Biomedical subjects

D H Moore

Publications and source records attributed to D H Moore.

At least 91 records · Page 5Linked to original sources

PubMed1995

The effects of age and lifestyle factors on the accumulation of cytogenetic damage as measured by chromosome painting.

Individual responses to the aging process are variable and are affected by genetic as well as environmental factors. Fluorescent in situ hybridization with whole chromosome probes ('chromosome painting') provides an efficient approach for detecting structural chromosome aberrations in human lymphocytes. This rapid and sensitive technique is an effective tool for quantifying chronic exposure to environmental agents which may result in an accumulation of cytogenetic damage with age. We have applied this technology to a normal, putatively unexposed, population to document the relationship between age and the accumulation of cytogenetic damage, as well as to establish a baseline frequency of stable aberrations. Using probes for chromosomes 1, 2 and 4 simultaneously, the equivalent of 1000 metaphases was scored for stable and unstable aberrations from each of 91 subjects ranging in age from newborns (umbilical cord bloods; n = 14) to adults aged 19 to 79 years. Each subject (or one parent of each newborn) completed an extensive questionnaire to identify possible lifestyle factors that may influence the frequency of cytogenetic damage. Our findings show a significant increase in stable aberrations (translocations and insertions) with age (p < 0.0001). We also observed age-related increases with dicentrics (p < 0.0001) and acentric fragments (p < 0.0001). Relative to the frequencies observed in cord bloods, the frequencies of stable aberrations, dicentrics, and acentric fragments in adults aged 50 and over were elevated 10.6-fold, 3.3-fold, and 2.9-fold, respectively. Nine variables other than age are significantly associated with the frequency of stable aberrations; these are: smoking (two variables), consumption of diet drinks and/or diet sweeteners (4 variables), exposure to asbestos or coal products (1 variable each), and having a previous major illness (1 variable). Newborns whose mothers smoked during pregnancy had a 1.5-fold increase in stable aberrations (p = 0.029). Repeat samples from a subset of the adults indicate that for most subjects there is little change in individual translocation frequencies over a period of two to three years. These results support the hypothesis that stable chromosome aberrations show a greater accumulation with age than do unstable aberrations and suggest that lifestyle factors contribute to the accumulation of cytogenetic damage.

Adolescent↗

PubMed1995

Impact of age and environment on somatic mutation at the hprt gene of T lymphocytes in humans.

Analysis of two human populations for dependence of somatic mutation on age has revealed both similarities and differences. The studies performed employed peripheral blood lymphocytes and measured the efficiency with which these cells form clones in vitro (cloning efficiency, CE) and the frequency of cells with inactivating mutations of the hypoxanthine phosphoribosyltransferase gene (mutant frequency, MF). The people studied were between 19 and 64 years of age. In one population, composed of 78 never smokers and 140 current smokers from the United States (US), both CE and MF were dependent on age: CE declined with age (p = 0.005); MF increased 0.15 per 10(6) cells per year of age for nonsmokers (p < 0.001) and at 1.3 times that rate for smokers (p = 0.01). In the second population, 80 people of unknown smoking status from Russia, the increase in MF per year was even greater, 2.5 times that of the US nonsmokers (p = 0.001) but the dependence of CE on age was the same as for the US population (p = 0.043). Because the increase of MF of the Russians with age is 2-fold greater than that of the US smokers, the intensity of smoking and/or other environmental exposures, or the susceptibility to these exposures, must account for the difference in age dependent MF increase, not the proportion of Russians that are smokers. Differences in the lymphocyte subpopulations that survived the longer transit from Russia may have contributed to the observed differences in MF. However, overall, the mutant frequency results suggest that the Russians were chronically exposed to higher levels of agents that induce somatic mutation and that, on an age adjusted basis, the Russia population studied is at increased risk for health consequences from accumulated genetic damage.

Adult↗

PubMed1995

Validation of chromosome painting. II. A detailed analysis of aberrations following high doses of ionizing radiation in vitro.

