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Biomedical subjects

R H Weisbart

Publications and source records attributed to R H Weisbart.

At least 37 records · Page 2Linked to original sources
PubMed1987

Human monoclonal IgG rheumatoid factor has structural homology with bacterial Fc receptor proteins.

A cloned lymphoblast cell line, hRF-1, that secreted human monoclonal IgG4 rheumatoid factor autoantibody was produced by Epstein-Barr virus transformation of lymphocytes from rheumatoid arthritis synovium. The binding of hRF-1 rheumatoid factor to IgG globulins of different mammalian species was similar to the binding specificity of Staphylococcus aureus protein A (SpA) and to antibodies found in the sera from patients with rheumatoid arthritis. hRF-1 also had the same binding pattern to human IgG subclasses as SpA. Direct competition was observed between SpA and hRF-1 in binding IgG Fc. These results provide evidence for structural homology between a bacterial Fc receptor protein (SpA) and the monoclonal IgG rheumatoid factor.

Antibodies, Anti-Idiotypic↗
PubMed1987

Human GM-CSF primes neutrophils for enhanced oxidative metabolism in response to the major physiological chemoattractants.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a T cell-derived lymphokine which induces hematopoietic precursor cells to proliferate in vitro and differentiate to neutrophils and macrophages. GM-CSF also inhibits the motility of mature neutrophils (NIF-T activity), and primes neutrophils to enhance oxidative metabolism in response to the bacterial chemoattractant, N-formyl-methionyl-leucyl-phenylalanine (f-MLP). The present study was designed to determine whether this lymphokine also enhances neutrophil oxidative metabolism in response to the other major physiological chemoattractants which include complement-derived C5a, and the 5-lipoxygenation product of arachidonic acid, leukotriene B4 (LTB4). Superoxide anion production was measured as superoxide dismutase-inhibitable cytochrome C reduction. Purified biosynthetic GM-CSF enhanced superoxide anion production by neutrophils in response to f-MLP, C5a desArg, and LTB4. In contrast to several other factors which prime neutrophils, GM-CSF did not prime for an enhanced oxidative response to phorbol myristate acetate (PMA). These results suggest that GM-CSF may be an endogenous regulator of neutrophil inflammatory responses induced by the major physiological chemoattractants.

Chemotactic Factors↗
PubMed1986

Biosynthetic human GM-CSF modulates the number and affinity of neutrophil f-Met-Leu-Phe receptors.

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) modulates the function of mature neutrophils by priming for enhanced chemotaxis and oxidative metabolism in response to N-formyl-methionyl-leucyl-phenylalanine (f-Met-Leu-Phe). Our studies establish a relationship between f-Met-Leu-Phe receptor number and affinity and neutrophil chemotaxis and oxidative metabolism. A brief (5- to 15-min) exposure to physiologic concentrations of GM-CSF (10 pM to 100 pM) enhances f-Met-Leu-Phe-induced neutrophil chemotaxis by 85%, correlating with a rapid threefold increase (46,000/cell to 150,000/cell) in high-affinity neutrophil f-Met-Leu-Phe receptors. More prolonged incubation (1 to 2 hr) of neutrophils with GM-CSF is accompanied by a change to low-affinity f-Met-Leu-Phe receptors (Kd = 29 nM to Kd = 99 nM) concomitant with priming for enhanced neutrophil oxidative metabolism. Moreover, enhanced chemotactic responses to f-Met-Leu-Phe are no longer evident after more prolonged incubation of neutrophils with GM-CSF. These results show that a single lymphokine (GM-CSF) induces sequential changes in neutrophil f-Met-Leu-Phe receptor number and affinity that may enhance different physiologic responses.

Chemotaxis, Leukocyte↗
PubMed1986

Wegener's granulomatosis in the elderly.

Wegener's granulomatosis is a systemic necrotizing granulomatous vasculitis in which the average age at onset is in the forties. The disease has an excellent response to treatment with cyclophosphamide. We proposed that the tendency to accept multisystem disease in elderly patients (greater than or equal to 60 years old) and a reluctance to administer aggressive therapy would be reflected in the diagnosis and treatment of Wegener's granulomatosis in the elderly, and that as a consequence, the delay in diagnosis and implementation of therapy could result in a needlessly higher morbidity and mortality rate for this population of patients.

