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Biomedical subjects

R J Powell

Publications and source records attributed to R J Powell.

At least 73 records · Page 4Linked to original sources
PubMed1998

IgE and non-IgE mediated allergic disorders in systemic lupus erythematosus.

OBJECTIVE: To ascertain the prevalence of IgE and non-IgE mediated allergic disorders in patients with systemic lupus erythematosus (SLE). METHODS: 49 SLE cases (all satisfying at least four "Revised ARA Criteria") and 98 healthy, age, and sex matched controls (randomly selected through two urban general practices and one rural general practice) were interviewed by telephone to screen for a history of allergy. Subjects with a history of allergic rhinitis, asthma or atopic eczema then underwent skin prick testing to confirm underlying IgE mediated disease. RESULTS: Analysis of the data by conditional logistic regression revealed no significant difference in frequency of allergic disorders in SLE cases and controls (odds ratio (OR) 0.92, 95% confidence intervals (CI) 0.45, 1.86). In addition a subgroup analysis of subjects with IgE mediated/associated atopic disorders, showed that cases and controls were at a similar risk of having these conditions (OR 0.90, 95% CI 0.41, 1.96). CONCLUSIONS: This study suggests that people with SLE are not at an increased risk of IgE mediated/associated allergic disorders, in contrast with previous reports.

Adult↗
PubMed1998

Smoking history, alcohol consumption, and systemic lupus erythematosus: a case-control study.

OBJECTIVE: To investigate the effect of smoking on the development of systemic lupus erythematosus (SLE), and the association between alcohol consumption and the disease. METHODS: 450 subjects (150 SLE patients and 300 controls) from Nottingham, UK were interviewed in a case-control study. Controls were matched to cases for age and sex. All patients met at least four of the American Rheumatology Association criteria for SLE. Controls were randomly selected from the Nottingham Family Health Services Authority register. Information was collected by interview administered questionnaire concerning demographic variables, smoking histories, and drinking habits. RESULTS: Analysis of the data by conditional logistic regression revealed current smokers to have a significantly increased risk of development of SLE compared with never smokers (odds ratio (OR) 1.95, 95% confidence intervals (CI) 1.14, 3.31), although ex-smokers were not at increased risk. There was also suggestion of a marked, highly significant negative association between SLE and alcohol consumption, the magnitude of which increased with units consumed. CONCLUSIONS: This study suggests that current smokers are at increased risk of developing SLE compared with non-smokers and ex-smokers. In contrast, alcohol consumption seems to be negatively associated with the disease.

Adult↗
PubMed1998

Exclusion of the familial Mediterranean fever locus as a susceptibility region for autosomal dominant familial Hibernian fever.

Autosomal dominant periodic fevers constitute a range of syndromes characterised by recurrent attacks of fever and abdominal pain. Familial Hibernian fever (FHF) has been described in only one United Kingdom based family, but two other Irish families have been found with similar clinical features. FHF resembles familial Mediterranean fever (FMF) in several clinical features, but the mode of inheritance of FHF is dominant whereas FMF is recessive. We have investigated whether autosomal dominant periodic fevers, in particular FHF, map to the FMF susceptibility locus (MEFV) on chromosome 16p13.3. We have used informative microsatellite markers flanking this locus to genotype members of the three families mentioned above. Two point and multipoint lod scores definitively excluded linkage to MEFV in the two larger families. A haplotype study confirmed these findings, indicating that FHF is genotypically as well as phenotypically distinct from FMF.

Chromosomes, Human, Pair 16↗
PubMed1998

Coculture conditions alter endothelial modulation of TGF-beta 1 activation and smooth muscle growth morphology.

