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Biomedical subjects

E White

Publications and source records attributed to E White.

At least 19 recordsLinked to original sources
PubMed1992

The adenovirus E1A proteins induce apoptosis, which is inhibited by the E1B 19-kDa and Bcl-2 proteins.

Cooperation between the adenovirus E1A and E1B oncogenes is required for transformation of primary quiescent rodent cells. Although expression of E1A alone will stimulate cell proliferation sufficient to initiate transformed focus formation, proliferation fails to be sustained and foci degenerate. Coexpression of either the 19-kDa or 55-kDa E1B oncoproteins with E1A permits high-frequency transformation by overcoming this cytotoxic response. Without E1B 19-kDa protein expression, however, transformants remain susceptible to induction of cell death. Rapid loss of viability is coincident with nucleolytic cleavage of DNA in intranucleosomal regions and chromatin condensation, hallmarks of programmed cell death (apoptosis). Furthermore, overexpression of a known suppressor of apoptosis, the Bcl-2 protooncogene, can rescue E1A-induced focus degeneration. Thus E1A-dependent stimulation of cell proliferation is accompanied by apoptosis and thereby insufficient to singly induce transformation. High-frequency transformation requires a second function encoded by the E1B 19-kDa protein to block apoptosis.

Adenoviridae↗
PubMed1992

Noncontraceptive hormone use and risk of breast cancer.

All British Columbia (Canada) women under 75 years of age who were diagnosed with breast cancer during 1988-89 were asked to complete a postal questionnaire which included detailed information on menopausal estrogen use. Controls were drawn from the Provincial Voters List, matched by five-year age category to the cases. The present analysis consists of 699 cases and 685 controls who were postmenopausal due to natural causes or to a hysterectomy. There was no overall increase in risk of breast cancer associated with ever-use of unopposed estrogen (odds ratio [OR] = 1.0, 95 percent confidence interval [CI] = 0.8-1.3). For estrogen use of 10 years or longer, the relative risk [RR] was 1.6 (CI = 1.1-2.5). The risk estimate for current users was somewhat elevated (OR = 1.4, CI = 1.0-2.0). Compared with women who never used hormone preparations, women who had used estrogen plus progestogen had an RR of 1.2 (CI = 0.6-2.2). Our results suggest that ever-use of estrogen, with or without progestogen, does not appreciably increase the risk of breast cancer. However, long-term and recent use of unopposed estrogen may be associated with a moderately increased risk.

Aged↗
PubMed1992

Correlates of maintenance of a low-fat diet among women in the Women's Health Trial.

BACKGROUND: The Women's Health Trial (WHT) was a feasibility study for a randomized controlled trial designed to test the hypothesis that a reduction in dietary fat reduces breast cancer incidence among women age 45 to 69. Between 1984 and 1988, 2,064 women participated in its two phases. METHODS: A follow-up study of 525 women who were randomized to receive the WHT dietary intervention program was conducted to assess maintenance of the diet 1 year on average after the trial ended. Among 448 participants, the mean percentage of energy from fat as measured by a food frequency questionnaire was 40.0% at baseline, 26.3% at the end of the trial, and 27.7% at follow-up. Based on 408 women with complete data, a recursive model was estimated, describing the influence of baseline characteristics of the women on attendance at intervention program sessions, adherence to the diet during the trial, and long-term maintenance of the diet after the trial ended. The effects of women's experiences during the trial on adherence and long-term maintenance were investigated as well. RESULTS: Attendance at the educational sessions was strongly related to adherence to the diet during the trial (P less than 0.001), and adherence was the most important predictor of long-term maintenance (P less than 0.001). The percentage of energy from dietary fat at baseline was an important correlate of both adherence (P less than 0.001) and long-term maintenance (P less than 0.001). College-educated women were more likely to adhere to the diet during the trial (P less than 0.001). Feelings of deprivation adversely affected long-term maintenance (P less than 0.01), primarily through their effect on adherence during the trial (P = 0.01). Costliness of the diet in time and money negatively influenced long-term maintenance (P less than 0.05). Development of a distaste for fat encouraged adherence (P = 0.06). CONCLUSIONS: The low-fat dietary pattern established during the WHT was maintained for as long as 20 months after the trial ended. A recursive model was useful in analyzing the process and correlates of long-term maintenance of dietary behavior change. Both predisposing variables and women's experiences while on a low-fat diet were associated with long-term maintenance. The results suggest that feelings of deprivation should be avoided, perhaps by use of low-fat substitutes, by those attempting to lower their dietary fat and that more research is needed on the development of a distaste for fat among individuals who adopt low-fat diets.

Aged↗
PubMed1992

Urodynamics in the early stages of spinal cord compression from prostate adenocarcinoma.

