Biomedical subjects
J S Foster
Publications and source records attributed to J S Foster.
Calcium ion involvement in the action of Pasteurella haemolytica leukotoxin.
The influence of Ca2+ ions on the cytotoxic activity of Pasteurella haemolytica leukotoxin was investigated. The divalent cation influenced the cytotoxic effect of the leukotoxin for sensitive BL-3 target cells, but its absence did not eliminate cytotoxicity. In short-term 1-h assays using neutral red uptake as a measure of cell viability, depletion of Ca2+ either by exhaustive dialysis or by addition of the Ca2+ chelators EDTA and EGTA eliminated the cytolytic effect of low doses of the toxin. Addition of Ca2+ to target cell cultures depleted of the divalent cation restored the cytolytic effect of the leukotoxin. Prolonged exposure of the BL-3 cells to the toxin abrogated the protective effect of EDTA and EGTA. Cell death measured by uptake of neutral red, exclusion of trypan blue and 51Cr release indicated that protection observed in the absence of free Ca2+ was temporary. Toxin-induced cytolysis equivalent to that observed in the presence of Ca2+ occurred following the initial 2-h exposure. In addition, verapamil, a Ca2+ channel blocker, prevented cell death during 1-h cytotoxicity assays. The protection afforded by verapamil was dose-dependent and was influenced by the concentration of Ca2+ in the buffer medium. The results suggest that Ca2+ positively influences the rapid initial phase of cell death resulting from exposure to the toxin, but is not required for the entirety of the cytolytic process.
Bradykinin sensitization of CSF-1-responsive murine mononuclear phagocyte precursors to prostaglandin E.
Bradykinin (BK) inhibited clonal proliferation of CSF-1-stimulated mononuclear phagocyte precursors derived from murine marrow. This inhibitory effect of BK was restricted to the subpopulation of precursors that required two signals, CSF-1 and LPS, for clonal proliferation. No effect was observed on stimulated colony formation by precursors that responded solely to the addition of CSF-1. Inhibition of colony formation by the two signal-dependent precursors required the presence of adherent marrow cells and was mediated by endogenously produced PG. Although evidence was obtained indicating that BK augmented PG production by adherent cells, an additional effect of BK appeared to be a significant sensitization of the two signal-dependent precursors to inhibition by PGE.
Molecular manipulation using a tunnelling microscope.
In a very short time the scanning tunnelling microscope has become an important tool in surface science, and physics in general. Its primary use has been to obtain atomic-resolution images of surfaces, but recently, efforts have been made to use it to manipulate materials as well as image them. One may now reasonably ask if it is possible to move and alter matter predictably on an atomic scale. Here we report the accomplishment of the smallest yet, purposeful, spatially localized changes in matter, effected on a graphite surface. We believe that the changes result from the pinning of individual organic molecules to the graphite. The reverse manipulation, the removal of pinned molecules, has also been demonstrated. Finally, we have evidence that we can remove a portion of a pinned molecule, effectively performing transformations on single molecules using the tunnelling microscope.
Enhanced killing of Candida albicans by murine macrophages treated with macrophage colony-stimulating factor: evidence for augmented expression of mannose receptors.
The effect of macrophage colony-stimulating factor (CSF-1) on killing of Candida albicans by murine peritoneal macrophages was determined. The killing capacity of resident peritoneal macrophages was unaffected by CSF-1. However, proteose-peptone-elicited peritoneal exudate macrophages that had been pretreated with CSF-1 (greater than or equal to 1000 U/ml) for 24 or 48 hr exhibited a significantly enhanced capacity to kill C. albicans. CSF-enhanced killing appeared to be independent of endogenously produced interferon-alpha/beta (IFN) in that enhancement by these two agents differed with regard to onset of the effect, target cell responsiveness, and duration of augmented killing. In addition, a highly specific anti-IFN antiserum that totally neutralized IFN augmentation of candidacidal activity had no effect on CSF-induced enhancement. Evidence was obtained indicating that CSF, unlike IFN, augmented mannose-inhibitable binding and ingestion of C. albicans, suggesting that augmented expression of mannose-receptors by CSF-treated macrophages was at least partially responsible for the enhanced killing.
Dynorphin and related opioid peptides enhance tumoricidal activity mediated by murine peritoneal macrophages.
The influence of dynorphin A (DYN) and related opioid peptides on the tumoricidal function of activated murine peritoneal exudate macrophages (PEM) was investigated. Addition of DYN to macrophage cultures previously activated with mixed alpha + beta-interferon (IFN-alpha/beta) and bacterial lipopolysaccharide (LPS) significantly enhanced their ability to lyse P815 murine mastocytoma cells in a 16 hr chromium-release assay. The effects of DYN were dependent on prior macrophage activation. Peptide subfragments of DYN were effective in a manner similar to that of the 17-amino-acid parent molecule, indicating that peptide interaction with either kappa or delta-opioid receptors on the effector cell is effective in potentiating lytic function. The involvement of opiate receptors was confirmed by inhibition of the effects of DYN and leucine enkephalin by the opioid receptor antagonist naloxone. Finally, in addition to IFN-alpha/beta-primed macrophages, DYN also augmented tumoricidal function in PEM primed for cytotoxicity by either gamma-interferon (IFN-gamma) or the calcium ionophore A23187, indicating that DYN potentiates function in activated macrophages independent of the specific mode of activation.
Natural killer cell resistance in K-562 cell sublines.
Sublines of the hematopoietic stem cell line K-562 were tested for their susceptibility to human natural killer (NK) cell activity. A correlation was found between the degree of NK-mediated lysis and the presence or absence of particular chromosomal markers. K-562 subline susceptible to lysis by NK were found to express karyotypically a deletion 9- and a marker 8(t1-18), whereas resistant sublines did not express these markers. A cloned K-562 subline B1V was chosen as representative of a resistant subline. This subline was resistant to lysis even after prolonged incubation and activation of the NK cells with interferon. However, it was found that B1V was lysed by both antibody-dependent, complement-mediated and antibody-dependent cellular mechanisms at levels comparable to those seen with NK-sensitive K-562 sublines. Subline B1V did compete poorly with NK-sensitive K-562 in cold-target inhibition; however, conjugate-formation assays demonstrated that the binding of NK cells to B1V cells is comparable to that of NK-sensitive K-562 cells. We suggest that cells of the cloned line B1V are recognized normally by NK cells but do not activate the lytic mechanism of the bound NK cell. Treatment of the resistant clone B1V with neuraminidase did not lead to enhanced levels of lysis. Protein extracts of NK-sensitive K-562 sublines efficiently inhibited lysis by NK cells but extracts of the resistant clone, B1V, did not inhibit lysis, suggesting that the clone lacks cell surface determinants involved in the post-recognitive activation of the NK cytolytic mechanism.
Treatment of fungal sinusitis with autogenous vaccine. (A case report).
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