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Biomedical subjects

Richard Reece

Publications and source records attributed to Richard Reece.

7 recordsLinked to original sources
PubMed2006

Uncoupling of endothelial nitric oxidase synthase by hypochlorous acid: role of NAD(P)H oxidase-derived superoxide and peroxynitrite.

OBJECTIVE: The aim of the present study is to determine whether hypochlorous acid (HOCl), the major oxidant of leukocyte-derived myeloperoxidase (MPO), oxidizes the zinc-thiolate center of endothelial nitric oxide synthase (eNOS) and uncouples the enzyme. METHODS AND RESULTS: Exposure of purified recombinant eNOS to HOCl (> or = 100 micromol/L) released zinc and disrupted the enzyme-active eNOS dimers. In parallel with increased detections of both O2*- and ONOO-, clinically relevant concentrations of HOCl disrupted eNOS dimers in cultured human umbilical vein endothelial cells (HUVEC) at concentration 10- to 100-fold lower than those required for recombinant eNOS. In HUVEC, HOCl increased the translocation of both p67(phox) and p47(phox) of NAD(P)H oxidase and the phosphorylation of atypical protein kinase C-zeta. Further, genetic or pharmacological inhibition of either NAD(P)H oxidase-derived O2*- or PKC-zeta or NOS abolished the effects of HOCl on eNOS dimers. Consistently, HOCl increased both O2*- and ONOO- and eNOS dimer oxidation in isolated mouse aortas from C57BL/6 but less in those of gp91(phox) knock-out mice. Finally, in human carotid atherosclerotic arteries, eNOS predominantly existed as monomers in parallel with increased staining of both MPO and 3-nitrotyrosine. CONCLUSIONS: We conclude that HOCl uncouples eNOS by ONOO- generated from PKC-zeta-dependent NAD(P)H oxidase.

Animals↗
PubMed2004

Regional variation and differential response to therapy for knee synovitis adjacent to the cartilage-pannus junction and suprapatellar pouch in inflammatory arthritis: implications for pathogenesis and treatment.

OBJECTIVE: To use magnetic resonance imaging (MRI) to investigate the importance of knee joint synovitis at the cartilage-pannus junction (CPJ) in rheumatoid arthritis (RA) as compared with synovitis at a distant site in the suprapatellar pouch (SPP) and as compared with CPJ synovitis in the spondylarthropathies (SpA), and to assess the relative response of knee joint synovitis to therapy at the CPJ and SPP sites. METHODS: Dynamic contrast-enhanced MRI (DEMRI) of actively involved knee joints in 24 patients (13 with RA and 11 with SpA) was undertaken. The area of synovitis was calculated at the CPJ and SPP regions of interest in patients with RA and in patients with SpA. Differences in CPJ and SPP synovitis were determined using calculated DEMRI parameters which included the initial rate of contrast enhancement (IRE) and the maximal enhancement (ME). Changes in the synovial area at the CPJ and SPP were also measured in 10 patients with early RA, following treatment with disease-modifying antirheumatic drugs (DMARDs) (either methotrexate or leflunomide). RESULTS: In patients with RA or SpA, the area of synovitis was significantly larger immediately adjacent to the CPJ compared with a distant site at the SPP (in RA, mean synovitis area 162 mm2 at the CPJ versus 114 mm2 at the SPP [P = 0.010]; in SpA, mean synovitis area 214 mm2 at the CPJ versus 143 mm2 at the SPP [P = 0.002]), but the differences in the areas of synovitis at these sites were not significant between the RA and SpA patients. The IRE and ME values were also higher at the CPJ compared with the SPP, both in the RA patients (IRE P = 0.054, ME P = 0.018) and in the SpA patients (IRE P = 0.002, ME P = 0.001). A larger reduction in the area of synovitis was seen at the SPP compared with the CPJ following DMARD therapy in the RA patients (mean reduction 35% at the SPP [P = 0.023] and 12% at the CPJ [P not significant]). CONCLUSION: The non-disease-specific variations in synovitis and the differential responses to therapy in RA patients have implications for improving our understanding of CPJ synovitis. The results suggest that the pathophysiologic events at the CPJ reflect common anatomic, immune system, or biomechanical factors that play a role in modulating the severity of arthritis, and these events are not specific to RA since the same process was observed in other arthritides.

Aged↗
PubMed2003

Turnover of type II collagen and aggrecan in cartilage matrix at the onset of inflammatory arthritis in humans: relationship to mediators of systemic and local inflammation.

