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Biomedical subjects

E White

Publications and source records attributed to E White.

At least 127 records · Page 7Linked to original sources
PubMed1997

The effect of the venom of a Chilean tarantula, Phrixotrichus spatulatus, on isolated guinea pig ventricular myocytes.

We have investigated the effect of the venom of a Chilean tarantula, Phrixotrichus spatulatus, on cell contraction, intracellular [Ca2+] ([Ca2+]i), and the L-type Ca2+ current (ICa,L) in cells isolated from the ventricles of guinea pig hearts. Whole-cell voltage clamp techniques were used to monitor ICa,L. The action potential was recorded using whole cell current clamp. [Ca2+]i was monitored using the fluorescent indicator indo-1. The venom of P. spatulatus decreased ICa,L in a dilution-dependent manner, with half-maximal inhibition at a dilution of 1.1/10(4) (v/v). At a dilution of 1/10(4), this inhibition occurred at all potentials so that the current-voltage relationship of ICa,L was depressed. However, inhibition of ICa,L by the venom was relieved by positive potentials, the venom being less effective following pulses to positive potentials. The venom reduced the duration of the action potential (at 50% repolarization) by between 26 and 43%. The venom also decreased the amplitude of the [Ca2+]i transient and cell contraction. It is concluded that the venom of P. spatulatus is a potent, voltage-dependent inhibitor of ICa,L; this inhibition of ICa,L may account for the effects of the venom on action potential duration, [Ca2+]i, and contraction.

Action Potentials↗
PubMed1997

Bcl-2 and the ICE family of apoptotic regulators: making a connection.

Apoptosis, a genetically programmed mechanism of eliminating cells in response to a variety of stimuli, provides protection against cancer and viral infections as well as maintenance of homeostasis in living organisms. Two classes of molecules, the Bcl-2 family of regulators and the ICE family of proteases, have emerged from different vertebrate, invertebrate and viral systems that have been used to elucidate the pathways leading to apoptosis. However, no connection between these two disparate families of apoptotic regulators has been convincingly established. In reviewing the recent advances pertaining to the Bcl-2 and ICE-related protein families, one can address the question of a functional relationship between the two classes of proteins.

Animals↗
PubMed1997

Leisure-time physical activity in relation to breast cancer among young women (Washington, United States).

It has been hypothesized that women who participate in vigorous physical activity may have lower risk of breast cancer due to lower lifetime exposure to ovarian hormones. A population-based case-control study was conducted to investigate the association between leisure-time physical activity and risk of breast cancer among women aged 21 to 45 years. Cases were 747 women diagnosed with invasive breast cancer between 1983 and 1990 in three counties of western Washington state (United States), and were identified through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) registry. Controls were 961 women selected from the same area by random-digit telephone dialing. Physical activity was assessed through personal interview, with questions on frequency and duration of each type of recreational activity during the two-year period immediately prior to reference data (date of diagnosis for cases and a comparable assigned date for controls) and between ages 12 and 21. For the two-year time period before diagnosis, there was no association with frequency of activity (age-adjusted odds ratio [OR] = 0.93, 95 percent confidence interval [CI] = 0.71-1.22 for four or more episodes per week cf none), total hours spent in physical activity (age-adjusted OR = 0.92, CI = 0.71-1.22 for four or more hours per week cf none) or MET (metabolic equivalent energy expenditure unit) (age-adjusted OR = 0.95, CI = 0.73-1.23 for 18 or more METs per week of none), nor any trend is risk with increasing activity levels. Similarly, there was no association between leisure activity during adolescence and breast cancer risk. These results were not confounded further by body mass index (wt/ht2), age at menarche, age at first full-term pregnancy, parity, family history of breast cancer, or other measured health behaviors. Our findings do not support a protective effect of leisure-time physical activity either in the adolescent years or in adulthood on breast cancer in young women.

Adult↗
PubMed1997

Vitamin supplements and cancer risk: the epidemiologic evidence.

