Biomedical subjects

S S Williams

Publications and source records attributed to S S Williams.

31 records · Page 2Linked to original sources

PubMed1994

Empirical tests of an information-motivation-behavioral skills model of AIDS-preventive behavior with gay men and heterosexual university students.

This article contains empirical tests of the information-motivation-behavioral skills (IMB) model of AIDS-preventive behavior (J.D. Fisher & Fisher, 1992; W.A. Fisher & Fisher, 1993a), which has been designed to understand and predict the practice of AIDS-preventive acts. The IMB model holds that AIDS-preventive behavior is a function of individuals' information about AIDS prevention, motivation to engage in AIDS prevention, and behavioral skills for performing the specific acts involved in prevention. The model further assumes that AIDS-prevention information and motivation generally work through AIDS-prevention behavioral skills to influence the initiation and maintenance of AIDS-preventive behavior. Supportive tests of the model, using structural equation modeling techniques, are reported with populations of gay male affinity group members (n = 91) and heterosexual university students (n = 174).

Acquired Immunodeficiency Syndrome↗

PubMed1993

Arrest of human lung tumor xenograft growth in severe combined immunodeficient mice using doxorubicin encapsulated in sterically stabilized liposomes.

Incorporation of polyethylene glycol-derivatized phospholipids into liposomes results in carriers that can enhance the therapeutic efficacy of encapsulated drugs by imparting the ability to evade the reticuloendothelial system and remain in the circulation for prolonged periods. In this study, doxorubicin encapsulated in these sterically stabilized liposomes (S-DOX) is shown to completely arrest the growth of human lung tumor xenografts in severe combined immunodeficient (scid) mice. Doxorubicin administered at equivalent doses as free drug or encapsulated into conventional liposomes was ineffective at completely arresting the growth of this human tumor, although a decrease in tumor growth rate compared to untreated controls was observed. Scid mice were found to be significantly more susceptible to the toxic effects of doxorubicin than were immunocompetent C.B-17 control mice, a characteristic that is likely to result from the deficit in DNA repair mechanisms previously identified in scid mice. However, doxorubicin toxicity in scid mice could be minimized while maintaining the antitumor activity of doxorubicin encapsulated in sterically stabilized liposomes by administering the drug in multiple weekly injections at low doses. This report provides the first evidence that antitumor drugs delivered in sterically stabilized liposomes are more effective at arresting the growth of human tumors than are conventional delivery systems. In addition, the scid mouse is presented as a viable model in which to study novel chemotherapeutic approaches to the treatment of human cancer.

Animals↗

PubMed1993

The study of human neoplastic disease in severe combined immunodeficient mice.

Experimental models of human neoplastic diseases are used in attempts to reconstruct events that occur in patients with cancer. Although in vitro systems provide a wealth of information about the cellular and molecular biology of tumor cells, they are inadequate for studies that address the complexities of human neoplasia pertaining to metastasis, experimental therapeutics, and immunity. Since the late 1960s, athymic nude mice have provided an opportunity to study the growth and, in some cases, the metastasis of xenografted human tumors in vivo. Recently, the availability of severe combined immunodeficient (scid) mice has provided an alternative model for studying human malignancies and has led to numerous reports of its distinct advantages over nude mice. When direct comparisons have been made, it has often been apparent that human tumors grow better and are more likely to metastasize in scid mice than in nude mice. Indeed, some human tumors which have never before been propagated in vivo will engraft in scid mice. Furthermore, the unique capability of scid mice to support human immunocompetent cells offers the potential to study the human immune response to tumors. This article outlines the current progress toward defining and using scid mice in models of human neoplastic disease. Characteristics which distinguish scid mice from nude mice are emphasized and a discussion of future prospects is included.

Animals↗

PubMed1992

Engraftment of human peripheral blood leukocytes into severe combined immunodeficient mice results in the long term and dynamic production of human xenoreactive antibodies.

