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Biomedical subjects

D Chia

Publications and source records attributed to D Chia.

At least 73 records · Page 4Linked to original sources

Avidity indices of anti-IgG antibodies in diseases.

Anti-IgG antibodies were detected in 69% of 235 sera tested. A simple and reproducible method was developed to measure the avidity index of anti-IgG antibodies. It was found that subjects with systemic lupus erythematosus and progressive systemic sclerosis and normal controls had antibodies with lower avidity index than those with rheumatoid arthritis and Down's syndrome. The difference in avidity seems to be disease specific. Avidity does not correlate with antibody titers, but all sera with high avidity antibody are positive in the latex test. The anti-IgG as measured by this method was shown to be mainly of IgM class. The avidity indices of whole sera and purified IgM fractions were similar.

Antibodies, Anti-Idiotypic↗

Cytotoxicity of anti-Fab antibodies against B lymphocytes in rheumatoid arthritis.

Anti-Fab antibody titers were positive in 70% of rheumatoid arthritis patients (54 of 77) and 3% (1 of 35) of healthy donors. Their specificity was examined by inhibition of the radioimmunoassay for anti-Fab antibodies, which demonstrated that they are against the Fd region of the intact immunoglobulin molecule. In addition, anti-Fab antibodies have broad specificities for IgG antigens, shown by inhibition with myeloma IgG. They are cytotoxic against B (20% of B cells from most healthy donors) but not T lymphocytes, with cytotoxicity greater at 5 degrees C than 37 degrees C. These studies show that the anti-Fab antibodies interact with allotypic or idiotypic determinants on subpopulations of B lymphocyte cell surface antigens.

Antibodies, Anti-Idiotypic↗

Abnormalities of pulmonary vascular dynamics and inflammation in early progressive systemic sclerosis.

Abnormalities of pulmonary function were studied in 10 patients with progressive systemic sclerosis (PSS) and 3 control subjects. All underwent 81M krypton lung scanning and total body gallium scanning. Immune complexes were measured by Raji cell radioimmunoassay and polyethylene glycol (PEG) assay. Perfusion scans were abnormal in 7 of 9 patients, and 5 of 9 showed a decrease in pulmonary perfusion after cold challenge. Increased gallium uptake was noted in the lungs of 6 of 9 patients. Krypton scans were normal in the control group. Elevated immune complexes were noted in 8 of 10 patients by the Raji assay and in 5 of 10 with the PEG assay. Efforts to separate patients with PSS into subgroups may lead to a better understanding of and advances in therapy for PSS.

Adult↗

Effects of pulse cyclophosphamide on NZB/W disease.

Induced IgM anti-ss-DNA antibodies in NZB/W female mice did not alter the time of onset nor the course of nephritis. Monthly pulse doses of cyclophosphamide suppressed the mortality of these mice, and also prevented a switch of anti-ss-DNA from IgM to IgG class. The production of IgM anti-SRBC was markedly reduced in old NZB/W mice, but IgG anti-SRBC was only moderately reduced and this hyporesponsiveness towards SRBC could be reversed by CPA treatment. These observations are discussed in relation to cyclophosphamide as an effective therapeutic agent for the murine lupus syndrome.

Age Factors↗

Increased Fc receptor activity in monocytes from patients with rheumatoid arthritis: a study of monocyte binding and catabolism of soluble aggregates of IgG in vitro.

We studied the binding and catabolic function of adherent monocytes from patients with rheumatoid arthritis (RA) and normal subjects using stable, heat aggregates of IgG125I (A-IgG) as a model for soluble immune complexes. Scatchard plots of 4 degrees C binding data showed that RA monocytes had increased binding avidity and higher maximal binding capacity for A-IgG compared with monocytes from normal subjects. These data suggest that RA monocytes have increased numbers of Fc receptors for IgG, although a concomitant increase in the avidity of individual Fc receptors could not be excluded. At 37 degrees C, RA monocytes; kinetic analysis suggested that increases in catabolized A-IgG were due to increased binding of A-IgG with no change in the fractional rates of catabolism. Latex titers of RA patients correlated with the number of Fc receptors detected on RA monocytes. Mononuclear phagocytes from RA patients are often exposed to endogenous immune complexes that may be present in the blood of such patients; immune complexes may stimulate monocytes and possibly other mononuclear phagocytes to increase their capacity to bind and catabolize soluble immune complexes.

