Disease and psychological status in ankylosing spondylitis.

Objectives. Psychological factors may be important in the assessment and management of ankylosing spondylitis (AS). Our primary objective was to describe associations between disease and psychological status in AS, using AS-specific assessment tools and questionnaires. Our secondary objectives were to identify patient subgroups based on such associations and to determine the stability of the measures over time. Methods. A total of 110 patients were assessed at 6-monthly intervals up to four times using tools to measure disease [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Metrology Index (BASMI)], psychological [Hospital Anxiety and Depression Questionnaire (HADS), Health Locus of Control—Form C Questionnaire (HLC-C)] and generic health [Short form (SF)-36] status. Results. Eighty-nine participants completed all four assessments. Throughout the study, BASDAI, BASFI and BASMI scores correlated significantly with anxiety, depression, internality and health status, but not with levels of belief in chance or powerful others. Clinically anxious or depressed subgroups had significantly worse BASDAI and BASFI, but not BASMI, scores. BASMI scores were the least closely linked to psychological status. Mean scores for disease, psychological and health status were clinically stable over the 18 months period. Conclusions. Disease status scores in AS correlated significantly with anxiety, depression, internality and health status. Interpretation of AS disease scores should take an account of psychological status and the choice of measures used. These findings have important potential applications in AS management and monitoring, including the identification of patients for biological therapies

C-reactive protein binds to alphaIIbbeta3.

C-reactive protein binds to alphaIIbbeta3

Amperometric separation-free immunosensor for real-time environmental monitoring

Immunoanalytical techniques have found widespread use due to the characteristics of specificity and wide applicability for many analytes, from large polymer antigens, to simple haptens, and even single atoms. Electrochemical sensors offer benefits of technical simplicity, speed and convenience via direct transduction to electronic equipment. Together, these two systems offer the possibility of a convenient, ubiquitous assay technique with high selectivity. However, they are still not widely used, mainly due to the complexity of the associated immunoassay methodologies. A separation-free immunoanalytical technique is described here, which has allowed for the analysis of atrazine in real time and in both quasi-equilibrium and stirred batch configurations. It illustrated that determinations as low as 0.13 muM (28 ppb) could be made using equilibrium incubation with an analytical range of 0.1-10 muM. Measurements could be made between 1 and 10 mM within several minutes using a real-time, stirred batch method. This system offers the potential for fast, simple, cost-effective biosensors for the analysis of many substances of environmental, biomedical and pharmaceutical concern. (C) 2001 Elsevier Science B.V. All rights reserved

Gsα signalling suppresses PPARγ2 generation and inhibits 3T3L1 adipogenesis

Since TSH receptor (TSHR) expression increases during adipogenesis and signals via cAMP/phospho-cAMP-response element binding protein (CREB), reported to be necessary and sufficient for adipogenesis, we hypothesised that TSHR activation would induce preadipocyte differentiation. Retroviral vectors introduced constitutively active TSHR (TSHR*) into 3T3L1 preadipocytes; despite increased cAMP (RIA) and phospho-CREB (western blot) there was no spontaneous adipogenesis (assessed morphologically, using oil red O and QPCR measurement of adipogenesis markers). We speculated that Gβγ signalling may be inhibitory but failed to induce adipogenesis using activated Gsα (gsp*). Inhibition of phosphodiesterases did not promote adipogenesis in TSHR* or gsp* populations. Furthermore, differentiation induced by adipogenic medium with pioglitazone was reduced in TSHR* and abolished in gsp* expressing 3T3L1 cells. TSHR* and gsp* did not inactivate PPARγ (PPARG as listed in the HUGO database) by phosphorylation but expression of PPARγ1 was reduced and PPARγ2 undetectable in gsp*. FOXO1 phosphorylation (required to inactivate this repressor of adipogenesis) was lowest in gsp* despite the activation of AKT by phosphorylation. PROF is a mediator that facilitates FOXO1 phosphorylation by phospho-Akt. Its transcript levels remained constantly low in the gsp* population. In most measurements, the TSHR* cells were between the gsp* and control 3T3L1 preadipocytes. The enhanced down-regulation of PREF1 (adipogenesis inhibitor) permits retention of some adipogenic potential in the TSHR* population. We conclude that Gsα signalling impedes FOXO1 phosphorylation and thus inhibits PPARγ transcription and the alternative promoter usage required to generate PPARγ2, the fat-specific transcription factor necessary for adipogenesis

PLANTS HAVING INCREASED BOMASS AND METHODS FOR MAKING THE SAME

The impact of plastid size change in both monocot and dicot plants has been examined. In both, when plastid size is increased there is an increase in biomass relative to the parental lines. Thus, provided herein are methods for increasing the biomass of a plant, comprising decreasing the expression of at least one plastid division protein in a plant. Optionally, the level of chlorophyll in the plant is also reduced

