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Biomedical subjects

A L Bell

Publications and source records attributed to A L Bell.

At least 37 records · Page 2Linked to original sources
PubMed1999

Increased apoptotic peripheral blood neutrophils in systemic lupus erythematosus: relations with disease activity, antibodies to double stranded DNA, and neutropenia.

OBJECTIVE: To quantify the percentage of apoptotic peripheral blood neutrophils in systemic lupus erythematosus (SLE) and to determine the relations with disease activity and neutropenia. METHODS: Neutrophil apoptosis in SLE patients (n =50) was assessed by flow cytometry using annexin V binding and fluorescent labelled anti-fas. Rheumatoid arthritis (RA, n =20) and inflammatory bowel disease patients (IBD, n =20) were studied as disease controls. RESULTS: The percentage of apoptotic neutrophils, determined by annexin V binding, was increased in peripheral blood of SLE patients (median = 3.25%) compared with normal healthy donors (n =20, median = 1.20%) and disease controls (RA: median = 1.15%) (IBD: median = 1.15%). SLE neutrophil apoptosis correlated positively with lupus disease activity measured by SLAM score. SLE patients with increased antibodies to dsDNA (>10 mg/ml) had increased apoptotic neutrophils. Eight of 14 neutropenic SLE patients had increased apoptotic neutrophils. Increased neutrophil fas expression compared with normal controls was observed in SLE, RA, and IBD. CONCLUSION: Neutrophil fas expression is increased non-specifically in inflammatory disease. Increased circulating apoptotic neutrophils in SLE correlate positively with disease activity (SLAM) and may contribute to autoantigen excess including dsDNA.

Antibodies, Antinuclear↗
PubMed1999

Lymphocyte apoptosis in systemic lupus erythematosus: relationships with Fas expression, serum soluble Fas and disease activity.

Lupus specific autoantigens are exposed on apoptotic cells. The increased number of apoptotic lymphocytes reported in systemic lupus erythematosus (SLE) may be attributable to abnormalities of lymphocyte Fas expression or serum soluble Fas. In the present study we analysed the count of circulating apoptotic lymphocytes in SLE patients (n=50), by flow cytometry using Annexin V, compared to rheumatoid arthritis patients (RA, n=20), inflammatory bowel disease patients (IBD, n=20) and normal controls (n=20). Lymphocyte Fas expression and serum soluble Fas were measured and related to numbers of apoptotic lymphocytes. The percentage of apoptotic lymphocytes, determined by Annexin V binding, was significantly increased in peripheral blood of SLE patients (median=4.2%) compared with normal healthy donors (median=1.1%) and IBD patients (median=2. 0%) but not RA (median=3.9%). SLE lymphocyte Fas expression was not significantly different from RA or IBD patients. Serum soluble Fas in SLE patients correlated positively with apoptotic lymphocytes and antibodies to double stranded DNA. This study suggests that increased apoptotic lymphocytes and increased lymphocyte Fas expression may not be specific to SLE. Serum soluble Fas may have a role in the regulation of lymphocyte apoptosis in SLE.

Adrenal Cortex Hormones↗
PubMed1997

Age-related changes in non-receptor dependent generation of reactive oxygen species from phagocytes of healthy adults.

Several authors have shown that neutrophil generation of reactive oxygen species (ROS) declines with advancing age. Similar changes have also been suggested in monocytes. In both cases alterations in second messenger activity have been implicated as the most likely explanation for these observations. The aim of this study was to investigate the effect of age on phagocyte ROS generation, stimulated by the direct activation of protein kinase C (PKC). Venous blood was drawn from normal healthy subjects, cells were separated on a double density gradient into mononuclear and polymorphonuclear (pmn) cells. Phorbol myristate acetate (PMA) was employed as a cell stimulus. Superoxide generation was measured by cytochrome c reduction and myeloperoxidase (MPO) products by measurement of peak luminol chemiluminescence (CL). Fifty-eight subjects, 25 males and 33 females, were studied, median age 49 years (range 26-88 years). Polymorphonuclear cell superoxide generation was significantly higher in males and there was a trend towards higher pmn MPO product generation in males. Using Spearman's ranked correlation coefficient, monocyte superoxide generation was negatively correlated with age (r = -0.473, P < 0.001). No changes in the generation of MPO products was found. There were also trends towards a negative correlation of pmn cytochrome c reduction and peak luminol CL with age in males but not females. Since PMA directly activates protein kinase C, reduced monocyte superoxide generation with increasing age appears to be related to alterations in the ROS generating system downstream of the cell receptor. Impaired monocyte superoxide generation may have implications for non-specific defence against certain infections and early tumour growth in the elderly. Factors underlying these changes in monocyte function therefore require further study.

Adult↗
PubMed1997

A comparison of two nomenclature systems for primary systemic vasculitis.

