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Biomedical subjects

D E Trentham

Publications and source records attributed to D E Trentham.

At least 91 records · Page 5Linked to original sources
PubMed1982

Augmentation of collagen arthritis by synthetic analogues of retinoic acid.

We evaluated the effect of administering orally two synthetic analogues of retinoic acid, 13-cis-retinoic acid and all-trans-N-(4-hydroxyphenyl)-retinamide to age-matched female Sprague-Dawley rats immunized with native chick type II collagen in incomplete Freund's adjuvant. Ingestion of a diet containing 13-cis-retinoic acid was associated with a significant increase in the severity of collagen arthritis, but there was no effect on weight gain or hemagglutinating antibody titers and delayed-type hypersensitivity to type II collagen. In two separate trials, ingestion of 4-hydroxyphenyl retinamide also significantly enhanced the severity of arthritis. Monolayer cultures of dissociated synovial cells taken from arthritic rats, but not nonarthritic rats, released prostaglandin E2 (PGE2) and collagenase into the medium. The level of PGE2 production was significantly decreased by in vivo or in vitro exposure to 4-hydroxyphenyl retinamide, whereas the addition of 13-cis-retinoic acid to the cultures had no effect on PGE2 release by the arthritic synovial cells. Five rats fed the 13-cis-retinoic acid-containing diet for 5 mo did not develop clinical or histologic evidence of arthritis. These data demonstrate that both retinoids possess potent enhancing properties for an experimentally inducible autoimmune arthritis, that synovial cells produce PGE2 and collagenase in this model, and that production of PGE2 can be suppressed by 4-hydroxyphenyl retinamide.

Animals↗
PubMed1981

Clinical and immunologic effects of fractionated total lymphoid irradiation in refractory rheumatoid arthritis.

Ten patients with refractory rheumatoid arthritis were given 3000 rad of fractionated total lymphoid irradiation in an uncontrolled therapeutic trial. Total lymphoid irradiation was associated with objective evidence of considerable clinical improvement in eight patients and with reduced blood lymphocyte counts in all 10. On completion of irradiation, there was an abrogation of lymphocyte reactivity in vitro in the patients with clinical responses, but abnormal antibody activities characteristic of rheumatoid arthritis and normal components of humoral immunity were not suppressed. Partial recrudescence of arthritis occurred shortly after a year after the completion of irradiation and was paralleled by a restitution of lymphocyte concentrations and responsiveness to mitogens to levels similar to those observed before irradiation. These data provide further evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis and demonstrate that total lymphoid irradiation can induce temporary relief, but they do not ascertain whether the natural history of this disease was altered.

Aged↗
PubMed1980

Gold does not alter the arthritic, humoral, or cellular responses in rats with type II collagen-induced arthritis.

We assessed the effects of administration of gold sodium thiomalate on the clinical and immunologic manifestations of type II collagen-induced arthritis in rats. Injections of varying doses of gold did not alter these parameters significantly. Thus, there was no evidence in this animal model that gold possesses either antiinflammatory or immunosuppressive properties.

Animals↗
PubMed1980

Effect of psychological stress on the induction of arthritis in rats.

To determine whether emotional states could influence susceptibility to type II collagen-induced arthritis in rats, we studied the effects of experimentally produced psychological stress on the clinical, histologic, and immunologic manifestations of this autoimmune disease. Stress, induced by exposure to a cat, abrogated the development of arthritis in rats immunized with type II collagen. The incidence of arthritis was also decreased in rats subjected to transportation and handling. These environmental factors dissociated the development of humoral and cellular sensitivity to collagen from the occurrence of arthritis. This study provides a unique demonstration that psychosomatic processes can influence an animal mode of autoimmunity.

Animals↗
PubMed1980

Autoimmunity to collagen in adjuvant arthritis of rats.

