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S Izui

Publications and source records attributed to S Izui.

194 records · Page 11Linked to original sources
PubMed1978

Increased spontaneous polyclonal activation of B lymphocytes in mice with spontaneous autoimmune disease.

Early in life, mice of four kinds [NZB, (NZB X NZW)F1, MRL/1, and male BXSB] with autoimmune disease spontaneously produced far more (greater than 3 S.D.) anti-hapten antibody-forming cells in spleens and greater concentrations of anti-hapten antibodies in sera than immunologically normal strains of mice (AKR, BALB/c, C57BL/6, DBA/1-J, DBA/2J, LG/J, 129, NZW, and female BXSB). This increased nonspecific antibody production by the abnormal animals' B cells correlated well with the spontaneous development of anti-single-stranded DNA antibodies, but not with serum levels of the viral envelope glycoprotein, gp70. These results suggest that the spontaneous formation of autoantibodies in mice whose immunologic disorder is manifested by a lupus-like disease may result from polyclonal activation of B cells by endogenous or exogenous B cell activators.

Animals↗
PubMed1977

Features of systemic lupus erythematosus in mice injected with bacterial lipopolysaccharides: identificantion of circulating DNA and renal localization of DNA-anti-DNA complexes.

After injection of lipopolysaccharides (LPS) in mice, there is first a release of DNA into plasma and secondly an induction of anti-DNA antibodies. The circulating DNA was purified from plasma and physico-immunochemically characterized. This DNA has a similar density to mammalian cellular DNA,is 4--6S insize, and probably represents a mixture of single-stranded DNA (SSDNA) and double-stranded DNA (DSDNA) or DSDNA with some single-stranded regions. This purified DNA was shown to react with anti-DNA antibodies which appeared as early as 3 days after a single injection of LPS in mice. In serum, DNA-anti-DNA complexes were not detected, although unidentified circulating immune complex-like material was demonstrated 5-8 days after the injection of LPS. In tissues, particularly in renal glomeruli, fine granular immune complex-type immunoglobulin deposits appeared along the glomerular capillary walls and in the mesangium 3 days after the injection of LPS. There is a direct correlation between the level of anti-DNA antibodies and the intensity of glomerular deposits and about 40% of immunoglobulins eluted from kidneys are anti-DNA antibodies, indicating that some of the immune complexes localized in kidneys are DNA-anti-DNA complexes. Based on these observations, the following hypothetical mechanism for the glomerular localization of DNA-anti-DNA complexes after the injection of LPS in mice is proposed. First, DNA, which has been released in circulating blood after injection of LPS, might bind to renal glomeruli, probably on glomerular basement membranes (GBM) through a high affinity of GBM for DNA; secondly, circulating anti-DNA antibodies, which appear later, might react with the glomerular-bound DNA and form immune complexes independently of circulating immune complexes. However, the possibility of direct deposition of immune complexes is not ruled out.

Animals↗
PubMed1977

Mechanism for induction of anti-DNA antibodies by bacterial lipopolysaccharides in mice; II. Correlation between anti-DNA induction and polyclonal antibody formation by various polyclonal B lymphocyte activators.

The capacity of various polyclonal B lymphocyte activators (PBA) to induce, in mice, the formation of anti-DNA antibodies was compared with their ability to mediate the release of DNA in circulating blood and to stimulate polyclonal antibody synthesis in vivo. Anti-DNA antibodies or polyclonal antibody synthesis were induced in mice after the injection of at least 10 microgram lipopolysaccaride (LPS) from Salmonella typhimurium, 1 mg dextran sulfate (DS), or 2 mg purified protein derivative of tubercle bacteria RT32 (PPD). Smaller quantities of LPS (0.1 microgram) or DS (500 microgram) were sufficient to cause the release of DNA in circulating blood, whereas PPD was not able to provoke such a release at any concentration used. The association of anti-DNA antibodies with polyclonal antibody synthesis in mice injected with various PBA contrasts with the lack of correlation between the formation of anti-DNA antibodies and the release of measurable amounts of DNA in circulating blood. These results strongly suggest that the induction of anti-DNA antibodies by PBA is a consequence of the polyclonal B lymphocyte activation.

Animals↗
PubMed1977

Failure to detect circulating DNA--anti-DNA complexes by four radioimmunological methods in patients with systemic lupus erythematosus.

The presence of DNA-anti-DNA complexes in sera from patients with systemic lupus erythematosus (SLE) was investigated by two new radioimmunoassays (RIA) developed for this purpose and by measuring the C1q and DNA binding activity of serum before and after treatment with DNAse. Two direct RIA developed in this study were based on the reactivity of [3H]actinomycin D ([3H]ACT-D) or solid-phase methylated bovine serum albumin (mBSA) with DNA-anti-DNA complexes. DNA-anti-DNA complexes prepared in vitro could be efficiently detected at various antigen--antibody ratios by these two RIA. Increased levels of circulating immune complexes as indicated by the C1q binding test were found in 52% of SLE sera. However, the frequency of specific DNA-anti-DNA complexes detected in SLE sera was very low. Only 6% of sera exhibited an increased value deviating by more than three s.d. from the normal mean when tested with the [3H]ACT-D binding RIA or the solidphase mBSA RIA. On the other hand, there was no significant difference in the serum C1q or DNA binding activity after treatment with DNAse. These results suggest that DNA-anti-DNA complexes do not occur frequently in circulating blood and represent only a very small portion of the immune complexes detected in serum from patients with SLE.

