Search PubMed⌕ Search

Biomedical subjects

S Cooper

Publications and source records attributed to S Cooper.

At least 289 records · Page 16Linked to original sources
PubMed1988

Growth characteristics of marrow hematopoietic progenitor/precursor cells from patients on a phase I clinical trial with purified recombinant human granulocyte-macrophage colony-stimulating factor.

Bone marrow cells from patients with leukemia, myelodysplastic syndromes, cancer, and other disorders on a phase I clinical trial with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) were assessed in vitro for numbers of granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells, and for growth patterns (colony-to-cluster ratio) of CFU-GM, cycling rates of CFU-GM, and responsiveness in vitro to colony-stimulating and colony-inhibiting factors. The colony-to-cluster ratio of CFU-GM and the dose-response curves of CFU-GM to stimulation by rhGM-CSF in vitro did not change during the clinical trial. However, the percentage of CFU-GM in DNA synthesis, which is a measure of the proliferative rates of these cells, determined by the high specific activity tritiated thymidine kill technique in vitro, was markedly enhanced in a reversible fashion after administration in vivo of rhGM-CSF. The increased cycling rates of CFU-GM were consistent with the induced increase in neutrophil counts in these patients that has been reported elsewhere. Additionally, marrow CFU-GM from patients given rhGM-CSF in vivo were increased in sensitivity to inhibition in vitro by recombinant human H-subunit (acidic) ferritin in two of eight cases, and were increased in sensitivity to inhibition by lower dosages of recombinant human tumor necrosis factor alpha in all patients evaluated. The sensitivity of CFU-GM to inhibition in vitro by recombinant human interferon gamma and prostaglandin E1 did not change during the clinical trial. These studies demonstrate that the rhGM-CSF is having an effect on CFU-GM in the patients on the phase I clinical trial. This information may be of significance in planning future clinical studies combining rhGM-CSF with chemotherapy and/or other biotherapy.

Bone Marrow↗
PubMed1988

Synergistic interaction of hematopoietic colony stimulating and growth factors in the regulation of myelopoiesis.

Synergistic interactions in the regulation of myelopoiesis have been noted in vitro and in vivo and are discussed. Moreover, data is presented to highlight such synergistic interactions in vitro and in vivo. It is shown that purified recombinant human B-cell stimulating factor-1/interleukin-4 (rh BSF-1/IL-4) synergizes with rh Granulocyte (G)-Colony Stimulating Factor (CSF), but not with rh Granulocyte-Macrophage (GM)-CSF, rh IL-3, or rh Macrophage CSF (CSF-1) to enhance colony formation in vitro by normal human bone marrow cells. This synergism is restricted to granulocyte progenitors. Also, it is shown that rh G-CSF or rh CSF-1 enhance the proliferation of granulocyte-macrophage progenitor cells (CFU-GM) in vivo in mice pretreated with human lactoferrin, and when added together these preparations of CSF act synergistically. It is apparent that a true understanding of how myeloid blood cell production is regulated requires insight into how molecules collaborate with or antagonise one another.

Animals↗
PubMed1988

Introduction and expression of the human Bs-globin gene in transgenic mice.

Owing to the episodic and unpredictable nature of the sickling crisis, many aspects of the disease sickle cell anemia have resisted in vivo analysis. The lack of an animal model has hindered the pathophysiological investigation of this disease, as well as deterred the development of pharmacological therapies. The transgenic mouse system offers a new means for creating animals that make a specified mutant gene product, and we have used this system to create a series of mice that contain the human beta s-globin gene. These animals express this gene in the appropriate tissues and at the same point in development as the adult mouse globin genes are expressed. We have crossed the human beta s-containing transgenic mice with a beta-thalassemic mouse line and examined the hemoglobins produced by these mice. Their red cells contain 10% mouse alpha/human beta s hybrid hemoglobin, which partially corrects the thalassemic phenotype of the homozygous beta-thalassemic animals. Though the red cells do not sickle, other properties of the human beta s gene in these mice indicate the potential for the eventual development of a transgenic animal model for sickle cell anemia.

