The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Colin A. Sieff - One of the best experts on this subject based on the ideXlab platform.
-
DIAMOND-BLACKFAN ANEMIA
Hematology-oncology Clinics of North America, 1997Co-Authors: Oleg I. Krijanovski, Colin A. SieffAbstract:Diamond-Blackfan anemia (DBA) is a rare congenital hypoplastic anemia 32,66 that usually presents early in infancy. Retrospective studies in the United Kingdom and the Netherlands are consistent with an incidence of 4–5 per million live births, 12,24 with evidence of inheritance (dominant and recessive) in perhaps 12% to 25% of cases. 3,48,126 Congenital anomalies, in particular of the head and upper limbs, are present in about a quarter of reported patients. The disease is characterized by a moderate-to-severe macrocytic anemia, occasional neutropenia and/or thrombocytosis, and a normocellular bone marrow with erythroid hypoplasia. Although proerythroblasts may be present or even increased, Normoblasts are usually markedly diminished or absent. The majority of patients (75%) respond to prednisone, and erythropoiesis can then be maintained in some cases with almost homeopathic doses of the drug. Nonresponders are usually transfusion-dependent, although responses to androgen have been observed. 33,58,73,110
Oleg I. Krijanovski - One of the best experts on this subject based on the ideXlab platform.
-
DIAMOND-BLACKFAN ANEMIA
Hematology-oncology Clinics of North America, 1997Co-Authors: Oleg I. Krijanovski, Colin A. SieffAbstract:Diamond-Blackfan anemia (DBA) is a rare congenital hypoplastic anemia 32,66 that usually presents early in infancy. Retrospective studies in the United Kingdom and the Netherlands are consistent with an incidence of 4–5 per million live births, 12,24 with evidence of inheritance (dominant and recessive) in perhaps 12% to 25% of cases. 3,48,126 Congenital anomalies, in particular of the head and upper limbs, are present in about a quarter of reported patients. The disease is characterized by a moderate-to-severe macrocytic anemia, occasional neutropenia and/or thrombocytosis, and a normocellular bone marrow with erythroid hypoplasia. Although proerythroblasts may be present or even increased, Normoblasts are usually markedly diminished or absent. The majority of patients (75%) respond to prednisone, and erythropoiesis can then be maintained in some cases with almost homeopathic doses of the drug. Nonresponders are usually transfusion-dependent, although responses to androgen have been observed. 33,58,73,110
Bo Thorell - One of the best experts on this subject based on the ideXlab platform.
-
Characterization of the Normoblast Population in β‐Thalassaemic Blood by Rapid‐Flow Cytofluorometry
Scandinavian Journal of Haematology, 2009Co-Authors: Eliezer A. Rachmilewitz, Bo ThorellAbstract:Samples of peripheral blood from patients with beta-thalassaemia major which contained significant numbers of nucleated Normoblasts were stained with acridine orange and analyzed with rapid-flow cytofluorometry. The pyknotic Normoblast-nuclei gave less green 'DNA' fluorescence than the (diploid) leucocytes and constituted a separate, distinct subpopulation. Mean values of the fluorescence intensities and standard deviations as displayed by multichannel analyses gave a numerical value for Normoblasts with regard to their maturation stages. These mean values correlated with the differential counts of 'early and late' Normoblasts in the light microscope under rigidly standardized conditions. Rapid-flow cytofluorometry thus provides an objective and quantitative way to monitor and define peripheral blood Normoblast populations as a measure of the severity of 'erythropoietic stress'.
-
characterization of the Normoblast population in β thalassaemic blood by rapid flow cytofluorometry
Scandinavian Journal of Haematology, 2009Co-Authors: Eliezer A. Rachmilewitz, Bo ThorellAbstract:Samples of peripheral blood from patients with beta-thalassaemia major which contained significant numbers of nucleated Normoblasts were stained with acridine orange and analyzed with rapid-flow cytofluorometry. The pyknotic Normoblast-nuclei gave less green 'DNA' fluorescence than the (diploid) leucocytes and constituted a separate, distinct subpopulation. Mean values of the fluorescence intensities and standard deviations as displayed by multichannel analyses gave a numerical value for Normoblasts with regard to their maturation stages. These mean values correlated with the differential counts of 'early and late' Normoblasts in the light microscope under rigidly standardized conditions. Rapid-flow cytofluorometry thus provides an objective and quantitative way to monitor and define peripheral blood Normoblast populations as a measure of the severity of 'erythropoietic stress'.
Virginia Cruz-vallejo - One of the best experts on this subject based on the ideXlab platform.
