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Biomedical subjects

E M Lance

Publications and source records attributed to E M Lance.

At least 19 recordsLinked to original sources
PubMed1994

Differentiation antigens of human articular chondrocytes and their tissue distribution as assessed by monoclonal antibodies.

Five monoclonal antibodies (HuMC1, HuMC2, HuMC3, HuMC4 and HuMC5) raised against intact human articular chondrocytes were tested with chondrocyte samples from arthritic and non-arthritic patients by surface immunofluorescence and by immunoperoxidase labeling of fixed cells. All acetone-fixed samples reacted strongly with the monoclonal antibodies but some variation in the percentages of intact chondrocytes positive by immunofluorescence was noted. Under culturing conditions which induced de-differentiation, epitopes recognized by HuMC1, HuMC3 and HuMC4 disappeared with time in culture. In contrast, reactivities to HuMC2 and HuMC5 either persisted or increased as the culture became more fibroblastic and these antibodies bound to antigens on human fibroblast cell lines. HuMC1, HuMC3 and HuMC4 reacted with purified adult and fetal proteoglycan. HuMC2 and HuMC5 exhibited only slight or no reactivity to either proteoglycan. All five monoclonal antibodies reacted with chondrocytes in frozen articular cartilage but HuMC2 and HuMC5 failed to react to chondrocytes in paraffin-embedded cartilage sections. Only HuMC1, HuMC3 and HuMC4 recognized matrix components in both frozen and paraffin-embedded cartilage. When tested against 29 different non-cartilaginous tissues, each of the monoclonal antibodies had distinctive reactivity patterns, suggesting that each reacted to different epitopes. HuMC3 reacted with neurons in the cerebral cortex and cerebellum, indicating that it may recognize epitopes shared on the S-100 protein. HuMC1 showed the greatest specificity for chondrosarcomas. These antibodies are useful for identifying differentiated chondrocytes, providing information on the distribution of chondrocyte antigens shared by other human tissue, assessing the extent of chondrocyte heterogeneity in a population and aiding in the classification of chondrosarcomas.

Antibodies, Monoclonal↗
PubMed1993

Enhanced chondrocyte destruction by lymphokine-activated killer cells. Possible role in rheumatoid arthritis.

OBJECTIVE: The lysis of chondrocytes, the parenchymal cells of cartilage, by lymphocytes may provide a potent mechanism by which the immune system participates in sustaining joint damage in rheumatoid arthritis (RA). We studied the capability of lymphocytes from healthy individuals and patients with arthritis to lyse chondrocytes. METHODS: Peripheral blood mononuclear cells (PMBC) were tested for their ability to lyse chondrocytes in a 51Cr-release assay. Enhancement of the chondrolytic activity was determined by preincubating the cells with T cell growth factor (TCGF) or recombinant interleukin-2 (rIL-2) before cytotoxic testing. RESULTS: PBMC from healthy individuals possessed a low ability to lyse chondrocytes, whereas cells from the synovial fluid of patients with RA displayed higher chondrolytic activity. In RA, modulating factors must come into play because not all synovial fluid sample cells showed high chondrolytic activity and cells from synovial tissue had little or no lytic action on chondrocytes. Chondrolytic activities of cells from all sources, including PBMC from healthy subjects and patients with arthritis and cells isolated from synovial fluid or from the synovial tissue of RA patients, were greatly increased by incubating the cells with TCGF or rIL-2. In contrast, treatment of chondrocytes with interferon-gamma, which enhances major histocompatibility complex gene expression, decreased the susceptibility of chondrocytes to lysis. CONCLUSION: These observations suggest a mechanism for joint damage in which the destruction of chondrocytes by lymphocytes is controlled by cytokines released during the inflammatory process in arthritic diseases.

Arthritis, Rheumatoid↗
PubMed1993

The expression of major histocompatibility antigens on human articular chondrocytes.

