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Biomedical subjects

A Ganser

Publications and source records attributed to A Ganser.

At least 271 records · Page 15Linked to original sources
PubMed1987

Effect of recombinant interferons alpha and gamma on human bone marrow-derived megakaryocytic progenitor cells.

Interferons (IFNs) have been shown to suppress the proliferation of human pluripotent hematopoietic progenitor cells, CFU-GEMM, and committed erythroid (BFU-E, CFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells. However, no information is yet available concerning the effect of IFNs on human megakaryocytic progenitor cells CFU-Mk. Furthermore the mechanisms underlying the inhibitory activity of IFNs are still controversial. Therefore highly purified recombinant IFN preparations, rIFN-alpha and rIFN-gamma, were assessed for their influence on in vitro growth of human bone marrow-derived CFU-Mk as well as CFU-GEMM. In addition, the role of hematopoietic accessory cells, that is, adherent cells and T lymphocytes, in the mediation of the suppressive effect of rIFNs was examined. When added to unseparated bone marrow cells, both rIFN preparations significantly inhibited colony formation with 50% inhibition of CFU-Mk occurring at 22 U/mL for rIFN-alpha and 59 U/mL for rIFN-gamma, while 50% inhibition of CFU-GEMM occurred at 59 U/mL for rIFN-alpha and 101 U/mL for rIFN-gamma. The suppressive effect of rIFN-alpha and rIFN-gamma was selectively abolished by monoclonal antibodies (MoAbs) against rIFN-alpha and rIFN-gamma, thus confirming that the inhibitory activity was due to the rIFN preparations used. The antiproliferative effect of rIFN-alpha and rIFN-gamma on CFU-GEMM growth was not associated with a decrease in the percentage of mixed colonies containing megakaryocytic cells as assessed by use of the MoAb C17.28 against platelet glycoprotein IIIa. Removal of adherent cells and T lymphocytes from the target bone marrow cells had no influence on the suppressive effect of rIFN-alpha, whereas it significantly reduced the inhibitory effect of rIFN-gamma on the growth of megakaryocytic colonies and the other hematopoietic progenitors. The data indicate that (1) human megakaryocytopoiesis is markedly inhibited by rIFN-alpha and rIFN-gamma, and (2) the inhibitory effect of rIFN-alpha is due to a direct action on hematopoietic progenitor cells, whereas the effect of rIFN-gamma is mediated to a significant degree through accessory cell populations.

Bone Marrow Cells↗
PubMed1987

Deletion of c-fms sequences in the 5q- syndrome.

Southern blot analyses demonstrated hemizygosity of c-fms sequences in three cases of the 5q- syndrome, cytogenetically characterized by del(5)(q13;q35) or del(5)(q31;q35). In situ hybridization studies revealed a deletion of this oncogene from the 5q- chromosome in two cases; moreover, we localized c-fms to region 5q31-33.

Chromosome Aberrations↗
PubMed1986

Effect of intensified chemotherapy on the pluripotent haematopoietic progenitor cells CFU-GEMM in adult acute lymphoblastic leukaemia.

In order to analyse the short-term and long-term effects of intensified induction chemotherapy, the frequency, cellular composition and proliferative state of the pluripotent haemopoietic progenitor cells CFU-GEMM was investigated in a total of 35 patients with acute lymphoblastic or acute undifferentiated leukaemia at diagnosis, as well as during and after therapy. At diagnosis, the number of CFU-GEMM/ml bone marrow aspirate was significantly reduced to 12.1 (95% confidence interval 2.1-70) as compared to healthy controls (50.4/ml; 95% confidence interval 66-3846/ml). While immediately after the end of induction therapy, the respective values for CFU-GEMM were still decreased (30.4/ml; 95% confidence interval 8.4-108); values not significantly different from normal were reached within the following 4 weeks. During and after cessation of maintenance therapy again no significant deviation from normal values was observed. Immunological analysis of single colonies revealed that during the early phase after remission induction only 60 +/- 7% of mixed colonies contained megakaryocytic cells (normal 86 +/- 3%; P less than 0.01) while normal values were found during and after maintenance therapy. Cell cycle analysis disclosed highly increased proliferative activity of pluripotent progenitor cells during marrow regeneration after induction therapy as well as during maintenance therapy, but a return to the resting state after cessation of maintenance therapy. It is concluded that this intensive chemotherapy regimen does not result in any apparent long-term damage to the pluripotent haemopoietic progenitor cells.