Age Factors↗
PubMed1986

High-affinity binding of granulocyte-macrophage colony-stimulating factor to normal and leukemic human myeloid cells.

Purified natural and biosynthetic (recombinant) human granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulate colony formation by myeloid progenitor cells and enhance the function of mature neutrophils. Both of these actions occur at concentrations between 1 and 100 pM, with half-maximal stimulation at 10-20 pM. We have examined specific binding of 125I-labeled GM-CSF to responsive target cells in this range of concentrations. The results show a low number (50-250) of high-affinity (15-30 pM) binding sites on GM-CSF-responsive leukemic cells (KG-1, HL-60), as well as on peripheral blood neutrophils from normal donors. This high-affinity binding component was absent from unresponsive cell lines (KG-1a, K562). These results suggest that this binding site mediates the biological activities of GM-CSF on both proliferation and function of myeloid cells.

Cell Line↗
PubMed1986

Antiguanosine antibodies: a new marker for procainamide-induced systemic lupus erythematosus.

Antinuclear antibodies are present in most patients receiving procainamide. To ascertain whether IgG antiguanosine antibodies are associated with the development of the symptoms of systemic lupus erythematosus, we compared the levels of these antibodies in the sera of 65 patients receiving procainamide: 18 with procainamide-induced symptoms and 47 asymptomatic patients. Antinuclear antibodies measured by immunofluorescence were present in the 18 patients with drug-induced symptoms but also in 24 asymptomatic patients. Similarly, elevated serum levels of antibodies to single-stranded DNA were found in 15 patients with symptoms and in 20 asymptomatic patients. In contrast, levels of IgG antiguanosine antibodies were elevated in 15 patients with drug-induced symptoms, but in only 3 asymptomatic patients. Antiguanosine antibodies binding to single-stranded DNA were found primarily in patients with arthritis, pleuritis, and pericarditis. These results suggest a strong association between IgG antiguanosine antibodies and major manifestations of procainamide-induced systemic lupus erythematosus.

Adult↗
PubMed1986

Granulocyte-macrophage colony-stimulating factor enhances phagocytosis of bacteria by human neutrophils.

In order to determine whether human granulocyte-macrophage colony-stimulating factor (GM-CSF) can enhance phagocytosis, neutrophils were combined with Staphylococcus aureus (S aureus), and both the number of bacteria per neutrophil and the percent of neutrophils phagocytizing were assessed in the absence and presence of GM-CSF. Exposure to GM-CSF did not enable neutrophils to ingest unopsonized bacteria. When bacteria were opsonized with serum, both the number of bacteria per neutrophil and the percent of cells phagocytizing were increased by treatment with GM-CSF. Digestion of extracellular organisms by lysostaphin was used to substantiate phagocytosis. These results indicate that another effect of GM-CSF on the mature neutrophil is the enhancement of phagocytosis.

Blood Bactericidal Activity↗
PubMed1985

The fine specificity of IgG antiguanosine antibodies in systemic lupus erythematosus.

The antigen specificity, isotype, and subclass of antinuclear antibodies may be related to their pathogenicity in systemic lupus erythematosus (SLE). Our laboratory found that IgG antibodies that bound the nucleoside, guanosine, occurred frequently in SLE patients. In contrast, sera from healthy subjects contained IgM but not IgG antiguanosine antibodies. The present studies were designed to characterized the fine specificity of IgG antiguanosine antibodies in SLE and compare them with IgM antiguanosine antibodies in normal sera. Serum antinuclear antibodies from six healthy subjects and six SLE patients were isolated by affinity binding to guanosine and measured by an enzyme-linked immunosorbent assay (ELISA). IgM in normal sera, and both IgM and IgG in SLE sera bound guanosine. IgM antiguanosine antibodies in normal sera were polyspecific and bound other nucleosides and 1-methylguanosine but not denatured DNA (ssDNA). In contrast, IgG antiguanosine antibodies from the SLE patients bound guanosine and ssDNA but not other nucleosides or 1-methylguanosine. SLE IgM antiguanosine antibodies had the same fine specificity and bound guanosine and ssDNA but not any of the other nucleosides. These results suggest that SLE IgG and IgM antiguanosine antibodies have fine specificity in contrast to the polyspecific IgM antibodies in normal sera. In addition, subclass analysis indicated that all SLE patients had either IgG1 or IgG3 subclass of antiguanosine antibodies that bind complement. Characterizing the isotype, subclass, and fine antigen specificity of antiguanosine antibodies should assist in evaluating their potential pathogenicity in SLE.

