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Biomedical subjects

R J Powell

Publications and source records attributed to R J Powell.

At least 19 recordsLinked to original sources
PubMed1995

Quantitating intestinal ischemia with nitroblue tetrazolium salts.

We evaluated a spectrophotometric nitroblue tetrazolium (NBT) reduction assay as a technique to quantitate experimental intestinal ischemic injury. NBT is a tetrazolium salt that is reduced by mitochondrial coenzymes to form a blue formazan dye which can be measured on a spectrophotometer. We used a rat model of progressive intestinal ischemia to compare NBT reduction with standard histologic grading by light microscopy. Isolated segments of small intestine were made ischemic for periods of 15, 30, 60, 90, and 120 min in each of five rats (no reperfusion). A portion of each segment was prepared for both NBT reduction assay and blinded histologic grading. The reproducibility of these results was then tested in a second identical study of four rats (Part 2). When compared to nonischemic segments of intestine, NBT reduction was significantly decreased after 30 min of ischemia (P < 0.05, ANOVA) and continued to decrease as ischemic time increased. These findings were reproduced in the second experimental group. Overall, NBT reduction correlated closely with duration of ischemia (r = 0.81, P < 0.001) and histologic grade (r = 0.77, P < 0.001). Based on criteria developed in Part 1, NBT reduction had a sensitivity of 100% and a specificity of 94% for detecting ischemia > or = 30 min in Part 2. We conclude that the spectrophotometric NBT assay in an accurate technique for quantitating small intestinal ischemic injury which also gives useful information about the functional status of mitochondria.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1995

Arthropathy, leucopenia and recurrent infection associated with a TcR gamma delta population.

This report documents the presence of clonal gamma delta T-cell receptor (TcR) population in the blood of a patient who presented with an arthropathy of undetermined cause, leucopenia and splenomegaly. There was no evidence for lymphoid malignancy clinically or at post-mortem. The phenotype and genotype of the clonal T-cell population were not associated with the predominant TcR delta rearrangement found in peripheral blood gamma delta cells, but were similar to those found in gamma delta TcR cells infiltrating rheumatoid synovium. The data indicate the presence of a monoclonal population of gamma delta cells TcR cells which in the face of continued immunosuppression behaved benignly. The case may represent a cytomorphologically atypical example of the large granular lymphocytes, neutropenia and arthropathy syndrome/lymphoproliferative disease of granular lymphocytes and, although the patient's clinical features were not 'classical', rheumatoid arthritis (RA) may have been the underlying primary disorder.

Arthralgia↗
PubMed1995

Enhanced expression of MHC class I molecules on cultured human thyroid follicular cells infected with reovirus through induction of type 1 interferons.

Certain viruses are known to modulate the cellular expression of MHC molecules. We have investigated whether reovirus types 1 or 3 can alter the normal MHC molecule expression on cultured human thyroid follicular cells (TFC). Primary TFC cultures were established from eight human thyroid donors and MHC class I and II expression was assessed by indirect immunofluorescence microscopy. Both types of reovirus enhanced MHC class I expression on TFC from all thyroid donors. Class II MHC protein was strongly induced by type 1 reovirus on TFC from one donor, while weak induction of expression, by either reo-1 or reo-3 virus, was noted on the TFC of five other donors. Studies on the mechanism(s) of MHC class I hyperexpression showed that mouse MoAb against the type 3 reovirus haemagglutinin (anti-HA3) reduced the ability of the virus to induce hyperexpression of class I MHC molecules on TFC. However, supernatant harvested from type 3 reovirus-infected TFC cultures maintained its ability to enhance class I expression after incubation with anti-HA3. Moreover, adding rabbit anti-sera to interferon-alpha (IFN-alpha) or IFN-beta inhibited the increased class I MHC expression on TFC by both types of reovirus. These data suggest that reoviruses (types 1 and 3) can enhance MHC class I on cultured TFC. The mechanism of MHC class I enhancement is most probably through the release of IFN-alpha and IFN-beta.

Antibodies, Monoclonal↗
PubMed1995

Interferon-gamma and urine neopterin in attacks of the hyperimmunoglobulinaemia D and periodic fever syndrome.

