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Biomedical subjects

C J Morris

Publications and source records attributed to C J Morris.

At least 73 records · Page 4Linked to original sources
PubMed1989

Hypoxic-reperfusion injury in the inflamed human joint.

A series of experiments showed that, on exercise of the inflamed human knee, intra-articular pressure rises above synovial capillary perfusion pressure, causing intra-articular hypoxia; and that, on cessation of exercise, there is oxidative damage to lipids and IgG within the joint. These findings are consistent with the hypothesis that persistence of synovial inflammation can be due to exercise-induced hypoxic-reperfusion injury mediated by reactive oxygen species.

Adult↗
PubMed1989

Investigation of the anti-inflammatory properties of hydroxypyridinones.

Synovial iron deposition associated with rheumatoid disease may result in the production of highly reactive oxygen free radicals, leading to tissue damage. This chain of events can be interrupted by iron chelation. Families of strong iron (III) chelators have been tested for their iron scavenging properties in vitro and their effects assessed in vivo using a rat model of inflammation. All the chelators competed successfully for iron with apotransferrin, and some removed up to 34% of iron from ferritin. The best anti-inflammatory effects were achieved with the most hydrophilic chelators and those which chelated iron most avidly. Activity was dependent on dose. The route of administration was also an important factor with lower affinity chelators. This work introduces a range of simple bidentate iron chelators, which under certain conditions exceed desferrioxamine in their iron scavenging abilities, and some of which, in this simple animal model, approach indomethacin in their anti-inflammatory capabilities.

Animals↗
PubMed1989

Cytoskeletal rearrangement by oxidative stress.

The cytoskeleton is susceptible to oxidative stress and this occurs prior to membrane blebbing and cell lysis. Vimentin intermediary filaments in rheumatoid synoviocytes are more susceptible than in normal synoviocytes and this may have pathological significance. They are however no more susceptible to heat shock than other cell types.

Cells, Cultured↗
PubMed1988

Conservation of structure in the human gene encoding argininosuccinate synthetase and the argG genes of the archaebacteria Methanosarcina barkeri MS and Methanococcus vannielii.

The DNA sequences of the argG genes of Methanosarcina barkeri MS and Methanococcus vannielii were determined. The polypeptide products of these methanogen genes have amino acid sequences which are 50% identical to each other and 38% identical to the amino acid sequence encoded by the exons of the human argininosuccinate synthetase gene. Introns in the human chromosomal gene separate regions which encode amino acids conserved in both the archaebacterial and human gene products. An open reading frame immediately upstream of argG in Methanosarcina barkeri MS codes for an amino acid sequence which is 45 and 31% identical to the sequences of the large subunits of carbamyl phosphate synthetase in Escherichia coli and Saccharomyces cerevisiae, respectively. If this gene encodes carbamyl phosphate synthetase in Methanosarcina barkeri, this is the first example, in an archaebacterium, of physical linkage of genes that encode enzymes which catalyze reactions in the same amino acid biosynthetic pathway.

Amino Acid Sequence↗
PubMed1988

Mechanisms of persistent synovitis.

Rheumatoid arthritis is characterised by persistent and symmetrical synovitis. In this article we propose two linked hypotheses to explain these observations. A mechanism to explain symmetry of synovitis is described whereby fine afferent nerve fibres from joints become bilaterally sensitized to movement with resultant release of neuropeptides promoting an inflammatory response. Clinical and experimental evidence is reviewed and shows that movement and resulting hypoxic reperfusion injury leads to a persistent synovitis.

Animals↗
PubMed1987

Xanthine oxidoreductase is present in human synovium.

It is postulated that the mobile inflamed joint may be subject to cyclical ischaemic reperfusion injury. Xanthine oxidoreductase is an enzyme thought to contribute to oxidative reperfusion injury, and the detection of this activity in human synovium is described. Three normal and five rheumatoid tissues were assayed with a carbon-14 radioassay detecting the conversion of [14C]xanthine to [14C]uric acid. Rheumatoid synovia contained 0.67-305 microU/g tissue (n = 5), while normal synovia contained 1.2-5.0 microU/g tissue (n = 3).

Allopurinol↗
PubMed1987

Effect of nutritional iron deficiency on acute and chronic inflammation.

