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Biomedical subjects

A B Miller

Publications and source records attributed to A B Miller.

At least 91 records · Page 5Linked to original sources
PubMed1998

Immunohistochemical detection of c-erbB-2 and p53 in benign breast disease and breast cancer risk.

BACKGROUND: We studied the associations between c-erbB-2 protein overexpression and p53 protein accumulation in benign breast tissue and the risk of subsequent breast cancer. METHODS: We conducted a case-control study nested within the cohort of 4888 women in the National Breast Screening Study (NBSS) who were diagnosed with benign breast disease during active follow-up. Case subjects were the women who subsequently developed breast cancer (ductal carcinoma in situ [DCIS] or invasive carcinoma). Control subjects were matched to each case subject on NBSS study arm, screening center, year of birth, and age at diagnosis of benign breast disease. Histologic sections of benign and cancerous breast tissues were analyzed immunohistochemically. Information on potential confounding factors was obtained by use of a self-administered lifestyle questionnaire. RESULTS: Accumulation of p53 protein was associated with an increased risk of progression to breast cancer (adjusted odds ratio [OR] = 2.55; 95% confidence interval [CI] = 1.01-6.40), whereas c-erbB-2 protein overexpression was not (adjusted OR = 0.65; 95% CI = 0.27-1.53). The findings for c-erbB-2 and p53 did not differ among strata defined by menopausal status, allocation within the NBSS, history of breast disease, and whether the benign breast disease was detected at a scheduled screen or between screens. The results were also similar after exclusion of case subjects whose diagnosis of breast cancer occurred within 1 year of their diagnosis of benign breast disease and after exclusion of subjects with DCIS. CONCLUSIONS: p53 protein accumulation, but not c-erbB-2 protein overexpression, appears to be associated with an increased risk of progression to breast cancer in women with benign breast disease.

Adult↗
PubMed1998

Alcohol and breast cancer in women: a pooled analysis of cohort studies.

OBJECTIVE: To assess the risk of invasive breast cancer associated with total and beverage-specific alcohol consumption and to evaluate whether dietary and nondietary factors modify the association. DATA SOURCES: We included in these analyses 6 prospective studies that had at least 200 incident breast cancer cases, assessed long-term intake of food and nutrients, and used a validated diet assessment instrument. The studies were conducted in Canada, the Netherlands, Sweden, and the United States. Alcohol intake was estimated by food frequency questionnaires in each study. The studies included a total of 322647 women evaluated for up to 11 years, including 4335 participants with a diagnosis of incident invasive breast cancer. DATA EXTRACTION: Pooled analysis of primary data using analyses consistent with each study's original design and the random-effects model for the overall pooled analyses. DATA SYNTHESIS: For alcohol intakes less than 60 g/d (reported by >99% of participants), risk increased linearly with increasing intake; the pooled multivariate relative risk for an increment of 10 g/d of alcohol (about 0.75-1 drink) was 1.09 (95% confidence interval [CI], 1.04-1.13; P for heterogeneity among studies, .71). The multivariate-adjusted relative risk for total alcohol intakes of 30 to less than 60 g/d (about 2-5 drinks) vs nondrinkers was 1.41 (95% CI, 1.18-1.69). Limited data suggested that alcohol intakes of at least 60 g/d were not associated with further increased risk. The specific type of alcoholic beverage did not strongly influence risk estimates. The association between alcohol intake and breast cancer was not modified by other factors. CONCLUSIONS: Alcohol consumption is associated with a linear increase in breast cancer incidence in women over the range of consumption reported by most women. Among women who consume alcohol regularly, reducing alcohol consumption is a potential means to reduce breast cancer risk.

Alcohol Drinking↗
PubMed1998

Alternate indices of electric and magnetic field exposures among Ontario electrical utility workers.

Epidemiologic studies examining the risk of cancer among occupational groups exposed to electric fields (EF) and or magnetic fields (MF) have relied on traditional summaries of exposure such as the time weighted arithmetic or geometric mean exposure. Findings from animal and cellular studies support the consideration of alternative measures of exposure capable of capturing threshold and intermittent measures of field strength. The main objective of this study was to identify a series of suitable exposure metrics for an ongoing cancer incidence study in a cohort of Ontario electric utility workers. Principal components analysis (PCA) and correlational analysis were used to explore the relationships within and between series of EF and MF exposure indices. Exposure data were collected using personal monitors worn by a sample of 820 workers which yielded 4247 worker days of measurement data. For both EF and MF, the first axis of the PCA identified a series of intercorrelated indices that included the geometric mean, median and arithmetic mean. A considerable portion of the variability in EF and MF exposures were accounted for by two other principal component axes. The second axes for EF and MF exposures were representative of the standard deviation (standard deviation) and thresholds of field measures. To a lesser extent, the variability in the exposure variable was explained by time dependent indices which consisted of autocorrelations at 5 min lags and average transitions in field strength. Our results suggest that the variability in exposure data can only be accounted for by using several exposure indices, and consequently, a series of metrics should be used when exploring the risk of cancer owing to MF and EF exposure in this cohort. Furthermore, the poor correlations observed between indices of MF and EF reinforce the need to be take both fields into account when assessing the risk of cancer in this occupational group.