Fluorescence in situ hybridization with chromosome-specific composite DNA probes ('chromosome painting') is useful for quantifying radiation-induced cytogenetic damage. Recently we showed that the frequency of aberrations observed with painting is similar to that seen with conventional cytogenetic methods, at least at doses of < or = 2 Gy. Above this dose, however, the agreement was not as good. We describe here the results of additional work designed to clarify our earlier findings, and provide a detailed analysis of the type and frequency of aberrations induced in human peripheral lymphocytes following acute exposure to 137Cs at doses of 0 (unexposed control), 1, 2, 3 and 4 Gy. The newly-developed nomenclature for chromosome aberrations detected by painting (Protocol for Aberration Identification and Nomenclature Terminology, 'PAINT') was used to classify all aberrations. Our results indicate that if the guidelines of the PAINT system are followed, chromosome painting can provide meaningful biodosimetry at high doses, and that the observation of complicated rearrangements not only does not interfere with dose estimation, but also the information provided by these exchanges can be easily broken down into the component aberrations and included in the dose estimate. We also show that the inequality between translocations and dicentrics that we previously observed can be explained by an excess of one class of translocated chromosomes, specifically those in which the centromere is from an unpainted chromosome. Translocated chromosomes in which the centromere is painted were found to occur at a frequency equal to dicentrics. These results should help clarify the use of painting for radiation biodosimetry by improving our understanding of the frequencies of various types of stable aberrations observed shortly after exposure. This will improve our ability to perform meaningful biodosimetry long after the frequencies of unstable aberrations have ceased to be informative.

Adult↗

PubMed1995

Tumor angiogenesis correlates with lymph node metastases in invasive bladder cancer.

Neovascularization of tumor tissue (tumor angiogenesis) is considered essential for tumor growth, proliferation and eventually metastasis. Microvessel density or count, a measure of tumor angiogenesis, correlates with clinical outcome in skin, breast, lung and prostate carcinomas. To determine whether an association of tumor angiogenesis and nodal metastasis exists in invasive bladder cancer, microvessel counts in 41 primary invasive stages (T2 to 4,NX,M0) bladder cancers were assessed. Microvessels were identified by immunostaining of endothelial cells for factor VIII-related antigen. Microvessels were scored in selected areas showing active neovascularization, either counting a 200 x field (0.74 mm.2) or by using a 10 x 10 square ocular grid (0.16 mm.2). The microvessel count correlated with the presence of occult lymph node metastases (p < 0.0001) by both techniques. The mean microvessel count in 27 patients without lymph node metastases was 56.2 microvessels per 200 x field (standard deviation [SD] 29.5, range 7 to 130) or 28.6 microvessels per grid (SD 14.4, range 4 to 65). The 14 patients with histologically proved lymph node metastases showed mean 138.1 microvessels per 200 x fields (SD 37.9, range 82 to 202) or 74.7 microvessels per grid (SD 14.4, range 43 to 115). Good correlation was noted between area and grid counting (r = 0.97). Tumor T stage, grade and the presence of vascular or lymphatic invasion did not correlate with the presence of lymph node metastases (p = 0.41, 0.59 and 0.26, respectively). Microvessel count may provide important information regarding the risk of occult metastasis in patients with invasive bladder carcinomas.

Capillaries↗

PubMed1994

Epithelial ovarian cancer complicating renal transplantation.

Patients taking immunosuppressive therapy are at substantial risk for malignant disease. We report two cases of epithelial ovarian cancer occurring in women after renal transplantation with subsequent poor clinical outcome. Clinicians are advised to thoroughly investigate adnexal masses in this patient population.

Adult↗

PubMed1994

Correlation of Ki-67 antigen expression with mitotic figure index and tumor grade in breast carcinomas using the novel "paraffin"-reactive MIB1 antibody.

