Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis

Antibodies to citrullinated proteins (anti-cyclic-citrullinated peptide [anti-CCP] antibodies) are highly specific for rheumatoid arthritis (RA) and precede the onset of disease symptoms, indicating a pathogenetic role for these antibodies in RA. We recently showed that distinct genetic risk factors are associated with either anti-CCP-positive disease or anti-CCP-negative disease. These data are important as they indicate that distinct pathogenic mechanisms are underlying anti-CCP-positive disease or anti-CCP-negative disease. Likewise, these observations raise the question of whether anti-CCP-positive RA and anti-CCP-negative RA are clinically different disease entities. We therefore investigated whether RA patients with anti-CCP antibodies have a different clinical presentation and disease course compared with patients without these autoantibodies. In a cohort of 454 incident patients with RA, 228 patients were anti-CCP-positive and 226 patients were anti-CCP-negative. The early symptoms, tender and swollen joint count, and C-reactive protein level at inclusion, as well as the swollen joint count and radiological destruction during 4 years of follow-up, were compared for the two groups. There were no differences in morning stiffness, type, location and distribution of early symptoms, patients' rated disease activity and C-reactive protein at inclusion between RA patients with and without anti-CCP antibodies. The mean tender and swollen joint count for the different joints at inclusion was similar. At follow-up, patients with anti-CCP antibodies had more swollen joints and more severe radiological destruction. Nevertheless, the distribution of affected joints, for swelling, bone erosions and joint space narrowing, was similar. In conclusion, the phenotype of RA patients with or without anti-CCP antibodies is similar with respect to clinical presentation but differs with respect to disease course

Internal Wave Turbulence Near a Texel Beach

A summer bather entering a calm sea from the beach may sense alternating warm and cold water. This can be felt when moving forward into the sea (‘vertically homogeneous’ and ‘horizontally different’), but also when standing still between one’s feet and body (‘vertically different’). On a calm summer-day, an array of high-precision sensors has measured fast temperature-changes up to 1°C near a Texel-island (NL) beach. The measurements show that sensed variations are in fact internal waves, fronts and turbulence, supported in part by vertical stable stratification in density (temperature). Such motions are common in the deep ocean, but generally not in shallow seas where turbulent mixing is expected strong enough to homogenize. The internal beach-waves have amplitudes ten-times larger than those of the small surface wind waves. Quantifying their turbulent mixing gives diffusivity estimates of 10−4–10−3 m2 s−1, which are larger than found in open-ocean but smaller than wave breaking above deep sloping topography

Model studies concerning the first step in the hydrolysis of ribonucleic acids by RNase A

Low-temperature NMR measurements of the reaction of two cyclic oxyphosphoranes with FSOaH in CHCl2F are described. An equilibrium is observed of the ring-opened phosphonium ions with the neutral oxyphosphoranes. From the activation parameters it is concluded that the rigidity introduced by a five-membered ring facilitates ring closure of the phosphonium ion, whereas a six-membered ring is less effective. Similarly, ring closure is found to occur in the solvolysis of a bicyclic phosphate where a five-membered ring makes the ring-opened product relatively rigid. This results in exocyclic ester cleavage to a greater extent than predicted by a pseudorotation mechanism. The reactions suggest that intramolecular phosphorylation of the 2'-OH group in RNA is facilitated by the ribose ring

Protonation as a driving force for pentacoordination of phosphorus

CNDO/2 calculations are reported on four caged phosphorus compounds, Y-P(OCH2CH2)3X (X = N, CH; Y = O, OH+, H+). Structures with and without a transannular bond between P and X were taken into account; the influence of this bond on the stability of the compounds was examined. For X = N and Y = H+ the lowest-energy structure corresponds with the geometry found by X-ray analysis. If X = CH, formation of a transannular bond proves to be unlikely, as expected. The calculations predict the formation of a P-N bond upon protonation of the phosphate (X = N, Y = O). The net atomic charges in the protonated phosphite were used to calculate its NMR coupling constant, 1JPH, which correlates well with the value found experimentally

A comparison of transoesophageal echocardiographic Doppler across the aortic valve and the thermodilution technique for estimating cardiac output.

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