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Biomedical subjects

A B Miller

Publications and source records attributed to A B Miller.

At least 37 records · Page 2Linked to original sources
PubMed2002

Obesity and colorectal cancer risk in women.

BACKGROUND: Several large studies of obesity and colorectal cancer risk have found no association among women but a reasonably consistent positive association among men. In women, a positive association that is stronger among, or limited to, those who are premenopausal has been suggested by studies that stratified analyses by age, although no previous study has examined the association by menopausal status. METHODS: We used proportional hazards analyses to estimate hazard ratios relating obesity to colorectal cancer risk among 89,835 women aged 40-59 years at recruitment into the Canadian National Breast Screening Study, a multicentre randomised controlled trial of mammography screening for breast cancer. During an average 10.6 years of follow up (936,433 person years), a total of 527 women were diagnosed with incident colorectal cancer (363 colon and 164 rectal). RESULTS: We found that obesity (body mass index > or = 30 kg/m(2)) was associated with an approximately twofold increased risk of colorectal cancer among women who were premenopausal at baseline (hazard ratio 1.88, 95% confidence interval 1.24-2.86). There was no association among postmenopausal women (p for interaction=0.01), and there was only a weak positive association in the entire cohort. CONCLUSIONS: Our data suggest that obesity is associated with a twofold increased risk of colorectal cancer in premenopausal women but is not associated with altered risk in postmenopausal women. Effect modification by menopausal status may better explain the inconsistent or weak findings in previous studies than the presumed lack of an association among women.

Adult↗
PubMed2001

Effect of lipid-lowering agents, angiotensin-converting enzyme inhibitors, and calcium antagonists on coronary disease risk.

Dyslipidemia is a causative, yet modifiable risk factors for the development of adverse outcomes secondary to coronary artery disease. Recent trials have focused on the level of low-density lipoprotein cholesterol (LDL-C) necessary to achieve maximum reduction in clinical events. Data also exist demonstrating that intensive lowering of LDL-C in patients with unstable angina reduces the incidence of adverse clinical events. The statins appear to be fundamental therapy in patients with established coronary disease as well as a mainstay for those with early evidence of atherosclerosis. The angiotensin-converting enzyme (ACE) inhibitors have demonstrated a reduction in ischemic events in patients with heart failure. Recent trials of ACE inhibitors in patients with vascular disease who do not have the traditional indications for ACE inhibition have shown a reversal of endothelial dysfunction and a reduction in adverse clinical endpoints. A role for the use of calcium antagonists in patients with atherosclerosis is less well established, despite the evidence of excellent results in patients with symptomatic coronary disease. A recent clinical trial, using a third-generation dihydropyridine calcium antagonist with novel mechanisms, found promising results with regard to its effects on atherosclerosis

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Types of dietary fat and breast cancer: a pooled analysis of cohort studies.

Recently, there has been interest in whether intakes of specific types of fat are associated with breast cancer risk independently of other types of fat, but results have been inconsistent. We identified 8 prospective studies that met predefined criteria and analyzed their primary data using a standardized approach. Holding total energy intake constant, we calculated relative risks for increments of 5% of energy for each type of fat compared with an equivalent amount of energy from carbohydrates or from other types of fat. We combined study-specific relative risks using a random effects model. In the pooled database, 7,329 incident invasive breast cancer cases occurred among 351,821 women. The pooled relative risks (95% confidence intervals [CI]) for an increment of 5% of energy were 1.09 (1.00-1.19) for saturated, 0.93 (0.84-1.03) for monounsaturated and 1.05 (0.96-1.16) for polyunsaturated fat compared with equivalent energy intake from carbohydrates. For a 5% of energy increment, the relative risks were 1.18 (95% CI 0.99-1.42) for substituting saturated for monounsaturated fat, 0.98 (95% CI 0.85-1.12) for substituting saturated for polyunsaturated fat and 0.87 (95% CI 0.73-1.02) for substituting monounsaturated for polyunsaturated fat. No associations were observed for animal or vegetable fat intakes. These associations were not modified by menopausal status. These data are suggestive of only a weak positive association with substitution of saturated fat for carbohydrate consumption; none of the other types of fat examined was significantly associated with breast cancer risk relative to an equivalent reduction in carbohydrate consumption.

Breast Neoplasms↗
PubMed2001

Intake of fruits and vegetables and risk of breast cancer: a pooled analysis of cohort studies.