Tumor proliferation is inversely associated with survival in patients with breast carcinoma. Although the proliferation marker Ki-67 antigen correlates with mitotic figure count (MFC) in breast carcinoma (number of mitotic figures per high-powered field), the more precise association of Ki-67 antigen expression with mitotic figure index (MFI) (number of mitotic figures per tumor cells) and histologic grade remains incompletely defined, especially when using the new "paraffin"-reactive monoclonal antibody MIBI to mark the Ki-67 antigen. To determine the association of Ki-67 antigen expression with mitotic figure content we immunostained 50 formalin-fixed, paraffin-embedded breast carcinomas with the MIB1 monoclonal antibody and correlated the results with MFC, MFI, and Scarff-Bloom-Richardson grade. The Ki-67 antigen-labeling index (K67LI) was the number of MIBI-positive cells/1,000 tumor cells, the MFI was the number of mitotic figures/1,000 tumor cells, and the MFC was the number of mitotic figures/10 high-powered fields. The K67LI correlated highly with the MFI (r = .76, P < .0001), MFC (r = .78, P < .0001), and Scarff-Bloom-Richardson grade (r = .73, P < .0001). In addition, analysis of variance showed that MFI was more precise than MFC in estimating K67LI and thus a more repeatable measure of tumor proliferation. Moreover, measurements made by MFI were as precise as those made by K67LI. Therefore, the correlation of K67LI with mitotic figure content was strong enough to suggest that a very carefully measured MFI provides an estimate of tumor growth fraction equivalent to the K67LI. However, which method is optimal for estimating tumor proliferation rate remains unclear.

Adenocarcinoma↗

PubMed1994

Effect of cooking time and temperature on the heterocyclic amine content of fried beef patties.

The mutagenic heterocyclic amines 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) were measured in ground-beef patties fried at 150, 190 and 230 degrees C for 2-10 min on each side. Heterocyclic amines were purified using solid-phase extraction and analysed by HPLC. Recovery-corrected amounts of each heterocyclic amine were determined by the method of standard addition based on spiked samples with recoveries ranging from 40 to 70%. Mutagenic activity measured by the Ames/Salmonella test was determined for each sample. The amounts of MeIQx, PhIP, DiMeIQx and IQ increased with time and temperature of cooking. 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and 2-amino-9H-pyrido[2,3-b]indole (A alpha C) were not detected in any sample. The mutagenic activity response measured for the meat extracts (TA98 revertants) was similar to the mutagenic activity calculated from the mass of heterocyclic amines present. The rate of formation of PhIP in a model system containing creatinine and phenylalanine heated in 80% diethylene glycol was compared with PhIP formation during meat frying. The apparent heats of activation were 6.5 kcal/mol in the model system compared with 6.0 kcal/mol in the fried meat patties. The increase in PhIP and MeIQx formation fitted an exponential function over the range 0 to 11 min and from 150 to 230 degrees C. This report shows clearly that increases in cooking temperature and time can have a profound effect on the amounts of heterocyclic amines generated and subsequently consumed in the diet.

Animals↗

PubMed1994

Nevus counting as a risk factor for melanoma: comparison of self-count with count by physician.

BACKGROUND: The number of total body nevi is a major risk marker for malignant melanoma. No previous study has evaluated the accuracy of whole body large nevus (> or = 5 mm) self-counts. OBJECTIVE: Our purpose was to evaluate the accuracy of large nevus self-counts by sex, age, educational level, body site, family history of skin cancer, and nevus characteristics. METHODS: Self-counting of large nevi by 125 patients was compared with physician counting, with attention to nevus characteristics. RESULTS: Overall, 79% of the self-counts agreed to within +/- 3 nevi of the physician's count. Analysis of variance revealed that the presence of nonpigmented or flat nevi significantly increased the chance of subject undercount, as did male sex. CONCLUSION: Self-counts of large nevi are comparable to physician's counts and may be useful for melanoma screening.

Adult↗

PubMed1994

Llama cardiology.

Auscultatory, ECG, and echocardiographic data have been presented for healthy llamas. The literature, however, contains little information on the incidence of congenital and acquired heart disease in the llama. Data compiled from the medical records at CSU-VTH and the VMDB provide an indication of the types of cardiac disease to be found in llamas in North America. A wide variety of congenital cardiac defects are found in llamas, the most prevalent defect of which is VSD. Llamas tend to do well with this defect but are unlikely to be useful pack animals. Acquired heart disease primarily involved inflammatory processes of the pericardium, endocardium, epicardium, and myocardium, and pericardial effusion without documented inflammatory disease. Although not every cardiac murmur necessitates a complete cardiac work-up, every effort should be made to compile accurate medical histories and physical findings related to the cardiac disease in llamas in order to advance our knowledge of these disorders. There also is a need to use available technologies to better define cardiac abnormalities in the llama and accurately report these findings in the literature before cardiology of llamas is fully understood.

