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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

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

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

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

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

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

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

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

Interferon induces tryptophanyl-tRNA synthetase expression in human fibroblasts.

A cDNA clone complementary to an interferon (IFN)-induced mRNA was isolated and used to characterize the regulation of expression of its RNA by the IFNs and to identify the protein its RNA encodes. This cDNA hybridizes to IFN-induced 3.1- and 2.3-kilobase mRNAs that are synthesized in response to both IFN-alpha and IFN-gamma. IFN-gamma induces the sustained accumulation of these mRNAs while IFN-alpha induces their transient accumulation. Cycloheximide (50 micrograms/ml) failed to inhibit the induction of these mRNAs by either IFN-alpha or IFN-gamma, suggesting that their induction does not require de novo protein synthesis. DNA sequence analysis of this cDNA reveals that it encodes a protein of Mr 53,168 that has sequence homology with and the biological activity of a tryptophanyl-tRNA synthetase, an enzymatic activity that has been demonstrated to play a role in and be modulated by the growth of cells. Elevated levels of this enzyme may be involved in the cell growth inhibitory activity of the IFNs.

Amino Acid Sequence

Clinical immunology.

Explore the source record for details and available documents.

Antibodies, Monoclonal

Effect of oxygen-free radical scavengers on survival in sepsis.

UNLABELLED: Sepsis remains a leading cause of death in the surgical intensive care unit (SICU) patient following major surgery or trauma. Recent work has demonstrated that oxygen-free radicals (OFR) generated during sepsis contribute to the pathogenesis of this syndrome. The purpose of this study was to evaluate the effect of various new free radical scavengers on survival in sepsis. A total of 85 male Sprague-Dawley rats were placed into one of the following treatment groups. CONTROL: cecal ligation and puncture (CLP); PRE-AT: pretreatment with alpha-tocopherol (AT) 10 mg/100 gm SC x 3 days, and 5 mg/100 gm IV prior to CLP; AT: 20 mg/100 gm at time of CLP and 4 hours following CLP; U74006F: (21-aminosteroid which inhibits lipid peroxidation) 3 mg/kg IV at the time of and 4 hours following CLP; U78517F: (alpha-tocopherol analogue) 3 mg/kg at the time of and 4 hours following CLP. Survival was determined at various time points up to 72 hours. Pretreatment with AT resulted in improved survival, whereas the novel OFR scavengers U78517F and U74006F significantly improved survival and were efficacious without pretreatment. It was concluded that OFR scavengers can improve survival in sepsis.

Animals

Oxygen free radicals: effect on red cell deformability in sepsis.

OBJECTIVE: To examine the effect of alpha-tocopherol, a free radical scavenger, on RBC deformability, mixed venous hemoglobin saturation (SvO2), arterial-venous oxygen content difference (C[a-v]O2), pHv, and survival during sepsis. DESIGN: Randomized controlled study. INTERVENTIONS: Sprague-Dawley rats were randomized to three groups: sham, cecal ligation and puncture, or alpha-tocopherol/cecal ligation and puncture (pretreatment with alpha-tocopherol before cecal ligation and puncture). MEASUREMENTS AND MAIN RESULTS: The cecal ligation and puncture group had a significantly (p less than .05) higher SvO2 and lower C (a-v)O2, pHv, and survival rate when compared with alpha-tocopherol/cecal ligation and puncture and sham groups. No difference in pHa existed between groups. CONCLUSIONS: The alpha-tocopherol treatment improves survival in sepsis. RBC deformability during sepsis is prevented by alpha-tocopherol, suggesting that free radicals may cause the decrease in RBC deformability. This study provides indirect evidence that decreased RBC deformability may play a role in the physiologic peripheral shunting and decreased microcirculatory flow that occurs during sepsis.

Animals

The hilar snare, and improved technique for securing rapid vascular control of the pulmonary hilum.

Massive hemorrhage from pulmonary injuries is often refractory to hilar crossclamping. We report a simple technique, the hilar snare, to control such injuries and compare it to the standard technique of hilar occlusion with a vascular clamp. Standardized lacerations were made in the lung in each of six adult dogs. Blood loss from the injured lung was measured before and after placement of the hilar snare and compared to that following hilar occlusion with a Satinsky clamp (occlusive surface, 5.5 cm). The rate of blood loss before control was not significantly different between the two groups. Blood loss from the lacerated lung was significantly less (p less than 0.05) in the Hilar Snare group (9 +/- 4 ml/min) when compared to the Satinsky group (46 +/- 14 ml/min). The snare's flexible nature ensures complete occlusion of the hilar vessels and is a useful adjunctive technique to present methods of controlling severe pulmonary hemorrhage.

Adult

Toxoplasmosis and systemic lupus erythematosus.

The toxoplasma serological status of 50 patients with systemic lupus erythematosus (SLE) was compared with that of 50 healthy controls; high titres of toxoplasma antibody were significantly more common in the patients with SLE. These titres did not correlate with any of the routinely measured indices in SLE nor with the patients' prior treatment. A case history is used to illustrate the difficulty in diagnosing toxoplasmosis in the presence of SLE.

Adult