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Biomedical subjects

A L Ellis

Publications and source records attributed to A L Ellis.

16 recordsLinked to original sources
PubMed1996

The impact of "media contact" on attitudes toward gay men.

In order to understand better the relation between "media contact" and attitudes, college students were asked to view a documentary film depicting events surrounding the life and death of a prominent gay politician. The participants completed the Attitudes Toward Homosexuals Scale during screening sessions and either prior to or after viewing the documentary. The film had a significant and positive effect on attitudes. In addition, data on the mood of the subjects were collected and analyzed in light of Devine's (1989) model of prejudice. The findings suggest possible extensions for Devine's model.

Attitude↗
PubMed1996

Phase I clinical and plasma and cellular pharmacological study of topotecan without and with granulocyte colony-stimulating factor.

Topotecan, a semisynthetic water-soluble analogue of camptothecin, inhibits human topoisomerase I (topo I). We performed a Phase I clinical and plasma pharmacological study of topotecan administered by 24-h continuous infusion without and with granulocyte colony-stimulating factor (G-CSF). We also measured topo I-DNA complexes in peripheral blood mononuclear cells (PBMCs) in an attempt to correlate formation of topo I-DNA complexes in patients treated with topotecan with toxicity and/or response. One hundred four courses of topotecan at doses of 2.5-15.0 mg/m2 were administered to 44 patients with solid tumors. The maximum tolerated dose without G-CSF was 10.0 mg/m2; granulocytopenia was the dose-limiting toxic effect. The maximum tolerated dose could not be increased with G-CSF because of severe thrombocytopenia. Plasma pharmacology was obtained in 11 patients treated at 12.5 mg/m2 and 15.0 mg/m2. The topotecan lactone end-infusion plasma levels correlated strongly with the area under the curve. Lactone elimination was biexponential with a mean t1/2alpha of 28 min and a t1/2beta of 3.8 h at 12.5 mg/m2. Topo I-DNA complexes were measured before and after treatment in PBMCs from seven patients. Pretopotecan topo I-DNA complexes were available on two additional patients treated at 15 mg/m2. The mean increase in topo I-DNA complexes at the end of the topotecan infusion was 1.25 times the pretreatment value. There was a statistically significant relationship (P = 0.02) between lack of disease progression and the level of topo I-DNA complexes measured in PBMCs before therapy. For Phase II studies of minimally treated adults with solid tumors, the recommended topotecan starting dose administered by 24-h continuous infusion is 10 mg/m2 without G-CSF.

Adult↗
PubMed1995

The relation of job satisfaction and degree of openness about one's sexual orientation for lesbians and gay men.

The social environment of the workplace is an important component of job satisfaction. Different groups perceive that environment in different ways. For gay men and lesbians an important factor may be how "open" they can be about their sexual orientation in the workplace. This study assesses the relation between openness about one's sexual orientation in the workplace and job satisfaction among gay men and lesbians. Results based on responses to the Job Descriptive Index from samples in Indianapolis and San Francisco indicated a strong relationship between openness and satisfaction with co-workers. In addition, individuals who were not completely "out" in the workplace were more satisfied with their pay and tended to make more than those who were "out" to both their bosses and their co-workers. Possible implications of these results regarding job satisfaction issues for lesbians and gay men are discussed.

Adult↗
PubMed1994

Time course of phorbol-12-myristate-13-acetate (PMA)-induced down-regulation of topoisomerase II in human leukemia cells.

The time course of the down-regulation of topoisomerase II associated with phorbol-induced differentiation was quantified in two human HL-60 leukemia cell lines. In the line sensitive to phorbol-induced differentiation (S cells), immunoreactive topoisomerase II levels did not begin to fall until 12 hr following exposure of the cells to phorbol ester. Thereafter, levels declined over the next 36 hr. By contrast, phorbol treatment of the phorbol ester tolerant cell line (PET cells) produced a transient decrease in topoisomerase II only to be followed by a recovery to pretreatment levels. The patterns of the alterations in topoisomerase II mRNA levels mirrored those of the alterations in immunoreactive topoisomerase II. Unexpectedly, nuclear run-on studies revealed that transcriptional start sites were not reduced in either cell line following their exposure to phorbol esters. These data suggest that the down-regulation of topoisomerase II is a consequence rather than a cause of phorbol-induced differentiation in HL-60 cells. Furthermore, this down-regulation is not mediated by a decrease in the number of topoisomerase II transcription sites.

