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Biomedical subjects

M J Forrest

Publications and source records attributed to M J Forrest.

45 records · Page 3Linked to original sources
PubMed1987

A pharmacological and histological examination of the microcirculation of the rat subcutaneous air-pouch: microcirculation of the rat air-pouch.

The effects of histamine, 5-hydroxytryptamine (5-HT) and prostaglandin E2 (PGE2) on plasma protein extravasation in the rat subcutaneous air-pouch have been studied. Both histamine and 5-HT produced increases in plasma protein extravasation which were inhibited by specific receptor antagonists. Plasma protein extravasation induced by PGE2 was partially inhibited by either a 5-HT receptor antagonist (methysergide) or by a combination of H1 and H2 receptor antagonists (mepyramine and cimetidine). A combination of all three antagonists further reduced plasma protein extravasation. These results suggest that PGE2 increases vascular permeability indirectly via the degranulation of mast cells. This supposition was confirmed by histological evidence of extensive mast cell degranulation following the injection of PGE2 but not following histamine, 5-HT or saline injection. Using a technique of vascular labelling, following the intravenous injection of Monastral blue dye, plasma extravasation induced by histamine, 5-HT or PGE2 was observed to be restricted to post-capillary venules and was not observed in arterioles or capillaries. Electron microscopic examination of the tissue revealed the presence of monastral blue particles trapped between endothelial cells. These findings suggest that the microcirculation of the rat subcutaneous air-pouch behaves in an analogous manner to that of other tissues.

Air↗
PubMed1986

Kinetics of the generation and action of chemical mediators in zymosan-induced inflammation of the rabbit peritoneal cavity.

Acute inflammation was induced by intraperitoneal injection of zymosan (yeast cell walls) in the rabbit. Peritoneal inflammation was monitored by the local accumulation of intravenously-injected Evans blue dye (which binds to plasma albumin) and of polymorphonuclear leukocytes (PMNLs). The zymosan-induced exudate fluid contained a microvascular permeability-increasing factor or factors which, unlike histamine and bradykinin, had a long duration of action when tested in rabbit skin and was dependent on circulating PMNLs. Using radioimmunoassay, high levels of rabbit C5a, or C5a des Arg, were detected in the exudate fluid and accounted for much of the permeability-increasing activity, as judged by skin bioassay after separation on Sephadex G-100. The vasodilator prostaglandin, prostaglandin I2 (PGI2), was generated in the inflammatory reaction, as judged by the presence of high levels of 6-oxo-PGF1 alpha detected in the exudate by radioimmunoassay. However, in contrast to observations in rabbit skin, inhibition of prostaglandin generation had a relatively small effect on peritoneal oedema formation. C5a and C5a des Arg increase microvascular permeability by a PMNL-dependent mechanism in the rabbit. However, in response to zymosan, protein leakage was detected considerably earlier than PMNL accumulation. A hypothesis to account for this difference is proposed.

Animals↗
PubMed1985

Generation of C5a and prostacyclin (PGI2) in an inflammatory response to zymosan and a reversed passive Arthus-type reaction in the peritoneal cavity of the rabbit.

Exudate fluids were removed from the rabbit peritoneal cavity 2 h after the injection of zymosan or the initiation of a reversed passive Arthus-type reaction. Inflammatory oedema was measured using Evans blue dye extravasation and the concentrations of C5a and the PGI2 metabolite, 6-oxo-PGF1 alpha, were measured by radioimmunoassay. High levels of C5a were found in these inflammatory exudates and we suggest that the extravascular generation of C5a is important in the induction of increased microvascular permeability. The presence of PGI2 may have an enhancing effect on plasma protein leakage.

Animals↗
PubMed1985

Lymphocyte subpopulations in patients with hydroxocobalamin responsive megaloblastic anaemia.

Lymphocyte subpopulations and intrinsic factor and gastric parietal cell antibodies have been measured in 23 patients with megaloblastic anaemia who responded to treatment with hydroxocobalamin. The ratio of helper (OKT4) to suppressor (OKT8) lymphocytes was significantly increased in patients with intrinsic factor antibody compared with those who lacked the antibody. No such correlation was found for gastric parietal cell antibody. Alterations in the lymphocyte helper to suppressor (OKT4:OKT8) ratio may be associated with pernicious anaemia.

Anemia, Macrocytic↗
PubMed1983

Detection of the complement fragment C5a in inflammatory exudates from the rabbit peritoneal cavity using radioimmunoassay.

We describe a radioimmunoassay for rabbit C5a and its use to obtain evidence of extravascular C5a generation in two inflammatory reactions in the peritoneal cavity. These observations, together with the potent activity of C5a in inducing increased microvascular permeability involving circulating PMN leukocytes, strengthen the case for considering C5a an important inflammatory mediator. These findings offer an explanation for the many different experimental inflammatory reactions where oedema formation can be suppressed either by systemic depletion of complement or by depletion of circulating PMN leukocytes.

Animals↗
PubMed1981

Human C5a des Arg increases vascular permeability.

C5a were generated in human plasma by incubation with zymosan in the presence of a carboxypeptidase B inhibitor. The carboxypeptidase inhibitor was added to prevent cleavage of the carboxyl terminal arginine from C5a and enabled it to be purified on the basis of spasmogenic activity on the guinea-pig isolated ileum. When injected into rabbit skin, purified C5a induced marked plasma leakage over a 30-min period, but only if the substance was first mixed with a vasodilator substance such as prostaglandin (PG)E2. The responses to C5a + PGE2 did not appear to be related to anaphylatoxic, histamine-releasing activity because an antihistamine, mepyramine, had only a small effect on plasma leakage. Further, removal of the carboxyl terminal arginine by carboxypeptidase B abolished activity on the ileum but not in the skin. The observation that both human C5a and C5a des Arg were able to increase vascular permeability in vivo suggested a parallel with leukotactic activity in vitro. In support of this, no responses to C5a + PGE2 were obtained in rabbits depleted or circulating polymorphonuclear leukocytes. Thus, inflammatory edema resulting from extravascular complement activation may be dependent on 2 components: a leukocyte/endothelial cell interaction triggered by C5a, and the concomitant generation of a vasodilator, prostaglandin.

Anaphylatoxins↗