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Biomedical subjects

P Waring

Publications and source records attributed to P Waring.

61 records · Page 4Linked to original sources

Structural relationship of epipolythiodioxopiperazines and their immunomodulating activity.

Epipolythiodioxopiperazines were tested for their immunoregulatory activity in vitro. Using the macrophage adherence test as a measure of inhibition of phagocytosis, their effect on stimulator cells in mixed lymphocyte cultures and their ability to inhibit mitogen stimulation of T lymphocytes, a hierarchy of activity was observed, with sporidesmin being the most active, followed by gliotoxin and 1,4-dimethyl-3,6-epidithio-2,5-dioxopiperazine. Derivatives of gliotoxin such as dehydro-, trisulfide and tetrasulfide gliotoxin have activities comparable to gliotoxin. The dimethylthioether derivative of gliotoxin was devoid of activity. The presence of reducing agents abrogated the activity of epipolythiodioxopiperazines. This suggests that the bridged disulfide moiety is the single most important chemical entity for their activity. The differential activities of the active compounds may be attributable to their variations in lipophilic properties.

Animals↗

Identification of an agent in cultures of Aspergillus fumigatus displaying anti-phagocytic and immunomodulating activity in vitro.

When cultured in vitro, Aspergillus fumigatus generated a metabolite(s) with anti-phagocytic activity as tested by macrophage adherence to plastic and phagocytosis of particulate matter. The metabolite(s) appeared after 3 d culture and reached a peak concentration after 5-6 d. The action of the anti-phagocytic agent(s) was rapid (5-15 min) and appeared not to alter membrane permeability or cause rapid cell death. Treatment of stimulator spleen cells with the agent(s) inhibited their ability to induce alloreactive and major histocompatibility complex restricted cytotoxic T cells. The metabolite(s) was chloroform-soluble and separated into three biologically active compounds on thin-layer chromatography. These compounds were purified greater than 1000-fold and one of them was identified as gliotoxin, a known metabolite of A. fumigatus, based upon NMR and IR spectroscopy, mass spectrometry, biological properties and other data.

Adhesiveness↗

Inhibition of human brain dihydropteridine reductase [E.C.1.6.99.10] by the oxidation products of catecholamines, the aminochromes.

Dihydropteridine reductase from human brain has been purified to homogeneity using a naphthaquinone affinity column followed by chromatography on a 5'-AMP-Sepharose column. Contrary to earlier findings, dopamine (I), noradrenaline (II), and adrenaline (III) do not inhibit this enzyme at concentrations below 200 microM, but their oxidation products, the respective aminochromes (IV, V and VI) are inhibitors. The Ki values for adrenochrome (VI) are reported.

Benzopyrans↗