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D D Taylor

Publications and source records attributed to D D Taylor.

At least 55 records · Page 3Linked to original sources
PubMed1988

Characterization of plasma membrane shedding from murine melanoma cells.

Tumor cells release intact portions of their plasma membranes in the process of membrane fragment shedding. This released material has been shown to inhibit various synthetic functions of normal cells, which may play an important role in certain patho-physiological events occurring in advanced-stage cancer patients. Our studies on metastatic variants of the murine B16 melanoma, B16-F1 (low incidence of lung colonization) and B16-F10 (high incidence of lung colonization) indicate that the shed membrane fragment material is composed predominantly of vesicles, ranging in size from 20 to 100 nm in diameter. The release of membrane fragments represents a small percentage (approximately 16%) of the total shedding of plasma membrane components. Membrane fragments were shed at a higher rate from the highly "metastatic" (colonizing) B16-F10 cells than from poorly metastatic B16-F1 cells, resulting in a 2-fold greater accumulation of membrane fragment material by cultures of B16-F10 cells than by B16-F1 cultures during the 48-hr assay period. The study of various intracellu ar metabolic processes (protein and RNA synthesis, glycosylation, and generation of ATP) required for the shedding of membrane fragments indicated that the shedding event is only dependent on energy when inhibitors of the above processes are present for 2 hr. Treatment of cells with these inhibitors for 8 hr results in cessation of the shedding process, indicating both a limited pool of components to be shed and the requirement for further synthesis of the shed material. Glycoprotein components of the shed membrane fragments were analyzed by SDS-polyacrylamide gel electrophoresis. In addition to quantitative differences, 2 additional bands were present in fluorographs from SDS-PAGE gels from the B16-F10 membrane fragment material which were not present in fluorographs from B16-F1 fragments. The glycoprotein components of shed membrane fragments were shown to represent selected domains of the cell's plasma membranes, in that only certain plasma membrane glycoproteins are shed as part of membrane fragments. The glycoproteins released as non-particulate molecules into the extracellular environment failed to exhibit these quantitative and qualitative differences.

Adenosine Triphosphate↗
PubMed1988

Evaluation of the 'golden period' for wound repair: 204 cases from a Third World emergency department.

Uncertainty about the existence and duration of a "golden period" for suture repair of simple wounds led us to evaluate prospectively the consequences of delayed primary closure on wound healing. Wounds were eligible for study if they were not grossly infected, and had no associated injuries to nerves, blood vessels, tendons, or bone. Three hundred seventy-two patients underwent suture repair; 204 (54.8%) returned for review seven days later. The mean time from wounding to repair for all patients was 24.2 +/- 18.8 hours. Wounds closed at up to 19 hours after wounding had a significantly higher rate of healing than those closed later: 82 of 89 (92.1%) compared with 89 of 115 (77.4%) (P less than .01). Of 23 wounds sutured 48 or more hours (mean, 65.3) after wounding, 18 (78.3%) were healing at follow-up. In contrast to wounds involving other body areas, the healing of head wounds was virtually independent of time from injury to repair: 42 of 44 (95.5%) wounds involving the head and repaired later than 19 hours after injury were healing, compared with 47 of 71 (66.2%) of all other wounds (P less than .001). On the basis of these data we conclude that there is a 19-hour "golden period" for repair of simple wounds involving body areas other than the head, after which sutured wounds are significantly less likely to heal, and the healing of clean, simple wounds involving the head is unaffected by the interval between injury and repair.

Adult↗
PubMed1987

Effects of retinoic acid on lipolytic activity of tumor cells.

Tumor-producing substances that promote lipolysis in vitro may also account for fat mobilization in cachectic cancer patients. Cachexia might improve if this lipolytic action of cancer cells could be halted. This study examined the lipolytic activities of media from four tumor cell lines after treatment with retinoic acid (RA), a cell differentiation inducer. An in vitro adipocyte bioassay measured lipolysis. All four tumor cell lines were intrinsically lipolytic, with elevated baseline lipolytic activities relative to fibroblast-conditioned controls (128% to 287% of control, p less than 0.05). After a 2-week exposure to RA in culture medium followed by 3 days of continued growth in fresh medium, two of four cell lines (both rat prostatic adenocarcinomas) showed significantly reduced lipolytic activities (16% and 61% of corresponding untreated controls, p less than 0.05). These reductions in lipolytic activity after RA treatment were not generalized phenomena; nor were they simply caused by cell differentiation, as the other cell lines (human malignant melanoma and human ovarian teratocarcinoma) showed no reductions despite evidence of cell differentiation. No effect on lipolytic activity was seen after only a 24-hour exposure to RA. We conclude that RA can affect the lipolytic activity of certain tumor cells in vitro, perhaps by influencing tumor-producing lipolytic factor(s).

