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Biomedical subjects

J R Ward

Publications and source records attributed to J R Ward.

At least 109 records · Page 6Linked to original sources
PubMed1981

Mycoplasma-mediated activation of normal mouse lymphocytes: induction of cytotoxic lymphocytes and lymphocyte transformation by Mycoplasma arthritidis are under Ir gene control.

The ability of M. arthritidis, a potent arthritogenic agent, to induce normal unsensitized lymphocytes to undergo blast transformation and to become nonspecifically cytotoxic for syngeneic and allogeneic target fibroblasts was found to be dependent upon the donor strain of mouse. Lymphocytes from CBA (H2k) and BALB/c (H2d) mice were identified as high responders and lymphocytes from C56BL/10 mice (H2b) as low or nonresponders. In the cytotoxicity assay the extent of cell lysis was dependent upon the origin of both the effector cell and the target cell. By comparing the ability of M. arthritidis to activate lymphocytes from various congenic and H-2 recombinant mouse strains we demonstrated that control of the degree of responsiveness was determined by the H2 gene complex. Further studies revealed that the region controlling induction of cytotoxic lymphocytes is located to the right of the I-J subregion and to the left of the D region, most probably the I-E and/or I-C subregions of the major histocompatibility complex. These observations may be of importance in regard to the susceptibility of different mouse strains to the pathogenic effects of M. arthritidis.

Animals↗
PubMed1981

Stimulation of mouse lymphocytes by a mitogen derived from Mycoplasma arthritidis. I. Transformation is associated with an H-2-linked gene that maps to the I-E/I-C subregion.

Cell-free supernatant derived from broth cultures of Mycoplasma arthritidis functions as an effective T cell mitogen for lymphocytes from H2k and H2d strain mice. Lymphocytes from animals of the H2b, H2q, and H2s haplotypes failed to respond to this mitogen. By employing lymphocytes derived from congenic and recombinant strains we established the H2 linkage and mapped the controlling gene to the I-E/I-C subregion. In addition, these studies suggested that a correlation existed between responsiveness to this microbial product and the presence of the Ia7 specificity, a product of the I-E subregion.

Animals↗
PubMed1980

Comparison of high and low dose cyclophosphamide therapy in rheumatoid arthritis.

Eighty-eight patients with active rheumatoid arthritis from 8 Cooperating Clinics were evaluated in a 32-week controlled, double-blind trial comparing 150 mg daily to 75 mg cyclophosphamide daily. Improvement in the arthritis was seen in both groups, and there were no important differences between the two treatment groups in any of the 8 variables used to measure disease activity. Untoward effects were also similar for the two groups. These results differ from preliminary results reported earlier.

Adult↗
PubMed1980

Chronic arthritis of rabbits induced by mycoplasmas. I. Clinical microbiologic, and histologic features.

Mycoplasma arthritidis and Mycoplasma pulmonis induced chronic arthritis in rabbits on intraarticular injection, characterized by joint swelling and histologic evidence of chronic active inflammation persisting at least one year. Cartilage and bone destruction was a prominent late feature of M arthritidis but not M pulmonis disease. Despite the progressive nature of the disease and persistence of active inflammation for many months after inoculation, mycoplasmas and mycoplasma antigens were not found in joint tissues after 7 weeks.

Animals↗
PubMed1980

Chronic arthritis of rabbits induced by mycoplasmas. II. Antibody response and the deposition of immune complexes.

Chronic mycoplasms-induced arthritis of rabbits was accompanied by a highly active humoral immune response. Peak antibody titers coincided with the "disappearance" of mycoplasmas from joint tissues at 7 weeks. High synovial fluid antibody titers and immunoglobulin-producing cells in frozen sections of synovial membrane suggested local antibody production. Persistence of granular deposits containing IgG and complement in synovium and cartilage may be a mechanism for continuing inflammation in the apparent absence of cultivable mycoplasmas.

Animals↗
PubMed1980

Mycoplasma-dependent activation of normal mouse lymphocytes: requirement for functional T lymphocytes in the cytotoxicity reaction mediated by Mycoplasma arthritidis.

Syngeneic and allogeneic target cells were killed in the presence of CBA mouse lymphocytes and viable Mycoplasma arthritidis. Medium supplementation had no effect on the response. Nonviable M. arthritidis was also capable of stimulating lymphocytotoxicity, although to a much lesser extent. Cytotoxicity was shown to be largely dependent upon the lymphocytes, since lymphocytes preincubated with mycoplasmas and treated to remove remaining organisms were highly toxic to target cells, whereas supernatants prepared from lymphocyte/mycoplasma mixtures exhibited minimal effects. A 6-h exposure of lymphocytes to mycoplasmas at a ratio of 100:1 was sufficient for commitment to target cell killing. Functional lymphocytes were required for the reaction, since gamma-irradiated lymphocytes did not develop cytotoxic potential despite the fact that the mycoplasmas replicated equally well in the presence of these and untreated lymphocytes. Furthermore, lymphocytes already activated with mycoplasmas lost cytotoxic potential after disruption. The kinetics and degree of lymphocytotoxicity induced by M. arthritidis and phytohemagglutinin toward 51Cr-labeled syngeneic fibroblasts were similar. Removal of most B cells and other adherent cells by column separation did not abrogate the cytotoxic effect. Lymphocyte suspensions treated with anti-Thy 1 antiserum and complement exhibited a marked decrease in their cytotoxic potential when added to labeled target cells in the presence of M. arthritidis. We conclude that the cytotoxic reaction is dependent upon the T-lymphocyte subpopulation.