The hyperimmunoglobulinaemia D and periodic fever (hyper-IgD) syndrome is typified by recurrent unpredictable febrile attacks with abdominal pain, joint involvement (arthralgias/arthritis), headache, skin lesions and a polyclonal elevation of serum IgD (> 100 U mL-1). Interferon-gamma (IFN-gamma) is a major proinflammatory cytokine which could play a role in the pathogenesis of the attacks. There is a need for parameters (if possible non-invasive) to monitor disease activity. A potential candidate is neopterin which is released by monocytes/macrophages when stimulated with IFN-gamma, excreted unchanged in urine, and appears to be an early and sensitive marker for activation of the immune system. We measured rectal body temperature, serum IFN-gamma, and urine neopterin in 10 hyper-IgD patients both during and between attacks. The body temperature rose to a mean of 38.9 degrees C on the first day of the attack and normalized within 5 days. Serum IFN-gamma during the first day of the attack was 2.98 IU mL-1 and was significantly lower during remissions. The urine neopterin excretion was 268 +/- 170 mumol mol-1 creatinine between attacks and was significantly increased to 638 +/- 275 mumol mol-1 creatinine on the first day of symptoms. Maximal urine neopterin values were reached on the fourth day of the attack (1051 +/- 387 mumol mol-1 creatinine) and excretion gradually declined and attained values below 400 mumol mol-1 creatinine after 9 days. There was a good correlation between serum IFN-gamma and urine neopterin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Distribution of cases of systemic lupus erythematosus at time of first symptom in an urban area.

OBJECTIVES: To determine the geographical distribution of cases of systemic lupus erythematosus (SLE) in a defined geographical area in the East Midlands, UK, and, in particular, to search for spatial variation in cases that may implicate the role of environmental factors in SLE aetiology. METHODS: Six methods of case ascertainment were used. The postcode of the patient's domicile at time of first definite symptom of SLE was used for analysis which included case mapping, probability mapping by electoral ward, and variogram analysis. RESULTS: The study area population of 613,700 contained 200 SLE patients, 188 of whom experienced their first symptom whilst residing in the area. Case mapping revealed 12 SLE patients residing within an area of one square mile, including four men and six patients with RNP antibodies. The use of probability mapping showed five wards in close proximity to each other to have a greater number of SLE cases than would be expected by chance (p < 0.1). The 'cluster' of patients seen on the case map fell into two wards which showed a significant excess of cases only when combined (p = 0.006). The variogram of the incidence rates for each ward did not confirm any structure or pattern to the distribution of cases for the whole area. CONCLUSIONS: Some areas have a greater than expected prevalence of SLE. The normal result from variogram analysis suggests that the cause(s) for these excess number of cases does not have an effect across the whole study area.

Adolescent↗
PubMed1995

Investigation of the prevalence and clinical associations of antibodies to human fibronectin in systemic lupus erythematosus.

OBJECTIVES: To assess the prevalence of antibodies to human fibronectin (anti-Fn) in sera of patients with certain connective tissue diseases and to determine their association with disease activity and the pattern of organ involvement in patients with systemic lupus erythematosus (SLE). METHODS: A capture enzyme linked immunosorbent assay (ELISA) was developed to quantify anti-Fn antibodies in serum samples from 65 patients with well characterised SLE, 50 with rheumatoid arthritis (RA), 15 with Behçet's disease (BD), 15 with systemic vasculitis and 36 healthy subjects. An anti-Fn antibody titre greater than mean + 3SD of the healthy control log values after back transformation to the normal scale was considered positive. Disease activity in SLE patients was scored using the British Isles Lupus Assessment Group (BILAG) Index. Erythrocyte sedimentation rate (ESR), concentrations of anti-dsDNA antibody, soluble interleukin-2 receptors (sIL-2R), C3, C4, C3 degradation products (C3dg) and immunoglobulin, and antinuclear antibody (ANA) titres were measured in blood samples from SLE patients; neopterin concentration was measured in corresponding urine samples. RESULTS: Anti-Fn antibodies were found in 22 of 65 SLE patients (33.8%), seven of 50 with RA (14%), one of 15 with BD (6.6%) and none of the 15 subjects with vasculitis. Thirty SLE patients had active disease and 35 had inactive disease; their median anti-Fn concentrations were 117 u/ml (range 47-450) and 68 u/ml (range 17-334), respectively (p = 0.0001). The presence of anti-Fn did not correlate with immunoglobulin concentrations or ANA titres in these sera. No significant difference was found between SLE patients with disease activity in one major organ system compared with multiple organ involvement, as defined by BILAG (p = 0.19). However, patients with musculoskeletal manifestations had consistently greater anti-Fn concentrations compared with patients with other clinical manifestations. There were significant correlations between amounts of anti-Fn in SLE sera and ESR (rs = 0.25, p = 0.045), sIL-2R (rs = 0.28, p = 0.024) and urine neopterin (rs = 0.3, p = 0.016) but not with serum anti-dsDNA antibody titres, plasma C3, C3dg or C4. However multiple regression analysis showed a low significant correlation only with sIL-2R and BILAG score (p = 0.047 and 0.042, respectively). CONCLUSION: Anti-Fn antibodies were detected in 34% of SLE patients and in small proportions of RA and BD patients. An association between serum anti-Fn and disease activity in SLE has been identified and most SLE patients with musculoskeletal involvement had increased anti-Fn antibody concentrations.

