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Biomedical subjects

I M Hunneyball

Publications and source records attributed to I M Hunneyball.

At least 37 records · Page 2Linked to original sources
PubMed1984

Inflammatory involvement in rabbit knee following immobilization and resulting in osteoarthritis.

The inflammatory involvement of the synovium in immobilization-induced experimental osteoarthritis in rabbit knees has been investigated. One knee of each of 33 rabbits was immobilized for up to 5 weeks in extension and then allowed to remobilize for up to 8 weeks. Histological examination revealed the presence of marked inflammatory changes in the synovium which were evident after 4 days of immobilization. These were characterized by a rapid proliferation of synovial lining cells followed by mononuclear cell infiltration and fibrosis. The synovial cell proliferation decreased during the latter part of the immobilization period but reappeared in a more severe form during remobilization, at which time gross changes could be demonstrated in the joints. Synovial fluid levels of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase were elevated on day 3 and day 10 but had returned to baseline levels by day 24 of immobilization. Treatment of the animals with the nonsteroidal anti-inflammatory agent flurbiprofen (10 mg/kg/day) had neither a beneficial nor a deleterious effect on any of the parameters measured. This study has shown that immobilization-induced experimental osteoarthritis in rabbits is associated with a marked inflammatory component and that during the remobilization phase of this model the inflammation appears to be a secondary event.

Acetylglucosaminidase↗
PubMed1984

Facb rosette-forming cells in mice: studies on their functional significance.

Lymphocytes bearing receptors for the Facb fragment of IgG have been shown previously to be elevated in the peripheral blood of patients with rheumatoid arthritis. The generation of these cells and their possible functional role in immune regulation have been investigated in mice. Facb rosette-forming (Facb-R+) lymphocytes were found to be elevated in the spleens of mice mounting a secondary plaque-forming cell (PFC) response to sheep erythrocytes but not during the primary response. Splenic Facb-R+ lymphocytes were also elevated when a cross-reacting antigen (goat erythrocytes) was used for the secondary immunization but not when a non-cross-reacting antigen (chicken erythrocytes) was used. Both primary and secondary immunization with bacterial lipopolysaccharide resulted in elevation of splenic Facb-R+ lymphocytes. Administration of antigen-specific Facb fragment in conjunction with antigen (calf erythrocytes) produced a suppression of the secondary PFC response. However, F(ab')2 fragments produced no such effect. This suppressive effect was shown to be antigen-specific since administration of Facb fragment of anti-calf erythrocyte IgG had no suppressive effect on the secondary PFC response to sheep erythrocytes. No change in splenic Facb-R+ lymphocytes was observed during delayed hypersensitivity responses to either sheep erythrocytes or the contact-sensitizing agent oxazolone. These results indicate that Facb-R+ lymphocytes are generated during secondary humoral responses but not cell-mediated immune responses, and suggest that these cells may exert a suppressive influence on antibody production. These findings are discussed in relation to the occurrence of these cells in patients with rheumatoid arthritis.

Animals↗
PubMed1983

The role of fibronectin in the pathogenesis of antigen-induced arthritis in the rabbit.

Fibronectin (FN), a high molecular weight glycoprotein, is present in plasma and is a normal structural component of the synovium in the rabbit, as it is in man. FN is also involved in the sequence of changes seen in synovium in experimental antigen-induced arthritis. Its widespread distribution in inflamed synovia in the initial acute phase of induced arthritis probably merely reflects the presence of FN of plasma origin in serous exudates. In established experimental arthritis, FN co-distributes with fibrin, while in synovia undergoing organisation, FN is present intracellularly in several types of mesenchymal cells (suggesting local synthesis) and is deposited on immature collagen fibrils. However, it is no longer present when mature collagen is formed. The persistence of FN, along with fibrin, in inflamed joints, and its involvement in fibrosis, suggest that it may play a significant part in determining the chronicity of this form of experimental arthritis.

Animals↗
PubMed1983

Investigations into the induction of chronic experimental arthritis in the common marmoset (Callithrix jacchus).

