Biomedical subjects

L Kreja

Publications and source records attributed to L Kreja.

At least 37 records · Page 2Linked to original sources

PubMed1987

Trisomy 15 as a regular finding in chemically induced murine T-cell leukemogenesis.

Trisomy 15 is described as a common finding in all T-cell leukemias induced by a single dose of methylnitrosourea (MNU) in BDF1 mice and in the leukemias induced by 7 doses of benzo(a)pyrene. Additional trisomies were found in about half of the leukemias. The organ distribution suggests that the leukemic cells with trisomy 15 originate in the thymus. Trisomy 15 was detected in the thymus as early as 6 weeks after the application of MNU, i.e. during the latency period.

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PubMed1986

Natural killer cells in leukemogenesis.

In order to relate a reduced natural killer (NK) cell function to leukemogenesis, NK cells in the spleen and peritoneal exudate cells, with and without stimulation by Corynebacterium parvum, were tested in mice of various strains after split dose irradiation and after leukemogenic treatment with butyl- and methylnitrosourea. The investigations included also mice submitted to non-leukemogenic irradiation (1 X 1.5 and 1 X 4.5 Gy) and mice submitted to an additional treatment with hydrocortisone, which delays leukemia development after methylnitrosourea. There was, indeed, a NK-cell depression, but no major differences were seen between mice prone to leukemia development and those after cytotoxic, but nonleukemogenic, treatment.

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PubMed1986

T-cell markers in the thymus during methylnitrosourea-induced leukemogenesis.

T-cell leukemias were induced in adult BDF1 mice by a single i.v. injection of 50 mg/kg of methylnitrosourea (MNU). During the latency period and in leukemic mice the expression of peanut agglutinin (PNA) receptors, terminal deoxynucleotidyl transferase (TdT) and thymus leukemia antigen (TLm4) in the thymus was studied. First, TLm4-positive thymocytes were found 6 wk after MNU. Further, there was a continuous reduction of the percentage of PNA-positive thymocytes. The expression of TdT remained unaltered late in the latency period and in leukemic mice. Four phenotype patterns could be defined for the expression of TdT and PNA in thymocytes: PNA+ TdT+, PNA+ TdT-, PNA- TdT+ and PNA- TdT-. Thymuses negative for TdT were rare, the majority was PNA+ TdT+. However, thymuses late after MNU treatment and leukemic thymus were PNA- TdT+. The discrepancy in the expression of PNA and TdT as cellular markers in leukemic mice as compared to normal cell populations is discussed.

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PubMed1986

Effects of a hemoregulatory peptide (HP5b) on erythroid and myelopoietic colony formation in vitro.

A hemoregulatory peptide (HP5b) associated with mature human granulocytes has been investigated for inhibitory effects on murine hemopoietic stem cells in vitro. Both highly purified peptide from natural sources and a synthetic analog peptide have been investigated in parallel. Strong inhibitory effects were found on myelopoietic colony formation in the dose range 10(-13)-10(-5) mol/l. On exceeding this dose, the inhibitory effect disappeared. Moderate to slight inhibitory effects on erythroid colony formation (BFU-E and CFU-E) from adult animals were only seen in 1,000 X the optimal doses for myelopoiesis. No effect was found on CFU-E from fetal liver. The peptide thus has a selective effect on myelopoiesis in a certain dose range. A regulatory mechanism for the peptide on hemopoiesis is proposed.

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PubMed1986

T-cell subsets in the murine thymus during chemically induced leukemogenesis.

T cell leukemias were induced in BDF 1 mice by methylnitrosourea (MNU). The phenotype of the leukemic cells is Thy1.2 +, PNA-, TdT+, TL+ and heterogeneous with respect to Lyt-1 and Lyt-2. About 70% of the leukemias have elevated amounts of gp70. During latency period of at least 9 + 12 weeks an early reduction in the various thymic cells and the CFU-S is observed, with almost complete recovery. Later PNA+ cells are reduced. Hydrocortisone treatment delays or enhances leukemogenesis, dependent on the time interval between hydrocortisone and MNU. Some mice show elevated amounts of gp70 in their bone marrow 2--3 weeks after MNU. The problem of target cells in the bone marrow and the thymus is discussed.

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PubMed1985

RNA virus expression during and after methylnitrosourea-induced T-cell leukemogenesis in mice.

