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Biomedical subjects

D E Trentham

Publications and source records attributed to D E Trentham.

At least 73 records · Page 4Linked to original sources
PubMed1984

Total lymphoid irradiation therapy in refractory rheumatoid arthritis. Fifteen- to forty-month followup.

Twelve patients with refractory rheumatoid arthritis were treated with total lymphoid irradiation (TLI) to a total cumulative dose of 3,000 rads. Post-TLI morbidity/mortality included 8 patients with xerostomia, 4 with weight loss of greater than 10 kg, 3 with loss of 4 or more teeth, 3 with herpes zoster, 4 with bacterial infection that was fatal in 2, 3 with hypothyroidism, 1 with cutaneous vasculitis, and death from myocardial infarction in 1 patient and cardiorespiratory arrest in another. Ten of the patients were reevaluated 15-40 months (mean +/- SE, 30 +/- 2) after completion of TLI, and significant improvement was noted in several disease parameters including number of swollen joints, duration of morning stiffness, and 50-foot walking time. Blood lymphopenia and a decrease in helper T cells (T4) were also noted. These data suggest that changes in immunoregulation induced by TLI can produce longlasting alterations in rheumatoid arthritis, although adverse effects may limit its efficacy.

Adult↗
PubMed1984

HLA-DR4 is not a requisite for autoimmunity to collagen in rheumatoid arthritis.

Immunogenetic studies in rheumatoid arthritis have demonstrated an increased frequency of the HLA-DR4 alloantigen in individuals with both the sporadic and familial forms of the disease. To investigate the significance of this association, we ascertained whether the possession of DR4 is necessary for the expression of cellular and humoral immunity to native human type II collagen. Our results indicate that the presence of DR4 is not required for the development of autoimmunity to collagen in rheumatoid arthritis.

Adult↗
PubMed1984

Effect of antithymocyte serum on collagen arthritis in rats: evidence that T cells are involved in its pathogenesis.

To assess the role of T cells in collagen arthritis, a heterologous T cell-specific antiserum (ATS) was administered intraperitoneally to female Wistar-Furth rats. ATS treatment on Day -1, 1, 3, and 5 and immunization with native chick type II collagen on Day 0 resulted in a decreased incidence of arthritis (5 of 19, 26%) compared to immunized rats given either nonimmune heterologous serum on these days (20 of 25, 80%) or ATS injected on Day 5, 7, 9, and 11 (17 of 20, 85%) (P less than 0.001 for both comparisons). The early-ATS protocol also was associated with a delayed onset and reduced disease severity in the few rats in this group that did develop arthritis. Both delayed-type hypersensitivity (DTH) and serum IgG antibody titers to native type II collagen, measured on Day 10, were decreased significantly (P less than 0.002) in rats administered ATS beginning on Day -1 compared to the other two groups. These data suggest that T cells contribute to the inception of collagen arthritis and that their critical function occurs within the first 5 days after immunization.

Animals↗
PubMed1984

Suppressive effects of anti-mu serum on the development of collagen arthritis in rats.

Sprague-Dawley rats were maintained in environmentally isolated conditions and some of them were injected beginning at birth with rabbit anti-mu serum to suppress B-cell maturation. All rats were subsequently immunized with chick type II collagen. Ten (28%) of 36 rats injected with anti-mu antiserum failed to develop serum hemagglutinating antibodies to collagen, and there was a significant (P less than 0.0003) reduction in the IgG-specific antibody titer to collagen in these 10 rats compared to the other 26 rats in this group. Only 1 (10%) of the antibody-suppressed rats developed arthritis compared to 20 (77%) of the 26 other rats in the anti-mu-treated group (P less than 0.001). Twenty-two (61%) of 36 immunized rats administered rabbit anti-ovalbumin serum and 14 (88%) of 16 immunized rats kept in the axenic conditions developed arthritis. Delayed-type hypersensitivity to collagen did not differ significantly between the groups. These data provide indirect evidence that antibodies play a role in the inception of collagen arthritis.

Animals↗
PubMed1984

Antigen-specific suppression of collagen arthritis by adoptive transfer of spleen cells.

