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Biomedical subjects

H J Seidel

Publications and source records attributed to H J Seidel.

At least 73 records · Page 4Linked to original sources
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.

Animals↗
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.

Animals↗
PubMed1980

Characterization of early leukemic cells in spleen and bone marrow of Friend virus infected mice.

Nonidentity of leukemic cell populations of DBA/w mice (TCFU and CRVEI) early after Friend Visus infection has been demonstrated for spleen by different growth kinetics of these cell populations during leukemogenesis and for spleen and bone marrow of DBA/w mice by the velocity sedimentation technique. In addition the velocity sedimentation data indicate a heterogeneity of the TCFU population. Stem cell analysis of TCFU and CFUS derived spleen colonies showed that TCFU colonies contain significantly more CFUEI than the surrounding tissue. The erythroid nature of TCFU colonies is confirmed by the almost complete absence of CFUC from these colonies as compared to CFUS derived spleen colonies.

Animals↗
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.

Animals↗
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

Hematopoietic stem cells in Friend murine leukemia virus-infected mice undergoing chemotherapy: remission and relapse of erythropoietin-independent erythropoiesis induced by hydroxyurea.

Hydroxyurea (HU), given ip four times, each time at 500 mg/kg in 6-hour intervals, was used to treat DBA/2 mice with Friend murine leukemia virus-induced polycythemia (F-MuLV-P). In these mice a new cell type, found after virus infection, gave rise to erythropoietic colonies in vitro without addition of erythropoietin (Ep) and completely replaced Ep-dependent normal erythropoietic colonies in vitro. The colony-forming units in the spleen (CFUs), the colony-forming units in culture (CFUc), and the erythropoietic colony-forming units (CFUE) were studied. Two days after treatment, CFUs were reduced to about 20% in controls and F-MuLV-P-infected animals, and CFUc were reduced to 6-11% in controls and F-MuLV-P-infected animals. CFUE were not detectable. At day 4 after the first HU dose, when CFUs has regenerated to about normal levels, a sharp rise in Ep-dependent CFUE was seen in the marrow; this rise was not present before HU treatment. The subsequent fall at day 7 coincided with a regeneration of CFUE in the spleen, but in the spleen these CFUE were all Ep-independent. Possibly, the normal Ep-dependent CFUE during regeneration in the marrow might have derived from previously resting CFUs that were not killed by HU. The subsequent conversion to Ep independency could have been due to reinfection by F-MuLV-P persisting in the animal.

Animals↗
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.

Animals↗
PubMed1979

Erythroid stem cell regeneration in normal and plethoric mice treated with hydroxyurea.

Hydroxyurea (4 x 500 mg/kg at 6 hour intervals) was used to study hemopoietic regeneration in normal and in hypertransfused mice. All recognizable granuloid and erythroid cells, most granulopoietic (CFU-C) and all erythroid (CFU-E) precursors and about 80% of the pluripotent stem cells were eliminated after this treatment. Regeneration started between days 2 and 3 in the marrow and 1 day later in the spleen. An overshoot in CFU-C and CFU-E per femur was seen at day 4. In parallel to their committed precursors granulopoietic cells reappeared between days 2 and 4, erythroblasts between days 3 and 5. In the spleen a maximum CFU-S and CFU-C concentration was seen at day 7. The early increase of CFU-E in the marrow was followed by a fall to low levels, then the CFU-E concentration in the spleen increased. The regeneration was further studied in hypertransfused mice. CFU-S and also CFU-E in the marrow regenerated in exactly the same way as in normal mice and erythroblasts were found in marrow smears. The further maturation of erythroblasts to reticulocytes was impaired in hypertransfused mice, but not in normal mice. The role of erythropoietin (Ep) in the regulation of the CFU-E regeneration is discussed; early differentiation steps seem to be possible without Ep.

Animals↗
PubMed1978

Studies on the target cell for the Friend virus (FV-P strain) using the CFU-E technique.

In order to characterize the target cell for the polycythemia inducing Friend virus (FV-P) in vivo, mice were treated by induction of plethorism, bleeding, Actinomycin D, and Busulfan before virus infection. The development of the Friend leukemia was then studied mainly using the CFUE technique for erythroid colony growth in vitro. This technique allows the quantification of a new cell type, an erythropoietin (Ep) independent colony forming cell. These Ep independent colonies were taken as marker for the disease. Their number with time after infection was correlated with the compartment size of pluripotent, granuloid committed and erythroid stem cells at the time of infection. The results indicate that the development of the Friend leukemia does not require the actual presence of CFUE, as seen using Actinomycin D, and is not correlated with the number of pluripotent or granuloid stem cells, as seen after Busulfan. It is, however, dependent on the erythropoietic state of the animal, as seen in plethoric mice and mice after bleeding. It is, therefore, concluded that the target cell for FV-P is located within the Ep-responsive cell compartment, between early (BFUE) and late (CFUE) erythroid precursor cells.

Animals↗
PubMed1978

Erythroid stem cells in Friend-virus infected mice.

