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D O Haskard

Publications and source records attributed to D O Haskard.

At least 145 records · Page 8Linked to original sources
PubMed1989

T-cell adhesion to endothelial cells in systemic lupus erythematosis.

To investigate the pathogenesis of the lymphopenia in systemic lupus erythematosus (SLE), we examined the adhesion of these T cells to endothelial cells (EC). T cells from 10 lymphopenic patients with active SLE showed significantly reduced adhesion to unstimulated and interleukin-1 (IL-1)-stimulated human EC monolayers when compared with T cells from age, sex, and race matched normal control individuals. Percentage decreases from control values (delta) in the measured percentage of T cells adherent to unstimulated and IL-1-stimulated EC were 36.4% (P less than 0.025) and 34.0% (P less than 0.005), respectively. Percentage adhesion of phorbol ester-treated T cells of SLE patients was also reduced compared with similarly treated T cells of control patients; the decrease was 22.8% (P less than 0.025). No abnormality was detected in the adhesion to EC of T cells from patients with asthma who were receiving corticosteroids, suggesting that the abnormality in the SLE T cells was related to the disease process itself. The reduced adhesion of the circulating T cells may be a consequence of the withdrawal from the blood of more strongly adherent cells in the course of the inflammatory response. The loss of strongly adherent lymphocytes may contribute to the lymphopenia of SLE.

Adult↗
PubMed1989

Mechanisms of lymphocyte adhesion to endothelial cells: studies using a LFA-1-deficient cell line.

In order to investigate the role of lymphocyte function-associated antigen 1 (LFA-1) in lymphocyte adhesion to endothelial cells (EC), we have studied the adhesion of a LFA-1-deficient lymphoblastoid cell line, ICH-KM, which has < 10% of the cell surface LFA-1 expressed on a normal lymphoblastoid cell line, ICH-BJ. The adhesion of ICH-KM cells to unstimulated EC was 49.9 +/- 8.6% (mean +/- SD) that of ICH-BJ cells. Moreover, phorbol ester-stimulated ICH-KM cells showed a considerably weaker increase in adhesion to unstimulated EC compared with ICH-BJ cells (mean +/- SD increase in percentage adhesion, 3.8 +/- 2.3 compared with 18.5 +/- 8.0; P<0.025). In contrast, there was no significant difference between the enhanced adhesion of ICH-KM cells and ICH-BJ cells to interleukin-1 (IL-1)-stimulated EC. Thus ICH-KM cells showed a 22.7 +/- 11.0 (mean +/- SD) increase in percentage adhesion to IL-1-stimulated EC compared with the 24.8 +/- 8.5 increase in percentage adhesion of ICH-BJ cells. Anti-LFA-1 monoclonal antibodies had no effect on the enhanced adhesion of ICH-KM and ICH-BJ cells to IL-1-stimulated EC but abolished the differences in adhesion between the two cell lines. The study therefore indicates that although a major part of unstimulated and phorbol ester-stimulated lymphocyte-EC adhesion is dependent upon LFA-1, the enhanced adhesion due to stimulation of EC with IL-1 is not dependent upon this molecule. The data therefore supports the existence of cytokine-inducible LFA-1-independent adhesion molecules for lymphocytes on EC.

Antibodies, Monoclonal↗
PubMed1988

Separation and characterization of human T lymphocytes with varying adhesiveness for endothelial cells.

