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Biomedical subjects

E White

Publications and source records attributed to E White.

At least 163 records · Page 9Linked to original sources
PubMed1996

A possible mechanism for large stretch-induced increase in [Ca2+]i in isolated guinea-pig ventricular myocytes.

OBJECTIVES: The aim of the study was to investigate the mechanisms responsible for provoking and maintaining a large, stretch-induced, increase in the level of resting calcium in single guinea-pig ventricular myocytes. In particular, we wished to test the relative importance of intracellular and extracellular sources of calcium in this phenomenon. METHODS: Carbon fibres were used to stretch cells loaded with the fluorescent calcium indicator Indo-1. Sarcomere length and internal calcium activity ([Ca2+]i) were measured. Experimental results from our present and previous studies were compared with those predicted by the OXSOFT HEART (version 4) model of the guinea-pig ventricular myocyte incorporating a stretch-activated channel. RESULTS: The stretch-induced increase in [Ca2+]i was found to be sensitive to removal of [Ca2+]o and application of the Ca(2+)-channel blocker verapamil (1 microM). The phenomenon was not sensitive to disruption of sarcoplasmic reticulum function by ryanodine (1 microM) nor to the Na+ channel blocker TTX (30 microM). Our experimental findings were reproduced in the modelling study. CONCLUSIONS: The stretch-induced increase in [Ca2+]i is modulated by extracellular sources of Ca2+ rather than intracellular Ca2+ stores and is not indiscriminately sensitive to blockers of depolarizing current. We propose that the stretch-induced increase in [Ca2+]i may be triggered by activation of stretch-activated channels but that a combination of stretch-activated current and Ca(2+)-window current maintain the increased levels of resting [Ca2+]i.

Animals↗
PubMed1996

Relationship of food groups and water intake to colon cancer risk.

The association between food groupings and adenocarcinoma of the colon was investigated in a population-based case-control study of men and women ages 30-62 years. Colon cancer cases (238 men and 186 women) diagnosed from 1985 to 1989 were identified from the Seattle-Puget Sound Surveillance, Epidemiology, and End Results Registry. Controls (224 men and 190 women) were selected using a random digit telephone dialing method. Dietary information was gathered using an 80-item food frequency questionnaire. Foods were grouped and analyzed by quartile of intake, with adjustment for age and total energy intake. Among women, a reduced risk of colon cancer was associated with a high intake of fruits and vegetables [adjusted odds ratio (OR) for highest versus lowest quartile, 0.48; 95% confidence interval (CI), 0.26-0.86; P for trend, P = 0.02]. Inverse associations were also observed for the consumption of total (hot and cold) cereals (OR, 0.47; 95% CI, 0.25-0.91; P = 0.05), dairy products (OR, 0.40; 95% CI, 0.21-0.79; P = 0.05), and water (OR for > 5 glasses/day versus < or = 2 glass/day, 0.55; 95% CI, 0.31-0.99; P = 0.004). Among men, colon cancer risk was inversely associated with the intake of breads and cereals (OR, 0.43; 95% CI, 0.22-0.82; P = 0.02) and hot cereal (OR for weekly versus never eating, 0.53; 95% CI, 0.32-0.87; P = 0.01). Water consumption was marginally associated with a decreased colon cancer risk among men as well (OR for > 4 glasses/day versus < or = 1 glass/day, 0.68; 95% CI, 0.38-1.22; P = 0.16). Total meat consumption was associated with an increased risk of distal colon cancer among men (OR, 2.20; 95% CI, 1.08-4.48; P = 0.01). These results were not confounded by body mass index or other measured health behaviors. Results of this research support previous findings which associate intake of fruits, vegetables, grains, and dairy products with reduced colon cancer risk, and meat intake with an increased colon cancer risk. This study also reports a new finding of a possible inverse association of water consumption (glasses of plain water per day) with colon cancer risk.

Adenocarcinoma↗
PubMed1995

c-Myc induces apoptosis in epithelial cells by both p53-dependent and p53-independent mechanisms.

