PubMed Health⌕ Search

Biomedical subjects

J C Mason

Publications and source records attributed to J C Mason.

At least 19 recordsLinked to original sources
PubMed2006

Takayasu's arteritis--recent advances in imaging offer promise.

Takayasu's arteritis (TA), a rare large vessel vasculitis of unknown aetiology, remains a difficult disease to manage with diagnosis often delayed until the late occlusive stage when irreversible vascular damage has occurred. Recent studies suggest that non-invasive imaging modalities including magnetic resonance imaging, ultrasound and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) allow diagnosis of TA earlier in the disease course than standard angiography and provide a means for monitoring disease activity. Choice of appropriate therapy for TA is limited by a lack of evidence and a combination of corticosteroids and immunosuppressive drugs is most commonly used. Novel therapeutic approaches such as the use of anti-tumour necrosis factor alpha (TNF-alpha) inhibitors and drug-eluting arterial stents show promise for improving the prognosis in severe disease. In addition, strict management of traditional cardiovascular risk factors such as dyslipidaemia, hypertension and lifestyle factors is mandatory to minimize secondary cardiovascular complications, which are the major cause of death in this disease.

Angiography↗
PubMed2006

Peritoneal mesothelioma: an unusual cause of an acute phase response presenting to the rheumatologist.

The presence of an acute phase response may pre-date the eventual diagnosis of malignant disease by months or even years. We describe two patients referred to the rheumatology clinic, in which extensive investigation failed to identify an underlying cause to account for the presenting symptoms and an associated acute phase response. Several months later, repeated abdominal CT scans revealed an abnormality and subsequent laparoscopic biopsy confirmed a diagnosis of peritoneal mesothelioma.

Acute-Phase Reaction↗
PubMed2006

Takayasu's arteritis: a cause of prolonged arterial stiffness.

OBJECTIVES: Cardiovascular disease is a major cause of mortality and morbidity in patients with Takayasu's arteritis (TA). Increased arterial stiffness is an independent risk factor and predictor of cardiovascular mortality in a variety of diseases. Pulse wave velocity (PWV) and the augmentation index (AI) are used as clinical measurements of arterial stiffness. METHODS: Data are presented from 10 patients with TA and 11 normal controls obtained between 2000 and 2004. Arterial compliance was assessed non-invasively by measurement of PWV, using the Complior system, and calculation of the aortic AI. RESULTS: TA patients (mean age 40.8+/-13.2 yr) were compared with a control group of healthy women from a parallel study (mean age 32.3+/-5.5 yr). The mean carotid-femoral PWV (PWV-CF) was higher in TA patients (P = 0.03). In addition, both aortic AI derived from the radial artery (P = 0.002) and carotid AI (P = 0.03) were higher in TA patients compared with controls. PWV-CF did not correlate with CRP (r = - 0.23, P = 0.23) or ESR (r = - 0.19, P = 0.27). Similar results were obtained for the correlation of carotid-radial PWV with CRP (r = 0.15, P = 0.32) and ESR (r = 0.33, P = 0.14). CONCLUSIONS: Our data show that TA is associated with elevated arterial stiffness in the central aorta, which may persist when the disease is quiescent. These data suggest that PWV represents a means by which cardiovascular risk can be detected and monitored in TA, and highlights the importance of effective management of cardiovascular risk factors in these patients.

Adult↗
PubMed2006

Both Fcgamma and complement receptors mediate transfer of immune complexes from erythrocytes to human macrophages under physiological flow conditions in vitro.