The expression of RNA tumor virus was studied in BDF 1 mice after leukemogenic treatment with a single dose of methylnitrosourea (MNU) and in leukemic thymuses by a cell ELISA using antibodies against the viral glycoprotein gp 70 and by co-culture for the detection of eco- and xenotropic virus. The majority of the thymomas were positive for gp 70; ecotropic, but not xenotropic infectious virus could be detected in some of them. Early after MNU application the thymus and the bone marrow were positive for gp 70 in some animals. Later, after a phase with positive results with spleen cells, the bone marrow and the spleen were negative again. Only the thymus of some mice were positive during the last weeks before the first leukemias appeared.

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PubMed1985

T-cell phenotypes in chemically induced leukemia in mice.

T-cell leukemias were induced in adult BDF mice by a single i.v. injection of 50 mg kg-1 of methylnitrosourea (MNU). Leukemic cells from the thymus and other organ sites showed the theta antigen and were peanut-negative, but were heterogeneous with respect to Lyt-1 and Lyt-2. The acute cytotoxic effect of the MNU showed no preferential toxicity to a special T-cell subset in the thymus. During the latency period of leukemogenesis a continuous fall in peanut-positive cells in the thymus was found.

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PubMed1985

The sensitivity to methylnitrosourea-induced T-cell leukemogenesis in mice is modified by the injection of hydrocortisone.

T-cell leukemias were induced in adult BDF1 mice by a single i.v. injection of methylnitrosourea (MNU). Leukemogenesis was delayed by a single or repeated injections of hydrocortisone (HC) after MNU and also when HC was given one day before MNU. Enhancement of leukemogenesis was seen in experiments with 10 and 14 days' intervals between HC and MNU. The T-cell subset composition of the thymus after HC treatment was studied at these time intervals, but a specific target cell for the action of MNU, reduced one day after HC and increased in number during the thymic regeneration at 10 and 14 days could not be defined. HC did not prohibit the toxic action of MNU as measured by hemopoietic stem cell numbers in the femur.

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PubMed1985

On the role of the spleen in Friend virus (F-MuLV-P) erythroleukemia.

About 30% of Friend virus (F-MuLV-P)-infected C57BL/6 mice became leukemic more than ten weeks after virus infection. This late leukemia development could not be essentially influenced by drug treatment, such as injection of hydroxyurea (2 X 500 mg/kg), actinomycin D (3 X 120 micrograms/kg), phenylhydrazine (3 X 60 mg/kg), or 30 micrograms endotoxin or by bone marrow transplantation following lethal irradiation. Endotoxin (30 micrograms) given prior to virus caused the loss of resistance to F-MuLV-P, but it had only a slight effect if applied one or three months after virus infection. Leukemia development has never been observed in C57BL/6 mice after splenectomy. In DBA/2 mice, highly susceptible to F-MuLV-P, leukemia development was markedly impaired if the mice were splenectomized. These results clearly indicate that the spleen plays a crucial role in the mechanism of susceptibility or resistance to the Friend virus.

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PubMed1985

Leukemogenesis by methylnitrosourea in BDF1 mice. The origin of transplantable cells and the activity of the natural killer cells during the preleukemic period.

BDF1 mice injected with methylnitrosourea (MNU, 50 mg/kg) developed T cell leukemias within 9-35 weeks (median induction time 18 weeks). Leukemic cells, determined by transplantation, were found 2-5 weeks before the death of the animals. Natural killer (NK) cell activity in the spleen and peritoneal exudate cells was studied using YAC-1 cells as targets. MNU-treated mice showed reduced lytic activity with or without stimulation by Corynebacterium parvum. NK activity was essentially the same in mice with and without transplantable leukemic cells. No correlation could be demonstrated between the degree of NK cell depression, as studied in the spleen after splenectomy, and the survival time of individual mice.

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PubMed1984

Leukemia induction by methylnitrosourea (MNU) in selected mouse strains. Effects of MNU on hemopoietic stem cells, the immune system and natural killer cells.

T cell leukemias were induced by a single dose of methylnitrosourea (MNU) in DBA/2, C57/Bl/6, NMRI, BDF1, and CBA mice. The latency period in the CBA strain was much longer than in the others. Studies on the pluripotent stem cells in the bone marrow and T cell reactions of thymus and spleen cells showed a toxicity of MNU for these parameters but no significant differences between the strains. The activity of the natural killer (NK) cells in the spleen and peritoneal exudate cells, studied also after additional stimulation by injection of Corynebacterium parvum, was influenced by MNU, but again no relation to leukemogenesis could be established. The first leukemic (transplantable) cells were found in the thymus. The presence of leukemic cells could be responsible for low NK cell activities found in BDF1 and DBA/2 mice late after MNU.

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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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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

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

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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