Aging-associated inflammation in healthy Japanese individuals and patients with Werner syndrome.

Minor inflammation-driven aging (inflammaging) has been proposed to explain human aging mechanism. To study the inflammatory condition associated with normal human aging, highly sensitive CRP (hsCRP) was examined in the sera collected from 217 healthy Japanese individuals aged between 1 and 100years and 41 mutation-proven Japanese Werner syndrome (WS) patients. The serum hsCRP was assayed by ELISA. The serum hsCRP level increased significantly (p<0.001) with normal aging from both sexes. The serum hsCRP was significantly elevated in WS (mean±SE: 11.0±1.6µg/ml) compared with age-matched normal population (1.3±0.3µg/ml, p<0.001) and normal elderly population ages between 71 and 100years (4.2±0.7µg/ml, p<0.001). Both normal aging and WS were associated with minor inflammation that can be evaluated by serum hsCRP. WS may be a good candidate to study inflammaging.

Efficacy and safety of ketoprofen patch in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled study.

This study assessed the efficacy and safety of ketoprofen patch compared with placebo in patients who had rheumatoid arthritis and persistent wrist pain. Patients (N = 676)who had achieved systemic disease control with a disease-modifying antirheumatic drug and/or systemic corticosteroid, but still had persistent wrist pain, were randomized to a 2-week course of once-daily treatment with application of a 20-mg ketoprofen patch or a placebo patch to the wrist. The primary efficacy end point was the percent change from baseline to the end of treatment in the intensity of wrist pain scored by each patient on a 100-mm visual analog scale. The mean ± SD percent change on the pain intensity scale was significantly larger in patients treated with ketoprofen than in those receiving placebo (31.2% ± 30.3% [95% confidence interval: 28.0-34.4] vs 25.5% ± 31.2% [95% confidence interval: 22.1-28.8]; P = .020). However, the actual difference of the mean pain intensity scale between the 2 groups was small at the end of treatment. The frequency of adverse events was similar in both groups. The ketoprofen patch was more effective than placebo for relieving persistent local joint pain in patients with rheumatoid arthritis. The patch was also safe and well tolerated during the 2-week treatment period.

Prolonged shedding of rotavirus in a geriatric inpatient.

This study concerns a nosocomial rotaviral infection of a geriatric patient with clinical symptoms of acute gastroenteritis. The virological diagnosis was based on the detection of rotaviral antigens using a Rota kit, viral genome RNA by reverse transcription-polymerase chain reaction method, and viral particles by electron microscopy in the stool samples. Prolonged rotaviral shedding was suggested to be due to impaired natural killer cell activity, possibly together with deficiency of specific local immune response of the patient.

Molecular cloning and characterization of chondroitin polymerase from Escherichia coli strain K4.

Escherichia coli strain K4 produces the K4 antigen, a capsule polysaccharide consisting of a chondroitin backbone (GlcUA beta(1-3)-GalNAc beta(1-4))(n) to which beta-fructose is linked at position C-3 of the GlcUA residue. We molecularly cloned region 2 of the K4 capsular gene cluster essential for biosynthesis of the polysaccharide, and we further identified a gene encoding a bifunctional glycosyltransferase that polymerizes the chondroitin backbone. The enzyme, containing two conserved glycosyltransferase sites, showed 59 and 61% identity at the amino acid level to class 2 hyaluronan synthase and chondroitin synthase from Pasteurella multocida, respectively. The soluble enzyme expressed in a bacterial expression system transferred GalNAc and GlcUA residues alternately, and polymerized the chondroitin chain up to a molecular mass of 20 kDa when chondroitin sulfate hexasaccharide was used as an acceptor. The enzyme exhibited apparent K(m) values for UDP-GlcUA and UDP-GalNAc of 3.44 and 31.6 microm, respectively, and absolutely required acceptors of chondroitin sulfate polymers and oligosaccharides at least longer than a tetrasaccharide. In addition, chondroitin polymers and oligosaccharides and hyaluronan polymers and oligosaccharides served as acceptors for chondroitin polymerization, but dermatan sulfate and heparin did not. These results may lead to elucidation of the mechanism for chondroitin chain synthesis in both microorganisms and mammals.

Decreased IL-4 producing CD4+ T cells in patients with active systemic lupus erythematosus-relation to IL-12R expression.

The balance of interferon-gamma (IFN-gamma) and/or interleukin-4 (IL-4) producing T cells and interleukin-12 receptor (IL-12R) expression on T cells were evaluated in patients with active systemic lupus erythematosus (SLE). Assessment of intracellular IFN-gamma and/or IL-4 were conducted with cytoplasmic staining. IL-12R presenting T cells were also assessed by flowcytometry without in vitro stimulation. In SLE, the number of IFN-gamma producing CD4+ T cells was increased, and the absolute number of IL-4 producing CD4+ T cells was significantly decreased. Although the ratio of IL-12R presenting CD4+ T cells was significantly greater, the absolute number did not increase. The ratio of IFN-gamma/IL-4-producing CD4+ T cells correlated with the SLE disease activity index (SLEDAI) and was significantly higher among patients with lupus nephritis. Therefore, the imbalance of IFN-gamma/IL-4 producing CD4+ T cells was due to the decrease in IL-4 producing CD4+ T cells and may play an important pathogenic role in active SLE.