PubMed Health⌕ Search

Biomedical subjects

C Eckert

Publications and source records attributed to C Eckert.

At least 19 recordsLinked to original sources
PubMed1998

Mutagenic activity of carcinogens detected in transgenic rodent mutagenicity assays at dose levels used in chronic rodent cancer bioassays.

Data on transgenic rodent mutagenicity of five human carcinogens were summarised and compared with the results from rodent carcinogenicity studies. Four out of five carcinogens showed mutagenic activity already at daily dose levels which induced cancer in long-term rodent bioassays in at least one target tissue of carcinogenesis. In several of these studies, even single dose applications were sufficient to significantly increase the mutation frequency in vivo. Other genotoxic carcinogens required application of multiple dosing at dose-levels used in rodent cancer bioassays to show their in vivo mutagenicity. A rodent respiratory tract carcinogen, 1,2-dibromoethane (DBE), following inhalation exposure, displayed no mutagenic activity, neither in lung nor in nasal mucosa, at a single 2-h exposure to 30 ppm, which is below the highest concentration used in a NTP cancer bioassay. In contrast, after multiple treatment for 10 days at the same daily doses, a significant increase of the mutation frequency in nasal mucosa was apparent. We conclude, that especially when studying new chemicals in these transgenic rodent mutation assays, a multiple dosing protocol should be preferred. For dose selection, the same criteria could be applied as for chronic rodent bioassays.

Animals↗
PubMed1998

Use of transgenic mutational test systems in risk assessment of carcinogens.

Two transgenic in vivo mutation assays are described which are based on LacZ (Muta Mouse) and LacI (Big Blue) shuttle vector systems. Their utility has already been explored by a number of investigators including our laboratory. The evaluation of data derived from these assays confirm that they offer a practical method for studying mutagenic activity and mechanism in a wide range of tissues including those of the respiratory and gastrointestinal tract. Therefore, these transgenic mutation assays are valuable tools to assess the organotropic effects of genotoxic carcinogens.

Animals↗
PubMed1997

Mapping of the human P84 gene to the subtelomeric region of chromosome 20p.

P84 is a novel neural adhesion molecule that may play an important role in synaptogenesis. We have recently cloned a murine cDNA encoding the P84 adhesion molecule. The human homologue of P84 has previously been isolated (by others) as a brain specific cDNA containing CCA repeats. We have mapped the human P84 gene to the subtelomeric region of chromosome 20p (20p13) by FISH. In addition, we have been able to place P84 onto the high resolution physical map of the human genome by utilizing the Unigene database. P84 maps to several YAC clones, between STS markers IB255 and WI-9632, and very close to the polymorphic marker D20S199, in an interval of less than 1 Mb on 20p13. P84 is a strong candidate gene for neurological disorders which map into this region.

Animals↗
PubMed1996

Morality play.

Explore the source record for details and available documents.

Drug Industry↗
PubMed1996

Breast and cervical cancer screening among low-income women: impact of a simple centralized HMO intervention.

In 1994, it was estimated that about 44,500 American women would die from breast cancer and 7000 women from cervical cancer. While early detection methods (screening mammography, breast examinations, and pap smears) have proven to be effective means of decreasing these cancers, they are underused by all groups. In particular, low-income women use them least, resulting in their lower survival and higher mortality rates than the rest of the population. This article quantifies the effect of a simple intervention undertaken by a health maintenance organization (HMO) serving the indigent to improve breast and cervical cancer screening rates. The HMO mailed personal letters and newsletter articles to women members > or = 40 years about the need for cancer prevention. Articles also were printed in the monthly HMO newsletters to providers about the benefits of using these early detection methods. A review of provider claims from 574 women showed that baseline utilization rates for screening mammograms and pap smears before the intervention in year 1 (1990) were 14% and 16.4%, respectively. After the intervention, in years 2 and 3, mammograms had increased to 41% and pap smears to 38% for both years, indicating a levelling off effect of the intervention by year 3. These data show that while a significant improvement in screening behaviors was achieved, the intervention impact was limited to only about one third of the sample on the long term. Further, data do not indicate whether behavioral change was initiated as the member or provider level. More research is needed to increase overall screening behavior among the indigent and their physicians. The results reported here provide a baseline against which more intensive interventions can be measured in this setting.

