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Biomedical subjects

D D Taylor

Publications and source records attributed to D D Taylor.

At least 73 records · Page 4Linked to original sources
PubMed1980

Binding of specific peroxidase-labeled antibody to placental-type phosphatase on tumor-derived membrane fragments.

Monospecific antiserum to human placental alkaline phosphatase was purified by immunoabsorption and labeled with horseradish peroxidase. The binding of this labeled antibody to membrane fragments prepared from placental and tumor tissue was measured using agarose gel filtration to separate bound antibody. The antibody bound only to membrane fragments which contained placental phosphatase, and the amount bound varied in the order ascitic fluid membrane fragments greater than tumor extracts greater than placental extracts. Absorption of the antibody with crude placental membrane yielded a population of antibody which reacted with tumor tissue and pure placental enzyme, but only slightly with placental membranes. These results are interpreted to suggest that some antigenic sites are exposed in tumor tissue membranes which are not in placental membranes.

Adenocarcinoma↗
PubMed1978

Planning student work-study time in an objectives-based medical curriculum.

By developing, validating, and using a formula for predicting students' time commitment to their studies, those responsible for developing curricula can make their planning more precise. Overloads and underloads can be identified a priori, competition between concurrent courses can be reduced, and changes in course content and structure can be based on empirical data. The formula should be useful at all undergraduate levels and with a variety of educational formats.

Curriculum↗
PubMed1978

The SIU medical curriculum: systemwide objectives-based instruction.

The Southern Illinois University School of Medicine has completed a five-year experience applying an objectives-based approach to an entire curriculum in a medical school setting. Approximately 250 students have worked and studied within the system, and three classes have been graduated. This paper describes the instructional system and the procedures for monitoring, maintaining, and improving it and provides available outcome data.

Attitude↗
PubMed1975

Microsomal activation to mutagens of antischistosomal methyl thioxanthenones and initial tests on a possibly non-mutagenic analogue.

Five methylthioxanthenone and methylbenzothiopyranoindazole analogues, including lucanthone (Miracil D), are non-mutagenic for Salmonella typhimurium but are activated to mutagens by a rat liver microsome preparation. Hydroxymethyl analogues, including hycathone (Etrenol), are mutagenic in the absence of microsomes. It seems reasonable to assume that the hydroxymethyl derivatives are the more proximal mutagens and that Salmonella is unable to carry out the hydroxylation necessary for mutagen activation. During the pase 24 years, several million patients with schistosomiasis have been treated with lucanthone, and in recent years about 700 000 persons with hycanthone. The possible long-term deleterious effects of these agents for man even now remain to be determined. Our studies indicate that particular modifications in the structure of thioxanthenones drastically alter their mutagenicity. One apparently non-mutagenic thioxanthenone has been found. A number of the less mutagenic compounds also exhibit decreased acute toxicity in the mouse while retaining appreciable antischistosomal activity, suggesting that genetic and schistosomicidal activities may be dissociated from each other.

Animals↗
PubMedDate not supplied

Expression and shedding of CD44 variant isoforms in patients with gynecologic malignancies.

OBJECTIVES: The presence of CD44 isoforms was evaluated in ascitic fluid and serum samples of patients with gynecologic malignancies. Previously, the shedding of tumor-associated cell surface antigens has been demonstrated in the blood and malignant effusions of gynecologic cancer patients. Thus, the shedding of CD44 was also studied in ascitic fluids and sera of these patients, to address variant isoform expression as a biomarker of gynecologic cancer. METHODS: The expression of CD44 isoforms by ovarian tumor cells was examined by flow cytometry using variant-specific monoclonal antibodies. The release of these isoforms into the peripheral circulation and ascites was assayed by Western immunoblot analysis. RESULTS: Flow cytometric analysis of ovarian tumor cell lines revealed a strong expression of CD44 with significant levels of v4/5 and v6 isoforms. The presence of circulating CD44 isoforms was detectable in the sera of six of eight cancer patients, as well as in 12 of 16 ascitic fluids. Of the CD44-positive specimens, all six positive sera expressed detectable levels of variant CD44. The CD44v6 was present in all of the positive sera samples tested. In the ascites, the "shed" CD44 appeared to be associated predominantly with shed particles (vesicles) of plasma membranes (membrane fragments). Of ten CD44-positive ascites samples, all expressed significant levels of variant CD44. CONCLUSIONS: In addition to mediating metastasis, the differential expression and shedding of CD44 isoforms into the circulation may represent important determinants in the escape of tumors from immune surveillance, and their detection may be a diagnostic or prognostic marker.

