A fault in the design of the deoxyuridine suppression test.
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Deoxyuridine↗
Biomedical subjects
S N Wickramasinghe
Publications and source records attributed to S N Wickramasinghe.
Intracellular localization of 55Fe after serum-mediated uptake by human erythropoietic cells.
Marrow cells of 3 patients with normoblastic erythropoiesis and 1 with sideroblastic erythropoiesis were incubated with serum-bound 55Fe Cl3 and studied by the technique of electron microscope autoradiography. In the 3 normoblastic marrows, both the mean grain counts and the percentages of grains situated over the cytoplasm (excluding the mitochondria) were higher in the early erythroblasts than in the intermediate and late erythroblasts. The percentages of autoradiographic grains situated over the mitochondria of early intermediate and late erythroblasts were 11.9-27.4, 56.5-61.1 and 65.3-65.9, respectively. Although the mean grain counts over these three cell classes in the sideroblastic marrow were similar to those in the normoblastic marrows, the proportions of grains over the mitochondria were higher, particularly in the early erythroblasts. In all 4 cases (1) some grains were situated at the junction between heterochromatin and euchromatin and (2) a few of the 55Fe-labelled immature-looking cells did not display the ultrastructural features usually attributed to pronormoblasts.
Adult↗
Synthesis of nucleic acids by bone marrow cells from patients with iron deficiency anaemia.
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Anemia, Hypochromic↗
High resolution autoradiographic studies of RNA, protein and DNA synthesis during human eosinophil granulocytopoiesis: evidence for the presence of RNA on or within eosinophil granules.
Human bone marrow cells which had been incubated with [3H]uridine or [3H]leucine for I h were studied using the technique of electron microscope-autoradiography. The autoradiographs revealed the presence of newly-synthesized RNA and protein molecules within or on a proportion of (I) the primary and secondary granules in all classes of eosinophil precursors and (2) the secondary granules in eosinophil granulocytes. It is suggested that the granule-associated RNA molecules may be concerned with the synthesis of at least some of the new protein molecules which were incorporated into the limiting membrane or substance of eosinophil granules long after the immature primary granule stage. Studies of eosinophil precursors which had been incubated with [3H]thymidine for I h showed that the eosinophil granules do not label with this DNA precursor.
Autoradiography↗
Capacity of ringed sideroblasts to synthesize nucleic acids and protein in patients with primary acquired sideroblastic anaemia.
Bone marrow cells from two patients with primary acquired sideroblastic anaemia were studied using the technique of electron microscope autoradiography. Whereas a significant proportion of erythroblasts containing small to moderate quantities of intramitochondrial deposits incorporated [3H]thymidine into DNA, the majority of cells containing large quantities of intramitochondrial deposits did not. These results are consistent with the idea that several of the early polychromatic cells with large quantities of deposits become arrested in their progress through the cell cycle. The data also revealed that the accumulation of increasing quantities of iron-containing material within the mitochondria of an erythroblast was frequently (but not invariably) associated with and was possibly responsible for (I) a depression of RNA synthesis and (2) a more marked depression of protein synthesis. A small proportion of the erythroblasts showing a depression of protein synthesis also displayed various non-specific ultrastructural abnormalities indicative of cellular injury such as the presence of intranuclear clefts, nuclear membrane-associated myelin figures and lipid-laden intracytoplasmic vacuoles.
Aged↗
Some features of bone marrow macrophages in patients with homozygous beta-thalassaemia.
The bone marrow macrophages of patients with homozygous beta-thalassaemia were frequently situated adjacent to collagen fibres and sometimes formed intrasinusoidal cytoplasmic protrusions. They also appeared to phagocytose processes of erythroblast cytoplasm (at times containing precipitated alpha-chains) which projected into them from neighbouring erythroblasts. The cytoplasm of the macrophages included large numbers of heavily-iron-loaded secondary lysosomes of various sizes and shapes in addition to phagocytosed erythroblasts, erythrocytes and extruded erythroblast nuclei. Numerous ferritin molecules were found in the cytoplasmic matrix but there were hardly any in the mitochondria, endoplasmic reticulum or golgi saccules. A small number of ferritin molecules were present within the nucleus. Electron microscope autoradiographs of marrow fragments which had been incubated with [3H]leucine for 1 h revealed the presence of newly-synthesized protein molecules in all types of secondary lysosomes. Light microscope autoradiographs showed the [3H]thymidine labelling index of the bone marrow macrophages was less than 1% and suggested that only a very small proportion of these cells were actively preparing for division.