Acute urinary retention developed in 2 patients with a history of prostate cancer. Urodynamic evaluation revealed autonomic dysfunction, which contrasted with a prior urodynamic study, indicating a possible spinal lesion. Radiographic evaluation led to early diagnosis and treatment of spinal cord compression from metastatic prostate adenocarcinoma. We discuss the diagnostic role of urodynamics in such cases.

Adenocarcinoma↗
PubMed1992

Inactivation of Ca current during the action potential in guinea-pig ventricular myocytes.

The inactivation of Ca channels during the action potential plateau of guinea-pig ventricular myocytes was investigated by interrupting action potentials with voltage clamp pulses to assess Ca channel availability. The influence of the bulk cytosolic calcium [( Ca]i) transient on Ca channel inactivation was also studied by impaling cells with microelectrodes containing the Ca chelator BAPTA (1,2 bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; 125-200 mM). Ca channel availability decreased progressively with action potential duration, reaching approximately 20% of maximum availability after 100 ms and falling close to zero at the end of the plateau. When membrane potential became more negative than -40 mV Ca channel availability increased. Elevation of the action potential plateau to more positive levels increased Ca channel availability (even though this was expected to increase peak [Ca]i). When the cytosol was loaded with BAPTA Ca channel availability during the plateau increased. Inactivation of Ca channels was not, however, abolished. The observations are consistent with the hypothesis that in guinea-pig ventricular myocytes the majority of Ca channels are inactivated during the plateau and recovery does not occur until repolarization is almost complete. It may be that while the cytosolic Ca transient (that is generated in part by release of Ca from the intracellular Ca stores) modulates Ca channel availability, significant inactivation of the Ca channel during the action potential plateau is due to voltage dependent inactivation and to Ca-induced inactivation resulting from the Ca which enters the myocyte via Ca channels.

Action Potentials↗
PubMed1992

The 19-kilodalton adenovirus E1B transforming protein inhibits programmed cell death and prevents cytolysis by tumor necrosis factor alpha.

The adenovirus E1A and E1B proteins are required for transformation of primary rodent cells. When expressed in the absence of the 19,000-dalton (19K) E1B protein, however, the E1A proteins are acutely cytotoxic and induce host cell chromosomal DNA fragmentation and cytolysis, analogous to cells undergoing programmed cell death (apoptosis). E1A alone can efficiently initiate the formation of foci which subsequently undergo abortive transformation whereby stimulation of cell growth is counteracted by continual cell death. Cell lines with an immortalized growth potential eventually arise with low frequency. Coexpression of the E1B 19K protein with E1A is sufficient to overcome abortive transformation to produce high-frequency transformation. Like E1A, the tumoricidal cytokine tumor necrosis factor alpha (TNF-alpha) evokes a programmed cell death response in many tumor cell lines by inducing DNA fragmentation and cytolysis. Expression of the E1B 19K protein by viral infection, by transient expression, or in transformed cells completely and specifically blocks this TNF-alpha-induced DNA fragmentation and cell death. Cosegregation of 19K protein transforming activity with protection from TNF-alpha-mediated cytolysis demonstrates that both activities are likely the consequence of the same function of the protein. Therefore, we propose that by suppressing an intrinsic cell death mechanism activated by TNF-alpha or E1A, the E1B 19K protein enhances the transforming activity of E1A and enables adenovirus to evade TNF-alpha-dependent immune surveillance.

Adenovirus Early Proteins↗
PubMed1992

A filamentous-like mutant of Listeria monocytogenes with reduced expression of a 60-kilodalton extracellular protein invades and grows in 3T6 and Caco-2 cells.

We describe a spontaneous rough mutant of Listeria monocytogenes that produces reduced amounts of a 60-kilodalton major extracellular polypeptide (p60) as shown by sodium dodecyl sulfate--polyacrylamide gel electrophoresis and Western blot analysis. The cells of this mutant are filamentous, do not give rise to smooth wild-type colonies, and produce listeriolysin O in amounts equal to that of the wild-type cells, but they show a reduced virulence in the mouse LD50 model and in the Caco-2 tissue culture virulence assay. Light and electron microscopic studies show that this mutant invades and remains filamentous during in vivo growth in both Caco-2 and 3T6 tissue culture monolayers. The reduced virulence of the rough mutant is not due to the inability of its filamentous forms to invade or to grow in nonprofessional phagocytes since invasion and growth of the smooth wild-type and the rough mutants are comparable in both Caco-2 and 3T6 monolayers.

Animals↗
PubMed1992

How women's adopted low-fat diets affect their husbands.

