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Biomedical subjects

C J Meade

Publications and source records attributed to C J Meade.

49 records · Page 3Linked to original sources

Mice bearing the ob/ob mutation have impaired immunity.

The obese mutant mouse C57BL/6J ob/ob showed impaired ability to reject skin grafts or react to a contact-sensitising agent in comparison with littermate controls (either +/ob or +/+). Ability of spleen cells from mice bearing the ob/ob mutation to produce a graft-versus-host reaction in C57BL/6J X DBA/2J F1 hybrid mice was not impaired.

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Importance of the spleen for the immuno-inhibitory aciton of linoleic acid in mice.

Certain immuno-inhibitory effects of a polyunsaturated fatty acid, linoleic acid (C18:2), no longer occur after splenectomy of young adult CBA mice. This observation suggest that the spleen is a major intermediary in the action of C18:2 on the lymphoreticular system. Pathways of this action remain to be elucidated. Possibilities include C18:2-stimulated suppressor cell generation in the spleen, or excess biosynthesis of immuno-inhibitory prostaglandins by splenic macrophages.

Animals↗

A mechanism of migration inhibition involving components of the coagulation system.

Lymph from pigs given bacillus Calmette-Guérin (BCG) and stimulated in the drainage area of a cannulated lymph node with tuberculin (PPD) had potent in vitro macrophage migration inhibitory activity. A similar observation has previously been made in sheep by other workers. In the sheep, part of, and in the pig, almost all of, this inhibitory activity was produced, not by a factor resembling the so-called 'migration inhibitory factor', but by a mechanism involving a protease and fibrinogen. It is suggested that exudate cells, having potent coagulation-promoting activity, can promote the deposition of fibrin about themselves, and thus 'trapped' are unable to migrate.

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The mechanism of immunoinhibition by arachidonic and linoleic acid: effects on the lymphoid and reticulo-endothelial systems.

Subcutaneous injection with certain polyunsaturated fatty acids (PUFA), in particular linoleic acid (C18:2), has recently been shown to prolong the survival of skin allografts in mice and to reduce both primary and secondary cytotoxic responses by isolated spleen cells. In this study we have examined changes in the lymphoid and reticulo-endothelial systems of both grafted and ungrafted mice treated according to the schedules shown to prolong allograft survival. Many of the changes in the lymphoid and reticulo-endothelial systems which can be produced by allografting could also be produced in ungrafted animals by PUFA treatment. These changes included: increased 125IudR uptake by spleen, lymph nodes, and bone marrow, increased spleen and lymph node weight, increased proportion of red pulp and granulocyte precursors in the spleen, and reticulo-endothelial activation as shown by an increased rate of carbon clearance. The combined effects of allografting and C18:2 on peripheral lymph node weight were greater than the effect of either treatment alone, but fell short of the sum of both treatments. Allografting increased 125IudR uptake/unit organ weight, not only in the peripheral lymph nodes, but also in bone marrow, thymus and spleen. When allografted animals were C18:2 treated, this increase was considerably reduced, uptake being little different from that in C18:2 treated ungrafted controls. The number of theta-positive cells in the spleen was markedly increased by a tumor allograft, but such an increase could not be seen in allografted animals when treated with C18:2. Whilst prolonged C18:2 treatment led to destructive changes in the spleen, immunoinhibition could still be demonstrated after shorter treatments with C18:2 when no gross histological evidence for tissue destruction was apparent. Partial reversibility of inhibition of cytotoxic activity of isolated spleen cells could be domonstrated when treatment was discontinued.

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Hetrazepine PAF antagonists.

Hetrazepines such as WEB-2086 or WEB-2170 are potent, specific, competitive PAF antagonists binding at the same site as the PAF molecule. Despite their structural similarity to known hypnotic drugs they lack hypnotic actions. They almost certainly bind not only cell-surface but also intracellular PAF receptors, which may explain their activity in disease models in which adherence of neutrophils or other cell types to the vascular endothelium plays a role.

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