Cell Differentiation↗
PubMed1994

Phorbol regulation of topoisomerases I and II in human leukemia cells. Studies in an additional cell pair sensitive or resistant to phorbol-induced differentiation.

We previously reported (Zwelling et al., Cancer Res 50: 7116-7122, 1990) that etoposide-induced DNA cleavage and mRNA coding for topoisomerase II are reduced in HL-60 cells induced to differentiate by phorbol ester. Reduction of etoposide-induced cleavage and topoisomerase II message did not occur in the derived cell line 1E3 (which is resistant to phorbol-induced differentiation), implying that topoisomerase II activity may be related to the state of cell differentiation. We have extended these studies using a new phorbol sensitive/resistant cell pair, S (sensitive) and PET (phorbol ester tolerant). Phorbol ester exposure not only reduced etoposide-induced DNA cleavage and topoisomerase II mRNA in S cells but also decreased the amount of immunoreactive topoisomerase II enzyme in whole S cells. However, immunoreactive topoisomerase II extracted from the nuclei of phorbol-treated S cells was not reduced compared with that from the nuclei of untreated S cells. This suggests that topoisomerase II contained in nuclear extracts is not always representative of the total cellular enzyme. Dramatic decreases in the amount, activity, or gene expression of topoisomerase II were not observed after phorbol treatment of the resistant PET cells; this is consistent with the potential involvement of topoisomerase II in monocytoid differentiation. Levels of topoisomerase I enzyme and mRNA fell in both S and PET cells after phorbol treatment; therefore, the genes for topoisomerases I and II did not appear to be regulated coordinately.

Cell Differentiation↗
PubMed1994

Quantification of topoisomerase-DNA complexes in leukemia cells from patients undergoing therapy with a topoisomerase-directed agent.

Several clinically important drugs utilized in cancer chemotherapy inhibit type I (Topotecan) or type II (amsacrine, etoposide) DNA topoisomerases by stabilizing the formation of DNA-topoisomerase complexes (topoisomerase-DNA cross-links). In various cell lines, the magnitude of drug-induced DNA-protein cross-link production correlates with the magnitude of cytotoxicity induced by the drugs. We developed a simple filter-binding assay that can measure drug-induced DNA-protein cross-links in leukemia cells obtained directly from patients because the assays most widely used for assessment of drug-induced DNA-protein cross-links in cells [sodium dodecyl sulfate (SDS)/KCl precipitation and alkaline elution] are not readily applicable for use on patient material. HL-60 human leukemia cells or freshly isolated patients' leukemia cells were incubated with Topotecan, etoposide, or amsacrine; lysed with SDS; and applied to nitrocellulose filters in a low-salt buffer. DNA is retained on the filter only if it is covalently bound to protein. The amount of DNA retained on the filter is quantified by hybridization to the alu sequence of DNA, which is distributed ubiquitously in the human genome. Using radiolabeled cells, we compared the filter-binding assay directly with the SDS/KCl precipitation assay in the detection of etoposide- or amsacrine-induced DNA-protein cross-links in HL-60 cells and amsacrine-resistant HL-60/AMSA cells. Both the SDS/KCl precipitation assay and the filter-binding assay detected etoposide-induced DNA-protein cross-links in HL-60 and HL-60/AMSA cells and detected a greater frequency of amsacrine-induced DNA-protein cross-links in HL-60 cells than in HL-60/AMSA cells. The filter-binding assay detected DNA-protein cross-links in freshly isolated leukemia cells exposed to Topotecan in vitro. The ratios of DNA retention for Topotecan-treated versus untreated cells from leukemia patients ranged from 1.8 to 11.5. The heterogeneity of this detected cross-linking was as might be expected if the assay were predictive of the antileukemic action of Topotecan, which is variable. This new filter-binding technique may be useful for predicting the sensitivity of individual patients' tumors to drugs that inhibit type I or type II DNA topoisomerases.