We tested the hypothesis that wild-type p53 activity is required for c-Myc-dependent apoptosis in epithelial cells. Primary baby rat kidney epithelial cell lines were generated by immortalization through the concerted action of c-Myc and a temperature-sensitive (ts) dominant inhibitory mutant allele of p53 (BRK myc/p53ts cells). When shifted to the permissive temperature for wild-type p53 activity, the BRK myc/p53ts cells underwent growth arrest and apoptosis. However, apoptosis also could be induced by serum deprivation at the nonpermissive temperature, when p53 was in the mutant state. Bcl-2 suppressed both modes of cell death. Apoptosis induced by wild-type p53 but not by serum deprivation was accompanied by G1 cell cycle arrest and increased expression of the Bcl-2 antagonist Bax. We concluded that c-Myc could induce apoptosis in epithelial cells by at least two mechanisms that could be distinguished by their p53 requirement. Our results support the possibility that c-Myc-dependent cell death might be exploited for therapeutic ends during carcinoma development, without regard to p53 status of the target cell.

Animals↗
PubMed1995

Population-based study of tamoxifen therapy and subsequent ovarian, endometrial, and breast cancers.

BACKGROUND: The success of tamoxifen in reducing the occurrence of contralateral breast cancer among breast cancer patients in clinical trials has prompted the study of its use in the primary prevention of breast cancer. Long-term risks associated with tamoxifen therapy, however, are still being evaluated, particularly with respect to subsequent cancer occurrence at sites other than the breast. PURPOSE: This population-based, nested case-control study investigated the risks of second primary cancers of the ovary, endometrium, and contralateral breast among women receiving tamoxifen for breast cancer in conventional medical practice. METHODS: A cohort of women diagnosed with breast cancer during 1978 through 1990 was identified from a population-based cancer registry. Case subjects included all women in the cohort who subsequently developed second primary ovarian (n = 39), endometrial (n = 42), or contralateral breast (n = 234) cancer prior to 1992. Control subjects were a random sample of the cohort who did not develop a second primary malignancy; they were matched to the case subjects on age, disease stage, and year of initial breast cancer diagnosis (approximately two control subjects per case subject). Information on tamoxifen use as well as on potential risk factors for the second primary cancers was obtained through medical record abstractions and physician questionnaires. RESULTS: The percentage of women who had received tamoxifen was 18% and 20%, respectively, among ovarian cancer case subjects and control subjects; 26% and 31%, respectively, among endometrial cancer case subjects and control subjects; and 10% and 18%, respectively, among contralateral breast cancer case subjects and control subjects. The mean duration of tamoxifen use was less than 2 years for all groups. The relative risks for ovarian and endometrial cancers in women who took tamoxifen were relatively low but were consistent with no association (for ovarian cancer, matched odds ratio [mOR] = 0.6 and 95% confidence interval [CI] = 0.2-1.8; for endometrial cancer, mOR = 0.6 and 95% CI = 0.2-1.9). Tamoxifen therapy was associated with a decreased risk of contralateral breast cancer (mOR = 0.5; 95% CI = 0.3-0.9), especially if the drug had been taken for more than 1 year (mOR = 0.4; 95% CI = 0.2-0.9) or if the women were postmenopausal at initial breast cancer diagnosis (mOR = 0.4; 95% CI = 0.2-0.8). CONCLUSIONS AND IMPLICATIONS: These data suggest that short durations of tamoxifen therapy are not associated with an increased risk of endometrial or ovarian cancer but are associated with a reduction in contralateral breast cancer risk. It would not be appropriate, however, to generalize these results to women who receive tamoxifen for longer periods.

Adult↗
PubMed1995

Essential role for p53-mediated transcription in E1A-induced apoptosis.

Baby rat kidney (BRK) cell lines transformed by E1A and a temperature-sensitive p53 [tsp53(val135)] undergo rapid apoptosis when p53 assumes the wild-type conformation at the permissive temperature. Wild-type p53 function is therefore required for induction of apoptosis in response to growth deregulation by E1A. BRK cells transformed by E1A and a transcriptionally defective temperature-sensitive p53 [tsp53(22-23val135)] are dramatically impaired for the ability to mediate E1A-induced apoptosis at the permissive temperature. The tsp53(22-23val135), however, still retains some ability to suppress cell growth. Thus, the activity of p53 as a transcription factor is directly correlated with the ability of E1A to induce apoptosis. In addition, there may exist at least two different mechanisms by which p53 can suppress cell-cycle progression, only one of which is dependent on p53-mediated transcription.

Adenovirus E1A Proteins↗
PubMed1995

The effects of mechanical loading and changes of length on single guinea-pig ventricular myocytes.

