Algorithm to predict radiological erosions in early rheumatoid arthritis. Messages from paper are incorrect.
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Algorithms↗
Biomedical subjects
P Emery
Publications and source records attributed to P Emery.
RFX proteins, a novel family of DNA binding proteins conserved in the eukaryotic kingdom.
Until recently, the RFX family of DNA binding proteins consisted exclusively of four mammalian members (RFX1-RFX4) characterized by a novel highly conserved DNA binding domain. Strong conservation of this DNA binding domain precluded a precise definition of the motif required for DNA binding. In addition, the biological systems in which these RFX proteins are implicated remained obscure. The recent identification of four new RFX genes has now shed light on the evolutionary conservation of the RFX family, contributed greatly to a detailed characterization of the RFX DNA binding motif, and provided clear evidence for the function of some of the RFX proteins. RFX proteins have been conserved throughout evolution in a wide variety of species, including Saccharomyces cerevisiae, Schizosaccharomyces pombe, Caenorhabditis elegans, mouse and man. The characteristic RFX DNA binding motif has been recruited into otherwise very divergent regulatory factors functioning in a diverse spectrum of unrelated systems, including regulation of the mitotic cell cycle in fission yeast, the control of the immune response in mammals, and infection by human hepatitis B virus.
Amino Acid Sequence↗
Minocycline induced autoimmune hepatitis and systemic lupus erythematosus-like syndrome.
Monocycline is the most widely prescribed systemic antibiotic for acne largely because it needs to be given only once or twice a day and seems not to induce resistance. Up to April 1994 11 cases of minocycline induced systemic lupus erythematosus and 16 cases of hepatitis had been reported to the Committee on Safety of Medicines. An analysis of these cases together with seven other cases shows the severity of some of these reactions. Two patients died while taking the drug for acne and a further patient needed a liver transplant. Acne itself can induce arthritis and is often seen in association with autoimmine liver disease, but the clinical and biochemical resolution seen after withdrawal of the drug, despite deterioration of the acne, suggests a drug reaction. In five cases re-exposure led to recurrence. Because reactions may be severe early recognition is important to aid recovery and also to avoid invasive investigations and treatments such as corticosteroids and immunosuppresants. Safer alternatives should be considered for treating acne.
Acne Vulgaris↗
Antibodies to type II collagen in early rheumatoid arthritis. Correlation with disease progression.
OBJECTIVE: To establish that frequencies and levels of IgG antibodies to type II collagen are higher in early rheumatoid arthritis (RA), and to correlate these results with disease activity. METHODS: Forty-four patients were characterized as having early RA. Patient sera obtained at initial presentation and at 12 months were tested by enzyme-linked immunosorbent assay for IgG antibodies to native and denatured type II collagen. RESULTS: IgG antibodies to native and denatured type II collagen were detected at initial presentation in 27% and 82% of patients, respectively, and after 12 months in 14% and 50%, respectively. The presence of antibodies to native collagen was associated with activity of RA and severity of symptoms, and loss of antibodies at 12 months was associated with initially erosive RA and the DRB1 disease susceptibility motif. CONCLUSION: Levels of serum IgG antibodies to collagen in RA decrease over time and, therefore, are not attributable simply to cartilage destruction. The presence of early positivity for these antibodies, together with the RA susceptibility motif, appears to be predictive of rapidly progressive RA.
Adult↗
DXA scanning.
The steady improvement in densitometric technique is reviewed in this paper culminating in the newest generation of DXA scanners. The suitability of the lumbar spine, femur and hand as sites for the densitometric measurement of bone loss in rheumatoid disease is assessed. The recent improvement in hand scanning technique using DXA has led to improved clinical utility in the detection of juxta-articular bone loss. The enhanced resolution offered by the newest, solid state detector DXA scanners, and their ability to detect bone loss where no systemic features are evident, makes it possible that DXA scanning of the hand will be a useful modality for the monitoring of early rheumatoid disease.
Absorptiometry, Photon↗
Clinical associations of dual-energy X-ray absorptiometry measurement of hand bone mass in rheumatoid arthritis.
Hand bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry (DXA) has potential as a marker of progression in early rheumatoid arthritis (RA). We examined a DXA methodology and studied in a cross-sectional manner 202 patients with RA. Hand BMD correlated inversely with age and was higher in males. Hand BMD correlated with lumbar and femoral sites. In females, BMD of the hand correlated positively with grip strength and negatively with disability. Those with higher C-reactive protein (CRP) had significantly lower hand BMD than those with normal CRP. In patients with a normal CRP, the hand BMD:lumbar BMD ratios were significantly higher in patients with longer disease duration. Hand BMD correlates with measures of disease activity, functional capacity and also with lumbar and femoral BMD. Hand bone loss occurs in early disease, in the absence of detectable systemic disease, and before lumbar BMD loss. It has the potential to be an outcome measure in early disease.
