5 results on '"Amanda A, Watkins"'
Search Results
2. Promotion of Inflammatory Arthritis by Interferon Regulatory Factor 5 in a Mouse Model
- Author
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Pierre Duffau, Carla M. Cuda, Harris Perlman, Lisa M. Rice, G. Kenneth Haines, Ian R. Rifkin, Ellen M. Gravallese, Tamar Aprahamian, Paul A. Monach, Salina Dominguez, Rebecca Baum, Kei Yasuda, Hanni Menn-Josephy, Robert Lafyatis, Christophe Richez, Ramon G. Bonegio, and Amanda A. Watkins
- Subjects
Inflammatory arthritis ,Immunology ,virus diseases ,Arthritis ,Biology ,medicine.disease ,Proinflammatory cytokine ,Rheumatology ,TRIF ,Rheumatoid arthritis ,medicine ,TLR4 ,Immunology and Allergy ,IRF5 ,Interferon regulatory factors - Abstract
Objective Polymorphisms in the transcription factor interferon regulatory factor 5 (IRF5) are associated with an increased risk of developing rheumatoid arthritis (RA). This study was undertaken to determine the role of IRF5 in a mouse model of arthritis development. Methods K/BxN serum–transfer arthritis was induced in mice deficient in IRF5, or lacking IRF5 only in myeloid cells, and arthritis severity was evaluated. K/BxN arthritis was also induced in mice deficient in TRIF, Toll-like receptor 2 (TLR2), TLR3, TLR4, and TLR7 to determine the pathways through which IRF5 might promote arthritis. In vitro studies were performed to determine the role of IRF5 in interleukin-1 (IL-1) receptor and TLR signaling. Results Arthritis severity was reduced in IRF5-deficient, TRIF-deficient, TLR3-deficient, and TLR7-deficient mice. The expression of multiple genes regulating neutrophil recruitment or function and bioactive IL-1β formation was reduced in the joints during active arthritis in IRF5-deficient mice. In vitro studies showed that TLR7 and the TRIF-dependent TLR3 pathway induce proinflammatory cytokine production in disease-relevant cell types in an IRF5-dependent manner. Conclusion Our findings indicate that IRF5 contributes to disease pathogenesis in inflammatory arthritis. This is likely due at least in part to the role of IRF5 in mediating proinflammatory cytokine production downstream of TLR7 and TLR3. Since TLR7 and TLR3 are both RNA-sensing TLRs, this suggests that endogenous RNA ligands present in the inflamed joint promote arthritis development. These findings may be relevant to human RA, since RNA capable of activating TLR7 and TLR3 is present in synovial fluid and TLR7 and TLR3 are up-regulated in the joints of RA patients.
- Published
- 2015
3. New mothers' experiences of social disruption and isolation during the severe acute respiratory syndrome outbreak in Hong Kong
- Author
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Amanda L. Watkins, Yuet Oi Chee, Joan E. Dodgson, and Marie Tarrant
- Subjects
medicine.medical_specialty ,business.industry ,media_common.quotation_subject ,Daily stress ,Outbreak ,General Medicine ,Disease ,Prenatal care ,medicine.disease ,Spouse ,medicine ,Medical emergency ,Psychiatry ,business ,Social disruption ,General Nursing ,Qualitative research ,Vigilance (psychology) ,media_common - Abstract
In Hong Kong during the severe acute respiratory syndrome outbreak of 2003, sustained uncertainty caused daily stress for residents for > 3 months. Expectant women experienced unexpected social disruption and isolation within their day-to-day life that have not been described in their own voice. The purpose of this study was to describe the experiences of women who became mothers during the outbreak and the ways in which these experiences impacted their early post-partum mothering. A phenomenological research design was chosen. The participants' responses then led the interview process. As the women's experiences had many similarities, saturation was reached after eight interviews. Four themes emerged: living with uncertainty, intense vigilance, isolation, and disrupted expectations. The participants spoke of disrupted daily routines as they tried to eliminate their risk of contracting this disease, including relationship difficulties with their spouse. None of the women had the birth experience they had hoped for because of changes in hospital practices.
