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Biomedical subjects

A B Miller

Publications and source records attributed to A B Miller.

At least 73 records · Page 4Linked to original sources
PubMed2000

Mammographic densities and the prevalence and incidence of histological types of benign breast disease. Reference Pathologists of the Canadian National Breast Screening Study.

There is now a large amount of evidence indicating that women with extensive areas of mammographic densities are 4-6 times more likely to develop breast cancer than those with little or no density in the mammogram. We have examined one potential biological explanation for this association by estimating the incidence of various histological types of benign breast disease in relation to mammographic density. We studied the large cohort of women taking part in the National Breast Screening Study (NBSS), a randomized trial of screening with mammography. Mammograms from subjects with biopsies (n = 423) and from a comparison group of subjects randomly selected from the NBSS (n = 465) were included. Histological slides from biopsied subjects (n = 353) were classified independently by the pathologists of the NBSS and by a review pathologist (H.M.J.). Mammographic density in more than 75% of the breast area was associated with an increased risk of incidence of hyperplasia without atypia, and of atypical hyperplasia and/or carcinoma in situ. The classifications of the review pathologist showed that, compared to women with no density, the relative risk of incident lesions for women with density in more than 75% of breast was 13.85 (95% CI 2.65-72.49) for hyperplasia, and 9.23 (95% CI 1.66-51.48) for atypical hyperplasia and/or carcinoma in situ. These findings suggest that the association between extensive mammographic density and breast cancer risk may, at least in part, be attributable to biological processes in the breast that give rise to these histological features that are known to be related to breast cancer risk.

Adult↗
PubMed2000

Non-Hodgkin's lymphoma among electric utility workers in Ontario: the evaluation of alternate indices of exposure to 60 Hz electric and magnetic fields.

OBJECTIVES: To examine associations between non-Hodgkin's lymphoma (NHL) and exposures to 60 Hz magnetic and electric fields in electric utility workers with a series of indices that capture a variety of aspects of field strength. METHODS: The study population consisted of 51 cases of NHL and 203 individually matched controls identified from within a cohort of male electric utility workers in Ontario. Odds ratios were calculated for several exposure indices with conditional logistic regression models. Aspects of exposure to electric and magnetic fields that were modelled included: the percentage of time spent above selected threshold field intensities, mean transitions in field strength, SD, and the arithmetic and geometric mean field intensities. RESULTS: For the most part, there was a lack of an association between exposure indices of magnetic fields and the incidence of NHL. Subjects in the upper tertile of percentage of time spent above electric field intensities of 10 and 40 V/m had odds ratios of 3.05 (95% confidence interval (95% CI) 1. 07 to 8.80) and 3.57 (1.30 to 9.80), respectively, when compared with those in the lowest tertile. Moreover, the percentages of time spent above these electric field thresholds were significant predictors of case status over and above the association explained by duration of employment and the arithmetic or geometric mean exposure. CONCLUSIONS: These data suggest that exposures above electric field threshold intensities of 10 and 40 V/m are important predictors of NHL. Consequently, the findings support the hypothesis that electric fields may play a promoting part in the aetiology of this cancer. Further occupational studies that include assessment of exposure to electric fields and measures of field strength above similar threshold cut off points are needed to confirm these findings.

Case-Control Studies↗
PubMed2000

Later-life planning: promoting knowledge of options and choice-making.

The effectiveness of a person-centered later-life planning training program designed to teach older adults (N = 60) with mental retardation about later-life planning issues and increase their participation in choice-making was examined. Using quantitative data analyses, we assessed the impact of the program on intervention and control groups. Results indicated that the intervention group gained more knowledge of concepts in the curriculum and made more choices over time than did the control group. The wide variety of goals that participants set were examined through qualitative analyses; 87% of the participants met or partially met their goals. Information on the supports and barriers to meeting goals is provided.

Adult↗
PubMed2000

Breast adipose tissue concentrations of polychlorinated biphenyls and other organochlorines and breast cancer risk.

