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Biomedical subjects

E White

Publications and source records attributed to E White.

At least 73 records · Page 4Linked to original sources
PubMed2000

Evaluation of the PuriLens contact lens care system: an automatic care system incorporating UV disinfection and hydrodynamic shear cleaning.

PURPOSE: This study evaluates lens care using the PuriLens System, an advanced way to clean and disinfect soft hydrophilic lenses using subsonic agitation and UV radiation, respectively. METHODS: A two-period crossover lens cleaning and safety investigation was conducted using 80 patients. Disinfecting efficacy was tested in accordance with standard FDA protocols. Lens compatibility was studied with Group I and Group IV lenses during the equivalent of a 6-month care regimen by measuring: lens power, base curve, wet diameter, refractive index, clarity, and tint. Safety was evaluated through slit-lamp findings, wearing time, comfort, and visual acuity. RESULTS: The mean wearing time of patients in the study was 13.79 hours. No slit lamp findings greater than grade 2 were noted. Visual acuity was 20/25 or better in 92.5% of examinations. None of the patients lost more than two lines of acuity. Lens surface evaluation showed no deposits (grade 0) to very slight deposits (grade 1) in 94.4% of examinations. Lenses cleaned with the PuriLens System were cleaner by a statistically significant margin (P=0.02) compared to lenses digitally cleaned with a leading multi-purpose solution (ReNu, Bausch & Lomb). Overall, neither the Group I nor Group IV lenses were affected after 180 cleaning cycles. CONCLUSIONS: The PuriLens System provides automatic lens care compliance, superior antimicrobial efficacy, and eliminates the need for daily digital cleaning.

Adolescent↗
PubMed2000

TNF-alpha signals apoptosis through a bid-dependent conformational change in Bax that is inhibited by E1B 19K.

The adenovirus E1B 19K gene product is an inhibitor of apoptosis induced by tumor necrosis factor-alpha (TNF-alpha) during viral infection. We report that E1B 19K inhibited neither caspase-8 activation nor caspase-8-dependent Bid cleavage by TNF-alpha. Rather, TNF-alpha induced a tBid-dependent conformational change in Bax that allowed an interaction between E1B 19K and conformationally altered Bax, which caused inhibition of cytochrome c release and caspase-9 activation. E1B 19K expression interrupted caspase-3 processing, permitting cleavage to remove the p12 subunit but not the prodomain consistent with caspase-8 and not caspase-9 enzymatic activity. Thus, E1B 19K blocks TNF-alpha-mediated death signaling by inhibiting a specific form of Bax that interrupts caspase activation downstream of caspase-8 and upstream of caspase-9.

Adenovirus E1B Proteins↗
PubMed1999

Breast tumor characteristics as predictors of mammographic detection: comparison of interval- and screen-detected cancers.

BACKGROUND: Although mammographic screening is useful for detecting early breast cancer, some tumors are detected in the interval between screening examinations. This study attempted to characterize fully the tumors detected in the two different manners. METHODS: Our study utilized a case-control design and involved a cohort of women undergoing mammographic screening within the defined population of a health maintenance organization (the Group Health Cooperative of Puget Sound). Women were classified as having "interval" or "interval-detected" cancers (n = 150) if their diagnosis was made within 24 months after a negative-screening mammogram or one that indicated a benign condition. Cancers were classified as "screen detected" (n = 279) if the diagnosis occurred after a positive assessment by screening mammography. Tumors from women in each group were evaluated for clinical presentation, histology, proliferative characteristics, and expression of hormone receptors, p53 tumor suppressor protein, and c-erbB-2 protein. RESULTS: Interval-detected cancers occurred more in younger women and were of larger tumor size than screen-detected cancers. In unconditional logistic regression models adjusted for age and tumor size, tumors with lobular (odds ratio [OR] = 1.9; 95% confidence interval [CI] = 0.9-4.2) or mucinous (OR = 5.5; 95% CI = 1.5-19.4) histology, high proliferation (by either mitotic count [OR = 2.9; 95% CI = 1.5-5.7] or Ki-67 antigen expression [OR = 2.3; 95% CI = 1.3-4.1]), high histologic grade (OR = 2.1; 95% CI = 1.2-4.0), high nuclear grade (OR = 2.0; 95% CI = 1.0-3.7), or negative estrogen receptor status (OR = 1.8; 95% CI = 1.0-3.1) were more likely to surface in the interval between screening examinations. Tumors with tubular histology (OR = 0.2; 95% CI = 0.0-0.8) or with a high percentage of in situ components (50%) (OR = 0.5; 95% CI = 0.2-1.2) were associated with an increased likelihood of screen detection. CONCLUSIONS: Our data from a large group of women in a defined population indicate that screening mammography may miss tumors of lobular or mucinous histology and some rapidly proliferating, high-grade tumors.