Antibodies, Antinuclear↗
PubMed1984

Purified human granulocyte-macrophage colony-stimulating factor: direct action on neutrophils.

Neutrophil migration inhibition factor from T lymphocytes (NIF-T) is a lymphokine that acts to localize granulocytes. Medium conditioned by the Mo human T-lymphoblast cell line was used to purify NIF-T, a glycoprotein with a molecular weight of 22,000. The NIF-T was found to potently stimulate the growth of granulocyte and macrophage colonies from human bone marrow and colony formation by the KG-1 myeloid leukemia cell line. Thus a human lymphokine (NIF-T) that modulates the activities of mature neutrophilic granulocytes is also a colony-stimulating factor acting on precursors to induce growth and differentiation of new effector cells.

Bone Marrow Cells↗
PubMed1984

Further purification of neutrophil migration inhibition factor from T lymphocytes (NIF-T): evidence that NIF-T and leukocyte inhibitory factor (LIF) are immunologically distinct.

Neutrophil migration inhibition factor from T lymphocytes (NIF-T) purified by antibody affinity chromatography and gel filtration chromatography was radioiodinated and identified as a 26,000-MW protein by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). NIF-T was identified by elution of biological activity from gel fractions and selective adsorption of a radioiodinated mediator by HL60 cells differentiated in the presence of dimethyl sulfoxide (DMSO) to develop receptors for NIF-T. A goat neutralizing antibody for NIF-T neutralized and immunoprecipitated migration inhibition activity in the conditioned medium from Mo T-lymphoblast cells and human peripheral blood lymphocytes (PBL) cultured with concanavalin A (Con A), but not from RPMI 1788 B-lymphoblast cells with leukocyte migration inhibitory factor (LIF) activity. These studies distinguish NIF-T both chemically and immunologically from LIF.

Animals↗
PubMed1984

Effect of corticosteroids on serum antinuclear antibodies in man.

The effect of prednisone on serum levels of IgG antibodies to viral and bacterial antigens was measured and compared to its effect on IgG antibodies to nuclear antigens in 8 patients with systemic lupus erythematosus. Prednisone at 15-80 mg/day (mean 55 mg/day) for 14-30 days (mean 19 days) lowered the serum IgG by an average of 22% (p less than 0.005). An even greater reduction in IgG antinuclear antibodies occurred (mean 43%, p less than 0.001) including responses to double stranded DNA, single stranded DNA, and the nucleosides, adenosine, guanosine, cytidine and thymine riboside. In contrast, there was no alteration in serum IgG antibody levels to influenza virus vaccine and pneumococcal vaccine antigens. These results suggest that prednisone has a selective effect on the expression of autoimmunity which may, in part, be responsible for its clinical efficacy in systemic lupus erythematosus.

Adolescent↗
PubMed1984

Characterization of mouse and human monoclonal antibodies cross-reactive with SLE serum antibodies to guanosine.

Two new monoclonal antibodies, one a mouse IgM and the other a human IgM that reacted with guanosine, were compared to human serum antibodies from patients with systemic lupus erythematosus (SLE). The human monoclonal antibody was polyspecific in its binding to the nucleoside bases, whereas the mouse monoclonal antibody was relatively specific for guanosine when compared by using an enzyme-linked immunosorbent assay (ELISA). Neither antibody bound polyguanylic acid or denatured single-stranded (ss) DNA, however. Serum IgG antibodies from seven patients with SLE cross-reacted with the mouse monoclonal antibody and showed considerable specificity for guanosine. In contrast, the human serum IgG antiguanosine antibodies also bound ssDNA but not dsDNA or polyguanylic acid. Serum IgG antibodies to guanosine measured by ELISA from the seven SLE patients had a decreased response when compared to the total serum IgG response to ssDNA, and most of the antibodies that bound guanosine also bound ssDNA. These studies provide new evidence that there are specific IgG antibodies to guanosine in SLE sera that are a small fraction of the antibodies to ssDNA. Further efforts to define the role of these guanosine antibodies in SLE may provide a better understanding of the basic mechanisms responsible for the development of SLE in man.