In an attempt to produce a superior model of rheumatoid arthritis, experiments have been performed to investigate the ease of induction of experimental arthritis in marmosets by immunological means. Marmosets were sensitised with the following combinations of antigen and adjuvant: ovalbumin in Freund's complete adjuvant (FCA), ovalbumin in FCA + Bordetella pertussis, methylated-BSA in FCA + B. pertussis or human fibrin in FCA + B. pertussis, and subsequently injected with the corresponding antigen in saline into one knee joint. Animals receiving ovalbumin, with or without B. pertussis, produced only a weak transient monoarticular synovitis. Animals receiving Met-BSA + B. pertussis produced a chronic synovitis but only mild erosive changes were apparent even 21 weeks after intraarticular injection. Animals receiving human fibrin produced a transient monoarticular synovitis of moderate intensity. These results indicate that the marmoset offers no obvious advantages over the rabbit for the induction of experimental rheumatoid arthritis.

Animals↗
PubMed1983

The successful use of asialylated IgG as an immunogen and arthritogen in the rabbit.

Joint lesions, closely resembling the main features of those seen in rheumatoid patients, were produced by intra-articular injections of asialylated homologous IgG into presensitized rabbits. The inflammatory changes were characterized by areas of extremely dense chronic inflammatory cell infiltration, where the lymphocytes were often aggregated into lymphoid follicles. There were also signs of involvement of the contralateral, saline-injected knee. Formation of an experimental rheumatoid factor-like antibody, detected by its ability to agglutinate sheep erythrocytes sensitized with baboon IgG, was also demonstrated. In addition, the rabbits developed other manifestations associated with rheumatoid arthritis, namely increases in erythrocyte sedimentation rate, serum haptoglobin concentration and joint size.

Animals↗
PubMed1982

Biochemical and pharmacological studies on synovium-cartilage interactions in organ culture.

Traumatised normal pig synovium has been cultured with normal pig articular cartilage for 14 days. The breakdown of cartilage collagen and proteoglycan during culture was accompanied by the appearance in the culture medium of collagenase and proteoglycanase respectively which appeared to be derived from the synovium. There was good correlation between culture medium levels of collagenase and cartilage collagen breakdown, but the relationship between synovial proteoglycanase and cartilage proteoglycan breakdown was not so clear-cut. Corticosteroids consistently inhibited breakdown of cartilage collagen but not proteoglycan, and inhibited the production of the proteolytic enzymes. High concentrations of aurothiomalate (10(-3)M) inhibited collagen breakdown and partially reduced culture medium enzyme levels. Non-steroidal antiinflammatory agents such as flurbiprofen and indomethacin had no effect on the breakdown of collagen or proteoglycan and tended to increase culture medium enzyme levels. This culture system may be used to provide further information concerning the action of antirheumatic drugs.

Animals↗
PubMed1981

Some further effects of prednisolone and triamcinolone hexacetonide on experimental arthritis in rabbits.

Prolonged treatment of rabbits with an established bilaterally symmetrical experimental arthritis with prednisolone (0.5 mg/kg day) reduced both the swelling and the histopathological changes in the arthritic joints whereas short-term treatment suppressed only the swelling. Such prolonged treatment also suppressed both the humoral and cell-mediated immune responses measured systemically in these animals and the cell-mediated immune responsiveness of the synovium determined by lymphokine production by cultured explants. The results suggested that the suppressive effect of the drug on the arthritis was related to the inhibition of cell-mediated immune responsiveness. Prednisolone treatment also had deleterious effect on cartilage proteoglycan metabolism determined both histologically and biochemically. Intra-articular administration of triamcinolone hexacetonide (three injections of 2 mg per joint at fortnightly intervals) also reduced the swelling and histopathological changes, although there was no effect on circulating antibody levels.

Administration, Topical↗
PubMed1979

Effect of oral D-penicillamine treatment on experimental arthritis and associated immune responses in rabbits. III: Reduction of the monoarticular arthritis.

