Faculty Bibliography

A biokinetic model for absorption and distribution of 222Rn in the body following ingestion in drinking water was developed. The rate parameters for the model are derived from historical human data reported in experiments of Harley et al. (1958) and Hursh et al. (1965). The biokinetic model fits the human data of Hursh et al. well for whole body retention following ingestion of 222Rn in water on an empty stomach. The equivalent dose to stem cells for stomach and colon cancer is estimated to be 1.6 x 10(-9) Sv B(q-1). The model calculations yield 4 and 3 calculated stomach and colon cancers from continuous intake of water at the estimated U.S. average of 5.5 B(q) L-1

The alpha dose to cells in tissues or organs other than the lung has been calculated using the solubility coefficients for Rn-222 measured in human tissue. The annual alpha dose equivalent from Rn-222 and decay products in most tissues is a maximum of 30% of the annual average natural background dose equivalent (1 mSv) for external and internally deposited nuclides (not including the dose equivalent for Rn-222 decay products to cells in bronchial airways). The dose to the small population of lymphocytes located in or under the bronchial epithelium is a special case and their annual dose equivalent is essentially the same as that to basal cells in bronchial epithelium (200 mSv) for continuous exposure to 200 Bq.m-3. The significance of this dose is uncertain because the only excess cancer observed in follow-up studies of underground miners with high Rn-222 exposure is bronchogenic carcinoma

The alpha dose to cells in bronchial airways in the beagle dog during historical exposures to Rn-222 decay products is calculated using updated information on airway morphometry, cell nucleus depth, mucus thickness, physical dosimetry and atmospheric characteristics. The alpha dose per unit exposure to basal cell nuclei in the upper airways ranges from 2 to 7 mGy.WLM-1 (excluding the trachea) depending upon the exposure protocol used by the Institute (Battelle Northwest Laboratories versus University of Rochester). The dose to alveolar tissue is 3 mGy.WLM-1. In the human lung, the dose factor for the bronchial airways is 9 mGy.WLM-1 and for the pulmonary parenchyma 0.5 mGy.WLM-1. The human tumours appear primarily in the first few branching airway generations while the only tumours observed in the animals were in the bronchioloalveolar region suggesting a difference in cell sensitivity to alpha radiation

We have previously shown that the binding of Trypanosoma cruzi trypomastigotes to glutaraldehyde-fixed mammalian cells has the characteristics of a receptor-mediated process and that it mimics the attachment step of the invasion of live cells by this parasite. In this study we examined the metabolic requirements for the attachment of trypomastigotes to glutaraldehyde-fixed fibroblasts. The attachment of trypomastigotes to fixed cells is prevented when the energy conservation mechanisms are inhibited with the drugs 2-deoxyglucose, sodium azide, antimycin, crystal violet, oligomycin, N,N'-dicyclohexylcarbodiimide, and carbonyl cyanide 3-chlorophenylhydrazone. However, under the same experimental conditions, the movement of parasites is not significantly affected. Several of these drugs totally inhibit the penetration of the parasite into live target cells. We conclude that the attachment of trypomastigotes to mammalian cells is an active process that requires trypomastigote energy. In addition, we present evidence that penetration into nonphagocytic cells can also be an active process. Trypomastigotes can be seen in scanning electron micrographs traversing extended lamellipodia and entering paraformaldehyde-fixed epithelial cells. Cytochalasin D, a drug that disrupts microfilaments and prevents the formation of plasma membrane extensions mediated by actin, had little or no effect on trypomastigote invasion, while it inhibited Salmonella entry into epithelial cells

The protozoan parasite Trypanosoma cruzi can infect many distinct mammalian cell types. The parasites enter cells through the formation of phagocytic vacuoles, but later are found free in the cytosol, where they multiply as amastigotes. Using transmission electron microscopy we found that within 2 h after infection 70% of the parasites, including examples of both mammalian forms (trypomastigotes and amastigotes), were inside partially disrupted vacuoles or free in the cytosol. We demonstrated that the pH of vacuoles containing recently interiorized parasites is acidic, through immunocytochemical localization of the acidotropic compound DAMP (18) in their interior. Increasing the vacuolar pH with chloroquine, ammonium chloride, methylamine, or monensin significantly inhibited the escape of the parasites into the cytosol. These results are compatible with the hypothesis that an acid-active hemolysin of T. cruzi (15) might be involved in the escape mechanism

Utilizing the scanning electron microscope, we compared a new guidewire with copolymer coating with standard Teflon-coated, coiled-spring guidewires in both clinical and in vitro settings. Intense thrombogenicity was observed with the Teflon-coated guidewires with formed thrombi ranging in size from 50-100 microns. No formed thrombus was noted on any of the specimens of the copolymer guidewire, although isolated clumps of platelets and erythrocytes without fibrin strands were seen infrequently. We conclude that the copolymer guidewire is markedly less thrombogenic than Teflon-coated guidewires

The role of basic fibroblast growth factor-(bFGF) induced proteinases in basement membrane (BM) invasion by bovine capillary endothelial (BCE) cells was studied using a quantitative in vitro assay previously described (Mignatti et al., 1986). 125I-iododeoxyuridine-labeled BCE cells were grown for 72 h on the human amnion BM, and cell invasion was determined by measuring the radioactivity associated with the tissue after removal of the noninvasive cell layer. BCE cells were noninvasive under normal conditions. Addition of human bFGF to either the BM or to the stromal aspect of the amnion induced BCE cell invasion with a dose-dependent response. This effect was maximal in the presence of 70 ng/ml bFGF, and was inhibited by anti-FGF antibody. Transforming growth factor beta, as well as plasmin inhibitors and anti-tissue type plasminogen activator antibody inhibited BCE cell invasion. The tissue inhibitor of metalloproteinases, 1-10 phenanthroline, anti-type IV and anti-interstitial collagenase antibodies had the same effect. On the contrary, anti-stromelysin antibody and Eglin, an inhibitor of elastase, were ineffective. The results obtained show that both the plasminogen activator-plasmin system and specific collagenases are involved in the invasive process occurring during angiogenesis