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Biomedical subjects

M Ziff

Publications and source records attributed to M Ziff.

At least 55 records · Page 3Linked to original sources
PubMed1986

Anti-HLA-B27 antibodies in sera from patients with gram-negative bacterial infections.

Several forms of seronegative polyarthritis are strongly associated with HLA-B27, and a number of microorganisms have been implicated in the etiology of these diseases. To explain the association between HLA-B27 and arthritis initiated by infection with these organisms, it has been proposed that there is immunologic cross-reactivity between the B27 molecule and 1 or more microbial antigens, and that this cross-reactivity leads to tolerance to such infection and/or to the production of anti-HLA-B27 cross-reactive antibodies. Such cross-reactive antibodies were detected in the sera of only 2 of 63 patients recently infected with Shigella flexneri, Campylobacter jejuni, or Yersinia enterocolitica who had highly significant antibody levels against the infecting bacterial species. Most striking was the absence of anti-HLA-B27 antibody in the serum of 16 of 17 patients who developed reactive arthritis following Yersinia infection.

Antibodies↗
PubMed1986

Interleukin-1 lymphocyte chemotactic activity in rheumatoid arthritis synovial fluid.

We examined the role of interleukin-1 (IL-1) in the chemotactic activity of rheumatoid arthritis (RA) synovial fluid (SF). Crude RA SF was found to be chemotactic for B cells and T cells. After AcA 54 gel filtration, the principal peaks of chemotactic activity were found in the 5-kd, 16-kd, and 60-kd fractions. The majority of the chemotactic activity for both the B cells (74-85%) and the T cells (69-78%) was removed from these fractions by treatment with anti-IL-1 antibody. However, in crude SF, approximately 60% of the chemotactic activity for B cells and 40% of that for T cells was removed, indicating the presence of additional chemotactic factors in RA SF. IL-1 activity, measured by the thymocyte proliferation assay, was demonstrated in RA SF AcA 54 Ultrogel fractions after separation from inhibitors of thymocyte proliferation that are present in crude SF. On chromatofocusing of the 16-kd fraction, the principal peaks of both thymocyte proliferation activity and chemotactic activity were present in the same fractions with pI values of 6.8, 5.7, and 5.2, which are characteristic of IL-1. The demonstration of IL-1-associated chemotactic activity in RA SF may reflect the presence in the RA synovial membrane (including both the lining layer and the subsynovial layer) of activated macrophages, interstitial histiocytic cells, and other IL-1-producing cells, such as endothelial cells. These findings suggest that such cells may attract lymphocytes to their environment by secretion of IL-1.

Arthritis, Rheumatoid↗
PubMed1986

Electron microscopic study of HLA-DR and monocyte/macrophage staining cells in the rheumatoid synovial membrane.

We examined synovial membrane samples from 6 rheumatoid arthritis (RA) and 3 osteoarthritis patients and from 1 normal subject, by an immunoelectron microscopic technique using anti-HLA-DR (anti-Ia) and anti-monocyte/macrophage (63D3) monoclonal antibodies. In the lining layer, the type A macrophage-like cells were strongly DR+ and 63D3+, whereas the type B fibroblast-like cells were almost completely negative. Lymphocyte-rich areas (containing more than 90% densely packed lymphocytes) showed weak and patchy DR staining of the lymphocytes. In these areas, 3-5% of the cells were macrophage-like cells which were 63D3-, a type of staining compatible with that of the interdigitating cell (IDC). In the plasma cell-containing (transitional) areas, many strongly DR+ macrophage-like cells were observed in close contact with lymphocytes and plasma cells. Ten to twenty percent of these cells were 63D3-, which suggests that they were IDC. Cells with the structural appearance of IDC were most frequently seen in those transitional areas which contained elevated concentrations (50-70%) of lymphocytes. In uninfiltrated interstitial areas, approximately 50% of the cells stained strongly with both anti-DR and 63D3 antibody, indicating that they were cells of monocyte/macrophage lineage, presumably histiocytes. This investigation has demonstrated the presence of the DR antigen in the RA synovial membrane on 1) phagocytic cells of the lining area, 2) lymphocytes and small numbers of IDC-like cells in dense, lymphocyte-rich areas, 3) large numbers of macrophage-like cells, of which some had the morphologic appearance of IDC, in transitional or plasma cell-containing areas, and 4) histiocytic cells in uninfiltrated interstitial areas. The observation of large numbers of DR+ macrophages and IDC-like cells in close contact with lymphocytes and plasma cells in the RA synovial membrane emphasizes their role in an active immune response. The observation of substantial numbers of potentially immunocompetent, DR+ histiocytic cells in uninfiltrated regions of the synovial membrane suggests that such cells may play a role in the progression of the synovial inflammatory reaction.