Adult↗
PubMed1999

Adenovirus-mediated cytotoxicity of chronic lymphocytic leukemia cells.

We have studied adenovirus-mediated cytotoxicity after infection of malignant cells obtained from patients with chronic lymphocytic leukemia (CLL). Our studies indicate that adenoviruses can infect primary CLL cells and that infection of CLL cells with a replication-competent strain of human adenovirus 5 (Ad5dl309) results in cytotoxicity. Adenovirus-mediated cytotoxicity was also seen after infection of CLL cells with a variety of viruses attenuated by mutations in the adenovirus early region 1 (E1) or early region 2 (E2). Even viruses attenuated by deletion of the entire E1 region resulted in cytotoxicity after infection of the CLL cells obtained from some patients. Although there was variability in the degree of cytotoxicity induced by different viruses in different patients cells, a virus with a mutation in the E1B 19K gene resulted in the greatest degree of cytotoxicity in most of the CLL samples tested. These studies demonstrate that infection of CLL cells by attenuated adenoviruses with specific mutations in the E1 or E2 region results in cell death. Attenuated adenoviruses should be developed further as therapeutic agents for patients with CLL.

Adenoviridae↗
PubMed1999

Breast conservation therapy in the United States following the 1990 National Institutes of Health Consensus Development Conference on the treatment of patients with early stage invasive breast carcinoma.

BACKGROUND: A National Institutes of Health (NIH) Consensus Development Conference on the treatment of patients with early stage invasive breast carcinoma, held in June 1990, recommended breast conservation therapy for the majority of women with Stage I or II breast carcinoma. The authors evaluated the national use of breast conservation therapy before and after the conference to determine whether the conference had had an impact on utilization. METHODS: Women with Stage I or II breast carcinoma (n = 109,880), diagnosed during the years 1983-1995, were identified via 9 population-based cancer registries of the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute. The likelihood of breast conservation surgery versus mastectomy and, among women who underwent breast conservation surgery, the likelihood of postoperative radiation therapy versus none, were assessed for 3 time periods (January 1983 to April 1985, May 1985 to June 1990, and July 1990 to December 1995). Associations between the use of breast conservation surgery or postoperative radiotherapy according to patient stage, age, race, and region were compared among women diagnosed before and after the NIH Consensus Development Conference. RESULTS: From 1985 (the year that the U.S. randomized controlled trial demonstrating equivalent efficacy between breast conservation therapy and mastectomy was published) through 1989, approximately 35% of women with Stage I and 19% of women with Stage II breast carcinoma underwent breast conservation surgery; these percentages remained constant throughout this period. Beginning in 1990, the year of the NIH Consensus Development Conference, the use of breast conservation surgery increased in each subsequent year; by 1995, 60% of women with Stage I and 39% of women with Stage II breast carcinoma received such treatment. However, regional variation in use was observed (Stage I, range 41.4-71.4% for 1995) and no registry reported breast conservation therapy for the majority of women with Stage II disease (range, 23.8-48.0%). The use of postoperative radiotherapy for women who underwent breast conservation surgery was similar in the periods before and after the conference. CONCLUSIONS: Although breast conservation therapy was performed more frequently following the NIH Consensus Development Conference, variation in use by region of the U.S. suggests the continued presence of barriers to widespread adoption of the recommendations formulated at the conference.

Adult↗
PubMed1999

Home collection versus publicly funded HIV testing in San Francisco: who tests where?