Mild nutritional iron deficiency significantly reduced the severity of adjuvant induced joint inflammation assessed by histology, microfocal radiography, and subjective scoring. Other indices of adjuvant induced inflammation, such as increased levels of serum acute phase reactants, characteristic pathological changes in the inguinal lymph nodes, and granuloma formation at the site of adjuvant injection, were not different from those of control animals. The level of iron deficiency used did not affect the acute inflammatory response to a range of irritants and was not sufficient to suppress immune function. Both the hypersensitivity reaction to oxazalone and lymphocyte tritiated thymidine incorporation were normal. These observations support the view that iron has a selective influence on joint mediated inflammation.

Acute-Phase Proteins↗
PubMed1987

Effect of free radical altered IgG on allergic inflammation.

The rheumatoid synovium is capable of producing large amounts of IgG which may become modified by the actions of free radicals. A rat model of synovitis was established and challenged with both normal and free radical altered IgG. IgG was prepared from homologous pooled serum by high performance liquid chromatography, and free radical damage was induced by 15 minutes ultraviolet (UV) irradiation. The results showed a worsening in gross assessments of inflammation, increases in biochemical indices of lipid peroxidation, and also a rise in the proportion of IgG which, on reisolation, showed the characteristic fluorescence associated with free radical damage. This demonstrated how the presence of free radical altered IgG might convert an inflammatory insult to a more persistent stimulus, and the capacity of an environment subjected to continuing antigenic stimulation to induce further free radical damage to IgG.

Animals↗
PubMed1987

Effect of iron chelation on inflammatory joint disease.

Mild iron deficiency induced by treatment with the iron chelator desferrioxamine reduced the incidence and severity of joint inflammation associated with adjuvant disease in rats but did not alter the local primary inflammatory response or the systemic sequelae. Both rats treated with desferrioxamine and control rats showed increased levels of alpha 1 acid glycoprotein, characteristic pathological changes in the liver and inguinal lymph nodes, and the primary inflammatory response at the site of injection. Histology, microfocal radiography, and gross assessment of the joints, however, showed a suppression or reduction in soft tissue swelling and bone erosion in the rats treated with desferrioxamine. This is a novel observation suggesting an apparently selective influence of iron on joint mediated inflammation.

Animals↗
PubMed1987

Macrophage ferritin and iron deposition in the rat air pouch model of inflammatory synovitis.

Using a rat air pouch model of red cell promoted allergic inflammation, we have investigated the relation between ferritin synthesis and iron deposition in pouch wall lining cells. These cells have structural and immunohistochemical similarities to human synovial intimal cells and studies of them are pertinent to the clinical situation. In control air pouch wall tissue after single or double antigenic challenge the (apo)ferritin containing macrophages are most numerous seven days after antigenic challenge when there is active connective tissue proliferation and a generalised mononuclear cell response in the pouch wall, suggesting that (apo)ferritin is produced in macrophages as part of the tissue inflammatory response. In contrast with control tissue, where there is a steady decrease in positive cells over the ensuing weeks, injection of blood into both single and double challenge air pouches produces a significant (p less than 0.001) and continuing rise in the numbers of ferritin containing macrophages after day 7. Also, after 14 days Perls' positive ferric iron is detectable in increasing numbers of ferritin containing macrophages, a trend which is more marked in double challenge, blood injected air pouches. The histological data clearly show that there is a close relation between the presence of Perls' iron and proliferation of vascular and connective tissue elements in the pouch wall. We propose that this proinflammatory role of iron is the result of its ability to promote oxidative damage in tissues, and discuss ways in which this may take place.

Animals↗
PubMed1987

The operant conditioning of response variability: Free-operant versus discrete-response procedures.

The operant conditioning of response variability under free-operant and discrete-response procedures was investigated. Two pigeons received food only if their pattern of four pecks on two response keys differed from the patterns emitted on the two immediately preceding trials. Under the free-operant procedure, the keys remained illuminated and operative throughout each trial. There was little variability in the response patterns that resulted, and the pigeons received fewer than one third of the available reinforcers. Under the discrete-response procedure, a brief timeout period followed each response. Variability increased under this procedure, and the pigeons obtained three fourths of the available reinforcers. Previous successes and failures to produce response variability may have been due to the use or failure to use, respectively, a discrete-response procedure. Respondent effects inherent in the free-operant procedure may encourage the development of response stereotypy and, in turn, prevent the development of response variability.

Journal Article↗
PubMed1986

Relationship between iron deposits and tissue damage in the synovium: an ultrastructural study.