We examined whether endothelial cells (ECs) inhibit smooth muscle cell (SMC) transforming growth factor-beta 1 (TGF-beta 1) activation in bilayer coculture. Western analysis showed that SMCs cocultured with ECs as a bilayer had lower amounts of active TGF-beta 1 protein compared with SMCs cultured alone and SMCs cocultured with ECs as a monolayer. EC inhibition of TGF-beta 1 activation could be blocked with plasminogen activator inhibitor-1 (PAI-1) antibody. Similarly, SMC hill-and-valley growth, a marker for TGF-beta 1 activity, was present in SMCs cultured alone and SMCs cocultured with ECs as a monolayer but was absent in SMCs cocultured as a bilayer. SMCs cocultured with ECs as a bilayer migrated at a greater rate than SMCs cultured either alone or cocultured as a monolayer. The EC effect on SMC migration was inhibited by the addition of 5 ng/ml TGF-beta 1. ECs had no effect on SMC RNA levels of TGF-beta 1. PAI-1 levels were increased in ECs and ECs cocultured with SMCs compared with SMCs cultured alone. ECs inhibit TGF-beta 1 activation in bilayer coculture. This appears to be mediated through an increase in EC PAI-1 release. Alterations in coculture conditions, in particular the degree of EC-SMC cell contact, have profound effects on this process.

Animals↗
PubMed1998

Basaloid follicular hamartoma, total body hair loss and SLE.

We describe a patient with systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APLS) who developed a plaque-like lesion around the mouth and lost all body hair. Biopsies of the circumoral lesion and scalp, were originally reported as containing extensive basal cell carcinoma, but on review, both showed the typical appearance of a benign malformation of the hair follicle known as basaloid follicular hamartoma. Regrowth of hair and partial resolution of the peri-oral plaque occurred with more aggressive treatment of her SLE, but the basaloid follicular hamartomas in her scalp skin persisted. There is a known, but rare, association between this pattern of basaloid follicular hamartoma, alopecia and myasthenia gravis, but only two cases have been described in association with SLE and none with APLS.

Adult↗
PubMed1998

Wegener's granulomatosis--a review of diagnosis and treatment in 53 subjects.

We reviewed 79 patients with clinically suspected Wegener's granulomatosis (WG) diagnosed in Nottingham between 1990 and 1997. Fifty-three patients were confirmed as having WG. We describe the symptoms and signs, features of diagnostic significance, ANCA results, biopsy sites, histology, treatment and outcome in this group. Nasal symptoms and signs had a positive predictive value of 63%, c-ANCA at presentation 100%, and positive nasal biopsy 100%. The negative predictive values were 41%; 79% and 74% respectively. From this study, we recommend that patients who have a negative ANCA and where there remains a clinical suspicion of WG, an ENT examination should be undertaken. Whilst a suspicious lesion should be biopsied and a positive histological picture has a 100% positive predictive value, a negative nasal biopsy does not exclude WG as 5 patients went on to develop a positive ANCA up to 4 years later. In 11 ANCA negative patients where there were signs of nasal mucosal disease, 6 had a positive biopsy and this highlights the importance of nasal biopsy. The c-ANCA should be repeated in patients with a negative c-ANCA and biopsy results at presentation, in whom there remains a clinical suspicion of WG.

Adult↗
PubMed1997

Peripheral blood lymphocyte binding to a soluble FITC-fibronectin conjugate.

Fibronectin receptors are critical to lymphocyte-mediated inflammation, and binding between immobilised plasma fibronectin and peripheral blood lymphocytes (pbl) is enhanced in patients with inflammatory diseases. Such enhancement could be due to an overall increase in receptor capacity and/or be a feature of a subset of cells. It could also depend on the initial binding and/or on events that follow receptor occupancy (e.g., cell spreading). To address these questions, we used fluorescein isothiocyanate-conjugated soluble fibronectin (FITC-FN) in a flow cytometric assay of lymphocyte-fibronectin binding. EDTA-inhibitable adhesiveness to FITC-FN is enhanced in lymphocytes cultured with Interleukin 2 and in fresh peripheral blood lymphocytes (pbl) from untreated patients with acute exacerbations of chronic inflammatory diseases. The enhanced binding was noted on both CD4+ and CD8+ subsets, and decreased with anti-inflammatory therapy.

CD4-Positive T-Lymphocytes↗
PubMed1997

Coculture of endothelial cells and smooth muscle cells in bilayer and conditioned media models.