Numerous studies have examined the relationship between organochlorines and breast cancer, but the results are not consistent. In most studies, organochlorines were measured in serum, but levels in breast adipose tissue are higher and represent cumulative internal exposure at the target site for breast cancer. Therefore, a hospital-based case-control study was conducted in Ontario, Canada to evaluate the association between breast cancer risk and breast adipose tissue concentrations of several organochlorines. Women scheduled for excision biopsy of the breast were enrolled and completed a questionnaire. The biopsy tissue of 217 cases and 213 benign controls frequency matched by study site and age in 5-year groups was analyzed for 14 polychlorinated biphenyl (PCB) congeners, total PCBs, and 10 other organochlorines, including p,p'-1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene. Multiple logistic regression was used to assess the magnitude of risk. While adjusting for age, menopausal status, and other factors, odds ratios (ORs) were above 1.0 for almost all organochlorines except five pesticide residues. The ORs were above two in the highest concentration categories of PCB congeners 105 and 118, and the ORs for these PCBs increased linearly across categories (Ps for trend < or =0.01). Differences by menopausal status are noted especially for PCBs 105 and 118, with risks higher among premenopausal women, and for PCBs 170 and 180, with risks higher among postmenopausal women. Clear associations with breast cancer risk were demonstrated in this study for some PCBs measured in breast adipose tissue.

Adipose Tissue↗
PubMed1999

Specific sequence elements are required for the expression of functional tumor necrosis factor-alpha-converting enzyme (TACE).

The tumor necrosis factor-alpha-converting enzyme (TACE) is a membrane-anchored zinc metalloprotease involved in precursor tumor necrosis factor-alpha secretion. We designed a series of constructs containing full-length human TACE and several truncate forms for overexpression in insect cells. Here, we demonstrate that full-length TACE is expressed in insect cells inefficiently: only minor amounts of this enzyme are converted from an inactive precursor to the mature, functional form. Removal of the cytoplasmic and transmembrane domains resulted in the efficient secretion of mature, active TACE. Further removal of the cysteine-rich domain located between the catalytic and transmembrane domains resulted in the secretion of mature catalytic domain in association with the precursor (pro) domain. This complex was inactive and function was only restored after dissociation of the complex by dilution or treatment with 4-aminophenylmercuric acetate. Therefore, the pro domain of TACE is an inhibitor of the catalytic domain, and the cysteine-rich domain appears to play a role in the release of the pro domain. Insect cells failed to secrete a deletion mutant encoding the catalytic domain but lacking the inhibitory pro domain. This truncate was inactive and extensively degraded intracellularly, suggesting that the pro domain is required for the secretion of functional TACE.

ADAM Proteins↗
PubMed1999

A case-control study of childhood leukemia in southern Ontario, Canada, and exposure to magnetic fields in residences.

A population-based case-control study was conducted in Ontario, Canada, to assess the relation between the risk of childhood leukemia and residential exposure to magnetic fields. Participating subjects consisted of 201 cases, diagnosed at 0 to 14 years of age during 1985-1993, ascertained from the records at the Hospital for Sick Children (Toronto), and 406 individually matched controls. Where possible, point-in-time measurements of magnetic fields were made in all residences occupied by subjects during the period of inquiry in the defined catchment area. Three different classification schemes of wire code were assigned to each residence. Detailed information was collected by interviewer-administered questionnaires, which enabled risk estimates to be adjusted for socio-economic characteristics, medical history of parent(s) and child and environmental exposures. Inconsistent elevations in risk were associated with time-weighted averages of magnetic fields both inside and outside the home for subjects having residential point-in-time measurements that represented at least 70% of their etiological period. These risks increased in magnitude when analysis was restricted to children under 6 years of age at diagnosis or to those with acute lymphoblastic leukemia. For children younger than 6 years at diagnosis, outside perimeter measurements of the residence, > or = 0.15 microT, were associated with increased leukemia risk (OR = 3.45, 95% CI = 1.14-10.45). Evaluation of different exposure times for point-in-time magnetic field measurements and wire configuration suggested that exposures earliest in the etiological period were associated with greater risks for children diagnosed at a younger age (OR = 2.50, 95% CI = 1.14-5.49). Our findings did not support an association between leukemia and proximity to power lines with high current configuration.

Adolescent↗
PubMed1999

A cohort study of oral contraceptive use and risk of benign breast disease.

