PubMed Health⌕ Search

Biomedical subjects

M M Dale

Publications and source records attributed to M M Dale.

At least 37 records · Page 2Linked to original sources
PubMed1985

Phorbol myristate acetate causes in guinea-pig lung parenchymal strip a maintained spasm which is relatively resistant to isoprenaline.

The effect of phorbol myristate acetate (PMA) was compared with that of histamine on the guinea-pig lung parenchymal strip. PMA, 10(-5) M, caused a slowly developing sustained contraction which had approximately the same magnitude as the maximal histamine contraction. Isoprenaline, at 10(-5) M, caused 86% relaxation of the histamine contraction but only 22% relaxation of the PMA contraction. Forskolin, at 10(-5) M had a similar action to isoprenaline on the effects of both spasmogens while aminophylline, 5 X 10(-4) M, was considerably less effective. Sodium nitroprusside had little effect on the histamine contraction and actually increased the PMA spasm. It is suggested that protein kinase C may have a role in the tonic phase of the contraction of bronchiolar smooth muscle. These findings could have relevance for the delayed phase of asthma, which is known to be insensitive to beta-agonists.

Aminophylline↗
PubMed1985

Superoxide generation by either 1-oleoyl-2-acetylglycerol or A23187 in human neutrophils is enhanced by indomethacin.

Indomethacin at a concentration (10(-4) M) which depressed the effect on O2- generation by fMet-Leu-Phe, markedly enhanced O-2 generation by both 1-oleoyl-2-acetylglycerol and the calcium ionophore, A23187. These results are explicable in terms of the hypothesis that synergism between cytosolic calcium and protein kinase C is involved in signal transduction for the respiratory burst in the human neutrophil.

Calcimycin↗
PubMed1985

Prostaglandins E1 and E2 enhance the stimulation of superoxide release by 1-oleoyl-2-acetylglycerol from human neutrophils.

Superoxide release from human neutrophils was stimulated either by receptor activation (using fMet-Leu-Phe) or by activating, independently, each of the two pathways considered to be involved in signal transduction--calcium mobilization (using the ionophore, A23187) and protein kinase C activation (using phorbol myristate acetate or 1-oleoyl-2-acetylglycerol). Prostaglandin E1 (3 X 10(-5) M) decreased fMet-Leu-Phe-stimulated superoxide release, had no effect on superoxide release stimulated by A23187, or by phorbol myristate acetate, and markedly enhanced the superoxide release stimulated by 1-oleoyl-2-acetylglycerol. Similar enhancement was obtained with prostaglandin E2.

Alprostadil↗
PubMed1985

The inhibitory effect of histamine on lymphoid tissue proliferation in mice.

Histamine, injected subcutaneously (10 mg/kg), inhibited the DNA synthesis response to a contact-sensitizing agent (picryl chloride) and also had an inhibitory effect on DNA synthesis in untreated mice. The synthesis was measured by 5-[125I]iodo-2'-deoxyuridine incorporation in spleen, lung, liver, and peripheral lymph nodes and the inhibitory effect was marked and consistent in spleen in both sensitized and nonsensitized animals, but was variable in the other tissues. Since histamine is believed to activate suppressor cells, it is suggested that the inhibition of DNA synthesis in picryl chloride-treated mice is due to the activation of those suppressor cells which limit the specific DNA synthesis in response to the contact-sensitizing agent. The inhibition of DNA synthesis in untreated mice could be due to the activation of suppressor cells that control the ongoing immune response to environmental antigens.

Animals↗
PubMed1984

Synergism between A23187 and 1-oleoyl-2-acetyl-glycerol in superoxide production by human neutrophils.

Concentrations of the calcium ionophore A23187 and 1-oleoyl-2-acetyl-glycerol, which on their own are minimally effective in stimulating superoxide release from human neutrophils, show marked mutual potentiation when given simultaneously. The potentiating effect of the diacylglycerol can be shown to be dose-related. These results support the hypothesis that synergism between cytosolic calcium and protein kinase C is involved in signal transduction for the respiratory burst in the human neutrophil.

Calcimycin↗
PubMed1984

Synergism between phorbol ester and A23187 in superoxide production by neutrophils.

Concentrations of phorbol myristate acetate and the calcium ionophore, A23187, which by themselves are minimally effective in stimulating superoxide generation in human neutrophils show marked mutual potentiation when given together. This supports the hypothesis that synergism between cytosolic calcium and protein kinase C is involved in the stimulus/activation coupling of the respiratory burst in the neutrophil.

