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S H Robinson

Publications and source records attributed to S H Robinson.

At least 19 recordsLinked to original sources
PubMed1994

Nursing care delivery models in ambulatory oncology.

Oncology nurse leaders are challenged to design ambulatory nursing care delivery models that are cost-effective, efficient, and facilitate positive patient outcomes. Many of the models used in the inpatient setting can be adapted to the ambulatory setting. Whatever model is implemented, it is important to delineate practice expectations.

Ambulatory Care↗
PubMed1991

Cooperative effects of hemin and anthracyclines in promoting terminal erythroid maturation in K562 human erythroleukemia cells.

Simultaneous exposure to 30 microM hemin and 3 x 10(-8) M aclacinomycin (ACL) or mussetamycin for 6 days led to terminal differentiation of K562 cells. The number of hemoglobinized cells and the total hemoglobin content of cells treated with both ACL and hemin exceeded the sum of the corresponding values induced in response to each of these two agents when used alone. Although neither ACL nor hemin alone induced substantial morphological maturation, 40%-45% of cells treated with both agents developed the morphological characteristics of orthochromatophilic normoblasts, a level of maturation not previously reported for this highly malignant cell line. Subcloning of K562 cells that had been treated with both ACL and hemin in inducer-free plasma clots revealed a 50% decrease in the clonogenic potential of these cells, even though the cells in the original cultures were still growing at only a moderately decreased rate. Despite the apparent terminal maturation of K562 cells induced with both ACL and hemin, with an advanced level of morphologic maturation and hemoglobin synthesis accompanied by a loss of proliferative capacity, these cells remained incapable of producing beta-globin chains and hence hemoglobin A.

Aclarubicin↗
PubMed1989

Hemin increase production of beta-like globin RNA transcripts in human erythroleukemia K-562 cells.

Previous studies have indicated that control and hemin-treated human erythroleukemia K-562 cells fail to produce adult-type beta-globin mRNA transcripts and to translate them into nascent beta-globin chains. Expression of the beta-globin DNA sequences in K-562 cells can occur, however, under certain conditions. To readdress this issue and to examine the possibility of whether these cells produce immature and untranslatable beta-globin RNA transcripts, we prepared total cytoplasmic RNA from control and inducer-treated cells and performed Northern blot hybridization analysis using 5' end-labeled fragments of the human beta-globin DNA rather than 3' end fragments as probes. Although hybridization of both cytoplasmic and nuclear K-562 RNA with a 32P-labeled 3' end fragment (1.6kb Bam H1 cut) coding for a large part of the first exon of beta-globin failed to detect beta-globin RNA transcripts, hybridization with a 5' end 32P-Labeled 2.0kb Bam H1 fragment (coding for the third exon and part of the second) revealed the presence of relatively small (less than 7S) RNA molecules both in nuclear and cytoplasmic fraction. S1 nuclease mapping of both cytoplasmic and nuclear RNA with the use of 5' end-labeled 2.0 kb Bam H1 fragment of human beta-globin DNA indicated protection of a small portion located 64 bp 5' upstream from the Bam H1 site of the second exon. The amount of protected portion was relatively higher in K-562 cells undergoing erythroid maturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Northern↗
PubMed1988

Analysis of hemin-induced protection of human hemopoietic cells from the cytotoxic effects of anthracyclines.

Experiments were performed with K562 erythroleukemia cells to further characterize the observation that hemin protects hemopoietic cells from the cytotoxic effects of anthracycline drugs. The present studies demonstrate that this protective effect of hemin applies only to anthracyclines and not to other classes of antineoplastic agents. Hemin interferes with the cellular accumulation of various anthracyclines, as measured by cytofluorography, and prevents binding of anthracyclines to isolated cell nuclei. Exposure of K562 cells to hemin retards the anthracycline-induced arrest of cells at the G2-M interphase of the cell cycle and permits cells to undergo continuing division as demonstrated by clonal growth in plasma clot cultures. Furthermore, hemin decreases the ability of anthracyclines to unwind simian virus 40 supercoiled DNA in vitro. The protective effect of hemin fails to occur if cells have been preincubated with this agent for 72 h before they are exposed to Adriamycin in the absence of hemin. The findings suggest that hemin prevents anthracycline-induced cytotoxicity by acting at several levels. These effects may be mediated by direct interactions of hemin with DNA and perhaps other cellular constituents or by molecular complex formation between hemin and anthracyclines at intracellular sites.