Alleles↗
PubMed1987

Who has nightmares? The personality of the lifelong nightmare sufferer.

Twelve lifelong nightmare sufferers, 12 vivid dreamers who had no nightmares, and 12 persons who had neither nightmares nor vivid dreams were studied in a series of structured interviews, psychological tests, and other tests. The group with nightmares had significantly higher scores on the "psychotic" side of the Minnesota Multiphasic Personality Inventory profile than the other two groups, scored higher on a "boundary deficit" score of the Rorschach test, and had more first- and second-degree relatives with nightmares, psychological problems, and psychiatric hospitalization. There were no significant differences between the groups with vivid and nonvivid dreams. On interview, the frequent nightmare sufferers were a group of sensitive, open persons who had features of the "schizophrenic spectrum disorders," but who also had artistic and creative tendencies and interests, in contrast to the other groups. These results confirm and extend our previous findings in a group of 38 frequent nightmare sufferers.

Adult↗
PubMed1987

The influence in vivo of natural murine interleukin-3 on the proliferation of myeloid progenitor cells in mice recovering from sublethal dosages of cyclophosphamide.

Purified natural murine interleukin-3 (IL-3) was assessed for its effects in vivo in mice pretreated 7 days earlier with a sublethal dosage of cyclophosphamide. The multipotential (CFU-GEMM), erythroid (BFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells in these mice were in a slowly- or non-cycling state. Three hours after the i.v. administration of 200 units IL-3 into these mice, the hematopoietic progenitor cells in the marrow and spleen were placed into rapid cell-cycle. At this time, no effects were noted on marrow or spleen nucleated cellularity, numbers of progenitor cells per organ, or peripheral blood counts. No endotoxin was detected in the IL-3 preparation, by Limulus lysate assay. Treatment of IL-3 in vitro at 100 degrees C for 20 min partially decreased its colony stimulating activity in vitro and completely inactivated its proliferation stimulating effects in vivo. These findings suggest that the effects of IL-3 in vivo were not due to contaminating endotoxin or to a non-specific protein effect. These studies do not allow us to conclude whether the effects of IL-3 in vivo are directly on the progenitors and/or are indirect effects mediated by accessory cells.

Animals↗
PubMed1987

Synergistic myelopoietic actions in vivo after administration to mice of combinations of purified natural murine colony-stimulating factor 1, recombinant murine interleukin 3, and recombinant murine granulocyte/macrophage colony-stimulating factor.

Combinations of low dosages of purified murine hematopoietic colony-stimulating factors (CSFs)--L-cell CSF type 1 (CSF-1), recombinant interleukin 3 (IL-3), and recombinant granulocyte/macrophage CSF (GM-CSF)--were compared with single CSFs for their influence on the cycling rates and numbers of bone marrow granulocyte/macrophage, erythroid, and multipotential progenitor cells in vivo in mice pretreated with human lactoferrin. Lactoferrin was used to enhance detection of the stimulating effects of exogenously administered CSFs. Concentrations of CSFs that were not active in vivo when given alone were active when administered together with other types of CSF. The concentrations of CSF-1, IL-3, and GM-CSF needed to increase progenitor cell cycling rates were reduced by factors of 40-200, 10-50, and 40- greater than 400, respectively; the concentrations needed to increase progenitor cell numbers were reduced by factors of 40-500 (CSF-1), 20-80 (IL-3), and greater than 40- greater than 200 (GM-CSF) when these forms of CSFs were administered in combination with low dosages of one of the other forms of CSFs. The results demonstrate that different CSFs can synergize when administered in vivo to increase the cycling rates and numbers of marrow hematopoietic progenitor cells. These findings may be of relevance physiologically to the regulation of myeloid blood cell production by CSFs.