Adult↗
PubMed1994

Tissue-specific induction of mutations by streptozotocin in vivo.

Streptozotocin has been reported to induce DNA damage in mouse liver although malignant tumors were not induced in this organ. DNA damage had not yet been monitored in the mouse kidney which was the tumor target organ in two mouse studies. In order to elucidate target organ specificity of genotoxicity and of tumorigenesis, we investigated the induction of DNA damage (microgel electrophoresis assay) and mutations (LacI transgenic mouse mutation assay) in the liver and kidney of male C57BL/6 mice. Our results show that the microgel electrophoresis assay was more sensitive and revealed the genotoxic potential of streptozotocin at lower doses than the mutation assay. It was, however, less specific in that DNA damage was induced both in target and non-target tissues of carcinogenesis at a similar potency. In contrast, the mutation analysis revealed the kidney to be more sensitive when the induced mutation frequencies are expressed as a multiple of the respective spontaneous rates. We conclude, therefore, that the carcinogenic organotropy of streptozotocin correlates better with its tissue-specific mutagenicity than with its pattern of inducing DNA damage when the two in vivo genotoxicity assays mentioned above are used. A combined use of the microgel electrophoresis assay and the transgenic mouse mutation assay is proposed for investigations of tissue-specific genotoxicity.

Animals↗
PubMed1994

Identification and characterization of an Epstein-Barr virus nuclear antigen 2-responsive cis element in the bidirectional promoter region of latent membrane protein and terminal protein 2 genes.

Epstein-Barr virus (EBV) transforms resting B cells in vitro very efficiently. The nuclear viral protein EBV nuclear antigen 2 (EBNA2) is absolutely required for this process and also acts as a transcriptional activator of cellular and viral genes. As shown previously, EBNA2 transactivates the promoters of the viral latent membrane proteins. It interacts indirectly with an EBNA2-responsive cis element of the terminal protein 1 (TP1) promoter. To identify the sequences mediating EBNA2 transactivation of the bidirectional promoter region driving expression of the latent membrane proteins LMP and TP2 in opposite directions, we assayed the effects of EBNA2 on the activities of promoter deletion and site-directed mutants of TP2 and LMP promoter luciferase reporter gene constructs by cotransfections into EBNA2-negative Burkitt's lymphoma cells. We were able to delineate an 80-bp EBNA2-responsive region (EBNA2RE) between -232 and -152 relative to the LMP RNA start site which could also mediate EBNA2-dependent activation on a heterologous promoter. Sequences of 20 and 32 bp located at the 5' and 3' ends, respectively, of the EBNA2RE were both essential for EBNA2 responsiveness. Full transactivation of the LMP and TP2 promoters seemed to require 20 bp of 5' adjacent sequences in addition to the 80-bp element. Electrophoretic mobility shift assays revealed specific protein-DNA complexes formed at the EBNA2RE. Oligonucleotides from -181 to -152 and -166 to -132 relative to the LMP RNA start site visualized one B-cell and one B-cell-plus-HL60-specific retarded protein-DNA complex, respectively. Additionally, an oligonucleotide from -253 to -210 revealed two specific protein-DNA complexes with nuclear extracts from different B and non-B cells, suggesting also the binding of ubiquitously expressed proteins on the EBNA2RE. Thus, these experiments defined a 80-bp cis element sufficient for conferring EBNA2 inducibility and demonstrated specific interactions of cellular proteins at DNA sequences within the EBNA2RE, which are critical for transactivation by EBNA2.

Antigens, Viral↗
PubMed1983

Adjuvant endocrine therapy, cytotoxic chemotherapy, and immunotherapy in stage-II breast cancer: five-year results.