Animals↗
PubMed1998

A case-cohort study of diet and risk of benign proliferative epithelial disorders of the breast (Canada).

A case-cohort analysis of the association between diet and risk of benign proliferative epithelial disorders (BPED) of the breast was undertaken within a cohort of 56,537 women who were enrolled in the Canadian National Breast Screening Study (NBSS) and who completed a self-administered dietary questionnaire. (The NBSS is a randomized controlled trial of screening for breast cancer in women aged 40 to 59 years.) BPED are thought to have premalignant potential. Specific hypotheses were that risk of BPED would increase with increasing energy-adjusted fat intake and decrease with increasing energy-adjusted vitamin A and fiber intake. Additionally, we explored the association between calcium intake and risk of BPED. During the active follow-up phase of the NBSS, 657 women in the dietary cohort were diagnosed with biopsy-confirmed incident BPED. For comparative purposes, a subcohort consisting of a random sample of 5,581 women was selected from the full dietary cohort. After exclusions for various reasons, the analyses were based on 545 cases and 4,921 non-cases. Overall, the results were almost uniformly null, and provided little support for the study hypotheses. Rate ratios (95 percent confidence intervals [CI]) for the highest cf the lowest quintile levels for total fat, retinol, beta-carotene, fiber, and calcium were 0.88 (CI = 0.65-1.20), 0.97 (CI = 0.71-1.31), 0.94 (CI = 0.70-1.27), 1.11 (CI = 0.82-1.50), and 0.81 (CI = 0.60-1.07), respectively. There were too few cases of atypical BPED for meaningful analysis, but results for those whose BPED showed no atypia were similar to the overall results. Further analyses conducted separately in the screened and control arms of the NBSS also failed to provide strong support for dietary associations, as did those conducted separately for screen-detected and interval-detected BPED.

Adult↗
PubMed1998

Environmental characteristics of nursing homes and community-based settings, and the well-being of adults with intellectual disability.

The present study examined whether characteristics of the environment of nursing homes and community-based residential settings are associated with the adaptive behaviour, health and community integration of adults with intellectual disability living in those settings. The specific characteristics of the environment were type of facility, size, level of residential involvement in policy-making, and the degree of variety and stimulation of the physical environment. The study assessed 249 residents with intellectual disability over a 3-year period who lived in nursing homes at baseline. At follow-up, 50 of the residents had moved to community-based facilities while 199 of the residents remained in nursing homes. The results indicated that type, size and characteristics of the environment were related to the level of adaptive behaviour and community integration at follow-up. Residents living in community-based settings had better health and greater levels of community integration than residents living in nursing homes. Residents living in smaller facilities had greater adaptive behaviour at follow-up than residents living in larger facilities. More variety and stimulation in the residential physical environment was associated with greater adaptive behaviour among residents at follow-up. Residential facilities that permitted greater resident involvement in policy-making, and had greater variety and stimulation in their physical environment were associated with greater levels of community integration among their residents at follow-up.

Adaptation, Psychological↗
PubMed1998

Alcohol consumption and risk of benign proliferative epithelial disorders of the breast: a case-cohort study.

OBJECTIVE: To study the association between alcohol consumption and risk of benign proliferative epithelial disorders (BPED) of the breast (conditions which are thought to have premalignant potential). DESIGN: Case-cohort study. SETTING: The study was undertaken within the 56,537 women in the Canadian National Breast Screening Study (NBSS) who completed self-administered dietary questionnaires. (The NBSS is a randomized controlled trial of screening for breast cancer in women aged 40-59 years at recruitment.) SUBJECTS: The study subjects were the 657 women in the dietary cohort who were diagnosed with biopsy-confirmed incident BPED. For comparative purposes, a subcohort consisting of a random sample of 5681 women was selected from the full dietary cohort. After exclusions for various reasons, the analyses were based on 557 cases and 5028 non-cases. RESULTS: When compared to non-drinkers, rate ratios (95% CI) for those consuming > 0 and < or =10 g of ethanol day(-1), >10 and < or =20 g day(-1), >20 and < or =30 g day(-1) and >30 g day(-1) were 0.35 (0.27-0.45), 0.26 (0.18-0.39), 0.29 (0.18-0.48), and 0.23 (0.13-0.40), respectively (the associated P value for the trend was 0.089). Similar findings were obtained from analyses conducted separately in the screened and control arms of the NBSS, in premenopausal and postmenopausal women, and for non-atypical and atypical forms of BPED, and there was little difference between the results for screen-detected and interval-detected BPED. CONCLUSIONS: Alcohol consumption was associated with a non-dose-dependent reduction in risk of BPED.