Animals↗
PubMed1987

Comparative effects in vivo of recombinant murine interleukin 3, natural murine colony-stimulating factor-1, and recombinant murine granulocyte-macrophage colony-stimulating factor on myelopoiesis in mice.

Purified murine colony-stimulating factors (CSF) recombinant interleukin 3 (IL-3), natural CSF-1, and recombinant granulocyte-macrophage (GM) CSF were assessed in vivo for their effects on BDF1 mouse bone marrow and spleen granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells in untreated mice and in mice pretreated with purified iron-saturated human lactoferrin (LF). The CSF and LF preparations did not contain detectable endotoxin (less than 0.1 ng). Mice pretreated with LF were more sensitive to the effects of CSF. In mice pretreated with LF, 2,000 U IL-3 or 20,000 U CSF-1 significantly enhanced the cycling status and absolute numbers of all progenitors, whereas 20,000 U GM-CSF significantly increased the cycling status of CFU-GM and CFU-GEMM, but had no effect on cycling of BFU-E or on numbers of any of the progenitors. The effects of CSF in mice pretreated with LF were not mimicked by 0.1-100 ng E. coli lipopolysaccharide.

Animals↗
PubMed1987

Interactions between purified murine colony-stimulating factors (natural CSF-1, recombinant GM-CSF, and recombinant IL-3) on the in vitro proliferation of purified murine granulocyte-macrophage progenitor cells.

Purified preparations of natural CSF-1 (nCSF-1), recombinant GM-CSF (rGM-CSF), and recombinant IL-3 (rIL-3), alone and in combination, were investigated for their proliferative effects on highly enriched murine granulocyte-macrophage progenitor cells (CFU-GM). These CFU-GM had cloning efficiencies of 62%-95% in the presence of 10% (vol/vol) pokeweed mitogen-stimulated spleen cell-conditioned medium, and contained few, if any (less than or equal to 3%), contaminating morphologically recognizable monocytes or lymphocytes. The combination of low concentrations of nCSF-1 plus rIL-3, or nCSF-1 plus rGM-CSF, increased colony number greater than additively compared to the sum of colony formation with each factor alone, whereas total aggregate (colony plus cluster) number increased additively. At plateau concentrations, the previous CSF combinations increased colony number additively. Colony size was increased when nCSF-1 plus either rGM-CSF or rIL-3 were added simultaneously at either low or plateau concentrations, when compared to the size of colonies with any of the CSFs alone. Addition of rGM-CSF plus rIL-3 demonstrated no cooperative proliferative effect on either colony number or size. It is likely that these effects are mediated at the progenitor cell level and do not require accessory cell participation.

Animals↗
PubMed1987

The effects of purified recombinant murine interleukin-3 and/or purified natural murine CSF-1 in vivo on the proliferation of murine high- and low-proliferative potential colony-forming cells: demonstration of in vivo synergism.

Purified natural murine L cell (macrophage) colony-stimulating factor (nCSF-1) and purified recombinant murine interleukin-3 (rIL-3) were administered to normal or lactoferrin-pretreated mice 20 to 24 hours before sacrifice. rIL-3 and nCSF-1 administered separately increased the percentage of macrophage high-proliferative potential colony-forming cells (HPP-CFC) and low-proliferative potential colony-forming cells (LPP-CFC) in active cell cycle. Endotoxin was not detected in the samples of nCSF-1 or rIL-3 with the Limulus lysate test, and the in vitro and in vivo hematopoietic stimulatory effects of both molecules were abolished or markedly reduced by 30 minutes' treatment at 100 degrees C, which demonstrates that the effects noted in vivo were not due to endotoxin. Combinations of low concentrations of rIL-3 and nCSF-1, which by themselves were inactive, increased the percentage of HPP-CFC and LPP-CFC in active cell cycle in a synergistic fashion. No significant change in the number of HPP-CFC or LPP-CFC per femur or femoral nucleated cellularity was observed. Thus, rIL-3 and nCSF-1 can synergize to effect the proliferation of the same cell populations in vivo.

Animals↗