Existing joint erosions increase the risk of joint space narrowing independently of clinical synovitis in patients with early rheumatoid arthritis

IntroductionClinical synovitis is often associated with damage to bone and cartilage. Previous data have suggested that joint erosions (JE) are more prevalent than joint space narrowing (JSN) and that the two processes are partly independent of each other. The objective of this study was to evaluate whether the presence of JE in an individual joint can lead to development of JSN and if existing JSN leads to new onset of JE, in the absence of synovitis.MethodsThe Prospective Multi-Centre Randomised, Double-Blind, Active Comparator-Controlled, Parallel-Groups Study Comparing the Fully Human Monoclonal Anti-TNFα Antibody Adalimumab Given Every Second Week With Methotrexate Given Weekly and the Combination of Adalimumab and Methotrexate Administered Over 2 Years in Patients With Early Rheumatoid Arthritis (PREMIER) enrolled early rheumatoid arthritis (RA) patients who were randomized to one of three treatments: methotrexate (MTX), adalimumab (ADA), or ADA + MTX. All evaluable joints with JE and JSN measures at 26 and 52 weeks and synovitis assessments from week 26 to 52 were included. Synovitis was assessed every 2–8 weeks by swollen joint counts between weeks 26 and 52. Radiographs were taken at week 26 and 52. Two readers, blinded to time and sequence, scored 14 bilateral joints individually for JE and JSN. Multivariate logistic modeling was used to characterize the dependence of JE/JSN onset at 52 weeks. Analyses were performed based on treatment arm and were also performed within individual joints.ResultsJE and swelling were independently and comparably associated with onset of JSN at week 52. Assessment by individual joints indicated that existing JE, independent of swelling, was significantly associated with JSN onset in higher proportions of metatarsophalangeal (MTP; 7/10) than proximal interphalangeal (PIP; 1/8) or metacarpophalangeal (MCP; 1/10) joints. Treatment with ADA + MTX prevents JE/JSN progression independently of its ability to suppress synovitis and limits JE/JSN onset and progression in joints with existing damage.ConclusionsExisting JE predisposes individual joints to development of JSN independently of synovitis in the same joint. Weight-bearing MTP joints with JE may be at increased risk for JSN when compared with MCPs and PIPs.

Trial registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00195663","term_id":"NCT00195663"}}NCT00195663. Registered 13 September 2005.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0626-1) contains supplementary material, which is available to authorized users.     

The Presence of Clostridium botulinum in Indonesian Waters

S ummary . In initial surveys of Indonesian waters and marine animals, Clostridium botulinum , predominantly of types A and C, was detected in 10% of all enrichment cultures tested.     

Isolation of Radiosensitive Mutants of Micrococcus radiodurans

Sulfated polysaccharides (SP) isolated from freshwater green algae, Spirogyra neglecta (Hassall) Kützing, and fractionated SPs were examined to investigate their molecular characteristics and immunomodulatory activity. The crude and fractionated SPs (F₁, F₂, and F₃) consisted mostly of carbohydrates (68.5–85.3%), uronic acids (3.2–4.9%), and sulfates (2.2–12.2%) with various amounts of proteins (2.6–17.1%). d-galactose (23.5–27.3%), d-glucose (11.5–24.8%), l-fucose (19.0–26.7%), and l-rhamnose (16.4–18.3%) were the major monosaccharide units of these SPs with different levels of l-arabinose (3.0–9.4%), d-xylose (4.6–9.8%), and d-mannose (0.4–2.3%). The SPs contained two sub-fractions with molecular weights (M_w) ranging from 164 × 10³ to 1460 × 10³ g/mol. The crude and fractionated SPs strongly stimulated murine macrophages, producing considerable amounts of nitric oxide and various cytokines via up-regulation of their mRNA expression by activation of nuclear factor-kappa B and mitogen-activated protein kinases pathways. The main backbone of the most immunoenhancing SP was (1→3)-l-Fucopyranoside, (1→4,6)-d-Glucopyranoside, and (1→4)-d-Galactopyranoside.     

