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S N Wickramasinghe

Publications and source records attributed to S N Wickramasinghe.

At least 163 records · Page 9Linked to original sources
PubMed1982

Cell cycle distribution of erythroblasts in P. falciparum malaria.

The cell cycle distribution of the erythroblasts of 6 Gambian children with P. falciparum malaria was determined using the technique of combined Feulgen microspectrophotometry and 3H-thymidine autoradiography. The data showed evidence of a perturbation of erythroblast kinetics in all 6 children. The abnormalities were more marked in the children with chronic malaria than in those with acute malaria and predominantly affected the early polychromatic erythroblasts. The disturbances observed in chronic malaria included an increased proportion of cells in the G2 phase and an arrest during the progress of some cells through the S phase. The latter defect was not seen in the children with acute malaria.

Acute Disease↗
PubMed1982

A new case of congenital dyserythropoietic anaemia, type III: studies of the cell cycle distribution and ultrastructure of erythroblasts and of nucleic acid synthesis in marrow cells.

The clinical and laboratory findings in an asymptomatic 19-year-old Welshman with congenital dyserythropoietic anaemia (CDA) type III are described. The blood film showed macrocytosis and red cell fragmentation and there was biochemical evidence of intravascular haemolysis. The bone marrow showed erythroid hyperplasia, megaloblastic erythropoiesis and several giant multinucleate erythroblasts. Some mononucleate erythroblasts were large and had relative DNA contents of 4-8c and the bi- and multinucleate erythroblasts had total DNA contents of 2-16c. Some of the multinucleate erythroblasts displayed a variety of ultrastructural abnormalities, including marked differences in the appearances of the individual nuclei within the same cell. The marrow cells gave a normal deoxyuridine-suppressed value indicating that the megaloblastic changes were not caused by an impairment of the methylation of deoxyuridylate. The rates of incorporation of 14C-glycine and 14C-adenine into both the DNA and RNA of bone marrow cells were within the normal range. Furthermore, the average rate of elongation of newly-synthesised, 3H-thymidine-labelled daughter DNA strands, assessed by hydroxyapatite chromatography of alkali-denatured DNA was found to be normal. The results suggest that there is no impairment of DNA replication in the majority of the erythroblasts and that the abnormality of erythropoiesis resulted from disturbances during mitosis and the G2 phase.

Adenine↗
PubMed1982

Interaction between a synthetic analogue of vasopressin and human peripheral blood lymphocytes.

The interaction between 1-desamino-8-D-arginine vasopressin (DDAVP) and human peripheral blood lymphocytes was investigated in vitro, using DDAVP concentrations ranging between 1 pg and 10 microgram per ml. DDAVP did not display any mitogenic activity in the absence of phytohaemagglutinin (PHA). Neither did DDAVP have any significant effect on the PHA-stimulated incorporation of 3H-thymidine into DNA, provided that optimally mitogenic concentrations of PHA were present. However, DDAVP either enhanced or inhibited lymphocyte transformation initiated by suboptimally mitogenic concentrations of PHA: the direction of the response depended on the magnitude of the transformation response induced by the PHA alone. Experiments employing 125I-DDAVP demonstrated that DDAVP bound reversibly to untransformed lymphocytes, and that at 20 degrees C, the amount bound increased rapidly to reach a plateau value after 60 minutes. The binding of DDAVP was inhibited in the presence of Pitressin or arginine vasopressin suggesting that human peripheral blood lymphocytes have surface receptors for the vasopressins which also react with DDAVP.

Adult↗
PubMed1982

The interaction of DMSO-induced murine Friend leukaemia erythroblasts with cultured syngeneic mouse peritoneal macrophages: an in vitro model for the study of ineffective erythropoiesis.

The interaction between dimethyl sulphoxide-induced Friend leukaemia erythroblasts (IFLE) and cultured syngeneic mouse peritoneal macrophages (PM phi) was assessed radiochemically as well as by light and electron microscopy. The data revealed that a small number of the IFLE either became attached to or were ingested by the PM phi and that the interacting IFLE were usually well differentiated. Interactions of a similar nature were also seen when IFLE were co-cultured with macrophages derived from mouse bone marrow. The extent of interaction between IFLE and PM phi provides a useful system in which mechanisms underlying ineffective erythropoiesis can be defined.

Animals↗
PubMed1981

Ineffective erythropoiesis in haemoglobin E beta -thalassaemia: an electron microscope study.

Electron microscope studies have been performed on the bone marrow cells of two non-splenectomized patients and the circulating erythroblasts and reticulocytes of three splenectomized patients with HbE/beta-thalassaemia. Some intracellular precipitates (probably consisting of alpha-chains) and mild dyserythropoietic changes were found in the early polychromatic erythroblasts within the bone marrow. Larger quantities of precipitate and more marked dyserythropoietic changes were found in the late polychromatic erythroblasts and reticulocytes both within the marrow and within the circulation. The bone marrow macrophages contained phagocytosed erythroblasts within their cytoplasm. These data indicate that the anaemia in HbE/beta-thalassaemia results largely from dyserythropoiesis and ineffective erythropoiesis. The ultrastructural abnormalities encountered in the cases of HbE/beta-thalassaemia were qualitatively and quantitatively similar to those seen in homozygous beta-thalassaemia.