Wistar-Furth (W-F) rats were given 10(9) syngeneic spleen cells, suspended in Hanks' balanced salt solution (HBSS), intravenously on Day 0 to investigate the mechanisms involved in antigen-specific suppression of collagen arthritis. These cells were pooled from W-F donors which had been injected iv on Days -21, -14, and -7 with rat red blood cells (RBC) coupled with glutaraldehyde to either native chick type II collagen, denatured type II collagen, or native type I collagen. All recipients were immunized with an emulsion of native type II collagen in incomplete Freund's adjuvant on Day 1 to induce collagen arthritis. There was a decreased incidence of arthritis, by clinical and radiographic assessments, in rats receiving spleen cells from donors previously administered native type II collagen-coupled RBC compared to those given spleen cells obtained from donors treated with denatured type II or native type I collagen-coupled RBC [18 of 30 (60%) arthritic vs 20 of 20 (100%) and 19 of 20 (95%) arthritic, for the three groups, respectively, P less than 0.01 for both comparisons]. The incidence of arthritis in 35 rats administered HBSS iv 1 day prior to immunization (83%) and 10 immunized rats given no iv injections (100%) was also significantly higher (P less than 0.05) than the incidence in the antigen-relevant experimental group. Hemagglutinating antibody titers and delayed-type hypersensitivity (DTH) to collagen were lower in the recipients of cells from donors administered native type II collagen-coupled RBC, whereas IgG antibody titers to collagen were unaltered. These results demonstrate that passively transferred spleen cells can attenuate collagen arthritis and sensitization in an antigen-specific manner.

Animals↗
PubMed1984

Dietary fish oil augments the induction of arthritis in rats immunized with type II collagen.

Certain dietary-induced changes in tissue levels of polyunsaturated fatty acids are known to modify inflammatory reactions, possibly through changes in the synthesis of mediators of inflammation derived from fatty acids, including prostaglandins and leukotrienes. We have therefore examined the effects of a fish oil diet, enriched in highly unsaturated (delta-17) long chain fatty acids, on collagen arthritis. Weanling female Sprague-Dawley rats were maintained on a diet with fat provided by either fish oil (containing 14.5% 5, 8, 11, 14, 17-eicosapentaenoic acid; EPA) or, as a control, beef tallow (containing less than 0.05% EPA). They were immunized with native chick type II collagen emulsified in incomplete Freund's adjuvant 5 to 6 wk later. There was an increased incidence of arthritis in the rats receiving the fish oil compared with the group receiving the beef diet (88 vs 61%, p less than 0.001), but there was no significant difference in the severity of joint inflammation of arthritic rats in the two groups. The mean serum titer of IgG antibodies to type II collagen, measured by an enzyme-linked immunosorbent assay (ELISA), was decreased in the group receiving the fish oil (p less than 0.001), whereas the hemagglutinating antibody titer and delayed-type hypersensitivity to collagen were similar in the two groups. Primary synovial explant cultures from fish oil-treated rats produced only 21 to 24% as much PGE2 as beef tallow-treated controls, and this reduction in the experimental group was not accompanied by any detectable increase in PGE3, the E-prostaglandin derived from the arachidonic acid analogue, EPA, in fish oil. These data demonstrate that inductive mechanisms in collagen arthritis can be altered by diet-induced changes in tissue fatty acid composition without essential fatty acid deficiency. The reason(s) for this effect is unknown, but it is possible that changes in the cyclooxygenase or lipoxygenase products of polyunsaturated fatty acids are involved.

Alprostadil↗
PubMed1983

Attenuation of an adjuvant arthritis by type II collagen.

Subcutaneous injection of the nonimmunogenic synthetic alkyldiamine, N,N-diotadecyl-N',N'-bis(2-hydroxyethyl) propanediamine (CP-20961), which possesses potent adjuvant properties for cellular sensitization, can induce an inflammatory arthritis in rats. To study whether a host reaction to native type II collagen plays a role in the pathogenesis of the arthritis in this model, CP-20961-injected Lewis rats received i.v. on four occasions native type II collagen coupled to syngeneic spleen cells with ethylcarbodiimide (CDI), native type II collagen added to spleen cells without CDI, or native type II collagen coupled to rat red blood cells (RBC) with glutaraldehyde. There was a significant suppression of the severity of arthritis in all three groups compared with a control group injected with CP-20961 but not receiving cells. In addition, the prevalence of arthritis was decreased in the group receiving native type II collagen-coupled RBC. Injection of cells coupled to denatured type II collagen, native type I collagen, and ovalbumin did not affect significantly the morphologic aspects of this disease. These data provide evidence that material possessing the quaternary epitope(s) of type II collagen functions in an as yet unidentified effector pathway in this adjuvant arthritis.

