Synthesis of the 3-O-demethyl and 2"-N-formimidoyl derivatives of istamycin B.
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Biomedical subjects
Publications and source records attributed to Y Horiuchi.
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Guinea pigs were immunized with complete Freund adjuvant and PPD was inhaled seven times at three-week intervals. Histological examination revealed a tendency to fibrotic changes in comparison with control animals.
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Effect of oral administration of mite antigen was studied in homocytotropic antibody production in mice. Anti-mite IgE and IgG, antibodies were undetectable if the large amount of mite antigen was given prior to primary immunization. It was noted that the larger the dosage given the more clearly the suppression of homocytotropic antibody production was obtained and the shorter the interval between feeding and primary immunization the more marked tolerance was induced. No significant effect was observed by oral administration of antigen in on-going homocytotropic antibodies.
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An index was devised to estimate the hypersensitivity states of mast cells and basophil leukocytes on the basis of serum concentrations of total IgE immunoglobulins and specific IgE antibodies. Correlation between improvement of blindly determined clinical states and the indices (stability index: SI) was subjected to statistical analysis. Close correlation between them was found in atopic asthmatic patients who were receiving hyposensitization therapy.
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Various methods have been employed for standardization of potency of allergen extracts. We used passive cutaneous anaphylaxis (PCA) inhibition in a mouse-to-rat system as a new means of standardization. Several allergen extracts, including mite, short ragweed, house dust, Aspergillus, Candida, and Japanese cedar, were examined. Mouse IgE antibodies were produced after two or three injections of antigen and alum. The potency measured by PCA inhibition in the mouse-to-rat system was compared with that of protein nitrogen (PN) content, end point of prick test in humans, and 50% radioallergosorbent test (RAST) inhibition. Our studies suggest that the mouse-to-rat system could be used to determine allergenic potency and to standardize allergen extracts.
IgE levels in nude mice were estimated by the one-step single radial radiodiffusion method antisera prepared by immunization of guinea pigs with an IgE-rich fraction obtained from sera of normal mice infected with Nippostrongylus brasiliensis and immunized with DNP-ovalbumin in alum gel. 3 out of 8 nude mice had IgE levels significantly higher than those of normal mice.
The effects of levamisole on the formation of antibody to double-stranded DNA (ds-DNA), an auto-antibody, and to some thymus-dependent antigens were studied in nude (nu/nu) mice. The antibody titre to ds-DNA in nu/nu mice treated with levamisole was lower than that in control animals. The number of Thy-1-antigen-positive (Thy-1+) cells in the spleen from nu/nu mice treated with levamisole was higher than that from non-treated animals. It is suggested that the Thy-1+ cells were induced by levamisole in nu/nu mice and these cells suppressed the formation of antibody to ds-DNA, whereas the formation of antibody to a DNP-conjugate (OVA) and SRBC, thymus-dependent antigens, was not evoked in nu/nu mice after the treatment with levamisole.
Two T lymphocyte-specific antisera, i.e. naturally-occurring auto-antibody to T cells of systemic lupus erythematosus patients (natural T cell toxic autoantibody) and heterologous antiserum against human brain tissue (antibrain-associated T-cell antigen), were used to detect cell surface antigens of human peripheral T lymphocytes. Nylon column-purified T cells from normal aged individuals and patients with Werner's syndrome (a premature aging syndrome) were reacted with these auto- and heterologous antibodies followed by staining with appropriate fluorescence reagents. The cells were subjected to the automated analysis with fluorescence-activated cell sorter. Fluorescence profiles to T cells of both aged individuals of over 90 yr and Werner's syndrome showed a very similar pattern, with a drastic decrease in the population that had high fluorescence intensity stained with either antiserum accompanied by the relative increase in the cell population that had low fluorescence intensity. Natural T cell toxic autoantibody comparable to that detected in systemic lupus erythematosus patients was found in the serum of six out of seven patients with Werner's syndrome, whereas normal aged individuals produced no such an autoantibody. The results suggest that Werner's syndrome has a change in the lymphocyte population very similar to old individuals, and that such a change is caused by the production of autoantibodies reactive to T lymphocytes.
The two-color method originally described by Van Rood et al. (Van Rood, J. J., A. Van Leeuwen, and J. S. Ploen. 1976. Simultaneous detection of two cell populations by two-color fluorescence and application to the recognition of B-cell determinants. Nature (Lond.). 262: 795-797) for the typing of homologous leukocytic antibodies, D-region was used for the detection of antilymphocyte antibody (ALA) in systemic lupus erythematosus. In this method, surface immunoglobulin-bearing cells were identified with fluorescein isothiocyanate-labeled anti-immunoglobulin and nuclei of killed cells were stained with ethidium bromide. Therefore, cell type (T or B) of the target cells can be identified without fractionating them. ALA was detected in 87% of lupus sera and had a preferential reactivity with T cells. Its major immunoglobulin class was shown to be immunoglobulin (Ig)M. The subspecificity of ALA was further analyzed using fractionated T-cell subsets as target cells. When T lymphocytes were separated into Fc receptor-bearing (Tgamma) and lacking (Tgamma[-]) cells, 64% of ALA showed preferential reactivity with Tgamma cells and 14% with Tgamma(-) cells. The remainder had no selective reactivity against Tgamma or Tgamma(-) cells. Tgamma cells were shown to have suppressor activity, whereas Tgamma(-) cells were indicated to contain helper cells. The above finding was in agreement with the observation that treatment of T cells with ALA that preferentially react with Tgamma cells considerably enhanced immunoglobulin synthesis in vitro, whereas treatment of T cells with ALA reactive with Tgamma(-) cells clearly suppressed the formation of immunoglobulins. Treatment of ALA with no selective reactivity showed variable effects on in vitro immunoglobulin synthesis. These results indicate that ALA in lupus have heterogeneous specificities against human T-cell subsets.
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