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Biomedical subjects

H J Seidel

Publications and source records attributed to H J Seidel.

At least 55 records · Page 3Linked to original sources
PubMed1984

Natural killer (NK) cells and interferon in Friend-virus-infected susceptible and resistant mice.

Natural killer (NK) cells, as determined by the lysis of YAC-1 and Eveline target cells, were determined in F-MuLV-P susceptible DBA/2 and resistant C57/Bl/6 and in beige mice. No difference was found between DBA/2 and C57/Bl/6 mice. Spleens from beige mice showed, as expected, a much lower lysis. The NK cell activity and interferon levels were also studied in these mice after F-MuLV-P infection. Peak NK activities of spleen cells against both target cell types were found at day 3; peak interferon levels were detected in the serum 24 h after infection in all three strains. At day 12, the splenic NK cell activity remained above control levels only in C57/Bl/6 mice. Beige mice were as resistant to Friend leukemia development as C57/Bl/6 mice. The injection of endotoxin, which makes C57/Bl/6 mice virus-susceptible, was followed by increased NK cell activity. The significance of the NK cell system for the resistance of C57/Bl/6 mice against the development of Friend leukemia is discussed.

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PubMed1984

[T-cell lymphomagenesis induced by chemical carcinogens in mice].

Investigations were performed on models of murine leukemogenesis induced by butylnitrosourea or methylnitrosourea in DBA/2, C57B1/6, NMRI, BDF and CBA mice. The latency period in CBA mice was longer than in mice of the other strains. The first transplantable cells appeared mostly in the thymus, and only in two cases in the bone marrow. Methylnitrosourea suppressed the activity of natural killer cells, but not to the same extent as leukemogenic irradiation. Heterogeneity of leukemic T-cell phenotypes with respect to the expression of the ly-1 and ly-2 antigens was detected. At the same time leukemic cells revealed consistent inability to be agglutinated by peanut agglutinine. When hydrocortisone was injected to mice after the carcinogene treatment or within 24 h before it, the leukemogenesis was delayed.

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PubMed1983

Stem cells and immunological parameters in mice during the latency period and after the development of chemically induced leukemia.

T-cell leukemias have been induced in adult BDF1 mice by 12 or 15 weeks of exposure to butylnitrosourea (BNU) in the drinking water. This led to a depression of CFU-S numbers and reduced T- and B-cell responses to mitogens. These parameters were then studied during the BNU-free preleukemic latency period in individual mice. At the same time, leukemic cells were traced in the thymus, the spleen, and the bone marrow by transplantation. In mice without leukemia and mice with leukemic cells in only one organ, there was a general tendency to normal CFU-S numbers and T- and B-cell responses with time after BNU, although control levels were reached in only a few of the mice. The reaction of mixed lymphocyte cultures (MLC) remained low during the latency period. In the thymus an imbalance of the Con A, PHA, and MLC responses was observed. Out of 25 mice with induced leukemia, 8 had leukemic cells in the thymus only and 2 in the marrow only. In mice with leukemic cells in all 3 hemopoietic organs and an enlargement of the spleen, a shift of CFU-S from the marrow to the spleen was observed.

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PubMed1983

Hemopoietic stem cells in the liver of mice with Friend leukemia.

Hemopoietic stem cells were studied in the marrow, spleen and liver of individual, FV-P infected DBA/2 mice. At more than 17 days after infection there was a tendency for CFU-EI numbers in the spleen to be reduced compared to earlier intervals after virus infection; CFU-EI numbers in the marrow were low. At the same time all hemopoietic stem cells (CFU-S, CFU-C, BFU-E and CFU-EI) could be found in the enlarged liver. The migration of stem cells from the marrow to the spleen and further to the liver is discussed.

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PubMed1983

Effects of radiation on murine T-cell leukemogenesis induced by butylnitrosourea.

