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D H Moore

Publications and source records attributed to D H Moore.

At least 109 records · Page 6Linked to original sources
PubMed1993

Correlation of bromodeoxyuridine (BRDU) labeling of breast carcinoma cells with mitotic figure content and tumor grade.

Tumor proliferation is inversely associated with survival in patients with breast carcinoma. Labeling of tumor cells with bromodeoxyuridine (BRDU) correlates highly with that seen with [3H]thymidine, the current "gold standard" for measuring tumor S-phase. However, the relationship of BRDU labeling to mitotic figure content and tumor grade remains incompletely defined. To determine this, we labeled 55 breast carcinomas with BRDU in vivo and correlated the results with mitotic figure content. The BRDU labeling index was the number of BRDU-positive cells/2,000 tumor cells, the mitotic figure index was the number of mitotic figures per 1,000 tumor cells, and the mitotic figure count was the number of mitotic figures per 10 high-powered fields. BRDU labeling was also correlated with tumor grade (Scarff-Bloom-Richardson). The BRDU labeling index correlated highly with the mitotic figure index (r = 0.814, p = 7.0 x 10(-14)), mitotic figure count (r = 0.725, p = 6.0 x 10(-10)), and tumor grade (r = 0.68, p = 1.1 x 10(-8)). The correlation of BRDU labeling with mitotic figure content was strong enough to suggest that a very carefully measured mitotic figure index provides an estimate of tumor growth fraction equivalent to the BRDU labeling index. Also, analysis of variance showed that the mitotic figure index was twice as precise as the mitotic figure count in estimating BRDU labeling, and thus was a more accurate measure of tumor proliferation. Moreover, measurements made by the mitotic figure index were as precise as those made by BRDU labeling. However, which method is optimal for estimating tumor proliferation rate remains unclear. Further studies are indicated.

Adult↗
PubMed1993

Analysis of somatic cell mutations at the glycophorin A locus in atomic bomb survivors: a comparative study of assay methods.

The glycophorin A (GPA) assay for in vivo somatic cell mutations was performed on blood samples from 39 survivors of the atomic bomb at Hiroshima. Parallel analyses were performed at two laboratories using three different GPA assay methods to enumerate cells lacking expression of either the M- or N-allele of GPA. All assay methods yielded significant dose-dependent increases in hemizygous GPA variant cell frequencies (VFs) and smaller increases in homozygous VFs. The slopes of the fitted linear dose-response functions did not differ significantly among assay methods used in the present study, or from slopes obtained in a study reported previously. The version of the assay described most recently (BR6) appears best suited for future studies because the assay has a higher precision than earlier methods. Variant frequencies from different assay methods measuring the same variant cell type agreed with each other better than with the estimated dose, suggesting that the imprecision in the assay is not primarily responsible for VFs that differ from the fitted dose response. Consistent deviations from the dose response were seen for some individuals, suggesting either errors in dose estimates for these individuals or interindividual differences in susceptibility or other exposures. For the study population as a whole, however, discrepancies between assays for M-loss and N-loss variants suggest stochastic factors may have an important effect on individual VFs for A-bomb survivors.

Chromosome Mapping↗
PubMed1993

Effects of short-term culture on benign and malignant human breast epithelium analyzed by image analysis.

The ability to culture malignant breast cells is crucial to the success of many scientific studies. However, short-term cultures of breast cancers are composed predominantly of DNA diploid cells, leading to doubt regarding the presence of bonafide cancer cells in these cultures. Morphology by conventional light microscopy is not helpful since cultured benign cells take on features usually associated with malignancy. In this study we examined by image analysis both benign and malignant breast cancer cells before and after culture. Consistent changes in both benign and malignant cells were found following culturing. There also were consistent differences distinguishing the cultures derived from benign and malignant specimens. While the features used were not sufficiently powerful to identify individual cells or cultures as benign or malignant, our results strongly suggest that malignant breast cells do indeed grow in short-term cultures.

Adult↗
PubMed1992

Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma.