Antibiotics, Antineoplastic↗
PubMed1987

Immunoarchitecture of the bone marrow in neutropenia: increased HNK-1 + cells define a subset of neutropenic patients.

An immunoperoxidase technique was used to examine the distribution of lymphocyte subsets in bone marrow biopsies of 15 patients with neutropenia and seven non-neutropenic controls. The bone marrow of most patients and controls had similar distributions of immune effector cells characterized by a diffuse array of predominantly cytotoxic/suppressor T-cells and occasional nodular aggregates of helper T-cells. Cells displaying the natural killer cell marker HNK-1 were sparse in controls and most neutropenic patients. However, marked increases in marrow HNK-1 + cells were identified in four of the 15 patients. Three of these patients had diffuse HNK-1 + infiltrates associated with increased Leu 4+ (OKT-3+) T-cells while one had a nodular HNK-1+ infiltrate associated with small B-cell follicles. Each of these patients had clinical features similar to those described in the large granular lymphocyte (LGL) lymphocytosis (leukemia) syndrome, but only one of four demonstrated persistently increased numbers of LGLs in the peripheral blood. Thus, this study extends the association of neutropenia and increased numbers of cells with a T/NK phenotype to include patients whose bone marrow is the only demonstrable site of involvement. Since morphologic examination of the bone marrow could not identify the bone marrows with increased HNK-1+ cells, immunologic techniques are required to detect these cases.

Agranulocytosis↗
PubMed1986

Efficacy of platelet transfusions in immune thrombocytopenia.

Records of 11 patients with immune thrombocytopenia (idiopathic and quinidine-induced) were evaluated retrospectively for response to platelet transfusion. Good post-transfusion platelet count increments occurred on one or more occasions in seven of the 11 patients, with 13 of 31 platelet transfusions (42 percent) resulting in immediate post-transfusion increments of 20,000/mm3 or more. Next-day platelet counts remained elevated in association with five of these 13 transfusions. This study demonstrates that, contrary to common opinion, platelet transfusions can raise the platelet count in many patients with immune thrombocytopenia, and therefore may be beneficial in actively bleeding or high-risk patients with this disorder.

Adult↗
PubMed1986

Prevention of anthracycline-induced cytotoxicity in hemopoietic cells by hemin.

Anthracyclines such as Adriamycin (ADR) and daunomycin markedly inhibit cell growth in vivo and in vitro. These studies demonstrate that 30 microM hemin, which induces hemoglobin synthesis in human and murine erythroleukemia cells in culture, markedly decreases the cytotoxicity of ADR in a variety of hemopoietic cell lines (K562, HEL-1, MEL-745, HL-60, and U937) and in erythroid burst-forming cells from normal human marrow. Hemin failed to protect four of the five nonhemopoietic cell lines tested, including MCF-, breast adenocarcinoma cells, C-205 colon carcinoma cells, mouse 3T3 fibroblasts, and mouse kidney VERO cells. Hemin did protect human neuroblastoma IMP-32 cells from ADR cytotoxicity; however, this nonhemopoietic cell line undergoes dendrite formation in response to hemin induction. Cytofluorographic analysis of cellular ADR content and labeling studies with [3H]daunomycin demonstrated that hemin decreases the intracellular accumulation of these anthracyclines by more than 50% in K562 erythroleukemia cells. These studies indicate that small doses of hemin prevent intracellular accumulation of anthracyclines and thereby markedly reduce anthracycline toxicity to cells. Since this protective effect is observed preferentially with hemopoietic cells, it is possible that this finding could be exploited to protect the bone marrow from the cytotoxic action of anthracyclines during therapy for nonhemopoietic tumors.

Animals↗
PubMed1986

Microtopography of growth of normal and leukemic murine cells in diffusion-chamber cultures.