Animals↗
PubMed1983

Specificity of anti-nucleoside antibodies in systemic lupus erythematosus.

The titer of IgG antinucleoside antibodies in the sera of 162 individuals was determined by an enzyme-linked immunosorbent assay. The nucleosides used in the assay were adenosine, cytidine, guanosine, and thymine-riboside conjugated to human serum albumin. The specificity of IgG antinucleoside antibodies was indicated by appropriate reduction in antibody binding after solid-phase adsorptions of antibody with specific immobilized nucleoside conjugates. Disease-associated increases in serum IgG antibodies to cytidine and guanosine but not to adenosine or thymine-riboside occurred in patients with systemic lupus erythematosus (SLE). The epitope density of nucleosides in the conjugates and differences in the sensitivity of each nucleoside assay were not responsible for disease-associated IgG antinucleoside antibody responses. These findings support a possible pathogenic role for cytidine and guanosine as antigens or crossreactive antigenic determinants in some patients with SLE.

Adenosine↗
PubMed1983

Impaired response of neutrophils to a lymphokine by sera from patients with connective tissue disease.

The studies reported here were designed to determine whether sera from various patients could prevent neutrophils from responding to the lymphokine, neutrophil migration inhibition factor from T lymphocytes (NIF-T). Neutrophils from healthy donors were treated with sera from 84 subjects and assayed for responses to NIF-T. Serum from 7 of 37 patients (19%) with rheumatoid arthritis, systemic lupus erythematosus, and various forms of vasculitis showed blocking activity. In contrast, none of 47 subjects, including healthy individuals and patients with spondylarthropathies, cancer, and active infections had a serum factor that prevented neutrophils from responding to NIF-T (P less than 0.01). Serum blocking activity occurred transiently in association with infection by Staphylococcus aureus in one patient with rheumatoid arthritis. Moreover, autologous neutrophils from this same patient showed impaired responses to NIF-T. Blocking activity could be eluted from protein A-Sepharose in three of three patients studied. In three of seven patients, blocking activity was detected in serum cryoprecipitates, with a recovery of 46 to 78% of the blocking activity and overall enrichment (purification) of 137- to 281-fold. Analysis of cryoprecipitates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed the predominance of immunoglobulins M and G. In one patient, the serum blocking activity was not cryoprecipitable, and cryoprecipitates from a patient with essential cryoglobulinemia failed to prevent neutrophils from responding to NIF-T. Blocking activity was relatively specific for NIF-T, as there was no effect on F-met-leu-phe-induced chemotaxis of neutrophils. Serum blocking activity in patients with connective tissue disease showed some correlation (r = 0.50; P less than 0.01) with immune complexes detected by polyethylene glycol precipitation but not Clq binding. These studies suggest that the response of neutrophils to NIF-T may be blocked by serum, possibly as a result of immune complexes or autoantibodies found primarily in patients with connective tissue disease.

Antigen-Antibody Complex↗
PubMed1981

Effect of methylprednisolone on the production of neutrophil migration inhibition factor by T lymphocytes (NIF-T).

Glucocorticoids may suppress cell-mediated immunity by inhibiting lymphocyte mediator production or reducing the responsiveness of target cells to these mediators. Our laboratory recently described a newly recognized T-lymphocyte mediator, neutrophil migration inhibition factor from T-lymphocytes (NIF-T). In this report we assessed the effect of glucocorticoids on NIF-T activity. Methylprednisolone (MP) at concentrations as low as 10-7 M inhibited NIF-T activity from peripheral blood lymphocytes (PBL) in response to staphylococcal protein A (SPA) and concanavalin A (Con A). However, MP at concentrations as high as 10-4 M did not after the responsiveness of neutrophils to NIF-T. Therefore, the effect of MP on NIF-T activity was due to inhibition of mediator production. The effect of MP on NIF-T production was reversible in 24 hours. This finding is consistent with the clinical observation that alternate day therapy does not suppress cell-mediated immunity. Serum taken from a patient as early as one hour after oral administration of 100 mg of prednisone inhibited NIF-T production in vitro; serum obtained at 48 hr after prednisone had no measurable effect on NIF-T activity, In addition. MP inhibited NIF-T production by previously activated lymphocytes.

Cell Migration Inhibition↗