Five-year results of a prospective, randomized clinical trial of three treatment regimes--(a) cytoxan, methotrexate, and 5-fluorouracil (CMF); (b) CMF plus the antiestrogen drug, tamoxifen (CMFT); and (c) CMFT plus bacillus Calmette-Guerin (BCG) vaccinations--in 312 women with stage-II breast cancer are reported. Estrogen receptors (ER) were measured in all of the primary tumors. Addition of tamoxifen to CMF therapy significantly decreased the number of recurrences at five years in ER positive patients with four or more positive axillary lymph nodes. Addition of tamoxifen to CMF had no effect on disease-free survival in ER-positive patients with 1-3 positive axillary lymph nodes or in patients with ER-negative tumors. Addition of BCG vaccinations had no discernible effect on disease-free survival. ER measurements in the primary tumor provide important prognostic information regardless of treatment, with ER-positive patients having lower recurrence rates and mortality after five years. ER measurements also have predictive value for response to endocrine therapy. Further follow-up is needed to determine whether tamoxifen is delaying recurrence or preventing it in a subset of these patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1981

Adjuvant therapy of stage II breast cancer: 48-month follow-up of a prospective randomized clinical trial.

A prospective, randomized clinical trial of adjuvant treatment of 318 stage II breast cancer patients, using chemotherapy, the antiestrogen tamoxifen, and immunotherapy is reported at 48 months follow-up. Women whose primary tumors have no estrogen receptors fall into a significantly poorer prognostic group than those whose tumors contain estrogen receptors. None of the adjuvant regimens appeared to offer any clear-cut advantage for the estrogen receptor negative patients. Those women whose primary tumor contains estrogen receptors appear to be in a prognostically favorable group, when their treatment regimen included the antiestrogen, tamoxifen. The adjuvant use of BCG immunotherapy does not appear to offer additional benefit, but the follow-up period of these treated patients is too brief to be conclusive. A longer period of observation is needed to determine whether this systemic treatment in estrogen receptor positive patients is preventing recurrence or merely delaying it.

Antineoplastic Agents↗
PubMed1980

Adjuvant chemotherapy, antiestrogen therapy and immunotherapy for stage II breast cancer: 45-month follow-up of a prospective, randomized clinical trial.

The results of adjuvant chemotherapy (CMF), endocrine therapy (t), and immunotherapy (BCG) in 318 women who had undergone mastectomy for Stage II breast cancer are reported after 45 months of life table analysis. CMFT therapy was found to be more effective than CMF alone in increasing recurrence-free survival. This beneficial effect appears to be limited to patients with estrogen receptor-positive tumors (ER+). Patients with estrogen receptor-negative tumors (ER-) (< 3 fmol/mg) have increased recurrence rates and higher mortality.

Antineoplastic Agents↗
PubMed1980

Antiestrogen, cytotoxic chemotherapy, and bacillus Calmette-Guerin vaccination in stage II breast cancer: a preliminary report.

A prospective, randomized clinical trial of three treatment regimens: (1) Cytoxan, methotrexate, and 5-fluorouracil (CMF), (2) CMF plus the antiestrogen drug, tamoxifen (CMFT), and (3) CMFT plus bacillus Calmette-Guerin (BCG) vaccinations in women with stage 22 breast cancer is reported. All patients underwent mastectomy and estrogen receptor (ER) analysis was performed. The results of this study show that patients with ER- tumors have recurrences more rapidly and have a higher mortality rate than patients with ER+ tumors (P less than 0.0001). In ER+ patients CMFT treatment is more effective in delaying recurrence than CMF alone at 33 months (P = 0.0176). This effect appears to be occurring in both premenopausal and postmenopausal women. In ER- patients the recurrence rate is high, and there is no significant difference among the three treatment groups. In premenopausal patients treated with CMF alone, however, ER- patients recur more rapidly than ER+ patients (P = 0.0313) and suggests that the effect of CMF may be related to the suppression of ovarian function. These findings have demonstrated a significant role for the use of antiestrogen therapy in patients with state II, ER+ breast cancer.

Actuarial Analysis↗
PubMed1979

Cost analysis in a CMHC: determining the cost of staff time.

The program evaluation and research unit of a community mental health center developed and field-tested a survey form to measure how employees spend their time. The form is divided into direct patient care activities, which include interviewing and testing, conducting therapy, and prescribing medications, and administrative or support activities, which include filling out charts, attending meetings, and training staff. All staff record daily, for one week, the hours and minutes they spend in each activity. Using that data as a base, the evaluation unit can determine the percentage of time staff spend in each activity and the cost of each activity based on staff members' paychecks.

Community Mental Health Centers↗