Synovial cells are potential sources of inflammatory mediators in bacterial-induced arthritis but their involvement in the inflammatory response to Candida albicans-induced septic arthritis is ...largely unknown.
Primary cultures of rat synovial fibroblasts were infected with C. albicans (ATCC90028). Immunocytochemistry, western blotting, and RT-PCR were performed to assess cyclo-oxygenase 2 induction. Phosphorylation of extracellular-regulated kinase (ERK1/2) following infection in the absence or presence of U0126 was assessed by western blotting whilst prostaglandin E2 production was measured by ELISA. Nuclear factor kappaB (NFkappaB) translocation was evaluated by an electrophoretic mobility shift assay.
Infection of synovial fibroblasts with C. albicans resulted in cyclo-oxygenase 2 expression and prostaglandin E2 production. Cyclo-oxygenase 2 expression and prostaglandin E2 production was dependent upon extracellular-regulated kinase 1/2 phosphorylation, associated with activation of NFkappaB and significantly elevated in the presence of laminarin, an inhibitor of dectin-1 activity. Synovial fibroblasts adjacent to C. albicans hyphae aggregates appeared to be the major contributors to the increased levels of cyclo-oxygenase 2 and phosphorylated extracellular-regulated kinase 1/2.
C. albicans infection of synovial fibroblasts in vitro results in upregulation of cyclo-oxygenase 2 and prostaglandin E2 by mechanisms that may involve activation of extracellular-regulated kinase 1/2 and are associated with NFkappaB activation.
Pathology of soft tissue tumours Oniscu, Anca; Salter, Donald
Surgery (Oxford),
February 2020, 2020-02-00, Letnik:
38, Številka:
2
Journal Article
Recenzirano
Soft tissue tumours are a heterogeneous group of neoplasms with differentiation towards mesenchymal tissue. They may arise anywhere in the body and show similar clinical presentation. Traditional ...histopathological diagnosis is now complemented by molecular diagnostic techniques that have become firmly established ancillary diagnostic methods. This article provides a short overview of the aetiology and clinical features of soft tissue sarcomas with an update on how molecular genetics is influencing classification and management of these rare tumours.
The aim of this study was to demonstrate that differences in the local composition of bi-zonal fibrocartilaginous tissues result in different local biomechanical properties in compression and ...tension. Bovine articular chondrocytes were loaded into hyaluronan-based meshes (HYAFF
®-11) and cultured for 4 weeks in mixed flask, a rotary Cell Culture System (RCCS), or statically. Resulting tissues were assessed histologically, immunohistochemically, by scanning electron microscopy and mechanically in different regions. Local mechanical analyses in compression and tension were performed by indentation-type scanning force microscopy and by tensile tests on punched out concentric rings, respectively. Tissues cultured in mixed flask or RCCS displayed an outer region positively stained for versican and type I collagen, and an inner region positively stained for glycosaminoglycans and types I and II collagen. The outer fibrocartilaginous capsule included bundles (up to 2
μm diameter) of collagen fibers and was stiffer in tension (up to 3.6-fold higher elastic modulus), whereas the inner region was stiffer in compression (up to 3.8-fold higher elastic modulus). Instead, molecule distribution and mechanical properties were similar in the outer and inner regions of statically grown tissues. In conclusion, exposure of articular chondrocyte-based constructs to hydrodynamic flow generated tissues with locally different composition and mechanical properties, resembling some aspects of the complex structure and function of the outer and inner zones of native meniscus.
Cells need to rapidly and precisely react to multiple mechanical and chemical stimuli in order to ensure precise context‐dependent responses. This requires dynamic cellular signalling events that ...ensure homeostasis and plasticity when needed. A less well‐understood process is cellular response to elevated interstitial fluid pressure, where the cell senses and responds to changes in extracellular hydrostatic pressure. Here, using quantitative label‐free digital holographic imaging, combined with genome editing, biochemical assays and confocal imaging, we analyse the temporal cellular response to hydrostatic pressure. Upon elevated cyclic hydrostatic pressure, the cell responds by rapid, dramatic and reversible changes in cellular volume. We show that YAP and TAZ, the co‐transcriptional regulators of the Hippo signalling pathway, control cell volume and that cells without YAP and TAZ have lower plasma membrane tension. We present direct evidence that YAP/TAZ drive the cellular response to hydrostatic pressure, a process that is at least partly mediated via clathrin‐dependent endocytosis. Additionally, upon elevated oscillating hydrostatic pressure, YAP/TAZ are activated and induce TEAD‐mediated transcription and expression of cellular components involved in dynamic regulation of cell volume and extracellular matrix. This cellular response confers a feedback loop that allows the cell to robustly respond to changes in interstitial fluid pressure.