Aged↗
PubMedDate not supplied

Inhibition of endometrial cancer cell lines by mifepristone (RU 486).

OBJECTIVE: To determine the role of mifepristone (RU 486) in the growth of endometrial cancer cell lines, and the mechanism associated with this regulation. METHODS: Three endometrial cancer cell lines (Hec-1A, KLE, and RL95-2) were used in this study. Growth inhibition was demonstrated by sulforhodamine B cytotoxicity assay. Mode of inhibition by RU 486 was studied by induction of DNA fragmentation. The effect of RU 486 on steady-state accumulation of the progesterone and glucocorticoid receptors (PRs and GRs, respectively) and apoptosis-associated gene products was studied by Western blotting. RESULTS: We demonstrated a dose-dependent inhibition of growth in all of the three endometrial cancer cell lines. Following treatment with 5.0 micrograms/mL of RU 486, there was 39.3%, 66.3%, and 75.5% inhibition of KLE, Hec-1A, and RL95-2 cells, respectively. Decreased expression of GR in RL95-2 (0.1-10 micrograms/mL) and in KLE cells (10 micrograms/mL) was observed. A marked decrease of PR was seen with RL95-2 cells at 10 micrograms/mL, there was no change in the KLE cells, and a dose-dependent decrease was seen with Hec-1A cells. Various levels of apoptosis were demonstrated by DNA fragmentation in all three cell lines. Of the genes associated with apoptosis, dose-dependent reduction of bax expression was demonstrated in KLE cells, while induction of WAF-1 was seen in Hec-1A and RL95-2 cells, and reduction of bcl-2 was demonstrated in RL95-2 cells. CONCLUSION: Clinically achievable doses of RU 486 inhibit endometrial cancer cell lines. The mechanism of inhibition involves apoptosis, and regulation of bax, bcl-2, and WAF-1 is demonstrated. Therapeutic application of these findings remains to be determined.

Apoptosis↗
PubMedDate not supplied

Comparison of serum vascular endothelial growth levels between patients with and without ovarian malignancies.

The objective of this study was to determine if there was a relationship between serum vascular endothelial growth factor (VEGF) levels and ovarian malignancies by contrasting a population with ovarian malignancies and a population free of gynecological neoplasms. Two hundred forty four serum samples were obtained from the US National Cancer Institute's Prostate, Lung, Colon, and Ovarian Cancer Screening Project. These samples were analyzed by enzyme-linked immunosorbent assays in duplicate, and on completion of the assays, the samples were decoded for age and disease type. Average VEGF values for the nongynecological control group was 4.399 ng/ml; for benign gynecologic cases, 2.515 ng/ml; and for patients with malignancies, 4.287 ng/ml. Specifically, there was no difference between the mean value of VEGF in patients with ovarian malignancies and the patients with benign gynecological tumors (P = 0.8823). Also, there was no difference between the mean value of VEGF in patients with ovarian malignancies and the control patients who did not have gynecological disease (P = 0.3110). Using the Mann-Whitney U-test, no significant differences were found between the three populations of this study. Based on our data, due to the lack of significant difference in mean serum VEGF values between patients with and without ovarian malignancies, we feel that serum VEGF cannot be used as a possible screening tool for ovarian cancer.

Adenocarcinoma↗
PubMedDate not supplied

"Membrane-associated" immunoglobulins in cyst and ascites fluids of ovarian cancer patients.

