Biomedical subjects

H E Bryant

Publications and source records attributed to H E Bryant.

At least 19 recordsLinked to original sources

PubMed2004

Poly(ADP-ribose) polymerase inhibitors as potential chemotherapeutic agents.

PARP [poly(ADP-ribose) polymerase] activity is up-regulated by binding to DNA strand breaks and its association with DNA repair is well documented. Many anticancer therapies work by inducing breaks in DNA, if unrepaired these can lead to cell death. As PARP promotes DNA repair there is a strong rational to suggest that its inhibition may increase the efficiency of certain cytotoxic treatments. This review discusses the advances made in PARP inhibitor design and the mechanism by which they enhance anti-tumour therapies.

Antineoplastic Agents↗

PubMed2001

Case-control study of lifetime physical activity and breast cancer risk.

A population-based case-control study of 1,233 incident breast cancer cases and 1,237 controls was conducted in Alberta, Canada, in 1995-1997 to examine the effect of lifetime physical activity patterns on breast cancer risk. No associations between physical activity and breast cancer were found for premenopausal women. For postmenopausal women in the highest quartile (> or =161 metabolic equivalent (MET)-hours/week per year) versus the lowest quartile (<104.8 MET-hours/week per year) of lifetime total physical activity, the adjusted odds ratio was 0.70 (95% confidence interval (CI): 0.52, 0.94). When the risks associated with each type of activity were examined for postmenopausal women, household and occupational activity conferred the largest risk reductions (odds ratio (OR) = 0.57, 95% CI: 0.41, 0.79 and OR = 0.59, 95% CI: 0.44, 0.81, respectively, for highest vs. lowest quartiles of activity), while recreational activity was not associated with any risk reductions. For postmenopausal women, the authors found stronger risk reductions for those who were also nonsmokers (OR = 0.64, 95% CI: 0.46, 0.88), non-alcohol-drinkers (OR = 0.39, 95% CI: 0.11, 0.77), or nulliparous (OR = 0.22, 95% CI: 0.07, 0.70) when they compared the highest with the lowest quartile of lifetime total physical activity. This study provides evidence that lifetime total activity reduces risk of postmenopausal breast cancer.

Adult↗

PubMed2001

Influence of physical activity in different age and life periods on the risk of breast cancer.

We conducted a population-based case-control study of 1,237 incident breast cancer cases and 1,241 controls in Alberta between 1995 and 1997 to examine the effect of physical activity performed at different ages and life periods on breast cancer risk. In this study, we measured all types of physical activity done throughout life with a questionnaire developed and tested specifically for this study. We found that breast cancer risk was most associated with a risk reduction for activity done later in life, particularly between menopause and the reference year, for which we observed an odds ratio of 0.70 (95% confidence interval = 0.52-0.95). We also stratified the study participants into four categories according to their patterns of physical activity performed before and after menopause. For the women who sustained physical activity throughout life vs those who were never active, we found an odds ratio of 0.58 (95% confidence interval = 0.41-0.83). This study suggests that sustained activity throughout life and particularly activity done later in life may have the most benefit in reducing breast cancer risk.

Adolescent↗

PubMed2001

Relation between intensity of physical activity and breast cancer risk reduction.

PURPOSE: To examine the influence of frequency, duration, and intensity of physical activity on risk of breast cancer and to compare breast cancer risks associated with self-reported versus assigned intensity levels of activity. METHODS: A population-based case-control study of 1233 incident breast cancer cases and 1241 controls was conducted in Alberta between 1995 and 1997. The frequency, duration and intensity of occupational, household, and recreational activities were measured throughout lifetime using the Lifetime Total Physical Activity Questionnaire and cognitive interviewing methods. Unconditional logistic regression analyses were used to estimate odds ratios and a full assessment of confounding and effect modification was undertaken. Odds ratios for self-reported and compendium-based assigned levels of activity were compared for lifetime total activity and by type of activity. RESULTS: Breast cancer risk reductions were comparable when self-reported and assigned intensity values were used, although the results and trends were more evident with the assigned intensity data. Moderate-intensity occupational and household activities decreased breast cancer risk, whereas recreational activity, at any intensity level, did not contribute to a breast cancer risk reduction. CONCLUSION: This study found that moderate-intensity activities were the major contributors to the decrease in breast cancer risk found in this study and that risk reductions were more evident when the frequency and duration of activity alone were modeled. Of the three types of activity considered, the greatest risk reductions observed were for occupational and household activities.