We examined records of all HIV antibody tests performed at anonymous publicly funded (PF) sites and by home collection (HC) testing for residents of San Francisco from August 1996 to December 1997. Although far fewer tests were performed by HC testing than at PF sites (715 versus 8712, respectively), a higher proportion of HC testers reported no prior history of HIV testing (33.1% versus 17.9%). HIV seroprevalence was higher among PF tests (1.8%) than among HC tests (0.9%). Compared with PF testers, HC testers were less likely to be gay men, lesbian or bisexual women, heterosexual women, African American, or Latino. HC testers were more likely to report sex with a known HIV-positive partner. HC testers were also more likely to reside in affluent neighborhoods. HC testing reaches some high-risk persons who may not otherwise seek PF testing, although, overall, the risk profile of HC testers appeared lower than that of PF testers. HC testing reaches some individuals who can financially afford HC testing, thus saving public prevention resources for hard-to-reach, high-risk populations.

AIDS Serodiagnosis↗
PubMed1999

DNA damage increases sensitivity to vinca alkaloids and decreases sensitivity to taxanes through p53-dependent repression of microtubule-associated protein 4.

Taxanes and Vinca alkaloids are among the most active classes of drugs in the treatment of cancer. Yet, fewer than 50% of previously untreated patients respond, and clinicians have few ways of predicting who will benefit from treatment and who will not. Mutations in p53 occur in more than half of human malignancies and may alter the sensitivity to a variety of anticancer therapies. We have shown that the transcriptional status of p53 determines the sensitivity to antimicrotubule drugs and that this is mediated through the regulation of microtubule-associated protein 4 (MAP4). Expression of MAP4 is transcriptionally repressed by wild-type p53. Increased expression of MAP4, which occurs when p53 is transcriptionally inactive, increases microtubule polymerization, paclitaxel binding, and sensitivity to paclitaxel, a drug that stabilizes polymerized microtubules. In contrast, overexpression of MAP4 decreases microtubule binding and sensitivity to Vinca alkaloids, which promotes microtubule depolymerization. To determine whether induction of endogenous wild-type p53 by DNA-damaging agents alters the expression of MAP4 and changes the sensitivity to antimicrotubule drugs, we assayed cell lines with wild-type or mutant p53 for the expression of MAP4 and drug sensitivity before and after DNA damage. UV irradiation, bleomycin, and doxorubicin increased wild-type p53 expression and decreased MAP4 expression. These changes were associated with decreased sensitivity to paclitaxel and increased sensitivity to vinblastine. These changes in drug sensitivity were no longer observed when p53 and MAP4 returned to baseline levels. Changes in drug sensitivity following DNA-damaging agents were associated with decreased binding of paclitaxel and increased binding of Vinca alkaloids. In contrast, DNA damage did not alter the sensitivity to non-microtubule-active drugs, such as 1-beta-D-arabinofuranosylcytosine and doxorubicin. Changes in drug sensitivity following DNA-damaging drugs were not observed in cells with mutant p53. These studies demonstrate that induction of wild-type p53 by DNA-damaging agents can affect the sensitivity to antimicrotubule drugs through the regulation of MAP4 expression and may have implications for the design of clinical anticancer therapies.

Animals↗
PubMed1999

Effect of the microtubule polymerizing agent taxol on contraction, Ca2+ transient and L-type Ca2+ current in rat ventricular myocytes.

1. Microtubules form part of the cytoskeleton. Their role in adult ventricular myocytes is not well understood although microtubule proliferation has previously been linked with reduced contractile function. 2. We investigated the effect of the anti-tumour drug taxol, a known microtubule polymerizing agent, on Ca2+ handling in adult rat ventricular myocytes. 3. Treatment of cells with taxol caused proliferation of microtubules. 4. In taxol-treated cells there was a reduction in the amplitude of contraction, no significant effect on the amplitude of L-type Ca2+ current, but a significant reduction in the amplitude of the Ca2+ transient. 5. Caffeine was used to release Ca2+ from the sarcoplasmic reticulum (SR). There was a significant reduction in the ratio of electrically stimulated : caffeine-induced Ca2+ transients in taxol-treated cells. This observation is consistent with the hypothesis that taxol reduces fractional SR Ca2+ release. 6. We suggest that the negative inotropic effect of taxol may, at least in part, be the result of reduced release of Ca2+ from the SR. Microtubules may be important regulators of Ca2+ handling in the heart.

