Biomedical subjects

Iain B McInnes

Publications and source records attributed to Iain B McInnes.

39 records · Page 3Linked to original sources

PubMed2002

Novel pathways that regulate tumor necrosis factor-alpha production in rheumatoid arthritis.

Clinical intervention studies have clearly shown the benefit in suppressing tumor necrosis factor-alpha (TNF-alpha) rheumatoid arthritis (RA). In consequence, considerable interest has arisen in those pathways that in turn regulate TNF-alpha production, because they may offer further possible therapeutic targets. Several candidate pathways are currently being investigated. They include T cell/macrophage interactions mediated primarily through cell-cell membrane contact; novel cytokine activities; microbial-derived products, in particular bacterial deoxyribonucleic acid sequences; autoreactive T cells, and immunoglobulins. At the subcellular level, there is further interest in targeting signaling and mRNA processing and cytokine cleavage pathways required for optimal TNF-alpha production. The key recent observations in these areas, particularly in the extracellular compartment, are reviewed.

Arthritis, Rheumatoid↗

PubMed2002

Human platelets stimulate mesangial cells to produce monocyte chemoattractant protein-1 via the CD40/CD40 ligand pathway and may amplify glomerular injury.

Platelets are thought to play an important role in the initiation and the progression of a variety of glomerulonephritides. This study examined whether platelets induce production of monocyte chemoattractant protein-1 (MCP-1), a chemokine involved in leukocyte recruitment and glomerular injury, by cultured human mesangial cells (MC). To this end, platelets isolated from normal human donors were cocultured with MC at various ratios. MCP-1 synthesis was evaluated by quantitative real-time PCR and enzyme-linked immunosorbent assay. Platelets at 1:100 ratio (MC to platelets) induced an approximately 20-fold increase in mesangial MCP-1 mRNA and protein expression through an obligatory cell-to-cell contact-dependent mechanism. Importantly, blockade of the CD40/CD40 ligand (CD40L) pathway with neutralizing antibodies decreased MCP-1 production by approximately 60%. It was confirmed that CD40 was functionally expressed on MC. Gel-shift assays and inhibitors of phosphorylation were used to demonstrate that activation of p38 mitogen-activated protein kinase, protein tyrosine kinases, and nuclear factor-kappa B activation were essential for MCP-1 production. These data indicate that platelet/MC contact stimulates the production of MCP-1 and may contribute to glomerular inflammatory responses by recruiting leukocytes from the peripheral blood.

Blood Platelets↗

PubMed2002

Ultrasound guided versus conventional joint and soft tissue fluid aspiration in rheumatology practice: a pilot study.

OBJECTIVE: To compare joint and soft tissue aspiration using a conventional technique with an ultrasound (US) guided technique. METHODS: In the conventional group, 32 joints in 30 consecutive patients referred for joint aspiration and injection to an experienced consultant rheumatologist were aspirated. In the US guided group, 31 consecutive patients were examined by US to confirm the presence and location of fluid. Following US examination, aspiration was performed by a second rheumatologist based on the US localization of fluid or under direct US guidance. RESULTS: In the conventional group, successful aspiration was achieved in 10 (32%) joints. In the US guided group, successful aspiration was achieved in 31 (97%) joints. The mean volume of fluid obtained from successful aspirations was similar in both groups (11.7 ml in the US group and 14 ml in the conventional group). CONCLUSION: The use of US to localize joint and soft tissue fluid collection greatly improves the rate of diagnostic synovial fluid aspiration, particularly in small joints. This has important implications for accurate administration of local steroid therapy and emphasizes the importance of US as a useful tool in clinical rheumatological practice.

Adult↗