Biomedical subjects

L Kreja

Publications and source records attributed to L Kreja.

46 records · Page 3Linked to original sources

PubMed1982

In vivo studies on hemopoietic stem cells and target cells for Friend virus infection in vitro.

Friend virus replicating target cells have been characterized by in vitro infection of bone marrow cells from DBA/2 mice after multiple injections of hydroxyurea (HU), after bleeding and/or hypertransfusion and after busulfan treatment. The concentration of CFUS, BFUE and CFUE in the cell suspension was correlated with the number of infectious centers (IC) induced after infection. HU treated mice were also infected in vivo. The results demonstrate that there is almost no target cell 4 h after the last of 4 HU injections. The number of IC induced could correlate with the numbers of CFUS in the HU experiment, but this possibility can be rejected based on the busulfan experiments. All results, including those after bleeding and/or hypertransfusion are compatible with a target cell between BFUE and CFUE, as suggested by other in vitro infection methods and also in vivo experiments.

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PubMed1982

Hematopoietic stem cells in Friend murine leukemia virus-infected mice undergoing chemotherapy: effects of 5-FU.

Uninfected DBA/2 mice and those infected 12 days previously with the polycythemia-inducing Friend murine leukemia virus were treated with 5-FU in doses of 18.75--200 mg/kg ip, and the effects on spleen weight, reticulocytosis, and hematopoietic stem cell compartments CFU-S, CFU-C, and CFU-E was studied. The CFU-E population of virus-infected mice, which had been completely independent of erythropoietin (Ep) in vitro before treatment, showed a considerable proportion of normal Ep-requiring CFU-E at Days 2--6 after doses less than or equal to 50 mg/kg, indicating a chemotherapy-induced remission. Later, Ep-independent growth was seen again, most probably due to a reinfection by the virus at the target cell level. The regeneration of all stem cell types was quicker in uninfected mice than in those infected with virus. These data are discussed in relation to results obtained with hydroxyurea treatment, where Ep-dependent CFU-E were also seen, and with respect to the effects of busulfan, carmustine, and dactinomycin, with their different modes of actin. The importance of effective antiviral therapy for the cure of such a virus-induced malignancy is emphasized.

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PubMed1982

Role of BPA and erythropoietin for BFU-E growth from Friend virus-infected mice.

The dependency of BFU-E growth in vitro on burst-promoting activity (BPA) was studied in F-MuLV-P-infected DBA/2 mice. As standard source of BPA, the supernatant of a mixed lymphocyte culture (MLC-BPA) was used in varying concentrations in the cultures of bone marrow and spleen cells. The serum content in the BFU-E cultures was reduced to 4% of fetal calf serum. This reduction had to be compensated in normal and F-MuL V-P-infected cell cultures by the addition of higher BPA concentrations. The results show that the F-MuL V-P infection did not abolish the dependency of BFU-E growth on BPA. Furthermore, in cultures with 4% of fetal calf serum and 20-30% of MLC-BPA about 50% of the BFU-E of normal mice grew without addition of erythropoietin. In virus-infected mice this number increased to about 100% in bone marrow and spleen. In F-MuL V-P resistant C57Bl/6 mice the percentage of BFU-E grown without addition of erythropoietin did not change after virus infection.

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PubMed1981

Normal and Friend virus specific cell compartments in Friend leukemia characterized by their sensitivity to actinomycin D in vivo.

DBA/2 mice were infected with the polycythemia inducing Friend Virus (F-MuLV-P) and treated with different doses of Actinomycin D (Act D) when the whole erythroid cell system, as measured by the CFU-E technique with and without addition of erythropoietin (Ep), had been transformed into Ep-independence. During and after this therapy the different stem cell pools CFU-S, CFU-C, BFU-E and CFU-E (with and without Ep) were studied and their sensitivity to Act D in bone marrow and spleen was compared to that of normal mice, recently published by other authors. There seemed to be no difference in the Act D sensitivity between normal erythropoiesis and Ep-independent erythropoiesis caused by F-MuLV-P. Furthermore a cell called ICPC (infectious centers producing cell) was studied. This cell system, detected by spleen colony formation due to high local virus production in an unirradiated host, proved to be Act D sensitive in the spleen but not in the marrow. When the erythroid cell system regenerated after Act D chemotherapy, all erythroid colony growth was Ep-independent. This means that Act D did not induce normal erythropoiesis as seen with hydroxyurea treatment.

Animals↗

PubMed1981

Studies on the resistance of the C57B1/6 mouse strain to the polycythemia-inducing strain of the Friend virus (FV-P).

