Citations

Abstract NKX3.1 is a homeobox gene located at chromosome 8p21.2, and one copy is frequently deleted in prostate carcinoma. Prior studies of NKX3.1 mRNA and protein in human prostate cancer and prostatic intraepithelial neoplasia (PIN) have been conflicting, and expression in focal prostate atrophy lesions has not been investigated. Immunohistochemical staining for NKX3.1 on human tissue microarrays was decreased in most focal atrophy and PIN lesions. In carcinoma, staining was inversely correlated with Gleason grade. Fluorescence in situ hybridization showed that no cases of atrophy had loss or gain of 8p, 8 centromere, or 8q24 (C-MYC) and only 12% of high-grade PIN lesions harbored loss of 8p. By contrast, NKX3.1 staining in carcinoma was correlated with 8p loss and allelic loss was inversely related to Gleason pattern. Quantitative reverse transcription-PCR for NKX3.1 mRNA using microdissected atrophy revealed a concordance with protein in five of seven cases. In carcinoma, mRNA levels were decreased in 6 of 12 cases but mRNA levels correlated with protein levels in only 4 of 12 cases, indicating translational or post-translational control. In summary, NKX3.1 protein is reduced in focal atrophy and PIN but is not related to 8p allelic loss in these lesions. Therefore, whereas genetic disruption of NKX3.1 in mice leads to PIN, nongenetic mechanisms reduce NKX3.1 protein levels early in human prostate carcinogenesis, which may facilitate both proliferation and DNA damage in atrophic and PIN cells. Monoallelic deletions on chromosome 8p are associated with more advanced invasive and aggressive disease. (Cancer Res 2006; 66(22): 10683-90)

ABSTRACT Purpose. A widely advocated approach to increasing spectacle magnification in minus lenses is to increase center thickness and reduce vertex distance. Conventionally, a steeper base curve is to be avoided because of the accompanying increased vertex distance in a minus lens and the reduction of spectacle magnification that results. This approach works when small amounts of spectacle magnification are needed. However, when large amounts are needed for high minus lenses with flat base curves, the conventional approach does not provide sufficient magnification. Facial features such as eyelash length limit the contribution of reducing vertex distance, and the flat base curves limit the efficacy of increasing center thickness. Steeper base curves are required to increase the optical “leverage” of increasing center thickness. Methods. Through use of an example, a steeper base curve is shown to increase the spectacle magnification of a high minus lens. The gain in spectacle magnification is preserved by maintaining a nearly constant vertex distance through bevel location. Results. In the example, changing the base curve of a −6.50‐D lens by +4.50 D while increasing the center thickness by 4.1 mm resulted in a +4.4% increase in spectacle magnification. The lens bevel was kept as close as possible to the front surface, allowing the increased center thickness to keep the back vertex at essentially a constant vertex distance in the presence of the steeper base curve. Without the steeper base curve, it was not possible to attain the needed spectacle magnification. Conclusions. When large amounts of spectacle magnification are needed for high minus lenses, both steeper base curves and increased center thicknesses are necessary. The reduction in spectacle magnification from increased vertex distance that is expected with steeper base curves can be neutralized by keeping the bevel close to the front surface on the thicker lens.

AbstractLong‐chain N‐acylethanolamines (NAE), including the endocannabinoid, anandamide, accumulate in mammalian tissues under a variety of pathological conditions. They have also been shown to inhibit the growth of various cancer cell lines in vitro. Here, we report the presence, in widely differing amounts (3.88–254.46 pmol/μmol lipid P), of NAE and their precursor phospholipids in various human tumors and some adjacent unaffected tissue. Anandamide ranged from 1.5 to 48% of total NAE, and incubation of tissue homogenates suggested possible NAE biosynthesis by both the established transacylation‐phosphodiesterase pathway via N‐acyl PE and by direct N‐acylation of ethanolamine.

ABSTRACT Recombinant human adenovirus is a useful gene delivery vector for clinical gene therapy. Minor capsid protein IX of adenovirus has been of recent interest since multiple studies have shown that modifications can be made to its C terminus to alter viral tropism or add molecular tags and/or reporter proteins. We examined the structure of an engineered adenovirus displaying the enhanced green fluorescent protein (EGFP) fused to the C terminus of protein IX. Cryoelectron microscopy and reconstruction localized the C-terminal EGFP fusion between the H2 hexon and the H4 hexon, positioned between adjacent facets, directly above the density previously assigned as protein IIIa. The original assignment of IIIa was based largely on indirect evidence, and the data presented herein support the reassignment of the IIIa density as protein IX.

There is little consensus on what constitutes adequate health insurance coverage. The concept of a lack of adequate coverage, or underinsurance, is a matter of ongoing debate. A measure of adequate coverage is of critical importance as the nature of health insurance products evolves. Changes to health coverage include more direct out-of-pocket spending by consumers and a reduction of covered benefits. This article updates and extends an earlier review of underinsurance measurement published in 1993. We present a conceptual approach to measuring underinsurance and provide a review of the empirical findings obtained from the application of these approaches. A discussion of the limitations in the selection of a measurement approach includes a review of the extant data sources used. We recommend a national effort to develop a consistent approach to monitor changes in the economic and structural dimensions of health insurance coverage with a concerted effort to define and measure underinsurance.