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Biomedical subjects

E White

Publications and source records attributed to E White.

At least 235 records · Page 13Linked to original sources

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↗

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Diaspirin crosslinked hemoglobin (DCLHb), a hemoglobin based oxygen carrying solution prepared from outdated human blood, is subjected to a heat treatment step to inactivate viruses in our manufacturing process.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↗

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↗

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↗

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↗

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↗

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↗

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↗

Increased frequency of the null allele at the complement C4b locus in autism.

Associations between C4 deficiency and autoimmune disorders have been found over the past several years. Since autism has several autoimmune features, the frequencies of null (no protein produced) alleles at the C4A and C4B loci were studied in 19 subjects with autism and their family members. The autistic subjects and their mothers had significantly increased phenotypic frequencies of the C4B null allele (58% in both the autistic subjects and mothers, compared with 27% in control subjects). The siblings of the autistic subjects also had an increased frequency of the C4B null allele, but this increase was not significant. The fathers had normal frequencies of this null allele. All family members had normal frequencies of the C4A null allele, all normal C4A and C4B alleles and all BF and C2 alleles.

Alleles↗

Action potential duration and the inotropic response to reduced extracellular potassium in guinea-pig ventricular myocytes.

The mechanism of the inotropic effect of a reduction of extracellular potassium from 5.4 to 2.7 mM was investigated in myocytes isolated from guinea-pig ventricle. Action potentials were recorded using intracellular microelectrodes and cell shortening was measured by analysis of a video image. Changes in cytosolic calcium transients were estimated from calcium-activated currents under voltage-clamp conditions. The aim was to determine whether the prolongation of action potential duration which was observed to occur in low potassium might contribute to the increased shortening and increase in calcium-activated current under these conditions. Using a voltage-clamp waveform to mimic the waveform of the action potential, it was found that reduction of potassium caused a marked increase in cell shortening and of calcium-activated current in the absence of prolongation of the 'action potential' waveform. No change in inward calcium current was detected when extracellular potassium was reduced. The sensitivity to strophanthidin appeared to be increased under these conditions. We conclude that prolongation of the action potential is not a major factor contributing to the increased cell shortening and to the increased cytosolic calcium transient when extracellular potassium is reduced.

Action Potentials↗

Stretch-induced increase of resting intracellular calcium concentration in single guinea-pig ventricular myocytes.

Single guinea-pig ventricular myocytes were loaded with the fluorescent Ca2+ indicator Indo-1 AM and stretched by carbon fibres. Stretching increased resting tension. Sarcomere lengths were increased by 2-18%. It was observed that a stretch increased resting [Ca2+]i in seven out of eight cells. The change in [Ca2+]i increased with the size of the stretch and returned to pre-stretch levels on return to resting cell length. These observations suggest a means by which changes in resting muscle length can modify the contractile state of cardiac muscle.

Animals↗

Adenovirus E1B 19-kilodalton protein overcomes the cytotoxicity of E1A proteins.

Infection with adenovirus mutants carrying either point mutations or deletions in the coding region for the 19-kDa E1B gene product (19K protein) causes degradation of host cell and viral DNAs (deg phenotype) and enhanced cytopathic effect (cyt phenotype). Therefore, one function of the E1B 19K protein is to protect nuclear DNA integrity and preserve cytoplasmic architecture during productive adenovirus infection. When placed in the background of a virus incapable of expressing a functional E1A gene product, however, E1B 19K gene mutations do not result in the appearance of the cyt and deg phenotypes. This demonstrated that expression of the E1A proteins was responsible for inducing the appearance of the cyt and deg phenotypes. By constructing a panel of viruses possessing E1A mutations spanning each of the three E1A conserved regions in conjunction with E1B 19K gene mutations, we mapped the induction of the cyt and deg phenotypes to the amino-terminal region of E1A. Viruses that fail to express conserved region 3 (amino acids 140 to 185) and/or 2, (amino acids 121 to 185) or nonconserved sequences between conserved regions 2 and 1 of E1A (amino acids 86 to 120) were still capable of inducing cyt and deg. This indicated that activities associated with these regions, such as transactivation and binding to the product of the retinoblastoma susceptibility gene, were dispensable for induction of E1A-dependent cytotoxic effects. In contrast, deletion of sequences in the amino terminus of E1A (amino acids 22 to 107) resulted in extragenic suppression of the cyt and deg phenotypes. Therefore, a function affected by deletion of amino acids 22 to 86 of E1A is responsible for exerting cytotoxic effects in virally infected cells. Furthermore, transient high-level expression of the E1A region using a cytomegalovirus promoter plasmid expression vector was sufficient to induce the cyt and deg phenotypes, demonstrating that E1A expression alone is sufficient to exert these cytotoxic effects and that other viral gene products are not involved. Finally, placing E1A expression under the control of a strong promoter did not alter the requirement for E1B in the transformation of primary cells. One possibility is that the E1B 19K protein is required to overcome the cytotoxic effects of E1A protein expression and thereby enable primary cells to become transformed.

