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Biomedical subjects

D Baker

Publications and source records attributed to D Baker.

391 records · Page 22Linked to original sources

Multiple actions of synthetic 'progestins' on the growth of ZR-75-1 human breast cancer cells: an in vitro model for the simultaneous assay of androgen, progestin, estrogen, and glucocorticoid agonistic and antagonistic activities of steroids.

This study was designed to assess the multiple steroid receptor mediated activities of a series of synthetic 'progestins' on breast cancer cell growth, using the human ZR-75-1 cell line which possesses functional estrogen (ER), androgen (AR), and glucocorticoid (GR) receptors as well as progesterone (PgR) receptors. Four 17-hydroxyprogesterone derivatives (chlormadinone acetate, CMA; cyproterone acetate, CPA; medroxyprogesterone acetate, MPA; and megestrol acetate, MGA) and two 19-nortestosterone derivatives (norethindrone, NRE, and norgestrel, NRG) were thus investigated. Based on the requirement of estrogens for PgR-mediated antiproliferative effects and the reversal of PgR-mediated action by insulin, it was found that although all 'progestins' could inhibit ZR-75-1 cell growth through the PgR at low concentrations, the relative contribution of this receptor in cell growth control is highly variable between compounds. The quantitative importance of PgR-mediated inhibition of cell proliferation was inversely related to the amplitude of the androgenic effects induced by the compounds, the AR-mediated effects increasing in the order CPA less than MGA less than CMA less than NRE less than NRG less than MPA. The specificity of these androgenic effects is further supported by their reversal upon addition of the antiandrogen hydroxyflutamide. In addition, the 17-hydroxyprogesterone derivatives, but not the 19-nortestosterone derivatives, had glucocorticoid activities at high (micromolar) concentrations, as shown by reversal of growth inhibition by the antagonist RU486 in the presence of saturating concentrations of 5 alpha-dihydro-testosterone. All 'progestins' tested, except MPA and NRE, also had some antiglucocorticoid activity, NRG being the most potent in this respect. Finally, NRE and NRG exerted a marked mitogenic effect in estrogen-free medium which was clearly mediated through the ER as shown by the competitive reversal of their action by the steroidal antiestrogen EM-139. The present results show that growth measurements of the human breast cancer cells ZR-75-1 permit, with the appropriate steroid additions, the assay of progestin, androgen, estrogen, and glucocorticoid agonistic as well as antagonistic activities of test compounds. The present study shows, somewhat surprisingly, that while the AR is almost completely responsible for the action of MPA at low concentrations, the majority of the action of NRE, NRG, and MGA is also exerted through AR, while the androgenic action of CPA plays a lower role in the growth inhibition induced by this compound.(ABSTRACT TRUNCATED AT 400 WORDS)

Binding, Competitive↗

The effectiveness of a group discrete trial instructional approach for preschoolers with developmental disabilities.

Group behavioral classroom instruction for children with developmental disabilities has been shown to allow for increased efficiency, approximation to naturalistic arrangements, and enhanced opportunity for interaction, social teaching and observational learning. This study examines the effectiveness of a group instructional extension of one to one discrete trial teaching, which involves the overlapping of trials between students along with the use of sequential and choral group teaching. A multiple baseline design across tasks was employed to examine the effectiveness of the group instructional approach in promoting acquisition of educational skills among preschoolers with autism and other developmental disabilities. A time sample interval assessment of components of the group instruction was also conducted. The approach was demonstrated to consistently increase correct responding across the task areas. Results are discussed in terms of the advantages of the group instructional approach as an adjunct to one to one discrete trial instruction.

Child, Preschool↗

Validity of testing alanine aminotransferase in refrigerated whole blood.

Alanine aminotransferase (ALT) was tested in the sera and plasma of in-line segments as well as the main bags of whole blood units collected from blood donors. The purpose of this study was to evaluate the stability of enzyme activity during blood storage when the analysis of ALT is postponed over weekends or holidays. In addition, when validation of a particular result is requested, an in-line segment may be convenient for confirmatory testing. While a dilutional effect was found, the anticoagulant in the main collection bag was not shown to have affected enzyme activity. During storage the mean enzyme concentration decreased. Appropriate plasma ALT cutoffs for respective time periods during storage were calculated to compensate for downward drift. This correction prevented the use of the blood units (40% of total) that would erroneously have appeared transfusable if the serum cutoff had been used. If the Day 0 plasma cutoff was used throughout the total storage time period, 14 percent of the blood would erroneously have appeared transfusable.