Adult↗

Human IgM anti-IgM cytotoxin for B lymphocytes.

B lymphocytes were shown previously to be killed at 5 degrees C by some autologous and allogeneic human sera. We show here that such cold cytotoxins are directed against immunoglobulins on the surface of B lymphocytes. The activity is partially removed by passing serum through IgG-coupled Sepharose and usually completely removed by passing serum through IgM-coupled Sepharose. Activity is regained from the columns by acid elution and IgM inhibits the cytotoxicity of these eluates. 125I-labeled eluates bind to IgG- and IgM-coupled Sepharose beads and binding is inhibited by IgM and to a lesser degree by IgG thus showing a primarily more avid binding to IgM as compared to IgG. Furthermore, the 125I-labeled cytotoxic eluates recognize the same determinant(s) on IgM and IgG. We suggest tht IgM anti-IgM antiimmunoglobulin may regulate immune reactivity by binding to B-lymphocyte surfaces.

Absorption↗

Circulating immune complexes in cystic fibrosis.

Recurrent respiratory infections associated with "mucoid" Pseudomonas aeruginosa characterize the advanced stages of cystic fibrosis. To determine if chronic antigenic stimulation is associated with circulating immune complexes (CIC), we assayed the sera of 20 hospitalized patients using the technique of precipitation with 4% polyethylene glycol. Elevated CIC levels, defined by > 310 micrograms IgG per ml, were found in 18 of 20 patients, (range, 350 to 3200 micrograms/ml). Serum, supernatant, and resuspended precipitates were assayed for hemagglutinating antibodies against pseudomonas lipopolysaccharide (LPS or endotoxin) and exotoxin A antigens. Both serum anti-LPS (range, 1:64 to 1:2048) and antitoxin titers (range, 1:64 to 1:16, 384) were markedly elevated and higher than titers in supernatants and resuspended precipitates, indicating antibody excess. "Enrichment" ratios for antibodies present in CIC were calculated by proportion of titer to immunoglobulin in the precipitated complex relative to these values in serum. Mean enrichment ratios of 13.1 and 13.9 were obtained for LPS antibody before and after 2 mercaptoethanol reduction, but the mean enrichment ratio for antitoxin was only 2.07. Serially diluted supernatants and precipitates were boiled for 1 hr and tested for endotoxin-like activity by the limulus test. At > 1:8 dilutions, precipitates were positive, and supernatants were negative. These findings indicate that CIC's are common in advanced cystic fibrosis, and analysis of the precipitated complexes demonstrates significant (> 13-fold) enrichment of antibodies against LPS but not exotoxin antigens, as well as endotoxin-like activity in boiled precipitates.

Antibodies↗

Characterization and measurement of anti-IgG antibodies in human sera by radioimmunoassay (RIA).

A sensitive direct binding radioimmunoassay (RIA) was developed which detected low avidity anti-IgG antibodies in sera negative in the latex fixation test (LFT). IgG class antibodies could be detected and were commonly found along with IgM class antibodies. Additionally, the RIA was more reproducible than the LFT, was easily adapted to measure relative avidities of anti-IgG antibodies, and had other technical advantages over the LFT.

Antibodies, Anti-Idiotypic↗

Quantitation and characterization of soluble immune complexes precipitated from sera by polyethylene glycol (PEG).

Polyethylene glycol (PEG) was used to isolate immune complexes from sera. Complexes were then quantified and partially characterized by a variety of immunological techniques. Complexes were detected in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Felty's syndrome and vasculitis, but not in polymyositis, scleroderma or Behçets syndrome. The level of immune complexes correlated with disease activity in SLE and RA patients. Rheumatoid factors and anti-DNA antibodies were enriched by PEG precipitation of RA and SLE sera, respectively, thus these antibodies appeared to be present in the form of soluble immune complexes. Immune complexes usually contained all three immunoglobulin classes, IgG, IgM and IgA. Complexes from RA patients were generally larger and often contained Clq, while C3 was found almost exclusively in SLE complexes which also tended to be smaller. Such compositional differences may one day explain the differences in clinical manifestations of various immune complex-mediated diseases.

Antibodies, Antinuclear↗

IgM anti-IgM cold lymphocytotoxins to B cells.

Cytotoxic antibodies to B lymphocytes have been shown to be IgM. They are not absorbed by red blood cells and therefore not absorbed by red blood cells and therefore not directed against the I antigen of red cells. They are also not inhibited by mannose, as are certain natural cytotoxins against lymphocytes. Methods for producing purified eluates of IgM anti-IgM antibodies are given. These antibodies are postulated to be immunoregulative by acting on B lymphocytes.