Activities of Daily Living↗

PubMed2001

Herpes simplex virus IE63 (ICP27) protein interacts with spliceosome-associated protein 145 and inhibits splicing prior to the first catalytic step.

The multifunctional herpes simplex virus type 1 (HSV-1) protein IE63 (ICP27) interacts with the essential pre-mRNA splicing factor, spliceosome-associated protein 145 (SAP145), and in infected cells IE63 and SAP145 colocalize. This interaction was reduced or abrogated completely using extracts from cells infected with IE63 viral mutants, with mutations in IE63 KH and Sm homology domains, which do not exhibit host shutoff or inhibit splicing. In the presence of IE63, splicing in vitro was inhibited prior to the first catalytic step and the B/C complex formed during splicing was shifted up in mobility and reduced in intensity. With the use of splicing extracts, IE63 and SAP145 both comigrated with the B/C complex, suggesting that they interact within this complex to inhibit B/C complex formation or conversion. The inhibition of splicing may facilitate the export of viral or cellular transcripts, possibly via other protein partners of IE63. These data provide important new insights into how IE63 influences pre-mRNA processing during HSV-1 infection.

Binding Sites↗

PubMed2001

Risk factors for benign breast biopsies: a nested case-control study in the Alberta breast screening program.

A nested case-control study was conducted to identify risk factors for benign breast biopsies in 382 cases (women with a benign biopsy result) and 399 controls (women who had not undergone a biopsy) who were sampled from the Alberta breast cancer screening program. The breast biopsy specimens of the cases were reviewed by a panel of pathologists, and percent fibroglandular tissue density was assessed. The multivariable odds ratios for the risk of open benign breast biopsy associated with current cigarette smoking was 2.04 (95% CI 1.32-3.13), for ever regular smoking was 1.61 (1.20-2.16), and for passive smoking was 1.41 (0.99-2.02). A risk reduction was found for ever alcohol consumption (0.61 [0.44-0.85]). Some risk reductions were found when the highest and the lowest quintiles of total aerobic recreational activity were compared (0.71 [0.42-1.20]), stair climbing (0.61 [0.37-1.01]) and walking pace (0.13 [0.02-0.741). Lifestyle risk factors may be implicated in the continuum between detection of an abnormality on a screening mammogram and a breast biopsy specimen. By considering these risk factors, breast screening programs may be better able to identify those women who require a breast biopsy and reduce the number of benign breast biopsies.

Aged↗

PubMed2000

Interaction between herpes simplex virus type 1 IE63 protein and cellular protein p32.

The herpes simplex virus type 1 (HSV-1) immediate-early gene IE63 (ICP27), the only HSV-1 regulatory gene with a homologue in every mammalian and avian herpesvirus sequenced so far, is a multifunctional protein which regulates transcriptional and posttranscriptional processes. One of its posttranscriptional effects is the inhibition of splicing of viral and cellular transcripts. We previously identified heterogeneous nuclear ribonucleoprotein (hnRNP) K and casein kinase 2 (CK2) as two protein partners of IE63 (H. Bryant et al., J. Biol. Chem. 274:28991-28998, 1999). Here, using a yeast two-hybrid assay, we identify another partner of IE63, the cellular protein p32. Confirmation of this interaction was provided by coimmunoprecipitation from virus-infected cells and recombinant p32 binding assays. A p32-hnRNP K-CK2 complex, which required IE63 to form, was isolated from HSV-1-infected cells, and coimmunoprecipitating p32 was phosphorylated by CK2. Expression of IE63 altered the cytoplasmic distribution of p32, with some now colocalizing with IE63 in the nuclei of infected and transfected cells. As p32 copurifies with splicing factors and can inhibit splicing, we propose that IE63 together with p32, possibly with other IE63 partner proteins, acts to disrupt or regulate pre-mRNA splicing. As well as contributing to host cell shutoff, this effect could facilitate splicing-independent nuclear export of viral transcripts.

Amino Acid Sequence↗

PubMed1998

The lifetime total physical activity questionnaire: development and reliability.