The purpose of the cohort study reported here was to investigate the association between oral contraceptive use and risk of benign breast disease (BBD), overall and by histological subtype, within the 56,537 women in the Canadian National Breast Screening Study (NBSS) who completed self-administered lifestyle and dietary questionnaires. The NBSS is a randomized controlled trial of screening for breast cancer in women aged 40-59 at recruitment. Cases were the 2,116 women in the dietary cohort who were diagnosed with biopsy-confirmed incident BBD. For comparative purposes, a subcohort consisting of a random sample of 5,681 women (including 197 subjects with incident BBD) was selected from the full dietary cohort. After exclusions for various reasons, the analyses were based on 2,116 cases and 5,338 non-cases. There was an inverse association between use of oral contraceptives and risk of all types of BBD combined. The reduction in risk was confined largely to proliferative forms of BBD (BPED), and in particular, to those forms of BPED without histological atypia, in whom there was a progressive reduction in risk with increasing duration of use (the IRR (95% CI) for use of more than 7 years was 0.64 (0.47-0.87)); risk of BPED with atypia was increased somewhat in association with oral contraceptive use (the IRR (95% CI) for use of more than 7 years was 1.43 (0.68-3.01 )), but not in a dose-dependent manner. The results were similar when examined separately in the screened and control arms of the NBSS and for screen-detected and interval-detected BPED.

Adult↗
PubMed1999

A peroxisome proliferator-activated receptor gamma ligand inhibits adipocyte differentiation.

The peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that regulate glucose and lipid homeostasis. The PPARgamma subtype plays a central role in the regulation of adipogenesis and is the molecular target for the 2, 4-thiazolidinedione class of antidiabetic drugs. Structural studies have revealed that agonist ligands activate the PPARs through direct interactions with the C-terminal region of the ligand-binding domain, which includes the activation function 2 helix. GW0072 was identified as a high-affinity PPARgamma ligand that was a weak partial agonist of PPARgamma transactivation. X-ray crystallography revealed that GW0072 occupied the ligand-binding pocket by using different epitopes than the known PPAR agonists and did not interact with the activation function 2 helix. In cell culture, GW0072 was a potent antagonist of adipocyte differentiation. These results establish an approach to the design of PPAR ligands with modified biological activities.

Adipocytes↗
PubMed1999

Natural history of dysplasia of the uterine cervix.

BACKGROUND: A historical cohort of Toronto (Ontario, Canada) women whose Pap smear histories were recorded at a major cytopathology laboratory provided the opportunity to study progression and regression of cervical dysplasia in an era (1962-1980) during which cervical squamous lesions were managed conservatively. METHODS: Actuarial and Cox's survival analyses were used to estimate the rates and relative risks of progression and regression of mild (cervical intraepithelial neoplasia 1 [CIN1]) and moderate (CIN2) dysplasias. In addition, more than 17,000 women with a history of Pap smears between 1970 and 1980 inclusive and who were diagnosed as having mild, moderate, or severe dysplasia were linked to the Ontario Cancer Registry for the outcome of any subsequent cervical cancers occurring through 1989. RESULTS: Both mild and moderate dysplasias were more likely to regress than to progress. The risk of progression from mild to severe dysplasia or worse was only 1% per year, but the risk of progression from moderate dysplasia was 16% within 2 years and 25% within 5 years. Most of the excess risk of cervical cancer for severe and moderate dysplasias occurred within 2 years of the initial dysplastic smear. After 2 years, in comparison with mild dysplasia, the relative risks for progression from severe or moderate dysplasia to cervical cancer in situ or worse was 4.2 (95% confidence interval [CI] = 3.0-5.7) and 2.5 (95% CI = 2.2-3.0), respectively. CONCLUSION: The risk of progression for moderate dysplasia was intermediate between the risks for mild and severe dysplasia; thus, the moderate category may represent a clinically useful distinction. The majority of untreated mild dysplasias were recorded as regressing to yield a normal smear within 2 years.

Chi-Square Distribution↗
PubMed1999

Chromosomal localization of acidic and basic keratin genes of the domestic dog.