Animals↗

PubMed1994

Prognostic value of Cathepsin D expression in breast cancer: immunohistochemical assessment and correlation with radiometric assay.

BACKGROUND: The prognostic significance of Cathepsin D and optimal methodologies to measure Cathepsin D in breast cancers are controversial. PATIENTS AND METHODS: Quantitative (immunoradiometric) and semiquantitative (immunohistochemical) assays for Cathepsin D expression were compared using 25 breast carcinomas. Immunohistochemical Cathepsin D results were derived using 3 different anti-Cathepsin D antibodies and significant associations between immunohistochemical and radiometric Cathepsin D data were observed for each reagent. Immunohistochemical analysis of Cathepsin D expression was performed on nearly 500 fixed-embedded archival breast cancers with long-term patient follow-up using 2 anti-Cathepsin D antibodies (CDR2-11/23, IC11). RESULTS: The immunohistochemical reagents recognized generally overlapping subsets of Cathepsin D positive tumors (correlation co-efficient 0.54; p = 0.00016). Correlations between Cathepsin D data and clinical, histologic or biologic features differed for each antibody. For the node-negative patient subset, Cathepsin D immunopositivity correlated with erbB-2 and stress-response protein 27 overexpression but not survival. Cathepsin D positivity was associated with subsequent distant metastasis and estrogen receptor positivity in node positive patients. Univariate analysis of all patients suggested that Cathepsin D immunopositivity may be predictive of a reduced metastasis-free but not overall survival. Multivariate analysis, however, failed to confirm an independent prognostic value for Cathepsin D in breast cancer patients. CONCLUSIONS: These data do not confirm an independent prognostic significance for Cathepsin D using immunohistochemical methods on breast cancers.

Breast Neoplasms↗

PubMed1994

Ovarian cancer in the elderly patient.

Ovarian cancer is a disease of the elderly, with more than 50% of cases occurring in women over 65 years of age. Studies from national databases, reporting institutions, and cooperative groups conducting clinical cancer research indicate that elderly women with epithelial ovarian cancer have a worse prognosis than younger women. Elderly women present with more advanced cancers that are usually of high grade and with aneuploid DNA content. In contrast to younger patients, elderly women more frequently do not receive definitive chemotherapy or surgery and seemingly undergo less aggressive treatments. Age alone does not appear to be a risk factor for surgical morbidity or drug treatment toxicity. Research is needed regarding age-related genetic alterations in ovarian cancer. Clinical trials of ovarian cancer treatment in elderly women should include quality of life measurements, recognizing the specific functional and psychosocial expectations of this patient population.

Age Factors↗

PubMed1994

Risk factors for melanoma incidence in prospective follow-up. The importance of atypical (dysplastic) nevi.

BACKGROUND AND DESIGN: Assessment of melanoma risk factors can help identify individuals at greatest risk for melanoma. Previous studies were retrospective case-control or prospective without control groups. A prospective group of 3889 employees without previous melanoma or family history of multiple melanoma at the Lawrence Livermore (Calif) National Laboratory were examined as part of a melanoma screening program. Their subsequent incidence of melanoma in relationship to potential melanoma risk factors, which were recorded at the first examination, was determined. RESULTS: Nine invasive melanomas developed after initial examination among the studied population over an 8-year period with an average follow-up of 5 years. The presence of an easily recognized pattern of definite clinically atypical (dysplastic) nevi was present in 7% of employees and was associated with a cumulative melanoma risk of 1.9%. It was the strongest risk factor, with a relative risk of 47 compared with the 0.04% cumulative melanoma risk in the 64% of employees with no atypical (dysplastic) moles (chi 2 for equal risk, P = 7 x 10(-8). Significant, but less marked associations with melanoma risk were found for the total number of moles and for a history of many moles in other family members, with a maximal relative risk of 11.6 and 10.4, respectively. CONCLUSION: A small subgroup of the population with easily recognizable definite atypical (dysplastic) nevi have a marked increased risk of melanoma. Smaller significant melanoma risks were found for a total number of moles and a family history of many moles.