Absorptiometry, Photon↗
Active systemic lupus erythematosus is associated with the recruitment of naive/resting T cells.
The aim of this study was to determine whether active systemic lupus erythematosus (SLE) is associated with recruitment of resting CD45RA+ T cells or reactivation of CD45RO+ memory T cells. Three-colour immunofluorescence was used to determine CD45 isoform expression by CD4+ T cells from 28 patients with SLE. Newly recruited and highly differentiated primed T cells were distinguished by their CD45RB expression. The pattern of CD45 isoform expression varied directly with time since the onset of symptoms in patients with active SLE. Shortly after symptoms appeared, most cells were CD45RA+ resting cells or CD45RO(dull)RB(bright) early primed cells. However, over the course of active disease, patients accumulated CD45RO(bright)RB(dull) cells which represent an advanced state of differentiation. The switch from an early to late primed phenotype correlated significantly with time since the onset of symptoms. The recruitment of resting T cells in active SLE, rather than the simple reactivation of existing memory clones, has implications for understanding the pathology of this disease and for treating it.
Biomarkers↗
New perspectives on controlling progression of severe rheumatoid arthritis--a summary of the potential role of cyclosporin.
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Arthritis, Rheumatoid↗
A consensus motif in the RFX DNA binding domain and binding domain mutants with altered specificity.
The RFX DNA binding domain is a novel motif that has been conserved in a growing number of dimeric DNA-binding proteins, having diverse regulatory functions, in eukaryotic organisms ranging from yeasts to humans. To characterize this novel motif, we have performed a detailed dissection of the site-specific DNA binding activity of RFX1, a prototypical member of the RFX family. First, we have performed a site selection procedure to define the consensus binding site of RFX1. Second, we have developed a new mutagenesis-selection procedure to derive a precise consensus motif, and to test the accuracy of a secondary structure prediction, for the RFX domain. Third, a modification of this procedure has allowed us to isolate altered-specificity RFX1 mutants. These results should facilitate the identification both of additional candidate genes controlled by RFX1 and of new members of the RFX family. Moreover, the altered-specificity RFX1 mutants represent valuable tools that will permit the function of RFX1 to be analyzed in vivo without interference from the ubiquitously expressed endogenous protein. Finally, the simplicity, efficiency, and versatility of the selection procedure we have developed make it of general value for the determination of consensus motifs, and for the isolation of mutants exhibiting altered functional properties, for large protein domains involved in protein-DNA as well as protein-protein interactions.
Amino Acid Sequence↗
Should patients with recent onset of rheumatoid arthritis be offered genetic screening?
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Arthritis, Rheumatoid↗
Intra-articular guanethidine injection for resistant shoulder pain: a preliminary double blind study of a novel approach.
OBJECTIVE: To study the effect of intraarticular (IA) sympathetic blockade for the relief of resistant shoulder pain. METHODS: Eighteen patients with shoulder pain resistant to conventional treatment were allocated randomly to two groups, to receive either IA guanethidine 20 mg or IA saline. They were assessed for pain, and range of active movements, before injection and at one, four, and eight weeks after injection. RESULTS: There were no significant differences between groups, but the group receiving guanethidine showed greater improvement in pain relief at all three follow up visits compared with those receiving placebo (9% v 7% at one week; 15% v 6% at four weeks and 36% v 16% at eight weeks). The improvement reached significance (p < 0.05) at the eight week visit compared with baseline. The range of movement was not significantly improved in either group. CONCLUSION: The results suggest that IA guanethidine produced measurable improvement in resistant shoulder pain and that further studies of this novel approach are indicated.
Arthralgia↗
The clinical implications of inhibition of the inducible form of cyclo-oxygenase.
There are 2 isoenzymes of cyclo-oxygenase (COX). There is a constitutive enzyme COX-1 which has a wide tissue distribution. In addition there is an inducible enzyme COX-2 which has a restricted tissue distribution. The inducible enzyme COX-2 is responsible for the generation of prostaglandins at sites of tissue inflammation and its inhibition is associated with an anti-inflammatory action. The constitutive enzyme, COX-1 is responsible for the production of prostaglandins with multiple functions. One well known and clinically important function is the gastroprotective effect of the prostaglandins produced in the gastric mucosa. While selective COX-2 inhibition may be associated with a reduced incidence of gastric adverse effects, a concern remains that its inhibition at other locations may be associated with other adverse effects.
Anti-Inflammatory Agents, Non-Steroidal↗
Clinical implications of selective cyclooxygenase-2 inhibition.