BACKGROUND: Axillary lymph node status has been the most important prognostic factor in operable breast carcinoma, but it does not fully account for the varied disease outcome. More accurate prognostic indicators would help in selection of patients at high risk for disease recurrence and death who are candidates for systemic adjuvant therapy. Our recent findings indicated that microvessel density (count or grade) in invasive breast carcinoma (a measure of tumor angiogenesis) is associated with metastasis and thus may be a prognostic indicator. PURPOSE: This study was designed to further define the relationship of microvessel density with overall and relapse-free survival and with other reported prognostic indicators in breast carcinoma. METHODS: In a prospective, blinded study of 165 consecutive patients, the microvessels within primary invasive breast carcinoma were highlighted by immunocytochemical staining to detect factor VIII-related antigen. Using light microscopy, we counted microvessels per 200x field in the most active areas of neovascularization and graded microvessel density. These findings were correlated, by univariate and multivariate analyses, with overall and relapse-free survival, axillary node status, and other prognostic indicators (median follow-up, 51 months). RESULTS: There was a highly significant (P < or = .001) association of microvessel density with overall survival and relapse-free survival in all patients, including node-negative and node-positive subsets. All patients with breast carcinomas having more than 100 microvessels per 200x field experienced tumor recurrence within 33 months of diagnosis, compared with less than 5% of the patients with breast carcinoma having 33 or fewer microvessels per 200x field. Moreover, microvessel density was the only statistically significant predictor of overall survival among node-negative women (P < .001). Only microvessel density (P < .001) and histologic grade (P = .04) showed statistically significant correlations with relapse-free survival in the node-negative subset. CONCLUSIONS: Microvessel density in the area of the most intense neovascularization in invasive breast carcinoma is an independent and highly significant prognostic indicator for overall and relapse-free survival in patients with early-stage breast carcinoma (I or II by International Union Against Cancer criteria). IMPLICATIONS: Such an indicator would be useful in selection of those node-negative patients with breast carcinoma who are at high risk for having occult metastasis at presentation. These patients could then be given systemic adjuvant therapy.

Adult↗
PubMed1992

Cutaneous melanoma at Lawrence Livermore National Laboratory: comparison with rates in two San Francisco bay area counties.

During the period 1974 through 1985, employees at Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States) were diagnosed with cutaneous malignant melanoma at approximately three times the rate of the surrounding community. We investigated two explanations for this excess: the first explanation examined was that the recorded incidence of the neighboring community underestimates actual incidence. We estimated the amount of excess attributable to underreporting by using data from a survey conducted among San Francisco Bay Area clinicians and pathologists to determine previously unrecorded occurrences. We found that underreporting has negligible impact on melanoma incidence. The second explanation examined was that heightened medical awareness of the disease among LLNL employees and their physicians has led to greater detection. We found that LLNL melanomas are thinner than those from the surrounding community and that no excess was observed if we limited our attention to thicker, more invasive melanomas.

Adult↗
PubMed1992

Mechanism of soman-induced contractions in canine tracheal smooth muscle.

The actions of the irreversible organophosphorus cholinesterase (ChE) inhibitor soman were investigated on canine tracheal smooth muscle in vitro. Concentrations of soman greater than or equal to 1 nM increased the amplitude and decay of contractions elicited by electric field stimulation. The effect on decay showed a marked dependence on stimulation frequency, undergoing a 2.4-fold increase between 3 and 60 Hz. Soman also potentiated tensions due to bath applied acetylcholine (ACh). Little or no potentiation was observed for contractions elicited by carbamylcholine, an agonist that is not hydrolyzed by ChE. Concentration of soman greater than or equal to 3 nM led to the appearance of sustained contractures. These contractures developed with a delayed onset and were well correlated with ChE activity. Alkylation of muscarinic receptors by propylbenzilylcholine mustard antagonized the actions of soman on both spontaneous and electrically-evoked muscle contractions. The results are consistent with a mechanism in which the toxic actions of soman are mediated by accumulation of neurally-released ACh secondary to inhibition of ChE activity. An important factor in this accumulation is suggested to be the buffering effect of the muscarinic receptors on the efflux of ACh from the neuroeffector junction.

Acetylcholine↗
PubMed1992

Description of a spheroid model for the study of radiation and chemotherapy effects on hypoxic tumor cell populations.

The presence of poorly oxygenated cells in solid tumors may account for clinical resistance to ionizing radiation and some chemotherapy in many cancers. Studies of the presence and spatial distribution, sensitivity to cancer therapies, and other physiological characteristics of hypoxic cells are hindered by the lack of markers specific for hypoxia and a relevant yet easily manipulated model system. We have chosen to use multicellular spheroids composed of murine EMT6 (fibrosarcoma) tumor cells as a model system and have applied an immunohistochemical marker specific for hypoxic cells with the ultimate goal of determining how cell populations change in response to radiation and/or chemotherapy. Large spheroids (500-700 microns in diameter) were selected and incubated in the presence of a hexafluorinated 2-nitroimidazole derivative, designated CCI-103F, which undergoes reductive metabolism and irreversibly binds to cellular macromolecules only under low oxygen tensions. A rabbit polyclonal antibody raised against a CCI-103F/protein adduct was used to visualize hypoxic cells using standard streptavidin-biotin-peroxidase immunohistochemical methods. Investigations using this spheroid model system promise to further our understanding of hypoxic cell resistance to cytotoxic therapies and of hypoxic cell biology in general.

Animals↗
PubMed1992

Quantitative correlation of mutagenic and carcinogenic potencies for heterocyclic amines from cooked foods and additional aromatic amines.

