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Biomedical subjects

C Travis

Publications and source records attributed to C Travis.

12 recordsLinked to original sources
PubMed2001

Risk analysis: an overview.

Risk analysis increasingly is considered as an integral part of the environmental management decision-making process. Risk, defined as the probability of occurrence of a particular adverse effect on human health or the environment, should not be confounded with hazard, defined as a source of potential injury independent of occurrence. Risk analysis has to be followed by risk management. Some opponents of risk analysis make the reproach that the science used in risk analysis is immature and consequently that the entire process in laden with hidden value judgments. Attempts to overcome these critics are increasingly based on the use of robust biologic data the final considered values system being efficacy-based, efficiency-based or equity-based. Globalization has brought with it new problems, and there is an urgent need to improve risk analysts; to increase its public acceptability and to establish consensus regarding solutions to global environmental problems. In this context biologic-based models and biomarkers hold, the greatest promise for improving risk assessment. These considerations are illustrated by a few examples, also pertaining to low-dose extrapolation and to the problem of thresholds for carcinogenesis. Future directions for development are evoked.

Biomarkers↗
PubMed1999

Evaluating residency applicants: stable values in a changing market.

BACKGROUND AND OBJECTIVES: A 1994 study found significant differences in the way family practice and OB-GYN residency directors ranked the importance of components of the residency application package. Family practice residency directors favored qualitative measures (dean's letter, personal statement), and OB-GYN residency directors favored quantitative measures (transcripts, National Board of Medical Examiners score). The authors of the 1994 study hypothesized that the differences could be attributed to specialty competitiveness and philosophy. Our study reexamined family practice rankings of these same application components to determine if the programs, with increased competition for residency positions, had changed their values. METHODS: We surveyed all Accreditation Council for Graduate Medical Education-approved residency directors, using the core questions from the 1994 study, plus 2 additional questions. RESULTS: The component rankings in 1997 were virtually identical to the rankings in 1994. The new variables, computed to identify competitiveness, failed to elicit any meaningful or consistent differences. CONCLUSIONS: Program directors have remained relatively stable in favoring the qualitative aspects of the application package, ranking the dean's letter and personal statement consistently in the top 3 positions. This stability is found across time and independent of success in the National Resident Matching Program and number of US graduate applicants. Residency directors have not increased their reliance on quantitative measures.

Career Choice↗
PubMed1996

Phenotypic and genotypic analysis of rat liver epithelial cells infected with retroviral shuttle vectors.

Rat liver epithelial cells (RLE) are suspected to be pluripotent hepatic stem cells that give rise to a diverse variety of liver tumors. The molecular events responsible for transformation of these cells and the diversity of the tumor phenotypes remains to be fully elucidated. We examined the genotype and phenotype of RLE cells infected with retroviral shuttle vectors carrying a neomycin resistance (neor) Ha-ras or a lacZ gene. WBneoIII, WBrasIII and WBlacZ cell lines were examined for evidence of a transformed phenotype by comparing their behavior with the parental strain (WB-344) and with WBneo-C-II and WBrasII cells. Confluent cultures of WBneo-C-II and WBrasII cells were found to contain significantly higher numbers of total cells than the other cell lines. The growth rate of WBneo-C-II and WBrasII cells were faster than that of the parental cell line. Addition of epidermal growth factor (EGF) to the medium was found to stimulate the growth rate of WBneo-C-II cells and to induce anchorage independent growth (AIG). No cell line produced tumors in nude mice (nu/nu) except WBrasII cells. Radioimmunoprecipitation studies and sequencing of the p53 exons 5-8 indicate WBneo-C-II, and WBrasII cells produce a mutant p53. Northern blot analysis showed an increased expression of c-myc mRNA in WBneo-C-II and WBrasII cells. These results demonstrate that alterations in critical growth and differentiation controlling genes have occurred in WBrasII cells which may, independent of or in conjunction with ras insertion, cause the transformed phenotype.

Animals↗
PubMed1996

Effects of 60-Hz fields, estradiol and xenoestrogens on human breast cancer cells.

