A novel 'multistep molecular mimicry' mechanism for induction of rheumatoid arthritis (RA) by bacterial antigens that activate T lymphocytes previously 'educated' by peptides derived from a class of human histocompatibility antigens is reported here. These antigens have the amino acid sequence QKRAA, which is also present on the Escherichia coli heat-shock protein dnaJ. Synovial fluid cells of early RA patients have strong immune responses to the bacterial antigen, but cells from normal subjects or controls with other autoimmune diseases do not. The activated T cells may cross-react with autologous dnaJ heat-shock proteins that are expressed at synovial sites of inflammation. Our findings may have direct relevance to new strategies for the immune therapy of RA.
The current study examined the differences between three types of violent men based on Holtzworth-Munroe and Stuart's (1994) tripartite typology and a group of non-intimate violent men. First, a cluster analysis was conducted on a sample of 91 domestically violent men, resulting in three clusters that approximated the tripartite model for psychopathology as measured by the MMPI-2, that is, non-pathological, borderline/dysphoric, and antisocial. Based on the violence variables (i.e., severity of violence, family-only violence, and exposure to family of origin violence) only severity of violence approximated what would be expected across the three clusters, that is, the less the psychopathology, the less severe the violence. The other two violence variables had approximate frequencies/percentages of occurrence that would be expected for individual typologies with some but not all three typologies. In comparing the three intimate violent typologies to the non-intimate violent group, the non-intimate and non-pathological groups were within normal limits and did not differ significantly on any of the MMPI-2 scales. These non-intimate and non-pathological groups differed significantly from the antisocial and borderline/dysphoric groups on all the scales that defined the psychopathology of these two groups. On the violence variables, the non-intimate groups reported significantly less severe violence than the borderline/dysphoric and antisocial groups.
Physical trauma to the brain has always been known to affect brain functions and subsequent neurobiological development. Research primarily since the early 1990s has shown that psychological trauma can have detrimental effects on brain function that are not only lasting but that may alter patterns of subsequent neurodevelopment, particularly in children although developmental effects may be seen in adults as well. Childhood trauma produces a diverse range of symptoms and defining the brain's response to trauma and the factors that mediate the body's stress response systems is at the forefront of scientific investigation. This paper reviews the current evidence relating psychological trauma to anatomical and functional changes in the brain and discusses the need for accurate diagnosis and treatment to minimize such effects and to recognize their existence in developing treatment programs.
Clinical multiplex diagnostic proteomics is the application of proteomic technologies to improve a patient's clinical outcomes. The future holds impact potential for testing prognosis, diagnosis, and drug therapy, while monitoring efficacious treatment with qualitative and quantitative data. Multiplex clinical diagnostic use of novel biomarkers in body fluids to confirm presence and severity of clinical disease states, holds great promise for clinical use. Challenges for diagnostic clinics include awareness of proteome complexity in clinical samples, the effects of high-abundance proteins, such as albumin, that could mask detection of other and low abundance disease proteins or biomarkers. Standardized approaches to sample collection and preparation, new analytical techniques and novel algorithms for bio-statistical analysis will facilitate release of the great potential of clinical multiplex diagnostic proteomics. A sensitive RA assay has been developed for the simultaneous measurement of the three rheumatoid factors (RFs), RF-IgA, IgG, and IgM, with the option to simultaneously measure anti-cyclic citrullinated peptide (anti-CCP) IgG antibodies using IgXPLEX™: technology. Testing 10-μL serum samples, SQI's multiplex microarray rheumatoid arthritis assay provides both positive/negative as well as qualitative/semi-quantitative results for anti-CCP IgG, RF-IgA, IgG, and IgM in each sample well on a 96-well microtiter-formatted microarray plate. Signal detection uses sensitive fluorescent-tagged markers captured onto planar microarray spots and read in a microarray scanner. Each result is verified with confidence confirmation technology and validating quality controls in every sample well. For an 80-RA positive patient cohort, the 4-PLEX profile sensitivity was determined at 82.5%. The specificity for the 44 RA healthy control cohort was determined at 97.7%. The multiplex data also demonstrated that a patients' severity of disease profile, mild to severe, correlates the status of RA biomarkers to disease status.
In inflammatory arthritis, disease activity in MCP joints can be reliably assessed at the bedside by examining for joint-line tenderness (TJC) and visual inspection for swelling. Clinical assessment may have to be complemented by other methods for evaluating disease activity in the joint, such as MRI, particularly in patients with PsA.
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