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E Frindel

Publications and source records attributed to E Frindel.

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

Regulation of splenic CFU-S kinetics after cytosine arabinoside treatment in mice II. In vitro studies: long-range modulators of the splenic CFU-S.

A single injection of 20 mg of Ara-C to mice provokes an acceleration of splenic CFU-S differentiation, followed by their entry in DNA synthesis. In this protocol, splenic CFU-S are induced to differentiate preferentially towards erythropoiesis. The present studies show that substances secreted by spleen cells from Ara-C treated mice are responsible for the modifications in the splenic CFU-S population. This indicates that splenic CFU-S kinetics is under the control of pluripoietins as previously demonstrated for marrow CFU-S. The serum of Ara-C treated mice is shown to have stimulating effects on splenic CFU-S as well as on medullary CFU-S proliferation. It also has the capacity of channelling the differentiation of both splenic and medullar CFU-S towards erythroid lineage. These data suggest the existence of long-range humoral regulators for both populations of CFU-S.

Animals↗
PubMed1984

Effects of various treatments of CFU-S seeding efficiency in mice.

Stem cell seeding efficiency and the proportion of CFU-S in the S phase after cytosine arabinoside (Ara C) treatments were assessed. We found no difference in the "f" factor between quiescent and cycling CFU-S. A survey of the literature indicates conflicting data regarding the possible correlation between the kinetic status of CFU-S and the "f" factor, but there is no question that the "f" factor can vary with treatment of either the donor or the recipient. It seems, therefore, important to determine the "f" factor for each new treatment protocol regardless of the cycling state of the stem cells if one is interested in knowing the absolute number of CFU-S in the marrow.

Animals↗
PubMed1984

Characterization of possible receptor of colony-promoting activity (CPA) by comparison with that of colony-stimulating factor (CSF).

Supernatants of long-term mouse bone marrow cell cultures contain colony-promoting activity (CPA). CPA itself does not stimulate colony formation of granulocyte-macrophage progenitor cells (GM-CFC) when added to a semisolid agar culture of bone marrow cells, but augments colony formation in the presence of colony-stimulating factor (CSF). The CPA-responsive cells are postulated to be pre-GM-CFC, a cell compartment younger than GM-CFC. In absorption experiments, CSF-coated bone marrow cells failed to absorb CPA, whereas normal bone marrow cells absorbed the activity. Cholera toxin (CT) is known to inhibit GM-CFC colony formation of bone marrow cells, probably by binding to GM-CFC-receptors [8, 9]. In the present studies, preincubation of the cells with CPA, before exposure to CT, reduced the suppressive effect of CT on GM-CFC colony formation. CT also inhibited pre-GM-CFC colony formation. Such suppressive effects, however, were reduced by preincubation of the cells not only with CPA but also with CSF. These results suggest that CSF and CPA might share the same receptors. It may also suggest that CT does not bind to specific sites. A difference in the susceptibility of GM-CFC and pre-GM-CFC to suppression by CT was also observed. Incubation of the cells with a low concentration of CT resulted in the substantial decrease of the number of GM-CFC, whereas the number of pre-GM-CFC remained high. Therefore, it seems that CPA shares some but not all of the CSF receptors.

Absorption↗
PubMed1983

Statistical analysis of splenic colony histology: an attempt to confirm that external factors could affect the channelling of CFUS differentiation.

The aim of this work was to analyze quantitatively experimental data, which suggest that CFUS determination can be manipulated by external fibers. This hypothesis was based on the comparison of the ratio of erythroid to granulocytic spleen colonies generated by normal bone marrow exposed to factors released by either untreated or arabinoside cytosine treated mouse bone marrow. To investigate mechanisms able to produce this modification of spleen colony histology, statistical analysis was performed by testing three different schemes of evolution of the number of splenic colonies according to this histology from normal to treated groups. The total number of colonies per spleen is similar in both groups, but a significant increase of the number of erythroid colonies per spleen and a significant decrease of the number of granulocytic colonies are observed in the treated group as compared to control. Bias due to the used experimental technique are investigated but could not explain the observed differences. A unique mechanism acting on only one committed stem cell population does not fit the experimental data. Although other possible mechanisms are suggested, the experimental observations can be interpreted as the consequence of a shift of CFUS differentiation toward the erythroid pathway at the expense of at least the granulocytic lineage due to some humoral factors, secreted by treated mouse bone marrow.