Our laboratories are interested in characterizing genes involved in the myriad of heritable diseases affecting the domestic dog, Canis lupus familiaris, and in development of detailed genetic and physical maps of the canine genome. Included in these efforts is examination of conservation of the genetic organization, structure, and function of gene families involved in diseases of the canine skin, skeleton, and eye. To that end, study of the highly conserved keratin gene family was undertaken. Keratins belong to the superfamily of intermediate filaments and are the major structural proteins of the epidermis, hair, and nail. The keratins are highly conserved throughout vertebrate evolution both at the DNA and amino acid sequence levels. Mutations in genes encoding epithelial keratins are known to cause various diseases in humans, and similar histopathological presentations have been reported in the dog. The keratins are divided into two groups, type I (acidic) and type II (basic). In the human, the genes encoding the acidic and basic keratins are clustered on Chrs 17 and 12, respectively. The same genetic arrangement is seen in the mouse with the acidic and basic keratin gene clusters found on Chrs 11 and 15, respectively. Reported here are the chromosomal localization of acidic and basic canine keratin genes as well as supportive sequence data. Fluorescence in situ hybridization (FISH) experiments with clones isolated from a canine genomic library suggest that the acidic keratin gene cluster resides on CFA9 and the basic keratin gene cluster is located on CFA27.

Amino Acid Sequence↗
PubMed1999

Childhood leukemia and personal monitoring of residential exposures to electric and magnetic fields in Ontario, Canada.

OBJECTIVES: To evaluate the risk of childhood leukemia in relation to residential electric and magnetic field (EMF) exposures. METHODS: A case control study based on 88 cases and 133 controls used different assessment methods to determine EMF exposure in the child's current residence. Cases comprised incident leukemias diagnosed at 0-14 years of age between 1985-1993 from a larger study in southern Ontario; population controls were individually matched to the cases by age and sex. Exposure was measured by a personal monitoring device worn by the child during usual activities at home, by point-in-time measurements in three rooms and according to wire code assigned to the child's residence. RESULTS: An association between magnetic field exposures as measured with the personal monitor and increased risk of leukemia was observed. The risk was more pronounced for those children diagnosed at less than 6 years of age and those with acute lymphoblastic leukemia. Risk estimates associated with magnetic fields tended to increase after adjusting for power consumption and potential confounders with significant odds ratios (OR) (OR: 4.5, 95% confidence interval (CI): 1.3-15.9) observed for exposures > or = 0.14 microTesla (microT). For the most part point-in-time measurements of magnetic fields were associated with non-significant elevations in risk which were generally compatible with previous research. Residential proximity to power lines having a high current configuration was not associated with increased risk of leukemia. Exposures to electric fields as measured by personal monitoring were associated with a decreased leukemia risk. CONCLUSIONS: The findings relating to magnetic field exposures directly measured by personal monitoring support an association with the risk of childhood leukemia. As exposure assessment is refined, the possible role of magnetic fields in the etiology of childhood leukemia becomes more evident.

Adolescent↗
PubMed1999

Hormone replacement therapy and risk of benign proliferative epithelial disorders of the breast.

Use of hormone replacement therapy (HRT) has been associated with increased risk of breast cancer, and it is possible that this reflects a positive association between HRT use and risk of proliferative forms of benign breast disease (BBD), conditions which are thought to have pre-malignant potential. The purpose of the present investigation was to study the association between HRT use and risk of benign proliferative epithelial disorders of the breast (BPED). The study was undertaken using the 56,837 women within the Canadian National Breast Screening Study (NBSS) who completed self-administered lifestyle and dietary questionnaires. (The NBSS is a randomized controlled trial of screening for breast cancer in women aged 40-59 at recruitment.) During the course of the follow-up period, a total of 691 women in the dietary cohort were diagnosed with biopsy-confirmed incident BPED. For comparative purposes, a sub-cohort consisting of a random sample of 5681 women (including 65 of the subjects with BPED) was selected from the full dietary cohort. After exclusions for various reasons, the analyses were based on 691 cases and 5443 non-cases. In post-menopausal women, in whom most of the reported use occurred, there was a positive association between duration of HRT use and risk of BPED, the adjusted incidence rate ratio (95% confidence interval) in those who had used HRT for more than 8 years being 1.70 (1.06-2.72). 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 were similar to those observed overall, as were those conducted separately for screen-detected and interval-detected BPED.

Adult↗
PubMed1999

Autonomy in residential facilities and community functioning of adults with mental retardation.

Over a 3-year period, we examined whether the autonomy of 58 adults living in residences for people with developmental disabilities was associated with their adaptive behavior and community integration. Degree of resident autonomy included measures of opportunities for choice-making and level of involvement in policymaking. All of the participants lived in nursing homes at baseline and in residential settings for people with developmental disabilities at follow-up. Results indicated that opportunities for autonomy in residential settings were related to residents' adaptive behavior and community integration. More opportunities for choice-making in residences was associated with greater adaptive behavior, whereas smaller residence size and more resident involvement in decision-making were associated with greater community integration.

