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Biomedical subjects

R Michalevicz

Publications and source records attributed to R Michalevicz.

At least 37 records · Page 2Linked to original sources
PubMed1987

Interferons regulate the in vitro differentiation of multilineage lympho-myeloid stem cells in hairy cell leukemia.

In vitro 14-day cultures of peripheral blood mononuclear cells from hairy cell leukemia patients consistently showed the presence of hematopoietic stem cells giving rise to multilineage colonies containing a high proportion of lymphoid cells associated with the myeloid and erythroid progenitors. These stem cells are not the hairy cells but appear to be pluripotent lymphomyeloid primitive stem cells persisting in this leukemia. Interferon alpha c or beta 1 did not inhibit the growth of these colonies, as they did the growth of colonies of normal hematopoietic progenitors, but markedly decreased the ratio of lymphoid to myelomonocytic cells, by increasing the formation of monocytes and other nonlymphoid cell types in these multilineage colonies. Interferon gamma did not have the same effects on differentiation.

Aged↗
PubMed1987

Fenbufen induced pure red cell aplasia in rheumatoid arthritis.

Pure red cell aplasia occurred after fenbufen administration in a patient with severe rheumatoid arthritis. In vitro studies were performed to determine the pathogenesis of the selective red cell aplasia. No cellular or humoral inhibitory mechanisms were demonstrated on growth of erythroid and multipotent bone marrow progenitors. Also, no direct effect of fenbufen alone or in combination with IgG and/or patient serum was found. It is possible that a metabolite of the drug formed from its metabolism was responsible for the aplasia and that the target marrow cell precursor affected is later than both erythroid bone marrow progenitors (BFU-E and CFU-E) and therefore not apparent in our studies. Recovery upon cessation of fenbufen suggests its implication in the pure red cell aplasia.

Aged↗
PubMed1986

Platelet-derived growth factor stimulates growth of highly enriched multipotent haemopoietic progenitors.

Platelet-derived growth factor (PDGF) has been shown to stimulate growth of normal and malignant fibroblasts, glial cells and smooth muscle cells. A growth promoting effect on human haemopoietic precursors has also been described, but the interpretation of this haemopoietic proliferative response to PDGF has been hampered by the lack of purity of the target population. In this study we show that PDGF promotes growth of early bone marrow haemopoietic progenitors depleted of either monocytes or T lymphocytes which are known to influence haemopoiesis. Moreover, the action of PDGF is even increased on a highly enriched BI-3C5 early bone marrow population. BI-3C5 is a novel monoclonal antibody which recognizes an antigen present on all multilineage colony-forming cells (CFU-mix) (Tindle et al. 1985). BI-3C5 positively and negatively sorted fractions were obtained by fluorescence activated cell sorting (FACS) and PDGF was found to stimulate growth of CFU-mix in the BI-3C5-positive fraction (consisting of only 4-6% of the marrow population), the effect being more marked than that on unsorted bone marrow. The results suggest that the product of the cellular proto-oncogene c-sis (the putative structural gene for the beta chain of PDGF) may play a regulatory role in the in vivo proliferation of multipotent haemopoietic progenitors.

Adult↗
PubMed1986

Quantitation by flow cytometry of anthracycline drug uptake by peripheral blood and bone marrow cells in human leukemias.

The inherent fluorescence of the anthracycline drugs can be combined with flow cytometry to obtain a convenient and rapid method for the quantitation of anthracycline drug uptake by human leukemic cells. A good correlation exists between the average cellular fluorescence intensity and the amount of drug associated with the cell as measured by extraction. Cellular incorporation of adriamycin and daunomycin was determined in peripheral blood and bone marrow cells of human leukemic patients after standardized in vitro exposures. Differences in uptake were found between the different cell types, with cells of lymphatic origin incorporating less of the drugs than nonlymphatic cells. Preliminary observations made in two patients with nonlymphatic leukemia showed a correlation between the in vitro uptake of adriamycin and the clinical response.

Aged↗
PubMed1985

Interleukin-2 induces rapid phosphorylation of an 85 kilodalton protein in permeabilized lymphocytes.

Lymphocytes were induced to express receptors for interleukin-2 by stimulation for 5 days with phytohaemagglutinin and subsequently permeabilized by treatment with L-alpha-lysophosphatidylcholine. Phosphorylation of an 85 kDa protein was stimulated when these cells were treated with interleukin-2 or with an antibody directed against the interleukin-2 receptor.

Cell Membrane Permeability↗
PubMed1985

The effect of the leukemic cell line HL60 and acute myeloblastic leukemic cells before and after induction of differentiation on normal pluripotent hematopoietic progenitors (CFU-GEMM).

A leukemic cell line (HL60) and acute myeloblastic leukemia (AML) cells from six patients were co-cultured with normal marrow cells to assess their effects on growth of normal CFU-GEMM. The effects of the following inducers: 12-0-tetradecanoyl-phorbol-13-acetate (TPA), retinoic acid (RA), dimethylsulphoxide (DMSO), 1-25 (OH) D3 (Vitamin D3) and PHA-LCM on both the HL60 and AML cells, were studied. Inhibition of growth of normal CFU-GEMM was observed in the co-cultures in the presence of 1 X 10(4) HL60 or AML leukemic cells/ml. This inhibition was reversed by pretreating the HL60 line with vitamin D3, TPA and RA. No effect on growth of CFU-GEMM was noted when DMSO and PHA-LCM were used. AML cells were morphologically induced to differentiate by TPA or RA in all six cases. In three cases, reversal of inhibition of growth of normal pluripotent hemopoietic progenitors occurred and in three the inhibition of growth persisted. Regulation of inhibition by different inducers did not seem to correlate in all cases with morphological differentiation.

