Search PubMed⌕ Search

Biomedical subjects

D H Pluznik

Publications and source records attributed to D H Pluznik.

89 records · Page 5Linked to original sources
PubMed1976

Control mechanisms of endotoxin and particulate material stimulation of hemopoietic colony forming cell differentiation.

Through injection of particulate materials and endotoxins (ET), possible control mechanisms of murine hemopoietic colony forming cells (CFC) were investigated. The experimental system employed two inbred strains of mice that responded with a similar increase in splenic CFC after injection of particulate materials, sheep red blood cells (SRBC) and colloidal carbon (cc), but differed in their response to ET. The strains similarly phagocytosed radiolabelled SRBC and ET, suggesting that the CFC changes were not dependent solely on phagocytosis of ET. The CFC from low ET responder strain responded in vitro to colony stimulating factor (CSF) elicited by ET in serum of the high responder strain, demonstrating that lack of response to ET is due, at least in part, to failure to produce CSF. Subjection of serum from either strain to chloroform extraction did not significantly increase its stimulating capacity, suggesting that the increased stimulatory ability in response to ET was due to increase in the CSF level rather than to a decrease in the level of inhibition.

Animals↗
PubMed1976

Correlation between splenic phagocytic activity and increase in splenic granulocyte/macrophage progenitors.

The possible connection between changes in splenic phagocytic activity and increase of splenic macrophage/granulocyte progenitors (colony forming cells - CFC) in mice was studied. Intravenous administration of increasing amounts of colloidal carbon, or sheep red blood cells (SRBC), 3 hours prior to injection of 10(7) 51Cr labeled SRBC caused a decrease in phagocytic activity in liver and an increase in spleen. Under the same experimental conditions, injection 10(7) unlabeled SRBC induced an increase of splenic CFC. Increase in splenic phagocytic activity and in numbers of splenic CFC showed a linear relationship. Both activities depended on the amounts of colloidal carbon or SRBC injected prior to injection of 10(7) SRBC. These findings suggest that mature macrophages may participate in controlling the increase in number of splenic CFC after injection of particulate substances such as SRBC or colloidal carbon. It was also found that increase of splenic CFC, under the experimental conditions described, was not affected by neonatal thymectomy.

Animals↗
PubMed1976

Sensitivity of murine hemopoietic stem cells to lectin cytotoxicity.

The response of normal murine bone marrow and mastocytoma cells to the cytotoxic effect of the four lectins WGA, PHA, SBA and Con A was studied. It was found that the two types of cells had similar sensitivities to each of the four lectins, as judged by decreased ability to develop colony growth in soft agar. They differed, however, in their sensitivity to particular lectins. The cells were most sensitive to WGA, less sensitive to PHA and SBA, and least sensitive to Con A. In further experiments, carried out on bone marrow cells, it was found that pluripotent stem cells (CFU-S) and committed stem cells (CFU-C) were equally sensitive to the cytotoxic effect of WGA. Incubation of bone marrow cells with 12 mug/ml WGA at 37 degrees C for 30 minutes had no effect on CFU-C; incubation for 60 minutes produced a 70% decrease in CFU-C. Additional periods of incubation up to 120 minutes did not further affect CFU-C, suggesting that some particular phase of the cell cycle may be sensitive to the cytotoxic effect of lectins.

Animals↗
PubMedDate not supplied

A c-myc antisense oligodeoxynucleotide inhibits entry into S phase but not progress from G0 to G1.

Initiation of T-lymphocyte proliferation by mitogen or antigen involves a cascade of gene activation events. Thus, by the time mitogen-activated T cells have reached the G1/S interface, many genes that are transcriptionally silent in G0, like the c-myc, IL-2, IL-2 receptor (IL-2R) and transferrin receptor (TfR) genes, have been transcriptionally activated. To understand the role of the individual genes in the activation process, one must be able to interfere specifically with the expression or function of each particular gene product. In this way, by blocking the IL-2R with an antibody, it has been demonstrated that IL-2/IL-2R interaction is required to induce TfR expression in activated T cells. When the function or expression of intracellular proteins is to be blocked, however, the need to introduce antibodies into the cytoplasm of viable cells, although possible, is a limiting factor. We have taken another approach, namely the exogenous addition to bulk cell cultures of small antisense oligomers. Sequence-specific antisense oligodeoxyribonucleotides have been reported to inhibit intracellular viral replication without interfering with cellular protein synthesis. Similarly, rabbit globin mRNA translation in a cell-free system and in rabbit reticulocytes has been inhibited by oligomers complementary to the globin mRNA initiation codon region. Recently, a pentadecadeoxyribonucleotide complementary to the initiation codon and four downstream codons of human c-myc mRNA was reported to inhibit the proliferation of the human leukaemic cell line HL-60 specifically. We report here that the same c-myc complementary oligonucleotide inhibits mitogen-induced c-myc protein expression in human T lymphocytes and prevents S phase entry. Interestingly, c-myc antisense treatment did not inhibit G0 to G1 traversal as assessed by morphologic blast transformation, transcriptional activation of the IL-2R and TfR genes, or induction of 3H-uridine incorporation.

Cell Division↗
PubMedDate not supplied

Defective responses to lipid A in C3H/HeJ mice: approaches to an understanding of lipid A-cell interaction.

C3H/HeJ mice have diminished responses to lipopolysaccharide (lipid A) that are due to a mutation in a gene located on chromosome 4. Studies employing this strain o mice have contributed significantly to our understanding of cellular interactions, mediators, and the genetic control involved in various host responses to lipid A. The present review emphasizes areas of research that require further elucidation, such as binding versus triggering sites for lipid A and the state of differentiation of the responding cells that is required for activation by lipid A. Certain experimental approaches to the investigation of the mechanisms of interaction of lipid A with target cells are suggested. Insertion of membrane fragments obtained from lipid A-sensitive cells into nonresponder cells has focused attention on the cell membrane as the primary target for lipid A. Thus, a clearer definition of either binding or triggering sites for lipid A could be gained by employing monoclonal antibodies to specific cell-surface components.

Animals↗
PubMedDate not supplied

B lymphocyte derived hematopoietic growth factors.

The present study was undertaken to elucidate the effect of bacterial lipopolysaccharides (LPS) on B lymphocyte derived hematopoietic growth factors. Bone marrow-derived (BM) B cells and homogeneous B cell lines (lymphomas and hybridomas) were used to study the production of granulocyte-macrophage colony stimulating factor (GM-CSF). The BM B cells required two signals for GM-CSF production: LPS and a tumor promoting phorbol ester (TPA). In the B cell lines, GM-CSF production was inducible with LPS alone. Molecular analysis of the GM-CSF gene expression revealed that steady state levels (as determined by Northern analysis) of GM-CSF mRNA could be detected only in LPS-induced cells, whereas it was found by nuclear transcription analysis that the GM-CSF gene is transcribed even in uninduced cells. However, biological activity of GM-CSF was detected only in supernatants from LPS-induced cells. These data suggest a post-transcriptional regulation of this gene.

Animals↗