1. The effects of mechanical loading and changes of length on the contraction of single guinea-pig ventricular myocytes has been investigated. 2. Cell shortening was monitored during isotonic contractions (in which the cell shortened freely) and after attaching carbon fibres of known compliance to the ends of the cell, so that the cell contracted auxotonically (the cell both shortened and developed force). 3. Mechanically loading the cells decreased the amount of shortening during a contraction and abbreviated the contraction. There were, however, no consistent changes in the action potential or the [Ca2+]i transient (measured with the fluorescent dye fura-2). 4. Increasing stimulation rate increased the size of the contraction and the [Ca2+]i transient in both isotonic and auxotonic conditions. The increase in the size of the contraction induced by an increase in stimulation rate was greater in auxotonic conditions but the increase in the size of the [Ca2+]i transient was not. 5. When cells were stretched, there was a step increase in the size of the contraction and a prolongation of its time course. However, neither the size nor the time course of the accompanying [Ca2+]i transient was significantly altered by this intervention. 6. When a stretch was maintained, a further, slow increase in the size of the contraction occurred during the following 3-11 min, in about half the cells studied. The probability of this slow response occurring was increased if the initial degree of activation of the cell was decreased. 7. These data suggest that the mechanisms underlying the responses to mechanical loading and changes of length are the same in both multicellular and single cell preparations of cardiac muscle.

Animals↗
PubMed1995

Community organization to promote breast cancer screening among women ages 50-75.

BACKGROUND: To reduce breast cancer mortality, ways to promote the use of mammography screening among women age 50 and above are needed. Community organization may be a useful approach. METHODS: The Washington State Community Breast Cancer Screening Project involved implementation of promotional activities initiated by physician and lay community boards in two communities. Two comparable communities served as controls for evaluation purposes. Random-digit-dial telephone interviews were used to assess recent use of mammography at baseline and follow-up in independent samples of women ages 50 to 75 from the four communities. The extent of exposure to intervention activities and the relationship between exposure to intervention activities and mammography use were estimated from data collected at follow-up. RESULTS: Exposure to patient reminders from physicians, wallet reminder cards, and newspaper advertisements were consistently related to mammography use. Physician office staff encouragement and a display board were significantly related to mammography use only in Intervention Communities A and B, respectively. Neither exposure to promotional activities nor the change in prevalence of mammography use was significantly higher in the intervention communities than in the comparison communities at follow-up. CONCLUSIONS: Although several activities were useful in promoting mammography use, organization of the community did not enhance efforts undertaken spontaneously by comparable communities.

Aged↗
PubMed1995

The mechanism underlying the cardiotoxic effect of the toxin from the jellyfish Chironex fleckeri.

We have investigated the mechanisms underlying the cardiac effects of the toxin from the box jellyfish Chironex fleckeri. Papillary muscles isolated from the hearts of ferrets and ventricular myocytes isolated from the hearts of ferrets and rats were used. Force, intracellular [Ca2+], and membrane potential were monitored in the papillary muscles; contraction, intracellular [Ca2+], intracellular [Na+], and membrane currents were monitored in the isolated myocytes. Application of the toxin to these preparations resulted in a large increase in intracellular [Ca2+] and the adverse symptoms of Ca2+ overload (aftercontractions, spontaneous contractions, a decrease in developed force, and an increase in resting force). The response of papillary muscles to the toxin was not inhibited by blockers of Ca2+ or Na+ channels or by inhibitors of the sarcoplasmic reticulum, Na+/K+ ATPase, or Na+/H+ exchange. The response to the toxin was, however, blocked by prior exposure to a solution which contained no Na+ and by Ni2+. In the isolated myocytes, as well as an increase in intracellular [Ca2+], the toxin also caused an increase in intracellular [Na+] and the appearance of a current which was inward at negative potentials and reversed at about -10 mV. These data can be explained by the toxin increasing Na+ influx into the cell. The increase in intracellular [Na+] will then increase intracellular [Ca2+] via the Na+/Ca2+ exchange mechanism, thus producing the observed Ca2+ overload.

Animals↗
PubMed1995

Case report: the diagnostic value of contrast-enhanced computed tomography in acute bilateral renal cortical necrosis.

