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Biomedical subjects

S Fong

Publications and source records attributed to S Fong.

At least 109 records · Page 6Linked to original sources
PubMed1983

Increased frequency of rheumatoid factor precursor B lymphocytes after immunization of normal adults with tetanus toxoid.

Vaccination of normal adults with tetanus toxoid induced a two-three-fold rise in the frequency of IgM anti-IgG (rheumatoid factor, RF) B lymphocytes inducible by the polyclonal B cell activator, Epstein-Barr virus. The increase in IgM-RF precursors occurred earlier, was greater in magnitude, and was more sustained than the change in plasma IgM-RF. It was associated with a rise in total IgM levels, and correlated positively with the magnitude of the IgG anti-tetanus antibody response, but not with levels of circulating immune complexes. The ability of apparently innocuous infections and immunizations to increase the frequency of IgM-RF precursor B lymphocytes may be the reason for the previously noted expansion in this autoreactive B cell pool between birth and adulthood.

Adult↗
PubMed1983

Complement activation by antibodies to Sm in systemic lupus erythematosus.

An enzyme linked immunosorbent assay was developed to quantitate antibodies to Sm (anti-Sm) and to measure complement activation by anti-Sm in vitro. Anti-Sm in plasma of patients with systemic lupus erythematosus (SLE) were bound to purified Sm bound to polyvinyl chloride microtitre plates and assayed for bound IgG or IgM using enzyme linked anti-gamma or anti-mu. The activation of C4 by anti-Sm was measured by adding diluted normal human serum (complement) to the wells and quantitating the amount of C4 bound to the well surface using (Fab')2 goat anti-C4 followed by enzyme linked rabbit anti-goat IgG. The plasmas of 12 of 36 patients with SLE contained anti-Sm and all 12 activated complement (complement activating anti-Sm). Twenty-eight plasmas containing anti-Sm from 12 patients with SLE were studied. Ten of the 12 patients had anti-Sm of the IgG class whereas two had anti-Sm of both IgG and IgM classes. The amount of C4 activating anti-Sm correlated significantly with the in vivo activation of C4 measured by rocket immunoelectrophoresis for C4d and C4, suggesting that complement activation by anti-Sm is important in vivo.

Antibodies, Antinuclear↗
PubMed1983

A novel cell surface antigen (T305) found in increased frequency on acute leukemia cells and in autoimmune disease states.

Monoclonal antibody T305, prepared by immunizing mice with the T-ALL derived cell line RPMI-8402, immunoprecipitates a single chain glycoprotein with m.w. 160,000 daltons (under reducing conditions) or 180,000 daltons (under nonreducing conditions). In immunofluorescence assays, antibody T305 reacted with a subpopulation of T cells in normal blood (22 +/- 6%), thymus (28 +/- 11%), and lymph node (24 +/- 6%). Increased frequency of T cells reactive with antibody T305 was found in peripheral blood of patients with infectious mononucleosis (greater than 80%), graft-vs-host disease after bone marrow transplantation (65 +/- 11%), acquired immunodeficiency syndrome (53 +/- 12%). The T cells in synovial fluid of patients with rheumatoid arthritis had increased frequency of antibody T305 reactive cells (59 +/- 8%) as compared to their peripheral blood (18 +/- 7%). Two color immunofluorescent studies demonstrated that the T305+ T cells predominantly co-stained with antibody Leu 2a (suppressor/cytotoxic subset) in both normals and disease state blood. After cell sorting to obtain T305+ and T305- subpopulations, we demonstrated that a) natural killer and antibody-dependent cellular cytotoxicity activity in normal blood was in the T305+ but not T305- T cells; b) cytotoxic T cells induced by mixed lymphocyte reaction were predominantly T305+; c) T305- T cells could be induced in vitro to express T305 antigen by mitogens or allogeneic B cells; d) the DNA content of T305+ and T305- T cells in normal blood was similar (greater 95% of cells with G0/G1 level); e) after mitogen stimulation, T305 antigen induction on previously T305- cells occurs before S-phase; and f) significantly more [3H]-thymidine after mitogen stimulation was incorporated by originally T305- cells than by originally T305+ cells (p less than 0.001). The T305 antigen was not restricted to T cells because it was also found on myeloid precursors in bone marrow but was not present on polymorphonuclear leukocytes, red blood cells, platelets, muscle, liver, skin, kidney, lung, or brain. Antibody T305 was found on 24/25 cases of acute leukemia (6 T-ALL, 10/11 cALL, 7 AML, and 1 AMOL) but not on 18 cases of chronic leukemia (B-CLL, T-CLL, null CLL, CML). The importance of the T305 antigen is that it is present on a high number of T cells in certain autoimmune diseases and on virtually all acute leukemia cells. Its distribution on immature and in vitro activated cells suggests that it may represent a receptor for signals related to cellular replication or differentiation.