Adenocarcinoma↗
PubMed1986

Shedding of plasma membrane fragments. Neoplastic and developmental importance.

The phenomenon of shedding of cell surface macromolecules and their importance in the cancer process has been reviewed with particular emphasis on tumor membrane fragments. With cell activation (during growth or stimulation of normal cells), there is an increase in synthesis, processing, insertion, and eventual, intact release of certain membrane proteins, some of which are proteases. In cancer, these events occur spontaneously and without the temporal, physiological, or hormonal control apparent in normal cells. In a previous review (Black, 1980), many of the consequences of shedding tumor products were described, but the nature of the shed material was not clear. It now seems likely that some proteolytic, procoagulant, and immunosuppressive activities of shed material are contained within membrane particulate material (vesicles). Under normal conditions, shed membrane material (particularly proteolytic activity) may be necessary for cell movement and tissue remodeling which occur during embryogenesis. In cancer, shedding of plasma membrane fragments may be responsible for the key features of the malignant phenotype by the presence and release of proteolytic activity producing the separation of tumor cells from the primary site, invasion of the surrounding tissues by tumor cells, and formation of distinct metastases. Shed plasma membrane fragments may play a central role in tumor progression by enhancing the steps of the metastatic cascade, in particular by increasing tumor embolus formation (by enhanced fibrin deposition and platelet aggregation) and vascular permeability, as well as increasing basement membrane degradation. Shed membrane fragments (containing tumor antigens) either alone or complexed with antibody, may be responsible for blocking the cell-mediated immune reaction by the formation of "blocking factors" or by suppressing the formation of cytotoxic immune pathways. The suppression of immune response formation may be due to blocking of antigen presentation by macrophages (due to inhibition of Ia) or by the induction of Ts1 cells.

Animals↗
PubMed1986

Demonstration of lipolytic activity from cultured human melanoma cells.

Cancer bearing is often accompanied by debilitating cachexia manifested as body weight loss and derangements of host metabolism. We studied lipolytic (fat-mobilizing) activity and glycerol accumulation in culture media exposed to six different human cell lines. An in vitro adipocyte bioassay measured lipolysis. Media from three of four human melanoma cell lines demonstrated significantly elevated lipolytic activities (279-817% of fibroblast-exposed, control medium), as well as significantly more glycerol accumulation (276-1643% of fibroblast medium) which directly correlated with the increased lipolytic activity. Increased lipolytic activity and glycerol accumulation were not generalized phenomena seen with all growing tumor cells, as two cell lines (a human colon carcinoma and the fourth human melanoma line) demonstrated neither significantly increased lipolytic activity nor increased glycerol accumulation compared to fibroblast control medium. This study suggests that certain tumor cells are capable of transferring a lipolysis-promoting activity to the media which bathe them. This activity is demonstrable both as increased lipolytic activity in a bioassay of lipolysis, and as an accumulation of glycerol (an end product of triglyceride lipolysis), in the medium exposed to the growing cells. The tumor factor(s) responsible for this lipolysis-promoting activity may account for the fat wasting that often accompanies malignancy.

Carcinoma↗
PubMed1985

Turnover and fate of I-Ak antigen on the murine macrophage cell surface.

The macrophage plasma membrane is a major site of the cell's activities, including phagocytosis, antibody-dependent cellular cytotoxicity, and antigen presentation. To present antigen, the expression by the macrophage of immune region-associated (Ia) antigen is required. The turnover and fate of this cell surface constituent was studied in macrophages cultured with lymphokine or recombinant interferon-gamma. Surface-labeled subregion I-Ak antigen was lost from the cell surface at a rapid rate, with a half-life of approximately 24 hours. However, the shedding of I-A antigen into the culture fluid was not detected. Therefore, the loss of I-A antigen from the macrophage surface is most likely by its degradation. Upon removal of lymphokine or interferon from macrophage cultures, I-A antigen expression declined, with an apparent half-life of 2 days.

Animals↗
PubMed1985

Late deaths following radiotherapy for pediatric tumors.

