Tufts University

About: Tufts University is a education organization based out in Medford, Massachusetts, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 32800 authors who have published 66881 publications receiving 3451152 citations. The organization is also known as: Tufts College & Universitatis Tuftensis.

The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants.

Abstract: Estrogens are defined by their ability to induce the proliferation of cells of the female genital tract. The wide chemical diversity of estrogenic compounds precludes an accurate prediction of estrogenic activity on the basis of chemical structure. Rodent bioassays are not suited for the large-scale screening of chemicals before their release into the environment because of their cost, complexity, and ethical concerns. The E-SCREEN assay was developed to assess the estrogenicity of environmental chemicals using the proliferative effect of estrogens on their target cells as an end point. This quantitative assay compares the cell number achieved by similar inocula of MCF-7 cells in the absence of estrogens (negative control) and in the presence of 17 beta-estradiol (positive control) and a range of concentrations of chemicals suspected to be estrogenic. Among the compounds tested, several "new" estrogens were found; alkylphenols, phthalates, some PCB congeners and hydroxylated PCBs, and the insecticides dieldrin, endosulfan, and toxaphene were estrogenic by the E-SCREEN assay. In addition, these compounds competed with estradiol for binding to the estrogen receptor and increased the levels of progesterone receptor and pS2 in MCF-7 cells, as expected from estrogen mimics. Recombinant human growth factors (bFGF, EGF, IGF-1) and insulin did not increase in cell yields. The aims of the work summarized in this paper were a) to validate the E-SCREEN assay; b) to screen a variety of chemicals present in the environment to identify those that may be causing reproductive effects in wildlife and humans; c) to assess whether environmental estrogens may act cumulatively; and finally d) to discuss the reliability of this and other assays to screen chemicals for their estrogenicity before they are released into the environment.

Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kappa B.

Abstract: NF-κB, which consists of two polypeptides, p50 (Mr 50K) and p65/RelA (Mr 65K), is thought to be a key regulator of genes involved in responses to infection, inflammation and stress1. Indeed, although developmentally normal, mice deficient in p50 display functional defects in immune responses2. Here we describe the generation of mice deficient in the RelA subunit of NF-κB. Disruption of the relA locus leads to embryonic lethality at 15–16 days of gestation, concomitant with a massive degeneration of the liver by programmed cell death or apoptosis. Embryonic fibroblasts from RelA-deficient mice are defective in the tumour necrosis factor (TNF)-mediated induction of messenger RNAs for IκBα and granulocyte/macrophage colony stimulating factor (GM-CSF), although basal levels of these transcripts are unaltered. These results indicate that RelA controls inducible, but not basal, transcription in NF-κB-regulated pathways.

Self-management education for adults with type 2 diabetes: a meta-analysis of the effect on glycemic control

Abstract: Objective To evaluate the efficacy of self-management education on GHb in adults with type 2 diabetes. Research design and methods We searched for English language trials in Medline (1980-1999), Cinahl (1982-1999), and the Educational Resources Information Center database (ERIC) (1980-1999), and we manually searched review articles, journals with highest topic relevance, and reference lists of included articles. Studies were included if they were randomized controlled trials that were published in the English language, tested the effect of self-management education on adults with type 2 diabetes, and reported extractable data on the effect of treatment on GHb. A total of 31 studies of 463 initially identified articles met selection criteria. We computed net change in GHb, stratified by follow-up interval, tested for trial heterogeneity, and calculated pooled effects sizes using random effects models. We examined the effect of baseline GHb, follow-up interval, and intervention characteristics on GHb. Results On average, the intervention decreased GHb by 0.76% (95% CI 0.34-1.18) more than the control group at immediate follow-up; by 0.26% (0.21% increase - 0.73% decrease) at 1-3 months of follow-up; and by 0.26% (0.05-0.48) at > or = 4 months of follow-up. GHb decreased more with additional contact time between participant and educator; a decrease of 1% was noted for every additional 23.6 h (13.3-105.4) of contact. Conclusions Self-management education improves GHb levels at immediate follow-up, and increased contact time increases the effect. The benefit declines 1-3 months after the intervention ceases, however, suggesting that learned behaviors change over time. Further research is needed to develop interventions effective in maintaining long-term glycemic control.

Identification of RIP1 kinase as a specific cellular target of necrostatins.

Abstract: Necroptosis is a cellular mechanism of necrotic cell death induced by apoptotic stimuli in the form of death domain receptor engagement by their respective ligands under conditions where apoptotic execution is prevented. Although it occurs under regulated conditions, necroptotic cell death is characterized by the same morphological features as unregulated necrotic death. Here we report that necrostatin-1, a previously identified small-molecule inhibitor of necroptosis, is a selective allosteric inhibitor of the death domain receptor-associated adaptor kinase RIP1 in vitro. We show that RIP1 is the primary cellular target responsible for the antinecroptosis activity of necrostatin-1. In addition, we show that two other necrostatins, necrostatin-3 and necrostatin-5, also target the RIP1 kinase step in the necroptosis pathway, but through mechanisms distinct from that of necrostatin-1. Overall, our data establish necrostatins as the first-in-class inhibitors of RIP1 kinase, the key upstream kinase involved in the activation of necroptosis.

A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease

Abstract: Background Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease. Although darbepoetin alfa can effectively increase hemoglobin levels, its effect on clinical outcomes in these patients has not been adequately tested. Methods In this study involving 4038 patients with diabetes, chronic kidney disease, and anemia, we randomly assigned 2012 patients to darbepoetin alfa to achieve a hemoglobin level of approximately 13 g per deciliter and 2026 patients to placebo, with rescue darbepoetin alfa when the hemoglobin level was less than 9.0 g per deciliter. The primary end points were the composite outcomes of death or a cardiovascular event (nonfatal myocardial infarction, congestive heart failure, stroke, or hospitalization for myocardial ischemia) and of death or end-stage renal disease. Results Death or a cardiovascular event occurred in 632 patients assigned to darbepoetin alfa and 602 patients assigned to placebo (hazard...