Smooth muscle cell (SMC) growth characteristics are affected by endothelial cells (ECs) in vivo and in vitro. In this study, we compare a bilayer EC/SMC coculture model that allows cell contact with a model of SMCs growing in media continuously conditioned by ECs, but without physical contact. Bovine aortic SMCs were plated on one side of a 13-microns-thick, semipermeable membrane. Three models were compared: (1) SMCs cultured alone (with no cells on the opposite side of the membrane, O/SMC); (2) SMCs cultured with ECs on the opposite side of the membrane in a bilayer coculture system that allows physical contact between ECs and SMCs (EC/SMC); and (3) SMCs cultured in media continuously conditioned by adjacent ECs, without contact (conditioned media, CM). After cultures were established, SMCs were harvested at 7 and 14 days after plating (n = 5 cultures/day/group). SMC DNA and protein content and [3H]thymidine incorporation were measured in each group. On Days 7 and 14 after plating, ECs in both the EC/SMC and CM models stimulated SMC proliferation > 50% compared to O/SMC controls (P < 0.05). SMC density was similar for the EC/ SMC and CM models at Day 7, but SMC density was higher in the EC/SMC group at Day 14 in culture (P < 0.05). At Day 7, protein synthesis was similar in the three groups, but by Day 14, SMCs in the EC/SMC group had produced significantly less cellular protein/ DNA than SMCs in the CM group (P < 0.05), which in turn had less protein/DNA than the control (O/SMC) group (P < 0.05). SMCs in the EC/SMC and CM groups retained a thin, spindle shape with filamentous projections, compared to the hypertrophic appearance of SMCs in the absence of ECs. Electron microscopy revealed projections from SMCs which traversed the pores in the coculture membrane and made intimate contact with ECs. The degree of EC/SMC contact increased from 7 to 14 days (P < 0.05). Compared to SMCs alone, ECs in bilayer coculture or conditioned media altered SMCs growth characteristics similarly after 7 days in culture. By 14 days, however, the bilayer coculture had a significantly greater effect on SMC density and protein synthesis. The bilayer model is unique in terms of luminal/abluminal orientation of the cells, the proximity of the cell layers, and the presence of physical cell contact. Since the bilayer model amplifies the effect of ECs on SMCs, it may be more useful than conditioned media to study EC-SMC interactions.

Animals↗
PubMed1997

Elephantfish proinsulin possesses a monobasic processing site.

Total pancreatic RNA from the holocephalan species Callorhyncus milii (elephantfish) was used to make cDNA as a template for the polymerase chain reaction. Three redundant primers based on the known amino acid sequence of elephantfish insulin were used to amplify a fragment of proinsulin comprising truncated B-chain, complete C-peptide, and complete A-chain. Whereas the C-peptide/A-chain junction contained the expected dibasic cleavage site (-Lys-Arg-), the B-chain/C-peptide junction was found to contain only a single Arg, the first such site to be unequivocally associated with the proteolytic processing of a proinsulin to insulin. Examination of the flanking sequences around this site shows that a typical endocrine/neuroendocrine PC3 conversion enzyme should still be able to cleave, as the general requirements for precursor processing at a monobasic site are satisfied, notably a basic residue (Lys) at the -4 position. An acidic residue (in this case Asp) at the +1 position, which is seen in all known proinsulins, is maintained. The corresponding genomic DNA fragment of elephantfish proinsulin was also amplified by PCR, revealing a 402-bp intron at the conserved IVS-2 position within the C7 codon.

Amino Acid Sequence↗
PubMed1997

Endothelial cell effect on smooth muscle cell collagen synthesis.