OBJECTIVES: One way of promoting a reduction in dietary fat intake is by changing the diet of family members. This study investigated the long-term effects of a low-fat dietary intervention on husbands of women who participated in the Women's Health Trial (WHT). METHODS: An average of 12 months after the end of the WHT, a randomly selected sample of participants' husbands was sent dietary and health questionnaires as part of a follow-up study of the maintenance of the low-fat diet among WHT participants. RESULTS: We found an absolute difference in fat intake between groups of 4 percentage points (32.9% energy from fat among intervention husbands [n = 188] vs 36.9% among control husbands [n = 180]). The wife's attitude and fat intake were among the most important predictors of her husband's fat intake, indicating that the effect of the WHT intervention on the husbands of participants was more likely due to their acceptance of lower-fat foods being served at home than to overt actions by the men. CONCLUSIONS: Our results suggest that a dietary intervention aimed at women can have an effect on their husbands and may be a cost-effective approach to healthy dietary change for both women and men.

Adult↗
PubMed1992

Validation of virus inactivation by heat treatment in the manufacture of diaspirin crosslinked hemoglobin.

Diaspirin crosslinked hemoglobin (DCLHb), a hemoglobin based oxygen carrying solution prepared from outdated human blood, is subjected to a heat treatment step to inactivate viruses in our manufacturing process. To validate the efficacy of this inactivation, we have simulated the heat treatment procedure at a reduced scale using hemoglobin solution spiked with representative viruses. Human Immuno-deficiency Virus (HIV), Cytomegalovirus (CMV), and Duck Hepatitis B Virus (DHBV) were used in this validation. Inoculation with concentrated virus was performed just prior to the heat treatment to determine the effect of that specific process step. Samples were taken before, during, and after heat treatment and assayed for virus titer in an attempt to assess the rate as well as the extent of virus inactivation. CMV was analyzed in a plaque assay using MRC-5 indicator cells. The titer was reduced from 3.3 x 10(6) plaque forming units (PFU) per mL to less than 5 x 10(1) PFU/mL (detection limit) within 30 minutes. DHBV was analyzed by inoculation of serially diluted samples into Pekin ducklings, followed at intervals by screening sera for DHBV DNA by dot blot hybridization. The titer was reduced from 5.0 x 10(6) duck infectious units (DIU) per mL to less than 5 x 10(0) DIU/mL (detection limit) within 1 hour. HIV titers were determined through an ELISA assay for p24 antigen present in peripheral blood lymphocyte cocultivation supernatants. The titer was reduced from 2.0 x 10(4) infectious units (IU) per mL to less than 2 x 10(0) IU/mL (detection limit) within 1 hour. These data indicate that high titers of these blood borne viruses are rapidly inactivated by this heat treatment process.

Aspirin↗
PubMed1992

Long-term maintenance of a low-fat diet: durability of fat-related dietary habits in the Women's Health Trial.

The Women's Health Trial (WHT) was a feasibility study for a randomized trial of a low-fat diet for the prevention of breast cancer. One year after the WHT was terminated, a random sample of 894 participants who had been active in the WHT for an average of 16 months (range = 5 to 37) completed questionnaires about their dietary habits (a 21-item instrument that measures five dimensions of low-fat dietary habits) and food intake (a food frequency questionnaire). Women who participated in the intervention program maintained most of the low-fat dietary habits adopted during the study: mean total fat intake increased from 37.8 g to 41.0 g and scales describing substitution of specially manufactured low-fat foods and modification of meats to be lower in fat increased only slightly (by 0.11 and 0.14, respectively, on a scale of 1 = always to 4 = never). Scales describing avoiding meat and avoiding fats as a flavoring increased by 0.23 and 0.22, respectively, which suggests some recidivism. Women in the control group lowered their dietary fat intake from 65.0 to 57.5 g, but all differences in fat intake and fat-related dietary habits scales between women in the control and intervention groups remained highly statistically significant. In multiple regression models, all five low-fat dietary habits scales were independently associated with percentage of energy from fat, but the strongest association was for avoiding fats as flavorings. These results suggest that substitutions of specially manufactured low-fat foods are easily adopted and maintained dietary changes, but that maintenance of new habits related to avoiding fats as flavorings and avoiding meat will require long-term reinforcement strategies.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Underutilization of breast-conserving surgery and radiation therapy among women with stage I or II breast cancer.