Animals↗
PubMed1983

The internal image of IgG in cross-reactive anti-idiotypic antibodies against human rheumatoid factors.

A network of idiotypes and anti-idiotypes has been hypothesized to modulate antibody production against exogenous antigens. Idiotypic antigens on autoantibodies have been studied because of their potential use for specific immunomodulation. The present studies describe the preparation and characterization of rabbit anti-idiotypic antibody against human IgM anti-IgG autoantibodies (rheumatoid factors, RF) that bear the "internal image" of the human IgG-Fc fragment, and hence react specifically with the majority of RF from patients with rheumatoid arthritis. The anti-idiotype was isolated from rabbit anti-RF antisera by either immunodepletion of anti-immunoglobulin antibodies, or more simply by a single affinity purification step on a rabbit anti-human IgG Fc column. As measured by an enzyme-linked immunoassay, the anti-idiotype prepared by both methods bound to plates coated with purified IgM RF, but not to plates coated with non-RF IgM proteins. The anti-idiotype dose dependently blocked the binding to IgG of IgM-RF in 83% of sera from multiple patients with rheumatoid arthritis, Sjogren's syndrome, and macroglobulinemia. The anti-idiotype did not inhibit the activity of human IgM antibodies against DNP, tetanus toxoid, or thyroglobulin. The antigen recognized by the cross-reactive anti-idiotype was not apparently associated with a particular light or heavy chain amino acid sequence, but rather was intrinsic to most immunoglobulins with RF activity. Broadly cross-reactive anti-idiotypes with the "internal image" of IgG are simple to generate, and react with most RF. They may facilitate studies on the specific regulation of the human anti-IgG autoantibody response.

Animals↗
PubMed1982

Activation of the classical pathway of complement by rheumatoid factors. Assessment by radioimmunoassay for C4.

A simple, sensitive solid-phase radioimmunoassay to quantitate the activation of the classical pathway of complement by rheumatoid factor (RF) is described. RF (purified, in serum or synovial fluid) was bound to reduced and alkylated IgG adsorbed to polyvinyl chloride microtiter plates and reacted with diluted normal human serum (complement). The activation and binding of C4 were quantitated with 125I-Fab'2-anti-C4. Purified, polyclonal IgM--RF was 100- to 1,000-fold more effective than purified IgG--RF in activating complement. The amount of complement activation produced by RF in each of the 57 sera and 2 synovial fluid samples correlated directly with the amount of IgM--RF present. The complement activating abilities of polyclonal IgM--RF in the sera of 15 rheumatoid arthritis patients were homogeneous. This novel technique is readily applicable to the investigation of complement activation by RF in disease.

Animals↗
PubMed1982

Use of monoclonal antibodies to analyze peripheral blood and salivary gland lymphocyte subsets in Sjögren's syndrome.

