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Biomedical subjects

J C Edwards

Publications and source records attributed to J C Edwards.

At least 145 records · Page 8Linked to original sources
PubMed1987

Temperature sensitive pet mutants in yeast Saccharomyces cerevisiae that lose mitochondrial RNA.

This is a description of a new class of temperature sensitive pet mutants in Saccharomyces cereviase that lose all or part of their mitochondrial RNA at the restrictive temperature. These mutants fall into 8 different complementation groups, mna1 to mna8, and 2 different classes based on their phenotype. Class I mutations, mna1-1 through mna5-1, cause complete or partial loss of mitochondrial RNA at the restrictive temperature. The mutation, mna1-1, is especially interesting since it causes a loss of both mitochondrial DNA and RNA when the mutant is grown on a fermentable carbon source at the restrictive temperature. However, when this mutant is grown at the permissive temperature on a non-fermentable carbon source then shifted to the restrictive temperature, only the mitochondrial RNA is lost. This indicates that the primary cause for the pet phenotype is due to the loss of mitochondrial RNA and not DNA. Class II mutations, mna6-1 through mna8-1, cause complete loss of the 14S rRNA after growth at the restrictive temperature in a fermentable carbon source. This loss appears to be specific for the 14S rRNA, since all other transcripts probed by Northern analysis are normal.

DNA, Mitochondrial↗
PubMed1987

A double blind controlled trial of methylprednisolone infusions in systemic lupus erythematosus using individualised outcome assessment.

Twenty one patients with severe systemic lupus erythematosus (SLE) were treated with three daily infusions of either 100 mg or 1 g of methylprednisolone on a randomised double blind basis. Nine patients with unsatisfactory outcome subsequently received the alternative therapy. Patients were rated for improvement on a four point scale using individualised criteria. On three occasions patients improved to 'ideal', on 12 there was 'useful' improvement, on 11 the patient remained static, and on four occasions there was deterioration. There was no significant difference between the clinical states after the two doses. The results suggest that any additional benefit of 1 g of methylprednisolone over 100 mg by repeated infusion in the treatment of active SLE is probably not enough to justify the potential hazards and cost involved.

Adult↗
PubMed1987

A new approach to patient indexing.

A computer based rheumatology patient index is described. Patients are indexed according to essential clinical and laboratory data without reference to Procrustean diagnostic labels. The stored information can be searched for a wide range of practical and scientific purposes. The software was devised in the windows environment for the Apricot Xen for maximum speed and intelligibility.

Humans↗
PubMed1986

Long-term evaluation of training residents in clinical teaching skills.

In the present study, the authors examined the long-term effectiveness of a course for residents on how to teach students, patients, and peers. Residents of various specialties attended a mandatory short course on clinical teaching skills in the middle of their first year of postgraduate medical training. Three types of evaluation data were collected at three times during a two-year period: self-ratings by the residents, questionnaires completed by the residents, and ratings completed by students taught by the residents. Complete data for 18 residents indicated that the residents rated their teaching skills significantly higher after the course (at the end of both the first year and the second year) than before it. At the end of the second year, 94 percent of the residents stated that the course was helpful, 67 percent could recall and explain specific principles of teaching, and 61 percent reported using principles from the course in their teaching. Students' ratings of these 18 residents were too scanty to be interpreted validly. The study suggests that residents of varying specialties can profit from an introductory course on teaching skills and that the effects endure for at least one and a half years.

Clinical Competence↗
PubMed1986

Connective tissue abnormalities in MRL/1 mice.