Acute Disease↗
PubMed1986

Treatment of AIDS-related Kaposi's sarcoma with recombinant gamma-interferon.

Four patients with the acquired immunodeficiency syndrome and Kaposi's sarcoma were treated with subcutaneous human recombinant gamma-interferon at a dosage of 200 micrograms = 2 X 10(6) U twice daily for at least 28 days. While the dosage of interferon was well tolerated, progressive disease was observed in all four patients studied. These results might be due to the selection of the patients presenting advanced stages (3 out of 4) with recurrent disease after previous chemotherapy.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Acute undifferentiated leukemia: implications for cellular origin and clonality suggested by analysis of surface markers and immunoglobulin gene rearrangement.

Although B cell leukemias and, recently, T cell leukemias can be identified both by surface marker and molecular analysis, there remains a population of acute undifferentiated leukemias (AUL) that cannot be allocated definitively to a single cell lineage. AUL was diagnosed in nine patients according to stringent criteria. We combined both immunologic and molecular approaches to analyze further the ambiguous origin of AUL cells. Southern blot analysis revealed rearranged Ig heavy-chain genes in seven patients and indicated a biclonal or oligoclonal leukemic cell population in three of them, including one case of AUL with translocation (4;11). Analysis of cell surface markers showed expression of at least one early B cell-associated antigen (BA-1, BA-2, B4, UL-38) in six of these seven patients, with coexpression of a myeloid antigen (VIM-2) in three patients. Leukemic cells of two other patients neither exhibited Ig chain gene rearrangements nor expressed B cell-associated antigens. T cell receptor beta-chain genes showed germline configuration in all nine cases. Our results demonstrate heterogeneity among AUL patients based on molecular and surface marker analyses and suggest that most AUL blast cells are derived from a precursor cell that shares phenotypic and genotypic characteristics of early B cells with certain surface antigens of myeloid cells, in some cases of AUL more than one abnormal cell clone or subclone may exist, and the cellular origin, at least of some AULs exhibiting t(4;11), may be truly B cell lineage committed.

Antibodies, Monoclonal↗
PubMed1985

Mixed megakaryocytic-granulocytic differentiation during diffusion chamber culture of peripheral blast cells from the blast crisis of chronic myelocytic leukemia.

Morphologically and cytochemically undifferentiated peripheral blast cells from three patients in blast crisis of Ph'-positive chronic myelocytic leukemia were analysed morphologically, immunologically and cytogenetically prior to and during in-vivo diffusion chamber culture (DC) to investigate their differentiation capacity. In two patients immunological markers characteristic of the megakaryocytic lineage were found on the original cells, but lineage-specific differentiation markers were absent on the blast cells of the third patient. During DC culture multilineage differentiation capacity could be demonstrated immunologically and morphologically in all three patients with expression of megakaryocytic and granulocytic markers as well as terminal differentiation along these lineages. Cytogenetic analysis prior to and during DC culture provided evidence that the cells differentiating in culture were derived from the blast crisis clones and that the event leading to blast crisis might have occurred in a pluripotent precursor cell which retained its differentiation capacity along several lineages.

Adult↗
PubMed1985

Megakaryocytic cells in mixed haemopoietic colonies (CFU-GEMM) from the peripheral blood of normal individuals.