Animals↗
PubMed1999

Emergence of vancomycin resistance in Staphylococcus aureus. Glycopeptide-Intermediate Staphylococcus aureus Working Group.

BACKGROUND: Since the emergence of methicillin-resistant Staphylococcus aureus, the glycopeptide vancomycin has been the only uniformly effective treatment for staphylococcal infections. In 1997, two infections due to S. aureus with reduced susceptibility to vancomycin were identified in the United States. METHODS: We investigated the two patients with infections due to S. aureus with intermediate resistance to glycopeptides, as defined by a minimal inhibitory concentration of vancomycin of 8 to 16 microg per milliliter. To assess the carriage and transmission of these strains of S. aureus, we cultured samples from the patients and their contacts and evaluated the isolates. RESULTS: The first patient was a 59-year-old man in Michigan with diabetes mellitus and chronic renal failure. Peritonitis due to S. aureus with intermediate resistance to glycopeptides developed after 18 weeks of vancomycin treatment for recurrent methicillin-resistant S. aureus peritonitis associated with dialysis. The removal of the peritoneal catheter plus treatment with rifampin and trimethoprim-sulfamethoxazole eradicated the infection. The second patient was a 66-year-old man with diabetes in New Jersey. A bloodstream infection due to S. aureus with intermediate resistance to glycopeptides developed after 18 weeks of vancomycin treatment for recurrent methicillin-resistant S. aureus bacteremia. This infection was eradicated with vancomycin, gentamicin, and rifampin. Both patients died. The glycopeptide-intermediate S. aureus isolates differed by two bands on pulsed-field gel electrophoresis. On electron microscopy, the isolates from the infected patients had thicker extracellular matrixes than control methicillin-resistant S. aureus isolates. No carriage was documented among 177 contacts of the two patients. CONCLUSIONS: The emergence of S. aureus with intermediate resistance to glycopeptides emphasizes the importance of the prudent use of antibiotics, the laboratory capacity to identify resistant strains, and the use of infection-control precautions to prevent transmission.

Aged↗
PubMed1999

Relation between obesity and breast cancer in young women.

This study was conducted to assess the relation between body size and risk of breast cancer among young women. A case-control study was conducted among women aged 21-45 years living in three counties in Washington State. Cases were women born after 1944 with invasive or in situ breast cancer that was diagnosed between January 1, 1983, and April 30, 1990. Controls were selected using random digit dialing and were frequency-matched to cases on the basis of age and county of residence. Interviews took place between 1986 and 1992. Body size was evaluated using indices from several different time periods. After adjustment for confounders, a decreased risk of breast cancer was found for women in the highest quintile of body mass index (weight (kg)/height (m)2) as compared with the lowest quintile (for maximum lifetime body mass index, odds ratio = 0.69, 95% confidence interval (CI) 0.51-0.94). Age modified the relation between body size and risk of breast cancer. The odds ratio for women in the highest quintile of maximum body mass index who were aged 21-35 years was 0.29 (95% CI 0.16-0.55), as compared with an odds ratio of 1.5 for women aged 36-45 years (95% CI 0.9-2.5) (p for interaction = 0.003). This study supports prior research showing a decreased risk of breast cancer associated with increased body size among premenopausal or young women. More detailed analysis in this study found a strong effect that was limited to the youngest age group (< or = 35 years).