Recently, two new systems have been proposed for the nomenclature of primary vasculitides: the 1990 American College of Rheumatology (ACR) classification criteria and the 1992 Chapel Hill Consensus Conference (CHCC) definitions. We compared these two systems in the same cohort of patients with primary systemic vasculitis. Twenty-four patients were studied and, applying the 1990 ACR criteria, the diagnoses were Wegener's granulomatosis (WG) (15), Churg Strauss syndrome (CSS) (4), polyarteritis nodosa (PAN) (2) and unclassified (3). Using the CHCC definitions, the diagnoses were WG (5), microscopic polyangiitis (MPA) (8), possible MPA (1), PAN (1) and undefined (9). There was concordance in only five patients (all WG). Significant discordance exists between these two criteria sets. Since the ACR criteria set does not include MPA, WG tends to be overdiagnosed. The Chapel Hill definitions are biopsy dependent and surrogate features for the defining histology are required to allow their practical application.

Adult↗
PubMed1997

The prevalence of systemic lupus erythematosus in Northern Ireland.

Using six sources of patient ascertainment, 467 patients were initially identified as having a diagnosis of systemic lupus erythematosus (SLE) in Northern Ireland. The diagnosis was subsequently altered in 45 of these, either by the patient, their family, or their physician. The corrected source data were then reanalysed by the 'capture-recapture' technique, which suggested a further 71 patients missed during the initial identification process. Eighty-eight patients underwent physical examination, and 14 were found to have a diagnosis other than SLE. A final estimated figure of 415 patients was obtained, giving a point prevalence on August 1, 1993 of 25.4 per 10,000 for the Province (95% confidence interval 22.1-28.7 per 100,000).

Adolescent↗
PubMed1997

Enhanced endothelium-dependent vasodilator responses in patients with systemic vasculitis.

The aim of the study was to investigate endothelium-dependent vasodilator responses in the forearm vasculature of patients with systemic vasculitis. We studied 10 patients with systemic vasculitis and 16 healthy control subjects using forearm venous occlusion plethysmography to assess changes in forearm blood flow in response to acetylcholine (ACh). NG-monomethyl-L-arginine (L-NMMA), was also used to assess the contribution of endothelium derived relaxing factor/nitric oxide (EDRF/NO) to the vasodilator responses to acetylcholine. A significantly greater vasodilator response to ACh was seen in the patient group at all doses infused (p < 0.01). After pre-infusion of L-NMMA, the differences in ACh dilator responses were no longer significant. There was a greater magnitude of inhibition of ACh responses by L-NMMA in the patient group. The enhanced vasodilator response to ACh observed was in part abolished by L-NMMA, suggesting that EDRF/NO is produced in excess in systemic vasculitis. The precise role played by EDRF/NO in the pathogenesis of systemic vasculitis requires further study.

Acetylcholine↗
PubMed1996

Clinical features associated with a positive anticardiolipin antibody in Irish patients with systemic lupus erythematosus.

Anticardiolipin antibodies (ACA) are one of a number of autoantibodies found in patients with systemic lupus erythematosus (SLE) and their presence has been associated with clinical features of the antiphospholipid syndrome (APS). The aim of this study was to determine which clinical features are associated with a positive anticardiolipin antibody in Irish patients with SLE. Ninety-five Irish patients with SLE were studied. All were examined thoroughly, had their full history taken, and had case records reviewed. The presence of any clinical feature associated with the APS was noted. Sera from these patients were tested for IgG and IgM ACA. The only significant association found was between a history of venous thrombosis and the presence of ACA, although several other features were more common in ACA positive patients. There were no significant associations with one or other isotype. This study serves as a reminder to consider the possibility of venous thrombosis, and other clinical features, if an SLE patient is positive for ACA.

Adolescent↗
PubMed1996

Contact stress distributions in malreduced intraarticular distal radius fractures.

Residual articular incongruity of the distal radius following intraarticular fracture has been correlated with early osteoarthritis (OA) and a poor clinical outcome. We developed a simple in vitro fracture model of the distal radius to investigate the relationship between degree of articular incongruity and the resulting distribution of radiocarpal contact stress. Twelve fresh-frozen cadaver arms were dissected, packets of Fuji Pressensor film were inserted into the wrist, and the wrist was loaded through its flexor and extensor tendons. We created a simple intraarticular fracture that allowed controlled distal radius articular incongruity. Loading trials were performed for the intact distal radius, for a fully reduced case, and for step-offs of 0.4, 1, 2, and 3 mm. Mean contact stress was significantly greater than the anatomically reduced case at only 3 mm of step-off. Contact area was greater than the anatomically reduced case at 0.4, 1, and 2 mm of step-off. The elevations in contact stress that we observed were only modest, suggesting that other factors may be involved in the pathogenesis of radiocarpal OA in the presence of residual articular incongruity.