Synopsis
YAP/TAZ transcriptional co‐activators are central regulators of cellular response to changes in the extracellular and intracellular mechanical environment. This study identifies oscillating hydrostatic pressure as a new regulator of cell volume via YAP/TAZ activation.
YAP/TAZ regulate cell volume and plasma membrane tension
Oscillating hydrostatic pressure induces rapid and reversible changes in cellular volume
YAP/TAZ activation are essential for the cellular response to hydrostatic pressure
Cellular response to oscillating hydrostatic pressure involves clathrin‐dependent endocytosis and the actin cytoskeleton
Oscillating hydrostatic pressure induces changes in cell volume by activating transcriptional co‐activators YAP/TAZ via a process involving clathrin‐dependent endocytosis and actin cytoskeleton.
Aims: CD98 is a component of the large neutral amino acid transporter (LAT), which is a cell surface amino acid transporter. CD98 also binds to and activates β1‐integrin, promoting ...anchorage‐independent growth. CD98 expression is increased in a variety of carcinomas but its distribution in the normal and neoplastic thyroid gland has not been reported. The aim was to examine the immunohistochemical expression of CD98 in normal and diseased thyroid tissue.
Methods and results: One hundred and forty thyroid cases were selected from the archives of the Department of Pathology, including normal controls, neoplasms (follicular adenoma, follicular carcinoma and papillary carcinoma) and non‐neoplastic conditions (multinodular goitre, Graves’ disease and Hashimoto’s thyroiditis). Immunohistochemistry for CD98 was performed and each case was scored for proportion of cells and intensity of immunoreactivity. In normal thyroid, there was moderately strong expression of CD98 in the lateral cell membranes of follicular cells. A similar pattern of expression was seen in follicular adenoma, minimally invasive follicular carcinoma, multinodular goitre and Graves’ disease. In most cases of papillary carcinoma and in the inflamed areas of Hashimoto’s thyroiditis, expression of CD98 was decreased.
Conclusions: CD98 expression is down‐regulated in thyroid papillary carcinoma; this may relate to the better prognosis associated with many of these tumours.
The standardized maritime pine bark extract (Pycnogenol®) has previously shown symptom alleviating effects in patients suffering from moderate forms of knee osteoarthritis (OA). The cellular ...mechanisms for this positive impact are so far unknown. The purpose of the present randomized pilot controlled study was to span the knowledge gap between the reported clinical effects of Pycnogenol® and its in vivo mechanism of action in OA patients.
Thirty three patients with severe OA scheduled for a knee arthroplasty either received 100 mg of Pycnogenol® twice daily or no treatment (control group) three weeks before surgery. Cartilage, synovial fluid and serum samples were collected during surgical intervention. Relative gene expression of cartilage homeostasis markers were analyzed in the patients' chondrocytes. Inflammatory and cartilage metabolism mediators were investigated in serum and synovial fluid samples.
The oral intake of Pycnogenol® downregulated the gene expression of various cartilage degradation markers in the patients' chondrocytes, the decrease of MMP3, MMP13 and the pro-inflammatory cytokine IL1B were statistically significant (p ≤ 0.05). Additionally, protein concentrations of ADAMTS-5 in serum were reduced significantly (p ≤ 0.05) after three weeks intake of the pine bark extract.
This is the first report about positive cellular effects of a dietary supplement on key catabolic and inflammatory markers in patients with severe OA. The results provide a rational basis for understanding previously reported clinical effects of Pycnogenol® on symptom scores of patients suffering from OA.
ISRCTN10754119 . Retrospectively registered 08/10/2015.