Cell Differentiation↗
PubMed1985

The role of platelet-derived growth factor on human pluripotent progenitor (CFU-GEMM) growth in vitro.

The effect of serum on the proliferation of human bone marrow pluripotent progenitor cells (CFU-GEMM), was compared to that of fresh frozen plasma (FFP). Serum significantly increased the number of mixed erythroid-granulocytic-megakaryocytic colonies (CFU-GEMM) and erythrocytic bursts (BFU-E) in this assay system (p less than 0.01 and 0.02, respectively). Two possible explanations for this finding were considered: first the presence of citrate-phosphate-dextrose (CPD) in plasma but not in serum, and second the presence of platelet-derived growth factor (PDGF) in serum but not in plasma. CPD was indeed found to have an inhibitory effect on growth of colonies of all types when added to serum-stimulated cultures. Nevertheless, when heparinized plasma was compared to serum from the same donors, growth of CFU-GEMM and BFU-E was higher in the serum-stimulated cultures (p less than 0.001 and p less than 0.05, respectively). PDGF at concentrations of 120-240 pM was found to enhance the formation of CFU-GEMM and BFU-E by three- and four-fold respectively when added to cultures containing FFP but not when added to cultures containing serum derived from whole blood (WBS). Purified PDGF added at the same concentrations, to cultures containing platelet-poor derived serum (PDS), promoted similar increases in growth of CFU-GEMM and BFU-E but not of granulocytic-macrophage or megakaryocytic colonies. Whether PDGF has a direct action on CFU-GEMM or its growth promoting activity is via an interacting cell population is currently being studied.

Cells, Cultured↗
PubMed1985

Studies of sub-human primate (marmoset) pluripotent hemopoietic stem cells (CFU-GEMM) in vitro.

Pluripotent hemopoietic progenitor cells (CFU-GEMM) grow in vitro from marmoset bone marrow using a modified human CFU-GEMM assay. Characteristics of growth are similar to those reported in the human CFU-GEMM assay. The number of CFU-GEMM/10(5) marrow cells from marmoset bone marrow is approximately four times that grown in human marrow in our laboratory. Data concerning EPO and other requirements for growth of CFU-GEMM demonstrate an assay for the pluripotent hemopoietic progenitor in the marmoset. This assay may be useful in designing preclinical primate bone marrow transplant experiments.

Animals↗
PubMed1984

A and B blood group antigen expression on mixed colony cells and erythroid precursors: relevance for human allogeneic bone marrow transplantation.

Using anti-A and anti-B blood group monoclonal antibodies and fluorescent activated cell sorting of human bone marrow, A (or B) blood group antigen was shown to be on 5.2 +/- 5.9 (mean +/- SD) % of CFU-GEMM and 12.5 +/- 19.6% of the erythroid burst forming cells (designated BFU-GEMM) as defined by the mixed colony assay, and 49.5 +/- 20% of the BFU-E and 83.5 +/- 9.9% of the CFU-E as defined by the erythroid colony assay. This antigen expression on the BFU-GEMM is consistent with the concept that erythroid bursts stimulated by leucocyte conditioned medium are less mature, and are closer in development to the pluripotent stem cell than the BFU-E. These results help to explain the delayed erythropoiesis, and perhaps impaired engraftment of all cell lineages, that may occur in some recipients of ABO incompatible bone marrow transplants with persistent and high anti-A titres.

ABO Blood-Group System↗
PubMed1983

Chronic myeloid leukaemia and the Philadelphia translocation: do the c-sis oncogene and platelet-derived growth factor provide the link?

The study of cellular oncogenes and of chromosomal abnormalities in human tumours has, in several instances, suggested a link between a specific oncogene translocation and oncogenesis. It was recently suggested that the translocation of the c-abl gene (the human cellular homologue of the transforming sequence of Abelson murine leukaemia virus) from chromosome 9 to 22 in Philadelphia translocation, might have a role in the generation of chronic myeloid leukaemia (CML). We propose an alternative hypothesis and suggest that the translocation of another gene, c-sis, may be more important.

Cell Division↗
PubMed1978

The in vitro effect of thymic humoral factor and levamisole on peripheral blood lymphocytes in systemic lupus erythematosus patients.

The in vitro effect of thymic humoral factor (THF) and levamisole on E rosette-forming cells in the peripheral blood of seventeen patients with systemic lupus erythematosus (SLE) was studied. Patients with active disease showed a low number of E rosette-forming cells. A significant rise in the number of E rosettes was obtained after incubation with both THF and levamisole. No such effect was observed on lymphocytes from patients with inactive disease and normal controls. In seven patients, three with active disease and four with well-controlled disease, short-term cultures were performed. The effect of THF on E rosettes was found to be the same before and after the short-term cultures. Possible mechanisms, by which THF (on the one hand) and levamisole (on the other) may increase the number of E rosettes in vitro, are discussed.

Adult↗
PubMed1977

Peripheral blood lymphocytes in systemic lupus erythematosus. Relation to activity.

Peripheral blood lymphocytes from 20 patients with systemic lupus erythematosus (SLE), 3 patients with drug-induced lupus and 20 normal controls were studied. The absolute number of E-rosette-forming cells (ERFC) and surface immunoglobulin-bearing cells were determined during active and inactive stages of the disease. An attempt was made to establish the relationship between the number of ERFC and the clinical stages of the disease on one hand and treatment on the other. A decrease in ERFC was observed in all SLE patients, but it was most prominent in patients with active disease. No correlation was found between treatment and the decreased numbers of ERFC.

Humans↗