BDF1 mice were exposed to butylnitrosourea for 12 weeks (BNU, 0.02% in the drinking water) and died of thymic lymphomas with median latency periods of 12-20 weeks. In addition to BNU, groups of mice received weekly radiation doses of 0.0625-1.0 Gy; 12 X 0.25 Gy enhanced leukemogenesis, 12 X 0.75 Gy delayed it and 12 X 0.50 Gy had no effect. Lower doses had marginal enhancing effects. After a dose of 12 X 1.0 Gy, the mice died earlier than after treatment with BNU alone and, as with 12 X 0.75 Gy, some extrathymic lymphomas were observed. The numbers of CFU-S in the femur and the spleen showed a dose-dependent depression, in addition to the effect of BNU alone. In lymphocyte stimulation assays with Con A und LPS and also in the mixed lymphocyte reaction, a reduced proliferation was found, again dependent on the radiation dose. Therefore, there was no correlation of leukemogenesis and the degree of stem-cell reduction or depression of these immune parameters. The delay of leukemogenesis by 12 X 0.75 Gy in addition to BNU may be caused by an enhanced target cell kill.

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PubMed1983

The seeding of a transplanted murine leukemia and its influence on hemopoietic stem cells and immune function of the host.

A butylnitrosourea-induced murine T-cell leukemia, L40, was transplanted in BDF1 mice; 1 X 10(3) cells killed all recipients after conditioning with 400 rad, whereas 1 X 10(5) were needed with normal recipients. No leukemic cells could be detected by transplantation or cytogenetic analysis in the femur or the spleen at day 6 after L40 inoculation and, at day 11, leukemic cells were found in one out of two experiments, more if the host had been irradiated. Up to day 17, when leukemic cells were present, the CFU-S and CFU-C content of the femur was normal, but later a loss was observed with an increase in the enlarging spleen. Lymphocyte-stimulation assays with spleen cells gave normal results up to day 17, but later the 3H-thymidine uptake of stimulated T and B cells was reduced. The NK-cell activity with and without stimulation by Corynebacterium parvum in the spleen began to fall at day 17 and was absent later; this loss was also observed with peritoneal exudate cells. In vitro mixing experiments of L40 cells with normal spleen cells showed "cold target inhibition" by L40 cells in the NK-cell assay as well as interference with the lymphocyte stimulation.

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PubMed1982

Chromosome changes in butylnitrosourea (BNU)-induced mouse leukemia.

G-banding analysis was carried out in 45 mice after exposure to the leukemogen butylnitrosourea (BNU). Of 27 animals without clinical signs of leukemia, 2 had chromosomal rearrangements (7%) while, of 18 leukemic mice, 5 showed abnormal karyotypes (28%). The chromosomal abnormalities were not random and showed preferential changes of chromosomes Nos. 14 and 15. The organ distribution of the chromosomal abnormalities showed a preferential involvement of the thymus with a secondary presence of chromosome anomalies in peripheral lymphoid organs and the bone marrow. The findings are discussed in relation to the recent reports on the specificity of trisomy 15 in murine leukemia and lymphoma.

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PubMed1982

Differences in BFU-E growth in different mouse strains after stimulation with a mixed lymphocyte culture supernatant (MLC-BPA).

The growth of hemopoietic colonies in methylcellulose from bone marrow and spleen of CBA/Ca, DBA/2, BDF1, C57Bl/6, and NMRI mice was studied under stimulation by a mixed lymphocyte culture supernatant (MLC-BPA) which was necessary for the burst-forming unit E (BFU-E) growth in all strains. The number of pure and mixed BFU-E and non-BFU-E and their proportion varied between the strains; the BFU-E concentrations in the marrow were high in CBA/Ca and DBA/2 mice and low in C57B1/6. Furthermore, differences were seen in the requirement for serum and for erythropoietin. Optimal growth conditions were 4% fetal calf serum, 20% MLC-BPA, and 1 U erythropoietin/ml, but BFU-E growth was also obtained in the absence of serum. The differences in the BFU-E concentrations did not correlate with the numbers of colony-forming units S or the proportion of erythroblasts in the bone marrow smears.

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PubMed1982

Hemopoietic activity in bone marrow chimeras prepared with total lymphoid irradiation (TLI).