Adenoviridae Infections↗

Determination of serum uric acid by isotope dilution mass spectrometry as a new candidate definitive method.

A new isotope dilution mass spectrometric method for uric acid is described. A known weight of [1,3-15N2]uric acid is added to a known weight of serum, and the mixture is allowed to equillibrate. The serum is put through an anion-exchange resin, and the isolated uric acid is converted to the tetrakis-(tert-butyldlmethylsilyl) derivative of uric acid. For measurement, the derivative is injected into a gas chromatograph interfaced with a low-resolution, magnetic sector mass spectrometer. Isotope ratio measurements are made from the abundances of the [M - tert-butyl]+ ions at m/z 567 and 569. Bias is investigated by measuring the uric acid level in the same samples under different chromatographic conditions and with different ionization techniques. If these confirmatory measurements agree with the principal measurements, we have strong evidence for the absence of measurement bias. Uric acid was determined in three lyophilized human serum pools by this method. For Standard Reference Material (SRM) 909, four sets of six samples each were prepared. For Candidate SRM 909a, which consisted of two pools, each with a different level of uric acid, six sets of two samples of each level were prepared. The coefficient of variation for a single measurement ranged from 0.34% to 0.42%, while the relative standard error of the mean ranged from 0.08% to 0.14%. The results from the confirmatory measurements demonstrated that there was no significant bias in the measurements. The combination of high precision and absence of significant bias in the results qualifies this method as a candidate definitive method as defined by the National Committee for Clinical Laboratory Standards.

Humans↗

Evaluation of the increase in breast cancer incidence in relation to mammography use.

The breast cancer incidence rate (i.e., the detected number of new cases per 100,000 women) increased by 31% in western Washington State between the time periods 1974-1978 and 1986-1987. If this increase is largely due to earlier detection of cases through mammography, it is encouraging; otherwise (if it cannot be attributed to mammography alone), investigation of other factors may be needed. The observed increase, based on 18,559 documented breast cancer cases from the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) registry, was compared with the predicted increase based on mammography utilization by year from a survey of 1,212 women in western Washington and on data from published studies regarding the impact of mammography on the detection rate for new breast cancer cases. Among women aged 45-64, all of the increase was associated with local stage disease and with tumors detected at a smaller size. Further, the 15% observed increase in incidence in this age group was less than the 20% increase predicted due to the utilization of mammography. However, the observed increase was approximately twice the predicted increase for women aged 65-74 (observed 57%, predicted 26%) and for women aged 25-44 (observed 29%, predicted 12%). Thus, all of the increase in detected breast cancer among 45-64 year old women appears to be explained by the increased use of mammography, while among older women and younger women there may be other contributing factors. The limitations and implications of this analysis are discussed.

Adult↗

Melanoma risk by age and socio-economic status.

To explore the relationship between melanoma incidence, socio-economic status (SES), and site of occurrence, 1,804 cases of melanoma in Washington State from 1974-85 were analyzed by mean income of census tract of residence. (Census tracts are geographic divisions of state counties for which demographic information is provided by state agencies.) For males aged 30-69, as expected, the risk increased with income. Unexpectedly, at age 70 and over the trend was reversed (the heterogeneity of the age relationship was unlikely to be due to chance). In the older men, the increase with low income was found in the cases reported as Hutchinson's melanotic freckle and those which were not, being statistically significant in the latter. These findings suggest a role for long-continued sun exposure in the etiology of malignant melanoma.

Age Factors↗

A case-control study of Alzheimer's disease.

A case-control study of Alzheimer's disease (AD) was conducted to evaluate the roles of family history of dementing disease and AD, and medical conditions, particularly those related to the viral and immune hypotheses in AD. One hundred and eighty-three clinically diagnosed patients were identified between 1980 and 1985 through the Geriatric and Family Services clinic at the University of Washington hospital, and 18 patients were identified during the same time period through the Veteran's Administration Medical Center in Seattle, Washington. Telephone interviews were conducted with spouses (87.7%) and children (12.3%) of the patients. Each patient was matched to a friend or nonblood relative of the patient by age, sex, and the relationship between the patient and his or her respondent, for a total of 130 matched pairs. The odds ratio for AD was elevated if a first-degree relative was reported to have a history of dementia (odds ratio, 2.21; 95% confidence interval, 1.17 to 4.18). This risk was especially elevated if a sibling was affected (odds ratio, 4.04; 95% confidence interval, 1.37 to 11.90); the highest risk to the proband was observed if a sibling had presumed AD (odds ratio, 5.92; 95% confidence interval, 1.59 to 21.96). The risk increased with increasing numbers of first-degree family members affected for both a history of dementia and presumed AD. We found little difference between patients and control subjects with respect to the age of the mother or father at the time of the subject's birth. No statistically significant differences were observed between the two groups with regard to conditions that might support the immune and viral hypothesis in AD, smoking, or alcohol problems.

Adult↗