Pathological changes in the connective tissue of the limbs of MRL/1 mice are described. Focal infiltrates of polymorphs or large mononuclear cells, or both, were seen both in synovial lining and subcutaneous tissue. Infiltrates were associated with vasculitis in some cases. Deposits of amorphous material were seen in and around joints and in foot pads. The material was more particulate and refractile than typical 'fibrinoid' and showed a positive Feulgen reaction. It was not surrounded by palisading cells and when seen in synovial tissue was not usually associated with changes in synovial lining cells. No obvious difference was seen between intra-articular and extra-articular lesions. Lesions in subcutaneous tissue occurred exclusively in the foot pads. Lymphocyte infiltration was not prominent at any site and no follicle formation was seen. Of two colonies studied, only one showed a significant increase in lining cell numbers in synovial tissue. Exercised animals had a similar distribution and severity of disease to those of matched controls. All lesions described were distinguishable from non-specific inflammatory lesions in normal control mice and MRL/++ mice on assessment of unmarked sections. The relation between these connective tissue lesions and the changes found in human chronic synovitis is discussed.

Animals↗
PubMed1986

Nailfold capillary microscopy in connective tissue disease: a quantitative morphological analysis.

Photomicrographs were taken of front line nailfold capillary loops in 18 healthy women (controls) and 42 women with established connective tissue disease (14 rheumatoid arthritis, 19 systemic lupus erythematosus, nine scleroderma). Measurements were made of apex width, maximum limb and loop widths, capillary length, interpeak distance, and frequency per linear millimetre. A numerical index for assessing capillary dilatation was derived, based on the mean of the apex plus maximum limb widths. Results show considerable overlap in subject means. Statistical analysis showed no difference between rheumatoid arthritis and control groups. Patients with systemic lupus erythematosus had slightly larger loops at a lower frequency (not statistically significant); three patients with an abnormal capillary index also had high titres of ribonucleoprotein antibody. Six scleroderma patients had abnormal indices, two of whom had high titre ribonucleoprotein antibody. No relation between capillary morphology and clinical features was found.

Adult↗
PubMed1986

Degradation of cartilage in contact with soft tissue.

Observations have been made on histological changes in femoral-head articular cartilage transplanted into soft tissue in rats under a variety of conditions. Articular cartilage was implanted either whole or minced. Implants were made into deflated subcutaneous air pouches with or without an inflammatory irritant and into normal subcutaneous tissue. Cartilage-matrix loss occurred in four patterns: marginal zone encroachment, loss of metachromatic staining without loss of tissue mass, surface invasion and lacunar enlargement and coalescence. The presence of an inflammatory reaction had no discernible effect on loss of cartilage matrix. Changes at the marginal zone preceded changes at the centre. Loss of metachromatic staining without loss of tissue mass occurred in areas of chondrocyte death. Surface invasion was not affected by the viability of the underlying chondrocytes. Surface invasion occurred earliest in cartilage transplanted into subcutaneous tissue, and latest in cartilage implanted into air pouches inflamed with carrageenan. The onset of surface invasion appeared to be dependent on soft-tissue adhesion to the cartilage surface. Mincing of cartilage was associated with an increase in surface invasion in the deeper cartilage zone with large lacunae but not in the superficial zone with small lacunae. Occasional cut surfaces showed outgrowth of new cartilage matrix. These observations on artefactual modes of cartilage degradation may assist in analysing the critical steps in cartilage degradation in arthritic joints.

Air↗
PubMed1985

Characterization of a yeast mitochondrial promoter by deletion mutagenesis.

We have generated collections of mutants of the promoter for the small rRNA gene from the mitochondria of yeast deleted from either the 3' or 5' end. Plasmids containing the partially deleted promoter were assayed for their ability to direct correct transcriptional initiation in a homologous in vitro system. We find that the region required for high-efficiency promoter function lies between positions -10 and +2. Our methods detected no effect of flanking sequences on the strength of this promoter.

Base Sequence↗
PubMed1985

Radiosensitivity of peripheral blood lymphocytes in autoimmune disease.