Aspartate Aminotransferases↗

Intimate partner abuse among women diagnosed with depression.

Domestic violence is a pervasive problem for women, and depression is the most prevalent negative mental health consequence of domestic violence. This study investigates the extent to which domestic violence is part of the history of women diagnosed with depression. Eighty two women with a diagnosis of depression were surveyed. A 61.0% lifetime prevalence of domestic violence was found. Lifetime prevalence for forced sex was 29.3%. Demographics of abused and nonabused women were not significantly different. Abused women were found to be less healthy. Prevalence of headaches, chronic pain, rape or marital rape, and sleep problems or nightmares were significantly higher. Severity of abuse was significantly correlated (p < .01) to severity of depression. Implications for mental health practice and training of peer support group leaders for women with depression are described, as well as directions for future research.

Adult↗

Detection of protein coding sequences using a mixture model for local protein amino acid sequence.

Locating protein coding regions in genomic DNA is a critical step in accessing the information generated by large scale sequencing projects. Current methods for gene detection depend on statistical measures of content differences between coding and noncoding DNA in addition to the recognition of promoters, splice sites, and other regulatory sites. Here we explore the potential value of recurrent amino acid sequence patterns 3-19 amino acids in length as a content statistic for use in gene finding approaches. A finite mixture model incorporating these patterns can partially discriminate protein sequences which have no (detectable) known homologs from randomized versions of these sequences, and from short (< or = 50 amino acids) non-coding segments extracted from the S. cerevisiea genome. The mixture model derived scores for a collection of human exons were not correlated with the GENSCAN scores, suggesting that the addition of our protein pattern recognition module to current gene recognition programs may improve their performance.

Algorithms↗

Rate of pull-out strength gain of dual-etched titanium implants: a comparative study in rabbits.

The purpose of this study was to investigate the rate of pull-out strength gain of an etched titanium implant surface. Rabbit tibiae were used to compare machined titanium and proprietary dual-etched titanium implants. Two custom cylindric implants (3 mm in diameter and 4 mm in length) were placed in each right anteromedial tibia in 31 rabbits. At weeks 1, 2, 3, 4, 5, and 8, the implants in 5 rabbits were subjected to failure shear loading in a pull-out test. For shear failure testing, each tibial segment was mounted in a precision alignment jig, and an Instron pull-out test was performed on each implant. Beginning at week 3, there was a statistically significant difference (P < .01) between the dual-etched and the machined implants. There was a significant increase in strength for dual-etched implants between week 5 and week 8, while the machined implants did not show an increase during this time interval. The etched implants maintained a significantly greater pull-out strength for the remainder of the study, with a 3.2-fold greater mean strength at 8 weeks, equivalent to 6 months in humans. At 3 weeks, the etched implant's strength exceeded the strength that the machined implant had achieved at 8 weeks. In short-term healing in the rabbit tibia, the dual-etched surface demonstrated a more rapid rate of pull-out strength gain than the machined surface and remained significantly stronger throughout the 8 weeks of the study.

Acid Etching, Dental↗

Why the workplace and cardiovascular disease?

Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in the industrialized world. Current approaches to managing the CVD epidemic are based on powerful engineering models and advanced medical techniques. Innovative research has identified a number of risk factors for hypertension and CVD. However, our understanding of these disorders and our ability to manage the epidemic remain limited. A social epidemiologic paradigm suggests that essential hypertension and CVD are diseases of industrialized society of rather recent historical origins. To better understand and manage the CVD epidemic, current models need to incorporate a heretofore relatively neglected realm of social life in the workplace.

Cardiovascular Diseases↗

The workplace and cardiovascular health: conclusions and thoughts for a future agenda.

The evidence in this book provides convergent validation of a causal relationship between workplace stressors and CVD. Here, the editors explore new strategies for enhanced prevention and clinical management, work place interventions, and social policy to reduce the impact of CVD. These strategies acquire an urgent public health dimension, given the magnitude of the CVD epidemic and the current deterioration in conditions of working life.

Burnout, Professional↗