Adult↗
PubMed1997

Effect of breast self-examination techniques on the risk of death from breast cancer.

OBJECTIVE: To measure the effect of breast self-examination (BSE) technique and frequency on the risk of death from breast cancer. DESIGN: Case-control study nested within the Canadian National Breast Screening Study (NBSS). SETTING: The Canadian NBSS, a multicentre randomized controlled trial of screening for breast cancer in Canadian women. SUBJECTS: The case subjects were 163 women who had died from breast cancer and 57 women with distant metastases. Ten control subjects matched by 5-year age group, screening centre, year of enrolment and random allocation group were randomly selected for each case subject. EXPOSURE MEASURES: Self-reported BSE frequency before enrolment in the NBSS, annual self-reports of BSE frequency during the program and annual objective assessments of BSE technique. OUTCOME MEASURES: Odds ratios (ORs) associated with BSE practice were estimated by conditional multiple logistic regression modelling, which permitted control of covariates. RESULTS: Relative to women who, when assessed 2 years before diagnosis, examined their breasts visually, used their finger pads for palpation and examined with their 3 middle fingers, the OR for death from breast cancer or distant metastatic disease for women who omitted 1, 2 or 3 of these components was 2.20 (95% confidence interval [CI] 1.30 to 3.71, p = 0.003). The OR for women who omitted 1 of the 3 components was 1.82 (95% CI 1.00 to 3.29, p = 0.05), for those who omitted 2 of the 3 components, 2.84 (95% CI 1.44 to 5.59, p = 0.003), and for those who omitted all 3 components, 2.95 (95% CI 1.19 to 7.30, p = 0.02). The results remained unchanged after adjustment for potential confounders. CONCLUSION: The results, obtained with the use of prospectively collected data, suggest that the performance of specific BSE components may reduce the risk of death from breast cancer.

Adult↗
PubMed1997

Functional domains of a geminivirus replication protein.

Tomato golden mosaic virus, a member of the geminivirus family, has a single-stranded DNA genome that is replicated and transcribed in infected plant cells through the concerted action of viral and host factors. One viral protein, AL1, contributes to both processes by binding to a directly repeated, double-stranded DNA sequence located in the overlapping (+) strand origin of replication and AL1 promoter. The AL1 protein, which occurs as a multimeric complex in solution, also catalyzes DNA cleavage during initiation of rolling circle replication. To identify the tomato golden mosaic virus AL1 domains that mediate protein oligomerization, DNA binding, and DNA cleavage, a series of truncated AL1 proteins were produced in a baculovirus expression system and assayed for each activity. These experiments localized the AL1 oligomerization domain between amino acids 121 and 181, the DNA binding domain between amino acids 1 and 181, and the DNA cleavage domain between amino acids 1 and 120. Deletion of the first 29 amino acids of AL1 abolished DNA binding and DNA cleavage, demonstrating that an intact N terminus is required for both activities. The observation that the DNA binding domain includes the oligomerization domain suggested that AL1-AL1 protein interaction may be a prerequisite for DNA binding but not for DNA cleavage. The significance of these results for AL1 function during geminivirus replication and transcription is discussed.

Amino Acid Sequence↗
PubMed1997

Impact of cancer screening on women's health.

Worldwide, 31% of cancers in women are in the breast or uterine cervix. Prevention of cervical cancer is effective with the use of the cervical Pap smear test if applied in an organized and continuous fashion, including treatment of precancerous lesions. At best such programs have led to a 60% decrease in cervical cancer incidence and mortality in the Nordic countries. Early detection of breast cancer in a population based screening may lead to a 30% reduction of mortality from this disease in the screened population. Measures to guarantee high coverage and attendance, adequate field facilities, organized program for quality control and adequate facilities for diagnosis and treatment are prerequisites of successful programs. In absolute terms the contribution of screening to the total mortality reduction among middle-aged populations is small, much smaller than the potential gains from cancer prevention.

