 0 . 49 and 0 . 53, respectively). In the two infants available for this investigation, reduced gamma-chain production was found shortly after birth. In parallel with the switch from fetal to adult haemoglobin, the deficient gamma-chain production was replaced by a similar reduction of beta-chain synthesis. These results suggested, therefore, a combined deficiency of gamma- and beta-chain production. The normal levels of Hb A2 were compatible with a defective delta-chain synthesis as well. Analysis with restriction enzymes had shown previously a large deletion, comprising gamma and delta genes, in one of the chromosomes of the affected individuals. The same procedure had established that, in spite of the defective beta-chain production, the beta-globin structural gene is intact.

Adolescent↗

PubMed1981

[Hemolytic disease of the newborn and chronic hypochromic microcytic anemia in one family: gamma-delta-beta thalassemia].

Ten newborn infants, all belonging to one family, suffered from severe hemolytic anemia. Four babies died shortly before or after birth, six recovered (one spontaneously, 5 after one or more exchange transfusions). In 5 out of 8 patients a mixed hyperbilirubinemia was observed in the immediate postnatal period, with elevated levels of indirect- as well as direct-reacting bilirubin. After the neonatal period, a slight hypochromic, microcytic anemia persisted, without icterus but with decreased osmotic fragility of the erytrocytes and with target cells in the blood smear. The same hematological picture was observed in one of the parents of each affected baby. All anemic adults belong to one large family; therefore, a dominant mode of inheritance is most likely. Although the hematological findings are suggestive for beta-thalassemia normal HbF and HbA2 levels were observed. In vitro incorporation of radioactive leucine into globin chains in reticulocytes demonstrated defective synthesis of beta chains in the affected adults; in two affected infants the same technique showed defective gamma-chain synthesis as well. Analysis of the hemoglobin genes proved that the affected family members are suffering from heterozygous gamma-delta-beta-thalassemia, as originally described by Kan et al. (1972).

Adult↗

PubMed1980

gamma-beta-Thalassaemia studies showing that deletion of the gamma- and delta-genes influences beta-globin gene expression in man.

In gamma-beta-thalassaemia, human gamma- and beta-globin gene expression is suppressed; this results in a severe anaemia in newborns which subsequently develops into a beta-thalassaemia syndrome in adult life. This hereditary disease is now shown to be the result of a deletion of at least 40,000 base pairs of the gammadeltabeta-globin gene locus. The gamma- and delta-globin genes are deleted in the affected chromosome but, surprisingly, the beta-globin gene is still present, together with a large segment of the DNA sequences flanking the gene on its 5'-side and the entire region on the 3'-side of the gene. Hence, a deletion of DNA far from the beta-globin gene results in the suppression of its activity.

Chromosome Deletion↗

PubMed1980

Subpopulations of T lymphocytes from human blood differing in density and stage of maturation.

Previous investigations have shown that peripheral lymphocytes with a low specific gravity are much more active than are heavy lymphocytes in the proliferative response towards mitogens, antigens and allogeneic lymphocytes. We have now studied the biological significance of this difference in human peripheral T lymphocytes with two independent parameters generally regarded as maturation criteria. Heavy human T lymphocytes contain about one-third of the amount of cyclic AMP found in light T cells, but the increase in cyclic AMP produced by isoproterenol or prostaglandin E1 is much higher in the heavy T cells. The lactate dehydrogenase isoenzyme pattern of heavy human T lymphocytes is intermediate between that of human thymocytes and light T lymphocytes, the latter showing the most mature pattern. A high correlation was found between these two parameters, the cell density and the reactivity towards phytohemagglutinin. We conclude that human peripheral T lymphocytes are heterogeneous in maturation level: heavy, nonreactive T lymphocytes are less mature than light T lymphocytes.

Cell Differentiation↗

PubMed1980

Protection of human neutrophils against oxidative damage.

