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Biomedical subjects

D R Blake

Publications and source records attributed to D R Blake.

At least 271 records · Page 15Linked to original sources
PubMed1984

The oxidation of serum sulph-hydryl groups by hydrogen peroxide secreted by stimulated phagocytic cells in rheumatoid arthritis.

Levels of free sulph-hydryl (SH) groups are depressed in the sera of patients with rheumatoid arthritis, especially during active disease. However, the mechanism underlying this effect is not known. We have investigated several oxidative species generated during the inflammatory process for their ability to react with serum SH in vitro. Our results show that serum oxidase enzymes (e.g. caeruloplasmin) do not have this activity but that "active oxygen species" generated either by an enzymatic reaction (xanthine plus xanthine oxidase) or by neutrophils stimulated with heat-aggregated IgG cause rapid oxidation of serum SH groups. The use of selective inhibitors of active oxygen species has demonstrated that this reaction is mediated by hydrogen peroxide. This compound is secreted in considerable amounts by activated phagocytic cells, especially neutrophils. Thus, serum SH levels may reflect phagocytic activity in patients with rheumatoid arthritis. We suggest that serum SH groups act as important extracellular scavengers of peroxides and so help to protect cells from damage by these molecules.

Arthritis, Rheumatoid↗
PubMed1984

The nature of iron deposits in haemophilic synovitis. An immunohistochemical, ultrastructural and X-ray microanalytical study.

Using a computerized electron-probe X-ray microanalytical technique to measure phosphorus/iron ratios we have defined the iron saturation of ferritin in vitro from prepared ferritin standards of known iron loading. This technique has been applied to the study of 5 haemophilic synovial membranes. At light microscope level the distribution and relationship of iron/ferritin were defined using Perls' reaction and an immunoperoxidase technique respectively. The synovia from all cases contained intra and extra-cellular deposits of Perls' positive material which were granular in nature in the most superficial synovial cells. There were increasing numbers of pheomorphic (1-12 micron diameter ovate bodies in the deeper synovial layers. Immunoperoxidase ferritin staining produced a strongly positive reaction in the granular material but the ovate bodies were negative with the exception of some peripheral staining. X-ray microanalysis showed the granular material to be highly iron saturated ferritin and the ovate bodies to be almost pure iron. We suggest that iron saturated ferritin in the synovial membrane could increase/perpetuate inflammation by promoting lipid peroxidation.

Electron Probe Microanalysis↗
PubMed1984

Low density lymphocytes: their relationship to disease activity and to antirheumatic therapy.

The acquisition of low density by lymphocytes is the earliest detectable marker of their activation and may be utilized for the separation and quantification of these cells. Low density lymphocytes (LDL) are found in increased numbers in patients with rheumatoid arthritis compared with healthy controls (p less than 0.05). The number of LDL is raised in patients who failed to respond clinically to gold or D-penicillamine when compared with those who did respond (p less than 0.05), the latter group having LDL values in the normal range. Sequential studies have shown that successful antirheumatic therapy is associated with a return to normal LDL levels (p less than 0.01) and that any alteration occurs by three months. LDL are particularly associated with synovitis and there was a close correlation (p less than 0.01) with the Compound Thermographic Index in the sequential study, as well as with other markers of synovitis, but not with systemic disease. LDL thus appear to be important markers of the synovitis of rheumatoid arthritis and they may represent a population of lymphocytes closely involved in the maintenance of synovial inflammation.

Adult↗
PubMed1984

The effect of desferrioxamine on antigen-induced inflammation in the rat air pouch.

The effect of desferrioxamine, a relatively specific iron chelating drug, has been examined in an allergic air pouch model of inflammation in the rat. The model has both an acute and chronic phase and allows quantitative measurements of the cellular and exudative response within the pouch fluid and the tissue response in the membrane that develops around the preformed cavity. Desferrioxamine given as a single bolus injection, directly into the cavity, stimulated the acute inflammatory phase, increasing both the exudative and leukocyte response, in a dose-dependent fashion. In marked contrast, repeated injections during the acute to chronic phase or during the established chronic reaction, led to a reduction in both leukocyte numbers within the cavity and the amount of granulation tissue surrounding it. The exudative response was, however, unaltered. These results are discussed in relation to the potential role of iron in promoting an acute and chronic inflammatory reaction.

