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Biomedical subjects

J C Edwards

Publications and source records attributed to J C Edwards.

At least 163 records · Page 9Linked to original sources

Effects of local administration of hydrocortisone on cartilage degradation in vivo.

The effect of corticosteroid on autologous minced cartilage transplanted into facsimile synovial cavities has been studied. The soluble form of hydrocortisone, as the sodium succinate, reduced proteoglycan loss from cartilage in a dose-dependent manner. In contrast, insoluble hydrocortisone acetate, if given directly into the cartilage-containing cavity, enhanced proteoglycan loss. Injection of the same dose of drug into the inflamed lining tissue reversed this effect. These findings suggest that intra-articular steroid injection may enhance cartilage damage if insoluble preparations are used, but that this may be overcome by injecting into the inflamed lining tissue rather than into the cavity itself.

Air↗

Microvascular filtration in subjects with connective tissue disorders.

A simple non-invasive method for studying microvascular filtration in the non-articular tissues of the forearm is described. Rates of filtration under a standard hydrostatic pressure were measured in 20 normal female subjects and 44 female subjects with connective tissue disorders. An increased mean filtration rate was found in 14 subjects with rheumatoid arthritis. In 20 subjects with systemic lupus erythematosus and 10 subjects with scleroderma no such generalised increase in filtration rates was seen, but isolated cases had very high filtration rates, suggesting a more heterogeneous physiological disturbance. Increased filtration was not associated with the presence of oedema. This confirms doubts raised by other workers about the importance of filtration in the genesis of clinical oedema.

Adult↗

Relaxation of intrapulmonary artery and vein by nitrogen oxide-containing vasodilators and cyclic GMP.

The present study examines the relationship between tissue cyclic nucleotide levels and relaxation of bovine intrapulmonary arterial and venous smooth muscle in response to nitroglycerin, nitroprusside, S-nitroso-N-acetylpenicillamine and isoproterenol. Recent studies have suggested that cyclic GMP may be involved in the relaxation of vascular smooth muscle produced by nitrogen oxide-containing vasodilators and that S-nitrosothiols may act as intermediates of the latter agents. In the present study, nitroglycerin, nitroprusside and S-nitroso-N-acetylpenicillamine were more potent as relaxants of venous than arterial segments. Each of these agents elevated tissue cyclic GMP levels, but not cyclic AMP levels, before relaxation. These nitrogen oxide-containing agents were more potent as elevators of cyclic GMP levels in venous than arterial tissue and this correlated generally with their effects on vascular smooth muscle tone. Methylene blue antagonized both relaxation and increased cyclic GMP levels elicited by nitroglycerin, nitroprusside and S-nitroso-N-acetylpenicillamine. In contrast to the nitrogen oxide vasodilators, 8-bromo-cyclic GMP was equally effective in reducing induced tone in arterial or venous segments. Similarly, isoproterenol relaxed arterial and venous segments with equivalent sensitivities. Relaxation by isoproterenol was preceded by or occurred concomitantly with increased levels of cyclic AMP but not cyclic GMP and both effects were antagonized by propranolol. These findings are consistent with the hypothesis that vascular smooth muscle relaxation in response to nitrogen oxide-containing vasodilators or isoproterenol may be mediated or modulated by the intracellular accumulation of cyclic GMP or cyclic AMP, respectively.

Animals↗

Subcellular lesions: the current position.

There continues to be an oversimplification of the approach to correlate cellular lesions with radiation induced cell death. Both in the prokaryotic and eukaryotic cell the relationship between vital macromolecules such as DNA, RNA, membrane and proteins is not yet fully understood either in a structural or functional sense. These macromolecules are often closely associated and interdependent. In spite of these recognised relationships much work is still devoted to measuring relatively early changes induced only in the DNA molecule. However, at the present time the quaternary structure of DNA and its closely neighbouring macromolecules is becoming better defined, and disturbances in these vital interrelationships may prove to be the most important radiation lesions. In the attempts to relate identifiable radiation damage to cell malfunction several criteria must be applied. For instance, the measured lesions must exhibit sensitization, protection and shoulder changes in response to the variety of agents and conditions which produce these phenomena at cellular level. In addition the radiation doses employed to produce measurable change must be within the same dose range as those used to study cellular and tissue effects. In much of the published work these criteria have not been applied.

Animals↗

Initiation of transcription of the yeast mitochondrial gene coding for ATPase subunit 9.

We have determined transcriptional initiation sites for the ATPase subunit 9 gene on the yeast mitochondrial genome. Using S1 nuclease mapping, in vitro capping of primary transcripts with GTP and guanylyl transferase, and in vitro transcription analysis with purified mitochondrial RNA polymerase, we find the major site of transcriptional initiation to be at a point 630 nucleotides upstream of the coding region for the gene. In addition, we find much lower levels of initiation at a second site 78 nucleotides downstream of the first. Both initiation sites occur at the same position within a nonanucleotide sequence which we have previously found associated with initiation of rRNA synthesis. This work further supports the notion that this nonanucleotide sequence is an integral component of mitochondrial promoters and indicates that the same RNA polymerase is used for transcription of both mRNA and rRNA in yeast mitochondria.