OBJECTIVE: To develop and test the intra-rater reliability of an interview-administered questionnaire that assesses lifetime patterns of total physical activity including occupational, household, and exercise/sports activities. METHODS: The questionnaire was developed and pretested using cognitive interviewing techniques on a sample of women with and without previous breast cancer diagnoses. A pilot study was conducted with 115 women who were interviewed twice, 6 to 8 wk apart by interviewers trained in cognitive interviewing methods. Respondents used recall calendars to record their education, occupations, life events, and physical activity patterns before the interviews. Interviewers helped respondents recall their lifetime exposures, including their occupational, household, and exercise/sports activities, using these calendars and memory-probing strategies. Activity levels were estimated as the average number of hours of activity per week over different time periods. Means and correlation coefficients were estimated and compared for the two time periods. RESULTS: The questionnaire was found to be highly reliable. The test-retest correlations for hours per week spent in total lifetime physical activity was 0.74, for lifetime occupational activity was 0.87, for household activity was 0.77, and for exercise/sports activities was 0.72. CONCLUSIONS: This is the first questionnaire to measure lifetime physical activity by collecting data on each type of physical activity separately over lifetime and by measuring frequency, intensity, and duration of each activity. It is also the first physical activity questionnaire to be developed, refined, and administered using cognitive-based methods employed in survey research. Respondents were able to reliably recall their lifetime physical activity patterns. This instrument can be used for any disease outcome for which physical activity may be a risk factor.

Breast Neoplasms↗

PubMed1997

The role of past mammography and future intentions in screening mammography usage.

Screening mammography is effective in the early detection of breast cancer among women aged 50 through 69, but under utilization by the target age group is common. The present study determined how past mammography behavior and intentions to have a mammogram were related to screening behaviors, attitudes, and beliefs. Participants were 1211 Alberta women aged 40 through 75 without breast cancer who were surveyed in a population-based random digit dial telephone interview. The response rate was 78%. Based on the stages of change and adoption models, women were grouped as Screeners (N = 363, 30%), who had had a "checkup" mammogram in the past 24 months and intended to have another in the next 24 months; Intenders (N = 355, 28%), who had not had a mammogram in the past 24 months but intended to have one in the next 24 months; and Nonparticipants (N = 513, 42%), who neither had had a mammogram in the past 24 months nor intended to have one in the next 24 months. Compared with Screeners, both Intenders and Nonparticipants were more likely to live in the rural areas and to have lower educational levels. Nonparticipants were also older, less likely to be married, of lower income, and less likely to be employed outside of the home. Separate logistic regression analyses showed that both Intenders and Nonparticipants were significantly less able to encourage a friend to have a mammogram (OR = 2.7 and 4.4, respectively), more likely to believe that most women were not getting screening mammograms (OR = 1.7 and 2.9, respectively), and less likely to believe symptoms were not needed for mammograms (OR = 0.3 and 0.1, respectively). In addition, Nonparticipants were also significantly more likely to believe that getting a mammogram would not reassure others (OR = 4.0) and less able to talk to a doctor about getting a mammogram (OR = 5.2). Adoption of screening can be seen as a continuum in which Screeners had the most positive and Nonparticipants the most negative breast cancer screening attitudes, beliefs, and early detection behaviors. The importance of physician referral and utilization of other information dissemination channels was highlighted.

Adult↗

PubMed1994

Risks and probabilities of breast cancer: short-term versus lifetime probabilities.

OBJECTIVE: To calculate age-specific short-term and lifetime probabilities of breast cancer among a cohort of Canadian women. DESIGN: Double decrement life table. SETTING: Alberta. SUBJECTS: Women with first invasive breast cancers registered with the Alberta Cancer Registry between 1985 and 1987. MAIN OUTCOME MEASURES: Lifetime probability of breast cancer from birth and for women at various ages; short-term (up to 10 years) probability of breast cancer for women at various ages. RESULTS: The lifetime probability of breast cancer is 10.17% at birth and peaks at 10.34% at age 25 years, after which it decreases owing to a decline in the number of years over which breast cancer risk will be experienced. However, the probability of manifesting breast cancer in the next year increases steadily from the age of 30 onward, reaching 0.36% at 85 years. The probability of manifesting the disease within the next 10 years peaks at 2.97% at age 70 and decreases thereafter, again owing to declining probabilities of surviving the interval. CONCLUSIONS: Given that the incidence of breast cancer among Albertan women during the study period was similar to the national average, we conclude that currently more than 1 in 10 women in Canada can expect to have breast cancer at some point during their life. However, risk varies considerably over a woman's lifetime, with most risk concentrated after age 49. On the basis of the shorter-term age-specific risks that we present, the clinician can put breast cancer risk into perspective for younger women and heighten awareness among women aged 50 years or more.