Abnormal clearance by the mononuclear phagocytic system of immune complexes (IC) is important in the pathogenesis of systemic lupus erythematosus (SLE). We have developed an in vitro model to investigate the cellular mechanisms involved in the transfer of soluble IC from erythrocytes to human macrophages under physiological flow conditions. In this assay, erythrocytes bearing fluorescently labelled IC are perfused over monolayers of human monocytes or monocyte-derived macrophages in a parallel-plate flow chamber, and transfer quantified using confocal microscopy and flow cytometry. Using aggregated human IgG as a model IC, we have been able to demonstrate transfer of IC from erythrocytes to macrophages. Blocking studies with specific neutralizing antibodies have shown that both complement and Fcgamma receptors are required for IC transfer. Blockade of CR4 (alpha(x)beta(2) integrin), FcgammaRIIa or FcgammaRIII reduced transfer, while anti-CR3 (alpha(m)beta(2) integrin) had no effect. Blockade of CR3, FcgammaRIIa or FcgammaRIII also reduced the number of adhesive interactions between fluorescently labelled IC-bearing erythrocytes and macrophage monolayers. Taken together with the transfer data, this suggests differing roles for these receptors in the human IC transfer reaction that includes an adhesive function which facilitates IC processing by mononuclear phagocytes. Finally, a functional effect of the FcgammaRIIa R131/H131 polymorphism, important in susceptibility to SLE, has also been demonstrated using this model. Uptake of IgG(2) but not IgG(1)-containing soluble IC was reduced by macrophages from individuals homozygous for the R131 allelic variant of the receptor.

Antigen-Antibody Complex↗
PubMed2004

Expression of Fcgamma and complement receptors on peripheral blood monocytes in systemic lupus erythematosus and rheumatoid arthritis.

OBJECTIVES: Fcagamma and complement receptors play an important role in the interaction between immune complexes (IC) and monocytes/macrophages. Recent work has demonstrated that their relative expression on these cells may be modified by cytokines, including TNF-alpha and IL-4. Furthermore, cytokines may alter the expression of adhesion molecules such as ICAM-1. However, little data exist on the in vivo expression of specific Fcgamma and complement receptors in systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA), two diseases in which IC are important in pathogenesis. METHODS: Venous blood was obtained from 30 patients with SLE, 25 with RA and 25 healthy controls. Monocyte phenotype was determined by flow cytometric analysis of whole blood samples, with selective gating using forward and side scatter signals. Surface expression of Fcgamma receptors RI (CD64), RII (CD32) and RIII (CD16), complement receptors CR1 (CD35) and CR3 (CD11b/CD18), and adhesion molecules ICAM-1 (CD54) and CD11a (LFA-1) was determined. The effects of disease activity and corticosteroid therapy on the expression of these molecules were also examined. RESULTS: The expression of FcgammaRII was reduced on monocytes from patients with SLE compared with healthy controls and patients with RA (P = 0.002). This did not correlate with disease activity using conventional indices [SLEDAI (SLE disease activity index), C3/C4 levels and anti-double-stranded DNA antibody titres], and was independent of prednisolone therapy. There was no significant difference in FcgammaRI or RIII expression on SLE monocytes compared with healthy controls. In contrast, the expression of FcgammaRIII was increased on RA monocytes (P = 0.01), this being highest in patients with active disease. The proportion of FcgammaRIII-positive monocytes was also increased in RA, and prednisolone therapy was associated with a lower proportion of FcgammaRIII-positive cells. An increase in CR3 expression was seen on RA monocytes (P = 0.002), whilst CR1 was increased on monocytes from patients with active SLE or active RA. ICAM-1 expression was reduced on monocytes from patients with SLE (P = 0.002), although high-dose prednisolone therapy was associated with the lowest level of surface ICAM-1 on monocytes. CONCLUSIONS: Peripheral blood monocytes from patients with SLE or RA display significantly altered phenotypes compared with those from healthy controls. The observed reduction in SLE of FcgammaRII may represent a mechanism by which monocytes are protected from IC-mediated activation. Prednisolone therapy and disease activity had little effect on phagocytic receptor expression. The observed changes may reflect the different cytokine profiles seen in SLE and RA.

Adult↗
PubMed2004

Non-invasive imaging in the diagnosis and management of Takayasu's arteritis.