Adult↗

PubMed1994

The association of p53 immunopositivity with tumor proliferation and other prognostic indicators in breast cancer.

Abnormal accumulation of the p53 tumor suppressor gene product was analyzed in 198 primary invasive human breast carcinomas. In 47 of these cases, single-strand conformational polymorphism was used to detect mutations in the highly conserved exons 5-9 of the gene. Mutations as determined by single-strand conformational polymorphism were found in 15 of 15 strongly immunopositive cases (100%) and 3 of 23 immunonegative cases (13%). There were also nine cases with < 1% immunopositive cells (borderline immunopositivity); p53 mutations were detected in seven of these cases. The results suggest that p53 immunopositivity is a highly specific, albeit somewhat insensitive surrogate for p53 mutations. p53 accumulation, detected by immunohistochemical methods using antibody PAb 1801, was noted in 29.8% of the cases and was associated with estrogen receptor (ER) negativity (P = 0.0003), progesterone receptor (PR) negativity (P = 0.008), and high histological grade (P = 0.037) by univariate analysis. Incorporation of bromodeoxyuridine was used to determine the percentage of cells synthesizing DNA (proliferative fraction). When bromodeoxyuridine was administered either in vivo (n = 93) or in vitro (n = 79), p53 accumulation was only marginally related to proliferative fraction (P = 0.067 by chi 2; P = 0.055 by Mann-Whitney). When tumors were segregated by ER status, the aforementioned associations of p53 immunopositivity with PR negativity, high histological grade, and increased proliferation rate lost their significance. p53 accumulation did not correlate with tumor size, clinical stage, axillary node metastases, or age at diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Primary adenocarcinoma of the gallbladder presenting as primary gynecologic malignancy: a report of two cases.

BACKGROUND: Carcinoma metastatic to the uterus from extragenital sites is rare. Such metastatic disease is typically diagnosed at autopsy or in patients with known primary malignancies. This report discusses two cases of primary carcinoma of the gallbladder presenting as abnormalities in gynecologic screening procedures. CASES: A 71-year-old woman presented with postmenopausal bleeding. Uterine curettage revealed poorly differentiated adenocarcinoma of presumed endometrial origin. Intraoperative frozen-section analysis of the uterus showed carcinoma involving the lymphatics, but no primary tumor. Further exploration revealed primary adenocarcinoma of the gallbladder, with widespread metastases. The second case was a 67-year-old asymptomatic woman. Routine cervical cytology showed adenocarcinoma, but tissue studies were negative. She developed jaundice 1 month later. Computed tomography of the upper abdomen revealed a mass in the gallbladder fossa, and needle biopsy of the lesion showed adenocarcinoma. CONCLUSIONS: Metastatic carcinoma of non-genital tract origin may present as primary gynecologic malignancy. The physician should be aware of the implications of both the common and unusual interpretations of screening and diagnostic procedures. When the clinicopathologic presentation is atypical, a thorough knowledge of the differential diagnoses of abnormal test results allows appropriate and expeditious patient management.

Adenocarcinoma↗

PubMed1993

Tumor labeling indices of primary breast cancers and their regional lymph node metastases.