This report reviews published epidemiologic research on the associations of vitamin and mineral supplementation with cancer risk. Although the literature on nutrition and cancer is vast, few reports to date have addressed supplemental nutrients directly (seven clinical trials, 16 cohort, and 36 case-control studies). These studies offer insight into effects of nutrients that are distinguishable from effects of other biologically active compounds in foods. Randomized clinical trials have not shown significant protective effects of beta-carotene, but have found protective effects of: alpha-tocopherol against prostate cancer; mixtures of retinol/zinc and beta-carotene/alpha-tocopherol/selenium against stomach cancer; and selenium against total, lung, and prostate cancers. Cohort studies provide little evidence that vitamin supplements are associated with cancer. Case-control studies have reported an inverse association between bladder cancer and vitamin C; oral/pharyngeal cancer and several supplemental vitamins; and several cancers and vitamin E. A randomized clinical trial, a cohort study, and a case-control study have all found inverse associations between colon cancer and vitamin E. Overall, there is modest evidence for protective effects of nutrients from supplements against several cancers. Future studies of supplement use and cancer appear warranted; however, methodologic problems that impair ability to assess supplement use and statistical modeling of the relation between cancer risk and supplement use need attention.

Case-Control Studies↗
PubMed1997

Fluid intake and the incidence of bladder cancer among middle-aged men and women in a three-county area of western Washington.

This population-based case-control study reports on the relationship between fluid intake and the incidence of bladder cancer among 262 bladder cancer cases from Western Washington and 405 controls identified through random-digit dialing Cases were identified from the Surveillance. Epidemiology, and End Results (SEER) registry and were diagnosed between January 1987 and June 1990. All eligible subjects were Caucasian 45- to 65-year-old residents of King, Pierce, or Snohomish counties and completed a structured telephone interview. Analyses were conducted by logistic regression with adjustment for age, county, and smoking (current, former, never). Among women there was a positive association between total fluid intake and the incidence of bladder cancer [p (trend = 0.02] and a moderate positive association between the use of decaffeinated coffee and the incidence of bladder cancer [p (trend) = 0.08]. Among men there was an inverse association between the consumption of regular soft drinks and the incidence of bladder cancer [p (trend) = 0.03]. No association was found between the incidence of bladder cancer and the intake of water, coffee, tea, diet soft drinks, alcohol, or liquids from tap for men or women. This study suggests that the intake of water and specific beverages is overall not associated with risks of bladder cancer. This study provides limited evidence of a positive association between total fluid intake and bladder cancer among women.

Beverages↗
PubMed1997

Age when maximum height is reached as a risk factor for breast cancer among young U.S. women.

We evaluated height as a potential risk factor for breast cancer in a case-control study of 747 young women diagnosed with invasive breast cancer before age 46 years and 961 control subjects recruited by random digit dialing. We found that total height attained did not affect a woman's risk of the disease. The age when a women reached her maximum height, however, was a risk factor for breast cancer. There was a trend of decreasing risk of breast cancer in relation to increasing age of height attainment, culminating in a 30% reduction in the risk of breast cancer for women who reached their maximum height when they were 18 years or older compared with women who reached their maximum height when they were 13 years old or less (odds ratio = 0.7; 95% confidence interval = 0.5-1.0). Although the age at menarche was correlated with the age at maximum height, the effect of age at maximum height persisted after adjustment for age at menarche. Previous studies have reported that age at menarche is an important determinant of risk, but this study indicates that age when maximum height is reached may be another, and possibly more important, landmark of puberty that is related to breast cancer risk. The physiologic basis for this claim may lie in the influence on breast development of exposure to growth hormone and insulin-like growth factor during puberty, and on a decreased time between the end of puberty and a woman's first livebirth, both of which are believed to affect a woman's risk of breast cancer.

Adolescent↗
PubMed1997

Gadolinium blocks the delayed rectifier potassium current in isolated guinea-pig ventricular myocytes.

The effect of Gd3+ on the delayed rectifier potassium current (IK) in single guinea-pig ventricular myocytes was tested using whole-cell patch-clamp techniques. It was found that Gd3+ blocked 70% of the IK tail current at a concentration of 100 microM. The EC50 was 24 microM. Action potential durations were, however, reduced, consistent with a predominant effect on depolarizing L-type Ca2+ current (Ica.L). In the presence of 5 microM nifedipine Gd3+ prolonged the action potential. Using carbon fibres to stretch cells we observed that 10 microM Gd3+ was not effective in reducing a large stretch-activated increase in resting calcium. Modelling studies using the OXSOFT HEART program suggest that this lack of response is influenced by blockade of repolarizing current but is best reproduced by additional blockade of Ca2+ extrusion via the Na(+)-Ca2+ exchanger. When Gd3+ is used as a blocker of stretch-activated channels its actions upon both Ica.L and IK must therefore be accounted for.