Bone Marrow↗
Effects of azathioprine therapy on the MCV of patients with renal grafts: evidence for alterations in the kinetics of erythropoiesis over a prolonged period.
The changes in MCV at various times after renal transplantation were studied in a group of patients with functioning cadaveric renal grafts who had received azathioprine from the time of transplantation and in a constant dose from 2-8 weeks later. A post-transplantation increase in the MCV was seen in the majority of the cases studied and in these cases the MCV did not reach a maximum value until as long as 11-40 months after transplantation. In most cases the MCV then feel although frequently not to within the normal range and in some cases it showed further fluctuations. These data suggest gradual alterations over a period of years in the various cytokinetic changes which serve to maintain a reasonably high output of red cells from the marrow despite the cytotoxic effects of azathioprine.
Azathioprine↗
Electron microscope autoradiographic studies of the erythroblasts of a case of congenital dyserythropoietic anaemia, type II.
The bone marrow cells of a patient with congenital dyserythropoietic anaemia, type II, were incubated with 3H-thymidine, 3H-uridine or 3H-leucine for 1 h and studied using the technique of electron microscope autoradiography. Several of the erythroblasts which either displayed the characteristic subsurface double membranes or showed various non-specific abnormalities of the nuclear membrane were found to be actively engaged in DNA, RNA and protein synthesis. Both members of some pairs of erythroblasts which were joined together by a spindle bridge were found to be engaged in DNA synthesis, indicating that some spindle bridges persist for a period longer than the duration of the G1 phase. A small proportion of mononucleate and binucleate late (non-dividing) erythroblasts showed a marked depression or arrest of protein synthesis and some or all of such cells were presumably destined to be phagocytosed by the bone marrow macrophages.
Anemia↗
An investigation into the development and fate of neutrophil giant metamyelocytes using the techniques of electron microscopy and high resolution autoradiography.
The neutrophil giant metamyelocytes present in vitamin B12-and folate-deficient patients were studied using the techniques of electron microscopy and electron microscope autoradiography. The ultrastructural features of the cytoplasm of a proportion of these cells resembled those of promyelocytes and myelocytes, particularly with respect to the types of neutrophil granules present. This finding suggests that the giant metamyelocytes result from an abnormal type of development in promyelocytes and myelocytes which have been arrested or retarded in their progress through the cell cycle. The hypothesis that giant metamyelocytes eventually die within the marrow was supported by the observations that a significant proportion of these cells contain intracytoplasmic autophagic vacuoles, that some giant metamyelocytes suffer from a marked depression of RNA and protein synthesis and that degenerating giant metamyelocytes can be recognized within the cytoplasm of some bone marrow macrophages.
Bone Marrow↗
An electron microscope study of the intercellular contacts between the erythroblasts of patients with hypersiderotic bone marrows.
When stained and unstained sections of hypersiderotic marrow fragments are examined in the electron microscope, some of the ferritin molecules present between a variable proportion of the erythroblasts are found to be aligned more or less transversely. These linearly arranged ferritin molecules are particularly evident in regions in which the opposing cell membranes have been sectioned obliquely and may be confused with the septa-containing intercellular junctions characteristically present between some types of invertebrate epithelial cells.
Anemia↗
Red cell indices and serum ferritin levels in children.
The blood counts of 187 non-anaemic children who attended hospital with minor illnesses and who were between the ages of 12 months and 6 years were studied retrospectively. As many as 76-8% of these children were found to have MCVs below the normal adult range. A prospective study of a further 28 non-anaemic children in the same age group showed that the majority of children with low MCVs have normal haemoglobin A2 and F levels and have serum ferritin levels within the normal adult range. These findings indicate that microcytosis is an intrinsic feature of erythropoiesis in early childhood and that in most instances this feature cannot be attributed to iron deficiency or beta-thalassaemia syndromes.
Anemia, Hypochromic↗
Results of three years' experience with the deoxyuridine suppression test.
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Alcoholism↗
Electron microscope and high resolution autoradiographic studies of megaloblastic erythropoiesis.