Animals↗
PubMed1983

Exacerbation of collagen arthritis by noise stress.

We evaluated the effect of noise exposure on collagen arthritis in rats. Ninety-eight female Wistar rats were transported and subjected to a 90-decibel noise during a 1-h period for 7 days commencing 3 days prior to immunization with type II collagen. As a control, 99 rats received simultaneous immunizations but were otherwise left undisturbed. Noise exposure was associated with statistically significant increases in the prevalence of arthritis (p less than 0.05) and, early in its course, in the severity (p less than 0.001) of arthritis.

Animals↗
PubMed1983

Dimethyl sulfoxide does not suppress the clinical manifestations of collagen arthritis.

Parenteral administration of dimethyl sulfoxide (DMSO) to rats did not diminish the incidence or severity of collagen arthritis compared to groups receiving either saline injections or no injections. In contrast, hemagglutinating antibody responses to collagen were significantly (p less than 0.0001) decreased in the DMSO group. Delayed-type hypersensitivity responses to collagen were similar in the 3 groups. These data extend the previous finding that DMSO can decrease antireceptor antibody titers in experimental myasthenia gravis in rats.

Animals↗
PubMed1982

Modulation of human lymphocyte function by C3a and C3a(70-77).

Human C3a and the synthetic octapeptide C3a (70-77), which retains the activities of an anaphylatoxin, inhibit in a concentration-dependent manner the generation of leukocyte inhibitory factor (LIF) activity by human mononuclear leukocytes and T lymphocytes cultured with the mitogens phytohemagglutinin (PHA) or concanavalin A (Con A) or the antigen streptokinase-streptodornase (SK-SD). The generation of LIF activity was inhibited by 50% by 10(-8) M C3a or C3a(70-77) with PHA or Con A as the stimulus, whereas a more than 10-fold higher concentration of C3a(70-77) than C3a was required to achieve the same level of suppression with SK-SD as the stimulus. Similar concentrations of C3a(70-77) inhibited to the same extent the migration of T lymphocytes stimulated by alpha-thioglycerol of Con A. Neither C3a nor C3a(70-77) altered significantly the uptake of [3H]thymidine by human mononuclear cells exposed to PHA, Con A, or SK-SD. The capacity of C3a(70-77)-Sepharose,m but not Sepharose alone, to adsorb or inactivate mononuclear leukocytes required for the generation of LIF activity established a direct interaction. Analysis of the lymphocytes in the effluent from C3a(70-77)-Sepharose columns, using monoclonal antibodies to surface antigens, showed a selective depletion of the helper/inducer population of lymphocytes. C3a might represent an important mediator of the functionally selective regulation of human T lymphocyte activities by the complement system.

Cell Division↗
PubMed1982

Type II collagen-induced auricular chondritis.

Sensitization to type II collagen induced inflammatory destruction of elastic ear cartilage, as well as arthritis, in Sprague-Dawley rats. This auricular lesion morphologically resembled relapsing polychondritis in humans. Moreover, in the experimental model, as has been reported in human disease, extraarticular chondritis occurred in the context of immunologic sensitivity to native type II collagen. These similarities suggest that type II collagen-induced auricular chondritis may provide insights about the pathogenesis of relapsing polychondritis.

Adjuvants, Immunologic↗
PubMed1982

Immunosuppression by fractionated total lymphoid irradiation in collagen arthritis.

Treatments with fractionated total lymphoid irradiation (TLI) and cyclophosphamide were evaluated for rats injected with type II collagen. Preadministration of TLI and repeated injections of cyclophosphamide suppressed the severity of arthritis and lowered antibody titers to collagen significantly. TLI initiated at the onset of collagen arthritis decreased humoral and cellular responses to collagen but did not affect the severity of arthritis. These data demonstrate that both TLi and cyclophosphamide are immunosuppressive in an experimentally inducible autoimmune disease.

Animals↗
PubMed1982

Collagens act as ligands to stimulate human monocytes to produce mononuclear cell factor (MCF) and prostaglandins (PGE2).