Arthritis can be induced in rats by intradermal injection of oil containing bacterial derivatives (adjuvant-induced arthritis) or cartilage collagen (type II collagen-induced arthritis). It was of interest, therefore, to determine whether collagen functions as an autoantigen in rats with adjuvant arthritis. Blood mononuclear cells from the majority of rats with adjuvant arthritis exhibited enhanced thymidine incorporation to homologous types I and II collagens, as well as to purified protein derivative of tuberculin. In contrast, cells from rats remaining nonarthritic after injection of adjuvant did not respond to collagen, although they did react to tuberculin. Similar results were obtained with a radiometric ear assay used to quantify intradermal delayed-type hypersensitivity in vivo. Using passive hemagglutination, autoantibodies to these collagens and their denatured alpha-chains were frequently detected in the sera of rats late in the course of adjuvant arthritis. Rats with inflammation of a hindlimb induced by turpentine did not acquire sensitivity to collagen. These data indicate that autoimmunity to collagen is a common feature of adjuvant- and collagen-induced arthritis, both of which are considered to be mediated by immunologic mechanisms.

Animals↗
PubMed1979

Abrogation of type II collagen-induced arthritis in rats by psychological stress.

This study shows that psychological stress, produced either by exposure to a predator or by movement and handling, can profoundly suppress the clinical and histologic manifestations of collagen-induced arthritis. In addition, stress can dissociate the development of humoral and cellular sensitivity to collagen from the occurrence of arthritis. Thus stress modalities provide a means of acquiring additional insights into the pathogenesis of collagen-induced arthritis in rats. Such studies may lead to a further understanding of the relationship between emotional states and the functioning of the immunologic system. This study further illustrates the need to identify and control for the effects of stress in animal studies of immunopathology. Finally, the therapeutic implications of this study for autoimmune diseases would appear self-evident (Fig. 7).

Animals↗
PubMed1978

Cellular sensitivity to collagen in rheumatoid arthritis.

We examined patients with rheumatoid arthritis for cellular sansitivity to native human Types I, II and III collagens. Mononuclear cells from 50 patients with rheumatoid arthritis, 21 with other inflammatory arthritides, 20 with osteoarthritis and 20 normal subjects were evaluated for the in vitro production of leukocyte inhibitory factor in response to collagen and a control antigen, streptokinase-streptodornase. By this assay, cells from 37 (74 per cent) and 39 (78 per cent) of the patients with rheumatoid arthritis responded to Types II and III collagens, respectively. In contrast, cells from the 41 patients with other kinds of arthritis and the normal group did not produce this lymphokine to collagens. There was no response to Type I collagen or to denatured alpha chains of these collagens. All four groups responded equivalently to streptokinase-streptodornase. These data demonstrate that most patients with rheumatoid arthritis exhibit cellular sensitivity to Types II and III collagens.

Adult↗
PubMed1978

Humoral and cellular sensitivity to collagen in type II collagen-induced arthritis in rats.

We have recently described a new animal model of arthritis induced by intradermal injection of a distinct type of collagen found in cartilage (type II collagen). Since immunologic sensitivity to collagen could play a role in the pathogenesis of this type II collagen-induced arthritis in rats, the ability of purified types of native collagens to induce cellular and humoral responses was quantified by antigeninduced tritiated thymidine incorporation into lymphocytes by collagen and passive hemagglutination, respectively. Rats injected intradermally with native heterologous or homologous type II collagens in adjuvant developed type-specific cellular as well as humoral reactivity. Types I and III collagens were less immunogenic than was type II. The latter collagen induced brisk cellular and humoral responses that were equivalent whether complete Freund's adjuvant or incomplete Freund's adjuvant were employed. Both responses could be induced by native type II collagens modified by limited pepsin digestion, indicating that they are not attributable to determinants in the telopeptide regions of the molecule. Thus, these studies demonstrate the unique immunogenic as well as arthritogenic properties of the type II collagen molecule and indicate that both result from a helical conformation of its structurally distinct alpha-chains. Further, they suggest that type II collagen may, by humoral or cellular mechanisms, provoke or perpetuate inflammation in other arthritic diseases.

Animals↗
PubMed1978

Passive transfer by cells of type II collagen-induced arthritis in rats.

