Recent Publications by CFE Educators

Five families of outer membrane porins that function in protein secretion in Gram-negative bacteria are currently recognized. In this report, these five porin families are analyzed from structural and phylogenetic standpoints. They are the fimbrial usher protein (FUP), outer membrane factor (OMF), autotransporter (AT), two-partner secretion (TPS) and outer membrane secretin (Secretin) families. All members of these families in the current databases were identified, and all full-length homologues were multiply aligned for structural and phylogenetic analyses. The organismal distribution of homologues in each family proved to be unique with some families being restricted to proteobacteria and others being widespread in other bacterial kingdoms as well as eukaryotes. The compositions of and size differences between subfamilies provide evidence for specific orthologous relationships, which agree with available functional information and intra-subfamily phylogeny. The results reveal that horizontal transfer of genes encoding these proteins between phylogenetically distant organisms has been exceptionally rare although transfer within select bacterial kingdoms may have occurred. The resultant in silico analyses are correlated with available experimental evidence to formulate models relevant to the structures and evolutionary origins of these proteins.

PURPOSE

This study was designed to investigate whether nuclear receptor agonists can be used as potential differentiation therapy agents for human osteosarcoma.

EXPERIMENTAL DESIGN

Four osteosarcoma cell lines (143B, MNNG/HOS, MG-63, and TE-85) were treated with proliferator-activated receptor (PPAR)gamma agonists, troglitazone and ciglitazone, and a retinoid X receptor (RXR) ligand, 9-cis retinoic acid. The proliferation and induction of apoptosis in the treated cells were assessed, as was the induction of alkaline phosphatase, a differentiation marker of osteoblasts.

RESULTS

The expression of PPARgamma was readily detected in all tested osteosarcoma lines. On treatment with the PPARgamma and RXR ligands, all four osteosarcoma lines exhibited a significantly reduced proliferation rate and cell viability. Among the four lines, 143B and MNNG/HOS were shown to be more sensitive to ligand-induced apoptosis, as demonstrated by the Crystal Violet and Hoechst staining assays. Of the three tested ligands, troglitazone was shown to be the most effective in inducing cell death, followed by 9-cis retinoic acid. Moreover, a strong synergistic effect on the induction of cell death was observed when both troglitazone and 9-cis retinoic acid or ciglitazone and 9-cis retinoic acid were administered to osteosarcoma cells. Troglitazone was shown to effectively induce alkaline phosphatase activity, a well-characterized hallmark for osteoblastic differentiation.

CONCLUSIONS

Our findings suggest that PPARgamma and/or RXR ligands may be used as efficacious adjuvant therapeutic agents for primary osteosarcoma, as well as potential chemopreventive agents for preventing the recurrence and metastasis of osteosarcoma after the surgical removal of the primary tumors.

For both primary and secondary prevention of coronary heart disease (CHD), it is prudent to use strategies that are of proven benefit and that do not harm patients. In all women, these strategies include lifestyle approaches such as smoking avoidance, proper nutrition, and regular exercise. Lipid-lowering and blood pressure control with pharmacotherapy are indicated in women who do not meet target lipid or blood pressure levels with lifestyle interventions. For women with CHD, aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors should be considered. Widespread under-use of established preventive therapies has been documented in women. These interventions should be emphasized in clinical practice. For secondary prevention of CHD in women, the American Heart Association (AHA) recommends against initiating hormone replacement therapy (HRT) based on studies that have shown no benefit and early harm. For patients with CHD already on HRT, the decision to continue or stop HRT should be based on established noncoronary benefits and risks and patient preference. There are insufficient data to suggest that HRT should be initiated for the sole purpose of primary prevention of CHD. Because the new AHA guidelines recommend placing significant weight on the noncardiac benefits and risks of HRT, it is important to become familiar with these noncardiac effects. It is also important to understand the evidence supporting the AHA's decision to recommend placing relatively less weight on the cardiac effects of HRT.

STUDY OBJECTIVES

To measure the accessibility and quality of currently available asthma education World Wide Web sites using the following criteria: accessibility by readability, language, and download time; information quality based on inclusion of core educational concepts and compliance with Health On the Net (HON) principles; and utilization of innovative technology.

DESIGN

Objective evaluation of 145 Web sites.

MEASUREMENTS AND RESULTS

Four search engines or directories (Yahoo, HON, Alta Vista, and Healthfinder) were searched for "asthma, patient information." A maximum of 50 Web sites from each search engine or directory was evaluated. Only 90 of the 145 Web sites actually contained asthma educational material. The mean (+/- SD) time necessary to open each Web site on a 28.800-bits-per-second modem was 33.6 ( +/- 36.6) s. The mean number of graphics on the Web sites was 24.6 ( +/- 30.2) files per page. The educational material required a mean reading level beyond the 10th grade. Only nine Web sites contained multilingual asthma education material. The mean number of HON principles with which the Web sites conformed was 6.3 ( +/- 1.0) of 8 principles; 14 Web sites conformed to all the HON criteria. The average Web site contained 4.9 (+/- 2.5) of 8 core asthma educational concepts, and only 20 Web sites contained all 8 educational concepts. Very few Web sites utilized innovative educational technology.

CONCLUSIONS

While patient asthma education Web sites are common, asthma educational material contains many accessibility barriers, is highly variable in quality and content, and takes little innovative use of technology. Patient educational material currently available on the World Wide Web fails to meet the information needs of patients.