Biomedical subjects

J M Bathon

Publications and source records attributed to J M Bathon.

21 records · Page 2Linked to original sources

PubMed1989

Preincubation of human synovial cells with IL-1 modulates prostaglandin E2 release in response to bradykinin.

Kinins are vasoactive peptides whose potent inflammatory and bone resorbing properties suggest a role for these autacoids in the pathogenesis of inflammatory arthritis. We used cultured human synovial cells as a model to evaluate the effects of bradykinin on articular tissue. In resting synovial cells, bradykinin was a relatively ineffective stimulus for PGE2 production. However, after a period of preincubation with the cytokine, IL-1, which is itself a stimulus for PGE2 production, synovial cells exhibited a further striking time- and dose-dependent response to bradykinin. Maximal release of PGE2 was observed in response to 10(-7) to 10(-6) M bradykinin after first pretreating the cells for 24 h with 5 to 10 U/ml of IL-1. rIL-1 alpha and IL-1 beta, as well as rTNF-alpha, induced a similar response to bradykinin in synovial cells, whereas recombinant IL-2 did not. The bradykinin analog, lysylbradykinin, was equipotent in inducing PGE2 release from IL-1 pretreated synovial cells, whereas des(Arg9) bradykinin, substance P, and neurokinins A and B were ineffective in this regard in both IL-1-pretreated and in resting cells. Synovial cells derived from patients with rheumatoid arthritis and osteoarthritis responded similarly to bradykinin. The synergistic response in PGE2 production induced by IL-1 and bradykinin was significantly inhibited by pretreatment with 1 microM indomethacin or dexamethasone (96 and 94% inhibition, respectively). In addition, the response was abrogated by pretreatment with 10 micrograms/ml of cycloheximide or actinomycin D (81 and 97% inhibition, respectively). These data provide the first description of synergism of IL-1 with a noncytokine peptide in human synovial cells. The ability of IL-1 to increase the responsiveness of synovial tissues to bradykinin may play an important role in potentiating inflammatory responses within the joint.

Adjuvants, Immunologic↗

PubMed1989

Inflammatory central nervous system involvement in rheumatoid arthritis.

We describe a patient with seropositive rheumatoid arthritis who developed pachymeningitis resulting in optic atrophy. Clinical, histopathologic, and radiologic findings in 18 additional cases of inflammatory CNS disease associated with rheumatoid arthritis are reviewed. The three characteristic neuropathologic findings were rheumatoid nodules, pachymeningitis or leptomeningitis, and vasculitis. In most cases, more than one of these histopathologic processes were found. The typical host was middle-aged with long-standing severe nodular disease. However, contrary to previous reports, CNS disease occurred in a significant number of patients without active synovitis and extracranial vasculitis and nodules. Although no correlation between specific neurologic symptoms and neuropathology was noted, patients with CNS nodules tended to be asymptomatic more often than patients with vasculitis or meningitis. CSF analysis and computed axial tomography were helpful diagnostic tools, but diagnosis was ultimately made only by directed biopsy or at autopsy. Treatment with surgical decompression and/or corticosteroids has proved beneficial in several cases. Inflammatory CNS involvement in rheumatoid arthritis should be considered in any patient with neurologic symptoms in whom infectious and malignant processes are ruled out. An aggressive, invasive approach for diagnostic biopsies seems warranted.

Adult↗

PubMedDate not supplied

The Early Rheumatoid Arthritis (ERA) trial comparing the efficacy and safety of etanercept and methotrexate.

The Early Rheumatoid Arthritis (ERA) trial compared monotherapy with etanercept or methotrexate in patients with early erosive rheumatoid arthritis. Over the initial period of 12, and subsequently 24, months both treatments were associated with a profound reduction in radiographic progression of joint damage, as well as a reduction in signs and symptoms of disease. Etanercept showed slight superiority to methotrexate in reducing subsequent radiographic erosions and in the rapidity of the clinical response. Both therapies proved to be safe and well tolerated and, importantly, the relative safety and tolerance of a rapidly escalated dosing regimen for methotrexate was demonstrated. In summary, early aggressive treatment of RA is associated with clinical and radiographic benefit that can be demonstrated after a relatively short period of treatment.

Arthritis, Rheumatoid↗