Adult↗
PubMed1981

Morphology and kinetics of erythropoiesis in haemoglobin H disease.

Some aspects of erythroblast function have been investigated in two Thai patients with haemoglobin H disease. Electron microscope and high resolution autoradiographic studies revealed that (1) some erythroblasts and marrow reticulocytes contained branching intracytoplasmic inclusions and (2) the presence of such inclusions did not necessarily prevent the entry of cells either from the G1 phase into the S phase or from the G2 phase into mitosis. The distribution of early polychromatic erythroblasts in the different stages of the cell cycle was determined by the technique of combined Feulgen microspectrophotometry and 3H-thymidine autoradiography and found to be essentially normal. It is concluded that although the presence of an excess of alpha-chains in the beta-thalassaemia syndromes has been previously shown to be associated with a gross impairment of erythroblast proliferation, the presence of an excess beta-chains in HbH disease is not.

Adult↗
PubMed1981

Ultrastructure of red cells containing haemoglobin H inclusions induced by redox dyes.

Electron microscope studies have been performed to investigate the ultrastructural basis of the characteristic golf-ball-like light microscope appearance which develops when the erythrocytes of patients with HbH disease are stained supravitally with brilliant cresyl blue or new methylene blue. The data indicate that the golf-ball appearance resulted from the formation of many spherical or biconvex masses of electron-dense material which were attached to and which bulged the cell membrane. These masses presumably consisted of denatured HbH. A variable proportion of the red cells of the four patients investigated failed to form such membrane-associated inclusions even after treatment with redox dyes for 24 h. Studies of subpopulations of red cells which were separated according to cell age suggested that there was a considerable variation in the HbH content of young red cells and indicated that with increasing cell age there is an increase in the proportion of red cells which do not contain appreciable quantities of HbH.

Coloring Agents↗
PubMed1981

Metabolism of ethanol by human bone marrow cells.

The ability of human bone marrow cells to metabolise has been studied. After incubation of suspensions of bone marrow cells with [1(-14)C] ethanol (0.1 mg/ml) for 1.5 h, radioactivity was present in the evolved CO(2) and in the cellular lipids. Only a part of the 14CO2 generated was dependent on the presence of contaminating blood cells in the marrow cell suspensions. These findings indicate that one or more cell types in the marrow are capable of oxidising ethanol to acetaldehyde and acetate. Our date raise the interesting possibility that the effects of chronic alcoholism on the bone marrow may not be caused by a direct action of ethanol, but may be related to some intracellular or extracellular changes resulting from the metabolism of ethanol within the marrow cells themselves.

Bone Marrow↗
PubMed1981

Effects of low concentrations of pyrimethamine on human bone marrow cells in vitro: possible implications for malaria prophylaxis.

The effects of low concentrations of pyrimethamine on the enzyme dihydrofolate reductase in human bone marrow cells were investigated in vitro using the deoxyuridine suppression test. The results indicated that drug concentrations which are achieved in the plasma of adults receiving 25 mg pyrimethamine per week inhibited the activity of this enzyme in a proportion of the marrow samples studied. Experiments using vitamin B12- or folate-deficient marrow cells showed that these concentrations of pyrimethamine may aggravate a pre-existing impairment of the methylation of deoxyuridylate. These in-vitro findings emphasize the importance of further studies into the toxicity of pyrimethamine when this drug is used for malaria prophylaxis in malnourished individuals.

Bone Marrow↗
PubMed1980

The anaemia of P. falciparum malaria.

The haematological changes in a group of young Gambian children with P. falciparum malaria have been analysed. In children with acute infection anaemia was most marked during the period after treatment. Although many of these patients developed a positive direct Coombs test during this period of the illness it is not clear whether the anaemia which occurs after treatment has an immune basis. A second group of children showed quite different haematological findings. They appear to have a more chronic form of P. falciparum malaria infection, were profoundly anaemic at presentation, showed gross dyserythropoietic changes in their bone marrows, and had a full reticulocyte response and rise in haemoglobin after treatment. A third group of children were encountered whose haematological abnormalities were intermediate to those of the acute and chronic groups. These findings indicate that the patho-physiological mechanisms responsible for the anaemia of P. falciparum malaria are different at different stages of the illness.

Anemia↗
PubMed1980

Ultrastructural studies of erythropoiesis in beta-thalassaemia trait.