Previous studies in this laboratory have demonstrated that the adhesion of T lymphocytes to endothelial cell (EC) monolayers in vitro can be increased by preincubation of the EC with interferon-gamma, interleukin 1 (IL-1), tumor necrosis factor-alpha (TNF), or lipopolysaccharide (LPS), or by stimulation of the T cells with phorbol esters. In this report, we have demonstrated that three subpopulations of human peripheral blood T cells can be identified on the basis of their abilities to bind to EC: (1) a strongly binding group which binds to unstimulated EC; (2) an intermediately binding subset which adheres to EC only if these cells have been stimulated with IL-1, TNF, or LPS; and (3) a weakly binding subpopulation which adheres poorly to either unstimulated or stimulated EC. The more adhesive subgroups had larger cellular volumes than the less adhesive cells, were relatively enriched in cells bearing the OKM1 surface marker, and expressed relatively greater amounts of the lymphocyte-function-associated-1 molecule. Stimulation of the EC to bind increased numbers of T cells by IL-1, TNF, and LPS appeared to be mediated by the expression of a common adhesion molecule on the EC.

Antigens, Differentiation↗
PubMed1987

Human dermal microvascular endothelial cells behave like umbilical vein endothelial cells in T-cell adhesion studies.

The adhesion of T lymphocytes to human dermal microvascular endothelial cells (DMVEC) in vitro has been tested after stimulation of the DMVEC with gamma interferon (IFN-gamma), interleukin 1 (IL-1), or a bacterial lipopolysaccharide (LPS). These agents enhanced T-cell adhesion in a manner similar to that previously observed with human umbilical vein endothelial cells (UVEC). Moreover, phorbol ester stimulation of T cells enhanced T-cell adhesion to both DMVEC and UVEC. Unstimulated and phorbol ester-enhanced T-cell adhesion to both DMVEC and UVEC was strongly inhibited by monoclonal antibody (Mab) 60.3 against the surface membrane CDw18 glycoprotein complex. In contrast, Mab 60.3 had a much weaker inhibitory effect on the binding enhancement due to IL-1, LPS, or IFN-gamma, suggesting that these agents may enhance adhesion by a mechanism at least partially independent of CDw18. These observations suggest that DMVEC behave in a similar fashion to UVEC in T-cell adhesion studies, and support previous conclusions that modulation of lymphocyte endothelial cell adhesion by cytokines, bacterial products, and phorbol esters may be relevant to lymphocyte adhesion and migration in vivo.

Antibodies, Monoclonal↗
PubMed1987

Factors associated with joint mobility in an adolescent population.

Fixed torque devices were used to measure joint mobility at three sites in 364 adolescents including 39 families with at least two siblings. Increasing age and being male were associated with reduced laxity, and a strong effect of family was observed in the 39 sibling sets studies. The population included 47 Asians whose mobility was similar to that of the non-Asians, though the female/male difference was apparently greater in the former group. None of the above conclusions apply to index finger hyperextension, and it is apparent that genetic and constitutional factors only affect mobility at some sites. Such observations could lead to a review of current scoring systems for clinical hypermobility.

Adolescent↗
PubMed1986

Interleukin 1 increases the binding of human B and T lymphocytes to endothelial cell monolayers.

Lymphocyte binding to specialized high-endothelial venules (HEV) in lymph nodes and Peyer's patches is the first step in normal lymphocyte emigration and recirculation. The development and maintenance of HEV in these lymphoid organs are thought to be immunologically controlled. Because postcapillary venules in chronic inflammatory tissue often resemble the HEV of lymphoid tissue and may also be a site of lymphocyte emigration, examination of the effects of immunologic and inflammatory mediators on endothelial cells (EC) may provide important information about the physiology of both normal lymphocyte recirculation and chronic inflammation. It is reported here that treatment of human umbilical vein EC monolayers in vitro with affinity-purified human interleukin 1 (IL 1) markedly enhances the binding of both B and T lymphocytes. Increased binding was observed within 1 h of treatment of EC with as little as 0.04 U/ml IL 1. This effect of IL 1 was EC-specific, because pretreatment of T cells or human skin fibroblasts with IL 1 did not increase the binding of lymphocytes. Stimulation of binding required active EC metabolism because incubation of EC with IL 1 at 4 degrees C, or prior fixation of EC, prevented enhanced binding. The action of IL 1 was not associated with EC damage. The secretion of IL 1 by macrophages and perhaps other cells in inflammatory lesions may exert a positive feedback signal on EC to enhance further emigration of lymphocytes into the inflammatory focus.