UNLABELLED: Extracellular matrix (ECM) constitutes the bulk of mature intimal hyperplastic lesions. To determine if endothelial cells (ECs) inhibit smooth muscle cell (SMC) collagen synthesis, bovine aortic SMCs were cultured on plastic semipermeable membranes either alone or opposite ECs. SMCs were pulsed with 4 microCi/ml [3H]proline for 3 days and collagen synthesis was measured as trichloroacetic acid-precipitable counts in conditioned media and in cell lysate fractions. Each was standardized to SMC DNA (cpm/microgram DNA). EC effect on SMC gene expression of type I collagen was studied using Northern analysis. To determine whether TGF-beta 1 activation is involved in collagen synthesis regulation, parallel studies were performed in the presence of a neutralizing antibody to TGF-beta 1 (25 micrograms/ml) or aprotinin (a plasmin inhibitor, 200 micrograms/ml). SMCs cocultured with ECs were either untreated or treated with 5 ng/ml TGF-beta 1. The effect of culture substrate on EC-SMC interaction was studied by repeating experiments on type I collagen (CI), matrigel (MG), fibronectin (FN), and type IV collagen (CIV). RESULTS: Compared to SMCs cultured alone, ECs inhibited SMC collagen synthesis by 40 +/- 5% (P < 0.01) and gene expression of type I collagen by 60 +/- 4% (P < 0.01). The addition of neutralizing TGF-beta 1 Ab or aprotinin to SMCs cultured alone had no effect on collagen synthesis. Collagen synthesis in SMCs cultured alone on MG was reduced by 49% and by 16% on CIV when compared to SMCs cultured on plastic (plastic: 100 +/- 12% vs MG: 51 +/- 15% vs CIV: 84 +/- 18%, P = 0.10). Collagen synthesis was increased in SMCs cultured alone on FN (195 +/- 14% vs plastic: 100 +/- 12, P < 0.001) and CI (207 +/- 17 vs plastic: 100 +/- 12, P < 0.001). ECs decreased SMC collagen synthesis by 18 +/- 4% when cocultured on CI (P < 0.05) and by 22 +/- 2% when cocultured on MG (P < 0.05). FN prevented EC inhibition of SMC collagen synthesis. CONCLUSIONS: ECs inhibit SMC collagen synthesis and downregulate SMC type I collagen gene expression. TGF-beta 1 does not appear to be involved in this process. Culture substrate composition can affect SMC collagen synthesis and EC modulation of this process.

Animals↗
PubMed1997

Effect of renal insufficiency on outcome following infrarenal aortic surgery.

BACKGROUND: This study reviewed the effect of preoperative renal insufficiency on outcome following elective infrarenal aortic surgery. METHODS: The charts of 210 consecutive patients undergoing aortic surgery (occlusive disease, 15%; aneurysmal disease, 78%; or combined disease, 7%) from 1990 to 1995 were categorized into three groups based on preoperative creatinine ([Cr] group 1 Cr < 1.5, n = 171; group 2 Cr 1.5 to 1.7, n = 22; and group 3 Cr > or = 1.8, n = 17) and calculated creatinine clearance ([CrCl] CrCl > 45 mL/min, n = 162 versus CrCl < 45 mL/min, n = 48). Patients with renal artery stenosis or those who required suprarenal cross clamping or emergency procedures were excluded. Differences in postoperative intensive care unit (ICU) stay, ventilator days, dialysis dependence, morbidity, and, mortality were compared. RESULTS: Patients in groups 2 and 3 had an increased incidence of postoperative dialysis dependence (group 2 9%, group 3 8%) when compared with patients in group 1 (group 1: 0%, P < 0.05). Patients in the CrCl > 45 group had a lower mortality rate when compared with patients with a CrCl < 45 (CrCl > 45 0.6% versus CrCl < 45 8%, P <0.05) a lower incidence of dialysis (0% versus 7%, P <0.05), and a lower incidence of postoperative serum creatinine elevation from baseline (CrCl > 45 8% versus CrCl < 45 18%, P <0.05). There was no significant difference in morbidity, ICU stay, or ventilator days between the groups. Upon regression analysis, preoperative CrCl but not Cr was predictive of postoperative mortality (P <0.05). Serum Cr was more predictive than CrCl of impaired renal function postoperatively. CONCLUSIONS: Preoperative CrCl is more accurate than Cr as a predictor of postoperative mortality. Patients with preoperative CrCl < 45 mL/minute who undergo elective aortic surgery have a significant increase in postoperative cardiac-related mortality and dialysis.

Aged↗
PubMed1997

Superficial femoral artery stenoses: characteristics of progressing lesions.