If exposure to xenoestrogens or electromagnetic fields (EMFs) such as 60 Hz contributes to the etiology of breast cancer, it is likely that they must stimulate the growth of breast cells, damage genetic material or enhance the effects of other mitogenic or mutagenic agents (co-promotion). Therefore, the ability of xenoestrogens or exposure to 60-Hz fields to stimulate the entry of growth-arrested human breast cancer cells into the cell cycle was determined using cyclin-dependent kinase 2 (Cdk2) activity, synthesis of cyclin D1 and cdc2 activity. Exposure of estrogen receptor-positive MCF-7 or T-47D cells to estrogen and xenoestrogens (DDT and Red No. 3) increased Cdk2 and cyclin B1-cdc2 activity and cyclin D1 synthesis. Exposure of breast cancer cells to 12 mG or 1 or 9 G electromagnetic fields at 60 Hz failed to stimulate Cdk2 or cyclin B1-cdc2 activity or cyclin D1 synthesis. Simultaneous co-exposure of cells to 60-Hz fields and chemical promoters did not enhance Cdk2 activation above the levels produced by the chemical promoter alone. Estrogen and xenoestrogens also stimulated binding of the estrogen receptor to the estrogen receptor element but the EMF did not. Phorbol 12-myristate 13-acetate (PMA) induced phosphorylation of p53 and pRb1O5 in MCF-7 cells, but EMF exposure had no effect. DNA-damaging chemotherapeutic agents and Red Dye No. 3 were found to increase p53 site-specific DNA binding in breast cancer cells, but EMF exposure did not. Differential display analysis failed to detect any effect of EMF exposure on gene expression in MCF-7 cells, whereas the effects of estradiol were detected. These studies suggest that estrogen and xenoestrogens stimulate growth-arrested breast cancer cells to enter the growth cycle, but EMF exposure does not. Site-specific p53-DNA binding was increased in MC F-7 cells treated with DNA-damaging agents, but not by EMF exposure. EMF exposure does not appear to act as a promoter or DNA-damaging agent for human breast cancer cells in vitro.

Base Sequence↗
PubMed1994

Hyperphosphorylation of p53 induced by benzene, toluene, and chloroform.

Phorbol 12-myristate, 13-acetate (PMA) is a known protein kinase C activator (PKC); benzene, chloroform, and toluene have also been reported to be PKC activators. We examined the effects of these three solvents on the phosphorylation of p53 in treated cells. Hyperphosphorylated p53 was found when p53 was immunoprecipitated from rat liver epithelial cell extracts treated with any of the solvents or PMA. The solvents also resulted in hyper-phosphorylation of human p53 produced by transfection of Saos-2 cells with a eucaryotic expression vector. Increased phosphorylation of p53 induced by the solvents was also observed through in vitro assays. Hyperphosphorylation of p53 may be involved in tumor promotion by benzene, toluene and chloroform.

Animals↗
PubMed1994

Trichloroacetate stimulation of liver DNA synthesis in male and female mice.

Male and female B6C3F1 mice were given trichloroacetate (TCA) by gavage for 11 days. Livers from untreated male and female mice were unremarkable by histopathologic examination. In livers from mice receiving 1000 mg/kg body weight, the centrolobular hepatic cords showed slight changes, which included increased eosinophilic staining and rare apoptosis. Areas in the intermediate zone were noted where the architecture of the liver hepatic cords was subtly changed. The changes in cord architecture seemed to define nodular areas where cellular proliferation in animals treated with TCA had occurred. No histopathologic differences were noted between the livers of treated or control, male and female animals. Mitosis and DNA synthesis were examined using incorporation of [3H]thymidine into liver cells. [3H]Thymidine incorporation into extracted liver DNA of animals receiving TCA was significantly increased over controls in all treatment groups. Autoradiographic examination of liver sections showed that the incorporation of label in control animals was predominantly in peri-sinusoidal cells, whereas the majority of radiolabel incorporation in TCA-treated animals was found in intermediate zone cells that appeared to be mature hepatocytes. No outstanding differences in the distribution of radiolabel in the liver sections from male or female mice were noted. When incorporation of [3H]thymidine was quantified by enumeration of labeled liver cells following autoradiography, incorporation of the radiolabel into hepatocytes increased with the dose of TCA given but there was no increase in radiolabel in peri-sinusoidal cells. Increased mitotic figures in intermediate zone cells resembling mature hepatocytes were noted in all mice treated with TCA. These results suggest that increased DNA synthesis and mitosis may contribute tumorigenesis by TCA.