Breast Neoplasms↗
PubMed1997

Variable region gene segment utilization in rhesus monkey hybridomas producing human red blood cell-specific antibodies: predominance of the VH4 family but not VH4-21 (V4-34).

Structural analyses of human immunoglobulin gene segments from monoclonal cell lines provide valuable information regarding the antibody repertoire. This information, in conjunction with a nearly complete knowledge of the human immunoglobulin germline repertoire, now allows further investigation into the underlying molecular basis responsible for some of the observed biases found in the expressed repertoire. One human heavy chain variable region gene segment, V4-34 (VH4-21), is one of the most prevalent gene segments in the expressed repertoire. The overwhelming presence of the V4-34 gene segment suggests that it may play an important role in immune responses. However, there is currently little information regarding its presence and potential importance in nonhuman primates. In order to determine if this gene segment is used by lower primates in a similar manner we determined the molecular structure of the variable region gene segments that are expressed by macaque monoclonal heterohybridomas that are specific for human red blood cell antigens. Eleven of the 12 hybridomas are derived from Rhesus monkeys (Macaca mulatta) and one is from a cynomologous monkey (Macaca fascicularis), all of which have been immunized with human red blood cells. The predominance of a VH4-like family and the specific absence of a VH4-21 equivalent led us to further characterize the macaque VH4 gene family at the germline level. Therefore, germline gene segments from the macaque equivalent to the human VH4 gene family are also described.

Animals↗
PubMed1997

Tumor characteristics and survival of breast cancer patients in relation to premorbid diet and body size.

Nutritional factors have been suggested to play an important role in the prognosis of breast cancer through their effect on tumor characteristics. This study evaluated four tumor characteristics and prognosis in relation to premorbid diet and body size. From a cohort of 89,835 women in the National Breast Screening Study (NBSS) in Canada, data on 676 incident cases of invasive carcinoma of breast, on whom we had dietary information, were used. A high energy intake lowered the likelihood of being ER positive and PR positive but after adjusting for ER status, was still associated with a higher risk of dying of breast cancer. Total fat and various types of fats were associated with a greater likelihood that a woman would be ER and PR positive, however the likelihood of dying from breast cancer was higher with higher fat consumption. There was no significant effect of higher intakes of beta carotene or vitamin C on ER status, nodal status or tumor size, but a significantly lower risk of dying from breast cancer was observed. Higher intake of carbohydrates and calcium was associated with a lowered frequency of ER and PR positive status but also with a lower risk of dying. Of the five indicators of body size studied, higher triceps skinfold thickness was associated with a slightly lower chance of being ER positive, PR positive, and node negative, and a significantly higher likelihood of dying. It appears that while there are significant associations between some of the diet and body size variables and tumor characteristics, the effect of most nutritional factors on prognosis in breast cancer may not be mediated via their effect on tumor characteristics.

Adult↗
PubMed1997

Non-dietary factors as risk factors for breast cancer, and as effect modifiers of the association of fat intake and risk of breast cancer.

To assess more precisely the relative risks associated with established risk factors for breast cancer, and whether the association between dietary fat and breast cancer risk varies according to levels of these risk factors, we pooled primary data from six prospective studies in North America and Western Europe in which individual estimates of dietary fat intake had been obtained by validated food-frequency questionnaires. Based on information from 322,647 women among whom 4,827 cases occurred during follow-up: the multivariate-adjusted risk of late menarche (age 15 years or more compared with under 12) was 0.72 (95 percent confidence interval [CI] = 0.62-0.82); of being postmenopausal was 0.82 (CI = 0.69-0.97); of high parity (three or more births compared with none) was 0.72 (CI = 0.61-0.86); of late age at first birth (over 30 years of age compared with 20 or under) was 1.46 (CI = 1.22-1.75); of benign breast disease was 1.53 (CI = 1.41-1.65); of maternal history of breast cancer was 1.38 (CI = 1.14-1.67); and history of a sister with breast cancer was 1.47 (CI = 1.27-1.70). Greater duration of schooling (more than high-school graduation compared with less than high-school graduation) was associated significantly with higher risk in age-adjusted analyses, but was attenuated after controlling for other risk factors. Total fat intake (adjusted for energy consumption) was not associated significantly with breast cancer risk in any strata of these non-dietary risk factors. We observed a marginally significant interaction between total fat intake and risk of breast cancer according to history of benign breast disease; with fat intake being associated nonsignificantly positively with risk among women with a previous history of benign breast disease; no other significant interactions were observed. Risks for reproductive factors were similar to those observed in case-control studies; relative risks for family history of breast cancer were lower. We found no clear evidence in any subgroups of a major relation between total energy-adjusted fat intake and breast cancer risk.