CONTEXT: Some epidemiologic studies suggest that elevated fruit and vegetable consumption is associated with a reduced risk of breast cancer. However, most have been case-control studies in which recall and selection bias may influence the results. Additionally, publication bias may have influenced the literature on associations for specific fruit and vegetable subgroups. OBJECTIVE: To examine the association between breast cancer and total and specific fruit and vegetable group intakes using standardized exposure definitions. DATA SOURCES/STUDY SELECTION: Eight prospective studies that had at least 200 incident breast cancer cases, assessed usual dietary intake, and completed a validation study of the diet assessment method or a closely related instrument were included in these analyses. DATA EXTRACTION: Using the primary data from each of the studies, we calculated study-specific relative risks (RRs) that were combined using a random-effects model. DATA SYNTHESIS: The studies included 7377 incident invasive breast cancer cases occurring among 351 825 women whose diet was analyzed at baseline. For comparisons of the highest vs lowest quartiles of intake, weak, nonsignificant associations were observed for total fruits (pooled multivariate RR, 0.93; 95% confidence interval [CI], 0.86-1.00; P for trend =.08), total vegetables (RR, 0.96; 95% CI, 0.89-1.04; P for trend =.54), and total fruits and vegetables (RR, 0.93; 95% CI, 0.86-1.00; P for trend =.12). No additional benefit was apparent in comparisons of the highest and lowest deciles of intake. No associations were observed for green leafy vegetables, 8 botanical groups, and 17 specific fruits and vegetables. CONCLUSION: These results suggest that fruit and vegetable consumption during adulthood is not significantly associated with reduced breast cancer risk.

Adult↗
PubMed2001

Dual interaction of a geminivirus replication accessory factor with a viral replication protein and a plant cell cycle regulator.

Geminiviruses replicate their small, single-stranded DNA genomes through double-stranded DNA intermediates in plant nuclei using host replication machinery. Like most dicot-infecting geminiviruses, tomato golden mosaic virus encodes a protein, AL3 or C3, that greatly enhances viral DNA accumulation through an unknown mechanism. Earlier studies showed that AL3 forms oligomers and interacts with the viral replication initiator AL1. Experiments reported here established that AL3 also interacts with a plant homolog of the mammalian tumor suppressor protein, retinoblastoma (pRb). Analysis of truncated AL3 proteins indicated that pRb and AL1 bind to similar regions of AL3, whereas AL3 oligomerization is dependent on a different region of the protein. Analysis of truncated AL1 proteins located the AL3-binding domain between AL1 amino acids 101 and 180 to a region that also includes the AL1 oligomerization domain and the catalytic site for initiation of viral DNA replication. Interestingly, the AL3-binding domain was fully contiguous with the domain that mediates AL1/pRb interactions. The potential significance of AL3/pRb binding and the coincidence of the domains responsible for AL3, AL1, and pRb interactions are discussed.

Cell Cycle↗
PubMed2001

Cloning, sequence analysis and radiation hybrid mapping of a mammalian KRT2p gene.

We report here on the cloning, characterization and radiation hybrid mapping of the canine basic keratin gene KRT2p. The gene spans 8.3 kb, consists of nine exons and eight introns, and is characterized by the typical features of both basic keratins and keratins in general, including glycine-rich head and tail domains, which flank an alpha-helical rod domain of approximately 310 amino acids. Comparisons of sequence and structure reveal that canine KRT2p is strikingly similar to human KRT2p. Alignment of the predicted amino acid sequences for human and dog reveals greater than 80% identity. In the rod domain, the amino acid identity exceeds 90%. We note, however, that canine KRT2p encodes a protein 21 residues longer than human K2p due to the insertion of a glycine repeat motif, GG(G)X, in the head and tail domains of the canine gene. This is the first report of the nearly complete genome sequence for KRT2p of any organism. Radiation hybrid mapping of canine KRT2p to chromosome 27 of the dog is also reported.

Amino Acid Sequence↗
PubMed2001

Is there a role for calcium channel blockers in congestive heart failure?

Over the past several decades, we have made great strides in understanding the pathophysiology of heart failure and have developed new therapeutic targets based on utilizing several different models in clinical trials. Currently, standard therapy involves angiotensin-converting enzyme inhibitors and beta-blockers. In an effort to further reduce mortality, investigators focused on other vasodilators (calcium channel blockers) that might prove to be advantageous when added to standard therapy. Large- scale trials showed that the calcium channel blockers did not have a specific role in mortality reduction, but the third-generation dihydropyridine calcium channel blockers were safe to use in patients with heart failure.