Human articular chondrocytes were analyzed for major histocompatibility (MHC) antigens. The cells were obtained by enzymatic digestion of surgical specimens from patients with osteoarthrosis and rheumatoid arthritis having joint replacement. The analyses of Class I and Class II antigens were performed using microcytotoxicity techniques, as with conventional human leukocyte antigen (HLA) typing, and by immunofluorescence on a flow cytometer with monoclonal antibodies. Eighty-five percent of the chondrocytes had strong representation of Class I molecules, and individual specificities for HLA-A, HLA-B, and HLA-C could be detected. Class II antigens generally were not expressed on chondrocytes from noninflammatory states. In osteoarthrosis, some cells expressed HLA-DP and HLA-DQ, whereas in rheumatoid arthritis, there was an increase in the expression of all Class II antigens. Incubation of chondrocytes with gamma-interferon caused the strong induction of HLA-DR and HLA-DP, whereas HLA-DQ expression was largely unaffected. These results have broad implications for tissue transplantation and autoimmune disease.

Antibodies, Monoclonal↗
PubMed1989

Immunological reactivity towards chondrocytes in rat and man: relevance to autoimmune arthritis.

Immunological investigation of articular chondrocytes obtained from rat and man have shown the presence of unique differentiation antigens on the cell surface demonstrated by poly- or monoclonal antibodies in both species, and by the analysis of T cell reactivity in the rat. Both species of chondrocytes express Class I antigens in common with all nucleated mammalian cells and, in man, individual specificities of the MHC A, B, and C locus can be identified using standard histocompatibility testing. Class II antigens are strongly expressed in the rat but are expressed poorly in the human specimens we have analyzed. This finding is at variance with the reports of others and may depend upon the antisera we have used or the diseased state of our patient donors. In the rat, T cell reactivity to chondrocyte antigens is strong and can be demonstrated in both proliferation and cytotoxic assay. Moreover, syngeneic reactivity is present in naive animals, suggesting that rats are not tolerant of their own CSDA. The cross-reactivity found on analysis of cytotoxic killing suggests a sharing of differentiation antigens amongst the different strains of rats and possibly a limited polymorphism for this system. In man, conventional assays for T cell reactivity are hampered by the presence of a soluble inhibitor of lymphocyte proliferation released by chondrocytes and as yet unidentified. The poor representation of Class II antigens on our chondrocyte specimens may further contribute to the difficulty in producing proliferation. On the other hand, early success is reported in finding a significant number of T cell clones isolated from the inflammatory membrane of patients with rheumatoid arthritis, which respond to chondrocyte antigens. The possibility that these antigens may play a role in the pathogenesis of inflammatory arthritis may be more readily explored by exploring these approaches.

Animals↗
PubMed1978

On the mechanism of action of adjuvants.

Evidence is presented that one a way which adjuvants exert their effect is by initiating an enduring increase in the localization of labelled cells in draining lymphoid tissues. Agents not generally considered to be adjuvants (carbon, latex, sheep erythrocytes) but capable of altering lymphocyte recirculation are shown to prevent the induction of tolerance by soluble bovine gamma globulin (BGG). These properties fulfil the criteria for adjuvanticity as defined by Dresser (1968) and link the expression of adjuvanticity to alterations in lymphocyte circulation.

Adjuvants, Immunologic↗
PubMed1976

Toleracne to equine IgG after immunosuppression in patients with multiple sclerosis.

Fourteen patients with multiple sclerosis were given two tolerizing doses of equinine gammaglobulin followed by equine antilymphocyte globulin. Twelve were sufficiently tolerant to have no clinical symptoms of hypersensitivity, no skin reactivity and normal plasma clearance rates. Some tolerance was lost in the following months revealed by immediate wheal and flare skin reactions. No correlation between success in tolerance induction and beneficial effects on the disease process could be established in the short term follow-up period of this pilot study.

Animals↗
PubMed1976

The stimulation of lymphocytes by chondrocytes in mixed cultures.

The stimulation of lymphocytes by allogeneic and syngeneic cells other than lymphocytes has been shown to result in poor or no stimulation. We have been able to demonstrate that lymphocytes and chondrocytes mixed in culture both allogeneically and syngeneically has resulted in siginificant lymphocyte stimulation. The inference from this data suggest the presence of histocompatibility antigen as well as tissue-specific antigen on the surface of chondrocytes.