Antigens, Surface↗
PubMed1985

Human gamma interferon increases the binding of T lymphocytes to endothelial cells.

Binding of lymphocytes to human umbilical vein endothelial cells (EC) was quantitated by measuring adhesion of 51Cr labelled lymphocytes to endothelial cell monolayers and rosette formation between lymphocytes and EC in suspension. Mitogen stimulated human peripheral blood mononuclear cell culture supernatants and mixed lymphocyte reaction supernatants enhanced the binding of T lymphocytes to EC monolayers or suspensions preincubated with such supernatants. The active component of these supernatants appeared to be gamma interferon (IFN-gamma) since culture supernatants lost activity after heating at 56 degrees C for 60 min, exposure to pH 2.0 or treatment with anti-IFN-gamma. In addition, purified IFN-gamma increased the binding of T lymphocytes to EC (T-EC). This occurred in a concentration dependent manner when IFN-gamma was preincubated with EC but not with lymphocytes. While the optimum concentration of IFN-gamma was 250 u/ml, a significant enhancement was seen with as little as 10 u/ml. These findings suggest that IFN-gamma may play a part in the emigration of lymphocytes to perivascular chronic inflammatory sites by augmenting the adhesion of lymphocytes to the endothelium of small blood vessels.

Cell Adhesion↗
PubMed1985

Human monoclonal antibodies from patients with rheumatoid arthritis: cross reactions against cellular constituents.

Hybridization of peripheral blood lymphocytes from patients with rheumatoid arthritis has yielded 14 monoclonal antibodies which react with cultured human epithelial cells. Immunofluorescence staining identifies at last five different types of antibody. Solid phase immunosorbent assays show a variety of cross-reaction patterns with nucleic acids, proteoglycan, cardiolipin and plastic, confirming that the various antibodies react with epitopes which are at least slightly different. These conclusions are confirmed by SDS gel electrophoresis and immunoblotting on epithelial cell extracts. Similar antibodies previously found in association with lupus-like disease have been thought to be representative of the high antinuclear antibody response characteristic of lupus. Our data are more consistent with the hypothesis that all or many of these antibodies are part of the normal inflammatory response.

Antibodies, Monoclonal↗
PubMed1984

The production of human monoclonal autoantibodies from patients with rheumatoid arthritis by the EBV-hybridoma technique.

Rheumatoid lymphocytes tend to transform 'spontaneously' in vitro because of prior infection with Epstein Barr virus (EBV). They are particularly difficult to use in experiments involving cell hybridisation, because in the conventional half-HAT system unfused transformed cells may be confused with hybrids. We describe how the HAT-sensitive, ouabain-resistant human B lymphoblastoid cell line KR4, originally developed to 'rescue' EBV induced B cell clones, can be fused successfully with peripheral blood lymphocytes from patients with rheumatoid arthritis to produce unequivocal hybrids.

Antibodies, Monoclonal↗
PubMed1984

Methods of assessing the synovial fluid cell count.

We have compared a rapid side-room testing strip and an automated cell counter with the conventional haemocytometer counting chamber as methods for assessing the synovial fluid cell count. The testing strip was shown to be very sensitive in detecting esterases derived from granulocytes, but to the experienced clinician it offered little clinical advantage over naked-eye judgement. The automated counter provides a fast and reliable alternative to the haemocytometer and in situations where an accurate cell count is required it could replace the haemocytometer.

Humans↗
PubMed1983

Spontaneous rupture of the spleen in rheumatoid arthritis.

Two patients with rheumatoid arthritis without splenomegaly or Felty's syndrome developed spontaneous rupture of the spleen. The histological appearance was consistent with involvement of the splenic capsule by the rheumatoid process, and this may have predisposed to splenic rupture.

Aged↗