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Biomedical subjects

E M Tan

Publications and source records attributed to E M Tan.

At least 271 records · Page 15Linked to original sources
PubMed1979

Antibodies reacting with ribosomal ribonucleoprotein in connective tissue diseases.

Precipitating antibody to an antigen present in cytoplasm was detected in the sera of 7 patients with systemic lupus erythematosus, 1 patient with an overlap toid arthritis, and 1 patient with mixed connective tissue disease. By physicochemical and enzymatic studies, the antigen was shown to have the properties of ribosomal ribonucleoprotein (gamma-RNP). Cytoplasmic staining in immunofluorescence was observed with all the 9 sera containing antibodies to gamma-RNP. In certain cases, cytoplasmic staining was associated with nucleolar staining. Antibody to gamma-RNP is different in immunologic specificity and clinical significance from antibody to nuclear RNP and is present primarily in patients with systemic lupus erythematosus.

Arthritis, Rheumatoid↗
PubMed1979

Autosensitization to DNA: evidence for an immunologic basis.

A 59-year-old female with spontaneous painful ecchymoses developed ecchymoses after intracutaneous injection of washed autologous whole blood cells and calf thymus DNA. Immunofluorescent studies of the spontaneous lesions revealed granular deposits of IgM, C3, factor B and properdin at the dermal-epidermal junction but no deposits in her normal skin. T cells were decreased in number but responded normally to polyclonal mitogens and did not transform in response to DNA containing antigens. Repair of UV-damaged DNA by her lymphocytes appeared to be depressed. The findings presented here are the first immunologic abnormalities uncovered in this disorder and may help in understanding the pathogenesis of the inflammatory lesions seen in autosensitization to DNA.

Autoantibodies↗
PubMed1979

Plasma complement and histamine changes in atopic dermatitis.

Fifteen patients with atopic dermatitis were investigated to evaluate the total of complement and histamine. In five patients total serum complement haemolytic activity (CH50) was significantly decreased as was the haemolytic activity of complement components C2 (C2H50) and C3 (C3H50). By counter immunoelectrophoresis split products of C3 were detected. There was no evidence for alternative pathway activation or the presence of an activator of the alternative pathway. In three patients plasma histamine concentrations were elevated. The intensity of the complement and histamine changes observed seemed to be correlated to the severity of the disease.

Adolescent↗
PubMed1979

Autoantibodies and the spectrum of Sjögren's syndrome.

In studies reported recently, the sera of patients with Sjögren's syndrome were found to contain precipitating antibodies to nuclear antigens that can be identified by immunodiffusion analysis. These precipitating autoantibodies have been termed SS-A and SS-B antibodies. We show that identification of these autoantibodies helped in establishing the diagnosis of Sjögren's syndrome in 12 of 30 patients in whom the diagnosis had not been considered at the time of the physician's initial examination. The reasons for this were related to lack of spontaneous complaints of keratoconjunctivitis sicca and xerostomia and prominence of symptoms associated with arthritis, myalgia, pulmonary fibrosis, and cardiac disease. This study re-emphasizes the importance of multisystem disease in Sjögren's syndrome and shows that specific serologic assays for autoantibodies aided in diagnosis.

Aged↗
PubMed1979

Activation of the alternative pathway of complement by antiserum to factor B.

Monospecific rabbit and goat antisera to human complement proteins and human immunoglobulins were tested for their ability to activate the alternative complement pathway. This activation was detected by two methods where classical pathway activation was blocked with EGTA and alternative pathway activation was promoted with added magnesium ions. These two methods consisted of lysis of GSHE and conversion of factor B into split products. C1q-depleted serum was used in a third assay system. Only antiserum to human factor B was able to activate the alternative pathway in the various systems used. None of the other anticomplement sera showed such activity. When antiserum to factor B was fractionated by ammonium sulfate and column chromatography, activation of the alternative pathway was found in the IgG fraction, and this activity was completely removed by absorption with purified factor B but not with other purified complement components.

Animals↗
PubMed1978

Human blood cells ultrastructural changes and mediator release after exposure to roentgenographic contrast media.

Adverse reactions to roentgenographic contrast media (RCM) are associated with the release of mediators including complement components (anaphylatoxins), histamine and serotonin. In an in vitro study of platelets and leukocytes from 20 healthy individuals, RCM-induced release of granules from basophils and platelets was correlated with the release of histamine and serotonin respectively. The release of histamine from basophils was augmented in the presence of exogenous complement; in contrast, the release of serotonin from platelets was not dependent on the addition of exogenous complement. Although individual differences were noted, iothalamate most effectively released serotonin, whereas diatrizoate most effectively released histamine.

Adult↗
PubMed1978

Immunological detection of O6-methylguanine in alkylated DNA.

