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Biomedical subjects

W R Bruce

Publications and source records attributed to W R Bruce.

144 records · Page 8Linked to original sources

A model for the action of vinblastine in vivo.

A model for the action of vinblastine (VLB) on cells multiplying exponentially in vivo with a generation time, T(G), has been derived. It is based on the assumption that cells attempting to pass through mitosis in the presence of VLB lose their proliferative capacity and that this lethal effect occurs only when the cells are exposed to a concentration of VLB which is above a critical value, C(k). The model leads to two predictions. First, that the percentage of cells surviving at any time after exposure to a dose, D, of VLB is 100% if D < D(k) and decreases to 0% after a time, T(G), following a dose D >/= D(k).2(T G/T1/2), where D(k) represents the dose of VLB required to produce the concentration C(k), and T(1/2) is the half-life of the VLB in vivo. Second, that the time, T(G), at which the percentage of cells surviving an exposure to VLB, at doses greater than D(k).2(U G/T1/2), decreases to zero should be equal to the generation time of the cells. Both of these predictions were confirmed experimentally which indicates that the model adequately explains the action of VLB in vivo.

Animals↗

The effect of dietary ascorbic acid and alpha-tocopherol on fecal mutagenicity.

The effect of supplemental ascorbic acid and alpha-tocopherol on fecal mutagenicity was examined in 2 studies involving 20 healthy human donors aged 22-55 years. The vitamins were given at a dose of 400 mg daily each. The mutagen was extracted from individual frozen feces samples with dichloromethane, and assayed with Salmonella Typhimurium tester strain TA100 without microsomal activation. In the first study, with a single donor on a controlled diet, the fecal mutagenicity decreased (P less than 0.001) on treatment to 21% of control. In the second study, with 19 donors on free-choice diets, the mutagenicity in producers on treatment decreased (P less than 0.01) to 26% of control. Addition of ascorbic acid and alpha-tocopherol directly to feces led to no change in mutagenicity. Antioxidants in the diet may have a role in lowering the body's exposure to endogenously produced mutagens.

Adult↗

Concanavalin A (NSC-143504): its action on experimental tumor cells and possible use in cancer chemotherapy.

Concanavalin A administered to mice kills KHT fibrosarcoma tumor cells and, less markedly, AKR lymphoma cells at doses where it has no effect on numbers of normal hematopoietic colony-forming cells. Concanavalin A in vitro agglutinates suspensions of cells prepared from murine and human tumors but does not agglutinate suspensions prepared from most normal mouse tissues. In spite of its selective action against tumor cells at the cellular level, the possibilities for using concanavalin A therapeutically are limited by its unusual toxicity, a generalized vasculitis that is seen in the mouse, monkey, and pig at approximately the same dose level.

Agglutination↗

Classification of aberrant crypt foci and microadenomas in human colon.

Aberrant crypt foci (ACF) can be observed and quantified on the mucosal surface of formalin-fixed human colon resections after staining with methylene blue. To determine whether these ACF could be identified in fresh tissue, 10 colon resections were collected after surgery for colorectal cancer. Unfixed and fixed flat normal colonic mucosa from each colon were scored for ACF under a dissecting microscope after methylene blue staining. The number of ACF per cm2 and the average number of crypts per foci correlated highly in unfixed and fixed mucosa (r = 0.93 and 0.78, respectively). A significantly higher frequency of lesions was found in left-sided compared to right-sided colon resections. To determine whether the topographic features of the ACF gave an indication of the histological appearance, 68 specimens containing ACF or normal mucosa were examined histologically. The presence of slit-like lumen in the crypts of ACF on the mucosal surface correlated with the presence of dysplasia at histology, thus identifying microadenomas. These two observations suggest that the topographic classification of ACF in vivo could be used to distinguish microadenomas, a putative precursor lesion of colon cancer.

Adenoma↗