Air↗
PubMed1984

A model of persistent antigen-induced chronic inflammation in the rat air pouch.

Continuing antigen-induced inflammation was established in a subcutaneous air pouch in rats by recurrent local challenge. The animals were sensitized using bovine serum albumin in Freund's complete adjuvant and were challenged 14 days later by injection of the antigen in a solution containing sodium carboxymethylcellulose into the air pouch to produce allergic inflammation. A single antigenic challenge induced acute inflammation with a predominantly polymorph infiltration in the first 48 h. Later samples showed a low-grade mononuclear response which persisted for 4-5 days. Repeated challenge produced chronic inflammation with an accentuated mononuclear response. Connective tissue activation involving fibronectin and collagen was seen as the inflammation progressed, and this was associated with production of ferritin by mononuclear cells. Discontinuation of challenge injections resulted in resolution of the granuloma. We suggest this model can be used to investigate the mechanisms involved in chronic inflammatory diseases with an immunological component and to evaluate the effects of therapeutic intervention upon chronic allergic inflammation.

Animals↗
PubMed1984

Studies into the effects of the iron chelator desferrioxamine on the inflammatory process.

We have examined the effect of the iron chelating agent, desferrioxamine on different models of acute inflammation initiated by the irritants carrageenan or calcium pyrophosphate crystals. Depending on the dose of drug used and the time at which the lesion is examined both pro- and anti-inflammatory effects were observed as judged by measurement of leucocyte accumulation and oedema formation. The anti-inflammatory effects of desferrioxamine were supported by a decrease in concentration of the acute phase reactant alpha 1 glycoprotein. Our findings suggest that iron has a complicated relationship with the inflammatory process.

Animals↗
PubMed1983

Ferroxidase and ascorbate oxidase activities of caeruloplasmin in synovial fluid from rheumatoid patients.

1. The protein caeruloplasmin inhibits certain free radical reactions, in part probably due to its ability to oxidize Fe2+ into Fe3+ (ferroxidase activity). Since caeruloplasmin is present in synovial fluid from rheumatoid patients, we investigated its properties in relation to protection of the joint from damage by oxygen radicals produced by activated phagocytes. 2. The ferroxidase and ascorbate oxidase activities of serum from both normal and rheumatoid patients could be accounted for by the caeruloplasmin present, as determined immunologically. More caeruloplasmin is present in the serum of rheumatoid patients than in normal serum. 3. Synovial fluid from rheumatoid patients contains caeruloplasmin protein but its ferroxidase and ascorbate oxidase activities are abnormally low. It is suggested that ferroxidase deficiency contributes to radical damage in the rheumatoid joint.

Arthritis, Rheumatoid↗
PubMed1983

Effect of a specific iron chelating agent on animal models of inflammation.

Iron is an important catalyst of oxidative radical reactions and promotes the formation of the hydroxyl radical from the superoxide anion radical and hydrogen peroxide. The stimulatory effect of the hydroxyl radical on lipid peroxidation prompted the speculation that free iron may directly promote inflammation and that iron chelating agents may have useful anti-inflammatory properties. This hypothesis is tested in animal models of inflammation with a specific iron chelating agent, desferrioxamine. At low doses (6 . 6 mg/kg) intraperitoneal desferrioxamine stimulated the induction of acute foot pad swelling in rats by monosodium urate but at higher doses (above 200 mg/kg) it suppressed this inflammatory reaction. A similar anti-inflammatory effect was observed in carrageenan-induced foot pad swelling. In guinea-pigs in which a Glynn-Dumonde synovitis was induced with bovine gammaglobulin, desferrioxamine (100 mg/kg) stimulated the acute inflammatory induction phase of this chronic allergic monoarthritis model. Repeated administration of desferrioxamine (100 mg/kg) from the seventh to the twelfth day after intra-articular challenge with bovine gammaglobulin markedly depressed the chronic inflammatory phase. In-vitro experiments suggest that desferrioxamine inhibits iron-catalysed lipid peroxidation when it is poorly saturated with iron, but loses this effect when it is iron saturated. Such an effect may explain our results with desferrioxamine in the animal studies and suggests that effective iron chelation and its removal may modify the inflammatory process in man.

