Biomedical subjects

K J Whaley

Publications and source records attributed to K J Whaley.

4 recordsLinked to original sources

PubMed1992

Controlled vaginal delivery of antibodies in the mouse.

Controlled delivery of monoclonal antibodies to the mucus secretions of the vagina might provide women with passive immunoprotection against both sexually transmitted diseases and unwanted pregnancy. We have developed intravaginal devices composed of poly(ethylene-co-vinyl acetate) (EVAc) that continuously release IgG antibodies for over 30 days into buffered saline, and we have tested these devices in the vagina of mice. Polymeric devices containing either BSA (as a test reagent for proteins) or anti-hCG antibody, when inserted into the vaginas of mice, provided a continuous supply of either BSA or hCG-binding antibodies to the vaginal mucus for 30 days. Antibodies released by the devices achieved high concentration in the mucus within the lumen of the vagina, but did not significantly ascend into the uterine horns, as determined by epifluorescence microscopy of fluorescently labeled mouse IgG and by immunohistochemical localization of rabbit IgG. Our results suggest that long-term intravaginal delivery of functionally intact antibodies can be achieved with devices composed of EVAc.

Administration, Intravaginal↗

PubMed1990

Macromolecules released from polymers: diffusion into unstirred fluids.

Polymers that release macromolecules may be useful for preventing and treating human disease. In certain applications of polymeric controlled release, like drug therapy of brain disease and immunoprotection of mucus epithelia, effectiveness may be limited by diffusion through an unstirred fluid near the polymer. Using computer-assisted epifluorescence microscopy, we have examined the local distribution of fluorescently labelled macromolecules released from an ethylene-vinyl acetate copolymer matrix into unstirred layers of phosphate-buffered water and mid-cycle human cervical mucus. Diffusion coefficients in the fluid were determined by observing the concentration profiles as a function of time. Diffusion coefficients determined for fluorescein, bovine serum albumin, and three classes of human immunoglobulins (IgG, sIgA and IgM) in phosphate-buffered water were in good agreement with literature values. For fluorescein, albumin and IgG, diffusion in mucus was comparable with diffusion in water: the largest molecule tested was slowed by only a factor of 3.

Biocompatible Materials↗

PubMed1986

Monkey lactate dehydrogenase-C4 as a model for the interaction of enzymes with gossypol.

Lactate dehydrogenase-C4 (LDH-C4) plays a central role in the metabolism of spermatogenic and mature sperm cells as well as being an enzyme which is inhibited by gossypol, a male contraceptive. Racemic and (+)-gossypol have equivalent potency as inhibitors of LDH-C4 purified from ejaculated sperm of cynomolgus monkeys. Analogues of gossypol (gossypol-glycine ester Schiff's base, 6,6-dimethoxygossypol and ethyl gossypol) have quantitatively similar inhibitory effects of LDH-C4 activity; apogossypol hexaacetate, however, has no inhibitory effect. Other effective inhibitors of LDH-C4 are antimycin, naphthoquinones and lithocholic acid. LDH-C4 may serve as a model for understanding gossypol binding domains and contraceptive action.

Animals↗

PubMedDate not supplied

Kinetic characterization of the inhibition of purified cynomolgus monkey lactate dehydrogenase isozymes by gossypol.

This report describes the results of the first step in a sequence of experiments designed to test the hypothesis that the sperm-specific isozyme of lactate dehydrogenase (LDH-C4), is a site of action of the potential male contraceptive agent gossypol. Cynomolgus monkey LDH-A4, LDH-B4 and LDH-C4 were purified and kinetically characterized. LDH-A4 and LDH-B4 exhibited "linear mixed-type" inhibition by gossypol with both lactate and pyruvate as variable substrates. LDH-C4 also exhibited "linear mixed-type" inhibition with lactate as substrate. However, the C4 isozyme exhibited "parabolic mixed-type" inhibition by gossypol and substrate inhibition with pyruvate as substrate, the latter due to abortive complex formation. Of the three isozymes, LDH-C4 exhibited the lowest apparent Km for pyruvate and the highest apparent Km for lactate. The LDH-C4 form was found to be the most sensitive isozyme to gossypol inhibition, since it had the lowest apparent Ki values for gossypol inhibition. The effect of gossypol on coenzyme binding to LDH-C4 was examined and gossypol binding was found to inhibit binding and release of NADH but not NAD+, an effect possibly due to its interaction with the more hydrophobic loop region of LDH-C4.

Animals↗