Adenosine Triphosphatases↗

Cardiac surgery in Wessex.

The results of 3000 consecutive operations using cardio-pulmonary bypass show that the overall early mortality was 6.1%, dropping from 8.9% in the first 1000 to 4.4% in the third 1000. Operations for valve disease have been the most common, the early mortality for aortic valve replacement being 3.1% and for mitral valve replacement 2.9%. Combined aortic and mitral valve replacement had an early mortality of 4.4%. The number of patients undergoing isolated coronary artery bypass grafting has increased from 59 in the first 1000 to 292 in the third 1000 operations, with an overall early mortality of 1.3%. Six hundred and ninety seven patients underwent surgery for congenital heart disease with an overall early mortality of 10.9% (7.5% in the last 2000 cases). The patients have been followed up from one to 8.5 years. A high proportion have returned to work and enjoy a normal life. At the time of review, 87% of the 3000 patients were alive. Long waiting times for outpatient and inpatient care indicate underprovision of facilities relative to regional demand.

Adolescent↗

Increased inflammatory reactivity in newly formed lining tissue.

The air pouch has been shown to provide a convenient model for studying the behaviour of synovial lining tissue. Air pouches of different ages were used to study the reactivity of newly developing lining tissue towards irritants known to cause inflammation. Pouches of 1 day in age were relatively inert in their reactivity as judged by the number of cells and volume of the exudate accumulating in the pouch. In contrast, 3-day-old pouches responded to a much greater extent, and 6-day-old pouches were highly responsive with a further increase in cell numbers and fluid volume. The different responses of 1-, 3- and 6-day-old pouches could be explained by (a) developing vascularity of the pouch, (b) formation of an organised lining of phagocytic cells, or (c) an increasingly organised mechanical barrier that retains the irritant and products of the inflammatory response. These studies of air pouch lining development permit a dissection of those components necessary for inflammatory reactivity of a lining tissue and may help explain the sensitivity of synovium to chronic inflammation.

Air↗

The value of radiography in the management of rheumatoid arthritis.

All radiographs of joints requested on 50 consecutive clinic patients with rheumatoid arthritis were reviewed; 1094 films were available. With few minor exceptions, all information relevant to diagnosis and medical management was provided by one view of each joint: postero-anterior hands, dorsi-planar feet, antero-posterior (AP) elbow, AP shoulder, AP pelvis and lateral flexion cervical spine. Norgaard's 'ballcatcher's' projection of the hands provided no extra information. Radiographs of the hands were consistently more sensitive in showing progression of erosion than those of the feet. Radiography of both hands and feet was required to avoid missing earliest erosions. Radiographs requested at times when drug treatment was under review did not consistently affect decisions, which were largely dependent on clinical findings.

Arthritis, Rheumatoid↗

Identification of a single transcriptional initiation site for the glutamic tRNA and COB genes in yeast mitochondria.

We have identified a single transcriptional initiation site for the glutamic tRNA and COB (cytochrome b) genes by using the complementary techniques of in vitro capping of RNA and in vitro transcription. In the capping reaction, mitochondrial RNA is labeled with [alpha-32P]GTP by vaccinia virus guanylyltransferase. This reaction is specific for the 5' ends of RNA retaining the terminal triphosphate of transcriptional initiation. Exploiting the extremely low G+C content (18%) of yeast mitochondrial DNA, we digested in vitro capped transcripts from various petite deletion mutants with the G-specific RNase T1. By petite deletion mapping, a capped transcript giving rise to a 51-base RNase T1-generated oligonucleotide was localized near the glutamic tRNA gene. When the sequence of this oligonucleotide was determined, it perfectly matched the DNA sequence 391 base upstream of the glutamic tRNA. Purified yeast mitochondrial RNA polymerase initiated transcription in vitro at the same site as shown by the sequence of the 33-base oligonucleotide product of the reaction performed in the absence of CTP. Initiation starts at a nonanucleotide sequence previously implicated in yeast mitochondrial transcriptional initiation. Because there is no evidence of an initiation site in the 1,050 bases between the glutamic tRNA and COB genes, the two genes are likely to be transcribed together. Further evidence of a long common transcript was provided by RNA blot hybridization.

Base Sequence↗

Radiation studies of Acholeplasma laidlawii: the role of membrane composition.

