Howard S Ramsdell

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Physiologically based pharmacokinetic modeling (PBPK) and gas uptake experiments have been used by researchers to demonstrate the competitive inhibition mechanism between trichloroethylene (TCE) and 1,1-dichloroethylene (DCE). Expanding on their work, we showed that this pharmacokinetic interaction was absent at levels of 100 ppm or less of either chemical(More)
Bullfrog (Rana catesbeiana) tadpoles were exposed to malathion in water in a 28-d static renewal test. The effects of malathion on survival, growth, development, and loss of equilibrium posture were determined. Survival was significantly decreased at malathion concentrations of 2,500 micrograms/L and higher. Development of tadpoles was delayed significantly(More)
A recent study by Hayes et al. (J. Natl. Cancer. Inst., 83: 1226-1231, 1991) found an increased risk of malignant lymphoma associated with exposure to 2,4-dichlorophenoxyacetic acid (2,4-D) in pet dogs. We conducted a study to determine the extent to which dogs absorb and excrete 2,4-D in urine after contact with treated lawns under natural conditions.(More)
Hepatic cytosolic fractions prepared from 14 human donors were analysed for glutathione S-transferase (GST) activity towards synthetic aflatoxin B1-8,9-epoxide (AFBO). In addition, GST-AFBO activity of pooled human liver cytosols was compared with rat, hamster, and mouse liver cytosol GST-AFBO activities. Consistent with previous studies, human liver(More)
The biotransformation of the potential human carcinogen aflatoxin B1 (AFB1) was studied using hepatic microsomes from the rat, mouse, monkey, and human. Initial rates of AFB1 oxidation to aflatoxins Q1, M1, and P1, as well as the reactive intermediate AFB1-8,9-epoxide, were determined using a high performance liquid chromatography assay. The rates of(More)
Senecio jacobaea (SJ) was incubated in sheep rumen fluid-buffer mixtures to determine if metabolism and(or) detoxication of pyrrolizidine alkaloids (PA) was occurring. The nontoxic reduction metabolite, 7 beta-hydroxy-l-methylene-8 alpha-pyrrolizidine, was not detected when SJ-rumen fluid incubation extracts were subjected to high performance liquid(More)
Previous studies have suggested that mice are resistant to the carcinogenic effects of aflatoxin B1 (AFB1) and that this resistance is largely the result of expression of an isoenzyme of glutathione S-transferase (GST) with high activity toward AFB1-8,9-epoxide. Significant interstrain differences in cytosolic GST activities toward a variety of substrates(More)
As part of the studies of the biochemical basis for species differences in biotransformation of the carcinogen aflatoxin B1 (AFB1) and its modulation by phenolic antioxidants, we have investigated the role of mouse liver glutathione S-transferase (GST) isoenzymes in the conjugation of AFB1-8,9-epoxide. Isoenzymes of GST were purified to electrophoretic(More)
A distinct, nonfocal expression pattern was observed for glutathione S-transferase P1-1 (rGSTP1-1) in rats exposed to either hexachloro-(HCB) or pentachlorobenzene (PeCB). The nonfocal expression was localized to the centrilobular region with the most intense staining nearest the central vein. A Western blot analysis revealed a 5- and 15-fold induction of(More)
[Alpha-13C]- and [alpha,beta-13C]valine were administered sequentially to a patient with methylmalonicacidemia to clarify the metabolic pathway of valine from methylmalonic acid semialdehyde to methylmalonyl-CoA. Methylmalonic acid was isolated from multiple urine samples, purified, and analyzed by 13C nuclear magnetic resonance spectroscopy. Contrary to(More)