β-Defensin-2 Protein Is a Serum Biomarker for Disease Activity in Psoriasis and Reaches Biologically Relevant Concentrations in Lesional Skin

BACKGROUND: Previous studies have extensively documented antimicrobial and chemotactic activities of beta-defensins. Human beta-defensin-2 (hBD-2) is strongly expressed in lesional psoriatic epidermis, and recently we have shown that high beta-defensin genomic copy number is associated with psoriasis susceptibility. It is not known, however, if biologically and pathophysiologically relevant concentrations of hBD-2 protein are present in vivo, which could support an antimicrobial and proinflammatory role of beta-defensins in lesional psoriatic epidermis. METHODOLOGY/PRINCIPAL FINDINGS: We found that systemic levels of hBD-2 showed a weak but significant correlation with beta defensin copy number in healthy controls but not in psoriasis patients with active disease. In psoriasis patients but not in atopic dermatitis patients, we found high systemic hBD-2 levels that strongly correlated with disease activity as assessed by the PASI score. Our findings suggest that systemic levels in psoriasis are largely determined by secretion from involved skin and not by genomic copy number. Modelling of the in vivo epidermal hBD-2 concentration based on the secretion rate in a reconstructed skin model for psoriatic epidermis provides evidence that epidermal hBD-2 levels in vivo are probably well above the concentrations required for in vitro antimicrobial and chemokine-like effects. CONCLUSIONS/SIGNIFICANCE: Serum hBD-2 appears to be a useful surrogate marker for disease activity in psoriasis. The discrepancy between hBD-2 levels in psoriasis and atopic dermatitis could explain the well known differences in infection rate between these two diseases

New automated fluoroscopic systems for pediatric applications.” J Appl Clin Med Phys 6:88–105

Pediatric patients are at higher risk to the adverse effects from exposure to ionizing radiation than adults. The smaller sizes of the anatomy and the reduced X-ray attenuation of the tissues provide special challenges. The goal of this effort is to investigate strategies for pediatric fluoroscopy in order to minimize the radiation exposure to these individuals, while maintaining effective diagnostic image quality. Modern fluoroscopy systems are often entirely automated and computer controlled. In this paper, various selectable and automated modes are examined to determine the influence of the fluoroscopy parameters upon the patient radiation exposures and image quality. These parameters include variable X-ray beam filters, automatic brightness control programs, starting kilovolt peak levels, fluoroscopic pulse rates, and other factors. Typical values of radiation exposure rates have been measured for a range of phantom thicknesses from 5 cm to 20 cm of acrylic. Other factors that have been assessed include spatial resolution, lowcontrast discrimination, and temporal resolution. The selection menu for various procedures is based upon the examination type, anatomical region, and patient size. For pediatric patients, the automated system can employ additional filtration, special automatic brightness control curves, pulsed fluoroscopy, and other features to reduce the patient radiation exposures without significantly compromising the image quality. The benefits gained from an optimal selection of automated programs and settings for fluoroscopy include ease of operation, better image quality, and lower patient radiation exposures. PACS numbers: 87.59.-e, 87.62.+n Key words: digital fluoroscopy, pediatric radiation exposur

Metnase mediates chromosome decatenation in acute leukemia cells

After DNA replication, sister chromatids must be untangled, or decatenated, before mitosis so that chromatids do not tear during anaphase. Topoisomerase IIα (Topo IIα) is the major decatenating enzyme. Topo IIα inhibitors prevent decatenation, causing cells to arrest during mitosis. Here we report that acute myeloid leukemia cells fail to arrest at the mitotic decatenation checkpoint, and their progression through this checkpoint is regulated by the DNA repair component Metnase (also termed SETMAR). Metnase contains a SET histone methylase and transposase nuclease domain, and is a component of the nonhomologous end-joining DNA double-strand break repair pathway. Metnase interacts with Topo IIα and enhances its decatenation activity. Here we show that multiple types of acute leukemia cells have an attenuated mitotic arrest when decatenation is inhibited and that in an acute myeloid leukemia (AML) cell line this is mediated by Metnase. Of further importance, Metnase permits continued proliferation of these AML cells even in the presence of the clinical Topo IIα inhibitor VP-16. In vitro, purified Metnase prevents VP-16 inhibition of Topo IIα decatenation of tangled DNA. Thus, Metnase expression levels may predict AML resistance to Topo IIα inhibitors, and Metnase is a potential therapeutic target for small molecule interference