PURPOSE: The purpose of this study was to assess the effect of superficial femoral artery (SFA) stenosis morphologic characteristics and lesion location on the rate of atherosclerotic disease progression. METHODS: We identified 19 patients who required arteriography for treatment of critical leg ischemia and who had previously undergone arteriography of that leg when minimal or no symptoms were present. These initial incidental arteriographic evaluations were performed during evaluation of arterial disease in another vascular bed from 4 to 81 months (mean, 32 months) previously. Distinct SFA stenoses or occlusion on the final arteriogram (n = 98) were characterized by their location, length, stenosis severity, and morphologic appearance on the initial arteriogram. The contribution of patient-specific risk factors to disease progression was also assessed. RESULTS: Stenosis progression occurred independently among multiple lesions within the same patient (negligible intraclass correlation coefficient, r = 0.06). Lesions in the adductor canal region were more likely to occlude than lesions elsewhere in the SFA (adjusted odds ratio = 10.7; p = 0.03). Severity of initial lesion stenosis also was predictive of occlusion (adjusted odds ratio = 1.8; p = 0.04). However, most progressing lesions (93%) actually arose in areas of initially mild disease (stenoses < 50%) despite more severe initial lesions elsewhere. Increasing age (p = 0.023) and previous contralateral leg bypass (p = 0.036) were also associated with increasing rates of lesion progression. Smooth-asymmetric lesions progressed 11% more slowly than other lesion types (p = 0.003). CONCLUSIONS: Our analysis of atherosclerotic SFA lesion progression in patients with critical ischemia shows that initial stenosis severity was associated with higher occlusion rates and that smooth-asymmetric lesions progressed more slowly than lesions with other morphologic characteristics. Severe stenoses usually arose from minimally diseased regions and progressed more rapidly than preexisting, more highly stenotic lesions. Most SFA occlusions resulted from disease progression in the adductor canal region whether or not antecedent lesions were seen on arteriography and whether or not more severe stenoses were initially present elsewhere. Increased age and history of previous contralateral bypass were patient-specific predictors of lesion progression.

Aged↗
PubMed1997

A comparative study of treadmill tests and heel raising exercise for peripheral arterial disease.

OBJECTIVES: This two part study validated a 1 min treadmill exercise test and compared this with simple heel raising exercise. METHODS: In an initial study of 24 claudicants (aged 43-79, median 63 years), ankle pressures were measured immediately after repeated treadmill exercises: for 1 min, until onset of claudication, and until maximum tolerated walking distance. Absolute value, fall and percent change in pressures were calculated. The results of this part of the study were then used as a "gold standard" for comparison with 30 s of heel raising and treadmill exercise. This second stage was performed on 21 symptomatic limbs (14 claudicants aged 42-73, median 69 years). RESULTS: Variability was least for pressures expressed as percent change after 1 min of exercise. The paired t-test revealed a significant correlation between the two methods of exercise (p < 0.05). CONCLUSION: Heel raising produced changes in ankle pressure which correlated well with those induced by treadmill exercise. We recommend the use of simple heel raising when a stress test is required to diagnose lower limb arterial insufficiency in the outpatient clinic.

Aged↗
PubMed1997

An investigation into variability in microvascular skin blood flow and the responses to transdermal delivery of acetylcholine at different sites in the forearm and hand.

AIMS: Transdermal iontophoresis in combination with laser Doppler fluxmetry (LDF) are useful techniques for examining dermal microcirculatory responses to different vasodilators. Differences in skin and microcirculation structure could influence the recorded baseline flux, and the observed vasodilatation. To examine this we compared baseline flux and the response of microvascular blood flow to a single vasodilator, acetylcholine, at sites in the forearm and hand. METHODS: Baseline microcirculation flow was recorded by LDF in a temperature controlled laboratory. The change in flux with iontophoresis of identical doses of acetylcholine, 150 microA for 40 s, was recorded at 12 different sites in the forearm and hand in 10 female and 3 male subjects. RESULTS: Baseline flux patterns and the vasodilatation to identical periods of iontophoresis of acetylcholine were site dependent. Palmar sites showed a higher baseline flux, but no vasodilatation to iontophoresis of acetylcholine. In contrast the volar forearm, dorsal hand and finger sites showed lower site-dependent baseline flux, but did vasodilate. CONCLUSIONS: Patterns of baseline flux are specific to sites on the hand and forearm reflecting differences in underlying microvascular structure. The vasodilatation to transdermal delivery of acetylcholine is also site dependent, but differences in skin structure may be more important than the underlying microvasculature in determining the response.

Acetylcholine↗