Amsacrine↗
PubMed1994

Political tolerance of homosexuals: the role of group attitudes and legal principles.

Individuals' attitudes toward and acceptance of general legal principles were assessed along with their willingness to extend application of these principles to various social and political groups, including homosexuals. Respondents then indicated their attitudes toward various social and political groups, including the groups to whom they had applied the general principles. Regression analyses were used to determine to what degree acceptance of the general principle and attitude toward the social group predicted application of the general principle to the group. For disliked groups such as the Ku Klux Klan and Nazis, individuals' acceptance of the general principle alone predicted the specific application. For homosexuals, however, the application of the general principle was affected both by acceptance of the general principle and by individuals' attitudes toward homosexuals. The implications of this difference in light of research addressing the cognitive and affective nature of attitudes and attitude change is discussed.

Adult↗
PubMed1993

Prior interpersonal contact with and attitudes towards gays and lesbians in an interviewing context.

The impact of previous interpersonal contact or exposure to male homosexuals and lesbians on interviewing strategy was assessed. Previous research on attitudes toward homosexuals suggests that prior exposure reduces the negativity of attitudes toward homosexuals. In support of that research and research looking at the use of confirmatory questioning strategies in social interactions, it was expected that individuals with prior exposure to homosexuals and/or positive attitudes toward homosexuals would choose fewer negative information-seeking questions for a proposed interview. The results support previous research findings regarding attitudes towards gay men and lesbians and suggest that pre-interview attitudes and prior exposure may influence interviewer strategy.

Adult↗
PubMed1992

Components of intrinsic drug resistance in the rat hepatoma.

A carcinogen-transformed rat hepatoma cell line (Reuber H-35) was utilized as a model system for investigation of the biochemical factors which may limit the effectiveness of chemotherapy in intrinsically resistant tumors such as hepatocellular carcinoma. Northern blotting demonstrated expression of mRNA coding for the P-170 membrane-glycoprotein associated with the multi-drug resistance phenotype, while Western blotting identified the P-170 glycoprotein in the hepatoma cell membrane. Consistent with these observations, tumor cell sensitivity to the vinca alkaloids, vincristine and vinblastine, to the anthracycline antibiotics, Adriamycin and daunorubicin, and to the demethylepipodophyllotoxin derivative, VM-26, was enhanced by continuous incubation in the presence of the calcium channel antagonist, verapamil. Verapamil produced a minimal change in cell sensitivity to the demethylepipodophyllotoxin derivative, VP-16, and to the aminoacridine, m-AMSA. Relatively high detoxification potential via the glutathione metabolic pathway was also observed in the hepatoma cell. The capacity of topoisomerase II in nuclear extracts from the hepatoma cell to mediate cleavable complex formation stimulated by VM-26, VP-16 and m-AMSA appeared to be at least comparable to, if not greater than that from drug-sensitive HL-60 cells, suggesting that drug resistance may not occur at the level of this enzyme. Consistent with findings in a number of tumor cell lines resistant to antineoplastic drugs, the antiproliferative activity of the topoisomerase II inhibitors VM-26, VP-16 and m-AMSA appeared to be dissociable from the induction of DNA strand breaks, suggesting that such lesions in DNA may fail to fully account for the antiproliferative activity of these agents in the hepatoma cell.

Animals↗
PubMed1990

Biochemical lesions in DNA associated with the antiproliferative effects of mitoxantrone in the hepatoma cell.

The H-35 rat hepatoma cell was markedly more sensitive to the anthracenedione mitoxantrone (IC50, 0.05 microM) than to the anthracycline antibiotics daunorubicin (IC50, 0.5 microM) and Adriamycin (IC50, 2.5 microM). In the rat hepatoma cell, mitoxantrone inhibited DNA and protein syntheses, with minimal effects on RNA synthesis. In contrast to daunorubicin, mitoxantrone induced both DNA strand breaks and DNA-protein cross links. The capacity of mitoxantrone to induce more extensive DNA cleavage than anthracycline antibiotics such as daunorubicin may be related to the sustained cellular retention of mitoxantrone (62% of accumulated drug) as compared to that for daunorubicin (32% of accumulated drug). Protein-associated DNA cleavage is likely to be one of the primary lesions contributing to the antiproliferative activity of mitoxantrone in the hepatoma cell, although marked growth inhibition was observed without corresponding alterations in DNA integrity.