Blood mononuclear cells from patients with rheumatoid arthritis produce the lymphokine, leukocyte inhibitory factor (LIF) in response to collagens in vitro, and blood monocytes release prostaglandins (PGE2) and a factor, mononuclear cell factor (MCF) which stimulates collagenase and PGE2 production by cultured synovial cells. We therefore examined the effect of collagens on the production of PGE2 and MCF. Blood mononuclear cells from 6 patients with rheumatoid arthritis and 6 normal subjects were cultured in native human types I, II, or III collagen-coated tubes, or with streptokinase-streptodornase (SK-SD), and the supernatant media derived from these cultures analyzed for the presence of MCF, PGE2, and LIF. Types II and III collagens, as well as SK-SD, markedly stimulated MCF production by the cells from all 12 subjects (MCF activity, expressed as a mean stimulation index (SI) +/- SEM, was 43 +/- 12 for type II, 33 +/- 7 for type III, and 37 +/- 23 for SK-SD). Type I collagen was less stimulatory (mean SI 10 +/- 7). Cells from the patients with rheumatoid arthritis, but not the normal subjects, produced LIF in response to types II or III collagens but not to type I collagen. PGE2 production by blood mononuclear cells paralleled that of MCF, although abrogation of PGE2 release with indomethacin did not reduce MCF production. alpha chains purified from denatured collagens also stimulated MCF production. Using cells from patients with rheumatoid arthritis, type II collagen stimulated production of all three factors in the presence of polymyxin B or fibronectin-depleted serum, suggesting, respectively, that neither endotoxin nor fibronectin were responsible for their generation. Monocytes, purified from normal blood by an adherence technique, but not lymphocytes depleted of monocytes, released MCF and PGE2 when cultured with type II collagen. These results demonstrate that collagens can act as ligands to stimulate monocytes, as well as antigens to stimulate sensitized lymphocytes, to produce soluble factors that may contribute to the destruction of connective tissue.

Arthritis, Rheumatoid↗
PubMed1982

Antigen-specific suppression of type II collagen-induced arthritis by collagen-coupled spleen cells.

The induction of arthritis in Wistar-Lewis rats was suppressed by i.v. injections of spleen cells coupled to native type II collagen, beginning 14 days before intradermal injection of native type II collagen in incomplete Freund's adjuvant and continuing at 7-day intervals for the next 3 weeks. Cells coupled to native type I collagen or to denatured type II collagen were ineffectual, suggesting antigen-relevant cells were required for suppression. The phenomenon appeared to be mediated by a humoral effector mechanism; IgG antibody titers but not hemagglutinating antibody titers or delayed-type hypersensitivity to collagen were decreased by the injection of type II collagen-coupled cells. These data demonstrate the potential of antigen-specific immunotherapy for autoimmune disease.

Animals↗
PubMed1982

Morphologic demonstration of two stages in the development of type II collagen-induced arthritis.

The infrapatellar fat pad, fibrous synovium, and cartilage joint surfaces of the tibia, patella, and femur of the knee joints of 17 normal rats and 38 rats with type II collagen-induced arthritis were examined by light and electron microscopy. In the normal animals, the synovium covering the fat pad was structurally variable in that the mesothelium was flattened and two to three cell layers thick in the central region but rounded and three to five layers thick at the tibial and patellar ends. Large vacuoles were more numerous in the synovial cells at either end of the fat pad, and these cells contained less endoplasmic reticulum than those in the central region. The fibrous synovium consisted of a flattened mesothelium composed of cells similar to those found in the central region of the fat pad. The normal cartilage was not covered by a mesothelium. Knees from animals immunized with collagen showed no structural changes until 5 days after immunization, when fibrin could be detected in the synovium by immunofluorescence. By day 12, fibrin deposition was found throughout the synovium covering the fat pad and fibrous tissue, as well as over the cartilage. In addition, hyperplasia of the synovium over the soft tissues was present, and synovial cells extended over the cartilage. On day 19, in approximately 20 per cent of the animals, inflammatory infiltrates, composed of mixtures of polymorphonuclear leukocytes and mononuclear cells, were observed within the synovium covering the soft tissues. Infiltrates were also seen at the edges of the cartilage. When the 80 per cent of the animals that did not have cellular infiltrates were examined 30 days after immunization, neither hyperplasia nor fibrin deposition were seen by light microscopy. By day 45, in 20 per cent of the animals, the synovium was hyperplastic, and granulation tissue, scarring, and granulomata were found in the soft tissues. It is concluded that there are two distinct stages in the development of this synovial disease--the first is characterized by hyperplasia and fibrin deposition, and the second by the presence of inflammatory infiltrates.

Animals↗