Adult↗
PubMed1999

Cyclic AMP but not phosphorylation of phospholamban contributes to the slow inotropic response to stretch in ferret papillary muscle.

cAMP has been suggested to mediate the increased intracellular Ca2+ transient and contraction seen during the slow response to stretch in cardiac muscle. We measured cAMP in ferret papillary muscles stretched from 80-85% to 98% of their length at which maximum active tension is produced (Lmax) for 15 min. cAMP was significantly (P<0. 05) increased by 53% in muscles at the longer length which showed the slow response compared with controls. By contrast, in a population of muscles that were stretched but did not show the slow response, cAMP was not significantly different from that in muscles at the short length. Although cAMP can increase sarcoplasmic reticulum (SR) Ca2+ uptake by phosphorylation of phospholamban, we found no significant effect of stretch on phosphorylation of phospholamban at either Ser16 or Thr17. Further support for the hypothesis that cAMP is a mediator of the slow response was obtained by exposure of some muscles to the cell-permeable cAMP antagonist 8-bromo, adenosine 3',5'-cyclic monophosphorothioate, Rp isomer (Rp-8-Br-cAMPS, (2.5-10 microM). The slow response was reduced by 30% (P<0.05) in the presence of this antagonist. Our results not only provide evidence for the mediation of the slow response to stretch by cAMP, they also suggest that cAMP may rise in an intracellular compartment inaccessible to the SR.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

The role of calcium in the response of cardiac muscle to stretch.

This review focuses on the complex interactions between two major regulators of cardiac function; Ca2+ and stretch. Initial consideration is given to the effect of stretch on myocardial contractility and details the rapid and slow increases in contractility. These are shown to be related to two diverse changes in Ca2+ handling (enhanced myofilament Ca2+ sensitivity and increased intracellular Ca2+ transient, respectively). Interaction between stretch and Ca2+ is also demonstrated with respect to the rhythm of cardiac contraction. Stretch has been shown to alter action potential configuration, generate stretch-activated arrhythmias, and increase the rate of beating of the sino-atrial node. A variety of Ca(2+)-dependent mechanisms including attenuation of Ca2+ extrusion via Na+/Ca2+ exchange, Ca2+ entry through stretch-activated channels (SACs) and mobilisation of intracellular Ca2+ stores have been proposed to account for the effect of stretch on rhythm. Finally, the interaction between stretch and Ca2+ in the secretion of natriuretic peptides and onset of hypertrophy is discussed. Evidence is presented that Ca2+ (entering through L-type Ca2+ channels or SACs, or released from sarcoplasmic reticular stores) influences secretion of both atrial and B-type natriuretic peptide; there is data to support both positive and negative modulation by Ca2+. Ca2+ also appears to be important in the pathway that leads to expression of precursors of hypertrophic protein synthesis. In conclusion, two of the major regulators of cardiac muscle function, Ca2+ and stretch, interact to produce effects on the heart; in general these effects appear to be additive.

Action Potentials↗
PubMed1999

Tamoxifen and risk of large bowel cancer in women with breast cancer.

BACKGROUND: The increasingly consistent association between estrogen replacement therapy and colorectal cancer suggests that the anti-estrogen tamoxifen may also be associated with large bowel cancer incidence. METHODS: Women with new diagnoses of breast cancer were identified from the Surveillance Epidemiology and End Results (SEER) Program, a set of geographically defined, population based cancer registries representing approximately ten percent of the U.S. population. Of 85,411 women with local or regional breast cancer diagnosed from 1983-90, 14,984 women were reported to have received hormonal therapy and 70,427 were not known to have received hormonal therapy. Subsequent cancer diagnoses were identified in this cohort beginning 6 months after initial breast cancer diagnosis until death, or December 31, 1994. Multivariate Cox proportional hazards models were used to estimate the risk of developing colorectal cancer and other second cancers according to hormonal therapy use. RESULTS: Over the follow-up period 793 colorectal, 2,648 contralateral breast, 506 endometrial, 250 ovarian, 98 gastric, and 1,765 other cancers were identified in the study cohort. While overall there was no association between hormonal therapy use and colorectal cancer (relative risk (RR) 1.09, 95% confidence interval (CI) 0.88-1.35), in the period five or more years after diagnosis, risk was increased significantly by about 50% (95% CI 1.00-2.15). As expected, based upon clinical trials data, cancers of the contralateral breast were significantly decreased, and cancers of the uterine endometrium were significantly increased. No other meaningful associations were observed. When women were excluded for whom hormonal therapy might represent therapy other than tamoxifen (premenopausal women and those who received chemotherapy), this did not meaningfully alter these estimates. CONCLUSIONS: The results of this large population based cohort study suggest that tamoxifen therapy may modestly increase risk of large bowel cancer in women, but only after 5 years following initiation of breast cancer therapy.