Inducible cyclooxygenase-2 (COX-2), but not constitutive COX-1, can be upregulated in rheumatoid synovial tissue by interleukin-1 beta and phorbol esters and is inhibited by dexamethasone. This supports the role of COX-2 in acute inflammation in arthritis. Selective inhibition of COX-2 by non-steroidal anti-inflammatory drugs (NSAIDs) has been proposed as an approach to reduce their associated side effects while maintaining efficacy. The improved safety profile of selective COX-2 inhibitors will allow more widespread and sustained use than is currently possible with standard NSAIDs. In rheumatoid arthritis they may be used as effective symptomatic relief, in combination with disease modifying therapy at an early stage of disease. In osteoarthritis, and, more particularly, soft tissue rheumatism, pain contributes to the development of chronic disease, therefore the main benefit of selective COX-2 inhibition will be to provide safe, effective pain relief to maintain mobility and reduce disability.
Anti-Inflammatory Agents, Non-Steroidal↗
Considerations for nonsteroidal anti-inflammatory drug therapy: benefits.
In a Gallup survey of general practitioners, rheumatologists, and arthritis patients in six European countries, results indicated that nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed by physicians for their patients with arthritis. In addition, the surveyed patients reported that NSAIDs were effective in relieving arthritic pain, the most prominent symptom of their disease. Thus, NSAIDs continue to be useful and valuable drugs in the management of arthritis.
Anti-Inflammatory Agents, Non-Steroidal↗
Laboratory markers of disease activity.
Rheumatoid arthritis is associated with numerous abnormalities measurable in a laboratory. These are most commonly used to monitor disease but can also provide prognostic information; less frequently they are used to support a clinical diagnosis. In general, quantitative markers are used for monitoring early disease. By contrast, qualitative markers can provide prognostic information of particular relevance to early therapy. The markers with the best features for predication of radiological erosions are the MHC conserved epitope and rheumatoid factor. In established disease most of the quantitative measures indicate poor prognosis. Therefore, the choice of the best marker depends not only on the purpose for which it is desired, but also on the stage of disease.
Acute-Phase Reaction↗
Purified X2 binding protein (X2BP) cooperatively binds the class II MHC X box region in the presence of purified RFX, the X box factor deficient in the bare lymphocyte syndrome.
The conserved X2 box sequence of MHC class II promoters is homologous to TRE/CRE elements, and is required for B cell expression and IFN-gamma induction of MHC class II genes. The X2 binding protein (X2BP) was initially identified as a DNA-binding activity that specifically interacts with the conserved X2 box sequence in both the MHC HLA-DRA and HLA-DRB promoters. To begin to demonstrate that X2BP is the X2 box factor responsible for class II expression in B cells, we have purified X2BP to homogeneity from B cell nuclear extracts using DNA-affinity chromatography. X-box DNA-affinity purification indicates that X2BP is most likely composed of two polypeptides of 120 kDa and 46 kDa. The 120-kDa protein was specifically cross-linked to an X-box probe by exposure to UV irradiation. The 46-kDa subunit of X2BP cross-reacted with anti-rat CREB polyclonal Abs but not to anti-human CREB Abs in Western analysis and supershift assays, indicating that it may be a novel member of the ATF/CREB family. Purified X2BP interacted with purified RFX, a factor that binds to the adjacent X1 box and is absent in some cell lines that are mutant for MHC class II transcription. This interaction increases the DNA-binding half-life of RFX from 5 to at least 60 min, suggesting that X2BP functions in class II MHC gene expression by forming a stable complex with RFX.
Base Sequence↗
Tenidap-modulated proinflammatory cytokine activation of a monocyte cell line.
Dysregulated cytokine production, in particular of the monokines IL-1, IL-6, and TNF, has been implicated in the inflammatory response in rheumatoid arthritis and in promoting the ensuing tissue destruction. The 3-substituted 2-oxindole tenidap has proven anti-inflammatory actions both in vivo and in vitro, among which is the inhibition of TNF and IL-1 production by monocytes following activation by LPS. We have investigated this ability to modulate cytokine activity by studying its effects on cytokine-monocyte interactions and in particular IL-6 production, with the THP-1 monocyte cell line. Tenidap inhibited IL-6 production in a dose-dependent manner when cells were stimulated with a combination of TNF-alpha and IFN-gamma. It also inhibited the priming effect of IFN-gamma, preventing the super-induction of IL-6 production following subsequent stimulation with TNF-alpha and IFN-gamma. These effects occurred under conditions in which the cells were not irreversibly altered with respect to their protein synthetic activity. IFN-gamma-induced up-regulation of HLA-DR was also inhibited by tenidap. Tenidap appears to affect some aspect of the IFN-gamma activation pathway, possibly the differentiation of these immature monocytes to a more mature phenotype. The data presented here indicate that tenidap has the potential to modulate the cytokine network in chronic disease.
Anti-Inflammatory Agents, Non-Steroidal↗