Administration, Oral↗
PubMed1993

The mitogenic potential of trichloroethylene in B6C3F1 mice.

Male and female B6C3F1 mice were given TCE by gavage for 10 days. No histopathologic changes in the livers from control male and female mice were found. Moderate changes around central veins were noted in male or female mice that received 1000 mg/kg/body weight TCE. Histopathological changes included an increase in cytoplasmic eosinophilic staining and apoptosis around the central veins. Mitosis and DNA synthesis were examined using incorporation of [3H]thymidine into liver cells. Incorporation of [3H]thymidine was significantly increased in the DNA of animals receiving TCE. Total liver DNA extracted from TCA-treated mice was not significantly different than those of control groups. Autoradiographic examination of liver sections showed that the incorporation of label in control animals was primarily in perisinusoidal cells. The majority of radiolabel incorporation in TCE-treated mice was found in intermediate zone cells that appeared to be mature hepatocytes. No outstanding differences in the distribution of radiolabel in the liver from male or female mice were noted. When incorporation of [3H]thymidine was quantified by enumeration of labeled hepatocytes following autoradiography, incorporation of the radiolabel into hepatocytes increased proportionally to the applied dose of TCE, but did not increase in peri-sinusoidal cells. Increased mitotic figures in intermediate zone cells resembling mature hepatocytes were found in all mice treated with TCE. These results suggest that liver cell DNA synthesis and mitosis are stimulated by TCE and that these effects may be in part responsible for transformation of liver cells in these mice.

Administration, Oral↗
PubMed1987

Deep-freezing versus 4 degrees preservation of avascular osteocartilaginous shell allografts in rats.

Osteocartilaginous allografts (distal femurs of rats) were stored at 4 degrees for six, 12, 24, and 48 hours and at -80 degrees for five days and then evaluated for viability of the bone and cartilage. Storage at 4 degrees for 12 or 24 hours had little effect on cartilage viability but decreased bone viability to 40% and 10% of controls, respectively. Storage at -80 degrees for five days resulted in nonviable bone in all cases but showed an either/or response of cartilage, with high viability in two cases and nonviability in the other eight cases. In a second set of experiments, femurs from rats were stored in situ at 4 degrees for 12 or 24 hours or were harvested and stored at -80 degrees for five days, after which they were transplanted into rats of a different strain. The antibody response to each set of femurs was measured at two, six, and 12 weeks after operation. The 4 degrees storage resulted in a moderately decreased immunogenicity, whereas the storage at -80 degrees resulted in significantly reduced immunogenicity.

Animals↗
PubMed1982

Long-term effects of azathioprine in rheumatoid arthritis.

Efficacy and safety of azathioprine in 'high' and 'low' dose regimens in rheumatoid arthritis (RA), both in short-term studies and in follow-up over 40 months, have previously been shown. In the present report, 36 patients with RA treated with azathioprine (group I) and 49 age-matched patients with RA (group II), were studied to detect potential early markers of malignancy. Chest x-rays were similar to both groups. One patient in group I had a positive PAP smear and was subsequently found to have uterine carcinoma. Alpha-fetoprotein was positive in one patient in group I and none in group II. CEA was negative in all patients in group I, but positive in seven in group II. On chromosomal analysis group I showed a greater frequency of breakage. Group I showed lower serum folates and a highly significant number of megaloblastic features in marrow aspirates. In group I seven tumours, three being malignant, occurred while taking azathioprine, and in group II six tumours, one malignant, were identified (p = 0.17). The apparent increased risk of malignancy previously suggested by others warrants further studies with larger populations and over a continuous longer period.

Adenocarcinoma↗