Animals↗
PubMed1976

The effect of intensive immunosuppression on the in vitro activity of lymphocytes from multiple sclerosis patients.

During a small clinical trial of intensive immunosuppression in multipel sclerosis (MS, 14 patients) the changes of in vitro lymphocyte responses to mitogens were followed. A variable depression of the normal responses to phytohaemagglutinin (PHA), Concanavalin A (Con A) and pokeweed mitogen (PWM) was seen in the patinets during the inital week of treatment with prednisone (150 mg/day tapered to 20 mg/day by day 7), and azathiprine (3 mg/kg daily). They were further depressed during antilymphocyte globulin therapy (ALG 500 mg/day on weekdays, weeks 2-5 of treatment). These responses returned rapidly to the lower normal range after the three weeks of ALG despite the continued prednisone and azathipprine therapy. A complex effect of immunosuppression on lymphocyte subpopulations was suggested by three findings. Firstly, in contrast with the reduction in response to plant mitogens no lowering of the response to allogeneic lymphoid cell line cells (LCL) was seen during the first week of treatment. Secondly, some patinets, particularly those expressing the HLA-7 antigen, had a low pre-treatment response to LCL which showed an improvement during treatment and which was maintained through the first week of ALG treatment. Thirdly, single inviduals sometimes showed different degrees of suppression of different responses during and after ALG treatment. Occasionally, responses showed some recovery even during the ALG treatment, suggesting that higher ALG doses were required in these patients. The results suggest that the action of immunosuppressive drugs on lymphocyte activity differs between individuals due to the heterogeneity of the lymphocyte subpopulations present.

Antilymphocyte Serum↗
PubMed1975

Study of lymphoid cells from inflamed synovial membranes.

Synovectomy specimens from patients with rheumatoid arthritis were cultured and after 24 hours the nonadherent cells were removed. These were found to include cells with the morphological characteristics of lymphocytes. Using the sheep-cell rosetting test, up to 94% of these cells were found to be T cells, and while T cells could be found in all the supernatant cell populations studied, not all made a mitogen response. None or only a very small number of B cells were found by staining for surface immunoglobulin. The possible roles which T lymphocytes might play in chronic inflammation in the rheumatoid synovium are discussed in relation to experimental work, and factors which attract T cells into areas of nonspecific inflammation are similarly considered in the light of animal experiments.

Arthritis, Rheumatoid↗
PubMed1975

Intensive immunosuppression in patients with disseminated sclerosis. III. Lymphocyte response in vitro.

Lymphocytes from fifteen multiple sclerosis patients gave responses to phytohaemagglutinin (PHA), conconavalin A (con A) and pokeweed mitogen (PWM) which were in the normal range. However, the responses of lymphocytes to stimulation by an allogeneic lymphoid cell line (LCL) were significantly lower in HLA-7-positive than in HLA-7-negative patients (a distinction not found in control groups). Depression of con A, PHA and PWM responses were observed during intensive immunosuppression. Responses to LCL were unaltered or increased during initial azathioprine and prednisone treatment. The depression of this response following antilymphocyte globulin (ALG) treatment was delayed in the HLA-7-positive patients. One week after the end of ALG treatment, most PHA, con A and PWM responses had returned to low normal values. Reduction of azathioprine and prednisone treatment at the end of 1 year resulted in a sharp rise in PHA and con A responses in some patients. Relapses in patients were frequently associated with low responses to LCL cells.

Antilymphocyte Serum↗
PubMed1975

Intensive immunosuppression in patients with disseminated sclerosis. II. Tolerance to equine IgG and effect on immunoglobulin and complement levels.

Fourteen patients with multiple sclerosis were given two tolerizing doses of equine gamma-globulin before treatment with anti-lymphocyte globulin. Twelve patients had no clinical symptoms of hypersensitivity and most of them had no detectable antibody to the equine globulin until several months later. Even then, antibody could only be shown by immediate type skin reactions but not by any in vitro assay. We conclude that a state of partial tolerance was established in these patients for the period of treatment but that later they may develop traces of hypersensitivity.

Animals↗