Treatment of rabbits with D-penicillamine at doses up to 30 mg/kg, beginning either before or after the onset of antigen-induced experimental arthritis, diminished the severity of the inflammatory synovitis in a considerable proportion of animals as judged by both external joint measurements and terminal histopathological assessment. D-penicillamine treatment had no effect on serum haptoglobin concentration, haemoglobin concentration, or platelet count. The venous blood white cell count was raised when D-penicillamine treatment was started before immunisation but not when treatment began after the onset of arthritis. A transient loss of appetite was observed in animals starting D-penicillamine treatment.

Animals↗
PubMed1979

Studies on immune tolerance to heat-aggregated human IgG in rabbits: its relevance to the production of rheumatoid factors.

Rabbits neonatally tolerized with native monomeric human IgG and subsequently immunized with heat-aggregated human IgG emulsified in Freund's complete adjuvant, at a time when B cells but not T cells should have spontaneously recovered from tolerization, resulted in the production of an antibody resembling human rheumatoid factors directed against a single antigenic determinant in the Fc region of the IgG molecule. Rabbits immunized in an identical fashion after adult tolerization treatments failed to respond during the period corresponding to B-cell tolerance, but subsequently produced antibody or similar specificity to that produced by neonatally tolerized animals. These results indicate that no completely new antigenic determinants are created on heat aggregation of IgG, but there appears to be some potentiation of immunodominance of an already existing determinant. A possible mechanism for the production of rheumatoid factors in rheumatoid arthritis is suggested.

Animals↗
PubMed1978

The effects of oral D-penicillamine treatment on experimental arthritis and the associated immune response in rabbits.

D-penicillamine given orally to rabbits at a dose of 15 mg/kg body weight, administered daily for long periods commencing prior to and at the time of immunization, reduced the concentration of specific IgG antibodies directed against ovalbumin. This effect was not observed when treatment with the drug commenced after immunization and the onset of a mono-articular arthritis. The concentration of serum IgA rose abruptly after antigen was injected intra-articularly to induce the arthritis. This increase was not affected by treatment with D-penicillamine. The concentration of serum IgA decreased markedly during the chronic phase of the mono-articular arthritis, falling below the lower limit of the normal range. Treatment with D-penicillamine for at least 50 days restored the serum IgA concentration to the middle of the normal range. D-penicillamine treatment had no significant effect on the concentration of IgG, or IgM in serum either before or after the onset of mono-articular arthritis.

Administration, Oral↗
PubMed1978

The effects of oral D-penicillamine treatment on experimental arthritis and the associated immune response in rabbits. II. The effects on cellular parameters.

Prolonged oral treatment (up to 410 days) of rabbits with D-penicillamine at a dose of 15 mg/kg body weight commencing either before or after immunization and the onset of arthritis, diminished and eventually abolished the delayed hypersensitivity response to intradermally administered tuberculin PPD. The 48 h cutaneous hypersensitivity response to the immunizing antigen (ovalbumin) was also significantly reduced, as was the inhibition of leucotye migration by ovalbumin. Cutaneous Arthus reactivity to ovalbumin was unaffected by D-penicillamine treatment. D-penicillamine treatment of normal rabbits was also found to increase the phagocytic index of the reticuloendothelial system as measured by carbon clearance.

Animals↗
PubMed1977

Effect of D(-)penicillamine on chronic experimental arthritis in rabbits.

Preliminary observations on the effect of D(-)penicillamine on chronic antigen-induced experimental arthritis in rabbits are reported. Daily oral administration of penicillamine, at a dose equivalent to that usually administered to rheumatoid arthritis patients, diminished the arthritis in 2 out of 3 animals as assessed by both measurement of joint circumference and histological examination.

Animals↗
PubMed1976

Subfragmentation of the Fc fragment of human IgG1 myeloma protein by thermolysin.

Human IgG1 Fc fragment was digested at neutral pH by thermolysin, producing two large subfragments: one comprising the major part of the Fc fragment but devoid of the hinge region; the other comprising the Cgamma3 domain. The former fragment retained the capacity to react with "general" rheumatoid factors whereas the latter did not, indicating that the binding site for "general" rheumatoid factors on the Fc fragment of human IgG1 does not involve the hinge region of the molecule.

Amino Acids↗