OBJECTIVES: Takayasu's arteritis (TA) is a rare disease, in which early diagnosis and assessment of treatment efficacy remain a problem. Signs and symptoms may be non-specific and conventional blood tests unreliable, with vascular inflammation often persisting in the face of a normal acute phase response. The current "gold standard" investigation, x ray angiography, is invasive and only identifies late, structural changes in vessels. Recently, non-invasive imaging methods have shown promise in the assessment of patients with TA. METHODS: The invasive and non-invasive imaging performed on all patients in the rheumatology department at the Hammersmith Hospital between May 1996 and May 2002 who fulfilled the ACR criteria for TA were reviewed. All patients were clinically active at diagnosis and were treated with high dose oral prednisolone and additional oral or intravenous immunosuppression. RESULTS: Non-invasive imaging methods ([(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) and magnetic resonance imaging (MRI)) provided important additional information about disease activity ([(18)F]FDG-PET) and progression of vessel wall thickening (MRI) when compared with x ray angiography. CONCLUSIONS: Non-invasive imaging methods provide useful additional information towards the diagnosis and management of TA. Such techniques may allow earlier diagnosis and more accurate assessment of response to treatment than conventional clinical assessment and/or angiography. Non-invasive imaging is likely to be useful in the management of other large vessel vasculitides.

Adult↗
PubMed2003

Hemoglobin scavenger receptor CD163 mediates interleukin-10 release and heme oxygenase-1 synthesis: antiinflammatory monocyte-macrophage responses in vitro, in resolving skin blisters in vivo, and after cardiopulmonary bypass surgery.

The recently described hemoglobin scavenger receptor CD163 mediates the endocytosis of hemoglobin:haptoglobin (Hb:Hp) complexes and thereby counters Hb-induced oxidative tissue damage after hemolysis. Although CD163 has been indirectly associated with antiinflammatory and atheroprotective activity, no ligand-receptor-effector pathway has yet been described for this receptor. To understand the significance of CD163 and more clearly define downstream pathways linked to inflammatory resolution, we studied the expression and function of CD163 in human monocytes/macrophages using both in vitro and in vivo models. Differentiation of human blood monocytes into macrophages either by in vitro culture or in resolving cantharidin-induced skin blisters led to an equivalent increase (>15x) in CD163 expression. Elevated CD163 levels were also noted on circulating monocytes in cardiac surgical patients during the resolution phase of the systemic inflammatory response to cardiopulmonary bypass surgery. In each case, binding of Hb:Hp to CD163-bearing cells elicited potent interleukin-10 secretion, and this was inhibited by the anti-CD163 antibody RM3/1. Release of interleukin-10, in turn, induced heme oxygenase-1 stress protein synthesis via an autocrine mechanism. Such induction of heme oxygenase-1 was observed in vivo 24 to 48 hours after the onset of cardiopulmonary bypass surgery. These results identify novel antiinflammatory and cytoprotective effector pathways in human monocytes/macrophages related to Hb scavenging and metabolism, which may have relevance in atheroprotection, wound healing, and patient recovery postoperatively.

Aged↗
PubMed2002

An unusual abdominal mass in a renal transplant recipient.

Renal transplant recipients are at increased risk of malignancy and infection. We present the case of a 72-year-old-man with recurrent bladder carcinoma, abdominal aortic aneurysm repair, and end-stage renal failure due to renovascular disease. He received a cadaveric renal allograft into his left iliac fossa, was given cyclosporin A, azathioprine, and prednisolone triple therapy immunosuppression, and had no rejection episodes. He presented four years post-transplantation with a two-year history of intermittent sweats and fevers. Previous episodes had been investigated with no firm diagnosis made. This time he had right iliac fossa pain of three weeks' duration. Examination revealed a tender mass. Investigations showed unchanged graft function, but elevated inflammatory indices. Ultrasonography and computed tomography detailed an infiltrating mass associated with the sigmoid colon, which colonoscopy failed to visualise. At laparotomy a 6-cm tumor was removed, with adherent sigmoid colon and bladder dome. Macroscopically the mass was an abscess, and microscopy found acute and chronic inflammatory giant cells and fibrillary masses suggestive of actinomycosis, with no malignancy. The patient recovered uneventfully on antibiotics. At six months' follow-up, examination, inflammatory markers, and radiographic imaging showed no evidence of recurrence. Twelve months later the patient died of rupture of his proximal abdominal aorta. There was no evidence of recurrence at postmortem examination. We conclude with a brief review of actinomycosis in transplant recipients.