From 1953 to 1975, 341 children received megavoltage radiation and survived at least 5 years. Chemotherapy was administered to 189 of these children. Although the expected age-adjusted 30-year survival was 97%, the observed survival was only 83%. Late recurrence of primary tumor was responsible for 24 of 37 deaths. Other causes of death included second neoplasm (4 patients), infection (4 patients), central nervous system complication (2 patients), inanition (1 patient), motor vehicle accident (1 patient), and miscellaneous (1 patient). Thus, 36 of the 37 late deaths were secondary to either the original cancer, a new cancer, or the effects of treatments. Brain tumors and Ewing's sarcoma have more late deaths while neuroblastomas have fewer late deaths than expected. Even after 25 years of follow-up, the survival of this cohort does not parallel that of the general population.

Actuarial Analysis↗
PubMed1985

Membrane vesicles shed by murine melanoma cells selectively inhibit the expression of Ia antigen by macrophages.

We previously demonstrated that membrane vesicles shed by the F10 variant of the murine B16 melanoma cell line inhibited the induction by interferon-gamma (IFN) of murine macrophage immune response region-associated (Ia) antigen expression. In this paper we present evidence that the inhibition of macrophage Ia antigen expression is a selective effect of vesicles and characterize its temporal requirements. Membrane vesicles shed from F10 cells did not affect the expression of macrophage H-2K or H-2D antigens under conditions shown to profoundly inhibit Ia antigen expression. Similarly, the induction of plasminogen activator and interleukin 1 from macrophages was not inhibited by the vesicles. The vesicles did not measurably decrease total cellular RNA or protein synthesis. Macrophages were sensitive to the inhibitory effects of the vesicles during the induction and maintenance phases of Ia expression. Pretreatment of macrophages with vesicles before culture with IFN did not reduce the induction of Ia. The rate of decline of Ia expression after removal of IFN was unaffected by the presence of vesicles. Removal of vesicles from cultures of IFN-treated macrophages resulted in only a partial recovery of Ia expression, suggesting that the inhibition of Ia expression may be a slowly reversible process. The selective and partially reversible inhibition of Ia expression by vesicles shed from the plasma membrane of tumor cells is a possible mechanism whereby tumor-bearing hosts may become immunocompromised.

Animals↗
PubMed1985

Inhibition of recombinant interferon-gamma-induced Ia antigen expression by shed B16 F10 melanoma cell membrane vesicles.

The expression of immune region-associated (Ia) antigens by macrophages is a prerequisite for antigen presentation, which is necessary for the activation of T helper cell function. A decrease in macrophage Ia expression is associated with a decrease in immune function in vitro. However, the effect of diseases accompanied by immunosuppression, such as cancer, on macrophage Ia expression has not been studied. The expression of Ia antigen was induced by the culture of murine peritoneal macrophages with recombinant interferon-gamma (IFN). Maximal expression was achieved after 4 days of culture. Membrane vesicles shed from the murine B16 F10 melanoma cell line inhibited the in vitro induction of Ia expression by 40 to 90% in allogeneic and syngeneic systems. Inhibition was not due to toxicity, a reduction in IFN activity, phagocytosis or contamination of the vesicle preparation with endotoxin, which is an inhibitor of Ia expression. Inhibition exerted by vesicles was prostaglandin-dependent and was over-come by increasing concentrations of IFN. It is possible that the reduction of macrophage Ia antigen expression by tumor cell products, such as shed membrane vesicles, contributes to the immunosuppression of tumor-bearing hosts. Employing IFN to reverse the inhibition provides a strategy for improving the therapy of patients with cancer.

Animals↗
PubMed1985

Inhibition of macrophage Ia antigen expression by shed plasma membrane vesicles from metastatic murine melanoma lines.

Shed plasma membrane-derived vesicles from metastatic variants of the murine B16 melanoma were examined for their ability to inhibit the induction of murine immune region-associated (Ia) antigen expression on macrophages, the initial step in the formation of an immune response. Membrane material that appears as a greater than 50 million-dalton fraction on column chromatography is found only in conditioned media from tumor cells and not in culture media from normal cells, such as murine 3T3 cells. Membrane vesicles from both metastatic variants B16-F1 (low lung colonizing) and B16-F10 (high lung colonizing) were taken up by macrophages; however, only membrane vesicles isolated from the B16-F10 cultures exhibited significant inhibitory activity for Ia induction. This inhibition appears to result from enhanced prostaglandin synthesis, since treatment with aspirin can reverse the membrane vesicle-induced inhibition. The inhibitory component(s) released into the media was demonstrated to be predominantly associated with membrane vesicles; however, the component(s) retained its activity after Triton X-100 treatment, indicating that the intact membrane vesicle was not necessary for the action of the inhibitory material. Treatments with heat (65 degrees C) and proteases (papain) indicated that the inhibitory component(s) is a heat-labile protein.

