A large amount of chromosomal DNA is degraded during programmed cell death and definitive erythropoiesis. DNase II is an enzyme that digests the chromosomal DNA of apoptotic cells and nuclei expelled from erythroid precursor cells after macrophages have engulfed them. Here we show that DNase II-/-IFN-IR-/- mice and mice with an induced deletion of the DNase II gene develop a chronic polyarthritis resembling human rheumatoid arthritis. A set of cytokine genes was strongly activated in the affected joints of these mice, and their serum contained high levels of anti-cyclic citrullinated peptide antibody, rheumatoid factor and matrix metalloproteinase-3. Early in the pathogenesis, expression of the gene encoding tumour necrosis factor (TNF)-alpha was upregulated in the bone marrow, and administration of anti-TNF-alpha antibody prevented the development of arthritis. These results indicate that if macrophages cannot degrade mammalian DNA from erythroid precursors and apoptotic cells, they produce TNF-alpha, which activates synovial cells to produce various cytokines, leading to the development of chronic polyarthritis.

Purpose: To investigate age-related changes in the locus ceruleus (LC) in healthy subjects using neuromelanin magnetic resonance (MR) imaging at 3 Tesla.Methods: We examined 64 healthy volunteers (aged 23 to 80 years) using neuromelaninsensitive T 1 -weighted images and measured the contrast of areas of high signal intensity corresponding to the LC.Results: A pair of punctate areas of high signal intensity that represented neuromelanin within the noradrenergic neurons of the LC was easily recognized in all subjects. The contrast ratio of the LC to the adjacent pontine tegmentum increased to the age of 40 to 59 years and gradually and signiˆcantly decreased in elderly subjects. This correlates well with pathologically proven age-related changes in neuromelanin content within the LC.Conclusion: Age-related variance should be considered when determining the existence of abnormalities in the LC.

Purpose: To investigate the diŠerence in enhancement eŠects and relaxivities of the gadolinium chelate at 1.5 and 3 Tesla (T) and to elucidate the contribution of the high magneticˆeld to contrast enhancement in spin-echo (SE) and gradient-echo (GRE) images.Methods: Phantoms containing water with or without gadopentetate dimeglumine (Gd-DTPA) at diŠerent concentrations were scanned using 1.5T and 3T MRI scanners of the same manufacturer and under the same temperature conditions and scanning parameters. Relaxivities of gadolinium, R 1 and R 2 , were estimated from serial T 1 and T 2 values of the phantoms using linear regression. Contrast enhancement ratios in SE and GRE T 1 -weighted images were compared at 1.5 and 3T.Results: The R 1 and R 2 of Gd-DTPA at 1.5 and 3T were 4.79 and 5.14, and 4.50 and 5.09, respectively. Although the relaxivities at 3T were slightly lower than those at 1.5T, the contrast enhancement ratio improved in both SE and GRE images as a result of T 1 prolongation of the water at 3T.Conclusion: The decrease in relaxivities of the Gd-DTPA at 3T appears to be so small that T 1 prolongation of the water improves contrast enhancement, suggesting a potential clinical advantage in administration of Gd-DTPA at highˆeld strength.

The FA value calculated from preoperative MR DT imaging predicts meningioma consistency.

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