Abdomen↗
PubMed2001

Use of non-covalent labeling in illustrating ligand binding to human serum albumin via affinity capillary electrophoresis with near-infrared laser induced fluorescence detection.

This paper demonstrates the use of a near-infrared (NIR) dye as a non-covalent label for human serum albumin (HSA). The dye is a water soluble, heptamethine cyanine dye. The utility of the dye as a tracer illustrating the binding of various drugs to HSA is demonstrated via affinity capillary electrophoresis with near-infrared laser-induced fluorescence detection (ACE-NIR-LIF). Additionally, the factors affecting the separation of relevant species were investigated. The change in quantum yield of the dye upon complexation with HSA was calculated. Spectrophotometric measurements were conducted to study the stoichiometry of the dye albumin complex.

Binding Sites↗
PubMed2001

Binding constant determination of drugs toward subdomain IIIA of human serum albumin by near-infrared dye-displacement capillary electrophoresis.

Drug binding to serum albumin influences several important pharmacological properties such as toxicity, solubility, activity, distribution, and excretion. It is therefore of interest to have methodologies that allow for the determination of drug-albumin affinity constants while simultaneously providing information on the location of the drug binding site. In the present work we describe a method for the determination of binding constants of drugs known to bind to subdomain IIIA of serum albumin. Drugs used in the study were ketoprofen, ibuprofen, quinidine, naproxen, imipramine, and clofibrate. Binding constants of the drugs were determined by near-infrared dye-displacement capillary electrophoresis. The dye-displacement technique uses a competitive-type interaction between the drug of interest and a dye probe to arrive at a binding constant. A heptamethine cyanine dye was used as a probe for drug binding at subdomain IIIA of serum albumin. The utility of the dye as a noncovalent label for serum albumin was investigated. Additionally, the ability of the method to illustrate enantioselective binding is shown. The dye displacement technique has advantages over current electrophoresis-based techniques in that it is faster and uses less reagent.

Binding, Competitive↗
PubMed2001

Induction of endothelial cell decay-accelerating factor by vascular endothelial growth factor: a mechanism for cytoprotection against complement-mediated injury during inflammatory angiogenesis.

OBJECTIVE: Decay-accelerating factor (DAF) is a widely expressed, multifunctional cell surface protein involved in complement regulation and cell signaling. Previous studies have demonstrated that endothelial cell (EC) DAF is up-regulated by tumor necrosis factor alpha and inhibits complement binding. Because vascular endothelial growth factor (VEGF) is cytoprotective to endothelium and is expressed at sites of chronic inflammation, we hypothesized that VEGF may induce DAF expression during inflammatory angiogenesis. METHODS: Human umbilical vein and dermal microvascular EC were isolated using routine procedures, and the regulation and function of DAF, as well as other complement-regulatory proteins (membrane cofactor protein and CD59), were analyzed following stimulation with VEGF. RESULTS: Incubation of large- or small-vessel EC with VEGF led to increased expression of DAF, with maximal expression after 48-72 hours of stimulation. This effect depended on the activation of protein kinase C (PKC) and required increased steady-state messenger RNA levels and de novo protein synthesis. Although VEGF-induced EC proliferation was inhibited by both p38 and p42/44 mitogen-activated protein kinase (MAPK) antagonists, DAF up-regulation in response to VEGF was only sensitive to inhibition of p38 MAPK. VEGF-stimulated EC showed a 60% reduction in C3 deposition following complement activation, and this resulted in a marked reduction in complement-mediated EC lysis. These protective effects were abolished by anti-DAF monoclonal antibody 1H4. CONCLUSION: This study confirms the importance of PKC for the regulation of DAF expression by EC and reveals VEGF to be a physiologic agonist for this pathway. The up-regulation of DAF expression by VEGF may represent an important mechanism for the protection of EC from complement-mediated injury during angiogenesis in inflammatory rheumatic diseases.