Adolescent↗

PubMed1993

Quality assurance and cancer detection rates in a provincial screening mammography program. Work in progress.

In 1990, a provincial screening program was inaugurated in Alberta, a Canadian province of 2.4 million people. The goal of the program is to decrease the number of deaths from breast cancer by 30% in women aged 50-69 years. In the first 18 months of program operations, efforts were concentrated on high levels of quality assurance in all areas of program activities. In particular, the abnormality referral rates, cancer detection rates, and size and stage of mammographically detected cancers were evaluated. Of the 9,553 women seen, 8,524 were between the ages of 50 and 69 years. Reported abnormality rates were initially more than 16%, but were brought down steadily to less than 5%. Cancer detection rates increased with age, ranging from 1.9 cancers detected per 1,000 women aged 40-49 years to 14.1 cancers per 1,000 women aged 70 years and older. Forty-one of the 61 cancers detected (67%) were less than 1.5 cm in diameter. Forty-three of the 52 cancers (83%) in which the nodal status was known were node negative. At the conclusion of the first 18 months of operation, interpretation parameters were within the target zones expected for a population-based screening program.

Adult↗

PubMed1991

Frequency of hereditary nonpolyposis colorectal cancer in southern Alberta.

The frequency of hereditary nonpolyposis colorectal cancer was evaluated in a group of colorectal cancer patients under age 50 diagnosed in southern Alberta between 1973 and 1987. Families were identified as positive for this syndrome if three first-degree relatives in the kindred had colorectal cancer. Of the 390 patients with adenocarcinoma, 318 patients participated. The frequency of hereditary nonpolyposis colorectal cancer was 3.1% (12 families) in this group (Ci95 1.6-5.3%). Clinical characteristics reported on from the index patients include tumor location, Dukes stage at presentation, frequency of synchronous and metachronous tumors, frequency of second primaries, and survival. The 5- and 10-year actuarial survival was 86% and 69%, respectively.

Adenocarcinoma↗

PubMed1991

Effect of employment and its correlates on spontaneous abortion risk.

While several studies have examined the role of employment during pregnancy on reproductive risk, few have taken into account the potential selection pressures which may cause a woman to choose employment or non-employment during pregnancy. This study was designed to test the hypothesis that employment, or certain types or preconditions of employment, places a woman at increased risk for spontaneous abortion. A case-control study design, utilizing two control groups matched to the 334 cases for age and parity (total N = 981) allowed detailed comparisons of exposures and correlates during the index pregnancy. Control groups consisted of pregnant women (less than 25 wk gestation) and postnatal women. Detailed histories of employment in the 3 months preceding and 4 months following the last menstrual period (LMP), were taken, as well as data on such potential confounding variables as past obstetrical history and socioeconomic status. No significant differences were found between groups in terms of overall employment status. In addition, particular characteristics of jobs, such as hours worked per week, physical activity level, shift work or flexibility of hours were found to be non-significant when analyzed several ways. However, a marked difference in risk (OR for prenatal comparison 1.79, P less than 0.01; OR for postnatal comparison 2.13, P less than 0.001) was found for job motivation amongst full-time workers for risk, with those women stating they worked primarily out of financial need being at highest risk for abortion. This remained after using multiple logistic regression to control for family income and other socioeconomic variables, job characteristics and subjective measures of job satisfaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous↗

PubMed1991

Gender, family status, and career patterns of graduates of the University of Calgary Faculty of Medicine.

In 1986 the authors sent a questionnaire to 745 physicians who had graduated between 1973 and 1985 from The University of Calgary Faculty of Medicine. The survey obtained information on the graduates' status as parents, the "breaks" they had taken from their practices, and the hours per week they devoted to direct patient care, in order to observe what relationship the graduates' gender and status as parents had on the other variables. The women were far more likely to have taken breaks for parental leave, but the differences in the frequencies of breaks taken by the men and the women for other reasons were less striking. The women were working fewer hours in direct patient-care settings, and those women who were parents and under 35 years old spent fewer hours on patient care than did the men (from all age groups) who were parents. The authors discuss their findings in terms of the impacts of age and cohort effects and the possible lessening of gender-based differences in present-day physicians' practices.