Using monoclonal antibodies to cell surface antigens, we studied lymphocyte subsets in 15 patients with primary Sjögren's syndrome. The absolute number of OKT8-positive cells (reactive with T suppressor/cytotoxic cells) was significantly decreased in such patients (353 +/- 186/mm3) compared to age-matched controls (631 +/- 150/mm3) (P less than 0.001). The number of OKT4-positive cells (reactive with T helper/inducer cells) was comparable in both groups (932 +/- 588/mm3 versus 1.073 +/- 290/mm3). The ratio of OKT4/OKT8-reactive peripheral blood lymphocytes was increased (greater than 2.4) in 67% of these patients and ranged from 1.0 to 6.4 (normal = 1.8 +/- 0.3). OKT4-positive cells were the predominant subset in lip biopsy specimens stained with immunofluorescence or immunoperoxidase techniques; the OKT4/OKT8 ratio exceeded 3.0 in all 5 patients examined. In 1 patient with pseudolymphoma, a lymph node biopsy specimen contained 80% T cells with an OKT4/OKT8 ratio of 3.2. Thus, OKT4-positive cells predominated in the peripheral blood lymphocytes as well as in sites of inflammation in primary Sjögren's syndrome. The decreased number of OKT8-positive cells in primary Sjögren's syndrome was probably not caused by circulating autoantibody, since patients' sera did not react with normal OKT8-positive cells. Functional studies using pokeweed mitogen demonstrated that T helper cell activity for immunoglobulin synthesis was contained in the OKT4-positive subset in both normal and patients' peripheral blood lymphocytes. Removal of OKT8-positive cells by complement-mediated lysis did not lead to increased immunoglobulin synthesis or production of rheumatoid factor. The identification of peripheral blood lymphocyte subsets by use of monoclonal antibodies and the relationship of these subsets to tissue infiltrates and autoantibody production provide further insight into the pathogenesis of primary Sjögren's syndrome.

Adolescent↗
PubMed1982

Frequencies of Epstein-Barr virus-inducible IgM anti-IgG B lymphocytes in normal children and children with juvenile rheumatoid arthritis.

The relative frequencies of IgM antiIgG autoantibody (rheumatoid factor) producing cells induced by the polyclonal B cell activator Epstein-Barr virus were measured in peripheral blood lymphocyte cultures of normal children and patients with juvenile rheumatoid arthritis. The frequencies of rheumatoid factor precursor B cells in normal children were lower than adults, but higher than neonates. The frequency increased with the age of the donor. In seronegative children with the systemic-onset or pauciarticular-onset types of juvenile rheumatoid arthritis, the number of IgM antiIgG inducible B cells was not significantly different (P greater than 0.05) from age-matched controls. Patients with seropositive juvenile rheumatoid arthritis or seropositive adult rheumatoid arthritis had significantly higher IgM antiIgG precursor cell frequencies than age-matched normal subjects (P less than 0.01 and P less than 0.02, respectively). In contrast, the patients with seronegative polyarticular-onset juvenile rheumatoid arthritis had an average precursor frequency significantly lower than normal age-matched controls (P less than 0.05), analogous to results previously noted in adult seronegative rheumatoid arthritis. Thus, both children and adults with seronegative polyarticular rheumatoid arthritis had a deficiency in B cells that produce IgM antiIgG and that are induced by Epstein-Barr virus. This distinguished them from seropositive juvenile rheumatoid arthritis and rheumatoid arthritis patients, normal subjects, and patients with the pauciarticular-onset and systemic-onset types of seronegative juvenile rheumatoid arthritis.

Adolescent↗
PubMed1982

Histochemistry of NADH diaphorase and gamma-glutamyltranspeptidase in rat bladder tumors.

To improve identification of preneoplastic bladder cancer cells, we have studied two enzyme histochemical changes in bladder tumors induced in male Fisher 344 rats by the carcinogen N-butyl-N-(4-hydroxybutyl)-nitrosamine. In early areas of focal nodular hyperplasia there was a dramatic increase in staining for NADH:menadione oxidoreductase (diaphorase)activity. In nonfocal areas as well, there were many individual cells with intense staining, while the controls were of uniform moderate staining. Large papillomas and carcinomas often showed heterogeneous staining. gamma-Glutamyltranspeptidase (GGT) was absent from normal urothelium and from all tumors except the most advanced carcinomas and large papillomas. In old, carcinogen-exposed animals, GGT activity was seen in the luminal surface of tumors and in the interlesion urothelium. In newborn rats and in rats with regenerative hyperplasia following wounding of the urothelium, the diaphorase staining was less than that in the untreated adult. Our findings suggest that increased diaphorase activity may serve to identify early islands of carcinogen-induced, enzymatically altered bladder cells, while GGT will not.

Animals↗
PubMed1982

The radioimmunoassay of a carcinoembryonic antigen fraction.

A qualitative and clinical evaluation of a radioimmunoassay for a carcinoembryonic antigen (CEA) fraction in serum is presented. The technique shows cross-reactions with normal organs' extracts lower than 0.05% and a 0.9977 correlation coefficient. The coefficients of variation indicate satisfactory precision. In the clinical study it was found that sensitivity for lung cancer was higher than for colorectal cancer. Specificity for cancer was 98.3%. These results suggest that the CEA fraction employed shows more lung cancer determinants than for digestive cancer.