The erythropoietic cells of six cases of beta-thalassaemia trait were studied by electron microscopy and electron microscope autoradiography. Intracytoplasmic and intranuclear alpha-chain precipitates were found in some late polychromatic erythroblasts and intracytoplasmic precipitates were found in several marrow reticulocytes. This provides direct morphological evidence of unbalanced globin chain synthesis in the marrow. Several of the polychromatic erythroblasts and marrow reticulocytes contained autophagic vacuoles and showed a variety of other dyserythropoietic changes. Erythroblast profiles containing moderate quantities of precipitated alpha-chains usually suffered from a marked depression of protein synthesis. The proportions of marrow cells containing alpha-chain precipitates and displaying dyserythropoietic changes varied considerably from patient to patient. It is proposed that this variation largely reflects variations in the proteolytic capacity of the erythropoietic cells in different individuals and leads to different degrees of ineffective erythropoiesis in beta-thalassaemia trait.

Adult↗
PubMed1980

Electron microscope and high resolution autoradiographic studies of the erythroblasts in haemoglobin H disease.

Electron microscope studies of bone marrow from a patient with haemoglobin H (HbH) disease have revealed the presence of highly condensed branching intracytoplasmic inclusions within a proportion of the early and late polychromatic erythroblasts and reticulocytes. Intraerythroblastic inclusions of this type have not yet been described in any other haematological disorder and may well be a specific feature of HbH disease. Electron microscope autoradiographic studies of the marrow cells from the patient with HbH disease revealed that (1) active protein synthesis continues in inclusion-containing erythroblasts and (2) there is a rapid precipitation of a considerable proportion of the newly synthesized free beta chains onto the surfaces of preformed inclusions, presumably after conversion to HbH. These electron microscope and electron microscope autoradiographic findings are quite different from the findings previously reported in homozygous beta thalassaemia using the same techniques.

Autoradiography↗
PubMed1979

Development of human granulocyte and monocyte Fc receptors.

Bone marrow cells were examined for the presence of IgG-Fc receptors using a red cell rosette technique. Receptors were demonstrated on some of the neutrophil promyelocytes, almost all of the neutrophil myelocytes, and a few of the eosinophil myelocytes. Cells which appeared on morphological grounds to be promonocytes also expressed Fc receptors.

Bone Marrow↗
PubMed1979

Effect of T-lymphocytes on normal haemopoiesis: studies in congenitally athymic nude mice.

The germ-free nude mouse represents a most useful animal for investigating the effects of a congenital deficiency of T-lymphocytes on various physiological processes, including haemopoiesis. Nude mice (nu/nu) of the CBA strain, nonmutant inbred CBA mice, and inbred C3H mice were reared in germ-free isolators and used to compare (1) the haematological parameters of nu/nu mice and CBA mice at different ages and (2) the labelling pattern of circulating leucocytes at various times after a single intraperitoneal injection of 3H-thymidine into 3-month-old nu/nu and C3H mice. The data suggest that the deficiency of T-lymphocytes in nu/nu mice may lead to a disturbance of haemopoiesis in 2 to 6-month animals which is characterised by a mild macrocytosis and a very marked reduction in the proportion of labelled leucocytes which can be seen in the blood after an injection of 3H-thymidine. Despite these perturbations, unstressed nu/nu mice were able to maintain adequate numbers of blood cells (other than lymphocytes) in their circulation. Nine-month-old nu/nu mice did not show a macrocytosis and the disappearance of the marcrocytosis at this age was associated with an increase both in the blood lymphocyte count and in the mass of lymphoid tissue in the spleen and mesenteric lymph nodes.

Animals↗
PubMed1979

Some aspects of the biology of multinucleate and giant mononucleate erythroblasts in a patient with CDA, type III.

Marrow cells of a patient with CDA, type III, were (1) incubated with 3H-thymidine for 0.5 h and studied using a combination of Feulgen microspectrophotometry and light microscope autoradiography and (2) incubated with 3H-thymidine, 3H-uridine or 3H-leucine for 1 h and studied using the technique of electron microscope autoradiography. The data revealed multiple abnormalities in the proliferation of erythroblasts but no abnormality in the distribution of neutrophil promyelocytes and myelocytes in the different stages of interphase. Some mononucleate erythroblasts had DNA contents of 4-20c and the multinucleate erythroblasts had total DNA contents of 2-40c. In about 40% of the multinucleate erythroblasts, only some of the nuclei within the same cell incorporated 3H-thymidine and the electron microscope autoradiographic studies revealed that the nuclei which failed to synthesize DNA virtually always showed abnormalities in the electron-density of the heterochromatin or euchromatin or a Swiss-cheese appearance of the heterochromatin. Furthermore, in some multinucleate cells but not in others, the ultrastructurally abnormal nuclei showed a marked depression of RNA synthesis when compared with the normal-looking nuclei within the same cell. An occasional binucleate, multinucleate and giant mononucleate erythroblast showed ultrastructural changes suggestive of advanced degeneration and such cells, which showed a marked depression of RNA and protein synthesis, appeared to be phagocytosed by macrophages.

Anemia↗