Objective. To evaluate digital x-ray radiogrammetry (DXR) and the Radiogrammetry Kit program as new diagnostic tools for quantifying disease-related periarticular osteoporosis and for measuring joint space narrowing according to the severity and duration of rheumatoid arthritis (RA).Methods. Using DXR, we performed computerized calculations of bone mineral density (BMD) and the metacarpal index (MCI) in 258 patients with active RA. Using the Radiogrammetry Kit program, we also performed semiautomated measurements of joint space width(JSW)atthesecondthroughthefifthmetacarpophalangeal (MCP) joints in these patients.Results. All correlations between the different parameters of both techniques (BMD and the MCI as measured by DXR and MCP JSW as measured by the Radiogrammetry Kit) were significant (0.36 < R < 0.63; P < 0.01). As expected, a significant negative association was shown between the different MCP JSW results and the results of all scoring methods (؊0.67 < R < ؊0.29). The BMD and the MCI measured by DXR both decreased significantly between Steinbrocker stage I and stage IV (by 32.7% and 36.6%, respectively; both P < 0.01). Reductions in the overall (mean) MCP JSW varied from 35.3% (Larsen score) to 52.9% (Steinbrocker stage). Over a period of 6 years, we observed relative decreases in BMD and the MCI as measured by DXR (32.1% and 33.3%, respectively), as well as in the overall (mean) MCP JSW (23.5%), and these were pronounced in early RA (duration <1 year). In addition, excellent reproducibility of DXR and Radiogrammetry Kit parameters was verified (coefficients of variation <1%).Conclusion. DXR with the integrated Radiogrammetry Kit program could be a promising, widely available diagnostic tool for supplementing the different RA scoring methods with quantitative data, thus allowing an earlier and improved diagnosis of RA and more precision in determining disease progression.

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Arachidonic acid lipoxygenases (ALOXs) have been implicated in the immune response of mammals. The reaction specificity of these enzymes is decisive for their biological functions and ALOX classification is based on this enzyme property. Comparing the amino acid sequences and the functional properties of selected mammalian ALOX15 orthologs we previously hypothesized that the reaction specificity of these enzymes can be predicted based on their amino acid sequences (Triad Concept) and that mammals, which are ranked in evolution below gibbons, express arachidonic acid 12-lipoxygenating ALOX15 orthologs. In contrast, Hominidae involving the great apes and humans possess 15-lipoxygenating enzymes (Evolutionary Hypothesis). These two hypotheses were based on sequence data of some 60 mammalian ALOX15 orthologs and about half of them were functionally characterized. Here, we compared the ALOX15 sequences of 152 mammals representing all major mammalian subclades expressed 44 novel ALOX15 orthologs and performed extensive mutagenesis studies of their triad determinants. We found that ALOX15 genes are absent in extant Prototheria but that corresponding enzymes frequently occur in Metatheria and Eutheria. More than 90% of them catalyze arachidonic acid 12-lipoxygenation and the Triad Concept is applicable to all of them. Mammals ranked in evolution above gibbons express arachidonic acid 15-lipoxygenating ALOX15 orthologs but enzymes with similar specificity are only present in less than 5% of mammals ranked below gibbons. This data suggests that ALOX15 orthologs have been introduced during Prototheria-Metatheria transition and put the Triad Concept and the Evolutionary Hypothesis on a much broader and more reliable experimental basis.