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Biomedical subjects

H Osaki

Publications and source records attributed to H Osaki.

At least 19 recordsLinked to original sources
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

Biological activity of obiopeptide-1, a synthetic peptide derived from the native immune-regulator obioactin.

Tachyzoites of Toxoplasma gondii were killed in mouse macrophage and human somatic cell monolayers by a novel synthetic peptide (Obiopeptide-1) which is a Glycil-penta-Glutaminate (GpG) derivative of native Obioactin. In view of the worldwide prevalence of this protozoan disease and the lack of effective treatments, Obiopeptide-1 may be a new and unique antimicrobial active substance of non-antibiotic chemotherapeutic agents for intracellular parasites, T. gondii and associated nonspecific hypoimmune responses that occur in infected hosts.

Adjuvants, Immunologic↗
PubMed1989

Inhibitory effect of Toxoplasma lysate antigen on the multiplication of transplanted tumor in mice.

Tachyzoites of the RH strain of Toxoplasma gondii were pretreated by a process of freezing and thawing followed by ultrasonication. After ultracentrifugation at 144,000 g for 120 minutes, the resulting supernatant contained a protein (TLA 144), which consisted mainly of a component of protozoan origin with a molecular weight of 10,000-20,000, and additional sugars, peptides, and amino acids. TLA 144 was soluble in water and of very low toxicity. Mice that had been inoculated with allogeneic (S-180) and syngeneic (Meth A) transplantable tumor cells, were injected intramuscularly with 100 micrograms of TLA 144 once a week for some time beginning one week after transplantation. It was found that after TLA treatment the multiplication of tumor cells was more intensely inhibited than following administration of OK-432, one of the biological response modifiers (BRMs).

Animals↗
PubMed1987

In situ microfluorometry of kinetoplast and nuclear DNAs in Trypanosoma gambiense. Unusual repairment of DNA after treatment with bleomycin.

The blood stream form of Trypanosoma gambiense was smeared on a nonfluorescent slide glass with 1 microgram/ml of Hoechst 33258 in 1 mM Tris-HCl buffer (pH 7.2) containing 1% 2-mercaptoethanol and subjected to the in situ microfluorometry. Effects of bleomycin (BL) on the kinetoplast (K)-DNA and nuclear (N)-DNA of T. gambiense were examined in the time course to 6 h after injection of BL into the infected mice. An enhancement of fluorescence occurred 30 min after the injection and then slowed down. This enhancement was due to DNA synthesis both in the K-DNA and N-DNA. This suggests that the strong repairment occurs in both DNAs after treatment with BL.

Animals↗
PubMed1987

Modulator effect of Toxoplasma lysate antigen in mice experimentally infected with Plasmodium berghei.

Normal mice were pretreated twice at an interval of 2 weeks with an emulsion of TLA (Toxoplasma lysate antigen), PLA (Plasmodium lysate antigen) or both in LMO (light mineral oil) or with a combination of the emulsion and Obioactin or Tp-LKs (Toxoplasma lymphokines) as an immunopotentiator. They were then given Obioactin or Tp-LKs 3 and 25 days after the first treatment and were further given parasitized erythrocytes with 1 X 10(2)-10(4) P. berghei 2 weeks after the second treatment. Thirty (3/10, number of survival/number of examined) per cent of mice treated with TLA, 50 (5/10)% of those treated with a combination of TLA and Tp-LKs and 60 (6/10)% of those treated with a combination of TLA and Obioactin survived as long as 20 days postinfection while none of untreated controls survived more than 15 days postinfection. Only 18.2 (2/11)% of mice treated with PLA or TLA + PLA survived and 20 (2/10), 18.2 (2/11) and 60 (6/10)% of those treated with TLA + Obioactin, PLA + Obioactin or TLA + PLA + Obioactin survived throughout the experiment, respectively while none of controls survived more than 13 days postinfection. Five mice of each group were killed right before infection, and 5, 10 and 15 days postinfection. In mice treated with TLA + Obioactin, more macrophage phagocytosis and macrophage migration inhibition induced by sensitized T-cells were observed than in those treated otherwise. No appreciable differences were noted according to the method of treatment in blood examination values. Cross immunities between Toxoplasma and Plasmodium antigens were tested by counter-immunoelectrophoresis and indirect fluorescent antibody technique. By using counter-immunoelectrophoresis, a specific precipitin line was observed between TLA and anti-PLA which was absorbed by mouse erythrocytes, leucocytes and liver powder. By the indirect fluorescent antibody technique, anti-Plasmodium IgM and IgG titers were detected in sera from mice treated with TLA or TLA-Obioactin before infection.

Adjuvants, Immunologic↗
PubMed1987

Correlation between release of reactive oxygen intermediates and inhibition of Toxoplasma multiplication in mouse peritoneal and alveolar macrophages and kidney cells after in vitro incubation with Obioactin, lonomycin A, muramyl dipeptide, lipopolysaccharide or Toxoplasma lysate antigen.