To investigate the role of immunologic hypersensitivity to collagen in the causation of type II collagen-induced arthritis in rats, passive transfer experiments were performed. Wistar/Lewis rats used in these experiments were demonstrated to be histocompatible by prolonged skin graft survival and mixed lymphocyte cultures. Popliteal lymph node weight assays excluded a potential for graft-vs.-host reactivity in this strain. 9 of 32 naive rats developed arthritis after intravenous receipt of pooled spleen and lymph node cells from donors that had been injected intradermally with type II collagen emulsified in incomplete Freund's adjuvant. This passively transferred synovitis was evident clinically as well as histologically. In control cell transfer experiments involving a total of 97 recipients, transfer of arthritis was shown to require viable cells sensitized to type II collagen. These controls included 17 rats receiving cells from unimmunized donors, 20 recipients of cells from donors injected with incomplete Freund's adjuvant alone, and 24 recipients of cells from rats injected with type I collagen in adjuvant. Deliberate addition of solubilized type II collagen to unsensitized cells at the time of transfer or injection of heat-killed sensitized cells also did not cause arthritis in a total of 36 recipients. These latter two control groups indicate that disease transfer was not the result of antigen carry-over. Intravenous injection of sera from arthritic donors was incapable of passively transferring clinical or histologic synovitis in 30 recipients. Thus, these studies directly implicate immunologic sensitivity to the cartilage type of collagen in the etiology of this autoimmune disease.

Animals↗
PubMed1978

Cellular sensitivity to collagen in rheumatoid arthritis.

Using an assay to measure antigen-induction of a lymphocyte mediator, LIF, we detected cellular sensitivities to native human types II and III collagens in three-quarters of a group of 50 patients with rheumatoid arthritis. There was no cellular response to type I collagen. Cellular reactivities to collagen were absent in a group of 41 patients who had other kinds of arthritis, such as osteoarthritis, crystalline-induced synovitis, or arthropathies associated with a high prevalence of the HLA-B27 antigen. Lymphocytes, responding to an unknown persistent antigenic stimulus, are thought to play a major role in the pathogenesis of rheumatoid arthritis. It has previously been hypothesized that collagen might function as an autoantigen in this disease. Based on the disease specificity of our findings and the tissue distribution of types II and III collagens, we propose that cellular sensitivities to these structural proteins may be involved in the pathogenesis of rheumatoid arthritis.

Adult↗
PubMed1977

Autoimmunity to type II collagen an experimental model of arthritis.

We have found that intradermal injection of native type II collagen extracted from human, chick or rat cartilage induces an inflammatory arthritis in approximately 40% of rats of several strains whether complete Freund's adjuvant or incomplete Freund's adjuvant is used. Type I or III collagen extracted from skin, cartilage proteoglycans and alpha1(II) chains were incapable of eliciting arthritis, as was type II collagen injected without adjuvant. The disease is a chronic proliferative synovitis, resembling adjuvant arthritis in rats and rheumatoid arthritis in humans. Native type II co-lagen modified by limited pepsin digestion still produces arthritis, suggesting that type-specific determinants residing in the helical region of the molecule are responsible for the induction of disease. Since homologous type II collagen emulsified in oil without bacterial preparations regularly causes the disease, this new animal model of arthritis represents a unique example of experimentally-inducible autoimmunity to a tissue component.

Animals↗
PubMed1976

Low dose penicillin for gonococcal arthritis. A comparative therapy trial.

Sixty-three patients with gonococcal arthritis completed a double-blind randomized penicillin therapy trial comparing a low dose regimen (procaine penicillin G, 600,000 units intramuscularly, given every 12 hours for up to ten days) with a high dose (the same procaine penicillin regimen and intravenous aqueous penicillin G, 10 million units daily, for the first three days). Pretherapy features were similar in the 36 patients allocated to low-dose vs the 27 to high-dose therapy. All patients had definite improvement within 48 hours of the initiation of either regimen. No therapeutic response variable studied differed significantly between the groups. Thus, no additional therapeutic benefit accrued from the high doses of penicillin. The absence of complications or failures in either treatment group indicate that gonococcal arthritis is ordinarily quite responsive to low doses of penicillin given intramuscularly, and that massive intravenous therapy is unnecessary.

Arthritis, Infectious↗