The cellular composition of mixed haemopoietic colonies CFU-GEMM from the peripheral blood of normal individuals was investigated using both an improved in vitro culture assay and a monoclonal antibody reactive with the earliest megakaryocytic precursor cells. The frequency of CFU-GEMM was found to be 22 +/- 7/ml blood (mean +/- SE; n = 8) and 4.9 +/- 1.8/10(6) mononuclear cells. Double-labelling of single colonies with monoclonal antibodies against megakaryocytic as well as granulocytic cells revealed that only 18% of mixed colonies from the peripheral blood contained megakaryocytic cells as compared to 87% of mixed colonies from the bone marrow, while no difference existed with regard to granulocytic cells. It is concluded that circulating multilineage progenitor cells either require different culture conditions to express their megakaryocytic component or, alternatively, that the circulating pluripotent stem cell pool mainly consists of bipotent rather than multipotent progenitor cells.

Blood Cell Count↗
PubMed1985

Megakaryocytic differentiation capacity of human pluripotent bone marrow progenitor cells CFU-GEMM in vitro after cryopreservation.

The effect of cryopreservation on the pluripotent haemopoietic progenitors CFU-GEMM as well as on the megakaryocytic (CFU-Mk), erythroid (BFU-E) and granulocytic-monocytic (CFU-GM) progenitor cells was analyzed. Progenitor cell recovery after freezing, as determined in 5 experiments, averaged 89% for CFU-GEMM (range: 63% - 194%), 85% for CFU-Mk (range: 62% - 96%), 92% for BFU-E (range: 43% - 174%) and 60% for CFU-GM (range: 31% - 93%). Immunological analysis of individual mixed colonies using a double labelling immunoalkaline phosphatase slide technique and monoclonal antibodies against megakaryocytic and granulocytic cells revealed megakaryocytic cells in more than 79% (range: 73% - 94%) and 84% (range: 75% - 87%) of mixed colonies before and after freezing, respectively. Our results indicate that cryopreservation of human bone marrow cells does not alter the megakaryocytic differentiation capacity of the haemopoietic progenitor cells CFU-GEMM and CFU-Mk in vitro.

Bone Marrow Cells↗
PubMed1984

Low-dose Ara-C in the treatment of acute leukemia. Cytotoxicity or differentiation induction?

The differentiation inducing effect of low-dose Ara-C on human myeloid leukemic cells was studied in two patients with subacute myelocytic and subacute myelomonocytic leukemia in vivo and in vitro. By continuous i.v. administration of 10 mg Ara-C/m2 over 12 h daily for 12 or 20 days complete remissions were obtained in both patients with normalization of the incidence of the committed progenitor cells BFU-E and CFU-C in the marrow while the incidence of pluripotent CFU-GEMM remained subnormal. Parallel cultures of the patients' bone marrow cells in diffusion chambers (DC) implanted in mice demonstrated a clear cytotoxic effect of low-dose Ara-C. The greater increase of granulopoietic cells within DC in the Ara-C exposed group than in control mice after the end of drug administration is, in addition, an indication for differentiation induction by this kind of Ara-C therapy.

Adult↗
PubMed1984

Growth kinetics of CFU-GEMM, BFU-E, and CFU-C in diffusion-chamber cultures of normal human bone marrow cells.

The proliferation and differentiation of human pluripotent hemopoietic precursor cells CFU-GEMM as well as of the committed precursors BFU-E and CFU-C within conventional diffusion chambers (DC) was studied. Low-density human bone marrow cells from eight normal donors were cultured in DC implanted into 750-rad-preirradiated mice. Cells harvested from DC after 1-14 days were assayed for the content of CFU-GEMM, BFU-E, and CFU-C. The mean number of progenitor cells inoculated per DC on day 0 was 59 (range 12-144) for CFU-GEMM, 367 (range 165-878) for BFU-E, and 632 (range 122-1168) for CFU-C. After an initial decrease in the number of all progenitors, an increase of CFU-GEMM was observed in five out of eight experiments and in the number of BFU-E and CFU-C in seven and five experiments, respectively. The assessment of the percentage of precursor cells sensitive to ara-C demonstrated a rise in the proportion of cells in S phase after implantation into DC consistent with reentry into active proliferation. From the observed behavior of the CFU-GEMM it is concluded that the earliest detectable human precursor cells do proliferate within DC.

Bone Marrow Cells↗