Histologic examination of "suspension" diffusion-chamber (DC) cultures of normal murine bone marrow cells demonstrates that hemopoietic cell growth in this system takes place in clonal form. Soon after implantation, marrow cells are arrayed on the filter membranes in a circumferential fashion adjacent to the surrounding lucite ring. Colonies of granulocytic cells soon form in this location and increase in size and number with increasing time of culture. Eventually cells begin to approach confluence over the entire filter membrane. Growth of C1498 murine acute myelogenous leukemic cells in DC cultures also takes place on the filter membranes and begins in a circumferential pattern. However, the leukemic cells grow diffusely and soon overspread the entire filter membrane, often growing several layers thick. Thus, although normal marrow cells are implanted into and are harvested from DC cultures in liquid-suspension form, they grow in a clonal pattern similar to that observed with the plasma-clot and fibrin-clot DC culture methods.

Animals↗
PubMed1985

Differentiation of leukemic cell lines: a review focusing on murine erythroleukemia and human HL-60 cells.

Several acute leukemia cell lines respond to chemical or pharmacologic inducing agents by undergoing variable degrees of differentiation. This review focuses on the manner in which murine erythroleukemia (MEL) and HL-60 cells can be induced to differentiate into virtually fully mature erythroid cells and mature granulocytes or macrophages respectively. In this process the cells undergo irreversible "commitment" to terminal differentiation which is followed by loss of proliferative capacity and alterations in the expression of genes whose products are related to specific aspects of cell maturation in the corresponding cell pathways.

Animals↗
PubMed1985

Loss of suppression of normal bone marrow colony formation by leukemic cell lines after differentiation is induced by chemical agents.

The human leukemic cell lines K562 and HL-60 were cocultured with normal bone marrow (BM) cells. Coculture with 10(4) K562 or HL-60 cells results in 50% inhibition of normal CFU-E and BFU-E colony formation. However, when the same number of K562 and HL-60 cells is first treated for two to five days with agents that induce their differentiation, a gradual loss in their capacity to inhibit CFU-E and BFU-E colony formation is observed. The inhibitory material in K562 cells is soluble and present in conditioned medium from cultures of these cells. The degree to which leukemic cell suppression of CFU-E and BFU-E growth is reversed is correlated with the time of exposure to the inducing agent. Suppression is no longer evident after five days of prior treatment with inducers. In fact, up to a 90% stimulation of CFU-E growth is observed in cocultures with K562 cells that have been pretreated with 30 to 70 mumol/L hemin for five days. K562 cells treated with concentrations of hemin as low as 30 mumol/L demonstrate increased hemoglobin synthesis and grow normally, but no longer have an inhibitory effect on CFU-E growth. Hence, reversal of normal BM growth inhibition must be caused by the more differentiated state of the K562 cells and not by a decrease in the number of these cells with treatment. Thus, induction of differentiation in cultured leukemic cells not only alters the malignant cell phenotype but also permits improved growth of accompanying normal marrow progenitor cells. Both are desired effects of chemotherapy.

Animals↗
PubMed1985

Analysis of commitment of human leukemia HL-60 cells to terminal granulocytic maturation.

Analysis of commitment of human promyelocytic leukemia HL-60 cells to terminal granulocytic maturation induced by dimethyl sulfoxide (DMSO) or retinoic acid (RA) was accomplished using biochemical measurements and a plasma clot clonal assay system that permits a high plating efficiency of 40 to 60%. Commitment to granulocytic maturation occurs very rapidly. When cells are exposed to these inducers for only 8 to 18 h, an interval much shorter than a single generation time, and are then subcultured in inducer-free plasma clots, they demonstrate a decrease in proliferative capacity and form colonies composed of mature nitroblue tetrazolium (NBT)-positive cells along with occasional colonies containing both NBT-positive and NBT-negative cells; in both types of colony, the NBT-positive cells are widely dispersed. Undifferentiated HL-60 cells give rise to compact NBT-negative colonies of large size without cell migration. HL-60 cell differentiation induced by either DMSO or RA is associated with a progressive decline in both DNA and RNA synthesis; this includes transcriptional inactivation of ribosomal DNA sequences. In contrast to DMSO, which induces development primarily of metamyelocytes, RA treatment leads to the accumulation of more mature band and segmented neutrophils; sequential exposure of cells pretreated with DMSO to RA alone fails to cause rapid appearance of segmented neutrophils. From these studies, we conclude that HL-60 cells become very rapidly committed to terminal maturation and that DMSO and RA appear to induce granulocytic maturation via two different mechanisms.