A new column chromatography technique, utilizing peroxidase-labeled antihuman immunoglobulins, is described, which can measure the binding of specific antibodies to membrane fragments containing relevant antigens. Using this assay, the presence of bound immunoglobulin is demonstrated on membrane fragments isolated from ascites fluids, but not from tumor tissues. In this study, two populations of immunoglobulins were examined: 'free' immunoglobulins and immunoglobulins bound to ascites fluid-derived membrane fragments. Immunoglobulins eluted from membrane fragments of the ascites fluids were capable of binding to the tumor. These were specific for binding to tumor membrane preparations, in that there was two orders of magnitude greater binding of these immunoglobulins at a given concentration than 'free' immunoglobulins at the same concentration.

Antibodies, Neoplasm↗
PubMedDate not supplied

Tumor-reactive immunoglobulins in ovarian cancer: diagnostic and therapeutic significance? (review).

Inhibition of the immune system has been observed in association with most stages of ovarian cancer; however, the mechanisms involved in the induction and maintenance of this chronic immune unresponsiveness associated with cancer progression are poorly understood. This immunosuppressed state is primarily defined as the failure to eradicate the tumor. This immunosuppressed state is generally associated with decreased numbers and reactivity of lymphoid cells in women with ovarian cancer. The degree of immune dysfunction in ovarian cancer patients has been demonstrated to correlate with patient survival. While ovarian cancer patients generally fail to exhibit effective immunosurveillance, as manifested by continued tumor growth and progression, the presence of tumor-reactive immunoglobulins can be demonstrated in these women, indicating the continued presence of immune recognition. We have not only demonstrated the presence of tumor-reactive antibodies in ovarian cancer patients, but have also shown that the levels of these antibodies increase as the disease progresses. The antigens recognized by the patients' humoral response have been identified as either membrane-associated or intra-cellular. In general, the localization of these antigens tend to be linked to the patient's prognosis. The presence of a humoral response against intracellular proteins are correlated with poor prognosis, while autoantibodies reactive with surface components appear to have a better prognosis. In addition to general antigen recognition, these reactive antibodies have been utilized to define specific epitopes on tumor-associated proteins. Certain specific antigenic epitopes exhibit common recognition among patients with the same tumor type. The specific recognition of certain epitopes can provide early evidence of aberrant protein expression and this aberrant expression of certain proteins, such as procathepsin D, appear to be linked to the tumor's acquisition of specific malignant characteristics, including metastasis formation and chemoresistance. Despite the existence of circulating tumor-reactive immunoglobulins, their presence correlates, in general, with poor prognosis and poor host survival. Since tumor-reactive immunoglobulins are elicited and can be detected early in the development of tumors and their enhanced synthesis is induced prior to the clinical manifestation of recurrence, the assessment of the tumor-reactive immune response against specific antigenic epitopes should represent an early significant diagnostic and prognostic marker in ovarian cancer.

Antibodies, Neoplasm↗
PubMedDate not supplied

Evaluation of cell proliferation and cell death based assays in chemosensitivity testing.

BACKGROUND: Drug sensitivity testing (DST) is used to predict the clinical response to chemotherapy with limited success. Our objective was to evaluate assays that measure cell proliferation or apoptosis in determining sensitivity of ovarian cancer cells to cisplatin and paclitaxel. MATERIALS AND METHODS: Four ovarian cancer lines were used. LD10-LD90 doses were determined by viability assays. Assays measuring cell proliferation, sulforhodamine-B (SRB), tritiated thymidine; and cell death, diphenylamine or DNA histone ELISA were compared. RESULTS: SRB assay was consistent and sensitive. Histone ELISA correlated with the viability assay at high doses. The [3H] thymidine test was not sensitive and resulted in false positive responses. While less sensitive, detection of apoptosis by diphenylamine assay shows a similar trend to histone ELISA. CONCLUSIONS: We demonstrate significant differences between the various assays. Most of these assays are better predictors of resistance. Further studies are needed to determine the best correlation between in vitro testing and responses in vivo.

Antineoplastic Agents↗