Acute bilateral renal cortical necrosis is a relatively rare cause of acute renal failure accounting for only 2% of cases in the Western World. The pathophysiology of this condition is complex, but ultimately leads to the destruction of the renal cortex with sparing of the renal medulla. A definitive diagnosis is based on renal histology. In this report we describe a patient in whom this diagnosis was made using contrast-enhanced computed tomography as renal biopsy was contraindicated.

Acute Kidney Injury↗
PubMed1995

Clinical support and the Project 2000 nursing student: factors influencing this process.

This paper reports on research commissioned by the English National Board for Nursing, Midwifery and Health Visiting into mentorship and clinical support arrangements for Project 2000 nursing students in the adult and mental health branches. Interviews and observation data were gathered from staff and students in three of the demonstration centres. Findings showed that the terms 'mentorship', 'assessor' and 'supervisor' were used interchangeably and covered diverse roles in both clinical and community settings. Generally there was an impression that staff were willing to help students learn from their experience but felt unprepared for the 'new nursing students'. Several factors emerged which seemed either to promote satisfactory experiences for students or inhibit their learning and enjoyment of the placement. These are discussed under the themes 'supernumerary status', 'team spirit', 'theory and practice', 'diploma level practice' and 'organization of nursing teams'.

Education, Nursing↗
PubMed1995

Viral proteins E1B19K and p35 protect sympathetic neurons from cell death induced by NGF deprivation.

To study molecular mechanisms underlying neuronal cell death, we have used sympathetic neurons from superior cervical ganglia which undergo programmed cell death when deprived of nerve growth factor. These neurons have been microinjected with expression vectors containing cDNAs encoding selected proteins to test their regulatory influence over cell death. Using this procedure, we have shown previously that sympathetic neurons can be protected from NGF deprivation by the protooncogene Bcl-2. We now report that the E1B19K protein from adenovirus and the p35 protein from baculovirus also rescue neurons. Other adenoviral proteins, E1A and E1B55K, have no effect on neuronal survival. E1B55K, known to block apoptosis mediated by p53 in proliferative cells, failed to rescue sympathetic neurons suggesting that p53 is not involved in neuronal death induced by NGF deprivation. E1B19K and p35 were also coinjected with Bcl-Xs which blocks Bcl-2 function in lymphoid cells. Although Bcl-Xs blocked the ability of Bcl-2 to rescue neurons, it had no effect on survival that was dependent upon expression of E1B19K or p35.

Adenovirus E1A Proteins↗
PubMed1995

The effect of mechanical loading on the response of rat ventricular myocytes to acidosis.

The effect of mechanical loading on the negative inotropic effect of acidosis in isolated rat ventricular myocytes was investigated. The mechanical loading of the myocytes was changed by attaching carbon fibres to the ends of the cell. To monitor intracellular Ca2+ and Na+ concentrations, cells were loaded with fluorescent dyes (fura-2 for Ca2+ and SBFI for Na+) using the acetoxymethyl (AM) esters. Mechanical loading reduced cell shortening by 73.0 +/- 3.5% (mean +/- S.E.M., n = 16) and abbreviated the time course of contraction. CO2-induced acidosis caused a rapid decrease in contraction followed by a slow partial recovery. The percentage changes in contraction were not significantly different in mechanically loaded and unloaded conditions. Mechanical loading had little effect on the time course of contraction during acidosis. Changes in intracellular Ca2+ and Na+ concentrations during acidosis were unaffected by mechanical loading. The mechanical loading conditions of a region of the heart can be modified by ischaemia and the subsequent acidosis. Our results suggest that the response of cardiac muscle to acidosis is not markedly modified by such changes in mechanical loading.

Acidosis↗
PubMed1995

Inhibition of apoptosis in human immunodeficiency virus-infected cells enhances virus production and facilitates persistent infection.

Apoptosis is one of several mechanisms by which human immunodeficiency virus type 1 (HIV-1) exerts its cytopathic effects. CD4+ Jurkat T-cell lines overexpressing the adenovirus E1B 19K protein, a potent inhibitor of apoptosis, were used to examine the consequences of inhibition of apoptosis during acute and chronic HIV-1 infections. E1B 19K protein expression inhibited HIV-induced apoptosis, enhanced virus production, and established high levels of persistent viral infection. One E1B 19K-expressing line appeared to undergo HIV-induced death via a nonapoptotic mechanism, illustrating that HIV infection results in lymphocyte depletion through multiple pathways. Increased virus production associated with sustained cell viability suggests that therapeutic approaches involving inhibition of HIV-induced programmed cell death may be problematic.

