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Objectives To confirm the effectiveness and safety of the interleukin 6-receptor antagonist tocilizumab in patients with rheumatoid arthritis (RA) in a setting close to real-life medical care in Germany. Methods A multicentre open-label phase IIIb study was undertaken. Patients with active RA with a 28-joint Disease Activity Score (DAS28) >3.2 despite previous disease-modifying antirheumatic drugs (DMARDs) were treated with tocilizumab 8 mg/kg every 4 weeks. The primary end point was the proportion of patients achieving LDAS ≤3.2 at week 24; secondary end points included American College of Rheumatology (ACR), European League Against Rheumatism (EULAR) or Clinical Disease Activity Index (CDAI) responses and decrease in acute phase. Analyses in subgroups such as rheumatoid factor (RF)-positive versus RF-negative patients and patients with an inadequate response to treatment with DMARDs (DMARD-IR) versus those with an inadequate response to tumour necrosis factor (TNF) antagonists (TNF antagonist-IR) were performed. Safety was assessed by adverse event documentation. Results 286 patients were treated and 83.6% completed the study. 41.6% had previously been treated with TNF antagonists. 57% of the intention-to-treat patients achieved the primary end point of LDAS, 47.6% achieved DAS remission <2.6 and a EULAR ‘good response’ was achieved by 54.9%; ACR50/70 response rates at week 24 were 50.7% and 33.9%, respectively. The mean±SD decrease in CDAI from baseline to week 24 was 71±29%. C reactive protein levels normalised rapidly within 1 week. Major improvements in fatigue, pain and morning stiffness were observed in the first 4 weeks and further improved until week 24. DAS28, EULAR and ACR responses at week 24 did not differ between RF-positive and RF-negative patients. TNF antagonist-naive patients responded better than patients who had previously failed on TNF antagonists. The safety profile of tocilizumab was comparable to that previously observed in the phase III trial programme. Serious infections were observed in 3.1% of patients. Conclusions Tocilizumab is highly effective in a setting close to real-life medical care with a rapid and sustained improvement in signs and symptoms of RA. A manageable safety profile was seen over the 24-week study period. [ABSTRACT FROM PUBLISHER]

Myrioconium sp. strain UHH 1-13-18-4 is an ascomycete anamorph isolated from the river Saale, Central Germany. An extracellular, monomeric, and glycosylated laccase with a molecular mass of 72.7 kDa as determined by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry and an isoelectric point below 2.8 was purified from CuSO4 and vanillic acid amended liquid fungal cultures grown in malt extract medium. The catalytic efficiencies ( k cat/ K m) for the oxidation of syringaldazine, 2,6-dimethoxyphenol, and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonate) were 67.3, 46.9, and 28.2 s−1 mM−1, respectively, with K m values of 4.2, 67.8, and 104.9 μM. After pre-incubation at different pH values and temperatures for 1 h, more than 80% of the initial laccase activity was retained between pH 4 to 6 and 15°C. The laccase-encoding gene was identified and sequenced at both the genomic and complementary DNA (cDNA) level, and corresponding structural characteristics and putative regulatory elements of the promoter region are reported. The identification of two tryptic peptides of the purified enzyme by mass spectrometry confirmed the identity of the functional laccase protein with the translated genomic sequence of the Myrioconium sp. laccase. Myrioconium sp. laccase shows the highest degree of identity with laccases from ascomycetes belonging to the family Sclerotiniaceae, order Helotiales. [ABSTRACT FROM AUTHOR]

Notes that, by using still photographs, teachers can encourage their students to produce more imaginative compositions. Includes examples of the use of pictures to give students the impetus they need to begin expressing themselves with greater enthusiasm. (FL)

For rationalizing molecular analysis of field-collected roots in diversity studies on arbuscular mycorrhiza, we compared three different approaches. After DNA extraction from 50 root samples of Plantago lanceolata grown on monoculture plots at a former arable field site, (1) DNAs were amplified separately by nested PCR and each amplicon was cloned separately; (2) DNAs were amplified separately by nested PCR, 1 μl of each amplicon was pooled, and a single cloning was made from the resulting amplicons mix; and (3) DNAs were pooled and the single amplicon derived from the nested PCR was cloned. Based on these three different methods, 109 nuclear ribosomal internal transcribed spacer sequences were obtained. Methods 1 and 2 enabled the detection of almost similar levels of arbuscular mycorrhizal fungal diversity. However, method 1 was expensive and time-consuming as much more cloning had to be done. Method 3 was completely biased by preferential amplification of nontarget organisms, which were only detected in low frequencies by the other methods. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Treatment of ankylosing spondylitis (AS) with infliximab, an anti-tumor necrosis factor alpha monoclonal antibody, was shown to be efficacious in patients with active disease during a 3-month treatment period. The purpose of this study was to evaluate the efficacy and safety of infliximab treatment of AS for a 1-year period. METHODS: This study was an open, observational, extension study of a 3-month, randomized, placebo-controlled trial. All patients who had tolerated infliximab (infliximab/infliximab group) or placebo (placebo/infliximab 12-week crossover group) therapy for 3 months entered the open extension trial (n = 65). Infliximab was administered at a dosage of 5 mg/kg every 6 weeks after the induction phase (weeks 0, 2, and 6). The primary end point was a 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). RESULTS: At week 54, a total of 54 of the 69 patients (78%) continued to take infliximab. The intent-to-treat primary efficacy analysis at week 54 showed that 47% of patients in the infliximab/infliximab group (95% confidence interval 31-63) and 51% of the patients in the placebo/infliximab group (95% confidence interval 36-67) achieved 50% improvement in BASDAI scores. In the analysis of those who completed the study, the mean BASDAI scores improved between weeks 0 and 54 in both treatment groups: from 6.6 to 2.4 in the infliximab/infliximab group and from 6.3 to 2.6 in the placebo/infliximab group. The dosage of nonsteroidal antiinflammatory drugs was reduced in approximately 70% of the patients. There were significant improvements in measures of functioning, metrologic parameters, and quality of life. Between weeks 12 and 54, a total of 4 patients had serious adverse events that were possibly related to infliximab and resulted in their discontinuing the study. CONCLUSION: Infliximab therapy in AS patients resulted in a rapid and significant improvement in BASDAI scores (>50% improvement) and a durable response for 1 year. The safety profile of infliximab in AS was comparable to that observed in the postmarketing experience for the approved indications. [ABSTRACT FROM AUTHOR]