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Biomedical subjects

H Osaki

Publications and source records attributed to H Osaki.

8 recordsLinked to original sources

Selective absorption of anti-DNA antibodies and their idiotype-positive cells in vitro using an anti-idiotypic antibody-affinity column: possible application to plasma exchange.

We examined the possibility of using affinity columns coupled with anti-idiotype (Id) antibodies to selectively remove nephritogenic anti-DNA antibodies in order to determine their possible application to therapeutic plasmapheresis. Monoclonal anti-Id antibodies termed D1E2 or 1F5 were directed to idotypes of human anti-single-stranded and anti-double-stranded DNA antibodies. The mixture of D1E2- and 1F5-coupled Sepharose absorbed 26 to 92% of human anti-DNA antibodies in sera. The affinity columns were also effective in removing anti-DNA idiotype-positive cells from the blood samples of patients, especially those with active lupus nephritis. Thus, an anti-idiotypic antibody-coupled affinity column could, in theory, serve as a tool for selective plasma exchange in the therapy of autoimmune disease.

Adsorption

Heterogeneity of immune complex-derived anti-DNA antibodies associated with lupus nephritis.

The mechanisms responsible for the tissue injuries associated with lupus nephritis have not yet been well explained. We have investigated the characteristics of anti-DNA antibodies in circulating immune complexes (CIC) and in the deposits of renal glomeruli in patients with active lupus nephritis. The CIC-derived antibodies expressed anti-DNA idiotypes (Id) designated as 0-81 Id and NE-1 Id, and bound mainly to single-stranded DNA but never to glomerular basement membrane (GBM) antigens. On the other hand, the immunoglobulins (Ig) eluted from renal glomeruli of lupus patients reacted not only with DNA but also with GBM, proteoglycan, and heparan sulfate. The binding of glomeruli-deposited Ig was markedly low when GBM antigens were used after treatment with heparitinase, suggesting that some anti-DNA antibodies may bind directly to GBM antigens associated with heparan sulfate, and form in situ IC in renal glomeruli. It was also revealed that the renal eluates obtained after passing through GBM antigen-coupled Sepharose lost the binding ability with GBM but still retained DNA-binding and 0-81 Id activity, showing the participation of circulating IC-derived anti-DNA antibodies in the glomerular deposits. Theoretically there may be two mechanisms in the pathogenesis of lupus nephritis through the deposition of circulating IC and through in situ formation of anti-DNA IC in renal glomeruli. The diversity of histological features in lupus kidneys may be attributed to the heterogeneity of the mechanisms.

Antibodies, Antinuclear

Therapeutic treatment of New Zealand mouse disease by a limited number of anti-idiotypic antibodies conjugated with neocarzinostatin.

-81 and NE-1 idiotypes (Id) of human nephritogenic anti-DNA antibodies are interspecies Id expressed also in NZB/W F1 mice. We tried to manipulate the synthesis of spontaneously occurring anti-DNA antibody using monoclonal anti-Id antibodies (D1E2 and 1F5) conjugated with a cytotoxic agent, neocarzinostatin (NCS). In vivo administration of anti-Id antibodies conjugated with NCS brought about an improvement in the survival rate of female NZB/W F1 mice. It also caused a retardation of development of lupus nephritis and decreased the numbers of anti-DNA-producing cells. The suppression of anti-DNA antibody synthesis was specific and Id-mediated. The results indicate that the use of a limited number of anti-Id antibodies in combination with a cytotoxic agent may be applicable therapeutically to autoimmune diseases.

Animals

Protective immune response in mice immunized with antigens from Trypanosoma gambiense-infected mouse blood.

Immunogenicity and property of antigens obtained from Trypanosoma gambiense-infected mouse blood (IMP) were examined. A strong vaccine effect against intravenous challenges with 3 x10(3) parasites given on study day 3, 5, or 14 (day 0 = immunization) was observed in mice immunized with a combination of IMP (2 mg protein/mouse) and Freund's complete adjuvant (FCA). But when the challenge was given on day 21 or 30, per cent survival in mice dropped to the 20- and 40-per cent level, respectively. Among fractioned components of IMP, IMP-1, IMP-2, and imp-3, by gel filtration with Sephadex G-200, all of the mice immunized with IMP-1 antigen alone or together with FCA and challenged on day 5 were able to conquer intraperitoneal challenges with 1 x10(2) parasites. Mice immunized with IMP-2 or IMP-3 died within 6 days after challenge. Moreover, protection efficacy shown by IMP-1p (144,000 xg sediment of IMP-1) antigen in mice was similar to that by IMP and IMP-1 antigens. IMP-3 yielded a single precipitin line against mouse anti-IMP serum by Ouchterlony double diffusion method but this response was eliminated when the antiserum was absorbed by IMP-1p. No precipitin line was identified between mouse anti-IMP serum and IMP-1 or IMP-2. From electron microscopic observations, elements of IMP-1 and IMP-1p are possibly corresponded to the fragments of filopodia of the parasites.

Agglutination Tests

In situ microspectrofluorometry of nuclear and kinetoplast DNA in Trypanosoma gambiense.

Using a spectrofluorometer with the Zeiss Universal Micro-Spectrophotometer 1 (UMSP 1), both nuclear and kinetoplast DNA (N-DNA and K-DNA) in the trypomastigote form of Trypanosoma gambiense (Strain Wellcome) were measured in situ without being extracted. As the fluorescent dye, ethidium bromide was preferably employed because there was a very marked increase in the ethidium fluorescence when the dye was intercalated between the base paires of the DNA helix. According to this method, it became possible to demonstrate the existence of double-stranded DNA in both nucleus and kinetoplast clearer than before.

DNA

Hand-Schüller-Christian disease with occult diabetes insipidus, cardiac failure and renal dysfunction.

A 60-year-old man was diagnosed as Hand-Schüller-Christian disease due to the triad of exophthalmus, decalcification of the bone, and diabetes insipidus. He had xanthogranuloma on the face and a nuchal region, and unusual complications of ADH-resistant diabetes insipidus due to renal dysfunction, and chronic cardiac failure. Urine osmolality was hypotonic, but urine volume was within the normal limit, despite the presence of central diabetes insipidus. Hypophyseal, adrenal and thyroid function were not remarkable. The skin biopsy showed the infiltration of eosinophilic granuloma cells. Treatment with vincristine was effective to regress the xanthogranuloma. Diabetes insipidus was not treated because of the absence of polyuria and polydipsia.

Acute Kidney Injury