The Fc receptor-cytoskeleton complex from human neutrophils

The Fc receptor complex and its associated phagocytic cytoskeleton machinery were captured from the surface of live cells by IgG coated microbeads and identified by mass spectrometry. The random and independently sampled intensity values of peptides were similar in the control and IgG samples. After log transformation, the parent and fragment intensity values showed a normal distribution where ≥99.9% of the data was well above the background noise. Some proteins showed significant differences in intensity between the IgG and control samples by ANOVA followed by the Tukey-Kramer honestly significant difference test. However many proteins were specific to the IgG beads or the control beads. The set of detected cytoskeleton proteins, binding proteins and enzymes detected on the IgG beads were used to predict the network of actin-associated regulatory factors. Signaling factors/proteins such as PIK3, PLC, GTPases (such CDC42, Rho GAPs/GEFs), annexins and inositol triphosphate receptors were all identified as being specific to the activated receptor complex by mass spectrometry. In addition, the tyrosine kinase Fak was detected with the IgG coated beads. Hence, an activated receptor cytoskeleton complex and its associated regulatory proteins were captured from the surface of live human primary leukocytes.     

Identification and quantification of peptides and proteins secreted from prostate epithelial cells by unbiased liquid chromatography tandem mass spectrometry using goodness of fit and analysis of variance

The proteins secreted by prostate cancer cells (PC3(AR)6) were separated by strong anion exchange chromatography, digested with trypsin and analyzed by unbiased liquid chromatography tandem mass spectrometry with an ion trap. The spectra were matched to peptides within proteins using a goodness of fit algorithm that showed a low false positive rate. The parent ions for MS/MS were randomly and independently sampled from a log-normal population and therefore could be analyzed by ANOVA. Normal distribution analysis confirmed that the parent and fragment ion intensity distributions were sampled over 99.9% of their range that was above the background noise. Arranging the ion intensity data with the identified peptide and protein sequences in structured query language (SQL) permitted the quantification of ion intensity across treatments, proteins and peptides. The intensity of 101,905 fragment ions from 1421 peptide precursors of 583 peptides from 233 proteins separated over 11 sample treatments were computed together in one ANOVA model using the statistical analysis system (SAS) prior to Tukey-Kramer honestly significant difference (HSD) testing. Thus complex mixtures of proteins were identified and quantified with a high degree of confidence using an ion trap without isotopic labels, multivariate analysis or comparing chromatographic retention times.     

Distribution of Clostridium botulinum Around Fishing Areas of the Western Part of Indonesian Waters

A survey was carried out to determine the presence of Clostridium botulinum in samples of sediment and seafoods from the fishing areas of the western part of Indonesian waters. Among the 3,433 samples, 82 (2.4%) were positive for C. botulinum. Type E was not found.     

The endogenous peptides of normal human serum extracted from the acetonitrile-insoluble precipitate using modified aqueous buffer with analysis by LC–ESI–Paul ion trap and Qq-TOF

Many peptides of biological or medicinal importance may be derived from proteolytic actions and are found at low concentrations in human blood fluids. Endogenous polypeptides from human serum were precipitated in acetonitrile and the precipitate was then selectively extracted with water modified by organic solvents and collected over C18 resin. Extraction of serum with C18 alone, and the acetonitrile supernatant or ultrafiltration collected over C18, served as controls. The samples were analyzed by SDS-PAGE, or C18 high pressure liquid chromatography with electrospray ionization using a Paul ion trap and Qq-TOF. Spectra were correlated without specifying an enzyme using the X!TANDEM or the Paragon algorithms. Multiple endogenous peptides from plasminogen, coagulation factors, collagens, serum amyloid, receptors, zinc finger/bromo peptide proteins, ryanodine receptor, calmodulin binding activator, erythroid differentiation factor, testes cancer antigen, extracellular matrix protein, myeloid/lymphoid leukemia 2 and many low abundance proteins were correlated by X!TANDEM with protein expect values of ～ E-16 or less. Proteins with binding sites for nucleic acids, phosphoinositides, and other cellular locations were also observed using the Qq-TOF and Paragon algorithm. Proteins with low expectation scores and overlapping peptides sequences were observed. The existence of these proteins in serum has been confirmed by tryptic digestion and LC–ESI–MS/MS. The presence of plasminogen, serum amyloid and zinc finger RNA binding proteins were confirmed by Western blot. There was agreement on the detection of endogenous peptides from low abundance proteins associated with the biology of cancer from the examination of the blood peptides by ion trap and Qq-TOF, tryptic digests of blood proteins, and Western blot.