PLANTS HAVING INCREASED BOMASS AND METHODS FOR MAKING THE SAME

The impact of plastid size change in both monocot and dicot plants has been examined. In both, when plastid size is increased there is an increase in biomass relative to the parental lines. Thus, provided herein are methods for increasing the biomass of a plant, comprising decreasing the expression of at least one plastid division protein in a plant. Optionally, the level of chlorophyll in the plant is also reduced

Expression of endogenous putative tsh binding protein in orbit

Thyroid stimulating antibodies (TSAB) cause Graves’ disease and contribute to Graves’ Orbitopathy (GO) pathogenesis. We hypothesise that the presence of TSH binding proteins (truncated TSHR variants (TSHRv)) and/or nonclassical ligands such as thyrostimulin (α2β5) might provide a mechanism to protect against or exacerbate GO. We analysed primary human orbital preadipocyte-fibroblasts (OF) from GO patients and people free of GO (non-GO). Transcript (QPCR) and protein (western blot) expression levels of TSHRv were measured through an adipogenesis differentiation process. Cyclic-AMP production by TSHR activation was studied using luciferase-reporter and RIA assays. After differentiation, TSHRv levels in OF from GO were significantly higher than non-GO (p = 0.039), and confirmed in ex vivo analysis of orbital adipose samples. TSHRv western blot revealed a positive signal at 46 kDa in cell lysates and culture media (CM) from non-GO and GO-OF. Cyclic-AMP decreased from basal levels when OF were stimulated with TSH or Monoclonal TSAB (M22) before differentiation protocol, but increased in differentiated cells, and was inversely correlated with the TSHRv:TSHR ratio (Spearman correlation: TSH r = −0.55, p = 0.23, M22 r = 0.87, p = 0.03). In the bioassay, TSH/M22 induced luciferase-light was lower in CM from differentiated GO-OF than non-GO, suggesting that secreted TSHRv had neutralised their effects. α2 transcripts were present but reduced during adipogenesis (p < 0.005) with no difference observed between non-GO and GO. β5 transcripts were at the limit of detection. Our work demonstrated that TSHRv transcripts are expressed as protein, are more abundant in GO than non-GO OF and have the capacity to regulate signalling via the TSHR

Clinical Evaluation of Niflumic Acid (Squibb) in Rheumatoid Arthritis

The effect of 750 mg of niflumic acid per day administered orally was studied in 15 patients with active rheumatoid arthritis in a double-blind crossover trial. The patients were followed over a two-week period with three assessments of joint pain and tenderness, duration and severity of morning stiffness, digital joint circumference, grip strength and radioactive pertechnetate (99m Tc) knee and wrist joint uptakes. The results show that niflumic acid was more effective in relieving pain than placebo. Anti-inflammatory effects could not be demonstrated

Decreases in markers of monocyte/macrophage activation after hepatitis C eradication in HIV/hepatitis C virus coinfected women

Objective:Eradication of hepatitis C virus (HCV) in HIV disease decreases liver and non-liver-related morbidity and mortality. Elevated markers of monocyte/macrophage activation (soluble CD163 and sCD14) are associated with excess non-AIDS morbidity and mortality in HIV. We examined the effect of HCV eradication on these markers in relation to change in hepatic fibrosis.Design:A nested substudy within a longitudinal observational cohortMethods:We studied 126 HIV/HCV-coinfected women successfully treated for HCV, with undetectable HCV RNA at least 12 weeks after therapy completion. sCD163 and sCD14 were measured in serum collected before and after HCV eradication. Results were correlated with changes in markers of hepatic fibrosis.Results:Mean age of participants was 56.3 years, mean CD4+cell count was 615, and 72% had suppressed HIV RNA. After treatment, sCD163 and sCD14 levels significantly decreased from pre-treatment levels in unadjusted analyses. After adjusting for age, race, hepatic fibrosis status, baseline HCV RNA, CD4 count and HIV RNA status, cigarette smoking, and alcohol use, the decreases in sCD163 and sCD14 remained significant. Decrease in pre-treatment to post-treatment sCD163 were significantly positively correlated with changes in FIB-4 (r = 0.250, P = 0.005) and APRI (r = 0.262, P = 0.003); similarly decrease in sCD14 was significantly positively correlated with changes in FIB-4 (r = 0.333, P = 0.0001) and APRI (r = 0.457, P < 0.0001).Conclusion:HCV eradication is associated with significant reductions in monocyte/macrophage activation markers that correlate with reductions in markers of hepatic fibrosis. These findings support broad access to and early initiation of HCV treatment in order to decrease immune activation and improve health in HIV-infected persons

A classification system for argumentation schemes

This paper explains the importance of classifying argumentation schemes, and outlines how schemes are being used in current research in artificial intelligence and computational linguistics on argument mining. It provides a survey of the literature on scheme classification. What are so far generally taken to represent a set of the most widely useful defeasible argumentation schemes are surveyed and explained systematically, including some that are difficult to classify. A new classification system covering these centrally important schemes is built