Animals↗
PubMed1989

Enhanced sensitivity of the rat hepatoma cell to the daunorubicin analogue 4-demethoxydaunorubicin associated with induction of DNA damage.

The H-35 rat hepatoma, a cell line which is relatively resistant to the classical anthracycline antibiotics such as Adriamycin [the concentration of drug which inhibits cell proliferation by 5090 (IC50) = 2.5 microM] and daunorubicin (IC50 of 0.5 microM), is markedly more sensitive to the 4-demethoxydaunorubicin derivative, idarubicin (IC50 of 0.025 microM). In contrast to daunorubicin, which has previously been shown to inhibit hepatoma cell proliferation in the absence of perceptible DNA cleavage, idarubicin induces concentration-dependent DNA damage which may account for its enhanced capacity to inhibit proliferation of the rat hepatoma. Free radical scavengers fail to interfere with inhibition of cell proliferation induced by idarubicin. Damage to the cell membrane or alterations in mitochondrial integrity do not appear to represent components of idarubicin toxicity in this tumor cell line. Inhibition of DNA synthesis by idarubicin parallels inhibition of cell growth; however, sensitivity of DNA synthesis to idarubicin is significantly less than that for cell proliferation (IC50 values of 0.5 microM and 0.025 microM, respectively). It is postulated that the antiproliferative effects of idarubicin in the H-35 rat hepatoma model may be a consequence of alterations in DNA integrity which ultimately result in the inhibition of cellular biosynthetic processes.

Animals↗
PubMed1989

Expression of protein-associated DNA damage in the alkaline elution assay in the absence of enzymatic deproteinization.

In the alkaline elution assay, expression of protein-associated DNA damage induced by topoisomerase II antagonists is facilitated by proteinase K digestion of the drug-stabilized topoisomerase-II-DNA complex. In the absence of this enzymatic deproteinization step, drug-induced DNA strand breaks are masked by the binding of the topoisomerase-II-DNA complex to the synthetic filter from which DNA is eluted subsequent to alkaline denaturation. In this manuscript, we report that as the number of cells lysed on the filter is increased, binding of the topoisomerase-II-DNA complex to the filter is compromised, permitting expression of DNA damage in the absence of enzymatic deproteinization.

Animals↗
PubMed1987

Dose-response relations in urinary excretion of trimethylselenonium in the rat.

75Se-labeled selenite was administered to fasting rats by orogastric intubation (1.5-3000 micrograms/kg body wt). Urine was collected and characterized for total radioactivity as well as for radiolabeled trimethylselenonium (TMSe). At lower doses of selenite (up to 500 micrograms/kg body wt), 30% of the administered dose was excreted. At higher doses of selenite, fractional urine excretion decreased as a function of the dose. The observed decrease in fractional urine excretion was not caused by changes in the absorption of the administered radiolabel. There was a direct relationship between the amount of the administered dose of selenite (up to 1500 micrograms/kg body wt) and the proportion of urinary [75Se] excreted as TMSe. Pretreatment with seleno compounds (10 or 100 micrograms Se/kg body wt as selenite, or selenomethionine) for 35 d before a challenge dose of [75Se]selenite did not influence the excretion of total [75Se] or of [75Se]TMSe in urine. Ingestion of a choline-deficient diet, which should deplete the availability of methyl groups, did not have any effect on excretion of total [75Se] or of [75Se]TMSe in urine after a challenge dose of [75Se]selenite (500 micrograms/kg body wt). The data presented here permit the following conclusions: 1) Production of TMSe is dose dependent, 2) production of TMSe from a single acute dose does not depend on the history of selenium intake and 3) rats fed a methyl-deficient diet are able to eliminate Se via formation of TMSe.

Animals↗