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R H Adamson

Publications and source records attributed to R H Adamson.

At least 181 records · Page 10Linked to original sources
PubMedDate not supplied

A model for interpreting the tracer labeling of interendothelial clefts.

We extended the model describing the low molecular weight electron dense tracer wake in the interendothelial cleft and surrounding tissue to describe the time-dependent transport of intermediate size solutes of 1.0-3.5 nm radius by convection and diffusion in an interendothelial cleft containing a fiber matrix. This model provides a quantitative basis on which to reinterpret electron microscopic studies of the distribution of tracers such as horseradish peroxidase (HRP; molecular weight = 40,000; Stokes radius = 3.0 nm) along the interendothelial cell cleft from the lumen to the tissue. For example, we show that, in contrast to our results with low molecular weight tracers, the wake of large molecular weight tracers on the abluminal side of the junctional strand is not likely to be detected, because the concentration of the tracer is predicted to be very low in most experiments. Thus the lack of a tracer such as HRP on the abluminal side of the junctional strand and in the tissue is not as strong evidence against the presence of a cleft pathway as suggested previously. The model does provide the basis for the design of experiments to locate both the principal molecular sieve and breaks in the junctional strand from the standing gradient on the luminal side of the junctional strand. An important experimental variable is the pressure in the vessel lumen which can be varied between 0 and 30 cm H2O to change the contributions of diffusive and convective transport to transcapillary exchange through he interendothelial cleft. This approach will also allow the testing of models for transcapillary pathways for large molecules by measuring the distribution of fluorescent traces across the microvessel wall and in the tissue surrounding the microvessel using confocal microscopy.

Algorithms↗
PubMedDate not supplied

Studies on the antitumor activity of gallium nitrate (NSC-15200) and other group IIIa metal salts.

Several group IIIa metal salts, eg, aluminum nitrate, gallium nitrate, indium nitrate, and thallium chloride, have been evaluated for in vivo toxicity in mice and rats, for cytotoxicity in tumor cells in vitro, and for activity against a broad spectrum of experimental rodent tumors. The position of these agents in the periodical table roughly parallels their toxicity, the LD50s decreasing with increasing atomic weights. This parallel also exists with regard to in vitro cytotoxicity to Walker 256 carcinosarcoma cells. Although all of the metal salts had activity against the ascites Walker 256 carcinosarcoma, they were ineffective in ascites leukemias, plasma cell tumors, or Ehrlich carcinoma. Gallium nitrate was particularly active against solid tumors transplanted subcutaneously, suppressing the growth of six of eight tumors more than 90%. Because of its demonstrated antitumor activity in rodents and its uptake and concentration by various animal and human tumors, gallium nitrate has potential usefulness in the treatment of solid tumors in man and has been entered into a phase I study at the National Cancer Institute.

Aluminum↗
PubMedDate not supplied

The pharmacologic disposition of 4'-(9-acridinylamino)methanesulfon-m-anisidide in mice and rats.

The pharmacologic disposition of 4'-(9-acridinylamino)methanesulfon-m-anisidide (AMSA; NSC-141549), a new antitumor agent presently under consideration for phase I evaluation in man, was studied in mice and rats with 14C-AMSA labeled in the 9-carbon of the acridine ring. Radioactivity was selectively localized in the liver where it was present mainly as metabolites of AMSA. After 2 hr, nearly 50% of the plasma radioactivity was bound to protein and did not dissociate upon Sephadex G-200 chromatography. Radioactivity was rapidly eliminated in the bile; greater than 50% of the administered dose was excreted by this route in 2 hr. Bile/plasma ratios of greater than 400:1 indicated an active transport mechanism. The biliary transport mechanism was saturable with therapeutic doses. AMSA was found to be especially vulnerable to nucleophilic attack by alkylthiols resulting in displacement of 4-amino-3-methoxymethanesulfonanilide and the formation of the corresponding 9-alkylthioether of acridine. The major radioactive biliary metabolite (accounting for 90-95% of the biliary radioactivity) possessed the same chromatographic properties as the thiolysis product of AMSA and glutathione (GSH). A 40% reduction in liver GSH and a 20% reduction of liver GSH-transferase activity occurred after AMSA administration to mice. The pharmacologic disposition of AMSA can best be explained by a nonenzymatic nucleophilic attack on the 9-carbon atom of AMSA by endogenous thiols, resulting in the formation of 9-thioethers of acridine. Such an attack by low molecular weight thiols results in a product that is eliminated in urine and bile, whereas interaction with protein-thiol groups results in prolonged retention of the acridine moiety.

Acridines↗