Expansion of extracellular matrix with fibrosis occurs in many tissues as part of the end-organ complications in diabetes, and advanced glycosylation end products (AGE) are implicated as one causative factor in diabetic tissue fibrosis. Connective tissue growth factor (CTGF), also known as insulin-like growth factor-binding protein-related protein-2 (IGFBP-rP2), is a potent inducer of extracellular matrix synthesis and angiogenesis and is increased in tissues from rodent models of diabetes. The aim of this study was to determine whether CTGF is up-regulated by AGE in vitro and to explore the cellular mechanisms involved. AGE treatment of primary cultures of nonfetal human dermal fibroblasts in confluent monolayer increased CTGF steady state messenger RNA (mRNA) levels in a time- and dose-dependent manner. In contrast, mRNAs for other IGFBP superfamily members, IGFBP-rP1 (mac 25) and IGFBP-3, were not up-regulated by AGE. The effect of the AGE BSA reagent on CTGF mRNA was due to nonenzymatic glycosylation of BSA and, using neutralizing antisera to AGE and to the receptor for AGE, termed RAGE, was seen to be due to late products of nonenzymatic glycosylation and was partly mediated by RAGE. Reactive oxygen species as well as endogenous transforming growth factor-beta1 could not explain the AGE effect on CTGF mRNA. AGE also increased CTGF protein in the conditioned medium and cell-associated CTGF. Thus, AGE up-regulates the profibrotic and proangiogenic protein CTGF (IGFBP-rP2), a finding that may have significance in the development of diabetic complications.

ObjectiveTo evaluate the capacity of a computer-aided detection (CAD) system to detect lung nodules in clinical chest CT.Materials and MethodsA total of 210 consecutive clinical chest CT scans and their reports were reviewed by two chest radiologists and 70 were selected (33 without nodules and 37 with 1-6 nodules, 4-15.4 mm in diameter). The CAD system (ImageChecker® CT LN-1000) developed by R2 Technology, Inc. (Sunnyvale, CA) was used. Its algorithm was designed to detect nodules with a diameter of 4-20 mm. The two chest radiologists working with the CAD system detected a total of 78 nodules. These 78 nodules form the database for this study. Four independent observers interpreted the studies with and without the CAD system.ResultsThe detection rates of the four independent observers without CAD were 81% (63/78), 85% (66/78), 83% (65/78), and 83% (65/78), respectively. With CAD their rates were 87% (68/78), 85% (66/78), 86% (67/78), and 85% (66/78), respectively. The differences between these two sets of detection rates did not reach statistical significance. In addition, CAD detected eight nodules that were not mentioned in the original clinical radiology reports. The CAD system produced 1.56 false-positive nodules per CT study. The four test observers had 0, 0.1, 0.17, and 0.26 false-positive results per study without CAD and 0.07, 0.2, 0.23, and 0.39 with CAD, respectively.ConclusionThe CAD system can assist radiologists in detecting pulmonary nodules in chest CT, but with a potential increase in their false positive rates. Technological improvements to the system could increase the sensitivity and specificity for the detection of pulmonary nodules and reduce these false-positive results.

This case illustrates that the MRI findings for osteoblastoma can be misleading and caution should be used when evaluating benign tumors with known inflammatory responses on MRI. CT features seem to more accurately reflect the true nature and extent of the tumor.