Adult↗
PubMed1994

Human anti-fibronectin antibodies in systemic lupus erythematosus: occurrence and antigenic specificity.

Sera from patients with connective tissue diseases exhibit autoantibodies to a spectrum of extracellular matrix proteins. Antibodies binding to solid phase bovine fibronectin (Fn) were investigated by ELISA in patients with systemic lupus erythematosus (SLE). Sera showing binding of 2 s.d. above the mean of the normal human control were considered positive and 43/150 SLE sera (28.7%) demonstrated such binding. These antibodies were mainly IgG and IgA as determined by isotype-specific ELISA. Specificity studies on selected positive sera revealed that binding was inhibited by preincubation with soluble Fn, but not with thyroglobulin or type 1 collagen. The binding was demonstrated not to be related to interactions with rheumatoid factor, complement components or immune complexes. Additional studies to determine which Fn fragment is bound by naturally occurring anti-Fn antibodies demonstrated that the binding was predominantly to the 30-kD collagen binding domain (CBD) of Fn molecule. Inhibition studies using 120-kD, 40-kD and 30-kD Fn fragments confirmed that this binding site was the 30-kD CBD.

Adolescent↗
PubMed1993

Distribution of cell adhesion molecules in skeletal muscle from patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the pathophysiology of perivascular mononuclear cell infiltrates observed in skeletal muscle from patients with systemic lupus erythematosus (SLE). METHODS: Immunocytochemical techniques were used to examine frozen 5 microns sections from the quadriceps needle muscle biopsy specimens of 14 patients with SLE (including seven with infiltrates) for the expression of the cytokine inducible adhesion molecules intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. RESULTS: Vessels in 6/7 SLE biopsy specimens with perivascular infiltrates expressed VCAM-1 at a density of > 2 vessels/mm2 in contrast with 0/7 SLE biopsy specimens without infiltrates and 1/6 control specimens. In contrast, E-selectin expression was increased ( > 0.3 positive vessels/mm2) in SLE biopsy specimens compared with control tissue regardless of the presence of perivascular infiltration. VCAM-1 and ICAM-1 were also noted on extravascular cells in the infiltrates, being particularly prominent on the intermuscle fibre dendritic processes of CD68+ HLA-DR+ cells. CONCLUSION: Expression of these cytokine inducible adhesion molecules may be important in the migration of mononuclear cells into skeletal muscle and may be involved in intercellular interactions within the tissue.

Adult↗
PubMed1992

Autoantibodies in pet dogs owned by patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) occurs in human beings and in dogs. There is evidence to suggest that the disease is caused by a transmissible factor that may cross the species barrier. We investigated this possibility by looking for autoantibodies and serum protein abnormalities in serum samples from 15 pet dogs owned by patients with SLE and comparing results with those obtained with serum from 10 healthy dogs kept in a controlled environment and 9 dogs with autoimmune diseases. We used standard immunological assays modified for use with canine samples. Compared with the normal dogs, increased amounts of antibody to double-stranded DNA were found in serum from the SLE patients' dogs (median optical density [405 nm] = 0.117 vs 0.299; p = 0.0001), this latter amount being similar to that found in serum from the autoimmune group (0.201; p = 0.6). Abnormal serum protein electrophoresis patterns were found in samples from the autoimmune and SLE patients' dogs but not the normal dogs. These findings support the idea that exposure to common environmental factors or transmissible agents may have a role in causing SLE.

Animals↗
PubMed1992

Autoantibodies, immunoglobulins and Gm allotypes in nodal generalized osteoarthritis.

The frequencies of autoantibodies, including class specific rheumatoid factors, Gm allotypes, and levels of immunoglobulins were determined in 86 patients with nodal generalized osteoarthritis (NGOA), 79 patients with non-nodal large joint osteoarthritis (LJOA), and 90 non-osteoarthritic controls. NGOA patients had a higher frequency of IgG rheumatoid factor (P less than 0.0001) compared to LJOA and normal subjects. Both osteoarthritic groups had lower mean levels of IgA than normals (P less than 0.05), and NGOA patients had a higher frequency of subnormal IgA levels than normals. No differences in other rheumatoid factors nor in frequencies of Gm allotypes were seen. These data support characterization of NGOA as a distinct subset of osteoarthritis, and suggest involvement of immune processes in its pathogenesis.

Aged↗
PubMed1992

Selective activation of circulating CD4+ lymphocytes in severe adult atopic dermatitis.