CD55 Antigens↗
PubMed2001

Aggressive endoscopic resection of inverted papilloma: an update.

OBJECTIVE: Endoscopic resection has been proposed for sinonasal inverted papilloma (IP). Our objective was to determine the efficacy of aggressive endoscopic resection of IP. METHODS: Retrospective analysis was performed on patients undergoing endoscopic resection of IP at the University of Virginia between 1990 and 1996. Total ethmoidectomies, wide maxillary antrostomies, frontal recess explorations, sphenoidotomies, and turbinate resection were performed as required. Once all visible papilloma was removed, residual mucosa was removed by using a diamond burr to polish bone at the site of origin. RESULTS: Twenty-one patients were treated with endoscopic resection of IP. Only 1 of 21 patients had an adjunctive external procedure (an osteoplastic flap without obliteration). Average follow-up was 41.9 months after initial aggressive endoscopic resection at the ureterovesical angle. Recurrences occurred in 19% (4/21) of patients. One of the 4 had two recurrences. Recurrences occurred in 16 months or less, except for one noted at 35 months and another at 56 months. CONCLUSIONS: Aggressive endoscopic resection of IP by experienced rhinologists is an acceptable treatment.

Adolescent↗
PubMed2000

Induction of decay-accelerating factor by thrombin through a protease-activated receptor 1 and protein kinase C-dependent pathway protects vascular endothelial cells from complement-mediated injury.

There is increasing evidence for functional crosstalk between inflammatory and thrombotic pathways in inflammatory vascular diseases such as atherosclerosis and vasculitis. Thus, complement activation on the endothelial cell (EC) surface during inflammation may generate thrombin via the synthesis of tissue factor. We explored the hypothesis that thrombin induces EC expression of the complement-regulatory proteins decay-accelerating factor (DAF), membrane cofactor protein (MCP), and CD59 and that this maintains vascular integrity during coagulation associated with complement activation. Thrombin increased DAF expression on the surface of ECs by 4-fold in a dose- and time-dependent manner as measured by flow cytometry. DAF up-regulation was first detectable at 6 hours and maximal 24 hours poststimulation, whereas no up-regulation of CD59 or MCP was seen. Thrombin-induced expression required increased DAF messenger RNA and de novo protein synthesis. The response depended on activation of protease-activated receptor 1 (PAR1) and was inhibited by pharmacologic antagonists of protein kinase C (PKC), p38 and p42/44 mitogen-activated protein kinase, and nuclear factor-kappa B. The increased DAF expression was functionally relevant because it significantly reduced C3 deposition and complement-mediated EC lysis. Thus, thrombin-generated at inflammatory sites in response to complement activation-is a physiologic agonist for the PKC-dependent pathway of DAF regulation, thereby providing a negative feedback loop protecting against thrombosis in inflammation. (Blood. 2000;96:2784-2792)

CD55 Antigens↗
PubMed2000

An anti-inflammatory property of aprotinin detected at the level of leukocyte extravasation.