Animals↗
PubMed1983

Further purification of a CFU-S inhibitor: in vivo effects after cytosine arabinoside treatment.

This paper describes a large scale extraction procedure which allows the preparation of a stable CFU-S inhibitor from fetal calf bone marrow. The use of BioGel P-2 gels results in an increase of the specific activity of the inhibitor as well as in the yield of the preparation. When injected into mice, the inhibitory fraction (Ve/Vo 1.17-1.8) prevent CFU-S entry into cycle after cytosine arabinoside at a dose of 4 micrograms per mouse. When administered during lethal protocols of Ara-C treatment, it significantly increases the percentage of surviving animals. Thus, this low molecular weight factor (below 2,000 D), devoid of species-specificity, enhances the tolerance of animals to high doses of chemotherapy and might be of interest in cancer treatment.

Animals↗
PubMed1982

Some effects of chemotherapeutic drugs. III. Short- and long-term effects of cis-platinum on various hematopoietic compartments and on the kidney of the mouse.

cis-Platinum is a relatively new active anticancer drug. In the study described in this paper, its toxicity was tested in the hematopoietic and renal systems of mice after six injections of 3 mg per kg body weight at 10-day intervals. Acute hematopoietic toxicity was studied by determining the survival of pluripotent (CFU-S) and granulo-macrophagic unipotent (GM-CFC) stem cells. The number of nucleated cells in the bone marrow and in the spleen and the number of granulocytes in the blood were determined. Renal toxicity was studied by histological examination of kidneys from treated mice compared with control animals. The number of stem cells in the bone marrow and in the spleen decreased during the treatment. One year after treatment, the autorepopulating ability of CFU-S was still diminished in spite of normal numbers of these cells. No renal damage could be demonstrated by light microscopy when the protocol described was used.

Animals↗
PubMed1982

Modifications of pluripotent stem cell differentiation after ARA-C treatment: clonal analyses of CFU-S progeny.

The nature of the mechanisms controlling CFU-S differentiation is a crucial problem in haematology and, thus far, little is known concerning these phenomena. Work done in our laboratory has shown that the distribution of the histologic cell types represented in spleen colonies (CFU-S) differ depending on whether normal bone marrow or marrow from Ara-C treated mice is injected into the irradiated recipients. As measured by the mean of the absolute number of colonies per spleen, bone marrow from Ara-C treated mice gives more erythroid colonies and fewer granulocytic colonies than do cells from normal bone marrow. We have demonstrated that these modifications are under the control of humoral factors. Two significant questions arise from these observations. First, are the colonies after Ara-C treatment derived from a single multi-potential cell rather than from already committed progenitors and, second, is this shift in granulocytic-erythroid representation a reflection of modifications at the CFU-S level introduced by our Ara-C system? To answer these questions, we analysed the progeny of each individual spleen nodule either by reinjecting each colony unit into a secondary recipient or by cloning these cells in methyl cellulose with appropriate stimulating factors. We thus determined the number of retransplantable stem cells, as well as the number of committed precursors present in each spleen nodule. Our results demonstrate that most spleen colonies are transplantable and give rise to secondary colonies. These secondary colonies are of all haematological types, therefore proving that the nodules contain CFU-S and that these CFU-S are pluripotent. All spleen colonies contain GM-CFC, even in the nodules that were histologically erythroid. We thus conclude that modifications in the E/G ratio of spleen colonies after injection of bone marrow from Ara-C treated mice are a reflection of changes in CFU-S differentiation pathways.

Animals↗
PubMed1982

Involvement of T-lymphocytes in the stimulatory effects of EMT6 tumors on medullary pluripotent stem cells of BALB/c mice.