Antibodies to O6-methyldeoxyguanosine were produced in rabbits and utilized in a radioimmunoassay to detect this nucleoside at picomole levels. The specificity of the antibodies was demonstrated by the use of nucleoside analogues as inhibitors in the radioimmunoassay. The antibodies cross-reacted with O6-methylguanosine, O6-methylguanine, and O6-ethylguanosine. There was 10(4) to 10(6) times less sensitivity to inhibition by deoxyadenosine, deoxyguanosine, and guanosine than by O6-methyldeoxyguanosine. The radioimmunoassay also detected O6-methylguanine in DNA alkylated by agents known to produce O6-methylguanine, such as N'-methyl-N-nitrosourea. DNA alkylated with dimethyl sulfate, which does not produce O6-methylguanine in DNA, cross-reacted with the antibodies to a very limited extent. Such an assay system for modified nucleic acid components would be very useful in following the production, persistence, and repair of these lesions in a variety of cells and tissues treated with a broad spectrum of carcinogens and suspected carcinogens.

Alkylation↗
PubMed1978

Lymphocytes transformed by Epstein-Barr virus. Induction of nuclear antigen reactive with antibody in rheumatoid arthritis.

Sera from approximately two-thirds of patients with rheumatoid arthritis contain an antibody which is reactive with a nuclear antigen present in human B-lymphocyte tissue culture cells. The immunological reaction can be demonstrated by precipitation and immunofluorescence. Evidence is present that the reactive nuclear antigen is associated with Epstein-Barr (EB) virus-transformed lymphocytes. Normal human peripheral blood lymphocytes did not contain the nuclear antigen reactive with rheumatoid arthritis sera, but after infection with EB virus, they showed increasing amounts of reactive nuclear antigen as the cells were transformed into continuous lines. Several established human and simian lymphocyte cell lines known to carry EB viral genomes were shown to contain rheumatoid arthritis-associated nuclear antigen. Evidence is presented which suggests that the rheumatoid arthritis-associated nuclear antigen is different from the previously described EB nuclear antigen.

Antibodies↗
PubMed1978

Presence of anti-Sm reactivity in autoimmune mouse strains.

The investigation of the fine specificities of antinuclear antibodies (ANAs) has been fruitful in terms of the nosology and immunopathogenesis of human autoimmune syndromes. Particular reactivities serve as "markers," in that patients with certain syndromes have a much higher incidence of such ANAs than do patients with other diseases. In this category is the almost exclusive against the nuclear acidic protein Sm. Reactivity to Sm can be detected by precipitation in agar, complement fixation, or passive hemagglutination (1,2). Autoimmune mouse strains have also provided a fertile field for the investigation of the basic phenomena of self-activity. In particular, the NZB strain and its hybrid NZB x NZW have been considered excellent models for human SLE and have therefore been studied in great detail (3,4). In addition, Murphy et al at The Jackson Laboratory, Bar Harbor, Maine, have developed several new inbred mouse strains that spontaneously develop SLE-like syndromes (5,6). These are the BXSB strain, which has a male dominant disease characterized by little antiative DNA antibody; the MRL/1, which develops massive, nonmalignant lymphadenopathy, associated with enormous increases in serum immunoglobulin levels and fulminant renal disease; and the MRL/n, which does not develop SLE-like disease until well into the 2nd yr of life, but like the MRL/1 develops high titers of ANA and fatal glomerulonephritis. The MRL/1 differs from MRL/n in only about 10 percent of its genome, including the gene responsible for the MRL/1's lymphoproliferation. In the current study, we have used the technique of double immunodiffusion (ID) in agarose with standard human reference sera (of known ANA specificity) to survey a large number of mice from the NZB x NZW, MRL/1, MRL/n, BXSB, and other strains. We report here the finding of the anti-Sm marker" antibody almost uniquely in MRL/1 and MRL/n animals. These two related strains may serve as experimental models to explore the mechanism stimulating the production of this unique autoantibody in SLE.

Animals↗
PubMed1978

Recent progress in the study of autoantibodies to nuclear antigens.

Autoantibodies to nuclear antigens can now be classified according to their immunologic specificities. They include antibodies that react with DNA, deoxyribonucleoprotein, nuclear histones, and nuclear acidic protein antigens. It has been established that there are several antinuclear antibodies that react with nuclear acidic proteins, and these include antibodies to Sm antigen, nuclear ribonucleoprotein, and SS-A and SS-B antigens. It has also been established that certain systemic rheumatic diseases, such as systemic lupus erythematosus, Sjögren's syndrome, and scleroderma, are characterized by antibodies of some specificities and not of others. Thus, distinct profiles of antibodies to nuclear antigens may be present, and these may be used as diagnostic aids. Further characterization of these specific nuclear antigen-antibody systems may help in unraveling the etiology and pathogenetic mechanims of these diseases.

Animals↗
PubMed1978

Microhemagglutination test for detection of antibodies to nuclear Sm and ribonucleoprotein antigens in systemic lupus erythematosus and related diseases.

A reproducible hemagglutination procedure to detect antibodies to Sm and ribonucleoprotein nuclear antigens is described. The application and interpretation is discussed. The hemagglutination test was found to be more sensitive than the immunodiffusion test; however, the hemagglutination test may not detect the presence of low titers of anti-ribonucleoprotein in the presence of a high level of anti-Sm antibody. Anti-ribonucleoprotein antibodies in the presence of high titers of anti-Sm antibodies are best identified by gel precipitation methods where precipitin lines can be characterized by their interaction with precipitin lines produced by known prototype antisera.