Age Factors↗

PubMed1991

Oral acyclovir therapy of recurrent herpes simplex virus type 2 infection of the hand.

Acyclovir was evaluated as treatment of recurrent herpes simplex virus type 2 infection of the hand in a double-blind, placebo-controlled crossover study. In nine fully evaluable patients, oral acyclovir (2 g/day in three doses for 10 days) initiated during the earliest phase of a recurrence reduced the mean durations (+/- standard deviation) of clinical symptoms from 10.1 (+/- 3.6) to 3.7 (+/- 3.0) days (P = 0.008), signs from 11.1 (+/- 3.7) to 6.2 (+/- 3.3) days (P = 0.024), and viral positivity from 5.3 (+/- 3.8) to 0.6 (+/- 1.1) days (P = 0.011).

Acyclovir↗

PubMed1990

Gastrointestinal function and structure in HIV-positive patients.

We examined 19 patients (17 men) with human immunodeficiency virus (HIV) infection and gastrointestinal symptoms to determine whether those symptoms were due to either a gastrointestinal tract infection or a defect in mucosal absorption because of an enteropathy. The erythrocyte folate and serum vitamin B12 levels were within normal limits in all of the patients. The serum ferritin level was elevated in 12. The xylose absorption test results were abnormal in 8 of the 13 patients able to complete the study. None of the duodenal aspirates yielded a pathogen. Light microscopy revealed nonspecific lymphocytic inflammation without infection in the stomach (in seven patients), the esophagus (in five), the duodenum (in two) and the rectum (in two). However, biopsy specimens were positive for Candida albicans in the esophagus (four patients), cytomegalovirus in the esophagus (one) and the rectum (two), Helicobacter pylori in the antrum (two), Treponema infection in the rectum (two) and Mycobacterium avium-intracellulare in the small intestine (one). Only three patients had a normal series of biopsy specimens. All of the patients had similar ultrastructural changes at the epithelial-stromal junction of the antral glands and in the intestinal crypts. We conclude that abnormal biochemical and endoscopic findings are common in HIV-positive patients with gastrointestinal symptoms. Defects in carbohydrate absorption and ultrastructural changes may be responsible for some aspects of HIV enteropathy.

Bacterial Infections↗

PubMed1990

Predictors of hospitalization early in the course of Crohn's disease. A pilot study.

A historical cohort was used to assess the ability of clinical features and laboratory values recorded at the time of initial diagnostic investigations to predict nondiagnostic hospital admissions in the first 3 months following the diagnosis of Crohn's disease. Data were abstracted from the medical records of 225 eligible patients at primary and secondary care level whose disease was diagnosed between 1977 and 1985. The total study group was randomly divided into two groups (group 1, n = 112; group 2, n = 113). Discriminant analysis was performed on data of patients in group 1. The resulting predictive model was then cross-validated on data of patients in group 2. The variables entered into the predictive model were identified using bivariate analysis. Results show that presence of abdominal mass, body temperature, absolute basophil and lymphocyte counts, aspartate aminotransferase and blood urea nitrogen serum levels, and place of residence (urban, rural, or out of province) were the most useful variables for predicting hospitalization in the first 3 months (P for model = 0.0010; accuracy = 88%). Cross-validation on group 2 showed an accuracy of 80%, a positive predictive value of 62%, and a negative predictive value of 84%. This predictive model could be useful for counseling purposes on the primary or secondary care levels.

Adolescent↗

PubMed1989

Investigation of a Streptococcus viridans pseudobacteremia epidemic at a university teaching hospital.

For several months in 1986, an outbreak of Streptococcus viridans pseudobacteremia occurred at a large teaching hospital. All sources of laboratory blood culture contamination were excluded. A retrospective epidemiological study indicated that one phlebotomist, "P," collected a disproportionate number of the positive blood cultures. Further comparison of the paired blood culture results from the three months when the incidence was highest revealed a good concordance of results among all other phlebotomists (Kappa = 0.5), while P's results concurred with others less frequently than would be expected even by chance (Kappa less than 0.0). Clinical follow-up showed that P did not routinely wear gloves while drawing blood and had eczema of the hands. Skin scrapings from the hands, right index finger/fingernail grew predominantly S viridans species that were compatible with those recovered from contaminated blood cultures. This epidemic demonstrated the need for early detection of this source as a cause of nosocomial pseudobacteremia.

Alberta↗