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Biomedical subjects

P G Cunnington

Publications and source records attributed to P G Cunnington.

7 recordsLinked to original sources

Oxygen-binding and immunological properties of complexes between dextran and animal haemoglobins.

Complexes of dextran 20 000 with haemoglobins of sheep, rabbit, dog, bovine and human origin were prepared through alkylation of haemoglobin by N-bromoacetylaminoethylamino-dextran. The yields were uniformly high. Complex-formation in each case was accompanied by the disappearance of reactive thiol groups on the haemoglobin, and by an increase in the affinity of the haemoglobin for oxygen. The immunological properties of dog, rabbit and sheep dextran-haemoglobin were investigated in both homologous and heterologous species. The complexes were found to be non-immunogenic in the homologous species. In heterologous species the anti-haemoglobin response induced by each complex was generally of a similar level to that induced by the haemoglobin alone.

Animals↗

The activity of an anti-allergic compound, proxicromil, on models of immunity and inflammation.

A tricyclic chromone, proxicromil (sodium 6,7,8,9-tetrahydro-5-hydroxy-4-oxo-10-propyl-naphtho (2,3-b) pyran-2-carboxylate), has been tested for activity against certain immunological and inflammatory reactions. When given parenterally it suppressed the development of delayed hypersensitivity reactions in sensitized mice and guinea-pigs but did not affect the rejection of skin allografts in mice. The compound had no activity against certain in vitro correlates of delayed hypersensitivity reactions (lymphocyte transformation and lymphokine activity), but did have an inhibitory effect on lymphokine (MIF) productions at 10(-4) M but not at 10(-5) M. Proxicromil was also found to be active in non-immunologically mediated models of inflammation and in models having an immunological component which are known to be sensitive to non-steroidal anti-inflammatory drugs (adjuvant arthritis, reversed passive Arthus reaction). The activity of this compound was enhanced when administered in arachis oil when compared to its activity in saline. Proxicromil has not direct activity on the development of immune responsiveness but appear to suppress the expression of delayed hypersensitivity and immune complex mediated hypersensitivity reactions by virtue and its anti-inflammatory properties. This activity is not associated with inhibition of cyclo-oxygenase.

Animals↗

Clinical dextrans lack mitogenic activity for normal human lymphocytes in vitro.

In vitro studies on mitogenic stimulation of lymphocytes from a panel of normal volunteers revealed no transformation in response to the presence of dextran 40, 70, 110 or 150 at concentrations ranging from 0.8 to 8,000 microgram/ml. High molecular weight native dextran B512 was mitogenic in 1 individual only. In addition, neither Leuconostoc-derived nor fermentation medium-derived moieties, sometimes present in clinical dextrans, were implicated as lymphocyte mitogens. It is concluded on the basis of these findings that clinical dextrans of average molecular weight 40,000--150,000 are not B- or T-cell mitogens.

Dextrans↗

Naturally-occurring double-stranded RNA and immune responses. IV. Influence of molecular size on antigenicity and adjuvant activity.

The immunological properties of a naturally-occurring double-stranded ribonucleic acid (ds-RNA), obtained from a mycophage of Penicillium chrysogenum, have been studied in relation to molecular size. Materials of reduced size, as reflected by molecular weight measurements, produced by ultrasonication of native ds-RNA, exhibited progressively lowered ability to induce an anti-ds-RNA response in mice. Adjuvant and immunosuppressive activities were of similar magnitude in both high and low molecular weight fractions. Evidence was also obtained of increased toxicity in materials of reduced size.

Adjuvants, Immunologic↗

Naturally occurring double-stranded RNA and immune responses. Effects on plaque-forming cells and antibody formation.

A highly purified preparation of double-stranded RNA, obtained from virus-like particles in Penicillium cultures, was found to affert humoral immune responses in mice differentially depending on its time of administration in realtion to antigen. Double-stranded RNA administered with antigen, or a few hours after antigen, produced a variable degree of enhancement of plaque-forming cell numbers or agglutinating antibody levels depending on the antigen involved. Administration of double-stranded RNA 24 hours before antigen invariably produced a suppressed response. In mice which were either specifically hyporesponsive (tolerant) or non-specifically hyporesponsive (due to age or immunosuppressive drugs) double-stranded RNA administered with antigen resulted in a nearly normal immune response.

Agglutination Tests↗

Protection against gram-negative infections with antiserum to lipid A from Salmonella minnesota R595.

The ability of antisera to lipid A, induced in rabbits by immunization with lipid A complexed to various carriers, to protect mice against gram-negative infection and to inhibit the fluid loss caused by an enteropathogenic strain of Escherichia coli in the piglet ligated gut was investigated. No significant protection was obtained in either case, although passive hemolysis and quantitative precipitation tests showed the presence of antilipid A antibodies in the sera. Fluorescent antibody studies suggest that the lipid A is in a cryptic position on the surface of smooth strains of gram-negative bacteria.

Animals↗