Adult↗
PubMed1996

A clinical and serological comparison of familial and non-familial systemic lupus erythematosus in Ireland.

Seventeen families, in which the diagnosis of SLE could be verified in two relatives, were included in the study. The diagnosis was made according to the revised 1982 ARA criteria. We compared the 34 cases of familial SLE in these 17 families with 34 non-familial SLE controls matched for age, sex, ethnicity and duration of disease. Comparisons were made for the presence of 26 clinical and 11 serological features. The frequency of clinical features was similar between the groups. The frequency of anti-Ro antibody was higher in the non-familial group (15 out of 34 compared to 6 out of 34, P = 0.036, McNemar's test), although this was not significant after application of Bonferoni's correction for the number of comparisons. No cases of familial IgA or familial complement deficiency were identified. It was noted that 10 of the 34 non-familial patients and only one of the familial patients had the combination of anti-Ro antibody and photosensitivity. The findings of this study support the hypothesis that familial SLE and non-familial SLE are the same clinical entity, although there are differences in the subtypes of disease.

Adult↗
PubMed1995

Measurement of colony-stimulating factors in synovial fluid: potential clinical value.

In this study, 100 synovial fluid (SF) samples from patients with a variety of arthritides were assayed for levels of colony-stimulating factors (CSFs) using a human bone-marrow bioassay and enzyme immunoassays for granulocyte (G-) and granulocyte-macrophage (GM-) CSFs. GM-CSF was found more frequently in samples from rheumatoid arthritis (RA) subjects (49%) than in non-RA samples (29%). Absence of GM- but not G- or bioassay CSFs characterised samples from subjects with psoriatic arthritis and ankylosing spondylitis (n = 14). There was strong evidence of an antagonistic relationship between levels of G- and GM-CSFs in samples from RA patients, an effect independent of drug treatment. However, treatment with non-steroidal anti-inflammatory agents (NSAIDs) may affect reported CSF concentrations: G-CSF levels were significantly lower in samples from subjects not taking NSAIDs. These results suggest that SF-CSF estimations using commercially available assays could provide useful diagnostic clues for clinicians, but careful interpretation is warranted particularly in patients on long-term NSAID treatment.

Arthritis, Rheumatoid↗
PubMed1995

Kikuchi's disease as a presenting feature of mixed connective tissue disease.

Necrotising histiocytic lymphadenitis (Kikuchi's disease) is a recognised cause of benign lymphadenopathy. It has been reported in association with both adult Still's disease, systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCTD). We report a case of mixed connective tissue disease (MCTD), in which biopsy of enlarged lymph nodes occurring as a presenting feature showed the characteristic features of Kikuchi's disease. This finding supports the belief that Kikuchi's disease and the autoimmune rheumatic disorders may share a common aetiology.

Adult↗
PubMed1995

Human blood and synovial fluid neutrophils cultured in vitro undergo programmed cell death which is promoted by the addition of synovial fluid.

OBJECTIVE: To assess the influence of inflammatory synovial fluid (SF) on apoptosis of joint and blood neutrophils with particular reference to levels of colony stimulating factors (CSF) contained therein. METHODS: Neutrophils were separated from fresh synovial fluid and from peripheral blood by density gradient centrifugation. Apoptosis was assayed by light microscope morphology and DNA degradation. CSFs were assayed using bone marrow bioassay and enzyme linked immunosorbent assays for granulocyte (G-) and granulocyte macrophage (GM-) CSF. Separated neutrophils were cultured in vitro and exposed to: varying concentrations of SF in which CSF levels were measured, recombinant G-CSF and GM-CSF, and hyaluronic acid control solutions. Numbers of apoptotic neutrophils and CSF levels were also measured in fresh SF samples. RESULTS: The addition of autologous or heterologous inflammatory SF to blood or joint cavity neutrophils cultured in vitro caused a significant dose dependent increase in the percentage of cells becoming apoptotic with time as measured morphologically and confirmed by DNA degradation. The effect bore no relationship to levels of CSF in joint fluid, despite our finding that GM-CSF produced inhibition of neutrophil apoptosis in vitro. CONCLUSION: These data suggest that SF contains a factor or factors capable of directly or indirectly promoting neutrophil apoptosis and normally powerful enough to overcome the apoptosis inhibiting effects of cytokines such as GM-CSF at concentrations usually found in inflammatory synovial fluids.

Apoptosis↗
PubMed1995

Chronic suppurative lung disease with associated vasculitis.

We report a patient with chronic bronchiectasis who developed systemic vasculitis. The patient was initially treated with immunosuppression; however, the addition of antibiotic therapy improved control of her vasculitis and the need for immunosuppression was reduced. Chronic bronchial suppuration may have an aetiological role in the pathogenesis of this condition.

Bronchiectasis↗