The inhibition of Toxoplasma multiplication inside cells does not correlate with an enhanced release of oxygen intermediates except in the case of peritoneal macrophages treated with Obioactin. The inhibition observed in alveolar macrophages treated with Obioactin, in kidney cells treated with Obioactin or lonomycin A and in peritoneal macrophages treated with lonomycin A was not accompanied by an increment of release of oxygen intermediates. Lipopolysaccharide (LPS) and muramyl dipeptide (MDP) enhanced the release of toxic oxygen intermediates in peritoneal macrophages, but did not have any toxoplasmacidal effect. Adenosine triphosphate (ATP) content increased during Obioactin, MDP or Toxoplasma lysate antigen (TLA) treatment. The actual oxygen consumption of the peritoneal macrophages treated with Obioactin increased dose dependently, but that of TLA-, lonomycin A- or MDP-treated cells did not change. These results suggest that the relationship between the intracellular killing of Toxoplasma protozoa and the release of oxygen intermediates differs according to the cells and/or the stimuli, and that the cellular mechanism of Toxoplasma killing in the peritoneal macrophages treated with Obioactin involves an energy-dependent mechanism.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1987

Multi-point flicker recognition apparatus and its application for video display terminal work.

The apparatus to measure multi-point critical flicker fusion frequency (MCFF) was devised for more precise determination of the critical flicker fusion frequency (CFF). Using this apparatus, the variations in flicker value after the work load of the television (TV) game, the Kraepelin using the video display terminal (VDT-Kraepelin) and the paper-Kraepelin were examined in order to test its practical applicability. The following results were obtained. The degree of decrease in the CFF values of some peripheral eye fields was larger than that on the central field of both eyes (ordinary CFF) after work load. The variation rates of the central and the peripheral flicker values were measured before and after loading in each work, and the correlations of variation rates between two CFF values among them were calculated. The numbers of peripheral eye fields showing significant correlation of variation rates between two eye fields in the TV game and the VDT-Kraepelin, were greater than those in the paper-Kraepelin.

Adult↗
PubMed1984

Effects of bleomycin on kinetoplast DNA and nuclear DNA in Trypanosoma gambiense using in situ microfluorometry technique.

The effect of Bleomycin, an anti-tumour antibiotic, on either kinetoplast DNA(K-DNA) or nuclear DNA(N-DNA) in a single Trypanosoma gambiense cell was measured successfully utilizing the in situ microfluorometry technique. This microfluorometric assay clearly revealed that the relative fluorescence intensity (RFI) of K-DNA and N-DNA was greatly reduced by bleomycin, suggesting the occurrence of the single strand breaks in these DNAs. The present results have shown that bleomycin acts on N-DNA stronger than K-DNA at least in Trypanosoma gambiense. Microfluorometry technique can be employed valuably for studying the DNA damages of several anti-protozoan drugs.

Animals↗
PubMed1981

Agglutination antibody responses to Trypanosoma gambiense homogenate in mice treated with dextran sulfate 500 and carrageenan.

Dextran sulfate 500 and carrageenan, sulfated polysaccharides, have been considered as macrophage-toxic giving profound effects on the immune response. This work deals with agglutination antibody responses to T. gambiense homogenate in mice treated with dextran sulfate 500 and carrageenan. Antibody responses to the first immunization were suppressed in mice treated with the agents before the first immunization but reverse was the case with the response to the second immunization. These suppression and enhancement appeared to be dependent on the timing of treatment in regard to the time of the first immunization. The enhanced antibody response was abolished by either treating the mice with anti-thymocyte serum or transferring of spleen cells treated with anti-thymocyte serum into mice. Thus, the enhancement of antibody response is seemingly attributable for the most part to potent memory T cells induced by treatment with the agents.

Agglutination Tests↗
PubMed1980

Effects of dextran sulfate 500 on protective responses to sublethal Trichomonas foetus infection in mice.

In order to analyze the host-parasite interactions in experimental trichomoniasis, the growth of Trichomonas foetus in the peritoneal cavity and changes in the peritoneal exudate cells were followed in mice treated with dextran sulfate 500 (DS 500), a known macrophage-toxic agent. Light microscopic observation showed that DS 500 treatment induced degeneration of peritoneal macrophages within about 48 hr after the treatment and the damaged macrophages did not phagocytize the parasites, whereas peritoneal neutrophils and lymphocytes were not affected by the drug. In the DS 500-treated mice, growth of parasites in the peritoneal cavity was accelerated and a high susceptibility of the mice to T. foetus infection was observed. These results indicate that macrophages play the most important role among the peritoneal exudate cells in resistance to T. foetus infection, especially during the early stage of infection.

Animals↗
PubMed1979

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↗
PubMed1979

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↗