Rhythm in mitosis and cytoplasmic solid concentration in Landschütz ascites tumour cells.
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Biomedical subjects
Publications and source records attributed to E Mayhew.
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Syngeneic P91 mastocytomas undergo immunological rejection in the eyes of DBA/2 hosts by a process involving ischemic necrosis. Histopathological features of the ischemic necrotizing pattern of tumor rejection are consistent with a delayed-type hypersensitivity (DTH) effector mechanism. The present study sought to determine if selective depletion of cytotoxic T lymphocyte (CTL) or DTH effector functions by in vivo treatment with either CD8+ or CD4+ monoclonal antibodies would convert the pattern of tumor rejection from an ischemic necrosis DTH-like pattern to a piecemeal necrosis, CTL-like pattern. In vivo treatment with anti-CD4 antibody resulted in the elimination of both CTL and DTH responses, yet the intraocular tumor underwent a characteristic ischemic necrotizing pattern of rejection. By contrast, treatment with anti-CD8 antibody eliminated CTL activity without diminishing DTH responses. Surprisingly, intraocular tumors grew progressively in these hosts even though intense tumor-specific systemic DTH responses were demonstrable. Collectively, the results indicate that classical DTH effector mechanisms mediated by CD4+ T cells are either actively excluded from the intraocular milieu or are suppressed within the eye.
The calcium channel blockers 'DMDP' [N-3,4-dimethoxyphenethyl)-N-methyl-2-(2-naphthyl-m-dithane-2-prop ylamine)] and verapamil inhibited the active efflux of adriamycin from adriamycin-resistant P388 leukemia cells but had no effect on the drug-sensitive cell line. However, after removal of the calcium channel blockers, DMDP at a low drug concentration caused a much longer inhibition of this efflux pathway than verapamil. This may be attributed to the higher binding affinity of DMDP for receptor sites.
An extrusion technique was used to obtain multilamellar lipid vesicles (MLV, liposomes) of different size distribution. The larger MLV ranged in diameter from 0.1 to 2.6 mu and the smaller from 0.1 to 1.5 mu, and both were composed of phosphatidylserine/phosphatidylcholine/cholesterol in the molar ratio 1:4:5. After intravenous injection of large and small MLV containing encapsulated [3H]cytosine arabinoside (ara-C), their distribution in various organs showed that the fraction of the dose associated with lung was greater for large MLV relative to small MLV by factors of 3.6--10 after 1 hr, 5.3--14 after 4 hr, and 17--23 after 24 hr. For large MLV more than 50% of drug remaining in vivo after 24 hr was associated with the lung, compared with 2.5% for small MLV. Almost all of the 3H associated with lung at all times for both large and small MLV could be accounted for by unchanged ara-C. Differences in 3H levels between small and large MLV in other tissues were much less dramatic or were not significant. The apparent in vivo stability of the liposomes was not affected by size. The data are consistent with an initial trapping of large MLV during first passage in the lung, with subsequent binding and retention. Release of ara-C from large or small MLV in the lung is apparently slow relative to meatbolism.
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