Bizarre parosteal osteochondromatous proliferations (BPOP), also known as Nora's lesions, are rare tumors occurring most commonly in the hands and feet. They are benign and rarely exhibit ...radiological evidence of cortical invasion. We report a case of BPOP showing atypical magnetic resonance imaging features that are inconsistent with BPOP and having a novel chromosomal aberration. We also review the BPOP cases in our regional benign bone tumor database. Level of Clinical Evidence: 4
OBJECTIVES To determine the validity of the histological-histochemical grading system (HHGS) for osteoarthritic (OA) articular cartilage. METHODS Human articular cartilage was obtained from ...macroscopically normal (n = 13) and OA (n = 21) knee joints. Sections of central and peripheral regions of normal samples were produced. Sections of regions containing severe, moderate, and mild OA changes were produced from each OA sample. A total of 89 sections were graded by means of the HHGS (0–14) twice by three observers. RESULTS Average scores for regions designated severe (8.64) and moderate (5.83) OA were less than the expected (10–14 and 6–9, respectively) according to the HHGS, whereas average scores for the region designated mild (5.29) OA and central and peripheral regions (2.19) of normal cartilage were higher than expected (2–5 and 0–1, respectively). The HHGS was capable of differentiating between articular cartilage from macroscopically normal and OA joints and between the region designated severe OA and other regions. However, the HHGS did not adequately differentiate between regions designated mild and moderate OA. Values for sensitivity, specificity, and efficiency for all regions varied considerably. CONCLUSION The HHGS is valid for normal and severe OA cartilage, but does not permit distinction between mild and moderate OA changes in articular cartilage.
Objective
The purpose of this study was to determine if there were variations in chondrocyte viability, matrix glycosaminoglycan (GAG), and water content between different areas of the articular ...surface of a bovine metatarsophalangeal joint, a common and reliable source of articular cartilage for experimental study, which may compromise the validity of using multiple samples from different sites within the joint.
Methods
Nine fresh cadaveric bovine metatarsophalangeal joints were obtained. From each joint, 16 osteochondral explants were taken from 4 facets, yielding a total of 144 cartilage specimens for evaluation of chondrocyte viability, matrix GAG, and water content. A less invasive method for harvesting osteochondral explants and for processing the biopsy for the assessment of chondrocyte viability was developed, which maintained maximal viability within each cartilage explant.
Results
There was no significant difference between the 16 biopsy sites from the different areas of the joint surface with respect to chondrocyte viability, matrix GAG and water content. Pooled data of all samples from each joint established the baseline values of chondrocyte viability to be 89.4% ± 3.8%, 94.4% ± 2.2%, and 77.9% ± 7.8%, in the superficial quarter, central half, and deep quarter (with regard to depth from the articular surface), respectively. The matrix GAG content of bovine articular cartilage was 6.06 ± 0.41 μg/mg cartilage, and the cartilage water content was 72.4% ± 1.5%. There were also no significant differences of these 3 variables between the different joints.
Conclusion
It is thus reasonable to compare biopsies obtained from different sites, as a biopsy from one site would be considered representative of the whole joint.
Neutrophils act as a first line of defense against bacterial and fungal infections, but they are also important effectors of acute and chronic inflammation. Genome-wide association studies have ...established that the gene encoding the protein tyrosine phosphatase nonreceptor 22 (PTPN22) makes an important contribution to susceptibility to autoimmune disease, notably rheumatoid arthritis. Although PTPN22 is most highly expressed in neutrophils, its function in these cells remains poorly characterized. We show in this article that neutrophil effector functions, including adhesion, production of reactive oxygen species, and degranulation induced by immobilized immune complexes, were reduced in Ptpn22
neutrophils. Tyrosine phosphorylation of Lyn and Syk was altered in Ptpn22
neutrophils. On stimulation with immobilized immune complexes, Ptpn22
neutrophils manifested reduced activation of key signaling intermediates. Ptpn22
mice were protected from immune complex-mediated arthritis, induced by the transfer of arthritogenic serum. In contrast, in vivo neutrophil recruitment following thioglycollate-induced peritonitis and in vitro chemotaxis were not affected by lack of PTPN22. Our data suggest an important role for PTPN22-dependent dephosphorylation events, which are required to enable full FcγR-induced activation, pointing to an important role for this molecule in neutrophil function.
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