Action Potentials↗
PubMed1997

p300 binding by E1A cosegregates with p53 induction but is dispensable for apoptosis.

E1A expression during adenovirus infection induces apoptosis. E1A expression causes accumulation of the p53 tumor suppressor protein, and E1A-induced apoptosis is p53 mediated in primary rodent cells, implying that p53 induction may be linked to apoptosis induction by E1A. Adenoviruses containing mutations in the E1A gene were tested for the ability to trigger both p53 accumulation and the appearance of enhanced cytopathy (cyt phenotype) and degradation of DNA (deg phenotype), indicative of apoptosis in infected HeLa cells. The adenoviruses had mutations which disrupted the pRb- and/or p300-binding activities of E1A so that the relationship between p53 induction and apoptosis and binding to these cellular proteins by E1A could be determined. An E1A mutation that specifically disrupted the p300-binding activity failed to induce p53 accumulation, whereas mutations in E1A which affected pRb binding induced p53 accumulation. Thus, p300 binding was required and pRb binding was dispensable for E1A-mediated accumulation of p53 in HeLa cells. All the E1A mutant viruses, regardless of the ability to induce p53 accumulation, induced the cyt and deg phenotypes, suggesting that p53 induction in infected HeLa cells was not essential for apoptosis, nor was binding of E1A to the pRb and/or p300 protein. The possibility that E1A induced a p53-independent apoptosis pathway was tested by analyzing the appearance of the cyt and deg phenotypes in Saos-2 cells, which were null for both alleles of p53, upon adenovirus infection. An adenovirus expressing wild-type 12S E1A induced both the cyt and deg phenotypes in Saos-2 cells, as did all the E1A mutant viruses. Thus, E1A expression during infection of human cells may trigger redundant p53-independent and -dependent apoptotic pathways.

Adenovirus E1A Proteins↗
PubMed1997

Initial characterization of hamsters with spontaneous hypertension.

The purpose of this study was to begin to characterize a new inbred strain of adult male hamsters with established spontaneous hypertension along with their genetically/age-matched normotensive controls. We found that mean arterial pressure was 162+/-3 mm Hg in hypertensive hamsters and 94+/-4 mm Hg in controls (mean+/-SEM; P<.05). Body weight was significantly lower in hypertensive hamsters relative to normotensive hamsters (P<.05). Hypertension was associated with a significant increase in heart weight, thickness of the left ventricular wall, and amplitude of the QRS complex in standard electrocardiographic leads I and aVR (P<.05). No gross or microscopic abnormalities were observed in other organs. Plasma renin activity and the number of circulating neutrophils were significantly increased in hypertensive hamsters relative to controls (P<.05). Serum concentrations of creatinine, blood urea nitrogen, sodium, potassium, and calcium as well as urinalysis were similar in both groups. Overall, these data suggest that the spontaneously hypertensive hamster could be a suitable model for the study of spontaneous hypertension.

Animals↗
PubMed1997

Using a brief household food inventory as an environmental indicator of individual dietary practices.

OBJECTIVES: This study examined whether foods in household pantries are an indicator of house-hold members' diet. METHODS: In a random-digit-dial survey, the presence in the house of 15 high-fat foods was assessed with whoever answered the phone. A randomly selected household member was surveyed about diet-related behaviors (n = 1002). RESULTS: Individuals in the precontemplation stage of dietary change had more high-fat foods in their pantry than those in maintenance (means of 7.4 and 5.8, respectively). Individuals with low-fat pantries had an intake of 32% energy from fat vs 37% for those with high-fat pantries. CONCLUSIONS: Household food inventories are a practical and valid approach to monitoring dietary behaviors in community-based studies.

Adult↗
PubMed1997

Recent trends in breast cancer mortality among white and black US women.

