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A Champion

Publications and source records attributed to A Champion.

6 recordsLinked to original sources
PubMed1992

Comparison in different tissue preparations of the in vitro pharmacological profile of RP 67580, a new non-peptide substance P antagonist.

We describe the effects of RP 67580, a new non-peptide substance P (SP) antagonist, on tachykinin-induced contractions of guinea-pig ileum, trachea and urinary bladder, rabbit pulmonary artery and rat portal vein. All NK1 agonists tested (SP, Septide, SPOMe and [Pro9]SP) contracted guinea-pig ileum, trachea and urinary bladder (pD2 = 7.5 to 9.1), but they had no effect on rabbit pulmonary artery or rat portal vein (pD2 < 6). RP 67580 inhibited these effects: guinea-pig ileum, pA2 = 7.1 to 7.6; guinea-pig trachea and urinary bladder, pKB = 6.3 to 6.8. The difference in RP 67580 activity in these tissues might be due to the existence of subtypes of NK1 receptors. RP 67580 (1 microns) did not affect the contractions induced by the two NK2 agonists, NKA and [Lys5, MeLeu9, Nle10]NKA(4-10) (pA2 < 6), except in guinea-pig ileum (pA2 = 7.3-7.5) where these two NK2 agonists interact apparently with NK1 receptors. In the tissue preparations used, RP 67580 (1 micron) was without effect on contractions induced by the NK3 agonists: NKB and senktide. These results indicate the high selectivity for NK1 receptors of RP 67580. In all cases, similar results were obtained with another non-peptide SP antagonist, (+/-) CP-96,345. The present work provides further evidence that RP 67580 and (+/-) CP-96,345 exert in vitro a potent, selective and competitive antagonistic action on NK1 receptors and suggests the existence of at least two distinct NK1 receptor subtypes in some guinea-pig peripheral organs.

Animals↗
PubMed1991

Immunodominant carbohydrate determinants in the multicellular stages of Dictyostelium discoideum.

Two families of glycoprotein are defined in Dictyostelium discoideum by the presence of different glycoconjugates, both of which are highly immunogenic in mice. The previously described monoclonal antibodies MUD50 and MUD62 recognize the glycoconjugates and identify the respective glycoprotein families. Both types of glycosylation occur on vegetative and developmentally regulated glycoproteins. The immunodominant components of both families are reportedly O-linked sugars, but Western blots do not identify any glycoprotein that has both O-glycans, suggesting that there are two independently processed types of O-linked glycosylation in D. discoideum. The synthesis of the two O-glycan families is affected by glycosylation-defective mutations. Strains with a mutation at the modB locus lack one of these glycosylation types (that recognized by MUD50) and this mutation alters the size of two minor glycoproteins in the second family. Two new mutants, HU2470 (mod-352) and HU2471 (mod-353), lack the epitope recognized by MUD62. The two mutations map to different chromosomes. The mod-353 mutation also affects the size of PsA, a cell surface glycoprotein carrying the modB-dependent O-glycan.

Animals↗
PubMed1990

IgG-dependent generation of platelet-activating factor by normal and low density human eosinophils.

We have compared normal and low density human eosinophils for their ability to generate platelet activating factor (PAF) in response to IgG-dependent and nonimmunologic stimulation. After 45 min incubation with IgG-coated Sepharose beads the concentrations of cell-associated PAF recovered from normal density eosinophils were significantly greater than from low-density eosinophils or neutrophils. Moreover, eosinophils stimulated with calcium ionophore A23187 had a considerably greater capacity to generate PAF than had previously been described. Although the quantities of cell-associated PAF recovered from normal and low density eosinophils and neutrophils after A23187 stimulation were similar, the amounts of extracellular PAF recovered from both eosinophil populations were significantly greater than from neutrophils. The amounts of PAF recovered from the low density eosinophils may not reflect the full synthetic capacity of these cells, because PAF-turnover was found to be more rapid than that observed with normal density eosinophils. When exogenous [3H]PAF was added to the two stimulated eosinophil populations subsequent analysis of the [3H]PAF metabolites by DIOL-HPLC revealed that low density eosinophils incorporated PAF into the phosphatidylcholine (PC) pool more rapidly than did normal density eosinophils or neutrophils. Alkaline hydrolysis of the PC fraction from whole cell extracts followed by treatment with acetic anhydride resulted in all the PC-associated radioactivity being converted to [3H]PAF, confirming PAF incorporation to PC via this pathway. These findings suggest that the contribution of eosinophils to inflammatory processes through the generation of PAF may be greater than previously appreciated, and that Ig-mediated stimulation may be important in initiating generation of the mediator. Low density eosinophils, that are presumed to be similar to tissue eosinophils, may have a role in regulating PAF concentrations in tissues through their enhanced rate of metabolism.

Calcimycin↗
PubMed1989

The activated eosinophil in allergy and asthma.

Our studies indicate that human eosinophils can be activated in terms of up-regulation of surface receptors, increased membrane lipid generation, and enhanced cytotoxicity by a variety of pharmacological mediators, through IgE-, IgG-, and complement-dependent pathways. PAF is an impressive activator of eosinophil function and is the most potent chemotactic mediator for eosinophils so far described. It is not selective in that neutrophils are also attracted by PAF. In our hands, IL-1, IL-2, granulocyte/macrophage-colony stimulating factor, tumor necrosis factor, interferon-gamma, and IL-5 tested over a wide concentration range gave very weak chemotaxis for eosinophils in vitro. Nevertheless, in vivo infiltration of eosinophils into the site of allergic tissue reactions is closely associated with the local accumulation of activated (CD4+, IL-2 rec+) T cells. We suggest, therefore, that the selective eosinophil infiltration seen in allergic inflammation may result from the initial recruitment and activation of granulocytes by lipid mediators and the subsequent selective activation of eosinophils by cytokines.

Asthma↗
PubMed1977

The contribution of an adult educationalist to a trainers' group.

I have summarized my findings as a non-medically qualified educationalist attending regularly at meetings of a group of general-practitioner trainers. I believe that it is essential for trainers to learn to draw general principles from specific examples in order to help trainees to learn. Two other contributions an educationalist can make are promoting counselling relationships and helping trainers understand more deeply their own relationships with their patients.

England↗