Arthritis, Rheumatoid↗
PubMed1986

Binding of normal human mononuclear cells to blood vessels in rheumatoid arthritis synovial membrane.

We examined the binding of mononuclear cells to blood vessels in the rheumatoid arthritis synovial membrane. Two of 4 synovia that had lymphocyte-rich areas contained blood vessels adhesive for mononuclear cells. These reactive vessels showed striking similarities to high endothelial venules of the paracortical region of lymph node, where normal lymphocyte-endothelial cell adhesion and lymphocyte emigration into tissue occurs.

Animals↗
PubMed1986

Superoxide anion release by human endothelial cells: synergism between a phorbol ester and a calcium ionophore.

In order to study the signal transduction mechanism of human endothelial cells (EC), the regulation of superoxide anion (O2-)release in EC has been investigated using the calcium ionophore A23187 and phorbol myristate acetate (PMA), a potential activator of the Ca2+ activated, phospholipid-dependent protein kinase, designated "protein kinase C." PMA enhanced O2- release from EC, and this enhancement occurred regardless of the presence or absence of extracellular Ca2+. A similar increase was produced by A23187; omission of extracellular Ca2+ prevented this increase. Simultaneous stimulation with PMA and A23187 produced a large increase in O2- release at submaximal concentrations of these agents, which, when added separately, caused minimal effects. These findings indicate that the activation of protein kinase C and mobilization of Ca2+ evoked by PMA and A23187 respectively are synergistically effective for eliciting a full physiological response of EC in the generation and release of O2-.

Anions↗
PubMed1986

Electron microscopic study of rheumatoid synovial vasculature. Intimate relationship between tall endothelium and lymphoid aggregation.

The relationship between (a) "tallness" and (b) cross-sectional area of the endothelial cells (EC) of postcapillary venules (PCV) and capillaries and the cellular composition of adjacent perivascular mononuclear cell infiltrates in rheumatoid (RA) synovial membrane has been examined by electron microscopy. "Tallness" of the EC was measured as the ratio of the height of the EC to its base (H/B). H/B showed a strong positive correlation with the number and percent of perivascular lymphocytes, i.e., the denser the lymphoid aggregation, the taller the EC. In contrast, H/B showed negative correlations with percent perivascular plasma cells, macrophages, and fibroblast(cyte)s. No such correlations were observed with pericapillary infiltrates. A computer-based morphometric technique yielded similar relationships between the cross-sectional area of the EC and the composition of the perivascular infiltrates. These results indicate that the EC of PCV in lymphocyte-rich areas of synovium tend to be tall and to occupy an increased fraction of the cross-sectional area of the vessel. In contrast, in areas rich in macrophages and plasma cells, EC tend to be flat and to occupy a smaller fraction of the cross-sectional area. PCV in uninfiltrated interstitial areas and in normal synovium had flat EC, and capillaries had flat EC regardless of the character of the surrounding infiltrate. Finally, PCV in lymphocyte-rich areas closely resembled those of tonsil in appearance. Our findings indicate that the PCV of the RA synovial membrane from which lymphocytes emigrate to form perivascular lymphoid aggregates resemble those of lymphoid tissue. They suggest that chronic inflammatory tissue and normal lymphoid tissue share mechanisms of lymphocyte emigration.

Arthritis, Rheumatoid↗
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↗
PubMed1986

Effects of bacterial lipopolysaccharide on the binding of lymphocytes to endothelial cell monolayers.

Preincubation of human umbilical vein endothelial cell (EC) monolayers with 1 ng to 10 micrograms/ml lipopolysaccharide (LPS) increased the binding of T lymphocytes to EC. The effect was maximal at LPS concentrations of 0.1 to 10 micrograms/ml, and occurred with LPS derived from Escherichia coli (serotypes 0111:B4 and 0127:B8), Shigella flexneri (serotype 2a), Serratia marcescens (serotype 0:3), and Yersinia entercolitica (serotype 0:3). The increased binding appeared to be mediated primarily through an action on EC; preincubation of T cells rather than EC with LPS did not lead to enhanced binding. The onset of enhanced binding was very rapid, being observed after 2 to 3 min of preincubation and becoming maximal after 1 hr. EC were unresponsive to LPS after fixation with 2% paraformaldehyde-L-lysine-periodate and also when the LPS was incubated with EC at 4 degrees C. Enhanced binding was seen with lipid A and with LPS from Salmonella minnesota Re 595 (mainly lipid A) and was abolished by conjugation with polymyxin B. The observed increase in the binding of lymphocytes to EC exposed to LPS suggests that the lymphocytopenia induced by endotoxemia may result from augmentation of the adherence of lymphocytes to altered endothelium.

