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C Fewtrell

Publications and source records attributed to C Fewtrell.

51 records · Page 3Linked to original sources
PubMed1980

Larger oligomers of IgE are more effective than dimers in stimulating rat basophilic leukemia cells.

The relative activity of rat IgE oligomers in eliciting secretion from mast cells and tumor basophils was examined using stable oligomers prepared by cross-linking IgE with dimethyl suberimidate. Oligomers were tested in vivo using passive cutaneous anaphylaxis (PCA) and in vitro by measuring their capacity to induce histamine release from normal rat mast cells and [3H]-5-hydroxytryptamine release from rat basophilic leukemia (RBL) cells. The PCA results confirmed previous work that showed no large differences in the activity of dimers, trimers, and higher oligomers of IgE. The same was also true with normal rat mast cells; however, the RBL cells sharply discriminated between the variously sized oligomers. The stimulatory activity of all oligomers on the RBL cells was enhanced by D2O. The findings imply that the manner by which the clustering of the receptors for IgE leads to generation of signals in RBL cells involves a mechanism capable of discriminating between a variety of polymeric states of the receptors. In addition, our results suggest that no more than a few hundred trimers or an even smaller number of higher oligomers are capable of inducing a considerable amount of secretion from these cells.

Animals↗
PubMed1979

IgE mediated triggering of rat basophil leukemia cells: lack of evidence for serine esterase activation.

Inhibition of mediator release from mast cells and basophils by diisopropylfluorophosphate (DFP) and other organophosphorus compounds known to inhibit serine esterases has in the past led to the hypothesis that immunologic triggering of these cells involves an activatable serine esterase. In this study we have shown that two nonphosphorylating or poorly phosphorylating structural analogs of two potent phosphorylators inhibit release of incorporated serotonin from cultured rat basophil leukemia cells. We conclude that, by itself, inhibition of immunologic mast cell triggering by phosphorylating organophosphorus compounds can no longer be considered evidence for involvement of an activatable serine esterase in mast cell triggering.

Animals↗
PubMed1978

Localized mast cell degranulation induced by concanavalin A-sepharose beads. Implications for the Ca2+ hypothesis of stimulus-secretion coupling.

Concanavalin A (Con A) covalently linked to Sepharose 4B beads induced localized degranulation of sensitized rat peritoneal mast cells in regions of contact between beads and cells. This degranulation was Ca2+ dependent and was not seen when sensitized mast cells bound to beads conjugated with a nonstimulating lectin, wheat germ agglutinin, or when unsensitized mast cells bound to Con A-Sepharose. The finding that sensitized mast cells which had adhered to Con A-Sepharose beads degranulated in regions of the cell away from the area of bead contact if exposed to soluble Con A excluded the possibility that the localized release was due to a redistribution of the IgE receptors or putative Ca2+ channels to the region of bead contact. The results suggest that, if an influx of Ca2+ is the mechanism for initiating mast cell degranulation, then the opening of Ca2+ channels in the plasma membrane of activated mast cells is a localized event and that Ca2+ acts locally within the cell to initiate exocytosis.

Animals↗
PubMed1977

Molecular events during membrane fusion. A study of exocytosis in rat peritoneal mast cells.

We have used thin section and freeze-fracture electron microscopy to study membrane changes occurring during exocytosis in rat peritoneal mast cells. By labeling degranulating mast cells with ferritin-conjugated lectins and anti-immunoglobulin antibodies, we demonstrate that these ligands do not bind to areas of plasma membrane or granule membrane which have fused with, or are interacting with, granule membrane. Moreover, intramembrane particles are also largely absent from both protoplasmic and external fracture faces of plasma and granule membranes in regions where these membranes appear to be interacting. Both the externally applied ligands and intramembrane particles are sometimes concentrated at the edges of fusion sites. The results indicate that membrane proteins are displaced laterally into adjacent membrane regions before the fusion process and that fusion occurs between protein-depleted lipid bilayers. The finding of protein-depleted blebs in regions of plasma and granule membrane interaction raises the interesting possibility that blebbing may be a process for exposing the granule contents to the extracellular space and for the elimination of excess lipid while conserving membrane proteins.

Antibodies↗
PubMed1975

Anti-immunoglobulin-induced histamine secretion by rat peritoneal mast cells studied by immunoferritin electron microscopy.

We have used ferritin-conjugated divalent and monovalent anti-Ig antibodies to study simultaneously, histamine secretion and the ultrastructural distribution and redistribution of Ig receptors on rat peritoneal mast cells. We conclude that (a) divalent anti-Ig is required for both receptor redistribution and for calcium-dependent degranulation and histamine release, (b) divalent anti-Ig induces patching and pinocytosis but not capping of Ig molecules, (c) neither capping nor pinocytosis are required for triggering and if clustering is necessary, then less than 10 Ig molecules are required per cluster, and (d) degranulation (and histamine release) is not an all or none response of the mast cell.

Animals↗
PubMedDate not supplied

GP fundholding--half a good policy.

GP fundholding has arguably achieved more desirable changes in health provision than any other facet of the health service reforms, but as a policy it remains incomplete and deeply flawed. The challenge is to build on the policy without losing the considerable positive achievements of the scheme. Christopher Fewtrell describes how North Derbyshire Health Authority approached this complex policy dilemma.

Cost-Benefit Analysis↗