Animals↗
PubMed1978

Complement and immunoglobulin deposits in the skin of patients with atopic dermatitis.

The immunofluorescent patterns of uninvolved and involved skin biopsies from eight patients with atopic dermatitis were studied, using direct immunofluorescence techniques to identify deposits of the immunoglobulins G, A and M as well as the complement factors C1q, C3, C4, C5, factor B and properdin. Immunoglobulin deposits (mainly IgG) were found in five patients, complement deposits in three patients in the basement membrane zone. In three patients the immunofluorescence was positive for C3, in two patients for C1q, C4 and C5. Regarding the factors of the alternative pathway of the complement system, two patients showed deposits of properdin, one of factor B. The changes were not confined to the eczematous lesions, but were found in uninvolved skin too. The most prominent changes were observed in patients with severe disease.

Adolescent↗
PubMed1978

Antibodies to histones in drug-induced and idiopathic lupus erythematosus.

When tissue sections are extracted with 0.1 N HCl, cellular nuclear proteins, including histones, are removed but nuclear DNA is retained. Histones can be reconstituted back to nuclear DNA in acid-extracted tissue sections so that the resulting nuclear substrate is composed only of DNA and histones and does not contain acidic nuclear protein antigens. The resulting DNA-histone tissue substrate can be used in the immunofluorescent method for specific detention of antibodies to histones. Sera from 23 patients with drug-induced lupus erythematosus (procainamide 19, isoniazid 2, nitrofurantoin 2) and 20 patients with idiopathic (not drug-induced) systemic lupus erythematosus (SLE) were studied. All 23 patients with drug-induced lupus erythematosus (LE) lost nuclear staining on acid-extracted sections. In contrast, only 12 of 20 with idiopathic SLE lost nuclear staining on acid-extracted tissues, and in the remaining 8, there was no significant fall in titer. In the drug-induced LE group, loss of nuclear staining was due to the absence of histones on the substrate because with histone-reconstituted sections, 22 of 23 again became positive for nuclear staining at titers equal to or at one doubling dilution below titers on unextracted tissues. In contrast, of the 12 idiopathic SLE sera which lost nuclear staining, only 5 regained nuclear staining on histone-reconstituted tissue sections. In idiopathic SLE, antinuclear antibodies are heterogeneous in specificities and may consist of antibodies to native DNA, histones, or nonhistone proteins. In contrast, antinuclear antibodies in drug-induced LE are less heterogeneous and mainly consist of antibodies to histones.

Antibodies, Antinuclear↗
PubMed1978

In vitro histamine and serotonin release by radiographic contrast media (RCM). Complement-dependent and -independent release reaction and changes in ultrastructure of human blood cells.

Peripheral leucocytes and platelets from twenty healthy volunteers were incubated in vitro with radiographic contrast media (diatrizoate-Hypaque, iothalamate-Conray and iodipamide-Cholografin) under varying conditions. All radiographic contrast media (RCM) were able to induce histamine release from peripheral leucocytes and the release reaction was dose-dependent. There were individual differences in the sensitivity of leucocytes to different RCM. The highest values (up to 80% histamine release) were found with high concentrations (0.07-0.3 M) of diatrizoate. The addition of normal human serum (NHS) to the reaction mixture led to a further increase in histamine release (P is less than 0.01), probably due to complement activation. The mechanism seems to be mediated by proteins of the alternative pathway, because serum depleted of complement components (factor B, factor D, properdin) did not show this synergistic effect. IgG-depleted serum, however, was able to show the augmented release reaction. Washed platelets incubated with RCM released serotonin in a dose- and time-dependent reaction. The most powerful serotonin-releasing RCM was found to be iodipamide, which produced a release reaction in all people investigated at concentrations of 0.04-0.09 M, while diatrizoate and iothalamate were effective only in half of the tested individuals at high concentrations (0.3 and 0.2 M respectively). The addition of plasma proteins to the reaction mixture inhibited the serotonin release quantitatively. There was no difference in inhibitory potency between autologous and heterologous plasma or serum; sera depleted of various complement components showed similar effects as NHS. The serotonin release was not due to platelet lysis, as determined by the concentration of lactic dehydrogenase present in the supernatant during serotonin release. Incubation of the leucocytes with RCM produced ultrastructural changes, including degranulation of basophils, aggregation of platelets and infiltration of the aggregates by polymorphonuclear leucocytes. The most prominent changes were observed when complement was present in the reaction mixture.

Basophils↗
PubMed1977

DNA-binding property of Sm nuclear antigen.

Antibodies in the sera of patients with systemic lupus erythematosus reacted with a nuclear acidic protein called Sm antigen, and these antibodies were used as reagents to identify Sm antigen in preparative fractionation procedures. DNA affinity chromatography showed that Sm antigen was associated with nuclear protein fractions which had DNA-binding capacity. Evidence was also presented that Sm antigen showed preferential binding for single-strand DNA over double-strand DNA. These studies demonstrate that spontaneously occurring anti-nuclear antibodies in disease states may be used to study the properties of cellular proteins which are present in trace amounts.

Animals↗