Calcimycin↗
PubMed1984

The effect of inhibitors of macromolecular synthesis on neutrophil-mediated antibody-dependent cellular cytotoxicity: exacerbation by mitomycin C.

Previous work correlating 51chromium release with aggregate formation between neutrophils and target cells had indicated that unlike killing by lymphocytes, neutrophil-mediated antibody-dependent cellular cytotoxicity (NADCC) in the guinea-pig against hepatoma cells required that three or more neutrophils were simultaneously attached to the target cells. There was virtually no lysis when only one or two neutrophils were attached. This raised the possibility that the target cells could repair lesions inflicted by one or two cells and this was investigated using inhibitors of macromolecular synthesis. Actinomycin D, cycloheximide, puromycin and adriamycin had no effect--militating against a repair mechanism. Surprisingly, mitomycin C led to an exacerbation of NADCC. Chlorambucil, which like mitomycin C is an alkylating agent, had a similar effect though less marked. One explanation of this phenomenon which seemed likely was that the drugs were affecting the cell cycle of the target cells, i.e. that being alkylating agents they might be holding the target cells in a susceptible phase of the cycle. Experiments in which the target cells alone were preincubated with mitomycin C for varying periods of time (2-18 h) before the start of the assay, did not confirm this. However a thirty minute preincubation with mitomycin C of either the neutrophils or neutrophils plus the target cells resulted in increased cytolysis. The results indicate that the effect of mitomycin C in exacerbating NADCC is primarily on the neutrophil.

Animals↗
PubMed1984

A comparison of dimaprit, nordimaprit, methylamine and chloroquine as inhibitors of mitogen-induced lymphocyte activation.

Methylamine and chloroquine both 'lysosomotropic' agents (i.e. agents which sequester in lysosomes) caused a dose-related inhibition of mitogen-induced lymphocyte activation in the concentrations which have previously been shown to increase the pH of lysosomes. The dose-response curves of inhibition of mitogen-induced lymphocyte activation for chloroquine and methylamine are very steep and are similar to the dose-response curves obtained with dimaprit and nordimaprit, but very different from the flat dose-response curves previously described for histamine. Approximate IC50 values were methylamine 6.4 mM, dimaprit 0.13 mM, nordimaprit 0.03 mM and chloroquine 18 microM. It is suggested that the mechanism of action of methylamine and chloroquine may be related to their lysosomotropic action and consequent interference with ligand-receptor processing, and that dimaprit and nordimaprit but not histamine may act by a similar mechanism.

Cells, Cultured↗
PubMed1980

ADCC mediated by non-adherent mononuclear and polymorphonuclear cells of the guinea-pig.

Various cell populations of the guinea-pig have been assessed for their capacity to mediate antibody-dependent cellular cytotoxicity (ADCC) against guinea-pig and mouse tumour cell targets. Activity was found to be present in the spleen and blood but was absent in lymph nodes. Macrophages did not appear to lyse target cells in the system used and cytotoxicity among the mononuclear (MN) cells was confined to the non-adherent cells. Considerable lysis was induced by polymorphonuclear (PMN) cells in the presence of antiserum and their activity was greater than that of equivalent numbers of spleen MN cells. The lytic activity of PMN cells appeared to be specific for antibody coated target cells since uncoated bystander cells were not lysed.

Animals↗
PubMed1979

Inhibition of guinea-pig lymphocyte activation by histamine and histamine analogues.

1 The incorporation of [3H]-thymidine into guinea-pig lymphocytes stimulated by a plant lectin (concanavalin A), soluble antigen (tuberculin (P.P.D.)) and syngeneic hepatoma cells, was partially inhibited (50%) by histamine in vitro. 2 The effect of histamine on both mitogen and antigen dose-response curves suggests a non-competitive, probably physiological antagonism. 3 The inhibitory dose range of histamine lay between 10 nM and 30 microM with an ID50 of approximately 400 nM. 4 The potency order for histamine analogues for the inhibition of lymphocyte activation was histamine greater than or equal to 4-methylhistamine greater than 2-methylhistamine greater than 3-methylhistamine. This is in accord with the mediation of the response through an H2-receptor. 5 H2-receptor antagonists reversed the inhibitory effect of histamine in a dose-related manner, but both metiamide and burimamide, in high concentrations, augmented lymphocyte activation in their own right. This precluded the determination of affinity constants and made it impossible to state with certainty that the inhibition of lymphocyte activation by histamine was mediated by an H2-receptor.

Animals↗
PubMed1978

A mammalian muscle with the pharmacological characteristics of slow tonic muscle.