Bone marrow fragments from 10 patients with a megaloblastic anaemia due to vitamin B12 or folate deficiency were studied by electron microscopy and electron microscope autoradiography. A proportion of the erythroblasts showed ultrastructural abnormalities. Some of the cells containing autophagic vacuoles, large siderosomes, iron-laden mitochondria, irregularly shaped nuclei, membrane-bound nuclear clefts, or incomplete nuclear membranes were found to be capable of DNA, RNA and protein synthesis. Other cells showed advanced degenerative changes such as the distension of the perinuclear space, the clumping of cytoplasmic organelles near the nucleus and a reduction in the electron density and ribosome content of the cytoplasm. Most of these grossly abnormal cells suffered from either a marked depression or an arrest in protein and RNA synthesis, and were presumably destined for phagocytosis by reticulum cells.
Anemia, Macrocytic↗
Effect of azathioprine on the cell cycle of haemopoietic cells.
The megaloblastic erythropoiesis encountered in 3 azathioprine-treated patients with renal transplants was found to be associated with a marked increase in the proportion of early polychromatic erythroblasts in the G2 phase of the cell cycle. By contrast, there was only a slight increase in the proportion of G2 cells in the neutrophil promyelocyte-myelocyte pool of these patients.
Azathioprine↗
Correlations between the deoxyuridine-suppressed value and some conventional haematological parameters in patients with folate or vitamin B12 deficiency.
The correlations between the deoxyuridine-suppressed value and some conventional haematological parameters (Hb concentration, red cell count, MCV, total white cell count, red cell folate level and serum vitamin B12 level) have been investigated in 40 patients with megaloblastic haemopoiesis due to folate or vitamin B12. deficiency. The only statistically significant correlations found were (a) an inverse correlation between the deoxyuridine-suppressed value and the Hb level or red cell count in both the folate- and vitamin B12-deficient groups and (b) a direct correlation between the deoxyuridine-suppressed value and MCV in the vitamin B12-deficient group. The results indicated that the deoxyuridine-suppressed value was a better index of the magnitude of the disturbance in red cell production induced by folate or vitamin B12 deficiency than either the red cell folate or serum vitamin B12 levels.
Bone Marrow↗
Effects of anticonvulsant drugs on the synthesis of DNA and protein by human bone marrow cells in vitro.
Suspensions of human bone marrow cells were incubated with various concentrations of phenobarbitone or phenytoin sodium for 2 h, and the effects of this incubation on the subsequent incorporation of 3H-thymidine and3H-leucine into DNA and protein, respectively, were studied. Both drugs caused a depression of 3H-thymidine incorporation and this phenomenon was not prevented by the addition of 100 mug of pteroyl-glutamic acid, folinic acid or 5-methyltetrahydrofolate per ml of marrow culture. The lowest concentration of drug which caused a statistically significant depression of 3H-thymidine incorporation was 200 mug per ml for phenobarbitone and 50 mug per ml for phenytoin sodium. Both phenobarbitone and phenytoin sodium also caused an increase in the incorporation of 3H-leucine at concentrations of 50 and 20 mug per ml, respectively, suggesting the possibility that a stimulation of protein synthesis within erythropoietic cells may play an important role in the development of anticonvulsant-induced macrocytosis.
Bone Marrow↗
Relationship between the concentration of neutrophils and monocytes in venous blood.
A striking linear relationship was found between the logarithms of the medians of the circulating neutrophil (granulocyte plus metamyelocyte) counts and the monocyte counts in 5 groups of individuals studied. These groups consisted of (1) 100 normal adult males, (2) 100 normal, non-pregnant females, (3) 50 females in the last trimester of pregnancy, (4) 15 patients with a persistent neutrophil leucocytosis and (5) 20 patients with polycythaemia rubra vera, essential thrombocythaemia or myelofibrosis. A different relationship appeared to exist between the circulating neutrophil and monocyte counts in a group of 16 patients with chronic granulocytic leukaemia.
Blood Cell Count↗
Megaloblastic erythropoiesis and macrocytosis in patients on anticonvulsants.
The results of deoxyuridine suppression tests on the bone marrow cells of 14 patients on anticonvulsant drugs, 11 of whom had evidence of megaloblastic erythropoiesis, indicated that the megaloblastic changes and macrocytosis encountered in treated epileptics are often not caused either by folate deficiency or by drug-induced impairment of the 5, 10-methylenetetrahydrofolate-dependent methylation of deoxyuridylate to thymidylate. A folate-related abnormality in the methylation of deoxyuridylate was found in only two of the 11 patients with megaloblastic erythropoiesis.
Adult↗