A detailed ultrastructural study was made of the synovial iron deposits in cases of haemophilic synovitis (HS), pigmented villonodular synovitis (PVNS), rheumatoid arthritis (RA), osteoarthritis (OA), seronegative inflammatory arthritis (SNA), and in controls, to investigate the relationship between iron deposits and tissue damage. Iron was seen by electron microscopy in about 75% of synovial lining cells in HS and PVNS but only in about 25% of synovial cells from cases of RA and SNA. In cases of OA and in controls iron deposits were scarce. The iron was usually deposited within pleomorphic siderosomes and in HS was most common in type A synovial cells. In contrast, deposits in all other cases were more common in type B cells, which were frequently the predominant cell type, and siderosomes were smaller, more homogeneous, and were more common in deeper synovial tissue. Considerable tissue damage was noted in the vicinity of iron rich siderosomes in synovial A cells from cases of HS, but such deposits in B cells in the synovium from the other cases had relatively little effect. We discuss the possibility that such differences directly reflect the differing functions of type A and B synovial cells, and particularly their relative ability to produce metabolically active oxygen metabolites with tissue destructive potential in the presence of iron.

Arthritis↗
PubMed1985

Immunohistochemical findings in rheumatoid nodules.

Eighteen nodules from patients with rheumatoid disease were studied histologically and immunohistochemically. A continuum of microscopic changes was observed with varying degrees of fibrinoid necrosis, mononuclear cell infiltration and healing by fibrous scarring. In two cases there was focal evidence of arteritis. Fibrin was plentiful in the necrotic areas of nodules. Small amounts of immunoglobulin were identified in plasma cells and as irregular extracellular deposits in and around areas of necrosis. In a single small vein abnormal IgG was detected. Mononuclear cells surrounding areas of necrosis stained strongly with antisera to ferritin and a cytoplasmic macrophage antigen, stained variably with muramidase (lysozyme) and negatively with alpha-1 antitrypsin antibodies. Perls' stain for ferric iron was almost entirely negative and ultrastructural x-ray microanalysis indicated that the cytoplasm of these cells were entirely free of iron. These findings confirm the chronic inflammatory nature of rheumatoid nodules but provide no support for the view that they originate in areas of vasculitis. A relative lack of cytoplasmic antiprotease along with a strong expression of ferritin appears to be a characteristic feature of macrophages in rheumatoid tissue.

Adult↗
PubMed1985

Ultrastructural changes in the rectal mucosa of patients with rheumatoid arthritis.

The rectal mucosa from patients with severe rheumatoid arthritis has been examined by electron microscopy. Initially the patients were biopsied for investigation into the diagnosis of amyloidosis or vasculitis, which proved to be negative. A range of ultrastructural abnormalities was found which included proliferation of the rough endoplasmic reticulum, mitochondrial inclusions, association of the mitochondria with cytoplasmic filaments, and marked increase in the number of iron containing siderosomes. Most of these abnormalities have already been reported in rheumatoid synovial tissue, and attention is drawn to the similarity in findings between these two sites.

Adult↗
PubMed1985

A monoclonal antibody identifies a 215 000-dalton nuclear envelope protein restricted to certain cell types.

The monoclonal antibody, AGF2.3, was isolated from mice immunised with the human promyeloid cell line HL60. By immunofluorescence and immunoelectron microscopy the antibody was shown to bind to the nuclear envelope in uninduced HL60 cells. Immunofluorescent staining was reduced to very low levels in HL60 cells induced to mature to monocytes or neutrophils by addition of 12-0-tetradecanoylphorbol-13-acetate or dimethyl sulfoxide respectively. Blood neutrophils did not express the antigen. Weak immunofluorescent staining of cell nuclei was observed in peripheral blood lymphocytes and in sections of normal human kidney, tonsil and skin epithelium. The AGF2.3 antigen was strongly expressed on the nuclei of 21/21 haemopoietic cell lines and 21/25 permanent non-haemopoietic cell lines representing various cell types. In contrast, the antigen was not expressed by any of six primary (untransformed) cell cultures. These included fibroblasts, endothelial cells and keratinocytes. The antigen was expressed in the Q10 SV-40 transformed cell line derived from a non-expressing primary fibroblast culture. AGF2.3 antibody precipitated a protein with an apparent subunit molecular weight of approximately 215 kDa from Triton X-100 extracts of HL60 and HeLa cells labelled with 35S-methionine. This protein was not detectable in extracts of primary skin fibroblasts prepared in parallel. We conclude that AGF2.3 antibody recognises a previously undescribed protein associated with the nuclear envelope which is expressed at high levels in most transformed cell lines but which is weakly expressed or absent in normal tissues and primary cell cultures.

Animals↗
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↗