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Biomedical subjects

A C Stern

Publications and source records attributed to A C Stern.

36 records · Page 2Linked to original sources

Granulocyte-macrophage colony-stimulating factor to harvest circulating haemopoietic stem cells for autotransplantation.

Granulocyte-macrophage colony-stimulating factor (GM-CSF), given to accelerate recovery from cytopenia induced by high-dose (7 g/m2) cyclophosphamide, reproducibly brought about a dramatic increase (up to 1000-fold) in the number of peripheral blood granulocyte-macrophage colony-forming units (CFU-GM). These circulating progenitors were harvested by leucapheresis and reinfused, together with autologous bone marrow cells, in seven patients with cancer after total body irradiation and melphalan. Complete haemopoietic recovery occurred in all seven transplanted patients in a very short time: mean (SD) 9.1 (0.9) days (range 8-11) to achieve more than 0.5 x 10(9)/l neutrophils, 9.9 (1.7) days (range 8-13) to over 1 x 10(9)/l neutrophils, 10.7 (2.6) days (range 9-16) to over 0.5 x 10(11)/l platelets, and 13.6 (4.2) days (range 13-21) to over 1.0 x 10(11)/l platelets. A reduction in the severity of mucositis was also observed. The rapid haematological recovery made possible by this approach promises to increase the therapeutic index of high-dose chemoradiotherapy regimens and to widen their role as treatment for chemoradiosensitive tumours.

Adult↗

[In vitro treatment of human bone marrow in the elimination of tumor cells: initial experiences with cytotoxic monoclonal anti-T-cell antibody LAU-A1].

The authors present evidence that elimination of tumor cells in the bone marrow is essentially possible by in vitro purging with the monoclonal anti-T-cell antibody LAU-A1 and complement; this procedure does not interfere with regeneration capacity of stem cells. These findings have an important bearing with regard to candidates for autologous bone marrow transplantation.

Adult↗

Differentiation markers and accessory function of murine macrophages derived from cultured bone-marrow stem cells.

Murine bone-marrow cells cultured in the presence of colony-stimulating factor from mouse-lung-conditioned medium give rise to macrophages which function as accessory cells in antigen-specific T helper cell induction. Virtually all Ia+ bone-marrow stem cell-derived macrophages express determinants encoded in the I-A subregion. A second set of macrophages bears I-A as well as I-E/C-endoced determinants. The products of the I-A and I-E/C subregion, but not those of the I-J subregion, are involved in T helper cell induction.

Animals↗

Characterization of accessory cells required for helper T cell induction in vitro: evidence for a phagocytic, Fc-receptor, and Ia-bearing cell type.

The nature of the accessory cell type required for the in vitro induction of antigen-specific helper T (Th) cells to soluble antigen was determined. Two different sources of adherent accessory cells were investigated: peritoneal exudate cells (PEC) and macrophages derived from bone-marrow cells (BMM phi), which were cultured for 8 days in vitro with colony-stimulating factor. PEC and BMM phi were rosetted with EA-SRBC and separated by sedimentation into Fc gamma receptor-positive and negative fractions. Only the Fc gamma receptor-positive fraction was active in Th-cell induction. By means of the fluorescence-activated-cell sorter (FACS-II), PEC or BMM phi were separated either into phagocytic and nonphagocytic, or Ia-positive and Ia-negative cell populations. Only phagocytic and Ia-positive accessory cells induced antigen specific Th cells. In conclusion, the accessory cell is adherent, phagocytic, carries Fc gamma-receptors and Ia products, and thus expresses the most important characteristics of the macrophage lineage.

Animals↗

Ia-bearing bone marrow-cultured macrophages induce antigen-specific helper T cells for antibody synthesis.

In bone marrow cell (BMC) cultures supplemented with colony-stimulating factor (CSF), accessory cells develop that are capable of inducing specific helper T cells. These accessory cells become effective after 4 days in culture and can be found not only in the adherent but also in the nonadherent cell population. On the other hand, very few accessory cells with helper cell-inducing capacity are obtained in BMC cultures without CSF. The active BMC-derived cell type has been shown to carry Ia surface antigen, since pretreatment with anti-Ia serum and complement abolished the capacity of these cells to function like macrophages in helper T cell induction. Moreover, the appearance of functional accessory cells in these cultures coincided with the presence of Ia-bearing cells.

Animals↗

Role of human recombinant GM-CSF in the prevention and treatment of leukopenia with special reference to infectious diseases.

Recombinant human GM-CSF has been shown to be effective in reversing severe neutropenic states associated with the underlying disease or caused by cytotoxic drugs, and during engraftment after bone marrow transplantation. Preliminary evidence supports the view that restoration of adequate myelopoiesis results in better control of infection. The use of rhGM-CSF in special infectious diseases to activate cell function is currently being studied. Preliminary in vitro and in vivo data allow high expectations for the usefulness of rhGM-CSF in contributing to the control of these diseases.

Granulocyte-Macrophage Colony-Stimulating Factor↗