- Published
- 2010
4. Dexmedetomidine preconditioning reduces ischaemia-reperfusion injury in equine model of large colon volvulus.
- Author
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Watkins A, Engiles J, Long A, Brandly J, and Hopster K
- Subjects
- Animals, Horses, Male, Female, Adrenergic alpha-2 Receptor Agonists pharmacology, Adrenergic alpha-2 Receptor Agonists administration & dosage, Adrenergic alpha-2 Receptor Agonists therapeutic use, Ischemic Preconditioning veterinary, Ischemic Preconditioning methods, Colon pathology, Dexmedetomidine pharmacology, Dexmedetomidine administration & dosage, Dexmedetomidine therapeutic use, Reperfusion Injury veterinary, Reperfusion Injury prevention & control, Horse Diseases prevention & control, Horse Diseases drug therapy, Horse Diseases pathology, Intestinal Volvulus veterinary, Intestinal Volvulus prevention & control, Colonic Diseases veterinary, Colonic Diseases prevention & control
- Abstract
Background: Large colon volvulus is a cause of colic in horses with high morbidity and mortality when not promptly treated. More treatment options are needed to improve the outcome of these cases by protecting against the damage caused by ischaemia and reperfusion injury., Objectives: To determine the effect of preconditioning with dexmedetomidine prior to induction of ischaemia-reperfusion (IR) injury in a large colon volvulus model in the horse., Study Design: Randomised blinded in vivo experiments., Methods: Horses received either a dexmedetomidine (DEX) or saline (CON) constant rate infusion (CRI) immediately following induction of anaesthesia. Venous, arterial, and transmural occlusion of a section of the large colon was performed for 3 h, after which the ligatures and clamps were removed to allow for reperfusion for 3 h. Biopsies of the large colon were taken at baseline, 1 and 3 h of ischaemia, and at 1 and 3 h of reperfusion., Results: The severity of crypt epithelial loss (DEX = 2.1 [0.8-2.8], CON = 3.1 [2.5-4], p = 0.03) and mucosal haemorrhage was decreased (DEX = 2.1 [1.3-3], CON = 3.5 [2.5-4], p = 0.03) in group DEX compared to group CON when graded on a scale of 0-4. Crypt length remained longer (DEX = 369.5 ± 91.7 μm, CON = 238.5 ± 72.6 μm, p = 0.02) and interstitium to crypt (I:C) ratio remained lower (DEX = 1.4 (1-1.7), CON = 2.6 [1.8-5.9], p = 0.03) in group DEX compared to group CON during reperfusion., Main Limitations: Clinical applicability of pharmacologic preconditioning is limited., Conclusion: Preconditioning with a dexmedetomidine CRI prior to IR injury demonstrated a protective effect histologically on the large colon in the horse. Further investigation into postconditioning with dexmedetomidine is warranted as a possible intervention in colic cases suspected of being large colon volvulus., (© 2024 The Author(s). Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)
- Published
- 2024
- Full Text
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5. Loss of effective lubricating viscosity is the primary mechanical marker of joint inflammation in equine synovitis.
- Author
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Vishwanath K, Secor EJ, Watkins A, Reesink HL, and Bonassar LJ
- Subjects
- Animals, Horses, Viscosity, Horse Diseases metabolism, Dinoprostone metabolism, Dinoprostone analysis, Osteoarthritis, Synovitis, Synovial Fluid chemistry, Synovial Fluid metabolism, Biomarkers metabolism, Biomarkers analysis
- Abstract
Inflammation of the synovium, known as synovitis, plays an important role in the pathogenesis of osteoarthritis (OA). Synovitis involves the release of a wide variety of pro-inflammatory mediators in synovial fluid (SF) that damage the articular cartilage extracellular matrix and induce death and apoptosis in chondrocytes. The composition of synovial fluid is dramatically altered by inflammation in OA, with changes to both hyaluronic acid and lubricin, the primary lubricating molecules in SF. However, the relationship between key biochemical markers of joint inflammation and mechanical function of SF is not well understood. Here, we demonstrate the application of a novel analytical framework to measure the effective viscosity for SF lubrication of cartilage, which is distinct from conventional rheological viscosity. Notably, in a well-established equine model of synovitis, this effective lubricating viscosity decreased by up to 10,000-fold for synovitis SF compared to a ~4 fold change in conventional viscosity measurements. Further, the effective lubricating viscosity was strongly inversely correlated (r = -0.6 to -0.8) to multiple established biochemical markers of SF inflammation, including white blood cell count, prostaglandin E
2 (PGE2 ), and chemokine ligand (CCLs) concentrations, while conventional measurements of viscosity were poorly correlated to these markers. These findings demonstrate the importance of experimental and analytical approaches to characterize functional lubricating properties of synovial fluid and their relationships to soluble biomarkers to better understand the progression of OA., (© 2024 Orthopaedic Research Society.)- Published
- 2024
- Full Text
- View/download PDF
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