Binding Sites↗
PubMed1985

Effects of long-term procainamide therapy on immunoglobulin synthesis.

Procainamide is a potent inducer of autoantibodies. In order to evaluate the immunologic effects of this drug in vivo, 23 cardiac disease patients who had received procainamide for at least 6 months and an equal number of matched cardiac disease control subjects were studied, and percentage of circulating T cell subsets, concanavalin A-induced suppressor cell activity, and pokeweed mitogen--stimulated generation of immunoglobulin-secreting cells was quantitated. There was no significant difference between patient and control groups in the percentage of T cell subsets defined by OKT4 and OKT8 monoclonal antibodies or in concanavalin A-induced suppressor cell activity. The numbers of pokeweed mitogen--induced immunoglobulin-secreting cells were markedly decreased in the patient group, as measured by the protein A-augmented reverse hemolytic plaque assay (3,000 +/- 644, mean +/- SEM in patients versus 10,826 +/- 1,529, mean +/- SEM in control subjects, P less than 0.005). Removal of the adherent cell fraction did not improve the hyporesponsiveness. When B and T cell fractions of 6 patients were mixed with normal T and B cell fractions, all of the patients demonstrated diminished B cell responses, and one-half also had diminished T cell responses. Addition of patient adherent cells to a co-culture of normal B cells with deficient patient T cells restored plaque formation to normal levels, suggesting that the T cell defect was correctable by a macrophage-derived factor. The data obtained suggest that procainamide exerts an immuno-suppressive action on both B and T cell function in patients receiving this drug.

Aged↗
PubMed1985

IgG and IgM rheumatoid factor synthesis in rheumatoid synovial membrane cell cultures.

The detection of rheumatoid factors (RFs) in synovial membranes and fluids of patients with rheumatoid arthritis (RA) has suggested that local production of these antiimmunoglobulin autoantibodies may have a role in the pathogenesis of synovitis. To quantitate RF synthesis in the rheumatoid synovial membrane, 12 synovial specimens were obtained from patients with seropositive RA, 5 from patients with seronegative RA, and 6 from patients with other arthritides. Single cell suspensions were cultured, and supernatants were analyzed for IgG, IgM, IgG-RF, and IgM-RF by solid-phase radioimmunoassays. IgM-RF was detected in all of the 12 seropositive culture supernatants, and IgG-RF was detected in 8 of the 12. Addition of cycloheximide to the cultures resulted in a greater than or equal to 40% decreased in the amount of IgM-RF. A similar decrease in IgG-RF occurred in the 4 cultures in which the largest amounts of IgG-RF were detected. IgM-RF synthesis represented 7.3 +/- 0.7% (mean +/- SEM) of the total IgM produced, and IgG-RF represented 2.6 +/- 1.1% (mean +/- SEM) of the IgG synthesized in those cultures with detectable IgG-RF. Cultures of synovial membrane cells (SMC) from seronegative RA patients or patients with other arthritides did not contain detectable amounts of IgM-RF or IgG-RF. Selective synthesis of RF by seropositive synovium was suggested by the observation that the fractions of synthesized IgM with RF activity were greater in the SMC supernatants than in paired sera in all cases, and the fractions of IgG with RF activity were greater in the SMC supernatants of 3 of the 4 cases in which substantial amounts of IgG-RF were produced. Comparison of the percentages of newly synthesized IgM with RF activity in paired cultures of SMC and peripheral blood mononuclear cells similarly indicated selective synthesis of IgM-RF by the synovium. These results demonstrate active and selective synthesis of both IgG-RF and IgM-RF by seropositive SMC. However, RFs account for only a minor fraction of the total Ig produced.

Arthritis, Rheumatoid↗
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↗
PubMed1984

Human IgG aggregates induce selective stimulation of IgM rheumatoid factor synthesis by rheumatoid blood mononuclear cells.

Peripheral blood mononuclear cells (PBM) from patients with active rheumatoid arthritis (RA) contain precursor B lymphocytes specific for IgM rheumatoid factor (IgM-RF) synthesis. In this study, human IgG aggregates (HaIgG) were used to stimulate monocyte-depleted PBM from 46 patients with RA and 21 normal controls. The cells were incubated with HaIgG and pokeweed mitogen for 72 hours, washed, and then cultured in microwells for an additional 11 days. HaIgG induced an increase in IgM-RF synthesis by RA cells with optimum response at 0.1 microgram/ml (P less than 0.001). Total IgM synthesis remained unchanged. In contrast, HaIgG did not stimulate IgM-RF production by normal cells. Specificity of the IgM-RF response was shown by the concomitantly increased IgM-RF/IgM ratios, while IgM anti-trinitrophenyl antibodies did not increase. Aggregation of the IgG was required for it to be an effective stimulus. The findings suggest that circulating immune complexes in RA patients may provide the stimulus for sustained production of IgM-RF in vivo.