The proliferation of peripheral blood lymphocytes, cultured with Con A, can be inhibited by ionizing radiation. Lymphocytes from patients with conditions associated with autoimmunity, such as rheumatoid arthritis, systemic lupus erythematosus and polymyositis, are more radiosensitive than those from healthy volunteers or patients with conditions not associated with autoimmunity. The nuclear material isolated from the lymphocytes of patients with autoimmune diseases is, on average, lighter in density than the nuclear material from most healthy controls. This difference in density is not related to increased sensitivity to ionizing radiation but the degree of post-irradiation change in density (lightening) is proportional to the initial density, i.e. more dense nuclear material always shows a greater upward shift after radiation. The recovery of preirradiation density of nuclear material, 1 h after radiation exposure, taken as an indication of DNA repair, correlates with the radiosensitivity of lymphocyte proliferation (Con A response); failure to return to pre-irradiation density being associated with increased sensitivity of proliferative response. These results require extension but, taken with previously reported studies of the effects of DNA methylating agents, support the idea that DNA damage and its defective repair could be important in the aetio-pathogenesis of autoimmune disease.

Adult↗
PubMed1985

Studies into the influence of carrageenan-induced inflammation on articular cartilage degradation using implantation into air pouches.

We describe a novel system for examining the degradation of articular cartilage in vivo. Implantation of rat femoral head cartilage into six day old subcutaneous air pouches allows the examination of the degradation of cartilage in contact with a synovial lining-like structure. Femoral head cartilage was removed 1, 2 or 3 weeks after implantation and the proteoglycan content measured using 1,9-dimethyl methylene blue. Chondrocyte viability was confirmed using 35S sulphate incorporation. Increasing proteoglycan loss was observed over 3 weeks. Loss was similar in transplants between inbred and between outbred animals, suggesting that allograft rejection did not contribute significantly. Introduction of the irritant carrageenan into pouches produced a massive and prolonged inflammatory response characterized by exudation of leucocyte-rich fluid. Induction of inflammation with carrageenan did not alter the profile of proteoglycan loss from whole, minced, live or dead cartilage, as compared to that seen in non-inflamed pouches. These results indicate that when the relationship between articular cartilage and its normal tissue surroundings is disturbed, rapid proteoglycan loss may occur. The conditions induced by carrageenan inflammation have, in comparison, little or no effect on cartilage degradation. This raises the possibility that the direct effects of inflammatory products are of relatively minor importance to cartilage destruction in human arthritis.

Animals↗
PubMed1985

The immune response to pertussis in the 6-day air pouch: a model of chronic synovitis.

We have developed a model of prolonged immunological inflammation in the rat which has a structural resemblance to the synovial changes in rheumatoid arthritis. Pertussis vaccine was injected into 6-day-old subcutaneous air pouches in animals previously sensitized with pertussis vaccine. The resulting inflammatory response persisted up to 30 days. Examination of exudates showed a wave of polymorphonuclear leucocytes over a 13-day period followed by a mononuclear cell predominance up to 30 days. Histologically, an early polymorphonuclear cell infiltration was followed by the formation of a lining layer of large eosinophilic mononuclear cells, together with deep collections of lymphocytes and plasma cells. Concentrations of the acute-phase reactant alpha 1-glycoprotein, in both serum and exudate, peaked at 3 days. This suggests that the local production of interleukin I in this type of tissue reaction is more closely related to the acute inflammatory phase than to more chronic interactions between monocyte derived cells and lymphocytes.

Air↗
PubMed1984

The effects of ionizing radiation on the peroxide content of a pure polyunsaturated lipid dispersion and of lipids and membranes derived from Acholeplasma laidlawii.

Dispersions of a pure unsaturated phospholipid, dilinoleoylphosphatidyl choline, formed conjugated diene hydroperoxides when irradiated in air with 7 MeV electrons (150 Gy and 300 Gy). Peroxide formation was optimized when the dispersions were irradiated in air at 37 degrees C at a dose rate of 5 Gy/min. No significant loss of linoleic acid from the irradiated phospholipid dispersions was observed after doses of 150 or 300 Gy. Small amounts of thiobarbituric acid-reactive material were formed in irradiated unsaturated phospholipid dispersions. However, lipids or membranes isolated from 48 hour cultures of Acholeplasma laidlawii grown in media supplemented with either linoleic or linolenic acid did not appear to be peroxidized by irradiation under the same conditions.

Acholeplasma laidlawii↗