Adenovirus E1B Proteins↗
PubMed1995

Modulation of p53-mediated transcriptional repression and apoptosis by the adenovirus E1B 19K protein.

BRK cell lines that stably express adenovirus E1A and a murine temperature-sensitive p53 undergo apoptosis when p53 assumes the wild-type conformation. Expression of the E1B 19,000-molecular-weight (19K) protein rescues cells from this p53-mediated apoptosis and diverts cells to a growth-arrested state. As p53 likely functions as a tumor suppressor by regulating transcription, the ability of the E1B 19K protein to regulate p53-mediated transactivation and transcriptional repression was investigated. In promoter-reporter assays the E1B 19K did not block p53-mediated transactivation but did alleviate p53-mediated transcriptional repression. E1B 19K expression permitted efficient transcriptional activation of the p21/WAF-1/cip-1 mRNA by p53, consistent with maintenance of the growth arrest function of p53. The E1B 19K protein is thereby unique among DNA virus-transforming proteins that target p53 for inactivation in that it selectively modulates the transcriptional properties of p53. The E1B 19K protein also rescued cells from apoptosis induced by inhibitors of transcription and protein synthesis. This suggests that cell death may result from the inhibition of expression of survival factors which function to maintain cell viability. p53 may induce apoptosis through generalized transcriptional repression. In turn, the E1B 19K protein may prevent p53-mediated apoptosis by alleviating p53-mediated transcriptional repression.

Adenovirus E1B Proteins↗
PubMed1995

Activated H-ras rescues E1A-induced apoptosis and cooperates with E1A to overcome p53-dependent growth arrest.

The adenovirus E1A oncogene products stimulate DNA synthesis and cell proliferation but fail to transform primary baby rat kidney (BRK) cells because of the induction of p53-mediated programmed cell death (apoptosis). Overexpression of dominant mutant p53 (to abrogate wild-type p53 function) or introduction of apoptosis inhibitors, such as adenovirus E1B 19K or Bcl-2 oncoproteins, prevents E1A-induced apoptosis and permits transformation of BRK cells. The ability of activated Harvey-ras (H-ras) to cooperate with E1A to transform BRK cells suggests that H-ras is capable of overcoming the E1A-induced, p53-dependent apoptosis. We demonstrate here that activated H-ras was capable of suppressing apoptosis induced by E1A and wild-type p53. However, unlike Bcl-2 and the E1B 19K proteins, which completely block apoptosis but not p53-dependent growth arrest, H-ras expression permitted DNA synthesis and cell proliferation in the presence of high levels of wild-type p53. The mechanism by which H-ras regulates apoptosis and cell cycle progression is thereby strikingly different from that of the E1B 19K and Bcl-2 proteins. BRK cells transformed with H-ras and the temperature sensitive murine mutant p53(val 135), which lack E1A, underwent growth arrest at the permissive temperature for wild-type p53. p53-dependent growth arrest, however, could be relieved by E1A expression. Thus, H-ras alone was insufficient and cooperation of H-ras and E1A was required to override growth suppression by p53. Our data further suggest that two complementary growth signals from E1A plus H-ras can rescue cell death and thus permit transformation.

Adenovirus E1A Proteins↗
PubMed1995

Effect of stretch on contraction and the Ca2+ transient in ferret ventricular muscles during hypoxia and acidosis.

The effect of stretch on cardiac muscle contraction and the Ca2+ transient was studied during hypoxia and acidosis in isolated ferret ventricular muscles. In control conditions, a maintained stretch produced an immediate increase in tension followed by a slow increase in tension and the Ca2+ transient. A stretch between contractions (diastolic stretch) caused only a slow increase in tension and the Ca2+ transient, whereas a stretch during the period of contraction (systolic stretch) produced an immediate increase in tension followed by a small slow increase in tension and the Ca2+ transient. In hypoxia, the immediate percent increase in tension was the same as in control. However, the slow increase was smaller during all three types of stretch. In acidosis, the immediate percent increase in tension was larger than in control. The slow change was the same during maintained stretch. However, the slow increase in tension was smaller during diastolic stretch and larger during systolic stretch. Thus the stretch-dependent increase in contraction is inhibited during hypoxia and modulated by acidosis.

Acidosis↗