Animals↗
PubMed1984

Identification of antigenic components recognized by "membrane-bound" antibodies from ovarian cancer patients.

Immunoglobulins, eluted from ascites fluid-derived membrane fragments, were used to identify antigens with which they react from ovarian cancer patients. These immunoglobulin preparations were demonstrated to bind antigens from ovarian tumors, but not from normal ovaries. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to identify the components responsible for the reactivity. The different patients' immunoglobulin preparations were reactive with a similar group of antigens; however, the level of response to each individual component varies. In previous studies, the acid-eluted immunoglobulin was shown to be reactive with tissues other than ovarian tumors. Relating this cross-reactivity with the antigens found in ovarian tumors, we found that some components were found only in ovarian tumors, and others appear to be shared by gynecologic tumors, in general. Of these antigens, most are apparently placental antigens. Two proteins were found in normal ovaries.

Antibodies, Neoplasm↗
PubMed1984

The design of a new physician licensure examination.

Many health professions include written examinations among their licensing procedures, and constructing these examinations poses special difficulties. For physician licensure the central dilemma is manifested by the longstanding tradition of undifferentiated licensure contrasting with the strong specialty orientation of contemporary physician training. This article details the authors' response to this problem and describes the resulting design of a new physician licensure examination. Using a combination of empirical data and expert judgment, descriptions of selected clinical encounters have been assembled as a practice model of a physician licensed for the delivery of general health care of patients. Application of an explicitly situational framework to the design of a physician licensure examination is unusual, and the approach is advocated for use with other health professions.

Clinical Competence↗
PubMed1983

Isolation of plasma membrane fragments from cultured murine melanoma cells.

The various manipulations involved in the isolation of membrane fragments from culture fluids of murine melanoma cells were examined to discern their effect on membrane fragment structure. Ultracentrifugation and gel chromatography were compared using the presence of marker enzymes and the sensitivity to a non-ionic detergent (Triton X-100). Fractionation of media by gel chromatography resulted in only one major form of membrane particles, while ultracentrifugation, followed by resuspension, produced at least two major populations from the identical material. These results indicate that the optimal procedure for membrane fragment isolation is fractionation by an agarose-containing gel, followed by concentration using PEG 20,000.

Animals↗
PubMed1983

Biochemical effects of thiabendazole and cambendazole on Hymenolepis diminuta (Cestoda) in vivo.

An investigation of the chemotherapeutic and biochemical effects of two benzimidazole anthelmintics, thiabendazole (TBZ) and cambendazole (CBZ), on Hymenolepis diminuta in experimentally infected rats is reported. Thiabendazole was active against H. diminuta at a relatively high dosage. A single oral dose of TBZ at 250 mg/kg body weight on day 15 of infection eliminated 100% of the tapeworms as determined at necropsy 5 days after treatment. The chemotherapeutic actions of TBZ on H. diminuta were accompanied by marked changes in worm weight and chemical composition. Tapeworms recovered from rats that had received a therapeutically effective dose of TBZ 24 hr earlier were significantly smaller and contained much less glycogen (as a percent of the wet weight) than worms from unmedicated controls. Protein concentrations increased in TBZ-treated worms and at a rate sufficient to offset the decline in glycogen concentration. Glycogen/protein ratios in TBZ-treated worms were significantly lower than the corresponding control values. Cambendazole proved to be five times more potent than TBZ against H. diminuta and produced the same basic changes in worm weight and chemical composition within 18 hr of treatment of the host. Administration of a single oral dose of TBZ or CBZ to the host produced in H. diminuta another change, the onset of which coincided with, or preceded, the gross alterations in worm weight and chemical composition. That change, observed in in vitro studies carried out 14 hr after treatment, revealed that tapeworms from drug-treated rats absorbed and metabolized much smaller quantities of exogenous glucose than did the controls, and the ability of the worm to accumulate glucose against a concentration difference was significantly depressed.

Animals↗
PubMed1980

Mebendazole therapy of parenteral trichinellosis.

Mebendazole was highly effective against the helminth parasite Trichinella spiralis in mice subjected to a 3-day course of treatment during the invasive and encystment phases of experimental trichinellosis. When treatment began either 2 or 4 weeks after the mice were inoculated with parasites, the number of larvae developing in the host musculature was greatly reduced by twice-daily oral administration of 3.125, 6.25, or 12.5 milligrams of mebendazole per kilogram of body weight.

Administration, Oral↗