Antigen-Antibody Complex↗
PubMed1976

Anti--DNA antibodies in patients with leukemia and lymphoma.

217 sera from 33 patients with acute myeloid leukemia (AML), 42 with chronic myeloid leukemia (CML), 12 with acute lymphatic leukemia (ALL), 22 with lymphoma, and 20 with other malignant diseases were examined by a radioimmunological technique for the presence of antibodies against DNA. The levels of single-stranded DNA binding activity was significantly higher in all 3 types of leukemia and lymphoma compared to those of healthy controls. In contrast, none of these sera exhibited a positive reaction with double-stranded DNA. In some cases of leukemia, the level of serum anti-DNA antibodies increased after the decrease of the leukocytes count.

Antibodies↗
PubMed1976

In vitro demonstration of a particular affinity of glomerular basement membrane and collagen for DNA. A possible basis for a local formation of DNA-anti-DNA complexes in systemic lupus erythematosus.

In vitro, collagen and collagen-like material in GBM, were demonstrated to have a particular high affinity for any DNA tested (mammalian, bacterial, viral, and plant). GBM fixed DNA 40-80 times more than HGG and BSA and 10-40 times more than bacterial LPS. GBM has a higher affinity for SSDNA than for DSDNA. This binding was inhibited at low pH, low ionic strength, and in the presence of anionic detergents, indicating that the highly negatively charged DNA may interact with the basic site on collagen or GBM by electrostatic forces. This interaction was competitively interfered with by DNA-binding proteins such as Clq. Complexes formed of DNA and anti-DNA antibodies did not exhibit the same binding property as free DNA. However, DNA which was already bound to GBM or to collagen could very efficiently bind anti-DNA antibodies and form immune complexes which would remain on these structures. The biological significance of the binding of DNA to GBM or to collagen should be particularly considered in relation to the pathogenesis of SLE. It is possible that DNA released from disrupted or degenerating cells would bind to surrounding collagen fibers or to basement membranes and then act as an immunoabsorbant for circulating anti-DNA antibodies. Some evidence for an in vivo binding of SSDNA to renal structures was obtained in mice treated with bacterial LPS 2 days before the injection of SSDNA.

Animals↗
PubMed1976

Genesis and pathogenicity of anti-DNA antibodies.

The formation of anti-DNA antibodies appears to be under a genetic control similar to that regulating the immune response to complex antigenic compounds. The ability to develop a high immune response to DNA seems to be predominantly dependent on the nature of the B-cell population whereas a major role of the T-cell suppressor population is not evident in this response. The immune response to DNA does not necessarily need the presence of thymus-derived lymphocytes, but in some cases T-cells may exert a helper effect. The development of anti-DNA antibody response may be triggered by various factors: viral, bacterial or parasitic agents, tissue destruction or some drugs. A mechanism that may play an important role is the "nonspecific" triggering of anti-DNA antibodies by substances that, like bacterial lipopolysaccharides, exert a potent stimulatory effect on B-cells and simultaneously induce a release of DNA in extracellular fluids. In lupus diseases as well as in mice injected with lipopolysaccharide, pathogenic effects of anti-DNA antibodies appear to be closely related to the formation of DNA-anti-DNA complexes. The demonstration that injections of lipopolysaccharide lead to the localization of DNA-anti-DNA complexes in kidney glomeruli stressed the possible importance of stimuli responsible for a release of DNA in circulating blood in the expression of the pathogenic effects of anti-DNA antibodies.

Animals↗
PubMed1976

The occurrence of antibodies against single-stranded DNA in the sera of patients with acute and chronic leukaemia.

One hundred and seventy-five sera from thirty-three patients with acute myeloid leukaemia, forty-two patients with chronic myeloid leukaemia and twelve patients with acute lymphatic leukaemia were examined by a radioimmunological technique for the presence of antibodies against single-stranded and double-stranded DNA. The levels of single-stranded DNA binding activity was significantly higher in all three types of leukaemia compared to those of healthy controls. In contrast, none of these sera exhibited a positive reaction with double-stranded DNA. In some cases the level of serum anti-DNA antibodies increased after the decrease of the leucocyte count. The presence of anti-DNA antibodies in leukaemic patients may have some biological significance.

Antibodies, Neoplasm↗
PubMed1976

Determination of anti-DNA antibodies by a modified 125I-labelled DNA-binding test. Elimination of non-specific binding of DNA to non-immunoglobulin basic proteins by using an anionic detergent.

A modified 125I-labelled DNA-binding test was developed. By using an anionic detergent, 0-025% sodium dodecyl sulphate, the non-specific binding of DNA by basic proteins was completely eliminated, while the specific binding of DNA by anti-DNA antibodies was not interfered with. The level of DNA-binding activity in normal human sera was decreased in the modified DNA-binding test, while its sensitivity was similar to that of the Farr assay in presence of sera from SLE patients.

Antibodies↗
PubMed1975

[Pathophysiological implications of antigen-antibody complexes (author's transl)].

Seventy years after the description of the Arthus phenomenon, the concept of immune complex mediated pathology is widely recognized in clinical pathophysiology. The availability of methods for the detection of soluble immune complexes opens new paths for clinical investigation in this field. This is demonstrated for systemic lupus erythematosus, viral hepatitis B and herpes zoster disease. New experimental approaches deal with the question of tissue localization of immune complex mediated diseases, e.g. through affinity of antigens for certain tissue structures.

Animals↗