Cell Differentiation↗
PubMed1985

Relationship of mitochondrial membrane potential to hemoglobin synthesis during Friend cell maturation.

Previous studies have shown that exposure to imidazole dissociates hemoglobin synthesis from other aspects of cell maturation in dimethylsulfoxide (DMSO)-treated mouse erythroleukemia (MEL) cells. In the present study, we have found that imidazole causes hyperpolarization of the mitochondrial membrane in MEL cells exposed to DMSO, in contrast to the depolarization observed with DMSO alone. Like the defect in hemoglobin synthesis, membrane hyperpolarization is reversible upon removal of imidazole and incubation of cells with DMSO alone. These correlations suggest that alterations in the electrostatic properties of the mitochondrial membrane, due directly or indirectly to the effects of imidazole, interfere with heme synthesis but not with other aspects of the maturation process in these developing erythroid cells.

Animals↗
PubMed1983

Dissociation of iron transport and heme biosynthesis from commitment to terminal maturation of murine erythroleukemia cells.

Treatment of murine erythroleukemia (MEL) cells with imidazole in the presence of dimethyl sulfoxide (Me2SO) has been shown to dissociate hemoglobin accumulation from commitment to terminal maturation. To explore the mechanism(s) of this effect, we studied iron transport and heme and hemoglobin synthesis in Me2SO-induced MEL cells that were then exposed to imidazole. Imidazole treatment (i) causes moderate inhibition of 125I-labeled transferrin binding to both control and Me2SO-treated MEL cells; (ii) markedly suppresses Me2SO-induced activation of iron uptake into MEL cells; (iii) markedly decreases the incorporation of iron into ferritin; and (iv) abolishes heme biosynthesis from [2-14C]glycine and hemoglobin accumulation in Me2SO-treated cells. Imidazole treatment does not inhibit other aspects of cellular maturation; cells treated with Me2SO in the presence or absence of imidazole exhibit similar changes in proliferative activity and protein synthesis and, as shown previously, in cell morphology. Inhibition of hemoglobin accumulation in MEL cells is reversible on withdrawal of imidazole but is not altered by exogenous hemin. These data indicate that commitment to terminal maturation is regulated independently from the systems for iron transport and heme biosynthesis during early phases of erythroid cell differentiation.

Animals↗
PubMed1983

Transition from granulocyte to macrophage predominance in bone marrow cultures.

These studies examine the mechanisms underlying the transition from granulocytes to macrophages that characterizes cultures of bone marrow cells. Normal mouse marrow was cultured for several weeks in diffusion chambers (DCs) implanted in previously irradiated host mice. Previous studies with this system have shown that there is a period of logarithmic cell growth for 7 d following by a plateau in both total cell number and the numbers of CFU-S and CFU-C. The present studies show that this plateau in cell growth is associated with high cycling rates of both CFU-S and CFU-C. The plateau phase ends with a rapid decrease in the numbers of these progenitor cells. This is associated with a decline in the number of granulocytes, whereas macrophages persist at approximately the plateau level for the entire 48 d of culture. Transplantation of plateau phase cells into secondary DC cultures leads to a more rapid decline in the numbers of CFU-S and CFU-C followed by the total disappearance of granulocytes; in contrast, macrophage number undergoes a small increase which is maintained thereafter. When regular injections of 3H-thymidine are given to host mice bearing late phase secondary cultures, macrophage labelling rises to a plateau of only 30-40%, indicating that most macrophages at this stage of culture are long-lived cells. The kinetics of the stem cell changes implicate the CFU-C as the immediate precursor of granulocyte development in DC cultures but suggest that the CFU-S is the major determinant of overall cell renewal in this system. Macrophages doubtless also originate from CFU-C but, unlike granulocytes, these are often long-lived cells probably with some capacity for continuing cell division. These properties account for the often observed propensity of macrophages to repopulate bone marrow cultures from which stem cells and granulocytes have been depleted.

Animals↗