-
Genotoxicity kinetics in murine Normoblasts as an approach for the in vivo action of difluorodeoxycytidine
Cancer Chemotherapy and Pharmacology, 2017Co-Authors: Pedro Morales-ramírez, Teresita Vallarino-kelly, Virginia Cruz-vallejoAbstract:Purpose This study analyzed the kinetics of in vivo micronucleus induction in Normoblasts by determining the kinetics of difluorodeoxycytidine (dFdC)-induced micronucleated polychromatic erythrocytes (MN-PCEs) in the peripheral blood of mice. The kinetic indexes of MN-PCE induction of dFdC were correlated with the previously reported mechanisms DNA damage induction by this compound. In general, this study aimed to establish an in vivo approach for discerning the processes underlying micronucleus induction by antineoplastic agents or mutagens in general. Methods The frequencies of PCEs and MN-PCEs in the peripheral blood of mice were determined prior to treatment and after treatment using dFdC at doses of 95, 190, or 380 µmol/kg at 8 h intervals throughout a 72 h post-treatment. Results The area beneath the curve (ABC) for MN-PCE induction as a function of time, which is an index of the total effect, indicated that the dose response was directly proportional and that the effect of dFdC on micronucleus induction was reduced compared with that of aneuploidogens and monofunctional and bifunctional alkylating agents but increased compared with that of promutagens, which is consistent with our previous results. The ABC showed a single peak with a small broadness index, which indicates that dFdC has a single mechanism or concomitant mechanisms for inducing DNA breaks. The time of the relative maximal induction ( T _rmi) indicated that dFdC requires more time to achieve MN-PCE induction compared with aneugens and monofunctional and bifunctional alkylating agents, although it requires a similar time to achieve MN-PCE induction as azacytidine, which is consistent with evidence showing that both agents must be incorporated into DNA for their action to be realized. The timing of maximal cytotoxicity observed with the lowest dFdC dose was correlated with the timing of the main genotoxic effect. However, early and late cytotoxic effects were detected, and these effects were independent of the genotoxic response. Conclusions A correlation analysis indicated that dFdC appears to induce MN-PCEs through only one mechanism or mechanisms that occur concomitantly, which could be explained by the previously reported concurrent inhibitory effects of dFdC on DNA polymerase alpha, polymerase epsilon, and/or topoisomerase. The timing of maximal cytotoxicity was correlated with the timing of maximal genotoxicity; however, an early cytotoxic effect that appeared to occur prior to the incorporation of dFdC into DNA was likely related to a previously reported inhibitory effect of dFdC on thymidylate synthase and/or ribonucleotide reductase.
-
Genotoxicity kinetics in murine Normoblasts as an approach for the in vivo action of difluorodeoxycytidine
Cancer Chemotherapy and Pharmacology, 2017Co-Authors: Pedro Morales-ramírez, Teresita Vallarino-kelly, Virginia Cruz-vallejoAbstract:Purpose This study analyzed the kinetics of in vivo micronucleus induction in Normoblasts by determining the kinetics of difluorodeoxycytidine (dFdC)-induced micronucleated polychromatic erythrocytes (MN-PCEs) in the peripheral blood of mice. The kinetic indexes of MN-PCE induction of dFdC were correlated with the previously reported mechanisms DNA damage induction by this compound. In general, this study aimed to establish an in vivo approach for discerning the processes underlying micronucleus induction by antineoplastic agents or mutagens in general. Methods The frequencies of PCEs and MN-PCEs in the peripheral blood of mice were determined prior to treatment and after treatment using dFdC at doses of 95, 190, or 380 µmol/kg at 8 h intervals throughout a 72 h post-treatment. Results The area beneath the curve (ABC) for MN-PCE induction as a function of time, which is an index of the total effect, indicated that the dose response was directly proportional and that the effect of dFdC on micronucleus induction was reduced compared with that of aneuploidogens and monofunctional and bifunctional alkylating agents but increased compared with that of promutagens, which is consistent with our previous results. The ABC showed a single peak with a small broadness index, which indicates that dFdC has a single mechanism or concomitant mechanisms for inducing DNA breaks. The time of the relative maximal induction ( T _rmi) indicated that dFdC requires more time to achieve MN-PCE induction compared with aneugens and monofunctional and bifunctional alkylating agents, although it requires a similar time to achieve MN-PCE induction as azacytidine, which is consistent with evidence showing that both agents must be incorporated into DNA for their action to be realized. The timing of maximal cytotoxicity observed with the lowest dFdC dose was correlated with the timing of the main genotoxic effect. However, early and late cytotoxic effects were detected, and these effects were independent of the genotoxic response. Conclusions A correlation analysis indicated that dFdC appears to induce MN-PCEs through only one mechanism or mechanisms that occur concomitantly, which could be explained by the previously reported concurrent inhibitory effects of dFdC on DNA polymerase alpha, polymerase epsilon, and/or topoisomerase. The timing of maximal cytotoxicity was correlated with the timing of maximal genotoxicity; however, an early cytotoxic effect that appeared to occur prior to the incorporation of dFdC into DNA was likely related to a previously reported inhibitory effect of dFdC on thymidylate synthase and/or ribonucleotide reductase.
Sunitha N. Wickramasinghe - One of the best experts on this subject based on the ideXlab platform.
-
Natural autoantibodies may play a role in ineffective erythropoiesis during megaloblastic haemopoiesis
Clinical and Experimental Immunology, 2008Co-Authors: E. Wiener, Sunitha N. WickramasingheAbstract:Marrow aspirates from 11 patients with megaloblastic haemopoiesis and from 14 healthy individuals with Normoblastic haemopoiesis were studied for antibodies associated with polychromatic/orthochromatic erythroblasts, using an 125I-labelled anti-human immunoglobulin reagent and autoradiography. In addition, the expression on these cells of receptors for FcIgG (FcR) and of the type I receptor for fragments of the third complement component (CR1) were investigated with receptor-specific monoclonal antibodies, 125I-labelled anti-mouse immunoglobulin and autoradiography. The percentages of immunoglobulin-positive erythroblasts were significantly greater in the megaloblastic than in the Normoblastic marrows. Abnormally high percentages of labelled erythroblasts were present in patients without any manifestations of an autoimmune disorder. The percentage of labelled erythroblasts in the marrows of the patients correlated well with the degree of anaemia. FcR were absent on the majority of megaloblasts or Normoblasts while the expression of CR1 was similar in both types of cell. The difference between the percentage labelling of megaloblasts and Normoblasts was therefore unlikely to be due to greater binding of immune complexes with or without associated complement to megaloblasts than Normoblasts. The megaloblast-bound immunoglobulin is, therefore, likely to have recognized abnormally expressed epitopes on the surface of megaloblasts. The results suggest that natural autoantibodies play a role in the destruction of erythroblasts during megaloblastic haemopoiesis.