This report reviews some of our work on the relative importance of the glutathione redox system and catalase in protecting human neutrophils in vitro against hydrogen peroxide, generated either by these cells during phagocytosis or artificially in the medium by an enzyme system. Neutrophils deficient in glutathione reductase were rapidly inactivated during phagocytosis, unless protected by scavengers of oxidative products in the medium. In contrast, normal neutrophils remained functionally active. Thus, despite the presence of a normal catalase activity, a defect in the glutathione system totally impairs the protection of neutrophils against their own metabolic products. In catalase-inhibited or catalase-deficient neutrophils, no damage was observed during phagocytosis. We conclude that the glutathione redox system is the most important protection system against damage by oxidative products of neutrophils. During incubation of neutrophils with glucose + glucose oxidase, an extracellular system that generates hydrogen peroxide, we found that both catalase and the glutathione redox system were needed for adequate protection against oxidative injury. Apparently, this extracellular stress cannot be efficiently dealt with by the glutathione system alone: co-operation with catalase is needed in this situation. Under certain conditions, oxidative damage was observed even when the level of reduced glutathione was still relatively high, indicating that perhaps catalase and glutathione each protect different cell structures, and that both systems are needed together for the preservation of the total cell function.

Acatalasia↗

PubMed1980

Characterization of the peroxidase in human eosinophils.

1. Human eosinophils contain a peroxidase that appears to be of the same type as horseradish peroxidase, lactoperoxidase and intestine peroxidase. 2. Electron paramagnetic resonance spectra of human eosinophils show high-spin ferric heme signals with rhombic symmetry (gx = 6.56, gy = 5.31 and gx = 6.33, gy = 5.59) for the heme group. Part of the more rhombic signal is due to catalase, whereas the other part is completely due to the peroxidase. In addition to these high-spin heme compounds a low-spin heme compound is detectable with g values (gx = 3.09, gy = 2.22 and gz = 1.48) characteristic of a bisimidazole heme iron complex. 3. The amount of heme iron derived from the eosinophil peroxidase, determined from electron paramagnetic spectra, is 13.2 X 10(-17) mol/eosinophil. This is in good agreement with the pyridine hemochrome spectra which yield a value of 13.5 X 20(-17) mol heme iron/eosinophil.

Electron Spin Resonance Spectroscopy↗

PubMed1980

Glutathione-dependent dehydroascorbate reduction: a determinant of dehydroascorbate uptake by human polymorphonuclear leukocytes.

Dehydroascorbate uptake and reduction are impaired in normal human polymorphonuclear leukocytes (PMN) preincubated with N-ethylmaleimide, and in glutathione reductase-deficient cells. We conclude that human PMN dehydroascorbate reduction is glutathione-dependent, and that dehydroascorbate reduction appears to be a necessary condition for cellular dehydroascorbate uptake.

Ascorbic Acid↗

PubMed1980

Protection of human neutrophils by endogenous catalase: studies with cells from catalase-deficient individuals.

To investigate the importance of catalase as a protecting enzyme against oxidative damage in phagocytic leukocytes, we have tested the functional capacity of neutrophils from two individuals homozygous for Swiss-type acatalasemia and from two individuals heterozygous for this deficiency. In the former cells, 25-30% of residual activity of catalase was present. In the latter cells, the values were close to normal. Chemotaxis towards casein, release of lysosomal enzymes and hydrogen peroxide during phagocytosis of zymosan, and intracellular killing of Staphylococcus aureus were normal in all cells tested. Inhibition of heme enzymes with azide (2 mM) enhanced the respiration and hexose monophosphate shunt activity of normal, but not of homozygous acatalasemic, neutrophils. This indicates that the enhancement in normal cells is, at least in part, due to catalase inhibition. After 15 min preincubation with an H(2)O(2)-generating system (glucose plus glucose oxidase), the respiratory response to zymosan phagocytosis was strongly depressed in the homozygous acatalasemic and in normal, azide-treated neutrophils, but not in normal, untreated cells. Under these conditions, the release of lysosomal enzymes was depressed and that of lactate dehydrogenase enhanced, in catalase-deficient and in catalase-inhibited, but not in normal, neutrophils. During prolonged incubation with the H(2)O(2)-generating system (30-60 min), the reduction level of intracellular glutathione remained high and the hexose monophosphate shunt continued to operate normally in all cells tested. Thus, although the function of neutrophils without catalase activity was depressed by extracellular hydrogen peroxide, the H(2)O(2) degradation via the glutathione redox system remained operative. The results indicate that the glutathione redox system by itself efficiently protects phagocytosing neutrophils against their own oxidative products. During heavy external oxidative stress, however, both catalase and the glutathione redox system are needed for adequate protection.

Catalase↗

PubMed1980