Biomedical subjects
Publications and source records attributed to W McWilliams.
Real three-dimensional models and three-dimensional images were used in a test of mental rotation. Although the 33 men performed better than the 33 women when presented three-dimensional images (14.4 and 11.2), this sex difference disappeared when real models were used (17.5 and 17.3).
The potentiation of the biological activity of recombinant porcine growth hormone (pGH) by immunologic manipulation was investigated. An anti-pGH monoclonal antibody, designated PS-7.6, was generated and its effect on pGH was evaluated in hypophysectomized (hypox) rats. As expected, administration with pGH for 5 consecutive days promoted these animals to grow. The effect was further augmented when pGH was given together with PS-7.6 antibody and the enhancing ability of the antibody lasted beyond the treatment period. The growth profile of rats receiving antibody alone did not differ from that of untreated controls, indicating that PS-7.6 antibody by itself was not a growth stimulant. The possible mechanism of action of the antibody was investigated by analyzing blood and tissue samples of animals following injection with 125I-labeled pGH either in its free form or complexed with PS-7.6 antibody. As compared to the pGH levels in animals receiving free pGH, approximately a half pGH was released into circulation from the injection sites when it was given in a complex form. Furthermore, 2-4-fold increases in pGH deposition were also found in various tissues of animals treated with pGH-antibody complexes over that of respective tissues of animals receiving free pGH. Therefore, the present findings suggest that PS-7.6 antibody is capable of augmenting the somatogenesis of pGH and the effect is, at least in part, explainable by its ability in altering the pharmacokinetics and biodistribution of pGH in animals.
1. Topical application of 14C-viprostol, a synthetic prostaglandin E2 analogue, to laboratory animals resulted in a significant depot of radioactivity in the skin at the application site in all species studied: mouse, rat, guinea pig, rabbit and monkey, with longer residence times in the larger species. 2. The location of the 14C-label in the skin in mice and monkeys was determined by microscopic autoradiography. Evaluation of the autoradiograms show rapid penetration of the drug into the skin via the hair follicles. 3. In mouse distribution of radioactivity was evident in the stratum corneum and down the hair shafts by 30 min. after dosing. By 2 h radioactivity was also observed throughout the viable epidermis; in the dermis only the hair shafts contained significant radioactivity. At 72 h after dose removal, radioactivity was evident only in the hair follicles and hair shaft. 4. In monkey the residence time of radioactivity in the skin was significantly longer than in mouse, but the general distribution pattern was similar in both species. 5. The presence of viprostol in the hair follicles and epidermal layer after topical administration is consistent with its extensive skin metabolism previously reported.
Single doses of 14C-labeled bisantrene, a new antitumor agent, were administered intravenously at 10 and 100 mg/kg to mice bearing intraperitoneally implanted B16 melanoma. At 24 hr after dosing, the tumors contained relatively high drug concentrations as compared to most of the other tissues. The concentrations averaged 2.4 and 28.3 micrograms/g tumor and the tumor/blood concentration ratios were 40/1 and 29/1 for the low and high doses, respectively.
A sensitive and specific radioimmunoassay for mitoxantrone in serum has been developed. The procedure allows direct measurement of mitoxantrone in unextracted serum samples, by using antisera from rabbits immunized with mitoxantrone-BSA antigen. Tritiated mitoxantrone of high specific radioactivity (ca. 15 Ci/mmol) was used as a radio-tracer ligand. The assay allows the detection of as little as 50 pg/ml and the quantitation of 75 pg/ml in 0.5 ml serum samples. Standard curves were linear in the concentration range of 75-2500 pg/ml, at antiserum dilutions of 1:15,000. The assay shows good reproducibility: coefficients of variation of 3-6% were obtained by analyzing five samples/concentration at 75, 100, 250, 500, and 1000 pg/ml. There was no cross reactivity with the major metabolite in human serum, having concentrations of up to 10,000 pg/ml. Serum samples collected at various time intervals from rats dosed intravenously with mitoxantrone (0.5 mg/kg), were analyzed for unchanged mitoxantrone by RIA. The drug concentrations decreased from 32 ng/ml at 0.5 h to 0.45 ng/ml by 24 h after dosing. Mitoxantrone, a dihydroxyanthracenedione derivative (1), is an antitumor agent currently used in clinical trials with very encouraging results, especially in metastatic breast cancer, and low incidence of adverse reactions (2-4). The drug is being administered intravenously at doses up to 14 mg/m2. Preliminary pharmacokinetic studies (to be published separately) indicate rapid distribution, followed by slow clearance rates from the tissues. The sensitivity of the currently available (HPLC) methods (5, 6) is of about 5-20 ng/ml in serum.(ABSTRACT TRUNCATED AT 250 WORDS)