Animals↗
PubMed1979

Septic arthritis mimicking cellulitis: distinction using radionuclide bone imaging.

Two patients originally diagnosed as having cellulitis involving the dorsum of the foot actually had bacterial arthritis of an underlying joint. In both patients, even after pyarthrosis was suspected, the wrong joint was aspirated. The arthropathies were located by subsequent 99mTc-phosphate bone imaging at a time when roentgenograms were normal. Early diagnosis and aggressive therapy of septic arthritis are essential to prevent joint destruction and osteomyelitis. Radionuclide bone imaging can identify inflammatory joint disease but it cannot specify etiology. In our patients, however, the differential diagnosis was between skin and joint infection. Radionuclide imaging was of great help in making this distinction.

Adult↗
PubMed1979

Endotoxin toxicity in rats with 6-sulfanilamidoindazole arthritis.

Seven oral administrations of 6-sulfanilamidoindazole (6-SAI) to 10- to 12-month-old rats sensitized the animals to endotoxin, with dosages as small as 2.5 microgram causing death in 80% of animals. Endotoxin in a dosage of 3,000 microgram was not lethal for nonmedicated control animals. 6-SAI-treated 1-month-old rats were not as sensitive to endotoxin as aged animals. The sulfonamide-induced sensitivity to endotoxin could not be passively transferred and could not be explained by blockade of the reticuloendothelial system or impairment of endotoxin detoxification. 6-SAI administration was associated with both depletion of liver glycogen and lowering of blood glucose concentration without changes in blood lactic acid concentration. Disseminated intravascular coagulation is believed to be involved in the pathogenesis of shock and death as evidenced by: (i) concomitant decreases in plasma fibrinogen concentration and elevations in fibrin degradation products after endotoxin challenge; (ii) protection against lethal actions of endotoxin by pretreatment with heparin. Treatment of 6-SAI-medicated rats with glucocorticoids before endotoxin challenge protected the animals against lethal doses of endotoxin and prevented deposition of fibrin thrombi in the glomerular capillaries.

Aging↗
PubMed1978

Naproxen vs. aspirin in osteoarthritis of the hip and knee.

This 12-week double-blind trial compared the efficacy and tolerance of naproxen (750 mg/day) with that of aspirin (3.6 gm/day). There was no statistical difference in efficacy between the two trial drugs for any of the objective (e.g., 25-foot walking time) or subjective (e.g., overall severity of symptoms) variables measured. No side effects were experienced by 69% of the naproxen patients and 37.5% of the aspirin patients. There were a statistically greater number and more severe side effects during aspirin therapy than during naproxen therapy (p = 0.002). The results show naproxen to be a potentially useful drug for the treatment of osteoarthritis.

Adult↗
PubMed1977

Chronic arthropathy associated with rubella vaccination.

Eleven children suffered recurrent ipisodes of knee stiffness ("catcher's crouch syndrome") after receiving HPV-77DK12 rubella vaccine. One was evaluated by arthroscopy and the synovium was found to be hypertrophied posteriorly and to protude in folds into the intercondylar notch and lateral joint space. Culture for rubella virus was unsuccessful. The author's observations provide evidence that "catcher's crouch syndrome" is a synovial disease and that chronic joint disease can be a sequela of rubella immunization.

Child↗
PubMed1977

A multicenter trial of sulindac in osteoarthritis of the hip.

Sulindac (cis-5-fluoro-2-methyl-l-[(p-methyl sulfinyl)-benzylidene]-indene-3-acetic acid) is a new nonsteroidal antirheumatic drug recently evaluated in a double-blind trial of 91 patients with hip osteoarthritis. Consecutive patients with documented flare following previous drug withdrawal were randomly assigned to one of 3 treatment groups: (1) sulindac given twice daily, (2) sulindac given 4 times daily, and (3) placebo. The dosage of sulindac, 100 to 300 mg daily, was adjusted according to patient global response and tolerance at 3- to 7-day intervals over 3 wk. Of 15 efficacy measurements evalulated, there was no difference between sulindac given 2 or 4 times daily, but differences were disclosed between one or both sulindac treatment groups and placebo in 11 of the 15 efficacy measurements (p less than 0.05, less than 0.01). The frequency of adverse reactions was of the same order for each treatment group. These included gastrointestinal upset, rash, and dizziness, usually transient and mild to moderate in severity. Serial laboratory studies revealed no evidence of renal, hepatic, or hematopoietic toxicity.

