Biomedical subjects
Publications and source records attributed to R A Hazelton.
A patient is reported who has had episodes of spontaneous haemarthroses of the shoulder. On aspiration of the acute haemarthrosis, amyloid was found after appropriate staining of the centrifuged sediment. This may be a predisposing factor for haemarthrosis in haemodialysed patients.
A polypeptide inhibitor of osteoblast proliferation is described which occurs in synovial effusions of patients with rheumatoid arthritis. Partial purification of the inhibitor showed a molecular weight of approximately 81,000 by gel electrophoresis. This polypeptide seems to be unique as no inhibitor of osteoblasts of similar molecular weight has been previously described in rheumatoid synovial effusions.
Six of 9 patients with previously documented adverse reactions to allopurinol exhibited transformation of their peripheral blood lymphocytes when these were exposed in vitro to the allopurinol metabolite, oxypurinol. In 2 of these subjects, intradermal skin challenge was positive at 48 hours with either allopurinol or oxypurinol. The evidence presented suggests that some adverse reactions to allopurinol represent delayed-type hypersensitivity to oxypurinol.
Plastic adherent and non-adherent mononuclear cells derived from synovial fluid were found to stimulate peripheral blood mononuclear cells of patients with rheumatoid arthritis (RA) in an autologous mixed lymphocyte reaction (AMLR). Stimulation produced by adherent cells was consistently greater than that produced by non-adherent mononuclear cells. CD11 enriched cells were not significant stimulators in the AMLR, however their presence was required for a significant reaction to occur. Limiting dilution studies revealed that the most plausible model involved two or more cells of the same type in each of the stimulator and responder populations for the AMLR to occur.
Using the protein immunoblot technique, antibodies to an Epstein-Barr virus-induced 92 kD polypeptide (EBNA-2) were more frequently present in the sera of patients with rheumatoid arthritis and their consanguineous relatives when compared with a control group. No association of anti-EBNA-2 antibody with the HLA-DR antigens was observed.
'Spontaneous' lymphoblastoid cell lines (LCL) were established from patients with either rheumatoid arthritis (RA) or infectious mononucleosis (IM) or from healthy donors. Differences in Epstein-Barr virus (EBV) strains were determined by measuring the mol. wt. and expression of viral antigens in each of the LCLs. In addition to the previously reported EBV nuclear antigens, the LCLs also contained EBV-induced antigens with mol. wt. of 48K and 58K which were present in all but two of the lines. One of the differences observed between each of the groups of cell lines was their ability to produce viral antigens. Early and late antigens were identified by immunoblotting in most of the RA lines, two of the normal lines but none of the cell lines from patients with IM. Many of the IM cell lines were also found to express multiple EBNA1 antigens. The results demonstrate that a variety of wild-type EBV strains exist. However, the similarities observed in a number of the lines suggest that the diversity of strains may be limited.
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The urate lowering effect of diflunisal, a fluorinated salicylate with an antiinflammatory action, was compared with that of allopurinol in a crossover study. When patients took diflunisal the mean serum urate was significantly greater than on allopurinol but still was within the optimal range in 6 of 8 patients studied. This effect was consistent with its uricosuric action. No inhibition of xanthine oxidase activity by diflunisal was found. Diflunisal could be particularly useful in patients who require a drug with both a uricosuric and an antiinflammatory effect.
The incidence of antibodies to Epstein-Barr nuclear antigen type 2 (EBNA-2) was determined in sera from rheumatoid arthritis (RA) patients and control subjects, by protein immunoblotting. Sixty-eight percent of the RA patients and 48% of the controls possessed anti-EBNA-2 antibodies. The titer of anti-rheumatoid arthritis nuclear antigen (RANA) in RA patient sera showed a stronger correlation with serum reactions to EBNA-2 than with reactions to EBNA-1. Our results indicate that the presence of EBNA-2 may make a major contribution to the RANA reaction.
Sera from families with at least two members suffering from seropositive rheumatoid arthritis (RA) were examined for the prevalence of antibodies to the RA associated nuclear antigen (RANA). It was found that consanguineous relatives of patients had a significantly increased prevalence of anti-RANA antibodies compared to sera from a control group of families. Anti-RANA antibodies were also significantly more prevalent in the sera of familial RA patients who possessed HLA-DR4. No correlation of anti-RANA antibodies with disease associated haplotypes was observed in these families.
T lymphocyte lines have been established, with the addition of interleukin-2 (IL-2), from the synovial fluid (SF) of patients with arthritis. Characterisation of seven of these SF-derived T cell lines showed them to be T3+, T11+, and to contain a significant proportion of T8+ cells (mean 41%). The proportion of T4+ cells varied among the lines, with a mean T4+/T8+ ratio of 0.6. A significant autologous mixed lymphocyte reaction (AMLR) was observed only in one of four T cell lines assayed. Two of four lines assayed showed natural killer (NK) cell-like activity, while one line displayed a significant suppressor activity, suggesting that the T cell population in SF contained NK-like cells or suppressor cells, or both, either of which may be selected in the establishment of SF-derived T cell lines.
Three cases of reactive arthritis associated with Yersinia enterocolitica bowel infection are reported. In one case Y. enterocolitica was cultured from stools while all three exhibited a significant increase in serum antibody titres to Y. enterocolitica. These are believed to be the first reports of Yersinia reactive arthritis in Australia. Synovial membrane biopsy in one case revealed a mixed inflammatory cell infiltrate the appearance of which was quite dissimilar to that of rheumatoid arthritis (RA). Mononuclear cells of the peripheral blood, but not the synovial fluid from another patient had reduced functional activity compared to RA patients as determined by response to phytohemagglutinin stimulation and allogeneic responses. Large numbers of HLA-DR and acid phosphatase positive macrophages were also found in the synovial fluid of this patient. The reason for joint involvement in Y. enterocolitica reactive arthritis is unknown and further work is necessary.
Ross River virus has been incriminated in the etiology of many sporadic and epidemic cases of polyarthritis in Australia and the Pacific. Both synovium and synovial exudate fluid recovered from the knee of an epidemic polyarthritis patient showed a predominantly mononuclear leucocyte infiltrate. Infectious virus could not be recovered from the synovial exudate. Functional natural killer cells were detected in the synovial fluid. Their level of cytotoxic activity was similar to that detected in the peripheral circulation.
The response of peripheral blood lymphocytes (PBL) to autologous synovial fluid lymphocytes (SFL) from patients with rheumatoid arthritis and Reiter's syndrome was investigated in an autologous mixed lymphocyte reaction (AMLR). SFL were found to be poor responders but strong stimulators of autologous and allogeneic PBL compared with autologous PBL. The plastic-adherent (macrophage) cells from the SFL were found to be highly stimulatory to autologous PBL, particularly when the adherent cells were removed from the responding PBL. The stimulation of these PBL non-adherent cells by SFL adherent cells follows two main trends: either no stimulation, or higher stimulation than using unseparated SFL and PBL. Patients in the high stimulator group were taking non-steroidal anti-inflammatory drugs while those in the low responder group were taking, in addition, second-line drugs such as D-penicillamine or gold. Autologous serum was found to inhibit the AMLR and this is probably due to drug metabolites in patients' sera. Initial results show that the AMLR in individual patients is highly correlated, over time, with the erythrocyte sedimentation rate (ESR).
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Lymphocytotoxic antibodies are a common feature in the sera of patients with systemic lupus erythematosus. This family study, however, has not confirmed the previous findings of an increased incidence in the sera of their relatives. Adsorption studies suggest that when lymphocytotoxins occur in the sera of normal subjects and relatives of patients they have a different specificity and thus significance.
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