ABSTRACT
Rheumatoid arthritis (RA) synovial fluid (SF)-T lymphocytes appear relatively inactive in situ and respond only weakly to diverse stimuli ex vivo. To characterize the molecular defects underlying this hyporesponsiveness we analyzed the expression level of several proteins involved in TCR-proximal signal transduction. As compared to peripheral blood (PB)-T lymphocytes, SF-T cells from some (but not all) of the patients analyzed expressed lower levels of TCRalphabeta, CD3epsilon, TCRzeta, p56(lck) and LAT, while p59(fyn), phospholipase C-gamma1 and ZAP-70 expression was unaltered. Semi-quantitative analysis of T cells from several patients revealed that the degree of TCRzeta chain and p56(lck) modulation correlated statistically significantly with the level of SF-T cell hyporesponsiveness. The differential reactivity of p56(lck) specific monoclonal and polyclonal antibodies in SF-T but not PB-T lymphocytes indicated that p56(lck) modulation consists of a conformational change rather than loss of expression. Our results indicate that multiple signaling molecules can be modulated in RA SF-T cells and show for the first time a direct quantitative correlation between T cell hyporesponsiveness and modulation of TCRzeta and of p56(lck), a critical protein tyrosine kinase required for T cell activation.
Subject(s)
Arthritis, Rheumatoid/enzymology , Autoimmune Diseases/enzymology , CD3 Complex , Defensins , Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/physiology , Synovial Fluid/immunology , T-Lymphocyte Subsets/immunology , Adult , Aged , Antibodies, Monoclonal/immunology , Arthritis, Rheumatoid/immunology , Autoimmune Diseases/immunology , Female , Humans , Knee Joint , Lymphocyte Activation , Male , Membrane Proteins/immunology , Middle Aged , Plant Proteins , Protein Conformation , Receptors, Antigen, T-Cell/analysis , Receptors, Antigen, T-Cell/immunology , Receptors, Antigen, T-Cell, alpha-beta/analysisABSTRACT
This report describes a 2-year, longitudinal study of one school district's effort to link site-based, collaborative evaluation with formal, centralized program evaluation. Participants formed a research team in partnership with a local university. Team members assisted leadership teams in identifying issues for informal, site-based assessments and then used the information to monitor progress toward established goals. Participants collaborated in designing and conducting informal assessments of student achievement, school climate and safety, discipline, and parent involvement. Leadership teams used these data in developing their school improvement plans. Researchers and administrators used these data to revise the districtwide survey. At the end of the 2-year cycle, analysis of school improvement plans showed that collaborative evaluation is creating a connection between dialogue and data. These 17 middle schools are approaching school improvement in a more integrated fashion by actively involving key stakeholders (students, parents, and teachers) in the evaluation process.
Subject(s)
Communication , Cooperative Behavior , Leadership , Program Evaluation/methods , Schools/standards , Total Quality Management/organization & administration , Adult , Attitude , Child , Data Collection , Data Interpretation, Statistical , Faculty , Humans , Models, Organizational , North Carolina , Organizational Objectives , Students/psychologySubject(s)
Methylene Blue/therapeutic use , Periodontitis/drug therapy , Adult , Bacteria, Aerobic/drug effects , Bacteria, Aerobic/isolation & purification , Bacteria, Anaerobic/drug effects , Bacteria, Anaerobic/isolation & purification , Chronic Disease , Female , Humans , Male , Middle Aged , Periodontitis/microbiologyABSTRACT
A small-scale clinical trial was carried out to evaluate the effect of a redox agent, methylene blue, on microbiological and clinical indices of chronic periodontitis. Methylene blue was applied subgingivally on a daily basis for 7 d to 25 test sites in 7 patients and the sites evaluated clinically and microbiologically for up to 14 d: 25 control sites in the same patients received sterile water. The test sites showed statistically significant differences from the control sites in terms of changes in a number of clinical and microbiological indices. In the test sites the proportions of anaerobes, Gram-negative anaerobes, spirochetes and motile bacteria decreased, as did the crevicular fluid flow, while the proportions of facultative anaerobes and cocci increased. These changes are indicative of a shift towards periodontal health. No significant differences were observed between the test and control sites in terms of bleeding on probing or pocket depth. The encouraging results of this preliminary study suggest that the use of redox agents in the treatment of chronic periodontitis warrants further investigation.