Breast Neoplasms↗
PubMed1997

The relationship between dietary fat intake and risk of colorectal cancer: evidence from the combined analysis of 13 case-control studies.

The objective of this study was to examine the effects of the intake of dietary fat upon colorectal cancer risk in a combined analysis of data from 13 case-control studies previously conducted in populations with differing colorectal cancer rates and dietary practices. Original data records for 5,287 cases of colorectal cancer and 10,470 controls were combined. Logistic regression analysis was used to estimate odds ratios (OR) for intakes of total energy, total fat and its components, and cholesterol. Positive associations with energy intake were observed for 11 of the 13 studies. However, there was little, if any, evidence of any energy-independent effect of either total fat with ORs of 1.00, 0.95, 1.01, 1.02, and 0.92 for quintiles of residuals of total fat intake (P trend = 0.67) or for saturated fat with ORs of 1.00, 1.08, 1.06, 1.21, and 1.06 (P trend = 0.39). The analysis suggests that, among these case-control studies, there is no energy-independent association between dietary fat intake and risk of colorectal cancer. It also suggests that simple substitution of fat by other sources of calories is unlikely to reduce meaningfully the risk of colorectal cancer.

Adult↗
PubMed1997

Mammography versus clinical examination of the breasts.

Using published data from screening trials, this article compares two-modality (mammography and clinical examination) and single-modality (clinical examination alone) screening by evaluating cancer detection rates, program sensitivities, mode of cancer detection in two-modality screening, nodal status at time of detection, survival 10 years post-diagnosis, and breast cancer mortality 10 years after entry. Consistently, two-modality screening achieved higher cancer detection rates and program sensitivity estimates than either modality alone; mammography alone achieved higher rates than clinical examination alone; interval cancer detection rates between screening examinations were higher following clinical examination alone than mammography alone; single-modality screening with mammography failed to detect breast cancers identified by clinical examination alone; the sensitivity of mammography was lower in younger than older women, while the reverse was true for clinical examination; and mammography identified a higher proportion of node-negative breast cancer than clinical examination. We conclude that combining clinical breast examination with mammography is desirable for women age 40-49 because mammography is less sensitive in younger than older women. Careful training and monitoring are, however, as essential with clinical examiners as with mammographers.

Adult↗
PubMed1997

The Canadian National Breast Screening Study: update on breast cancer mortality.

The Canadian National Breast Screening Study (CNBSS), conducted on women age 40-49, was designed to evaluate the efficacy of combined annual mammography and physical examination of the breasts in reducing breast cancer mortality in comparison to usual care (UC) controls. From January 1980 through March 1985, 25,214 women were individually randomized to the mammography/physical exam (MP) arm and 25,216 to the UC. The integrity of the randomization has been reviewed and confirmed to be unbiased. During an average, follow-up of 10.5 years from entry (range: 8.75-13 years), 82 women died from breast cancer in the MP arm and 72 in the UC, for a rate ratio of 1.14 (95% confidence interval: 0.83-1.56). All-cause mortality was almost identical comparing the two groups; the nonsignificant excess of breast cancer deaths in the MP arm was balanced by an excess of other cancer deaths in the UC arm.

Adult↗
PubMed1997

RRB1 and RRB2 encode maize retinoblastoma-related proteins that interact with a plant D-type cyclin and geminivirus replication protein.

Unlike mammalian and yeast cells, little is known about how plants regulate G1 progression and entry into the S phase of the cell cycle. In mammalian cells, a key regulator of this process is the retinoblastoma tumor suppressor protein (RB). In contrast, G1 control in Saccharomyces cerevisiae does not utilize an RB-like protein. We report here the cloning of cDNAs from two Zea mays genes, RRB1 and RRB2, that encode RB-related proteins. Further, RRB2 transcripts are alternatively spliced to yield two proteins with different C termini. At least one RRB gene is expressed in all the tissues examined, with the highest levels seen in the shoot apex. RRB1 is a 96-kDa nuclear protein that can physically interact with two mammalian DNA tumor virus oncoproteins, simian virus 40 large-T antigen and adenovirus E1A, and with a plant D-type cyclin. These associations are abolished by mutation of a conserved cysteine residue in RRB1 that is also essential for RB function. RRB1 binding potential is also sensitive to deletions in the conserved A and B domains, although differences exist in these effects compared to those of human RB. RRB1 can also bind to the AL1 protein from tomato golden mosaic virus (TGMV), a protein which is essential for TGMV DNA replication. These results suggest that G1 regulation in plant cells is controlled by a mechanism which is much more similar to that found in mammalian cells than that in yeast.

Amino Acid Sequence↗