An analysis of peripheral blood lymphocyte subsets and their expression of activation markers was performed using flow cytometry in 12 adult patients with severe atopic dermatitis, and compared with 14 normal individuals. Repeated measurements were made over an 8-week period during which disease activity was also assessed. Increased percentages of activated and unactivated CD4+ lymphocytes, and decreased percentages of CD8+ cells were observed in atopic dermatitis. Increasing disease activity was associated with an increase in the proportion of activated and unactivated CD4+ lymphocytes and a fall in the proportion of CD8+ cells. This study demonstrates that in adults with severe atopic dermatitis, increasing disease activity is associated with selective activation of CD4+ lymphocytes and a relative expansion of the CD4+ cell subset.

Adolescent↗
PubMed1992

Classical complement activation induced by pregnancy: implications for management of connective tissue diseases.

AIMS: To determine the effect of pregnancy on C4d concentrations and to assess whether C4d remains a useful disease activity marker in the management of connective tissue diseases during pregnancy. METHODS: Plasma C3, C4, and C4d concentrations were measured in 83 women at various stages of normal pregnancy and compared with those in 80 non-pregnant controls. RESULTS: C3 concentrations in the pregnant women were significantly raised (p = 0.0001) and the C4 concentrations were reduced (p = 0.0007), and accompanied by a significant increase in C4d (p = 0.0001). The C4d:C4 ratio was higher in the pregnant women (p = 0.0001). CONCLUSIONS: Pregnancy induces activation of the classical complement pathway. C4d concentrations cannot be used to monitor disease activity in patients with connective tissue diseases during pregnancy.

Adolescent↗
PubMed1992

Respiratory disease in systemic lupus erythematosus: correlation with results of laboratory tests and histological appearance of muscle biopsy specimens.

BACKGROUND: In systemic lupus erythematosus, certain laboratory tests and evidence from muscle biopsy specimens of lymphocytic vasculitis reflect disease activity. A study was designed to determine if such indices predict respiratory lesions, and in particular whether the presence of vasculitis in quadriceps muscle reflects respiratory muscle function. METHODS: Twenty seven 27 patients with systemic lupus erythematosus were studied, ten of whom were consecutive untreated patients and 17 having clinically active disease and being treated. They were prospectively evaluated on the basis of erythrocyte sedimentation rate, lymphocyte count, C3 degradation products, quadriceps muscle biopsy, spirometry, lung volumes, carbon monoxide transfer factor, and mouth pressure during a maximal sniff. RESULTS: Lung function test results were abnormal in 12 patients. Vital capacity was reduced in seven, carbon monoxide transfer factor capacity in five, and mouth pressure was low (< 70% predicted) in ten. Lymphocytic vasculitis was seen in the muscle biopsy specimens of ten patients. No correlation was found between laboratory tests and lung function or mouth pressure, or between the presence of lymphocytic vasculitis and mouth pressure. In untreated patients, those with lymphocytic vasculitis had lower spirometric values. CONCLUSIONS: In systemic lupus erythematosus, evidence from muscle biopsy specimens of lymphocytic vasculitis is not predictive of impaired inspiratory muscle function as measured by mouth pressure. In untreated patients there were relationships between some laboratory test results and respiratory function, but this was not the case for the whole group. In systemic lupus erythematosus, laboratory tests and evidence from muscle biopsy specimens of lymphocytic vasculitis are therefore unlikely to be helpful in the assessment of respiratory disease.

Adult↗
PubMed1992

Effect of moricizine on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers.

Moricizine HCl, a new orally active antiarrhythmic agent, induces its own hepatic metabolism and consequently may interfere with the metabolism of warfarin, a drug used commonly by cardiac patients that also is subject to extensive hepatic metabolism. Both drugs are also highly protein bound in plasma. To assess the possibility of an interaction, single-dose sodium warfarin (25 mg oral Coumadin, Du Pont Pharmaceuticals, Wilmington, DE) pharmacokinetics, pharmacodynamics; and plasma protein binding were examined in 12 healthy male volunteers 14 days before and 14 days after starting chronic oral moricizine HCl administration (250 mg every 8 hours). The terminal elimination rate constant of warfarin was increased by about 10% when measured in the presence of chronic moricizine administration. However, oral plasma clearance, apparent volume of distribution, maximum peak plasma concentration, time to reach peak concentration, and protein binding were unaffected. More importantly, there was no evidence of a pharmacodynamic interaction based on the prothrombin time profile. It was concluded that no clinically significant interaction occurs under these conditions.

Adult↗
PubMed1992

Screening of acute psychiatric admissions for previously undiagnosed systemic lupus erythematosus.

An auto-antibody screen for SLE, which included antinuclear antibodies, was performed on 296 patients admitted to acute psychiatric and psychogeriatric wards. Three cases (1% of those screened) of previously undiagnosed SLE were found, and one patient was found to have autoimmune chronic active hepatitis. An auto-antibody screen may be a useful investigation in psychiatric practice.

Adolescent↗