OBJECTIVE: To identify time trends and factors associated with breast-conserving surgery (BCS) and delivery of postoperative radiation therapy among women with stage I or II breast cancer. DESIGN: Survey. SETTING: Population-based cancer registry in the Seattle-Puget Sound (Wash) region. PARTICIPANTS: The study included 8095 women diagnosed with stage I or II breast cancer (American Joint Committee on Cancer staging criteria) from 1983 through 1989. MAIN OUTCOME MEASURES: Breast-conserving surgery with or without radiation therapy vs mastectomy, and, among women with BCS, a comparison of radiation therapy vs no therapy. RESULTS: In 1985 when results from a US randomized clinical trial of BCS were published, the frequency of BCS peaked (46.3% of stage I; 30.1% of stage II) followed by a return to levels before 1985 for women with stage II breast cancer and a more moderate decline for stage I breast cancer. The likelihood of BCS decreased with increasing age (P less than .001), with stage II disease, and with residence outside the region's major urban center, and it increased with education (P less than .001) or median income (P less than .001) by census tract. The proportion of women who received radiation therapy after BCS decreased with age (P less than .001), was lower for women with stage II than stage I disease, and was lowest in counties without radiation therapy facilities. CONCLUSIONS: Despite scientific evidence of the equivalent efficacy of BCS with radiation therapy and mastectomy, BCS is not performed on the majority of women with stage I or II breast cancer as recommended by the National Institutes of Health, and factors are associated with its use that differ from selection criteria outlined by the National Institutes of Health.

Aged↗
PubMed1991

Degradation of erythrocyte glycophorin results in increased membrane bound hemoglobin.

Degradation of glycophorin by trypsin in intact red cells results in an increase in hemoglobin bound to the membrane. Incubation of resealed ghosts made from these cells demonstrated that the hemoglobin was bound to the intracellular membrane surface. We found that treatment of hemoglobin with KCNO inhibited the ability of hemoglobin to bind to the membrane. Addition of KCNO to intact cells followed by trypsin treatment abolished the additional membrane-bound hemoglobin, indicating that the bound hemoglobin resulted from increased Band 3 binding. Treatment of intact cells with neuraminidase also resulted in increased membrane-bound Hb, which correlated with the amount of sialic acid released. Scatchard analysis revealed that enzyme treatment increased the affinity of hemoglobin for the high affinity Band 3 binding site, while KCNO treatment abolished this binding. Taken together, these studies demonstrate that extracellular proteolytic degradation of glycophorin by proteases similar to those released by cells of the reticuloendothelial system results in an increased ability of hemoglobin to bind to Band 3.

Binding Sites↗
PubMed1991

Differences in the hypoxic contraction of small isolated pulmonary arteries of cat and rabbit.

In small (less than 300 microns diameter) pulmonary arterial (PA) rings isolated from the cat, hypoxia induced a transient contraction (250 +/- 120 mg, n = 7), whereas in rings of rabbit PA of the same size, hypoxia had no significant effect (n = 19). Precontraction by 40 mmol KCl.1(-1), noradrenaline (NA) 10(-6) mol.1(-1), or histamine (His 10(-5) mol.1(-1)) did not modify this difference between the two species and did not potentiate the hypoxic contraction of small rings of the cat PA. Large rabbit pulmonary arterial segments (300-2000 microns) exhibited no response to hypoxia before precontraction (n = 15). In the presence of procaine (2%) rabbit PA rings (n = 6, small) exhibited no hypoxic contraction. These results in vitro reflect previous in vivo observations.

Animals↗
PubMed1991

Pharmacology of saccadic eye movements in man. 2. Effects of the alpha 2-adrenoceptor ligands idazoxan and clonidine.

The effects of alpha 2-adrenoceptor agonists and antagonists on saccadic eye movements were studied in normal volunteers using the agonist clonidine and the antagonist idazoxan. Changes in blood pressure, heart rate, and several psychological self-ratings were also recorded. Clonidine produced marked slowing of peak saccade velocity, acceleration and deceleration, with deceleration affected more than acceleration, but had no effect on saccade error or latency measurements. In contrast, most saccade parameters were not altered by idazoxan, although fatigue effects were eliminated. Blood pressure, heart rate, and self ratings of alertness were increased by idazoxan and reduced by clonidine, with opposite effects noted on sedation self-ratings. There were no correlations between the clonidine-induced changes in saccade parameters and changes in self-ratings. Although the slowing of some saccade parameters by clonidine may imply that alpha 2-adrenoceptors are involved in control of saccades, it may also be due to sedation. Although alpha 2-adrenoceptor antagonists may abolish fatigue effects, they cannot increase them over baseline values.

Adrenergic alpha-Antagonists↗
PubMed1991

Imipramine in the treatment of depressed Alzheimer's patients: impact on cognition.

A double-blind study evaluated the impact of imipramine on cognitive function in 61 patients with Alzheimer's disease. Twenty-eight patients had coexistent depression and dementia; 33 had dementia only. All were randomly assigned to an 8-week trial of imipramine or placebo. For both depressed and nondepressed subjects, the effect of imipramine on cognition was minimal. A subtle decrement in general cognitive function was evident in those treated with imipramine, as compared with those treated with placebo. No effects were observed on memory. Clinicians are advised that very low doses of imipramine (25 mg/daily) may be tolerated in depressed Alzheimer patients, but that cognitive changes do occur in some patients and should be carefully monitored.

Aged↗