The erythropoietic stem cell compartment was studied in Friend-virus (polycythemic strain, FV-P) infected DBA/2 and NMRI mice with the CFUE and BFUE technique. Early after infection there was a depression in CFUE number in bone marrow and spleen, followed by an increase of the CFUE concentration, earlier and more pronounced in the spleen than in the marrow. Three days after FV-P infection an erythropoietin (Ep) independent CFUE population started to grow and replaced the normal Ep-dependent population within 8 to 12 days. The shift to Ep independency was not gradual. CFUE colonies of FV-P infected bone marrow cells were two to three times larger than control colonies after three days in vitro incubation. BFUE colonies increased in number during the first days of infection, but were totally lost after more than ten days. After velocity sedimentation of bone marrow cells of FV-P infected animals, however, the BFUE containing fractions showed normal BFUE colony growth and normal Ep sensitivity. In unfractionated bone marrow cell cultures BFUE colony growth could be observed later than ten days post infection when the cultures were refed with medium. It was therefore concluded that the loss of BFUE colony growth after FV-P infection was an in vitro artefact due to inadequate culture conditions.

Animals↗
PubMed1977

Erythroid stem cells in Rauscher virusinfected mice.

Using the technique for erythroid colony formation in vitro, bone marrow and spleen cells from NMRI mice were studied after Rauscher virus (RLV) infection. There was a substantial decrease in CFUE concentrations during the first days after infection, this being more pronounced in the marrow than in the spleen. In the marrow values gradually return to and are maintained at control levels, while in the spleen a 40-50-fold increase is seen between days 8 and 18. In normal and RLV infected animals the same dose dependence of CFUE growth for erythropoietin was seen. For normal and RLV infected cells in the absence of erythropoietin there were only very few background colonies. In exhypoxic plethoric mice the increase in CFUE concentration seen in normal mice in the spleen, is delayed by 2-3 days.

Animals↗
PubMed1977

The effect of dimethylbenz(a) anthracene on murine hematopoiesis.

DMBA was given p.o. to young adult female CBA/J mice in two regimens, a single dose of 1 mg and 4 doses of 1 mg in weekly intervals. In the peripheral blood only a transient reticulocytopenia and thrombocytopenia was observed in both groups. After 4 doses the thymus and spleen weights were reduced up to 4 weeks after the last dose. In the bone marrow the cellularity was lower in treated animals than in controls. After 1 mg DMBA pluripotent stem cells (CFUc) in the marrow were reduced to about 50--70% over a 2- to 3-week period, in the spleen the CFUs concentration was reduced to 10% at day 3 with about normal levels after 3 to 4 weeks. The compartment of granulocytic committed stem cells (CFUs) in both organs followed the same pattern with an overshoot in CFUc concentration in the spleen after 3 to 4 weeks. After 4 doses CFUs and CFUc were more depressed, regeneration began about 2 weeks after the last dose in both organs. CFUc in the marrow had normal and in the spleen supra-normal concentrations 3 and 4 weeks after the last dose.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1977

Growth of bone marrow cells of normal and Rauscher virus infected mice in suspension cultures stimulated by CSA.

Bone marrow cells of normal and Rauscher virus (RLV) infected CBA/J mice were cultured under stimulation by postendotoxin serum. Cellular morphology and the number of granulocytic committed stem cells from day 1-5 after the onset of the cultures were studied with different amounts of postendotoxin serum added. There was a good correlation between total cellularity, the number of immature granulocytopoietic cells and the number of colony forming unit cells (CFUc) in suspension with the amount of postendotoxin serum. Postendotoxin serum delayed the appearance of macrophages in the cultures for 1-2 days. Cells from RLV infected animals showed a rather normal differentiation of the morphological recognisable cells 5 and 21 days after infection, but the CFUc survival in vitro 3 and 5 weeks after infection was reduced.

Animals↗
PubMed1977

Hematologic effects of a single dose of methylnitrosourea.

The hematological effects of a single dose of 50 mg/kg Methylnitrosourea (MNU),administered i.v. to CBA/J mice, are described. Special emphasis was given to the number of pluripotent (CFUS) and granulocytic committed (CFUc) stem cells found in the bone marrow and spleen. In the peripheral blood a decreased number of reticulocytes, granulocytes, lymphocytes and thrombocytes was seen. This was followed by a rapid return of reticulocytes and a very slow return of thrombocytes. The bone marrow cellularity was below normal for at least 2 weeks with a markedly reduced number of lymphocytes. A rapid decrease in bone marrow and splenic CFUS and CFUc to 20-50% of control values was observed within 3 hours in mice injected with MNU. Seven days after MNU treatment, CFUS was about 10% of normal in both tissues. Contrary to this, CFUc had undergone significant regeneration. After 3 weeks CFUS returned to normal levels. At no stage could colony stimulating activity be detected in the serum.

Animals↗
PubMed1976

Studies on the erythropoietic cell system in CBA mice after Rauscher virus infection.

Erythropoiesis in CBA mice was studied in Rauscher leukemia virus infected mice using the incorporation of 59Fe into spleen, bone marrow and peripheral blood. Beginning at day 4 an increased uptake into the spleen and a decrease in the bone marrow and the peripheral blood was observed. The increased uptake by the spleen was also found in plethoric mice. The erythropoietin responsive compartment was also enlarged in the spleen of these mice. The The dose-response-curve for erythropoietin was altered 4 days after infection, there was a higher background level of 59Fe incorporation and the response to low doses was better in infected animals. The reticulocytopenia which is usually seen in these mice, was overcome by administration of high doses of erythropoietin. It is concluded that the Rauscher virus acts in a similar manner to erythropoietin, but the erythropoiesis induced is ineffective since the cells do not mature. This maturation deficiency is influenced by administration of exogenous erythropoietin.

Animals↗