Severe combined immunodeficient (SCID) mice engrafted with human peripheral blood leukocytes (hu-PBL-SCID) represent a potentially important small animal model for the study of human immune function. Attempts to generate human primary immune responses to exogenous Ag in the hu-PBL-SCID have had limited success which raises questions about the functional capacity of human lymphocytes in the SCID environment. Here, we demonstrate that the spontaneously secreted human Ig in hu-PBL-SCID includes antibodies with specificity for several different mouse RBC (mRBC) proteins. These antibodies apparently reflect the transfer of peripheral B cells which are responsible for the production of naturally occurring xenoreactive antibodies in the donor. Western blot analysis showed that engraftment of anti-mRBC specificities was random among mice receiving PBL from the same donor sample. In at least one mouse, this engraftment was polyclonal and included human IgM and IgG which recognized at least 12 different mRBC proteins ranging in size from 35 to > 200 kDa. Anti-mRBC specificities were found to vary with time demonstrating a dynamic expression of the human xenoreactive repertoire in hu-PBL-SCID. In contrast to mice engrafted with human PBL, mice engrafted with another source of human B cells, i.e., tumor-infiltrating leukocytes, produced very little or no human anti-mRBC antibody. Ag-driven proliferation of xenoreactive clones may result in a skewing of the engrafted human B cells in hu-PBL-SCID which could account in part for the limited ability of hu-PBL-SCID to respond to exogenous Ag. The long term production of anti-mRBC antibodies and the modulation of the expressed xenoreactive repertoire observed in hu-PBL-SCID represents an opportunity to study the molecular genetics and cell biology of the human humoral immune response to a defined complex Ag.

Adsorption↗

PubMed1988

Electrophoretic analysis of P-glycoproteins produced by mouse J774.2 and Chinese hamster ovary multidrug-resistant cells.

P-glycoprotein (P-gp) plays a fundamental role in multidrug resistance. The quantity of P-gp relates to the degree of drug resistance. A comparison was made between P-gps in mouse and hamster cell lines in both Laemmli and modified Fairbanks gel systems. Both proteins are derived from precursors of similar size that undergo differential N-linked glycosylation. The electrophoretic mobility and the amount of P-gp are remarkably dependent on the conditions of analysis. Notably, boiling P-gp before Laemmli gel electrophoresis decreases its mobility by an amount that is equivalent to approximately equal to 15 kDa and results in an apparent diminution in the amount of protein. The latter effect can give a false impression concerning the quantity of P-gp in cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1988

Distinct P-glycoprotein precursors are overproduced in independently isolated drug-resistant cell lines.

A family of P-glycoproteins are overproduced in multidrug-resistant cells derived from the murine macrophage-like line J774.2. To determine whether individual family members are overproduced in response to different drugs, the P-glycoprotein precursors in several independently isolated cell lines, which were selected for resistance to vinblastine or taxol, were compared. Individual cell lines selected with vinblastine overproduced P-glycoprotein precursors of either 120 or 125 kDa. Taxol-selected cell lines overproduced either the 125-kDa precursor or both precursors simultaneously. Two similar but distinct peptide maps for the mature P-glycoproteins were observed. These maps corresponded to each precursor regardless of the drug used for selection. One vinblastine-resistant cell line switched from the 125- to the 120-kDa precursor when grown in increasing concentrations of drug. This change coincided with the overexpression of a distinct subset of mRNA species that code for P-glycoprotein. It is concluded that precursor expression is not drug-specific. These data suggest that individual overproduced P-glycoprotein family members are translated as distinct polypeptides. The results may help to explain the diversity in the multidrug-resistant phenotype.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1987

Biosynthesis of heterogeneous forms of multidrug resistance-associated glycoproteins.

Multidrug-resistant J774.2 mouse macrophage-like cells, selected for resistance to colchicine, vinblastine, or taxol, overexpress antigenically related glycoproteins with distinct electrophoretic mobilities. These plasma membrane glycoproteins are likely to play a pivotal role in the expression of the multidrug resistance phenotype. To determine how these multidrug resistance-associated glycoproteins differ, the biosynthesis and N-linked carbohydrate composition of these proteins were examined and compared. Vinblastineor colchicine-selected cells made a 125-kDa precursor that was rapidly processed (t1/2 approximately equal to 20 min) to mature forms of 135 and 140 kDa, respectively. Heterogeneity between the 135- and 140-kDa forms of the molecule can be attributed to N-linked carbohydrate. In contrast, taxol-selected cells made two precursors, 125 and 120 kDa, which appeared within 5 and 15 min after the onset of pulse labeling, respectively. They were processed to mature forms of 140 and 130 kDa. Since a single deglycosylated precursor or mature form was not observed after enzymatic removal of N-linked oligosaccharides, other differences, besides N-linked glycosylation, which occur in early processing compartments, are likely to account for the two multidrug resistance-associated glycoproteins in taxol-selected cells. These results demonstrate that a family of multidrug resistance-associated glycoproteins can be differentially expressed.

Alkaloids↗

PubMed1979