Acholeplasma laidlawii, a mycoplasma, is unable to synthesize unsaturated fatty acids but it will incorporate them into its plasma membrane if they are supplied exogeneously. Thus the fatty acid composition of the cell membrane can be defined by growing the organism in media containing specific fatty acids. We obtained cells with predominantly one type of unsaturated fatty acid (either oleic, linoleic or linolenic acid) or cells with only saturated fatty acid in the cell membrane. The cells were irradiated with 7 MeV electrons and the effect of membrane fatty acid composition on cell survival was examined. At 200 Gy/min and 0.5 degrees C (melting ice) there was little difference in the radiation sensitivities of the cells grown in unsaturated fatty acids either in aerated or anoxic radiation conditions. However, the cells containing saturated fatty acids irradiated in anoxic conditions were markedly more sensitive than the cells containing unsaturated fatty acids. At 200 Gy/min and 37 degrees C the two types of cells were of similar sensitivity both in aerated and anoxic radiation conditions. At 5 Gy/min at 0.5 degrees C the cells containing linolenic acid (18:3) were less sensitive than those containing solely saturated fatty acids. However, at 5 Gy/min at 37 degrees C there was no difference in sensitivity between these two types of cell. Our results strongly argue against the involvement of lipid peroxidation as a molecular change leading to cell death.

Acholeplasma laidlawii↗

Mode of formation of synovial villi.

Synovial tissue from 6 normal pigs and from 16 patients undergoing arthrotomy for joint disease was examined by dissecting microscopy. Scale models were constructed of 3 human synovial specimens from photographic magnifications of serial sections. Surface bridging and subintimal cavitation were observed, particularly in tissue from patients with rheumatoid arthritis. These features suggest that synovial surface projections (villi) do not form simply by outgrowth. Reference to original haematoxylin and eosin stained sections suggested that tissue splitting contributes to the formation of villi.

Adult↗

The effects of D-penicillamine on non-immune responses to tissue injury.

D-penicillamine was found to have a pro-inflammatory effect when given to rats during the formation of carrageenan air pouch granulomas or simple air cavity linings. Unlike dexamethasone, D-penicillamine had no effect on the strength of the cavity lining in either system. D-penicillamine had no effect on the chemoattractant properties of the carrageenan-induced exudates or on the responsiveness of cells from such exudates to a chemoattractant. These results suggest that D-penicillamine has a short-term pro-inflammatory effect on non-immune responses to tissue injury, but the mechanism remains unclear.

Animals↗

The structure of unsaturated lipid dispersions in aqueous systems influences susceptibility to oxidation.

The susceptibility of unsaturated lipids dispersed in aqueous systems to oxidation in the presence of decomposing peroxychromate has been examined. Almost complete oxidation of unsaturated monoenoic fatty acyl residues present in detergents such as Tween 80, which form micellar structures, was observed, whereas multibilayer liposomes of egg-yolk phosphatidylcholine could be oxidized only partially despite the presence of more susceptible polyenoic fatty acids. More vigorous methods of phospholipid dispersion or disturbing the structure of partially oxidize dispersions increased susceptibility of peroxidation, suggesting that substrate molecules located in the centre of large multibilayer dispersions are not accessible to free radicals generated in the bulk water.

Fatty Acids, Unsaturated↗

Studies on the ability of inflammatory exudate obtained from acute and chronic phases of the inflammatory process to promote leukocyte locomotion in vitro.

Using a modified Boyden chamber system, inflammatory exudates taken from the acute carrageenan pleural model and the chronic carrageenan air-pouch model were tested for their ability to promote leukocyte locomotion in vitro. Both exudates were able to induce polymorphonuclear leukocyte (PMN) and mononuclear leukocyte (MN) migration, suggesting that cell-specific chemoattractants are not responsible for the progression of the inflammatory process from the acute to the chronic phase. Checkerboard assay were used to establish whether the observed migration was in response to chemotactic stimulation and/or chemokinetic stimulation. Both acute and chronic exudates were able to induce MN chemotaxis and chemokinesis. Acute exudate was able to induce PMN chemotaxis and chemokinesis. Acute exudate was able to induce PMN chemotaxis and chemokinesis, but chronic exudate was only able to induce PMN chemokinesis. This may partly explain the predominance of MNs in chronic inflammation. However, our present in vitro results have failed to demonstrate that cell-specific chemoattractants are responsible for the in vivo observation that migration of polymorphonuclear leukocytes precedes the migration of mononuclear cells.

Animals↗

Analysis of transcriptional initiation of yeast mitochondrial DNA in a homologous in vitro transcription system.

We have developed an in vitro transcription system for yeast mitochondrial rRNA genes. Using highly purified yeast mitochondrial RNA polymerase and bacterial plasmids carrying DNA segments containing the mitochondrial rRNA sites of transcriptional initiation, we have been able to demonstrate correct initiation of transcription in vitro. By directly sequencing the transcription products, we show that transcription in vitro of both the 14S and 21S rRNAs is initiated at precisely the same site as it is in vivo. Transcription of the rRNA genes is highly sensitive to ionic strength and RNA polymerase concentration. Additional factors or modified conditions may be necessary to permit accurate transcription of mitochondrial protein genes.

Base Sequence↗