OBJECTIVE: To determine in vivo the extent of damage to, and changes in turnover of, articular cartilage type II collagen (CII) and the proteoglycan aggrecan following the onset of inflammatory arthritis in humans, and to examine the hypothesis that there are direct relationships between cartilage biomarkers of damage/turnover and clinical, histologic, and molecular markers of inflammation. METHODS: Synovial fluid (SF) and synovial membrane (SM) were obtained by arthroscopy, and a synovitis score was determined, in 32 patients with rheumatoid arthritis (RA) (13 with early untreated disease, 19 with established disease), 18 with psoriatic arthritis (PsA), and 10 with osteoarthritis (OA). Systemic disease activity markers were recorded, and SM CD3+ T cells, CD4+ T cells, CD68+ macrophages, and lining layer hyperplasia were quantified. SF levels of tumor necrosis factor alpha (TNFalpha), interleukin-10 (IL-10), matrix metalloproteinase 1 (MMP-1), MMP-3, Col2-3/4C(Long mono) neoepitope (C2C) (reflecting collagenase cleavage of cartilage CII), C-propeptide of type II procollagen (PIICP) (a biosynthesis marker), keratan sulfate (KS), and the 846 epitope of aggrecan (turnover) were measured by enzyme-linked immunosorbent assay or radioimmunoassay. RESULTS: Levels of cartilage degradation products in early RA or early PsA were not elevated above levels in OA, although in early inflammatory arthritis, TNFalpha and MMP-1 levels were similar to those observed in late inflammatory disease and higher than those in OA. PIICP was reduced in early RA. Correlations were observed between the SF C2C neoepitope level and the Health Assessment Questionnaire score, C-reactive protein level, plasma viscosity, synovitis score, and SF TNFalpha and MMP-1 levels. KS epitope content was reduced in direct relation to SM macrophage infiltration in the sublining and lining layers and in the presence of elevated SF MMP-3. Both SF MMP-1 and SF MMP-3 levels correlated with CD4+ T cell infiltration and lining layer hyperplasia in the SM, and MMP-1 levels correlated with lining layer CD68 levels, but TNFalpha and IL-10 levels did not. CONCLUSION: Except for CII synthesis, there were no significant changes in extracellular matrix turnover of aggrecan or CII in the early stages of human inflammatory arthritis. However, the direct correlation between the increases in TNFalpha and MMP-1 production and collagen degradation suggests that collagenase cleavage of cartilage collagen is related to the activities of TNFalpha and MMP-1. The reduction in CII synthesis in early RA may contribute to the developing pathology, since a lack of synthesis of this molecule would inhibit maintenance of cartilage matrix.

Adult↗
PubMed2003

Angiopoietins, growth factors, and vascular morphology in early arthritis.

OBJECTIVE: To examine angiogenic growth factors in patients with early, untreated inflammatory arthritides and controls. METHODS: Synovial membrane (SM) infiltrate and Ang1, Ang2, and vascular endothelial growth factor (VEGF) mRNA and protein expression were examined using immunohistochemistry and in situ hybridization. Synovial fluid (SF) VEGF, transforming growth factor-beta (TGF-beta 1), and tumor necrosis factor-alpha (TNF-alpha) protein were measured by ELISA. Vascular morphology was assessed at arthroscopy. RESULTS: Ang2 mRNA and protein expression was observed in early psoriatic arthritis (PsA) and rheumatoid arthritis (RA) SM. Expression of Ang2 and VEGF was significantly greater in early PsA SM and correlated strongly. SF VEGF and TGF-beta 1 concentrations were also significantly higher in early PsA compared to RA. Distinct vascular morphology, with tortuous vessels in PsA, correlated with microscopic vascular scores (r = 0.54, p = 0.005) and VEGF levels (r = 0.51, p = 0.01). Ang1 mRNA and protein expression was observed, but concentrations were markedly lower than for Ang2 and VEGF. Clinical disease activity, SM infiltration, and SF TNF-alpha concentrations were similar in both groups. CONCLUSION: This is the first report of angiopoietin expression in early inflammatory arthritis. There is a close relationship between angiopoietins, VEGF, TGF-beta, and vascular morphology. There is differential angiogenesis at an early stage of inflammation, with major pathogenic and therapeutic implications.

Adult↗
PubMed2002

The role of biomechanical factors and HLA-B27 in magnetic resonance imaging-determined bone changes in plantar fascia enthesopathy.

OBJECTIVE: To study the role of biomechanical factors and HLA-B27 in plantar fasciitis. METHODS: T1-weighted and T2 spectral presaturation with inversion recovery (fat suppressed) magnetic resonance imaging (MRI) sequences of the plantar fascia insertion and adjacent bone were performed on 28 patients with plantar fasciitis; 17 had spondylarthropathy (SpA)-associated disease, and 11 had mechanically induced disease. The relationship between the degree of bone edema, scored on a semiquantitative scale (from absent to severe), and the patient's HLA-B27 status was determined. RESULTS: On MRI, edema within the soft tissue at the enthesis was evident in both groups. Bone edema in the adjacent calcaneum was evident in 64.7% (11 of 17) of patients with SpA and in 45% (5 of 11) of those with mechanically induced disease (P = 0.441). HLA-B27 was identified in 9 (53%) of the patients with SpA but in none (0%) of those with mechanically induced disease. All 6 of the SpA patients with extensive bone edema but none of the 5 SpA patients with mild bone edema were HLA-B27 positive (P = 0.002). CONCLUSION: The association of HLA-B27 with bone pathology in early enthesitis may have implications for a better understanding of the pathogenesis of SpA.

Achilles Tendon↗
PubMedDate not supplied

Original PC developer doesn't hold much stock in paperless practice.

Ed Roberts, MD, helped invent one of the first home computers and once worked closely with two fledgling computer junkies: Bill Gates and Paul Allen. But three decades later, the former electrical engineer says computers can help a small medical practice be more efficient, but they aren't advanced enough to handle every task.

Attitude to Computers↗