OBJECTIVES: Time trends in breast cancer mortality were analyzed from 1970 to 1992 among White and Black US women aged 25 and over. METHODS: Mortality data from the National Center for Health Statistics were summarized within three periods 1970 to 1979, 1980 to 1988, and 1989 to 1992. The annual change was calculated as the average yearly percentage of change based on the logistic model. RESULTS: For White women of all ages, breast cancer mortality decreased by 1.6% (95% confidence interval = -2.0%, -1.1%) per year on average during 1989 to 1992, in contrast to the flat mortality rates observed during the 1970s and a 0.5% average annual increase during 1980 to 1988. The decline was observed for White women under age 60, among whom breast cancer mortality had been decreasing, and for White women aged 60 to 79, among whom breast cancer mortality had been increasing, but it was not observed among Black women. CONCLUSIONS: The long-awaited decline in US breast cancer mortality has finally appeared, although only among White women. The possible contributions are changes in inherent risk of disease, changes in treatment effectiveness, and increased use of screening mammography.

Adult↗
PubMed1997

Interleukin 1 beta converting enzyme-like proteases are essential for p53-mediated transcriptionally dependent apoptosis.

p53-mediated apoptosis in baby rat kidney (BRK) cell lines transformed by E1A and p53(val135) requires a transcriptionally functional p53. Coexpression of the E1B 19K protein in BRK cell lines transformed by E1A and p53(val135) rescues cells from p53-mediated apoptosis, and this is paralleled by the absence of both lamin and poly(ADP-ribose) polymerase cleavage. Therefore, the role of interleukin 1 beta converting enzyme (ICE)-like porteases in p53-mediated, transcriptionally dependent apoptosis was investigated. The ICE-like protease CPP32 was proteolytically activated during p53-mediated apoptosis in BRK cells, and this required a transcriptionally competent p53. Substitution of the p53 transactivation domain with the transactivation domain of herpes simplex virus VP16 (VP16/p53) resulted in accelerated kinetics of both apoptosis and Bax induction. Moreover, apoptosis induced by p53, VP16/p53, and Bax was abrogated by Z-VAD.FMK, an inhibitor of ICE-like proteases. These results indicate that all apoptotic pathways downstream of p53-mediated transcription converge upon the activation of ICE-like proteases.

Adenovirus E1A Proteins↗
PubMed1997

Mammography diffusion and trends in late-stage breast cancer: evaluating outcomes in a population.

The purpose of this study was to assess mammography diffusion in a population offered an organized breast cancer screening program, using intervals of 1-3 years, and to evaluate its effect on the late-stage cancer (tumors > or = 3 cm2) rates compared to rates in the surrounding community. We measured "ever-use" of mammography (1986-1992) among women enrollees of a consumer-controlled health care organization (n > or = 60,000/year; ages > or = 40), Group Health Cooperative of Puget Sound (GHC). Among these same women and the surrounding community (n = > or = 745,000/year), we measured late-stage cancer rates. Using unconditional logistic regression, we compared annual rates of ever-use among GHC women ages 40-49 and > or = 50 (1986-1992) and late-stage breast cancer (1983/84-1991/92) among all women. Among all GHC women ages 40 to 49, and 50 years of age and older, 67.4 and 82.8%, respectively, ever-used mammography by 1992. By 1992, approximately one-third of the mammograms among GHC women occurred in each of the three previous years. The rate of late-stage tumors declined significantly in the GHC and non-GHC populations among women 50 years of age and older (P < 0.001) but not among women ages 40 to 49. In conclusion, implementing a system of automated reminders was not sufficient to maximize mammography use in a population. Reductions in late-stage disease occurred among women ages > or = 50, even when regular" was not synonymous with "annual."

Adult↗
PubMed1997

Relationship between vitamin and calcium supplement use and colon cancer.

The relationship between vitamin supplement use and colon cancer was assessed in a population-based case-control study among men and women aged 30-62 years. Cases were 251 men and 193 women diagnosed with colon cancer in 1985-1989 in three counties in the Seattle metropolitan area who were identified from the Surveillance, Epidemiology, and End Results cancer registry. Controls were 233 men and 194 women identified by random digit dialing. Supplement use was assessed by questions on frequency, duration, and dose per day (for individual supplements) or type (for multivitamins) during the 10-year period ending 2 years before diagnosis. All results were adjusted for age and sex and were not confounded by other measured behaviors. The average daily intake of supplemental vitamins A, C, E, folic acid, calcium, and multivitamins during the reference period were each associated with reduced risk of colon cancer (all P for trend < 0.03). The strongest associations were for use of vitamin E (odds ratio, 0.43; 95% confidence interval, 0.26-0.71 for > or = 200 IU/day versus none) and multivitamins (odds ratio, 0.49; 95% confidence interval, 0.35-0.69 for daily use versus no use; both P for trend < 0.001). These two associations were also significant using a stricter test of trend limited to supplement users, which reduces the effect of colinearity among these exposures. Because almost all vitamin D supplementation comes from multivitamin pills, the association of vitamin D use with colon cancer could not be distinguished from that of multivitamin use. Clinical trials or cohort studies with long-term assessment would be needed before public health recommendations could be made about supplement use.