The guinea-pig isolated cremaster muscle gave tetrodotoxin-resistant dose-related contractures with acetylcholine, carbachol and the depolarizing neuromuscular blocking agents. The dose-response curve to suxamethonium in tetrodotoxin 2 X 10(-7)M could be shifted to the right with tubocurarine 10(-6)M. KCl, 0.1M, produced slow sustained contractures of the muscle. With the cremaster nerve-muscle preparation tetanic contractions at 20 Hz were maintained over several minutes. Tetrodotoxin eliminated the twitch response to single shock nerve stimulation but not the sustained increase in tension produced by suxamethonium. The results suggest either that there is a component of slow tonic muscle in the guinea-pig cremaster or that the cremaster consists of a type of focally innervated muscle which has pharmacological responses qualitatively different from those of most focally innervated muscles so far described.

Animals↗
PubMed1977

Failure to obtain positive MEM tests in either cell-mediated immune conditions in the guinea-pig or in human cancer.

The macrophage electrophoretic mobility test described by Caspary and Field (1971) and modified by Pritchard et al. (1973) was investigated in various models of cell-mediated immune conditions in the guinea-pig and in cancer in man. No positive results were obtained in 92 guinea-pig experiments. Only 17 of 154 experiments on 74 patients gave definite positives in experiments with human cancer and a few positive results were obtained with normal healthy subjects.

Animals↗
PubMed1977

Cytotoxicity of guinea-pig lymphoid cells against guinea-pig hepatoma cells in tissue culture.

The cytotoxic effect of guinea-pig lymphoid cells on guinea-pig hepatoma cell lines in tissue culture was investigated, using the microplate technique of Takasugi and Klein (1970). The effect of lymphoid cells from guinea-pigs immunized against tumor cells was compared to that of cells from normal controls. Several ratios of effector to target cells (10 : 1, 50 : 1, 150: 1, 250 : 1) were used. In Hartley guinea-pigs immunized with allogeneic tumour cells, peripheral blood lymphoid cells from 14/16 animals showed significant cytotoxicity against that tumour in culture. In a syngeneic tumour/host system, 7/13 animals showed cytotoxicity. Spleen cells gave less consistent results in both systems. The cytotoxic activity of subpopulations of immune lymphocytes against tumour cells in vitro was investigated. It was found that although both T-cell-enriched and T-cell-depleted cell populations exhibited cytotoxicity against tumour cells, the unfractionated cell population was the most effective. This suggests that some degree of cell cooperation may be involved in the cytotoxicity. Antibody-dependent cellular cytotoxicity was also obtained. A T-cell-depleted population of normal cells was shown to be cytotoxic to tumour cells in the presence of serum from immune animals. This type of cytotoxicity could be obtained concomitantly with cell-mediated cytotoxicity in the same animals.

Animals↗
PubMed1977

The effects of metiamide on cell-mediated immune reactions in the guinea-pig.

1 The effects of the H2-receptor antagonist, metiamide, on two types of cell-mediated immune response in vivo was investigated in the guinea-pig, in a test of the hypothesis that H2-receptor antagonists would result in 'runaway' unregulated hypersensitivity reactions. 2 Metiamide in doses of 5 mg-125 mg/kg given by 6-hourly injection during sensitization and challenge did not modify the delayed hypersensitivity reaction to tuberculin. 3 Metiamide in doses of 25-125 mg/kg given by injection, 6-hourly throughout sensitization to dinitrofluorobenzene (DNFB) and subsequent challenge six days later, did not modify the contact sensitivity reaction to DNFB. 4 It is concluded that metiamide, given during these cell-mediated immune reactions in the guinea-pig, does not enhance cell-mediated hypersensitivity responses.

Animals↗
PubMed1976

The denervated cremaster muscle of the guinea-pig as a pharmacological preparation.

The pharmacological responses of both denervated and innervated cremaster muscle preparations from the guinea-pig have been investigated and compared. Acetylcholine (ACh) dose-response curves were obtained in both preparations. The affinity constants for (+)-tubocurarine and for atropine were calculated and indicated that the ACh receptors in both preparations were nicotinic. Histamine dose-response curves could be obtained only in the denervated preparation. The response was unaltered by metiamide, and the affinity constant for mepyramine fitted in with those previously obtained by others on ileum and trachea, indicating that the histamine receptors are H1 in type. Sustained contractions were obtained to adrenaline and noradrenaline but not isoprenaline, with the denervated preparations. Schultz-Dale responses were obtained with denervated muscle in sensitized guinea-pigs. This preparation did not respond to 5-hydroxytryptamine, bradykinin, or the slow-reacting substance of anaphylaxis.

Acetylcholine↗