In previous studies it had been found that C57B1/6 marrow cells, normally resistant to infection by the Friend virus (FV-P), became susceptible after their transplantation into lethally irradiated leukemic DBA/2 mice. This loss of FV-P resistance was further analyzed and spleen weight and the number of erythropoietin-(Ep)-independent CFU-E in bone marrow and spleen were measured as the result of successful FV-P infection. C57B1/6 marrow was infected shortly before and in intervals after either isogeneic transplantation or transplantation into lethally irradiated DBA/2 hosts. After isogeneic transplantation there was some susceptibility for FV-P and this seemed to correlate with the regenerative activity of BFU-E at the time of infection. However, there was no difference in the BFU-E kinetics between normal DBA/2 and C57B1/6 mice. C57B1/6 were further pretreated by bleeding, irradiation with 150 R, injection of hydroxyurea and of endotoxin. After hydroxyurea treatment there was an increased proportion of BFU-E in S-phase, but only endotoxin, which did not alter the BFU-E kinetics after 48 h, made C47B1/6 mice susceptible to FV-P infection. These results suggest that the proliferative activity of BFU-E might be important for successful FV-P infection and induction of Ep-independent erythropoiesis but also other conditions regulate the resistance or susceptibility of a mouse strain.

Animals↗

PubMed1980

Effects of tilorone on hemopoietic stem cells and on the development of Friend leukemia.

Hematological effects of tilorone, an interferon inducer, on the hematopoietic cell system of normal CBA/Ca mice and on the development of Friend virus (FV-P)-induced polycythemia in DBA/2 mice were studied. In normal mice 80 mg/kg IP had a marked depressive effect on pluripotent (CFU-s), granuloid committed (CFU-C), and erythroid committed (CFU-E) stem cells with regeneration between days 5 and 12. In bone marrow smears only lymphopenia was detected. Treatment of mice before FV-P infection caused a slight retardation in the development of the splenomegaly and the transformation of bone marrow cells to Ep independence. Repeated treatment after FV-P infection also reduced the increase in spleen weight and the development of reticulocytosis, but the Ep independence of bone marrow and spleen cells was not influenced. In vitro exposure of normal cells and cells from FV-P-infected animals to the drug showed the same sensitivity of colony growth in normal as well as in Ep-independent CFU-E. The action of the drug on Friend leukemia is at least in part considered a toxic effect on the hematopoietic stem cell system.

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PubMed1980

Donor cell leukemia after bone marrow transplantation in the Friend leukemia in mice.

After lethal irradiation (800 R) Friend virus (FV-P)-infected leukemic DBA/2 mice were transplanted with normal bone marrow cells. Isogeneic transplantation led to an immediate relapse of leukemia. Therefore, allogeneic bone marrow cells were taken from almost FV-P resistant C57BL/6 mice. A measure of leukemia development was given by the number of erythropoietin-independent erythroid colonies (CFU-EI) in bone marrow and spleen, characteristic for the Friend leukemia. Even after allogeneic transplantation leukemia recurred after 5 to 19 days. By an electrophoretic analysis of the hemoglobin, it could be shown that the transformed erythropoiesis was donor derived. Thus, marrow of C57BL/6 origin loses its FV-P resistance in allogeneic leukemic lethally irradiated recipients and is transformed by the surviving virus.

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PubMed1980

Erythroid stem cell regeneration in normal and plethoric mice treated by cytosinarabinoside.

Cytosinarabinoside (6 x 40 mg/kg in 4 h intervals) was used to study hemopoietic regeneration in normal and in hypertransfused mice. About 70-80% of pluripotent stem cells (CFUs), more than 80% of granuloid committed precursors (CFUc) and more than 95% of erythroid committed precursors (CFUE) were eliminated after treatment, and also more than 99% of the erythroblasts in the bone marrow smears. There was no regular difference between normal and hypertransfused groups. Regeneration started at day 2, with control levels of CFUs at day 3 and then overshooting, control levels of CFUc at days 4-5 and a single increase of CFUE at day 3. This rise in CFUE, with values well above control levels, was also present in hypertransfused mice, although less pronounced. In hypertransfused mice the CFUE peak was not allowed by an increase in erythroblast numbers in the femora or 6 h 59Fe uptake into femora or spleen-in contrast to non-plethoric controls. The results indicate the partial Ep independence of regenerating CFUE, as found after treatment with hydroxyurea.

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PubMed1979

Comparison of the biological effects of anemia inducing and polycythemia inducing Friend virus complex.

The comparison of the biological effects of FVP and FVA showed that leukemogenesis appears to be delayed in FVA infected mice as compared to FVP infected animals after injection of comparable quantities of virus as measured in spleen focus forming units. In addition, no CFU-EI, characteristic for FVP induced leukemia, were found in leukemic spleen or bone marrow of FVA infected mice. Since it was possible to distinguish both viruses by their different host ranges, which are helper virus determined, it is suggested that the observed differences, especially the lack of CFU-EI in FVA infected mice, might be due to differences in the helper virus component of the FV complex.

Anemia↗

PubMed1979

Characterization of a Friend virus-replicating target cell.

The FV-replicating target cell characterized in this study is an erythroid precursor cell, as shown by its response to bleeding and hypertransfusion. The target cell is not identical with the BFU-E compartment as demonstrated by different model velocities and different cell cycle characteristics as compared to BFU-E. Different sensitivity of FV-target cells and CFU-E to AMD, differences in the growth kinetics of both cell populations in bone marrow and spleen of mice after bleeding, and large quantitative differences of both cell populations in hemopoietic organs, suggest only partial identity or non-identity of these two cell types. Finally it is shown that spleen colonies originating from FV-infected target cells are a primary erythroleukemic lesion, since they contain more Ep-independent CFU-E than do intercolony areas of the spleen.

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