Adult↗
PubMed1999

The brave new world--what can we realistically expect to achieve through cancer control early in the new millennium?

Cancer control requires strategic planning, and thus knowledge about the trends of incidence and mortality associated with cancer as well as future projections, in order that appropriate decisions on priorities can be made. Cancer prevention requires tobacco control and dietary modification. Screening should utilize only effective strategies. The trends in Canada are expected to be mainly favourable by the year 2020, apart from rising trends in non-Hodgkin's lymphoma. Tobacco control policies in Canada are having an impact, while dietary modification is probably having an impact on colorectal cancer incidence. Screening for cancer of the cervix has achieved maximum impact with present levels of compliance, but as yet there is no evidence of an impact of breast screening. Priority for the future will have to be placed on prevention, especially on encouraging young adults to quit smoking and on dietary modification starting at young ages, and care should be taken with cost-effective application of screening.

Adult↗
PubMed1999

A cohort study of cigarette smoking and risk of fibroadenoma.

BACKGROUND: This cohort study examines the association between cigarette smoking and risk of fibroadenoma. METHODS: The study was conducted among the 56,537 women in the Canadian National Breast Screening Study (NBSS) who completed self-administered lifestyle and dietary questionnaires. (The NBSS is a randomised, controlled trial of screening for breast cancer in women aged 40-59 at recruitment.) Cases were the 222 women who were diagnosed with biopsy-confirmed incident fibroadenoma. For comparative purposes, a subcohort, consisting of a random sample of 5,681 women was selected from the full dietary cohort. After exclusions for various reasons, the analyses were based on 222 cases and 5,488 non-cases. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were estimated using Poisson regression. RESULTS: Cigarette smoking was associated with reduced risk of fibroadenoma, the IRR (95% CI) for more than 550 cigarette-years of exposure being 0.66 (0.40-1.10). Although the reduction in risk was evident for all smokers combined (ex-smokers and current smokers), it was indicative largely of an inverse association in current smokers, in whom the IRR (95% CI) for > 300 cigarette-years of exposure was 0.49 (0.24-0.98). The results were mostly the same when examined in strata defined by method of detection of fibroadenoma, menopausal status and history of previous breast disease. There was no evidence for a reduction in risk with time since last use of cigarettes. CONCLUSIONS: The results of this study suggest that cigarette smoking is associated with reduced risk of fibroadenoma, especially in current smokers.

Adult↗
PubMed1998

Effect of amlodipine on mode of death among patients with advanced heart failure in the PRAISE trial. Prospective Randomized Amlodipine Survival Evaluation.

Investigations of calcium antagonists in patients with advanced heart failure have raised concern over an increased risk of worsening heart failure and heart failure deaths. We assessed the effect of amlodipine on cause-specific mortality in such patients enrolled in a randomized, double-blind, placebo-controlled trial. In total, 1,153 patients in New York Heart Association class IIIb or IV heart failure were randomized to receive amlodipine or placebo, along with angiotensin-converting enzyme inhibitors, diuretics, and digitalis. Over a median 14.5 months of follow-up, 413 patients died. Cardiovascular deaths accounted for 89% of fatalities, 50% of which were sudden deaths and 45% of which were due to pump failure, with fewer attributed to myocardial infarction (3.3%) or other cardiovascular causes (1.6%). Amlodipine treatment resulted in a greater relative reduction in sudden deaths (21%) than in pump failure deaths (6.6%) overall. When patients were classified by etiology of heart failure (ischemic or nonischemic), cause-specific mortality did not differ significantly between treatment groups in the ischemic stratum. In the nonischemic stratum, however, sudden deaths and pump failure deaths were reduced by 38% and 45%, respectively, with amlodipine. Thus, when added to digitalis, diuretics, and angiotensin-converting enzyme inhibitors in patients with advanced heart failure, amlodipine appears to have no effect on cause-specific mortality in ischemic cardiomyopathy, but both pump failure and sudden deaths appear to be decreased in nonischemic heart failure patients treated with amlodipine.

Amlodipine↗