The hemopoietic status was examined in the blood, bone marrow and spleen of (BALB/c X C57BL/6)F1 hybrid mice treated with fractionated total lymphoid irradiation (TLI), with or without reconstitution with 30 X 10(6) syngeneic or parental C57BL/6 marrow cells. Colony forming units of pluripotent (CFUS) and granuloid committed stem cells (CFUC) were assayed in non-irradiated (femur) and irradiated bone marrow (humerus), and in spleen 9, 18, 73 and 109 days following TLI. Recovery of CFUS and CFUC was nearly complete as early as day 18, and fully recovered on day 73 in endogenously as well as exogenously (syngeneic and semiallogeneic) reconstituted mice. Mice transplanted with C57BL/6 bone marrow exhibited a 10-fold increase of CFUC in the spleen on day 9 and maintained a 4-fold increase of CFUC on day 109, with normal CFUC in shielded, and near normal CFUC in irradiated bones. In contrast, the number of CFUS in the irradiated humerus was below 10% of all controls on days 18-73 and below 30% on day 109. Also, the number of CFUS in the spleen was very much reduced at days 73-109. Unirradiated femora contained normal CFUC and only mildly depressed CFUS. The data suggest that repopulation of bone marrow is adequate although somewhat less efficient in irradiated as compared to shielded bones, whether or not exogenous marrow is transplanted. Semiallogeneic chimeras (C57BL/6 leads to F1) show low CFUS relative to high CFUC levels, particularly in irradiated organs (spleen and humerus). This may suggest an advantage, from a hemapoietic standpoint, to selective irradiation of lymphoid tissues, rather than the less selective wide fields that overlap marrow containing bones.

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PubMed1982

Hematopoietic stem cells in Friend murine leukemia virus infected mice undergoing chemotherapy: failure to eradicate Ep-independent erythropoiesis by BCNU.

DBA/2 mice, 12 days after infection with the polycythemia-inducing Friend virus (F-MulV-P), were treated with a single dose of BCNU. The effect of 35 mg/kg and lower doses on the different stem cell pools (CFUS, CFUC, CFUE) and the F-MulV-P specific ICPC (infectious centers producing cells) and Ep-independent CFUE was studied in detail. The depression of CFUS and CFUC was comparable in normal and F-MuLV-P infected mice. The CFUE population of virus infected mice, which had been completely Ep independent before treatment, showed only some normal Ep dependent colony growth thereafter. This finding was in contrast to the effect of multiple doses of Hydroxyurea, studied previously, which had given the same quantitative depression of CFUS and CFUC. Possible reasons for this failure are discussed; they may be the more proliferation independent mode of action of BCNU and the delayed hemopoietic regeneration.

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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.

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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.

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PubMed1980

Haemopoiesis and immune status during BNU-induced leukaemogenesis in mice.

Female BDF1 mice were exposed to 0.04% BNU in the drinking water for 15 weeks. All animals except one observed for more than 3 weeks died of leukaemia. After 1, 2, 3, 5, 7, 10, and 15 weeks of exposure marrow smears, pluripotent (CFU-S) and ganuloid committed (CFU-C) stem cells from bone marrow and spleen, and the lymphocyte response to different T- and B-cell mitogens and to alloantigens were determined. There was a progressive fall of the CFU-S and CFU-C content of the femur and even more in the spleen, and a progressive decrease in the number of normal marrow lymphocytes. After 10 and 15 weeks new "lymphoid" cells, presumably leukaemic cells, were seen in marrow. The lymphocyte stimulation assays showed a depressed reactivity, rather uniform in the thymus after more than 1 week and also, with a partial recovery after 3 weeks, in the spleen. The implications of these results for the chemically induced leukaemogenesis are discussed.

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PubMed1980

Effects of ribavirin on the development of the Friend leukemia.

Ribavirin (300 and 250 mg/kg i.p., respectively) had a toxic effect on hemopoietic stem cells in normal mice CFU-S, CFU-C, and especially CFU-E were reduced after a single treatment. The drug was further studied in mice infected with the polycythemia-inducing strain of the Friend virus (FV-P). In these mice a specific erythropoietin-independent CFU-E population (CFU-EI) replaces the normal erythropoiesis and can be considered a tumor cell population. With the in vitro technique for CFU-E, CFU-EI can easily be quantified and used as a sensitive marker for the development of the disease. Repeated doses of ribavirin reduced the increase of spleen weight after FV-P infection and the progressive transformation of normal CFU-E into CFU-EI was delayed. The further development of the disease remained unaltered. In vitro CFU-E and CFU-EI were inhibited at the same concentrations when the drug was added to the culture medium. In mice pretreated with multiple doses of hydroxyurea, ribavirin delayed the recurrence of Friend leukemia as seen from the spleen weight increase, but the CFU-E population was predominantly Ep-independent. It is concluded that the effects of the drug were due to its cytotoxicity rather than to a specific antiviral effect.

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