Age Factors↗
PubMed1999

The 4th quinquennial national community mental health nursing census of England and Wales.

Since 1980, a survey of community mental health nursing has been conducted in the United Kingdom, at five-yearly intervals. These three data sets have been uniquely useful in plotting trends in Community Mental Health Nursing (CMHN) activity over time. Substantial administrative changes to the National Health Service have taken place in England and Wales since 1990, however, and these have impacted on the nature of mental health service provision. These changes have implications for all mental health service personnel and, in particular, the work of community mental health nurses. This article presents selected findings from the national census, conducted between 1996 and 1997. It sets these findings within the context of data derived from the three previous national studies in the series and within the contemporary national policy context and discusses the substantive implications which flow from the changes detected over time in the practice, organisation and management, and education of community mental health nurses in England and Wales.

Community Health Nursing↗
PubMed1999

Hormone replacement therapy and colon cancer among members of a health maintenance organization.

We investigated the association between hormone replacement therapy (HRT), primarily conjugated estrogens with or without medroxyprogesterone acetate, and colon cancer risk in a nested case-control study among women ages 55-79 years enrolled in Group Health Cooperative, a health maintenance organization in Washington state. Cases were diagnosed between 1984 and 1993. We selected controls randomly from enrollment files. HRT use was ascertained from a computerized database containing virtually all prescriptions dispensed since 1977. Among subjects with at least 5 years of pharmacy database information before reference date (1 year before diagnosis date), there were 341 cases of incident colon cancer and 1,679 controls. Estrogen use during the 5 years before reference date was not associated with risk of colon cancer [odds ratio (OR) = 0.85 and 95% confidence interval (CI) = 0.57-1.27 for 1-749 estrogen tablets; OR = 0.97 and 95% CI = 0.68-1.40 for > or =750 estrogen tablets]. An analysis including only women with at least 10 years of pharmacy database coverage found no association with use during the 10 years before reference date [OR = 1.07 (95% CI = 0.61-1.86) for 1-749 estrogen tablets; OR = 1.11 (95% CI = 0.69-1.80) for 750 or more estrogen tablets]. These results do not support the hypothesis that recent HRT use substantially reduces risk of colon cancer.

Adenocarcinoma↗
PubMed1999

Btf, a novel death-promoting transcriptional repressor that interacts with Bcl-2-related proteins.

The adenovirus E1B 19,000-molecular-weight (19K) protein is a potent inhibitor of apoptosis and cooperates with E1A to transform primary rodent cells. E1B 19K shows sequence and functional homology to the mammalian antiapoptotic gene product, Bcl-2. Like Bcl-2, the biochemical mechanism of E1B 19K function includes binding to and antagonization of cellular proapoptotic proteins such as Bax, Bak, and Nbk/Bik. In addition, there is evidence that E1B 19K can affect gene expression, but whether this contributes to its antiapoptotic function has not been determined. In an effort to further understand the functions of E1B 19K, we screened for 19K-associated proteins by the yeast two-hybrid system. A novel protein, Btf (Bcl-2-associated transcription factor), that interacts with E1B 19K as well as with the antiapoptotic family members Bcl-2 and Bcl-xL but not with the proapoptotic protein Bax was identified. btf is a widely expressed gene that encodes a protein with homology to the basic zipper (bZip) and Myb DNA binding domains. Btf binds DNA in vitro and represses transcription in reporter assays. E1B 19K, Bcl-2, and Bcl-xL sequester Btf in the cytoplasm and block its transcriptional repression activity. Expression of Btf also inhibited transformation by E1A with either E1B 19K or mutant p53, suggesting a role in either promotion of apoptosis or cell cycle arrest. Indeed, the sustained overexpression of Btf in HeLa cells induced apoptosis, which was inhibited by E1B 19K. Furthermore, the chromosomal localization of btf (6q22-23) maps to a region that is deleted in some cancers, consistent with a role for Btf in tumor suppression. Thus, btf may represent a novel tumor suppressor gene residing in a unique pathway by which the Bcl-2 family can regulate apoptosis.

Adenovirus E1A Proteins↗