C-terminal citrullinated peptide alters antigen-specific APC:T cell interactions leading to breach of immune tolerance

In rheumatoid arthritis, the emergence of anti-citrullinated autoimmunity is associated with HLA-antigen-T cell receptor complexes. The precise mechanisms underpinning this breach of tolerance are not well understood. Porphyromonas gingivalis expresses an enzyme capable of non-endogenous C-terminal citrullination with potential to generate citrullinated autoantigens. Here we document how C-terminal citrullination of ovalbumin peptide323-339 alters the interaction between antigen-presenting cells and OTII T cells to induce functional changes in responding T cells. These data reveal that C-terminal citrullination is sufficient to breach T cell peripheral tolerance in vivo and reveal the potential of C-terminal citrullination to lower the threshold for T cell activation. Finally, we demonstrate a role for the IL-2/STAT5/CD25 signalling axis in breach of tolerance. Together, our data identify a tractable mechanism and targetable pathways underpinning breach of tolerance in rheumatoid arthritis and provide new conceptual insight into the origins of anti-citrullinated autoimmunity

Maternal distress and perceptions of infant development following extracorporeal membrane oxygenation and conventional ventilation for persistent pulmonary hypertension

Neurodevelopmental outcome and concurrent maternal distress were examined for infants who suffered persistent pulmonary hypertension at birth and were treated with either extracorporeal membrane oxygenation (ECMO) ( n = 19) or conventional ventilation (CV) ( n = 15). Mothers were asked to complete inventories assessing their infant's (mean age 8.74 months) developmental growth as well as their own psychological health. Relevant sociodemographic and treatment parameters were also entered into the analysis. The results indicated that ECMO and CV infants did not differ on developmental indices and impairment rates were 15–23% respectively, similar to previous reports, in addition, ECMO and CV mothers did not differ in their reports of psychological distress. Correlational analyses revealed that length of treatment for ECMO but not CV infants significantly predicted developmental delay and maternal distress. For CV mothers, maternal distress was associated with the perception of delayed language. The results are discussed in terms of the limited morbidity associated with ECMO and CV interventions and the possible role of a ‘vulnerable child syndrome’ in understanding the maternal-infant relationship following ECMO therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73367/1/j.1365-2214.1995.tb00410.x.pd

Immunohistochemical Method and Histopathology Judging for the Systemic Synuclein Sampling Study (S4)

Immunohistochemical (IHC) α-synuclein (Asyn) pathology in peripheral biopsies may be a biomarker of Parkinson disease (PD). The multi-center Systemic Synuclein Sampling Study (S4) is evaluating IHC Asyn pathology within skin, colon and submandibular gland biopsies from 60 PD and 20 control subjects. Asyn pathology is being evaluated by a blinded panel of specially trained neuropathologists. Preliminary work assessed 2 candidate immunoperoxidase methods using a set of PD and control autopsy-derived sections from formalin-fixed, paraffin-embedded blocks of the 3 tissues. Both methods had 100% specificity; one, utilizing the 5C12 monoclonal antibody, was more sensitive in skin (67% vs 33%), and was chosen for further use in S4. Four trainee neuropathologists were trained to perform S4 histopathology readings; in subsequent testing, their scoring was compared to that of the trainer neuropathologist on both glass slides and digital images. Specificity and sensitivity were both close to 100% with all readers in all tissue types on both glass slides and digital images except for skin, where sensitivity averaged 75% with digital images and 83.5% with glass slides. Semiquantitative (0-3) density score agreement between trainees and trainer averaged 67% for glass slides and 62% for digital images

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Down regulation of PSA by C/EBPα is associated with loss of AR expression and inhibition of PSA promoter activity in the LNCaP cell line

10.1186/1471-2407-6-158BMC Cancer615