BACKGROUND: Tumor labeling index has emerged as a strong predictor of the clinical course of women with breast cancer. This study investigated whether labeling index of primary tumors correlates with labeling indices of concurrent regional node metastases. METHODS: With appropriate written consent, preoperative in vivo infusion of the thymidine analogue 5-bromodeoxyuridine (BrdUrd) was used to label 109 human breast cancers. Labeled S-phase cells were identified immunohistochemically with an antibody specific to DNA-incorporated BrdUrd. Labeling index was the fraction of labeled nuclei in 2000 tumor nuclei. For 30 women, there was sufficient cancer in axillary lymph nodes to compare labeling indices in primary breast cancer and regional lymph node metastases. RESULTS: The 30 women were from 25 to 82 years of age. Tumors were from 1 to 12 cm in size and there were from 1 to 26 positive nodes. Tumor labeling index ranged from 0.1% to 34%, (mean, 11.1%; median, 10.3%) and axillary lymph node metastasis labeling index ranged from 0.1% to 27.7% (mean, 10.8%; median, 10.0%). There was strong correlation between primary tumor labeling index and regional lymph node metastases labeling index (r = 0.82, with 95% confidence interval 0.65-0.91). The correlation persisted within subgroups according to age, tumor size, number of positive nodes, and hormone receptor status. Primary tumor and lymph node metastases labeling indices also had statistically similar relationships with age, level of hormone receptors, tumor size, and number of positive nodes. CONCLUSIONS: Primary tumor and regional node labeling indices correlate strongly; the relationship is not influenced by age, level of hormone receptors, tumor size, or number of positive nodes.

Adult↗

PubMed1993

Derivative domain fitting: a new method for resolving a mixture of normal distributions in the presence of a contaminating background.

Derivative domain least squares analysis is a new method for resolving multiple peaks superimposed on a slowly varying continuum into separate normal (Gaussian) distributions without developing a functional approximation for the continuum. The method is based on fitting the first derivative of the data with the first derivative of the sum of a series of normal distributions. A functional approximation for the continuum is not necessary as long as the first derivative of the continuum is approximately zero (i.e., the continuum varies slowly compared to the normal distributions).

Background Radiation↗

PubMed1993

Hexamethylmelamine/altretamine as second-line therapy for epithelial ovarian carcinoma.

The purpose of this report was to review second-line hexamethylmelamine (HMM) chemotherapy of epithelial ovarian cancer to determine if HMM was active in cisplatin-resistant disease. Forty-four women with measurable disease received 100-300 mg/day HMM for 14 days, courses repeated every 4 weeks. There were 6 complete and 3 partial responses for an objective response rate of 20%. Among responding patients disease-free survival was 55% and overall survival was 88% at 3 years. Five of the 6 patients with a complete response remained disease-free at 10-117 months. Only 7/35 (20%) nonresponding patients were alive with mean follow-up of 16 months, and all had persistent cancer. Five women manifesting disease progression during cisplatin or carboplatin were subsequently treated with HMM, and none responded. Seventeen patients developing progressive cancer while receiving HMM were subsequently treated with cisplatin or carboplatin and objective responses occurred in 5 (29%). HMM was an active drug against epithelial ovarian cancer previously treated with cisplatin, but further study is needed to determine its activity against cisplatin-resistant ovarian cancer.

Adult↗

PubMed1993

Effects of diet and folate on levels of micronucleated polychromatic erythrocytes.

We describe a study examining the effects of fried beef consumption on the frequency of micronuclei in RNA-positive polychromatic erythrocytes (PCEs) in humans. 5 splenectomized individuals participated in a 2-week experiment consisting of 3 phases. During the first and last phases the subjects refrained from eating cooked meat for 4-5 days. This was designed to clear their system of mutagens found in cooked-meat products. In the second phase each person ate a similar diet, but also consumed 4 quarter-pound well-done hamburgers per day for 4 days. Erythrocyte-folate levels were also measured for each donor. No association between diet phase and micronucleus frequencies was observed among the 2 subjects with normal levels of folate. However, among the 3 low-folate donors, the frequency of micronucleated PCEs appeared to be associated with diet. Micronucleus frequencies began to increase 1 day following onset of the beef phase, and started to decline 1 day after finishing this phase. These observations are in agreement with erythrocyte maturation kinetics following short-term exposure. A repeat study performed on one of the low-folate donors consisted of two beef phases separated by a vegetarian phase. Beef in one phase was fried (high in mutagenic amino-imidazoazaarenes [AIAs]) while the beef in the other phase was fried after first being microwave-cooked (low in AIAs). Significant increases in the micronucleus frequency were not observed in this experiment, suggesting that AIAs formed during frying were not solely responsible for the induction of micronuclei.

Adult↗