Adult↗
PubMed1977

Treatment of rheumatoid arthritis with flurbiprofen or ibuprofen.

Flurbiprofen and ibuprofen were compared in a six-week double-blind randomized study in 208 patients with rheumatoid arthritis. Daily dosages were 120 mg flurbiprofen and 2400 mg ibuprofen for six weeks. Both drugs were effective in providing partial control of RA symptoms. Either or both drugs produced statistically significant improvement in mean values of time of onset of fatigue, grip strength and tender and swollen joint counts. All other standard endpoints of efficacy (except ESR) were improved but not at a statistically significant level. Slightly more than half of the patients improved during the trial. There was no statistically significant difference in the efficacy of the drugs. The incidence of side effects was low with both drugs. Most side effects were related to gastrointestinal tract irritation.

Arthritis, Rheumatoid↗
PubMed1977

New models of chronic synovitis in rabbits induced by mycoplasmas: microbiological, histopathological, and immunological observations on rabbits injected with Mycoplasma arthritidis and Mycoplasma pulmonis.

A dose-dependent chronic synovitis was induced in rabbit knees after the intra-articular injection of both Mycoplasma arthritidis and Mycoplasma pulmonis. The inflammation progressed from an initial acute phase at 1 week characterized by edema, infiltration of the synovium with monocytes and heterophils, and desquamation of lining cells, to a more chronic phase at 1 and 3 months, in which villus hyperplasia, lymph "nodules," mononuclear cell infiltration, fibroplasia, and collagen deposition were prominent. With one exception, mycoplasmas could no longer be cultivated from the joints 1 month postinoculation. Both mycoplasma species evoked a humoral antibody response that was more marked in synovial fluids than in peripheral blood. A cell-mediated immune reaction, as evidence by enhanced uptake by [3H]thymidine by sensitized blood, spleen, or node lymphocytes in the presence of homologous antigen, was detected only in rabbits injected with M. pulmonis. Lymphocytes taken from arthritic rabbits were no more cytotoxic toward synovial cells derived from normal or arthritic rabbits than were normal lymphocytes. The models of synovitis described in this study offer a convenient probe for determining the mechanisms of mycoplasma-induced inflammation, since they require only a single injection of the initiating agent and, in addition, utilize an animal host large enough for detailed investigation into the nature of mycoplasma/synovium interactions.

Animals↗
PubMed1977

Mycoplasma-dependent activation of normal lymphocytes: induction of a lymphocyte-mediated cytotoxicity for allogeneic and syngeneic mouse target cells.

Mycoplasma arthritidis, M. hominis, and M. arginini were tested for their ability to induce a cytotoxic response from normal CBA mouse lymphocytes against 51Cr-labeled allogeneic target cells. In most cases, the mycoplasmas alone were not toxic for the target cells. Furthermore, the mycoplasmas did not result in decreased lymphocyte viability but, in fact, contributed to enhanced lymphocyte survival. In the absence of normal CBA lymphocytes, mycoplasmas alone did not induce a significant amount of cell damage in either the allogeneic or the syngeneic target cells. Strains of M. arthritidis and M. hominis, when added to the lymphocyte-target cell mixtures, induced statistically significant increases in 51Cr release from both target cell types at each assay period after 6 h. The release of 51Cr was taken as a measure of cell death. M. arginini induced only low levels of cytotoxicity or none at all. Both arthritogenic and non-arthritogenic strains of M. arthritidis induced the cytotoxic response. The degree of cytotoxicity produced was directly related to the size of the initial inoculum. The presence or absence of serum in the culture medium did not contribute significantly to the cytotoxicity response.

Animals↗
PubMed1977

Mycoplasma-dependent activation of normal lymphocytes: role of arginine and nonviable mycoplasma antigen in the induction of lymphocyte-mediated cytotoxicity for syngeneic mouse target cells.

The ability of arginine supplementation to abrogate or potentiate Mycoplasma arthritidis-mediated cytotoxicity induction by normal CBA mouse lymphocytes was investigated. Also, nonviable antigens of M. arthritidis were assayed for their ability to induce a cytotoxic response. The presence of additional arginine in the culture medium had no significant effect on the amount of cytotoxicity produced. In some cases, an increase in cytotoxicity was seen in the presence of additional arginine. Amino acid analysis of the culture supernatants showed that the arginine in the nonsupplemented medium was exhausted during the assay, whereas ample amounts of arginine were present in the supplemented medium. However in both cases the amount of cytotoxicity was comparable. Nonviable antigens of M. arthritidis were unable to induce a significant cytotoxic response in the presence of normal lymphocytes. The same antigens exhibited a suppressive response when tested for blastogenesis in the presence of normal lymphocytes. A discussion of lymphocyte involvement is presented.

Animals↗