Adolescent↗
PubMed1982

Selective induction of autoantibody secretion in human bone marrow by Epstein Barr virus.

The bone marrow is an important site for B lymphocyte differentiation and antibody synthesis in animal and man. However, few experiments have examined directly its immunologic functions in humans. In the present experiments, we have induced bone marrow B lymphocytes from human donors with degenerative arthritis of varying ages to secrete two autoantibodies, IgM and anti-IgG (rheumatoid factor) and IgM anti-human thyroglobulin (Tg), by stimulation with the polyclonal B cell activator Epstein Barr virus (EBV). The EBV-stimulated bone marrow cells secreted significantly more IgM anti-IgG (p less than 0.01) and IgG anti-Tg (p less than 0.01) than matched, identically treated peripheral blood cells. Bone marrow cultures from donors over the age of 60 yr, particularly females, produced more rheumatoid factor than cultures from younger donors (p less than 0.01). The EBV-inducible autoantibodies were immunospecific as demonstrated by adsorption studies. A potential pathogenic role in the inflammatory process was suggested by the finding that the EBV-inducible IgM anti-IgG autoantibodies were capable of activating the classical complement pathway as assessed by the cleavage of C4. These results indicate that the human bone marrow is a selective reservoir for EBV-inducible autoantibody precursor B lymphocytes, and that the size of the reservoir increases with age.

Adult↗
PubMed1982

Synovial fluid lymphocytes differ from peripheral blood lymphocytes in patients with rheumatoid arthritis.

Peripheral blood (PBL) and synovial fluid lymphocytes (SFL) from 12 patients with rheumatoid arthritis (RA) were analyzed using monoclonal antibodies that detect specific T cell surface antigens (OKT3, OKT4, OKT8, SC1) and antigens associated with lymphocyte activation (anti-Ia, OKT10, B3/25). RA patients' PBL contained 1010 +/- 74 OKT4+ and 401 +/- 62 OKT8+ cells/mm3 (ratio OKT4+/OKT8+ = 2.4 +/- 0.3). In contrast, SFL from these patients exhibited a significantly different proportion of T cell subsets (ratio OKT4+/OKT8+ = 1.1 +/- 0.5) (p less than 0.0001) with 630 +/- 180 OKT4+ and 595 +/- 225 OKT8+ cells/mm3. Synovial fluid contained significantly more activated T cells based on the presence of Ia-positive T cells (19 +/- 5%) and reactivity with antibody OKT10 (49 +/- 7%) compared with RA-PBL (8 +/- 3% Ia-positive T cells and 13 +/- 6% OKT10+). Compared with RA-PBL, normal PBL contained an elevated number of OKT8+ cells (610 +/- 48/mm3), a similar number of OKT4+ cells (1040 +/- 86/mm3), and a lower percentage of activated lymphocytes (3 +/- 2% Ia-positive T cells and 10 +/- 8% OKT10+ cells). SFL, RA-PBL, and normal PBL all showed less than 3% cells reactive with antibody B3/25 (anti-transferrin receptor antibody), a marker found on in vitro activated T cells. These findings demonstrate that the lymphocytes at the site of inflammation differ significantly from the lymphocytes present in the peripheral blood of the same patients. RA patients had a small but significant decrease in the number of OKT8+ cells/mm3 compared with normal PBL (p less than 0.01), suggesting that this lymphocyte subset may home to synovial tissues, where it becomes activated.

Antibodies, Monoclonal↗
PubMed1981

Selective lymphocyte deficiency in seronegative rheumatoid arthritis.

Prior studies have shown that in vitro infection with the Epstein Barr virus (EBV) is able to induce IgM rheumatoid factor production by normal lymphocytes, with a higher degree of production by seropositive rheumatoid arthritis lymphocytes. The present investigation demonstrates that EBV-infected lymphocytes from patients with seronegative rheumatoid arthritis produce in vitro significantly less IgM rheumatoid factor than do normal lymphocytes. The results suggest that the peripheral blood of seronegative patients is deficient in the rheumatoid factor precursor B cells responsive to stimulation by Epstein Barr virus.

Arthritis, Rheumatoid↗