Calcium Channel Blockers↗
PubMed2001

Angiotensin receptor blockers and aldosterone antagonists in chronic heart failure.

Prognosis in congestive heart failure is directly linked to neurohormonal activation. Angiotensin II through the activation of the renin angiotensin aldosterone system has been the principal focus therapy over the last 2 decades. New agents that target selective blockade of the angiotensin II receptor have been introduced in clinical trials for the treatment of heart failure. Aldosterone has been identified as a critically important neurohormone with direct detrimental effects on the myocardium. Aldosterone antagonists have been used in clinical trials to improve mortality in patients with chronic heart failure.

Aldosterone↗
PubMed2001

Health-related quality of life and cost-effectiveness studies in the European randomised study of screening for prostate cancer and the US Prostate, Lung, Colon and Ovary trial.

Decisions on policies for screening for prostate cancer require that information upon health-related quality of life (HRQL) and cost-effectiveness (CE) be available, as the lead time for some of the cases detected by screening will be very long and detriments in quality of life could have a major impact on the subjects remaining life-span. A framework within which both HRQL and cost-effectiveness of prostate cancer screening can be assessed is presented. Studies of both are ongoing in the European Randomised Study of screening for prostate cancer and the US Prostate, Lung, Colon and Ovary trial. Preliminary information confirms that it is important to study screened subjects and controls, and not to assume that inferences derived from study of prostate cancer outside screening trials can be extrapolated to the trials. However, it will require prolonged study to enable the overall effects on quality of life, and on cost-effectiveness to be determined. Such studies are ongoing for the two trials.

Colonic Neoplasms↗
PubMed2001

Understanding dignity in the lives of homeless persons.

The current investigation is a planned, systematic study of dignity as critical to understanding the experience of homelessness and improving services and programs for the homeless. Specifically, we conducted a thematic content analysis of interviews with 24 homeless men and women to identify their perception of specific environmental events that validate and invalidate dignity. In addition, we explored the impact that these events have on homeless persons. Eight types of events were identified that sustain dignity such as being cared for by staff and having resources available to meet basic needs. Eight types of events were found that undermine dignity, such as being yelled at or insulted by staff persons and having staff use rules in an excessive and arbitrary way. Two outcomes followed the sustenance of dignity including increased self-worth and motivation to exit homelessness. Three outcomes followed the undermining of dignity including anger, depression, and feelings of worthlessness. The results suggest that dignity is an important variable to consider in understanding the experience of homelessness. Policies and programs that support validating the dignity of homeless persons are encouraged.

Adult↗
PubMed2001

Organochlorines and breast cancer risk by receptor status, tumor size, and grade (Canada).

OBJECTIVE: We evaluated the association between organochlorines and breast cancer subtype defined by the tumor characteristics: estrogen receptor status, progesterone receptor status, tumor size, and grade. METHODS: A case-control study was conducted from 1995 to 1997 in Kingston and Toronto, Canada. Breast adipose tissue, taken from 217 cases and 213 biopsy controls frequency-matched on age, was analysed for 14 polychlorinated biphenyl (PCB) congeners and 10 pesticides. RESULTS: Adjusting for age, geometric means of several organochlorines differed by estrogen receptor status and tumor grade (p < 0.05). Odds ratios (ORs) for each organochlorine relative to the common control group for breast cancers of differing subtype were compared using polytomous logistic regression. Although the ORs did not differ significantly by subtype, the ORs of PCBs and p, p'-1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) were higher with risk of estrogen receptor-negative breast cancer than estrogen receptor-positive breast cancer. One of the most extreme differences was with DDE, where the OR for the association with risk of estrogen receptor-negative breast cancer was 2.4 (95% confidence interval (CI) 1.0-5.4) in the uppermost tertile relative to the lowest, whereas the corresponding OR for risk of estrogen receptor-positive breast cancer was 1.1 (95% CI 0.6-1.9). PCBs also tended to be more strongly positively associated with risk of larger and higher-grade tumors. CONCLUSIONS: The association between organochlorines and breast cancer risk did not significantly differ by subtype, but many PCBs were more strongly associated with tumors of poor prognosis.

Adipose Tissue↗