Acute Disease↗
PubMed1983

Complement-activating rheumatoid-factor-containing complexes in patients with rheumatoid vasculitis.

The role of complement and rheumatoid factor in immune complexes was examined in patients with a variety of rheumatic diseases. This was done by assessing the amount of rheumatoid factor (RF) bound from sera by F(ab)2 anti-C3 attached to a solid matrix. High levels of RF bound to C3 were detected in patients with rheumatoid arthritis complicated by vasculitis but rarely and in lower levels in patients with synovitis, ankylosing spondylitis, and systemic lupus erythematosus. The activity was bound to anti-C3 through anti-C3 antibodies because little was bound by normal F(ab)2 and was evidently complexed in the sera before in-vitro testing, since it was precipitated by 2 . 5% polyethylene glycol and sedimented with high molecular weight material on sucrose density gradient ultracentrifugation. It is considered that RF-containing complexes are present in vasculitic sera and have the potential to bind complement in vivo.

Antigen-Antibody Complex↗
PubMed1982

Penicillamine nephropathy and iron.

7 of 16 patients with rheumatoid arthritis in whom penicillamine glomerulonephritis had developed had been taking oral iron, usually without the knowledge of their hospital clinician, while the dose of penicillamine was being gradually increased to an effective level. In 4 patients glomerulonephritis had appeared after the patients had stopped iron, with proteinuria developing with 2-5 months of discontinuation. Chelation of penicillamine by iron in the gut reduces its absorption, and in these 4 patients toxicity only became apparent after iron was stopped and there was a sudden increase in penicillamine absorption.

Administration, Oral↗
PubMed1982

Methane: Interhemispheric concentration gradient and atmospheric residence time.

The ground level concentrations of methane in the atmosphere have been measured to be in the range from 1.45 to 1.62 parts per million by volume (ppmv) of dry air in remote locations between 62 degrees N and 54 degrees S latitudes during the time period from November 1977 to July 1979. The average (+/-rms) concentration for the northern hemisphere was 1.57 +/- 0.02 ppmv in January 1978 and 1.59 +/- 0.02 in July 1979. The average concentration in the southern hemisphere was lower-1.47 +/- 0.02 in January 1978 and 1.51 +/- 0.01 in July 1979. The ratio of concentrations between the two hemispheres was 1.068 +/- 0.016 in January 1978 and 1.055 +/- 0.013 in July 1979, for an average of 1.06 +/- 0.01. The higher concentrations in the northern hemisphere require either that the sources of methane lie preferentially in the northern hemisphere or that the removal processes operate more rapidly in the southern hemisphere or both. The primary removal process for CH(4) is reaction with tropospheric OH radicals and its estimated atmospheric lifetime is 10.5 +/- 1.8 yr. The observed interhemispheric gradient is consistent with this lifetime and preferential release of methane in the northern hemisphere. Measurements taken in the Amazon basin region indicate the presence of a substantial source of methane in that area.

Journal Article↗
PubMed1981

The importance of iron in rheumatoid disease.

The hypothesis is that iron, which accumulates in rheumatoid synovial membrane and fluid contributes to the variable expression of rheumatoid disease in two ways. Firstly, it catalyses oxidative radical reactions which lead to the formation of the hydroxyl radical and subsequent lipid peroxidation. Hydroxyl radicals and lipid peroxidation cause extensive disruption of cellular and organelle membranes and promote inflammatory tissue damage. Secondly, the infiltration of the rheumatoid synovium by chronic inflammatory cells may be due not to an antigenic process but to the tendency for these cells, which have receptors for iron-binding proteins, to migrate towards deposits of iron.

Acute Disease↗
PubMed1981

Assessment of iron stores in inflammation by assay of serum ferritin concentrations.

A serum ferritin concentration of below 15 microgram/l is accepted as indicating diminished iron reserves in an otherwise normal person. In patients with inflammatory disease this lower limit of normality may be inappropriate as inflammation may directly stimulate the production of ferritin protein. Results obtained in a survey of 150 patients with early inflammatory joint disease suggest that a ferritin concentration of 55 microgram/l is a more appropriate lower limit of normality.

Adult↗