Adenocarcinoma↗
PubMed1997

Effects of biomarker measurement error on epidemiological studies.

This chapter presents an overview of how measurement error in a biomarker affects epidemiological studies which use the biomarker. To estimate the effects of biomarker error, one must first measure the error using an appropriate validity or reliability study design and using appropriate parameters, i.e. parameters that are informative about the effects of measurement error on the 'parent' epidemiological study. These measures of the biomarker measurement error from the validity or reliability study can then be applied to what is known about the association under study in the parent study, in order to estimate the effects of the biomarker error on the results of the epidemiological study.

Bias↗
PubMed1996

Family history and survival of young women with invasive breast carcinoma.

BACKGROUND: This study investigates whether a positive family history of breast carcinoma is associated with improved survival after invasive breast carcinoma among women ages 21 through 45. METHODS: Subjects were 733 nonadopted women born after 1944 who were diagnosed with primary invasive breast carcinoma between January 1983 and April 1990 while residing in the metropolitan Seattle area and who provided information on family history of breast carcinoma. Information on clinical characteristics and survival was obtained from a population-based cancer registry. Subjects were followed for survival through 1994. Cox proportional hazards models were used to estimate the relative risk (RR) of dying in relation to family history of breast carcinoma, adjusting for selected clinical characteristics, age and year of diagnosis, and prior mammograms. RESULTS: The risk of dying among women with a first-degree family history of breast carcinoma was half that of women with no family history of breast carcinoma (RR = 0.5%; 95% confidence interval [CI], 0.3-0.9). There was no evidence of a reduction in the risk of dying among women with only a second-degree family history of breast carcinoma (RR = 1; 95% CI, 0.6-1.4). These associations were adjusted for age and year of diagnosis, stage of disease, tumor size, bilaterality, and mammogram history. These findings were not further influenced by adjustment for initial treatment or the numbers and ages of relatives at risk for breast carcinoma. CONCLUSIONS: Compared with women with neither a first- nor second-degree family history of breast carcinoma, the authors found that women who had a first-degree family history experienced increased survival. This finding did not appear to be attributable to differences in screening or treatment. To the extent that this difference is attributable to underlying biologic mechanisms, new insights into the natural history and treatment of breast carcinoma could result. Future studies should investigate whether specific susceptibility genes are associated with differential survival from breast carcinoma.

Adult↗
PubMed1996

Estimating relative risk functions in case-control studies using a nonparametric logistic regression.

The authors describe an approach to the analysis of case-control studies in which the exposure variables are continuous, i.e., quantitative variables, and one wishes neither to categorize levels of the exposure variable nor to assume a log-linear relation between level of exposure and disease risk. A dose-response association of an exposure variable with a disease outcome can be depicted by estimated relative risks at various exposure levels, and the functional relation between exposure dose and disease risk is here termed a relative risk function (RRF). A RRF takes values that are greater than zero: Values less than one imply lower risk; the value one implies no risk, and values greater than one imply increased risk, when compared with a reference value. The authors describe how a nonparametric logistic regression can be used to estimate and display these RRFs. Using data from a previously published case-control study of diet and colon cancer, RRFs for total energy, dietary fiber, and alcohol intakes are compared with the original results obtained from using categorized levels of exposure variables. For total energy and alcohol intakes, there were meaningful differences in study results based on the two analytic approaches. For energy, the nonparametric logistic regression detected a significant protective effect of low intakes, which was not found in the original analysis. For alcohol, the nonparametric logistic regression suggested that there were two underlying populations, non- or very light drinkers and moderate to heavy drinkers, with different relation of dose to disease risk. In contrast, the original analysis found a nonlinear increase in risk across intake categories and did not detect the complex, bimodal nature of the exposure distribution. These results demonstrate that nonparametric logistic regression can be a useful approach to displaying and interpreting results of case-control studies.

Adult↗