BACKGROUND: Aprotinin is a serine protease inhibitor used extensively in cardiac operations to reduce postoperative bleeding. It has also been used in trials aimed at reducing the systemic inflammatory response to cardiopulmonary bypass. It remains unclear whether the anti-inflammatory action of aprotinin is related to its general ability to suppress leukocyte activation or whether aprotinin can exercise effects during the leukocyte-endothelial cell adhesion cascade. METHODS: We used intravital microscopy to study the 3 main stages of the adhesion cascade (leukocyte rolling, firm adhesion, and extravasation) within the mesenteric microcirculation of rats. This in vivo technique allows leukocyte recruitment to be viewed directly through the transparent mesentery of anesthetized animals. RESULTS: Aprotinin, given by continuous infusion at a clinically relevant dose, exerted no effect on the rolling or firm adhesion responses toward local chemoattractant N -formyl-methyl-leucyl-phenylalanine but significantly inhibited extravasation of leukocytes (73% at 40 minutes, P =.04) into surrounding tissues. In parallel in vitro experiments, aprotinin (used at 200, 800, and 1600 kIU/mL) dose dependently inhibited neutrophil transmigration through cultured endothelial cells in response to 3 different chemoattractants: N -formyl-methyl-leucyl-phenylalanine (P <.001 at 800 and 1600 kIU/mL), interleukin 8 (P <.05 at 200 kIU/mL and P <.001 at 800 and 1600 kIU/mL), and platelet-activating factor (P <.05 at 1600 kIU/mL). CONCLUSIONS: Our studies have therefore revealed a novel anti-inflammatory mechanism of aprotinin operating at the level of leukocyte extravasation. These findings may be relevant in the prevention of systemic inflammation after cardiopulmonary bypass through the use of protease inhibitors.

Analysis of Variance↗
PubMed2000

Hearing results after primary cartilage tympanoplasty.

OBJECTIVES/HYPOTHESIS: Cartilage-perichondrium grafting of the tympanic membrane has been used in an effort to reduce recurrence or progression of middle ear disease. The rigidity of cartilage has obvious benefit in preventing tympanic membrane retraction, but concern has been raised regarding its sound conduction properties Few studies in the literature address hearing results after cartilage tympanoplasty. The purpose of this study was to investigate the hearing results after primary cartilage tympanoplasty and compare them with results after primary tympanoplasty with temporalis fascia. STUDY DESIGN: A retrospective review of all ear surgeries using cartilage between 1994 and 1999 was performed. METHODS: Only primary cases in which the ossicular chain was intact and no mastoid surgery was performed were included. Indications for surgery included tympanic membrane perforation, retraction, and cholesteatoma Pre- and postoperative speech reception thresholds and air-bone gaps at 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz were compared. RESULTS: Eleven patients comprised the cartilage study group, and there were 11 age- and temporally matched control subjects. The mean improvement in speech reception threshold for both the study group and the control group was 10 dB. The majority of patients in both groups had ABG closure to within 10 dB at all frequencies examined. There were no statistically significant differences in speech reception threshold improvement or air-bone gap closures between the two groups. CONCLUSIONS: These results demonstrate that hearing results after cartilage tympanoplasty are comparable to those after temporalis fascia tympanoplasty. Therefore, when indicated, a cartilage-perichondrium graft can be used for prevention of disease recurrence or progression without fear of impairing hearing.

Adolescent↗
PubMed2000

Resting and activated T cells induce expression of E-selectin and VCAM-1 by vascular endothelial cells through a contact-dependent but CD40 ligand-independent mechanism.

This study explored the effect on endothelial cell (EC) activation of contact with T lymphocytes, which occurs during lymphocyte emigration into inflamed tissues. Addition of T cells to umbilical vein or dermal microvascular EC monolayers stimulated expression of EC E-selectin and VCAM-1. This response required direct cell:cell contact, but not T-cell activation. The capacity of resting CD4+ T cells to activate EC was restricted to the CD45RO+ subset and could be enhanced by 6 h prestimulation of T cells with PMA and ionomycin. The EC-stimulating capacity of resting or activated T cells was independent of CD40 ligand. Furthermore, inhibition of TNF-alpha/beta and IL-1alpha/beta, together with CD40 ligand, failed to inhibit EC activation by resting T cells and only inhibited the response to PMA- and ionomycin-activated T cells by 40 +/- 18%. Our data suggest that T-cell-EC interactions can lead to EC activation through a novel contact-dependent, but CD40 ligand-independent, mechanism.

CD40 Antigens↗