Absorption↗

A simple, rapid micro-latex fixation test.

A micro-latex fixation test (LFT) for the determination of rheumatoid factor (RF) is presented. Its advantages compared to similar tests are greater precision, simplicity, increased sensitivity, lower cost, reproducibility and adaptibility to large-scale testing. Micro-LFT titres are presented from a wide range of sample populations. The majority of normal samples show measureable titres whereas rheumatoid patients show high titres. A large sampling of pre- and post-transplant sera from kidney patients was studied and the micro-LFT titres were in the range of normal persons. The transplant sera were tested for lymphocytotoxic antibodies and no correlation was observed with the micro-LFT titres.

Adult↗

The metabolism of nucleic acids in mice.

The metabolism of three forms of nucleic acid, native-DNA (N-DNA), single strand DNA (SS-DNA), and polyinosinic-polycytidylic acid (poly I : C), was investigated in vivo in randomly bred Swiss-Webster mice. Clearance of these substances from the circulation and tissue localization were determined at selected time intervals following the intravenous injection of 125I-labelled compounds. N- and ss-DNA were removed from the circulation more rapidly than was poly I : C. All three materials localized principally in reticuloendothelial-rich organs, i.e. liver and spleen. N-DNA was degraded by the liver more slowly than was poly I : C or ss-DNA. At 4 h following injection, the liver contained 26%, 13%, and 10% of the injected doses, respectively. Three days after injection, 4.5% of the N-DNA persisted in the liver, as compared to only 0.6% of the poly I : C, and 0.2% of the ss-DNA. The possiblity that these differences in metabolism of N-DNA, poly I: C, and ss-DNA may be related to their differing immunogenic potentials in experimental systems is discussed.

Animals↗

Effect of pulse dose cyclophosphamide on the anamnestic immune response in NZB/W mice.

Mice exhibiting a spontaneous SLE-like lethal autoimmunity (female NZB/W hybrids) were given monthly doses of cyclophosphamide (CPA) 240 mg/kg p.o. starting at four months of age. Antibodies to DNA and sheep red blood cells (SRBC) were measured as well as general well being of the mice. The CPA-treated group demonstrated a marked increased in survival compared to the untreated controls with reduction of anti-DNA antibody levels but only a slight inhibition of the anamnestic response to SRBC immunization.

Animals↗

Metabolism of exogenous single stranded DNA in normal and NZB/W mice.

Metabolism of ss-DNA in Swiss Webster mice and NZB/W mice was studied. The delay in intra-hepatic catabolism of ssDNA in old NZB/W female mice seems to correlate with the presence of increased anti-DNA antibodies; similar to effects produced in Swiss Webster mice that have been pretreated with a small dose of carbon black. Neither impairment in the phagocytic ability nor a decrease in DNase activity are found in the mice who are relatively unable to metabolize ssDNA. These observations are discussed in relation to possible pathogenesis in NZB/W mice.

Animals↗

Immune response of New Zealand mice to trinitrophenylated syngeneic mouse red cells.

NZB and NZB/W mice have reduced anti-sheep red cell (SRC) and 2,4,6-trinitrophenyl-plaque-froming cell (TNP-PFC) responses with age after injection of either the thymus-dependent antigen TNP-SRC or the thymus-independent antigen TNP-mouse red cells (MRC). However, the thymus-dependent response diminished much faster than the thymus-independent response. As a consequence, young New Zealand mice have a higher anti-TNP response after injection of TNP-SRC than after injection of TNP-MRC, while old New Zealand mice have a higher anti-TNP response after injection of TNP-MRC than after injection of TNP-SRC. The PFC avidity of NZB/W mice injected with TNP-SRC diminished with age, while the PFC avidity of mice injected with TNP-MRC did not change with agrc or TNP-SRC. Old NZB/W mice had few spontaneous anti-MRC-PFC. The number of anti-MRC PFC in old mice was increased 4 to 10 times after injection with either TNP-SRC or TNP-MRC. It is suggested that surveillance mechanisms are responsible for suppressing the autoimmune response to modified self-antigens. The unregulated immune system of NZB and NZB/W mice appears to be an expression of impairment of such a hypothetical surveillance mechanism.

Age Factors↗