Arthritis, Rheumatoid↗
PubMed1984

Lymphocyte chemotactic activity of human interleukin 1.

In the cellular immune response, there is an accumulation of mainly nonantigen-specific mononuclear cells that presumably is dependent on the local secretion of chemotactic factors. In view of the presence of large numbers of macrophages early in the delayed hypersensitivity response, the possible role of these cells in the chemotaxis of lymphocytes was investigated by studying the chemotactic activity of purified human interleukin 1 (IL 1) on T and B cells. Chemotactic activity for T and B cells was observed, the effect on B cells being greater than on T cells. At low concentrations (less than 1 U/ml), IL 1 had predominantly chemotactic activity for B cells and chemokinetic activity for T cells. At high concentrations (10 to 20 U/ml), IL 1 had pure chemotactic activity for both cell types. A relationship was found between levels of migration of T and B cells and mouse thymocyte proliferation induced by purified IL 1 and by lipopolysaccharide-stimulated monocyte supernatants. The principal peaks of both activities were found in 16,000 to 18,000 m.w. fractions. In additional studies, the chemotactic response to IL 1 was inhibited by preincubation of T and B cells with IL 1 or stimulated monocyte supernatant, demonstrating the role of binding of IL 1 in the chemotactic response.

Animals↗
PubMed1984

Spontaneous synthesis of IgM rheumatoid factor by blood mononuclear cells from patients with rheumatoid arthritis: effect of treatment with gold salts or D-penicillamine.

Spontaneous IgM rheumatoid factor (sIgM RF) synthesis in vitro by blood mononuclear cells (BMC) from rheumatoid arthritis (RA) patients has been previously shown to correlate with disease activity. Ten active RA patients were studied prior to and after the start of therapy with gold salts or penicillamine. sIgM RF decreased steadily over the period of study and was strongly correlated with mean joint count (r =0.94, p less than 0.001), erythrocyte sedimentation rate (r = 0.90, p = 0.014), and duration of morning stiffness (r = 0.78, p = 0.068). In 9 patients with significant decreases, mean sIgM RF was 8% of the initial value after 9 weeks of treatment. The decrease in sIgM RF was relatively specific since the ratio of sIgM RF to total spontaneous IgM synthesis (sIgM) declined during the treatment period. The results indicate that changes in sIgM RF constitute a sensitive indicator of disease activity and response to therapy in RA.

Adult↗
PubMed1983

Immunoelectron microscopic study of the distribution of T cell subsets in rheumatoid synovium.

The perivascular mononuclear cell collections of the rheumatoid synovium were examined both at the light and electron microscopic level by an immunoperoxidase staining technique using monoclonal antibodies directed against T cell subsets. These accumulations were variable in composition and size, not only in specimens from different patients but in the same specimen. Some areas (lymphocyte-rich areas) contained mainly small lymphocytes in clusters and others (transitional areas) contained blast cells, macrophages, and plasma cells in addition to lymphocytes. The percentage of T4 staining cells correlated positively and the percentage of T8 staining cells correlated negatively with the percentage of lymphocytes in any given area. In contrast, the percentage of T4 cells correlated negatively and the percentage of T8 cells correlated positively with the percentage of macrophage-like cells in these areas. Approximately 80% of the total lymphocytes, both in the lymphocyte-rich areas and transitional areas, were T lymphocytes (OKT3 staining). In lymphocyte-rich areas, helper/inducer T lymphocytes (OKT4 staining) were predominent over suppressor/cytotoxic lymphocytes (OKT8 staining), and in such areas the mean T4:T8 ratio was 2.9. Macrophage-like cells were seen only in small numbers in this type of area. In the transitional areas, suppressor/cytotoxic lymphocytes (OKT8 staining) predominated over helper/inducer lymphocytes (OKT4 staining). In such areas the mean T4:T8 ratio was 0.8. The T8 cells in the transitional areas tended to be large in size and often had a blastic appearance, and the abundant macrophage-like cells infiltrating these areas were frequently in close contact with T8 lymphocytes. These findings indicate that the ratio of T4 to T8 lymphocytes in rheumatoid synovium varies with the type of area examined. In lymphocyte-rich collections, made up largely of quiescent small lymphocytes, T4 cells are predominant. In areas of apparent immunological reactivity, T8 cells are predominant. It is suggested that T8 cells proliferate in immunologically active areas of the synovium as a result of local stimulation of a T cell-mediated immune response.

Animals↗