Aromatic amines have long been recognized as animal and human carcinogens. Recently heterocyclic aromatic amines (thermic amines) have been found in small amounts in cooked foods, primarily meats, and have proven to be potent mutagens and rodent carcinogens. Availability of quantitative databases for mutagenic potency in Salmonella and for carcinogenic potency in rodents has made possible a study of ten heterocyclic thermic amines and 24 aromatic amines. Potencies on mutagenic and carcinogenic scales were significantly correlated. By multiple linear regression analysis and multivariate analysis of variance, two descriptive structural factors were found to modulate the two modes of biological response. These factors were number of rings and methyl substitution at carbon atoms. The quantitative correlation between mutagenic and carcinogenic potencies and the modulating structural factors suggest a significant similarity of molecular mechanisms and support the utility of the short-term bacterial assay in evaluating hazard levels.

Amines↗
PubMed1992

Computed tomography: does it really improve the treatment of cervical carcinoma?

OBJECTIVE: The purpose of this study was to determine if computed tomography in cervical cancer staging resulted in treatment modifications leading to improved survival. STUDY DESIGN: Medical records of 246 consecutive women treated over a 3-year period for primary cervical cancer were reviewed. Frequency of recurrence was the outcome measure of interest and subjected to chi 2 analysis. RESULTS: Only eight patients had improved survival from treatment modifications based on computed tomography findings. Eight patients underwent additional surgical procedures because of computed tomography findings that proved to be erroneous. CONCLUSIONS: Considering the high cost and limited benefit, computed tomography for cervical cancer staging is not recommended.

Carcinoma↗
PubMed1992

Relaxation of soman-induced contracture of airway smooth muscle in vitro.

A possible role for beta-adrenergic agonists in the management of bronchoconstriction resulting from exposure to anticholinesterase compounds was investigated in vitro in canine tracheal smooth muscle. Norepinephrine, salbutamol and isoproterenol produced partial relaxation of soman-induced contractures. However, the relaxation induced was not sustained; muscle tensions returned to pretreatment levels within minutes despite the continued presence of beta-agonists. Increasing cAMP levels with the non beta-agonist bronchodilators such as theophylline, a phosphodiesterase inhibitor, or forskolin, a specific stimulator of adenylate cyclase, resulted in more complete and longer lasting relaxation, suggesting that beta-adrenoceptor desensitization may contribute to the failure by beta-agonists to produce sustained relaxation.

Acetylcholine↗
PubMed1992

Evaluation of a subcutaneously implanted chamber for antibody production in rabbits.

Polyclonal antibody production in subcutaneous chambers was compared to traditional antibody production methods in rabbits. The chamber, a sterilized plastic wiffle golf ball that had been surgically implanted in the subcutis of the thoracic region, was immunized via a percutaneous injection of antigen into the core of the ball through one of the perforations in the chamber wall. Rabbits bearing chambers were immunized on the same schedule and with the same concentrations of antigens as were provided the adjuvant injected rabbits. Fluid volumes of 12 to 22 ml could be removed from each chamber at weekly intervals. Chamber antibody to specific microbial antigens was equal to or better than serum antibody produced to the same antigens with Freund's or acrylamide adjuvants. The comfort of the rabbit, the ease in chamber immunization, and the recovery of high titer antibody in large volumes make the subcutaneous chamber an attractive method for polyclonal antibody production.

Animals↗
PubMed1991

Regulation of acetylcholine hydrolysis in canine tracheal smooth muscle.

The regulation of acetylcholine (ACh) lifetime by acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BuChE, EC 3.1.1.8) was evaluated in vitro in canine tracheal smooth muscle preparations. Selective inhibition of AChE by low concentrations of 1,5-bis(N-allyl-N,N-dimethyl-4-ammoniumphenyl)-pentane-3-one dibromide (BW 284C51) led to increases in the amplitude and half-relaxation time of contractions elicited by electric field stimulation. Maximal responses were observed in the presence of 10(-6) M BW 284C51, where the amplitude and half-relaxation time were increased by 84 and 198%, respectively. Higher concentrations of BW 284C51, on the other hand, depressed the amplitude and shortened the decay of electric field stimulation-induced contractions by a mechanism involving blockade of muscarinic receptors. Selective inhibition of BuChE by tetraisopropylpyrophosphoramide (iso-OMPA) led to monotonic increases in the electric field stimulation amplitude and duration. These alterations were less marked than those observed in the presence of BW 284C51. Co-application of BW 284C51 (10(-5) M) and iso-OMPA (10(-5) M) resulted in a 1330% prolongation in the decay of electric field stimulation-induced contractions and the development of a sustained contracture. Such contractures were not observed with either inhibitor alone at any concentration tested. The results indicate that both hydrolytic enzymes are involved in the regulation of ACh lifetime at the canine tracheal neuroeffector junction with AChE exerting the more prominent role. The finding that BuChE co-regulates ACh lifetime in canine trachealis muscle demonstrates a functional role for this enzyme.

Acetylcholine↗