Untreated EMT6 tumors and bone marrow of tumor-bearing BALB/c mice secrete factors capable of stimulating quiescent medullary splenic colony-forming units into cycle. Since the tumor population is heterogeneous, it is of interest to determine the nature of the cells which are involved in this phenomenon. Experiments with conditioned media from tumors of BALB/c and athymic mice show that EMT6 cells themselves may secrete a stimulating factor but that the presence of T-lymphocytes is necessary at some time in the development of the tumor. Likewise, the presence of the tumor is necessary for bone marrow to secrete these factors in our experimental model. This suggests reciprocal influences of the T-cells and the EMT6 tumor cells in the phenomena that we describe.

Animals↗
PubMed1982

Protection of mice against lethal doses of 1 beta-D-arabinofuranosylcytosine by pluripotent stem cell inhibitors.

The aim of this work was to study whether an inhibitor of pluripotent stem cell (CFU-S) recruitment, which we have shown previously to be able to increase the number of CFU-S after a fractionated treatment with 1-beta-D-arabinofuranosylcytosine, could increase the survival of mice given injections of lethal doses of the same drug. Two protocols of 1-beta-D-arabinofuranosylcytosine treatment were used in two different mouse strains, which both killed the mice within a week. An inhibitor of CFU-S was prepared by dialysis from fetal calf marrow, and a first step of purification was made by chromatography on Sephadex G-10. When given injections 2 hr before the drug, the number of surviving mice was increased significantly with the dialysate; fractions separated by chromatography appeared to be more effective to increase the animal survival. These preliminary results indicate that a factor of low molecular weight (below M.W. 3500) extracted from fetal calf marrow is able to protect animals during 1-beta-D-arabinofuranosylcytosine treatment. The inhibitor seems to be specific for CFU-S, without any inhibiting effect on tumor cell kinetics in vitro. If the absence of species specificity found for higher to lower species is confirmed for the lower to the higher species, then this inhibitor could be an effective tool during cancer chemotherapy.

Animals↗
PubMed1982

Effects of conditioned medium from bone marrow of normal and Ara-C-treated mice on hemoglobin synthesis.

Differentiation of CFUs toward erythropoiesis has been demonstrated in mice treated with a single dose of Ara-C, and this preferential differentiation was shown to be under the influence of diffusible factors. The aim of the work reported here was to determine whether these factors might include erythropoietin (Ep). This possibility was explored by testing the effect of the Ara-C-induced factor(s) on hemoglobin synthesis, and the effects of anti-mouse Ep on the activity of Ara-C-induced factors. When the late erythropoiesis stage of fetal liver cells was stimulated by bone-marrow-conditioned medium, no significant difference was observed between the effects of conditioned media obtained from normal versus Ara-C-treated bone marrow cells. Bone-marrow-conditioned medium induced a dose-dependent effect on hemoglobin synthesis by fetal liver cells (or adult bone marrow cells); the resulting curve was not parallel to the log-dose-response curve of purified mouse Ep. Anti-mouse Ep inhibited the activity of mouse Ep in fetal erythroblast cultures, but did not affect the stimulatory activity of conditioned media. Below the plateau doses no cumulative erythropoietic effect was observed in fetal erythroblast cultures when conditioned medium was added to Ep. Thus the present data suggest that the effect of bone-marrow-conditioned medium results from at least two independent factors: the first one active on CFUs differentiation towards erythropoiesis, and the second one active at a later stage of erythroid maturation. These factors can be considered to be molecules with an immunogenic structure unrelated to that of Ep.

Animals↗
PubMed1981

[Inhibitors of bone marrow stem cells proliferation. Possible applications during chemotherapy (author's transl)].

An inhibitor of bone marrow stem cell (CFU-S) proliferation, prepared from fetal calf marrow, was administered to mice during sequential treatments with Cytosine Arabinoside. Results show that the percentage of CFU-S survival is significantly increased when the inhibitor is given simultaneously with the drug. A purified fraction of the inhibitor obtained by chromatography permitted survival of mice receiving lethal doses of Cytosine Arabinoside. The inhibit seems to be specific for CFU-S and has no effect on EMT6 tumor cells in vitro. Since it is not specific for the animal species, its clinical use could be envisaged to protect bone marrow during chemotherapy.

Animals↗